Starting with Serotonin: How a High-Rolling Father of Drug Discovery Repeatedly Beat the Odds

When Albert Sjoerdsma, M.D., Ph.D., arrived at the National Institutes of Health in the early 1950s, hypertension still regularly debilitated and killed people. He resolved to change this. Sjoerdsma had read that, when given intravenously, serotonin dramatically elevated a person's blood pressure. Maybe, the young researcher reasoned, he could manipulate serotonin in the body, by blocking a key enzyme in its chemical "pathway," and bring blood pressure down. This was revolutionary thinking. Most drug discovery at the time was a matter of luck, not rational conception. And little was known about serotonin, a "garden-variety" neurotransmitter today, except that it played a role in blood clotting. For twenty years, Sjoerdsma explored wide-ranging, uncharted territory in his Experimental Therapeutics Branch of the National Heart Institute. Launched by his ground-breaking serotonin studies, he diagnosed and defined a cancer known as the carcinoid syndrome; established the mechanism of action of the first antidepressants, which originated in a major drug company's tuberculosis program; measured serotonin, dopamine, and other amines in bananas and other foods, discovered the antihypertensive, Aldomet, a former Top-10 drug; identified treatment for the skin scourge, scleroderma, and the unusual high-blood-pressure disorder, pheochromocytoma; probed the biochemical nature of rapid-eye movement sleep, and much, much more. Because of his inspired work at the NIH and the training he gave his young clinical associates--newly graduated physicians who later spread his research gospel to academia--the tough-talking and straight-shooting Sjoerdsma became known as the Father of Clinical Pharmacology. An advocate of designing drugs that work by inhibiting enzymes, Sjoerdsma went on to enjoy decades-long success as a worldwide leader in the pharmaceutical industry, eventually serving as president of the Merrell Dow Research Institute, headquartered in Cincinnati. With a talented cadre of scientists, the unpredictable innovator developed the first-ever rationally designed antiepileptic (Sabril), also used today to treat a devastating infantile spasm disorder, and the first-ever non-sedating antihistamine, Seldane, replaced in time by its metabolite, Allegra. His crowning glory was the first-ever 100-percent cure for deadly African sleeping sickness--a drug known simply as DFMO. Long before American eyes opened to Third World health tragedies, Sjoerdsma had a lab devoted to research on parasitic diseases, as well as more traditional cancer and heart disease programs. He also contributed to the early treatment of AIDS patients. Gifted at discovery, Al Sjoerdsma always practiced good science, "followed his nose," and optimized the experimental odds in his favor. The research that the Father of Clinical Pharmacology conducted--his brainstorming--still has relevance today in the era of gene-replacement therapy and "Big Pharma." "Starting with Serotonin" shows his prescription for scientific creative freedom and productivity in action--lead by lead by compelling lead.