Akira Murata

Akira Murata, 1975.

A year before being introduced to Fukumi Morishige‘s work, Linus Pauling was paying close attention to research being conducted by another Japanese colleague, Dr. Akira Murata, who was studying the inactivation of viruses by vitamin C.  Over the coming years, Morishige and Murata often worked together on research related to vitamin C.  And as with Morishige, Murata became a close colleague of Pauling’s, hosting him on numerous visits to Japan and, on at least a few occasions, traveling across the Pacific to visit Pauling in California.

Murata was born in Shimonoseki, Japan in 1935, and later attended Kyushu University, receiving his Ph.D. in microbiology in 1963.  In 1966 he accepted the position of Associate Professor at Saga University, where he has remained for the bulk of his career.

From early on, Murata was interested in vitamin C and, in particular, the impact that it could make on viruses.  In 1975 Murata summarized much of his early work in a paper written for the Intersectional Congress of the International Association of Microbiological Societies titled, “Virucidal Activity of Vitamin C: Vitamin C for Prevention and Treatment of Viral Diseases.” In it, he outlined a series of clinical trials that he had conducted with Morishige, which focused on the impact of vitamin C on viruses using phages for model systems and their host bacteria. A year later, in 1976, Murata went to the United States to study vitamin C and the immune system at the Linus Pauling Institute of Science and Medicine.

Murata and Pauling in Pauling's office, 1976.

A parallel track of research conducted by Murata and Morishige in the 1970s focused on the impact of vitamin C on hepatitis.  The duo authored an important paper titled “Vitamin C for Prophylaxis of Viral Hepatitis B in Transfused Patients,” (J. Int. Acad. Prev. Med. 1978;5(1):54–58) in which they discussed their hepatitis work.  In it, Murata and Morishige reported on a series of tests in which patients who had received blood transfusions were also given specific dosages of vitamin C.  From there, observations were made with respect to hepatitis contraction among the transfusion patients.

The researchers found that, between 1967 and 1976, no hepatitis B cases were recorded for those who received large doses of vitamin C following a blood transfusion. The paper concluded that vitamin C, in large amounts, has a “significant prophylactic effect against post-transfusion hepatitis, especially type B.”  Prior to its publication, Pauling annotated and edited Murata and Morishige’s text, adding his suggestions for how the manuscript could be improved.

In 1976, the year of his residency at the Pauling Institute, Murata also published observations made by Morishige on the effect of increased doses of ascorbic acid with respect to various viral and bacterial diseases. In their study, the duo found that ascorbic acid showed a therapeutic effect on infectious hepatitis, measles, mumps, viral orchitis, viral pneumonia and certain types of meningitis.

Murata continued this line of research through the 1980s, continually seeking out new ways to test the effects of vitamin C on human health. Like Pauling and Morishige, Murata was also highly interested in vitamin C and its possible therapeutic use with cancer. Several papers arose from this program of work, including one titled “Prolongation of Survival Times of Terminal Cancer Patients by Administration of Large Doses of Ascorbate,” (Int. J. Vitam. Nutr. Res. Suppl. 1982;23:103-113) and another listing viruses reported to be inactivated by vitamin C. Together, Pauling and Murata also served as chairmen and panel members for at least one workshop on vitamin C, immunology and cancer.

Akira Murata, Ava Helen Pauling and Linus Pauling. In Japan, 1980.

By the late 1980s, Akira Murata had contributed upwards of twenty-five publications on vitamin C and its effects upon various diseases, and Pauling continued to visit him and keep in contact. Murata typically hosted at least a portion of Pauling’s many visits to Japan, often acting in the duel capacity of scientific colleague and friend. Murata also translated a few of Pauling’s books into Japanese. Among these was Vitamin C, the Common Cold, and the Flu, the preface of which contains Pauling’s note of thanks to Murata and the observation that “it is important that everyone know about the great value that vitamin C has in improving health and in protecting against disease.” Murata also translated Pauling’s best-seller, How to Live Longer and Feel Better.

As with a few other contacts in Japan – especially Morishige – Pauling remained in close correspondence with Murata over the duration of their acquaintance, frequently discussing papers on vitamin C and exchanging ideas on new studies. The two remained friends and collaborators throughout the last two decades of Pauling’s life, both benefiting greatly from their cross-cultural exchange.

Biochemical Individuality

Roger J. Williams and Linus Pauling, 1972

[Part 4 of 4 in a series on Vitamin C and the Common Cold]

Toward the end of his book Vitamin C and the Common Cold, Linus Pauling included a chapter on human biochemical individuality.  In it, he addressed the fact that every human is different, and as a result, each individual has a unique need for specific amounts of vitamin C.

Pauling pointed out that when any characteristic, such as the concentration of a certain enzyme in the red blood cells, is studied in a sample of 100 human beings, a wide range of values are invariably observed. The “normal” range is that in which 95 percent of those values lie, while the remaining 5 percent are described as abnormal. Defining normalcy on a larger scale is a bit tricky however. Pauling stated that

If we assume that 500 characters are independently inherited, then we can calculate that there is only a small chance, 10 percent, that one person in the whole population of the world would be normal with respect to each of these 500 characters.

The situation is complicated further by the fact that humans possess some 100,000 genes, each of which performs a different function.  “Accordingly,” Pauling wrote, “we reach the conclusion that no single human being on earth is normal (within the range that includes 95 percent of human beings) with respect to all characters.”

Guinea pigs, like humans, are also genetically heterogeneous, as was demonstrated in a 1967 vitamin C experiment carried out by Roger J. Williams and Gary Deason of the University of Texas, Austin. The investigators obtained more than 100 young male guinea pigs, and initiated their experiment by closely observing the guinea pigs for a week while they were fed a healthy diet. This completed, the animals were then divided into eight groups of 10 to 15 animals, with each group receiving varying amounts of ascorbic acid, and one group receiving none.

Each of the guinea pigs reacted differently to the amount of ascorbic acid given to them.  About 80 percent of the guinea pigs that were fed no ascorbic acid or less than 0.5 mg of ascorbic acid per kilogram of body weight per day showed signs of scurvy. Only a quarter of those receiving between 1 mg and 4 mg per kilogram per day showed signs of scurvy, while those receiving 8 mg per day or more did not show any signs of the disease. These results were in accordance with the commonly held belief that guinea pigs need about 5 mg per day of ascorbic acid in order to prevent scurvy.

However, the experiment also produced anomalies: two of the guinea pigs receiving only 1 mg of ascorbic acid per kilogram per day stayed healthy, and gained weight over the course of the eight-week experiment. One of them even gained more weight than any of the animals receiving a larger amount of vitamin C.

Strangely, seven of the animals receiving 8, 16, or 32 mg per kilogram per day were unhealthy, and did not grow very much. Five of these were then provided with 64 mg per kilogram per day, and two of them were provided with 128 mg per kilogram per day. When they were provided with larger amounts of vitamin C they began to grow at a much faster rate: initially, they had only grown about 12 grams in ten days, but during the next ten day cycle, while receiving more vitamin C, they gained an average of 72 grams each. The conclusion reached was that these seven guinea pigs, out of the thirty that were placed on between 8 mg and 32 mg per kilogram per day, possessed a larger built-in vitamin C requirement.

Williams and Deason determined that out of 100 guinea pigs, there existed a requirement range of at least 20 different levels of vitamin C. From there, the duo extrapolated that “the population of human beings is presumably not more uniform than that of guinea pigs used in their experiments, and that accordingly the individual variation in human vitamin C needs is probably just as great.”

Pauling agreed with this conclusion, adding that the requirement of ascorbic acid for humans probably ranges from 250 mg per day to 10 g per day. And he continued to make reference to biochemical individuality throughout the book, suggesting that 1 g to 2 g per day is approximately the correct amount of ascorbic acid for the average human being to ingest.

Vitamin C Deficiency in Humans: An Issue of Evolution?

Linus Pauling and Irwin Stone, 1977.

[Part 3 of 4 in a series on Vitamin C and the Common Cold]

In the chapter “Vitamin C and Evolution” from his book Vitamin C and the Common Cold, Pauling wondered about the reasons why the rest of the animal world can synthesize vitamin C, while human beings, along with a very small group of mammals, cannot. His answer was gene mutation, using the instance of thiamine as evidence.

All animals need thiamine as an essential vitamin; in its absence they develop a disease similar to beriberi. Pauling theorized that over 500 million years ago, when the common ancestor to present-day birds and mammals lived, there existed an environment imbued with an abundance of green plants containing thiamine. By way of gene mutation, one of the animals living during that era must have lost the mechanism which allowed it to synthesize thiamine. This was advantageous to the animal – which was probably plant-eating – because it could obtain the thiamine it needed from the plants it ingested while simultaneously conserving the energy that it would have used to manufacture the vitamin.

Pauling pointed out that possessing this extra energy would have caused the animal to flourish and to have more offspring than others of its kind. The advantageous mutation would be passed on to certain of the progeny, who would in turn pass it on to their own offspring, and so on. Eventually the mutation would spread, and a few million years later all mammals and birds would possess the mutation.

Pauling believed that in the same way that all animals lost the biochemical machinery to produce thiamine, so too did human beings, primates, guinea pigs and a particular Indian fruit-eating bat lose the ability to synthesize vitamin C. A mutation that results in the inability to synthesize a substance is simple and occurs often; it only requires a single gene to be damaged or deleted. The reverse process is more complex and takes much longer. The mutation that removed the ability to synthesize vitamin C probably took place about 25 million years ago, in the ancestor of modern primates and humans.

In his book, Pauling next asked the question, why didn’t all mammals and birds lose the ability to synthesize vitamin C the way that they lost the ability to synthesize thiamine? Pauling theorized that the change likely occurred in the guinea pig and the Indian fruit-eating bat independently of the common precursor of the primates, due to an abundance of vitamin C in their diets. The fact that the majority of animals possess the ability to synthesize vitamin C indicates that there is not sufficient vitamin C in their dietary environment for them to obtain the vitamin solely from their nutrition intake.  To Pauling, this also suggested the existence of a deficiency of ascorbic acid in the human diet.

Dr. Irwin Stone, a biochemist in Staten Island, New York, was the person responsible for sparking Linus Pauling’s interest in vitamin C. Dr. Stone, a leader in the ascorbic acid field at the time, sent a letter to Pauling in 1966 informing him of a high-level ascorbic acid regimen that he had been developing over the past three decades, which Pauling and his wife began to follow. Stone believed that humans need between 3 and 5 grams of vitamin C per day, reinforcing this claim by citing the British researcher G. H. Bourne’s evidence that gorillas ingest about 4.5 g of ascorbic acid per day.

Gorillas, like humans, do not synthesize vitamin C, and so need to obtain it from their diet. In 1949 Bourne pointed out that before the development of agriculture, humans lived mainly off of raw, green plants with little meat; a diet similar to that of the modern gorilla. Bourne concluded that

it may be possible, therefore, that when we are arguing whether 7 or 30 mg of vitamin C a day is an adequate intake we may be very wide of the mark. Perhaps we should be arguing whether 1 g or 2 g a day is the correct amount.

Irwin Stone also took into consideration the amount of ascorbic acid that other animals, such as rats, manufacture. The rat synthesizes vitamin C at a rate of between 26 mg and 58 mg per day per kilogram of body weight. If the same rate of manufacture were applied to humans, a person weighing 70 kg (154 lbs) would need to ingest between 1.8 g and 4.1 g of ascorbic acid per day.

From there, Pauling verified the amounts of various vitamins contained in 110 different raw fruits and vegetables corresponding to a diet of 2,500 kilocalories per day, and found that “for most vitamins this amount is about three times the daily allowance recommended by the Food and Nutrition Board.” For ascorbic acid, the difference was much more drastic: the average amount of ascorbic acid in a day’s ration of the 110 raw foods was 2.3 g, which was about 42 times the recommended amount. Pauling argued that

If the need for ascorbic acid were really as small as the daily allowance recommended by the Food and Nutrition Board the mutation would surely have occurred 500 million years ago, and dogs, cows, pigs, horses, and other animals would be obtaining ascorbic acid from their food, instead of manufacturing it in their own liver cells.

Pauling found that the average ascorbic acid content for the fourteen most vitamin C-rich plant foods is 9.4 g per 2,500 kilocalories, leading him to the conclusion that the optimum daily vitamin C intake for an adult human being is between 2.3 g and 9 g – quantities in line with what he saw as existing in the natural diet of the human lineage and numbers far beyond the recommendations issued government nutritional authorities, then or now.

Physicians Anecdotes and the Safety of Large Doses

[Part 2 of 4 in a series on Vitamin C and the Common Cold]

“The medical profession itself took a very narrow and very wrong view.  Lack of ascorbic acid caused scurvy, so if there was no scurvy there was no lack of ascorbic acid.  Nothing could be clearer than this.  The only trouble was that scurvy is not a first symptom of lack but a final collapse, a premortal syndrome and there is a very wide gap between scurvy and full health.”

-Albert Szent-Gyorgyi

In writing his book Vitamin C and the Common Cold, one of Linus Pauling’s primary aims was to convince the general public of the safety and effectiveness of ingesting vitamin C in large doses. Early on in his text, Pauling stated that “an intake of about 10 mg per day is enough to provide protection against scurvy for most people, but to achieve the best health a much larger intake is probably needed.” The exact amount of vitamin C needed for optimum health is not known, since each person has a different requirement, but Pauling proposed that most people need between 250 mg and 10 g daily.

The range that Pauling prescribed was much higher than was the daily allowance recommended, at the time, by the Food and Nutrition Board of the National Research Council. In 1970, at the time that Vitamin C and the Common Cold was published, the Board was advising a healthy daily allowance of vitamin C of 35 mg for infants, 40 mg for children, 55 mg for women and 60 mg for men – amounts which were somewhat higher than the minimum 10 mg necessary to prevent scurvy, as calibrated to allow for individual variability and for potential losses in food. The current Recommended Daily Allowance for vitamin C is similar to that of the 1970s for infants and children, but has increased to 90 mg for men and 75 mg for women.

In his counterargument to the RDA, Pauling stressed that vitamin C is totally harmless, noting that guinea pigs given 0.5% of their body weight of vitamin C every day for a few days showed no adverse symptoms. He also noted that human subjects were known to have consumed as much as 40 g per day for a month without negative side effects. In fact, negative side effects seemed only to occur when a large amount of vitamin C was taken on an empty stomach.  As Pauling put it

A large amount (several grams) of ascorbic acid eaten without other food may cause an upset stomach and diarrhea in some people (hence the recommendation in Chapter 10 that it usually be taken at the end of a meal) but more serious side effects have not been reported.

Indeed, vitamin C is regarded to be as non-toxic as most cooking ingredients – no deaths or serious illnesses, Pauling wrote, have been attributed to it’s ingestion. Vitamin C is present in many fruits and vegetables, such as green peppers, red peppers, parsley, and turnip greens, as well as orange juice, lemon juice, lime juice, grapefruit juice, and tomato juice. Pauling noted, however, that cooked vegetables lose about half of their vitamin content, and as such should be cooked for the minimum amount of time and with a minimum amount of water.

Physicians Anecdote: Irwin Stone

Having made his case that vitamin C is totally harmless even in large amounts, Pauling moved on to include a few anecdotes from physicians who had personally benefited from a specialized ascorbic acid regimen. The influential Dr. Irwin Stone, a biochemist from Staten Island, New York, wrote in 1966 that he had ingested 3 g to 5 g of ascorbic acid per day for ten years. During this time he observed that he had not suffered a single cold. Stone’s recommended procedure for warding off the common cold was to take 1.5 g of vitamin C at the first sign of symptoms, and another 1.5 g again every hour. Stone’s experience suggested that the cold was usually eradicated by the time the third dose had been taken.

Edmé Régnier

Another physician, Edmé Régnier of Salem, Massachusetts, reported in 1968 that he had also found large doses of ascorbic acid to be useful in the prevention of the common cold. Régnier had suffered from chronic bouts of middle ear infection from the age of seven, an affliction for which he was unable to find a remedy and which led to his interest in vitamin C. Finally, after twenty years and several trials involving bioflavonoids and ascorbic acid, he found that “the serious and disagreeable manifestations of the common cold and the accompanying inflammation of the middle ear could be averted by the use of large amounts of ascorbic acid.” Régnier studied 22 subjects, giving them either ascorbic acid alone, ascorbic acid plus bioflavonoids, only bioflavonoids, or a placebo, over the course of five years. The subjects were not told which preparation they were receiving, but eventually one subject realized that he was not receiving the ascorbic acid that could have prevented his developing a cold.

Edmé Régnier

Régnier recommended the administration of 600 mg of ascorbic acid at the first manifestations of a cold, a quantity quite a bit lower than Stone’s recommendation of 1.5 g.  Régnier likewise suggested that the initial dose should be augmented by 600 mg of ascorbic acid every three hours, or 200 mg every hour, ending with a dose of 750 mg just before bedtime. This regimen, Régnier argued, should be continued for three or four days, decreasing to 400 mg every three hours, and then to 200 mg every three hours. According to Régnier’s study, 31 out of 34 colds were averted using ascorbic acid plus bioflavonoids, and 45 out of 50 colds were averted using only ascorbic acid. Neither bioflavonoids alone nor the placebo were effective. He cautioned, however, that if the ingestion of ascorbic acid were to be suddenly discontinued, a cold may resurface again, even if a week or more has passed by.

Douglas Gildersleeve

In the July-August 1967 issue of Fact magazine, Douglas Gildersleeve, M.D., added a somewhat conspiratorial tone to the conversation in his article “Why Organized Medicine Sneezes at the Common Cold.” In it, Gildersleeve stated that ascorbic acid, an “effective treatment” for the common cold, was being ignored because it would adversely affect “pharmaceutical manufacturers, professional journals, and doctors themselves.”

Gildersleeve studied more than 400 colds in 25 subjects, mostly his own patients, giving them about 4 g of ascorbic acid per day. He reported that the ascorbic acid was effective in 95 percent of his patients, eliminating completely the most common symptom – excessive nasal discharge – while drastically reducing other symptoms of a cold. None of his patients suffered negative side effects. Gildersleeve wrote a paper in 1964 detailing his observations, and submitted it to eleven different professional journals. Every single one rejected it. According to Gildersleeve, one editor told him that medical journals depended on the support of advertisements, over twenty-five percent of which were related to drugs for symptoms of the common cold or complications of colds. This same editor allegedly told him that it would be “harmful to the journal to publish a useful treatment for the common cold.”  And so it was that Gildersleeve’s data went unpublished until the Fact article three years later.

Five Controlled Trials

[Part 1 of 4 in a series on Vitamin C and the Common Cold]

Linus Pauling became interested in ascorbic acid thanks to Dr. Irwin Stone, a biochemist from New York. After meeting Pauling in 1966 and hearing Pauling speak of his desire to live for an additional fifteen or twenty years, Dr. Stone sent him his own high-dose ascorbic acid regimen, which Pauling and his wife Ava Helen soon began to follow. After adhering to this program for several years, the Paulings observed a shared feeling of increased well-being and a striking decrease in the number of colds that they were contracting.

Linus Pauling was convinced that vitamin C was powerful enough to cure the common cold, but he was also aware that many authorities did not share his opinion.  He addressed this conflict in Chapter Five of his book Vitamin C and the Common Cold (1970) noting his desire to

resolve the apparent contradiction between the opinions expressed by authorities in nutrition and my own experience, which supported the widely held belief that ascorbic acid has value in decreasing the incidence of infection and ameliorating the severity of the common cold.

Pauling argued that ascorbic acid provides a minimal amount of protection against colds when taken in small amounts, but that the effect is proportionately greater when it is taken in much larger doses. According to Pauling, protection against colds becomes “nearly complete” when, shortly after the onset of a cold, one ingests four to ten grams of ascorbic acid per day. In support of his argument, Pauling cited five controlled trials conducted with various groups of people around the world.  These trials, he felt, supported his idea that health can be improved by adding more vitamin C to one’s diet.

Cowan, Diehl and Baker, 1942

The first study Pauling listed was an analysis of about 400 students at the University of Minnesota, conducted by Cowan, Diehl, and Baker during the winter of 1939-1940, and published in 1942 in the Journal of the American Medical Association. In this study, for twenty-eight weeks about half of the Minnesota students received 100 milligram tablets of vitamin C twice per day, while the other half received a placebo. The investigators concluded that the young adults who were already on a healthy diet were not greatly influenced by the 200 mg of vitamin C per day.  However, the study also yielded other important results.

First, the group receiving ascorbic acid throughout the twenty-eight week period experienced an average of 1.9 colds per person, with a 0.07 cold margin of error. Meanwhile, those in the placebo group reported an average of 2.2 colds per person, with a 0.08 margin of error. The investigators concluded that

the actual difference between the two groups during the year of the study amounts to 1/3 of a cold per person…[o]ne may therefore consider this as probably a significant difference, and vitamin C supplements to the diet may therefore be judged to give a slight advantage in reducing the number of colds experienced.

Pauling pointed out that this amounted to a 15% decrease in the quantity of colds per person. And although the investigators seemed to judge this a bordering-on-negligible amount, Pauling thought differently, wondering in his text if increasing the dosage to 400 mg of ascorbic acid per day would have decreased the colds twofold.

Another point in the Minnesota data that Pauling found compelling was the fact that of the 233 students participating in the ascorbic acid group, only 25 dropped out over the course of the study.  On the other hand, 39 students dropped out of the control group, which had started with 194 participants. Pauling drew the conclusion that a greater percentage of the students receiving ascorbic acid felt that they were benefiting from the study. Pauling likewise noted that the group which received vitamin C only missed an average of 1.1 days of school over the twenty-eight week study, while those who received the placebo lost an average of 1.6 school days.

Glazebrook and Thomson, 1942

In 1942 Glazebrook and Thomson published a similar study in the Journal of Hygiene, though this one focused on an institution of about 1,500 students in Scotland, where the students ranged in age from 15 to 20 years old. Glazebrook and Thomson’s group consumed a total dietary intake of only about 5 to 15 mg of ascorbic acid per student per day. This number was so low mainly because the school’s food was kept hot for two hours or more before serving, a practice which caused the served vegetables to lose much of their vitamin content.

In the Scottish survey, 335 students were given extra ascorbic acid – 200 mg per day for six months – while the remaining 1,100 served as a control. The ascorbic acid group recorded a 30.1 percent incidence of colds and tonsillitis, while the control group reported a 34.5 percent incidence. From these results, Pauling extrapolated that among the students who were given ascorbic acid, there were 13 percent fewer colds – a number close to the 15 percent decrease found in the Minnesota study.

The Scottish students who displayed more severe symptoms of colds or tonsillitis were admitted to Sick Quarters – 23.0 percent of the ascorbic acid group compared to 30.5 percent of the control group. This meant that 25 percent fewer students in the ascorbic acid group were admitted to Sick Quarters than were those in the control group.

Likewise, those receiving vitamin C also managed to stay out of the hospital: the average number of days spent in hospital due to infection for the control group was 5, versus 2.5 for the ascorbic acid group.  Drilling even deeper, there were 17 cases of pneumonia and 16 cases of acute rheumatism reported among the controls, while neither illness showed up in the ascorbic acid group.  Pauling used this data to emphasize the power of ascorbic acid in countering serious infections as well as the common cold.

Linus Pauling at an international vitamin symposium, Sao Paulo, Brazil, 1980.

Franz, Sands and Heyl, 1956

From there, Pauling briefly recounted an observation of 89 volunteer medical students and student nurses whose health was tracked for three months. The paper that resulted was published in a 1956 issue of the Journal of the American Medical Association by Franz, Sands, and Heyl. The study was constructed such that 44 of the students received 195 mg of ascorbic acid per day, while the remaining 45 received none.  In this instance, students in both groups experienced about the same number of colds, but the colds were judged to be less severe for the ascorbic acid group. It was concluded that this decreased severity and rapid improvement was “statistically significant at the 0.05 level.”

Wilson and Low, 1970

While each of the above studies and their results were relevant to Pauling’s case, Wilson and Low’s 1970 Acta Allergologica paper was of greater importance because it was a double-blind investigation. In this instance, neither the subjects – 103 students at a girls’ school in Ireland – nor the investigators evaluating the effects of the preparation knew which subjects had been given the placebo and which ones had been given vitamin C; that is, not until the study had reached its conclusion. As with the previous trials, the amount of 200 mg per day was used, but in the Wilson-Low group, 57 students received ascorbic acid while 46 received a placebo tablet over a period of three winter months.

Wilson and Low’s data indicated that ascorbic acid “reduced the incidence, duration, and severity of the symptoms of both toxic colds (sore throat, headache, fever, malaise) and catarrhal colds (cold in the head, cough, nasal obstruction, nasal discharge).” Symptoms of catarrhal colds lasted 8 days for the ascorbic acid group as opposed to 14 in the placebo group.

Pauling also noted that laboratory work indicated that the girls receiving ascorbic acid showed a higher concentration of ascorbic acid in the white blood cells than did the control group: the girls who had been receiving 200 mg of ascorbic acid once a day for 6 months had, on average, 60 micrograms of ascorbic acid present per hundred million cells, while those in the control group averaged 43 micrograms per hundred million cells. Pauling believed that “[t]his increase may be in part responsible for the increased resistance to infection.”

Ritzel, 1961

While these four studies seemed to show that about 200 mg of vitamin C daily can lessen the duration and symptoms of the common cold, Pauling needed to reinforce his hypothesis that “a somewhat larger intake of ascorbic acid provides somewhat greater protection.” To do so, Pauling turned to another double-blind study carried out in 1961 by the Swiss investigator Gunther Ritzel and published in Helvetica Medica Acta.

Unlike the rest of the literature cited by Pauling, Ritzel used 1000 mg of ascorbic acid, and noted a much greater effect than did the previous 200 mg studies. In his test of 279 skiers, Ritzel provided half of the subjects with 1000 mg of ascorbic acid per day, while the other half received a placebo. Among the vitamin C group, the data indicated a reduction of 61 percent in the number of days of illness from upper respiratory infections, and a 65 percent decrease in individual symptoms. Pauling was quick to note the substantial improvement in Ritzel’s group as compared to the 15 percent decrease brought about in the earlier studies by the daily ingestion of 200 mg of vitamin C. The data all seemed to provide solid evidence for Pauling’s basic rule of thumb:  when it comes to the common cold, the more vitamin C the better.

Vitamin C, the Common Cold and Controversy

By Tom Hager

[Part 3 of 3. For the full text of this article, originally presented as a lecture sponsored by Oregon Health Sciences University, please see this page, available at http://thomashager.net]

Portuguese edition of Vitamin C and the Common Cold, a book that was translated into nine different languages.

Pauling’s reading of the literature convinced him that the more vitamin C you took, approaching megadose levels, the lower your chances of getting sick, and the less sick you got.  It was at this point that Pauling made what I consider to be a fundamental mistake. He decided to publish his ideas without peer review, in the form of a popular book.

He did not feel he could wait. He had, he thought, good evidence that a cheap, apparently safe, easily available nutrient could prevent at least an appreciable fraction of a population from suffering through an affliction that made millions of people miserable. And there might be even greater results. Pauling had read of small villages, snowbound in the winter, where no one got colds because there was no reservoir of respiratory viruses to pass around. When visitors arrived in the spring, they would bring colds with them, and everyone would suffer. What if, through the use of vitamin C, a great many more people strengthened their resistance to colds? The two hundred or so cold viruses rampant in the world would have many fewer places to replicate themselves. The spread of colds would lessen; the population of cold viruses would decrease. “If the incidence of colds could be reduced enough throughout the world,” Pauling thought, “the common cold would dis­appear, as smallpox has in the British Isles. I foresee the achievement of this goal, perhaps within a decade or two, for some parts of the world.” Vitamin C, properly and widely used, might mean the end of the common cold.

Packaging for commercial cold remedies pasted by Pauling into his research notebook, July 1970.

This, of course, would not only greatly lessen the amount of suffer­ing in the world; it would increase the fame of Linus Pauling. He was nearing seventy years of age. It had been nearly twenty years since he had captured international attention for his scientific work with proteins, and won the Nobel Prize for chemistry. His efforts had gone to politics in the years since, and none of his recent scientific work had had much impact. Science was moving on without him. He was becoming a historical figure.

Pauling did not feel like one. He was not ready for emeritus status, trotted out at honorary occasions, shunted aside while the young men made the discoveries. He was still strong, still smart, still a fighter. Or­thomolecular medicine was the newest of his grand plans, and no one had shown that his ideas about creating an optimal molecular environ­ment for the body and mind were wrong. The evidence he had uncov­ered about ascorbic acid and colds, evidence that showed human health could be improved by increasing the amount of vitamin C in the body, was the strongest indication yet that he was right. Bringing it to the public’s attention would not only be good for the public; it would be a striking example of the correctness of his general theory.

Pauling’s book Vitamin C and the Common Cold, written in his usual clear, well-organized, straightforward style, presented the results of his literature search. He discussed the findings of five controlled trials that supported his idea, several anecdotal instances of physicians who had treated colds with vitamin C, and evidence that ascorbic acid was safe in large doses. Pauling felt confident that a several-gram daily dose would do no more harm than to cause loose stools, that vitamin C was safe, especially compared with potentially toxic, commonly avail­able over-the-counter medications such as aspirin. The rest of the book was a summary of his orthomolecular thinking and Irwin Stone’s ideas about evolution. A good deal of space was devoted to the topic of bio­chemical individuality, which resulted in a wide personal variation in the need for vitamin C and other nutrients.

Excerpt from "Cold Preventive", New York Times, November 19, 1970.

On November 18, 1970, prepublication galleys were released to the press, and an unprecedented public roller-coaster ride began. The next day, the New York Times quoted Pauling as saying that humans needed between 1 and 4 grams of vitamin C per day to achieve optimal health and prevent colds. Pauling also took the occasion to slam the medical establishment – from drug companies to medical journals and physicians – for attempting to quash the evidence in favor of ascorbic acid. Why would they do that? the reporter asked. Look at the cold-remedy industry, Pauling said: It was worth $50 million per year, and that bought a lot of advertising space in medical magazines.

This quickly alienated both physicians and the editors of medical journals, neither of whom liked the implication that profits were more important than health. The medical establishment felt it necessary to respond, and respond quickly, once they saw how Pauling’s idea took off.

The book sold wildly, and so did vitamin C.  Pauling’s timing, at least on the public side, was superb. The 1960s had seen a resurgence of interest in “natural” health based on a holistic attitude that said body, mind, and soul were one. Many streams fed into this alternative health movement: a back-to-the-land, organic-foods orientation; a fas­cination with yoga, acupuncture, meditation, and other Eastern health practices; the rediscovery of the lost Western arts of naturopathy and homeopathy. Pauling’s message about vitamin C resonated with mil­lions of people who were reacting against corporate, reductionistic, paternalistic medicine, with its reliance on drug therapy, with people taking a renewed responsibility for their own health and trying to do it naturally. It was delivered just as natural food stores were popping up on corners in every town in America, each one stocked with a section for herbal remedies, a rack for magazines on alternative health regi­mens, and plenty of shelf space for vitamins.

The publication of Pauling’s book triggered a nationwide run on vitamin C. Sales skyrocketed, doubling, tripling, quadrupling, within a week of its appearance. Druggists interviewed in newspapers across the nation told of people coming in to buy all the vitamin C they had. Wholesale stocks were depleted. “The demand for ascorbic acid has now reached the point where it is taxing production capacity,” said a drug company spokesman less than a month after Pauling’s book ap­peared, adding, “It wouldn’t pay to increase production capacity since we’re sure it’s just a passing fad.”

The reaction was swift. The physician-head of the Food and Drug Administration (FDA), Charles C. Edwards, announced to the press that the national run on vitamin C was “ridiculous” and that “there is no scientific evidence and never have been any meaningful studies in­dicating that vitamin C is capable of preventing or curing colds.” The FDA, Pauling found, had proposed in 1966 that no vitamin C tablets over 100 mg be available without a prescription, and he responded to Edwards with sarcasm. If the FDA had its way and he wanted to take 10 grams of vitamin C to fight off a cold without going to a physician for a prescription, Pauling said, he would have to take 100 tablets. “I think I would have as much trouble swallowing all these tablets as I would swallowing some of the statements made by the Food and Drug Ad­ministration in proposing these regulations,” he said.

The medical press was equally critical of Pauling. The American Journal of Public Health said that Pauling’s book was “little more than theoretical speculation.” The Journal of the American Medical Association said of Pauling’s book, “Here are found, not the guarded statements of a philosopher or scientist seeking truths, but the clear, incisive sentences of an advertiser with something to sell. . . . The many admirers of Linus Pauling will wish he had not written this book.” The Medical Letter launched the harshest attack yet, saying Pauling’s conclusions “are derived from uncontrolled or inadequately controlled clinical studies, and from personal experience” and pointing out that there was no good evidence that vitamin C was safe when taken over a long period of time in large doses.

Extract from "The VIP Line," Miami Herald, June 7, 1971.

The controversy over Pauling’s book arose from a simple fact: He had not made his case. The book was a combination of his interesting but unproven speculations about orthomolecular medicine and the human evolutionary need for ascorbic acid, coupled with a select handful of studies that indicated that vitamin C could prevent or ame­liorate colds in a fraction of a population. That might make an inter­esting conference paper, but it was little reason to advocate a wholesale change in the dietary habits of a nation. His critics pointed out that he had no clear theory of how vitamin C exerted it powers and that there was no good study – no study at all – establishing that the long-term ingestion of megadoses of vitamin C was safe. The current dogma in the medical profession was that vitamins were needed only in the small amounts provided by a well-balanced diet. Taking grams of vitamin C every day might cause everything from gastric upset to kid­ney stones, and who knew what else?

The way he had gone about publicizing his ideas, sidestepping the normal channels of scientific peer review to publish a popular book, also fueled criticism. He was behaving like a health faddist, not a scien­tist. In the eyes of most physicians – generally conservative about new therapies, disdainful of the holistic health movement, trained to be­lieve that vitamin C was needed only to prevent scurvy – Pauling looked like a nutritional quack, a vitamin pusher who was essentially prescribing without a license.

Typically, Pauling fought back. To pursue his ideas, in 1973 he cofounded (with Arthur Robinson, a young colleague who later moved to Oregon and this year ran for Congress) the Institute of Orthomolecular Medicine in Palo Alto, California.

He went on to publish more books, adding the flu as another disease vitamin C could fight, then Vitamin C and Cancer, and finally compiled all his ideas into How to Live Longer and Feel Better.

Anecdote published in Chemtech, September 1994.

Criticism from the medical community has never let up. A general belief still exists in most – although not all – of the medical community that Pauling went off his rocker.

However, despite what many physicians believe, the jury is still out. A significant amount of active biomedical research research continues to examine the effects of micronutrients on a variety of conditions. For instance the Linus Pauling Institute at Oregon State University (successor to Pauling’s Orthomolecular Institute) maintains a highly successful research program in 12 laboratories funded with millions of dollars of competitive grant funding. The Institute’s head, Balz Frei, believes that Pauling’s basic approach remains sound – but that his arguments with physicians might have caused as much damage to the study of nutritional science as they did good. In my own view, by putting personal controversy ahead of reasoned consensus both Pauling and his critics polarized the public into groups that still have trouble communicating with each other.

Pauling’s work helped give birth to today’s booming market in nutritional supplements. Vitamin C remains the world’s largest-selling supplement. A large number of advocates strongly believe that ingesting vitamins in amounts far above the RDA can help optimize human health, especially by preventing chronic disease. There is a growing understanding that the key in these studies – as Pauling pointed out long ago – is not to look for vitamins to act like pharmaceuticals, exerting significant effects at low doses, but more like nutrients, with less dramatic effects that accumulate at much higher doses.

Linus Pauling himself lived an active life well into his nineties, performing useful research until the end. He was taking many grams of Vitamin C every day.

Will the controversy he started ever end? Was he a genius, or a crank?

The Birth of Orthomolecular Medicine

By Tom Hager

[Part 2 of 3.  For the full text of this article, originally presented as a lecture sponsored by Oregon Health Sciences University, please see this page, available at http://thomashager.net]

Linus Pauling and Irwin Stone, 1977.

The concept of orthomolecular medicine was Pauling’s grand theory of human health.

His approach was chemical, and viewed the body as a vast laboratory buzzing with chemical reactions: enzyme-substrate reactions, energy-producing reactions, antibody-antigen reactions, the chemical interactions that resulted in genetic duplication, and electrochemical reactions in the brain and nerves. Health, in this view, resulted when the lab was well-run and reactions were moving ahead properly; disease resulted if the proper reactions were hindered or stopped. Optimal health could be achieved by perfecting reaction conditions and making sure that the body maintained the proper balance of chemicals (nutrients, catalysts, and products).

After thinking about this balance for years, he coined a term to describe it: orthomolecular, meaning “the right molecules in the right amounts.”

He first used the term in print in 1967 in relation to psychiatric therapy. He had by then become convinced that conditions such as schizophrenia could be treated with nutrients such as niacin (an approach developed by Abram Hoffer and Humphrey Osmond). However, his theory of orthomolecular psychiatry was either ignored or criticized by the medical community.

Then came Vitamin C.

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In March 1966, in a speech Pauling gave after receiving the Carl Neuberg Medal – awarded for his work in integrating new medical and biological knowledge – he men­tioned to the audience that he wanted to live another fifteen or twenty years in order to see the wonderful new medical advances that would surely come. A few days later, he received a letter from Irwin Stone, a gregarious Staten Island biochemist he had met briefly at the Neuberg dinner.

Stone told him how much he appreciated his talk and then wrote that asking for twenty more years of life was asking for too little. Why not live another fifty years? It was possible, if Pauling listened to his ad­vice.

Letter from Irwin Stone to Linus Pauling, April 4, 1966. This is the communication that spurred Pauling's interest in vitamin C.

He then told him about vitamin C.

Irwin Stone had been interested in vitamin C since 1935, when he began publishing papers and taking out patents on the use of ascorbic acid, or ascorbate (both synonyms for vitamin C), as a food preserva­tive. Over the years his interest grew as he read a series of scattered re­ports from around the world indicating that ascorbate in large doses might have some effect on treating a variety of viral diseases as well as heart disease and cancer. Convinced of its health-giving power, Stone and his wife started taking up to 3 grams of the vitamin per day- many times the daily dose recommended by the government.

Stone felt better as a result, but it took a car crash to make him a true believer. In 1960 Stone and his wife, driving in South Dakota, both nearly died when they were hit head-on by a drunk driver. They not only survived the crash, however, Stone told Pauling, but healed with miraculous rapidity. This he attributed to the massive doses of vitamin C they took while in recovery.

He emerged from the hospital ready to convince others about the value of ascorbate. He began to read widely, noting that among mam­mals, only man, closely related primates, and guinea pigs were unable to synthesize their own vitamin C internally because they lacked an en­zyme critical in producing the vitamin. As a result, humans had to ob­tain it through their diet. If there was none available, the result was scurvy, the dreaded ailment that had killed thousands of sailors before a British physician discovered it could be prevented by providing lime juice or fresh oranges. The U.S. government had duly set the mini­mum daily requirement for vitamin C at a level just sufficient to pre­vent scurvy.

But Stone believed that it was not enough. Scurvy was not a simple nutritional deficiency, it was a genetic disease, the lethal end point of an inborn error of metabolism, the loss of an enzyme that robbed hu­mans of the ability to produce a needed substance. And it appeared from animal studies that simply preventing scurvy might not be enough to ensure optimal health. Only one good biochemical assess­ment of ascorbic acid production in another mammal had been done, on rats, and it indicated that on a weight-adjusted basis, a 150-pound adult human would need between 1.4 and 4 grams of vitamin C per day to match what rats produced to keep themselves healthy. Stone was convinced that taking less than this amount could cause what he called “chronic subclinical scurvy,” a weakened state in which people were more susceptible to a variety of diseases. In a paper he had writ­ten- and which had already been rejected by six medical journals – he concluded,

This genetic-disease concept provides the necessary rationale for the use of large doses of ascorbic acid in diseases other than scurvy and opens wide areas of clinical research, previously inadequately explored, for the therapeutic use of high levels of ascorbic acid in infectious diseases, collagen diseases, cardiovascular conditions, cancer and the aging process.

In other words, to Stone, giving someone enough vitamin C to pre­vent scurvy was like feeding them just enough to keep them from starv­ing. Full, robust health demanded more. He advised that Pauling start with about one and a half grams per day. It was especially good, Stone said, for preventing viral diseases like colds.

“I didn’t believe it,” Pauling later said jokingly of Stone’s letter. After all, Stone was no physician, nor was he a nutritionist exactly or a professional medical researcher.

Pauling's response to Stone's letter of April 4, 1966. Written in July 1966.

But Pauling was interested enough to try taking more vitamin C himself. He discovered that it helped him fight off the colds that had frequently afflicted him. He felt better. He took a little more. Then more.

But he told few people about it. He remained generally silent about ascorbic acid and its benefits through the late 1960s, limiting his few comments to ideas about how it might be used, along with other nutrients, in the treatment of schizo­phrenics. In late 1969, however, convinced by the theoretical argu­ments of Irwin Stone and impressed by his own success in preventing colds, Pauling began expanding his comments to include the subject of ascorbate and general health, noting in a speech he gave to physi­cians at the Mt. Sinai Medical School his success with the use of vita­min C as a cold preventive. His comments were reported in the newspapers.

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Cartoon of Linus Pauling in the laboratory, by Sidney Harris. 1985.

That is how it began. Then, two things happened. First, he received a “very strongly worded” letter from Dr. Victor Herbert, a leading clinical nutritionist and a man who helped set the U.S. recommended daily allowances (RDAs) for vita­mins, who assailed Pauling for giving aid and comfort to the quacks who were bleeding the American public with unsupported claims about the benefits of vitamins. Where, Herbert asked, were the care­fully controlled clinical studies to prove that ascorbic acid had a real effect on colds?

Pauling was taken aback. He had not, in fact, carefully reviewed the literature on vitamin C, limiting his reading to a few of the cita­tions in Irwin Stone’s original papers. But now, “sufficiently irritated by this fellow Herbert,” he began a typically comprehensive tour of the scientific journals.

Second, a writer for Mademoiselle magazine contacted Pauling to get his comments on vitamin C for an article on its health benefits. Pauling offered the reporter the general observation that “optimal amounts of vitamin C will increase health and intelligence” and re­ferred readers to his paper on orthomolecular psychiatry. When the article appeared in November 1969, he found his statement rebutted by Frederick Stare, a professor of nutrition at Harvard, who said Paul­ing “is not an authority on nutrition” and that there was no evidence that increased C helped prevent the common cold; in fact, just the op­posite was true. A large-scale study done with five thousand students in Minnesota twenty years earlier, Stare said, had proven definitively that vitamin C had no effect on colds.

Stung, Pauling quickly tracked down the study and decided that Stare had gotten his facts wrong. The 1942 University of Minnesota study involved 363 student subjects who had been given either a placebo or some extra ascorbic acid over a period of twenty-eight weeks. It was true that the authors had concluded in their summary that there was no “important effect” of vitamin C on infec­tions of the upper respiratory tract. But when Pauling took a closer look at their data, he decided they were wrong. Despite what Pauling considered the very low dose of vitamin C given the students – an aver­age of 180 mg per day compared to the 3,000 mg Pauling was now tak­ing – the researchers had in fact seen an effect:  Subjects receiving the extra vitamin had 15 percent fewer colds, and the colds they got were 30 percent less severe than those receiving the placebo. Vitamin C was not a preventive or cure, but the results were, Pauling estimated, statis­tically significant.

It was confusing, especially when Pauling saw the same thing hap­pening in other reports he found on vitamin C and colds: Partial ef­fects were discounted. The physicians who ran the studies seemed to be looking for total cures, not an indication of an effect. The doses they used were low (150-250 mg was common in these early studies -  several times the current RDA but many times lower than what Pauling and Stone considered a protective dose), and the effects they looked for were too strong.

The problem, Pauling decided, was that the researchers were look­ing for vitamin C to act like a drug. In traditional drug testing, small differences in dosage could have tremendous effects, and overdoses were deadly. The tendency was to use relatively small amounts and look for big effects.

Pauling research notebook entry on Gunther Ritzel's 1961 study. Notes dated February 22, 1971.

But to Pauling, vitamin C was a nutrient, not a drug. When the medical researchers saw a small effect, he thought the logical next step should have been to follow up with larger doses. His literature search uncovered at least one study that showed what might happen if they did. In 1961 a Swiss researcher named Gunther Ritzel had given half of a group of 279 skiers 1,000 mg per day of vitamin C – more than five times the Minnesota dose – and the other half a placebo. Ritzel found that those skiers receiving ascorbic acid had 61 percent fewer days of illness from upper respiratory tract infections and a 65 percent decrease in the severity of their symptoms compared to the placebo group.

This, Pauling thought, was very strong evidence in favor of his ideas. Plot the dose of vitamin C along the bottom of a graph and the effects on colds up the side and you could draw a straight line from the Minnesota results (a small effect with small dose) to the Swiss findings (a larger effect with larger dose). He found a few other papers in which the results fit the pattern. True, some of the research he looked at showed no effect at all – most of these studies, Pauling estimated, were flawed because they used too low doses, too short duration, shoddy oversight, or improper blinding – but the important thing was that a small group of careful clinical studies existed that supported Pauling and Stone’s general theory of vitamin C and health: The more C you took, approaching megadose levels, the lower your chances of getting sick, and the less sick you got.

Formulas, Pictures and Sports Drinks: The Pauling Chalkboard, Part III

Linus Pauling, 1985.

(Part 3 of 3)

While much of the real estate on Linus Pauling’s chalkboard is consumed by lists of names, a number of additional annotations, when examined, prove to be of keen interest.

Metabolic Profiling

On the right side of the board, below the last column of names, is the following text:

NSF – Mol. Str. 21 Mar.

Library 3000 21 Mar.

Aging – NIH Nutrition

American Cancer Society – Dr. Neville

Sample Bank

Mass Spectrometer

Muscular Dystrophy

Aging Patterns in mice

This particular sample of notes relates to the metabolic profiling program carried out for some time at the Linus Pauling Institute of Science and Medicine. As mentioned in part II of this series, a large number of names on the board were involved with the metabolic profiling program, and this particular column of text ties many of the names together. Pauling was working with numerous people from diverse backgrounds and professions. He was in contact with researchers at, among other organizations, the Institute on Aging and the American Cancer Society.

The words “sample bank” refer to urine and blood samples that were to be kept refrigerated for, potentially, decades, and ultimately to be analyzed by mass spectrometry. This particular undertaking was very ambitious, and could have provided a great deal of material for practical study. Unfortunately, the chronically underfunded Institute had trouble with their refrigeration units, and the project was eventually abandoned. (Despite the setbacks, some results of this program of research, headed by Pauling and Arthur Robinson, can be found in articles published at Stanford University as well as in certain of the Institute’s early news releases.)

A New Sports Drink

Another interesting bit of text can be found towards the lower right hand corner of the board:

C + glycine

dextrose

The text is likely the basic outline of a carbonated “sports drink” being worked on by the Institute in the 1980s. The drink was to be infused with vitamins, and the Institute was developing acids that would provide alternative sweeteners. Production and research eventually halted, but it is interesting to think about what may have resulted from a successfully marketed “Paulingaide.”

Vitamin C, Cancer and Heart Disease

The following words, located in the upper right portion of the column ark, have perhaps the most basic and relevant connections to Pauling’s work.

Ascorbate

stimulates

Production of Lymphocytes

The order simply implies that ascorbate, or vitamin C, stimulates the production of lymphocytes, the major cellular components of the body’s immune system. Several studies have shown that increased levels of ascorbate generally correlate with increased levels of lymphocyte production. If nothing else, this is the most centrally relevant theme of Pauling’s work with vitamin C, and the fact that it maintained such a substantial place on his overcrowded board underlines the significance that he himself placed upon it.

In the middle of the board towards its top, is the diagram of a mystery molecule that was crafted by Pauling. Mention of the molecule (given the name “2-azido-5,8-dihydroxy-1,3,4,5,7,9,9b-heptaazaphenalene”) appeared in an article titled “A Prized Collection: Pauling Memorabilia,” published in Chemical and Engineering News in August 2000.

The board's "mystery molecule."

In a 1977 interview, Pauling was asked about his chalkboard and, in particular, about the mystery molecule.  He reponded

I had an idea in the field of organic chemistry about 40 years ago. It involved this unusual compound. Benzine has a six-membered ring of carbon atoms and this compound has three six-membered rings consisting of six carbon atoms and seven nitrogen atoms and then it has these hydroxyl groups attached. It is known that the similar substance with only one ring can be made into certain derivatives that have anti-cancer activity. And I thought that this substance with only three rings might well operate in the same way and that we should study it.

In other words, Pauling was still actively contemplating an idea that had occurred to him 40 years prior – an idea that managed to stay on his chalkboard through his death in 1994. Indeed the mystery molecule exemplifies the function of Pauling’s chalkboard, not only as a mnemonic device, but as a place holder for people and ideas that span decades.

Left of the mystery molecule towards the top of the board, one finds a series of words written one above the other. The seemingly haphazard placement of the words diverts attention from their historical significance in terms of the latter portion of Linus Pauling’s life.

LDL

Cholesterol

Lipoprotein a

The words almost certainly refer to research that Pauling began supporting in conjunction with a German physician named Matthias Rath, which investigated the possibility of a link between vitamin C and heart disease. Over the final years of his life, Pauling spoke of the relationship between vitamin C and heart disease in much the same way that he talked about vitamin C in terms of colds and cancer.

This writing was likely one of the last times that Pauling touched chalk to his board, as his collaboration with Rath did not develop until the early 1990s. The three words both acknowledge and hide the significance of the interaction between Rath and Pauling – a mercurial relationship for much of its duration.

Sandbox

Beneath an ark of name columns, adorned with the mystery molecule at its pinnacle, is a half-circle filled with pictures, figures and chemistry formulas. This area is likely where Pauling exercised the least concern for preservation, and it is supposed that this area of the board was used to aide in his discussions with visitors to his office. The space likely represents over two decades of personal interactions between Pauling and others, a spot on the board where he could explain theories and manifest abstract ideas. In essence, this half circle is where Pauling used the board in a more traditional sense – writing and erasing as suited his needs.

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Linus Pauling’s chalkboard is covered in historical significance. It functioned as an important tool for a very busy man, and has preserved a telling aspect of both the history of the Linus Pauling Institute and the character of Pauling himself, in part reflecting the organization of his consciousness.

 

To be sure, the board is merely a fragment of Linus Pauling and his research, but it is unique and intriguing in a very personal sense. The names, pictures and diagrams on the board all represent important aspects of Pauling’s professional life. Not only does it make a valuable contribution to a room dedicated to the man’s work, it preserves the living memory of Pauling by displaying an intimate demonstration of his method.

Pauling's chalkboard, as preserved in the OSU Libraries Special Collections.

Pauling’s Work on Swine Flu

"Pauling's Weapon Against Swine Flu," San Francisco Chroncile, August 31, 1976.

The current concern over the world-wide spread of swine flu virus brings to mind research that Dr. Linus Pauling conducted on this very subject, some thirty-three years ago.

Pauling’s interest in swine flu seems to have been stoked by a convergence of two factors: 1) mounting fears over a potential swine flu epidemic that first emerged in the winter of 1976; and 2) his composition of the book Vitamin C, the Common Cold and the Flu, which was published in September, 1976.  In the book – which was essentially a revised and updated version of Pauling’s massively-popular Vitamin C and the Common Cold, published in 1970 – Pauling chronicles the development of the swine flu concerns contemporary to his authorship of the 1976 volume.

In February 1976 there was an outbreak of influenza in a large military establishment in Fort Dix, New Jersey.  One young serviceman, exhausted by his participation in strenuous exercises, died of pneumonia.  Typing of the virus showed that about 500 of the 12,000 persons in the camp had been infected by a swine-influenza virus, given the name A/NJ/76, whereas some others had been infected by another virus, A/Victoria/75, which was then sweeping over the United States and Europe.  Although the virus A/NJ/76 seemed to have died out after infecting only 4 percent of the people in the camp, the resemblance of the virus to that of the 1918-1919 pandemic [referenced in the San Francisco Chronicle article above] and the death by pneumonia of one person after a strenuous night-time military exercise while he was suffering from swine flu caused fears that another swine-flu epidemic might occur in 1976-1977.  President Ford announced in March that $135 million had been appropriated by the Federal Government to support the preparation of vaccine by pharmaceutical companies in an amount great enough to permit essentially all of the people in the United States to be vaccinated.

In Pauling’s view, this approach was problematic on many levels.  For one, the vaccines that were developed actually showed a tendency to make certain patients – especially children – sick.  Partly as a result of this, the companies manufacturing the vaccines were not able to obtain proper insurance from private vendors and were forced to solicit protection from the federal government.

More importantly, from Pauling’s vantage point, the threat posed by the 1976 swine flu outbreak was seemingly overblown.

The question of how serious the threat of a pandemic really is has also been raised.  During the last forty years the epidemics of influenza have shown remarkably little variation in their virulence.  The high mortality in the 1918-1919 epidemic, especially among the younger adults, might have resulted from the malnutrition and other stresses at the end of a long war, causing the virus to be more than usually virulent and favoring the occurrence of secondary bacterial pneumonia.

Crucially, certain statistical and anecdotal specifics of the 1976 outbreak lent support to Pauling’s position:

The facts that the infection in Fort Dix affected only 4 percent of the persons in the camp and that no other cases of swine flu have been reported since the Fort Dix outbreak lend support to the suggestion…that the Fort Dix episode may be an isolated occurrence.  It now seems quite unlikely that there will be a swine-flu epidemic, and there is now little justification for recommending mass vaccination.

For those familiar with Pauling’s later work, it should come as no surprise that he recommended the regular intake of vitamin C as an effective deterrent to influenza, including swine flu.  As noted in Pauling’s June 5, 1976 letter to the editor of the New York Times included below

I have advocated the use of Vitamin C in amounts of several grams per day to prevent or treat the common cold and other infectious diseases, including influenza, and I think that it may be of importance in relation to the expected epidemic of swine flu that people not be discouraged from making proper use of this valuable substance.

"On Fighting Swine Flu," Letter to the Editor of the New York Times, June 5, 1976.

Again referring to Vitamin C, the Common Cold and the Flu, Pauling broadly suggests that a daily intake of between 250 to 4,000 milligrams of vitamin C, scaling up to as much as 10,000 milligrams per day – the amount that Pauling himself was taking in 1976, according to the San Francisco Chronicle article above – would decrease one’s chances of contracting a whole host of maladies, including influenza and the common cold.

For more on the theory behind Pauling’s vitamin C advocacy, see “Orthomolecular Enhancement of Human Development” (pdf link), a speech that Pauling delivered in 1978 to the Institutes for Achievement of Human Potential.  For more on Pauling’s life, work and legacy, see the Linus Pauling Online portal.

Linus Pauling, Vitamin C and the AIDS Crisis

Ewan Cameron, Ava Helen and Linus Pauling. Glasgow, Scotland, October 1976.

“Many orthomolecular substances are so free from toxicity that they show beneficial effects over a 10,000-fold range of concentrations. Yet if you take even ten times the amount of aspirin that many patients take, for example, you’d be dead; hundreds of people do die every year from aspirin poisoning. And all of the other major drugs are highly toxic as well.“
- Linus Pauling, December 1986

Today, December 1, 2008, is World AIDS Day. In honor of the fight against AIDS, The Pauling Blog would like to discuss Pauling’s own attempts to find a cure.

Beginning in the early 1930s, stemming from early investigations into the chemical nature of hemoglobin, Linus Pauling became deeply interested in the application of chemistry to medical problems.  Once involved in a long-term study of the substance, he began to recognize the significance of hemoglobin to the health of individuals. In 1949, Pauling coined the term “molecular disease” in reference to a mutation in hemoglobin cells that caused sickle cell anemia.

His interest in medicine did not stop there, however. During World War II, Pauling designed a meter to measure oxygen levels aboard U.S. submarines. He later converted this meter to be used in incubators for premature babies with underdeveloped lungs, saving thousands of lives in the process.

In the early 1970s, Pauling developed an interest in the use of megadoses of vitamins as a means for both preventing and treating disease. He became particularly interested in vitamin C because, even in huge doses, it proved to be non-toxic.  Pauling began recommending its use to prevent colds and other illnesses, eventually suggesting that a high-dosage vitamin C regimen could help cancer patients by fortifying the immune system and potentially destroying carcinogens.

With the onset of the AIDS crisis in the early 1980s, Pauling saw potential for another area in which vitamin C could be put to good use. Though he did not officially endorse vitamin C as a treatment for AIDS until the early 1990s, he commonly noted its possible benefits and lack of side effects.

In 1988, Pauling headed a study on the effects of vitamin C in combating the AIDS virus, measuring the impact that ascorbic acid had on infected T-cells. The results, though not extraordinary, were promising.

In 1990, Pauling and his colleagues published the results of their study in the Proceedings of the National Academy of Sciences, claiming that vitamin C appeared to suppress the growth of the AIDS virus. As was true of Pauling’s previous claims regarding vitamin C and orthomolecular medicine, the studies were at least a source of intrigue to many, though likewise dismissed by a wide cross-section of the medical community.

At the same time that Pauling was embarking on his AIDS research, Ewan Cameron, a researcher at the Linus Pauling Institute of Science and Medicine in Palo Alto, approached Pauling regarding a book he was writing entitled The AIDS Disaster. The book was meant to serve as a comprehensive study of the AIDS virus, describing its history, socio-political context, and related research.

Cameron and Pauling's unpublished manuscript, "The AIDS Disaster." August 1988.

Cameron requested that Pauling serve as co-author, editing the book and providing a chapter on vitamin C and AIDS. Pauling agreed and, in late 1988, the book was completed. Due to a variety of publishing issues, the text never reached bookstore shelves, but several complete versions of the manuscript are held in Cameron’s papers here at Oregon State University.

Until his death in 1994, Pauling continued to emphasize the responsibility of the scientific community to help cure diseases such as AIDS and cancer. He gave frequent lectures on the subject of orthomolecular medicine and continually worked to increase support for medical research.

For additional reading on Ewan Cameron’s AIDS work and research, check out the Cameron Papers finding aid, hosted online by the OSU Libraries Special Collections.  Please also note that a few more of Pauling’s thoughts on the treatment of AIDS with ascorbic acid are linked off of this index page from the Linus Pauling Research Notebooks website.