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A Brief History of Great Discoveries in Pharmacology 0031-6997/07/5904-289–359$20.00 PHARMACOLOGICAL REVIEWS Vol. 59, No. 4 Copyright © 2007 by The American Society for Pharmacology and Experimental Therapeutics 70102/3301314 Pharmacol Rev 59:289–359, 2007 Printed in U.S.A A Brief History of Great Discoveries in Pharmacology: In Celebration of the Centennial Anniversary of the Founding of the American Society of Pharmacology and Experimental Therapeutics RONALD P. RUBIN The State University of New York at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, New York Foreword .............................................................................. 290 I. Prologue ............................................................................... 290 II. Major discoveries in pharmacology ....................................................... 291 A. Thomas Renton Elliott: elaboration of the concept of chemical neurotransmission .......... 291 B. Sir Henry Dale and Otto Loewi: chemical transmission of nerve impulses ................. 294 1. Sir Henry Dale ................................................................... 294 2. Otto Loewi ....................................................................... 295 C. Daniel Bovet: synthetic compounds that inhibit the action of certain body substances, and especially their action on the vascular system and skeletal muscle ....................... 298 D. Ulf von Euler, Julius Axelrod, and Sir Bernard Katz: humoral transmitters in the nerve terminals and the mechanism for their storage, release, and inactivation ................. 301 1. Ulf von Euler .................................................................... 301 2. Julius Axelrod.................................................................... 301 3. Sir Bernard Katz ................................................................. 305 E. Arvid Carlsson: signal transduction in the nervous system .............................. 306 F. Sir James Black, Gertrude Elion, and George Hitchings: important principles for drug treatment........................................................................... 308 1. Sir James Black .................................................................. 308 2. Gertrude Elion and George Hitchings............................................... 311 G. Paul Ehrlich: the magic bullet ........................................................ 314 H. Gerhard Domagk: antibacterial effects of prontosil ...................................... 315 I. Sir Alexander Fleming, Cecil Paine, Harold Raistrick, Ernst Chain, and Sir Howard Florey: penicillin and its curative effects in various infectious diseases........................... 318 1. Sir Alexander Fleming ............................................................ 318 2. Cecil Paine....................................................................... 320 3. Harold Raistrick.................................................................. 320 4. Ernst Chain and Sir Howard Florey ................................................ 320 5. Jack Strominger .................................................................. 323 J. Selman Waksman: streptomycin: the first antibiotic effective against tuberculosis ......... 324 1. Albert Schatz .................................................................... 326 K. Sir Frederick Banting, Charles Best, John Macleod, and James Collip .................... 327 L. Philip Hench, Edward Kendall, and Tadeus Reichstein: hormones of the adrenal cortex, their structure, and biological effects .................................................. 334 1. Philip Hench ..................................................................... 334 2. Edward Kendall and Tadeus Reichstein............................................. 335 M. Sune Bergstro¨m, Bengt Samuelsson, and John Vane: prostaglandins and related biologically active substances .................................................................... 338 1. Ulf von Euler and Sune Bergstro¨m................................................. 338 Address correspondence to: Dr. Ronald P. Rubin, The State University of New York at Buffalo, School of Medicine and Biomedical Sciences, 102 Farber Hall, Buffalo, NY 14214-3000. E-mail: [email protected] This article is available online at http://pharmrev.aspetjournals.org. doi:10.1124/pr.107.70102. 289 290 RUBIN 2. Bengt Samuelsson ................................................................ 339 3. John Vane ....................................................................... 340 N. Earl W. Sutherland: cyclic AMP....................................................... 342 O. Paul Greengard: signal transduction in the nervous system.............................. 345 P. Martin Rodbell and Alfred G. Gilman: G proteins and their role in signal transduction in cells ............................................................................. 347 1. Martin Rodbell ................................................................... 348 2. Alfred G. Gilman ................................................................. 350 Q. Robert Furchgott, Ferid Murad, and Louis Ignarro: nitric oxide as a signaling molecule in the cardiovascular system.......................................................... 352 1. Robert Furchgott ................................................................. 352 2. Ferid Murad ..................................................................... 353 3. Louis Ignarro .................................................................... 355 III. Epilogue ............................................................................... 356 References ............................................................................. 356 Foreword are developed in such a style that it would be difficult to fault their selection. The lead investigators that When the American Society of Pharmacology and Ex- Dr. Rubin highlights were (or are) remarkable individ- perimental Therapeutics (ASPET1) Centennial Commit- uals. Although each discovery discussed herein culimi- tee began considering ways to celebrate the Society’s nated in a Nobel Prize, many other familiar names are 100th anniversary in 2008, an early interest was ex- woven into the fabric, and the evolution of ideas from pressed in having a publication that presented the re- multiple individuals is emphasized. search history of the discipline. However, the Committee The Centennial Committee is pleased to sponsor recognized that such a tome would fill a very large this publication and hopes that the memories of more volume and be an immense task. senior scientists will be relived and that young scien- Several problems were perceived. First, it would take tists will find the stories inspiring. We give our thanks an enormous effort, one which few authors would be to Dr. Rubin for his efforts and for these fine results. willing to undertake. Second, the likelihood that a qual- ity publication of that magnitude could be produced by William W. Fleming 2008 was slight. Third, no matter how thorough an On behalf of the author might be, the work of many excellent pharmacol- ASPET Centennial Committee ogists would be omitted and could lead to conflicts. Fi- nally, possibly the most important problem would be I. Prologue that the shear mass of material would not attract many young pharmacologists as readers. More than anything This series of essays attempts to profile how extraor- else, the Centennial Committee wants this publication dinary individuals have shaped our concepts in various to be interesting to young scientists. areas of biomedical research, particularly as they relate It came to the attention of the Committee that to the discipline of pharmacology. These gifted research- Dr. Ronald Rubin had been independently considering ers broke through the shibboleths of scientific thought writing about key discoveries in the history of pharma- that dominated their time because of their cogent anal- cology. The Committee offered to sponsor the project. ysis and the accuracy of their hypotheses. Many of the What follows is the outcome of that effort by Dr. Rubin. discoveries that are chronicled in these essays are not In the view of the Committee, what Dr. Rubin has writ- only timeless in terms of their impact on the human ten avoids the major problems noted above. condition but are also inspirational and embody certain The history is written in a highly interesting vein and virtues espoused by Winston Churchill, including “a con- is of a length that can be read in a relatively short period stancy of mind and persistence of purpose.” These essays of time. The theses chosen are of such importance and will also attempt to illustrate how the collaboration of colleagues not only contributed immeasurably to the 1 Abbreviations: ASPET, American Society of Pharmacology and success of a project but may also have led to controver- Experimental Therapeutics; ACh, acetylcholine; NYU, New York sies that even extended into the courts. In perusing a University; NIH, National Institutes of Health; SSRI, selective se- number of documents on a given subject, one is often rotonin reuptake inhibitor; EPP, end-plate potential; ICI, Imperial presented from different perspectives. To deal with this Chemical Industries; DCI, dichloroisoproterenol; 6-MP, 6-mercapto- purine; ACTH, adrenocorticotrophin; NSAID, nonsteroidal anti-in- situation, I have tried to explore as many diverse ac- flammatory drug; PKA, protein kinase A; NO, nitric oxide; EDRF, counts that I felt were needed to paint as accurate a endothelium-relaxing
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