The Discovery of Reverse Transcriptase

COURTESY OF DAVID BALTIMORE

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.

His conclusion: "[Therefore,] There is an Enz." As he wrote those words, Baltimore says in an E-mail, he felt "elation, excitement, a future in a new field that I had opened." He published his discovery, alongside identical findings from Howard Temin of the University of Wisconsin, Madison, on June 27, 1970. ^1,2 Five years later, Baltimore and Temin shared the Nobel Prize in Medicine for their discovery of reverse transcriptase, a key enzyme for HIV, the subject of a feature article on page 36 .