Book Review

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

N Engl J Med 2008; 359:2622December 11, 2008

Article

Starting with Serotonin: How a High-Rolling Father of Drug Discovery Repeatedly Beat the Odds
By Ann G. Sjoerdsma. 617 pp., illustrated. Silver Spring, MD, Improbable Books, 2008. $27.50. ISBN: 978-0-615-16558-5

This book is about the great drug discoveries that were made by the legendary Albert Sjoerdsma and his team beginning in the 1950s. The first discoveries were made at the Experimental Therapeutics Branch of the National Heart Institute in Bethesda, Maryland, which became famous under Sjoerdsma's leadership, and later discoveries were made at the research laboratories of Richardson–Merrell in Strasbourg, France. Sjoerdsma was able to make these discoveries because he possessed a combination of unique qualities and competence, and he built on his strong belief that the enzymes involved in the synthesis or degradation of neurotransmitters were important targets for drug development. It all began with the discovery of the hypertensive effects of serotonin. This discovery moved Sjoerdsma to study the biochemistry of serotonin and catecholamines, their synthesis, and their metabolism. Collaborating with Sydney Udenfriend, Sjoerdsma was able to work out the mechanism and diagnosis of malignant carcinoid syndrome. It was the beginning of clinical pharmacology.

The investigations Sjoerdsma and his team made into the inhibition of catecholamine-synthesizing enzymes led to the discovery of drugs such as methyldopa (Aldomet), which is used to treat hypertension. While in Strasbourg, Sjoerdsma discovered an inhibitor of γ-aminobutyric acid (GABA) transaminase, vigabatrin, which irreversibly inhibits the enzyme, thereby increasing levels of GABA in the brain. When vigabatrin was introduced, it advanced the treatment of refractory epilepsy and became the drug of choice for the treatment of infantile spasms. Using a similar approach, Sjoerdsma developed an inhibitor of ornithine decarboxylase, eflornithine. Although eflornithine did not become an anticancer drug as was originally anticipated, it did find its place in the treatment of West African sleeping sickness.

Throughout the book, author Ann Sjoerdsma gives us insight into the scientific and private lives of her father and his team, who were known as “the Wild Bunch.” She interviews her father and many members of his team and gives historical background on the various fields that Albert Sjoerdsma explored.

This unique book is written in clear and vital prose, which allows nonscientists to enter the world of medical science. It enables them to understand the hard work scientists must do in the laboratory to obtain the data they need to develop concepts, their urge to resolve the mechanisms that underlie diseases, and their hope of discovering new drugs. This book opened the world of Albert Sjoerdsma to me, and it has enriched my life.

Kjell Fuxe, M.D.
Karolinska Institutet, 17177 Stockholm, Sweden
kjell.fuxe@ki.se