Linus Pauling, Vitamin C, and the Medical Establishment (1983)

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LINUS PAULING, VITAMIN C, AND THE MEDICAL ESTABLISHMENT A thesis presented by William Burton Hamner to The Committee on History and Science in partial fulfillment of the requirements for the degree of Bachelor of Arts Harvard University Cambridge, Massachusetts March 25, 1983 ACKNOWLEDGEMENTS I would like to thank my parents for teaching me the difference between truth and falsehood, and for inspiring the interest which made this work possible. I would very much like to thank Dr. Linus Pauling for his courage and perseverance in fighting for the welfare of all people, and for his graciousness in granting an admiring but rather confused young man the chance to talk to him about his views on science and its social context. Most of all, I would like to thank my fianct, Annette, for her invaluable assistance in preparing this thesis, and for many other, better reasons. TABLE OF CONTENTS chapter

page

Introduction. 1 The Effects of Vitamin C on Disease 4 PART ONE VITAMIN C: THE BOOK Orthomolecular Medicine

7

Pauling and Vitamin C

12

Vitamin C and the Common Cold The Nature of the Evidence

27

16

Quackery, Heresy, and 35 Orthomolecular Unorthodoxy PART TWO VITAMIN C: THE MOVIE Prologue

42

The Response to Orthomolecular

45

Psychiatry The Medical Establishment and Vitamin C The Eyes of the Public

50

61

PART THREE VITAMIN C: THE CRITIC'S REVIEW The Nature of the Response 64 Conclusion

81

Appendix

84

Bibliography

95

CHAPTER 1 INTRODUCTION The controversy over the effects of vitamin C or ascorbic acid in the prevention and treatment of illness other than scurvy remained largely a scientific debate among medical researchers until Linus Pauling, Nobel Laureate in Chemistry (1954) and Peace (1962) and one of the most famous scientists in the world, wrote Vitamin C and the Common Cold.' In his book Pauling developed a theory of the optimal daily allowance of vitamin C for humans, described the implications of his theory for human health, and presented evidence that his hypothesis that vitamin C could prevent and alleviate a large percen¬tage of colds was correct. Pauling's prestige brought his book national attention and made it a best-seller. Pauling said in his book that the medical estab¬lishment had ignored the evidence about the uses of vitamin C, which confirmed the feelings of many people that the medical establishment was more interested in its profits than the public's health. Pauling also said that the Recommended Daily Allowance of vitamin C, set by the Food and Nutrition Board of the National Research Council, was much too low to maintain good health. The medical establishment responded in heat and anger to Pauling's claims. The evidence for his theory was attacked and his recommendations for the use of vitamin C were called unjustified and socially irresponsible. He was accused of being in collusion with the vitamin and health food manufacturers and promoters.

This thesis is an answer to the question of whether Pauling's charge that the medical establishment was ignoring the benefits of Vitamin C use is correct, and, if he is right, why such a situation should exist. It is also an evaluation of Pauling's development of "orthomolecular medicine," an approach to the treatment of illness that is fundamentally different from the methodology and approach of orthodox medicine. The use of very large doses of vitamin C, from one to twenty grams (g) in size, to prevent and cure the common cold is an example of orthomolecular medicine known as megavitamin therapy. The response of the medical establishment to Vitamin C and the Common Cold is representative of the its response to the concept of ortho-molecular medicine and megavitamin therapy. Their reaction is similar to that of other interests which have been challenged in the past by scientists who have gone public with their claims. In the first part of the thesis, Vitamin C: The Book, the rela¬tionship of vitamin C therapy for colds to the more general concept of orthomolecular medicine will be shown. Because the contents of Vitamin C and the Common Cold seem to have been seriously misunderstood by the medical establishment, the theoretical and practical aspects of the book will also be explained. In the second part of the thesis, Vitamin C, The Movie, the response of the medical establishment to the concept of orthomolecular medicine and its use in treating illness will be presented. As this response has been aimed at persuading the public that the posi¬tion of the public is the correct one, I shall analyse their arguments for logical and factual consistency. The results will be shown in Table 1. In the third part of the thesis, Vitamin C: The Critic's Review, I will analyse the reasons why Table I looks the way it does. I will also present some historical information pertinent to the phenomenon of Linus Pauling and the efforts of vested interest groups and the establishment to control him and others like him. Finally, the prac¬tical implications of my thesis for the reader will be explained.

1 Linus Pauling, Vitamin L. and the Common Cold, San Francisco: W.H. Freeman, 1970.

CHAPTER 2 THE EFFECTS OF VITAMIN C ON DISEASE The large, well-controlled studies of Anderson, et al in Toronto (1972, 1974, 1975)1 confirm conclusively the findings of Cowan, et al (1942), Ritzel (1961), and Coulehan (1974) that daily supplementation with vitamin C, increased during colds, significantly reduces the duration and severity of colds and less significantly reduces their incidence. The

conclusiveness of the evidence for a beneficial effect of vitamin C was established with the third trial of Anderson et al, (1975), who concluded that "Taken in conjunction with the positive results of other investigators, there is now little doubt that the intake of additional vitamin C can lead to a reduced burden of winter illness." The reduction is not as large as that postulated by Pauling (1971b) that 1 gram of vitamin C per day would lead to 45% fewer colds and 60% fewer days of sickness; Anderson, et al (1972, 1975) reported a 7%-10% decrease in incidence of colds and a 25%-30% decrease in their severity. Pauling in his second book on the subject, Vitamin C, the Common Cold and the Flu, showed that fourteen controlled trials of vitamin C in treating colds demonstrated an average 35% reduction in illness from regular vitamin C ingestion.2 1References to scientific journal articles may be found in the journal bibliography, page 95, listed by author and year. 2Linus Pauling, Vitamin Q, Ike Common Cold, and the Flu, San Francisco: W.H. Freeman, 1976. Page 182. 6 metabolization of large amounts of the vitamin, and its complete lack of toxicity for normal people, support Pauling's theory that human Vitamin C requirements were set by evolutionary factors at approximately 1 to 2 grams per day. These considerations also imply that most people should have a much higher intake of the vitamin than they get in their normal diets. The premises of Pauling's theory have not been challenged. However, the implication of his theory that Vitamin C in the amounts required for optimal health will reduce illness have been attacked. The medical establishment has insisted for years that there is no benefit from the use of large doses of ascorbic acid. This position has been held with decreasing success as the evidence for a beneficial effect of large doses has increased. Nonetheless, it has been argued that the evidence is inconclusive, that theoretical risks outweigh potential benefits, and that the use of "megadoses" of vitamin C is unjustified. These statements have been supported by fallacious arguments and by misrepresenting the evidence. It is hypothesized that the reaction of the medical establishment has been influenced by a theoretical bias against vitamin therapy, the conflict of such therapy with the platform of elitist control over health, and by the effect that megavitamin use might have on the profits of the drug industry. (72 5 The evidence supports Pauling's theory that vitamin C, or ascorbic acid, potentiates the immune reaction of the body to disease as well as his claim that it will prevent and cure a

substantial percentage of colds. The most well-documented effect of ascorbic acid is its effect on leucocytes. The review by Thomas and Holt (1978) of this effect shows that leucocyte ascorbic acid levels are severely depressed under many conditions of ill health, including viral infection, steroid therapy, and leukemia. Dietary supplementation with ascorbic acid increases the phagocytic activity of leucocytes, and appears to stimulate the production of interferon, as Pauling hypothesized.3 The oldest myth about ascorbic acid, that it is excreted after the body has attained a state of "saturation", has no basis in fact. The studies of Johnson and Silva (1934) and Ahmed (1936), and more recently, Harris et al (1976), show that no more than 30 to 50% of an administered megadose of ascorbic acid is excreted as ascorbic acid. The latter authors reported that healthy women metabolized 70% per cent of a 10 gram dose of ascorbic acid. No side effects of ascorbic acid besides a small laxative effect have been demonstrated in man. Many side effects have been postulated; however, none have actually ever been seen to occur as a result of "megavitamin C" use (Thomas and Holt, 1978; Anderson, 1979). The therapeutic and prophylactic effects of ascorbic acid, its action in potentiating the immune system, the demonstrated 3Pauling, 1970. Page 38. PART ONE VITAMIN C: THE BOOK CHAPTER 3 ORTHOMOLECULAR MEDICINE Linus Pauling became interested in the effect of large doses of vitamins in treating illness in the course of his research on the molecular basis of disease. This avenue developed as a result of Pauling's theoretical and experimental inquiry into the structure of large molecules such as proteins. In the second half of the 1940's Pauling heard about sickle-cell anemia, a disease characterized by the sickle shape of diseased red blood cells. He thought that the hemoglobin protein might be responsible, and discovered that in fact the disease was caused by an aberration on the surface of the protein that caused them to bind together into large sickle-shaped aggregations (Pauling et al, 1949). Pauling decided that he did not want to compete with his students and coauthors on the subject of hereditary hemolytic anemias. So, he says, "I decided...that I should look for some other diseases that might well have a molecular basis. I remember thinking, too, that I might as well study some important diseases while I

was at it. Cancer of course was a possibility, and also mental illness. I chose to work on mental illness, on the grounds that almost everybody was doing research on cancer while practically nobody was doing anything in the area of mental illness."' 1Linus Pauling, interview, Mother Earth News, Jan./Feb. 1978. Page 8 Pauling received a grant of $450,000 from the Ford Foundation, and set up a group at the California Institute of Technology in 1954. The group was to explore Pauling's belief that, "significant progress can be made in the attack on mental deficiency by... fundamental research employing the most powerful techniques of modern chemist-try... to understand the causes and workings of certain abnormal molecules.“2 During this period Pauling became aware of the work of Abraham Hoffer and W.H. Osmond in Canada on the use of niacin in the treatment of schizophrenia. Hoffer and Osmond had found that massive doses of niacin were often beneficial to schizophrenics, and eventually began to also administer massive doses of Vitamin C to patients, with similar positive results.3 Pauling says, "This intrigued me. I was fascinated by the idea that these substances, which you usually take in very small amounts -- I believe the Recommended Daily Allowance for niacin is 16 mg daily and for vitamin C 45 mg -- could have valuable health-promoting effects when ingested in amounts 100 or 1000 times greater than the usual intake....

My initial interest in

Vitamin C was essentially my scientific interest, in that I'm always looking for something new, something that made an impression... I began scouring the literature to find out whether other vitamins or naturally occurring substances might be effective in promoting good health when taken in large quantities. Here, I didn't go to the textbooks on nutrition and medicine.... I went to the original papers -¬the original scientific reports upon which the textbooks are based -- to see what the investigators themselves had observed. Not even what they had concluded, but what they'd observed and reported. Perhaps surprisingly, I found a good 27ime, "Genes and Mental Defectives", Sept. 10, 1956. Page 110. 3Hoffer, Abraham. Niacin TheraDv11.1 Psychiatry, Springfield: Charles C. Thomas, 1962. 9 deal of evidence to support the idea that large doses of vitamins could be clinically useful."4 "Orthomolecular Psychiatry" Pauling has said:

"The use of very large amounts of vitamins in the control of disease has been called megavitamin therapy. Megavitamin therapy is one aspect of orthomolecular medicine. It is my opinion that in the course of time it will be found possible to control hundreds of diseases by megavitamin therapy."5 In 1968 Pauling published his paper "Orthomolecular Psychiatry" in Science (Pauling 1968). This paper was the culmination of Pauling's theoretical exploration of the nature of mental disease. Orthomolecular psychiatry, or using "the right molecules in the right amounts," involves "altering the amounts of the naturally occurring substances, vitamins, amino acids, and so on, in the human body until you find what corresponds to the concentration necessary for the best of health."6 One example of orthomolecular medicine is the treatment of phenylketonuria, a disease resulting from a genetic defect which decreases the effectiveness of a liver enzyme that catalyzes the oxidation of the amino acid phenylalanine to another, tyrosine. This results in abnormally high body levels of phenylalanine, which cause among other things mental deficiency and severe eczema. The disease is controlled by reducing the amount of phenylalanine in the diet, 4Pauling, interview, 1978 op. cit. 5Pauling, 1976. Page 90. 6Pauling, interview, 1978 op. cit. 10 bringing internal levels down to normal. In "Orthomolecular Psychiatry" Pauling cited a large number of studies which showed that mental disease, particularly schizophrenia, could possibly be caused and at the very least greatly influenced by an inadequate or excessive amount of particular chemicals in the brain, and could be cured or alleviated by the use of orthomolecular methods to restore the proper balance of chemical concentrations. He hypothesized that: "A physiological abnormality such as decreased permeability of the blood-brain barrier for the vital substance or increased rate of metabolism of the substance in the brain may lead to a cerebral deficiency and mental disease. Diseases of this sort may be called localized deficiency diseases. It is suggested that the genes responsible for abnormalities (deficiencies) in the concentration of vital substances in the brain may be responsible for the increased penetrance of the postulated gene for schizophrenia, and that the so-called gene for schizophrenia may itself be a gene that leads to a localized deficiency in one or more vital substances." Pauling suggested that to treat schizophrenia, megavitamin therapy could be used raise the concentration of nutrients in the body, causing increased penetrance of physiological barriers by vital substances, and resulting correction of localized cerebral deficiencies. Pauling's proposals for the treatment of disease are different from those generally used by the American Medical Association and the American Psychiatric Association in that, first,

his methods do not involved synthetic drugs at all but natural body substances, many of which are easily manufactured; second, they allow the patient to treat himself, often to the point of being able to eliminate the costs and discomfort of continued orthodox medical treatment. 11 Moreover, the methods Pauling espouses are aimed not at controlling the symptoms but at actually correcting the defective mechanisms of the body which create those symptoms. As such, it is a more fundamental and safe method of treating disease than many of the methods and synthetic chemicals used in orthodox medical treatment. CHAPTER 4 PAULING AND VITAMIN C In March of 1966 Dr. Irwin Stone overheard a talk given by Pauling at the dinner honoring Pauling's reception of the Carl Neuberg Award in New York. Pauling's comments that he hoped to live long enough to see the discoveries of the next 15 or 20 years inspired Dr. Stone to write him, saying that he wished Dr. Pauling would live another fifty years. Stone enclosed reprints of four papers he had recently published on the relationship between Vitamin C and good health (Stone, 1965, 1966a, 1966b, 1967), and prescribed a high level Vitamin C regimen which he said would cure Pauling of colds forever. Pauling thought Stone's papers made good sense, and he and his wife began taking three grams a day of Vitamin C as Stone suggested. They discovered, somewhat to their surprise, that Stone was right. "My wife and I both noticed an increased feeling of wellbeing colds. Prior to receiving Dr. Stone's letter, I had been taking 100 milligrams of Vitamin C a day for thirty years...but this obviously wasn't enough to keep catching bad colds over those years."1 Pauling has said, "My interest in the vitamins has developed to the extent that it has partially because of the obvious failure of the medical and nutritional establishments to look at the facts. It irritates me that there should be such a situation anymore."2 ibid. 2Stuckey, W. "Plain Harold and Linus Superstar," Science Digest, August, 1976. Page 25. 13 This situation became apparent to Pauling during the period from 1966 to 1970. In November 1969 Mademoiselle magazine ran an article quoting Dr. Frederick J. Stare, head of the Nutrition Dept. at the

Harvard University School of Public Health, as saying, "Vitamin C and colds - that was disproved twenty years ago." Stare described a study done at the University of Minnesota by Cowan, Diehl and Baker (1942), misrepresenting the study's size, duration, methodology, and conclu¬sions.3 Inspired by this bias to check further into the medical literature, Pauling found a 1967 editorial in Nutrition Reviews (1967) which reviewed ten studies of the effect of ascorbic acid on colds. The editor of Nutrition Reviews at the time was Frederick J. Stare. The author of the editorial concluded that the studies showed that there was no conclusive effect of ascorbic acid in curing the common cold, nor any evidence for a general antiviral or symptomatic prophylactic effect. In six of the seven controlled studies reviewed, the authors are reported as being of the opinion that ascorbic acid seems to be more beneficial than the placebo. The editorial author claims in each case without stating why that the report is inconclusive. Moreover, in discussing the study of Ritzel (1961), the author erroneously reported only a 39% reduction in the number of days illness and a 36% reduction in the number of colds. The correct values were, respectively, 61% and 65%, or more than twice as much.4 3Pauling, 1976. Page 3. 14 Linus Pauling wrote Vitamin C and the Common Cold, out of personal irritation with a doctor who refused to acknowledge the evidence suggesting that vitamin C had a preventive and therapeutic effect on illness. In 1969, three years after Pauling and his wife began taking high dose vitamin C on the advice of Irwin Stone, he was invited to speak at the opening ceremonies of the Mount Sinai Medical School in New York. Pauling gave a short 10-15 minute talk in which he mentioned the value of Vitamin C in preventing colds as something important to medicine. Victor Herbert, one of the professors, attending the ceremony wrote Pauling "a very strongly worded letter attacking me for having made the statement about Vitamin C. He said, 'Do you want to support the vitamin quacks that are bleeding the American public of hundreds of dollars a year?' And he asked, 'Can you show me a single doubleblind study which indicates that Vitamin C has any more value than a placebo in fighting colds?" When he got around to checking the literature, Pauling found not one but six double-blind studies, in which neither patients nor doctors knew if the patient was receiving a placebo or the vitamin, which showed that vitamin C was more effective than the placebo in fighting colds. Pauling sent this information to Herbert citing specifically a paper by Ritzel

(1961). First, according to Pauling, Herbert would not look up the paper, claiming he was too busy. Upon receiving the paper forwarded him by Pauling, Herbert wrote him saying he was not impressed by the work, but giving no reasons for his opinion. A further exchange of letters followed, in which Herbert 15 claimed that Ritzel had probably, again without giving evidence, designed the study incorrectly. "The upshot of this whole thing," says Pauling, "is that I finally became sufficiently irritated by this fellow that I decided I ought to do something about it. So I sat down one summer and in two months wrote Vitamin C and the Common Cold."5. Pauling wrote Vitamin

and the Common Cold for much the same

reasons that he campaigned against the dangers of radioactive fallout in the 1950s. In each case he was motivated by his concern for human welfare, and by his irritation with an established interest group which was denying that its activities were actually hurting the peo¬ple.6 ibid. Linus Pauling, personal interview, January 1, 1983. CHAPTER VITAMIN C AND THE COMMON COLD Judging by the reaction of a number of reviewers, Vitamin and the Common Cold is an easily misunderstood book. Although it is short and clearly and easily written, the line of argument Pauling puts forward is rather complex, especially in the structure of his specific premises. Therefore, in order to clarify the nature of Vitamin

Ana the Common Cold, I will first summarize very briefly

Pauling's order of argument. Then I shall divide my analysis into two parts. Pauling builds a theory of Vitamin C action in man by synthesizing a great deal of information. Each important premise will be measured against the weight of criticism it might have received, if any, in the ten years following the publication of Vitamin

and the Common Cold. Pauling's logical addition will be

evaluated. Is it correct? Does it need to be modified? Then I shall ask, what are the implications of Pauling's theory? Pauling worked out his theory after seeing the evidence; by analyzing his case in the opposite directions we can tell if the theory he built explained the implications he saw in the studies done on Vitamin

C and colds. Having examined the theory, we will examine the evidence to see if it supports the hypotheses that Pauling draws about the effect of ascorbic acid on the common cold. 17 Finally, Pauling's recommendations for curing the common cold will be discussed, and the possible success of the regimen evaluated. It has proved difficult for the medical establishment to understand Pauling's arguments, perhaps because of the order of his exposition. He presents chapters on: the Common Cold, Scurvy, The Discovery of Vitamins, the Properties of Ascorbic Acid, Ascorbic Acid and the Common Cold, Vitamin C and Evolution, Orthomolecular Medi-cine, Human Biochemical Individuality, Vitamin C and Drugs Compared, and How to Control the Common Cold. The discussion of scurvy, vitamins and orthomolecular medicine, while informative, is extraneous to the case he is making. Biochemical individuality is a necessary consideration in evaluating the implications of the theory developed in Vitamin C and Evolution, and The Properties of Ascorbic Acid. Evidence that the theory is correct is collected in Ascorbic Acid and the Common Cold. The action implications of this confirmation are presented in Vitamin C and Drugs Compared, and How to Control the Common Cold. I. The Theory of Human Ascorbic Acid Requirements Pauling's theory of vitamin C action in man is, essentially, that evolutionary and environmental factors have created in man the need for an intake of from 250 mg to 10 g of ascorbic acid a day for optimum health. He arrives at this position through reasoning by analogy and consideration of specific evolutionary advantages to an organism which does not have to synthesize vitamins. 18 Man, the higher primates, and a very small number of other animals, including the guinea pig, are the only organisms which cannot synthesize ascorbic acid. How could this come about? Pauling draws on an extremely interesting experiment in evolutionary competition. Zamenhof and Eichhorn (1967) studied competition between two strains of a bacterium, Bacillus subtilis, which differed only in a single characteristic, the ability to synthesize the amino acid tryptophan. One strain could synthesize tryptophan; the other had lost the biochemical machinery necessary to synthesize it. When the two strains were grown together on a medium which had every nutrient except tryptophan, the mutant Bacillus strain which had lost the ability to make its own tryptophan died out. It could not survive in such a deficient environment, regardless of competition from the normal strain. However, when the two strains were grown together on a medium containing adequate tryptophan, something surprising happened. The mutant strain, which did not carry around the now superfluous machinery for synthesizing

tryptophan, survived, and the normal strain died out after an average of about 50 generations. Zamenhof and Eichhorn concluded that the burden of using the machinery for tryptophan synthesis was disadvantageous to the strain possessing this ability, and hampered its competitive ability to the extent that it failed in competition with the less burdened mutant strain. The common ancestor of man and the higher primates must have 19 the ability to synthesize ascorbic acid. If no competitive advantage was gained the mutant type would have died out. This ancient animal and its descendants could only have survived if their environment contained enough ascorbic acid. The fact that no ascorbic acid-synthesizing primates have survived is testimony to the fact that the environment contained enough ascorbic acid that the mutant strain had a selective advantage over the normal type. We can assume that any organism would not synthesize more ascor¬bic acid than it needs, that is, more than the optimal amount, for to do so would be a wasteful expenditure of energy. In order for a mutant to replace the normal type the diet must have contained at least the optimal amount of ascorbic acid; any lesser amount would be suboptimal and would offset the advantage gained by losing the synthesis machinery. The fact that most species of animals have not lost the ability to manufacture their own ascorbic acid shows that the supply of ascorbic acid available generally in foodstuffs is not sufficient to provide the optimum amount of this substance. Presumably enough is synthesized so that the combined ingested and synthesized amounts of ascorbic acid are optimal for the animal. The question remains, then, how much ascorbic acid existed in the diet of man's ancestors? There are two ways of estimating this, by analogy and by extrapolation. I have shown that there could not have been less than the amount of ascorbic acid synthesized by the normal type in the diet of a mutant if it was to survive. This 20 provides an opportunity to work backwards by analogy from the amount of ascorbic acid synthesized by other animals to the amount that must have been in the diet of man's mutant forebears. Pauling quotes Irving Stone (1966) about the amount of ascorbic acid synthesized by the rat. This creature synthesizes between 26 and 58 mg per day per kilogram of body weight. "If the assumption is made that the same rate of production would be proper for a human being, a person weighing 70 kg should ingest between 1.8 and 4.1 g per day under ordinary circumstances."1

This assumption has been questioned. Beaton and Whalen (1970) note that the extrapolation should be based on metabolic size, or w0.75 , not on weight. Beaton and Whalen note, however, that even so the amount a man should need is still substantially greater than the Recommended Daily Allowance of the Food and Nutrition Board. I calculate that the amounts necessary using Beaton and Whalen's values for extrapolation are from 1.3 g to 3.1 g per day of ascorbic acid as the amount ingested by man's ancestors. This of course assumes that the biochemical processes for which ascorbic acid are used are essentially the same in the rat as in the human being, but this assumption is quite reasonable (the rat is one of the most useful experimental animals in the testing of drugs, for example). Pauling also calculates the amount of ascorbic acid in man's ancestral diet by extrapolating from the average amount of ascorbic acid contained in 110 raw natural plant foods. The amount of 1 Pauling, 1970. Page 41. 21 vitamins contained in 2500 kilocalories worth of these plant foods, about the amount of energy required per day for a man, is found to be around 3 times the RDA of most nutrients. However, the amount of ascorbic acid in this much plant food is 2.3g, or 42 times the RDA. "Therefore," says Pauling, "I conclude that 2.3 g per day is less than the optimum rate of intake for the adult human being."2 This conclusion only holds, however, if we assume that man's ancestors ate nothing but vegetables. However, if we assume that only 50% of the ancestral diet was fresh vegetables, the rest being meats, nuts, and grains, then we are still left with evidence that our ancestors received over a gram a day of vitamin C in their food. The amount is lower still if the fresh vegetables were generally of types low in Vitamin C content. However, Bourne (1949) has noted that gorillas receive about 4.5 g of ascorbic acid per day in their diet; this lends weight to the hypothesis that man's ancestors also had a relatively high vitamin C intake. In considering the amount of Vitamin C that is optimal for an individual, Pauling notes that biochemical individuality is capable of producing widely-differing responses to the same amounts of a substance. To support this he describes the work of Williams and Deacon (1967), showing that there is at least a twenty-fold range in the Vitamin C needs of variability in humans of the amount of Vitamin C needed to prevent scurvy, a variability which is due possibly to "conditioning" or increased metabolism of Vitamin C due to a period 2Pauling, 1970. Page 63. 22

of high intake, or to congenital diseases which reduce the amount of Vitamin C which is required to prevent scurvy. This evidence, he concludes, also points to a twenty-fold variation in optimal allowances of Vitamin C in humans. Pauling concludes: "The optimum daily intake of ascorbic acid for most human beings lies in the range of 2.3g to 9 g. The amount of individual biochemical variability is such that for a large population the range may be as great as from 250 mg to 10 g or more per day"3 It has been reported that some physicians question this conclusion, arguing that man is capable of adapting to different environments, which provide different nutrients .4 But a moment's reflection on human history will convince the reader otherwise. It is not possible that our vitamin C requirements could have adapted to keep pace with the rapid change in diet since the Industrial Revolution, when whole populations first started depending exclusively on foods supplied by others often days after its harvesting. As can be seen, Pauling's theory of human vitamin C requirements is an approach which can be used for determining the necessary daily allowances of all vitamins. Pauling saw evidence which inspired him to look at Vitamin C specifically, not just as one of a class of substances whose deficiency induces disease. The general case for Vitamin C is not that it reduces the incidence and severity 3Pauling, 1976. Page 63. 4O'Neil, P. "Vitamania". Life, September, 1971. Pages 72-80. 23 of colds, but that most people today are suffering from a severe vitamin deficiency induced by rapid changes in dietary habits. Given such a situation, it is hardly surprising that illness in the population can be reduced by raising the level of nutrition back up to where it was optimized by evolution. The evidence for the reduction of colds is not a conclusive argument in itself; an explanation why such is the case must be acceptable. Equally, the argument cannot be negated by merely ques-toning the validity of the evidence. If the general theory still stands, then all that a critic can prove is that a particular piece of evidence does not confirm the predictions of the theory. This by no means invalidates the theory, especially if the theory is of the statistical evolutionary kind that Pauling has developed. It usually just forces proponents to find another piece of evidence to confirm it. II. Confirmation of the Theory The Pauling theory of human vitamin C requirements is prior to the confirmation of that theory by the evidence he supports it with. Now we need to look at the implications of the theory to see if the evidence confirms it.

Pauling notes in the chapter on the Properties of Ascorbic Acid that ascorbic acid has been shown to be essential to the formation of the colloidal substance which serves as a pliable cement to bind tissue cells together. In the absence of ascorbic acid the cells tend 24 to separate, causing the hemorrhaging typical of scurvy symptoms. Ascorbic acid is necessary for the healing of wounds and the formation of strong scar tissue, as would be expected from its cellular binding properties. It has been used in large amounts for the treatment of burns, injuries, infections, rheumatism disease, allergies, back troubles, and infectious diseases. Pauling states: "Part of the mechanism of protection against disease is the destruction of bacteria by certain white cells in the blood, the phagocytes. In order to be effective in this way, the phagocytes must have a certain concentration of ascorbic acid in them. This fact provides a partial explanation of the effectiveness of ascorbic acid in providing protection against bacterial infection.... I have formulated the hypothesis that the effectiveness of ascorbic acid in providing protection against virus diseases results from its function in the synthesis and activity of interferon in preventing the entry of virus particles into the cells."5 Pauling notes that his hypothesis has not been tested; however, some form of functional hypothesis is necessary to explain the evidence that ascorbic acid increases resistance to viral infection. It has been claimed that ascorbic acid is a panacea (Stare, 1971) a new nostrum (Passmore, 1971), that is, a magic bullet whose advocates think it can cure anything. "One may ask how it is that Vitamin C can protect against so many diseases. I think it probably does this largely ¬though perhaps not entirely - by potentiating the body's natural protective mechanisms. There is much evidence for this. One of the most interesting studies along this line was carried out by three people - R.H. Yonemoto, P.E. Chretian, and T.F. Fehniger - at the National Cancer Institute. These 5Pauling, 1970. Pages 37-38. 25 workers studied the rate at which new lymphocytes - white blood cells are produced by a person... and they found that people who were given five grams of Vitamin C per day for 3 days showed a doubling in their rate of lymphocyte production."' Obviously, one of the most important functions of vitamin C is in potentiating the reactions of the immune system. Again, we need to relate this to Pauling's theory of Vitamin C

requirements. If it is true that our immune system evolved with a daily intake of over a gram of ascorbic acid, which seems reasonable, then an intake at the current RDA of 45 mg puts the immune system under a severe handicap. From the study Pauling describes above and the known information about the requirements of ascorbic acid for proper phagocytic activity, an intake at the amount of the RDA forces the body to function with its immune system at less than half-strength. Further, we should expect that such an intake would in general cause the intercellular cement to be weaker, and cells thus more susceptible to invasion by viruses and bacteria. III. Ascorbic Acid and Colds If Pauling's evolutionary theory is correct, then a widespread increased intake of ascorbic acid should lead to a decrease in the number of infections in a population. Pauling describes two controlled trials which show that an increase in vitamin C intake caused a substantial decrease in the number and severity of colds in the study group. In the third appendix to Vitamin D_And. ,the Common Cold 6Pauling, 1978, op. cit. 26 Pauling describes the results of eight more studies which show that administration of ascorbic acid in varying amounts generally increased resistance to cold viruses. In response to the criticism of his evidence by reviewers Paul¬ing published a paper on "The Significance of the Evidence about Ascorbic Acid and the Common Cold" (1971). Pauling averaged the P values for the results of 14 double-blind trials of ascorbic acid and concluded that the evidence rejected the null hypothesis that ascor¬bic acid has no effect on colds. This is an interesting change in Pauling's argument - the emphasis has changed from a positive state¬ment that high-dosage vitamin C can prevent colds to a simpler proof that Vitamin C has an effect on colds and should therefore be recom¬mended for preventing and treating them. Although the evidence does not show that Vitamin C will cure a particular cold, it will help prevent and alleviate them. The facts that it is quite harmless and reasonably efficacious justify its use. CHAPTER 6 THE NATURE OF THE EVIDENCE Because the controversy over the effects of megadoses of vitamin C has concentrated on the evidence Linus Pauling has gathered to support his thesis that it should be widely used to prevent and treat illness, an explanation of the nature of his evidence is required. It will be seen that the controlled trial, the only widely-accepted test of therapeutic effects, is unlikely to show that vitamin C use can prevent or cure all colds because of the inherently idiosyncratic response of individuals to specific vitamin C doses. The implications of this for the vitamin C controversy will be discussed.

Pauling relies on two studies, those of Cowan, et al (1942), and Ritzel (1961), for proof that vitamin C can prevent and alleviate the common cold. Both of these studies were controlled trials with randomization of the subjects. Speaking of methods for evaluating the effect of a substance on illness, Dr. Henry E. Simmons, director of the FDA's Bureau of Drugs, asserted, "If I had to pick one method, I would choose the controlled trial. It provides the best assurance of efficacy that I know how to make late in the 20th century"1 1Harvey, J.H., American Self-Dosage Medicines, Laurence, Kansas: Coronado Press, 1974. Page 54. 28 The best kind of controlled trial in therapy evaluation is the double-blind trial, where neither the patient nor the administering physician knows whether the patient is receiving the actual therapeutic agent or a placebo. All the records are kept by a third party who is not associated with the patient-doctor interaction. This is the only form of trial which can eliminate the placebo effect, where a patient or doctor is so convinced that treatment is taking place that sometimes astounding recoveries can occur even when the therapy is fake. Studies done in England and the U.S. have shown that the power of placebos is amazing . Rachman and Philipps, in their book psychology and Medicine, describe several studies which show that large numbers of people experience powerful effects, beneficial or adverse, when they take inert substances disguised in the form of pills. Also, there is independent evidence that the attitude of the prescribing doctor to his tablets and the way in which this attitude comes across to the patient are in fact important factors in the patient's reaction to placebos.2 Dykes and Meier (1975) note that this is an especially important consideration in those situations where evaluation depends substantially on a subjective report by the patient, or where there is a substantial element of judgement required of the investigator: "The evaluation of symptoms of the common cold involves both of these elements, and it has been generally recognized that 29 only carefully controlled studies can provide useful evidence on the prophylaxis and therapy of this condition.... Because of the great variability in experience with colds from one subject to another, and because of the considerable subjectivity inherent in the evaluation of a cold, even a slight fault in experimental design or procedure may open the way to a bias of considerable magnitude."

The question of significance of the results of a study is also important. The highest generally accepted level of statistical significance is when P = .05, that is, when the probability that a deviation as large as the one observed would not occur more than five times in a hundred if there were no differences due to the treatment. As Pauling (1973) has said, however, "It is not necessary that the results of a study be significant at the customary level of P =.05 (which is quite arbitrary) in order to constitute evidence." If the probability that a deviation larger than the one noticed in a controlled study is greater than .05, that does not mean that the deviation is not due to the agent being tested. For example, if the P level is 0.10, a level at which most investigators would reject the evidence as too uncertain, the probability that the agent was responsible for the deviation is still 90%. This is a high level of probability. As Pauling says, though, investigators have arbitrarily made the demanded level of probability 95% or higher, so that they can be as certain as possible that the agent under investigation is responsible for the effects seen. This is important to the vitamin C controversy because almost every study that has ever been done on the effects of vitamin C has shown some effect of the vitamin. However, in some of the studies 30 the effect has not been significant at the P < .05 level, and the investigators have concluded that no effect has been shown. For example, Anderson, et al (1972) reported that their study of the effect of one gram per day and more during illness of vitamin C showed a 7% decrease in the number of colds of the vitamin group as compared to a placebo group. This difference was not statistically significant, as the probability that such a result would occur at random was about eight times in a hundred. This does not mean that no effect was shown; however, the results of Anderson, et al were cited as proving that vitamin C does not decrease the incidence of colds (Thomas and Holt, 1978). There is general agreement that in order to test the effectiveness of ascorbic acid the best studies are those which involve large numbers of people over extended periods of time (Anderson, 1974; Dykes and Meters, 1975). Such studies minimize the probability of individual variations affecting the results. What should be expected from such studies? Pauling's theory of Vitamin C requirements assumes that a daily intake of 2 g per day of Vitamin C is less than optimum for most people, and that the optimal amount may range from .250 mg to 10 g per day. No studies have been done which have given subjects more than two grams of vitamin C per day. Thus according to Pauling's theory, which has not been challenged, no studies have been done which have given optimum amounts of Vitamin C to even half of the people involved. Hughes (1977) has made the only acknowledgement of this: 31

"It would appear that no matter how perfectly one structures a survey of this type the results are unlikely to approach an all-or-none type of response. A number of factors could contribute to this situation: (1) Ascorbic acid could be effective against only a small proportion of the viruses involved in the common cold: (2) a genetic factor could establish a biochemical individuality in terms of an infection-ascorbic acid response; (3) the relationship could be of a secondary or "derived" nature involving one or more of the AA metabolites - about which very little is known - or a quite separate 'mediator' molecule." All three of Hughes' suggestions are quite reasonable. I have a feeling, though, that his third suggestion concerning AA metabolites may be very important. Most people believe that Vitamin C above the body's daily needs is excreted in the urine. This belief has been fostered by the medical establishment, in direct contradiction of the evidence (Abt and Farmer 1938; Stare, 1971; Wolf, 1981). The studies of Johnson and Zilva (1934), Ahmed (1936), and Harris et al (1976) show that when 1 g to 10 g of Vitamin C is administered, only 30 to 50% of the vitamin is excreted. Harris et al administered 10 g of ascorbic acid a day to healthy women, and found that not more than 30% was excreted. Thus at least 7 grams must have been metabolized. Harris (1979) states that increasing the dosage of does not increase the blood plasma concentrations of the vitamin. Hume and Weyers (1973) show that the amount of leucocyte (white blood cell) vitamin C does not increase, regardless of dosage size.

This inconsistency is confusing; what happens

to all that vitamin C? It must be metabolized, but, as Hughes says, very little is known about such metabolites. If Pauling's theory of Vitamin C requirements is not correct, then a theory must be 32 developed to explain why the human body can metabolize five grams of Vitamin C a day. In his conclusions about the evidence for a beneficial effect of Vitamin C on colds Pauling cited Dr. Edmund Regnier's observation that a person must not suddenly stop taking large doses of Vitamin C (Regnier, 1968). This is because of a well known rebound effect: when the body adjusts the metabolization rate of vitamin C upward to compensate for additional vitamin C in the diet, as the above discussion shows it does, sudden cessation of vitamin supplementation causes the body pool of Vitamin C to be used up faster. T.W. Findley (1976) has raised this point in connection to large-scale field trials: "If one accepts Pauling's reasoning that cessation of daily intake of vitamin C results in abnormally low levels of the vitamin haphazard ingestion of the tablets may well prove deleterious to the health with increased susceptibility to illness on the days when blood levels are low after failure to ingest the daily dose. Any illness might lead to failure to ingest the vitamin at a time when it is most effective, the early stage of illness; this may be also be the time when failure to take Vitamin C could be actually unhealthy."

As Pauling writes in Vitamin L. and the Common Cold, "1 g taken at once when the first sniffle is noticed may protect, 1 g two hours later may fail to protect".3 Most of the largescale trials of vitamin C were done by giving people tablets to take in their homes; results were evaluated using cards on which the subjects described the incidence and severity of colds. One must suppose that the vitamin 3Pauling, 1970. Page 102. 33 and control groups are equally likely to miss a pill or two, or a few days worth of doses. Both groups should have experienced the same likelihood of rebound effects from missing a dose. If a benefit from ascorbic acid is shown then this consideration implies that the ascorbic acid would have been even more effective if every dose was taken on schedule. However, if no effect of ascorbic acid is shown, there is a possibility that each of the test groups missed enough doses to cancel out the effect of the ascorbic acid. This conclusion is by no means proven. However, it cannot be discounted. The medical establishment has insisted that well-controlled double blind studies are the only way of determining whether ascorbic acid has an important clinical effect on colds. According to the theory of vitamin C requirements such trials are unlikely to give even half of a typical population the optimum amount of protection against colds. The doubtful ability of a large population to take all its pills all the time creates the possibility of rebound effects leaving a delinquent subject more than usually susceptible to illness. I conclude that Hughes' hypothesis is correct. It is impossible for such a study to show allor-none response; the doses are too low, and the trial structure is unable to cope with the unique characteristics of ascorbic acid. Significant effects as compared to a placebo can be shown, but they are unlikely to be large, for the same reasons. This seems to imply that a substantially different approach will have to be developed to evaluate accurately the effectiveness of vitamin C in preventing and alleviating illness in large populations. At the least, the criteria demanded in the testing of drugs cannot be used without modification in the evaluation of vitamins. In its enthusiasm to show that vitamin C is useless in fighting colds the medical establishment has often translated "no statistically significant effect" as "no effect". This seems to be a necessary ruse on their part, for complete honesty would demand that they admit that the overwhelming majority of studies done on the effect of Vitamin C in fighting colds have shown some real effect. In concluding my discussion of the nature of Pauling's evidence, I must make one thing very clear. Pauling has made no errors in reporting studies or the statements of researchers. He has made errors I think only twice: in extrapolating the optimum amount of vitamin C in rats to man by weight rather than metabolic size (the correct method still supports his conclusions); and in assuming that man's early ancestors were herbivorous and not

omnivorous (again, the difference does not affect his theory). I have not found any others, nor has the medical establishment, who would very much like to do so. The theory of the Vitamin C requirements of man has not been challenged; orthodox medicine has been limited to claiming that his theory is unproven and his recommendations unjustified. CHAPTER 7 QUACKERY, HERESY, AND ORTHOMOLECULAR UNORTHODOXY Cortez F. Enloe, editor of Nutrition Today, wrote in a 1971 editorial that he had been at a recent conference where Vitamin _Q And the Common Coati was the rage of conversation. Not one person, he found, "would admit to having even read the book.". Enloe found much to admire in Pauling's "heretical little book"; his peers obviously were not willing to stoop to an acquaintance with "heresy." Vitamin .Q and the Common Cold has been characterized as a sales pitch by a paid tool of quacks (Bing, 1971; Jukes, 1975b; White, 1975b), and Pauling has been called socially irresponsible for writing it (Stare, 1971). The fact that a Nobel Prizewinner should be engaged in such activities leaves some sadly shaking their heads (White, 1975). Given the rigor with which Pauling makes his case, and his consistent accuracy and comprehensiveness of fact, we must ask what is meant by "unorthodox" here. The tenpoint profile of health quackery developed by Prof. Young describes the fundamental nature of most of the health unorthodoxies of the past. Therefore, we may use this tool to see if the definition of unorthodoxy as applied to Vitamin L, (Young, J.H., "Laetrile: A Historical Perspective", in G.E. Markle and J.C. Petersen, politics, Science, and Cancer: The Laetrile Phenomenon. Boulder, Colorado: Westview Press, 1980, for the American Association for the Advancement of Science. Quotations explaining headings are Young's. 36 and the Common Cold carries the same implications as it did for the "toadstool millionaires." 1. Exploitation of fear: "Quacks have traditionally scared their victims with disturbing language, frightening pictures, and grim statistics, stressing pain and threat of death." Objectively, Pauling's work does not fit this category. He is clinical in describing the symptoms of colds and scurvy, and quite matter-of-fact in his estimations of the annual economic costs of the common cold. Promise of painless treatment and good results: Pauling not only promises that ascorbic acid is virtually painless and certainly harmless, but that the literature shows that it works. He also invokes the promise of Utopia, as a world

without colds would be to anyone in the middle of a bad one. To attain Utopia, he does propose both a plausible mechanism and historical precedence for the complete disappearance of colds from a population. However, Pauling does not claim that ascorbic acid is a certain cure for colds. He claims that it raises the natural powers of resistance, so that a greater proportion of the people would never get colds, and most of those that do should get better faster. Claims of a miraculous scientific breakthrough: "Marvelous new discoveries are dime-a-dozen in the literature of quack promotions." 37 Pauling does nothing except present the existing evidence for public scrutiny, and offers more evidence to support the implications it has. 4. One Cause/One Therapeutic System "Quacks often win allegiance to their doctrines by promising to end confusion and doubt and to make complexity simple and comprehensible to the untutored mind. Disease, the quack says, has but one cause. One treatment, therefore, is all that is needed to fight it." Ascorbic acid is an essential nutrient which potentiates the body's immune system. Use of large doses, Pauling says, will make it much less likely that one might catch most diseases., Specifically, low levels of ascorbic acid have been shown to increase susceptibility to infection, and high levels to reduce it. Certainly Pauling never says that any disease but scurvy is caused by ascorbic acid deficiency. 5. The Galileo Ploy: "The unorthodox say the orthodox are wrong; just as earlier critics condemned pioneering explorers, inventors, and scientists. We are, the unorthodox assert, today surrounded by blind men but are destined to be the heroes of future generations." Pauling wrote his book because he felt that the orthodox establishment was deliberately holding a blind eye to the evidence. However he never equates his efforts with any kind of self-gratification other than that of seeing the health of more people improve. It should be remembered here that Pauling is the only person to have won two unshared Nobel Prizes. He has been accused of being a lover of 38 the limelight;2 if such is his reason for publicizing megavitamin therapy then we must also assume that such was his reason for discovering the cause of sickle-cell anemia, the complementarity of antibodies and antigens, the general theory of anesthesia, and his 40year campaign for nuclear disarmament, all of which brought him national attention. 6. The Conspiracy Theory:

"The scientific establishment doesn't dare recognize the validity of my great discovery, the quack claims, for it will undermine their power and prestige and eliminate their jobs." In considering the reasons for the lack of enthusiasm among physicians for an effective, harmless, cheap substance, Pauling says, "Another factor has probably been the lack of interest of the drug companies in a natural substance that is available at a low price and cannot be patented" In 1960 Pauling called for socialized medicine and condemned the prevalence of economic self-interest over concern for the patient's welfare in the AMA.14 A possible economic conspiracy is implied by Pauling; he also suggests fear of toxicity and preference for sure cures as sources of bias. An argument that will be advanced later in the discussion of orthodox resistance to megavitamin therapy will show a political difference between medicine and other sciences which makes Pauling's implication one of professional rather than purely scientific conspiracy. 2Stuckey, op. cit. 3Pauling, 1970. Page 4. New York Times, June 1, 1961. 39 7. Shifts to adjust to circumstances: "Quackery has never felt obliged to retain a given posture if some change might offer greater prosperity or safety. In the 19th century a cold cure that wasn't selling became a stomach remedy and reaped huge profits." So far no medical evidence has appeared to alter Pauling's opinion that he is right;5 it is unlikely that any will, if his theory of evolutionarily-developed optimal intakes is correct. 8. Reliance on Testimonials: "Through history the testimonial has been a major weapon in the arsenal of quackery. When someone just like you or me says, with urgent sincerity, 'I was cured,' the persuasive power ranks high." Despite claims by orthodoxy that Pauling’s theory relies mainly on testimonials (Passmore, 1971; Stare,1971; Medical Letter, 1970; Thomas and Holt, 1978), the only such evidence is his statement in the introduction of Vitamin S. and, the. Common Cold that taking 3 g a day of vitamin C made him and his wife feel better. Pauling also does not claim that he has been cured of colds, although he says he thinks he has beaten one or two off with vitamin C.6 9. Distortion of the ideas of freedom: "Before food and drug laws were enacted, quacks waved the banner of 'freedom' to smear criticism aimed at them by physicians and pharmacists." The freedom to use megavitamin therapy for serious illness has

Pauling, personal interview, January 1, 1983. Pauling, 1978, op. cit. 40 been fought for by unorthodox medical and political groups.? These groups have been instrumental in preventing the Food and Drug Administration from classifying vitamins as drugs or requiring limits on their strength. Pauling has supported these political actions, but denies that he has any association with these groups beyond the sharing of a belief in the right of people to know the facts and to maintain their health themselves.8 The president of the American Medical Association has said that Pauling is a spokesman for one of these political groups (White, 1975), a charge that was obviously false and seriously implicates its author (Sackler, 1976). 10. Large sums of money are involved: "It was Oliver Wendell Holmes who termed 19th Century nostrum vendors 'toadstool millionaires'. They might not make a million, but money was their goal." Ascorbic acid is not patentable and is relatively cheap. It is made in the U.S. by only four companies, the largest of which, Hoffman-Larouche, Inc., supports the Linus Pauling Institute of Science and Medicine with $100,000 per year, which is about 5% of its operating budget.9 Of course, money is also the objective of the drug industry which makes thousands of chemicals for the treatment of disease, and of many doctors and health specialists. Professor Young's profile of health quackery does not fit Vitagam

Ana The Common cold at all well. Only in one category,

7Marckle and Petersen, 1980. Page 161. 8Pauling, 1970. Pages 105-109. 9Linus Pauling, personal interview, January 1, 1983. 41 conspiracy theory, does Pauling echo the arguments of health promoters and quacks of the past. Pauling leaves it to Dr. Douglas Gildersleeve to make the accusation; Gildersleeve, as an insider, describes his personal experiences that led him to his conclusion that the medical establishment is resisting vitamin use because the drug industry, which advertises in medical journals, and doctors themselves stand to lose money if people take vitamins instead of patent medicines." Russell V. Lee, Professor of Medicine emeritus at Stanford University, has noted that "in making his points, [Pauling] has followed proper scientific guidelines -- review of the

literature, formulation of a hypothesis, experiments (on himself) to validate the nontoxicity of these large doses, and conclusions based on these data" (Lee, 1971). As there does not seem to be anything scientifically unorthodox about Vitamin sand I. Common Cold, I can only conclude that the term as used by the medical profession can only mean "Counter to our professional interests." 10Pauling, 1970. Pages 48-49. PART TWO VITAMIN C: THE MOVIE CHAPTER 8 PROLOGUE The debate over Pauling's evidence is one of "significance" and "conclusiveness." Both of these are terms of opinion which are the prerogative of any person. My own concept of what constitutes "good" science is firmly idiosyncratic; therefore, in tracing the history of the scientific debate over the effects of vitamin C my definition of "good" science will be merely that which is not logically fallacious. That is, I shall limit myself to examining whether sources are cited or described properly, whether the author contradicts himself, if experiment design is reflected in the conclusiveness of the author's opinion about his results, whether generalizations are supported, and whether the author has his facts straight. I assume an author is correct until and unless he is she is shown to be wrong, by a sound argument. A sound argument is any argument which S. Morris Engel, author of With Good Reason: An Introduction

Informal Fallacies,-1- would

not want to put in his book as an example. Engel defines many types of fallacious arguments which are used to justify unfounded conclusions. One of these fallacies is of particular relevance to the controversy over the effects and use of vitamin C in alleviating illness. Engel defines the fallacy of an appeal to ignorance as an 43 assertion that an opponent's inability to disprove a conclusion is proof of the conclusion's correctness. He gives as an example: "The chiropractors have failed utterly in their attempts to establish a scientific basis for their concepts. This ques-

tin can be therefore settled once and for all. Chiropractic has no basis in science."2 In other words, if you can't prove you are right, you must be wrong. This argument assumes first that the speaker knows what is "right", second, that he can correctly discern proof, and third, that the other will never be able to prove that he is right. In a controversy over health, however, a corollary to this fallacy exists which can justify it. If a proposed therapy has not been evaluated for safety, or is known to be toxic or dangerous, it is logical to assert: "Since you can't prove you are right, and the safety of your therapy is in question, you should not be allowed to dispense your therapy to un-informed people. If you can prove that it is effective, then its benefits must be weighed against its risks; if the balance is positive, then you are right to dispense the therapy." To evaluate whether this argument may be used to control something like the use of megadoses of Vitamin C, one thing, safety, must be known. The evidence of safety is prior to that of efficacy; of course, if a drug is definitely useless it should not be recommended even if it is safe. Whether "chiropractic" has a place in science is different from whether it has a place in medicine, as I have shown. 2Engel, Page 125. 44 Whether Vitamin C has a basis in medicine depends on its safety and efficacy. In describing the arguments used in the debate I refer definitions of informal fallacies to Engel's book. I will try to define them as best I can. CHAPTER 9 THE RESPONSE TO ORTHOMOLECULAR PSYCHIATRY Pauling's paper "Orthomolecular Psychiatry" (Pauling 1968) drew a response which in substance and style foreshadowed the response to Vitamin C and the Common Cold. Donald Oken, of the National Institute of Mental Health, said in a letter to Science: "The article, ‘Orthomolecular Psychiatry' illustrates elegant¬ly the pitfalls which occur when an expert in one field enters another area. With his characteristic brilliance, Linus Pauling describes a biochemical mechanism which could be responsible for some forms of mental illness (or, indeed, for illness of many other types)...Unfortunately for Pauling's thesis there is no adequate evidence to back up his view... The published reports suggesting that vitamin therapy may be useful in mental illness, several of them cited by Pauling, uniformly display serious methodological flaws,...which render them worse than useless." (Koen, 1968). Oken implied that Pauling's proposed therapy would increase the suffering of the mentally ill: "The suffering of the mentally ill and the distress of their friends and families creates a

situation where in every new 'finding' appears to be a 'breakthrough' which is grasped as a straw." Pauling is thus implied to be guilty of encouraging the hopes of these people with false promises. Finally, the conclusion that Pauling doesn't know what he's talking about: "The article is replete with statements of personal belief and opinion. If the topic were molecular biology, one could readily accept such views.... But it is unfortunately evident that he is unfamiliar with the subtleties of methodology in a field in which he is untrained.... It would be regrettable 146 if the impact of his prestige and brilliance in other fields led readers to believe otherwise and to accept unwisely what remains on the basis of current knowledge, a wild speculation." As evidence of Pauling's ignorance of the field, Oken discusses the work of Ackerfeldt (1957), which Pauling reviews. Ackerfeldt's studies, he says„ have "become a classic case in the social psychology of mental health research; it is used as a proto-typical example in teaching residents and students the dangers of lack of proper attention to controls." But does Pauling cite Ackerfeldt's authority? No, in fact, he does not. Pauling describes how researchers investigating Ackerfeldt's claim of discovery of a new test for schizophrenia found that a positive result to the test "is due to a smaller concentration of ascorbic acid in the serum of schizophrenics than of other persons. This difference has been attributed to the poor diet and increased tendency to infectious diseases of the patients, and has also been interpreted as showing an increased rate of metabolism of ascorbic acid by patients" (Pauling 1968). In the one example Oken gives of Pauling's inability to understand the methodology of disciplines other than his own Oken ignores both what Pauling actually said in his paper and the important implications the Ackerfeldlt case actually has for Pauling's thesis. Even more damaging to Koen’s case is the fact that he ignores the conclusions of the authors who he offers to support his claim that the studies relating possible vitamin therapy to treatment of schizophrenia 117 "uniformly display serious methodological flaws... This point has been well-documented by both Kety (1957) and Benjamin (1958)." Kety (1957) says: "It is not surprising that a dietary deficiency has been found to explain at least two of the biochemical abnormalities recently attributed to schizophrenia. It is more surprising that the vitamins and other dietary constituents whose role in metabolism has become so

clearly established, should so often be relegated to a position of unimportance in consideration of the intermediary metabolism of schizophrenics." The paper by Benjamin (1958), far from providing the serious critique of methodology Oken claims, is a dedication ceremony address which gives a condensed history of biological research in schizophrenia and bemoans the reductionist attitude of biologists who seek a purely physical causal mechanism for schizophrenia. Benjamin also describes a behavioral reaction of psychologists and psychiatrists which Oken obviously should have read more closely: "It is impressive to see how frequently the response to some over-simplified biological hypothesis about behavior is not simply an appropriate skepticism or an impulse to give evidence to the contrary, but rather an angry and anxious rejection, a response as to a threat. Clearly it is often so perceived, as a threat on a social level to our group prestige and coherence and on an individual level to our convictions and sometimes even to our bodily integrity. Stop it, you're taking away my tools!" Oken seems to have been so angered by Pauling's challenge, and so anxious to reply, that he forgot to check if either his references or his examples actually supported the charges he made against Pauling. It can be seen that Oken's response seems to be caused by pro48 fessional xenophobia; the claim that Pauling is out of his field is a defensive reaction against an intrusion that threatens to overturn the foundations of Oken’s methodology. Pauling as might be expected replied to Oken's accusations directly, (Pauling 1968a). He lists the organizations which have provided the funding for his 12 years of research on the molecular basis of mental disease, and his awareness of the wide opposition to his theories expressed by Oken. In response to Oken's insinuation that he is increasing the suffering of the ill by giving them false hopes, Pauling pointed out that almost all the synthetic drugs used in treating mental illness have pronounced side effects. However, the situation is different for ascorbic acid, nicotinic acid, nicotinamide and other natural nutrilites required for life. These materials, Pauling says, "are nontoxic (as safe and nontoxic as ordinary sucrose and sodium chloride). They are cheap..., and they have fewer side effects than the drugs that are ordinarily prescribed. For each mental patient there is a significant probability that improvement in health would result from the provision of the optimum amounts of nutrilites, in addition to whatever other therapy the physician might propose.... I believe that a psychiatrist who refuses to try the methods of orthomolecular psychiatry, in addition to the usual therapy, in the treatment of his patients is failing in his duty as a physician."

This is the most powerful argument Pauling has in defense of vitamin therapy for illness. He has repeatedly insisted that, although the positive evidence for vitamin therapy may be inconclusive , there is no reason not to try it; the treatment can only do good, and thus arguments about statistically significant success rates or of conflicting reports of success are practically irrelevant. In July 1973 an American Psychiatric Association Task Force of five physicians and one consultant issued a 54-page report titled Megavitamin and Orthomolecular Therapy in Psychiatry, which purports to present both theoretical and empirical reasons for completely rejecting the basic concept of orthomolecular psychiatry. Dr. Pauling's response to the report (Pauling 1974) shows that Dr. Oken's peers have not noticed that Oken's arguments have a rather strong smell to them. The Task Force members, like Oken, seem to believe that the smell is the invigorating scent of ruthless and damning logic. They have carefully applied Oken's factual and logical consistency to their task with only slightly less obvious passion, and their report has lost none of the odor of Oken's criticism of "Orthomolecular Psychiatry." CHAPTER 10 THE MEDICAL ESTABLISHMENT AND VITAMIN C The response of the medical establishment to Vitamin. Sc _and Ilk Common ColA, as I have said, has concentrated not on Pauling's theory of human vitamin C but on the evidence he has gathered to confirm it and on the implications his theory has for the health of the public. Pauling's evidence for an effect of vitamin C on colds rests mainly on the controlled trials of Cowan et al (1942) and Ritzel (1961), both of which showed a substantial reduction in the number and sever¬ity of colds in groups of subjects who took vitamin C as compared to groups who took a placebo. The medical establishment has not tried to objectively evaluate Pauling's evidence, but instead has tried to discredit it by falla¬cious arguments in order to advance their conclusions that vitamin C is worthless and should not be recommended to the public. The first method they have tried has been to say that the studies on which Pauling has relied were not properly done, and thus can be disre-garded. The foundation of this argument rests on the specific cri¬teria required for the acceptance of evidence pertaining to proposed therapeutics discussed in the chapter on the nature of Pauling's evi-dence. Having been unable, despite great efforts, to invalidate Pauling's evidence, the medical establishment has turned to the ques51 tion of toxicity in order to advance their conclusion that the risks of vitamin C use are greater than the benefits. This tactic has used evidence that vitamin C might cause

unpleasant side effects to sup¬port the claim that its widespread use cannot be recommended. In making both of these arguments the medical establishment, represented by the American Medical Association and its journal (JAMA), orthodox nutritionists led notably by Dr. Frederick J. Stare, editor of Nutrition Reviews, the Food and Nutrition Board of the National Research Council, and the Food and Drug Administration which follows the Board's recommendations, have misrepresented the facts, used fallaciously ambiguous statements to misrepresent the evidence, resorted to special pleading in order to discredit the evi¬dence, and, as Pauling claims, deliberately ignored the beneficial effects of vitamin C in the treatment of disease. The weakness of the arguments advanced by the medical establish¬ment has caused Dr. Abraham Hoffer (1971) to observe: "[These critics] use two sets of logic. Before they are prepared to look at Dr. Pauling's hypothesis, they demand proof of the most rigorous kind. But when arguing against his views, they refer to evidence of the flimsiest sort for the toxicity of ascorbic acid." I. The Nature of the Response In order to characterise the response of the medical establish¬ment to Pauling's book and the interest it created, I have divided their statements into misstatements of fact, fallacies of ambiguity, instances of special pleading, and irrelevant arguments designed to 52 disparage Pauling's interpretaton of the evidence. The relationships of the arguments and their natures are summarized in Table 1. Misstatements of Fact: Under this heading I have put incorrect conclusions, misrepresentations of Pauling's work, ad hominem attacks on his motives, incorrect citation of sources, correct citation of incorrect sources, and unfounded generalizations. This is by far the largest type of response to Pauling's arguments and to the general issue of whether or not vitamin C can prevent and alleviate colds. Some researchers have misrepresented the results of their own studies (Cowan, et al, 1942; Glazebrook and Thomas, 1942; Karlowski, et al, 1975); others have incorrectly concluded that their studies are proof that vitamin C should not be recommended to the general public (Anderson, 1974, 1979; Tyrell, et al, 1977). Many reviewers, as I have said, have misrepresented Pauling's arguments as being based on personal testimonials (Passmore, 1971; Stare, 1971; Medical letter, 1970; Coulehan, et al, 1974; Thomas and Holt, 1978). Some authori¬ties have incorrectly cited sources as proof that Pauling must be wrong (Wolf, 1981; Thomas and Holt, 1978); many others have cited incorrect sources without evaluating their contents (Coulehan, et al, 1974; A.M.A., 1975; Thomas and Holt, 1978; Lancet, 1979). Finally, a number of "authorities" have stated flatly that there is no evidence to support Pauling's claim (White, 1975; Jukes, 1975).1

53 Fallacies of Ambiguity Engel defines fallacies of ambiguity as "arguments that are unsound because they contain words that, either singly or in combina¬tion, can be understood in more than one sense."2 Many investigators and reviewers of the effects of vitamin C on colds have advanced their conclusions that vitamin C is not worth recommending by using ambiguous terminology which misleads the reader. One example of this is stating that the evidence is "inconclusive" when in reality the evidence is uniformly positive, but not uniformly statistically sig-nificant or rigorously collected. Another example is implying that because no evidence of toxicity has been found, no studies of toxi¬city have been performed. This is a particularly common, and partic¬ularly shallow, fallacy of ambiguity. A variation of this has been the claim that particular side effects can occur, when in fact they have only been hypothesized. Another common ambiguity is the claim that significant effects are "minor" or not "important." Any signifi¬cant result in the study of the effect of vitamin C in preventing and curing colds is of great importance to millions of people. Special Pleading Engel defines special pleading as "applying a double standard; one for ourselves and one for everyone else."3 The medical establish¬ment has been unable to hold its position in the face of the increas¬ing weight of evidence for a significant effect of vitamin C. As the 2Engel, page 51. 3Engel, page 83. 54 statements of Cowen,et al (1942) and others show, they have responded by denying that the evidence is actually important. This is a form of special pleading; they argue that they can choose any standards of significance they wish for the evaluation of the evidence. Thus well-collected significant results become "minor benefits of ques¬tionable validity," a reduction in colds has "no practical impor¬tance," and an almost completely uniform record of valuable therapeu¬tic use is "inconclusive." The most extreme case of special pleading is exhibited by those medical reviewers who claim that the theoretical risks of megadoses of vitamin C are so great that they outweigh their potential benefits (Medical Letter, 1970, 1971; Beaton and Whalen, 1971; Chalmers, 1975; Dykes and Meiers, 1975; Thomas and Holt, 1978). As I have been say¬ing, nothing except a mild laxative effect

and possibly mild gastro¬intestinal upset has ever been demonstrated to actually occur in man from megavitamin C use, and the medical establishment has continued to make fallaciously ambiguous statements about the possibility of side effects. Most of the medications recommended by doctors for the cure of colds can have very unpleasant sideeffects for a small per¬centage of people; moreover, most of these same drugs are highly toxic in large amounts. Vitamin C has no known serious side effects in any dosage size that would possibly be ingested by a person, and has been shown to help the body heal itself by potentiating the immune reactions To refuse to advise the public about the benefits of megavitamin C use on the grounds that someone might react badly to it 55 is ridiculous, given the incredible number of toxic substances which are dispensed with open hands by the pharmacuetical and drug com¬panies. Irrelevant Thesis Engel defines an irrelevant thesis as "an argument in which an attempt is made to prove a conclusion which is not the one at issue." Some of the reviewers who have criticised Vitamin L. Common Cold have tried to discredit it by focusing on irrelevant issues and claiming that they damage Pauling's argument. This is really a very silly way of trying to discredit an argument, but it has had important consequences for the Vitamin C debate. The review by Beaton and Whalen (1971), which claimed to show that Pauling's evidence was inconclusive, focused on insignificant parts of the work of Cowan, et al (1942) and claimed that because opinion differed over the significance of these irrelevant details, Pauling's interpreta¬tion was invalid. Pauling responded to the "astounding misrepresen¬tation of the well-controlled double-blind study of Cowan, et al," saying that he found it "shocking" that medical authorities should be misrepresenting matters concerning the public's health (Pauling, 1971b). Nonetheless, the review by Beaton and Whalen was cited by Coulehan (1974), Thomas and Holt (1978), and the editors of Lancet (1979) as proof that Pauling's evidence was invalid. II. The Arguments of the Medical Establishment 4Engel, page 107. 56 In order to concisely demonstrate the nature of the arguments used by the medical establishment to convince the public and the scientific community that Pauling is wrong, I have listed some of the most prominent authors and articles in the controversy and the

vari¬ous arguments, described above, that they have used in Table 1. The data points in the table refer to paragraphs in Appendix 1, in which I have quoted the author's words and explained the significance of their arguments. This has been done to] give the reader a feeling for the scope and intensity of the medical establishment's response. Authors who have written in the Journal of the American Medical Association are marked with a "J". It will be seen in examining the table that the period from 1974 to 1975 was a very busy one for the AMA. During this period the regulations proposed by the Food and Drug Administration to subject high-dosage vitamin supplements to medical review and prescriptory control were being challenged in Congress by vitamin manufacturers, public interest groups, and Linus Pauling and Professor Roger J. Willams. The AMA was the main lobbyist for the attempt to subject vitamins to control of the medical establishment. The position of the AMA over vitamins will be discussed in detail in the chapter on the nature of the medical resistance to vitamins.

Arguments of Misstatement Author of Fact

TABLE 1 the Medical

Fallacy of Ambiguity

Establishment*

Special Pleading Cowan, J

Irrelevant Thesis

et al. (1)

(22)

(30)

(1942).

Glazebrook,

et al. (2)

(1942). Tebrock, J

et al.

(23)

(1956).

Nutrition Reviews.

(3)

(1967). Goldsmith.

(4)(5)

(1961). Bing, F.

(7)

(25)

(24)

(34)

(1970). Medical Letter.

(8)

(26)

(9)

(27)

(1970). Medical Letter. (1971). Passmore. (1971). Stare, F.T. (1971) Beaton and Whalen.

(35)

(1971). Coulehan.

(13)

(1974). Chalmers,

T.C.

(28)

(31)

Dykes and Meyers.

(29)

(33)

(1975). Karlowski. J

(1975).

(1975). AMA Press Release. j

(1975).

White, P.L. (1975). Jukes, T.H. J

(1975).

Thomas and Holt. (1978). Laacet.

(32)

(1979). Ross, D.M. (1979).

(21)

III. The American Medical Association and Vitamin C Megatherapy In 1975 the President of the American Medical Association, Phil¬lip L. White, wrote and article in the Journal of the AMA entitled "Megavitamin This and Megavitamin That" which discussed the Congres¬sional battle over the control of vitamins between the FDA, supported by the AMA, and the supporters of House Bill S2801 which proposed to eliminate the FDA's authority to regulate vitamins. At the time the A.M.A. was lobbying for the FDA's proposed regulations to subject all vitamins containing more that three times the Recommended Daily Allowance to the review of the medical establishment, which would decide whether or not they should be available by presription only. White (1975) states: "Megavitamin therapy raises questions of propriety, regulato¬ry process, pharmacology and toxicology as well as profes¬sional and public responsibility.... Impressive public fig¬ures, from two-time Nobel Prizewinner Linus Pauling to members of Congress, apparently support the concept.... None of us could have guessed that it would have become popular to take gram quantities of vitamins in vain hope of preventing or curing a multitude of diseases. If there were some objec-tive evidence that megavitamin therapy or orthomolecular psychiatry produced benefical results, one would then use the role of reason in evaluating the risk/benefit ratio. For the present, we can only conclude that there is no benefit to massive daily doses of vitamins and that only one aspect can be evaluated, namely, the risk." White referred a detailed discussion of megavitamin therapy to an article in the same issue of JAMA by Thomas H. Jukes. Jukes (1975) in his article "Megavitamin Therapy," in JAMA 58 "Megavitamin Therapy is advocated, without basis, for treat¬ing numerous clinical disturbances, including degenerative diseases... [and] to promote a desirable but mythical condi¬tion of super health.... Megavitamin therapy... is largely based on an ancient and cherished delusion of the laity, if a small dose of a medicament is good, a larger one must be better.... Megavitamin therapy is advocated in the writings of Linus Pauling and the late J.I. Rodale.... Pauling's theory of 'orthomolecular pshychiatryl [is] a concept not un¬like Rodale's barrier proposal." J.I. Rodale was the publisher of Prevention Magazine, a lay publica¬tion promoting unorthodox health practices and holistic medicine. Arthur Sackler (1975) wrote a letter to JAMA critizing Jukes' circumstantial ad hominem article on Pauling. Jukes responded that he "did not link Pauling's name with that of Rodale; I quoted both of them as theorizing that massive doses of vitamins penetrate physio¬logical barriers." Jukes went on in his letter to say that "Pauling appeared on behalf

of the National Health Federation at the hearings I attended on Bill S2801 before Senator Kennedy on August 1, 1974." (Jukes, 1975b). In a letter following this Philip White stated: "The arguments in support of Senator Proxmire's bills have been provided by those who stand to gain the most financially from the unrestricted sale of vitamins. Dr. Pauling has been a spokesman for one of these groups."(White, 1975b). Both Pauling and Sackler replied to this. Pauling stated: "I have not been a spokesman for any group which stands to gain the most financially from the unrestricted sale of vita¬mins. The statement that I have been a spokesman for one of these groups is damaging to me and I ask that this letter be published in order to rectify the damage as far as possible" (Pauling, 1976). 59 Sackler replied: "Dr. Jukes ' reply to my correspondence is pre¬cisely the type of 'discussion' to which I took exception and which has no place in science." Sackler points out that Jukes misrepresents his statements that "orthomolecular psychiatry is a concept not unlike Rodale's barrier proposal." Sackler states: "I submit that to link a hypothesis by one of the world's greatest scientists with that of a layman of no scientific stature whatsoever is to derogate by association." Sackler also reprimands White: "To raise the question of professional and public responsi¬bility and then to follow it with a statement that 'no one thought the day would come when public figures would promote something as outlandish as megavitamin therapy' appears to me an ad hominem derogation of the scientist who raised the pos¬tulate of megavitamin therapy, Linus Pauling. It is my be¬lief that JAMA could hayed addressed these issues... in a manner both objective and impersonal, as befits reference to one of America's greatest scientists and the traditions of scientific debate and not with polemics that ill-become both their authors and JAMA itself." The statements of White and Jukes, made five years after Pauling pub¬lished Vitamin g. And. the, Common Cold, and three years after the stu¬dies of Anderson, et al (1972) confirmed his hypothesis that vitamin C can prevent colds, are rather incredible. That they are willing to stoop to libel in order to advance their conclusions shows that the medical establishment is not just unable to grasp the theoretical implications of Pauling's work. White and Jukes made their state¬ments as the strongest attempt of the medical establishment to con¬trol vitamins, making high concentration forms unavailable without prescriptions, was under attack. Their response is that of a tobacco 60 company executive who is asked if smoking causes cancer, that is, a vested interest which has its profits threatened by public health concerns. Unlike a tobacco company executive,

though, White and Jukes claim to be responsible medical professionals, and would have the public believe that they are protecting it from quacks and pro-fiteers. It is extremely unfortunate, in my opinion, that the medi¬cal establishment has managed to keep persuading the public that this is true. CHAPTER 11 THE EYES OF THE PUBLIC The attacks of the medical establishment on Pauling's evidence and conclusions were widely publicised and widely believed. An arti¬cle in Reader'A Digest repeated the claims of the editors of the Med¬ical, Letter that EulinglA evidence was worthless, and stated that people had actually developed kidney stones from taking vitamin C, which was untrue.1 The statements of the editors of the Medical Letter that Pauling's case was based on uncontrolled trials and per¬sonal testimonials and that vitamin C could cause kidney stones were also repeated in the New York Times (January 3, 1971). In 1971 Consumer Reports published an article entitled "Vitamin C, Linus Pauling, and the Common Cold."2 The article made, according to Pauling, ten false or seriously misleading statements,3 and ended with an allegation of social irresponsibility: "Whatever the merits of increasing Vitamin C allowances (and they should be explored), a socially responsible approach would dictate that toxicity studies should precede any ef¬forts to encourage people to take large amounts of the vita¬min." The careful clinical study of Lowry and Bessey (1952) showed no side effects from taking 1 g per day for four months; no other investiga1Ross, W.S. "Vitamin C: Does It Really Help?", Reader'A Digest, 98: 129-132, 1971. 2Consumer Reports, February 1971. Pages 113-114. 3Pauling, 1976. Pages 130-133. 62 tors have reported actual side effects that implicate vitamin C use. Consumer Reports relied on the statements of the medical authorities that no studies on toxicity had been done. According to Pauling Con¬sumer Reports refused to publish a correction of the false and misleading statements in the article. On November 25, 1971, the New York Times ran an article report¬ing the findings of Schwartz, Togo and Hornick (1973) that volunteers who had been injected with cold viruses

after receiving 3 g per day of ascorbic acid for three days showed no protective effect of ascor¬bic acid compared to controls. The author of the article, Jane Brody, said in the leading paragraphs that Pauling's ideas were based on poorly-controlled studies, and misinterpreted the study by Schwartz et al by claiming that its results proved that Pauling was wrong. Pauling responded that Brody had misinterpreted the study and made false statements (New York Times, December 30, 1971). In a sneeringly sarcastic article in Life Paul O'Neil ridiculed those who were inspired by Pauling to become vitamin "cultists", cal¬ling them "amateur ecologists, manure worshippers, and connoisseurs of the multi-vitamin capsule." Pauling himself, says O'Neil, "has created a great many noisy critics among doctors and fellow scientists who say anything is toxic if taken in big enough quantities, who warn that large amounts of Vitamin C sometimes causes diarhhea and who belabor him for postulating a cure without explaining how the mechanism supposedly works. Furthermore, they say, Pauling may be a brilliant chemist, but he has no medical training." 4O'Neil, 1971, op. cit. 63 O'Neil is correct - Pauling's critics do make these simplistic, incorrect and irrelevant statements. In 1982 Jane Brody, author of the misleading report in the N.Y. Times claiming that Pauling had been proven wrong (Nov. 28, 1971), repeated her unjustified allegations in the Personal Health Column of the N.Y. Times (Jan 20, 1982). She states: "Relying mostly on the experience of himself and his wife, and a few studies with serious limitations in design, Dr. Pauling hailed vitamin C as the long overlooked panacea for the peskiest of human conditions.... Some people have become ill from taking a remedy that might actually be worthless for their conditions.... Vitamin C consumed above and beyond body needs is excreted in the urine." All of these statements are untrue or seriously misleading. Brody seriously misrepresents the facts in this widely-read forum for pub¬lic health information. It can be seen that the public has relied on the statements of the medical establishment to some degree in evaluating the proposals Pauling has made. The point I want to make here is that the public has to rely on the medical establishment in evaluating new health issues. When the source of information that the public depends on becomes untrustworthy, we should be grateful that people like Linus Pauling have taken it upon themselves to campaign for the truth. Gratitude, however, needs to know why it exists. It is obviously imperative that we understand why the medical establishment has been refusing to accept the facts about vitamin C.

PART THREE VITAMIN C: THE CRITIC'S REVIEW CHAPTER 12 THE NATURE OF THE RESISTANCE The resistance of the medical establishment to orthomolecular medicine and megavitamin C, as I have shown, is not based on objectively-made decisions about the value of megavitamin therapy. But what is the reason for the impassioned, often vicious response Pauling has drawn? Pauling has surmised that several factors may contribute to the lack of enthusiasm of the medical establishment about a substance that was shown by the early 1960s to significantly prevent and alleviate illness. He hypothesizes that: "In the search for a drug to combat disease the effort is usually made to find one which is 100 percent effective... Also, there seems to have existed a feeling that the intake of vitamin C should be kept as low as possible, although this vitamin is known to have extremely low toxicity. This atti¬tude is of course proper for drugs -- substances not normally present in the human body and almost always rather highly toxic -- but it does not apply to ascorbic acid. Another factor has probably been the lack of interest of the drug companies in a natural substance that is available at a low price and cannot be patented."1 I believe that Pauling is partially correct. One factor in the response of the medical establishment that has become apparent to me is the bias against vitamin therapy in general, due to the incredibly active profiteering of vitamin promoters and manufacturers who seek to make money by convincing the people that they are under-nourished 1Pauling, 1970. Pages 4-5. 65 and therefore subject to disease which can be cured by buying the promoter's miraculous vitamins. As Pauling says, the search is usu¬ally made for a drug which is 100 percent effective; the quack claims of health food promoters therefore draw a strong response from medi¬cal authorities who wish to prevent people from being misled in their concern over their health. The Food and Drug Administration has been the active force in preventing quacks from enriching themselves off the fears of sick (or merely concerned) people. In evaluating the claims made by vitamin promoters the FDA has relied on the medical establishment to

define standards of efficacy and safety. But the medical establishment has some very strong theoretical biases, and this has interfered with its ability to make correct decisions about vitamins. One of these biases is that it is unwilling to differentiate between drugs and vitamins, which as Pauling says are not at all similar. The medical establishment also does not want its control over the health of the people to be undermined by promoters selling thera¬peutics. A position of elitist control has been demanded by the med¬ical establishment, on the grounds that specialists are the only ones who can properly evaluate the incredible profusion of medications and "health foods" which has appeared in this century. But this position has been maintained not for the good of the public, but for the good of the specialists. The American medical establishment is a monopoly in the classic sense, and this has been nowhere more apparent than in its efforts to control and suppress vitamin use. The history of 66 these efforts shows conclusively that the response of the medical establishment to vitamins has been aimed at monopolizing and per¬petuating its control over the health of Americans, even to the point where the public actually suffers because of it. This professional monopolization attempt is thrown into perspec¬tive when the control strategies used are compared to those developed by others in response to threats to their control. Linus Pauling's struggle to publicize the dangers of radioactive fallout, and Rachel Carson's alarms about the effects of DDT on the ecosystem and the blind rush of lethal environmental technology, both drew responses from vested interest groups identical in many respects to that of the medical establishment in the vitamin C controversy. I. The Fight Against Quackery. James Harvey Young's well-documented histories of health quack¬ery and promotion, The, Medical Messiahaa and American Self-Dosage Medieines,a show that the FDA and the Federal Trade Commission have had an uphill battle against the incredibly profitable trade in spurious therapeutics and preventatives promoted by unscrupulous manufacturers and entrepeneurs. As laws were passed tightening the regulations governing foods and drugs and more and more dangerous drugs were limited to use by prescription, the trade in overthe-counter medications has become the real battlefield between regula2Young, J.H., The Medical Messiahs. Princeton: Princeton Univer¬sity Press, 1967. 3Young, 1974. op. cit. 67 tors and promoters. The discovery and publicizing of vitamins opened up the door to a new flood of marketing which caused particular problems. First, vitamins were necessary to maintain health, as

opposed to drugs which are only used to restore it. Vitamin use by the public could hardly be banned. Second, there was very little information about the effects of vitamins in the body, especially when taken in large amounts. Nonetheless, promoters immediately began making outrageous claims for vitamins, the vast majority of which were completely spurious. It becomes obvious when reading about the history of food and drug regulation that without such regulations the people would have been poisoned by the thousands by the toxic effects of patent medi¬cines pushed by greedy promoters playing on legitimate health con¬cerns. This has been prevented by regulatory demands for correct labelling, honest advertising, consumer safety, and evidence of effectiveness. The first three demands have not been subjects of debate; the last, however, has provided more than enough fuel for controversy. The Bureau of Consumer Protection of the Federal Trade Commis¬sion has maintained: "It is an unfair practice to make performance or efficacy claims for a product without conducting prior scientific tests adequate to establish the truth of those claims. It is not sufficient if, by happenstance, the claims for a product turn out to be true. To make claims without prior testing 68 treats the public as guinea pigs." This position was modified by the full FTC. Individual testing by each manufacturer would not be required so long as a "reasonable basis" underlay claims for a therapeutic. The safety of the thera¬peutic for consumer use, of course, was a prior requirement admin¬istered by the FDA. For a definition of "reasonable basis", the government has relied on the medical establishment. II.

The Position of the Medical Establishment

The amounts of vitamins and nutrients necessary for health have been dictated to the government by the Food and Drug Board of the National Research Council, established in 1941. The Board sets Recommended Daily Allowances of these substances to prevent dietary deficiency diseases, allowing somewhat more than the minimum neces¬sary amounts to compensate for individual variability and losses in foods during processing. The Board has firm evidence about the minimum necessary amounts of vitamins; it has repeatedly insisted that this is all that is needed to maintain good nutritional health. If I may offer a reasonable analogy, this is equivalent to say¬ing that all you need to do to maintain your car is put just enough oil in it so that it actually moves. The Food and Nutrition Board and the medical establishment have refused to conduct trials to find out if the human body might run better with larger amounts of nutrients in it. I think this is due to the fact that there is no 4Young, 1974. Page 42.

uniform or dramatic improvement in health in people who increase their vitamin intake, and because some vitamins, especially A and D, can be dangerous when taken in very large amounts. The medical establishment has a strong bias against recommending anything as a therapeutic which does not have concrete proof of therapeutic efficacy behind it, as befits the marketing of drugs. It is obvious that this principle, if unmodified, would also create a bias against the ingestion of concentrated substances such as vita¬mins as preventatives, rather than as therapeutics. The established practice of medicine does not have a theoretical framework for coping with this revolutionary approach to health, or any revolutionary approach to health. Cortez F. Enloe, Jr. editor of Nutrition Today, has discussed this bias in relation to vitamin C and Pauling's hypothesis (Enloe, 1971). The comment of Benjamin (1958) that many orthodox doctors have reacted in fear and anger to a perceived personal threat seems substantiated by Enloe's observations. Enloe says that when he tried discussing Vitamin

the Com-

mon Cold at a medical meeting just after its publication, "not one physician would admit to having read the book." Enloe says that the commendable point of Pauling's book is not that he offers proof for his alleged cure: "What is important is that Pauling is a genius in chemis¬try... he has succeeded in bringing into question the validi¬ty of the fundamental principles upon which all of our as¬sumptions about minimum daily requirements, if not most of the assumptions that support our knowledge of nutrition, are 70 based. [Pauling] leaves no avenue of intellectual insight unexplored. He examines our vitamin C requirements in health and disease in their relation to evolution, orthomolecular medicine, biochemical individuality, and drugs. You can look through the best textbooks in nutrition and you won't find the subjects even mentioned." Enloe notes that the difference between medicine and, say, phy¬sics is that medicine demands rigorous proof before it will accept a theory. Physics, in contrast, begins with theoretical explorations which are then confirmed or not by experiment. "With our currently popular style of facing medical problems, it is doubtful whether Dr. Einstein would ever have got by a National Institute of Health grants board.... Instead of be¬ing willing to undertake experiments to see if many of these suppositions [about vitamin C] were valid, our profession has been prone to reject them out of hand because they are based on unproved theory."

Pauling's conclusions about the best method to cure a cold are actually a minor part of a generalized hypothesis about the ascorbic acid requirements of man and the higher primates. He says: "That's something these physicians don't understand. What I have done with Vitamin C is to organize a large body of in¬formation about Vitamin C, not just to look at a single clinical trial but to assess the whole body of knowledge about Vitamin C in order to draw conclusions that seem jus¬tified.... Fred Stare's been saying for forty years that large doses of vitamins have no value. He doesn't want to admit that this was wrong." As I have shown, the medical establishment has not tried to evaluate Pauling's theory of human vitamin C requirements; instead it has attacked his evidence on the mistaken assumption that discredit5Linus Pauling, personal interview, January 1, 1983. 71 ing the trials he has used as evidence will prove that his theory is wrong. It is likely that the medical establishment has developed its theoretical bias, i.e. its demand for conclusive proof of efficacy before it is willing to try administering a proposed therapeutic, because of the neccessity of separating the spurious claims of quacks from the truly efficacious medications that have been developed. Further, in the days when vitamins were new and mysterious sub¬stances, there was a sound rationale for rejecting the widespread use of their purified forms because of the unknown risks which might have been involved. However, the medical establishment has held to its position even after good evidence of efficacy and non-toxicity has appeared. I believe that this has been the case partly because of an inability of orthodoxy to adapt to new circumstances of health care due to theoretical inertia. However, this is not the only reason. The use of vitamins to prevent and treat illness has conflicted with the attempts of the medical establishment to maintain a complete monopoly over the ability of the public to maintain its health. III. The Medical Monopolizers. Helga Nowotny has commented on an interesting argument used by "pure" scientists to protect their positions from those who criticize their elitist exclusiveness: "Impressionistically, I have detected a certain amount of nostalgia in the reactions to anti-science. A by-gone state 72 of science is often evoked, and ideals are being upheld which no longer seem rooted in social reality. This is especially so with regard to an often-heard remedy. Everything would

be well with science and its relations to society, the to take care of itself. closely to the corrupting influence of poli¬tics and power could be cut loose. By separating off criti¬cism of the those directed against applications, science could be protected from is a naive wish, but understandabl9 as the strategy of an argument based on social rationality." Nowotny's impressions seem to ring true. The opposition of scientists to legislative review of research or censorship of the international flow of technological discoveries with military poten¬tial, an example which has appeared in the last few years, is charac¬terized by the fear of losing the authoritative monopoly to unquali¬fied laymen. This argument exposes a fundamental difference between medicine and the rest of the sciences. Unlike the leaders of the other sci¬ences, the medical authorities have thrived on government control of the discipline. The practice of medicine is a legally enforced mono¬poly. It is against the law to dispense most drugs without a license granted by stateapproved licensing boards who enforce regulation with the full power of law. Researchers in medical science are as jealous of their freedom to run their own research as other scien¬tists, but the practice of medicine is an area where the government is asked to control practitioners. This is done to prevent quacks from injuring people by giving them either toxic or worthless medica¬tions. But the result is that the medical establishment has been the 6Nowotny, H. "Science and Its Critics: Reflections on Anti-Science," in H. Nowotny and H. Rose, Counter-Movements „In the Sciences. Dordrecht: D. Reidel, 1979. Page 7. 73 judge of what constitutes effective and safe medical practice, and the Food and Drug Administration has enacted regulations to enforce those definitions. J.L. Berlant has applied the Weberian theory of monopolization to the medical establishment, showing that medical methods and stra¬tegies, and the resistance of the American Medical Association to health reforms such as community plans, government health insurance, and other economic proposals, are monopolization strategies which are designed to maintain the exclusiveness and high profits of the medi¬cal establishment.? Berlant's analysis shows I think conclusively that the medical establishment is not in the business of protecting the public, but is in the business of protecting its professional interests. J.P. Newhouse confirms Berlant's conclusion that the medical establishment is a successful monopolizer: "The most important feature of the medical care marketplace from the vantage point of economics is that the structure of existing health insurance has severely abridged price competition."8

Both Berlant and Newhouse show that the American Medical Associ¬ation has been the major legislative force in maintaining the exclusiveness and high profits of the profession. One of the strong¬est arguments the AMA has used to do this has been its appeal to the 7Berlant, J.L., Profession Ana Monopoly: A. Study at Medicine ja IlLe United States an Great Britain. Berkely: University of Califor¬nia Press, 1975. 8Newhouse, J.P., The Economics of Medical Care: A Policy Perspec¬tive. Philippines: Addison-Wesley, 1978. 74 necessity of an elite profession of specialists who are the only ones who can evaluate the complexities of modern medicine. The public, it is argued cannot be trusted to take care of itself. The position of the Acting Director of the National Cancer Institute shows that the medical elite consider themselves the only reliable judges of the effectiveness of any medication: "The average citizen in the country does not have the resources and technical skills necessary to select, develop and test materials for the treatment of disease. Neither does he have the background that will enable him to make en¬lightened decisions concerning the selection and use of therapeutic agents. The selection, development, testing, evaluation, marketing, prescribing, and administration of ma¬terials for disease treatment is an area in which large in¬stitutions and skilled professionals are uniquely qualified to take the measures necessary to protect the interests of the public."9 I think this statement shows very clearly why the medical estab¬lishment does not think the public should be treating itself with vitamins, even if such treatment is effective and safe. Medical spe¬cialists are pot uniquely qualified to administer vitamins to the public; the criteria required of drugs do not apply to vitamins. There is no reason why the public should depend on the medical pro¬fession for the selection, development, testing, evaluation, etc. of vitamins, especially those which have been shown to be harmless even in large amounts. Once the public is informed of the risks which might result from vitamin ingestion, if any, it has no need to depend on the medical establishment to maintain its nutritional health. 75 Such a course puts the public outside of the dependence on the medi¬cal establishment which doctors would like to foster. Orthodoxy makes no distinction between the case of the cancer patient who must rely on highly toxic forms of therapy for his life and the cold sufferer or the consumer worried about adequate daily nutrition. Nor have I found any difference in consideration of the

consumer use of drugs and of nutrition supplements in the statements of the medical authorities. The most incriminating evidence that the response of the medical profession to the use of vitamins is monopoly-oriented at the expense of the public is that first, the medical establishment acting through the FDA has attempted to deny, in the face of conclusive contradic¬tory evidence, that the public might need vitamins, and second, it has attempted to prevent vitamins in large doses from being available without a prescription. Widespread vitamin C deficiencies had been noticed as early as 1938 (Abt and Farmer, 1938). Surveys done in the 1940s showed widespread malnutrition among the nation's poor. A nation-wide, ran¬domized survey done in 1955 revealed that nearly half of America's families fell below the RDA with respect to at least one essential nutrient.10 In 1963 it was known that "a high percentage of the gen¬eral population does not now have ascorbic acid intakes which meet the RDA." (Nutrition Reviews, 1963). loYoung, 1967. Page 339. 76 In 1961 the Nutrition Foundation, an orthodox medical institu¬tion, announced a multimillion dollar campaign to convince Americans that they did not need vitamins, saying that the great abundance of foods available to Americans ensured that they received a balanced diet. (New York Times, April 25, 1961). The next year the FDA, act¬ing in response to lobbying from the AMA and other orthodox medical groups, announced that it was tightening the labelling rules on vita¬mins and limiting the claim of "special dietary value" to only eight of the vitamins; the FDA also said that dietary supplements were not needed in the U.S. diet (N.Y. Times, Nov. 22, 1962). The position of the AMA at this time was becoming more firmly fixed in its ideology. Rosemary Stevens has commented on the unwil¬lingness of the AMA to face the realities of malnutrition and the real need in some groups for inexpensive nutritional supplementation: "The American medical profession of 1965 was running in its political thinking at least three decades behind the social implications of specialized medicine.... Before 1965, report after report from governmental and other sources exposed the plight of the elderly, but the AMA had continued to take the position that the aged (and other dependent groups) were by no means as sick, as in need of medical attention, or as financially needy as other groups were claiming. This atti¬tude was more than a rationalization of pecuniary narrowmindedness or vested interest; it was a statement that organ¬ized merkiicine was the proper interpreter of the nation's health." Stevens makes it clear that the AMA was protecting its authori¬tative control over health. However, the many surveys of nutritional

77 habits in America had made it clear that the aged were one of the most severely malnourished groups of people in the country. Their poverty meant that they would particularly benefit from vitamin sup¬plementation which would at least reduce the severity of sickness enhanced by malnutrition. I think Stevens is wrong in underestimating the vested interest of the AMA. As events showed, the AMA and the nutritional authorities tried not only to convince the people that they were not as sick as some claimed, but actively tried to convince them not to improve their health by taking vitamins to at least give them the Recommended Daily Allowances which the medical establishment itself set. In 1966 the FDA announced new regulations based on the recommen¬dations of the Food and Nutrition Board requiring vitamin labels to say: "Vitamins and minerals are supplied in abundant amounts by the foods we eat. The Food and Nutrition Board of the Na¬tional Research Council recommends that dietary needs be sa¬tisfied by foods. Except for persons with special medical needs, there is no scientific basis for recommending routine use of vitamin supplements." Agency spokesmen said that many Americans had thought incorrectly that there might be nutritional benefit from taking vita¬mins in excess of the minimum requirements. In fact, they said, such excesses do no good. It was proposed to make illegal the statement: "that significant segments of the population of the U.S. are suffering or are in danger of suffering from a dietary defi¬ciency of vitamins and minerals." (N.Y. Times, June 18, 1966). 78 There is no other way to describe this action except as a pure power play on the part of the medical establishment. To make it a crime to state the well-known fact that many people have nutritional deficiencies, which could be cured by vitamin use, seems to me to be conclusive proof that the medical establishment was trying to main¬tain its profits at the expense of the people's health. That such a move was beyond the bounds of acceptable behavior was emphasised by the fact that the proposed regulations were defeated by plaintiffs who proved in court that the FDA had not even held public hearings on the matter, as required by law. Taken in conjunction with the position of the medical establish¬ment already described over the Congressional fight to remove vita¬mins from the regulatory compass of the FDA and the AMA, and the statements of Drs. White and Jukes that no evidence for a beneficial effect of vitamins exists and that Linus Pauling is a spokesman for groups who stand to make money from the unrestricted sale of vita¬mins, the above discussion shows I think conclusively that the medi¬cal establishment as represented by the AMA and the leading

medical journals have actively and deliberately tried to mislead the public about the effects of vitamin C, indeed, about all vitamins, in order to maintain its monopoly over the public's right to heal itself. IY. The Strategies At Scientific Repression. When Linus Pauling presented his petition signed by over 11,000 scientists calling for an end to atomic weapons testing to the Secre¬tary General of the United Nations in 1958, he was attacked by 79 right-wing scientists and politicians who claimed that he was a Com¬munist sympathizer. Most importantly for the purposes of this thesis, it was claimed that he had no right to say that radiation was harmful to the public health. Dr. Joel Hildebrand, a past president of the American Chemical Society, claimed that not 1 per cent of the scientists who signed the petition had a specialist's knowledge of the subject.12 When Rachel Carson's book Silent SDringla was published, it drew a reaction from the chemical industry and from chemists which was remarkably similar to that of the medical establishment to Vitamin the Common Cold. Carson, too, wrote her book because the estab¬lishment was refusing to listen to voices crying in alarm that its policies were damaging the environment and, ultimately, the people." The main response of her opponents was that she was not a scientist, and therefore was to be ignored. One review of Silent Spring was entitled, "Silence, Miss Carson."15 Frank Egler, a prominent historian of ecology, has written of the response to Silent Spring: There has been defense and counter-defense, a focusing upon minutiae, distortion, innuendo, bias, claims of emotionalism themselves written with extreme and apparent emotion... The story of pesticides in 1962-63 is that of the angry, emotion¬al, and salesconscious reacton of the industry and its dis12"Congress Is Told How Pressure Grew to Ban Bomb Tests," Q. News and Jorld Report, June 14, 1957. Pages 75-78. 13Carson, Rachel. Silent SDrina. Boston: Houghton-Mifflin, 1962. "Graham, F., Since Silent Spring. Boston: Houghton-Mifflin. 15Darby, W.J. "Silence, Miss Carson." Chemical and Engineering Pews, 40: 60-62, October, 1962. 80

ciples in government and agriculture, aided albeit innocently by the obsessively scientific, not that of the cool and calm progress of scientific knowledge through a democratic so¬ciety. n16 I am sure that one day a prominent nutritionist will say much the same of the controversy over the effects and requirements of vitamin C. However, it does not seem likely that specialists in any discipline which is closely connected to an industry, especially ones as large and powerful as the chemical and drug industries (which are rather closely related) will ever be able to learn from such observa¬tions. In the meantime, I suggest that the reader be aware that the traditional exclusiveness of science has been and probably will con¬tinue to be abused by those who disguise their vested interests as scientific skepticism. In particular, the claim that a challenge is invalid because the author is "unqualified" should be recognised for what it is: the mark of a closed and fearful mind.

CHAPTER 13 CONCLUSION Linus Pauling has developed a new approach to the treatment of mental disease and viral infection called "orthomolecular medicine." The fundamental difference between this approach and that of orthodox medical treatment of illness is that the substances Pauling recom¬mends for treating disease are natural, that is, found in the human body. They are also largely non-toxic, relatively cheap to make in large amounts, and unpatentable. Pauling has hypothesized that many forms of illness occur because of imbalances of these substances in the body. For example, he thinks that schizophrenia may be caused by localized cerebral deficiencies of particular substances, and that systemic deficiencies, particularly in the immune system, may lead to decreased resistance to infection by viruses responsible for the com¬mon cold and other diseases. According to Pauling, these deficiencies may be alleviated by megavitamin therapy, or the ingestion of very large amounts of the non-toxic vitamins, such as niacin and ascorbic acid (vitamin C). The latter substance potentiates the action of the immune system in fighting disease and may have other beneficial properties such as stimulating the cellular production of interferon. Pauling thus recommended in his widely-read book, Vitamin

and

the Common Cold, that the regular ingestion of much larger amounts of 82 vitamin C than the Recommended Daily Allowance be made a regular practice to maintain the immune system at its optimal level of func¬tioning, and said that the daily dose should

be greatly increased at the onset of infection to fight it off. He supported this contention with evidence that the human body was adapted to use large amounts of vitamin C because of its evolutionary history and by showing that almost all animals synthesize vitamin C in large amounts, which implies that man also has a similarly large demand for the vitamin. Further, Pauling said, well-done studies of the effects of vitamin C show that its regular ingestion in large amounts reduces the incidence and severity of the common cold. For his suggestions Pauling was attacked by the medical estab¬lishment, which denied that any evidence for a beneficial effect of vitamin C existed and said that its use should not be recommended. Pauling was also personal attacked by medical authorities who stated that he was in collusion with the vitamin industry and its lobbyists, who were seeking to create a state of "vitamania" with spurious claims that many people were malnourished and that vitamins had powerful therapeutic properties. The response of the medical establishment has been marked by numerous misstatements of fact and fallacious arguments which have been used to justify its position. A review of the history of the medical response to vitamin use and to Pauling's proposal of the use of orthomolecular medicine shows that the response has been one that of a vested interest group which is primarily interested in protec83 tiung its elite control over health matters, and which is blinded by this interest to developments that might change the stucture of health care in the United States. It is concluded that intelligent, well-educated doctors are ignoring the evidence that vitamins are of great value in preventing and treating illness because of an entrenched bias against public self-medication and an inability to grasp the implications of theoretical approaches to medicine, and because they are strongly influenced by the interests of the drug industries who stand to lose money if people start using vitamins instead of patent medicines to cure their illnesses. 84 APPENDIX The Statements of the Medical Authorities Cowan, et al (1942) discovered that the subjects in their study who received Vitamin C had 31% less illness than the control group. In a discussion of their paper printed in the same jour¬nal, one of the investigators, Dr. Diehl, states: "We certainly were not able to demonstrate that the vitamins were of any value." The statement by Dr. Diehl, and the statement in the summary that vitamin C had no important effect, is a misrepresentation of the data.

Glazebrook and Thomson (1942) also misrepresent their data. They gave 335 students in a school 200 mg of ascorbic acid a day for six months, keeping 1,100 others as controls. Table 1 of their study shows that 21% of the vitamin group developed colds, compared to 26% of the controls. The authors state eroneously , "It is obvious, therefore, that Vitamin C had no effect on the incidence either of common colds or tonsillitis." This is obvi¬ously wrong, but it is repeated in the summary. Nutrition Reviews (1967). The conclusion of Glazebrook and Tho¬mas (1942) that their study showed no effect of ascorbic acid is reported; no mention is made of the fact that the data of these two researchers directly contradicts their conclusion. The study of Ritzel (1961) is incorrectly reported. The decrease in illness of the vitamin group is reported as 30%; the correct amount is 65%. The author of the review also states: "There is no evidence for a general, anti-viral or symptomatic prophylac¬tic effect of ascorbic acid." This is a direct self-contradiction. In six out of 10 of the studies reviewed the authors describe positive evidence for such an effect. The author does not succeed in proving that any of these studies can be disregarded entirely. The statement that "There is no evi-dence for a general, anti-viral or prophylactic effect of ascor¬bic acid" is simply wrong.. Goldsmith (1961) published a comprehensive review entitled "Human Requirements for Vitamin C and Its Use in Clinical Medi¬cine." While noting the many uses of Vitamin C in treating injuries, she states that Vitamin C seems to show "no beneficial effect on the incidence and cure of the common cold,"' citing the study of Franz et al (1956). This was an incorrect cita¬tion: Pauling's 1976 analysis of the data.of Franz et al shows that the decreased duration of the colds of the vitamin group 85 amounts to 36% less illness for the vitamin group than the pla¬cebo group. Goldsmith (1961) states: "There is no danger of toxicity from Vitamin C in amounts much larger than those needed for rehabilita- tion or maintenance because of the rapid excretion of the excess from the kidneys." The studies of Johnson and Zilva and Ahmed show that Goldsmith's unsupported hypothesis is wrong. The fact that the safety mechanism she postulates does not exist, of course, does not mean that there is a danger of toxicity from large amounts of Vitamin C. In November 1969 Mademoiselle Magazine published an article on Vitamin C. The article quoted Frederick J. Stare of Harvard, editor of Nutrition Reviews and "one of the country's Big Names in nutrition" as saying: "Vitamin C and colds - that was disproved twenty years ago. I'll tell you about just one very careful study. Of five thousand students at the University of Minneso¬ta, half were given large doses of Vitamin C, half a placebo. Their medical histories were followed for two years - and no difference was found in the frequency, severity or duration of their colds."

The study Stare was referring to was that of Cowan et al (1942). This study involved only about four hundred students, lasted 6 months, involved use of only 200mg/day of vitamin C, which is not a large dose, and showed that the vitamin group had 15% fewer colds per subject. Stare totally misrepresented this "very careful study" to a national publication. Franklin C. Bing, M.D. (1970) reviewed Pauling's book in the Journal of the American Medical Association. He wrote: "Here are found... the clear incisive sentences of an advertiser with something to sell... The research which Pauling is recommending, it would seem, is not a study to determine the facts, but a compilation of data for him to fit into the pattern of his argument." The first statement by Bing is a circumstantial ad hominem attack (Engel, p. 111), implying that Pauling has hidden motives for publizing his data. The Medical Letter (1970) a publication on drugs and therapeu¬tics for physicians financed by the drug industry, published a review similar in nature to Bing's: "The book is an enthusiastic and uncritical endorse¬ment... Pauling's conclusions are derived from uncon¬trolled or inadequately controlled studies, and from personal experience.... A controlled trial of the ef¬fectiveness of Vitamin C against upper respiratory in¬fections must be conducted over a long period and in86 elude many hundreds of persons to give meaningful results. No such trial has been performed." Both of these claims are wrong; Pauling cites the studies of Cowan et al (1942) and Ritzerl (1961) which show meaningful results. The Medical Letter (1971) published another article entitled "Vitamin C - Were the Trials Well Controlled and Are Large Doses Safe?" The author(s) attempted to discredit Pauling's evidence by showing that it was uncontrolled. The author(s) give as rea¬sons for rejecting the study of Cowan et al (195 42) that the study was not double blind (Pauling quotes Dr. Cowan's statement that the study was double-blind (Pauling, 1976, p. 51)), and that the allocation of subjects to the vitamin and placebo groups was not randomized, although Cowan et al describe their method of randomization in their paper. The paper by Ritzel (1961) which Pauling relies on was submitted to five anonymous "experts" whose disparaging and incorrect comments were printed in the article. One of the anonymous reviewers states that "the population of subjects is not characterized as to age, sex, etc." Ritzel states that the subjects were all schoolboys. Ritzel does not document his study methods in great detail, which is a minor flaw. This however does not invalidate the great benefit the vitamin group received or Pauling's conclu¬sions about the evidence (Pauling, 1970, p. 44), as the anonymous reviewers say it does. The second article in Medical Letter like the first, misrepresents the evidence in order to prove its conclusions. Passmore (1971) seems rather confused.

Passmore says, "The

claim appears to rest on the subjective impressions of Dr. Paul¬ing, Mrs. Pauling, Dr. Irwin Stone, Dr. Szent-Gyorgyi and others who feel well and say that they have few colds when taking one gram or more of ascorbic acid daily." This is strange, for there are no testimonials in the book from anyone except Dr. Pauling about the personal feeling of well being he or she is experienc¬ing from Vitamin C. Passmore also says: "Pauling's claim is not supported by any theoretical concept of how the vitamin might work at the molecular level." This is incorrect, as he would have known if he had read the book. Frederick T. Stare (1971) in "Not Quite Cricket", is directly insulting. He says, Pauling's comments of recent times, "have disappointed us by the irresponsible way they arouse false hopes in those who have diseases which Pauling feels can be success¬fully treated by his 'vitamin therapy'.". Stare goes on to say that Pauling does not provide acceptable scientific evidence with appropriate controls to support his testimony. Interest¬ingly, Passmore (1971) describes Ritzel's work, cited by Paul¬ing, as "well done." His own peers evidence Stare's misstatements. Stare states that "most scientists knowledgeable in Vitamin C and its metabolism know that in amounts of more than 87 25 to 30 mg per day Vitamin C is readily excreted in the urine, and much more of it is excreted as the intake is increased." This statement is incorrect, as was shown in the 1930s. Beaton and Whalen (1971) state that, "the author and his critics seem to agree on one central point - at the moment there is no scientifically valid evidence that Pauling's proposed prophy¬laxis will work." Pauling points out that this is wrong: "In my book I stated that... no large scale study had been carried out with ascorbic acid in large amounts (i.e. greater than 1 g per day)." (Pauling, 1971b) The reviewers also say that the amounts Pauling proposed, 1 to 2 g per day, have never been subjected to controlled clinical tests. Coulehan et al (1974) stated that the studies on which Pauling had relied in drawing his contusions were defective, citing the reviews of Beaton and Whalen (1971) and the Medical Letter (1970, 1971) as evidence. Neither of these reviews showed that the studies actually were defective, as a careful reading and knowledge of the facts would have proved. Coulehan et al misrepresent Pauing's work by accepting unjustified criticism of it. Karlowski et al (1975) did a nine-month trial of 1 g/day prophy¬lactic ascorbic acid on employees of the National Institute of Health. The vitamin group had from 16% to 21% less illness than the placebo group, and 16% fewer colds. However, the study was flawed by the ability of subjects to distinguish by taste whether they had placebo or ascorbic acid tablets. The authors conclude "that ascorbic acid had at best only a minor influence on the duration and severity of colds, and that the effects might be explained well by a break in the double blind." They also say that "the effects of ascorbic acid on the number of colds seems to be nil." Karlowki et al misrepresent their own evidence, much as other investigators have done in evaluating the efficacy of Vitamin C in curing colds.

Dykes and Meiers (1975) in the summary of their article "Ascor¬bic Acid: Evaluation of its Efficacy and Toxicity." state: "Although one study tentatively supports the hypothesis that doses of ascorbic acid may be efficacious, a second study by the same group did not confirm the significant findings, and no clear reproducible pattern of efficacy has emerged from the review of all the evidence. Simi¬larly, there is currently little adequate evidence of either the presence or absence of serious adverse reac¬tions to the such doses, although many such reactions have been hypothesized. The unrestricted use of ascor¬bic acid for these purposes cannot be advocated on the basis of the evidence currently available." The paper by Dykes and Meiuer seriously misrepresents the evidence. Dykes and Meier insinuate that the studies of Cowan et 88 al (1942), Ritzel (1961), and Coulehan (1974) were not properly controlled. They do now show this to be true or that their insinuations justify rejecting the significants findings of these investigators. In their summary Dykes and Meier state that the second study of Anderson et al (1974) did not confirm the significant findings of the first. This is not surprising; the second study did not repeat the methods of the first, but used a different experimental organization. Most importantly, Anderson et al conclude that their observations are compatible with an effect of small magnitude from the prophylactic and the therapeutic regimens they tested, with an effect of somewhat greater magnitude from the combined regimen. Also the authors note that there were a number of problems in the trial and the analysis of the results that implicate their findings some¬what. The statement in the summary of their paper by Dykes and Meier that Anderson et al could not repeat their findings thus misrepresents the second study of Anderson et al. On March 10, 1975, the American Medical Association issued a press statement with the heading, "Vitamin C will not prevent or cure the common cold." The basis for this statement was the two papers by Karlowski et al and Dykes and Meier published that day in the Journal of the American Journal Association. Neither paper supports the statement of the AMA that vitamin C will not prevent or alleviate the common cold: the first demonstrated a 20% reduction in illness from ascorbic acid, and the second incorrectly reviewed the trials already performed to draw the conclusion that "no clear reproducible pattern of efficacy has emerged from a review of all the evidence." White (1975) states: "None of us could have guessed that it would have become popular to take gram quantities of vitamins in vain hope of preventing or curing a multitude of diseases. If there were some objective evidence that megavitamin therapy or orthomolecular psychiatry produced benefical results, one would then use the role of reason in evaluating the risk/benefit ratio.

For the present, we can only conclude that there is no benefit to massive daily doses of vitamins and that only one aspect can be evaluated, namely, the risk." White would have to be blind or illiterate to justify this statement, made five years after Pauling summarized the evidence and three years after the study of Anderson, et al (1972) con¬firmed that Pauling was right. However, White is President of the American Medical Association. Jukes (1975) in his article "Megavitamin Therapy," in JAMA wrote: "Megavitamin Therapy is advocated, without basis, for treating numerous clinical disturbances, including de89 generative diseases... [and] to promote a desirable but mythical condition of super health... Megavitamin therapy... is largely based on an ancient and cherished delusion of the laity, if a small dose of a medicament is good, a larger one must be better.... Megavitamin therapy is advocated in the writings of Linus Pauling and the late J.I. Rodale.... Pauling's theory of 'orthomolecular pshychiatry' [is] a concept not unlike Rodale's barrier proposal." J.I. Rodale was the publisher of Prevention Magazine, a lay pub¬lication promoting unorthodox health practices and holistic medicine. As Sackler (1976) pointed out, this is an ad hominem derogation of Linus Pauling, who cannot be compared to a layman when evaluating his scientific hypotheses. Thomas and Holt (1978) reviewed the information about "Vitamin C and Immunity: An Assessment of the Evidence". While the authors give a good discussion of the physiological effects of Vitamin C, they thoroughly misrepresent Pauling's hypothesis and the studies that have been done on the effect of vitamin C on colds. The authors quote Chalmers (1975) as showing that many of the trials which have been done are ill-conceived and poorly con¬trolled. Chalmers does not show this; in fact he evaluates 8 controlled studies without showing either that they were "ill-conceived" or poorly controlled. Thomas and Holt state: "There is general agreement that ascorbate supplementation is ineffec¬tive in reducing the incidence of colds and winter illness." They cite the review of Beaton and Whalen (1971), which does not show that this is true, and the studies of Anderson (1972, 1975), Wilson and Loh (1973) and Karlowsky (1975), who show that ascorbic acid does reduce the incidence of colds, to support this statement. The authors state, "In summary, there is evi¬dence for a positive role for ascorbate in some aspects of host defense, but no justification for prolonged or even short-term megatherapy." This statement contradicts the earlier statement of the authors that "there is general agreement that ascorbate supplementation does produce a reduction in the severity of symptoms following infection." In 1979 the Lancet published an editorial stating:

"The theoretically harmful effects of megadose ascorbate are as numerous as the potentially beneficial effects... There seems at present little justification for long¬term acorbic acid mega- therapy in cold prophylaxis in the general population. Perhaps it will be possible to define a subpopulation in which the benefits justify the risks." Which, we might add, are all hypothetical. The author of the editorial misrepresents the significance of the evidence about the value of ascorbic acid in reducing illnes; controlled 90 studies such as those of Anderson et al (1972, 1975) show a sig¬nificant benefit of reduced illness from megatherapy. David M. Ross, in a 1979 article entitled "The Megamyth of Megavitamins". reported a speech on Megavitamin therapy by Dr. George Wolf of MIT. According to the article, Dr. Wolf said that Pauling's evolutionary argument that man developed a 2 gm daily demand for Vitamin C because of his vitamin-C rich environment was wrong, because most vitamin C is just excreted. When Pauling responded challenging this claim (Pauling, 1979) Wolf said that the study of Hodges et al showed that excess Vitamin C was excreted. This is a misrepresentation of the evi¬dence: Hodges et al, as has been discussed, showed only that not all of a megadose is incorporated into the body pool of ascorbic acid. The studies of Johnson and Zilva (1934), Ahmed (1956) and Harris (1976) show that at least half of a megadose is not excreted as ascorbic acid. The summary of the paper by Cowan et al (1942) reads: "This con¬trolled study yields no indication that either large doses of vitamin C or large doses of vitamins A, B t , B

, C, D, and

nicotinic acid have any important effect on the nuiber or sever¬ity of infections of the upper respiratory tract when admin¬istered to young adults who presumably are already on a reason¬ably good diet." Cowan et al found that subjects who took vita¬min C had significantly fewer colds than those who took place¬bos. The difference ammounted to one-third of a cold per per¬son, which is significant if not dramatic. Their summary is therefore misleadingly ambiguous. Tebrock, Arminio and Johnston (1956) reported their evaluation of the usefulness of bioflavonoids and ascorbic acid in the treatment of the common cold in JAMA. They found no significant effect of either on colds. However, they say, "Thus far there is no convincing evidence that bioflavonoids or ascorbic acid can alleviate a cold when used alone or in conjunction with other therapies." This statement is unsubstantiated. The authors in their introduction cite Brody (1953), who describes the significant results observed by Cowan et al Therefore Tebrock et al must have known that there was strong evidence for an effect of Vitamin C on colds. I think that the statement that "there is no convincing evidence" for a beneficial effect of ascorbic acid is supposed to mean "no significant and valid evidence." If this is in fact the author's intention, they are committing a fallacy of ambiguity (Engel, p.

51), that is, using a key word that can be understood in more than one sense. The results of Cowan et al, which Tebrock et al must have known about, are significant and valid. A statement that there is no "conclusive" evidence for a positive effect of ascorbic acid, unless it is sup- ported by either a definition of "conclusive" or by significant and valid evidence that impeaches the positive evidence for ascorbic acid, is a fallacy of ambiguity, for it 91 implies that there is no justification for ascorbic acid use. Nutrition Reviews (1967) published an editorial about ascorbic acid in 1967. The summary of the anonymous article states: "There is no conclusive evidence that, in the absence of severe ascorbic acid depletion, ascorbic acid has any effect on the incidence, course, or duration of colds." The article reviews ten studies, of which eight show a positive effect of ascorbic acid in preventing colds. The author of the article claims that the studies were poorly done, but does not show that they were. Bing (1970) in his review of Vitamin .Q Ana the Common Cold states: "When used as recommended by Prof. Pauling, neither the safety of all dosage forms, nor the efficacy or ascorbic acid in any form has been proved..." Bing does not show anything to prove that Pauling's evidence is not conclusive, nor does he mention that no evidence of any toxicity has been found. His statement that safety and efficacy have not been proved is misleadingly ambiguous. The editors of Medical Letter (1970) wrote: "When 4 to 12 g of Vitamin C are taken daily for acidif¬ication of the urine, however, as in the management of some chronic urinary tract infections, precipitation of urate and cystine stones in the urinary tract can occur. Very large doses of vitamin C, therefore, should be avoided in patients with a tendency to gout, to forma¬tion of urate stones, or to crystinuria." This statment is wrong. Not a single case of has been reported in the medical literature of a person who formed kidney stones because of a large intake of vitamin C. Moreover, the possibil¬ity that they might occur is eliminated if vitamin C is taken as sodium ascorbate, which does not acidify the urine. It is of course proper to discuss the possibility that side effects might occur. To state that specific side effects can occur implies that they have occurred. As no one has even seen this hypothet¬ical possibility actually occur, the editors of Medical Letter are not justified in stating anything more conclusive than "A possible side effect of pure vitamin C might be the formation of kidney stones in patients with tendencies to gout, urate stones, or cystinuria." The statement that vitamin C can cause kidney stones, or any other merely hypothetical and undocumented side effect, is thus a fallacy of ambiguity.

The Medical Letter (1971) statement that Vitamin C can cause kidney stones, a fallacy of ambiguity, is repeated. Chalmers (1975) reviewed the data from 8 trials of vitamin C "considered well enough gathered to be creditable." In the sum¬mary of his paper Chalmers states: "Differences in mean prorated numbers of colds per year and durations of illness were 0.09 + 0.06, and 0.11 + 92 0.24, respectively, favoring ascorbic acid over the placebo...In most studies the severity of symptoms was significantly worse in the patients who received the placebo. Since there are no data on the long-term toxi¬city of ascorbic acid when given in doses of 1 g or more per day, it is concluded that the minor benefits of questionable validity are not worth the potential risk, no matter how small that might be." The last sentence of the summary argues that because no data on toxicity exists, therefore Vitamin C use is not justified. This is a fallacy of ambiguity; as Chalmer states in his article valid studies have not shown any toxicity from doses of ascorbic acid as large as 3 to 6 g per day. Chalmers implies that toxi¬city has not been investigated, a state of affairs which would justify his conclusion, not the correct meaning: no toxic effects have been found by valid investigations. The statement of Dykes and Meier (1975) that there is little adequate evidence of the presence of serious adverse reactions to ascorbic acid is also unjustified. They note that the sub¬jects who participated in the clinical trials of ascorbic acid remained free of any side effects. They should have finished the statement, that no side effects have ever been reported. The review by Dykes and Meier does not show that there any grounds for rejecting the use of ascorbic acid in the treatment of colds. Cowan, et al (1942) published an account in the Journal of the American Medical Association (JAMA) of a study they had made of the incidence of colds in students at the University of Min¬nesota during the winter of 1939-40 who were taking either 200mg/day of ascorbic acid, other vitamins, a combination of the two, or a placebo. In their paper they state: "It will be noted that the students who took Vitamin C throughout the 'cold season' experienced only 1.9 colds annually during the study...the controls re- ported an average of 2.2 colds per person a year during the study. The actual difference between the two groups during the year of the study amounts to one third of a cold per person. Statistical analysis of the data reveals that a difference as large as this would arise only 3 or 4 times in a hundred (.iP