David Baltimore

• Born: March 7, 1938
• Place of Birth: New York, New York

AMERICAN MOLECULAR BIOLOGIST

Molecular biologist and Nobel laureate David Baltimore has achieved great influence as a researcher, scientific policymaker, and leader of academic institutions. He is most celebrated for his molecular virology discoveries in recombinant DNA research.

PRIMARY FIELD: Biology

SPECIALTIES: Molecular biology; virology; microbiology

Early Life

David Baltimore was born in New York City on March 7, 1938, to parents Gertrude Lipschitz, an experimental psychologist, and Richard Baltimore, who worked in the garment industry. His decision to become a molecular biologist began in 1955 when he was a junior in high school and his mother arranged for him to spend a summer working on mouse genetics with a group of research biologists at the Jackson Memorial Laboratory in Bar Harbor, Maine. That summer, Baltimore also met future colleague and friend Howard Martin Temin, who had just graduated from college and served as a mentor.

Baltimore earned a BS degree with high honors in chemistry from Swarthmore College in 1960. He began graduate work in biophysics at the Massachusetts Institute of Technology (MIT) but left to concentrate on the study of animal virology at the Rockefeller Institute for Medical Research (now Rockefeller University), which awarded him a PhD in 1964. Baltimore completed his postgraduate work in eighteen months, a process that typically requires several years.

Baltimore joined the faculty of MIT in 1968, where he would remain for much of the next thirty years, and conducted research that was ahead of its time in its interdisciplinary nature. He envisioned an environment in which researchers approached complex scientific challenges from a multifaceted perspective. His laboratory thus relied not only on the tools of molecular biology, but also on those of virology and immunology.

Life’s Work

In 1970, Baltimore codiscovered reverse transcriptase with Howard Temin, his 1955 summer mentor, who was working independently of Baltimore at the time. Baltimore and Temin discovered separately, and within days of each other, that reverse transcriptase is an uncommon enzyme used by retroviruses to synthesize DNA from RNA. Baltimore showed that retroviruses have encoded in them genetic instructions for the manufacture of an enzyme (reverse transcriptase) capable of copying DNA from an RNA template. The newly-created viral DNA is then able to transform an infected cell into a malignant cell.

Baltimore’s co-discovery of reverse transcriptase had its roots in his early research on the ways in which poliovirus manages to penetrate cellular defenses and then replicate. He had conducted this work at the Salk Institute in California for three years beginning in 1965. This research led Baltimore to conduct experiments focusing on two particular RNA tumor viruses: one that causes leukemia in mice and another that causes sarcoma in chickens.

At the time that Baltimore began his experiments, scientists already knew that under certain conditions some viruses caused tumors in chickens and that some viruses could also cause different types of cancer in other animals such as mice. Researchers eventually discovered that both viruses containing DNA as their genetic material and viruses containing the kind of genetic material known as RNA were capable of triggering a normal cell to undergo growth characteristics typical of a tumor cell. A central mystery remained: How did the genetic material of a tumor-causing RNA virus apparently manage to infiltrate the DNA of a healthy cell?

Up until that time, most molecular biologists believed transfers of genetic information to be strictly one-way from DNA to RNA. Baltimore, who had been studying virus-specific enzymes that copy RNA from RNA, began using similar techniques to investigate whether some viruses were capable of copying DNA from RNA. Baltimore’s experiments clarified the molecular process and the role of reverse transcriptase by which cancer-causing RNA viruses succeed in infecting and permanently changing healthy cells.

In 1975, Baltimore shared the Nobel Prize in Physiology or Medicine with Howard Temin and Renato Dulbecco for groundbreaking insights into the interaction between tumor viruses and the genetic material of the cell. He continued at MIT as a professor of biology as well as a member of the staff at the MIT Center for Cancer Research until 1990.

In 1982, Baltimore established the Whitehead Institute for Biomedical Research, an independent entity affiliated with MIT. Baltimore served as the institute’s first director from 1982 until 1990.

In 1990, Baltimore left the Whitehead Institute to become president of Rockefeller University, but he stepped down the following year due to a controversy rooted in a 1986 scientific paper he had coauthored and published in the journal Cell with several colleagues, including MIT faculty member Thereza Imanishi-Kari. After a researcher in Imanishi-Kari’s laboratory was unable to replicate the results reported in the paper, she accused Imanishi-Kari of falsifying the data. Baltimore was never accused of misconduct, but as a coauthor of the paper, he was nonetheless associated with it.

After a lengthy investigation that lasted several years, the Office of Scientific Integrity at the National Institutes of Health, which had funded the research, determined in 1994 that Imanishi-Kari had falsified her data, and it was recommended that she be barred from receiving federal funding for ten years.

Baltimore stood behind Imanishi-Kari and defended her research and integrity; the paper, however, was eventually retracted. Baltimore remained on the Rockefeller faculty, but he left the university in 1994 and returned to MIT. In 1996, the appeals board at the Department of Health and Human Services, which had been appointed by the federal government to review the case, found that Imanishi-Kari was not guilty of misconduct, and the ruling was overturned. Baltimore was appointed president of the California Institute of Technology (Caltech) in 1997, a position he retained until September 2006. As of 2017, he remained Robert Andrews Millikan Professor of Biology at Caltech.

Baltimore has continued his research in using retrovirus vectors to modify the immune system. One of his major areas of inquiry is the potential use of gene therapy to ward off certain types of cancer and to ultimately protect against HIV infection. The therapy consists of introducing genetically reprogrammed immune cells into a subject in order to manufacture antibodies that might serve as a vaccine. The model has shown some promise in animal subjects, but it has not yet been perfected for human patients.

Although Baltimore has stated publicly that an effective HIV vaccine may never be found, he has also expressed a commitment to continue the quest. Baltimore has served on and presided over numerous boards including as president of the American Association for the Advancement of Science (AAAS) in 2008 and then as chairman of the board of directors for the organization.

Impact

Baltimore’s codiscovery helped lay the groundwork for recombinant DNA technology, which scientists have used to produce more disease-resistant food crops as well as a variety of medical products including insulin, growth hormone, and certain vaccines. In 1975, in response to early concerns about potential hazards or abuses his work helped unleash, Baltimore helped organize the International Congress on Recombinant DNA Molecules, better known as Asilomar (after the California location where the group first met), which created what amounted to the first ethical and safety guidelines for the use of recombinant DNA technology. The voluntary standards that were then adopted by the scientific community represented a landmark attempt at self-regulation in the face of rapidly advancing new technologies.

Baltimore’s unexpected discovery that RNA can be transformed into DNA also made possible new approaches to fighting HIV, the virus that causes AIDS. His work has had profound implications for understanding the role viruses play in the development of cancer and for understanding the molecular basis of human immune response.

Baltimore’s expertise has shaped U.S.-policy responses to the AIDS pandemic. An early proponent of federal funding for AIDS-related research, Baltimore cochaired the 1986 National Academy of Sciences committee charged with developing a national strategy for responding to AIDS. In 1996, he was also appointed to direct the National Institutes of Health AIDS Vaccine Research Committee. In 2006, he cofounded Calimmune, a private company dedicated to investigating gene therapies for HIV. He was chair of the company's board until 2015, when he stepped down, remaining a board member.

Baltimore has published over 600 peer-reviewed papers. In addition to winning the Nobel Prize, he was presented the Gustave Stern Award in Virology (1970) and the National Medal of Science (1999). In 2021, Baltimore received the Lasker-Koshland Special Achievement Award in Medical Science. The award was presented every two years to a scientist who has made significant contributions to medical science.

Bibliography

Baltimore, David. "7 Questions for Nobel Laureate David Baltimore." Interview by Mary Engel. Hutch News, 6 Aug. 2015, www.fredhutch.org/en/news/center-news/2015/08/questions-for-nobel-laureate-david-baltimore.html. Accessed 11 Oct. 2024.

Baltimore, David. “The Medicine of the Future.” Town Hall, Los Angeles. 11 Feb. 2003. Address.

Baltimore, David. “Limiting Science: A Biologist’s Perspective.” Daedalus104.4 (2005): 7–15.

Boyer, Lauren. "Fighting the Fight: Dr. David Baltimore." National Science & Technology Medals Foundation, 19 Dec. 2016, www.nationalmedals.org/stories/baltimore-and-the-cure. Accessed 11 Oct. 2024.

Crotty, Shane. Ahead of the Curve: David Baltimore’s Life in Science. Berkeley: U of California P, 2001.

"David Baltimore." Lasker Foundation, 2022, laskerfoundation.org/winners/fundamental-discoveries-academic-leadership-public-advocacy/. Accessed 11 Oct. 2024.

Kruglinski, Susan. “The Discover Interview: David Baltimore.” Discover Sept. 2006: 50–53.

Rothenberg, Albert. Flight from Wonder: An Investigation of Scientific Creativity. Oxford UP, 2015.