The Discovery of Reverse Transcriptase

In the spring of 1970 two young investigators shook the foundations of molecular biology's "central dogma," which holds that DNA is transcribed to RNA, which in turn is translated into protein.

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In the spring of 1970 two young investigators shook the foundations of molecular biology's "central dogma," which holds that DNA is transcribed to RNA, which in turn is translated into protein.

David Baltimore, then a 32-year-old virologist at the Massachusetts Institute of Technology, was studying RNA viruses, trying to understand how they replicate their genomes. Hypothesizing the presence of a virus-associated enzymatic activity, he began looking for an RNA-directed DNA polymerase in Rauscher mouse leukemia virus (R-MLV).

In this page from his lab notebook, dated May 4, 1970, Baltimore details how he uses a concentrated preparation of the virus and tritiated dTTP to assay for DNA synthesis, which is seen as an increase in acid-insoluble radioactivity. The data at bottom left tell the story: A 30-minute incubation yields 656 incorporated counts, compared to 109 cpm for the 0-minute incubation control. Doubling the input virus increased those numbers to 1,319 cpm.

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