David Baltimore – The Scientist Who Caught Viruses Running in Reverse

Many of history’s greatest scientists are remembered for shattering established paradigms. Copernicus, who placed the sun at the center and relegated Earth to a modest orbit; Darwin, who developed the idea of the evolution of species through natural selection; and the monk Gregor Mendel, who proposed laws of heredity that challenged the biology of his era. To their ranks we can add Einstein, Niels Bohr, Marie Curie, Alan Turing, and many others. Another such scientist walked among us until only a short time ago: American biologist David Baltimore, who upended accepted biological dogma, shook the field of virology in more ways than one, and whose discoveries permanently reshaped the life sciences. Baltimore, laureate of the 1975 Nobel Prize in Physiology or Medicine, passed away recently in Massachusetts at the age of 87.

Baltimore was born on March 7, 1938, in Manhattan, the son of Gertrude, a psychologist, and Richard, who worked in the garment industry. His father had grown up in an Orthodox Jewish household, and so, although his mother was a staunch atheist, Baltimore attended synagogue regularly until his bar mitzvah. During his youth, the family moved to Great Neck in the suburbs of New York City, where he completed high school. His early interest in biology led him to spend a summer at the Jackson Laboratory, a private institute in the state of Maine. It was there that he met an enthusiastic Jewish high-school student named Howard Temin — and the two of them would cross paths again, in a very significant way.

Baltimore earned his undergraduate degree in biology at Swarthmore College — not considered the most prestigious institution at the time, but known, at least by some accounts, as a welcoming place for Jewish students. This small private college has produced five Nobel laureates over the years, one of whom would be Baltimore himself. He graduated in 1960, around the time he met two energetic young researchers at the Massachusetts Institute of Technology (MIT), both Jewish as well: Salvador Luria and Cyrus Levinthal.

Progress in Reverse

Like young faculty members today, Salvador Luria and Cyrus Levinthal took on the task of “scouting”: identifying outstanding students with strong research potential who might eventually pursue graduate studies at their prestigious institution. They saw that David Baltimore fit the profile and invited him to MIT. Before long, however, he found himself a doctoral student not at MIT but in the laboratory of Prof. Richard Franklin at Rockefeller University, where his research focused on animal viruses.

In 1965, on the recommendation of his colleague Renato Dulbecco, Baltimore joined the faculty of the Salk Institute in San Diego, which had been established a few years earlier by Jonas Salk, developer of the polio vaccine. A few years later, Baltimore married Alice Huang, a Chinese-born virologist who was also working at the Salk Institute. The couple had one daughter.

In his early years as an independent researcher, Baltimore studied fairly conventional viruses, including poliovirus. At a certain point, however, he became interested in viruses linked to the development of cancers, particularly in birds. These are now known as oncoviruses. Together with his old acquaintance Howard Temin, Baltimore realized they were dealing with an entirely different kind of virus – unlike any previously known.

All the viruses known at the time were thought to replicate according to the accepted model (sometimes mistakenly referred to as the “central dogma of molecular biology”), which held that in living organisms—including viruses, even though they are not considered alive in the strict sense—messenger RNA (mRNA) molecules are transcribed from DNA in the cell nucleus. The mRNA then serves as a template for protein synthesis. 

But the evidence from the avian viruses pointed in the opposite direction—something considered inconceivable: DNA was being synthesized from an RNA template. Baltimore and Temin called this surprising process reverse transcription.

Working independently but in parallel with a team led by Renato Dulbecco, Baltimore and Temin demonstrated that reverse transcription was carried out by an enzyme, which they named reverse transcriptase.

New Worlds

The discovery of reverse transcriptase and the process of reverse transcription not only astonished the community of geneticists and molecular biologists—it required a fundamental paradigm shift. Baltimore embraced this challenge as well, devising a system that divided all viruses into six groups (later expanded to seven), each defined by its genome type and replication strategy. This system, still known today as the Baltimore Classification, remains a cornerstone of virology. The viruses studied by Baltimore and Temin became known as retroviruses.

Over the years, reverse transcriptase proved to be far more than a biological curiosity: it became the basis for the development of antiviral drugs designed to block viral replication by inhibiting the enzyme. Beyond therapeutics, it also assumed a central role in laboratory techniques, particularly PCR-based methods, by making it possible to convert viral RNA into DNA, which can then be amplified repeatedly to levels detectable for the identification and quantification of viruses in clinical samples.

From the moment Baltimore published his findings, he was on the fast track to the Nobel Prize. In October 1975, the Nobel Committee announced that the prize in Physiology or Medicine would be awarded jointly to Baltimore, Temin, and Dulbecco.  At 37, Baltimore was the youngest of the trio – a time in life when many scientists today are only beginning their independent research careers. Shortly after shaking hands with the King of Sweden, Baltimore turned to his next scientific challenge.

In addition to studying oncoviruses—cancer-causing viruses, many of which belong to the retrovirus group—Baltimore also investigated another prominent member of that group: HIV, the retrovirus responsible for AIDS. As the disease rose to the forefront of public and scientific concern in the 1980s, Baltimore became one of the leading figures studying the virus, its life cycle, and the immune system’s responses to it.

At the same time, in 1982 Baltimore was approached by philanthropist Jack Whitehead, who envisioned establishing an independent institute for basic biomedical research. Baltimore proved to be the right person for the task: within a short time, the Whitehead Institute was established adjacent to MIT. To this day it is administratively affiliated with MIT, though financially independent.The institute, which has earned an international reputation for excellence over the years, currently has 19 faculty members.

A Troubled Affair

Alongside the extraordinary success of these years, Baltimore’s career was overshadowed by an episode that ended with a muted conclusion. In 1986, his colleague Thereza Imanishi-Kari, who worked in another laboratory at MIT, faced serious allegations. A postdoctoral researcher in her group claimed that a paper co-authored by Imanishi-Kari and Baltimore and published in Cell was based on data fabricated by Imanishi-Kari. The complainant argued that the article – describing how the immune system rearranges its genes in order to produce antibodies against new antigens – contained serious flaws. Most notably, she maintained that the results could not be replicated in the laboratory, a matter regarded as a first-order breach of scientific integrity.

Baltimore stood firmly by the work and refused to distance himself from it. The postdoc eventually withdrew her complaint, but by then the damage had been done. The National Science Foundation (NSF), which had funded the research, decided to intervene and examine the matter thoroughly. The inquiry escalated into a congressional investigation led by Representative John Dingell, a seasoned political fighter. Remarkably, the Secret Service was even brought in to conduct forensic analysis of Imanishi-Kari’s lab notebooks.

Six years after the controversy began, a leaked Secret Service report appeared to clearly implicate Imanishi-Kari in data fabrication. Shocked and regretful, Baltimore apologized and resigned from his prestigious post as president of Rockefeller University, returning to MIT. In 1994, Imanishi-Kari was found guilty on 19 counts of scientific misconduct and was barred from receiving federal research grants for a decade.

Yet two years later, an unexpected twist occurred. Imanishi-Kari appealed the ruling, and a panel convened by the U.S. Department of Health and Human Services overturned all charges, fully exonerating her. She resumed her research career at Tufts University. The entire episode—often mislabeled as the “Baltimore Affair”—cast a shadow over Baltimore’s career, but it did not bring it to a halt.

A New Chapter on the Western Front

A year after the controversy faded from the headlines, Baltimore was appointed president of the California Institute of Technology (Caltech). There he established another laboratory, focusing on two main lines of research: understanding the development and function of the mammalian immune system, and exploring how the immune system might be harnessed more effectively to fight cancer.

The second line of research centered on close study of a molecule known as microRNA—a very small RNA molecule containing a short sequence of building blocks. Unlike messenger RNA, which encodes the instructions for building specific proteins, microRNAs do not encode a specific protein. Instead, they function as regulatory switches, helping determine how much protein is produced from a given gene. In this way, Baltimore’s long-standing relationship with RNA continued in a new and profound direction.

During his time at Caltech—years that were markedly calmer—Baltimore was awarded the National Medal of Science by U.S. President Bill Clinton. He stepped down from his position in 2006, although his laboratory continued to operate until 2019. 

In his final years, Baltimore was diagnosed with cancer, and on September 6, 2025, he passed away at the age of 87. Friends and colleagues recalled that, beyond his scientific stature, he was a man of culture and conversation who enjoyed wine and good food – a true citizen of the world. With his death, molecular biology lost one of its most influential figures.