The Death of Cancer - World without cancer - The story of research on Vitamin B17 - Laetrile Laetrille Vitamin B17 Amygdalin [1 ed.]

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DR.

HAROLD W. R ANNER

Steven J. DiSanti Thomas L. Michalsen \v ith

Update

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Harold W. Manner, Ph.D., 1988

The story of the research inuoluing Laetrile that dropped a bombshell on orthodoxy ^

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http://www.archive.org/details/deathofcancerOOmann

The Death .

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DR.

HAROLD W. MANNER

Steven J. DiSanti Thomas L. Michalsen Willi L

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Harold

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1988

The story of the research inuoluing Laetrile that dropped a bombshell on orthodoxy

Copyright

© 1989 by Metabolic Research Foundation

No part of this publication may be reproretrieval system or transmitted, in any form or stored in duced, mechanical, photocopying, recording electronic, any means, by or otherwise, without the prior permission of the publishers. All rights reserved.

Published by

METABOLIC RESEARCH FOUNDATION P.O.

Box 4280

San Ysidro, California 92073 1-706-680-4222

or 1-800-433-4962

Update edited by Nadine Rogers 1st Printing

-

1989

Printed and manufactured in the United States of America

FOREWORD As this Second sorrow Ph.D.,

I

Edition goes to print, it share with you our loss. Harold

left this life

October

11, 1988.

is

with deep

W. Manner,

Cause of death:

Myocardial Infarction. It was a privilege and honor to promote and work with Dr. Manner for the past 10 years. I would like to share with you a letter he sent to me before his untimely passing. ...I do not choose to be a common person. It is my right to be uncommon— if I can. I seek opportunity— not security. I do not wish to be a kept citizen, humbled

and dulled by having the state look after me. I

want

to take the calculated risk, to

build, to fail

and

dream and

to

to succeed.

I refuse to barter incentive for a dole; I prefer the challenges of life to the guaranteed existence; the thrill of fulfillment to the state calm of Utopia.

will not trade my freedom for beneficence nor dignity for a handout. I will never cower before any master nor bend to any threat. I

my

my

heritage to stand erect, proud and unafraid; to think and act for myself, to enjoy the benefit of my creations and to face the world boldly and say: It is

'This, with God's help, I have done." It ''My Way" is one of my favorite songs...

Yes, Dr. Manner.

And

-

In

The End

-

is

why

THE TRUTH

WILL WIN OUT.

We miss you, Nadine of Arkansas, P.R. Nadine Rogers, C.A., R.T.

'If God

he for us,

who can be against us— "

Romans 8:31

Harold W. Manner, Ph.D.

1925-1988

BIBLIOGRAPHY Dr. Harold of medical

and

W. Manner

is

no newcome to the

field

biological science. In addition to author-

ing over 50 scientific articles, he has also published six college level textbooks. He received his B.S. from John Carroll University and both his M.S. and Ph.D. degrees from Northwestern University. He is listed in the ''American Men of Science" and "Who's Who in America". He has been the Chairman of the Biology Departments of Syracuse University, St. Louis University and Loyola University of Chicago. After over 30 years of academic teaching and research. Dr. Manner retired in 1982 to devote full time to the Metabolic Therapy described in this book. He is the director of the world-famous Manner Clinic in Tijuana, Mexico and is the President of the Metabolic Research

Foundation.

He is recognized widely among his peers as a capable scientist, researcher, writer and professor. Dr. Manner was one of the most sought after professors at Loyola University. He is also sought after as a speaker for health conventions and is a frequent guest on radio and T.V. shows. Unerring in his commitment for factual, well-documented content and conceptual arrangement, he has, nevertheless, presented the material in this book in a simple and understandable style. No student of true science can fault this conceptual framework. For many, it will be a new and welcome approach.

PREFACE TO THE SECOND EDITION The

book was pubHshed in With most science this is an extremely small amount of time, for scientific advances come slowly. At that time I thought that a new edition would not be necessary for many, many years. However, Metabohc Therapy is a new field, and advances have come very rapidly. They came so first edition of this

1978, a full eleven years ago.

quickly that the first edition

was soon

outdated. It

would have been unethical to put old information in the hands of the public, so a decision was made to stop its distribution until I had a chance to update it. The updating is now complete, and consequently the new second edition is here.

Many

researchers have contributed to this second

The physician members of the Metabohc Research Foundation are constantly bringing in new ideas. The entire staff of the Manner Clinic in Tijuana have been extremely helpful in testing new treatedition.

keeping data and giving me their recommendations for improving the cancer therapy. I owe much also to the pharmaceutical companies who have developed new materials for use in our clinics. All of these contributions have enabled us to strengthen and improve the Metabolic therapy for Cancer, and to ments,

all

of them

I

am indebted.

A number of events have occurred since this book first written. A new clinic opened in Tijuana,

was

Mexico and the owners honored me by naming it after me. At about the same time, I was asked to take an early retirement from Loyola University in Chicago, primarily because all of the controversial publicity surrounding my life at that time was just too much for the administration to handle. As I would not be in Chicago,

move

the Metabolic Research Foundation You can see that it has been an years. eleven eventful I

decided to

to Tijuana, Mexico.

In spite of all of this activity, the work of the Metabolic Research Foundation and the physicians and clinics associated with it continues to move onward. I must also mention here the untiring effort of the Public Relations Director of the Foundation, Nadine Rogers. In addition to setting up all of my public appearances, she has tried to keep in personal contact with all of our patients and physicians. This has benefitted our patients and has resulted in an even greater percentage of successes than we have ever had. It is this new therapy that forms the basis of the new material in this new edition. I

in

am

spite

also indebted to all of those patients

of warnings

from well-meaning

who,

relatives,

and physicians, sought our treatment. Their faith in our work has provided the incentive we needed to continue to forge forward. As always I must acknowledge the support given to me by my wife and family. They have never left my side, in spite of what sometimes seemed like insurmountable odds. Finally, I want to thank that wonderful loving Father, who watches over all of us, and who never has stopped loving me. Thank you Father! friends,

Harold W. Manner, Ph.D. September 1,1988

(The original hook in

its

entirety

follows through page 191, then we pick up the updated information)

THE DEATH OF CANCER HAROLD

W. Steven

Thomas

MANNER, J.

Ph.D.

DiSanti

L. Michalsen

ADVANCED CENTURY PUBLISHING COMPANY CHICAGO U.S.A.

Copyright ©1978 by Dr. Harold W. Manner, Steven J. DiSanti and Thomas L. Michalsen All rights reserved.

No

part of this publication

may

be repro-

duced, stored in retrieval system or transmitted, in any form or

by any means,

electronic,

mechanical, photocopying, record-

ing or otherwise, without the prior permission of the publishers.

Published by

Advanced Century Publishing Company P.O. Box 1052, Evanston, Illinois 60204 Phone: 312-761-0232 First Printing, 1978 Second Printing, 1978 Third Printing, 1978 Fourth Printing, 1979

Printed and manufactured in the United States of America

CAUTION This book was written for the sole purpose of presenting scientific information. It is intended to broaden the scope of knowledge and to clarify certain points regarding a highly experimental and controversial subject. No information or interpretation of any part of this book

is

to

be used as

the

basis

for

home

We, the authors, are not suggesting or treatment. We are reporting the treatment. any prescribing in non-human reencountered have we experiences to use this decision any facts, these of light search. In of or in instead program this of part any or program on that decision is a therapies other with conjunction liable held be will himself he which for part individuals for its outcome.

PREFACE This book had to be written. Although lectures, tapes of lectures, magazine and newspaper articles have described the research which is reported in this This is not an book, none have been complete. indictment of those reporters. To fully understand the joys, the heartbreak, and the innermost thoughts of the researchers, it would be necessary to be one of those That is what makes this book unique. It scientists. written" by some professional outside "ghost was not of our laboratory, but rather was written by two of my graduate students and myself. For this reason it may not always represent the best literary style, and in anticipation of this criticism we all apologize. All of the material presented, however, is scientifically accurate. A complete bibliography is appended for those who wish to delve more deeply into any facet of our research. It is on our science that we hope we will be judged.

The work reported would not have been completed if we were funded by agencies, Federal or Private, that exerted any degree of control over our activities. Fortunately, loyal Americans, whose sole desire was to see an end to the hideous disease of cancer, completely supported us financially. To them we will always be grateful. Among these are the Memorial Library Fund of the National Health Federation, Biotics Laboratories, DaVinci Laboratories, and hundreds of individual donors. The administration of Loyola University of Chicago also deserves our sincere gratitude. Although they have been under continuous attack for allov;ing me to continue my work, they have steadfastly upheld my academic freedom, the right to conduct research and to report my results.

Many others could be mentioned. To list them would be impossible. They know who they are and to each we say "thank you." A few, however, must be singled out: my many graduate students over the past six years who kept the research going seven days a week; my untiring secretary, Josephine Johnson, who performed duties far above that required for her position; Bernard Banas who helped immensely in the production of this book; and finally, our families, who have endured our long absences, while this work was all

going

on.

To

all

of

them

I

ask

God's

Blessing.

Together we have worked, and together we have started on the trail which we are confident will lead to -

THE DEATH OF CANCER. Harold W. Manner Chicago, Illinois August 1, 1978

CONTENTS Preface 1.

2.

How

Got Started Research I

in

Cancer 1

The Natural vs. the Orthodox Approach to Cancer

3.

What

4.

How

is

16

Laetrile?

Is

9

Amygdalin Used by

the Body?

A

28

Cancer Therapy

5.

Vitamin

6.

Enzyme Rationale

84

7.

Nutrition

95

8.

Food Digestion and Utilization

102

9.

It's

Works

149

10.

In

in

"Unorthodox" But

Conclusion

It

72

156

Appendix

159

Bibliography

180

CHAPTER

HOW GOT STARTED I

IN

I

CANCER RESEARCH

It was a beautiful day, with sunshine streaming through the window, as I sat at my desk at St. Louis University, where I was Chairman of the Biology Department. What began as an ordinary day, turned out to be a day which would become the turning point I had finished with my daily series of in my life. meetings with my faculty and staff, and was about to begin the arduous task of reading and answering the morning mail. Most of the letters were routine, but As I read it I one looked particularly interesting. discovered that it was a firm offer to move to Chicago, Illinois and assume the chairmanship of the Biology Department of Loyola University of Chicago. Because I had always wanted to work at a large research-oriented institution, and I knew of the quality of Loyola University and the respect that they had for good scholarship, it was an opportunity of a lifetime and one that I certainly could not refuse. My letter of acceptance went back in the morning mail.

The next few months were extremely busy for I wanted to make I pondered the new position. the Biology Department of Loyola University truly unique. The one thing that separates Loyola University from other universities is the fact that its campus is located right on the shore of Lake Michigan. I felt

me

as

if I could, in some way, devise a technique by which our studies could be oriented towards the lake, we might truly distinguish ourselves as a Lake Michigan Biology center. Research funding would probably come easy because the federal government was at that time concerned about water pollution, particularly in

that

of the knowledge that Lake Erie had recently Lake Michigan was of particular concern for me because the citizens of Chicago and most of the suburbs surrounding Chicago drink their water directly My first meeting with my biology from the lake. light

"died."

faculty after I arrived in Chicago was directed towards that end. I asked if each researcher could change the direction of his research so as to reflect an interest in Lake Michigan. The entomologist, who studies insects, could profitably switch from those insects which live in the forests and grasslands to those that inhabit the lake. In a similar way, other specialists on my staff myself had to I could adapt to the new emphasis. biology developmental in my work of all because adapt salamanders, as frogs, such forms, land on had been mice. It was not a hard task to switch to the study of the development of the fish of Lake Michigan. I felt that I could use the embryonic tissues as an indicator of pollution, and in this way, because of the high sensitivity of embryonic tissues, I might be able to predict problems of pollution before they occurred.

started to work in this area, one thing became very apparent. Most of the pollutants in water are also carcinogenic, that is, they are cancer causing. My reading in the library and in other research papers began to focus on cancer and carcinogens. During this period of time I literally stumbled across a popular two-volume paperback book entitled "World Without

As

I

Cancer" by Ed Griffin.

The book was an extremely interesting one, but one part really caught my eye. A theory was proposed, the Laetrile theory, which was an attempt to control and ultimately cure, cancer. The proponent of the theory was Ernst Krebs, Jr., a west coast biochemist. I laughed when I read this theory because it appeared to me to be an extreme oversimplification of an answer to what I then felt was a highly sophisticated

Basically the theory stated that the extract of an apricot kernel - Laetrile or Vitamin B-17 - when taken into the body, circulated around in the blood stream until it met a cancer cell. At the site of the cancer cell, an enzyme, produced by the cancer cell, triggered the release of a deadly This compound, called hydrocyanic acid (HCN). cyanide compound killed the cancer cells. Any cyanide not so used was converted by another enzyme, found primarily in normal cells, to an innocuous compound,

and complicated disease.

sodium thiocyanate which was promptly excreted

in

the urine. I put the book away for a number of months but, with so many other things, those that are of extreme interest to us, it continued to "gnaw at my insides". Finally I had to get it out again. I called my graduate students together. (Two of these students, Steven DiSanti and Thomas Michalsen, are the coauthors of this book.) I explained the laetrile theory to them and indicated that that was all it was - just a theory. As a theory, it would have to be tested in a laboratory situation and thus, confirmed or denied. My graduate students were willing to switch their research interests from fish to a scientific study and evaluation of the laetrile hypothesis.

as

Our reading now had to turn to laetrile. We had know what type of work had preceded ours. During realized that I was about to this period of reading to

I

enter a situation which was not the typical one found in science. Instead of finding sound scientific dialogue in the available literature, we found charges and the country was counter charges. It seemed that divided into pro-laetrile and anti-laetrile groups. The pro-laetrile forces were championed by the McNaughton Foundation, and also by various citizen groups and organizations such as The International Association of Cancer Victims and Friends, The National Health

Federation, The Committee for Freedom of Choice in Cancer Therapy, and The Cancer Control Society. laetrile included the American The Food and Drug AdminiMedical stration, The American Cancer Society, The Memorial Sloan-Kettering Institute and The National Cancer Because of this divisiveness, the American Institute.

The opponents of Association,

people, particularly those affected by Cancer, fered. They did not know which way to turn.

suf-

What made the situation even worse was the fact that most of the charges and counter-charges were not based on scientific data. The controversy even had an air of political intrigue

about

it.

Political pressure

and

or pseudo-legality raised their ugly heads. This was so obvious that it was almost difficult to talk to anyone on the telephone about laetrile. Offers to meet in parked cars and in out-of-the-way coffee shops were very numerous. In spite of this, I felt that the whole laetrile theory warranted an investigation. legality

One thing became obvious immediately. I knew that because the issue was so highly political, I could not go to the governmental agencies for financial also that I could not go to those support. I knew organizations, such as the McNaughton Foundation, who were supporting laetrile, for any financial help. This is a true dilemma for a scientist, for research does cost money and it must be funded. I went to the administrators of Loyola University and explained my predicament. Their answer was heartwarming. They indicated that they appreciated my situation and would support my research out of university funds. This did not mean that they would support my work to the extent that I could indicate publicly that our position was Loyola University's position. We are, after all, a large university and are comprised of many different departments and many varied schools and colleges. We

have schools of medicine and dentistry as well as departments such as biology, and not everyone at Loyola University, even today, agrees with my thoughts. Consequently, the university administration simply asked that when I write or speak I indicate that the work and ideas are mine and do not necessarily This I reflect the opinion of the entire University. 1 do it now for the purpose of

have been glad to do, and this book.

With the University's financial support

was able to begin the studies

in

earnest.

hand, I thing an

in

One

investigator needs before he can work with laetrile is As background, let me the substance laetrile itself. indicate that I hold a controlled drug (hard drugs) license from the State of Illinois and the United States Government. I have also been given a key to the hard drug locker on our campus. I can assure you that I had been investigated thoroughly by the State of Illinois and the Federal Government before they entrusted me with this responsibility. I have never, in over twentyfive years of active research, had any trouble ordering any substance that I needed. 1 didn't have any trouble until I tried to order the extract of an apricot kernel (Laetrile). I deal with a number of scientific companies and one that listed laetrile, or as it is more properly called, amygdalin, in its catalog was the Sigma Chemical Co. of St. Louis, Missouri. I wrote an order for a fifty gram bottle of laetrile and sent it to Usually my order is the Sigma Chemical Company. delivered in 3 to 4 days. This time 3 or 4 days passed, one week passed, and finally two weeks passed and I still had not received my order. I called Sigma and was informed that they could not send it to me unless I sent to them an affidavit. When I asked them about this affidavit they said that the FDA required it. This was the first time that I fully realized how much influence the FDA had over this particular substance. I asked them what they needed in the affidavit and

~

FDA required a statement from me indicating that I would use the laetriJe only on my laboratory animals and would not use it on human beings. I thought that this was a fair request, but an odd one, for I am not licensed to use any pharmaceuticals or other substances on any human subjects. After all, I am a biologist, not a physician. Sigma recognized this but also indicated that it was such a firm directive from the FDA that they could not send therefore composed a I it without the affidavit. complete affidavit and sent it with my purchase order. The text of this affidavit follows: they said that the

GENTLEMEN:

AMYGDALIN WILL BE USED FOR RESEARCH MY LABORATORY TO DETERMINE THE MAXIMUM NON-TOXIC DOSE WHEN INJECTED INTRAMUSCULARLY INTO WHITE MICE. THESE WHITE

THIS IN

MICE ARE A TUMOR-BEARING STRAIN OBTAINED FROM THE JACKSON LABORATORIES. ONCE THE DOSE-RESPONSE CURVE IS OBTAINED, AMYGDALIN WILL BE USED IN TUMOR SUPPRESSION STUDIES WHICH ARE ALREADY UNDERWAY IN OUR LABORATORY. NONE OF THE AMYGDALIN WILL BE USED ON HUMAN SUBJECTS.

SINCERELY YOURS,

HAROLD W. MANNER, Ph.D. CHAIRMAN DEPARTMENT OF BIOLOGY Within a few days after submitting this affidavit my first bottle of amygdalin. Our laboratory is fairly large and contains thousands of mice. Laetrile does not last very long in the laboratory, and as a I

did get

was necessary

me

to reorder laetrile in and again the same no shipment for two weeks. A phone thing happened call revealed that the reason that they did not send it

result,

it

about a week.

I

sent

—

my

for

order

in

was because they needed an affidavit. I indicated to them that they already had the affidavit and that it They said that should be somewhere in their files. they had received it, but that the FDA required that I send a new affidavit each and every time I order laetrile. This appeared to me to be a rather ridiculous requirement. The FDA had evidently never heard of Xerox machines. I immediately xeroxed 100 affidavits and had them on hand so that I could send one each and every time I ordered a bottle of laetrile. This initial harrassment was soon to be followed by another request, for a second affidavit. The FDA now wanted two of these each time I ordered, one indicating that I would not use laetrile on human beings, and one stating that it would not be used on animals outside my own guess they felt that because veterinI laboratory. arians were beginning to find successful applications of laetrile that they would try to get some from me. The FDA simply did not want me to be a "fence" for "hot" laetrile.

Our experiments continued. We were at first interested in the FDA charges that laetrile was poisonous. They pointed to the fact that laetrile should not be considered safe because it contained cyanide. This type of half-truth, intended primarily to scare the American people, is something that I have run across continuously since starting to use laetrile. Certainly laetrile contains cyanide, but so do lima beans, and lentile beans, and buckwheat, and many other food products. In fact, Vitamin B-12 is loaded with cyanide. Cyanide, however, is not a poison when it is part of a complete chemical complex. The FDA knew this, but still the charge was being made that laetrile was toxic. We knew that this charge had to be answered and so

we set up our first experiments whiich will be detailed The result was, of course, that later in this book. laetrile was non-toxic, even in doses much higher than those given to any human being. Many intermediate types of experiments were performed, designed to demonstrate the laetrile theory, and each of them brought us closer to the realization that laetrile should work, by killing cancer cells.

The

last six years

have been truly remarkable.

It

the remarkability of these years that We were now prompted the writing of this book. involved with laetrile, but we were not out to demonstrate its efficacy. We were out to determine whether or not laetrile was a viable alternative to orthodox therapy. To this end my graduate students and I have pledged ourselves, and it is to this end that all of our experiments have been designed. is,

actually,

CHAPTER n

ORTHODOX VERSUS NATURAL TREATMENT search for treatment, the cancer patient of today is often understandably confused. After reading all the information that he can get his hands on in libraries and health food bookstores, he has probably come across such unorthodox natural treatments as the Gerson Diet, the Kelley regime, the Hoxsey treatment and others, including the very widely publicized and controversial treatment involving a substance called Many Americans however, because of the Laetrile. Food and Drug Administration's (FDA) ban on Laetrile's importation, manufacture and sale, are obtainA ing this drug from Mexico, Jamaica and Germany. talk with his physician will usually leave the patient with the impression that all of these treatments should be dismissed as unorthodox and "quackery" with noWhat is the thing good to be derived from them. patient cancer confused the should way Which truth? In his

There is no easy answer and the decision is one which ultimately must be made by the patient himself, for it is his body and his life that is being affected. This chapter will try to differentiate the various forms of treatment available to the patient so that he may be better able to make an intelligent decision concerning his choice of treatment.

go?

Why

the difference of opinion?

any philosophical system, the conclusions for If, drawn depend upon the basic premises. is gravity of force example, you believe that the follow automatically always operating, then it would that you would believe that something held in the hand In

would drop to the floor if released. If, on the other hand, you believed that the force of gravity was not necessarily operating at all times, then there would be a question in your mind regarding the ultimate fate of an object released. In a similar way, the differences and conclusions reached by various members of the healing professions depend to a great extent upon the various premises that they hold.

What

is

the Orthodox opinion?

first premise held by orthodoxy is that a local disease. A lesion, usually in the form of a bump or lump appears in the breast, on the lung, on the skin, or in some other location in the body. It is further thought that this primary lesion is the result of some activity in that area. This activity could be in the form of an invading virus, or the result of carcinogenic action at the site. It might also be the end product of some form of trauma such as a blow.

The

cancer

is

If the physician believes the above premise, it is obvious that his treatment plan would necessarily follow the localized route. The first type of treatment often suggested is surgery to remove the offending tumor mass. These surgical procedures have had an interesting history. The earliest surgeons were content to remove simply the tumorous mass. It later became evident that an individual or a group of cancer cells could easily have invaded the surrounding or adjacent normal tissue. As a result, subsequent surgery included the removal, not only of the tumorous mass, but also of a great amount of normal tissue in the area. In breast surgery, for example, a mastectomy (removal of the breast) removes not only the tumor itself, but also muscle, connective tissue, and lymph glands in the axillary area. More recently, surgeons seem to have become more ambitious. I had the opportunity to view a new surgical film recently.

10

order to stop a slow-growing tumor, a man was removed. In the most severe of quarter a full seen, a man was actually cut in two, ever case I have legs, the hips, and all of the external losing both This operation is called a reproductive organs. I w.U never forget. film hemicorpectomy. It is a In this film, in

of localized treatment is radiaThis involves the use of various types of tion. powerful rays which are known to kill cells. The rays are directed to the localized area of the tumor mass. As in surgery, the first objective of radiation is to kill the tumor, and the second is to kill a portion of the

A second type

adjacent normal tissue into which cancer cells may have infiltrated. The major problem with radiation is that the rays are in no way selective and burn damage Hair loss also frequently will result in normal tissue.

accompanies radiation.

A third type of treatment is chemotherapy. This treatment is designed to kill the cancer cells by taking advantage of their high rate of mitotic (reproductive) In addition to the effect on the primary activity. mass, chemotherapy should also kill cancer cells circulating in the blood stream and moving or metastiHowever, in sizing to other areas of the body. chemotherapeutic functions, these these out carrying agents are non-selective, consequently they do affect other organ systems of the body, and the list of These side effects undesirable side effects is long. individual and the upon the will differ depending chemotherapeutic agent used. thing that all of these treatments have in common is that they are unnatural to the human body. They mutilate, burn, or poison the body to various degrees, and the success rate of these treatments has been anything but spectacular. A recent report by the National Cancer Institute has indicated that the cure

One

11

rate for cancer has increased only one percent in the past twenty-five years. It is interesting to note that these statistics are reported to the public by the cancer research orthodoxy. It is usually reported as a A "success rate" of 12 per cent is "success rate." really a failure rate of 88 per cent, but of course if scientists tried to report their negative results in this fashion they would be severely chastised. It is obvious from the above that other means must be found to control, and to ultimately cure this pervasive and dehabilitating disease.

As a natural consequence of an adherence to the "local disease"

premise,

many

scientists

develop an

unwholesome obsession with and worship of carcinogens. Carcinogens are agents which "cause" cancer. Millions of dollars are spent each year looking for new Rarely does a week go by in types of carcinogens. which we are not informed of some element in the air, or some component of our food, or some pollutant in our water that is carcinogenic. The localized approach to the cancer problem would assume that the carcinogen works on a local area. The sun, working on the skin, causes skin cancer; cigarette smoke, irritating the lung membranes, causes lung cancer, etc. Although the search for these carcinogens has proved fruitful, and certainly carcinogens should be avoided as much as possible, it is becoming increasingly obvious that carcinogens do not always cause cancer. They can however cause cancer if the body conditions are proper.

A approach

consequential result of the localized an assumption that cancer cells are de-

third is

differentiated adult cells. An example of this dedifferentiation process would be the change of a complete muscle cell into an embryonic cell, with full

embryonic potential.

If

by the proper stimuli

this cell it

were to be acted upon

could then 12

become a nerve

etc. The majority of contemporary maintain a belief in this process of dedifferentiation. It is interesting to note that in 1953 in a paper with the unwieldly title "The origin of the blastema and of new tissues in the regenerating forelimb of the newt, Triturus viridescens viridescens" the basic hypothesis was set forth claiming that cells are incapable of this dedifferentiation process. The cell,

bone

cell,

scientists still

corollary to this

that cellular differentiation is a This concept was scoffed at by the scientific establishment at that time. believe, I however, that this non-dedifferentiation hypothesis still holds true. A liver cell does not become a cancer cell, nor does a gland cell become a cancer cell. As long as scientists and physicians continue to believe that dedifferentiation does occur, and that adult tissues do become cancer cells, another related area of research will continue to be funded heavily. This area is genetic research. The basic questions being asked in genetic research are: What are the gene 1) changes occurring which cause a full differentiated cell to become a cancer cell and 2) How does the environment affect the gene to cause it to change, to

one-way

is

street.

mutate?

The method and consequences of treatment, the preoccupation with carcinogens and the assumptions involving the dedifferentiation process are all rooted in the basic assumption that cancer is a local phenomenon.

What

is

the Alternative opinion?

A system of thinking that operates from a completely different basic premise than does the orthodox, would hold that cancer is not a local disease, but a systemic one that originates in the entire body. From this basic premise, conclusions are drawn which are very different from those of orthodoxy. It imme13

diately becomes apparent that any localized treatment of cancer would be absolutely worthless. To remove the tumor in one area of the body by radiation, surgery or chemotherapy, without first asking the question what caused this lump or bump to appear in the first place? - merely delays the reappearance of this tumor. The reason for this is that the complete and successful removal of the primary tumor will not remove the

underlying systemic cause. It has already been indicated that cancer cells are differentiated embryonic cells rather than dedifThese cells, once they do ferentiated adult cells. differentiate into cancer cells become significantly different from the normal cells of the body. The body is equipped with a system - the immune system whose primary function is to eliminate from the body We are all all materials that should not be there. familiar with the heart, kidney and other organ One of the major problems transplant operations. which arises after transplant surgery is rejection. The new organ, not being a normal part of the original body, is seen by the immune system as a foreign invader and is therefore destroyed by the system. I believe the same thing happens in a cancer cell. When an embryonic cell develops into a cancer cell it is immediately recognized as a foreign cell and it is rejected by our immune system. Everyone has these embryonic cells in his body at all times. They are

needed for wound and tissue repair. When, however, some type of carcinogenic agent stimulates these cells, they become abnormal cancer cells. This may happen very frequently during an individual's life. In most people, the body's immune system is able to recognize them as malignant cells and destroy them. However, as a result of poor nutrition, poor health habits, lack of exercise, or other weakening habits, the immune system becomes weak. The statement - "The resistance is low" - reflects a weakened immune 14

system. In this condition, the cancer cells will be unaffected by the immune system and will be allowed to grow and multiply. The result is a tumorous growth. It should be obvious that the treatment of cancer must involve a stimulation of the whole immune system to such a point that it can recognize and destroy these foreign bodies. It should be noted here that the emphasis is on the entire body, and the lumps and bumps on the body are of only secondary concern.

The following chapters will discuss in detail the techniques that would allow the tumor mass to be recognized by the immune system, and methods by which this immune system can be stimulated and brought back to its normal, fully functioning condition. The science upon which all of this is based is sound. The work from our own laboratory at Loyola University in Chicago, as well as the work of countless others in laboratories all over the world will be used and documented to form the basis of a comprehensive cancer therapy.

CHAPTER

in

WHAT IS LAETRILE? the past few years the word Laetrile has found into the vocabulary of thousands of people, from all walks of life. It seems, however, that the increased familiarity with the word has done little to shed light on the basic question: what is Laetrile? In

its

way

To most lay people, and astonishingly enough to some researchers, laetrile has become a catchall term that does not specifically refer to any exact chemical structure. This lack of understanding regarding something so fundamental to the issue at hand certainly has done much to keep this substance shrouded in a cloak of mystery, thus providing more fuel for political and scientific show-downs. The purpose of this chapter is to delineate for the reader the most current information regarding the structural chemistry of various compounds pertinent to the subject, and in so doing to try to clear up many misconceptions whose roots were firmly planted with the inception of the entire Laetrile hypothesis many years ago.

There is no doubt that Laetrile is a term that has been overplayed and misused. Most references to Laetrile are usually in error, and actually refer to other compounds. In most cases, the substance intended is amygdalin. The word "amygdalin" comes from a Greek word "amygdale," meaning almond. Since amygdalin was first found in bitter almonds, and its taste somewhat resembles almonds, it is properly befitted with its name. Amygdalin was first used by a Chinese herbalist (Pen T'Sao) in the year 2800 B.C. and has been used intermittently by various groups since 16

that time.

empirical formula of amygdalin The is Cr,oH^„NO,,, adding up to a molecular weight (the

weight of one molecule of amygdalin) of 457.42. The percent composition is C-52.51%, H-5.95%, N-3.06%, and 0-38.47%. Figure 3.1 is a structural representa-

iCcH 6"5

CN

BENZENE

CYANIDE

AN

AMYGDALIN

Figure 3.1

MOLECULE

An Amygdalin Molecule

Amygdalin consists of two glucose molecules and benzene.

(biose), cyanide,

of a molecule of amygdalin. The molecule consists of a six-carbon benzene ring attached to a carbon atom, which in turn carries a cyanide group (CN) together with two potential glucose molecules united as a double sugar or a biose. Again, it must be emphasized that this entire structure is one molecule of amygdalin and not laetrile or Laetrile (even a capital as opposed to a small L technically denotes different chemical compounds). Every new compound tion

must be named according to certain standards set up by an association called the International Union of Pure and Applied Chemistry, abbreviated as the 17

system. Henceforth, these synonyms will also be given in conjunction with the common and familiar names of all the compounds mentioned. The synonyms for amygdalin are: D-mandelonitrile-B-D-glucosido-6mandelonitrile-B-gentiobioside, and, B-D-glucoside, Amygdalin is also more commonly, amygdaloside. referred to as a cyanogenic glucoside which stated simply is a cyanide-producing, glucose-containing compound.

lUPAC

Amygdalin is usually found in the kernels of certain Rosaceae, including cherries, peaches, prunes, plums, bitter almonds and apricot kernels. Cyanogenic glycosides (which, like glucosides, are cyanide-producing but do not necessarily contain glucose as the sugar component) are present in most of the above kernels as well as in millet, cassava, maize, sorghum, field bean, lima bean, bamboo, sugar-cane, kidney bean, sweet potato, lettuce, linseed, almond and the seeds of lemons and limes. These cyanide-producing, sugarcontaining compounds are naturally occurring compounds and have a physiological or protective function. For example, the cassava plant contains these compounds throughout its system. However, the richest concentration is found in the cortex of the root. In this way the CN present in the root can protect the entire plant from the invasion of insects. Most of these foods serve as excellent sources for the isolation of amygdalin.

The isolation of this compound utilizes a relatively simple procedure known as an extraction process. First the kernels or seeds are defatted with ether. Then this fat-free residue is boiled in alcohol, filtered and cooled. The amygdalin is then separated from this residue and recrystallized. This newly obtained amygdalin, then, is the white crystalline substance which has been separated from other compounds existing naturally in the respective seeds or 18

kernels. (Robiquet and Boutron-Charland first isolated crystalline amygdalin in 1830.) Although many cyanogenic glycosides exist, they are, at most, amygdalinJust as each person is given an individual name like. referring to only that person, there is one and only one

true amygdalin with a chemical character and personality attributable only to

it.

In 1952 Ernst Krebs Jr. reported that he had synthesized a compound from the apricot kernel, "to make the empirical apricot formula safe for administration to humans." This new compound, ^hown in Figure 3.2, was patented and called Laetrile Note that this is a proper name referring to one and only Krebs had synthesized this new one compound. .

H

COOH I

compound in order to take advantage of an enzyme system which was particularly abundant in malignant tissue and that was capable of triggering the release of The next chapter will cyanide at the tumor site. present this mechanism

in detail.

Unlike amygdalin, one molecule of Laetrile has molecular weight of only 309.27 grams, and has an a empirical formula of C^ .H. rNO„ (versus amygdalin's

C^pHoyNO. J. the elements

in

The percent composition of each of Laetrile

is

as follows:

C-54.37%, H-

4.89%, N-4.53%, 0-36.21%. The lUPAC names include: 1-Mandelonitrile-B-glucuronic acid, 1-mandelonitrile-beta-glucuroniside, D(l)-mandelonitrile-B-glucuronide, and cyanophenylmethyl-B-EL-glucopyrnosiduronic acid. Like amygdalin, Laetrile consists of a benzene ring and cyanide(CN), but unlike amygdalin, it contains glucuronic acid in place of glucose. Therefore, Laetrile with a capital L and a registered patent mark is not a synonym for amygdalin, nor is it simply gmygdalin lacking a molecule of glucose. Laetrile is a synthetic derivative of glucuronic acid, and therefore designated as a glucuronide. Laetrile was developed at the John Beard Memorial Foundation of San Francisco. It was patented in 1958 by Ernst Krebs Sr. and Ernst K^ebs Jr. (Brit Pat. 788,855). The synthesis of Laetrile can be accomplished by the condensation of mandelonitrile with glucuronic acid, or the hydrolysis of amygdalin and the oxidation of the resulting 1-mandelonitrile-B-glucoside with platinum black, or finally, by the condensation of mandelonitrile with glucose and subsequent oxidation.

A compound which contains cyanide can be labeled with the suffix, -nitrile. Since Krebs' new compound contained cyanide and since it was laevorotary (turned plane polarized light to the left), Krebs combined the first three letters of laevorotary and the 20

fivg Laetrile

last

.

letters of nilrile and became As Laetrile

the wora more popular the

coined

word was borrowed by some when referring to any compound containing cyanide and exhibiting this laevorotary power. In this context, however, the capital L was dropped, and no registered patent symbol was made; such compounds then became known at laetriles. This is what we referred to at the beginning of this chapter as the catchall term, because it refers not to any one specific compound but to a group of compounds. As if this is not confusing enough, at one time at least two different Laetriles existed simultaneously; one was called Laetrile (U.S.), and the other was In 1965 a paper known as Laetrile (Canadian). entitled, "Laetrile: A Study of its Physiochemical and Biochemical Properties," compared these two comThe (The results are given in Table (1). pounds.

TABLE

I.

Laetrile

Physical criteria arid composition

Label identification

Canada ...

A

U.S.

^-Cyanogenetic gluooside

Amorphous

Appearance Optical rotation

—39

pH (10% in HoO). ... Amygdalin Di-isopropylammonium

87

solid

/3-Cyanogenetic glucoside Colourless solution

—42

± 2%

1" .

3.9

6.8 98

± 2%

5%

iodide

0.5%

Phenol Sucrose

'

8

±

7-Mandelonitrile-/S-

glucuronoside (1). Mandelonitrileglucuronoside di-isopropylam-

monium

0°

.

A

salt*

21

2%

conclusions reached indicate that the two formulations are different compounds with different chemical and biochemical properties. It is evident from table 1 that the major component of both Laetrile (U.S.) and The one Laetrile Laetrile (Can.) is amygdalin. contains almost 100% amygdalin, and the other has at best, 89% amygdalin, with sucrose making up the bulk. From our previous disaussion, it is evident that neither compound is Laetrile proper, but mixtures of amygdalin. Therefore, it is primarily the components of the mixture, excluding the amygdalin, which impart differences to each formulation. This is a good example of how confusion can result when a compound such as amygdalin is labelled a laetrile, and then this laetrile is CQjifused with the proper, unique, patented LaeThe scientific implications of such confusion trile are many. If a researcher published his data thinking and actually used a laetrilethat he used Laetrile like amygdalin, he would probably get different results than a researcher who actually used Laetrile . If this problem was not detected the results from the two researchers would look contradictory, for they both thought they were using the same compound. It is for this reason that extreme care must be taken when dealing with the language of laetrile. .

,

The next compound to be discussed is known as prunasin, Figure 3.3. Prunasin is a naturally occurring product, and can be formed by the breakdown of amygdalin. It is like amygdalin in that it is a glucoside, but unlike it in that it contains only one glucose molecule and not twp. Confusion still results

when

prujiasin and Laetrile are used interchangeably. Laetrile a synthetic glucuronide, contains glucuronic acid in place of the single glucose molecule that makes the naturally occurring prunasin a glucoside. ,

Prunasin has two other sister compounds which differ from each other only in their optical rotation

22

GLUCOSE

MANDELONITRILE

GLUCQSIDE

^^PinHiasir^^^

d

^^Sambunigrin

i-

C

)

Pr ulaurasin

Figure 3.3

d

Stereoisomer

-

Stereoisomer

H

i

-

Stereoisomer

Compounds Which may be Obtained from Amygdalin

Three

Sister

Breakdown Prunasin, Sambunigrin, Prulaurasin have the

same chemical structure buy vary ability to rotate plane

presented above.

23

in

their

polarized light, as re-

These are known as stereoisomers since they have the same exact atoms, but a slightly difThe only way to disferent arrangement of atoms. tinguish such compounds is by their effects on a beam of plane polarized light (more detail will be presented These three compounds are in the next chapter). known as Mandelonitrile Glucosides, (Fig. 3.3), a term which will be elucidated in the next chapter. Prunasin properties.

is specifically d-mandelonitrile glucoside since it is dextrorotary (turns plane polarized light to the right as It has an empirical designated by the letter d). weight of 295.28, molecular a .H^^NOg, formula of C^

and percent composition of C-56.94%, H-5.80%, N4.74%, 0-32.51%. Prunasin can be prepared via the action of yeast on amygdalin, or by relying on an established synthesis according to Mentzer. One of its sister compounds, called sambunigrin, is laevorotary (turns plane polarized light to the left) and specifically knov7n as 1-mandelonitrile glucoside. The other compound, relative to prunasin and sambunigrin, is prulaurasin or dl-mandelonitrile glucoside which is composed of half dextrorotary crystals and half laevorotary crystals. A compound with such a fifty-fifty mix is called a racemic modification, and is optically inactive since all of the d-crystals cancel the optical effects of the 1-crystals. Amygdalin MF manufactured by the McNaughton Foundation is such a racemic modification of amygdalin, where half of the mixture is dextrorotary and half is laevorotary. Sambunigrin and prulaurasin are usually not caught up in the laetrile labrynth and are considered unimportant by some. They may, however, be instrumental in the intermediate metabolism of amygdalin, explained in the next chapter.

Prunasin and amygdalin are sometimes considered the two most common laetriles. (Again, the small letter 1, already discussed above, refers to any compound containing cyanide and displaying laevoro24

Even though prunasin is dextrorotary it has somehow been included just the same. Using the above classification to designate a of laetrile, one might simplify matters by thinking and proper laetrile as a blanket term referring to specific compounds such as: amygdalin, prunasin, and optical

tary

Laetrile

activity.)

.

most of what is used today ii^research is very Laetrile is amygdalin. work and Narrowing prohibitive. is cost its presently and scarce the use of such compounds down to basically one does In reality,

clinical

alleviate the confusion experienced in previous years, however the importance of knowing the exact struc-

ture and purity of any compound tested cannot be stressed enough. Lack of this knowledge in the past has lead to an array of results which are extremely contradictory and ultimately useless. realized this problem while reviewing previously published work on the toxicity of amygdalin. The reported results were not very encouraging. Where one research team found toxicity at a certain dose, another reported no lethal toxicity using over one thousand times that amount. While the mode of administration accounted for some of the discrepancy, of confusion. It is it was by no means the only cause clear, however, that experiments by different scienalthough thought to be identical, differed in the

We

first

tists,

compound being

tested.

To avoid

falling

into

this

"bottomless pit" we decided to use amygdalin from the Sigma Chemical Company, a firm with which our lab As had done a good deal of business in the past. requirexplained in chapter one, many affadavits were ed to secure our orders of amygdalin, but we all agreed that this little inconvenience was well worth the quality control to which Sigma subjected our amygdalin.

25

Such quality consisted of grade-one amygdalin; a white crystalline compound tested to be 99% pure. Each bottle was properly labeled with a lot number which represented the batch from which each particular sample of amygdalin was obtained. In this way information regarding that particular batch could be obtained if desired (see the Analytical Information Report). In the past we have seen some analyses of compounds claiming to be pure amygdalin that reveal a complete absence of cyanide in the molecule, and other analyses which show samples that contain isopropyl alcohol which was left over from the extraction process from the kernel: this isopropyl alcohol could be very dangerous in itself. One compound which did pass rigorous testing was one from the Kaden Corp. of Germany. It was found to be of the same quality as that from Sigma and happened to be what we were using at the time our results were released at the National Health Federation convention September 10th

1977.

At this point the reader has been given some basic structural information about the different laeThis information should be used to set the triles. groundwork necessary to answer the next fundamental question; how is amygdalin proposed to work? the purpose of the next chapter to familmechanisms involved in the metabolic breakdown of amygdalin and other laetriles. It

is

iarize you with

26

Request thru Mr. Dan Broida f^a'-^'^

regarding your

Dr. Harold Knnner Biology Uepac tnent

.

Lovola Lniversity of Cliico^o

- Oj':j ' u.

':

'

-

''"

'

60626

ILlinois

ChicJjiO.

ANALYTICAL INFORMATION REPORT *-^"°^

Product Number

Lo'

^^"^°^^^^- ^"''''

Product

Th,o.e..c.l ..lu,. b,.o- «...

CcuU.^d

u..n,

IC*»liOn Ma'.AT0CR.\PHY: Approxirately light. Detection Method: Silver nitrate and ultra-violet

ENZYMATIC ANALYSIS: For Aaygdalin

-

approximately 991 pure

For Free GluCJSe

-

none detected Idetection limit 0.03;)

For Benialdehyde

-

none detected (detection licit 0.05*.)

no -.,r.n,y ..p-....d o, ,..p..-d ..ndvd.n, ,., cono„,.on w..h .h.. p-odvc. e.cep. fo. n. .ccvoc,

S.,n,. ,r,.W. .n

pJ,po.,l

.ni

,1

..

.f Iu-'^ed

Of .m.-uCC^. t'Om S.omj Scjmi

UK

S

fVl/\*CHE.VIICAL

pr

I

.-

I. /'''*'.

r^


,0*

ocl Ot i.ibf l0< Jny ."Cd-olU o. con«Qu»nl»l d>^»93

2Na*

HSCN

3).End Products

Thiocyanate

Na2S03

Sodium sulfite

Figure 4.7

The Neutralization of Cyanide

Deadly hydrogen cyanide in the presence of sodium thiosulfate and the enzyme rhodanese converts it to inactive thiocyanate and sodium sulfite. These are passed out in the urine. Reaction mechanisms are given in three steps emphasizing the disulfide bonding pattern of rhodanese.

Inspecting the equation, we see that free hydrocyanic acid on the left is combined with sulfur from the thiosulfate in the presence of rhodanese to yield thiocyanate (HSCN), which is a neutral non-toxic substance passed out in the urine. Lang found the

44

enzyme to be heat labile with an optimum pH of 8.0. He also found the optimum substrate concentration to mole of cyanide to three moles of sodium thiosulfate. The rate of the transfer reaction increases with temperature up to 38 degrees centigrade; be one

normal body temperature is approximately 36 degrees centigrade. Rhodanese has been found to exist in all normal tissues with the highest concentration in the This is consistent with the fact that the liver is the primary detoxification organ of the body. Remembering that thiocyanate is the neutralized form of cyanide, we can review some interesting data regardWokes reported .1 to 10 parts per ing thiocyanate. million in cows milk, or approximately .57 to 5.7 milligrams per pint. Gemeinhardt found that the thiocyanate concentration in all plant species ranges from about 30 to 950 milligrams per 100 grams with the highest figures in cabbage, carrots, and radishes. Wilson (1966) reported figures of 4.1 milligrams fop sprouts, 1.9 mgs.% for caneflower, and .4 mgs.% for pea and tomato. Williams (1967) obtained 600 mgs.% for "gari" made by fermenting cassava, 700-800 mgs.% for cassava flour and 500-600 mgs.% for yam flour. The content found in the urine also increased with heavy smoking. Back in 1845 Lang showed an increase in the excretion of thiocyanate following an injection of cyanide in rabbits, which was later confirmed by other investigators. It is extremely interesting to note that in all of the above cases whenever there is danger of cyanide poisoning there is also present a mechanism to neutralize it, even in plants. Work done on animals by Himwich and Sanders (1948), based on the distribution of rhodanese, calculated the capacity of a dogs liver to detoxify cyanide to be 4015 grams per 15 minutes, and the rate in skeletal muscles to be 1763 grams per 15 minutes. The amount of rhodanese in the dogs liver necessary to accomplish this rate of turnover was .78-1.46 mgs. per gram of tissue. This amount of rhodanese can be compared to the 10.08liver.

%

45

15.16 mgs. per gram that the rhesus monkey demands, the 7.98-18.92 RDgs./g that the rabbit requires, and 14.24-28.38 mgs./g that the rat needs. From this data can be concluded that even with the amazing it capacity of the dogs tissue to detoxify cyanide, this tissue has the least amount of rhodanese of all the other animals tested. The increased concentration of rhodanese in the tissues of the other animals should enable them to detoxify much more cyanide at a more The question may then be rapid rate than the dog. delicate anticontain such a bodies our asked; if any cyanide poisoning how is cyanide defense system possible? If

detoxification could keep up with the absorp-

CN no dose would be lethal. However, at very high doses the two can't keep up with each other, and absorption of CN exceeds its detoxification. The reason for the lag in the detoxification is due to the availability of sulfur which we saw to be a crucial ingredient in the process. Chen (1934) found that an injection of thiosulfate - the sulfur rich compound previously discussed - increased the minimum lethal A good dose of cyanide up to three or four times. portion of the thiosulfate present in us is excreted unchanged, even though it would serve the body better by circulating. Given quantities of thiosulfate are lost to the urine due to the thiosulfate's inability to penetrate tissues at an effective rate. CN does not have this penetration problem, and once inside the cell may not be counteracted. To alleviate this problem, several other compounds come to the rescue, and this is done in the following ways. Either another compound donates sulfur, thus making more sulfur available to the CN, or the excess CN is allowed to combine with another compound thereby inactivating the CN. Fig. 4.7 shows an example of the first type, that is, sodium thiosulfate, a sulfur donating compound. 3-B-mercaptopyruvate found in the conversion tion of the

46

of cystine and cysteine to pyruvic acid necessary for aerobic respiration can donate sulfur in the presence of rhodanese to form thiocyanate. Mercaptopyruvic acid also contains sulfur and, as observed by Wood and Fielder (1953), can convert HCN to HSCN as rapidly as thiosulfate.

Vitamin B12 is an example of a compound that can join with CN and in so doing inactivate the free CN and even make use of it. B12, or cyanocobalamin, contains cobalt which is tightly complexed to CN. The liver contains a precursor to B12 known as hydroxycobalamin which is devoid of CN, but which is capable of picking up any free CN it comes into contact with. When free CN and hydroxycobalamin complex, the result is cyanocobalamin or vitamin 812. This is not responsible for a very large percentage of CN detoxification, but does contribute to the overall protective system. Montgomery (1969) found that urinary thiocyanate excretion is increased not only by the ingestion of cyanide but also by a deficiency of vitamin B12. This is logical since a deficiency in B12 would imply a deficiency of its precursor hydroxycobalamin. With less hydroxycobalamin to neutralize the ingested cyanide, more of the CN would be shifted to the thiocyanate pathway resulting in more of it in the urine. Mushett (et. al. 1952) found that the administration of hydroxycobalamin can protect mice from cyanide poisoning to a remarkable extent. Tests run by Wokes and Pikard (1955) point to rhodanese, together with its sulfur donors, which may even include some sulfur containing amino acids, as the primary CN inactivating system. They postulate that when CN is introduced into the body, both B12 and rhodanese, with its sulfur donors compete for it. The cyanide inactivated by rhodanese and sulfur is then excreted in the urine as thiocyanate with a very small amount showing up in the feces. The cyanide-

47

forming vitamin B12, on the other hand, can be used normal metabolic functions.

in

One last method of cyanide detoxification is carbon dioxide (CO^). Bpxer and Rikards (1952) deCN given to dogs appeared monstrated that labelled in the exhaled CO^. They also found it in various lipid fractions such as choline and methionine, and in the They also substantiated ureide carbon of allantoin. previous work by finding the label in B12 as well as thiocyanate. A summary graph of the mechanisms of cyanide detoxification is given in Fig. 4.8. CN Cob

Cob OH

CN

Cyanide +Hydroxycobalamin Cyanocoba lamin cycobalamin ii^^^^Cyanocc

^

Cob OH

^

1

,C02

(lungs)

CN 4^

one- carbon fragments choline

SCN Thiocyanate 3

13

-

mere a pto pyruvate

mercaptopyruvic

sodium thiosulfate

Figure 4.8

Various Methods of Cyanide Detoxification

Cyanide can either be detoxified by sulfur donating compounds forming thiocyanate or via the hydroxy cobalamin mechanism.

48

It should be evident from the explanation that detoxification is a complex process. However, proof of its existance is reproduced every time we consume food substances containing CN, a few of which were mentioned in the last chapter. Osuntokun (1970) prepared a derivative of cassava called purupuru and fed it to rats. Purupuru is prepared by soaking the root of cassava in stagnant water for two or three days thus allowing it to ferment. The root is then mashed into balls, dried and powdered. The powder is then boiled to a pasty consistency and eaten with vegetable soup. The paste from purupuru contains from two to six milligrams of hydrocyanic acid per 100 grams (Oke, 1966; Osuntokun, 1968, 1969). Nigerians may consume up to two to three kilograms (2000-3000 grams) a day. Results from Osuntokun's rat study indicate that plasma thiocyanate levels were significantly higher in rats fed the purupuru diets than in those control rats fed a normal diet. This would be expected since the high dietary intake of hydrocyanic acid would call into play the neutralization mechanisms of the body. Osuntokun was prompted to initiate the study due to a condition called tropical ataxic neuropathy, a disorder of the nervous system, common in Nigerians. The purupuru he prepared for the rats simulated the diet of most Nigerians, in order to test the relationship between ataxic neuropathy and extremely high intake of cyanide. Some mice did develop neural disorders which depended on the length of time they were fed cassava and the percentage of cassava to total food intake. It has been said that even though people on such diets do not develop cancer at the rate we do, they suffer from degenerative neurological disorders. While this may be true, we must also keep in mind the fact that Nigerians eat this purupuru on the average of three times a day every day. It may be that they over consume cyanide containing foods past the level of affecting cancer all the way to a level creating other problems such as ataxic neuropathy. Again we see the

CN

49

abuse of a substance instead of its intelligent effective use. As we saw, not all CN containing compounds are poisons, and many of them are needed for normal metabolism. Perhaps we will not have a clear idea of just how important they are until future research is done. It is of the utmost importance to distinguish raw or free cyanide from a compound containing "potential CN." Certainly one mg. of a compound containing only this "potential CN" will not exhibit the same affects as one mg. of pure or raw cyanide when administered. This, coupled with the cyanide detoxification systems of our bodies, and the specific sites of release of CN from amygdalin, make the compound considerably less toxic than some results seem to indicate. Of course, the toxicity of amygdalin like any food, drug, or vitamin depends on its proper use, not abuse!

Much

of this chapter has dealt with cyanide; first we explained how it is released from amygdalin, and then discussed the many mechanisms responsible for What we its neutralization in normal somatic cells. must now probe is how cyanide produces its affects.

Cyanide, as an antineoplastic agent, had its Later on in the beginnings with Karczag in 1927. thirties it was tested further, but abondoned due to its high toxicity and the acceptance of radiation therapy. Cyanide again appeared in scientific literature in a 1960 publication by (Brown, Wood, and Smith). They not only retested the compounds on animals, but, because of the encouraging results they obtained, extended the treatment to terminally ill cancer patients. Doctor Brown did find a change in the malignant cells when the tumors were studied histologically (their cells were studied under a microscope). His concluding remarks were, "We think we may be on the track of a tool, which, when explored, may give us a useful adjunct to the usual forms of therapy." Lea, Koch, and Morris (1975) reported results which seem to 50

indicate

cyanide's

specificity

for

malignant

cells.

They injected sodium cyanate

at doses of 125 to 250 milligrams per kilogram intraperitoneally. The affects of the cyanide were measured by the amount of labelled amino acid uptake by proteins in malignant vs. normal liver cells. The results from this experiment were staggering. Incorporation of labelled amino acids into

cytoplasmic

hepatomas was

and

nuclear

proteins

of

various

The normal liver cells of the same affected livers showed no inhibition of amino The results indicate that more acid incorporation. than an 85% inhibition of amino acids in hepatomas and kidney tumors occurred due to administration of sodium cyanate. On the other hand the normal tissues such as the brain, skeletal muscle, intestinal mucosa and regenerating liver cells of these same malignant mice suffered no visible inhibition of amino acid inhibited.

uptake of their proteins. Amino acid uptake is a sign that a cell is actively synthesizing proteins which it must do to maintain life. is If protein synthesis stopped, in any cell, marked by the inhibition of amino acid uptake, as in this study, the affected cell is not able to maintain life or reproduce, and it dies. More recently, a paper published in 1977 reports on a new compound which, when irradiated, releases cyanide at the site of the neoplasm. It

is

astounding that amidst

all

of the strides

modern medicine has made regarding cancer, researchers still have not laid the idea of cyanide as an antineoplastic agent to rest. There is a good deal of scientific rationale for the use of cyanide in cancer lesions. A molecule of cyanide (CN) carries a negative charge which is strongly attracted to positive charges on other elements. Metals such as zinc (Zn), copper (Cu), iron (Fe) and others carry such positive charges. These metals are also part of, and responsible for, activity of most enzymes in our body. If the cyanide (CN) joins with the metals found in tiiese enzymes, the 51

result

is

inactivation or modification of these

enzymes

which would lead to abnormal or even lethal cellular metabolism. Fig. 4.9 illustrates an example of cyanide combining with the iron in the hemoglobin of red blood cells to form cyanohemoglobin, which is incapable of carrying oxygen to cells through our body to keep them Cyanocobalamin is incapable of transporting alive. the lungs to the cells where it is utilized. from oxygen As a result, in the presence of cyanide, the cells are deprived of oxygen and eventually die. In the absence of cyanide, oxygen is freely carried to the cells by the hemoglobin. This complex Fe

Fe

in

in

CYANIDE + HEMOGLOBIN

OXYGEN + HEMOGLOBIN

i