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Principles of Biotechnology David Baltimore One-Way from DNA to RNA

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Principles of Biotechnology David Baltimore One-Way from DNA to RNA Important Figures in Biotechnology David Baltimore its interdisciplinary nature. He envisioned an envi- ronment 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 Dr. David Baltimore, 2014. By Bob Paz. is an uncommon enzyme used by retroviruses to syn- thesize DNA from RNA. Baltimore showed that retro- American molecular biologist viruses have encoded in them genetic instructions for the manufacture of an enzyme (reverse transcriptase) BORN: March 7, 1938; New York, New York capable of copying DNA from an RNA template. The PRIMARY FIELD: Biology newly-created viral DNA is then able to transform an SPECIALTIES: Molecular biology; virology; microbi- infected cell into a malignant cell. ology Baltimore’s codiscovery of reverse transcriptase had its roots in his early research on the ways in which Molecular biologist and Nobel laureate David Baltimore poliovirus manages to penetrate cellular defenses has achieved great influence as a researcher, scientific poli- and then replicate. He had conducted this work at cymaker, and leader of academic institutions. He is most cel- the Salk Institute in California for three years begin- ebrated for his molecular virology discoveries in recombinant ning in 1965. This research led Baltimore to conduct DNA research. experiments focusing on two particular RNA tumor viruses: one that causes leukemia in mice and an- Early Life other that causes sarcoma in chickens. David Baltimore was born in New York City on March At the time that Baltimore began his experiments, 7, 1938, to parents Gertrude Lipschitz, an experi- scientists already knew that under certain condi- mental psychologist, and Richard Baltimore, who tions some viruses caused tumors in chickens and worked in the garment industry. His decision to be- that some viruses could also cause different types of come a molecular biologist began in 1955 when he cancer in other animals such as mice. Researchers was a junior in high school and his mother arranged eventually discovered that both viruses containing for him to spend a summer working on mouse ge- DNA as their genetic material and viruses containing netics with a group of research biologists at the the kind of genetic material known as RNA were ca- Jackson Memorial Laboratory in Bar Harbor, Maine. pable of triggering a normal cell to undergo growth That summer Baltimore also met future colleague characteristics typical of a tumor cell. A central mys- and friend Howard Martin Temin, who had just grad- tery remained: How did the genetic material of a uated from college and served as a mentor. tumor-causing RNA virus apparently manage to infil- Baltimore joined the faculty of MIT in 1968, where trate the DNA of a healthy cell? he would remain for much of the next thirty years, Up until that time, most molecular biologists be- and conducted research that was ahead of its time in lieved transfers of genetic information to be strictly 348 Principles of Biotechnology David Baltimore one-way from DNA to RNA. Baltimore, who had been As of 2017, he remained Robert Andrews Millikan studying virus-specific enzymes that copy RNA from Professor of Biology at Caltech. RNA, began using similar techniques to investigate Baltimore has continued his research in using whether some viruses were capable of copying DNA retrovirus vectors to modify the immune system. from RNA. Baltimore’s experiments clarified the mo- One of his major areas of inquiry is the potential lecular process and the role of reverse transcriptase use of gene therapy to ward off certain types of by which cancer-causing RNA viruses succeed in in- cancer and to ultimately protect against HIV infec- fecting and permanently changing healthy cells. tion. The therapy consists of introducing geneti- In 1975, Baltimore shared the Nobel Prize in cally reprogrammed immune cells into a subject in Physiology or Medicine with Howard Temin and order to manufacture antibodies that might serve Renato Dulbecco for groundbreaking insights into as a vaccine. The model has shown some promise in the interaction between tumor viruses and the ge- animal subjects, but it has not yet been perfected for netic material of the cell. He continued at MIT as a human patients. professor of biology as well as a member of the staff at Although Baltimore has stated publically that an the MIT Center for Cancer Research until 1990. effective HIV vaccine may never be found, he has In 1982, Baltimore established the Whitehead also expressed a commitment to continue the quest. Institute for Biomedical Research, an independent Baltimore has served on and presided over numerous entity affiliated with MIT. Baltimore served as the in- boards including as president of the American stitute’s first director from 1982 until 1990. Association for the Advancement of Science (AAAS) In 1990, Baltimore left the Whitehead Institute to in 2008 and then as chairman of the board of direc- become president of Rockefeller University, but he tors for the organization. stepped down the following year due to a controversy rooted in a 1986 scientific paper he had coauthored and Impact published in the journal Cell with several colleagues, in- Baltimore’s codiscovery helped lay the groundwork for cluding MIT faculty member Thereza Imanishi-Kari. recombinant DNA technology, which scientists have After a researcher in Imanishi-Kari’s laboratory was un- used to produce more disease-resistant food crops as able to replicate the results reported in the paper, she well as a variety of medical products including insulin, accused Imanishi-Kari of falsifying the data. Baltimore growth hormone, and certain vaccines. In 1975, in was never accused of misconduct, but as a coauthor of response to early concerns about potential hazards the paper, he was nonetheless associated with it. or abuses his work helped unleash, Baltimore helped After a lengthy investigation that lasted several organize the International Congress on Recombinant years, the Office of Scientific Integrity at the National DNA Molecules, better known as Asilomar (after the Institutes of Health, which had funded the research, California location where the group first met), which determined in 1994 that Imanishi-Kari had falsified created what amounted to the first ethical and safety her data, and it was recommended that she be barred guidelines for the use of recombinant DNA tech- from receiving federal funding for ten years. nology. The voluntary standards that were then ad- Baltimore stood behind Imanishi-Kari and de- opted by the scientific community represented a land- fended her research and integrity; the paper, how- mark attempt at self-regulation in the face of rapidly ever, was eventually retracted. Baltimore remained advancing new technologies. on the Rockefeller faculty, but he left the university Baltimore’s unexpected discovery that RNA can in 1994 and returned to MIT. In 1996, the appeals be transformed into DNA also made possible new ap- board at the Department of Health and Human proaches to fighting HIV, the virus that causes AIDS. Services, which had been appointed by the federal His work has had profound implications for under- government to review the case, found that Imanishi- standing the role viruses play in the development of Kari was not guilty of misconduct, and the ruling was cancer and for understanding the molecular basis of overturned. Baltimore was appointed president of human immune response. the California Institute of Technology (Caltech) in Baltimore’s expertise has shaped U.S.-policy re- 1997, a position he retained until September 2006. sponses to the AIDS pandemic. An early proponent of federal funding for AIDS-related research, Baltimore 349 David Baltimore Principles of Biotechnology DAVID BALTIMORE: TUMOR-GROWTH THROUGH VIRAL RNA In the 1950s, virologist Renato Dulbecco’s research helped proved the same hypothesis at the University of Wisconsin– to explain how DNA tumor viruses change normal cells Madison, utilizing an avian myoblastosis virus, a type of into cancerous cells. His work essentially revealed that the leukemia found in birds. This process came to be known as viral DNA gets into the nucleus of a cell, at which point it reverse transcriptase. combines with the cellular DNA. Thereafter, when the cell The trio waited five years to receive their Nobel Prize for divides, the characteristics of the viral DNA, and not the their discoveries, which was considered a short waiting pe- cellular DNA, are passed down. Accordingly, the disease riod in the scientific community; Baltimore was only thirty- spreads. Subsequently, virologist Harold Temin hypothe- seven years old when he received the Nobel Prize. Though sized in the 1960s that an RNA tumor virus—one that would they were awarded the Nobel Prize nearly forty years ago, cause cancer—could infect healthy cells by making a DNA the research and work of Baltimore, Dulbecco, and Temin copy of itself. on the reverse transcriptase has had significant implications In 1970, David Baltimore was studying leukemia and sar- for the understanding of and research into viruses and dis- coma viruses at the Massachusetts Institute of Technology eases. Specifically, discovery of reverse transcriptase led (MIT) and was able to demonstrate the occurrence of a cer- to a better understanding of retroviruses, most importantly tain enzyme in viral RNA called transcriptase. This enzyme human immunodeficiency virus (HIV), which causes ac- allowed the RNA virus to make a DNA copy of itself. In quired immune deficiency syndrome (AIDS). In fact, the other words, a molecule of RNA in a cancer-causing virus scientists who discovered that HIV causes AIDS were able could change into viral DNA, and then splice itself to the to make that discovery by using the reverse transcriptase DNA of a host cell.
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