Bridging Two Disciplines

Abstract

Bernard is a gambling man. Just before Christmas of his senior year at college, with his last $40 in hand, he sat down to a game of poker, won $1,000 and paid the tuition for his last semester at McGill University. That was in 1930. Since then, with his gambler's luck, a remarkable store of scientific intuition, a touch of genius-and 15 hours a day of hard work-Bernard has lead the infant discipline of pharmacology to adulthood as one of the most important and rapidly expanding fields of biomedical research. Guided by whose insights show no regard for traditional theories, drug studies evolved from an imprecise and descriptive activity to a sophisticated science. He has made his mark by supplying the two essential ingredients to fruitful scientific inquiry: ideas and manpower. Brodie intuitively knows where the interesting things are, branching out freely in any direction in pursuit of a hypothesis, and he's always had the ability to select damn good younger colleagues, according to Dr. Sidney Udenfriend whom Dr. describes as one of his more brilliant proteges. Dr. Udenfriend is one of some 300 scientists trained in Brodie's sprawling laboratory of chemical pharmacology which occupies two floors at the National Institutes of Health. There, a favorite laboratory activity is playing consequences. Having come up with a hypothesis to explain some chemical or physiological phenomenon, Dr. and co-workers gamble-following the consequences of its being true instead of looking for reasons why it cannot be true. One round-played by Dr. and two graduate students-developed the hypothesis that special enzymes in the liver metabolize drugs that simulate foreign organic compounds ingested in food and that these enzymes evolved as the need for them developed. Hence. not all species need enzymes to metabolize foreign compounds. Many fish and aquatic amphibia, for example, dispose of most foreign material by excreting them through permeable gill membranes. Land-living reptiles, however, with their impermeable skins, need and have enzymes to convert foreign substances to components their systems can handle. From reptiles, the enzymes next appeared in birds and mammals. The animals, in fact, inherited them from the reptiles. for nature usually retains a good thing, Dr. says. But consequences didn't end there. Out of these academic studies of the evolution of enzymes came a finding of considerable practical value. In trying to prove that 'ontogeny recapitulates phylogeny,' graduate student Roger Maickel and an English visitor discovered that the newborn of mammals lacked drug-metabolizing enzymes, Dr. points out. At first newborns drink their mother's milk which is free of organic substances that have to be metabolized and so they have no need of enzymes. From this it follows that drugs should be given to babies only under exceptional circumstances. For all the pharmacologists he's trained, Bernard Brodie-otherwise known as Steve because everyone named is called Steve-was not trained in his own field. His doctorate is in chemistry from New York University. He went into pharmacology afterward because, he says, he was lucky enough to have teachers who advised him while he was still young. My mentor, in organic chemistry, advised me to go into pharmacology because I was unable to remember simple structures or the Geneva nomenclature and because I was accident prone. He introduced me to Dr. George B. Wallace, that kind and gentle teacher who was willing to take into his department an ugly duckling because he foresaw that one day biochemistry and pharmacology would have to come together. From him I learned about intuition in science and the value of the working hypothesis. Later, Dr. worked under Dr. James A. Shannon, now director of