Cameron and Pauling’s Attack on Conventional Views of Cancer

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Announcement published in the LPISM Newsletter, Spring 1979.

[An examination of “Ascorbic Acid and Cancer: A Review,” published in 1979. This is part 2 of 2.]

Linus Pauling and Ewan Cameron began their paper “Ascorbic Acid and Cancer: A Review” – published with Brian Leibovitz in Cancer Research in March 1979 – by detailing the history of research on ascorbate and establishing a connection between cancer and scurvy. This line of thinking was predicated on the observation that cancer patients, like scurvy patients, were abnormally deficient in Vitamin C. The authors, in turn, traced this observation back to the importance of Vitamin C in maintaining the balance of the intercellular matrix. They likewise emphasized that cancer is a disease that originates in the body, emanating from the patient’s own cells.

The paper next identified the two main traits of cancer: abnormal cell proliferation and invasiveness. Keeping these characteristics in mind, the authors hypothesized that the release of an enzyme, hyaluronidase, contributed to occurrences of cancer. Hyaluronidase breaks down the gel-like substance that surrounds cells, they argued, and creates a pathway that allows cells of any kind to continue multiplying. In healthy individuals, this process is self-limiting. When the process goes completely unchecked however, cells can become malignant and invade the surrounding tissue. Pauling and Cameron believed this to be the likely mechanism for metastasis, the point in a cancer’s progression at which survival rates plummet.

While they knew that it was highly unlikely that a simple infusion of Vitamin C would cure a cancer patient – as it would do in the case of scurvy – Pauling and Cameron theorized that an infusion of this sort would contribute to the inhibition of hyaluronidase, thus keeping cell proliferation in check. As they repeatedly emphasized in their review, Vitamin C’s main benefit was to increase host resistance to diseases that caused unrestrained cell proliferation. What Vitamin C did not do was guarantee complete remission.

Once they had described ascorbic acid’s defensive role, the authors moved on to its limited ability to take the offensive. One function that increased Vitamin C was believed to carry out was the capacity to “encapsulate” a tumor or disseminated tumors to the point where they were no longer malignant. As Pauling pointed out to his colleagues, when his wife Ava Helen was first diagnosed with stomach cancer and surgeons went in to remove her tumor, they noted that the mass had unusual presentation for its location and appeared to be encapsulated. Ava Helen had been taking large doses of Vitamin C for several years before she was first diagnosed, and her husband attributed the nature of her tumor and the ease of its removal to her intake of Vitamin C.


Central to the review paper were the clinical results that Ewan Cameron had compiled at the Vale of Levin Hospital in Alexandria, Scotland. Cameron had begun to see positive results early on, but found that his studies were somewhat skewed because so many of his patients were terminal and ended up dying regardless of their treatment. Cameron was worried that his data did not present much of an argument in favor of Vitamin C, a situation that was further muddied by the fact that, “the terminal stages of cancer are a compound of so many human, individual, pathological and even emotional variables, as to be nearly impossible to quantify.”

In an effort to provide what the authors believed to be a more accurate picture of Vitamin C’s treatment benefits, Cameron’s later studies measured survival time in ascorbic acid patients and compared them with non-ascorbic acid patients. This comparison revealed that a patient on supplemental ascorbic acid survived, on average, four times as long as a patient with a similar prognosis who had not received ascorbic acid.

In conducting his trials, Cameron encountered the additional barrier of patients who failed to adhere to the Vitamin C regimen once they were released from the hospital. Cameron called this mode of behavior the “reverse placebo” effect, noting that some patients, when left to their own devices, would discontinue their ascorbic acid intake because it was “just Vitamin C.” Believing that it would be treated with greater respect if it sounded more like a drug, Cameron half-jokingly suggested that pharmacies rename Vitamin C as “Pauleron” to dissuade patients from underestimating its potential.


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In the final section of their review paper, Pauling and Cameron warned of unexpected and unexplained potential consequences associated with ascorbic acid therapy. In particular, some of Cameron’s patients, after showing marked improvement for several weeks or even months, succumbed to what Pauling called a “whirlwind” of cancer. Autopsies later revealed sudden massive tumor growth and dissemination.

Interestingly, most of these “whirlwind” tumors contained a large volume of necrotic cancer cells. Pauling put forth two possible explanations for this, which he included in the review. One explanation was that, though necrotic cancer cells can be less harmful than live cancer cells, the inflammation caused by their presence might cause rapid tumor growth or become toxic to the patient in such a large volume.

A second explanation, which he thought more plausible, was based on the understanding that abruptly discontinuing Vitamin C caused ascorbate levels to plummet. In this circumstance, if ascorbic acid was inhibiting tumor growth as believed, a drastic and sudden decrease in the treatment could lead to rapid, unrestrained tumor growth.

Pauling couldn’t provide solid evidence for either possibility, but he felt that both supported the review’s hypothesis. In the first instance, ascorbic acid could be killing the cancer cells. In the second, the negative consequences of withdrawing ascorbic acid inversely suggested the benefit of continued ascorbic acid use.

Pauling and Cameron concluded their review by listing areas of ascorbate research that were encouraging but had, to date, only received preliminary investigation. Specifically, the paper pointed out that no trials had been conducted to consider the effects of ascorbate in general cancer management.


The Cameron, Pauling and Leibovitz review provoked mixed reactions. Many readers, particularly aspiring physicians, were intrigued and encouraged by the results. On the other hand, quite a few others remained skeptical and focused on the aspects of treatment that Vitamin C could not promise to provide. Shortly after the review came out, Pauling received a letter from a medical student who reported that the paper had been torn out of archived copies of Cancer Research at both Cornell Medical College and the Sloan-Kettering Cancer Center. Pauling confirmed that this had happened at both locations, but was unable to persuade anyone to rectify the situation.

In the fall of 1979, a handful of months after the review was published, the Mayo Clinic released the results of its own clinical trial, which concluded that Vitamin C did not contribute to longer survival times, nor did it offer any therapeutic benefit for cancer patients. When the results were published in the New England Journal of Medicine, Cameron wrote a letter to the editor providing a rebuttal of sorts.

In Cameron’s letter, he pointed out that the Mayo Clinic hadn’t followed the same procedures as those used at the Vale of Leven. Importantly, in Cameron’s trial, only 5% of patients had received recent chemotherapy treatment. By contrast, in the Mayo Clinic trial, only 5% of patients hadn’t received recent chemotherapy. Cameron also suggested that patients, fearful that they were in the control group and not receiving supplemental ascorbate, were dosing themselves with Vitamin C, as it was easy to obtain outside of the trial setting. If this was indeed the case, the Mayo Clinic data likely supported the Cameron-Pauling hypothesis.

Despite Cameron’s centrality to the debate, the editor of the New England journal refused to print his letter, a decision that only increased the levels of skepticism surrounding Cameron and Pauling’s work.


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In publishing their review and the papers that led up to it, Pauling and Cameron sought to update the popular view of cancer as an invasion of foreign cells that needed to be entirely destroyed to produce clinical success. Once people accepted a new view of cancer, Pauling believed that attitudes toward cancer treatment would also change.

Perhaps most importantly, Pauling and Cameron wanted physicians to stop assuming that troubling side effects were a sign of a treatment’s success and instead to begin concentrating more on the overall health of patients. Though they focused primarily on Vitamin C, the duo hoped that their review would encourage researchers to gather more evidence for an orthomolecular approach to cancer, one that would emphasize vitamins and natural methods as opposed to cytotoxic chemicals.

Although Pauling and Cameron’s perspective was not widely accepted during their lifetimes, researchers today are increasingly focusing on alternatives to chemotherapy and radiation. Immunotherapy, still in its infancy during Pauling’s life, has now become a standard treatment for certain cancers. Additionally, researchers have been able to show that high-dose Vitamin C, administered intravenously at even higher levels than Pauling and Cameron had attempted, does indeed provide therapeutic benefits in some cancers.

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Ascorbic Acid and Cancer: A Review

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

[Ed Note: Today’s post is the first installment of a two-part look at Linus Pauling, Ewan Cameron and Brian Leibovitz’ extensive 1979 review of the published literature pertaining to research on ascorbic acid and cancer.]

Students of Linus Pauling’s life will know full-well that Pauling expended significant energy over his latter decades advocating for the use of ascorbic acid, or Vitamin C, in the treatment of cancer. One of his lengthier research endeavors, and certainly among his most controversial, Pauling’s interest in and advocacy of ascorbic acid therapy prompted a wide array of responses from scientists, journalists, and patients, among many others.

Pauling’s views also attracted the disdain of most medical professionals. One notable exception to this theme was Ewan Cameron, a Scottish surgeon who became so invested in the work that he eventually relocated to California to join the staff of the Linus Pauling Institute of Science and Medicine.

Prior to his immigration, Cameron had shared a rich correspondence with Pauling through which the colleagues bounced ideas off one another and even co-wrote papers. Cameron, who was head of his department at the Vale of Leven Hospital in Alexandria, was permitted to run a clinical trial testing the efficacy of ascorbic acid treatments on terminal cancer patients. He then relayed his data to Pauling, who studied the Alexandria results and contributed his thoughts on the chemical mechanisms that might be underlying them.

In 1979, Pauling, Cameron and a third author published a major literature survey titled “Ascorbic Acid and Cancer: A Review.” Appearing in the March 1979 edition of Cancer Research, the paper marked a crescendo of the duo’s eight years of work in the cancer field; work which they attempted to bolster using all of the previous and ongoing studies that they could find.

The survey, which took up ten journal pages and included 358 references, was published with the hope that it might serve to counter some of the skepticism that its authors were encountering, while also inspiring new researchers to turn their own attentions toward the potential benefits of ascorbic acid. As was typical during this period of Pauling’s career, the reception that the paper received was mixed at best.


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One of the 1,000+ references gathered by Brian Leibovitz for use in “Ascorbic Acid and Cancer: A Review.”

Pauling and Cameron first began toying with the idea of a grand literature review in 1976. Having struggled mightily with both the medical community and mainstream publishers for five years, the duo had, by 1976, finally managed to get a few papers into print. Encouraged by these successes, the co-authors agreed that gathering all available research on Vitamin C and cancer, and presenting it in one paper, would make for a very useful contribution to a decidedly nascent field.

There was a secondary ambition in play as well. Though brimming with ideas, the resources available to the two scientists were scarce and, as a result, they had arrived at an impasse of sorts. Lying at the heart of the matter was the fact that basically all of the leading medical journals had refused to publish the clinical work that Cameron and Pauling had conducted, because they hadn’t been able to follow a proper double-blind study protocol. Instead, Cameron had matched his ascorbic acid patients – by age, sex, and cancer type -with previous patients who had been treated at the Vale of Levin hospital but hadn’t received ascorbic acid.

Likewise, Cameron believed so strongly in the benefits of ascorbic acid that he refused to withhold it from incoming cancer patients who might otherwise populate a control group for his study. In his correspondence with Pauling, Cameron confided that to withhold ascorbic acid treatment from sick patients would stand as a violation of the Hippocratic Oath.

(Oddly enough, Dr. Thomas Addis – the doctor whose conservative therapies saved Pauling from an almost certain death sentence when he was diagnosed with glomerulonephritis in the 1940s – argued against the use of ascorbic acid for exactly the same reason. To discontinue traditional methods of cancer treatment he believed to be effective came at the cost of his patients, and Addis refused to do it.)

Memorial Sloan-Kettering Cancer Center in New York had conducted its own trial in 1974, but Cameron and Pauling suspected that there were problems with the scientific design of that study as well. Preventing this from happening again, especially as Pauling and Cameron were gaining increased attention from the medical community, was another motivation for publishing the review. Finally, the research that they had gathered also helped the co-authors in preparing a new book, Cancer and Vitamin C, which came out in 1979, only a few months after the review was published.


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Brian Leibovitz

In putting together their article, Pauling and Cameron enlisted the additional help of Brian Leibovitz, a graduate student at Stanford who had worked at LPISM from 1975 to 1977. Leibovitz’ main task was straightforward: obtain reprints of anything related to ascorbic acid and cancer. Pauling also requested that Leibovitz look into other papers that focused on the environment shared by cells, as he and Cameron both believed that the intercellular environment held important – if, as yet, undiscovered – resources for treating cancer.

Leibovitz expressed great dedication to the multi-year project, continuing to collect references even after finishing up at LPISM and moving to Oregon. In the end, Leibovitz gathered over a thousand sources; for his work, his name appeared on the review as a third co-author.


Once it had been completed, Pauling encountered trouble finding a home for the review. Originally a friend had offered to have it published in Cancer Research, but upon seeing the manuscript, the editor complained that the paper was much too long. In response, Cameron worked on shortening the text while Pauling looked into other avenues for publication, including The Journal of Preventative Medicine and Cancer Reviews.

While Cancer Reviews was kind enough to respond that they were not interested in publishing anything on ascorbic acid, The Journal of Preventative Medicine did not reply at all. Just as the authors were about to give up, the editor of Cancer Research got back in touch, suggesting a series of changes and promising to publish the survey once it met with the requirements that he had outlined.

Intravenous Vitamin C: The Historical Progression

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Jeanne Drisko

[Part 1 of 2]

Jeanne Drisko, MD, Director of Integrative Medicine at the University of Kansas Medical Center, Kansas City, was a featured speaker during the public session of the Linus Pauling Institute’s Diet and Optimum Health Conference, held September 13-16, 2017.  She delivered a public lecture titled “Intravenous vitamin C and cancer treatment: Does it work?” Dr. Maret Traber, a principal investigator at LPI, introduced Drisko, describing her as a “leading expert on intravenous vitamin C.”

Drisko began her talk by tracing the history of vitamin C research, noting the ways in which previous studies had made her own research possible. The first person Drisko spoke of was Nobel laureate Albert Szent-Gyӧrgyi (1893-1986), who isolated ascorbic acid while working at Cambridge University and the Mayo Foundation between 1927 and 1930. Drisko then pointed out that, in the 1940s, vitamin C was used widely in clinical settings to treat pertussis, or whooping cough, along with other bacterial and viral infections. Importantly, these treatments were not administered orally. At the time, pharmaceutical preparations of vitamin C were not of a quality that could be administered intravenously, so they was injected into the muscles.

The use of vaccines was also on the rise during this period and Drisko pointed out that the development of the polio vaccine was particularly connected to the clinical fate of vitamin C. Albert Sabin (1906-1993), who had developed an oral polio vaccine, also carried out trials on the effects of vitamin C injections on primates. Sabin found no benefit and suggested that focus turn toward vaccines instead. It was at this point, Drisko explained, that the use of vitamin C injections went “underground,” drifting well outside of the medical mainstream.

One individual who remained interested in the promise of vitamin C was Frederick Klenner (1907-1984), who began using intravenous ascorbic acid at his North Carolina clinic in the 1940s. Drisko described Klenner as keeping “vitamin C use alive,” by administering both muscular and intravenous injections, while the broader medical community turned elsewhere. In particular, Klenner used vitamin C to treat children suffering from polio and found that even advanced cases could be approached successfully. During this time, Klenner also trained other practitioners in the methods that he was pioneering at his clinic.


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

Next, Drisko turned to Linus Pauling. To begin, Drisko noted that since Pauling was already well known, his interest in oral vitamin C was written off by many who were familiar with his prior work. Others, however, did look to Pauling as an authority, and among them was the Scottish surgeon Ewan Cameron (1922-1991), who contacted Pauling after reading some of his papers in the early 1970s. In his initial correspondence, Cameron informed Pauling that he had been giving about ten grams of vitamin C to cancer patients and had observed that they tended to live longer. As a result of their shared interest, Pauling and Cameron decided to collaborate on a series of papers investigating the potential clinical import of large doses of vitamin C.

As they delved deeper into this work, Pauling became convinced of the need to carry out more rigorous trials. Lacking the funds to do so, he instead turned to the National Institutes of Health. Fatefully for Pauling, Charles Moertel (1927-1994), an oncologist at the Mayo Clinic who was eager to debunk the effectiveness of vitamin C, agreed to lead the NIH investigation. Specifically, Moertel carried out a double-blind placebo-controlled trial in which ten grams of vitamin C were administered orally, and he found no benefit. (He was not aware that Cameron had been injecting vitamin C intravenously.) Moertel published his results in the New England Journal of Medicine and the press picked it up. Once the negative conclusion had been widely circulated, subsequent mainstream interest in the medical application of vitamin C suffered a near fatal blow.


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Mark Levine

Research on intravenous vitamin C began to re-emerge during the 1990s, led in part by NIH scientist Mark Levine. Levine’s nutrition experiments were novel, and did not emerge from the types of medical training that he could have been expected to received. For context, Drisko described her own education, wherein courses on nutrition were optional and held on Saturday mornings. She attended them because she was interested, but she also went along with the convention of the time; one emphasizing that nutrition was of lesser importance relative to other aspects of medical practice.

Levine, on the other hand, did not follow this line and decided to study vitamin C in depth. In the trials that he carried out at the National Institutes of Health, Levine tracked patients deprived of vitamin C and showed that they had indeed become vitamin C deficient. He followed this by administering oral doses of vitamin C, which demonstrated repletion. At the end of his trial, Levine also administered one gram of vitamin C intravenously. He was not allowed to administer a higher dose to his subjects, due to fears of toxicity, but it was his guess that ten gram doses would yield peak blood levels of vitamin C.

Ultimately, Levine demonstrated that oral vitamin C was not capable of yielding maximal vitamin C blood levels, because the body does not absorb oral doses well and excretes it very quickly. Intravenous administration, on the other hand, bypassed these metabolic processes, leading to higher blood levels. With Levine’s work in mind, Drisko summarized the difference between Cameron’s research and Moertel’s Mayo Clinic trial: “Cameron gave a drug and the Mayo Clinic gave a vitamin.”


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Hugh Riordan

Drisko’s mentor, Hugh Riordan (1932-2005), was another individual responsible for keeping vitamin C research alive. The founder of what is now known as the Riordan Clinic in Wichita, Kansas, Riordan belonged to a group of orthomolecular physicians who saw vitamins as providing restoration of a healthy baseline in all humans.

After Levine published his paper on vitamin C absorption, Riordan went to visit him in Maryland to convince him to continue following this path of inquiry. The two ultimately collaborated on several case studies and welcomed others into their fold, a progression that helped incubate today’s group of researchers investigating the use of intravenous vitamin C.

As of 2016, the intravenous vitamin C group included Qi Chen, who works on basic research at the University of Kansas with Drisko; John Hoffer at McGill University, who explores the effects of high doses of vitamin C on cancer; Garry Buettner and Joseph Cullen at the University of Iowa, who looks at the redox capacity of vitamin C in patients undergoing radiation therapy; and Ramesh Natarajan at Virginia Commonwealth University, who is researching the use of vitamin C in the treatment of sepsis.

Drisko noted that there are differences in the lines of research followed within the current group. On the one hand, her cancer trials use megadoses of vitamin C at 75 to 100 grams. Natarajan, on the other hand, only uses 4 or 5 grams in the ICU for sepsis.  For Drisko, these differences emphasize that there is still a lot of research to be done to understand exactly what is going on.


At present, attitudes toward vitamin C within the medical community can be mostly lumped into two categories. One is comprised of “early adopters,” as Drisko defines herself, who continue to carry out research to refine vitamin C treatments. The other consists of those who adhere more closely to the conclusions of the Moertel study, and who thus believe that claims supporting the effectiveness of vitamin C have been disproven. The distance between these two groups was characterized by Drisko as a “gulf of disapproval.”

However, current trends suggest that the gulf is being bridged. While some state medical boards still restrict the therapeutic use of vitamin C, Drisko and others have succeeded in garnering increasing levels of support from both colleagues and institutions. Shifts in funding opportunities are also beginning to emerge: though Drisko was unable to secure federal dollars for her work on ovarian cancer, the Gateway for Cancer Research non-profit stepped in to provide crucial support. With evidence of the efficacy of the treatment building from a growing number of trials, the possibility of obtaining federal grants is becoming more realistic. Likewise, drug companies are now looking at ways to patent vitamin C therapy, and some vitamin C treatment patients have succeeded in receiving reimbursement from their insurance companies.

Next week, we will provide an overview of the science underlying this renewal in optimism about the potential to fight disease with intravenous ascorbic acid.

Pauling 115

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This is where we’ll be today.

This coming Sunday will mark the 115th anniversary of Linus Pauling’s birth on February 28, 1901. While we here at Oregon State University are commemorating the birthday anniversary with cake and conversation at the Linus Pauling Science Center, the Pauling Blog observes the occasion in our traditional manner, by looking back at Pauling’s life 100, 75, 50 and 25 years ago.

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Lucile, Linus, Belle and Pauline, 1916.

1916

As a junior at Washington High School in Portland, Oregon, Pauling took his first chemistry class in spring 1916.  That fall he began his senior year at Washington and then, in 1917, enrolled at Oregon Agricultural College, at the age of sixteen and lacking a high school diploma. Pauling did not graduate from high school because he neglected to take a required history course, and back then OAC didn’t require high school equivalency for admission.  Linus was always a good student, of course, but during his junior year at Washington he struggled a bit, earning C’s in English and Latin, alongside the expected A’s in solid geometry and chemistry.

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Pauling family portrait taken in 1941. Back of photograph is annotated, “1941. Daddy very ill.”

1941

With the onset of war in Europe, Pauling faced a major personal crisis of his own in 1941. While giving a lecture in New York, Pauling made light of his alarmingly swollen face:

I am happy also that this occasion has brought me in touch with many old friends – with Paul Emmett and Joe Mayer and many others. Several of them said to me tonight that I appeared to be getting fat. This is not so. You know, when I was a boy in Oregon I used to go around a great deal in the green, damp Oregon woods, and I always came into contact with poison oak, which caused my face to swell and my eyes to swell shut, and me to apply so much lead acetate solution that it is a wonder that I didn’t die of lead poisoning. Yesterday I must have bumped into something similar, for my face began to swell, and I began to be afraid that I would have to speak here tonight with my eyes swollen shut – which I could have done, with the practice I have had speaking in the dark. Well, while I was wondering what the responsible protein could have been, I decided that it was a visitation – that I was being punished for thinking wicked thoughts. The other day I said “It is too bad that something doesn’t happen to Senator Wheeler – nothing serious, just something that would lay him up with his eyes shut for two or three weeks” and my wife said “No what you want is something that would keep his mouth shut – his eyes are closed already.”

As it turned out, Pauling’s edema was the result of his having fallen ill with glomerulonephritis, a kidney disease that was usually fatal.  Fortunately for Pauling and for the history of science, he sought out an alternative treatment from Dr. Thomas Addis that saved his life.

Even prior to the Japanese attack on Pearl Harbor, the U.S. was shifting gears in response to the outbreak of World War II. This shift made a direct impact on Pauling’s work at Caltech, and he began putting the brakes on his massive program of research on the structure of proteins in favor of new studies funded by government war contracts, including, in 1941, investigations of elastic explosives and rocket propellants.

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Linus Pauling, 1966.

1966

Pauling’s life and work took another dramatic shift in 1966 when he made the acquaintance of Irwin Stone, initially through correspondence.  At a talk on “Science and World Problems” delivered in New York, Pauling had made mention of a desire to live another fifteen years, so that he might be able to witness some of the major advances that he foresaw as being on the close horizon.  Stone was in the audience and sent Pauling a hugely influential letter that detailed a “High Level Ascorbic Acid Regimen” that could “help you achieve this goal and possibly tack on a few extra decades.”  Pauling was intrigued and thus began his famous fascination with vitamin C.

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Linus Pauling and a guest in his office at the Linus Pauling Institute of Science and Medicine, 1991.

1991

Now 90 years old, Pauling experienced a difficult year in 1991.  As the year began, the United States was preparing to invade the Persian Gulf, an action that Pauling protested vehemently, taking out a paid advertisement in the New York Times imploring the government to “stop the rush to war.”

Closer to home, Pauling’s friend and close colleague Ewan Cameron, with whom he had published some of his most controversial papers on vitamin C, passed away at the age of 68, a victim of cancer.  That fall, Pauling himself was also diagnosed with prostate and rectal cancer, which he began treating using megadoses of vitamin C and an experimental hormone therapy.  He would live for three more years before passing away on August 19, 1994.

Vitamin C and Cancer: Raising the Stakes

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

[Part 3 of 4]

By 1970, the year that Linus Pauling published Vitamin C and the Common Cold, the federal government’s “war on cancer” was soon to arrive. The National Cancer Act, passed in 1971, increased federal funding for treatment and prevention research, embracing cytotoxic treatment solutions like chemotherapy. That same year, Pauling began to push for investigations between nutrition and cancer, especially concerning vitamin C. Since the role of vitamin C in immune defense is arguably much less significant than Pauling supposed, the idea that intake of vitamin C should prevent or treat cancer seemed ludicrous to many physicians. Incredibly, evidence is now emerging that the opposite might be true.

In hindsight, there is a tendency for critics to see Pauling simply as a politically liberal proponent of alternative medicine; one who lashed out against a consumerist medical establishment that was firmly supported by conservative citizens, among others. However, proponents of alternative health and holism in the 1960s and 1970s prescribed to a broad range of political ideologies; Pauling was just one among many people who were searching for better preventative and alternative treatments.

In 1980, when Pauling was actively campaigning for a vitamin C treatment for cancer, Americans spent 13.1 billion dollars on cancer diagnosis and treatment. Five years later, a survey of over one-thousand individuals showed that a majority believed clinics using unorthodox cancer therapies should be permitted to operate in the U.S., and just over half said they would seek alternative treatment if seriously ill.

Pauling and his ideological positions are remembered now as having been central to the vitamin C “movement.” Perhaps this is because he was renowned in many arenas and easily attracted a great deal of media attention. Or perhaps, especially knowing his penchant for protesting against nuclear weapons testing and war, this was another issue on which Pauling was the most outspoken opponent of what he saw as a wrong to be made right.


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Table from “Ascorbic acid and cancer: a review”, co-authored by Pauling and Cameron, 1979.

For Pauling, the continuing suffering of cancer victims was unnecessary, since a useful treatment was already cheap and readily available. He argued that,

The involvement of ascorbic acid (vitamin C) in the natural defense mechanisms is now known to be so great that we hope that a really significant control of cancer might be achieved by the proper use of ascorbic acid.

Of the studies that Pauling found so convincing, none were as crucial as those conducted at the Vale of Leven Hospital, near Glasgow, Scotland. There, Dr. Ewan Cameron found that mega doses of vitamin C (10 grams daily or more) seemed to slow and even reverse cancerous growth in some patients. He wrote to Pauling in 1971, who eagerly responded that this “attack” on cancer was the most promising application of vitamin C that he knew of.  Pauling, who had been studying the role of dietary vitamin C in issues of orthomolecular psychiatry such as schizophrenia, now shifted his focus to cancer.

Far from being the flaky alternative health guru that many came to see him as, Pauling’s work with vitamin C— like all his research on the subject of orthomolecular medicine (a field that he spearheaded)— was consistent with a biomedical model of molecular disease. Since Pauling saw this work as fitting within the framework of molecular biology, it was frequently unclear to him why the medical community resisted what was, to him, a straightforward and significant scientific endeavor.

Further complicating matters was the fact that Stanford University, Pauling’s academic home at the time, rejected his request for additional lab space to pursue cancer research. Now the target of regular media pummelings, Pauling’s ideas were becoming a potential source of bad press for the university. Refusing to take no for an answer, Pauling and his young lab assistant, Arthur Robinson, solicited private funding to continue their work on vitamin C outside of the university setting. Raising $50,000 in donations from wealthy supporters of vitamin therapies, the duo helped to found the Institute for Orthomolecular Medicine in 1973, subsequently renamed the Linus Pauling Institute of Science and Medicine (LPISM) one year later.

From 1973 to 1976, Pauling published co-authored articles with Cameron, who continued to study the effects of vitamin C on cancer from his base in Glasgow. And in 1975, Pauling and Robinson secured additional funds to begin their own animal testing. Two years later, the collaborators began reporting their results in the Institute’s newsletter.  In 1979 Cameron and Pauling likewise published an extensive review article in Cancer Research that cited previous studies corroborating their own conclusions. The duo published their book, Cancer and Vitamin C, that same year.


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A sample of Pauling’s notes compiled in response to the Mayo Clinic trials, 1979.

Cameron and Pauling’s data seemed to show that vitamin C would be especially valuable for cancer patients. Whereas a daily intake of 10 g of vitamin C in a healthy individual would bring the vitamin C level in the blood to a saturation point that could not be exceeded by increasing or prolonging intake, cancer patients showed a different pattern. Known already to have abnormally low blood levels of vitamin C, the patients in fact achieved just over half the same level of vitamin C blood saturation found in healthy individuals subscribing to a daily intake of 10 grams. For those afflicted with cancer, it was seen as necessary to take 10 grams a day just to reach the normal level of vitamin C found in healthy individuals who did not take supplements at all.

To Pauling, this alone justified continued research on the matter. After persistently stating his case to Dr. Vincent De Vita, director of the National Cancer Institute, two rounds of trials were conducted through the Mayo Clinic to solve what the medical community perceived to be problems in Cameron’s studies. When the trials indeed failed to produce anything like Cameron’s results, funding effectively dried up for vitamin C research – a significant blow to LPISM’s functional well-being.

In response, Pauling and his supporters argued that the Mayo Clinic was missing the point. The Mayo trials had attempted to measure the effectiveness of vitamin C in a manner similar to drug treatments, because the advent of chemotherapy and antibiotics, and the biases of the pharmaceutical industry, had placed primary medical emphasis on the disease, and not on the patient. Pauling saw the results of the Mayo studies not as a definitive defeat, but as the triumph of a complex of interdependent federal and private organizations that held a vested interest in supporting the chemotherapy status quo.


Pauling had claimed that, with vitamin C, lifespan could be increased, tumors could regress, and even full recovery was possible. For many in the medical community, these were not only foolish assertions, they were dangerous as well.

Dr. Charles Moertel, chairman of the Department of Oncology at the Mayo Clinic, was particularly vocal in his rebuke, stating that

For such a message to be conveyed to desperate and dying people, with the endorsement of a Nobel laureate, the presumption must be that it is based on impeccable scientific methodology.

Moertel’s implication, of course, was that Pauling’s argument was instead based on unsound science and certainly lacked the scientific basis to challenge the use of chemotherapy.

Yet vitamin C retained a broad appeal because many saw the prevailing treatment, and its manifold side effects, as inhumane. John Cairn, head of the Mill Hill Laboratory of the British Imperial Cancer Research Fund, provided a voice to the other side the coin by calling out the survivorship data. To wit: in 1986, 200,000 patients were receiving chemotherapy and, by 1991, five year survival rates for colon cancer remained at just 53%. Cairn spoke for many in suggesting that, when it came to the prevailing course of treatment, “the benefit for most categories of patients has yet to be established.”


1981i.3

Ava Helen Pauling, June 1981.

For Pauling, the debate turned from the public to the personal when, at the height of his study of vitamin C, his wife Ava Helen was diagnosed with stomach cancer. Following Ewan Cameron’s advice, she took 10 grams of vitamin C daily, and did not receive chemotherapy.  Throughout her treatment, Linus clung to the belief that mega doses of vitamin C would work for Ava Helen, just as it had for Cameron’s success stories in Scotland.

“Daddy was convinced that he was going to save her,” remembered Linus and Ava Helen’s daughter, Linda. “And that was, I think, the only reason he was able to survive… He said to me after she died that until five days before, he thought he was going to be able to save her.”

Ava Helen Pauling passed away in December of 1981. And though he was badly shaken by his wife’s death, belief in the value of vitamin C in the fight against cancer did not fade from Pauling’s mind. Suffice it to say, the medical community remained whole-heartedly unconvinced.

Irwin Stone’s Impact on Pauling

Linus Pauling and Irwin Stone, 1977.

Linus Pauling and Irwin Stone, 1977.

[Part 2 of 2]

Four years after Irwin Stone first convinced Linus Pauling to start taking megadoses of vitamin C, Pauling decided to share with the world the successes that he had observed in his own improved mental and physical health.

In 1970 Pauling began to work on a book, Vitamin C and the Common Cold, and he wrote to Stone asking permission to dedicate it to him. He also sent Stone a copy of the manuscript to review. Stone wrote back praising the work.

The book is excellent and should go far to eliminate this thoroughly unnecessary and annoying condition, at least among your readers. The audience will increase over the years, especially if Medicine can eventually see the light.

Stone continued to encounter difficulty getting his own scientific articles about ascorbic acid published and he certainly did not have the funding to run his own clinical trials. Partly as a result, he too was writing a book about vitamin C and all of the many diseases that he thought were related to hypoascorbemia. A  major thrust of the book was its plea for large scale research on the topic. Stone hoped to get popular opinion on board with his ideas in order to place pressure on physicians and nutritionists to do research in this area.

Pauling’s Vitamin C and the Common Cold was a popular success. Many readers around the world were persuaded by his ideas and began to take vitamin C supplements to prevent and treat colds. Some of his acclaim rubbed off on Irwin Stone, who wrote to Pauling telling him that he too was finally receiving recognition from popular media sources, including NBC.

In 1971 Stone retired to San Jose, California and devoted the rest of his life to researching and promoting the need for high consumption of vitamin C by humans. That same year he finished his book, The Healing Factor: Vitamin C Against Disease, and asked that Pauling write a foreword for it. Pauling was glad to do so, calling it “an outstanding contribution to knowledge.”

Stone's inscription to Pauling in a first edition of The Healing Factor, 1972.

Stone’s inscription to Pauling in a first edition of The Healing Factor, 1972.

Despite their popular appeal, Pauling and Stone continued to encounter problems convincing medical practitioners and researchers to take their ideas about ascorbic acid seriously. Stone believed that this was so because vitamin C would be a much more inexpensive cure than the current treatments of the time, causing pharmaceutical companies and doctors to lose money.

One medical doctor, Ewan Cameron, did believe in the effectiveness of vitamin C against cancer and was treating his terminal cancer patients with megadoses of it in Glasgow, Scotland. He formed a trans-Atlantic research partnership with Pauling in 1971 and they began to collaborate on papers discussing the use of vitamin C against cancer, eventually publishing ten articles together.

Through his partnership with Pauling, Cameron also began to correspond with Stone about the implementation of vitamin C against cancer and their shared difficulties getting the medical community to accept their hypotheses.

Cameron maintained a unique viewpoint on the treatment of cancer and how ascorbic acid might fit into a clinical regimen. In December 1974, he explained his views to Stone.

It is completely contrary to all contemporary medical thought to even suggest that such a mundane substance as ascorbic acid could have any value in such a complicated disease as cancer. This is because cancer research is concentrating all its energies in searching for more and more sophisticated ways of selectively destroying cancer cells. The research is becoming so complex and so unproductive, that it is natural to assume that ‘the answer’ must be extraordinarily complex and almost beyond human comprehension….We would make much more progress if we accept that cancer cells are normal cells that merely happen to be behaving in an abnormal way. We would then accept that cancer cells have an equal right to live, and concentrate our energies in suppressing the abnormal behavior pattern.

Throughout their correspondence, Cameron described his successes treating cancer with ascorbic acid. But he also noted that a number of patients showed no improvement from it or, at best, their cancer was brought to a standstill. He was disappointed that his primary successes were mostly by way of increasing patients’ survival time, not in curing them. Cameron thought that the greatest success would be in prophylaxis – taking megadoses of ascorbic acid throughout one’s life in order to prevent cancer.


In 1978 Stone wrote a letter to the editor of Nutrition Today in response to the publication’s recent issue focusing on ascorbic acid. His letter shows how fervently he believed in hypoascorbemia.

I regard our most serious medical problem to be the dangerous complacency that the orthodox medical establishment exhibits toward Chronic Subclinical Scurvy and its refusal to do anything to correct and alleviate this potentially-fatal human birth defect. Chronic Subclinical Scurvy has killed more human victims, caused more disease and misery among Mankind than any other single factor in the past and is continuing this evil record in the present. I’m worried about the future, because that is where I’m spending the rest of my life.

Meanwhile, Stone and Pauling’s relationship continued to flourish. In 1977 Pauling invited Stone to become a member of the Board of Associates of the Linus Pauling Institute of Science, an offer that was accepted. Pauling also attended Stone’s surprise 70th birthday party that year. In 1981 Stone was unable to make it to Pauling’s 80th birthday, but he did pass along a message.

You will recall the promise I made you in 1966 of 50 more healthy years of life with Megascorbics. You thought I was exaggerating and said you would be satisfied with 15 years. Well the 15th year is now and I am looking forward to attending your 115th birthday party in 2016. Megascorbics makes you practically indestructible.

In response, Pauling wrote, “I am glad to express my thanks to you for having written to me in 1966. Your letter and the reprints of your papers changed my life.” While Pauling did not make it to 2016, he did live until 1994, passing away at 93 years of age.

The last letter that Pauling wrote to Stone concerned a joint award from the Academy of Orthomolecular Psychiatry and the Orthomolecular Medical Society that Stone was to receive. The Linus Pauling Institute of Science and Medicine was also going to surprise him with a second award. Pauling wrote,

For many years you have been an inspiration to me, because of your devotion to vitamin C and your conviction that a high intake of vitamin C has great value in improving the health of human beings. You have rendered a great service to the people of the world through your continued study of vitamin C over a period of fifty years.

Unfortunately, Dr. Irwin Stone died on May 4, 1984, at the age of 77, while in Los Angeles to receive the award. He died by choking on regurgitated food, the result of a constricted esophagus that had plagued him ever since his car accident many years prior.

Irwin Stone received two honorary doctorates, many additional awards, and 26 patents. He also published over 120 scientific papers throughout his life (at least 50 were about vitamin C) and wrote one book, The Healing Factor, published in 1972. He was father to one son, Steven, and was married to his wife Barbara for over 50 years.

In December 1986, two years after his death, Barbara Stone sent Pauling a card congratulating him on the publication of his latest book, How to Live Longer and Feel Better. She wrote “Irwin would have enjoyed reading it and noting the many references to him and other colleagues.” Pauling hadn’t exaggerated in his 1981 letter: Irwin Stone really did change his life and made a profound impact on the scientific legacy that Pauling leaves behind today.

LPISM in the 1980s

Linus Pauling Institute of Science and Medicine staff portrait, 1989.

Linus Pauling Institute of Science and Medicine staff portrait, 1989.

[A history of the Linus Pauling Institute of Science and Medicine, Part 4 of 8]

In the spring of 1980, amidst a swirl of funding difficulties and legal actions, Emile Zuckerkandl was named President and Director of the Linus Pauling Institute of Science and Medicine. He quickly began working to expand LPISM into a more wide-ranging organization with a particular focus on cellular research. His leadership style was very different from the Institute’s previous presidents, but the staff liked him and generally supported his initiatives.

By this point, born of need, Linus Pauling’s relationship with the Institute began to assume a somewhat Faustian character. Pauling was contacted by, and began regularly meeting with, a man named Ryoichi Sasakawa to discuss future collaboration plans and possible donations. Sasakawa was a world-renowned philanthropist and famous businessman who had single handedly introduced and popularized motorboat racing in Japan. Sasakawa was also very controversial. An avowed fascist, he was an admirer of Benito Mussolini and a political strongman who had been charged with war crimes for his activities in support of the Japanese government during World War II.  He was also very wealthy and Pauling’s connection to Sasakawa would grow over time.

The summer and early fall of 1980 were largely preoccupied with the Art Robinson suits and fundraising. In August LPISM finally received some good news: the National Science Foundation had awarded the Institute a grant of $40,000 a year for two years to support research on the structure of molecules and complex ions containing transition metals. This provided a much needed financial boost, as finances were suffering greatly from the Mayo trials and the ongoing legal wrangling with Robinson.

The year ended somewhat stressfully when, in December, LPISM was forced to move from Menlo Park to 440 Page Mill Rd. in Palo Alto. The landlord of their building in Menlo Park had evicted all of his tenants while he was making structural repairs to the facility. Once completed, he decided not to welcome LPISM back, instead inviting more profitable companies to take their spot. The new building in Palo Alto was dramatically bigger and less expensive; it was also quite a bit shabbier, in part because it was made out of cinderblocks.  Employee Alan Sheets was able to help save the Institute a lot of money during the transition, as his father was a professional mover. As such, the Sheets family helped LPISM move itself instead of hiring the process out to a company.

Extracted from the LPISM Newsletter, Winter 1980.

Extracted from the LPISM Newsletter, Winter 1980.

The dawn of 1981 brought with it major financial relief for LPISM. After eight failed tries over eight long years, the National Cancer Institute finally agreed to fund a component of LPISM’s program – a two-year grant for $204,000 to research the effects of vitamin C on breast cancer in mice. At about the same time, Sasakawa’s company, the Japanese Shipbuilding Foundation, pledged $5 million to the Institute over the following ten years. As part of the deal, LPISM began working with Sasakawa to create the Sasakawa Aging Research Center, which was set up as a satellite facility on Porter Drive. Later in the 1980s, the building at Porter Drive suffered a major roof leak which destroyed thousands of pages of research and documentation. Thomas Hager, one of Pauling’s biographers, notes that LPISM successfully sued the landlord for neglecting to maintain the building.

Despite this influx of new cash, the close of 1981 proved to be an awful time for Linus Pauling and LPISM. In August, Ava Helen Pauling’s recurrent stomach cancer was declared inoperable and on December 7, after struggling with cancer for five years and three months, Ava Helen died. Linus Pauling was absolutely devastated, and the LPISM staff was greatly saddened by the loss as well. Pauling understandably did not cope well with the passing of the woman who was his wife for nearly 60 years, and he effectively ceased to be involved in LPISM except in the most cursory of ways, choosing instead to spend much of his time alone at his ranch in Big Sur, California.

The year that followed was, unsurprisingly, a tough one. Pauling remained in mourning and didn’t really contribute to LPISM, the Robinson suits dragged on, and the Institute’s fundraisers still struggled to cope with the fallout from the Mayo Trials. The NCI and Sasakawa donations helped to keep operations running, as did some of the revenue from Pauling and Cameron’s book, Cancer and Vitamin C. In the summer of 1982, Pauling took a trip throughout the Pacific Northwest where he visited many of his and Ava Helen’s favorite spots, as well as the cemetery where his maternal grandfather Linus Wilson Darling rested. The trip brought him closure and by the fall he became active at the Institute again.


In February 1983, the lawsuits with Arthur Robinson finally ended, with LPISM paying an out of court settlement of $575,000. The Institute adamantly maintained no wrong doing, instead acknowledging the fiscal prudence of settling as opposed to prolonging the court battle, which was nearly five years old by that point.

Their legal problems resolved, LPISM fundraisers redoubled their efforts to regain their financial momentum, as the lawsuits had drained them of resources. Past fundraising techniques were unable to generate much steam, so Rick Hicks began cultivating relationships with individual, extremely wealthy donors, notably Armand Hammer, Ryoichi Sasakawa and Danny Kaye. As a part of this strategy, LPISM began annually awarding individuals – typically major donors – the Linus Pauling Medal for Humanitarianism. Sasakawa was its first recipient.

In November 1983, LPISM researchers announced that they had discovered a new type of chemical bond that mimicked the bond believed to exist between bulk metals. This was a fairly important discovery, and also helped restore some measure of favorable public opinion as people saw the good work that LPISM was doing. The announcement also reminded folks that LPISM wasn’t just about vitamin C research. The next year, in 1984, Pauling received the extremely prestigious Joseph Priestley Medal from the American Chemical Society for his lifetime of work and dedication in the field of chemistry.

However, the controversy over vitamin C was never far from the Institute and more arrived in a hurry when, on January 2, 1985, the Mayo Clinic released the results of its second set of trials. The Institute was given no warning of the release or chance to read the results in advance. This infuriated Pauling who saw it as an obvious insult levied by the study’s principal investigator, Charles Moertel.

Pauling Note to Self, January 14, 1985.

Pauling Note to Self, January 14, 1985.

Perhaps unsurprisingly, Moertel announced that the study had reaffirmed his earlier assertion that vitamin C was useless in cancer treatment. Upon reading the report though, Pauling deduced that Moertel hadn’t actually examined Ewan Cameron’s papers, the very studies he was supposed to be replicating. Among other deviations, the amount of vitamin C used in the Mayo trials was lower than in Cameron’s studies, the amount of time that patients had been given vitamin C was shorter and patients were given vitamin C orally instead of intravenously. Both Pauling and Cameron publicly branded the Mayo report as “fraudulent” and angrily decried the false assertion that Moertel had closely replicated their work.

Many journals and newspapers refused to publish Pauling and Cameron’s rebuttals, or published them months after they were submitted such that the responses were no longer relevant. As a result, LPISM suffered still more financial hardships as public opinion once again swung away from the Institute and many people stopped donating. The direct-mail appeals that had been so successful in years past were only bringing in 25% of what they had a few months previously.

By 1986 LPISM was struggling with funding and also public awareness – the second Mayo Clinic trial seemed to have largely sealed public opinion on vitamin C research. But Pauling was still convinced that vitamin C had more merit than was being considered, and in support of this cause he published How to Live Longer and Feel Better. The book was well-received by critics and sold well.

For the Institute, its successes were manifold, as it provided a morale boost to LPISM staff, brought in sorely needed funds and dramatically raised awareness of the organization and its activities. Shortly afterward, Cameron and fellow LPISM employee Fred Stitt found themselves swamped with phone calls and letters to the Institute about health questions and recommendations. They quickly developed a standardized health information packet which they would mail out to people making more generic inquiries.

howtolivelonger

Nonetheless, as always, controversy was hovering over the Institute like a thunderhead. In 1987 Institute staffer Raxit Jariwalla began to research the effect of vitamin C on HIV/AIDS treatment. After a short period of time, Pauling became interested in the research and eventually Cameron did as well. Pauling began advocating increased usage of vitamin C in treating what seemed to be an incurable disease; the response was immediate and dramatic. Local donations increased, as the Bay Area was particularly sensitive to the hazards posed by HIV/AIDS. However, at the very same time, other sources of funding dropped as numerous groups and individuals pulled their support, stating that HIV/AIDS was a “moral disease.”

Through it all, the Institute continued to follow Zuckerkandl’s lead in expanding its research into areas outside the realm of orthomolecular medicine. In 1987 researchers began extensive work on protein profiling and the effect of phytic acid in cancer prevention, a program that was more or less entirely supported by a philanthropist based in New York.

The Institute also began working on superconductivity in 1988.  In particular, Pauling hoped to develop a room-temperature superconductor which he could then market as a stable revenue source for the Institute. Zuckerkandl, Steve Lawson, Pauling and even Cameron began working on this project, which utilized a material made out of borosilicate glass and tin. The process involved using a blowtorch and an inverted bicycle with its tires taken off the wheels. Pauling would often come down to the labs and help with the physical research and experimentation – it was the last research project he actively participated in. The process worked and the material was developed according to Pauling’s specifications. He received a patent for it early in 1989, and immediately began trying to market it, though ultimately without success.

The decade of the 1980s drew to a close on a mixed note for LPISM. The organization was, as always, struggling with controversy and financial problems. However, research was progressing well, popular support was increasing, and Pauling had come to terms with the death of his wife. The decade had seen its ups and downs, and what lay ahead would be no different.