Bernard B. Brodie
By Fridolin Sulser
Bernard B. Brodie was born August 7, 1907 in Liverpool, England. In 1911, his family moved to Ottawa, Canada.
Bernard B. Brodie received his PhD in Organic Chemistry in 1935 from New York University, New York, NY. After a few years at the Goldwater Research Service of New York University (NYU) where Brodie was involved with imaginative research on anti-malarial drugs, he joined in 1949 (together with Julius Axelrod, Sidney Udenfriend and Bob Berliner) James Shannon who became Scientific Director of the National Heart Institute of the National Institutes of Health (NIH). Thus began Brodie’s illustrious career culminating in two stellar achievements: The creation of the Laboratory of Chemical Pharmacology (LCP) that became the Mecca of Biochemical Pharmacology and Neuropsychopharmacology, and the “Brodie School” with its worldwide influence.
Brodie stressed the importance of asking scientifically relevant questions and then developing one’s own methodology to get answers to these questions. The overriding research philosophy of the LCP was that Methodology drives Science. In Brodie’s LCP, Bowman and Udenfriend developed the spectrophotofluorimeter that made it possible to measure quantitatively small amounts of drugs and their metabolites, and for the first time allowed to study drug-induced changes of biogenic amines in the central nervous system. The demonstration by Alfred Pletscher, Park Shore and B.B. Brodie that reserpine’s tranquilizing action is associated with a time-dependent depletion of brain serotonin opened up worldwide research on the role of biogenic amines in brain (1, 2). The heuristic and novel idea of explaining drug actions via their effects on neurotransmitter function (serotonin, norepinephrine, dopamine) was pursued at the LCP with such drugs as monoamine oxidase (MAO) inhibitors, other antidepressants, and hypotensive drugs. Altogether, these studies established important concepts of neurochemical pharmacology that included the action of psychotropic drugs on storage, uptake, release and metabolism of monoamines. They catalyzed research on psychotropic drugs worldwide and contributed to the evolution of Biological Psychiatry.
Brodie was also aware of the crucial role played by the postsynaptic transduction of the synaptic signal. Studies conducted at the LCP during the late 1960s and early 1970s have paved the way for elucidating the role of receptor – second messenger mediated activation of protein kinases, leading to phosphorylation of transcription factors (e.g., CREB), followed by changes in programs of gene transcription.
Besides studying the action of drugs on body function, the LCP pursued also studies on the action of the body on drugs. Importantly, Axelrod and Brodie discovered the drug metabolizing enzymes (P450) and, consequently, the metabolic disposition of drugs and their metabolites could be followed in animals and man. Examples of the biotransformation of drugs and the potential of drug metabolites include the transformation of phenylbutazone to the pharmacologically active oxyphenylbutazone, and the formation of the active metabolite of imipramine, desmethylimipramine (DMI), which, as a selective norepinephrine (NE) reuptake inhibitor became an important pharmacological tool. Collectively, the scientific achievements, catalyzed by the unique atmosphere of the LCP have shaped neuropsychopharmacological research worldwide.
Equally important to Brodie’s scientific leadership was his mentorship of younger colleagues who all became leaders in their own respective fields and/or chairmen of major departments at American universities and at scientific institutions throughout the world. Brodie’s LCP was nurturing ground of what is called the “Brodie School” with pupils sharing his love and enthusiasm for science all over the world. The first and second generation pupils took with them the inspiration, excitement and voracious appetite for novel experiments that characterized the spirit of the LCP. Robert Kanigel writes in “Apprentice to Genius “ : “ For years scientists from all over the world had flocked his lab just to work beside him, sample his frighteningly original mind, and absorb the raw electric energy of the place” (3). A count, of guest scientists, who trained at the LCP from 1950 – 1970 yielded 79 names from 29 different countries (4). Julius Axelrod, Arvid Carlsson and Paul Greengard (second generation pupil of Sidney Udenfriend) have received Nobel Prizes for their scientific accomplishments while many others of the Brodie School are equally worthy, chief among them Bernard B. Brodie.
Dr Brodie received many honors, among them in 1967 the Albert Lasker Award for Basic Medical Research, the Distinguished Service Award of the Department of Health, Education and Welfare, the Sollman Award in Pharmacology, the National Medal of Science and the Golden Plate Award from the American Academy of Achievement. In 1966, Dr. Brodie was elected as a member of the National Academy of Sciences.
Bernard B. Brodie, the creator of the “Mecca” of Biochemical Neuropharmacology and the Father of the ”Brodie School,” passed away in 1989, age 82, in Charlottesville , Virginia where he spent his last retirement years.
1. Pletscher A, Shore PA. Brodie BB. Serotonin release as a possible mechanism of reserpine action. Science 1955; 122: 374-5.
2. Brodie BB, Shore P, Pletscher A. Limitation of serotonin-releasing activity to those alkaloids possessing tranquilizing action. Science 1956; 123: 992-3
3. Costa E. Bernard B. Brodie and the rise of clinical pharmacology. Annu Rev Pharmacol Toxicol 1989; 29: 1-21.
4. Kanigel R. Apprentice to Genius. The Making of a Scientific Dynasty. New York: Macmillan; 1986.
Fridolin Sulser
October 24,2013