Photo: Christopher Michel (CC-BY-SA-4.0)
The world has lost a giant of virology, molecular biology and science communication with the death of David Baltimore at the age of 87. Baltimore demonstrated that RNA viruses that cause cancer contain an enzyme that can control the synthesis of DNA from an RNA template. We now know this enzyme as reverse transcriptase and viruses as retroviruses, reflecting the reverse flow of genetic information in this type of virus.
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The discovery of reverse transcriptase in 1970 explained the mystery of the capabilities of these viruses. It clarified how an RNA virus can generate a genomic copy of itself that can persist in an infected cell and be inherited by daughter cells. It also showed how, much later, cells could make additional copies of viral RNA. The idea that this mechanism might involve the formation of a DNA copy of the RNA genome was proposed by Howard Temin, who shared the 1975 Nobel Prize in Medicine with Baltimore and Renato Dulbecco. But accepting this theory required Baltimore to be unusually willing to challenge the central dogma of molecular biology, in particular the principle that information flows in all living systems from DNA to RNA to protein.
Reverse transcriptase has become an important tool in modern molecular biology because the ability to make DNA copies of any RNA molecule, combined with the extraordinary power of recombinant DNA techniques, allows the characterization of RNA molecules that define cell types and their functions.
Baltimore was born and raised in New York City. He received a degree in chemistry from Swarthmore College, Pennsylvania, in 1960. He then attended graduate school in biology at the Massachusetts Institute of Technology (MIT) in Cambridge and then moved on to The Rockefeller University in New York, where he completed his doctorate in animal virology. After a postdoc at the Salk Institute for Biological Studies in San Diego, California, he returned to MIT in 1968 to found his own group, where he made his first seminal discovery. His laboratory went on to show how reverse transcriptase, through an extremely complex series of steps, directs the formation of a double-stranded DNA copy of a single-stranded retroviral RNA genome.
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Baltimore uncovered aspects of the replication of many other viruses, including poliovirus and vesicular stomatitis virus. He discovered and characterized several cancer-causing genes, including the gene encoding the Abelson murine leukemia virus tyrosine kinase v-abl. The mammalian homolog, c-ABL, was later identified as the cause of chronic myeloid leukemia in humans, a cancer that is now successfully treated with the kinase inhibitor Gleevec (imatinib) and its successors.
