Starting With Serotonin: How a High-Rolling Father of Drug Discovery Repeatedly Beat the Odds
- Ann G. Sjoerdsma
Science is a gamble. Publication, applying for grants, student admissions and corporate relationships all involve high-stakes bets, a mixture of skill and luck, and often a bit of bluffing. Which game is science most like? It's not a slot machine, mindlessly addictive. In dark moments it may seem like roulette, with its powerful house advantage and long odds. Sometimes it's a horse race, when one thoroughbred laboratory noses out another in isolating a long-sought gene or subatomic particle. For Albert Sjoerdsma, sometimes called the father of clinical pharmacology, science was most like craps.
Craps, an intricate dice game that can involve many players and interweaving rounds of betting, is a thinking person's pastime. Winning depends on an understanding of probability and being able to weigh complex constellations of risks and payouts. In Starting with Serotonin, Sjoerdsma's biographer daughter Ann Sjoerdsma argues that craps was her father's favourite game of chance — and the key theme in his scientific life.
Craps was Sjoerdsma's favourite game of chance — and the key theme in his scientific life.
Albert Sjoerdsma came to the table with a modest stack of chips. Born in 1924 and raised near Chicago in Illinois, he grew up with little money or social sophistication, but with a first-class brain and a mountain of confidence. He was a rough-and-tumble child, more likely to be found playing sports or getting into mischief than curled up with his nose in a book. Yet his grades were nearly perfect, and he was accepted at the University of Chicago under president Robert Hutchins, whose innovative programmes helped to train some of the best minds of the late twentieth century. Sjoerdsma was cocky and sometimes disrespectful, especially when faced with arbitrary displays of power. His daughter describes him as a maverick, a clichéd but apt term.
Rather than fold with a bachelor's degree, Sjoerdsma stayed in the game, taking an MD and a PhD at Chicago. He then went east to Bethesda, Maryland, where he joined the National Institutes of Health (NIH) in 1951. After two years of residency at the Public Health Service's Marine Hospital in Baltimore, Sjoerdsma landed a position at the National Heart Institute back in Bethesda. There, he formed a team that became known locally as the “wild bunch”, a group of brilliant, hard-working and hard-playing researchers.
Sjoerdsma began exploring ways of reducing high blood pressure, leading to his investigation of the then recently discovered neurotransmitter serotonin. His analysis of its effects on different organ systems and metabolic pathways led him into a strongly applied style of pharmacology, in which he largely eschewed lab-based studies in favour of whole patients, and focused on bridging the gap between laboratory science and clinical medicine.
He was a pioneer in the development of monoamine oxidase inhibitors as antidepressants, such as iproniazid, originally developed as an anti-tuberculosis drug. With colleague Sidney Udenfriend, he found that monoamine oxidase was a major pathway for serotonin in both mice and humans, and that inhibitors such as iproniazid raised blood serotonin levels. This established the physiological basis of the antidepressant action of these drugs. Sjoerdsma's 20 years at NIH coincided with the 'golden age' of its intramural research, an era of Nobel prizes, headline-grabbing breakthroughs and major contributions to science.
In 1972, he parlayed his successes as a bench scientist into a job as director of a new research centre in Strasbourg, France, set up by the pharmaceutical company Richardson–Merrell. His blunt, incisive intellectual and administrative style was polarizing in genteel Europe. He won many devoted friends and colleagues — and lost some, too. But there was no arguing with his successes. The biggest was terfenadine (Seldane), the first antihistamine that did not cause drowsiness. Developed in the 1970s, it was a blockbuster drug until heart arrhythmias surfaced in some users.
Sjoerdsma remained with Richardson–Merrell through the 1980s, until a merger moved the company to Kansas City, Kansas, and gave the management over to a group of businessmen who knew everything about marketing and nothing about science. Sjoerdsma felt the house had changed the rules mid-game. Stripped of his title, and eventually even of his parking space, he felt as if he had lost the shirt off his back.
Ann Sjoerdsma's dual role, as daughter and as professional journalist, creates both windows and blind spots as she examines her father's life. She explains the science and integrates it into Sjoerdsma's career choices and decisions. She draws on interviews she conducted with her father and with his friends and colleagues. The numerous quotations from Sjoerdsma himself, set in italics and without attribution, make it seem as though he is looking over his daughter's shoulder, adding a story or colourful detail, or murmuring assent.
His assent is crucial, for her primary concern is to tell her father's version of his story. In Sjoerdsma's world, the US Food and Drug Administration is a stifling regulatory monster, and it is drugs, more than patients, that live or die. Sometimes he comes across as callous, whereas at other times he is a champion of humanitarian medicine, such as when he developed a therapy for African sleeping sickness. The author rarely questions such views or their motives. Also, she never inquires deeply into Sjoerdsma's emotions.
Particularly striking is the minor role of family in this life portrait. The other Sjoerdsmas feature from time to time, but we never get much sense of how Albert treated them or how he integrated work and family life. Understandably, the daughter's loyalty seems to trump the journalist's objectivity.
Yet perhaps only she could have played the theme of gambling so well, arguing that her father's strategy was the same at the bench and at the table. He played to win, not to get rich. He was disciplined and used gambling as a test of his willpower. Sjoerdsma's strategy was conservative, but he was willing to take big risks and to bet high stakes when the odds were good. As the author says, he repeatedly beat the odds.
Do not read Starting With Serotonin for a story of the selfless thirst for knowledge. Rather, read it for the strategy — both experimental and mercantile — and the passion for competition. Sjoerdsma did it for the love of the game, for better and for worse.
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Comfort, N. Playing to win. Nature 454, 826–827 (2008). https://doi.org/10.1038/454826a