J. Michael Bishop Biography (1936-)

molecular biologist

For work in cancer research, J. Michael Bishop shared the 1989 Nobel Prize inphysiology or medicine with Harold Varmus. He and Varmus found that cancer genes (oncogenes) could be derived from normal cell genes which had notbeen inherently cancer-causing, as was previously thought; they stopped normal functioning and became cancerous under certain conditions. In presenting the Nobel Prize, Erling Norrby of the Karolinska Institute praised them for their discovery of "the cellular origin of retroviral oncogenes," and claimed they had "set in motion an avalanche of research on factors that govern the normal growth of cells."

John Michael Bishop was born February 22, 1936, to John and Carrie Grey Bishop. The family, which included another son and daughter, lived in York, Pennsylvania, where John Bishop was a Lutheran minister. Bishop's early schooling was almost entirely devoid of science, and even when he entered Gettysburg College in 1953 as a premedical student, he had no firm plans for a career. He graduated with a chemistry degree in 1957 and went to Harvard Medical School but took several detours while he was there, first to work in the pathology department of the Massachusetts General Hospital and later to work with the virologist Elmer Pfefferkorn. He obtained his medical degree in 1962 and spent the required amount of time as an intern and resident at Massachusetts General, but his interest had finally focused on investigating the molecular biologyof viruses. He worked for three years at the National Institutes of Health as a postdoctoral fellow, learning to do fundamental research. After a year ofstudy in Germany with Gebhard Koch, Bishop took a teaching position in 1968at the University of California at San Francisco. He was eventually appointedprofessor in the department of microbiology and immunology, as well as the director of the G. W. Hooper Research Foundation of the University of California Medical Center.

A cancer cell's principal characteristic is unregulated growth and multiplication. Carcinogenesis is a particularly difficult field to study because thereappear to be many factors contributing to it (genetics and environment beingonly two), and also because a cell is an intricate structure with hundreds of different chemical reactions and enzymes controlling and affecting each other. Bishop studied the genetic component of cancer, and of this subject he has written in an article in Science: "Genetic damage remains undetected in the great majority of human tumors. We may have to invent new ways to search for this damage, and we must remain open to the possibility that we willnot always find it because it is not always there."

Many theories of cancer causation already existed when Bishop began his investigations, and new discoveries relevant to the field were made frequently. Robert Huebner and George Todaro had postulated that cancer genes (oncogenes) might lay hidden in cells, the result of viral infection many generations ago,waiting for particular environmental stresses to set them off. Peyton Rous had identified a sarcoma virus that caused tumors in chickens. G. Steven Martin found an oncogene, named src, src on the Rous sarcoma virus. Howard Temin identified the sarcoma virus discovered by Rous as a retrovirus--one that could somehow copy its own RNA information into the DNA ofthe host cell (which is reverse of the usual process of DNA to RNA reproduction). Temin also participated in David Baltimore's discovery of the enzyme called reverse transcriptase which accomplished that copying.

Bishop, Varmus, and their colleagues Deborah Spector and Dominique Stehelin conducted a search for src oncogenes src in different species and found src- like genes just about everywhere, apparently as Huebner and Todaro had predicted. They were astonished to find, however, that these geneswere not inherently oncogenes but functioned as a regular part of the cellular machinery, performing work for the cell until their normal functioning wassomehow changed. Bishop and his colleagues called these genes proto-oncogenes. Retroviruses apparently picked up these normal cellular genes and instigated changes that caused them to become cancerous, although retroviruses were only one possible cause of the transformation; some chemical carcinogens may also convert proto-oncogenes to oncogenes. In a review in Science, Bishop uses an analogy to describe proto-oncogenes, though he warns that the analogy is oversimplified: "The proliferation of cells is governed by an elaborate circuitry that reaches from the surface of the cell to the nucleus. The products of proto-oncogenes may represent some of the junction boxes in that circuitry.... What we now know of oncogenes allows us to view their actions as'short circuits' at the corresponding junction boxes."

For this discovery Bishop and Varmus received the 1989 Nobel Prize. Controversy erupted when Stehelin demanded a share of the prize for the work he had done with the two laureates, but the awarding committee remained firm. Stehelin, as well as Spector , had contributed important experiments, but the committee believed that the fundamental intellectual creativity belonged to Bishop and Varmus.

A strong proponent of basic research, in 1993 Bishop coauthored a paper in Science which sharply criticized the government's role in the field. The article mentioned "inadequate funding..., flawed governmental oversight ofscience, confusion about the goals of federally supported research, and deficiencies in science education," and offered a set of guidelines for solving these problems.

Bishop married Kathryn Ione Putnam in 1959; they have two sons. Among his other honors, Bishop won the Gairdner Foundation International Award and the Armand Hammer Cancer Prize in 1984, the American Cancer Society National Medal of Honor in 1985, and the American College of Physicians Award in 1987. He isknown as an outstanding teacher and outspoken individual, with a great fondness for music.

Recent Updates

February 21, 2005: It was announced that Bishop will receive one of three National Medals of Science for Biological Sciences at a White House ceremony in mid-March of 2005. The National Medal of Science is the nation's highest honor for science. It recognizes individuals in a variety of fields for pioneering scientific research that has led to a better understanding of the world around us. Source: National Academies, www.nationalacademies.org/headlines, February 21, 2005.

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