J. Michael Bishop, M.D.
"And what have
kings that privates have not too,
William Shakespeare, in Henry the Fifth, IV. 1, 243-244
held little forecast of a career in biomedical research. I was born on
February 22, 1936, in
I obtained eight years of elementary education in a two-room school, where I encountered a stern but engaging teacher who awakened my intellect with instruction that would seem rigorous today in many colleges. History figured large in the curriculum, exciting for me what was to become an enduring interest. But I heard little of science, and what I did hear was exemplified by the collection and pressing of wild flowers. My high school was also small: eighty students graduated with me, few of whom eventually completed college. Tests conducted before I graduated predicted a future for me in journalism, forestry, or the teaching of music; persons who know me well could recognize some truth in those seemingly errant prognoses.
I had taken naturally to school and was an excellent student from the beginning. But my aspirations for the future were formed outside the classroom. During the summer months of my high-school years, I befriended Dr. Robert Kough, a physician who cared for members of my family. Although he was practicing general medicine in a rural community when I met him, he was well equipped to arouse in me an interest not only in the life of a physician but in the fundaments of human biology. His influence was to have a lasting impact.
I graduated from college still knowing
nothing of original research in science. I knew that I would be going to
medical school, but I had little interest in practicing medicine. Instead,
under the influence of my college faculty, I had formed a vague hope of
becoming an educator - by what means and in what subject, I knew not.
Learning of this hope, an associate dean at the
Two pathologists rescued me. Benjamin Castleman offered me a year of independent study in his
department at the
I was slowly becoming shrewd. I recognized that the inner sanctum of molecular biology was not accessible to me, that I would have to find an outer chamber in which to pursue my passion. I found animal virology, in the form of an elective course taken when I returned to my third year of medical school, and in the person of Elmer Pfefferkorn. From the course, I learned that the viruses of animal cells were ripe for study with the tools of molecular biology, yet still accessible to the likes of me. From Elmer, I learned the inebriation of research, the practice of rigor, and the art of disappointment.
I began my work with Elmer in odd hours snatched from the days and nights of my formal curriculum. But an enlightened dean gave me a larger opportunity when he approved my outrageous proposal to ignore the curriculum of my final year in medical school, to spend most of my time in the research laboratory. In the end, I completed only one of the courses normally required of fourth year students. Flexibility of this sort in the affairs of a medical school is rare, even now, in this allegedly more liberal age.
My work with Elmer was sheer joy, but it
produced nothing of substance. I remained uncredentialed
for postdoctoral work in research. So on graduation from medical school, I
entered an essential interregnum of two years as a house physician at the
Clinical training behind me, I began
research in earnest as a postdoctoral fellow in the Research Associate
Training Program at the National Institutes of Health in Bethesda, Maryland,
a program designed to train mere physicians like myself in fundamental
research. In its prime, the program was a unique resource, providing
My mentor at the National Institutes of Health was Leon Levintow, who has continued as my friend and alter ego throughout the ensuing years. My subject was the replication of poliovirus, which had a test case for the view that the study of animal viruses could tease out the secrets of the vertebrate cell. I managed my first publishable research: my feet were now thoroughly wet; I had become confident of a future in research.
Midway through my postdoctoral training, Levintow departed for the faculty at the
My year in
I continued my work on poliovirus. But new departures were also in the offing. In the laboratory adjoining mine, I found Warren Levinson, who had set up a program to study Rous Sarcoma Virus, an archetype for what we now know as retroviruses. At the time, the replication of retroviruses was one of the great puzzles of animal virology. Levinson, Levintow, and I joined forces in the hope of solving that puzzle. We were hardly begun before Howard Temin and David Baltimore announced that they had solved the puzzle with the discovery of reverse transcriptase.
The discovery of reverse transcriptase was sobering for me: a momentous secret of nature, mine for the taking, had eluded me. But I was also exhilarated because reverse transcriptase offered new handles on the replication of retroviruses, handles that I seized and deployed with a vengeance. I was joined in this work by a growing force of talented postdoctoral fellows and graduate students. Among our early achievements were a description of the mechanisms by which reverse transcriptase copies RNA into DNA, the characterization of viral RNA in infected cells, and the identification and description of viral DNA in both normal and infected cells.
The work on viral DNA was particularly notable because it was the handicraft of Harold Varmus, who had joined me as a postdoctoral fellow in late 1970. Harold's arrival changed my life and career. Our relationship evolved rapidly to one of coequals, and the result was surely greater than the sum of the two parts. Together we decided to extend our interests beyond the problems of retroviral replication, to address the mystery of how Rous Sarcoma Virus transforms cells to neoplastic growth.
Others had shown that transformation by Rous Sarcoma Virus could be attributed to a single gene (eventually dubbed src) located near the 3' end of the viral genome. Two problems engaged us: what was the origin of src; and what was the protein product of the gene? It was not our lot to find an answer for the second question, although we later played a part in discerning the biochemical function of the src protein. But with experiments performed mainly by Dominique Stehelin and Deborah Spector, we found the answer to the first question: src is a wayward version of a normal cellular gene (which we would now call a proto-oncogene), pirated into the retroviral genome by recombination (in a sequence of events known as transduction), and converted to a cancer gene by mutation.
In the years that followed, we consolidated our evidence for retroviral transduction, generalized the finding to retroviral oncogenes other than src, helped elucidate the sorts of genetic damage that convert normal cellular genes into cancer genes, explored the contributions of proto-oncogenes to the genesis of human cancer, added to the repertoire of proto-oncogenes by several experimental strategies, pursued the physiological functions of proto-oncogenes in normal organisms, and shared in the discovery of the protein kinase encoded by src.
I began my career at UCSF as an Assistant Professor of Microbiology and Immunology. I am now a Professor in the same department and in the Department of Biochemistry and Biophysics. I serve as Director of the G. W. Hooper Research Foundation and of the Program in Biological Sciences -- the latter, an effort to unify graduate education at UCSF. I am as devoted to teaching as to research: I find the two vocations equally gratifying.
I am a member of the National Academy of Sciences, U.S.A; the American Academy of Arts and Sciences; the American Association for the Advancement of Science (elected an Honorary Fellow); the American Society for Biological Chemistry and Molecular Biology; the American Society for Microbiology; the American Society for Cell Biology; the American Society for Virology; the Federation of American Scientists; Alpha Omega Alpha; and Phi Beta Kappa.
My honors include several awards for teaching from the students and faculty of UCSF; a Doctor of Science Honoris Causa from Gettysburg College; the American Association of Medical Colleges Award for Distinguished Research; the California Scientist of the Year; the Albert Lasker Award for Basic Medical Research; the Passano Foundation Award; the Warren Triennial Prize from the Massachusetts General Hospital; the Armand Hammer Cancer Prize; the Alfred P. Sloan, Jr. Prize from the General Motors Cancer Foundation; the Gairdner Foundation International Award; the American Cancer Society National Medal of Honor; the Lila Gruber Cancer Research Award from the American Academy of Dermatology; the Dickson Prize in Medicine from the University of Pittsburgh; the American College of Physicians Award for Basic Medical Research; and the Nobel Prize in Physiology or Medicine for 1989. Most of these have been shared with Harold Varmus.
I am married to Kathryn Ione Putman and
have two sons with her, Dylan Michael Dwight and Eliot John Putman. These
three have given me a gift of affection and forebearance
that I cannot hope to repay. My mother and father have reached their eighth
and ninth decades, respectively, and were able to join us for a joyful time
at the Nobel ceremonies in
If offered reincarnation, I would choose the career of a performing musician with exceptional talent, preferably, in a string quartet. One life-time as a scientist is enough -- great fun, but enough. I am a self-confessed book addict, an inveterate reader of virtually anything that comes to hand (with the notable exceptions of science fiction and crime novels). I enjoy writing and abhor the dreadful prose that afflicts much of the contemporary scientific literature.
(Dr. Bishop became the eighth Chancellor of UCSF on July 1, 1998.)