a virologist whose discovery of an enzyme changed the understanding of cancer and HIV/AIDS

The world has lost a giant of virology, molecular biology and science advocacy with the death of David Baltimore, aged 87. Baltimore showed that cancer-causing RNA viruses contain an enzyme capable of directing the synthesis of DNA from an RNA sample. 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 in the abilities of these viruses. It explained how an RNA virus can create a genomic copy of itself that can exist in an infected cell and be inherited by daughter cells. It also revealed how, much later, the cells were able to produce further copies of the viral RNA. The idea that this mechanism might involve the creation 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 requires Baltimore’s unusual willingness to challenge a central dogma of molecular biology—namely, the principle that information flows in all living systems from DNA to RNA to protein.

Reverse transcriptase has become an essential tool in modern molecular biology, because the ability to make DNA copies of any RNA molecule, together with the extraordinary power of recombinant DNA methods, enables the characterization of RNA molecules that define cell types and their functions.

Baltimore was born and raised in New York. He graduated in chemistry from Swarthmore College in Pennsylvania in 1960. He then joined a graduate program in biology at the Massachusetts Institute of Technology (MIT) in Cambridge, before moving to Rockefeller University in New York, where he completed a PhD in animal virology. After a postdoctoral fellowship 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 fundamental discovery. His laboratory demonstrated how reverse transcriptase orchestrates, through an extremely complex series of steps, the formation of a double-stranded DNA copy of a single-stranded retroviral RNA genome.

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Baltimore discovered aspects of replication of many other viruses, including poliovirus and vesicular stomatitis virus. He discovered and characterized several cancer-causing genes, including one encoding the v-abl tyrosine kinase in the Abelson murine leukemia virus. The mammalian homologue, c-ABL, was later shown to be the driver of chronic myeloid leukemia in humans, a cancer now successfully treated with the kinase inhibitor Gleevec (imatinib) and its successors.