Pauling’s Study of Schizophrenia: Pushback

[Wishing an early happy birthday to Linus Pauling, who would have turned 120 years old this coming Sunday. To celebrate, we continue our survey of his work on schizophrenia; this is part 4 of 9.]

I feel that the use of substances normally present in the human body for improving health of human beings, and especially their mental health, has been unjustifiably ignored by the medical profession for some thirty or thirty-five years now, and that the possibilities of improvement in the health of the American people and of other people in the world by improved nutrition are truly great.

-Linus Pauling, speech to the American Schizophrenia Association, July 1971.

Though lauded in smaller circles, Linus Pauling’s work on the orthomolecular treatment of schizophrenia failed to earn the support of the mainstream psychiatric community. Members of the American Psychiatric Association (APA) and the National Institute of Mental Health (NIMH) for example, tended to marginalize Pauling’s ideas as existing on the fringe, and certain of their objections were quite critical.

Pauling’s disagreements with the psychiatric mainstream dated back several years. In one instance, at the 1956 annual meeting of the American Psychiatric Association in Chicago, Tulane University psychiatrist and researcher Robert Heath put forth an argument that schizophrenia was caused by misshapen protein molecules. For an “electrified audience of 4,000,” Heath’s ideas were viewed as extremely promising, particularly because of their implications for targeted treatment. Pauling though, was wary of the findings, and went to the media to caution that the results not be interpreted “too broadly.”

As time moved forward, one of the entities with whom Pauling most found himself at odds was the NIMH. Though Pauling had received grant funding from the NIMH, for many within the organization, his work had never delivered concrete or compelling evidence supporting the orthomolecular approach to schizophrenia. Many at the Institute also disagreed with the theoretical arguments underlying Pauling’s work.

These criticisms of Pauling’s ideas were voiced amidst a broader acknowledgement of the urgent need for more effective schizophrenia treatment options. By 1970, the situation had become so dire that the NIMH commissioned a special team to write a report on the subject. In it, the authors warned that schizophrenia diagnoses were increasing, with “more than 200,000 Americans…hospitalized” and an additional 2-6% of the U.S. population believed to have suffered at least one schizophrenic episode. These staggering numbers were estimated to be costing the country some “$14 billion [approximately $92 billion in 2020] annually.” The authors further warned that the magnitude of the actual problem was almost certainly even larger still, noting that “chronic institutionalization throughout the individuals’ most productive years…in terms of personal suffering and loss of productivity, are devastating.”

For these researchers then, the current state of schizophrenia in the United States was frightening; the costs to treat were high and the number of people suffering from the illness was growing at an alarming rate. Moreover, the current standard of care for schizophrenia – hospitalization and tranquilizers, namely – did little to alleviate these problems. Schizophrenia seemed to be a disease brimming with unanswered questions and hampered by partial solutions.

But even given this context, the NIMH report offered little enthusiasm for Pauling’s approach. Though the authors acknowledged that he had “made a major methodological contribution by developing new automated techniques for screening large numbers of samples of urine and other body fluids for screening abnormalities of vitamins and other essential nuritivites,” Pauling’s hypothesis was deemed “extremely proactive” and the “interpretations of [his] findings must wait further work.”

The controversy surrounding megadosing did not end with the NIMH report; the American Psychiatric Association (APA) had its own hesitations about Pauling’s findings and initiated its own study to try and replicate them.

The head of the APA study group was Dr. Morris Lipton, founding director of the Biological Sciences Research Center at the University of North Carolina School of Medicine and, at the time, deputy editor of the American Journal of Psychiatry. In the estimation of Pauling’s colleague Bernard Rimland, Lipton was also the “psychiatric establishment’s most vociferous and outspoken opponent to the megavitamin treatment.” For Rimland this was obviously problematic, because it meant that Lipton was far from impartial and that any assertions made by the task force would be colored by his point of view.

In mid-1973, after four years of data collection, the six-person task force published its results, which the APA itself characterized as a “broadside assault on megavitamin and orthomodular therapy in treatment of schizophrenia.” In their report, the task force noted in particular that they had found it difficult to “replicate studies” because of a perceived lack of sophistication underlying orthomolecular-based experiments. In this vein, megadosing studies had too often been tarnished by subjectivity and, for the task force, their results were “found wanting.”

In the estimation of the task force, the whole notion of “orthomolecular psychiatry” was “a misnomer,” the report’s authors adding that “there is nothing orthomolecular about” the way Pauling and his colleagues had been treating patients. The task force also made clear that prominent psychiatrists in the field agreed with their assessments and did not believe in vitamin megadosing.

The APA results were unveiled in July 1973 at the Kittay Scientific Foundation’s first international symposium, and unfortunately for Pauling and his supporters, the task force report was not the only negative press to emerge from the gathering. One of the conference presenters was John R. Wittenborn, the director of the Inter-Disciplinary Research Center at Rutgers University, who shared the results of an 18-month study that he had conducted on eighty-six patients with schizophrenia. Wittenborn’s project involved dosing a portion of the patient group with megavitamins while witholding them from a second control subset, and like the APA study, the work was done independently of Pauling. As with the task force, Wittenborn had found little to support Pauling’s research, noting that, after all factors had been controlled for, there were “no significant differences” in outcome for the study group versus the control group. In fact, the experimental patients – those who were given the vitamins – “may have been a bit worse off.”

Others at the symposium found Pauling’s work to be doubtful from a theoretical standpoint. One participant, Yale geneticist Leon Rosenberg, acknowledged that some diseases could be cured through megadosing, but that schizophrenia was not one of them. In cases where vitamins could cure disease, Rosenberg argued, there had always been a “very clear correlation between the particular biochemical defect and the rationale for the vitamin.” But in the case of schizophrenia, “no evidence exists” that there is a particular biochemical defect.

Ultimately, the Kittay symposium gave license to other scientists to express their disagreement with Pauling’s orthomolecular work. Dr. Michael Mendelson, director of the New Jersey Psychiatric Neuropsychiatric Institute, summed up the view of many in stating, “I believe in anything that is effective,” but “in my opinion megavitamins have not proven themselves.”