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.

Pauling at Stanford: Settling In

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Linus Pauling, 1969. Credit: Margo Moore.

[An examination of Linus Pauling’s years at Stanford University. Part 2 of 7.]

Linus Pauling began his appointment as Professor of Chemistry at Stanford University on July 1, 1969. During his years in Palo Alto, Pauling’s experimental work largely focused on developing and refining urine and breath analyses for use in diagnosing various diseases and genetic conditions ranging from schizophrenia to cancer, skin disease, heart disease, and Huntington’s chorea. In addition to funding from the National Institutes of Health and the National Science Foundation, Pauling and his laboratory were supported by a collection of smaller awards including a 1971 grant from the American Schizophrenia Association.

During his Stanford years, Pauling also continued to promote his research and peace work through a hectic travel schedule and regular publications. In January 1970, Pauling served as Visiting Professor at the Technical University of Chili, where he also received the Medal of the Senate of Chili. That same year, Pauling published an influential article, “Evolution and the Need for Ascorbic Acid” as well as his book Vitamin C and the Common Cold. The latter would become a bestseller.

In 1971 Pauling published six articles, one on nuclear weapons and others covering various topics in chemistry. He also completed revisions for, and saw published, the third edition of his hugely successful textbook, General Chemistry. In April 1971, he received the Lenin International Peace Prize at the Soviet Embassy in Washington, D.C. The next year, he partnered with Paul Wolf in the Department of Pathology to study sickle cell anemia. And in early 1973, Orthomolecular Psychiatry was published, which Pauling co-edited with David Hawkins. In short, though now in his early 70s, it was clear that Pauling had no intention of slowing down.


Not long after his arrival, Pauling identified a need to begin situating himself within the university’s administrative apparatus. One of the first items on his to-do list was to update his consent forms and put them on Stanford letterhead. Since he was now associated the university, doing so would help should any legal problems arise with his research.

As part of this process, Pauling also had to make sure that his experimental designs were in accordance with Stanford’s standards by running them by the university’s Committee on the Use of Human Subjects in Research. This process included, for one, clarifying whether or not the dose of Vitamin-B6 used in a particular study “approach[ed] the 4 GM/Kg that produces convulsions and death in animals.”

Perhaps most importantly, though he fully understood the modest circumstances governing his hire at Stanford, Pauling was nonetheless perturbed at times with the accommodations that had been made for him. In an undated letter to Alan Grundmann, a that time an assistant to the Stanford provost, Pauling complained about his small work area, emphasizing that space around him was sitting unused. As his mood soured, Pauling demanded that Stanford do a better job of acting in accordance with the space guarantees that had been stipulated in his contract. Pauling subsequently threatened to leave if the situation didn’t improve, suggesting that he might return to the University of California in San Diego, where he knew that they had enough space for him.


Though his relationship with administration may not have been perfect, other faculty members at Stanford were clearly very interested in Pauling’s research and teaching. Not long after he arrived, a variety of professors began asking Pauling to address classes varying from a general chemistry course, a psychiatry research seminar, and a postgraduate survey of basic medical science. Pauling also spoke to medical and psychiatry students about vitamin C and his newly developing concept of orthomolecular medicine.

Pauling’s understanding of social issues also proved to be a draw for his colleagues. In one instance, he and Ava Helen jointly addressed a freshman seminar on the social responsibility of scientists. Pauling also participated in Stanford’s Professional Journalism Fellowship Program series, at which he was asked to respond to the question, “What would you do if you were Secretary of State?”

Even Pauling’s personal medical examinations piqued interest within the Stanford community. Roy H. Maffly at the Department of Medicine conducted a renal evaluation of Pauling, a study that was possibly inspired by Pauling’s successful bout with glomerulonephritis in the 1940s. (a medical triumph that had been led by a Stanford physician, Thomas Addis) Maffly was also keen to learn more about Pauling’s own urine studies and agreed to interpret the results of Pauling’s evaluation using Pauling’s methods.

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Within the Chemistry Department, Pauling joined the Industrial Affiliates Committee, which was chaired by his friend Carl Djerassi. This committee sought to connect private corporations to the research being conducted within the Chemistry Department by addressing questions like the relationship between chemistry and chemical engineering. Pauling was also involved in organizing different symposia for the committee, speaking at its first such gathering in November 1969. He likewise represented the group when he presented on his vitamin C research at an international conference in 1973.

Pauling further integrated himself into the Chemistry Department by taking on graduate students. By the start of his second year, Pauling was chairing two doctoral committees and was a member of four others. His students included Robert Copland Dunbar, who was using ion cyclotron resonance to study the interactions between ions and molecules. Margaret Blethen and John Blethen, both of whom worked with Pauling on his schizophrenia studies, and David Partridge, who worked on the chromatographic analysis of urine samples, were also mentees of Pauling’s.

Working with doctoral students gave Pauling the opportunity to offer advice based on his experiences at the University of California San Diego, where graduate students rotated between different laboratories during their initial months. Pauling suggested to others in the Chemistry Department that first year students rotate through six different laboratories, spending six-week periods in each over the course of the year. Pauling believed this to be an effective way for new students to get to know staff and to better understand the different lines of research being conducted. Armed with these experiences, the students would then be better able to make a considered decision when it came time to choose the path that they would follow at the start of their second year. Pauling also suggested that graduate student research not be tied to funding.

 

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.

Farewell to Balz Frei

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Next week, a new school year will start here at Oregon State University. And with it, for the first time since 1997, the Linus Pauling Institute will enter into a fresh academic calendar without the leadership of its now emeritus director, OSU Distinguished Professor of Biochemistry and Biophysics, Dr. Balz Frei.  Last Spring, word of Frei’s retirement from LPI made its way into local headlines, and in this interview he confided that, in addition to relinquishing his administrative responsibilities, he will be closing down his research laboratory as well.

A native of Winterthur, Switzerland, Frei moved permanently to the United States in 1986, when he accepted a lengthy post-doctoral appointment in Dr. Bruce Ames’s lab at the University of California, Berkeley. Frei later moved on to a position in the Nutrition Department at the Harvard School of Public Health, and after four years at Harvard, he relocated to the Boston University School of Medicine. A widely respected scientist, Frei’s research has focused on the mechanisms causing chronic human disease, in particular atherosclerosis and cardiovascular disease, and the role that micronutrients, phytochemicals, and dietary supplements might play in ameliorating these diseases.

In 1997, Frei became the first and, until now, only director of the Oregon State University incarnation of the Linus Pauling Institute.  Founded in 1973 as the Institute for Orthomolecular Medicine, and renamed the Linus Pauling Institute of Science and Medicine a year later, the Institute struggled for much of its history in California, hamstrung in part by the intense controversy that it’s founder and namesake generated through his bold proclamations about vitamin C.

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Moving to OSU in 1996 helped to wipe the Institute’s slate clean, and the major progress that the Institute has enjoyed in the twenty years that have followed is a direct outcome of Frei’s vision, skill, and endeavor. Following Linus Pauling’s death in 1994, the Institute, crippled by funding problems and lacking a clear strategic vision, was nearly shuttered. Today, Frei leaves behind a thriving research enterprise that includes twelve principal investigators and a $10.2 million endowment.

We conducted a lengthy oral history interview with Frei in January 2014 and have included a few excerpts after the break.  The entire interview is worth a read as it details the life and work of a man who has made a true difference at our institution and within the fields of disease prevention and the quest for optimal health.

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The Decline of Orthomolecular Psychiatry

Abram Hoffer and Linus Pauling at the symposium, "Adjuvant Nutrition in Cancer Treatment," Tulsa, Oklahoma, November 1992.

Abram Hoffer and Linus Pauling at the symposium, “Adjuvant Nutrition in Cancer Treatment,” Tulsa, Oklahoma, November 1992.

We have written before on both the orthomolecular psychiatry of Linus Pauling and the birth of orthomolecular medicine, which has its roots in nutritional (later called orthomolecular) psychiatry. This post delves further into how orthomolecular psychiatry came to be, as well as its marginalization out of the scientific mainstream.

It all began with Albert Hofmann, the Swiss scientist who, in 1938, famously synthesized LSD and discovered its psychedelic properties. After several trials, some on himself, Hofmann developed the hypothesis that LSD mimics the effects of psychosis.

Hofmann’s idea inspired two English psychiatrists, Dr. Humphry Osmond and Dr. John Smythies, to further his research in the late 1940s. Using mescaline (derived from the peyote cactus) as their basic compound, the duo took Hofmann’s work a step further, eventually conjecturing that schizophrenics suffered from an overdose of an endogenous (made in the body) toxin that was similar in structure to mescaline and LSD.

Finding no sympathy in England – at the dominated by Freudian thought – Osmond and Smythies took their work to Saskatchewan, Canada, relocating there in late 1951. Once in Canada, Osmond met Abram Hoffer, a fellow psychiatrist with whom he would collaborate for decades. Together, Hoffer and Osmond ran the psychiatric sciences and therapies divisions of the psychiatric hospital in Weyburn, Saskatchewan, which housed a number of schizophrenic patients.

Hoffer and Osmond eventually discovered the toxin that Osmond and Smythies had suspected was causing the psychoses present in schizophrenics: adrenochrome, a byproduct of the body’s metabolic oxidization of adrenaline and noradrenaline. The next step in helping their patients, the doctors felt, was to find some way to alleviate the psychoses brought about by schizophrenia. This led them to nicotinic acid, also known as vitamin B3 or niacin. Niacin, they learned, was known anecdotally to help patients with neuropsychiatric disorders. This fit with the fact that pellagra, a disease caused by a deficiency of niacin, sometimes presents with psychiatric symptoms.

Eager to test their theory that vitamin B3 could help alleviate mental disease, Hoffer and Osmond began experimentation, dosing their schizophrenic patients with large amounts of niacin by adding it to their daily diets in the first double-blind tests performed in psychiatry. Once the experimentation was finished, Hoffer and Osmond followed their patients for ten years, measuring the effectiveness of their added-vitamin therapy in terms of readmission rates and ability to find outside employment once released from the hospital.

In 1962 Hoffer and Osmond published the book Niacin Therapy in Psychiatry, the text that introduced Linus Pauling to the duo’s megavitamin work. The book revivified his interest in the biochemical basis of mental illness, which he had been studying for a decade, having previously learned that phenylketonuria is a molecular disease in much the same way as sickle-cell anemia.

By the time Pauling read the niacin book, anecdotes about megavitamin therapy, as it was then called, had begun to spread. Additionally, it had already been discovered that niacin could lower cholesterol levels. When added to his prior knowledge, these facts led Pauling to find the evidence presented in the book compelling enough to merit further investigation. The final ingredient to Pauling’s interest appeared the next year, when Dr. Irwin Stone introduced Pauling to the potential health benefits of large doses of Vitamin C. .

It wasn’t until 1967 that Pauling coined the term “orthomolecular,” using it in print for the first time in a paper titled “Orthomolecular Methods in Medicine.” In 1968 Pauling wrote his more famous paper on the subject, “Orthomolecular Psychiatry,” published in the journal Science. Pauling, of course, went on to found the Institute of Orthomolecular Medicine with Art Robinson in 1973, (soon after renamed the Linus Pauling Institute of Science and Medicine) and co-edit the book Orthomolecular Psychiatry: Treatment of Schizophrenia in the same year. Around this time, Pauling also began broadening his theory of orthomolecular medicine to include the whole body, not just the mind.


But what happened to Hoffer and Osmond? The answer to this question plays a part in understanding why many doctors today still refuse to consider orthomolecular medicine a legitimate form of treatment.

In 1967 Hoffer and Osmond formed both the Canadian Schizophrenia Foundation and the American Schizophrenia Association. The two doctors had recently been encountering a great deal of resistance to the publication of their ideas, so they started their own journal, the Journal of Schizophrenia, in the same year. They asked Pauling to serve on the editorial board; Pauling agreed, participating in that capacity for the rest of his professional life.

In 1973 orthomolecular psychiatry was dealt a serious blow by the American Psychological Association Task Force. That year, the group published a report titled “Megavitamin and Orthomolecular Therapy in Psychiatry,” condemning the practice as unsupported at best and “deplorable” at worst. Hoffer and Osmond were subjected to humiliation and orthomolecular psychiatry was deemed unworthy of study or application. The following year, Pauling responded to the report, pointing out a number of flaws, including errors in methodology, lack of research, confusion of focus, and bias:

Orthomolecular psychiatry is the achievement and preservation of good mental health by the provision of the optimum molecular environment for the mind, especially the optimum concentrations of substances normally present in the human body, such as the vitamins….The APA task force report Megavitamin and Orthomolecular Therapy in Psychiatry discusses vitamins in a very limited way (niacin only) and deals with only one or two aspects of the theory. Its arguments are in part faulty and its conclusions unjustified.

But Pauling, Hoffer, and Osmond’s expressions of outrage at perceived mistreatment by the APA weren’t enough to overcome further obstacles that lay ahead. For one, in the mid-1970s, orthomolecular psychiatry, rather than sticking to megavitamin doses, expanded to include diet in the treatment of mental health, as well as avoiding stimulants like nicotine. However, no consensus was reached within the community with regard to precise standards for the practice, so recommendations varied from doctor to doctor, making the efficacy of orthomolecular psychiatry difficult to evaluate.

The mainstream introduction of tranquilizers and the phasing out of electroconvulsive therapy in the treatment of mental illness also proved a barrier to the orthomolecular community. Tranquilizers, unlike megavitamins, were immediately successful in alleviating symptoms, making orthomolecular medicine, which took time to work, appear ineffective by comparison.

Eventually, whenever a patient would ask about megavitamin or orthomolecular therapy as an alternative treatment, many doctors would simply cite the APA report, claiming that it had disproven orthomolecular methods. After a while, most patients simply stopped asking.

The American Schizophrenia Association eventually became the Huxley Institute for Biosocial Research, still led by Abram Hoffer. Dr. Hoffer asked Pauling to serve on its board of directors but Pauling declined, by then more interested in pursuing Vitamin C in the treatment of cancer and colds.  The flagging in his energy for the discipline of orthomolecular psychiatry was indicative of the lack of momentum within the field, a situation that persisted for the remainder of Pauling’s life.

The Founding of the Institute of Orthomolecular Medicine

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

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

[Ed Note: 2013 marks the fortieth anniversary of the founding of the Linus Pauling Institute, known variously over time as the Institute of Orthomolecular Medicine and the Linus Pauling Institute of Science and Medicine.  For the next several weeks, the Pauling Blog will be celebrating LPI’s anniversary by publishing an in depth history of the organization.  This is post 1 of 8.]

In 1969 Linus Pauling was given his own laboratory at Stanford University for his work on schizophrenia, where Art Robinson, a colleague and fellow researcher, joined him. By 1972 Pauling and Robinson had decided that their Stanford facility no longer afforded the space necessary to continue their research, and in May of that year Pauling requested that the university construct a new building to house an expanded lab for him to use.

The institution hesitated in responding, as its administration was somewhat wary of Pauling at that time, given the controversy that surrounded both his scientific interests and political activism.  Pauling had recently co-authored controversial work with the Scottish physician Ewan Cameron about vitamin C and its usefulness in treating cancer, research which alienated him from much of the medical community. For its part, Stanford was very unsure about the wisdom of giving him a new lab to further that research.

Likewise, Pauling was working hard and visibly for global peace in the middle of the Cold War, activities which had long caused many people to suspect that he harbored communist sympathies. Almost as if to verify that accusation in their minds, he had been awarded the Lenin Peace Prize by the Soviet Union in 1970. Pauling was a harsh and public critic of the war in Vietnam, President Richard Nixon, US nuclear policy, and US foreign policy, which only served to legitimize some people’s doubts about Pauling’s loyalty to the United States. And if that wasn’t enough, Pauling had also publicly protested Stanford’s firing of a tenured professor known to have leftist, anti-war leanings. Stanford took these numerous activities into consideration, and decided to deny his request.

In response, Robinson suggested that Pauling step down from the Stanford faculty and move their research off campus, which they did, relocating in early 1973 to a building that Robinson had found nearby. Their new home was at 2700 Sand Hill Rd. in Menlo Park, across the street from the Stanford Linear Accelerator building. The space was in an office building shared with Kemper Insurance, a location never designed to accommodate scientific research. Nonetheless, Pauling and Robinson adapted, figuring out how to fit their lab into a footprint of less than 20,000 square feet – an area designed to hold desks and chairs instead of wet labs.

An Institute employee working at the Sand Hill Rd. facility, 1974.

An Institute employee working at the Sand Hill Rd. facility, 1974.

Freed from their affiliation with Stanford University, Pauling, Robinson and Keene Dimick – a biochemist who agreed to help pay the rent for their new quarters – decided to form a brand new institute. On May 15, 1973, the Institute of Orthomolecular Medicine was founded as a California non-profit research corporation with the stated goal of researching biology and medicine.

(In late 1973, Pauling decided to sever all of his professional ties with Stanford, equally annoyed with the university as it seemed to be of him. However, he still retained a number of good friends amongst the faculty there, with whom he maintained close ties and corresponded frequently.)

Immediately the Institute began trying to solve a problem which would plague it for most of its existence: funding. Pauling and Robinson began by lobbying all of their friends and associates for money, trying to entice them in part by offering them largely honorific positions on the Board of Associates of their new Institute. Over thirty people agreed to help, including Francis Crick, Maurice Wilkins and a number of other Nobel laureates. The funds generated weren’t princely, but they were enough to get the Institute standing.

On the research end, the Institute began by continuing the program that Pauling and Robinson had been conducting at Stanford – mostly work on vitamin C and metabolic profiling. The new labs contained a large number of animal experiments, which took up a great bulk of the very limited space, as did the Volcano Source Field Ionization Mass Spectrometer, a new device that was being developed by Bill Aberth, a recent hire who had previously worked for SRI International.

Pauling wanted to help people with his research on vitamin C, and in 1974 he opened a small outpatient clinic which was run by John Francis “Frank” Catchpool, a doctor whom Pauling had met in 1959 while visiting Albert Schweitzer’s medical hospital in Africa. Unlike Schweitzer’s venture, the Institute’s clinic was immediately beset with major problems – liability was too high and funding was too low. Additionally, because vitamin C was cheaper than other medication, the clinic often found itself overwhelmed by destitute patients. The staff often ended up working for free, as people would arrive who were too poor to pay anything, but Cameron and other staff would still help out of sympathy and a desire to do good. Due to severe limitations on resources, the clinic closed in 1975, eight months after it opened.

Interior view of the Sand Hill Rd. facility, 1974.

Interior view of the Sand Hill Rd. facility, 1974.

As 1974 progressed, the Institute’s funding problems became increasingly ominous, exacerbated by the fact that Robinson was one of the only people on staff who was adept at fundraising. In July the Board decided to start addressing the problem by renaming the Institute of Orthomolecular Medicine. They came to the conclusion that the term “orthomolecular” was not only too difficult to explain to most potential donors, but that the term had been tainted by a recent barrage of attacks on vitamin C by the American Psychological Association. They also decided that having Pauling’s name attached to the Institute would help with funding, due to his international fame and respect.

On July 26, the Institute was renamed the Linus Pauling Institute of Science and Medicine (LPISM). The Board’s choice proved to be a good one, and more funding began to come in. Even still, it wasn’t enough, and for much of 1974 LPISM was kept afloat through financing from Pauling and Robinson’s personal accounts. Unsurprisingly this too proved to be insufficient and by early 1975 LPISM was in danger of succumbing to bankruptcy. Desperate, the Institute’s administrators were forced to exact pay cuts for all employees, but did so on a sliding scale designed to minimize the impact on workers with already low salaries.

It was at this point that Robinson confronted Pauling, accusing him of neglecting his work as president. Pauling had in fact been neglecting daily duties, boasting to the press at one point: “I don’t waste time on needless details.” Unfortunately, many of these details weren’t needless, and his administrative inattention was harming the Institute. Pauling asked Robinson if he thought he could do better, to which Robinson replied that he could. Pauling responded by making Robinson President and Director of LPISM. Still the financial issues became worse: Pauling donated 75% of his income to LPISM for the first half of 1975, and then 100% of his income in the second half of the year.

In the meantime, the Institute staff began experimenting on hairless mice. For a week before the tests, they would feed the mice food full of vitamins C and E. Next they began irradiating them with ultraviolet light to produce skin cancer and observed the effects of the high-vitamin diet on cancer growth. As a result of this research, Pauling developed a cocktail of vitamins, which he put into a single dose that he called the “Linus Pauling Super Pill.” The Institute considered marketing the pill to raise additional funds, but that plan fell through and the Pauling Super Pill was relegated to a formula in a filing cabinet.

The Institute found itself in a bad place by the end of 1975; saddled with massive financial problems, it was uncertain if it would survive. And amidst this struggle, fortunes were about to get both better and worse for the Linus Pauling Institute of Science and Medicine.

A Somber Return to China, 1981

The Paulings in Tianjin, June 1981.

In the summer of 1981, Linus Pauling participated in the First International Conference on Human Nutrition, which took place in Japan and China. The conference lasted from May 31 to June 8, and was sponsored by the China Medical Association and the Foundation for Nutritional Advancement, the latter of which Pauling was president. The conference took place in Tokyo, Japan and Tianjin, China, travels to which would comprise the first part of a trip that would also take the Paulings to Germany and to London. Their daughter Linda and her husband Barclay accompanied Linus and Ava Helen to the Orient.

Pauling made the opening remarks at the beginning of the conference in Tokyo on June 1. After the Tokyo sessions were completed three days later, the Paulings flew to Peking, traveled in an official vehicle to Tianjin (a “red flag limousine,” as recorded by Pauling in his journal) and stayed in the State Guest House in the same suite used by Richard Nixon during his iconic 1972 trip to China.  From June 4-8, Pauling participated in the conference, which was jointly planned by the FNA and Professor Chou Pei-yuan, the President of the University of Beijing. This was the second and last time Pauling was to visit China.

A day after arriving in China, the Paulings toured Tianjin Medical College, Tianjin Hospital and Tianjin Children’s Hospital before attending a formal reception given by Li Xiannian, who eventually became the Chinese Head of State in 1983. The conference in China formally opened on June 6, again with Pauling delivering the opening remarks. In them, he discussed the roots of his interest in the field of nutrition, and also reflected upon the early years of his scientific career beginning with his focus on minerals and later interest in the nature of life, which arose in 1929 largely because of the presence of Thomas Hunt Morgan (who had discovered the concept of the gene) at Caltech.

An unidentified individual, Arthur Sackler, the Chinese Minister of Health and Linus Pauling, June 1981.

In his talk, Pauling explained that he had decided to learn more about organic chemistry in order to understand how molecules are built and how they interact with each other, beginning with hemoglobin. During this time, Pauling also studied antibodies, immunology, sickle cell anemias, and other heretic anemias. In 1954 he decided to look at other groups of diseases to see if they could be classed as molecular diseases, and chose to study mental illness over cancer, because he felt that many people were working on cancer already. After researching mental illness for ten years, he became interested in vitamins.

According to Pauling, his interest in vitamins came about when he learned that the Canadian scientists Abram Hoffer and Humphry Osmond were treating schizophrenia patients with large amounts of niacin. Simultaneously, Gerald Milner had been giving large amounts of ascorbic acid to mentally ill patients, with positive results. Pauling later observed that vitamin C had value in the control of cancer, so he became involved with cancer. Near the end of his address, Pauling remarked, “As I look back on my life, I see that I have enjoyed myself very much and a good bit of this enjoyment has come from the continued recognition of something new about the universe.”

Other talks given over the course of the Tianjin conference included “Vitamin C and Cancer,” delivered by Pauling; “Extending Life Span of Patients with Terminal Cancer Using High Doses of Vitamin C,” given by Dr. Akira Murata from the Department of Agriculture at Saga University, Japan; and “A Study on Fortified Foods with Ascorbic Acid Phosphate,” given by Professor Chou Deqin, from the Chinese Institute of Military Hygiene.

The conference closed on Monday, June 8. The next day, the Paulings took part in a sight-seeing tour of the Great Wall and the Ming tombs. Later that week, Pauling gave a talk on chemical bonds in transition metals at Peking University, and continued to give lectures and meet with various scientists throughout the rest of his time in China.

Photo of Ava Helen Pauling taken in China, six months prior to her death.

The trip took a dramatic turn for the worse when, in the afternoon of June 19, Ava Helen had a heart attack and was taken to the hospital. Though she left the hospital the next day, she remained medicated and too sick to travel for a few days after, causing the Paulings to change their plans. She remained weak for the rest of their time in China, though recovered enough to complete their planned itinerary through Germany and London.

When the couple returned to California and Ava Helen underwent exploratory surgery, it was determined that she was facing a recurrence of stomach cancer, from which she had been suffering for the past five years. Her cancer was deemed inoperable and only a few short months later, on December 7, 1981, Ava Helen would pass away, three weeks shy of her 78th birthday.