This is the third volume of a series of interviews with psychopharmacologists conducted by David Healy. Some of those interviewed are basic scientists, and some are primarily clinicians, but all have had important roles in the development of today's psychotropic medications. These oral histories give the reader a fresh and personal view of the progress made in psychopharmacology over the past few decades.
The scope of the book is broad. For example, Healy interviewed Richard Barlow and Robert Stephenson of Edinburgh, Scotland, who did much of the early biochemical work with receptors. He also interviewed Solomon Snyder of Baltimore, who discovered the opiate receptor and used radiolabeling to locate the serotonin receptor, and who is now exploring the activities of strange neurotransmitters such as D-serine and nitric oxide. Joseph Knoll, from Budapest, Hungary, talked to Healy about his work suggesting that deprenyl (selegiline) can delay the development of Parkinson's disease and increase longevity.
Several of the interviewees discussed the role of the third edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-III). Some saw its formation as being influenced by the need for diagnoses for which insurance companies could provide reimbursement and that could be reliable for researchers. Robert Spitzer, the person most responsible for DSM-III, said that the main interests of his committee were not those at all but, rather, the desire to include all ``reasonable'' diagnostic concepts that could be ``operationalized.'' This debate will be important to those interested in psychiatric nosology.
There are many anecdotes in the book. Some involve scientists trying medications on themselves. For example, Zdenek Votava, a pharmacologist in Prague, Czech Republic, often volunteered to take drugs synthesized by Miroslav Protiva. Votava was sensitive to hypotensive effects, so his colleagues would know that Protiva had synthesized a new drug whenever they found him prostrate in the corridor. Ian Oswald of Edinburgh participated in an experiment in 1971 to determine the effects of heroin withdrawal on the electroencephalogram and on urinary morphine metabolites. He disliked the effects of the heroin. Oswald told Healy, with some bitterness, that 20 years later, he was portrayed as a heroin user by the pharmaceutical company Upjohn when he was testifying about what he saw as the ill effects of one of its products, triazolam. In a variation on the theme of self-experimentation, two clinicians administered new medication to their own young children. In the case of methylphenidate (Ritalin), the purpose was to see the effects in healthy controls; in the case of imipramine, it was to find out whether the drug was effective in treating separation anxiety. Interestingly, these two clinicians were the only women interviewed in this volume.
The influence of world events is discussed. The French student rebellions in May 1968 led to the premature retirement of Jean Delay, a professor of psychiatry in Paris linked to the discovery of chlorpromazine. Similar uprisings in the Netherlands led to police escorts for one of that country's leading psychiatrists, Herman Van Praag. Some of the Japanese scientists whom Healy interviewed talked about uprisings in their country. Japanese ``antiestablishment'' students occupied the department of psychiatry at Tokyo University for an astonishing 10 years.
Some odd coincidences emerge. For example, Fridolin Sulser was a Swiss postdoctoral student who came to the United States to work at the National Institutes of Health with Bernard Brodie, the coauthor, with Alfred Pletscher (later, research director at Hoffmann-LaRoche) and Parkhurst Shore, of an influential 1955 report demonstrating that reserpine depleted brain serotonin. Ordinarily, Sulser would have had to leave the United States to return to Switzerland (as Pletscher had). However, he had become friendly with a fellow graduate student in Brodie's laboratory, James Dingell, and his brother, John, perhaps because their mother was Swiss. John Dingell, a Michigan congressman, was able to have the foreign-residence requirement waived for Sulser. Sulser worked at Burroughs Wellcome and then at Vanderbilt University, where he described beta-receptor down-regulation by antidepressants. John Dingell had further involvement in medical research when he convened congressional hearings on the dispute over possible scientific misconduct between coauthors David Baltimore and Thereza Imanishi-Kari and their accuser, Margot O'Toole. I wish Healy had asked Sulser whether he had any thoughts about the role of his immigration sponsor in this controversial case.
Clinicians will enjoy the accounts of the introduction of chlorpromazine. Several of the people interviewed gave moving descriptions of the dramatic effects of this drug in people who had been floridly psychotic for many years.
Research is more cumbersome today. The need to comply with continually shifting and increasing regulatory requirements adds to the work and expense of clinical trials. It is doubtful that discoveries today could be introduced as rapidly as they were in the heady decade of the 1950s, which saw the introduction of lithium, antipsychotics, antidepressants, and new anxiolytic sedatives. Perhaps that is not important, as compared with the greater attention paid now to the right of subjects and patients to be fully informed and the higher quality of clinical data required before a new drug can be licensed.
This volume is not for readers who want a straightforward and well-organized description of medical progress in one book. Those willing to read contradictory and incomplete accounts of drug discoveries, however, will be rewarded by a multifaceted account of the travails and rewards of research in psychopharmacology.
Frances R. Frankenburg, M.D.
Copyright © 2001 Massachusetts Medical Society. All rights reserved. The New England Journal of Medicine is a registered trademark of the MMS.
