The heretical discovery that changed science forever
In 1970, a 32-year-old David Baltimore challenged one of the most fundamental principles in biology. His discovery of an enzyme that copies RNA into DNA—dubbed "reverse transcriptase"—shattered the established dogma that genetic information could only flow from DNA to RNA to protein. This revolutionary insight not only earned him a Nobel Prize at age 37 but would later prove essential in understanding and fighting one of humanity's most devastating viruses: HIV 1 .
For decades, molecular biology had operated under what Francis Crick termed the "Central Dogma of Molecular Biology"—the principle that genetic information flows unidirectionally from DNA to RNA to protein. The sequence was considered irreversible, much like a one-way street 2 9 .
Meanwhile, Howard Temin, then at the University of Wisconsin, had been gathering evidence suggesting that RNA tumor viruses might operate differently. Based on his experiments, he proposed that these viruses could create a DNA copy of their RNA genome when they infected cells. Temin's "DNA provirus hypothesis" was largely dismissed by the scientific community, as it directly contradicted the central dogma 9 . As Baltimore would later recall, the idea was considered "almost literally heretical" 8 .
Genetic information flows unidirectionally from DNA → RNA → Protein
RNA viruses could create DNA copies of their genome (RNA → DNA)
In 1970, working in his laboratory at MIT, Baltimore decided to investigate RNA tumor viruses from a different angle. While Temin had approached the problem through virology and genetics, Baltimore brought his expertise in molecular biology and enzymology to bear on the question 8 .
Baltimore's experimental design was elegant and direct. He worked with two RNA tumor viruses: the Rauscher murine leukemia virus and the Rous sarcoma virus 9 . His approach was to look inside these virus particles for a specific enzyme that could copy RNA into DNA.
Used nonionic detergents to gently disrupt viral membranes
Added deoxynucleotides to "call the enzyme into action"
Monitored whether DNA synthesis occurred using RNA as template
Confirmed enzyme transcribed RNA into double-helix DNA
| Research Reagent | Function in the Experiment |
|---|---|
| Rauscher murine leukemia virus | An RNA tumor virus model system for studying replication mechanisms |
| Rous sarcoma virus | Second RNA tumor virus used to confirm findings across different viruses |
| Nonionic detergents | Gently disrupted viral membranes to make internal enzymes accessible |
| Deoxynucleotides | Building blocks of DNA that "lured" the reverse transcriptase enzyme into action |
| Radioactive labels | Enabled detection and tracking of newly synthesized DNA molecules |
Baltimore had discovered what we now know as reverse transcriptase—the enzyme that transcribes RNA into DNA 2 9 . He immediately recognized the significance of his finding, later recalling: "There was an enzyme in the virus particles that copied RNA to DNA" 8 .
"There was an enzyme in the virus particles that copied RNA to DNA."
In a remarkable coincidence, Temin and his colleague Satoshi Mizutani had independently reached the same conclusion using a different approach. The two papers were published back-to-back in the journal Nature in 1970 2 8 .
The scientific community accepted this revolutionary concept with surprising speed. Baltimore noted two reasons for this rapid acceptance: "One was that we had done these independent experiments, and so to doubt them, you'd have to doubt both his work and my work. And the second thing is that we gave talks about the work and described it, and people went back to their labs and tested out the ideas and showed very quickly they could reproduce the experiments" 8 . Famously, researcher Sol Spiegelman attended their talks at Cold Spring Harbor, returned to his lab, worked through the weekend, and confirmed the results by Monday 8 .
| Virus Class | Genome Type | Replication Strategy | Examples |
|---|---|---|---|
| Class I | Double-stranded DNA | Standard DNA→RNA→protein | Smallpox, Herpes |
| Class II | Single-stranded DNA | DNA→RNA→protein | Parvovirus |
| Class III | Double-stranded RNA | RNA→RNA→protein | Rotavirus |
| Class IV | Positive-sense single-stranded RNA | RNA→protein | Poliovirus, SARS-CoV-2 |
| Class V | Negative-sense single-stranded RNA | RNA→RNA→protein | Influenza, Rabies |
| Class VI | Single-stranded RNA with DNA intermediate | RNA→DNA→RNA→protein | HIV, HTLV |
| Class VII | Double-stranded DNA with RNA intermediate | DNA→RNA→DNA→RNA→protein | Hepatitis B |
The discovery of reverse transcriptase fundamentally transformed multiple fields of biology and medicine:
Reverse transcriptase provided the key to understanding the life cycle of retroviruses, a group that includes HIV 5 . When HIV was identified as the cause of AIDS in the early 1980s, Baltimore's discovery offered the crucial insight needed to understand how the virus integrates into the host's genome 9 .
The understanding of reverse transcriptase led directly to the development of antiretroviral drugs that target this enzyme. These drugs have become cornerstone therapies for managing HIV infection 9 .
Baltimore's contribution extended far beyond this single discovery. He became a leading voice in science policy, helping organize the landmark Asilomar Conference that established safety guidelines for recombinant DNA research 2 8 . He also served as a key advocate for AIDS research during the early days of the epidemic, chairing the NIH AIDS Vaccine Research Committee and directing his own laboratory's research toward HIV 4 6 7 .
David Baltimore passed away on September 6, 2025, at the age of 87 1 6 7 . His legacy extends far beyond his paradigm-shifting discovery. As noted by IAVI CEO Mark Feinberg, a former postdoctoral researcher in Baltimore's lab: "David was the most brilliant, creative, insightful, and rigorous scientist I have ever met. While David's remarkable and diverse scientific accomplishments are widely known, his special commitment to mentorship and to fostering the careers of generations of scientists may be less well appreciated" 6 .
"David was the most brilliant, creative, insightful, and rigorous scientist I have ever met."
Baltimore's own philosophy of mentorship emphasized giving students "as much freedom as possible to develop their own way of doing science, their own skills, their own interests, their own programs" 8 . This approach nurtured generations of scientists who would go on to make their own important contributions.
Earned PhD from Rockefeller University - Completed doctorate in just two years with groundbreaking work on virus replication
Discovered reverse transcriptase - Revolutionized molecular biology by proving RNA could be copied to DNA
Awarded Nobel Prize in Physiology or Medicine - Recognized at age 37 for transformative discovery
Founded Whitehead Institute at MIT - Created pioneering biomedical research institute
President of Rockefeller University - Provided leadership during critical period
President of California Institute of Technology - Steered prestigious institution for nearly a decade
Received Lasker-Koshland Special Achievement Award - Honored for lifetime of scientific contribution and mentorship
From a high school student inspired by a summer at Jackson Laboratory to a Nobel laureate who reshaped modern biology, David Baltimore's journey demonstrates how challenging established dogmas with rigorous experimentation can unlock profound new understandings of life itself. His work continues to influence diverse fields from virology to immunology to cancer research, proving that one revolutionary discovery can indeed change the trajectory of science and medicine forever.