Pauling, Stanford and Research – Part 2

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Pauling in lecture at Stanford University, 1969. Photo by George Feigen.

[An examination of Linus Pauling’s tenure at Stanford University. This is part 5 of 7.]

Linus Pauling knew going into his appointment at Stanford University that grants and outside funding would of paramount importance to keeping his research afloat. In September 1972 – three years into his tenure – Pauling authored a memo describing his work for the chemistry department in which he explained that his Stanford salary was now coming exclusively from grants, and that he had no other assigned duties at the university besides heading research. He likewise noted that he was actively working to bringing in new sources of money as well. In particular, he had “negotiated” a sickle-cell anemia contract with NIH earlier in June, estimating that $92,000 would be necessary from the agency.

The previous year, in spring 1971, Pauling applied for a grant from the Department of Health, Education, and Welfare to build a field ionization spectrometer for use in his urine analysis diagnoses. This device had only recently become available, the result of new technological advances in instrument design. In his application, Pauling detailed the potentially profound impact that this piece of equipment would have on his work.

This device would make possible simultaneous quantitative analysis and identification of 500-1000 chemical substances in a human body fluid in a time period of a few minutes and with an expenditure of only a few dollars per sample.

Pauling requested $387,554 for the project. It appears from a later report on his activities that he received the grant.

While Pauling enjoyed a long track record of success in attracting funding for his work, it was not always enough. In August 1972, Perry West, an administrative officer at Stanford, wrote to Pauling’s colleague and lab-mate, Art Robinson, to inform him that the laboratory’s current NIH and NSF funds would only last until the end of the year, two months short of what they had been meant to cover. As it turned out, Pauling’s laboratory had been using more computer time than they had been allocated, and had “drastically overdrawn” one account which they needed reconcile for themselves. The group has also overdrafted a second computing account that West had been funding for them.


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In addition to finding money, establishing institutional support for his research was also important for Pauling as he began to push for something a bit more ambitious: the formation at Stanford of a new Department of Orthomolecular Medicine and Nutrition. In a pre-proposal written in August 1972, Pauling called for a revitalization of nutrition as an active field of research at the university. In that same memo he also defined orthomolecular medicine “as the preservation of good health and the treatment of disease by varying concentrations in the human body of substances that are normally present in the body and are required for health.”

A few months later, in January 1973, Pauling brought his proposal to William F. Miller, Stanford’s Vice President and Provost. In making his pitch, Pauling emphasized the potential for orthomolecular medicine to bring in “millions of dollars” of funding. He also described the ways in which interest in orthomolecular research had already been taking off. By way of evidence, Pauling noted several talks that he had given the previous fall, details of which had made their way into the press.

As became readily apparent in the years that followed, Pauling also saw potential for vitamin C to treat a number of maladies including cancer, skin diseases, schizophrenia, the common cold and other infections. To begin actively investigating these tantalizing possibilities, he wanted to establish research centers at both Stanford and the University of Chicago. Miller replied to Pauling that he would consider his proposal and discuss it with the Dean of the Medical School.


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The Institute of Orthomolecular Medicine, 2700 Sand Hill Rd. Menlo Park, CA.

During this time, Pauling was also being encouraged by others reaching out to him, particularly Ewan Cameron, a surgeon and medical researcher at the Vale Leven Hospital in Scotland. Cameron shared with Pauling data related to his own successful use of vitamin C in treating bladder cancer patients. Pauling wanted to follow up on Cameron’s success and, in 1972, the two attempted to publish a paper in the Proceedings of the National Academies of Science on ascorbic acid as a treatment for cancer and other diseases. Their paper was initially rejected and, after Pauling resubmitted it, it was rejected again, an action that was described as “professional censorship” in an editorial published within the Medical Tribune.

Undaunted, Pauling continued to push his interests in developing orthomolecular medicine at Stanford and, in May 1973, proposed that the university consider building a new laboratory dedicated to the topic. In addition to the direct benefit of providing support for orthomolecular research, Pauling argued that a new laboratory would remove this work from the chemistry building, allowing it to emphasize its closer sympathies with medical research. Pauling again approached William Miller, telling him that a donor had already promised to give $50,000 for construction, which was estimated to be about half of the total cost. Pauling also expected other grants to come in as well.

Ultimately, Miller did not think it wise to pursue construction of Pauling’s orthomolecular facility. In rendering this judgement, Miller explained that Pauling had only been at Stanford for a short period of time and that his position was subject to annual renewals. This being the case, Miller did not want to “institutionalize” Pauling’s work unless Pauling was able to convince others in the chemistry and medical departments of its importance.

In effect, Pauling was told that, if he wanted his space, he would have to win over his colleagues first and convince them to initiate their own research programs in orthomolecular medicine. If this were to come about and more faculty with plenty of years ahead of them were to push for the idea, then Miller would be more open to considering a new capital project. Short of this, Miller suggested that donor funds be steered toward a more general purpose facility that would be made available to all chemistry faculty members.

Miller’s decision was important as it directly led to Pauling’s departure from Stanford University. Motivated to develop a space to pursue what he believed to be an exciting line of research, Pauling began to look for a laboratory facility off campus. This search led him to a building in Menlo Park near the Stanford Linear Accelerator. Not long after, the building became home to the Institute of Orthomolecular Medicine which, in 1974, was renamed the Linus Pauling Institute of Science and Medicine.

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.

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 Current Science

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Jeanne Drisko with Murray Susser. Both Drisko and Susser are past presidents of the American College for Advancement in Medicine.

[Part 2 of 2]

At her public lecture, “Intravenous Vitamin C: Does it Work?” delivered at the Linus Pauling Institute’s Diet and Optimum Health Conference in September 2017, Dr. Jeanne Drisko of the University of Kansas Medical Center, Kansas City, provided an overview of current research on the potential impact of intravenous vitamin C in treating disease.

She began this portion of her talk by reflecting on the factors that have continued to propel her own scientific interest in the topic, despite the headwinds generated by critics of the work. For one, Drisko has taken heart in the fact that intravenous vitamin C is used in many clinics around the world. Indeed, at a 2006 integrative medicine conference, Drisko and colleague Mark Levine took a survey of participants and found that some 8,000 patients had received intravenous vitamin C from doctors attending the meeting. Because Drisko maintains contacts in both conventional and alternative medical circles, she knows that naturopaths have been using intravenous vitamin C as well.

Drisko then pointed out that one barrier to more widespread acceptance of vitamin C as a cancer treatment is that, conventionally, it does not make sense to administer it in tandem with chemotherapy, since vitamin C is known to be an antioxidant and chemotherapy is a prooxidant. That said, Levine and Drisko’s colleague in Kansas, Qi Chen, have found that when vitamin C is given intravenously, it actually works as a prooxidant because it produces hydrogen peroxide. As such, it actually becomes a very good compliment to chemotherapy. Moreover, studies conducted by Drisko and others have found no evidence of conflict arising as a result of vitamin C dosages given alongside chemotherapy. On the contrary, researchers have reported a synergistic relationship in many cases.

In explaining why this is so, Drisko noted that when vitamin C is injected into a vein, it takes on the form of an ascorbyl radical, which she described as a “very promiscuous and active molecule that likes to interact with transition metals” like copper and iron. These interactions lead to the formation of hydrogen peroxide, which is quickly turned into water and oxygen by the enzymes glutathione peroxidase and catalase, such that levels of hydrogen peroxide in the bloodstream are promptly rendered as unmeasurable.

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However, when vitamin C gets into the extracellular fluid it also becomes hydrogen peroxide. The difference in this case is that glutathione peroxidase and catalase do not intervene and the hydrogen peroxide is not broken down into water and oxygen. Instead, the hydrogen peroxide diffuses throughout the extracellular fluid, bathing the cells.

While the presence of hydrogen peroxide in the cells might seem unsafe, Levine’s cell culture tests have found that hydrogen peroxide caused harm only to cancer cells. In reporting his results, Levine explained that the glutathione peroxidase and catalase enzymes are not as efficient in attacking cancer cells because they direct their activity towards reproduction rather than other processes. The fact that glutathione peroxidase and catalase are not active in the extracellular fluid renders vitamin C as a pro-drug and hydrogen peroxide as an actual drug.


Drisko’s research portfolio on the use of intravenous vitamin C includes the first randomized controlled trial involving ovarian cancer patients, work that was published in 2014. The trial studied two groups of patients: one group received standard care, which included carboplatin and paclitaxel chemotherapy for six cycles. The other group received this same care along with 75 to 100 gram doses of intravenous vitamin C.

The trial made clear that this form and dosage of vitamin C therapy is safe to administer. It also yielded a statistically significant improvement in how certain types of patients felt during their cancer treatment. Drisko called this a “feel good effect” which she believes is neurological. This same impact, however, was not observed in patients suffering from more advanced stage three and stage four cancers. Drisko is currently following up on these results by looking at the role that vitamin C might play in brain chemistry.

While her work has generated positive results, Drisko is also aware that vitamin C should not be used in all cases. Importantly, vitamin C is known to be potentially harmful when given in large doses under certain conditions. One such case is in individuals suffering from a deficiency of Glucose-6-Phosphate Dehydrogenase, or G6PD. On its own, G6PD can cause anemia, but when combined with high levels of vitamin C it leads to hemolysis, or the destruction of red blood cells. As a matter of standard protocol, Drisko checks her own patients for G6PD deficiencies, but she knows of others who have been unaware of this biological conflict and who have had to send patients to the emergency room.

Drisko will likewise opt against administering intravenous vitamin C when a patient reports a history of oxalate kidney stones, which can form as a result of excessive vitamin C intake. For individuals who have gone ten years or more since their last instance of oxalate kidney stones, Drisko administers vitamin C, but she does so cautiously, monitoring kidney functions and liver enzymes throughout the process.


Another barrier to studying intravenous vitamin C is that it is a difficult substance to measure since it is processed by the body so quickly. To get around this difficulty, Drisko developed a finger stick method that emerged from her interactions with a diabetic ovarian cancer patient. Over the course of these interactions, Drisko found cause to contact a glucometer manufacturer who told her that, because vitamin C and glucose molecules are so similar, the glucometer would indicate levels of both. Making use of this similarity, Drisko started taking finger stick glucose readings both before and right after her patients received their doses, and using this process she is now able to ascertain a rough estimate of how much vitamin C has been absorbed by the body.


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Qi Chen

In attempting to achieve greater certainty about appropriate dosage levels of vitamin C to administer, Qi Chen and Mark Levine have conducted experiments wherein they give intravenous vitamin C to mice and rats with tumors. This work is a follow-up to Levine’s original studies in the 1990s, which showed that vitamin C given orally could not be absorbed above a 10 millimolar concentration. In their more recent invesigations, Levine and Chen have found that blood concentration levels of 20 to 30 millimolar can be achieved as a result of intravenous application. They also found that the tumors in their mice studies would take up the vitamin C and that hydrogen peroxide formed in the tumors and subcutaneous tissue, but not in the blood.

Drisko gives her patients two to three infusions of vitamin C per week in advanced cases. Ideally, the vitamin C would be administered as the fluid loading dose for chemotherapeutic drugs, but it is often difficult to carry out both vitamin C and chemotherapy treatments on the same day because patients are already burdened by a busy treatment schedule and the facilities providing the two types of treatments are often not in the same location. (A new dosing device that attaches to the hip, developed by Channing J. Paller at Johns Hopkins, could help to get around some of these barriers.) Drisko’s treatment schedule uses a “stair-step” methodology wherein doses ranging from 0 to 100 grams are able to achieve 20 millimolar blood concentrations.

The appropriate duration of vitamin C treatment for cancer is still an open question. What is known is that it takes at least a couple of months before effects start to show. This stands in stark contrast to chemotherapy, which makes a much quicker impact.


Drisko concluded her talk by sharing the hopeful story of a woman who had participated in her ovarian cancer trial. This patient had been part of the group that had received the standard chemotherapy treatment only. She had subsequently relapsed very quickly and was believed to have only months to live. In her conversations with Drisko, the patient expressed a strong desire to live long enough to give her grandson a present at Christmas, and she requested that Drisko give her vitamin C in addition to her chemotherapy, since she was no longer part of the trial.

Initial CT-PET images showed that the woman was suffering from an accumulation of fluid, or ascites, full of cancer cells that were pushing against her organs. At the start of her intravenous vitamin C treatment in 2004, a second CT-PET scan showed both the malignant ascites as well as a residual tumor that could not be removed surgically.

Subsequent scans after Drisko began her treatment showed gradual improvement. In 2007, the pictures included fewer ascites and the tumor was somewhat smaller, trends that continued to be seen in 2012. By 2014, calcification appeared in the tumor and around the fluid, with further calcification showing in 2015. In essence, what the scans were revealing was an eight-year process of “turning her cancer into a scar.” While this is only a single example, it is a powerful one, and may prove to be harbinger of medical breakthroughs to come.

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.

Leaving La Jolla

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Ava Helen and Linus Pauling near the beach at La Jolla, 1969.

[Pauling at UCSD, part 3 of 3]

In early 1969, Linus Pauling announced that he had accepted an appointment at Stanford University, and that he would be leaving the University of California, San Diego, where he had been on faculty for the past two academic years. In making this announcement, Pauling explained his feeling that Stanford would be a better fit for his orthomolecular research, in part because of the Palo Alto school’s well-established department of psychiatry. (Stanford was also significantly closer to the couple’s home at Deer Flat Ranch, which pleased Ava Helen Pauling immensely.)

Though Pauling and his colleagues had made significant progress on their psychiatric studies at UCSD, one problem that they had yet to conquer was the ability to control for other variables – especially those introduced by diet – that could contribute to variations in the levels of nutrients observed in test subjects’ bodies. Because of this, the group was not able to accurately track what Pauling called “individual gene defects.”

Moving the project to Stanford meant that the researchers would be afforded the opportunity to work with mental health patients at Sonoma State Hospital, all of whom were consuming the same diet, as provided by the Vivonex Corporation. Intrigued, Pauling coordinated with Vivonex to obtain copies of the diet that the company had tailored, the idea being that his control group could follow it as well.

By now, Pauling and his team felt confident that they had uncovered evidence of abnormal patterns of ascorbic acid elimination in individuals suffering from acute and chronic schizophrenia. He and his colleagues planned to continue their analyses of these abnormalities as they moved toward the identification of genetic defects, the creation of diagnostic tools, and the promotion of effective therapies for sufferers of mental disease.


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San Francisco Chronicle, May 27, 1969

Pauling’s final act at UCSD was appropriately radical. Shortly after the student occupation of People’s Park at UC-Berkeley and the subsequent death of James Rector, a Berkeley student who was shot by Alameda County Sherrifs in May 1969, UCSD students and faculty gathered to decide how they would respond to the tragedy at their sister school. Most of the faculty in attendance expressed a desire to simply mourn the death and voice their solidarity with Berkeley, but not to disrupt daily operations.

Pauling, on the other hand, stood in front of the hundreds of students who had gathered and encouraged them to go on strike in protest of recent actions taken by the National Guard, the police, and Governor Ronald Reagan. In so doing, Pauling claimed that the violence at Berkeley was

part of a pattern—the pattern of the war in Vietnam, the increasing militarism of the United States, the growth of the military-industrial complex, the suppression of the human rights of young men and others.

He further explained that those who held power would do whatever was necessary to protect and move forward with a deeply cynical plan. And in detailing his point of view, Pauling made it clear where he stood with regard to the next appropriate actions.

The plan is the continued economic exploitation of human beings. The purpose of the plan, which has been successful year after year, is to make the rich richer and the poor poorer…Everyone in the whole University of California, all the students, the faculties, the employees, should strike against the immorality and injustice of the act at Berkeley.

Less than a week later, Pauling participated in a march and rally at the State Capital in Sacramento, where he gave an impromptu speech that echoed his remarks in San Diego. “The university is not the property of Governor Reagan and the other regents,” he exhorted. “We must protest until the police and the National Guard are removed from the campus of the University of California…the university belongs to us, the students, the faculty, and the people.” So concluded Pauling’s final remarks on the UC system and its regents while a member of the UC faculty.


Although Pauling never worked within the University of California again, his short time at UCSD was undeniably productive and useful. For one, his two years in La Jolla marked a reemergence, of sorts, into the scientific realm following his frustrating tenure at the Center for the Study of Democratic Institutions.

UCSD also provided the opportunity for Pauling to incubate his partnership with Arthur Robinson. This relationship later proved key to the creation of the Institute for Orthomolecular Medicine, known today as the Linus Pauling Institute. The collaboration also provided a strong foundation from which Pauling worked doggedly to expand his research on all manner of topics related to orthomolecular medicine. Though the work ultimately proved to be very controversial, as he left La Jolla, Pauling had every reason to be optimistic about the bold new direction that his research was taking.

Pauling at UC-San Diego

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[Part 1 of 3]

We have written previously about Linus Pauling’s affiliation with the Center for the Study of Democratic Institutions (CSDI), and also of the difficulties that he encountered in what ultimately proved to be a doomed attempt at securing a position at the University of California, Santa Barbara in 1964. Over the next three weeks, we will focus on the years that Pauling spent at the University of California, San Diego, the institution where he began his experimental work in orthomolecular medicine. As we will see, Pauling’s tenure at UCSD, though short-lived, offered him the opportunity to pursue a mission that he had initially sought out, and failed to obtain, at the Center for the Study of Democratic Institutions: the application of scientific and medical research to political and social issues.


In 1966, UCSD Vice Chancellor for Research Fred Wall, an accomplished chemist who was eager to rectify the disappointment that Pauling had experienced with UC-Santa Barbara, invited Pauling to join the faculty at UC-San Diego. Pauling was initially hesitant. He remembered all too well the hostility that informed University of California Chancellor Vernon Cheadle’s refusal to consider his appointment at UCSB, a position that was fully supported by the UC regents. This history fresh in mind, Pauling saw no reason why he would be permitted to teach at UCSD; afterall, his political views hadn’t changed over the past two years and he’d become, if anything, even more vocal about them.

This time, however, Pauling’s case received far more support. For one, UCSD’s chancellor, John Galbraith, fought hard to garner faculty endorsement of a petition that aimed to

urge that every effort be made not only to induce him to accept the present appointment assured for one year, but also to press with all means possible for its renewal for whatever periods Dr. Pauling and the faculty involved agree to be appropriate.

Galbraith likewise went out of his way to praise Pauling’s excellent lecturing ability as being a potential asset to faculty and students alike. Similarly, he affirmed that Pauling’s appointment would prove valuable not only to the chemistry department, but to the physics and biology departments as well. In due course, faculty in all three departments signed the petition and the chemistry department unanimously voted in favor of Pauling’s appointment.

Pauling, buoyed by this strong show of support, accepted a one-year appointment with the university, a contract that carried with it the understanding that a tenured position might be offered in the coming years, so long as the UC regents didn’t interfere.


A letter from Ava Helen Pauling to her son Peter, as well as a statement made by Pauling in the Women’s International League for Peace and Freedom Newsletter, indicate that his initial take on UCSD was a positive one. Perhaps most importantly, the university offered him the means to return to scientific research, a clear source of invigoration following two years at the CSDI, which was not capable of providing him with adequate lab space. In her letter to Peter, Ava Helen confirmed this new feeling of enthusiasm, particularly as it was coupled with exciting, if nascent, investigations on orthomolecular topics. Pauling himself called UCSD a “first-rate” institution and expressed his satisfaction with the top scientific and medical researchers who had made it their academic home.

It didn’t take long for Ava Helen to find a house to rent in La Jolla and shortly thereafter, in September 1967, Pauling arrived at his new office on the UCSD campus. In their initial meetings, Bruno Zimm, the chemistry department chairman at the time, encouraged Pauling to develop customized coursework that might explore specialized subjects of Pauling’s choosing over the upcoming terms. Pauling replied that it was his preference to focus predominantly on research, as his salary was coming entirely from research funds. He remained active on campus however, participating enthusiastically in a lecture series targeting first year students.


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Linus Pauling, 1967.

Shortly after settling in, Pauling began partnering with Arthur Robinson, a former student at Caltech, and now an assistant professor in the UCSD biology department. Together, the duo would tackle Pauling’s latest research quest: an exploration of orthomolecular medicine. This fruitful collaboration eventually led to their co-founding of the Institute for Orthomolecular Medicine, now known as the Linus Pauling Institute at Oregon State University.

Pauling’s research was being supported by UCSD as well as lingering funds from CSDI, but soon it became clear that his team would need additional resources. As he delved further into his orthomolecular program, Pauling estimated that the work that he had in mind would take at least five years, a length of time that was extended, in part, by the small size of his research team. In addition to Pauling and Robinson, the UCSD group consisted of two lab technicians (Sue Oxley and Maida Bergeson), a post-graduate resident (Ian Keaveny), and two graduate students (John and Margaret Blethen).

When applying for grants, Pauling described his research as seeking to discover better diagnostic and treatment methods for mental illness. In his applications, Pauling asked mainly for equipment funds, and he usually received what he wanted. Pretty quickly, his team found that vapor-phase chromatography – a process that had been suggested by Robinson at the outset of the project – was the most effective technique for engaging in quantitative analysis, and the grant applications that followed sought to enhance these capabilities in the laboratory.

Pauling’s goal during these first years was to uncover and establish a link between mental illness and deficiencies of various vitamins. At the outset, the team specifically planned to look at the correlation between fluctuations in mental health and variations in intake of ascorbic acid (Vitamin C), nicotinic acid (B3), cyanocobalamin (B12), and pyridoxine (B6). Pauling believed that the brain and nervous system were especially sensitive to molecular composition and structure, and that certain mental illnesses were actually a problem of localized cerebral deficiency. This was, in essence, the guiding principle behind much of the team’s work.

Pauling also felt that schizophrenia had not received adequate scientific study, and so the group decided to focus their primary research on schizophrenics. If all went according to plan, the following three years would be devoted to developing diagnostic tools to identify deficiencies as well as effective therapies for correcting the deficiencies. The researchers would also use this time to explore the impact and consequences of other vitamin deficiencies. Though enthusiastic about this program, in several of his publications and speeches on the topic Pauling took pains to present orthomolecular therapy as being an adjunct to, and not a replacement for, traditional methods such as psychoanalysis, antipsychotics, and antidepressants.


During the CSDI years, Pauling’s grant funding from the National Science Foundation had been continuously delayed, largely because he didn’t have a lab in which to conduct the work. Once he was established at UCSD however, the NSF was quick to award him the grant money that he’d long ago requested. Pauling also received funding from the Department of Health, Education, and Welfare, and additional monies from the CSDI were likewise set aside, should he need them.

The group began working in earnest in late 1967, focusing on measurements of vitamin absorption, and by April 1968, Pauling had published his introductory paper, “Orthomolecular Psychiatry,” in Science. The article, which proved influential, drew from the existing literature, focusing especially on a study by Abram Hoffer and Humphry Osmond, who had reported improvement in mentally ill patients treated with a regimen of nicotinic acid and nicotinamide.

In short order, Pauling began to receive a growing volume of letters from community members who had been directly or indirectly affected by mental illness. Pauling took care in replying to these correspondents, often pointing them toward additional resources for more information and encouraging them to write again if they had further questions. The response from medical researchers and physicians to Pauling’s paper was mixed; on the whole, they remained largely unimpressed with Pauling’s work. Nonetheless, Pauling never failed to emphasize the importance of his research, and the general public responded favorably to this confidence.