Quantum Biology of the Eye: Understanding the Essentials 303132059X, 9783031320590

Citation preview

Quantum Biology of the Eye Understanding the Essentials Kambiz Thomas Moazed

123

Quantum Biology of the Eye

Kambiz Thomas Moazed

Quantum Biology of the Eye Understanding the Essentials

Kambiz Thomas Moazed New York, NY, USA

ISBN 978-3-031-32059-0    ISBN 978-3-031-32060-6 (eBook) https://doi.org/10.1007/978-3-031-32060-6 © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Preface

Entering the quantum era revolutionized our understanding and our concepts of molecular and atomic particle behavior and their interactions. Applying the rules of quantum physics to biology was considered impossible at the beginning. The wet, warm, and noisy environment of biological systems seems hostile to quantum interactions. Then comes the newer studies that one after another reveal the existence of quantum effects on biology. This started with the discovery of the quantum effect of photon energy transfer in plant’s green molecule of chlorophyll in the photosynthesis process. This was followed by the discovery of quantum vibration in olfactory receptors involved in the sense of smell, which was followed by detection of avian magneto-­ receptors in the bird’s retina required for their migration flights. The new studies have now opened the door for understanding the human consciousness and the perception of external senses. In retina, quantum processing has been observed and plays a major role in vision processing. Visual processing is very complex and is not limited only to the visual center at the visual cortex in the occipital lobe, but by simultaneous activation and stimulation of the entire brain. In this book we start with the orientation to the basics of quantum physics, then progress to the description of quantum biology and the basics of utilization of light energy and applied rules of quantum physics on biological systems. Here we start with the most basic form of light energy utilization which is photosynthesis in plants, to magnetoreceptors in the retina of the migrating birds, to the more complex role of retinal phototransduction of energy, and eventually the perception of visual inputs and the concept of human consciousness. New York, NY, USA

Kambiz Thomas Moazed

v

Acknowledgments

• There were no financial assistance or compensation received from any organization or companies towards the preparation of this book. • All expenses for the preparation of the book were financed by me. • Many thanks to my graphic designer David Folender who collaborated with me to create all the images of this book. • My sincere gratitude and thanks to my brother Hamid R. Moazed for his assistance in preparation and editing of this book.

vii

Contents

1

 Introduction to Quantum Physics����������������������������������������������������������    1 Discussion������������������������������������������������������������������������������������������������     1 What Is Quantum Physics?����������������������������������������������������������������������     2 Classical Physics Versus Quantum Physics ��������������������������������������������     2 Characteristics of Quantum Physics��������������������������������������������������������     3 Specific Behavior of Quantum Physics����������������������������������������������������     3 When Did It Start? ����������������������������������������������������������������������������������    11 What is Quantum Biology?����������������������������������������������������������������������    17 What Are Its Applications?������������������������������������������������������������������    17 References������������������������������������������������������������������������������������������������    18

2

 Introduction to Quantum Biology����������������������������������������������������������   21 Discussion������������������������������������������������������������������������������������������������    22 When Did It Start? ����������������������������������������������������������������������������������    22 Basic Information for Better Orientation������������������������������������������������    23 The Electron��������������������������������������������������������������������������������������������    23 Jablonski Diagram ����������������������������������������������������������������������������������    28 Quantum Biology Tools ��������������������������������������������������������������������������    32 Nitrogen Vacancy (NV) Centers in Diamond��������������������������������������    33 The Most Studied Fields of Quantum Biology������������������������������������    35 Photosynthesis in Plants��������������������������������������������������������������������������    36 References������������������������������������������������������������������������������������������������    41

3

 Classic Biology of Human Eye����������������������������������������������������������������   43 The Anatomy Highlights of the Eye��������������������������������������������������������    44 The Physiology of the Light Absorption in the Retina����������������������������    49 The Visual Cycle��������������������������������������������������������������������������������������    52 The Photoreceptors, the Rod Cells, the Cone Cells, and the Ganglion Cells ��������������������������������������������������������������������������������������������������������    53 Activation of Rods and Cones�����������������������������������������������������������������    54 The Retinal Pigment Epithelium��������������������������������������������������������������    58 The Bipolar Cell’s Function��������������������������������������������������������������������    60 ix

x

Contents

Activation of Bipolar Cells����������������������������������������������������������������������    60 The Amacrine Cells����������������������������������������������������������������������������������    61 The Horizontal Cells��������������������������������������������������������������������������������    61 The Ganglion Cells����������������������������������������������������������������������������������    61 Activation of Ganglion Cells ������������������������������������������������������������������    63 Visual Phototransduction Steps����������������������������������������������������������������    63 More Related Interesting Articles������������������������������������������������������������    64 References������������������������������������������������������������������������������������������������    64 4

Quantum Retina��������������������������������������������������������������������������������������   67 Discussions����������������������������������������������������������������������������������������������    67 Radiation and Human Eye ����������������������������������������������������������������������    70 Rhodopsin������������������������������������������������������������������������������������������������    71 Atomic Orbitals����������������������������������������������������������������������������������������    72 Molecular Orbitals ����������������������������������������������������������������������������������    74 Binding Orbitals Categories��������������������������������������������������������������������    74 Energy Level��������������������������������������������������������������������������������������������    75 Radiative Decay ��������������������������������������������������������������������������������������    77 Non-radiative Decay��������������������������������������������������������������������������������    77 Nuclear Response������������������������������������������������������������������������������������    78 Carbon������������������������������������������������������������������������������������������������������    78 Lysine (C6H14N2O2)����������������������������������������������������������������������������������    79 From (E) to (Z) Isomerization������������������������������������������������������������������    80 Isomerization��������������������������������������������������������������������������������������������    80 Time Fractions in Isomerization of 11-cis Retinal����������������������������������    82 Femto Scale����������������������������������������������������������������������������������������������    83 Femto Chemistry of Rhodopsin ��������������������������������������������������������������    84 References������������������������������������������������������������������������������������������������    85

5

Magnetoreception������������������������������������������������������������������������������������   87 Earth Magnetic Field (EMF)��������������������������������������������������������������������    88 References������������������������������������������������������������������������������������������������    99

6

 Quantum Biology of Circadian Rhythms����������������������������������������������  101 Important notes for clarification��������������������������������������������������������������   101 Discussions����������������������������������������������������������������������������������������������   102 Clock Genes and Signal Transduction Proteins ��������������������������������������   104 Molecular Effect��������������������������������������������������������������������������������������   106 List of Neurotransmitters Involved in Circadian Cycles��������������������������   106 List of Hormones Involved in Circadian Cycles��������������������������������������   107 Light Exposure����������������������������������������������������������������������������������������   108 Small Molecules and Drugs ��������������������������������������������������������������������   109 Transcriptional-Translational Feedback Loops (TTFLs)������������������������   110 Light Entrainment������������������������������������������������������������������������������������   112 Pupillary Reflexes������������������������������������������������������������������������������������   113 Suprachiasmatic Nucleus (SCN)��������������������������������������������������������������   113 Circadian Clock Networks:����������������������������������������������������������������������   113

Contents

xi

Cellular Transcription-Translation Feedback Loop (TTFL)��������������������   114 The Molecular Interplay in Circadian Cycles������������������������������������������   114 The Brain and Circadian Rhythms����������������������������������������������������������   115 Conclusion ����������������������������������������������������������������������������������������������   115 References������������������������������������������������������������������������������������������������   115 7

 The Quantum Biology of Consciousness and Visual Perception ��������  119 Knowledge and Consciousness����������������������������������������������������������������   120 Neurons����������������������������������������������������������������������������������������������������   121 Synaptic Connections������������������������������������������������������������������������������   122 Mitochondrion (Mitochondria = Plural)��������������������������������������������������   124 Mitochondrial Respiratory Chain Complexes������������������������������������������   125 Oxygen and Reactive Oxygen Species (ROS) ����������������������������������������   126 Radical Pair Mechanism (RPM)��������������������������������������������������������������   127 Singlet Oxygen: (1O2)��������������������������������������������������������������������������   127 Triplet Oxygen: (3O2) ��������������������������������������������������������������������������   129 Microtubules��������������������������������������������������������������������������������������������   130 Functional Architecture of Microtubules in Neurons��������������������������   131 Quantum Biology of Microtubules������������������������������������������������������   133 Microtubules Energy Transfer ������������������������������������������������������������   133 Microtubules, Mitochondria ROS and Biophotons Interactions����������   134 Conditions Associated with Microtubule Abnormalities ��������������������   136 Microtubule-Binding Core of the Tau Protein:������������������������������������   136 Biophoton or Ultraweak Photon Emission (UPE) ����������������������������������   137 The Müller Cells��������������������������������������������������������������������������������������   139 Retinal Müller Cells as Living Optical Fibers ������������������������������������   140 Müller Cell Intermediate Filaments (IFs) and Quantum Mechanism of Light Energy Transfer in the Retina����������������������������   141 Tryptophan ����������������������������������������������������������������������������������������������   142 Properties of Consciousness��������������������������������������������������������������������   146 Quantum Phenomena ������������������������������������������������������������������������������   146 Quantum Coherence����������������������������������������������������������������������������   146 Quantum Superposition ����������������������������������������������������������������������   147 Quantum Tunnelling����������������������������������������������������������������������������   147 Quantum Entanglement ����������������������������������������������������������������������   147 Magnetic Field Effect and Entanglement��������������������������������������������   147 Altered States of Consciousness����������������������������������������������������������   149 The Quantum Brain������������������������������������������������������������������������������   152 The Quantum Vision��������������������������������������������������������������������������������   154 Human Perception as a Phenomenon of Quantization������������������������   155 The Role of Symmetry in Biology and Consciousness ��������������������������   155 References������������������������������������������������������������������������������������������������   157

Addendum����������������������������������������������������������������������������������������������������������  161 Index������������������������������������������������������������������������������������������������������������������  171

Chapter 1

Introduction to Quantum Physics

Abstract Entering the era of quantum physics opened the door to the emerging new field of quantum biology. At first, its relevance to living organisms was not recognized, yet as scientific knowledge and experimental studies evolved the new correlation and recognition of quantum entities to the biology is being discovered. This chapter is to introduce the birth of quantum physics which is the source of the emergence of quantum biology. Basically, we discuss the birth of quantum mechanics and its transformation into quantum biology and the main figures that helped the evolution of quantum biology. In the next chapter, we will discuss the essential information on what is the role of quantum physics in biology, and how it affects the physiology of the different cellular structures and organs. As any biological cellular structure is composed of molecules that are composed of atoms and subatomic particles, it is expected that the quantum effect would be applied to them. It is interesting that nature has used quantum biology to its advantage and has billions of years of head start as we are beginning to learn how it works today.

Discussion One important note is that to think and understand the quantum world one should erase the “normal” way of thinking and enter into the unintuitive, strange, and spooky world that is called quantum physics.

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 K. T. Moazed, Quantum Biology of the Eye, https://doi.org/10.1007/978-3-031-32060-6_1

1

2

1  Introduction to Quantum Physics

Also, we cannot discuss the quantum biology without knowing the basic and fundamental information on quantum physics. • • • •

What is quantum physics? When did it start? How can it be applied to Biology? What is quantum Biology?

What Is Quantum Physics? The world of modern physics was established, but not started, by English mathematician Isaac Newton in the seventeenth century. The Newtonian physics, also called classical physics, was based on the three rules of motion that are essential for calculating the relationship between the motion of an object and the forces that acting on it. These rules are still applicable to large objects as a good approximation today. But when the scientist started to work on very small objects, say smaller than 10−9 m (1 nm), these laws could not be applied. There was a need for a new set of rules for small objects and that was the birth of quantum physics. The term quantum physics is the same as quantum mechanics though the term mechanics emphasizes doing calculations. The birth of quantum physics was inevitable in order to explain the strange world of small particles and their effect on all objects.

Classical Physics Versus Quantum Physics In the late nineteenth century and early twentieth century while physicists were studying atoms and their components, they noticed that the laws of physics for very small objects are different from the laws used for ordinary objects which are referred to as classical mechanics or Newtonian mechanics. This separated the field of physics into two categories: • Classical mechanics: which can explain macroscopic phenomena of large objects even the planets and the Maxwell equation in electromagnetics. However, there were exceptions that could not be explained by classical physics such as superconductors, superfluids, lasers, and crystal dynamics. • Quantum mechanics: which can explain microscopic phenomena such as photons and electrons. It has precise mathematical formulations as in Hermitian operators and Hilbert spaces (Fig. 1.1). Note that while there may appear to be a dichotomy of rules—one set for the ultra-small and another for large objects, there actually is only one set of rules— quantum mechanics—that governs the world of the small and the large. It is just that

Specific Behavior of Quantum Physics

3

Fig. 1.1  Quantum physics applies to small size particles as can be seen in the examples above

the effects of quantum mechanics are so minuscule on large objects that they can in most parts be ignored, and classical mechanics can be used instead as a very accurate approximation.

Characteristics of Quantum Physics Multiple interpretations: There are many interpretations on quantum phenomena and rules and there are still many controversies among the physicists [1]. • • • •

Copenhagen Multi-world Interpretation (MWI) Environmental decoherence Others

By the 1920s, key mathematical laws of quantum particles were established and developed by Erwin Schrödinger (Schrödinger’s Wave equation) and Werner Heisenberg (Heisenberg matrix mechanics) which established precise calculation and properties of particles such as electron’s position and speed.

Specific Behavior of Quantum Physics Here are specific properties of the quantum world that need to be explored and discussed:

4

1  Introduction to Quantum Physics

• Heisenberg uncertainty principle: This formula is the foundation of quantum physics which states that there is a fundamental limit to what one can know about a quantum system. For example, the more precisely one knows a particle’s position, the less one can know about its momentum. x p 



h 4

Δx = Uncertainty in position Δp =Uncertainty of momentum h = Planck’s constant π = pi • Wave particle duality: In quantum world small particles such as photons or electrons can act as both particles and waves. The observations and experiments interpretations for this phenomenon are still under controversy 100 years later. These observations can be narrowed down to two fundamental experiments which each represents one or the other. The experiment of photoelectric phenomena (The particle characteristic) and the double slit Experiment (The wave characteristic). 1. Particle Behavior of light (Photoelectric phenomena): Light can eject electrons from material such as metal only if its frequency is above the threshold frequency. The electrons are dislodged only when the light exceeds a certain frequency regardless of the light’s intensity [2]. This phenomenon is a clear example of the particle behavior of the light that cannot be explained by the wave behavior of the light (Fig. 1.2). The photon energy is directly proportional to its frequency:

E = hc / h

Fig. 1.2  Photons with different electronvolts energy cause the emission of electrons from the Potassium plate only if its frequency is above the threshold frequency of potassium (2.24 eV)

Specific Behavior of Quantum Physics

5

E (photon energy) (J) h (Planck’s constant) (6.626 × 10−34) c (Speed of light) (3.0 × 108) λ (Frequency) (Hz) One photon of visible light contains about 10−19 joules of energy (Fig. 1.3). eV (electron volt): is a common unit of energy and is the amount of kinetic energy that is gained by a single electron accelerated from a rest state through an electron potential difference of 1 volt in a vacuum. Characteristics of photoelectric effect [3]: • It is instantaneous • Occurs only when the radiation is above a cut-off frequency (the minimum frequency that is required for the emission of electrons from a metallic surface). • Does not depend on intensity of the radiation. • Particle energy only depends on its frequency. • Each metal has its own characteristic work function. • Work function is the binding energy of electrons to the metal surface. • At the surface, the entire energy of an emitting one photon is transferred to one photoelectron. List of some metalwork functions: 1. One electron volt (eV) is the kinetic energy acquired by an electron acted upon by a potential difference of 1 volt.

1 eV  1.6  1019 Joules “National Institute of Standards and Technology” [4] (Fig. 1.4)

Fig. 1.3  Chart representing photon energy (ev) according to the wavelength of the spectrum

6

1  Introduction to Quantum Physics

Fig. 1.4  Work function of sample metals in electronvolt

2. Wave behavior of light (Double slit phenomena): This is one of the most discussed phenomenon in the quantum world and is also one of the most important experiments which is easy to perform yet is the center of many interpretations [5] Fig. 1.5. The experiment is composed of a light source, a barrier with two parallel slits and a screen to show the image of the projected light from the light source. The light pattern on the screen behind the double slit creates an interference pattern, producing dark and light bands representing the wave behavior of the light. Repeating the experiment with single photon emission will produce individual discrete impact points which indicates that it is not a function of the wave behavior. This pattern of particle accumulation in certain locations that forms the same dark and light bands is based on probabilistic preference which is the particle behavior of the light. The issue here is that the moment the detector is placed to detect which slit the light particle is traveling through, the striped pattern disappears. When nobody is looking, no measurement or detection devices are present: • • • • •

Systems are described by wave function. Wave functions obey Schrödinger’s equation. When somebody looking, measurement or detection devices are present. Wave function collapses to a measurable particular value. Probability of each outcome is equal to the square of the wave function: 2

P  x   x

P: Probability Ψ: Wave function

The wave particle duality can also be observed in different circumstances which can be summarized as follows: –– Wave function only: Diffraction, Interference, and polarization. –– Particle function only: Photoelectric phenomenon.

Specific Behavior of Quantum Physics

7

–– Both wave and particle function: Reflection and refraction. • Probability theory: There is a superposition of a number of possible outcomes of measurement of physical properties in a quantum state. This was presented by Schrödinger’s formula. • Quantization of energy: In physics, quantization is to construct quantum field theory out of classical field theory, such as basics to particle physics, nuclear physics, and quantum optics.

Fig. 1.5  Image of Double Slit Experiment: A coherent source of light such as a monochromatic laser (Top) or electrons from an electron gun (Bottom) passes through two parallel slits on a plane between the source and screen behind the plate. The interference pattern appears on the screen in both experiments which mimics the wave nature of the light or even small particles such as electrons

8

1  Introduction to Quantum Physics

• Observer Problem (Schrödinger’s cat on the box) [6]. Quantum field alteration or interaction by observing or recording the experiments has produced many controversies and interpretations. Each of these theories has its shortcomings and yet only the theory of multiverse can reasonably explain the process and will be briefly discussed. The experiment was presented by Schrödinger who presented a hypothetical experiment as the destiny of a “cat in the box” was determined by release of radioactive particles from the source in the box. The cat would be alive or dead at the same time, due to the release of a poisonous gas which is attached to a source of radioactive monitor that detects the random subatomic event that may or may not occur at the same time. When the observer opens the box only one state (Dead or alive) can be observed. In another word, the quantum state collapses the moment it is observed. All the interpretations consider the observer as a classical physics and not as a quantum observer (Fig. 1.6). When incorporating the fact that the observer is not a part of classic physics and is made of atoms that obey the rules of quantum physics the interaction of observer. The event and the object’s destiny which is a cat in this experiment does not collapse, but it simply entangled with the corresponding universe with the specific status of the cat. All possible outcomes happen in a different universe at the same time which is very anti-intuitive as many fields of quantum mechanics (Fig. 1.7). • Quantum Decoherence (Measurement problem).

Fig. 1.6  Copenhagen Interpretation of the Cat in the Box: The moment that the observer opens the box and looks in it, the quantum state of the cat collapses into one outcome. The cat is either dead or alive

Specific Behavior of Quantum Physics

9

Fig. 1.7  Many worlds interpretation of the Cat in the Box: The observer is also in a quantum state in a parallel universe as the cat is, any possible scenario can happen at the same time with the entanglement of the observer and the cat with highest probability event

10

1  Introduction to Quantum Physics

The quantum closed system is coherent when there is a definite phase relation between all its states. According to the Copenhagen interpretation any attempt to investigate or measure the system causes the collapse of many possibilities of states into a single state. There are many interpretations on this strange phenomenon. According to the Multi-World Interpretation (MWI), all possible states continue to exist without the “collapse” into a single state. Another general interpretation is that the information interacts with the environment and as the result it gets lost [7]. The Copenhagen interpretation [8] sets rules of quantum physics regarding the observer or measurement problem. 1. When there is no observer (detector): • Systems are described by wave function. • Wave functions obey the Schrödinger equation. 2. When there is an observer (detector): • Wave function collapses to a particular value. • Probability of any outcome is the square of its wave function. Since particles can have wave particle duality, the behavior of a particle can be described using a wave function. • The wave function itself does not represent a physical variable but its square magnitude does 2

P  x    x

P: Probability. Ψ: Wave function.

Entanglement: Small particle can entangle with each other and interact instantly regardless of their distance. For example, decaying atomic particles can have 2 sub-­ particles that can entangle and interact with each other in a way that, for example, if one spins up the other always spins down (Fig. 1.8). The Multi-World interpretation (MWI): • Systems are described by wave function. • Wave functions obey the Schrödinger equation. • In MWI entanglement is implied and does not require instantaneous transfer of information. In the MWI, the observer is not treated using classical mechanics, instead he or she is part of the quantum mechanical system and follows the Schrodinger equation just as the rest of the system. This eliminates the need for the “collapse” of the wave function and results in a world that appears identical to the one described by Copenhagen interpretation [9].

W hen Did It Start?

11

Fig. 1.8  The Higgs has zero spin. When decaying produces two particles spinning in opposite directions

The physical properties of the particles such as position, momentum, spin, and polarization are perfectly correlated. In the Copenhagen interpretation the question is how the information in one entangled particle is accessible to the other instantly which defy the fact that no information can travel faster than the speed of light. Meanwhile for the MWI interpretation there is no need for transfer of information. One example is the Higgs Boson that has no spin, which can decay and split into two particles with opposite spins. Interestingly there is no separate wave function for each particle. There is only one wave function of the universe (Fig. 1.9) [10]. • Quantum tunnelling: Particles can pass through potential barriers. More precisely a particle can penetrate a potential energy barrier even though there is insufficient energy to overcome it. This effect is essential for chemical reactions [11]. • Random world of quantum: The second law of Thermodynamics indicates that the measure of randomness (entropy) increases in time. The definition of randomness can be used differently in quantum physics and quantum biology which the randomness is as an essential component of the intrinsic unpredictability of life. In another word, the biological randomness is required for the structural stability of a biological system [12].

When Did It Start? Although the history of modern physics goes back to early 1800s, it was not until 1900 that the revolutionary changes emerged, to the point that the terms pre 1900 physics (classical physics) and post 1900 physics (modern physics) are being referred to. This was the beginning of the major paradigm shift in physics. There are numerus scientists that contributed to the development of quantum physics, we only mention some of the essential figures with the summary of their work: • Henri Poincare (April 29, 1854–July 17, 1912) [13]: He elaborated Gravitation wave theory, Chaos theory, and Special relativity theory. His contributions were

12

1  Introduction to Quantum Physics

Fig. 1.9  The Table of elementary particles: The Mass Charge and the spin of each particle is indicated on the chart as shown

essential to the origin of special relativity theory, yet he did not get as much credit as he deserved. • Max Planck (April 23, 1858–October 4, 1918) [14]: (The first direct quantum hypothesis). He was a German scientist who received the Noble Prize in 1918. His work on blackbody radiation and in 1900 with the hypothetical assumption reached to the conclusion that electrically charged vibration emitted from blackbody radiation could only change in a minimal increment and the frequency is proportional to the frequency of its associated electromagnetic wave. He was one of the most essential pioneers of quantum physics and best known for his constant (Planck’s constant) (h) which was formulated as his effort to produce an accurate mathematical prediction of distribution of thermal radiation from blackbody radiation. This was fundamental physical constant with a fundamental importance in quantum mechanics. His equation was essential and simple:

 E  hv 

(E) energy of a single photon is equal to the (v) incident light frequency and the (h) Planck’s constant (h = 6.62606957 × 10−34).

W hen Did It Start?

13

• Neils Bohr (October 7, 1885–November 18, 1962) [15]: (Electron orbits). He was a Danish physicist who made a fundamental contribution to describe atomic structure and quantum theory. He received a noble prize in physics in 1922. He proposed that the energy levels of electrons are discrete with stable orbits around the nucleus and can move from one orbit to another. • Werner Heisenberg (December 5, 1901–February 1, 1976) [16]: (Uncertainty Principle). One of the pioneers of quantum physics. He was a German theoretical physicist and was awarded the 1932 noble prize in physics. His contribution to quantum physics is his work in the “uncertainty principle” and “subatomic particles.” Together with Neils Bohr developed the “Copenhagen interpretation” of the probabilistic nature of wavefunction. Louis de Broglie (August 15, 1892–March 19, 1987) [17]: (Wave particle duality). French physicist that made a major contribution to quantum theory and won the Noble Prize for physics in 1929. His hypothesis on the wave nature of electrons and that all matter has wave properties was a major breakthrough in quantum physics and carries his name. He suggested that the relation that is derived to relate momentum and wavelength for light should also be applied to particles. His formula:

  h / p λ (Wavelength) = h (Planck constant)/ P (Particle momentum). Which P (Particle momentum) = m (Mass) v (velocity). This formula can be used to describe atomic-scale systems.

• Wolfgang Paoli (April 25, 1900–December 15, 1958) [18]: (Spin and quantum physics) Austrian physicist who had important role in the field of spin in quantum physics. He presented his exclusion principle which states that only one fermion* can occupy a particular quantum state at a given time. If there are more than one, then their spin should be a different direction. He was the first to propose doubling the number of available electron states. *Particles with half-integer spin are fermions (all quarks, leptons, Baryons) associate with matter. *Particles with integer spin are bosons (Electrons, protons) associate with force carrier particles (Fig. 1.9). • Erwin Schrödinger (August 12, 1887–January 4, 1961) [19]: (Known for his book “What is life,” his wave function Formula and the Cat in the box hypothetical experiment). One of the most important pioneer figures in quantum physics and quantum biology.

14

1  Introduction to Quantum Physics

An Austrian Theoretical physicist who also won the Noble prize in physics for his contribution to quantum physics in 1933. His major contributions out of many can be summarized as follows: –– The application of quantum physics to living organisms. His book publication “What is Life” [20] for the first time the concept of life is the subject of atomic particles which expected to follow quantum rules. –– Schrödinger Equation provides the evolution of wave function over time in a system. This fundamental and precise calculation of the wave function of a state is essential in quantum mechanics and is applicable today, 100 years later. There are different versions of the equation but the most complete is the time-­ dependent formula: Description of Schrödinger formula: Schrödinger Equation  is the most fundamental and essential formula for quantum physics and it is important to understand it regardless of how complex it looks [21]. The wavefunction is referred to by “Psi” (ψ) and is a complex valued probability amplitude and is a mathematical description of quantum state of an isolated quantum system. At a glance the Schrödinger Equation looks intimidating to a non-physicist, yet when explained and simplified it can be understood by the majority of the readers. We identify each character and symbol in the equation with a short description. Schrödinger’s Equation (time dependent): 2   2 d   x ,t  V  x   x,t   dt 2m dx 2    Total Energy  Kinetic Energy  Potential Energy

i



d   x,t 



i: Imaginary unit (number) that in combination with real number forms a complex number C and is: −1. h: Plank’s constant (6.62607004 × 10−34 m2 kg / s). h ℏ (h bar): The Plank’s constant over 2 Pi:   . 2  π: 3.1415926535.

Ψ: Wave function. d: Derivative. m: Mass of the particle. x: Position of the particle. t: time. V: Potential energy. Simplification by color tool: (Fig. 1.10.) Due to the fact that quantum particles do not have the properties of large objects, it is not possible to directly and accurately measure them. In order to overcome this problem, the quantum operators are being used.

W hen Did It Start?

15

Fig. 1.10  The most fundamental and essential formula for quantum physics

Quantum operators  by manipulating and affecting the system make it possible to measure the affected system. In another word, quantum operators are associated with any measurable parameter in the system. These operators are needed to describe the system. The list of common quantum operators is as follows:

d • Energy Operator (time dependent) also called Hamiltonian:  H   i . 2 2 dt  d • Kinetic Operator: KE  . 2 2m dx • Function of x or potential operator: F(x), f(V). d Momentum operator (x component): Px = Fig. 1.11. i dx Schrödinger’s Cat in the Box –– The hypothetical experiment of the cat in the box (Discussed earlier) is the most discussed experiment for many years and it represents the basic example of quantum theory ambiguity. It is still the subject of many interpretations and discussions [6] (Figs. 1.6 and 1.7). –– Paul Dirac (August 8, 1902–October 20, 1984) [22]. –– English theoretical physicist who made a fundamental contribution to Quantum physics and shared the 1933 Nobel prize in physics with Ervin Schrödinger. His equation which carries his name is the relativistic counterpart of the Schrödinger equation. It describes the behavior of subatomic particles with ½ spin-like electrons and predicted the existence of antimatter. –– Max Born (December 11, 1882–January 5, 1970) [23]: with Werner Heisenberg, and Pascal Jordan developed “Matrix mechanics” formulation of Quantum Mechanics:

pq – qp  h / 2  i I P and q are matrices for location and momentum, is the identity matrix.

• Hugh Everett (November 11, 1930–July 19,1982) [24]: He was the first physicist that proposed the many worlds interpretation (MWI) or multiverse of quantum physics. Unlike Copenhagen's interpretation, in (MWI) The Schrodinger equation never collapses and all possibilities of the quantum

16

1  Introduction to Quantum Physics

Fig. 1.11  Quantum operators are being used and are needed to describe the system

superposition exist at the same time and are objectively real. At first, his idea was not taken seriously and it took years since its importance was recognized and became a major contribution to quantum physics. His proposed theory of multi-world interpretation (MWI) can be summarized as: –– –– –– ––

The Wave function represents reality, entirely and exactly. Wave function never collapses. Wave function always obeys the Schrödinger’s equation. Decoherence splits the wave function into branches representing different measurable outcomes. –– Distinct outcome branches will never affect each other in any way. –– The outcomes seem to belong to different and separate worlds. • Brian David Josephson (January 4, 1940) [25]: (Quantum Tunneling). • American scientist winner of the Noble Prize in 1973. His work on Quantum tunneling was essential for this phenomenon in quantum physics. Today there are many experiments that have confirmed this process and it is considered as one of the most important phenomena in the quantum world. The most common tunneling process can be seen in the photosynthesis process. • Richard Feynman (May 11, 2018–Feb. 15, 1988) [22]: An American theoretical physicist with his major role in the theory of quantum electrodynamics. The winner of Nobel prize in 1965. His simplification of the description of the behavior of subatomic particles which carries his name was a major contribution to quantum physics. • Alain Aspect (June 15, 1947) [26]: (quantum entanglement). A French scientist verified the process of quantum entanglement. His work was to establish that when a group of particles is generated, they interact and share spatial proximity with each other regardless of the distance between them.

W hat is Quantum Biology?

17

What is Quantum Biology? [27] The majority of organisms are composed of cellular structures and each of their cells contains approximately 1010 atoms, it is easy to conclude that each of these atoms will follow the quantum physics laws. On the other hand, a combination of atoms make formation of molecules and interaction between the molecules with the formation of DNA will result in cellular structures and eventually the multiple organs together, the complex life form evolves. Even noncellular life forms like viruses are composed of atoms that follow the quantum world rules. Schrodinger referred to the application of quantum physics to biology in his book “What is Life.” Since then, one by one the relevance of quantum physics to biology is being unveiled. The first on the list was the process of photosynthesis. We will discuss that in other chapters in detail. Then the studies on the sense of smell followed by magnetoreceptors in the retina of migrating birds and the essence of consciousness could be explained by quantum physics/biology. Summary of quantum biology fields that are established and are being studied at present: • • • • • • • • • • •

Enzymes’ super-fast reactions are accelerated by tunneling phenomena. Quantum effect on Photosynthesis. Protein tunneling and dynamics in enzymatic H-transfer reactions. Magnetic field effect on spin-dependent reactions. Proton tunneling in DNA. Fluorescent proteins as a model. Quantum coherence in neuronal Ion channels. Magnetoreception (Separate chapter) [28]). Neuron responses (Microtubules) (Chap. 10). Vision (Separate chapter) (Chap. 2-2a). Consciousness.

What Are Its Applications? There are infinite applications on every field of biology, biochemistry, and genetics as the main source of origin always points to the atomic structure that follows the quantum rules. For instance, we can apply the quantum physics laws to the effect of photons on the retina, the transformation of energy to neurons, and the process of seeing. The understanding of the visual input and the concept of the sense of seeing is similar to the human consciousness as a whole.

18

1  Introduction to Quantum Physics

We discuss this in detail in the second part of this chapter. The cell contains approximately 1010 atoms and each will follow the laws of quantum physics. There are atomic elements that combine and form molecules and interaction between the molecules makes the RNA and DNA and by using these blueprints the resultant cellular structures develop. Multiple cells organize the organs and finally, multiple organs communicate and the complex life forms emerge. By looking at this process in reverse all life forms are made of atomic and subatomic particle the all will obey the rules of quantum physics. We will discuss quantum biology in part 2 of Chap. 1.

References 1. Strumia A. A “Potency-Act” interpretation of quantum physics. J Modern Phys. 2021;12(7) https://doi.org/10.4236/jmp.2021.127058. 2. Niaz M. Reconstruction of the history of the photoelectric effect and its implications for general physics textbooks. Sci Educ. 2010; https://doi.org/10.1002/sce.20389. 3. Publishing, University. 44 Photoelectric Effect. University Phys. n.d.;3 https://opentextbc.ca/ universityphysicsv3openstax/chapter/photoelectric-­effect/. 4. Government, US. Fundamental Physical Constants. Phys Measur Lab. 2018; https://www.nist. gov/pml/fundamental-­physical-­constants 5. Hui P. Experimental study of mystery of double slit—comprehensive double slit experiments. Int J Phys. 2021;9(2):114–27. https://doi.org/10.12691/ijp-­9-­2-­6. 6. Wang. A Schrödinger cat living in two boxes. Science. 2016; https://doi.org/10.1126/science. aaf2941. 7. Garcia-Perez G. Decoherence without entanglement and quantum Darwinism. Phys Rev Res. 2020;2 https://doi.org/10.1103/PhysRevResearch.2.012061. 8. Jaeger. Developments in quantum probability and the copenhagen approach. Entropy. 2018; https://doi.org/10.3390/e20060420. 9. Maes SH.  The Multi-fold theory: a synopsis so far. shmaesphysics.wordpress.com; 2021. https://vixra.org/pdf/2105.0013v1.pdf. 10. Sirunyan. Evidence for Higgs boson decay to a pair of muons. Exp Phys. 2021; https://doi. org/10.1007/JHEP01(2021)148. 11. Schreiner. Quantum mechanical tunneling is essential to understanding chemical reactivity. Inst Organ Chem. 2020; https://doi.org/10.1016/j.trechm.2020.08.006. 12. Buiatti M. Randomness and multilevel interactions in biology. Theory Biosci. 2013; https:// doi.org/10.1007/s12064-­013-­0179-­2. 13. Muntersbjorn. On the intellectual heritage of Henri Poincaré. BSHM Bulletin: Journal of the British Society for the History of Mathemat. 2012; https://doi.org/10.1080/1749843 0.2012.658538. 14. Nauenberg. Max Planck and the birth of the quantum hypothesis. Am Assoc Phys Teachers. 2016; https://doi.org/10.1119/1.4955146. 15. Khrennikov. Bohr against Bell: complementarity versus nonlocality. Open Phys. 2017;22 https://doi.org/10.1515/phys-­2017-­0086. 16. Lindgren. The Heisenberg Uncertainty Principle as an Endogenous Equilibrium Property of Stochastic Optimal Control Systems in Quantum Mechanics. Symmetries Quantum Mech. 2020; https://doi.org/10.3390/sym12091533. 17. Butto. A New Theory on Electron Wave-Particle Duality. J High Energy Phys Gravitat Cosmol. 2020; https://doi.org/10.4236/jhepgc.2020.64038.

References

19

18. Kaplan. The Pauli exclusion principle and the problems of its experimental verification. Symmetry. 2020; https://doi.org/10.3390/sym12020320. 19. O’Connor. Erwin Schrödinger and quantum wave mechanics. Quanta. 2017; https://doi. org/10.12743/quanta.v6i1.60. 20. Schrödinger, E. 1944. What is life. http://herba.msu.ru/shipunov/school/univ_110/papers/ schroedinger1944_what_is_life.pdf. 21. Sandev. Effective potential from the generalized time-dependent schrödinger equation. Mathematics. 2016; https://doi.org/10.3390/math4040059. 22. Kim. Dirac matrices and Feynman’s rest of the Universe. Symmetry. 2012; https://doi. org/10.3390/sym4040626. 23. Gosson, de. Born–Jordan quantization and the uncertainty principle. J Phys. 2013; https://doi. org/10.1088/1751-­8113/46/44/445301. 24. Tappenden. Everett’s multiverse and the World as wavefunction. Quantum Rep. 2019; https:// doi.org/10.3390/quantum1010012. 25. Granados. Transverse Josephson vortices and localized states in stacked Bose–Einstein condensates. New JPhys. 2019; https://doi.org/10.1088/1367-­2630/ab09ad. 26. Bhaumik. How Does Nature Accomplish Spooky Action at a Distance? Quanta. 2018; https:// doi.org/10.12743/quanta.v7i1.82. 27. McFadden. The origins of quantum biology. Royal Soc. 2018; https://doi.org/10.1098/ rspa.2018.0674. 28. S.Y.Wong. 2021. Criptochrome magnitoreception: four tryptophans could be better than three. Jurnal of the Royal Scociety Interface. November 10. 10.1098/rsif.2021.0601 • Olfactory sensation .

Chapter 2

Introduction to Quantum Biology

Abstract Soon after the emergence and development of quantum physics in the early twentieth century, the possibility of applying these new rules of physics to the living cell was first suggested by Pascual Jordan and a year later by Erwin Schrödinger. This was the beginning of the new field of science called quantum Biology. At first, there was no interest in this phenomenon due to the general concept that quantum physics cannot be applied to the crowded, wet, and warm environment of the living cell. Also, the lack of necessary tools to experiment with these quantum events in the living cell contributed to it. It was not until a few decades ago that the relevance of quantum physics in biology was reinvestigated and new tools were invented to verify these processes. There are many discoveries in quantum biology in recent years and many are in process at present. There are many specific mechanisms within living cells that make use of the non-trivial features of quantum mechanics, such as coherence, superposition, tunnelling, and entanglement. These rules in the past were considered to be relevant only to subatomic levels and at temperatures near absolute zero. It should be noted that even today there are many controversies and differing opinions on quantum biology issues, and it will take time and further studies to clarify what had been proposed already. It took 3.5 billion years for living systems to learn and manipulate the quantum systems for their benefit via optimizing evolution, we have only had two decades to study and learn about these fundamental processes of life. The entire field of quantum biology has become so vast that will be beyond the scope of this chapter. We have chosen the best relevant and full access articles as references.

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 K. T. Moazed, Quantum Biology of the Eye, https://doi.org/10.1007/978-3-031-32060-6_2

21

22

2  Introduction to Quantum Biology

Discussion Quantum biology is the study of complex and dynamic biological processes to understand how living systems exploit quantum mechanical effects to enhance their biological functions. There is a growing list of quantum biological phenomena that will be summarized and discussed in this chapter. Due to the fact that all living organisms are made of atoms, it is reasonable to recognize that biology and life are governed by quantum laws. For example, the structure of electron orbitals, chemical bonds, and hydrogen transfer in enzymes are essential in structural biology in living organisms. There are so many publications on quantum biology in recent years that go beyond the scope of this introductory chapter. There are especially these review articles that are very helpful to orient the readers with the recent developments in quantum biology. • Quantum effects in Biology [1] • Quantum biology revisited [2] • Quantum Biology: An update and perspective [3]

When Did It Start? Soon after the birth of quantum physics in the early twentieth century, scientists started to see if they can apply the laws of quantum physics to biology, since the basis for any biological form is inevitably atoms and subatomic particles. The origins of quantum Biology have been discussed in more detail in the literature [4] and here we present a summary. The list of some of the pioneers in this field is presented below: • Neils Bohr (October 7, 1885–November 18, 1962) [5]: (Electron orbits) He was a Danish physicist who made fundamental contribution to describe atomic structure and quantum theory. He received a Noble prize in physics in 1922. He proposed that the energy levels of electrons are discrete with stable orbits around the nucleus and can move from one orbit to another. He was the first scientist who linked quantum theory with biology. • Pascual Jordan (October 18, 1902–July 31, 1980) [6]: (Pioneer of Quantum Biology). He published the first paper on quantum biology in 1932. His book “Physics and the Secret of Organic Life” was published in 1941 before Schrödinger’s well-­ known book “What is Life.” His affiliation with the German Reich made him unpopular after the WW ll to the point that he was not mentioned as one of the major pioneers of the quantum biology in many historical papers. • Erwin Schrödinger (August 12, 1887–January 4, 1961) [7]: (Pioneer of quantum physics and quantum Biology).

The Electron

• • • • •

23

He is well known for his book “What is Life” [8], his wave function formula, and the “Cat in the Box” hypothetical experiment. He was an Austrian Theoretical physicist who also won the Noble prize in physics for his contribution to quantum physics in 1933. He is considered as one of the most important pioneering figures in quantum physics and quantum biology. Luca Turin (November 20, 1953 [9]: Turin’s Theory of Olfaction was the first publication on vibration of the molecules on olfaction. Francis Crick (June 8,1916–July 28, 2004) and Watson (April 6, 1926) [10] Discovery of double helix of DNA in 1953 was another step toward understanding the living organism’s Genetic inheritance and mutations. Löwden (October 28, 1916–October 6, 2000) ([11]: Proton tunnelling mechanism for a point mutation in DNA. De Vault (1915–1990): Electron tunnelling in enzymes [12]. He proposed that the electron transfer in photosynthesis is a temperature-­independent reaction and the electron transport is due to “quantum tunnelling” process. Wiltschko [13]: Magnetoreceptor in birds. His original article on Magnetoreceptors represents the evidence of magnetic receptors in migrating birds.

Basic Information for Better Orientation Due to the fact that this book is not written for quantum physicists, there is some basic information that needs to be reviewed for a better understanding of the essentials of quantum biological phenomenon. This information is very general and can be reviewed, for instance, in any standard basic science textbook. We start with the basics of atomic structure and use the hydrogen atom as an example since it is the simplest (and the most abundant) atom in the universe. The majority of hydrogen in nature (99.9%) is composed of one proton and one electron. Other isotopes of hydrogen also have neutrons (deuterium and tritium) as well and are heavier. Hydrogen atoms can be found in various states: • Atomic hydrogen (no charge and not chemically bound). • Hydrogen can attach to other atoms, for example, oxygen to form water. • Hydrogen can lose its electron to become a cation (H+) and is called hydron which is a free proton, which has a major role in many biological processes. • Hydrogen can gain another electron to become an anion (H−) and is called hydride.

The Electron Electrons play an essential role in chemistry, magnetism, electricity, and thermal conductivity and are involved in many applications like electron microscopy lasers and radiation therapy.

24

2  Introduction to Quantum Biology

Bohr’s model: Niels Bohr described the electron orbits at the most probable distances from the nucleus which is approximately 5.29 × 10−11 m in its ground state and is still being used today as Bohr’s radius constant (Fig. 2.1). (The electrons travel in defined circular orbits around the nucleus. The orbits are labeled by the quantum number n. Electrons can jump from one orbit to another by emitting or absorbing energy.) In the early 1920s, the intrinsic spin of electrons was confirmed by “Stern-­ Gerlach experiment.” In this experiment, silver atoms (neutral particles) were sent through inhomogeneous magnetic field and their deflection was observed. The detection screen revealed two separate points of accumulation according to the spin up or spin down of the particles passed through. This was a historical moment in the field of quantum physics (Fig. 2.2). (Inert Silver atoms confined through collimators, travel through an inhomogeneous magnetic field. They will be deflected to two separate points according to their up or down spin) (Fig. 2.3). Bohr proposed specific characterizations for electrons: • Electrons can only be in certain discrete orbits or stationary states, n = (1,2,3,…). • Each first orbital can be occupied by up to two electrons and must have a different spin quantum number. • Electrons do not emit radiation while in these stationary states. • Electrons can gain or lose energy by jumping between the stationary states. “Transitional rule” for jumping is limited and is represented by values (n) the principal quantum number, (ι) the orbital angular momentum, and (m) the magnetic angular momentum since the absorption and/or emission of electromagnetic radiation involves changing in the electromagnetic dipole of the atom.

Fig. 2.1  The electrons travel in defined circular orbits around the nucleus. The orbits are labeled by the quantum number n. Electrons can jump from one orbit to another by emitting or absorbing energy

The Electron

25

Fig. 2.2  Inert Silver atoms confined through collimators, travel through an inhomogeneous magnetic field. They will be deflected to two separate points according to their up or down spin

Fig. 2.3  Schematic presentation of one electron spin, alpha with a spin up vector and beta with a spin down vector

Energy level: The energy level of electron in an atom has different states. The “ground state,” which after absorbing energy can jump into the higher state called “excited state.” • Singlet state: is when all the systems electrons are paired. The net angular momentum of the particles is zero and has one line in its spectrum reflecting its name. Except oxygen almost all molecules exist in a singlet state (S0) (Fig. 2.4). • Triplet State: is when a system has two unpaired electrons. The angular momentum of the system is 1, so as its quantum number is 1. It will allow three values

26

2  Introduction to Quantum Biology

Fig. 2.4  Schematic comparison of electron triplet states with S1 and electron singlet state with S0, using the Z access

Fig. 2.5 Schematic presentation of the vectors from + and – canceling each other so only the X and Y axes vector exists

of angular momentum as −1, 0 +1. The spectral line also will show three lines and it is called triplet. Molecular oxygen occurs in triplet state (Figs. 2.5 and 2.6). • The principal energy level at the orbit of electrons around the nucleus called shell can be numbered (1–2–3–4...) or alphabetically start from (K -L -M -N…). Each shell can contain only a certain number of electrons. The first shell can hold only up to two electrons. The second shell can hold up to 8 electrons (2 + 6). The third shell can hold up to 18 electrons (2 + 6 + 10) and so on. • The electron’s angular momentum is quantized and can be calculated as:

L = n L = angular momentum. n = Principal quantum number. ℏ = h (Plank constant) / 2π and is called “h-bar”.

The Electron

27

Fig. 2.6  Schematic presentation of two alpha vectors, combined together forming the larger vector S1. The beta vectors look similar but in the opposite direction and with a—sign

Later on, Schrödinger described the position of the electron as a wave function and the probability of its location in his fundamental equation that was described in part one of this chapter. Schrödinger’s Equation (time dependent): 2 - 2 d Y ( x,t ) V ( x )y ( x,t ) + dt 2m dx 2 ¯ ¯ ¯ Total Energy = Kinetic Energy + Potential Energy

i



d y ( x,t )

=

There are specific characteristics of electron, that is, the same in the entire universe and the most essential in the new era of quantum physics and biology. Electrons characteristics and specification highlights are as follows: • The electron symbol is (e−). • It is a subatomic particle belonging to Fermions (see subatomic particle charts). • It has a negative charge of (−1) and is bound to the nucleus with a positive charge. • It has an intrinsic angular momentum or Spin of half-integer (1/2) expressed in units of reduced Planck's constant ℏ which the projection vector axis would be as shown in Fig. 2.3.



ö æ  ç + or - ÷ 2 ø è 2

• It has a mass of 9.901 × 10−31 kg. • Electrons can collide with other particles.

28

2  Introduction to Quantum Biology

• It can have the dual property of wave and particle, the square of the wave function Ψ gives the probability of the particle location. • Electrons can be diffracted like light. • The exchange and sharing the electrons between the atoms is the main cause of chemical bonding maintained by a pair of electrons shared between two atoms. • Electrons can radiate or absorb energy in the form of photons. The electrons can go from ground state to the excited state by absorbing a photon only whose energy is equal to the energy difference between the levels. On the other hand, the excited electron can go to the lower level by spontaneously emitting a photon equal to the energy difference between the levels. The photon energy is equal to Planck’s constant(h) times the photon frequency (λ).

E = hf

This is the base for spectroscopy which is to analyze the detected frequency or wavelength of the emitted or absorbed photons. • Electromagnetic field can affect the motion of electrons.

Jablonski Diagram Is a schematic arranged electron energy diagram on a vertical axis. Horizontal lines are representations of the electronic states with multiple vibronic energy states that may be coupled with the electronic state [14] (Fig. 2.7).

Fig. 2.7  The diagram represents the ground state and excited state of electrons. After excitation, different pathways of relaxation are shown

Jablonski Diagram

29

The first diagram is usually the “absorbance” of a particular energy by the molecule of interest. For example, the energy of the photon is absorbed by the electron and excites it from a lower energy level to a higher energy level. Only certain wavelengths of light are possible for absorbance. The energy of the absorbing photon should correspond to the difference between the two different states of the particular molecule. The ground state electrons will transition to an excited electronic state as well as some excited vibrational state. The second diagram is the “vibration relaxation” and “Internal conversion.” When the electron is excited, there are many ways that the gained energy can be dissipated. –– Vibrational relaxation, is a non-radiative process. It occurs between vibrational levels and generally electrons do not change their level. –– Internal conversion can occur when the energy increases which causes the overlap of vibrational energy over the electronic levels. The third diagram is “Fluorescence” in response to the absorbed photon is to emit a photon. It is a slower process than the previous pathways and can compete with them only from the first excited electron state and the ground state. The dissipation of energy from higher excited energy states is through the internal conversion and vibrational relaxation. The energy of the fluorescence is the same energy as the difference between the states of the transition, however, the energy of fluorescence is always less than that of exciting photons. The last diagram is the “Intersystem crossing” and is another path for energy dissipation from higher excited levels. In this path, the electron changes spin multiplicity from a singlet state to an excited triplet state and is represented by a horizontal curved arrow from one column to another column. It is the slowest path in Jablonski diagram even slower than fluorescence. Intersystem crossing can lead to another route from the excited triplet back to the singlet ground state by emitting Phosphorescence. There are other non-emitting transitions from excited states to ground state exist and account for the majority of molecules that are not exhibiting fluorescence or phosphorescence behavior. • Two electrons cannot occupy the same quantum space or orbits (Pauli exclusion principle) and maximum 2 electrons with different spin quantum numbers (balanced spin). • Double-occupied orbitals are being repelled by an external magnetic field. • Single-occupied orbits are attracted by the external magnetic field and are unpaired or unbalanced spins and create a spin magnetic moment in which the electron behaves like a very small magnet. • The wave function changes (+ or-) sign when 2 electrons are swapped. • Electron magnetic moment: caused by an electron’s intrinsic properties of spin and its electric charge. It is approximately - 9.284764 × 10−24 J/T.

30

2  Introduction to Quantum Biology

Fig. 2.8  Schematic presentation of the region of probability where the electrons can be found and the different orbitals and their shapes; s, d, p, and f

• Atomic orbitals are the region of probability where the electron can be found. There are four orbitals with different shapes s, d, p, and f. Each can hold up to two electrons (Fig. 2.8). Spin quantum number: Is one of the four quantum numbers that describe the quantum state of an electron: 1. (n) the principal quantum number. It represents the energy of an electron. The n value can be 1–2–3-4 etc. the numbers are increasing as it gets further away from the nucleus. n = 1,2,3,4… 2. (ι) The orbital angular momentum. It can have a value from 0 to n-minus one. This describes the shape of the orbital. ι = 0, 1, 2…(n−1). ι = 0 describes s orbital. ι = 1 describes d orbital. ι = 2 describes p orbital. ι = 3 describes f orbital. 3. (mι) The magnetic angular momentum. Describes the number of the types per energy level. mι = −ι … to ι. Example: if ι =2 then mι = −2, −1, 0, 1, 2. 4. (ms) The spin quantum number. Only in +

1 1 or - . 2 2

Jablonski Diagram

31

Fig. 2.9  Chart of spin angular momentum and the assigned multiplicity numbers

Spin angular momentum (S) or simply called “Spin” is an intrinsic property of all elementary particles. All subatomic particles have assigned quantum spin number (see subatomic particle charts) (Fig. 2.9). There are very specific rules and characteristics of Spin that are fundamental in understanding the behavior of particles in nature. Spin implies that the particle’s phase changes with angle. • Particles with half-integer spins including electrons are fermions while the ones with integer spins are Bosons. They obey different rules. • Fermions (electrons included) cannot have the same spin at the same position, but bosons can bunch up together. • Fermions (electrons included) that make up the matter, have a spin of ½. • Boson particles (photon included) that carry forces, have spin 1. The spin direction is either up or down on the axis of the electron rotation (Z) (Fig. 2.3). Spin vectors are used to be able to easily picture the spin in a classic form. Phonon: Is a discrete unit or quantum of vibrational motion of uniformly oscillation of a lattice of atoms or molecules at a single frequency. Similar to photon that is a quantum of light energy. There are other specific effects and constants that need to be mentioned such as g-factor, Zeeman effect, and Bohr magneton: • g-factor: Dimensionless quantity that characterizes the magnetic momentum and angular momentum. Three magnetic moments are associated with electron:

1. Spin angular momentum. 2. Orbital angular momentum. 3. Total angular momentum, which is the sum of the two above.

• The electron g-factor (ge) = −2.002319304362 56. • Zeeman effect: This is the effect of an external static magnetic field on a spectral line which splits it into several components. It is very important in applications in nuclear magnetic resonance spectroscopy, magnetic resonance imaging (MRI), etc.

32

2  Introduction to Quantum Biology

• Bohr magneton (μB): Is a constant expressing the magnetic moment of an electron caused by its orbital or spin angular momentum.

( mB ) =

e = 9.274 ´ 10-24 2me

e: The elementary charge ℏ: The reduced plank constant me: The electron resting mass Electron spin resonance (ESR): Is similar to nuclear magnetic resonance (NMR) but the excited spin is from electrons, not the nucleus. The electron spin quantum 1 1 1 number s = and the magnetic components ms = ms = + or - . By exposure to 2 2 2 an external magnetic field Bo, the electron’s magnetic moment aligns itself parallel 1ö 1ö æ æ ç ms = + ÷ or antiparallel ç ms = - ÷ to the field. Each alignment having a specific 2 2ø è ø è energy due to the Zeeman effect with the following formula: E = m s g e m B Bo

E: Energy ms: Electron magnetic moment ge: Electron g-factor μB: Bohr magneton Bo: External magnetic field

Therefore, the separation between the unpaired electrons of the upper and lower state is:

E = g e m B B o

which implies that the splitting of the energy levels is directly proportional to the magnetic field’s strength since ge and μB are constant. The unpaired electrons can change their spin by absorbing or emitting a photon of energy hv (h = Planck’s constant, v = Photon’s frequency) such that the resonance condition, hv = ΔE is obeyed. This leads to the fundamental equation of electron paramagnetic resonance (EPR) spectroscopy:

hv = g e m B Bo

Quantum Biology Tools It was not until recently that the tools for measuring the quantum phenomenon in biology were discovered and the process of coming up with new tools is in progress at present. Here, we discuss only some essential tools that are being used today:

Quantum Biology Tools

33

• • • •

Entangled Spectroscopy [15]. Nonlinear-type spectroscopy of entangled photons [16]. Nitrogen vacancy centers in Diamond [17]. Super-resolution Fluorescence microscopy which is the combination of atomic force microscopy (AFM) with fluorescence-based super-resolution microscopy modalities [18]. • Fluorescence Fluctuation Spectroscopy [19]. • Ultrafast spectroscopy [20]. One very important factor in biological functions is the very short coherent times that are critical for the process to happen i [20]. The femtosecond processing has Been discussed in the Chapter on vision [21]. However, for sensing and measuring, a longer coherence time is preferable. That is why the long coherence time of diamond nitrogen vacancy centers of 2  ms, becomes very practical for quantum-related experiments.

Nitrogen Vacancy (NV) Centers in Diamond We will discuss Nitrogen Vacancy (NV) center in diamonds as it has become one of the most essential and reliable sensing devices in quantum biology. The idea started 30 years ago and yet it has been studied and perfected each year and still is playing a central role in many scientific research projects being done today. It is a powerful quantum system with very essential properties such as: • • • • • •

Long coherence time of up to 2 ms. The ability to work on an atomic size system such as individual molecules. Single photon source. Magnetic field measurement. Electric field measurement. Does not need near-zero temperatures and can perform under ambient temperature. • Can be used as a quantum sensor to optically detect NMR signals from chemically modified thin film on the surface of the diamond that contains NV centers [22]. • It is being used in many other fields such as qubits in quantum computers. The Nitrogen Vacancy (NV) center in diamonds is one of many point defects in the atomic structure of carbon lattice crystals in diamond. There are two charge states of this defect: • NV0 or neutral NV that has one unpaired electron and is paramagnetic, but hard to detect. It is generally not being used for quantum technology. • NV−or negative NV that has one extra electron forming the spin S = 1 pair. The NV0 centers can be converted to NV− by applying an extra voltage to a doped diamond.

34

2  Introduction to Quantum Biology

Fig. 2.10  Schematic presentation of nitrogen vacancy center in a diamond crystal

NV centers have a magnetically, electrically, and thermally sensitive electronic spin at ground state at room temperature at ambient conditions. By changing the evolution of the spin states and sensing the magnetic field, these changes can be precisely detected optically. NV− possesses spin-dependent fluorescence which allows to measure of its quantities. Carbon atom has 4 valance electrons, Nitrogen has 5 valance electrons which 3 of them covalently bonded to the carbon atoms and the other 2 remain non-bonded and are called “lone pair.” The vacancy has three unpaired electrons (Fig. 2.10). The principle of NV center spin detection: The photoluminescence property of NV centers is used to detect the spin state of its electrons. External optical absorption of green light (for example, green laser with a wavelength of 546 nm) can excite the NV electrons to the excited state which upon decay emits non-radiative and infrared radiation that can then be detected and measured by optical detection devices “optical read out” using the concept of optically detected magnetic resonance (ODMR). Pulses or continuous microwave a­ nd/ or application of external electric field can also excite the electrons to the excited state. There is additional splitting due to interaction with surrounding carbon nuclear spins and the NV’s own spin-orbit interaction that can affect the additional level splitting into the excited states. There is an inherent entanglement of the spin-orbit in the molecular structure of the diamond NV center under a zero magnetic field. As we mentioned above, the NV centers can be manipulated by external factors: • Electric fields (DC Current) • Magnetic fields • Microwave

Quantum Biology Tools

35

• Light (Laser) • Temperature and pressure The above external influences enable applications for imaging with high contrast and sensitivity. Detecting the small variations of photons is much easier with optical detectors than the small magnetic fields. That is why the detection of the emitted fluorescein plays an important role in sensing the spin status of the electrons. The quantum spin properties of NV centers in nanodiamonds can be used for in vitro biosensing, including brightness, low cost, and ability to manipulate their fluorescent emission [23]. The following are some of the essential applications of NV centers: Biological sensor: The use of NV centers in nanodiamonds as “quantum sensors” can detect many essential parameters inside the living cell such as PH, radical specious, magnetic fields, and rotational movements due to its stability and biocompatibility [24]. Navigation: The NV’s spin’s property can be coherently manipulated by optically detectable magnetic resonance for sensing and quantifying the precise local magnetic field and navigation without a need for a satellite [25]. Quantum Diamond Microscope (QDM): It consists of employing a dense layer of fluorescent NV Centers near the surface of a transparent diamond chip on which a sample of interest is placed. Microwave-­ initialized magnetic field; NV fluorescence is measured across the diamond surface resulting in a two-dimensional magnetic field image [26]. Magnetic force microscope: The interpretation of images acquired by magnetic force microscopy with specific near-field magnetostatic interaction between the probe and sample [27]: Intracellular Thermometry: Temperature is a fundamental indicator of cell function. Fluorescent nanodiamonds (FNDs) containing (NV-) centers are good candidates for detecting intracellular temperature due to their inherent biocompatibility, high photostability, sensitive temperature detection, and suitability for intracellular use (Wu, Intracellular Thermal Probing Using Aggregated Fluorescent Nanodiamonds [28]).

The Most Studied Fields of Quantum Biology The following are the list of the most common quantum biology phenomenon under study and research at present: • Quantum effect on Photosynthesis (Wang, Efficient quantum simulation of photosynthetic light harvesting [29]). • Enzymes’ super-fast reactions are accelerated by tunnelling phenomena [30]. • Protein tunnelling and dynamics in enzymatic H-transfer reactions [31]. • Magnetic field effect on spin-dependent reactions [32]. • Proton tunnelling in DNA [33].

36

• • • • • • •

2  Introduction to Quantum Biology

Fluorescent proteins as a model [34]. Quantum coherence in neuronal ion channels [35]. Magnetoreception (Separate chapter) [36]. Olfactory sensation [37]. Neuron responses (Microtubules) (Chap. 10). Vision (Separate chapter) (Chapters 2-2a). Consciousness [38].

Due to the wide variety of experiments, we will discuss only some of the most essential fields that the experiments have been very promising: –– Photosynthesis, which is the process of converting the sun’s energy into chemical reactions in plants and some bacteria is being discussed in this chapter. –– The other subjects will be discussed in other chapters: –– The enzymes’ reaction process which is essential for life. –– The olfaction processes. –– The magnetoreceptors [39].

Photosynthesis in Plants What is photosynthesis? Photosynthesis is one of the most essential processes for maintaining life on earth producing oxygen in the atmosphere and converting the sun’s energy into food. Complete detail of the physical, chemical, and biological principles of photosynthesis is described in a book publication [40]. Here, we summarize the process of photosynthesis with relevant references for more understandable and simplified details. In recent years, there has been much interest in discovering the quantum effect process in light-harvesting pigment chlorophyll. Many researchers are trying to uncover the role of quantum physics in this process. The anatomy of the plant harvesting process (Fig. 2.11): Plant cell Organelles (Chloroplasts) Thylakoids Chlorophyll structure with central Mg Stacks of thylakoids (sites of photosynthesis) Thylakoid membrane Pigment-protein complexes = Light-harvesting antenna complexes The Thylakoid membrane proteins Lumen of thylakoid space Stroma Ribosomes Plastidial DNA

Photosynthesis in Plants

37

Fig. 2.11  Schematic presentation of the entire anatomic process of photosynthesis

Fig. 2.12  Schematic comparison of a chlorophyll molecule and a hemoglobin molecule. The primary difference is that hemoglobin is built around iron (Fe), whereas chlorophyll is built around magnesium (Mg)

There are many different species that use photosynthesis such as plants some bacteria and algae but, in this chapter, we only focus on C3 plants. The general overview process of light harvesting can be summarized in order to understand the essentials. The entire process of photosynthesis is shown in Fig. 2.11. The sunlight hits the plant leaves containing chloroplast organelles. These organelles have multiple disc-like structures stacked on top of each other that are called Thylakoids that are floating in the fluid inside the chloroplast called stroma. Thylakoids are the structures that are involved with the light capturing tools such as chlorophyll molecule as antennae. Their membrane holds the essential proteins to capture and process electrons and ions necessary to start the process of photosynthesis. The inner space inside the thylakoid space is called the lumen (Fig. 2.12).

38

2  Introduction to Quantum Biology

Fig. 2.13  The specific wavelength of chlorophyll absorption is shown in the above image. The green wavelength is reflected out, giving plants their green color

The chlorophyll molecule structure contains MG in its center which has a role in the H+ flow and concentration in the stroma [41]. As represented in Fig. 2.12. There is a specific wavelength of the full spectrum that gets absorbed by chlorophyll in the blue and red zones. The green zone is just reflecting out that is why the plants are green (Fig. 2.13). What happens when photons of light hit the plant leaves: • The sun’s energy is captured by chlorophyll antenna [42]. • The energy is then transferred to the reaction center. • The excitation of the electrons forms “electron exciton” and are released from the reaction centers. • The transfer of the excited electrons to Photosystem II. • The electrons will be directed to the stroma via electron transport system Photosystem I. • Electrons help the hydrogen ion attaches to NAPD and forms the NADPH as a fuel. • At the same time, the generated Oxygen (O2) and Hydrogen (H+) from the splitting of the water molecule are being sorted out. • Oxygen is the waste product and will be sent out to the environment via the small openings on the plant surface called stomata. • Hydrogen gets transferred to the lumen and eventually passes through the membrane molecule called ATP Synthase into the stroma. There it will assist phosphorylation of ADP to ATP with the use of one inorganic phosphate. • ADPH and ATP are the necessary fuel to capture CO2 from the environment through the stomata. The process is called Calvin circle which involves in the production of carbon containing molecules such as glucose, cellulose, all kinds of starch and lipids. Overall formula:

6CO 2 + 12H 2 O + Photons ® C6 H12 O6 + 6O 2 + 6H 2 O

Photosynthesis in Plants

39

Fig. 2.14  Schematic representation of photosynthesis as it occurs in plants. These chemical reactions are shown corresponding to the specific anatomical locations where they occur

Process of photosynthesis: The process of event in the photosystems II and I in the Thylakoid membrane: Photosystem II → Excite electron (An Electron-hole pair) + Water photolysis To O2 and H + ATP synthase → ATP. Photosystem I → electron transport system → NADP+ H+ + NADP synthase → NADPH. The types of photosynthesis reactions happen: • Light-dependent reactions → H+ + electron + membrane enzymes → NADPH + ATP. Or more in a more complete version (Fig. 2.14.): (2 H2O + 2 NADP+ + 3 ADP + 3 Pi + light → 2 NADPH +2 H+ + 3 ATP + O2) • Light independent reactions → NADPH + ATP+ CO2 → Sugar production. Or in a more complete version: (3 CO2 + 9 ATP + 6 NADPH +6 H+ → C3H6O3-phosphate +9 ADP + 8 Pi + 6 NADP+ + 3 H2O) • Calvin Cycle (Stroma) → RUBP + RuBisCo + CO2 → Glucose + Fatty acids+ recycling RUBP. There are some issues in the process of photosynthesis that cannot be explained by classic physics and only make sense when quantum theories are applied: • The biological process of light conversion high efficiency of (84%–95%).

40

2  Introduction to Quantum Biology

Fig. 2.15  Schematic presentation of various pathways of quantum physics energy transfer theories, in photosynthesis

• The process of photosynthesis also has a very high efficiency of one photon being transduced to 1 electron-hole pair. • The time scale of femtoseconds that the electrons are transferred to the reaction center. Is extremely short (Femtosecond is a unit of time equal to 10−15 or 1/1,000,000,000,000,000 of a second). There are also many different theories and controversies in interpretations of light harvesting process and the role of quantum physics in energy transfer in photosynthesis, a good argument is discussed in this article [43] (Fig. 2.15). Ishizaki and Fleming [44] work titled “Photosynthetic Energy Transfer Gained from Free-Energy Structure: Coherent Transport, Incoherent Hopping, and Vibrational Assistance” They discussed the Coherent and incoherent energy transfer and the necessity of vibrational assistance in a typical photosynthetic system. Resonant tunnelling in natural photosynthetic systems has been proposed in this recent article [45]. Another article discusses that photosynthesis tunes the quantum-mechanical mixing of electronic and vibrational states to steer exciton energy transfer [46]. The vibrational and electronic effects with a review of literature were also discussed in this article [47]. One very recent publication suggests that the light coherently drains out of nanosized photosystems as a unit and its “quantumness” is linked to quantum confinement on the nanoscale [48]. Finally, “Quantum walk” was suggested as an energy dispersion in photosynthesis system [49].

References

41

References 1. Brookes. Quantum effects in biology: golden rule in enzymes, olfaction, photosynthesis and magnetodetection. Proc R Soc A. 2017; https://doi.org/10.1098/rspa.2016.0822. 2. Cao. Quantum biology revisited. Sci Adv. 2020; https://doi.org/10.1126/sciadv.aaz4888. 3. Kim. Quantum biology: an update and perspective. Quantum Rep. 2021; https://doi. org/10.3390/quantum3010006. 4. McFadden. The origins of quantum biology. rspa.royalsocietypublishing.org; 2018. https:// doi.org/10.1098/rspa.2018.0674. 5. Khrennikov. Bohr against Bell: complementarity versus nonlocality. Open Phys. 2017; https:// doi.org/10.1515/phys-­2017-­0086. 6. Strien V. the vienna circle against quantum speculations. J Int Soc History Philos Sci. 2022; https://www.marijvanstrien.com/uploads/7/4/2/1/74216723/the_vienna_circle_against_quantum_speculations_.pdf. 7. O’Connor. Erwin Schrödinger and quantum wave mechanics. Quanta. 2017; https://doi. org/10.12743/quanta.v6i1.60. 8. Schrodinger. What is life? Dublin Inst Adv Stud. 1943; http://www.whatislife.ie/downloads/ What-­is-­Life.pdf. 9. Turin L.  A Spectroscopic mechanism for primary olfactory reception. Chem Sences. 1996; https://doi.org/10.1093/chemse/21.6.773. 10. Watson. A structure for deoxyribose nucleic acid. Nature. 1953; https://doi. org/10.1038/171737a0. 11. Löwdin. Proton Tunneling in DNA and its Biological Implications. Rev Modern Phys. 1963; https://doi.org/10.1103/RevModPhys.35.724. 12. Vault D. Quantum mechanical tunnelling in biological systems. Cambridge University Press; 1980. https://doi.org/10.1017/S003358350000175X. 13. Wiltschko. Magnetoreception. Bioessays. 2006; https://doi.org/10.1002/bies.20363. 14. Libertexts. Jabloski Diagram. Chem Libertexts. 2022; https://chem.libretexts.org/ Bookshelves/Physical_and_Theoretical_Chemistry_Textbook_Maps/Supplemental_ Modules_(Physical_and_Theoretical_Chemistry)/Spectroscopy/Electronic_Spectroscopy/ Jablonski_diagram 15. Szoke. Entangled light–matter interactions and spectroscopy. J Mater Chem C. 2020; https:// doi.org/10.1039/D0TC02300K. 16. Lee. Entangled photon absorption in an organic porphyrin dendrimer. J Phys Chem. 2006; https://doi.org/10.1021/jp066767g. 17. Sekiguchi. Geometric entanglement of a photon and spin qubits in diamond. Nature. 2021; https://doi.org/10.1038/s42005-­021-­00767-­1. 18. Miranda. How did correlative atomic force microscopy and super-resolution microscopy evolve in the quest for unravelling enigmas in biology? Royal Scoc Chem. 2020; https://doi. org/10.1039/D0NR07203F. 19. Tedeschi. Fluorescence fluctuation spectroscopy enables quantification of potassium channel subunit dynamics and stoichiometry. Sci Rep. 2021; https://doi.org/10.1038/ s41598-­021-­90,002-­2. 20. Shahnawaz. Interplay of vibrational wavepackets during an ultrafast electron transfer reaction. Nat Chem. 2020; https://doi.org/10.1038/s41557-­020-­00607-­9. 21. Gualier. Coherent control of the vision process in living animals. Arch ouverte UNIGE. 2021; https://doi.org/10.13097/archive-­ouverte/unige:152542. 22. Liu. Surface NMR using quantum sensors in diamond. PNAS. 2022; https://doi.org/10.1073/ pnas.2111607119. 23. Miller. Spin-enhanced nanodiamond biosensing for ultrasensitive diagnostics. Nature. 2020; https://doi.org/10.1038/s41586-­020-­2917-­1. 24. Yingke W. Recent developments of nanodiamond quantum sensors for biological applications. Adv Sci. 2022; https://doi.org/10.1002/advs.202200059.

42

2  Introduction to Quantum Biology

25. Zhao. Inertial measurement with solid-state spins of nitrogen-vacancy center in diamond. Adv Phys. 2021; https://doi.org/10.1080/23746149.2021.2004921. 26. Levine. Principles and techniques of the quantum diamond microscope. Nanophotonics. 2019; https://doi.org/10.1515/nanoph-­2019-­0209. 27. Hartmann. Magnetic force microscopy. Ann Rev Mater Sci. 1999; https://doi.org/10.1146/ annurev.matsci.29.1.53. 28. Wu. Intracellular thermal probing using aggregated fluorescent nanodiamonds. Adv Sci. 2021; https://doi.org/10.1002/advs.202103354. 29. Wang. Efficient quantum simulation of photosynthetic light harvesting. Nature. 2018; https:// doi.org/10.1038/s41534-­018-­0102-­2. 30. Hong. The evolution of multiple active site configurations in a designed enzyme. Nat Commun. 2018; https://doi.org/10.1038/s41467-­018-­06305-­y. 31. Fereiro. Tunneling explains efficient electron transport via protein junctions. PNAS. 2018; https://doi.org/10.1073/pnas.1719867115. 32. Mishra. Spin-dependent electron transport through bacterial cell surface multiheme electron conduits. J Am Chem Soc. 2019; https://doi.org/10.1021/jacs.9b09262. 33. Serivastava. The role of proton transfer on mutations. Front Chem. 2019; https://doi. org/10.3389/fchem.2019.00536. 34. Babakhanova. Rapid directed molecular evolution of fluorescent proteins in mammalian cells. Protein Sci. 2021; https://doi.org/10.1002/pro.4261. 35. Song. The macroscopic quantum state of ion channels: A carrier of neural information. Sci China Mater. 2021; https://doi.org/10.1007/s40843-­021-­1644-­6. 36. Wong. Cryptochrome magnetoreception: four tryptophans could be better than three. J R Soc Interface. 2021; https://doi.org/10.1098/rsif.2021.0601. 37. Hoehen. Status of the vibrational theory of olfaction. Front Phys. 2018; https://doi.org/10.3389/ fphy.2018.00025. 38. Li. The finer scale of consciousness: quantum theory. Ann Transl Med. 2019; https://doi. org/10.21037/atm.2019.09.09. 39. Ritz. Quantum effects in biology: Bird navigation. Proc Chem. 2011; https://doi.org/10.1016/j. proche.2011.08.034. 40. Croce. Light harvesting in photosynthesis. Found Biochem Biophys. 2018; h t t p s : / / b o o k s . g o o g l e . c o m / b o o k s ? i d = 3 P y c D w A AQ BA J & d q = R . + C r o c e , + R . +van+Grondelle,+H. +van+Amerogen,+I. +Van+Stokkum,+Light-­Harvesting+in+Photosynth esis+(CRC+Press,+2018).&lr=&source=gbs_navlinks_s. 41. Johnson. Photosynthesis. Essay Biochim. 2016; https://doi.org/10.1042/EBC20160016. 42. Scheer. Chlorophylls: a personal snapshot. Molecules. 2022; https://doi.org/10.3390/ molecules27031093. 43. Ball. Is photosynthesis quantum-ish? Royal Soc Chem. 2018; https://physicsworld.com/a/ is-­photosynthesis-­quantum-­ish/. 44. Ishizaki. Insights into photosynthetic energy transfer gained from free-energy structure: coherent transport, incoherent hopping, and vibrational assistance revisited. J Phys Chem. 2021; https://doi.org/10.1021/acs.jpcb.0c09847. 45. Gerodias. Resonant tunneling in natural photosynthetic systems. Phys Scripta. 2021; https:// iopscience.iop.org/article/10.1088/1402-­4896/ac3c58/meta 46. Higgins. Photosynthesis tunes quantum-mechanical mixing of electronic and vibrational states to steer exciton energy transfer; 2021. https://doi.org/10.1073/pnas.2018240118. 47. Leske. An investigation of the vibrational and electronic effects on the efficiency of electron transfer in photosynthesis using quantum mechanics simulations. Univ Calgary. 2020; https:// www.rinaldog.com/uploads/1/0/8/5/108595347/robbie_ap_research_ppt_2020-­2021.pdf 48. Sordillo. Photosynthesis on the ultrafast time scale within the confinements of quantum nanostructured photosystems. Photochim Photobiol. 2021; https://doi.org/10.1111/php.13392. 49. Wang. Topological invariants of nonunitary quantum walk with chiral symmetry. Results Phys. 2022; https://doi.org/10.1016/j.rinp.2022.105279.

Chapter 3

Classic Biology of Human Eye

Abstract The role of quantum biology in the human eye has been studied in detail and yet there are many more facts that need to be investigated and discovered. This chapter is divided into two parts, to better understand the process of visual systems. Part one will summarize the classic anatomy/physiology of the normal human eye and in the second part the quantum effect on the visual system will be discussed. The focus will be on the process of a photon entering the eye and its absorption by the photoreceptors located in the posterior retinal layer, followed by the transformation of the photon energy into the neuronal signal to the brain. Note: The basic information on anatomy and terminology is standard and accessible in any information media sources. Due to the large collection of information in the literature, which is beyond the scope of this book, the most relevant open-access review articles have been selected and referenced for further and more detailed information on each subject. For light to reach the photoreceptors in the retina it must pass through many boundaries. Any defect or abnormality on these barriers will affect this process. To follow the photons from their sources (sun or projector or reflection), there are many different media with different indexes of refraction which it must pass to reach the retina to initiate the phototransduction system. Starting with a photochemical reaction the retina transforms the light energy to electrical signals to reach the brain. The density differences that the light should travel through are the following: • • • •

Air–cornea boundary. Cornea–anterior chamber (Aqueous Humor) boundary. Aqueous Humor–lens boundary. Lens–Vitreous boundary.

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 K. T. Moazed, Quantum Biology of the Eye, https://doi.org/10.1007/978-3-031-32060-6_3

43

44

3  Classic Biology of Human Eye

Fig. 3.1  Schematic presentation of light passing through different optical barriers entering the eye to reach the retina

• Vitreous–retina boundary (Fig. 3.1). Any physiological or pathological changes in these structures and barriers can affect the photon reaching the retina and as a result affects the vision. The visual perception and consciousness will be discussed in another chapter.

The Anatomy Highlights of the Eye • Cornea [1] –– –– –– –– –– ––

Tear film Epithelium Bowman’s membrane Stroma Descemet’s membrane Endothelium

• Lens [2, 3] –– –– –– –– ––

Index of refraction [4] Anterior capsule Cortex Nucleus Posterior capsule

• Vitreous. –– Vitreous body ([5]) –– Cloquet canal

The Anatomy Highlights of the Eye

45

• Retina –– –– –– –– –– –– –– –– –– –– –– • • • •

Anterior limiting membrane [6] [7] Nerve fiber layer Ganglion cells [8] Inner plexiform layer Inner nuclear layer Outer plexiform layer Outer nuclear layer Amacrine cells Muller cells Photoreceptor’s structure Photoreceptors: Molecular structure

RPE [9–11] Bruch’s membrane [12] Choroid [13] Sclera [14] (Figs. 3.2 and 3.3) The following articles are highly recommended:

Microstructure [15, 16]. Chemical reactions. [17, 18].

Fig. 3.2  Light microscopy (x 40) of the posterior segment of the eye. All retina layers, in addition to retinal pigment epithelium, choroid, and sclera are identified

46

3  Classic Biology of Human Eye

Fig. 3.3  Schematic description of the cellular structure of the retina and RPE and their correlation to the Bruch’s Membrane and Choroid. RPE size is exaggerated in the schematic illustration

Before going any further, we must refer to some basic biological information regarding the physiology of the visual system. The simplified highlights are as follows: • Photoisomerization: Isomers are molecules with identical molecular formulas with the same number of atoms but with different arrangements. The isomers may have different chemical or physical properties. When the isomerization is the result of photoexcitation it is called photoisomerization. A relevant example is the photoisomerization of 11-cis retinal to All-trans retinal in the retina. • Phototransduction: Phototransduction is the process of converting the detected photon into an electrical signal in the rod and cone cells of the retina. The process occurs via Opsin (G-protein-coupled receptor) that contains 11-cis retinal (Chromophore). When a photon hits this complex, 11-cis retinal undergoes photoisomerization to all-trans retinal which changes the conformation of opsin leading to the cascade of phototransduction. • Protein structure and folding: Proteins are the 3-dimensional chain of averaging 20 different amino acids that attach to each other by a peptide bond (C=O-N-H). The proteins are made inside the cytoplasm of the cell by ribosomes that are using messenger RNA as a template. The standard protein structure starts with the amino terminal (N) and ends with a carboxyl terminal (C). Each protein exists in an unfolded polypeptide after being synthesized by the ribosomes which then will fold into its characteristic 3-dimensional structure. The correct folding of amino acids is essential to their function as misfolding is associated with many pathological and neurodegenerative conditions. There is a different motif in the secondary structure of proteins such as alpha helix, beta sheet, and loops. These structures are most commonly presented as ribbon diagrams. Alpha-helices are presented as thick coiled ribbons, beta sheets are presented as arrows, and non-repetitive loops are represented as thin lines (Fig. 3.4). • Rhodopsin:

The Anatomy Highlights of the Eye

47

Fig. 3.4  Illustration of secondary structure of proteins

•

•

• •

•

• • • •

Rhodopsin is a G-protein-coupled receptor that is sensitive to light. It is composed of two parts opsin and retinal. Retinal: Retinaldehyde is a derivative of Vitamin A and is bound with opsin in photoreceptor cells of the retina and is the first step in the process of vision perception as light detectors. The retinal transport and cycle involve the absorption of vitamin A from choriocapillaris. The retinal cycle is involved in co-ordination and interplay of retinal pigment epithelium (RPE) and photoreceptors. Opsin: Opsins are a group of proteins that contains retinal, the light-sensitive molecule. Photons collisions with retinal changes the 11-cis retinal to all-trans retinal which causes the conformation of opsin, which will start the visual transduction cascade. 11 cis retinal and all-trans retinal (Fig. 3.5): G-Protein-coupled receptors: These receptors are located at the cell surface membrane and are usually composed of seven transmembrane domains. They have an extracellular N terminal that attaches to the ligand to start the intracellular cascade of events as in glutamate receptors or ligands directly binding to transmembrane helices as in Rhodopsin-­like family receptors. Cyclic guanosine monophosphate (cGMP): cGMP is a second messenger that acts as an activation of intracellular protein kinases in response to extracellular ligand binding. The main function is the control of the ion channels on the cell membrane. It is degraded by phosphodiesterase in the presence of light, which causes the sodium channels to close. This will lead to hyperpolarization of photoreceptor’s plasma membrane to activate visual signals. Guanosine triphosphate (GTP): GTP is essential to cellular signal transduction. It converts to guanosine diphosphate (GDP) by the enzyme GTPase. Phosphodiesterase Guanylate cyclase (GC): GC is an enzyme that converts GTP to cGMP. Cyclic adenosine triphosphate (cAMP): cAMP is a secondary messenger and is a derivative of ATP and is used for intracellular signal transduction. Adenosine triphosphate (ATP):

48

3  Classic Biology of Human Eye

Fig. 3.5 Schematic illustration of 11-cis retinal and all-trans retinal and their transformation by light

ATP is composed of a sugar molecule ribose and attached phosphate structure. It is commonly referred to as the molecular currency of intracellular energy transfer. It constantly converts back and forth to adenosine diphosphate (ADP) and adenosine monophosphate (AMP). • Transducin: This protein is essential for phototransduction in retina rods and cones. Light activation of rhodopsin that activates Transducin which results in activation of phosphodiesterase that in turn causes the breakdown of cGMP and closure of sodium ion channels which starts the visual signaling process. • Ion channels: Ion channels are membrane proteins that allow ions to pass through their channel pore. In general, they have a high rate of ion transport without using metabolic energy such as ATP. There are hundreds of types of ion channels and many forms of classifications according to their specific function. It can be just a pore that permits few ions to pass, or it may be gated channels that open and close. Non-gates potassium channels: There is a constant outward potassium current that tends to hyperpolarize photoreceptors to around −70 mV.

The Physiology of the Light Absorption in the Retina

49

cGMP-gated sodium channels: These channels depolarize photoreceptors to around −40 mV (dark current). There are many voltage-gated channels: 1. Voltage-gated sodium channels 2. Voltage-gated potassium channels 3. Voltage-gated calcium channels 4. Voltage-gated proton channels There are also ligand-gated ion channels such as GABA and Acetylcholine receptors. Sodium and potassium pumps: These pumps enable the photoreceptors to maintain a steady concentration of intracellular NA+ and K+ (Fig. 3.6).

The Physiology of the Light Absorption in the Retina The transition of light to neural signal is very complex and requires many steps [19]. This process can be summarized as follows: • Photon hits the photoreceptors that already have a steady background noise. The photon energy causes a sudden decrease in the background noise which will be translated into a biochemical signal. • A sudden decrease of background noise activates bipolar cells. • The bipolar cells activate ganglion cells via amacrine cells by negative feedback. • Ganglion cells transfer the input as an “action potential” to the Brain. Synaptic connections between the retinal cells [20]: • • • •

Photoreceptors and bipolar cells. Bipolar cells to Ganglion cells via amacrine cells. Ganglion cells to the lateral geniculate nucleus in the brain [21]. Muller cells, Horizontal cells, and amacrine synapses.

The processing of visual information is extremely complicated and involves many steps. Each step has multiple components and interactions. The summary of the interaction between the retinal cells is well described [22]. One way to simplify the essentials and make it more understandable is to present the process step by step from the moment that the light reaches the retinal photoreceptors. • Photoreceptors are rod cells or cone cells that are light detectors. The Rod cells are for night vision and have no color perception, the Cone cells are for day vision and are three different types that can perceive three different colors (blue, green, and red). • Retinal Pigment Epithelium (RPE) is a layer of pigmented cells that is in direct contact and interaction with photoreceptors (Fig. 3.7).

50

3  Classic Biology of Human Eye

Fig. 3.6  Schematic illustration of various different ion exchange channels and pumps in the photoreceptor cells

The Physiology of the Light Absorption in the Retina

51

Fig. 3.7  Light microscopy (x 100) of retinal pigment epithelium with adjacent structures including photoreceptors, Bruch’s membrane, and choriocapillaries

• Bipolar cells (ON and OFF Modifiers) ON bipolar cells are activated by light stimulation and OFF bipolar cells are activated by absence of light. • The ganglion cells and their axons that make up the nerve fiber layer and the optic nerve (long-distance signal transport to the brain). • Horizontal cells (modulating photoreceptors and bipolar cells). • Amacrine cells (moderating bipolar and ganglion cells). • Muller cells (Support system) for entire retina. Recommended articles for further detail: The architectures of neuronal circuits [23]. Synaptic specification of retinal cells [24].

The Visual Cycle Retinoids initiate the process of photochemical reactions that will start the photon signal transduction to the brain [25]. Retinoids are derivatives of vitamin A and cannot be produced inside the body. They are absorbed by digesting food containing vitamin A such as fish, dairy products, and meat. The first step is the chemical reaction that happens when the photon hits the rhodopsin molecule in the photoreceptors. There is a constant cycle of chemical

52

3  Classic Biology of Human Eye

reactions that utilizes and reproduces rhodopsin. That involves close coordination and cooperation between the photoreceptors and the retinal pigment epithelium. The chemical process of retinal cycle between the photoreceptors and retinal pigment epithelium: 1. Isomerization, the light converts 11-cis retinal to all-trans retinal inside the photoreceptors. 2. All-trans retinal converts to all-trans retinol by the enzyme all-trans retinal dehydrogenase (RDH) inside the photoreceptors. 3. All-trans retinol travels to retinal pigment epithelium (RPE). 4. All-trans retinol converts to all-trans retinyl ester by the enzyme lecithin retinol acyltransferase (LRAT) in RPE cells. 5. All-trans retinyl ester will convert to 11-cis retinol with the enzyme isomerohydrolase (RPE65) in RPE cells. 6. 11-cis retinol then converts to 11-cis retinal by the enzyme 11-cis retinal dehydrogenase (11-cis RDH) in RPE cells. 7. 11-cis retinal travels back to the photoreceptors to replenish them (Fig. 3.8).

Fig. 3.8  Diagram of the complete cycle of chemical reactions between photoreceptors and Retinal Pigment Epithelium for constant supply of retinal for use by photoreceptors

The Photoreceptors, the Rod Cells, the Cone Cells, and the Ganglion Cells

53

 he Photoreceptors, the Rod Cells, the Cone Cells, T and the Ganglion Cells There are three different types of photoreceptors in the retina. The rods and cones are located at the outermost layer of the retina and are directly involved with the vision processing cascade. Another type of photoreceptor is the small population of ganglion cells in the innermost layer of the retina that carry melanopsin that only involve with circadian rhythm and pupillary reflexes. Rods and cone cells are located in-between retinal pigment epithelium and bipolar cells. They produce neurotransmitter glutamate in synapses to bipolar cells and in direct contact with retinal pigment epithelium for multiple interactions. Rods and cones have somewhat similar structures with small differences. The inner segment of rods and cones contains mitochondria which provide ATP for the sodium-­ potassium pumps. The outer segments are composed of discs filled with opsin that reacts to light. The outer segments also contain voltage-gated sodium channels. Rod cells are specific for low light perception (night vision) and do not perceive color. The cones are specific for high light perception (day vision) and composed of three different types (S-cones for blue perception, M-cones for green perception, and L-cones for red perception) as they are sensitive to specific wavelengths for color perception (Fig. 3.9).

Activation of Rods and Cones Activation of rods and cones is the initial step in the phototransduction process of converting the photon energy to neural signal to be transferred to the brain. Many steps are involved in this complex process but can be simplified and separated into phototransduction in the dark and phototransduction in light. These processes are as follows: Phototransduction in Dark: There is a high level of cGMP which keeps the sodium channels open (dark current) and keep photoreceptors depolarized leading to release of glutamate to inhibit the excitation of neurons. Phototransduction in light: Decrease level of cGMP closes the sodium channels that switch off the (dark current) causes hyperpolarization of photoreceptors that reduces the release of glutamate that reduces the inhibition of neurons (Double negative feedback) (Figs. 3.10, 3.11, 3.12, and 3.13).

54

3  Classic Biology of Human Eye

Fig. 3.9  Schematic illustrated comparison of rods and cones photoreceptors

Activation of Rods and Cones

55

Rod Cell Outer Membrane

Rod Cell Outer Membrane Rhodopsin

Transducin

Phosphodiesterase

Disc Membrane cGMP

Na+ Open

Cytosol

β

α

α

α

γ

αβ

γ

α

cGMP Gated Channel

cGMP

cyclase

Extra Cellular Fluid

Closed

GTP Light

Step 1

GTP

GDP

Step 2

GMP

cGDP

Step 3-4

Step 5

Fig. 3.10  Illustration of early steps of phototransduction in photoreceptor disc

Fig. 3.11  Light microscopy image (x100) of cone cell of the retina with superimposed illustrations of schematic structures

56

3  Classic Biology of Human Eye

Fig. 3.12  Light microscopy image (x100) of three color cone cells of the retina with superimposed illustrations of schematic structures

Activation of Rods and Cones

57

Fig. 3.13  Light microscopy image (x 100) of rod cell of the retina with a superimposed illustration of schematic structures

58

3  Classic Biology of Human Eye

The Retinal Pigment Epithelium Retinal Pigment Epithelium (RPE) is the outer pigmented layer of the retina as the result of the invagination of the embryonic optic cup which the inner layer develops into retina and the outer layer develops into retinal pigment epithelium. It is located in between the retina and the choroid and can communicate and interact with photoreceptors and the choriocapillaris. It plays an important role in the maintenance and storage of visual systems. Multiple physiological functions can be summarized as follows (Fig. 3.14): • Darkroom function by absorbing scattered light entering the eye by its melanin contents. • Controlling and diminishing the high photo-oxidative stress by melanosomes. • Blood–retinal barrier due to its tight junctions, which isolates the inner retina from systemic influences. • Preserve immune privilege of the retina. • Supply nutrients to photoreceptors. • Controls ion homeostasis. • Eliminates water and metabolites. • Participation in the constant processing and replenishing of 11-cis retinol for photoreceptors. • Storage of the “retinal” and adaptation of reaction speed. • Phagocytosis of photoreceptors’ outer segments. • Secretion of multiple varieties of factors and signaling molecules: ATP, FGF, PDGF, VEGF, PEDF, etc (Figs. 3.15 and 3.16).

Fig. 3.14 Illustration of the entire phototransduction steps with RPE participation in the visual cycle

The Retinal Pigment Epithelium

59

Fig. 3.15  Illustration of RPE function with exaggeration of size proportion in order to emphasize the importance of RPE collaboration with photoreceptors

Rod Photoreceptor Discs

RPE Disc Fragments Lysosome

Bruch’s Membrane Choriocapillaries

Fig. 3.16  Light microscopy (x 100) highlighted the microscopic image of phagocytosis of photoreceptor (rod cell) discs

60

3  Classic Biology of Human Eye Ganglion Cells Inner Plexiform Layer Muller Cell Biopolar Cells

Outer Plexiform Layer

Nucleus of Rods & Cones External Limiting Membrane

Fig. 3.17  Light microscopy (x 100) of retinal bipolar cells with adjacent structures including ganglion cells and the nucleus of rods and cones

The Bipolar Cell’s Function • The bipolar cells connect photoreceptors to the ganglion cells. • There are different types of bipolar cells, metabotropic (ON) bipolar cells that terminate in the inner of the inner plexiform layer and ionotropic (OFF) bipolar cells synapse in the outer layer of the inner plexiform layer of the retina with their specific properties. • Bipolar cells also connect to other surrounding cells via receptors or secondary messengers. • Multiple different inputs from photoreceptors and from amacrine cells and horizontal cells (Fig. 3.17).

Activation of Bipolar Cells Bipolar cells receive synaptic input from both rods and cones. There are multiple forms of cone bipolar but only one type of rod bipolar cell. In the presence of light, rods and cones stop the production of glutamate. “ON” bipolar loses its inhibition and “OFF” bipolar cells lose their excitation. In the dark, rods and cones will release glutamate. This inhibits the “ON” bipolar cells and excites the “OFF” bipolar cells. Rod bipolar cells synapse onto amacrine cells and not directly to ganglion cells. The amacrine cells via gap junctions excite “ON” cone bipolar cells and inhibit the con

The Ganglion Cells

61

“OFF” bipolar cells which enables it to send signals to ganglion cells in a dim (scotopic) light.

The Amacrine Cells Amacrine cells interact with bipolar cells and ganglion cells. They operate in the inner plexiform layer of the retina. They induce lateral inhibition to the axon terminals with efficiency on signal transduction with high “signal-to-noise” ratio. Their mosaic arrangement ensures that all parts or retina have access to the full set of processing elements. There are different types of amacrine cells in the retina. GABAergic with subtypes of dopaminergic, glycinergic, and neither. These neurotransmitters contribute to many practical functions such as detection of directional motion, modulation of light adaptation, circadian rhythm, and control of high sensitivity in dark via connection with bipolar cells.

The Horizontal Cells The horizontal cells are located in the inner nuclear layer of the retina. The main function is the integration and regulation of the input from multiple photoreceptor cells. They induce lateral inhibition and adjust to bright and dim conditions. They have inhibitory or negative feedback to rods and cones.

The Ganglion Cells Ganglion cells are responsible to transfer the visual signals that are collected by retinal sensory cells to the brain via their long axons which form the nerve fiber layer of the retina and the optic nerve. Ganglion cells represent less than 1% of all retinal cells. At least around 30–40 subtypes have been identified. Each of these subtypes are differing in morphology, location, function, susceptibility to degeneration, and regenerative capability [26]. Some subsets of ganglion cells are intrinsically photosensitive and contain melanopsin that activates by light directly [27]. There is another uncommon signal transfer to Ganglion cells [28]. These melanopsin-expressing retinal ganglion cells play a major role in non-­ visual responses to light such as: • • • •

Regulation of sleep-wake cycles Pupillary reflexes Modulation of mood Some aspects of vision (Fig. 3.18)

Fig. 3.18  Schematic description of the cellular structure of the retina and RPE and their correlation to the Bruch’s membrane and choroid

62 3  Classic Biology of Human Eye

The Ganglion Cells

63

Activation of Ganglion Cells Multiple neurotransmitters are involved in transferring signals between ganglion cells and bipolar cells and amacrine cells. Glutamate is the primary source of excitation; however, Acetylcholine is an excitatory neurotransmitter that often acts as a modulator of glutamate receptors [29]. • The N-methyl-D-aspartate (NMDA receptor) is a glutamate receptor and ion channel found in neurons. NMDA receptor activity regulates synaptic connections between retinal ganglion cells and bipolar cells [30]. • The gamma-aminobutyric acid (GABA) receptors are the chief inhibitory receptors and are divided to GABAA that are ligand-gated ion channels or GABAB are G-protein-coupled receptors. The binary activation and suppression of these receptors are complex and have been studied and reported [31]. • Dopamine is a crucial neuromodulator for light adaptation. Dopamine receptors are expressed by horizontal cells and some bipolar cells, amacrine cells and ganglion cells [32]. • Retinal ganglion cells are strictly postsynaptic neurons. They feedback into the inner retina and participate in a recurrent circuit, not being a mere collector of retinal signals but actively involved in visual computation [33].

Visual Phototransduction Steps As complicated as the visual transduction seems to be, it can be simplified to the following steps which make it much easier to understand. 1. Photon hits 11-cis retinal inside the opsin molecule and converts it to all-trans retinal inside the rhodopsin molecule. 2. Opsin undergoes conformation and changes to metarhodopsin II. 3. Metarhodopsin activates Transducin which causes two events to happen; Transducin separates from its attached GDP and binds to cytoplasmic GTP, and its alpha subunit separates from its beta and gamma subunits while it is still attached to GTP. 4. Alpha subunit + GTP complex activates phosphodiesterase (PDE6). 5. PDE6 hydrolyzes cGMP to GMP cause the sodium channels to close. 6. Closure of sodium channels causes hyperpolarization of the photoreceptor cells due to constant potassium ion efflux. 7. Hyperpolarization causes voltage-gated calcium channels to close. 8. As calcium level drops neurotransmitter glutamate level drops as calcium is required for fusion of glutamate vesicles to cell membrane for release. 9. A decrease in glutamate level in photoreceptors causes the depolarization of ON bipolar cells and hyperpolarization of OFF bipolar cells.

64

3  Classic Biology of Human Eye

10. Bipolar cells with interaction with amacrine cells and horizontal cells transfer the signal to ganglion cells which initiate action potential to take a long journey to the brain (Fig. 3.14).

More Related Interesting Articles Pan [34] metabolism. Xu [35] Metformin. Ramachandra [36] Pic + physiology. Tsin [37] Visual Sycle. The interaction of rods and cones Gordon [38]. Retinal cell summary Muthuswamy [39].

References 1. Patel. Cornea: A review; 2019. https://doi.org/10.1016/j.clae.2019.04.018. 2. Borchman. Lipid conformational order and the etiology of cataract and dry eye. J Lipid Res. 2021a;62(January 1):100039. https://doi.org/10.1194/jlr.TR120000874. 3. Borchman. Lipid conformational order and the etiology of cataract and dry eye. J Lipids. 2021b;62:100039. https://doi.org/10.1194/jlr.TR120000874. 4. Khan. Change in human lens dimensions, lens refractive index distribution and ciliary body ring diameter with accommodation. Biomed Opt Exp. 2018;9(3):1272–82. https://doi. org/10.1364/BOE.9.001272. 5. Schultz A.  Novel vitreous substitutes: the next frontier in vitreoretinal surgery. Curr Opin Ophthal. 2021;32:288. https://doi.org/10.1097/ICU.0000000000000745. 6. Milstein. Multistep peripherin-2/rds self-assembly drives membrane curvature for outer segment disk architecture and photoreceptor viability. PNAS. 2020;117:4400. https://doi. org/10.1073/pnas.1912513117. 7. Kakakhel. Syntaxin 3 is essential for photoreceptor outer segment protein trafficking and survival. PNAS. 2020;117:20615. https://doi.org/10.1073/pnas.2010751117. 8. Sethuramanujam S, Awatramani GB, Slaughter MM.  Cholinergic excitation complements glutamate in coding visual information in retinal ganglion cells. J Physiol. 2018; https://doi. org/10.1113/JP275073. 9. Fu. Fatty acid oxidation and photoreceptor metabolic needs. J Lipid Res. 2021a;62:100035. https://doi.org/10.1194/jlr.TR120000618. 10. Fu Z.  Photoreceptor metabolic needs. J Lipid Res. 2021b; https://doi.org/10.1194/jlr. TR120000618. 11. Comitato. Pigment epithelium-derived factor hinders photoreceptor cell death by reducing intracellular calcium in the degenerating retina. Cell Death Dis. 2018; https://doi.org/10.1038/ s41419-­018-­0613-­y. 12. Meng. Lipid accumulation and protein modifications of Bruch’s membrane in age-related macular degeneration. Int J Ophthalmol. 2021; https://doi.org/10.18240/ijo.2021.05.19. 13. Myung. The choroid plexus is an important circadian clock component. Nature. 2018;9:1062. https://doi.org/10.1038/s41467-­018-­03507-­2. 14. Brown. A biphasic approach for characterizing tensile, compressive and hydraulic properties of the sclera. J Royal Soc Interface. 2021;18:20200634. https://doi.org/10.1098/rsif.2020.0634.

References

65

15. Lukowski. A single-cell transcriptome atlas of the adult human retina. EMBO J. 2019; https:// doi.org/10.15252/embj.2018100811. 16. Domdei. Ultra-high contrast retinal display system for single photoreceptor psychophysics. Biomed Opt Express. 2018;9:157. https://doi.org/10.1364/BOE.9.000157. 17. Zhongjie. Dyslipidemia in retinal metabolic disorders. EMBO Mol Med. 2019; https://doi. org/10.15252/emmm.201910473. 18. Rajala. Pyruvate kinase M2 regulates photoreceptor structure, function, and viability. Cell Death Dis. 2018;9:240. https://doi.org/10.1038/s41419-­018-­0296-­4. 19. Palczewski. Shedding new light on the generation of the visual chromophore. PNAS. 2020;117:19629. https://doi.org/10.1073/pnas.2008211117. 20. Ebert. Dynamical synapses in the retina. Science HAL Open. 2019; https://hal.inria.fr/ hal-­02317438 21. Covington. Neuroanatomy, nucleus lateral geniculate. NIH. 2021; https://www.ncbi.nlm.nih. gov/books/NBK541137/ 22. Thoreson. Diverse cell types, circuits, and mechanisms for color vision in the vertebrate retina. Physiol Rev. 2019;99(May 29):1527. https://doi.org/10.1152/physrev.00027.2018. 23. LUO.  Architectures of neuronal circuits. Neuroscience. 2021:eabg7285. https://doi. org/10.1126/science.abg7285. 24. Graham. Molecular mechanisms regulating synaptic specificity and retinal circuit formation. WIREs Developmental Biology. 2020;10:e379. https://doi.org/10.1002/wdev.379. 25. Choi. Retinoids in the visual cycle: role of the retinal G protein-coupled receptor. J Lipid Res. 2021; https://doi.org/10.1194/jlr.TR120000850. 26. Rheaume. Single cell transcriptome profiling of retinal ganglion cells identifies cellular subtypes. Nat Commun. 2018;9:2759. https://doi.org/10.1038/s41467-­018-­05134-­3. 27. Mure. Intrinsically photosensitive retinal ganglion cells of the human retina. Front Neurol. 2021;12 https://doi.org/10.3389/fneur.2021.636330. 28. Young. An uncommon neuronal class conveys visual signals from rods and cones to retinal ganglion cells. PNAS. 2021;118 https://doi.org/10.1073/pnas.2104884118. 29. Sethuramanujam. Cholinergic excitation complements glutamate in coding visual information in retinal ganglion cells. J Physiol. 2018;596:3709. https://doi.org/10.1113/JP275073. 30. Young B. NMDA receptor activity regulates synaptic connections between retinal ganglion and bipolar cells. July: IVOS; 2018. https://iovs.arvojournals.org/article.aspx?articleid=2693677 31. Ruan. Orexin-A differentially modulates inhibitory and excitatory synaptic transmission in rat inner retina. Neuropharmacology. 2021;187:108492. https://doi.org/10.1016/j. neuropharm.2021.108492. 32. Flood. Dopamine D1 and D4 receptors contribute to light adaptation in ON-sustained retinal ganglion cells. JNP. 2021; https://doi.org/10.1152/jn.00218.2021. 33. Vlasiuk. Feedback from retinal ganglion cells to the inner retina. PLoS One. 2021;16:e0254611. https://doi.org/10.1371/journal.pone.0254611. 34. Pan. Photoreceptor metabolic reprogramming: current understanding and therapeutic implications. Commun Biol. 2021;4:245. https://doi.org/10.1038/s42003-­021-­01765-­3. 35. Xu. Stimulation of AMPK prevents degeneration of photoreceptors and the retinal pigment epithelium. PNAS. 2018;115:10475. https://doi.org/10.1073/pnas.1802724115. 36. Ramachandra. Cholesterol homeostasis in the vertebrate retina: biology and pathobiology. J Lipid Res. 2021;62:100057. https://doi.org/10.1194/jlr.TR120000979. 37. Tsin. Visual cycle proteins: structure, function, and roles in human retinal disease. J Biol Chem. 2018;293:13016. https://doi.org/10.1074/jbc.AW118.003228. 38. Gordon. Rod and cone interactions in the retina. Natl Library Med. 2018; https://doi. org/10.12688/f1000research.14412.1. 39. Muthuswamy. Mammalian retinal cell quantification. Toxicol Pathol. 2020;49:505. https://doi. org/10.1177/0192623320976375.

Chapter 4

Quantum Retina

Abstract The new era of quantum physics and its application to quantum biology has revolutionized all fields of science and its applications, especially to the sense of smell and vision. Studying the fast chemical reactions in biological processes seemed impossible since some of these reactions happen in a very short time such as in femtoseconds. With the introduction of femtosecond laser spectroscopy and development of NV-diamond sensing (discussed in the previous chapter) and electron echo detection, these obstacles have been removed and a new era of science of the very small and very fast has begun. In this chapter, the initial process of phototransduction in the retina which can only be explained by means of quantum physics is simplified and explained.

Discussions The process of visual perception starts with the collision of a photon with the rhodopsin molecule in the photoreceptors of the retina. As discussed in the first part of this chapter, the isomerization of the retinal portion of the rhodopsin molecule initiates the phototransduction process. Retinal is what gives chromophore rhodopsin sensitivity to light (Figs. 4.1 and 4.2). Retinal is a derivative of vitamin A. It attaches to the opsin molecule via a covalent link to its lysine residue of opsin molecule by a Schiff base (–C=N–) bond. Recently, the most focus in vision has been on the quantum efficiency of rhodopsin which is almost 70%. The ultrafast excited state double bond isomerization of rhodopsin happens in a few femtoseconds, which leads to its distinct contribution to its quantum efficiency. Due to the small size of molecules, direct observation and evaluation is limited, however, by exciting the molecule with electromagnetic (EM) radiation and © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 K. T. Moazed, Quantum Biology of the Eye, https://doi.org/10.1007/978-3-031-32060-6_4

67

68

4  Quantum Retina

Fig. 4.1 Schematic illustrations of 11-cis “Retinal” molecules with their atomic carbon numbers

Fig. 4.2 Schematic illustration of all-trans “Retinal” molecules with their atomic carbon numbers

recording and analysis of the emitted, absorbed, or scatted waves more detailed information can be obtained. The process of interaction of electromagnetic radiation with matter can be studied by spectroscopy. The electrons fill orbitals to stay at the lowest energy level possible, called the ground state. By exposure to EM radiation, the electron absorbs energy from the incoming photon and moves to the excited states. Eventually, it will return to its ground state by different relaxation pathways, these can be either radiating relaxation with emission of a photon as fluoresceine or phosphorescence, or non-­radiating relaxation such as vibrational decay or rotational energy level decay, or heat. The process of absorption and emission is an essential factor in spectroscopy. The initiation of the phototransduction is a quantum phenomenon, that starts with the excitation of chromophore rhodopsin by light. The retinal segment of rhodopsin then becomes excited and is isomerized by rotation of its segment between carbon numbers 11 and 12 (it also affects 10 and 13), which separates it from opsin molecule and triggers the photoreceptor cells of the retina toward neural response. As the result, the hyperpolarization of the photoreceptor’s membrane occurs and causes the transmission of signals to ganglion cells of the retina via bipolar cells, which produce the action potential nerve response. The signals are then transmitted to the visual cortex where it is translated into a visual response with communication with multiple regions of the brain for conscious orientation and understanding of the source. Standard Jablonski excitation diagram and vibrational Jablonski diagram are shown below. Vibrational Spectroscopy [1] and Vibrational coherence rhodopsin [2] have been discussed thoroughly (Figs. 4.3 and 4.4).

Discussions

69

Fig. 4.3  The diagram represents the ground state S0 energy level and the excited state S1 energy state. After excitation, which is called absorption, the electron will return to its stable ground state via different pathways which is called relaxation. In radiative pathway, the electron releases photons in the form of fluoresceine of phosphorescence. In non-radiative pathway, the relaxation is via vibrational or intersystemic crossing or as heat dissipation

Fig. 4.4  The diagram represents the ground state S0 energy level and the excited state S1 and S2 energy states. After excitation/absorption, the different pathways of relaxation have been shown. There are multiple vibrational levels that are presented as V1, V2, V3, etc. The radiative and non-­ radiative pathways have been shown. S refers to singlet and T refers to triplet states

70

4  Quantum Retina

Fig. 4.5  Schematic presentation of regions of light spectrum used in spectroscopy to evaluate different properties of molecular and atomic structures

There are a wide range of spectroscopy techniques according to the molecule of interest and the type of information to be studied. Different wavelengths are assigned to evaluate different properties of the molecular behavior, for example: • Short wavelengths such as X-ray are used for bond breaking and ionization process. • UV wavelengths are used to evaluate electron excitation properties. • Infrared wavelengths are used to evaluate vibrational properties. • Microwave is used to evaluate the rotational properties (Fig. 4.5).

Radiation and Human Eye To have a physiological effect the energy of the radiation must be absorbed. Consider the full range of EM radiation from Gamma rays to Radio waves, which all have a different effect on the eye. These conditions will not be discussed in this chapter and only listed with their relevant references. • • • • • • •

Gamma rays: [3, 4]. X-rays: [5]. Ultraviolet: [6]. Visible light: [7]. Infrared light: [8]. Microwave: [9]. Radio waves: [10].

Since this book is for understanding the essentials for non-physicists, some basic quantum information must be explained and simplified for the reader to be able to follow the concepts of quantum biology of the retina.

R hodopsin

71

Rhodopsin Rhodopsin is a light-sensitive receptor protein that is composed of the chromophore retinal and a G-protein-coupled receptor Opsin which is located in the rod cells of the retina. Rhodopsin is extremely light sensitive and enables vision in the low-light conditions. Rhodopsin is embedded in the bilayer cell membrane of retinal photoreceptors (rods) with molecular weight of 40 kD. Rhodopsin is composed of two segments, Retinal molecule in the form of 11-cis Retinal a Vitamin A derivative and Opsin protein (Part of G-protein-coupled receptor family) which has 7 transmembrane alpha helix folds and contains 348 amino acids. Opsin attaches to Retinal via its lysine residue located on the seventh helix by covalently bonding to the protonated Schiff base (−NH+ = CH−). After activation with light, 11-cis Retinal will isomerize to all-trans (metarhodopsin II) which separates from opsin molecule by hydrolyzing the Schiff base, to start the phototransduction process. Eventually, the excited molecule all-trans retinal will terminally relax back to 11-cis retinal and will attach to opsin again in its docking pocket containing the docking site for the ring element and for the C19 methyl group, which is located next to the lysine residue [11]. Retinals have an extended conjugated chain (alternating single (C−C) and double (C=C) bonds) which reduces the excitation energy of the retinal molecule by light. Also, the protonated Schiff base with lysine residue, generated upon covalent binding of retinal with opsin, will further reduce the excited state of the retinal causing the red shifting of the absorbed frequency detection of 440 nm [12]. The N terminal of rhodopsin is in the extracellular space and the C terminal is located in the cytoplasm. The entire circle of rhodopsin isomerization and participation of retinal pigment epithelium (RPE) in the process has been described in the first part of this chapter [13, 14] Rhodopsin is categorized into 2 types: Rhodopsin Type I (microbial φ = 0.81). Rhodopsin Type II (animal φ = 0.15) (Fig. 4.6). Other good reviews that are recommended are as follows: –– Shedding new light on the generation of the visual chromophore [15]. –– Rhodopsin Activation in Lipid Membranes Based on Solid-State NMR Spectroscopy [16]. –– Opn5L1 is a retinal receptor that behaves as a reverse and self-regenerating photoreceptor [17]. –– Isorhodopsin: An undervalued visual pigment analog [11]. Quantum Yield ( j ) = number of photos emitted / number of photos absorbed Quantum efficiency ( QE ) = number of incident photon / number of converted electrons.

72

4  Quantum Retina

Fig. 4.6  Schematic presentation of Rhodopsin molecule. The seven transmembrane components of opsin molecule are presented in green. The docking site of Retinal is located on the seventh alpha helix fold as shown. The isomerization rotation site of the molecule Retinal is located at the double bond between carbon 11 and 12. The rotation outcomes in this region are presented in different colors orange and yellow. The 11-cis retinal segment is in orange color and the rotated segment that makes All-trans molecule is presented in yellow color. The position of neighboring two CH3 residues is also changing position as a result of isomerization. The protonated Schiff base and its attachment to opsin molecule via its lysine component through its sidechain is also presented in orange

Atomic Orbitals As it was described in previous chapters it is crucial to discuss the basics again to better understand the quantum biology concepts. Electrons according to quantum mechanics description are confined to certain discrete energy levels around the nucleus. There is an interaction between the positive protons of the atomic nucleus and the negative electrons which makes the composition of an atom. Neutrons carry no charge. The electron is not orbiting the nucleus like planets orbiting the stars. It only can be described as a cloud around the nucleus and can behave like a wave which will follow the Schrödinger equation as described in previous chapters. An electron does not really exist in one place but the probability of being in a certain position at certain time can be predicted and calculated.

Atomic Orbitals

73

Fig. 4.7  Schematic 2-dimensional presentation of atomic orbitals (shells), each in different colors and presented on the right side of the image. Each shell’s suborbital is presented on the left side of the image. Each subshell has a different number of suborbitals. Each suborbital s, p, d, and f can only occupy a certain number of electrons. The suborbital’s 3D images are illustrated on the lower part of the image. The s orbital can only have up to 2 electrons. The orbital p can have up to 6 electrons. The orbital d can have up to 10 electrons and orbital f can have only up to 14 electrons. Please notice that each shell except K shell is composed of suborbitals and the total number of electrons in each shell is the sum of the electrons located in the suborbital of that shell

The atomic orbitals are characterized for simplification and presented in a two-­ dimensional image. It is important to mention that the electrons cannot exist between these orbits, they can only jump up and down to the next orbit via excitation and relaxation events. There are a number of orbits (n) that are around the nucleus and start from n1 and increase to n2, n3, and so on. They are also called as shells K, L, M, N, and so on. Except n1, which is the K shell and contains only one s orbital, every other shell contains subshells. Subshells include s orbitals, p orbitals, d orbitals, and f orbitals (Fig. 4.7). Each suborbital contains a certain number of electrons:

74

4  Quantum Retina

s orbitals can take 2 electrons, one spin up one spin down. p orbitals can take 6 electrons, each pair one spin up and one spin down. d orbitals can take 10 electrons, each pair one spin up and one spin down. f orbitals can take 14 electrons, each pair one spin up and one spin down. The order of the suborbitals is in a specific arrangement as follows: 1s, 2s, 2p, 3s, 3p, 4s, 3d, 4p, 5s, 4d, 5p, 6s, 4f, 5d, 6p, 7s, 5f, 6d, 7p. For example, the carbon atom has 6 electrons, the first orbit, 1 s, contains 2 electrons (shell K or n−1), and in the second orbit or shell (shell L or n−2) 2 electrons in 2 s suborbital, and 2 electrons in 2p suborbital. The atomic configuration of carbon atom is then 1s2 2s2 2p2 and atomic configuration of Iron is 1s2 2s2 2p63s2 3p6 4s2 3d6 since it has 26 protons and 26 electrons. The first numbers are the number of the orbitals, the letters are the suborbitals and the superscripts are the number of electrons in that suborbital.

Molecular Orbitals Molecular orbitals describe the location and wave-like behavior of an electron in a molecule. Since the molecule is a combination of atoms, its orbitals are the combination of atomic orbitals to form the molecular orbital. They also follow the Schrödinger equation for the electron in the field of the molecule’s atomic nuclei. Molecular orbitals are usually constructed by combining atomic orbitals, or hybrid orbitals from the same or another molecule. There are three types of molecular orbitals: Bonding orbitals: Promote chemical bonding and are in phase and have less energy than the atomic orbitals that formed them. Antibonding orbitals: The interaction is out of phase and forms nodal planes in which the wave function between the interacting atoms becomes zero. The antibonding orbitals are higher energy than the atomic orbitals that formed them. Non-bonding orbitals: This is due to no interaction between atomic orbitals because of lack of compatible symmetries. The energy level is the same level as the atomic orbitals that form them.

Binding Orbitals Categories Molecular orbitals can be categorized according to bonding in their symmetry: Sigma bond: Strongest chemical bond with head on overlapping between atomic orbitals. A single bond is typically a Sigma bond, double bonds are usually one Sigma bond and one Pi bond, triple bonds are one Sigma and two Pi bonds (Fig. 4.8).

Energy Level

75

Fig. 4.8  Schematic presentation of s orbital bondings with each other in two different formats; antibonding and bonding

Fig. 4.9 Schematic presentation of p orbital bondings with each other in two different formats

Pi bond: covalent chemical bonds. Two lobes of an orbital on one atom overlap the two lobes of another atom’s orbital. They are weaker than Sigma bonds. This type of bonding is the most common form of p orbitals (Fig. 4.9). Delta bond: Covalent chemical bonds. Four lobes of one atomic orbital overlap with four lobes of the other involved atomic orbital. It is the usual form of bonding in d orbitals (Fig. 4.10). Phi bond: Covalent chemical bonds. Six lobes of one atomic orbital overlap with six lobes of another involved atomic orbital. It is the common form of bonding in f orbitals Fig. 4.11.

Energy Level In a Quantum mechanical system, electrons can only exist in certain discreet energy levels bound by positive electric charge of the nucleus. As described above, each electron shell and subshell represent a particular level of energy.

76

4  Quantum Retina

Fig. 4.10 Schematic presentation of d orbital bondings with each other

Fig. 4.11 Schematic presentation of f orbital bondings with each other

When not excited, the electrons always occupy the lowest possible energy level called ground state. When electrons absorb energy and are excited, they move up to higher energy levels, and the molecule or atom moves to an excited state. Excited states are unstable, and the electron will soon return to its ground states via different modes called relaxation. There are different modes of relaxation such as radiating decay which emits photons or non-radiating decay (relaxation) which does not emit photons. There are many forms of radiating decay, which is the release of photons during relaxation process such as fluorescence and phosphorescence. There are also many non-­ radiative relaxations such as vibrational decay, photochemical transformation, and heat. The excitation as was mentioned above can be induced with many different electromagnetic rays such as X-rays, Infrared, monochromatic lasers, UV, and microwaves. This stage is called absorption.

Non-radiative Decay

77

Radiative Decay When a ground state molecule interacts with light of the appropriate energy, an electron in the molecule moves to a higher electronic state called excited state. This excitation is dependent on the energy of the incident radiation. The excited state is very unstable and if the electron is excited to a high-energy state, then it will return to the lowest vibrational level of the lowest electronic state. At this point some energy will be lost as heat during the decent to the lower energy state. From the lowest excited state, the electron can return to the ground state via different pathways: 1. Fluorescence: Because the electron returns from a lower vibration state than from the one that was originally excited, the emitted fluorescent light will have less energy which will appear as in a longer wavelength. 2. Phosphorescence: If the electron is transferred to the lowest triplet state via intersystem crossing. This requires a reversal of the electron spin. The electron then returns to its ground state with the emission of light in a relatively long interval. 3. Energy transfer: The energy of the excited molecule is transferred to another molecule. 4. Internal conversion: The excited electron returns to the ground state with its energy dissipated as heat.

Non-radiative Decay Also called vibrational relaxation, is when an electron relaxes from a higher vibrational level to the lower vibrational level of the excited electronic state, as there are multiple vibrational states in each excited state. This process is much faster than the radiative decay and can be referred to as the quenching of luminescence. The relaxation in non-radiative decay to the ground state can happen via different pathways: 1. Vibrational relaxation: As mentioned above occurs between the different vibrational states of the same excited state. 2. Intersystem crossing: Relaxation proceeds between two different excited states with different spin multiplicity such as between S1 and T1. 3. Internal conversion: The excited energy dissipates as heat. 4. Crystal vibrations in solid state. In the case of Rhodopsin molecule, the process is non-radiative relaxation in which no light is emitted. Similar process happens in nuclear position when the excitation is associated with emission of a photon as fluoresceine which is a radiative relaxation process (Fig. 4.12).

78

4  Quantum Retina

Fig. 4.12  Schematic presentation of nuclear influence on destination of 11-cis isomerization toward either back to ground state in the intersection space with unsuccessful outcome or All-trans configuration by in-phase interaction with nucleus and a successful outcome

Nuclear Response Electron excitation is so fast that there is a delay in the nuclear response to the process. The nuclear response and position can be discussed as follows: 1. In the ground state S0, the nuclear fluctuation is near the lowest energy level S0. 2. After the excitation to S1, the nucleus response is to move from a higher excited state to the lowest energy level of the excited state S1. 3. The nucleus fluctuates at the lowest excited state of S1. 4. Eventually after the relaxation, the nucleus returns to its original lowest energy level of the ground state S0, Fig. 4.13.

Carbon Before we get to Isomerization, which is a fundamental step in phototransduction, we must have a quick review of the properties of a carbon atom which has a major role in the initiation of this process: Carbon symbol is C and has an atomic number 6 which means it contains 6 protons and 6 electrons. The outer shell contains 4 electrons (2 from 2s suborbital and 2 from 2p suborbital) which is why Carbon has 4 valence electrons in its outer shell. Carbon-to-carbon bonding can be single C-C (one Sigma bond) or double bond C=C (one Sigma bond and one Pi bond), or triple bond (one Sigma bond and two Pi bonds).

Lysine (C6H14N2O2)

79

Fig. 4.13  Schematic presentation of radiative photoisomerization and emission of fluorescent photon

When carbon atoms only attach to other carbon atoms, they form a diamond crystal. The use of diamond and its nitrogen vacancy space as a sensing device is a major forward step in quantum physics tools for experiments as was discussed in the earlier chapter. Carbon is the second most abundant element in the human body (about 18.5%) after oxygen. Carbon is the common element of all known life forms due to its unique diversity of forming organic compounds and polymers at ambient temperature. In a molecule, the carbon atoms are numbered, and this can be done by finding the longest carbon chain in the molecule and starting from the side that has the shortest substituent attached. For example, carbon numbering in a retinal molecule (C20H28O) is shown in Figs. 4.1 and 4.2.

Lysine (C6H14N2O2) Lysine is an amino acid that is a precursor to many proteins. It contains protonated amino group (-NH3+) and Carboxylic acid (-COOH) and a side chain ((CH2)4NH2) + H as protonated. Lysine’s most important functions are as follows: • • • • •

Proteinogenesis Crosslinking of collagen Polypeptides Uptake of mineral nutrients Fatty acid metabolism Production of Carnitine

80

4  Quantum Retina

• Histone modification • Participation in the phototransduction process. Lysine role in phototransduction: Ammonium group (NH3+) forms a Schiff base (–C=N–) with the conserved lysine residue and extra H+ (protonated) which is involved in its interaction with light. Protonated Schiff Base (PSB): The carbon double bond with nitrogen (-C=N-) forms the Schiff base on a general formula RN=CR’R”. For example, Retinal forms a Schiff base with opsin as shown above.

From (E) to (Z) Isomerization “From E to Z” is just another fraze for 11-cis to all-trance retinal isomerization. The primary event occurring during the E-Z photoisomerization of the protonated Schiff base is single-to-double bond conversion causing the unlocking of the C=C double bond. This “unlocking” process is the primary event during the rhodopsin photoisomerization [18]. There are several studies that discuss the E to Z isomerization with detailed descriptions. The reader can refer to the following article for a more in-depth review ([13]): (E) = German “entgegen” opposite for example, 11-cis Retinal (E) (Z) = German “zusammen” together for example, all-trans-Retinal (Z)

Isomerization Photoisomerization or photon-induced isomerization starts in the S1 excited state which is unstable and will decay to S0 ground state via non-radiative decay. The decay can cause the molecule to go back to the initial isomer or forward to the isomerized configuration. The initial step of this reaction proceeds via a coherent evolution primarily along the torsional and HOOP modes which both exhibit 90 degrees of rotation. At this point, the outcome depends on their relative phasing of HOOP and torsion. When in-phase rotation continues another 90 degrees to a total of 180 degrees to form “all-trans retinal” (Fig. 4.14). When out of phase, the rotation goes backward 90 degrees to 0 degree, which becomes “11-cis retinal,” back to its original isomer [2]. The isomerization is caused by the following changes in the rhodopsin molecule: 1. Bond Length Alteration (BLA). 2. Twisting of the dihedral angle (C10−C11 = C12−C13) which happens at Intersection Space (IS) between S1 and S0, which at first is 90 degrees, then another rotation

Isomerization

81

Fig. 4.14  The effect of intersection space known as Conical intersection (CI) which is under the influence of the nucleus vibrations. The destination of the isomerization is decided in CI with in-­ phase or out-of-phase interaction with the nucleus. In-phase becomes a successful reaction toward All-trans initiating the phototransduction and out of phase becomes unsuccessful and moves back to its original ground state

of 90 degrees either pro or con to original rotation, depends on “in phase” or “out of phase” in their vibrational relative phasing. Dihedral angle is the angle between the two planes, but which pass through the same bond. 3. Twisting of hydrogen out of a plane (C11−H+ C12−H) or (HOOP) [19]. 4. Hydrogen out of plane motion (HOOP) and molecular vibrational phase-­ dependent torsion dictates the outcome of the initial step of isomerization. 5. The splitting into subpopulations at the Intersection Space (IS), also called conical intersection (CI). The excited retinal splits into two destinations, either back to its original position as 11-cis or transforming into its isoform all-trans depending on if it is “in phase” or “out of phase” with nuclear motion of the molecule. 6. Potential energy surface (PES) induced by coherent motion with nucleus at the excited state imposes the specific mode relationship toward the outcome of the splitting process [20]. 7. Overall, the outcome of isomerization is governed by opsin electrostatics (Fig. 4.15). Immediately after “in phase” splitting, the first product is photorhodopsin with its transition within picoseconds to bathorhodopsin as the intermediate stage. The subsequent intermediates lumirhodopsin and metarhodopsin I maintain their reddish color due to their Schiff’s base linkage to all-trans retinal, as long as it remains protonated. The final conversion of metarhodopsin I to metarhodopsin II is associated with deprotonation of the Schiff’s base and as a result the color changes from red to yellow. Dual photoisomerization on distinct potential energy surfaces in a UV-absorbing Rhodopsin has been reported and can be reviewed in this article [21].

82

4  Quantum Retina

Fig. 4.15  The diagram illustrates isomerization of 11-cis retinal to all-trans retinal with hydrogen out-of-plane (HOOP) presented in green and protonated Schiff base in orange

Time Fractions in Isomerization of 11-cis Retinal From (E) to (Z The primary isomerization reaction) is completed in less than 150 femtoseconds [13]. The excitation process is extremely fast which is around 1 fs. Bond length alteration (BLA) begins at 15 fs.

Femto Scale

83

Fig. 4.16  The diagram represents the time scale of the events after excitation of electrons. After excitation, different pathways of relaxation are shown as seen in the schematic above

The splitting happens 30 fs to form subpopulations. Subpopulation decays at different times. The fastest decay is between 35 and 80 fs and the slowest decay happens between 170 and 200 fs (Fig. 4.16).

Femto Scale In recent years, there has been a lot of attention to femto scale since the creation of femtosecond lasers (Fig. 4.17).

84

4  Quantum Retina

Fig. 4.17  International System of Units with femto highlighted in red as being referred to in the text

Femto Chemistry of Rhodopsin Femtosecond laser spectroscopy is used to interpret the transition of rhodopsin through a conical intersection (CI) with retention of the coherence of the vibrational wave pockets generated during excitation [22]. The femtolaser pump-probe spectroscopy is performed by using an intense short laser wave to excite the molecule referred to as “pump.” To measure the ultrafast behavior of the molecule the second pulse is sent shortly after the first one which is referred to as “probe.” By changing the delay between the pump and probe multiple snapshots will be recorded. It is then possible to reconstruct the ultrafast motion of the molecule frame by frame. This allows a time resolution down to the femtosecond (1 × 10−15) [23] (Fig. 4.18). There is a basic article from 2014 that describes the fundamentals of “quantum retina” [24], since then multiple advances and more recent publications and new studies have been performed. The recent articles on quantum biology and vision are highly recommended to update the readers’ knowledge of quantum effects on the eye [25, 26].

References

85

Fig. 4.18  The diagram represents the ground state and excited states of electrons after excitation with the pump laser pulse, followed by femtosecond laser probes which effects the vibrational states

References 1. Gueye. Engineering the vibrational coherence of vision into a synthetic molecular device. Nat Commun. 2018;9:313. https://doi.org/10.1038/s41467-­017-­02668-­w. 2. Schenedermann. Mode-specificity of vibrationally coherent internal conversion in rhodopsin during the primary visual event. J Am Chem Soc. 2015;137:2886. https://doi.org/10.1021/ ja508941k. 3. Muranov. Biochemistry of eye lens in the norm and in cataractogenesis. Biochem Mosc. 2022;87(February 11):106. https://doi.org/10.1134/S0006297922020031. 4. Akagunduz. Radiation-induced ocular surface disorders and retinopathy: ocular structures and radiation dose-volume effect. Cancer Res Treat. 2022;54:417. https://doi.org/10.4143/ crt.2021.575. 5. Ke Q.  Multinucleated retinal pigment epithelial cells adapt to vision and exhibit increased DNA damage response. cells. 2022;11 https://doi.org/10.3390/cells11091552. 6. Marro. Assessing human eye exposure to UV light: a narrative review. Front Public Health. 2022;10 https://doi.org/10.3389/fpubh.2022.900979. 7. Fan. The molecular mechanism of retina light injury focusing on damage from short wavelength light. Oxidat Med Cell Longevity. 2022;2022 https://doi.org/10.1155/2022/8482149. 8. Praveena. Prevalence and pattern of ocular disorders due to chronic exposure to arc welding among occupational welders in Western Rajasthan. J Family Med Primary Care. 2022;11:2620. https://doi.org/10.4103/jfmpc.jfmpc_1880_21. 9. Bijlard. Direct microwave burns in an infant: description of burn characteristics, management and outcome. Burns Open. 2022; https://doi.org/10.1016/j.burnso.2022.07.001. 10. Moon. Health effects of electromagnetic fields on children. Clin Exp Pediatr. 2020;63:422. https://doi.org/10.3345/cep.2019.01494.

86

4  Quantum Retina

11. de Grip. isorhodopsin: an undervalued visual pigment analog. Colorants. 2022; https://doi. org/10.3390/colorants1030016. 12. Wenging. The photochemical determinants of color vision. BioEssays. 2013;36:65. https://doi. org/10.1002/bies.201300094. 13. Metternich. Photocatalytic E → Z Isomerization of Polarized Alkenes Inspired by the Visual Cycle: Mechanistic Dichotomy and Origin of Selectivity. Am Chem Soc. 2017; https://doi. org/10.1021/acs.joc.7b01281. 14. Broser. Far-red absorbing rhodopsins, insights from heterodimeric rhodopsin-cyclases. Frontiers in Molecular Biosciences. 2022; https://doi.org/10.3389/fmolb.2021.806922. 15. Palczewski. Shedding new light on the generation of the visual chromophore. PNAS. 2020;117:19629. https://doi.org/10.1073/pnas.2008211117. 16. Perera. Rhodopsin activation in lipid membranes based on solid- state NMR spectroscopy. Encyclopedia Biophysics. 2020; https://par.nsf.gov/servlets/purl/10264174 17. Sato. Opn5L1 is a retinal receptor that behaves as a reverse and self-regenerating photoreceptor. Nat Commun. 2018;9:1255. https://doi.org/10.1038/s41467-­018-­03603-­3. 18. Olivucci. Unlocking the double bond in protonated Schiff bases by Coherent superposition of S1 and S2. J Phys Chem Lett. 2021; https://doi.org/10.1021/acs.jpclett.1c01379. 19. Clarivate. Acylhydrazone switches: E/Z stability reversed by introduction of hydrogen bonds. Eur J Organ Chem. 2018; https://doi.org/10.1002/ejoc.201801466. 20. Xuchun. 2022. https://www.readcube.com/articles/10.1038/s41557-­022-­00892-­6?no_ publisher_access=1. Nat Chem March 3. https://www.readcube.com/articles/10.1038/ s41557-­022-­00892-­6?no_publisher_access=1. 21. Hontani. Dual Photoisomerization on distinct potential energy surfaces in a UV-absorbing rhodopsin. J Am Chem Soc. 2020;142:11464. https://doi.org/10.1021/jacs.0c03229. 22. Ostrovsky. Femtochemistry of rhodopsins. Russian J Phys Chem B. 2020;15:344. https://doi. org/10.1134/S1990793121020226. 23. Kiefer. Intrinsic photoisomerization dynamics of protonated Schiff-base retinal. Nat Commun. 2019; https://doi.org/10.1038/s41467-­019-­09225-­7. 24. Sia. Quantum biology of the retina. Clin Exp Ophthalmol. 2014;42:582. https://doi. org/10.1111/ceo.12373. 25. Mazzoccoli. Chronobiology Meets Quantum Biology: A New Paradigm Overlooking the Horizon? Front. Physiol. 2022; https://doi.org/10.3389/fphys.2022.892582. 26. Yang. Quantum–classical simulations of rhodopsin reveal excited-state population splitting and its effects on quantum efficiency. Nat Chem. 2022b;14(March 3):441. https://doi. org/10.1038/s41557-­022-­00892-­6.

Chapter 5

Magnetoreception

Abstract As we reviewed, the effect of quantum mechanics on biological phenomenon such as photosynthesis and visual phototransduction in the previous chapters, we hope that the quantum concepts and effects on cellular structures have become more familiar and understandable for the reader. Another field of biology that has been the center of attention in the past 40 years is the role of quantum physics in the process of magnetoreception in migrating birds. There have been multiple theories and experiments on the subject that we will summarize in this chapter, and we will discuss the latest info available in the literature at the present time. The ability of sensing the earth’s magnetic field has been reported in many living organisms, from plants to insects such as fruit flies and honeybees, fish such as salmon and migrating birds. Recently, the existence of human magnetic sense has been reported and is suggested that it is mediated by a light and magnetic field resonance-­dependent mechanism [1, 2]. The main use of magnetoreception is for navigation. Even though the exact mechanism of the effects of magnetic fields on biological systems is not completely understood, there are many researchers who have narrowed it down to specific mechanisms that will be discussed here [3]. The birds can sense the inclination of the magnetic field by a process that involves the absorbance of the blue light, indicating the involvement of photoreceptor proteins in their retina. The discovery of the chromophore proteins Cryptochromes and their ability to produce radical-pair mechanism seemed to match all the requirements for a magnetosensor. Recent studies also have provided strong evidence that European robin cryptochrome 4a (ErCry4a) and alpha subunit of a cone-specific G-protein interact in vivo, and this interaction could be the first trigger step of biochemical signaling in radical-pair-based magnetoreception Görtemaker [4, 5]). © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 K. T. Moazed, Quantum Biology of the Eye, https://doi.org/10.1007/978-3-031-32060-6_5

87

88

5 Magnetoreception

The light-dependent magnetic perception of night migratory songbirds can be disrupted by weak radiofrequency fields. This confirms that at least one of the components of the radical pair was involved in the magnetoreception which was a result of the existence of a substantial number of strong hyperfine interactions as would be in the case of flavin-tryptophan radical pair as a magnetic sensor [6]. The quantum nature of avian compass has been established recently and again is inspired by the cryptochrome protein qualifications for magnetoreceptor sensing [7]. The following review article is highly recommended which covers the basics of magnetic field effects from the perspective of the radical pair mechanism [8] At present, there are different theories regarding magnetoreception, but it is believed that the main source of magnetic field detection is the protein “Cryptochrome” in the eye and relies on the quantum radical pair mechanism to function. Again, we must review some biochemistry essentials to understand the magnetoreceptor process.

Earth Magnetic Field (EMF) Earth’s magnetic field is generated by electric currents produced by the motion of the molten iron and nickel in the Earth’s outer core convection currents. These currents are caused by heat escaping from the core. At the surface, the Earth’s magnetic field is very weak and ranges from 0.25 to 0.65  G (The international unit of magnetic-­B field is Tesla which is equal 10,000 Gauss). The interaction of Earth’s magnetic field with cryptochrome molecules causes interconversion between the singlet and triplet states of the radical pair.

It should be realized that the electrons in atoms and molecules except for oxygen are at singlet state which is referred to as a system in which all electrons are paired and are in a stable mode. Their net angular momentum is zero and overall spin quantum number s = zero. The excitation with electromagnetic waves can cause a transit to a singlet excited and/or to a triplet state. Paired electrons are two electrons that occupy the same molecular orbit but have opposite spins. Because the spin of paired electrons is opposite the magnetic moment of electrons cancels each other and the magnetic property is generally diamagnetic which is repelled by magnetic field and has no dipole moment. Unpaired electrons on the other hand have an electron that occupies an orbital singly. Unpaired electrons also occur briefly during reactions and radical formation. The unpaired electron has a magnetic dipole moment. Only elements with unpair electrons exhibit paramagnetic which attract by a magnetic field. Hyperfine Structure: Small shift and splitting of energy level of atoms, molecules, and ions due to electromagnetic multipole interaction between the nucleus and the electron cloud. Pauli exclusion principle: Two electrons with the same value occupying the same orbit must have opposite spins, if one has +1/2 spin the other must have −1/2 spin.

Earth Magnetic Field (EMF)

89

Free Radicals are atoms, molecules, or ions that have at least one unpaired valence electron. Free radicals have a major role in living organisms, for example, superoxide and nitric oxide and their reaction products regulate many processes such as controlling the vascular tone or as a messenger in redox signaling. Redox (reduction-Oxidation) is a chemical reaction in which the oxidation states of atoms are changed. Reduction is the gain of electrons or decrease in the oxidation state of atoms. Oxidation is the loss of electrons or increase in the oxidation states of atoms. Electron Transfer is when an electron relocates from one atom or molecule to another. It is the foundation of photo redox catalysis. Cryptochromes are 70–80 KDa proteins and are evolutionary proteins belonging to the flavoproteins superfamily found in plants, insects, and animals that are sensitive to blue light. The molecule contains two chromophores: Flavin in the form of Flavin Adenine dinucleotide (FAD) and Petrin (MHFR) [9, 10]. Immunohistochemical staining in migrating birds has located the cryptochrome in many locations in the retina such as ganglion cells’ inner nuclear layer and in both outer and inner segments of the photoreceptors [11]. The cryptochrome molecule has different segments and attachments that have non-covalent bonding. • The N-terminal, when activated with blue light undergoes dimerization. • The conserved body of around 500 amino acids which is called photolyase Homology Region (PHR), with non-covalently attached to two molecules, Pterin and FAD. • Pterin is the antenna that detects the blue light and transfers it to FAD. • Flavin adenine dinucleotide (FAD) is a coenzyme that interacts with many enzymes. • The central pocket for Flavin adenine dinucleotide (FAD) attachment. • The C-terminal “Cryptochrome carboxyl terminal (CCT) has a variable number of amino acids from 25 to 150 or more and is the (output domain). It involves phosphorylation and signal transduction to the nucleus. Cryptochromes work as a dimer when activated via their N-terminal. They are blue light sensing and their production increases at dark (night). Their formula is very similar to Photolyases except they do not have the ability to repair DNA (Fig. 5.1). FAD 450 nm

Pterin-MTHF 380 nm

N Terminal

Photolyase Homology Region (PHR) 500 Amino Acids

α/β Domain Interdomain

Dimerization

Loop

N Terminal

C Terminal

Helical Domain

Photolyase Homology Region (PHR) 500 Amino Acids Pterin-MTHF 380 nm

Carboxy-terminal Domain ~ 25-150 Amino Acids

Carboxy-terminal Domain ~ 25-150 Amino Acids

C Terminal

FAD 450 nm

Fig. 5.1  Schematic representation of two cryptochrome molecules dimerized by blue light. The dimerization, as shown by the red circular oval, which is through the N-Terminals causes the activation of the molecules

90

5 Magnetoreception

Multiple functions of cryptochromes are as follows: • Circadian rhythm [12]. • Phototropism determines the direction of plant growth toward the light source [13]. • Photomorphogenesis in plants is responsible for switching from the vegetative stage to the flowering stage [14]. • Photoreceptor and phototransduction in Drosophila [15]. • Magnetoreception in birds (Görtemaker, Direct Interaction of Avian Cryptochrome 4 with a Cone-Specific G-Protein [4, 5]). The molecules that are essential and are involved in magnetoreception is being individually discussed and presented in the following: • Petrin captures the energy and transforms it into flavin (Fig. 5.2). • Flavin is an organic compound that is required by most life forms to provide specific catalytic tasks. Humans obtain flavin as vitamin B2 in their diet. Flavin is usually found in the form of flavin mononucleotide or in the form of flavin adenine dinucleotide (FAD) which then is reduced to FADH which mediated phosphorylation of certain domains in Cryptochrome which then triggers the signal transduction chain of events (Fig. 5.3). • Flavin adenine dinucleotide (FAD) is a coenzyme associated with many enzymatic proteins. It can exist in different forms by accepting or donating electrons. FAD is the fully oxidized form (quinone), and when it accepts 2 electrons and 2 protons it becomes FADH2 (hydroquinone). FADH (semiquinone) can be formed either from reduction of FAD or from oxidation of FADH2 (Fig. 5.4). • Cofactor FAD exists in three interconvertible redox forms, FAD, FADH, and FADH. FAD = Non-signaling (Inactive)

Fig. 5.2 Structural representation of Petrin molecule

O N HN N

H2H

Fig. 5.3 Structural representation of Flavin molecule

N

O H3C

N

H3C

N

NH

R

N

O

91

Earth Magnetic Field (EMF) Fig. 5.4 Color presentation of the different molecular substructures of FAD. The top lavender square is the Adenine molecule, the rose square represents the Ribose molecules, the green rectangle represents Diphosphate and the bottom lavender rectangle contains Flavin molecule

NH2 N N

Adenine N

N O O O

OH

Ribose

P OH

O O O

Diphosphate

P O

O OH

HO

Ribose HO N

N

NH

N Flavin

O

O

FADH = Signaling (active) FADH- = fully reduced Non-signaling (Inactive) Blue light activates FAD to FADH. Green light deactivates FADH to FADH. The activation and deactivation of FAD and FADH involve radicals and are affected by the magnetic field. The radical pair is formed between flavin and an oxygen molecule, or between flavin and tryptophan side chins in a Cryptochrome molecule. Flavin Adenine Dinucleotide (FAD) consists of two portions (dinucleotide) the adenine nucleotide and the flavin nucleotide. • Adenine nucleotide (A) is one of the four nucleobases in nucleic acid of DNA. It participates in the formation of FAD and many other essential molecules like ATP and Coenzyme A (Fig. 5.5). • Flavin nucleotide is often attached to adenosine diphosphate to form Flavin adenine dinucleotide (FAD). It is also found as flavin mononucleotide (FMN), a phosphorylated form of riboflavin. Flavin group is capable of undergoing oxidation-­reduction reactions and can accept either one electron in a two-step

5 Magnetoreception

92 Fig. 5.5 Structural representation of Adenine molecule

NH2 N N N H

Fig. 5.6 Structural representation of Riboflavin molecule

N

O CH3

N

CH3

N

NH N OH

O

OH

HO

OH

Fig. 5.7 Structural representation of Ribose molecule

CH2OH

OH O

OH

Fig. 5.8 Structural representation of Tryptophan molecule

OH O OH

HN

NH2

process or two electrons at once. Reduction is made by addition of hydrogen atoms to the specific nitrogen atoms on the molecule (Fig. 5.6). • Ribose, a simple sugar with molecular formula C5H10O5. It is an important addition to other molecules such as RNA, and is a necessary compound for coding, decoding, regulation, and expression of genes. Ribose in adenosine triphosphate (ATP), with three phosphate groups and an adenine base is a product of cellular respiration and is an essential currency for energy that involve in cellular metabolism, signaling pathways, and nucleotide biosynthesis (Fig. 5.7). • Tryptophan (TRP) is an essential amino acid for humans which means the body cannot synthesize it and it must be obtained from diet. It is a polar molecule and a precursor to the neurotransmitter serotonin and the hormone melatonin. The tryptophan molecule has a critical role in electron transfer to flavin in crypto-

Earth Magnetic Field (EMF)

93

Fig. 5.9 Structural representation of Tyrosine molecule

O OH HO

•

• • •

NH2

chrome molecule and formation of unpaired radicals in the process of magnetoreceptor perception in migratory birds (Fig. 5.8). Tyrosine (Tyr) is one of 20 standard amino acids that is used by cells to synthesize proteins. Tyrosine residues play an important role in photosynthesis and magnetoreception. It can be tagged to a phosphate group and its phosphorylated form is one of the key steps in many signal-transduction processes. The tyrosine side chain location in the cryptochrome molecule is at a close distance to Tryptamine D which is close enough to be able to be oxidized by it and this will extend the electron transfer chain. Also, its interaction with Flavin causes the conformation of C-Terminal delays the relaxation to the favorite lifetime for ability of cryptochrome to start the signaling process (Fig. 5.9). HOMO, Highest occupied molecular orbital. LUMO, lowest unoccupied molecular orbital. SOMO, singly occupied molecular orbital such as in radicals. Asterisk symbol * on top of any atom or molecule refers to its excited state.

A chain of four tryptophan residues in animal cryptochrome molecules are involved in photoreduction of FAD cofactor. Radical pairs are formed between FADH and each of the tryptophan residues during the electron transfer process after blue light exposure which causes the singlet excited state which permits a magnetic field effect in cryptochrome molecule. In the cryptochrome molecule, the “Flavin adenine dinucleotide “FAD and four tryptophan amino acid side chains are positioned in a chain from center of the molecule toward the surface in around 1.9 nm. In the resting or ground state the combination of FAD and Tryptophan is in the fully oxidized state. This distance between the molecules is essential for electron transfer and interconversions between singlet and triplet states. Very small, or much longer distances prevent these processes to happen [16] (Fig. 5.10). When Flavin absorbs the blue light it triggers electron transfer from terminal tryptophan to the Flavin, which is from HOMO of terminal tryptophan to the LUMO of Flavin. This produces the radical state and formation of triplet states by oscillations due to an external magnetic field. It is the fast interconversion change of singlet to triplet back and forth which make the system susceptible to the EMF, in other words, The created radical pairs of flavin and tryptophan which their singlet-triplet interconversion rate, make them susceptible to and become modulated by earth’s magnetic field. From here, there are different pathways of non-radiative relaxation back to the ground state with different speeds:

94

5 Magnetoreception

Fig. 5.10  Schematic representation of electron transfer in the cryptochrome molecule. The sequence of electron transfer from Tryptophan D to Tryptophan C and Tryptophan B to Tryptophan A and then to the Flavin molecule. The sequence of events behaves like a wire for the transfer of electrons. The Tyrosine interaction affects the C-Terminal of the cryptochrome molecule and causes its conformation

• The excited radical flavin and Tryptophan can return directly to the ground state in about 1 microsecond. This process is too short for interaction with the earth’s magnetic field. • The excited radical flavin individually can gain a proton and become neutral in 1 microsecond and then return to the ground state in about 100 microseconds. This is enough time for interaction with the Earth’s magnetic field. • The excited radical Tryptophan individually can lose a proton and become neutral in 1 microsecond and then return to the ground state in about 100 microseconds. This is enough time for interaction with the earth’s magnetic field. • In vivo the Flavin C-Terminal can undergo conformation and interact with nearby tyrosine molecules which delayed lifetime of the relaxation to the ground state to about 1 second. This long lifetime will allow the 1.4-megahertz oscillation to happen and have a significant effect on the efficiency of FAD for signaling process and as a magnetoreceptor (Fig. 5.11). The latter is the most productive pathway and is when individually the flavin radical conformation occurs in its C-Terminal domain, causing the involvement of nearby tyrosine residue which slows down the reaction lifetime. This process in vivo

Earth Magnetic Field (EMF)

95

Fig. 5.11  The diagram represents excitation of the Cryptochrome molecule with blue light. Electron transfer from four Tryptophan side chains causes radical pair formation which makes the molecules susceptible to the Earth’s Magnetic Field. From there will be multiple pathways from an excited state to the ground state. There could be a fast (~1 μs) and immediate return to the ground state directly as shown or it can transform to the neutral state as Stabilized Radicals which can return to the ground state directly at a slower pace (~100 μs). Flavin can individually interact with Tyrosine which will slow down the process of relaxation to as long as about 1 second

could increase the lifetime to up to a second, allowing enough time for integration averaging signaling. As mentioned before, a reaction less than 100 microseconds cannot affect the phototransduction process [17]. Cryptochrome molecule also has a molecular pocket for oxygen radical trafficking. The molecular oxygen radical (superoxide) O2- enters the Cryptochrome pocket at a constant rate forming a radical pair (FADH+O2-) with 25% in a singlet state and 75% in a triplet state [18]. If the radical pair is in singlet state it forms (FADH- + O2-) which has lower energy state than (FADH+O2-) which separates the O2- radical which escapes from the molecular pocket. EMF effect in activation of cryptochrome (signaling state) happens via photoreduction process. However, cryptochrome can revert to its non-­ active state if the unpaired electron on FDAH back transfers to one of the three tryptophan molecules. The EMF interaction affects the interconversion between the singlet and the triplet states of the radical pair and depends on the orientation of the earth’s magnetic field. Once the FAD cofactor is reduced to the FADH state, Cryptochrome stops signaling. If the radical pair separates before signaling stops, the radical O2 escapes from the pocket and leaves the cryptochrome to stay in its signaling state. This state stays until another O2- radical arrives [19].

96

5 Magnetoreception

The separation and re-encounter of radical O2- delay the magnetic field-­dependent reaction, shifting it into the millisecond time scale relevant to biological signaling. Now that we reviewed the ingredients of the magnetoreceptors let us start with the recipe. What is necessary for humans to use Earth’s magnetic field for navigation: • Earth magnetic field. • Small dipole magnet to align itself with the magnetic field (a compass). This was done for hundreds of years by humans, is very simple and is still being used today. Magnetoreception has been reported in plants, insects, fish, and turtles and even in humans. In animals, the process of magnetoreceptors is much more complex, yet has been used for millions of years. Since animals cannot use technology, the process should have very specific criteria to be able to be accomplished. So, let us see what the requirements are for using magnetoreceptors for navigation in migrating birds since there is a vast body of studies done successfully. The requirements for migrating birds to use the earth’s magnetic field are: • • • • • • • • • • •

Blue light to start activation of specific light-sensitive molecules. Biological compass in the eyes and perhaps in the beak. Specific genes to manufacture the light-sensitive proteins. Photosensitive protein molecules. Unpaired electrons. Electron transfer. Spin selective chemistry. Photoreceptors. Photo signaling process. Ion channels. Transferring to the specific brain region to process the transferred information.

There has been lots of research to find the molecule that fits all the above criteria, and the only molecule that was qualified was finally identified as Cryptochrome. In vertebrates, cryptochromes are the only class of molecules known which form radical pairs upon activation with blue light. Cryptochrome molecules are capable of all the above requirements to be magnetic field sensors in animals (Fig. 5.12). The cryptochrome has been in the cone photoreceptors of the migrating bird’s retina. During the day, the cones are active with color perception in bright daylight. It is during the night that the cryptochromes get activated in the cones. So, from engagement of the blue light with the cryptochrome molecule in the cone

Earth Magnetic Field (EMF)

97

Fig. 5.12  Schematic representation of two cryptochrome molecules dimerized by blue light. The dimerization, as shown by the red circular oval, which is through the N terminals causes the activation of the molecules. The molecular structures of Pterin and FAD have been included

photoreceptor cells of the bird’s retina to the perception of magnetic field there is a long process and yet very fast, which can be summarized as follows (Fig. 5.13): The entire process of magnetoreception can be summarized in an image with all the required steps from exposure to blue light to perception of the magnetic field (Fig. 5.14). Blue light to the eye → • • • • •

Cryptochrome excitation → Light-induced excited singlet formation → Singlet state of FAD + Tryptophan → HOMO of tryptophan→ LUMO of Flavin →

98

5 Magnetoreception

Fig. 5.13  Schematic representation of cryptochrome molecule and its location on the photoreceptor disc. Influence of blue light and the earth’s magnetic field on the molecule and its activation is shown above

• • • • • • • • • • •

electron transfer → Unstable formation of radicals flavin and tryptophan → Magnetic field interaction → Neutral radical formation → C-Terminal conformation → Interaction of cryptochrome with tyrosine → Slowing down reaction time→ Ion channel response → phototransduction → Signaling to the brain → Magnetoreception.

We should keep in mind that many of the above steps can be reversible or bifurcate to different pathways as the process is very complicated. In conclusion, the process of magnetoreception can only be explained by quantum physics/Biology and the development of new tools in recent years has

References

99

Fig. 5.14  Blue light to the eye →Cryptochrome excitation →Light-induced excited singlet formation →Singlet state of FAD + Tryptophan →HOMO of tryptophan →LUMO of Flavin→Electron transfer→Unstable formation of radicals Flavin and tryptophan→Magnetic field interaction→Neutral radical formation→C-Terminal conformation→Interaction of cryptochrome with tyrosine→Slowing down reaction time→Ion channel response→Phototransduction→Signal ing to the brain→Magnetoreception

helped experimenting and confirming different steps of this process. Each step has been shown in the image above and has been simplified to make it tangible for the non-­physicist and non-quantum scientist readers.

References 1. Chae. Human magnetic sense is mediated by a light and magnetic field resonance-dependent mechanism. Sci Rep. 2022; https://doi.org/10.1038/s41598-­022-­12,460-­6. 2. Kwon. Human magnetic sense is mediated by a light and magnetic field resonance-dependent mechanism. Sci Rep. 2022; https://doi.org/10.1038/s41598-­022-­12460-­6. 3. Binhi. Theoretical concepts in magnetobiology after 40 years of research. Cells. 2022; https:// doi.org/10.3390/cells11020274. 4. Görtemaker. Direct Interaction of Avian Cryptochrome 4 with a Cone Specific G-Protein. Cells. 2022a; https://doi.org/10.3390/cells11132043.

100

5 Magnetoreception

5. Görtemaker. Direct Interaction of Avian Cryptochrome 4 with a Cone Specific G-Protein. Cells. 2022b; https://doi.org/10.3390/cells11132043. 6. Leberecht. Broadband 75-85 MHz radiofrequency fields disrupt magnetic compass orientation in night-migratory songbirds consistent with a flavin-based radical pair magnetoreceptor. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2022; https://doi.org/10.1007/ s00359-­021-­01537-­8. Epub 2022 Jan 12. 7. Smith. Observations about utilitarian coherence in the avian compass. Sci Rep. 2022; https:// doi.org/10.1038/s41598-­022-­09901-­7. 8. Zadeh. Magnetic field effects in biology from the perspective of the radical pair mechanism. J Royal Soc Interface. 2022; https://doi.org/10.1098/rsif.2022.0325. 9. Kavet. Cryptochromes in mammals and birds: clock or magnetic compass? J Am Physiol Soc. 2021; https://doi.org/10.1152/physiol.00040.2020. 10. Liedvogel. Cryptochromes—a potential magnetoreceptor: what do we know and what do we want to know? J Royal Soc Interface. 2009; https://doi.org/10.1098/rsif.2009.0411.focus. 11. Ahlers. Integration and evaluation of magnetic stimulation in physiology setups. PLoS One. 2022; https://doi.org/10.1371/journal.pone.0271765. 12. Smylie. Cryptochrome proteins regulate the circadian intracellular behavior and localization of PER2  in mouse suprachiasmatic nucleus neurons. PNAS. 2022; https://doi.org/10.1073/ pnas.2113845119. 13. Rai. Perception of solar UV radiation by plants: photoreceptors and mechanisms. Plant Physiol. 2021; https://doi.org/10.1093/plphys/kiab162. 14. Trojak. Effects of partial replacement of red by green light in the growth spectrum on photomorphogenesis and photosynthesis in tomato plants. Photosynthesis Res. 2021; https:// doi.org/10.1007/s11120-­021-­00879-­3. 15. Au. Mosquito cryptochromes expressed in Drosophila confer species-specific behavioral light responses. Curr Biol. 2022; https://doi.org/10.1016/j.cub.2022.07.021. 16. Xie. Searching for unity in diversity of animal magnetoreception: From biology to quantum mechanics and back. Innovation(Camb). 2022; https://doi.org/10.1016/j.xinn.2022.100229. 17. Wong. Cryptochrome magnetoreception: four tryptophans could be better than three. J Royal Society Interface. 2021; https://doi.org/10.1098/rsif.2021.0601. 18. Solovyov. Radical pair formation in cryptochromes. Quantbiolab.com; 2021. https:// quantbiolab.com/research/radical-­pair-­formation-­in-­cryptochromes 19. Mondal. Theoretical insights into the formation and stability of radical oxygen species in cryptochromes. Phys Chem Chem Phys. 2019; https://pubs.rsc.org/en/content/ articlelanding/2019/CP/C9CP00782B

Chapter 6

Quantum Biology of Circadian Rhythms

Abstract The 2017 Noble Prize in physiology or medicine was awarded to three scientists for their discoveries of molecular mechanisms that control circadian rhythms. The internal biological clock anticipates day/night cycles due to the rotation of the earth to optimize the physiology and behavior of organisms. The discovery of the genes involved such as Period (PER) and its partner TIMELESS (TIM) led to the discovery of a Transcription-Translation Feedback Loop (TTFL). Multiple regulations and modifications of TTFL generate autonomous oscillations in a period of 24 h. The central clock of mammalian circadian system is located in the suprachiasmatic nucleus (SCN) of the hypothalamus, functioning as a pacemaker. The circadian oscillation within individual cells responds differently to external signals and controls many physiological outputs, such as sleep patterns, body temperature, hormone release, blood pressure, and metabolism.

Important notes for clarification Oscillation: Repetitive or periodic variation in time of some measures from the central point of equilibrium between the two states. Vibration: The term is used to precisely describe a mechanical oscillation. Ubiquitination: Small protein “ubiquitin” that attaches to the protein substrates of a protein for degradation. Proteasome: Complex intracellular process that regulates the degradation of cellular proteins. Transcription: The process of copying a segment of DNA to RNA. Translation: The information from mRNA is used to create amino acids during protein synthesis. Enhancer box (E-box): Regulatory proteins that bind to a single strand of DNA to promote a wide range of gene expression. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 K. T. Moazed, Quantum Biology of the Eye, https://doi.org/10.1007/978-3-031-32060-6_6

101

102

6  Quantum Biology of Circadian Rhythms

Entrainment: The synchronization of different rhythmic cycles that interact with each other. Ganglion cells: The cells that are located on the innermost layer of the retina and are transferring the visual signals from photoreceptors via their axons through the optic nerve to the brain.

Discussions The two closely related superfamilies of cryptochromes and photolyases are blue light receptors. The former, cryptochromes, are involved in magnetoreception as was discussed in the previous chapter and are also involved in the process of circadian cycles. The latter, photolyases, are involved in the repair of damaged DNA. All the recurring chemical processes that sustain life (by repositioning and exchange of atoms, molecules, and ions in response to external interactions) obey the rules of quantum mechanics. The effects of quantum mechanics on biological processes such as quantum entanglement, quantum superpositions, quantum coherence, and quantum tunneling have been used by all life forms for millions of years. The recognition of this phenomenon which is called “quantum biology” has only begun in the twentieth century. In previous chapters, we reviewed the effects of quantum mechanics on photosynthesis, vision, and magnetoreception. In this chapter, we will explore the effects of quantum mechanics on the circadian biological clock. The active involvement of cryptochrome molecule and the role of radical pair states and electron transfer via tryptophan molecules to FAD have been discussed in detail in the previous chapter and are as relevant as in this chapter. The quantum biology of the cryptochromes and the role of radical pairs will not be repeated in this chapter, and instead, we will discuss the molecular interactions to better understand the process of this ancient biological response to the earth’s rotation. Cryptochromes are flavin-containing blue light sensors that play a key role in the circadian clock and entrain the circadian clock to light. Photoexcitation of cryptochrome molecules causes reduction of an oxidized flavin cofactor by a chain of tryptophan residues as discussed in the previous chapter. The photoinduced electron transfer process along the chain of conserved tryptophan residues reduces the excited state of the FAD cofactor [1]. The radical pair mechanism (RPM) is one of the most well-established models in quantum biology. Superoxide radicals O2-, and the formation of “FADH- O2-” can be an alternative partner for flavin as discussed in the previous chapter. The effect of Lithium on FADH-O2- formation on CRY molecule in the SCN directly affects the circadian cycle. It was suggested that Lithium’s nuclear spin modulates the dynamics of singlet-triplet interconversion in FADH-O2- radical pair complex. This also explains the different therapeutic effect of each Lithium isotope. This effect has been reported on avian magnetoreception and Xenon-induced anesthesia [2]. The cryptochrome genes (Cry1 and Cry2) are essential to circadian rhythms and are directly involved in circadian cycles by binding to the two master regulatory genes, CLOCK/BMAL1 genes (Circadian clock genes), and affect their regulation and the outcome [1, 3].

Discussions

103

Although the molecules involved in the circadian clock exist in all branches of the evolutional tree such as plants, insects, and animals, in this chapter we will concentrate on mammalian circadian systems [4]. The central clock of mammalian circadian system is located in the suprachiasmatic nucleus (SCN) of the hypothalamus, functioning as a pacemaker. The light signals are transferred to SCN via the Retinohypothalamic tract (RHT) which is regulating the peripheral clocks throughout the body. At the cellular level, each cell in the body is governed by its own independent clock, yet their oscillations are coupled with the central oscillator at SCN. The oscillatory coupling between the central and regional oscillators is critical for the functioning circadian clock which provides a wide range of adaptability for the organism. Cellular circadian clock exhibits intrinsic, self-sustaining cycles, close to 24 h and is called “free-running rhythms” which are independent of external signals and involve sleep–wakefulness behavior, body temperature, blood pressure, fluctuations of gene/protein expressions, and release of hormones such as testosterone, melatonin, and neurotransmitters (Fig. 6.1). Regardless, the circadian clock is also under the influence of cyclic changes in the environment such as day–night cycles, seasonal changes, and temperature changes. The circadian clock plays a critical role in the survival of species as a whole [5].

Fig. 6.1  Schematic representation of important events during 24  h time period influenced by circadian rhythms

104

6  Quantum Biology of Circadian Rhythms

The sleep cycle is also controlled by a balance between the SCN and the reticular activating system (RAS) in the brain stem. The activation of SCN will inhibit RAS from inducing sleep [6]. The alignment of the circadian clock to such environmental influence is referred to as “Zeitgebers” (Time givers in German), and for all organisms light is the strongest Zeitgeber, others including temperature, feeding time, and social interactions. These zeitgebers can influence the circadian clock by phase shifting it forward or backward. The mechanism of circadian rhythm depends on so many internal and external factors. Masking is the mechanism that is more prominent in nocturnal mammals. This effect of light can directly conceal the control from the circadian clock. Positive masking happens during the dim light conditions due to confidence based on visual input. The suppressive effect of bright light is called negative masking.

Clock Genes and Signal Transduction Proteins Multiple genes are involved in circadian rhythm regulations which are called clock genes, and new genes are being discovered as time goes by. The molecular mechanism of circadian rhythm depends on a negative feedback system by clock genes. The two important products CLOCK and BMAL1 bind to E-Boxes in the promoters of DEC1, DEC2, PER1 and CRY1 which produce the relevant proteins DEC1, DEC2, PER1 and CRY1, and CRY2. These proteins will be degraded by ubiquitination or phosphorylation, or by dimerizing and suppressing the CLOCK/BMAL1 transactivation. This negative feedback plays a crucial role in circadian cycle regulations in the central suprachiasmatic nucleus (SCN) and peripheral cells (Fig. 6.2). Here, we only refer to the most essential circadian genes: • Circadian Locomotor Output Cycles Kaput (CLOCK) is a transcription factor. CLOCK is synthesized in the cytoplasm and enters the nucleus which then dimerizes with BMAL1. This dimer then recruits coactivator CREB-binding protein and binds to the E-box of promoters of (PER) and (TIM), causing the production of proteins “per” and “Tim,” which in a negative feedback fashion stops their gene translation. • Brain & Muscle ARNT-Like 1 (BMAL1) is a transcription factor. It forms heterodimer with the protein “CLOCK.” This complex drives transcription from E-box elements to regulate the circadian rhythm of a spectrum of gene expressions [7]. • PERIOD (Per) 1,2, and 3, encoding PAS protein. Fig. 6.2 Structural representation of Melatonin molecule

H3 C

O

N H

HN

CH3 O

Clock Genes and Signal Transduction Proteins

105

• Cryptochrome (CRY) genes 1 and 2 binds to Clock/BMAL1. • TIMELESS (TIM) its effect on circadian clock in insects are established but not in mammals yet. • Jetlag (JET) ubiquitin ligase is responsible for TIM ubiquitination. • Immediate Early Genes (IEGs) part of the transcription network controlling Per 1 and 2 transcription. • cAMP response element binding (CREB) protein. Influences the target genes. • Cocaine and Amphetamine-Regulated Transcription (CART) genes, which modulate dopamine system and are linked to eating disorders, Obesity, drug addiction and circadian clock shift. • Extracellular signal-regulated kinase (ERK) 1 and 2, blocking light-induced response by SCN during the day. • Vasoactive Intestinal Peptide (VIP), its signaling is necessary for the maintenance the synchronization of the circadian oscillations in SCN. • Activator protein 1 (AP-1) is a family of transcription factors involved in cell proliferation and survival, apoptosis, transformation, and oncogenesis. They contain a basic leucine zipper (bZIP) domain. There are three subfamilies, Jun, Fos, and ATF. To bind to DNA these subfamilies need to form dimers [8]. • Mitogen-activated Protein Kinase (MAPK) is a cellular signaling pathway or cascade, which regulates both the expression and posttranslational modifications of AP-1. Many different ligands such as growth factors and cytokines, can trigger the MAPK cascade which activates transcription of target genes [8]. • Differentiated embryonic chondrocyte 1 and 2 (DEC1 and DEC2) play an important role in circadian system, cell proliferation, apoptosis, hypoxia response, and have opposite effects in regulating tumor progression [9]. • Retinoic acid-related orphan receptor elements (ROREs) alpha, beta, and gamma are subfamily of nuclear receptors that function as ligand-dependent transcription factors. ROR genes produce several isoforms, and most isoforms exhibit a distinct tissue-specific pattern of expression and regulate different biological processes and target genes. • RORs genes can regulate gene transcription by binding to ROR response element (ROREs). By competing for RORE binding, these receptors can antagonize each other’s effects on transcription. The cross talk between RORs and Rev-Erbs, for example, regulates transcription of clock genes. • (Rev-erb) is nuclear receptor subfamily “alpha” and “beta” that are Key regulators of clock gene expression via transcription repression of BMAL1. • Nicotinamide phosphoribosyltransferase (NAMPT), which is part of a separate feedback loop which creates metabolic oscillators. This plays a positive role in Clock-BMAL1 loop. • Salt inducible kinase 1 (SIK1) with CRTC1 is involved in a resetting of the clock by deactivating the CRTC1. • CREB-regulated transcription coactivator 1 (CRTC1), when activated by phototransduction stimulates activation of CREB, inducing the expression of Per1 and Sik1. • (SIRT1) gene encodes the protein “Sirtuin1” which is a NAD-dependent histone deacetylase.

106

6  Quantum Biology of Circadian Rhythms

Molecular Effect The “core” molecular feedback loop of the circadian clock consists of: CLOCK and BMAL1, PER1, PER2, CRY1, and CRY2 [10]. The molecular bases of circadian clock are self-sustaining molecular oscillators that constitute the transcriptional–translational feedback loop. Due to the fact that the circadian clock rhythm is not exactly 24  h, these oscillators must constantly readjust to remain in alignment with the external world through the process called “entrainment” which accomplishes the adjustment to SCN. In mammals, the primary time adjustor or zeitgeber of SCN is light. The SCN, in turn, entrains with the peripheral clock through the entire body. Within the SCN, light information is integrated with signals from other zeitgebers such as food, external temperature, and sleep to make a precise tuning with the environment. There are also other extra-SCN hypothalamic nuclei monitoring the fluctuation of nutrients and hormonal signals which function semi-autonomously or independent of SCN innervation. The extra-SCN in the brain participates in the control of the circadian cycles via the neural connections and rhythmic function of the autonomous systems, sympathetic, and parasympathetic. The endocrine system also participates in this complex interactive process via many hormones and neurotransmitters. The hormonal and neurotransmitter regulation of circadian cycles also involves communication between many centers, including hypothalamus, pituitary gland, and adrenal cortex [11].

List of Neurotransmitters Involved in Circadian Cycles The major neurotransmitters that are involved in communication system of circadian rhythms are: • Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter. Inducing sleep by affecting the neurons in the posterior hypothalamus that contribute to wakefulness. • Hypocretin is produced by hypothalamus and interacts with dopamine, histamine, norepinephrine, acetylcholine, regulating the sleep/wakefulness cycle. • Glutamate is the most common inhibitory neurotransmitter in the brain that regulates the sleep duration and regulation of REM and wakefulness. • Acetylcholine is a cholinergic neurotransmitter with inhibitory action. It is involved with initiation of REM sleep. • Norepinephrine acts both as neurotransmitter and a hormone. It plays an important role in sleep/wake cycle and is Involved in arousal from sleep. • Dopamine regulates initiation of sleep/wake cycles and can also downregulate melatonin synthesis which contributes toward waking up from sleep.

List of Hormones Involved in Circadian Cycles

107

• Serotonin is a neurotransmitter with a similar action as norepinephrine. Lack of serotonin is commonly associated with depression. It helps to maintain arousal and cortical responsiveness, as well as inhibiting REM. • Adenosine is an inhibitory neurotransmitter involved in promoting sleep. Its build up in the brain during the day promote sleepiness at night. Caffeine is an adenosine antagonist.

List of Hormones Involved in Circadian Cycles • Melatonin: Melatonin is a hormone that is released by pineal gland in the brain during the night. It is involved in synchronizing the circadian rhythms. It affects the sleep/wake cycle and also is involved in seasonal rhythmicity and other functions such as reproduction, molting, and hibernation. Melatonin level secretion changes and shifts during the aging process as delayed release in teenagers and decreased release in elderly. Melatonin secretion is regulated by norepinephrine which is released from the sympathetic nerve fibers [12] (Fig. 6.3).

Fig. 6.3  Schematic representation of circadian molecular transductions. The neurotransmitters released by ipRGCs Terminal activate the surface receptors of SCN which in turn activates CREB inside the nucleus to initiate the process of circadian gene transcription

108

6  Quantum Biology of Circadian Rhythms

Melatonin acts in the following ways: 1. As an agonist of melatonin receptors 1 and 2, which belong to G-Protein-­ Coupled Receptors (GPCRs). 2. As a free radical scavenger within mitochondria it also promotes the expression of antioxidant enzymes. 3. Increases the expression of clock genes Per1 and Per2. • The corticotropin-releasing hormone (CRH) also a stress hormone, it stimulates the anterior pituitary gland to produce adrenocorticotropin hormone (ACTH). It affects the REM sleep and promotes wakefulness. • Adrenocorticotropic hormone (ACTH) is a stress hormone that is released by the pituitary gland. regulates production of “cortisol” by adrenal cortex and androgens. • Cortisol is a stress steroid hormone and is released by the adrenal gland. It helps the body maintain hemostasis and the disruption of regular production can affect the sleep pattern. Cortisol has a strong effect on synchronizing the circadian clock. Cortisol has many other important roles: –– –– –– –– ––

Metabolism of fat, proteins, and carbohydrates Suppressing inflammation Regulating blood pressure Regulating blood sugar Release of sex hormones

• Growth hormone-releasing hormone (GHRH) promotes the release of growth hormone from anterior pituitary gland. Its contribution to interleukin-1 is involved in endogenous sleep promotion substances. • Norepinephrine, also as a hormone is a stress hormone, and one of the main components of fight-or-flight response. Its increased levels can decrease the REM sleep.

Light Exposure Exposure to light provides the primary cue to the SCN and suppresses melatonin synthesis by the pineal gland. • Norepinephrine release via adrenergic fibers from SCN to pineal gland causes synthesis of melatonin. • Melatonin feeds back to master circadian clock.

Small Molecules and Drugs

109

Small Molecules and Drugs Examples of some small molecules and drugs that can affect the circadian clock: • Dexamethasone can synchronize and amplify circadian clock which suggests that glucocorticoids are time signals for peripheral clocks. • Sildenafil, the words most used erectile dysfunction drug, inhibits cGMP-­specific phosphodiesterase 5, and enhances photoactivated phase advancement. • Caffeine, the world’s most widely consumed psychoactive drug, has antagonist effect on SCN receptors, enhancing the photic response and counteracting the effect of sleep deprivation. It causes the release of norepinephrine, dopamine, and serotonin in the brain and blocks adenosine receptors. • Amphetamine and cocaine, the world’s most popular recreational drugs, affect the (Cocaine- and Amphetamine-Regulated Transcript) System “CART” [13]. • Metformin, the world’s most popular anti-diabetic drug, affecting the circadian cycle by partial activation of AMPK [14]. • Lithium, which is used in bipolar disorders, affects the dynamics of radical pair in cryptochrome on FAD with superoxide radical oxygen pair [2]. The Phase shifting of circadian clock can happen in many ways. Even the effect of light, the powerful zeitgeber depends on the time of light exposure. The light detected during early morning causes “phase advance” to start activity. On the opposite side, the light exposure during the dusk causes “phase delay” or signal that it is time to retire. As we mentioned earlier, the main zeitgeber in mammals is light. The light input to the SCN is primarily provided by the retina. The primary photoreceptors responsible for photoentrainment are a small class of photosensitive ganglion cells (rod and cone cells of the retina are not primarily involved, however, they may contribute when ganglion cells are not present). These small groups of ganglion cells carry the photoreceptor “melanopsin” and are involved in transferring the light input to SCN via Retinohypothalamic Tract (RHT). The photosensitive ganglion cells are called “pRGCs” or The Intrinsically Photosensitive Retinal Ganglion Cells “ipRCGs” are the major source of light detection for circadian clock adjustment and are approximately 1–2% of ganglion cell population that contains the photosensitive molecule “melanopsin.” Melanopsins are encoded by the gene “Opn4” and absorb blue light of around 420–440 nm and are playing major role in non-image-forming signals to SCN. Melanopsin is a photopigment belonging to the large family of photosensitive proteins called opsins. It is activated most efficiently by blue light between 420 and 440 nm [15]. Its structure is similar to rhodopsin in retinal rod cells and photopsin in retinal cone cells. Melanopsins located in the ipRCGs are involved in signal transfer for circadian cycles.

110

6  Quantum Biology of Circadian Rhythms

Melanopsin have been located in many locations in the brain [16]. The Intrinsically Photosensitive Retinal Ganglion Cells (ipRGCs) consist of six subtypes (M1–M6) according to their anatomical and morphological differences. They also exhibit distinct electrophysiological properties and mediate different light responses: • • • • • •

Photoentrainment Pupillary response Sleep induction Masking Alertness Mood

Some studies have shown ultraviolet light could signal SCN via detection by rod and cone cells of the retina, although their contributions are limited [17, 18].

Transcriptional-Translational Feedback Loops (TTFLs) The connection of retinal ganglion cells “ipRGCs” to the SCN is via monosynaptic pathway of RHT, the process of molecular photoentrainment of SCN autoregulatory Transcriptional-Translational Feedback Loop (TTFL). Many feedback loops are involved in circadian rhythms. We will just mention the essential feedback loops. The summary is as follows: 1. Clock-BMAL1 and PER and CRY negative feedback: The clock and BMAL1 attach to each other and form a heterodimer. This will activate PER and CRY genes by directly interacting with the E-box element. The accumulation of resulting PER and CRY proteins inhibit the expression of BMAL1/Clock. 2. Clock-BMAL1 and Rev-erb and RORE: The clock and BMAL1 attach to each other and form a heterodimer. Their transcription is regulated by positive and negative feedbacks. The positive feedback is activated by RORs (alpha, beta, and gamma) and the negative loop is activated by REV-ERBs (alpha and beta). Clock and BMAL1 in turn regulate the expression of RORs and REV-Erbs (Fig. 6.4). 3. Clock-BMAL1 and NAMPT-SIRT1: Another feedback loop involves the rate-limiting enzymes synthesis nicotinamide phosphorybosyltransferase (NAMPT) regulating the level of nicotinamide adenine dinucleotide (NAD+). The inhibition of NAMPT promotes activation of PER2 by releasing CLOCK/BMAL1 from suppression by SIRT1. In turn, Clock binds to NAMPT completing the loop [19] (Fig. 6.5).

Transcriptional-Translational Feedback Loops (TTFLs)

111

Fig. 6.4  Schematic representation of Transcriptional-Translational Feedback Loop (TTFL). Two of the core feedback systems are represented here. On the top right is the BMAL1 and REV-ERB and ROR systems, and on the bottom right is the BMAL1 and PER & CRY feedback system

Fig. 6.5  Schematic representation of NAMPT feedback system in circadian rhythm. SIRT1 is required for the NAMPT PROMOTER and contributes to the synthesis of NAD+ which is important for its deacetylation activity

112

6  Quantum Biology of Circadian Rhythms

Fig. 6.6  Schematic representation of the most simplified core negative loops of the circadian system

4. CRTC1-SIK1 pathway: This feedback involves the activation of CREB-regulated transcription cofactor 1 (CRTC1) by light which induces the expression of Per1 and Sik1. Sik1 deactivates CRTC1 by phosphorylation and acts as a break on Per1 [20] (Fig. 6.6). The process of the feedback mechanism: • The activation of the primary neurotransmitters glutamate and Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) by light. • Release of Ca2+ and cAMP. • Activation of Kinase-based signaling cascade (PKA, PKC, PKG, MAPK, and CaMKll). • Activation of transcription factor “cAMP Response Element-Binding” Protein (CREB). • Modulation and transcription of clock genes PER1 and Per2. • Upregulation of PER1 (Dawn) and Per2 (Dusk) adjusts the TTFL which shifts the phase of the clock into alignment with the external light/dark cycles [21].

Light Entrainment The process of light “entrainment” on circadian clock and resetting of the circadian clock SCN is as follows: 1. The photons are detected mainly by melanopsin in retinal ganglion cells called Photosensitive Retinal Ganglion Cells (ipRGCs). 2. The signals are then transferred via Retinohypothalamic tract (RHT) to suprachiasmatic nucleus (SCN) in the brain.

Circadian Clock Networks:

113

3. The signals are transferred by neurotransmitters Glutamate and PACAP from the RHT nerve terminals. 4. The pathway between the ipRGCs and SCN is via a monosynaptic connection. 5. The result is an increase in intracellular Ca2+ and cAMP levels in the SCN. 6. This initiates the cascade of kinase-based signaling pathways such as Protein kinase A (PKA), Protein kinase C (PKC), Protein kinase G (PKG), Mitogen-­ activated protein kinase (MAPK), and Ca2+/calmodulin-dependent protein kinase ll (CaMKll). 7. Phosphorylation of Calcium-cAMP Response Element Binding (CREB) protein in the nucleus. 8. Transcription of Key clock genes PER1 and PER 2 (Fig. 6.4).

Pupillary Reflexes The ipRGCs are also involved in light-induced pupil reflex by connecting axons to the olivary pretectal nucleus of the pretectum.

Suprachiasmatic Nucleus (SCN) In Mammals, the SCN is a pair of oval nuclei in the anterior hypothalamus, located just above the optic chiasm. It is composed of two regions, the core and the shell [10]. • The core receives input from the retina via Retinohypothalamic tract (RHT) and its neurotransmitters and glutamate. Also, receives serotonergic input from the thalamic intergeniculate leaflet. • The shell plays an important role in rhythmic output and has communicating neurons to the core. • Almost all neurons in SCN are GABAergic neurons.

Circadian Clock Networks: There are three oscillators that have been identified in SCN: 1. M-oscillators, located in the posterior tip. 2. E-oscillators, located in the anterior part. 3. The cells in the central part, responding to light-on and light-off circumstances. 4. Intracellular Ca mediates input signals to the molecular clock of the cell such as phase-resetting stimuli to the SCN and output signals from the molecular clock via neurotransmitter release.

114

6  Quantum Biology of Circadian Rhythms

Cellular Transcription-Translation Feedback Loop (TTFL) The circadian clock is ultimately depending on 24-h rhythms at the cellular level. The detail of cellular transcription-translation feedback loop (TTFL) can be simplified and described as follows: 1. TTFL at cellular level promotes the key transcription factors and central transcriptional activators of the core clock mechanisms Clock and BMAL1. 2. Production of CLOCK and BMAL1 heterodimer promotes rhythmic expression of E-Box-containing output genes. 3. The promoted genes, Period (Per 1-3) and Cryptochrome (Cry 1-2) function as direct repressors of CLOCK: BMAL1 heterodimer. 4. Resumption of CLOCK: BMAL1 activity occurs by degradation of the above suppressors (Per 1-3 and Cry 1-2) in different pathways. (Per 1-2) are degraded by phosphorylation by Serin/Threonine casein kinases via ubiquitination. (Cry 1-2) is tagged by (AMPK) for proteasome degradation by direct phosphorylation. 5. Additional loops transactivate or repress the BMAL1 via retinoic acid receptor-­ related Orphan Receptors (RORs) and Nuclear subfamily 1 D member 1 (NR1D1). 6. Non-Circadian loops involved with nicotinamide adenine dinucleotide (NAD+) regulate CLOCK and BMAL1 transcription. Note: BMAL1 gene is the only single gene that when knocked out will result in the full loss of rhythmically at cellular and behavioral levels in a normal light-­ dark cycle.

The Molecular Interplay in Circadian Cycles Here are multiple molecular interplays between circadian clock and other molecular regulatory pathways with their relevant references for further information: • • • • • • • • •

Cell growth and cancer [22] DNA repair [23] Angiogenesis and Hypoxia [24] Apoptosis [25] Metabolism [26, 27] Redox state [28] Immune process [29, 30] Inflammatory process [31] Aging [32] :

References

115

The Brain and Circadian Rhythms Many brain functions, such as sleep/wake, food intake, emotions, motivations, and other cognitive processes are controlled by various regions, and are affected by the circadian rhythms. These centers are under direct or indirect communication with the SCN and their own internal molecular clockwork. The complex system of brain regions is beyond the scope of this chapter and can be accessed by this review article [33].

Conclusion In conclusion, the biological clock in a nutshell is based on quantum effect of Phototransduction, the main contributor to the complex process of circadian rhythms. This process, as was discussed, involves many interactions between the environment and the biological systems in almost all organisms. The study of circadian cycles involves combining many different fields of science, from quantum physics to molecular biology, genetics, organic chemistry, and in mammals the review of anatomy and physiology, to be able to understand the essentials. • • • • • •

Activation of cryptochrome by light. Phototransduction and membrane depolarization. Intracellular calcium flux. cAMP activation. Transcription of circadian genes. Tunning of the circadian rhythms process by interaction between multiple central and cellular responses via direct neural connection or neurotransmitters and hormones.

Suprachiasmatic nucleus; a responsive clock regulating homeostasis by daily changing the setpoints of physiological parameters.

References 1. Lin. Circadian clock activity of cryptochrome relies on tryptophan-mediated photoreduction. PNAS. 2018; https://doi.org/10.1073/pnas.1719376115. 2. Zahed-Haghighi. Radical pairs can explain magnetic field and lithium effects on the circadian clock. Sci Rep. 2022; https://doi.org/10.1038/s41598-­021-­04334-­0. 3. Cellini. Structural basis of the radical pair state in photolyases and cryptochromes. J Chem Commun. 2022; https://doi.org/10.1039/D2CC00376G.

116

6  Quantum Biology of Circadian Rhythms

4. Honma. The mammalian circadian system: a hierarchical multi-oscillator structure for generating circadian rhythm. J Physiol Sci. 2018; https://doi.org/10.1007/s12576-­018-­0597-­5. 5. Fagiani. Molecular regulations of circadian rhythm and implications for physiology and diseases. Signal Transduction Targeted Therapy. 2022; https://doi.org/10.1038/s41392-­022-­00899-­y. 6. Potter. Circadian rhythm and sleep disruption: causes, metabolic consequences, and countermeasures. Oxford Endocr soc. 2016; https://doi.org/10.1210/er.2016-­1083. 7. Wenqian. Emerging insight into the role of circadian clock gene BMAL1 in cellular senescence. Front Endocrinol. 2022; https://doi.org/10.3389/fendo.2022.915139. 8. Gustems. c-Jun/c-Fos heterodimers regulate cellular genes via a newly identified class of methylated DNA sequence motifs. Oxford Nucl Acid Res. 2013; https://doi.org/10.1093/nar/ gkt1323. 9. Nelson. Chronoradiobiology of breast cancer: the time is now to link circadian rhythm and radiation biology. Jefferson Digital Commons. 2022; https://jdc.jefferson.edu/radoncfp 10. Drunen V. Circadian rhythms of the hypothalamus: from function to physiology. Clocks Sleep. 2021;(February 25) https://doi.org/10.1210/er.2016-­1083. 11. Kalsbeek. SCN outputs and the hypothalamic balance of life. J Biol Rhythms. 2006; https:// doi.org/10.1177/0748730406293854. 12. Schomerus. Mechanisms regulating melatonin synthesis in the Mammalian Pineal Organ. Ann N Y Acad Sci. 2006; https://doi.org/10.1196/annals.1356.028. 13. Vicentic. The CART (cocaine- and amphetamine-regulated transcript) system in appetite and drug addiction. J Pharmacol Exp Therapeut. 2007; https://doi.org/10.1124/jpet.105.091512. 14. Vieira. The impact of Metformin on circadian clock genes. J Diabet Metabol Disord Contr. 2014; https://doi.org/10.15406/jdmdc.2014.01.00016. 15. Brown. Melanopsin—shedding light on the elusive circadian photopigment. Chronobiol Int. 2004; https://doi.org/10.1081/CBI-­120037816. 16. Nissilä. P-780  - The abundance and distribution of melanopsin (OPN4) protein in human brain. Eur Psychiatr. 2012; https://doi.org/10.3390/biom11030340. full, 2021 eye 17. Diepen V. Irradiance encoding in the suprachiasmatic nuclei by rod and cone photoreceptors. FASEB. 2013;(June 24) https://doi.org/10.1096/fj.13-­233098. 18. Güler. Melanopsin cells are the principal conduits for rod–cone input to non-image-forming vision. Nature. 2008; https://doi.org/10.1038/nature06829. 19. Ramsey. Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science. 2009; https://doi.org/10.1126/science.1171641. 20. Jagannath. The CRTC1-SIK1 pathway regulates entrainment of the circadian clock. Cell. 2013; https://doi.org/10.1016/j.cell.2013.08.004. 21. Ashton. Photic entrainment of the circadian system. Int J Mol Sci. 2022; https://doi. org/10.3390/ijms23020729. 22. Zhou. Circadian rhythms and cancers: the intrinsic links and therapeutic potentials. J Hematol Oncol. 2022; https://doi.org/10.1186/s13045-­022-­01238-­y. 23. Wang. Insights about circadian clock in glioma: from molecular pathways to therapeutic drugs. CNS Neurosci Therapeut. 2022; https://doi.org/10.1111/cns.13966. 24. Zhang. The circadian clock is essential for the crosstalk of vegf-notch-mediated endothelial angiogenesis in ischemic stroke. Res Square. 2022; https://doi.org/10.21203/ rs.3.rs-­1843132/v1. 25. Woo. Melatonin Induces apoptotic death through Bim stabilization by Sp1-mediated OTUD1 upregulation. J Pineal Res. 2021; https://doi.org/10.1111/jpi.12781. 26. Greco. Integration of feeding behavior by the liver circadian clock reveals network dependency of metabolic rhythms. Sci Adv. 2021; https://doi.org/10.1126/sciadv.abi7828. 27. Ruddick-Collins. Circadian rhythms in resting metabolic rate account for apparent daily rhythms in the thermic effect of food. J Clin Endocrinol Metabol. 2022; https://doi.org/10.1210/ clinem/dgab654. 28. Rutter. Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors. Science. 2001; https://doi.org/10.1126/science.106069.

References

117

29. Carroll. Immunometabolism around the clock. Trends Mol Med. 2019; https://doi. org/10.1016/j.molmed.2019.04.013. 30. Scheiermann. Circadian control of the immune system. Nat Rev Immunol. 2013; https://doi. org/10.1038/nri3386. 31. Spengler. Core circadian protein CLOCK is a positive regulator of NF-κB–mediated transcription. PNAS. 2012; https://doi.org/10.1073/pnas.1206274109. 32. Levine. NAD+ Controls Circadian reprogramming through PER2 nuclear translocation to counter aging. Mol Cell. 2020; https://doi.org/10.1016/j.molcel.2020.04.010. 33. Gall V. The effects of light and the circadian system on rhythmic brain function. Int J Mol Sci. 2022; https://doi.org/10.3390/ijms23052778.

Chapter 7

The Quantum Biology of Consciousness and Visual Perception There would be no such thing as science without conscious minds

Abstract Recently, there has been a lot of interest in the subject of consciousness and its quantum biology properties. Here, we discuss the role of the eye as an important source and participant, in the process of consciousness, and the quantum biology of consciousness. We have discussed the quantum biology of the retina in a process of phototransduction and transfer of information to the brain in the previous chapters. However, we will discuss the role of Müller cells in retina as it participates and facilitates the photon transfer in the inverted retinal thickness. The input of visual information has been recognized as the first step or first “wave” of initiation of the 3-wave processing of consciousness. The possible link between biology and quantum mechanics as first suggested by Schrödinger in his book “What is Life” has revolutionized the world and created the new field of quantum biology. Quantum biology could explain the process of photon harvesting and electron transfer, different states of excitation and relaxation of electrons, emission of photons, and the generation of ultraweak photon emission (UPE) in the neurons. Also, generation of biophotons, and possibly the process of complex neuronal activity and ultimately the consciousness. What brings all the chapters of this book together is the suggestion that the quantum effects may underlie the magnetic field effects on the microtubule dynamics. It is the similar mechanism behind magnetoreception in animals, the circadian clocks, Xenon-induced general anesthesia, and the Lithium effect on mania. So here, the old expression “All roads lead to Rome” can be replaced by

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 K. T. Moazed, Quantum Biology of the Eye, https://doi.org/10.1007/978-3-031-32060-6_7

119

120

7  The Quantum Biology of Consciousness and Visual Perception

“All roads to “neuron quantum Biology” lead to “Tryptophan” since it is the Tryptophan molecules that works like an antenna and transfer the electrons and biophotons for a quantum biological task. Due to the fact that all anesthesiainducing molecules and psychedelic drugs affect tryptophan molecules embedded in tubulin proteins, which are the building blocks of microtubules in neurons, points to the crucial role of this protein in consciousness. Quantum entanglement may also play a crucial role in brain function and consciousness, particularly the photoemission of singlet oxygen that serves as a quantum messenger to establish long-distance connections that might be essential for consciousness. The role of radical pairs in reorganization of microtubules and generation of biophotons are well recognized, and is an important part in neuronal function, and as the result, the brain function and consciousness. The fundamental task of the brain as consciousness, is to orchestrate the multiple parallel external events via sensory inputs, combined with the internal cognitive processing to obtain a stable perception of the environment. This is mainly dependent on the perception of conscious sensory experience based on rhythmic sampling of information most effectively by visual input. The process of quantum vision will be discussed with special focus on major components of quantum energy generation in the eye and its transportation to the brain. It is very interesting to note that nature was able to utilize both classical physics and quantum physics side by side without competition, to combine in order to obtain maximum benefits. It seems that, from photon transfer in retina to neuronal transfer to the brain and interactions in different centers in brain, there are both classic physics, which describe the chemical and electrical modes of communication, and there is quantum mechanical energy transfer via biophotons and vibrational energy transfer, which works hand in hand for optimal results. Recent studies on primates suggests that various visual cognitive functions exhibit slow rhythmic effects on task performance, which would be supported by low-frequency brain oscillations mainly in the 4–8 Hz frequency range. Alpha brain oscillations (8–12 Hz) play a role in many cognitive functions including visual perception. Alpha oscillation’s amplitude and phase, seem to predict cortical excitability. This will emphasize the significant role of visual input in the process of consciousness since about one-third of the cortical surface in primates brain is involved in visual processing tasks, however, in case of visually impaired or the blind, the plasticity of the brain compensates with rewiring the other sensory inputs instead of optical input to the process of consciousness Kienitz (Eur J Neurosci, 2021).Knowledge and Consciousness Consciousness is the individual awareness of thoughts, memories, senses, the environment, and even the sense of awareness itself [2]. Knowledge and consciousness are closely related since both are associated with the awareness of a physical object or phenomenon. We cannot claim knowledge of anything unless we are aware of the phenomenon of knowing, so at the core of the phenomenon of knowledge lies consciousness, as

Neurons

121

the sense of understanding is also closely related. Meanings, symbols, semantics, thinking, reasoning, and understanding are all associated with the conscious mind. As the current state of awareness, consciousness consists of things that we are currently experiencing either via our five senses, or mentally via thinking, or emotionally via feeling. We become conscious of anything that we direct our attention toward, since the active knowledge involves attention. Memory serves as repository of personal information in one’s mind, which in combination with consciousness creates knowledge. Also, the level of knowledge is proportional to the level of interest and attention of the learner, and thus the level of consciousness it involves [1]. Note In order to understand and comprehend this chapter, relevant components have been explained and discussed and references provided on each subject for further in-­ depth information if desired. We will step by step explain the essential factors involved, and that are fundamental to brain and its neurons to communicate. We also discuss the effect of quantum biology on these processes based on the information available in the literature at present time. • Brain anatomy (basics): • The basic anatomy of the brain is beyond the scope of this chapter and can be reviewed at: University [2]. • Cellular structures of the brain: • The brief review of the histology can be reviewed at: Tartu [3] • Neuron anatomy: • A well-presented structure of neurons can be reviewed at: Waymire [4] The major players on visual participants in the process of consciousness will be discussed individually and then the entire concepts as a whole will be discussed: 1. Neurons 2. Synaptic connections 3. Mitochondria 4. Oxygen radical species (ROS) 5. Radical pair mechanism (RPM) 6. Microtubules 7. Biophotons 8. Müller cells 9. Tryptophan

Neurons There are about 100 billion neurons in human brain [5].

122

7  The Quantum Biology of Consciousness and Visual Perception

Fig. 7.1 Schematic representation of a simplified neuron structure

Neurons are the main components of nervous system with the ability to transport and transfer energy with communication via synaptic spaces. Typical neurons consist of a cell body (Soma) with branch-like dendrites usually for the inflow of impulses and the axons for outflow. The axons are covered with a lipid-rich material called myelin. There are spaces along the myelinated section that are called nodes of Ranvier. The structure of a neuron is shown in Fig. 7.1 as a reference for its basic functional properties.

Synaptic Connections The communication between the individual neurons is fundamental for any neurological task including consciousness. This communication between the neurons has many modes of “information transport system.” This transfer of information can be via:

Synaptic Connections

• • • •

123

Chemical, as in synaptic spaces. Electrical, by ion transport as action potential. Optical, by biophotons via microtubules. Vibrational, by generated electric fields along the profilaments of microtubules

Each of these systems have their own specific properties and speed. One common classical mode of neuron communication is via synaptic spaces. That is usually when an axon of one neuron transfers the information to the dendrite of the next neuron. Many other types of synapses can also exist, but here we are referring to neuron-to-neuron synopses at central nervous system. Chemical synapse is when the electrical activity of the presynaptic neuron causes the release of neurotransmitters at its axonal terminals. This is via release of calcium at the voltage-gated calcium channels. The neurotransmitters will bind to the receptors located in the plasma membrane of the postsynaptic neuron which initiates a positive or negative response, and as the result, action potential. Chemical synapses usually classified according to the type of neurotransmitter that they carry such as (Fig. 7.2): 1. Glutamatergic (often excitatory) 2. GABAergic (often inhibitory) 3. Cholinergic (Neuromuscular junctions) 4. Adrenergic (Epinephrin release)

Fig. 7.2  Synapsis cleft showing the release of neurotransmitters by flux of calcium ions inside the axon terminal. The neurotransmitter receptors of the dendrites detect the neurotransmitters and initiate the transport of the information to the receiving neuron

124

7  The Quantum Biology of Consciousness and Visual Perception

Electrical synapses have much faster signal transfer due to the connection of presynaptic and postsynaptic neurons via a gap junction. This permits the passing of the electric current causing voltage changes passing through the junction and passing the signals to the next neuron. Optical and vibrational synapses are by generated biophotons, and the elastic vibrations of the tubulins around their equilibrium position within the microtubules which is called phonons.

Mitochondrion (Mitochondria = Plural) Mitochondria are double-membraned organelle inside the cells that use aerobic respiration to generate ATP (Adenosine Triphosphate) the energy currency of the cell and its referred to as the powerhouse of the cell. Mitochondria have a dynamic and transitional form depend on its activity of fusion or fission machinery [6]. –– Fusion causes longer mitochondria and produces more energy. –– Fission causes shorter mitochondria and more likely will go under degradations [7]. In mammalian cells, mitochondria are transported by motor protein Kinesin-1 and Dynein along microtubule tracks (Fig. 7.3). Structure of mitochondrion: [8] • The outer membrane is similar to cell membrane. Contained a large number of integral membrane proteins. • Intermembrane space, freely permeable to small molecules. • The inner membrane contains, ATP Synthase, Electron transport, and Protein transport. • The Cristae space, enhance expanded surface. • The matrix (Space within the inner membrane) production of ATP and contains many essential enzymes.

Fig. 7.3  Schematic presentation of mitochondrion. The outer membrane and inner membrane are creating space between them called intermembrane space. The most inner section is called the matrix of mitochondrial DNA and ribosomes

Mitochondrial Respiratory Chain Complexes

125

Mitochondrial Respiratory Chain Complexes (Fig. 7.4) Mitochondria has many functions in the cell: • • • • • • • •

Cellular energy supply adenosine triphosphate (ATP) Generating reactive oxygen species (ROS) Production of Biophotons Signaling, specially calcium signaling Cellular differentiation Apoptosis Cell growth Cell cycle (Fig. 7.5) Energy releasing reaction and production of adenosine triphosphate (ATP):

1. Glycolysis, when glucose is converted to pyruvate, which enters the mitochondria and is converted into acetyl-CoA and then into citrate. 2. Citric acid cycle (Krebs cycle), series of chemical reactions that occur in the matrix of the mitochondrion. It releases the stored energy through the oxidation of acetyl-CoA. The cycle consumes acetate from acetyl-CoA plus a water molecule, reduces NAD+ to NADH, releasing carbon dioxide (CO2). 3. Beta-oxidation: Catabolic process by which fatty acid molecules are broken in the mitochondria generating acetyl-CoA which enters citric acid cycle, and NADH and FADH2 in the electron transport chain.

Fig. 7.4  Magnified section of mitochondrion membranes and membrane proteins in charge of its respiratory processes. The respiratory chain complexes are numbered from left to right. Complex I, ubiquinone oxidoreductase transforms NADH to NAD+ and O2 and transfer electron to CoQ. Complex II, Succinate dehydrogenase transforms FADH2 to FADH. Complex III, Cytochrome c reductase releases O2 to SOD 1 and SOD 2 to generate H2O2. Complex IV, Cytochrome c oxidase transforms O2 to H2O. Complex V, ATP synthase Transform ADP to ATP. Complex I, III, and IV pump protons (H+) across inner membrane, creating a proton gradient that is utilized by complex V to produce ATP.  SOD1, Superoxide dismutase 2 located in the matrix convert O2 to Hydrogen peroxide. GPX, Glutathione peroxidase reduces hydrogen peroxide to water

126

7  The Quantum Biology of Consciousness and Visual Perception

Fig. 7.5  Chemical structure of adenosine triphosphate (ATP), the energy currency of the cell. By donating the phosphate to other molecules, it will transform into adenosine diphosphate (ADP) or adenosine monophosphate (AMP)

Oxygen and Reactive Oxygen Species (ROS) WE can start with Oxygen atom, the essential gas to living organisms with the atomic number 8 on the periodic table of elements. It is on nonmetal group 6 of the periodic tables of elements, which means it has 6 outer orbit electrons. Its electron configurations are: 1S22S22p4 (Discussed in previous chapters) which means it has 2 electrons on its first atomic orbital 1S (N1 orbital), 2 electrons on the second subatomic orbital 2S, and 4 electrons on the third subatomic orbit 2d (N2 orbital) makes total of 6 electron at its outer orbit and 8 electrons as a whole. Octet rule: As a very general rule (with many exceptions), there need to be 8 electrons on the outer orbit of each atom with the exception of Hydrogen that has 2 outer electron orbits. For molecular bonding, the 2 electrons of the first orbital “1S” is not counted and only covalent bonds are mentioned (2S, 2p, and higher energy orbitals) which makes a total of 8 electrons on the outer orbit. Lewis Diagram or dot structures: A network of covalent bonds is shown as number of dots around the atomic symbols. It refers to the number of the electron at the outer most orbital which has the highest energy level. Double dots represent paired electrons and single dots represent unpaired electron. The covalent bond between two atoms is shown as a short line and the double bond as double line and triple bond as three lines. Each covalent bond contains 2 electrons (Fig. 7.6). Oxygen forms compounds by reaction to many elements and particularly with hydrogen to form water molecule essential for life on earth. Oxygen has many different forms such as diatomic (O2) or triatomic (O3) as ozone, or in radical oxygen species with singlet or triplet configurations [9]. Reactive oxygen species (ROS) are numbers of reactive molecules and free radicals derived from oxygen molecule during aerobic respiration. These molecules are produced in mitochondria as a byproduct of electron transport, or by oxidoreductase enzymes, and by metal catalyzed oxidation. 1. ROS are generated from the transfer of electrons (e−) from molecular oxygen to form superoxide (O2−) at the mitochondrial electron transport chain complexes I and III.

Radical Pair Mechanism (RPM)

127

Fig. 7.6  Lewis diagram of triplet oxygen. Double dots represent paired electrons and single dots represent unpaired electrons. The covalent bond between two atoms contains two electrons in each bond

2. Superoxide is decomposed enzymatically by superoxide dismutase 1 (SOD1) in the intermembrane space and by superoxide dismutase 2 (SOD2) in the matrix to form hydrogen peroxide. 3. Hydrogen peroxide is then catabolized to water by the action of enzyme such as glutathione peroxidases (GPx), to avoid possible buildup of oxidative stress. 4. Hydrogen peroxide in the presence of Fe2 can form highly reactive hydroxyl radical (*OH). 5. Superoxide may react with nitric oxide to form the potent oxidant and nitrating agent peroxynitrite (ONOO−). ROS are involved in many essential metabolic processes: 1. 2. 3. 4. 5.

Production of ATP Pathogen response Cellular hemostasis Cellular signaling Biophoton production

Radical Pair Mechanism (RPM) Radical pair electrons are the unpaired electrons that spin coherently at the outer orbitals of the molecule and are created simultaneously. Radical pairs are usually created in either singlet or triplet states. Interaction of radical pairs with the nucleus happens via hyperfine (HF) reactions. Interaction of radical pairs can also happen with external magnetic field via Zeeman effect (splitting of spectral line into several components influenced by magnetic field). Altering external magnetic field or substituting isotopes with different spin can change the extent and timing of the singlet–triplet interconversion, resulting in altered yields of products [10].

Singlet Oxygen: (1O2) • A reactive oxygen species is generated by the excitation of ground state (triplet) oxygen.

128

7  The Quantum Biology of Consciousness and Visual Perception

• It is an inorganic gas with the formula (O=O) which is in a quantum state that all electrons are spin paired. • Unlike many other reactive oxygen species (ROS), it is not radical; instead, it is strongly “electrophilic” due to its low-lying lowest unoccupied molecular orbital (LUMO). • It is more reactive toward organic compounds. • Its intracellular lifetime is around (3 x 10-6) seconds. • Trace amount of singlet oxygen are found in upper atmosphere and in the polluted urban areas. • It has only one possible arrangement of electron spin with a total quantum spin of 0. • It has different chemical properties than triplet oxygen, including absorbing and emitting light at different wavelengths. • It is most commonly generated via transfer of energy from excited photosensitizer to ground state (triplet) oxygen. There is a need for three harmless components to interact with each other and generate the potent singlet oxygen: 1. Photosensitizer (PS) such as methylene blue or red Bengal. 2. Light, usually within the visible spectrum. 3. Molecular oxygen. The excitation of ground state photosensitizer (PS) results in formation of excites singlet (PS), which undergoes intersystem crossing to long living “triplet excited state,” which then will collide with an O2 molecule and form singlet oxygen (1O2) (Fig. 7.7). • Singlet oxygen: Intracellularly it is generated by neutrophils using NADPH oxidase and myeloperoxidase. • It can react with intracellular fatty acids, amino acids, and DNA base guanine. • It has an essential role in intracellular signaling transduction [11]. • In solutions, Singlet oxygen can be excited to its “singlet excited state” by the use of photosensitizer. Then by internal conversion (Intersystem crossing) transforms to “triplet excited state” [12].

00 ( 0) 3

2

Triplet Oxygen (Ground State)

Spin Inversion

00 (0) 1

2

Singlet Oxygen (Excited State)

Fig. 7.7  Lewis diagram of triplet to singlet oxygen spin inversion. Double dots represent paired electrons and single dots represent unpaired electrons. The covalent bond between two atoms contains two electrons in each bond

Radical Pair Mechanism (RPM)

129

Triplet Oxygen: (3O2) [13] • Unusually oxygen molecule is in triplet state in its ground state with formula (. O – O.). • Most other molecules are, except for oxygen, at singlet state while in the ground state. • It is the most stable and common form of oxygen. • It has three possible arrangements of electron spin with a total quantum number of 1. • It contains two unpaired electrons at its outer orbital. • It can get excited to singlet excited state and also the triplet excited state. • It has a non-zero spin magnetic moment makes it a paramagnetic molecule. • It does not directly interact with other molecules, which are often in the singlet state. • It reacts with molecules in a doublet states, such as radicals to form new radicals. (Fig. 7.8)

Fig. 7.8  Jablonski diagram of generation of radical oxygen species by activation of photosensitizers and energy transfer to produce different products via different pathways. Different relaxation pathways after the excitation produce different wavelength photons Excitation of photosensitizer (P) with light causes the absorption of that energy and transfers it from its Ground state S0 to its excited state S1. Direct relaxation back to the ground state releases fluorescence photons with a wavelength of around 500 nm. Intersystem crossing by conversion into excited triplet (P) T1. Relaxation from Excited Triplet (P) T1 to the ground state (P) S0 will release Phosphorescence photons with a wavelength of around 280  nm. The triplet (P) T1 can interact with oxygen in two different pathways. First pathway of interaction of triplet (P) T1 by transferring energy to the oxygen from the surrounding tissues to form reactive oxygen species (ROS). Second pathway of interaction of triplet (P) T1 is by transferring energy to the triplet 3O2 ground state T0, by spin inversion to form the excited singlet oxygen 1O2 state S1, which releases photons with a wavelength of around 1270 nm. It is a special property of oxygen that exists in a triplet state at the found state, most other elements are at singlet state in the ground state

130

7  The Quantum Biology of Consciousness and Visual Perception

Microtubules Microtubules are cylindrical structures that form the cytoskeleton of eukaryotic cells with many essential key functions. Recently, microtubules have been the center of attention due to their role in the quantum biology of neurons and the brain function. Microtubules are composed of polymerization of a dimer of two subunit proteins, alpha and beta tubulins. Their main role in the cell is in cell division and intracellular trafficking. Microtubules are formed by assembly from 13 protofilaments of alpha and beta tubulin dimers to form a hallow cylinders. The interior of the cylinder is filled with water molecules, which implies the existence of electric dipole and electric fields. They rapidly grow and shrink in length via GTP regulated process [14]. They can get as long as 50 micrometers and are around 25 nm wide, the inner hallow diameter is around 12 nm. The closest structure to nanotubules in nanotechnology is the carbon nanotube. Carbon nanotubes can display a striking similarity in size and morphology to microtubule biometric properties. This resemblance suggests that tubulin and microtubules could possibly serve as units for optoelectronic and quantum information devices in cells such as axons and dendrites of the neurons [15, 16]. Microtubules have a distinct polarity with (−) and (+) ends. The end with exposed beta-tubulin is (+) and the end with exposed alpha-tubulin in (−). Microtubule Assembly (Fig. 7.9): Each tubulin molecule contains four tryptophan molecules and when they form a dimer (alpha- and beta-tubulin) as the result they carry eight molecules of tubulin [17] (Fig. 7.10). Microtubule Cargo Transport (Fig. 7.11): The potential energy transfer in microtubules is mediated by aromatic amino acids and tryptophan specifically, which behave as an optical metamaterial and may serve as a template for bioinspired technologies [14]. Microtubule organizing centers like centrosomes are where the microtubules emerge for cell division process, which separates the DNA for the formation of daughter cells during mitosis. Summary of the main functions of microtubules are: • • • • • • •

Formation of cytoskeleton for the cell Cell division Cargo transport Cellular motility Electron transfer Biophoton transfer Phonon transfer

Microtubules

131

Fig. 7.9  The assembly of microtubules starts with dimerization of alpha-tubulin molecule with a beta-tubulin molecule. The dimers then attach together to form a filament called protofilament. These filaments attach together side by side to form microtubule sheets. When 13 filaments attach together, they form a hollow tube which is called a microtubule. There is always a positive end which is the beta-tubulin end and the negative end which is the alpha-tubulin molecules. Most of the growth happens at the positive end

Functional Architecture of Microtubules in Neurons Microtubules are essential structures for functioning neurons. There are differences in microtubule organization and their microtubule-associated proteins in axons and dendrites of the neurons. These differences have been identified in acetylation and their mechanisms of organization that regulate motor activity and cargo delivery. A neuron’s morphology and function depend on the underlying microtubule cytoskeleton. Another essential function of the microtubules which sustains neural function is the transport of RNAs, mitochondria, and other vesicles, proteins, and other organelles [18].

132

7  The Quantum Biology of Consciousness and Visual Perception

Fig. 7.10  Tubulin molecules alpha and beta contain four tryptophan residues. The dimer of an alpha-tubulin and beta-tubulin contains 8 tryptophan residues which participate in electron transfer and biophoton production in microtubules

Fig. 7.11  Microtubules play as a highway for transport of different cargo across the cell cytosol. The transport of mitochondria along the microtubules is by the transport proteins dynein and kinesin, each in different directions. Dynein direction of movement is towards the negative end of the microtubule and kinesin direction of the movement is toward the positive end of the microtubule

Microtubules

133

Quantum Biology of Microtubules At first, it was believed that biological systems are far too “warm and wet” to support quantum phenomena mainly due to thermal effects disrupting quantum coherence. Later studies proved that thermal energy may assist, rather than disrupt, quantum coherence transport. This can happen in the dry hydrophobic interiors of biomolecules. We discussed the arrangements of chromophores for coherent energy transfer in photosynthetic complexes in previous chapters. The tubulin subunits of microtubules contain tryptophan molecules with geometry and dipolar properties of their aromatic chains. These are similar to those found in photosynthesis units indicating that tubulin can support coherent energy transfer. The role of quantum biology in utilizing photon energy, as was discussed in previous chapters, refers to the biological networks of photoactive antenna molecules such as chlorophyl, FAD, and tryptophan, which are able to absorb sunlight and transport the excited states to specific molecule aggregates. The coherent wave behavior which is the property of quantum mechanics is responsible for the high efficiency of these processes due to superabsorption and supertransfer of excited states by these molecules. These light-harvesting molecules delocalize the excited state of the other photoactive molecules, which can be in toward an external molecule, or between different parts of the same system. The velocity of photoexcitation spreading is enhanced by the supertransfer effect between nearest-neighbor coupling between tryptophan molecules in the microtubules [19].

Microtubules Energy Transfer The tryptophan residues spatial distribution and orientation in tubulin molecule (4 tryptophan per tubulin) is about 11.4 and 41.6 Å. Which is comparable to the distances between chromophores in cryptophyte marine algae. This has been shown to support quantum-coherent transfer of electronic excitation [20]. The excited energy travels from one tryptophan molecule to the next, covering the length of the tubulin dimer. The interdimer spacing of tryptophan is uninterrupted which efficiently transfers the energy along the stack of tubulin dimers called protofilaments. The protofilaments form a hollow tube, which is the microtubule. The energy transfers along the protofilament length via a combination of coherent tunnelling and incoherent relaxation/excitation. The unique cylindrical lattice symmetries in tubulin lattices of microtubules can effectively serve to enhance transfer rates and distances, and potentially enable

134

7  The Quantum Biology of Consciousness and Visual Perception

Fig. 7.12  Schematic presentation of microtubules in the neuronal axon and dendrites. These microtubules are connected with microtubule-associated proteins (MAP). The MAP has a major role in the stabilization, orientation, and function of microtubules

energy transfer along helical arrangement of tubulin and its chromophores in microtubules pathways [21]. A closely packed group of molecules interacting under certain symmetry can collectively donate an excitation state with a rate much faster than each individual molecule. This will result in the excitation becoming highly delocalized, leading to a large dipole moment associated with the entire group. The resulting enhanced oscillator strength can lead to “Supertransfer” of excitation energy transfer [22] (Fig. 7.12).

Microtubules, Mitochondria ROS and Biophotons Interactions There is a close relationship and functional interaction between the generated biophotons and microtubules. It seems like interaction of biophotons generated by mitochondria in the neuron, causes transitions/fluctuations of microtubules between coherent and incoherent states [23]. The generated biophotons in the neuron cells, and their profound effect on microtubules, is partly due to their alteration in the microtubule orientation. The majority of generated biophotons have a wavelength of around 280 nm, which happens to be the peak absorption wavelength of tryptophan. Radical pairs also play a role in microtubule reorganization [24]. There is a delicate balance and correlation between the generation of radical oxygen species and generation of biophotons with normal brain function, since decrease or increase production of biophotons is associated with neural pathology [25].

Microtubules

135

Another interesting information is that the index of refraction of mitochondria and microtubules are much higher than the surrounding tissues which can act like optical waveguide or fiberoptic to transfer information [26] (Fig. 7.13). The role of Phonons in microtubules: The elastic vibrations of the tubulins around their equilibrium position within the microtubules are called phonons. The velocity of vibrational modes of microtubules are between 200 and 600 m/s as was mentioned above, the tubulins are made of dimers of tubulin alpha with a negative charge and tubulin beta with a positive charge with dipolar water molecules in the hollow space. Each monomer profilaments contains alpha and beta wells and their vibrations generate electric fields along the profilaments. By quantum tunnelling phenomenon, an electron may go from one well to another, thus depends on the situation of the mobile electron, the tubulin dimer can have the two basic states [27]. The quantum field theory of microtubules are fully discussed in the literature and can be reviewed at [28].

Fig. 7.13  Microtubules play as a highway for transport of different cargo across the cell cytosol. The transport of mitochondria along the microtubules are by the transport proteins dynein and kinesin. Photons generated in mitochondrion are absorbed by FAD (Flavin adenine dinucleotide) and tryptophan. The absorption causes the excitation from ground state S0 to excited state S1. Non-radiative intersystem crossing causes conversion from S1 to excited triplet state T1. Radical pair is formed between the flavin of FAD, tryptophan singlet, and triplet states. Relaxation at different stages causes the release of photons as fluorescence or phosphorescence. The generated photons are then transported via microtubules in the neuron axon

136

7  The Quantum Biology of Consciousness and Visual Perception

Conditions Associated with Microtubule Abnormalities Abnormalities in microtubules have been associated with many neurological conditions, such as: • • • • • • •

Cognitions abnormality Memory problems Intellectual impairment Autism Alzheimer’s Parkinson’s Huntington’s chorea

Microtubule-Binding Core of the Tau Protein: Tubulin Associated Unit (Tau): The group of six highly soluble protein isoforms that are primarily in charge of maintaining the stability of microtubules in axons of the neurons of central nervous system [29]. The other functions of tau proteins are: • • • • •

Regulation of long-term memory Cellular signaling Neuronal development Neuroprotection Apoptosis

Alteration in microtubule-associated protein (MAP) that is the key protein in stabilizing microtubule architecture that regulates neuron morphology and synaptic strength, is associated with neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s, and dementia. The production of reactive oxygen species (ROS) by mitochondria results in the ultraweak photon emission (UPE) or biophotons within the cell. These biophotons gets absorbed by aromatic amino acids such as tryptophan in the microtubules of the neurons. Functional microtubule networks utilize and traffic these ROS-generated endogenous biophoton energy for cellular signaling or channeling out or dissipation, and as the result protecting the cell from ROS toxic effects (Rahnama2011). Targeting microtubules and microtubule-associated proteins (MAPs) is the focus of many efforts to produce therapeutic intervention agents and drugs to treat neurodegenerative diseases. This includes factors such as microtubule modifying enzymes which modulate tubulin post-transitional modifications (PTM) that modulate microtubule stability or targeting tubulin PTMs, such as tubulin acetylation [30]. Due to the fact that microtubules are essential for both cellular mitosis and meiosis, tubulin has become a major target of chemotherapy drugs. The role of microtubules in neural function and cognitive process in the brain is well established.

Biophoton or Ultraweak Photon Emission (UPE)

137

The cognitive impairment in patients receiving chemotherapy (Chemo brain) have been related to damage to tubulin within microtubules [31].

Biophoton or Ultraweak Photon Emission (UPE) A very good review article on the subject of biophotons is by Wijk et al. [32]. There is a continuous release of photons in all living life forms tissues, such as plants and animals, involving radical oxygen species (ROS) and are called biophotons, or ultraweak photon emission (UPE). The process of biophoton emission is due to the generation of excited ROS (Singlet excited oxygen) from the mitochondria, and its return to its ground state (triplet oxygen). These biophotons are ranging from ultraviolet and visible light (100–800 nm) to infrared (800–1270 nm). These biophotons are absorbed by different chromophores and molecules, for example, flavins, collagen, NADH, and tryptophan, and emit different wavelengths accordingly. Tryptophan has an essential role in the transport of biophotons via microtubules. This generation of background biophotons is via aerobic metabolism in mitochondria. Glutamate is the most abundant excitatory neurotransmitter in the nervous system that can produce neural activities such as long-term potentiation, can also generate glutamate-induced biophoton activities. The glutamate-induced biophotons play a role in biophotonic transmission in neural cells and neural circuits [33]. The relation between the level of intelligence (problem solving and analytical properties) in different species have been shown by measuring the glutamate-­ induced biophotonic activities and transmission in the brain. There was a presence of increased spectral redshift from animals (bullfrog, mouse, chicken, pigs, and monkeys) to humans, which can explain the higher level of intelligence in humans [15, 16]. While a physiological level of mitochondrial ROS and normal biophoton release correlates with normal neural and brain function, increased or decreased biophoton production is associated with neural pathology. It is suggested that increased biophoton can alter the orientation of the microtubules. There is a significant release of biophotons that occurs at 280 nm, which corresponds to the peak absorption wavelength of tryptophan. Increased mitochondrial activity and biophoton release result in abnormal tryptophan metabolism and excess production of neurotoxic kynurenines, which in turn, damage microtubules [31]. Transsynaptic transfer of biophotons in mouse hippocampal slices opens the perspective for clarifying the information transmission and processing mechanism of the brain. The conventional chemical synaptic exchange of information from action potential at synaptic terminal and release of neurotransmitters to be detected by the receptors to transfer the information is too slow. For fast and simultaneous interaction between multiple neurons involved in complex brain tasks, that is why there is a need for a fast relay of information via biophotons. Even the ionic action

138

7  The Quantum Biology of Consciousness and Visual Perception

potential firing is too slow for fast processing tasks in the brain. filaments and nanotubules in neurons can fire a thousand times faster via their electromagnetic and vibrational transfer properties [34]. This non-delayed propagation of information in neural circuits becomes possible also via biophotons through quantum effects of entanglement, coherence, and superposition [35] (Fig. 7.14). The photons emitted from singlet oxygen in neurons are infrared and have a wavelength of [15, 16] nm. It is very close to the wavelength of infrared being used in fiberoptics for higher speed, longer distance multimode applications, for instance, LED with a wavelength of 1300 nm. The myelin coating of the nerve fibers not only act as an insulator that increases the signaling speed, but also its axon’s index of refraction profile plays an essential role in transmitting light as a waveguide. This process of optical waveguide behavior also happens in the presence of both axon and myelin with bends, myelin sheet variation of thickness, and the node of Ranvier [36]. Opsin molecules are well known for their ability to detect light in skin, retina, and the brain of mammals. The existence of opsin in deep brain suggests that they possibly serve as biophoton detectors and also suppress thermogenesis in the tissue. The photo detection response which causes opsin-mediated suppression of thermogenesis, could lead to more production of ATP by mitochondria, which results in more biophoton production. Thus, it could constitute a relay across the neuron in the photonic backpropagation channel. Mitochondria always balances ATP production versus thermogenesis [37].

Fig. 7.14  General overview of biophoton production by mitochondria. Step one is the generation of ATP and singlet-excited oxygen by mitochondrion. Step two is the electron transfer by tryptophan. Step three is radical pair formation. Step four is biophoton generation

The Müller Cells

139

The Müller Cells Müller cells are the support cells (glial cells) for the retinal neurons. They are the only retinal glial cells that share a common lineage with retinal neurons. While their cell bodies are located in the inner nuclear layer of the retina, they span across the entire retinal thickness, from the inner limiting membrane to the outer limiting membrane. The Müller cells exhibit radial morphology and cover the entire retina parallel to the photoreceptors. There are three main types of glial cells that maintain homeostasis in the retina: microglia, astrocytes, and Müller cells. Optical waveguide in the neurons via a quantum property of light has also been identified in Müller cells, the glial supportive cells in the retina that has the same origin lineage as neurons and has been shown that have a significant role in the perception of sharp images in the brain. We will discuss how the Müller cells as their participation in quantum visual perception have become more evident in its initiation of the process of information transport to the brain (Fig. 7.15). The main role of the Müller cells is to maintain the structural and functional stability of retinal cells, which includes [38]: • • • • • • • • •

Uptake of neurotransmitters. Removal of debris by phagocytosis. Regulation of K+ levels. Storage of glycogen. Electrical insulation. Mechanical support of retina Photon transport through the retinal thickness. Cell-mediated neuroprotection and neuron regeneration via progenitors. Blue light perception.

Fig. 7.15  Schematic description of the cellular structure of the retina and RPE and their correlation to the Bruch’s Membrane and Choroid. RPE size is exaggerated in the schematic illustration

140

7  The Quantum Biology of Consciousness and Visual Perception

There is a special focus on Müller cells in recent years, due to its multiple roles in vision as a whole and many essential functions that it carries. The complex cellular morphology of Müller cells makes it possible that they contact with many other cells such as photoreceptors, neurons, synaptic spaces, and blood vessels. Müller cells can respond to retinal damage by differentiation and proliferation and produce neuron progenitor cells that migrate to the injured retinal regions and differentiate into lost neuronal types, and eventually repair the damaged retina [39]. They also share many features with astroglia located throughout the brain including maintenance of homeostasis, modulation of neurotransmitters, and response to injury [40]. The use of zebrafish has become a valuable model for studying retinal cellular reprograming and regeneration due to its spontaneous reprograming of its Müller cells [41]. Unlike in mammals, that after injury, the retina enters the state of gliosis (scar formation) which damages the vision processing, Zebrafish reprogram its Müller cells to divide asymmetrically to maintain the glia and to produce a neural progenitor cell (NPC). This will continue to proliferate to produce a cluster of multipotent progenitors that differentiates into all retinal cell types, with a bias toward the cells lost to damage [42].

Retinal Müller Cells as Living Optical Fibers In order to understand the role of the Müller cells one should understand the structure of the retina. The retina is an upside-down structure. That is the photo sensors are located in the back and all the cellular structures and glial tissue are in front, as light approaches the retina (Fig. 7.15). In order for a photon to reach the photosensor discs of photoreceptors, they have to pass through many retinal layers such as internal limiting membrane, nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer, and outer limiting membrane. The Müller cell is participating by many mechanisms to prevent light scattering and distortion, in transferring light through the inverted retina [43]. • The Müller cells extend the entire thickness of the retina and bypass the retinal layers. • Higher index of refraction compared to surrounding tissues. • Cylindrical form as a light wave guide. • Bypass the light from scattering by nerve fiber layer and both plexiform layers. • Rare mitochondria in their cytoplasm decrease light scattering. • The existence of intermediate filaments along its axis. • The end feet projection of the müller cells cover the entire inner retinal surface, with low index of refraction permits light transfer from vitreous to the Müller cells as light collector.

The Müller Cells

141

• Parallel coupling with one cone for sharp daytime vision(photopic) preserve initial image resolution by guiding the light directly to their respective cone, minimizing image distortion. • Improve image contrast by increasing signal-to-noise ratio. • Work as an optical system on the inverted retina. Recent studies have confirmed the photosensitivity of the Müller cells and intrinsically respond to blue light. They also confirmed the interaction with all the neural elements within the retina. In addition, Müller cells express non-visual opsins and photoisomerases [44].

 üller Cell Intermediate Filaments (IFs) and Quantum M Mechanism of Light Energy Transfer in the Retina Intermediate filaments are components of cytoskeletal structure of vertebrate cells. They are composed of a family of proteins with an average diameter of 10 nm. Most are cytoplasmic except type V that is nuclear. The type lll intermediate protein called Vimentin functions against mechanical and other forms of stress. Mutated vimentin induces upregulation of Heat Shock Protein 70 (Hsp70) and leads to extensive cytoplasmic aggregation of proteasomes that causes posterior age-dependent cataract [45]. The quantum mechanism of light energy transfer from inner limiting membrane to the photoreceptors is proposed to be via the intermediate filaments of the Müller cells. This mechanism involves electronic excitation energy transfer in excited intermediate filaments by photons as the donor to the visual pigments in the photoreceptor cells as energy acceptor. It was shown that intermediate filaments with a diameter of 10 nm demonstrate properties of light energy guide, where excitation propagates along the filaments from Müller cell end feet area to photoreceptor area. The transfer is via contact exchange quantum mechanism. The estimated energy transfer efficiencies in such systems may exceed 80–90%. This quantum mechanism of light energy transfer in the inverted retina explains the high image contrast achieved in photopic conditions (daytime vision) [46]. Another study proposed two different modes of energy transfer by Müller cells. The high contrast and visual resolution in the daylight are provided by the quantum mechanism of energy transfer by intermediate filaments in the form of an excited state, whereas the retinal sensitivity of the night vision is provided by the classical mechanism of photon transmission by the Müller cell light guide [47].

142

7  The Quantum Biology of Consciousness and Visual Perception

Tryptophan Tryptophan is one of the 20 standard essential amino acids. It cannot be synthesized by primates and is produced by diet. It contains an alpha-amino group (R-NH2) an alpha-carboxylic acid group (R-COOH) and a side chain Indole (C8H7N). Tryptophan biosynthesis proceeds from chorismite, the common precursor of several aromatic metabolites in many single-cell organisms and plants. It is under the category of aromatic amino acids with tyrosine and phenylalanine. They carry an aromatic ring which is formed by ring shape carbon atoms, for example, like benzene molecule with 6 carbon cycle with hydrogen attached to each carbon. Tryptophan is synthesized in the chloroplast under correlated genes ASA1 and ASA2. Tryptophan is used to produce many indole-containing substances in plants, but animals cannot produce tryptophan and their intake is through diet [48] (Fig. 7.16). Tryptophan not only has a fundamental role in light absorption and electron transfer and biophoton absorption, production, and transport, but it is the precursor of many important metabolic products with direct effects on the central nervus system and other organs. The tryptophan function as a biochemical precursor can have a positive or negative effect depending on the pathway and the end product (Fig. 7.17). The following compounds are listed below: 1. Serotonin (Neurotransmitter) 2. Melatonin (Neurohormone) 3. Kynurenine (Catabolic metabolites) 4. Niacin (Vitamin B3) There are different pathways of tryptophan metabolism:

Fig. 7.16  Structural representation of Tryptophan molecule which is composed of an amino group (blue), a carboxylic group (orange), and a side chain of indole (green)

Tryptophan

143

Fig. 7.17  Tryptophan has a fundamental role in light absorption, electron transfer, biophoton absorption, production, and transport. It is also the precursor of many important metabolic products with a direct effect on the central nervous system and other organs

144

7  The Quantum Biology of Consciousness and Visual Perception

• Serotonin pathway: Serotonin is synthesized by the enzyme Tryptophan hydroxylase. Serotonin also synthesizes Melatonin via N-acetyltransferase and 5-hydroxyindole-O-methyltransferase enzymes. • Kynurenine pathway: Kynurenine is synthesized by enzymes Indoleamine2,3-­ dioxygenase (IDO) in the immune system and the brain, and by tryptophan 2,3-dioxygenase (TDO) in the liver. • Indole pathway: Indole is synthesized from tryptophan by the gastrointestinal microbiota in humans. The end product can vary due to bacteria involved. • The 3-indole propionic acid (IPA) is a highly potent neuroprotective antioxidant. Also, Indole-3-aldehyde (13A) increases the inflammatory responses (Fig. 7.18). The exposure of tryptophan to ultraviolet light (UV) will result in its metabolism along the kynurenine pathway. These metabolites are major ultraviolet-­ photooxidation products of tryptophan and oxygen has a key role in this process. The ultraviolet light stimulates the generation of superoxide anion and hydrogen peroxide. The process of UV exposure, generation of oxygen reactive species (ROS), and production of tryptophan toxic products have many consequences in humans, including [31]: • Skin damage due to sun exposure. • Damage to the lens of the eye due to modifying lens proteins and cataract formation. • Release of cytokines, interferon-gamma, and tumor necrosis factor (TNF-alpha) in the brain results in greater release of biophotons from mitochondria and as a result, many neurological disorders. • Toxicity to neurons can cause axonal degeneration and cell death. • Phosphorylation of microtubule-associated proteins (MAPs) causes disassembly of microtubules and development of many neurological diseases, including, Parkinson’s disease, Huntington’s chorea, amyotrophic lateral sclerosis (ALS), Alzheimer’s, dementia, multiple sclerosis (MS), AID’s dementia, Schizophrenia, and cognitive decline of aging. Tryptophan Role in Light Energy Harvesting and Electron Transfer. “All brain ‘quantum Biology’ lead to Tryptophan” In previous chapters, we discussed the essential role of tryptophan in quantum biology, from photosynthesis to magnetoreception and circadian rhythms, due to its specific molecular structure as light harvesting and ability to transfer electrons in microtubules. Sun energy as photons was the key to the origin of life on earth. The earliest life forms such as “cyanobacteria” captured the photons from sunlight to generate energy through photosynthesis. This was done by converting the photon energy to biological energy by tryptophan amino acid and the subsequent production of oxygen as a waste product, which eventually changed the earth’s atmosphere, and as a result, changed the living organisms. Early life on earth evolved in accordance with the earth’s rotation and as a result the circadian rhythm is tied to the sensitivity to sunlight patterns. Light absorption

Tryptophan

145

Fig. 7.18  Tryptophan metabolic pathways with the production of essential molecules with different functions. Serotonin pathway synthesizes serotonin by the enzyme tryptophan hydroxylase. Serotonin also synthesizes melatonin via N-acetyltransferase and 5-HydroxyindoleO-­ methyltransferase enzymes. Kynurenine pathway synthesizes serotonin to kynurenine by enzymes indoleamine2,3-dioxygenase (IDO) in the immune system and the brain, and by tryptophan 2,3-dioxygenase (TDO) in the liver. Indole pathway synthesizes tryptophan by the gastrointestinal microbiota in humans. The end product can vary due to bacteria involved. The 3-indole propionic acid (IPA) is a highly potent neuroprotective antioxidant. Also, Indole-3aldehyde (13A) increases inflammatory responses

of tryptophan is the property of its indole ring, which was carried through the evolution of all branches of plants and animals. Combining tryptophan with molecular oxygen and production of serotonin probably first started in photosynthetic single organisms such as blue algae. Tryptophan and its product serotonin play an essential role in the physiology of plants, animals, and humans (mood, sleep, cognition). It is very interesting to note that all photon-sensing molecules throughout evolution

146

7  The Quantum Biology of Consciousness and Visual Perception

utilize the aromatic amino acid tryptophan, residing at the center of their light-­ harvesting active sites. The unique capacity of electron transfer during photosynthesis due to tryptophan aromaticity in the earlier life forms was evolved in more complex functions, in the more complex organisms, and was carried out to allow the generation of the building blocks of neuronal energy transfer to fabricate “complex systems” in higher life forms. This proposed concept defines the role of tryptophan in the emergence of life and conciseness [49].

Properties of Consciousness A Dual utilization of classic physics and quantum physics by brain cells after millions of years of evolution. Understanding the biological basis of consciousness has been very challenging and has been investigated for many years via multiple fields of science including neuroscience, medicine, phycology, quantum physics, philosophy, and artificial intelligence. It seems that nature has learned to utilize all available tools in order to climb the ladder of evolution and harness the classic and quantum physics properties.

Quantum Phenomena In quantum biology, the quantum effects of coherence-decoherence, superposition, tunnelling, and entanglement play an important role. Before we get to quantum brain, we briefly refresh the basic concepts of quantum physics.

Quantum Coherence Quantum coherence is based on the idea that all objects have wave-like properties. It is the physical condition of two or more particles or systems being in the same quantum state or phase, for example, the state of photons is coherent in a laser beam. Quantum coherence refers to the ability of a quantum state to maintain its entanglement and superposition in the face of other interactions and the effects of thermalization. To maintain coherence, one should overcome noise, leakage, and decay channels that constitutes the main source of decoherence. Coherence and entanglement are two landmark features of quantum physics and are considered to be “operationally equivalent.” Decoherence is when the quantum states become out of phase.

Quantum Phenomena

147

Quantum Superposition The superpositioning concept allows a physical system to exist in two or more quantum states, until a measurement is made on it. The non-intuitive phenomenon prompted Erwin Schrödinger his famous “cat in the box” thought experiment. This allows the theoretical construction of a system built on qubits, which can have an array of values, either 1, or 0, or an indeterminate value.

Quantum Tunnelling Quantum tunnelling is the ability of a particle to pass through an energy barrier, lacking the energy required to overcome the barrier by classical physics. This phenomenon has been used in many technologies such as scanning tunnelling microscopy and flash memories.

Quantum Entanglement Quantum entanglement is a phenomenon that occurs when two particles are generated, interact, or share spatial proximity in a way that quantum state of each particle cannot be described independently of the state of the other, including when they are separated. Measurement of physical properties of particles such as position, momentum, spin, and polarization can be found to be perfectly correlated. For example, if a pair of entangled particles is generated such as their total spin of zero, and one particle has a clockwise spin on the first axis, the second particle will have a counter clock spin on the same axis. Entanglement is a primary feature of quantum mechanics and does not present in classical mechanics.

Magnetic Field Effect and Entanglement Magnetic field effect and its effect on initiated singlet states entangled oxygen has been shown to affect neurogenesis on adult hippocampus. It is interesting to note that triplet oxygen is not entangled, while the singlet state is entangled. This emphasizes the important role of entanglement in biology. As we discussed before the singlet oxygen generates biophotons which serve as quantum messengers to establish long-distance connections via microtubules [10].

148

7  The Quantum Biology of Consciousness and Visual Perception

All different states of human conscious, from conscious and subconscious states, sleep and awake states to coma and vegetative states or under anesthesia or influence of psychogenic drugs, have been studied in order to decipher the properties of human consciousness. With all the progress that have been made in the field of consciousness, there are still not complete explanation or universally agreed on theory exist as of today. Here, we discuss the present theories on human conscious state and its major component, the visual conscious state. The common list of the brain’s cognitive functions is summarized as follows: • • • • •

Generation of subjective experience. Memory formation, long term, and short term. Learning process. Computational properties. Cognition and Consciousness.

Due to the fact that visual input contains the majority of influx of information to the brain, two-third of the brain and 30% of cortical gray matter involved in visual information processing, many of the research is done using the visual system as a base to study human consciousness (Figure 7.19). The recent understanding of the role of quantum physics in biology, for example, in photosynthesis, magnetoreception, and circadian rhythms, opened the door to investigate other biological events. Another field that is becoming the center of attention is to convey the quantum process of energy transfer in the brain, which

Fig. 7.19  Schematic representation of an overall view of consciousness as the function of neurons in the brain. A complex interaction between the subatomic (electrons and photons), atomic (oxygen), and molecules (tryptophan). Many important players are involved and have important roles in this process, such as mitochondrion generating ATP and excited singlet oxygen, forming radical pairs, and electron transfer by tryptophan, to produce biophotons in microtubules

Quantum Phenomena

149

seems to have an essential role in many brain functions including neurogenesis and consciousness. So far, we have reviewed all the ingredients necessary for understanding the process of consciousness, yet it is not that easy. There are still many controversial theories regarding the cognitive properties of the brain. We try to summarize what is known today, and yet, there will be many more additions to explain such a complex phenomenon.

Altered States of Consciousness One way to understand consciousness is to see how it can be affected and manipulated by other small molecules and anesthetics. This includes understanding the effect of antidepressants and psychogenic chemicals as they induce altered states of consciousness. There are many levels in brain function, from a network of neurons to the molecular and atomic particles involved in neurons, and with the utilization of classic physics and quantum physics that combined together making the process of a complex mind. Even though many of the chemicals work on the synaptic neurotransmitters and many mental illnesses are associated with abnormality in neurotransmitters, it could not explain the complex functions of the brain. Many years of studies on the brain and its properties have narrowed its mechanism of function down to the essential work of microtubules inside the neurons. There are many new theories that explain the involvement of microtubules on brain function Hameroff [50]. According to these theories, the conductive resonances in microtubules, originate in terahertz quantum dipole oscillations, and optical interactions among pi electron resonance clouds of aromatic amino acid rings of tryptophan (also tyrosine and phenylalanine), initiate within each tubulin. The frequency starts in dendritic and somatic microtubules as gigahertz and megahertz and then it transfers to the distal axonal branches and synaptic spaces. In summary, the cognition in the brain originates in microtubules inside neurons. Vibrational Effect The classic theory of olfaction (the sense of smell) was based on the action of neurotransmitters as lock and key by the receptors at the synaptic spaces. The studies with different isotopes disqualified this theory, as using the isotopes had different effects due to their mass and spin difference without changing the shape of the isotope. Alternative theory suggests that olfaction may use principles of vibration-assisted quantum tunnelling. This theory is now has been applied to the action of other

150

7  The Quantum Biology of Consciousness and Visual Perception

neurotransmitters as well. Vibration-assisted tunnelling is when the energy of one molecule’s movement matches the energy necessary for an electron to tunnel through a potential barrier. This means the vibration of a particular neurotransmitter would be recognized by its specific receptor. Neurons are unique as they are non-dividing cells, therefore, their microtubules are not required to repeatedly disassemble and assemble to form mitotic spindles, which causes the neuron to stay in a stable state. This stability is crucial for neuron function as it maintains neuron morphology and prevents cell division. Many pharmaceutical products are based on their function on microtubules, as anesthetic agents are weak destabilizers of microtubules, and antimetabolite medications prevent microtubule polymerization. The Three-Wave Processing On a larger scale, the cellular layers of gray matter of the brain and their bidirectional functions are involved in sorting and transferring the neural signals. This would initiate the three steps or “waves” toward the processing of the information throughout the entire brain. It starts with the sensory inputs carrying impulses from all senses, for example, the retina (the main source) to lateral geniculate nucleus in the thalamus (wave1), then the impulses are relayed to visual cortex via optic radiation (wave2) and then the impulses will feedback through associative cortex in the frontal lobe (wave3) which initiates a global broadcast from frontal and pre-frontal cortex to all regions of the brain. In the gray matter, the input activity also conveys in 3 waves. Input arrives in layer IV (wave1), then to layers l, ll, lll, and Vl (wave2) and finally to layer V the giant pyramidal neurons (wave 3). The most likely site for the perception-action in psychology is layer V cortical pyramid neurons (Fig. 7.20). Anesthetic Action and Quantum Consciousness Anesthetic agents block the consciousness selectively, sparing nonconscious brain activities, and thus their specific action could unravel how the brain generates consciousness. One example is xenon gas that used to be used for general anesthesia. Xenon is an element with the symbol Xe and atomic number 54 and has many isotopes. The isotope of anesthetic xenon (129Xe) with the quantum property of nuclear spin ½ has a very different effect than their isotopes without the spin. ½ spin is optimal for entanglement since it has the longest coherence time. As we discussed before, the spin is a particular property of quantum physics and is related to angular momentum with a magnetic moment at discrete, quantized levels. Atoms with imbalance of protons and neutrons can have nuclear spin. It seems extraordinary, that changing something as small as the spin of a nucleus

Quantum Phenomena

151

Fig. 7.20  Schematic presentation of cellular layers of gray matter of the brain and their bidirectional functions. In the gray matter, the input activity also conveys in three waves. Input arrives in layer IV (wave1), then to layers I, II, III, and VI (wave2) and finally to layer V the giant pyramidal neurons (wave 3). The arrows represent the movement of signals between different layers

might result in a macroscopic change on the level of something as complex as consciousness [51]. These spin states can entangle by being intimately connected with other spin states. This implies that the consciousness involves quantum brain processes which supports the theory of quantum consciousness. The complexity of consciousness involves entanglement, coherence, and quantum computing via microtubules, in the brain that binds and integrates multiple sources of information from multiple regions of the brain into a unified conscious moment. In addition to nuclear spin entanglement, Quantum dipole oscillations among Pi electrons resonance clouds in the membrane proteins or cytoskeletal proteins have been implicated to be involved in the process of consciousness. Perhaps the rotational force of nuclear spin magnetic moments tunes quantum electromechanical activity in neuron membrane and/or microtubule proteins to increase their vibrational frequency, the opposite of anesthetic damping, and thus promote consciousness. Rather than a computer, the brain may be more like an orchestra; rather than a computational output, consciousness may be more like a music. Microtubules and “Orch OR” “Orch OR” is the most complete, and most easily falsifiable theory of consciousness [50].

152

7  The Quantum Biology of Consciousness and Visual Perception

In 1996, Penrose and Hameroff proposed microtubules orchestrated quantum superpositions, encoding inputs, and memory as entangled qubits of collective quantum dipole oscillations, which then compute and terminate by collapse of quantum wavefunction due to an (“objective reduction,” “OR”) in the fine-scale structure of the universe. This is referred to as Orchestrated Objective Reduction or “Orch OR” theory. Roger Penrose shared the Nobel prize in physics in 2020 for his work on black holes and Stuart Hameroff is an anesthesiologist and professor at the university of Arizona and is known for his studies on theories of consciousness. The summary of the concepts is as follows: 1. Photosynthesis proteins utilize superpositioned “Pi resonance” electrons. 2. Quantum electron states resonate in microtubules at terahertz, gigahertz, megahertz, and 10-kilohertz frequencies. 3. Anesthetics may selectively erase consciousness by quantum interactions inside microtubules. Computer modeling shows collective terahertz oscillations among tubulin’s 86 “Pi electron” resonance rings are specifically dampened by anesthetics Hameroff [52]. The “Orch OR” qubit inside tubulin “Pi electron” resonance forms quantum-­ friendly regions which extend to neighboring tubulins along helical lattice pathways to support collective “giant dipole oscillation” qubits [53].

The Quantum Brain Quantum Effects in the Brain Biological systems, such as brain, operate at physiological temperatures and is in direct contact with their environments. There are multiple tasks being performed instantaneously that require multiple modes of communication between the neurons of the brain. Different tasks require different modes with different speeds. Here the dual role of classic physics and quantum physics are being utilized hand in hand, through millions of years of evolution, which can provide a wide range of possibilities for the neurons to communicate. A variety of experimental techniques benign used to investigate the relationship between brain activity and the state of perceptual consciousness. The most common techniques are electroencephalography (EEG), magnetoencephalography (MEG), and functional magnetic resonance imaging (fMRI). The slower neuronal transmissions are the property of classical physics, this process is composed of a signal being received via dendrites be transferred through the axon to the next neuron via the synaptic cleft by neurotransmitters. The effect of neurotransmitters that binds to the receptors causing the openning of the ion channels and altering the next neurons action potential, passing along the signal.

Quantum Phenomena

153

The faster communications, that is, required for complex tasks, such as consciousness, requires high-speed communications. This was described by the generation of biophotons and involvement of microtubules which is a property of quantum physics and is 1000 times faster than classical neural ionic and chemical conduction. This system also exempts neurons from quantum effect of the surrounding environment, as standard quantum systems require isolation from quantum destructive forces of environment and near zero temperatures. Nuclear Spin and the Brain The Posner Molecule The possibility of quantum processing with nuclear spins has been suggested to operate in the brain information processing function. Phosphorus is identified as the unique biological element with a nuclear spin that can serve as qubit, whereas phosphate ion is the qubit transporter. “Posner molecule” is presented as the unique molecule that can protect the neural qubits for very a long time period and serve as a quantum memory utilizing quantum entanglement. When ATP beaks down it releases phosphates, the released pyrophosphate ion breaks down into two phosphate ions, they become quantum entangled pair of qubits. Posner molecule, formed by binding the phosphate pair with extracellular calcium ions, will inherit the nuclear spin entanglement. When two Posner molecules bind and subsequently melt, they release a shower of intracellular calcium ions that can further ignite postsynaptic firing [54].  rain Wide Web Collective Excitation of Neurons (World Wide B Web Concept) In all major areas of physics, a collective excitation has gained as much physical reality as a particle itself. The similarity of world wide web to the network of neurons in the brain represents similarities in regard to information distribution and transfer. The brainwide web extends into those neural networks where processed information is received from the senses, memories, and it unifies those regions via vast complexity of neuronal interactions with the multiple other regions in the brain [55]. Good review article is recommended, titled “From quantum chemistry to quantum biology: a path toward consciousness [56].

154

7  The Quantum Biology of Consciousness and Visual Perception

The Quantum Vision Human visual consciousness involves large-scale cortical and subcortical networks independent of task report and eye movement activity [57]. As we mentioned earlier, conscious vision is the key to unraveling the mysteries of the human consciousness. It represents the process that the information is being detected, processed, and interacts with multiple areas of the brain including the memories to achieve the sense of visual cognition. After the visual information is detected by retina, as was discussed earlier, the information will be transferred to the lateral geniculate nucleus via the optic nerve. Then to the visual cortex in the occipital lobe via optic radiation. The perceptual information for an object’s shape, color, motion, and meaning is processed at different times in different areas of the visual cortex (V1, V2, V3, and so forth). Yet somehow, the disparate contents are bound together in unified scenes. Entanglement may quite literally bind and integrate disparate brain contents into a unified conscious moment. The post-perceptual processing of the neural mechanisms of conscious perception are widely distributed across cortical and subcortical sites. These rich and complex overlapping systems can provide a satisfactory explanation for consciousness. The visual perception process to form conscious experience are summarized as follows [58]: 1. Early signal detection and activation of signal detection centers such as V1 in visual cortex. 2. Dynamic transient pulse of arousal and attention. 3. Limbic signal amplification. 4. Network switching off of the networks that interfere. 5. Wave of processing to many cortical regions to form consciousness. Manipulation of visual conscious is an ideal way to study the consciousness. This has been done by studying the difference between the consciously visible and consciously invisible perceptions. A human subject is presented with two different images to each eye at the same time, making one of them the dynamic image dominant and the other completely suppressed. This offers a controllable and reliable means to manipulate and study the subconscious and conscious perceptions, thus making it an ideal paradigm for studying consciousness [59]. As we mentioned, EEG has been used to study visual cognition. Many studies have associated the different EEG waves and their association with visual processing which is shown in the following: EEG (Electroencephalography): Noninvasive method of recording the spontaneous electrical activity of the brain by placing the electrodes along the scalp. The first human EEG was documented by German psychiatrist Hans Berger in 1924. EEG is a standard diagnosis procedure to confirm epilepsy.

The Role of Symmetry in Biology and Consciousness

155

Description of EEG waves: Delta waves: Frequency range up to 4 Hz. In adults reflects slow-wave sleep. Theta waves: Frequency range 4–7 Hz. Drowsiness or arousal and in meditation. Alpha waves: Frequency range 8–12 Hz. Relaxation or closing the eyes. Beta waves: Frequency range 13–30 Hz. Motor behavior and active thinking. Gamma waves: Frequency range 30–100 Hz. During cognitive or motor function. Mu waves: Frequency 8–13 Hz. Partly overlap other frequencies reflects resting state. Tuning alpha rhythms to shape conscious visual perception has been studied to further understanding the relationship between the waves and visual perception. The alpha wave amplitude and frequency have been linked to sampling sources and interpretation of sensory events, respectively [60]. Spontaneous alpha oscillations have been associated with various cognitive functions, including perception. Their phase and amplitude independently predict cortical excitability and subsequent perceptual performances [61].

Human Perception as a Phenomenon of Quantization Quantum mechanics has been used successfully in recent years to describe the human cognition process. The phenomenon of “Categorical perception” has been proposed to better understand the presence of the quantum structure in human cognition. According to this process, the human perception consists of two compartments. The reconciliation of a bottom-up stimulus and the cognitive expectation with a top-­ down pattern. The typical warping of categorical perception is when groups of stimuli clump together to form quanta, which move away from each other and lead to transfer the dynamic information. The individual concepts, which are these quanta, can be modeled by a quantum prototype theory by Schrödinger’s wave function. The super position of two such wave functions accounts for the interference pattern that occurs when these concepts are combined. Using a simple quantum measurement model, the human perception can be quantized [62].

The Role of Symmetry in Biology and Consciousness We cannot close this chapter without mentioning the role of symmetry and chirality in biology and consciousness. So, lets breifly review what is symmetry and biomolecular chirality and why its relevant to us. Symmetry: There are many interpretations of this fundamental entity according to the different fields of science.

156

7  The Quantum Biology of Consciousness and Visual Perception

• In Physics: It refers to “Invariance” which is lack of change under any kind of transformation. This concept has become one of the most powerful tools of theoretical physics. Apparently, all laws of nature originate in symmetry, on the other hand, the symmetries of the laws of physics determine the properties of all the particles found in nature. • In Mathematics: It occurs not only in geometry but in other branches of mathematics. In general, every kind of structure in mathematics will have its own kind of symmetry. For example, calculus, algebra, statistics, also as symmetric probability distributions. • In Chemistry: It essentially involves all specific interactions between molecules in nature. Understanding the symmetry explains fundamental observations in quantum chemistry, and in the applied areas of spectroscopy and crystallography. • In Biology: It is used mostly to describe body shapes. But the notion of symmetry is also used in physics. A remarkable property of biological evolution is the changes in symmetry corresponding to the appearance of new parts and dynamics. Chirality: This is the property of asymmetry and also is important in several branches of science. An object or system that is distinguishable from its mirror image, on the other hand it cannot be superimposed. Human hands are perhaps the most recognized example of chirality. They are non-superimposable mirror images of each other. • In Physics: It is found in particle spin, where the handedness of the object determined by the direction of the particle’s spin. • In Chemistry: Most often the cause of chirality in molecules is the presence of an asymmetric carbon atom. It has many applications in organic chemistry and stereochemistry. The question of the origin of life may be resolved assuming that non-biological and biological entities obey nature’s universal laws grounded on space-time symmetry. This symmetry governing the behavior of the elementary particles and galaxy structures, imposes its fundamental laws on all hierarchical levels of the biological world. All objects across spatial scales may be classified as chiral or achiral concerning a specific space-related symmetry transformation [63]. Chirality is the critical structural feature of natural systems, including subatomic particles and living matter. According to the Standard Model (SM) Theory and String Theory (StrT), elementary particles associated with the four fundamental forces of nature determine the existence of micro (atomic) and the macro (galaxies) scales of nature. The inheritance of molecular symmetry from the symmetry of elementary particles indicates a bidirectional causal pathway of biochirality. It is assumed that the laws of the physical world impact the biological matter’s appearance through both extremities and spatial dimensions. The chain of chirality transfer

References

157

links ribosomal protein synthesis, cell morphology, and neural signaling with the laterality of cognitive functions. The fundamental significance of biochirality at the molecular and cellular levels is grounded on the basic principle of spatial organization and function which includes brain morphology, behavior, cognition, and consciousness. The biochirality concept is closely associated with all vital events of the organism, including fertilization, asymmetric cell division, organism development, and aging [64]. The introduction of a new kind of symmetry ushered in a golden era for theoretical physics. The marriage of this theory with quantum field theory reached the highest point in the standard model of particle physics. The unification of all three nongravitation forces of the universe (strong nuclear force, weak nuclear force, and electromagnetism) was the momentous milestone in human knowledge. Inspired by this success, physicists hope for a “theory of everything” uniting the standard model with general relativity and the theory of gravity [65].

References 1. Çengel. A concise account of information as meaning ascribed to symbols and its association with conscious mind. Entropy. 2023; https://doi.org/10.3390/e25010177. 2. University. Central Nervous System. Queensland Brain Institute; 2023. https://qbi.uq.edu.au/ brain/brain-­anatomy. 3. Tartu. Morphology of nervous system. Cerebral Cortex. 2023; https://sisu.ut.ee/histology/ cerebral-­cortex. 4. Waymire. Neuroscience online. Introduct Neurons Glial Cells. 2023; https://nba.uth.tmc.edu/ neuroscience/m/s1/chapter08.html. 5. Herculano. The remarkable, yet not extraordinary, human brain as a scaled-up primate brain and its associated cost. PNAS. 2012; https://doi.org/10.1073/pnas.1201895109. 6. Andrieux. Mitochondria as a Cellular Hub in Infection and Inflammation. Int J Mol Sci. 2021; https://doi.org/10.3390/ijms222111338. 7. Mehta. Association of mitochondria with microtubules inhibits mitochondrial fission by precluding assembly of the fission protein Dnm1. J Biol Chem. 2019; https://doi.org/10.1074/ jbc.RA118.006799. 8. Kühlbrandt. Structure and function of mitochondrial membrane protein complexes. BMC Biol. 2015; https://doi.org/10.1186/s12915-­015-­0201-­x. 9. Krumova. Overview of Reactive Oxygen Species. Singlet Oxygen Appl Biosci Nanosci. 2016;1 https://doi.org/10.1039/9781782622208-­00001. 10. Rishabh. Radical pairs may explain reactive oxygen species-mediated effects of hypomagnetic field on neurogenesis. PLOS Biol. 2022; https://doi.org/10.1371/journal.pcbi.1010198. 11. Klotz. Singlet oxygen-induced signaling effects in mammalian cells. Photochem Photobiol Sci. 2003; https://doi.org/10.1039/b210750c. 12. Hackbarth. Singlet oxygen in  vivo: it is all about intensity. J Pers Med. 2022; https://doi. org/10.3390/jpm12060891. 13. Borden. Dioxygen: what makes this triplet diradical kinetically persistent? J Am Chem Soc. 2017; https://doi.org/10.1021/jacs.7b04232. 14. Zhang. Fano resonance line shapes in the Raman spectra of tubulin and microtubules reveal quantum effects. Biophys Rep. 2022; https://doi.org/10.1016/j.bpr.2021.100043. 15. Wang. Human high intelligence is involved in spectral redshift of biophotonic activities in the brain. Biol Sci. 2016a; https://doi.org/10.1073/pnas.1604855113.

158

7  The Quantum Biology of Consciousness and Visual Perception

16. Wang X. Quantum dot-like excitonic behavior in individual single walled-carbon nanotubes. Sci Rep. 2016b; https://doi.org/10.1038/srep37167. 17. Carreá. Tubulin is an inherent component of mitochondrial membranes that interacts with the voltage-dependent anion channel*. J Biol Chem. 2002; https://doi.org/10.1074/jbc. M203834200. 18. Kelliher. Microtubule control of functional architecture in neurons. Current Opinion in Neurobiology. 2019;(February 07) https://doi.org/10.1016/j.conb.2019.01.003. 19. Celardo. On the existence of superradiant excitonic states in microtubules. New J Phys. 2019; https://doi.org/10.1088/1367-­2630/aaf839. 20. Collini. Coherently wired light-harvesting in photosynthetic marine algae at ambient temperature. Nature. 2010; https://doi.org/10.1038/nature08811. 21. Craddock. The feasibility of coherent energy transfer in microtubules. J Royal Soc Interface. 2014; https://doi.org/10.1098/rsif.2014.0677. 22. Abasto. Exciton diffusion length in complex quantum systems: the effects of disorder and environmental fluctuations on symmetry-enhanced supertransfer. Royal Soc. 2012; https://doi. org/10.1098/rsta.2011.0213. 23. Rahnama. Emission of mitochondrial biophotons and their effect on electrical activity of membrane via microtubules. J Integr Neurosci. 2011;10(01):65–88. https://doi.org/10.1142/ S0219635211002622. 24. Zadeh. Radical pairs may play a role in microtubule reorganization. Sci Rep. 2022; https://doi. org/10.1038/s41598-­022-­10068-­4. 25. Wilson. Regulation of cytoskeletal dynamics by redox signaling and oxidative stress: implications for neuronal development and trafficking. Front Cell Neurosci. 2015; https://doi. org/10.3389/fncel.2015.00381. 26. Thar. Propagation of electromagnetic radiation in mitochondria? J Theoretical Biol. 2004; https://doi.org/10.1016/j.jtbi.2004.05.021. 27. Nganfo. Dynamics of exciton polaron in microtubule. Cell Press J. 2022; https://doi. org/10.1016/j.heliyon.2022.e08897. 28. Hiramatsu. Self-reduction rate of a microtubule. Int J Modern Phys. 2008; https://doi. org/10.1142/S0129183108012194. 29. Mammeri. Microtubule-binding core of the tau protein. Sci Adv. 2022; https://doi.org/10.1126/ sciadv.abo4459. 30. Sferra. Microtubule dysfunction: a common feature of neurodegenerative diseases. Int J Mol Sci. 2020; https://doi.org/10.3390/ijms21197354. 31. Sordillo. The mystery of chemotherapy brain: kynurenines, tubulin and biophoton release. Anticancer Res. 2020; https://doi.org/10.21873/anticanres.14061. 32. Wijk. Integrating ultra-weak photon emission analysis in mitochondrial research. Front Physiol. 2020; https://doi.org/10.3389/fphys.2020.00717. 33. Tang. Spatiotemporal imaging of glutamate-induced biophotonic activities and transmission in neural circuits. PLoS One. 2014; https://doi.org/10.1371/journal.pone.0085643. 34. Singh. Filaments and four ordered structures inside a neuron fire a thousand times faster than the membrane: theory and experiment. J Integr Neurosci. 2021; https://doi.org/10.31083/j. jin2004082. 35. Liu. Intracellular simulated biophoton stimulation and transsynaptic signal transmission. Appl Phys Lett. 2022; https://doi.org/10.1063/5.0128956. 36. Omidi. Simulation of nerve fiber based on anti-resonant reflecting optical waveguide. Sci Rep. 2022; https://doi.org/10.1038/s41598-­022-­23580-­4. 37. Zarkeshian. Photons guided by axons may enable backpropagation-based learning in the brain. Sci Rep. 2022; https://doi.org/10.1038/s41598-­022-­24871-­6. 38. Kobat. Importance of Müller Cells. Beyoglu Eye J. 2020; https://doi.org/10.14744/ bej.2020.28290.

References

159

39. Yang. Cellular signaling in Müller Glia: progenitor cells for regenerative and neuroprotective responses in pharmacological models of retinal degeneration. J Ophthalmol. 2019; https://doi. org/10.1155/2019/5743109. 40. Tworig. Müller Glia in Retinal Development: From Specification to Circuit Integration. Front Neural Circuits. 2022; https://doi.org/10.3389/fncir.2021.815923. 41. Lahne. Reprogramming Müller glia to regenerate retinal neurons annual review of vision science. Ann Rev Vision Sci. 2020; https://doi.org/10.1146/annurev-­vision-­121219-­081808. 42. Campbell. Retinal regeneration requires dynamic Notch signaling. Neural Regenerat Res. 2022; https://doi.org/10.4103/1673-­5374.327326. 43. Franze. Müller cells are living optical fibers in the vertebrate retina. PNAS. 2007; https://doi. org/10.1073/pnas.0611180104. 44. Marchese. Müller glial cell photosensitivity: a novel function bringing higher complexity to vertebrate retinal physiology. J Photochem Photobiol. 2023; https://doi.org/10.1016/j. jpap.2023.100162. 45. Bornheim. A dominant vimentin mutant upregulates Hsp70 and the activity of the ubiquitin-­ proteasome system, and causes posterior cataracts in transgenic mice. J Cell Sci. 2008; https:// doi.org/10.1242/jcs.030312. 46. Zueva. Quantum mechanism of light energy propagation through an avian retina. J Photochem Photobiol B: Biol. 2019; https://doi.org/10.1016/j.jphotobiol.2019.111543. 47. Khmelinskii. Spectral selectivity model for light transmission by the intermediate filaments in Müller cells. Journal of Photochemistry and Photobiology B: Biology. August. 2017; https:// doi.org/10.1016/j.jphotobiol.2017.06.001. 48. Mano. The pathway of auxin biosynthesis in plants. J Exp Botany. 2012; https://doi. org/10.1093/jxb/ers091. 49. Alachkar. Aromatic patterns: tryptophan aromaticity as a catalyst for the emergence of life and rise of consciousness. Phys Life Rev. 2022; https://doi.org/10.1016/j.plrev.2022.07.002. 50. Hameroff. Consciousness, cognition and the neuronal cytoskeleton – a new paradigm needed in neuroscience. Front Mol Neurosci. 2022; https://doi.org/10.3389/fnmol.2022.869935. 51. Li. Nuclear Spin Attenuates the Anesthetic Potency of Xenon Isotopes in Mice: Implications for the Mechanisms of Anesthesia and Consciousness. Anesthesiology. 2018; 52. Hameroff. ‘Orch OR’ is the most complete, and most easily falsifiable theory of consciousness. Cognit Neurosci. 2020; https://doi.org/10.1080/17588928.2020.1839037. 53. Fröhlich. The extraordinary dielectric properties of biological materials and the action of enzymes. PNAS. 1975;72(11):4211–5. 54. Fisher. Quantum cognition: The possibility of processing with nuclear spins in the brain. Ann Phys. 2015; https://doi.org/10.1016/j.aop.2015.08.020. 55. Lindström. Consciousness as the collective excitation of a brainwide web  – understanding consciousness from below quantum fields to above neuronal networks. J Phys Conference Series. 2018; https://doi.org/10.1088/1742-­6596/1275/1/012021. 56. Tuszynski. From quantum chemistry to quantum biology: a path toward consciousness. J Integr Neurosci. 2020; https://doi.org/10.31083/j.jin.2020.04.393. 57. Kronemer. Human visual consciousness involves large scale cortical and subcortical networks independent of task report and eye movement activity. Nature. 2022; https://doi.org/10.1038/ s41467-­022-­35117-­4. 58. Blumenfeld. Brain mechanisms of conscious awareness: detect, pulse, switch, and wave. Neuroscientist. 2021; https://doi.org/10.1177/10738584211049378. 59. Shan. Mapping the emergence of visual consciousness in the human brain via brain-wide intracranial electrophysiology. Innovation. 2022; https://doi.org/10.1016/j.xinn.2022.100243. 60. DiGregorio. Tuning alpha rhythms to shape conscious visual perception. Curr Biol. 2022; https://doi.org/10.1016/j.cub.2022.01.003. 61. Fakche. α phase-amplitude tradeoffs predict visual perception. eNeuro. 2022; https://doi. org/10.1523/ENEURO.0244-­21.2022.

160

7  The Quantum Biology of Consciousness and Visual Perception

62. Aerts. Human perception as a phenomenon of quantization. Entropy. 2022; https://doi. org/10.3390/e24091207. 63. Ocklenburg. Symmetry and asymmetry in biological structures. PNAS. 2022; https://doi. org/10.1073/pnas.2204881119. 64. Dyakin. Fundamental cause of bio-chirality: space-time symmetry—concept review. Symmetry. 2022; https://doi.org/10.3390/sym15010079. 65. Glattfelder. The Unification Power of Symmetry. Front Collect. 2019; https://doi. org/10.1007/978-­3-­030-­03633-­1_4.

Addendum

Quantum Biology Awareness Survey To understand the subjective response of random diverse population responses on quantum biology in the United States, we prepared a specific questionnaire and used a commercial survey company to collect the responses. Material and Methods We used 10 survey questionnaires that were conducted as three responses to each question (yes, No, and I don’t know) in October of 2022. There were 520 responses from 520 participants. The age of participants was categorized into four groups: • • • •

18–29 years old 30–44 years old 45–60 years old 60 years old Gender was categorized into three groups:

• Male • Female • Other US regions used for the study • • • •

New England Middle Atlantic East North Central West North Central

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 K. T. Moazed, Quantum Biology of the Eye, https://doi.org/10.1007/978-3-031-32060-6

161

162

• • • • •

South Atlantic East South Central West South Central Mountain Pacific Survey device type

• • • • •

O hsret

IOS phone/ tablet Android phone/ tablet Other phone/ table Windows desktop/ laptop Mac OS desktop/ laptop

Addendum

Addendum

163

164

Addendum

Addendum

165

166

Addendum

Addendum

167

168

Addendum

Addendum

169

170

Addendum

Index

A Absorption, 76 Acetylcholine, 106 Activator protein1, 105 Adenine nucleotide (A), 91 Adenosine, 107 Adenosine diphosphate (ADP), 48 Adenosine monophosphate (AMP), 48 Adenosine triphosphate (ATP), 47, 125 Adrenocorticotropic hormone (ACTH), 108 Altered states of consciousness anesthetic action and quantum consciousness, 150 microtubules and ‘Orch OR, 152 three-wave processing, 150 vibrational effect, 150 Amacrine cells, 51, 61 Amphetamine, 109 Antibonding orbitals, 74 Aspect, Alain, 16 Asterisk symbol *, 93 Atomic hydrogen, 23 Atomic orbitals, 29, 72–74 B Bathorhodopsin, 81 Beta-oxidation, 125 Biochirality, 157 Biophotons, 137 Bipolar cells, 51, 61, 65 BMAL1, 104 Bohr magneton (μB), 31 Bohr, Niels, 12, 22, 23

Bohr’s model, 23 Bond length alteration (BLA), 82 Bonding orbitals, 74 Born, Max, 15 Boson particles, 31 C Caffeine, 109 Calcium-cAMP Response Element Binding (CREB) protein, 113 Carbon, 78, 79 Carbon atom, 33 Carbon bonding, 78 Cellular circadian clock, 103 Central clock, 102 cGMP-gated sodium channels, 49 Chemical synapse, 122 Chirality, 156 Chloroplast organelles, 37 Circadian clock networks, 113–114 Circadian Locomotor Output Cycles Kaput, 104 Circadian rhythms, 89 brain and, 115 cellular transcription-translation feedback loop (TTFL), 114 circadian clock networks, 113–114 clock genes and signal transduction proteins, 104 light entrainment, 112 molecular effect, 106 molecular interplay in, 114, 115 neurotransmitters, in circadian cycles, 106

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 K. T. Moazed, Quantum Biology of the Eye, https://doi.org/10.1007/978-3-031-32060-6

171

172 Citric acid cycle (Krebs Cycle), 125 Classical mechanics, 2 Classical physics, 1 Cocaine, 109 Cocaine and Amphetamine-Regulated Transcription genes, 105 Computer modeling, 152 Cone cells, 53, 56 Conical intersection (CI), 84 Consciousness, 35, 119 Copenhagen interpretation, 8, 10, 11 Corticotropin-releasing hormone (CRH), 108 Cortisol, 108 Crick, Francis, 22 Cryptochrome, 88, 89, 95, 96, 102 Cryptochrome genes, 102 Cryptochrome molecule, 95, 102 Cryptochrome protein qualifications, 87 Crystal vibrations, 77 C-Terminal domain, 94 Cyclic adenosine triphosphate (cAMP), 47 Cyclic guanosine monophosphate (cGMP), 47 D de Broglie, Louis, 13 Delta bond, 75 Dexamethasone, 109 Differentiated embryonic chondrocyte, 105 Dopamine, 63, 106 Dot structures, 126 Double occupied orbitals, 29 Double slit phenomena, 6 E Earth’s magnetic field, 88 Electrical synapses, 123 Electroencephalography (EEG), 152, 154 Electromagnetic (EM) radiation, 67 Electron magnetic moment, 29 Electron microscopy lasers, 23 Electron paramagnetic resonance (EPR) spectroscopy, 32 Electron spin resonance (ESR), 31 Electron transfer, 89 Electron’s angular momentum, 26 Electrons fill orbitals, 67 11-cis retinal, 52 11-cis retinol, 52 Energy level, 24 Energy transfer, 77 Enhancer box (E-box), 101 Entangled spectroscopy, 32 Entanglement, 154

Index Entrainment, 101 Enzymes super-fast reactions, 35 European robin cryptochrome 4a (ErCry4a), 87 Everett, Hugh, 16 Excited radical flavin, 93, 94 Excited radical tryptophan, 94 Excited state, 76 F Faster communications, 153 Femto scale, 83 Femtosecond laser spectroscopy, 84 Femtosecond processing, 32 Fermions, 27, 31 Feynman, Richard, 16 Flavin, 90 Flavin adenine dinucleotide (FAD), 90, 91 Flavin C-Terminal, 94 Flavin nucleotide, 91 Flavin-tryptophan radical pair, 87 Fluorescence, 28, 77 Fluorescence fluctuation spectroscopy, 32 Fluorescent nanodiamonds (FNDs) containing (NV-) centers, 35 Fluorescent proteins, 35 Free radicals, 88 Functional magnetic resonance imaging (fMRI), 152 G GABAergic, 61 Gamma-aminobutyric acid (GABA), 63, 106 Ganglion cells, 51, 61, 101 g-factor, 31 Glutamate, 63, 106, 137 Glycolysis, 125 G Proteins-coupled receptors, 47 Growth hormone releasing hormone (GHRH), 108 Guanosine triphosphate (GTP), 47 H Heat Shock Protein 70 (Hsp70), 141 Heisenberg matrix mechanics, 3 Heisenberg uncertainty principle, 3 Heisenberg, Werner, 3, 12 Horizontal cells, 51, 61 Human eye, quantum biology in activation of rods and cones, 53 amacrine cells, 61 ganglion cells, 61, 63

Index horizontal cells, 61 photoreceptor, rod cells, cone cells, and ganglion cells, 53 retinal pigment epithelium (RPE), 58 visual cycle, 51–58 visual transduction, 63 Human perception, 155 Hydrogen, 23, 38 Hydrogen atoms, 23 Hydrogen peroxide, 126 Hyperfine structure, 88 Hyperpolarization, 63 Hypocretin, 106 I Immunohistochemical staining, 89 Indole pathway, 144 Infrared wavelengths, 68 Inner plexiform layer and ionotropic (OFF) bipolar cells, 60 Internal conversion, 28, 77 Intersystem crossing, 29, 77 Intracellular thermometry, 35 Intrinsically Photosensitive Retinal Ganglion Cells (ipRGCs), 110 Ion channels, 48 Isomerization, 52, 80, 82 J Jablonski diagram, 28–32 Jordan, Pascual, 22 Josephson, Brian David, 16 K Knowledge and consciousness, 119 Kynurenine pathway, 144 L Lecithin retinol acyltransferase (LRAT), 52 Lewis diagram, 126 Light absorption, in retina, 49 Light dependent reactions, 38 Light entrainment, 112 Light harvesting, 37 Light independent reactions, 39 Lithium, 109 Löwden, 22 Lumirhodopsin, 81 LUMO, 93 Lysine, 79, 80

173 M Magnetic field effect, 35 Magnetic force microscope, 35 Magnetoencephalography (MEG), 152 Magnetoreception, 35, 87, 90, 96, 98 Magnetosensor, 87 Melanopsins, 109 Melatonin, 107 Memory, 119 Metabotropic (ON) bipolar cells, 60 Metarhodopsin I, 81 Metarhodopsin II, 81 Metformin, 109 Microtubule-associated proteins (MAPs), 136, 144 Microtubules, 129, 130, 149 Microwave, 68 Mitochondria, 123 Mitochondrial respiratory chain complexes, 124–125 Mitogen-activated Protein Kinase, 105 Molecular orbitals, 74 Molecular oxygen radical, 95 Müller cells, 51, 139 Multi World Interpretation (MWI), 8, 10 N Net angular momentum, 24 Neuron responses, 35 Newton, Isaac, 1 Nicotinamide phosphorybosyltransferase, 105 Nitrogen-Vacancy (NV) center, 32, 33 N-methyl-D-aspartate, 63 Non-bonding orbitals, 74 Non-gates potassium channels, 48 Nonlinear-type spectroscopy, 32 Non-radiative decay, 77, 78 Norepinephrine, 106, 108 Norepinephrine release, 108 Nuclear magnetic resonance (NMR), 31 Nuclear response, 78 O Octet rule, 125 Olfactory sensation, 35 Opsin molecules, 138 Opsins, 47 Optically detected magnetic resonance (ODMR), 33 Optical synapses, 123 Oscillation, 101 Oscillatory coupling, 102

174 P Paired electrons, 88 Paoli, Wolfgang, 13 Pauli exclusion principle, 88 Petrin, 90 Phi bond, 75 Phonon, 31 Phosphodiesterase Guanylate cyclase (GC), 47 Phosphorescence, 29, 77 Photoelectric effect, characteristics of, 4 Photoelectric phenomenon, 4, 7 Photoisomerization, 46 Photomorphogenesis, 90 Photon energy, 4 Photoreceptors, 47, 51, 52, 54, 90 Photorhodpsin, 81 Photosensitive ganglion cells, 109 Photosynthesis, 35, 36, 38 Phototransduction, 46, 55, 90 Phototropism, 89 Pi bond, 75 Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP), 112 Planck, Max, 12 Planck’s constant, 12, 14 Plant harvesting process, 36 Poincare, Henri, 12 Potential energy surface (PES), 81 Probability theory, 7 Proteasome, 101 Protein structure and folding, 46 Protofilaments, 133 Proton tunneling, 35 Protonated Schiff Base (PSB), 80 Pupillary reflexes, 113 Q Quantization of energy, 7 Quantum biology, 16, 17, 102 Quantum brain nuclear spin and brain, 153 quantum effects, 152, 153 World Wide Web concept, 153, 154 Quantum coherence, 35, 146 Quantum decoherence, 8 Quantum diamond microscope (QDM), 35 Quantum dipole oscillations, 151 Quantum entanglement, 147 Quantum field alteration, 7 Quantum mechanics, 2, 155 Quantum operators, 15 Quantum phenomenon, 67 Quantum physics characteristics of, 3

Index classical physics vs, 2 specific behavior of, 3, 4, 7, 8, 10–15 Quantum retina binding orbitals categories, 74 carbon, 78, 79 energy level, 75 Femto chemistry of rhodopsin, 84 isomerization, 80, 82 lysine, 79, 80 molecular orbitals, 74 non-radiative decay, 77, 78 nuclear response, 78 radiation and human eye, 70 radiative decay, 77 rhodopsin, 70, 71 Quantum superposition, 147 Quantum theories, 39 Quantum tunnelling, 11, 147 Quantum vision, 154 Quantum walk, 40 R Radiation therapy, 23 Radiative decay, 77 Radical oxygen species (ROS), 137 Radical pair, 87, 135 Radical-pair-based magnetoreception, 87 Radical pair mechanism (RPM), 87, 102, 127–129 Random world of quantum, 11 Reactive oxygen species (ROS), 125, 126, 136 Redox (reduction-oxidation), 88 Reflection, 7 Refraction, 7 Relaxation, 76 Relaxation pathways, 67 Resonant tunneling, 40 Reticular activating system (RAS), 103 Retinaldehyde, 47 Retinal ganglion cells, 63, 64 Retinal Müller cells, 140, 141 Retinal pigment epithelium (RPE), 47, 58, 71 Retinals, 71 Retinohypothalamic tract (RHT), 102, 112, 113 Retinoic acid-related orphan receptor elements, 105 Retinoids, 51 Rhodopsin, 46, 70, 71 Ribose, 91 Rod bipolar cells, 60 Rod cells, 49–53

Index S Schrödinger, Erwin, 3, 13, 22 Schrödinger’s equation, 14, 27, 74 Schrödinger’s wave equation, 3 Serotonin, 107 Serotonin pathway, 144 Short wavelengths, 68 Sigma bond, 74 “Signal-to-noise” ratio, 61 Sildenafil, 109 Single occupied orbits, 29 Singlet oxygen, 127–128 Singlet state, 24 Slower neuronal transmissions, 153 Small dipole magnet, 96 Spectroscopy techniques, 68 Spin angular momentum, 30 Spin-dependent reactions, 35 Spin-orbit interaction, 33 Spin quantum number, 29 Spin vectors, 31 Standard Jablonski excitation diagram, 68 Stern-Gerlach experiment, 24 Superoxide radicals O2, 102 Super-resolution Fluorescence microscopy, 32 Suprachiasmatic nucleus (SCN), 102, 113 Symmetry, 155 T Three-wave processing, 150 Thylakoids, 37 Transcription, 101 Transcriptional-Translational Feedback Loops (TTFLs), 110–112 Transducin, 48 Transitional rule, 24 Translation, 101 Triplet oxygen, 128–129 Triplet State, 25 Tryptophan (TRP), 92, 93, 142 Turin, Luca, 22 Tyrosine (Tyr), 92 U Ubiquitination, 101 Ultrafast spectroscopy, 32 Ultraweak photon emission (UPE), 136 Unfolded polypeptide, 46 Unpaired electrons, 32, 88 UV wavelengths, 68

175 V Vasoactive intestinal peptide, 105 Vibration, 101 Vibrational Jablonski diagram, 68 Vibrational synapses, 123 Vibration relaxation, 28, 77 Vision, 35 Visual participants, consciousness light energy transfer, in retina, 141 magnetic field effect and entanglement, 147, 148 microtubules, 129, 130 abnormalities in, 136 energy transfer, 133, 134 functional architecture of, 130 mitochondria ROS and biophotons interactions, 134, 135 quantum biology of, 132, 133 role of Phonon, 135 tau protein, 136 mitochondrion, 123, 125 Müller cell intermediate filaments (IFs), 141 Müller cells, 139, 140 neurons, 120, 121 oxygen and reactive oxygen species (ROS), 125, 126 quantum coherence, 146 quantum entanglement, 147 quantum superposition, 147 quantum tunnelling, 147 radical pair mechanism (RPM), 127–129 retinal Müller cells, 140, 141 synaptic connections, 121, 123 tryptophan, 142, 144 Voltage-gated channels, 49 W Wave particle duality, 3 Wiltschko, 22 X Xenon, 150 Z Zebrafish reprogram, 140 Zeeman effect, 31 Zeitgeber, 103