Pauling at Stanford: Settling In

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.

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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.

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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.

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.

 

Leaving La Jolla

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.

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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

[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.

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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.

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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.

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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.

The Decline of Orthomolecular Psychiatry

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.

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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.

Humphry Osmond, the Original Psychedelic Psychiatrist

Humphry Osmond (front row seated, far left), with the Paulings and others at a gathering in Tulsa, Oklahoma. April 1972.

Dr. Humphry Fortescue Osmond, while never a direct collaborator of Linus Pauling’s, was nonetheless a professional influence in his life and a friend. Alongside Dr. Abram Hoffer, Osmond helped to establish orthomolecular psychiatry, the precursor to the larger body of work on orthomolecular medicine that consumed Pauling for close to three decades. Later in life, Pauling and Osmond wrote numerous letters back and forth, in which Osmond often shared interesting articles on the uses of vitamin C, schizophrenia, nutrition, and orthomolecular medicine.

Osmond is famous to both the medical community and to the public for related, yet separate reasons. In the field of medicine, Osmond, along with Abram Hoffer, is best known for his work in orthomolecular psychiatry. Working together, the two doctors performed extensive studies on schizophrenic patients in psychiatric hospitals in Saskatchewan, Canada, using niacin (vitamin B3) and ascorbic acid (vitamin C) as potential cures for the disease. Osmond is also known for his work with lysergic acid diethylamide, or LSD, in the treatment of alcoholism and as a way for psychiatrists and psychologists to experience something approximating what he believed to be the state that schizophrenics experience as they struggle with their illnesses.

To the public however, Humphry Osmond will forever be known as the man who coined the term “psychedelic” and the man who “turned on,” in the words of the famous LSD advocate Timothy Leary, acclaimed British author Aldous Huxley, a man with whom he developed a close friendship. In the early 1950s, Huxley approached Osmond after reading an article on his research with mescaline; Huxley expressed a desire for Osmond to run a human trial of the drug with Huxley as subject. Osmond wasn’t fond of the proposal, not relishing “the possibility, however remote, of finding a small but discreditable niche in literary history as the man who drove Aldous Huxley mad.” Despite his misgivings, Osmond dosed Huxley with 400 mg of mescaline in 1953.  The result was recorded in Huxley’s cult hit The Doors of Perception (1954), a book that both takes its name from William Blake’s poem “The Marriage of Heaven and Hell” and inspired the name of the legendary 1960s rock band, The Doors.

Later, when discussing his flight of hallucinogenic fancy, Huxley, writing to Osmond, penned this bit of verse:

To make this mundane world sublime, / take half a gram of phanerothyme.

The word phanerothyme, cobbled together from the Greek, translates roughly to “manifest spirit.”

In response Osmond wrote some poetry of his own, in the process coining a term that soon spread around the world:

To fathom Hell or soar Angelic, / just take a pinch of psychedelic.

Psychedelic – again from Greek etymology – translates to “mind-manifesting.” By 1957 Osmond had introduced the word to the medical community as a way to describe the euphoric, perception-altering, mind-expanding effects of hallucinogenic drugs like LSD, mescaline, DMT, and psilocybin. Previously the only well-known description of this concept was “psychotomimetic,” a mimicry of the symptoms of psychosis.

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Humphry Osmond was born in July 1917 in Surrey, England, gaining his primary and secondary education from Haileybury, a long-established boarding school in Hertfordshire. After Haileybury, Osmond earned his medical degree from Guy’s Hospital Medical School, London, in 1942, and from there joined the Royal Navy, commissioning as a surgeon-lieutenant and training to be a ship’s psychiatrist.

After the Second World War concluded in 1945, Osmond returned home and accepted a position as a resident psychiatrist at St. George’s Hospital, Tooting. It was here that he met his future wife, Amy “Jane” Roffey, and his first major research partner, Dr. John Smythies. Together, Smythies and Osmond performed a number of studies in the late 1940s on the chemical composition and effects of the drug mescaline – a hallucinogenic derived from the peyote cactus – having been inspired by the work of Albert Hofmann, who had discovered the hallucinogenic properties of LSD a decade prior.

From their research, Smythies and Osmond hypothesized that because the experience of subjects on mescaline seemingly mimicked the symptoms of schizophrenia, and that because mescaline is structurally related to adrenaline, it could be possible that schizophrenics were over-producing a chemical related to both mescaline and adrenaline. They called this hypothesis, fittingly, the “M-hypothesis.” The idea, when presented to the British psychiatric medical community – which at the time was dominated by Freudian thinking – was not well received. Feeling isolated in the UK, in 1951 Humphry and Jane Osmond, along with John Smythies, immigrated to Canada, where Osmond had been offered a job as the clinical director of the psychiatric hospital in Weyburn, Saskatchewan.

“How to Live with Schizophrenia,” by Abram Hoffer and Humphry Osmond, 1966.

It was at Weyburn that Osmond met Dr. Abram Hoffer, director of psychiatry at the hospital, with whom Osmond would collaborate for the next decade. Working together with the patients at Weyburn and at neighboring hospitals, Osmond and Hoffer developed what became known as the “Hoffer-Osmond Adrenochrome-Hypothesis.” Using the M-hypothesis as their basis, Osmond and Hoffer claimed that it was adrenochrome, a byproduct of adrenaline that is structurally similar to mescaline and other hallucinogens, that schizophrenics were overproducing.  In theory, schizophrenics were suffering from their disease either as a result of their bodies producing too much adrenochrome or through an inability to properly metabolize adrenaline.

Working from this hypothesis, Osmond and Hoffer next searched for a way to reduce the overproduction of adrenochrome, hoping to find a cure for schizophrenia as well as additional evidence for their idea. Learning that niacin might limit the production of adrenaline, they decided to dose their schizophrenic patients with “megavitamin” amounts of B3, adding it to their diets in the first double-blind studies ever conducted in the field of psychiatry. The results were encouraging: according to their studies, the recovery rate for the schizophrenics that they treated over the next few years doubled from 35% to 75%.

In addition, the Osmond and Hoffer studies provided data that added to the finding that niacin could reduce cholesterol, a result that was replicated and confirmed by the Mayo Clinic in 1956. This finding is now globally accepted and niacin is presently used in the treatment of high cholesterol all over the world.

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An example of Hoffer’s “memos,” October 1976.

In 1967 Linus Pauling – who had learned of Hoffer’s work on niacin two years before – read the Osmond and Hoffer studies and, finding the subject interesting enough to pursue further, wrote to the duo asking for more information.  The data that he received was eventually included by Pauling alongside his own theories in his seminal paper, “Orthomolecular Psychiatry” (published in Science in 1968) as well as in the book that he co-edited with Dr. David Hawkins, Orthomolecular Psychiatry: Treatment of Schizophrenia (1973). Over time, Pauling expanded his orthomolecular theory from the study of the mind to include the whole body, thus creating the field of orthomolecular medicine.

This initial contact between Drs. Pauling and Osmond led to a nearly thirty-year correspondence between the two men, with Osmond regularly sending to Pauling selected copies of his “memos” – commentaries in which Osmond would paste a news article onto the left side of a sheet of blank paper, then cover the right side and the back with prodigious, elegant essays on the context, significance, and meaning of the article. (These memos were collected into a book, Predicting the Past, and published in 1981). Osmond made special effort to forward to Pauling those memos concerning ways in which orthomolecular medicine was being used around the world as well as any material on mental illnesses.

Exchanges between the two men were often personal as well as professional. For example, after learning of Ava Helen Pauling’s trouble with cataracts, Osmond sent Dr. Pauling any information that he could find on the ocular malady, of which Osmond was also a sufferer. Osmond also wrote letters filled with his thoughts on Pauling’s activism and increasing celebrity, including a letter in which he agreed with Pauling’s negative assessment of physicist Edward Teller, a major advocate for U.S. nuclear armament and the hydrogen bomb, as well as a letter congratulating Pauling on his 1977 appearance on NOVA.

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In 1961 Osmond was appointed Director of the Bureau of Research in Neurology and Psychiatry at Princeton University. While there, he continued his research into schizophrenia as a physical illness. In 1970, hallucinogenic drugs like mescaline, LSD, and DMT were declared controlled substances, and studies on the effects of these drugs on psychiatric patients was curtailed.

In 1971 Osmond resigned his position at Princeton and moved to Alabama, where he taught at the University of Alabama, Birmingham as a professor of psychiatry. He worked there alongside his old friend, John Smythies. Osmond also consulted at Bryce Hospital in Tuscaloosa, the oldest and largest in-patient psychiatric hospital in Alabama. He retired from the university and the hospital in 1992. A decade later, by then an octogenarian, Osmond granted an interview for a documentary on the history of LSD, titled “Hofmann’s Potion.” Not long after, in February 2004, Osmond died of natural causes at his daughter’s home in Appleton, Wisconsin. Abram Hoffer wrote an obituary on the event of Osmond’s passing, which was featured in the British newspaper, The Guardian.

Some of Humphry Osmond’s more well-known books include The Chemical Basis of Clinical Psychiatry (with Abram Hoffer, 1960); How to Live with Schizophrenia (with Hoffer, 1966); Psychedelics: The Uses and Implications of Hallucinogenic Drugs (with Bernard Aaronson, 1970); and Models of Madness, Models of Medicine (with Miriam Siegler, 1974). A complete bibliography of his works can be found here.

Two More Years in the Life

We’re pleased to announce the addition of two more years to the ever-expanding Linus Pauling Day-by-Day project.  Now in its fifteenth year of production and growth, the website seeks to document as many days of Linus and Ava Helen Pauling’s lives as possible – painstaking work that has been carefully mined, by a cast of hundreds, from our holdings in the Pauling Papers.  With this latest release, the project now covers four full decades, from 1930-1969.

The new years in question are 1968 and 1969 – awkward years for the Paulings and difficult ones for the world at large.  While the war in Vietnam escalated, activism in the streets turned violent and cultural shifts accelerated, the Paulings found themselves well within the nomadic period that had defined their lives ever since Linus Pauling’s departure from Caltech in Fall 1963.

Prior to arriving at some measure of stability at Stanford University, where he began setting up a small laboratory in the summer of 1969, Pauling had bounced from the Center for the Study of Democratic Institutions to the University of California, San Diego, never with fully satisfactory results. Partly because of the uncertainties surrounding his institutional affiliation, Pauling found it increasingly difficult to attract the sort of research funding to which he had been accustomed during his glorious run in Pasadena.

The situation deteriorated to the point where he was compelled to appeal to a private source for support: his ex-daughter in law.  Anita Oser, an heiress to the Rockefeller and McCormick fortunes and, by 1968, long since divorced from Linus Pauling Jr., had provided funding for Linus Sr.’s work in the past.  By Spring 1968, the elder Pauling’s financial footing had deteriorated to the point where he was asking Anita for nearly half of the estimated $100,000 that he needed to keep his program afloat. Fortunately the other half had already been pledged by Chester Carlson, a founder of Xerox and a former student of Pauling’s.

Linus and Ava Helen Pauling among a group drinking coffee in a Wilson College laboratory. April 14, 1969

The gloom that surrounded Pauling’s professional concern permeated other aspects of his and Ava Helen’s lives.  Both Linus and Ava acknowledged that La Jolla, where the Paulings lived while based at UCSD, was not to Mrs. Pauling’s liking, (“I have felt uprooted and purposeless here,” she wrote to her son, Peter) and it was a welcome turn of events indeed when the couple purchased a new home in Portola Valley, California, not far from the Stanford campus, once the move north had been finalized.

Of far greater consequence though, was the tumult that defined world events during the time period.  On multiple occasions, the Paulings reveal themselves in their correspondence to be burdened by the pressures of the day: “we are going through a terrible time,” Pauling admits in a letter to Prof. Carroll Richardson; “The times are horrible here in the U.S. and I’m sure they will get much worse…one could cry,” Ava Helen lamented, again to her son Peter.

Though relatively conservative in their own habits, it was clear that the Paulings were in near full support of, at least, the sentiments of the student uprisings of the era.  In a stirring letter dated July 3, 1969, Linus Pauling made his feelings readily apparent

I agree with the statement in your letter that some of the university students fail to act in accordance with my statement that we must bring law and order into the world as a whole. I do not think that their actions have been nearly so violent and basically unlawful as those of their elders. The war in Vietnam and the institution of the draft for the military service are probably the most significant reasons for the present student unrest. I myself feel strongly that a young man who does not want to kill any of his fellowmen should not be forced by the government to do so.

I estimate the ratio of the violence done by the government to that done by the revolting students as about one million to one.

The rhetoric that Pauling employed in certain of his speeches also intensified with the times.  See, for instance, a commencement address that he delivered at Windham College in May 1969:

We are trying to stop the REVOLUTION of the miserably poor, the starving, the economically exploited people of the world, by use of our military might….

I have confidence in you young people, who are revolting against the greed, the hypocrisy, the immorality of your elders….

Linus Pauling in lecture at the Second International Congress of Social Psychiatry. August 1969

Likewise, Pauling’s thinking on matters of peace and world affairs was steadily moving in new directions.  While still focusing on the dangers of the atomic age, he increasingly began to speak more on issues of economic equality, decrying with fiery rhetoric the global maldistribution of wealth. Whereas his previous activism – especially with respect to radioactive fallout from nuclear weapons tests – had been largely borne of scientific interests, later talks were based in a more thorough study of the material world; of the conditions world-wide that were dividing rich and poor. By 1969 he had developed a logarithmic “wellbeing scale” and was advocating “a great decrease in the amount of human suffering…effected by only a moderate redistribution of the world’s wealth.”

Pauling’s first love was forever science and scientific inquiry surely did not disappear during this time.  While work continued on more abstract investigations into structural chemistry and molecular architecture, the defining publication of this period was “Orthomolecular Psychiatry,” Pauling’s theory that optimum mental health is dependent upon achieving an ideal chemical balance within the body – a balance attained through nutrition and nutritional supplementation.

The paper, which was published in Science in April 1968, generated a great deal of discussion and, for Pauling, a large volume of mail.  So it is that we are able to tease out interesting subcomponents and offshoots of the theory: the possibility that niacin may help to control anxiety; the potential for treatment of brain damage through nutrition; the likelihood that criminal activity is caused by a “diseased or injured brain.”  It was not much longer before Pauling became more fully infatuated with the idea of orthomolecular medicine and launched head on into his crusade in favor of vitamin C.

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Thanksgiving Day photo used in a Kamb family greeting card. From left are Linda Pauling Kamb, with Ava Helen and Linus Pauling, and Linda’s four boys.

Linus Pauling Day-by-Day presently consists of over 118,000 document summaries, nearly 2,300 scanned documents and over 3,000 full-text transcripts.  The larger themes of Pauling’s life are, of course, easily traced within the resource.  But the project has also allowed us to play a little bit, posting notice of lesser known items from the collection: Pauling’s favorite book as a child; a patient reply to the concept of a “love bomb“; thoughts on alternatives to shaving.  It’s these little nuggets that bring a smile to our face and help to keep us energized as we continue to move forward with the project. We’re glad to make it available to our users, whatever their research interest may be.

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.

The Birth of Orthomolecular Medicine

By Tom Hager

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

Linus Pauling and Irwin Stone, 1977.

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

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

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

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

Then came Vitamin C.

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

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

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

He then told him about vitamin C.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Remembering Abram Hoffer

Abram Hoffer and Linus Pauling, November 1992.

“As a physician, I am ambivalent about my association with the medical fraternity.  I am happy to be in a profession which has discovered so much information in the field of disease and health, but I am unhappy and distressed with such an association which almost invariably rejects at first hand the discoveries and views of scientists which it will eventually embrace with equal fervor.  Is there no end to this irresponsible hostility of physicians towards scientists such as Linus Pauling?  But this is the way it is.”

-Abram Hoffer, May 1986.

The Canadian physician Abram Hoffer, a pioneer of orthomolecular medicine, died in May 2009 at the age of 91.  The Hoffer name is stamped throughout the Ava Helen and Linus Pauling Papers as, in many respects, his career mirrored the final decades of Linus Pauling’s own work.

Hoffer’s career achievements are summed up nicely in this obituary published by the CNW Group:

Abram Hoffer became a pioneer of progress early on his career, challenging the dominant view at the time that schizophrenia was the result of poor mothering, and was instrumental in the authoring of research on the genetics of this common mental illness with the renowned geneticist Ernst Mayer. After co-discovering the first effective lipid-lowering agent, Vitamin B3 (niacin), the native of Saskatchewan became equally as instrumental in the development and execution of the first controlled clinical trials in psychiatry. This resulted in the creation of the then-controversial treatment of acute schizophrenia through principles of respect, shelter, sound nutrition, appropriate medication and the administration of large doses of water-soluble vitamins. In particular, Dr. Hoffer identified through research that large doses of Vitamin B3 (niacin) and Vitamin C could eliminate the symptoms of schizophrenia and reduce relapses. He dedicated his life to curing-not palliating-schizophrenia.

Hoffer’s breakthroughs in the medical understanding of schizophrenia paralleled similar work being conducted by Linus Pauling.  As Pauling noted in 1991

Dr. Hoffer, over 40 years ago, developed the basic principles of megavitamin therapy, a part of orthomolecular medicine.  I devised the word ‘orthomolecular’ to describe substances, such as vitamins, that are present in the human body, and are required for life.  I proposed, in 1968, that significant improvement in health and in the control of disease could be achieved by varying the concentrations of these substances in such a way that they would have their maximum effects.  Many physicians now call themselves orthomolecular physicians.

For the bulk of their association, Hoffer and Pauling, though inhabiting similar orbits, retained their independence from one another as researchers – each supported the other in various ways, but no scientific collaboration actually occurred.

This arrangement would change in the late 1980s as Hoffer became increasingly interested in the potential treatment of cancer using orthomolecular methods.  Based on his study of fifty patients Hoffer concluded that Pauling and Ewan Cameron’s hypothesis “that vitamin C in large doses did improve enormously the outcome of treatment for cancer,” was correct.  As he recalled in 2000

Linus asked me if I intended to publish the data. I replied that I did not. I added that in my opinion there was little point in trying to do so since it would be impossible to gain entry into any medical journal, that they would not accept any paper that dealt favorably with megadose vitamin therapy. The New England Journal of Medicine, which had published the Mayo Clinic attack on Pauling, refused to publish his rebuttal. Linus urged me to do a complete follow up study of every patient I had treated. I was flattered and agreed that I would. He said that he would see that the material would be published. But when I returned home I decided not to do the follow up. It would have meant an enormous amount of work. I thought that Dr. Pauling was being kind to me. Two years later I received a letter from Linus in which he said, bluntly, ‘Abram where is the study?’ I decided that he was serious about it.

Hoffer and Pauling’s shared interest in the vitamin C and cancer issue would result in two published papers as well as a book manuscript intended as a follow-up to Cameron and Pauling’s Cancer and Vitamin C (1979).  Despite Pauling’s enthusiasm for the project (“It is wonderful,” he wrote of Hoffer’s 1988 typescript. “It should have a great effect in convincing cancer patients, people in general, and even physicians that vitamin C has value in the control of cancer.”) the book and its unorthodox approach could not find a publisher, an issue further hampered by Pauling’s own flagging health.

Linus Pauling greatly admired Abram Hoffer’s work, to the point of declaring his support for a 1990 effort to nominate Hoffer for the Nobel Prize in Medicine.  Though both men are now gone, the record of their shared interests and collaboration remains extant in the Pauling archive.

For more information on the Hoffer-Pauling cancer work, see Pauling’s “Hoffer” research notebook listings or the finding aid description for their proposed book How to Control Cancer with Vitamins.  For more on Abram Hoffer, including a short film, see this memorial page.

Orthomolecular Psychiatry

“Ortho means ‘right’ — the right molecules in the right amounts. Orthomolecular medicine is the use of the right molecules or orthomolecular substances that are normally present in the human body in the amounts that lead to the best of health and the greatest decrease in disease. It is the most effective prevention in the treatment of disease.”

-Linus Pauling. Interview by Deborah Kesten. Healthline. April 1983.

Linus Pauling was well known — though not always celebrated — for his steadfast endorsement of the health benefits of megadoses of vitamin C. He began promoting the use of vitamin C as a preventative measure against colds in the mid-1960s. In the late-1960s, he published some of his early findings, calling his theory of vitamins and health “orthomolecular medicine” stemming from the Greek root ortho meaning “right” or “correct”.

Pauling applied his orthomolecular research to mental health as well, describing numerous psychological problems as the result of an imbalance of molecules.

Listen: Pauling describes the rapid evolution of his research agenda

In 1968, Pauling introduced the concept of orthomolecular psychiatry to the medical community with his publication of “Orthomolecular Psychiatry: Varying the concentrations of substances normally present in the human body may control mental disease” [PDF]. This article first appeared in Science and has since been reprinted in a number of other journals as well as the book Orthomolecular Psychiatry: Treatment of Schizophrenia, for which Pauling was a co-editor.

In his article, Pauling stated his belief that mental disease is caused almost entirely by the combination of abnormal reaction rates and abnormal molecular concentrations of substances essential to the human body.

The majority of chemical reactions that take place in humans employ an enzyme as a catalyst. As such, if a certain enzyme fails to function properly, the rate of the reaction that utilizes the enzyme will be severely reduced. Pauling developed two ways to push reactions in the forward direction, consequently solving the problem of rate reduction. He stated that this molecular propulsion could be accomplished by either introducing large amounts of the enzyme’s substrate or by somehow increasing the amount of the enzyme that is synthesized. He came to these conclusions by manipulating the Michaelis-Menten equation, which gives the rate law for a reaction catalyzed by an enzyme.

In his 1968 article, Pauling likewise described a variety of vitamins and other essential substances as well as the consequences of deficiencies of each. Among the substances discussed are vitamin B12, nicotinic acid, and vitamin C. Pauling believed that simply introducing more of a deficient substance would alleviate the effects of the deficiency.

Pauling’s concept of orthomolecular psychiatry is in application today. For example, Phenylketonuria, or PKU, is caused by poor functioning of the enzyme that processes phenylalanine. According to Pauling, this disease could be treated in two ways. One option is the introduction of mass amounts of the enzyme’s substrate to counterbalance the effects of the dysfunction. The second, and practiced, treatment is to require PKU patients to adhere to a strict low-protein diet, which significantly lowers the amount of phenylalanine they consume. (This approach also happened to have been an important component of the treatment that Pauling himself followed when battling glomerular nephritis in the 1940s)  Nevertheless, both treatment possibilities are examples of orthomolecular therapy.

Anecdote published in Chemtech, September 1994.

Orthomolecular psychiatry was an exciting theory for Pauling. The orthomolecular concept was originally applied only to the brain, but it wasn’t long before Pauling began to extend it to the entire body. Eventually, he would consider problems ranging from diabetes to cavities as treatable using the orthomolecular concept.

For more information on orthomolecular psychiatry and related topics, visit It’s in the Blood! A Documentary History of Linus Pauling, Hemoglobin, and Sickle Cell Anemia. To view more content related to Linus Pauling, visit Linus Pauling Online.