Howard Martin Temin
Howard Martin Temin was an influential American biologist born on December 10, 1934, in Philadelphia, Pennsylvania. He demonstrated an early passion for science and history, later earning a degree in biology from Swarthmore College. Temin's significant contributions to molecular biology emerged during his tenure at the California Institute of Technology and later at the University of Wisconsin’s McArdle Laboratory for Cancer Research. His most notable work involved the study of RNA tumor viruses, particularly the Rous sarcoma virus (RSV), leading to the development of the provirus hypothesis, which posited that these viruses could replicate through a DNA intermediate. This groundbreaking idea initially faced skepticism but was later validated by the discovery of the enzyme reverse transcriptase, which plays a vital role in the replication of retroviruses, including the human immunodeficiency virus (HIV). Temin received the Nobel Prize in Physiology or Medicine in 1975 for his pivotal research. Throughout his career, he remained dedicated to laboratory work and continued to publish significant findings even after being diagnosed with cancer, demonstrating resilience and commitment to science until his death on February 9, 1994. His work has had lasting implications in virology and cancer research.
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Howard Martin Temin
American molecular biologist
- Born: December 10, 1934; Philadelphia, Pennsylvania
- Died: February 9, 1994; Madison, Wisconsin
Howard Temin discovered the presence of a reverse transcriptase enzyme in the capsid of ribonucleic acid (RNA) tumor viruses, providing an explanation for how their genome is copied into deoxyribonucleic acid (DNA). His work greatly influenced the development of treatments for deadly viruses.
Primary field: Biology
Specialties: Molecular biology; virology; biochemistry
Early Life
Howard Martin Temin was born December 10, 1934 in Philadelphia, Pennsylvania, the second of three sons in the family of Henry and Annette Lehmann Temin. Temin developed a love of history and science at a young age. He attended Charles W. Henry Elementary in Germantown, a suburb of Philadelphia. In 1951, he graduated from Central High School, a school for advanced students in Philadelphia. Temin presented the valedictory address, during which he spoke of the challenges of the new atomic age.
Beginning in 1950, Temin attended the first of three summer sessions at Jackson Laboratory in Bar Harbor, Maine. His work included the study of gonadotropic hormones and their relationship to ovulation in rabbits. In 1953, he published his first scientific paper in the Journal of Heredity under the direction of biochemist Theodore Ingalls. The article discussed congenital abnormalities in mice.
In 1951, Temin enrolled at Swarthmore College, graduating with a degree in biology four years later. Temin demonstrated his independent streak by refusing to participate in graduation ceremonies following a dispute with faculty. Nevertheless, he was described in the class yearbook as a future giant in the field of molecular biology.
Life’s Work
Temin entered graduate school at the California Institute of Technology (Caltech) in 1955, working with biologist Albert Tyler, a student of geneticist Thomas Hunt Morgan. Temin and Tyler studied the embryological development of fruit flies. Temin’s colleagues at Caltech included biochemist John Cairns, geneticist Matthew Meselson and molecular biologist Frank Stahl, all of whom would subsequently leave significant imprints in the field of genetics. In 1957, Temin joined the laboratory of virologist Renato Dulbecco. In the early 1950s, Dulbecco had published a method for quantitating poliovirus in monolayers of cells, based on the ability of the virus to produce foci of killing plaques on cells. Harry Rubin, a postdoctoral student, was attempting to develop an analogous method for the quantitation of a tumor virus, the Rous sarcoma virus (RSV), and Temin joined Rubin in this work. By 1958, Temin and Rubin published their first joint paper on the subject. They produced an assay test to determine the ability of RSV to transform normal cells into those with malignant properties, a procedure known as a focus assay.
Temin’s and Rubin’s research on the subject of RSV produced several scientific publications during the next year, including one of their observations that sensitivity of RSV to irradiation suggested a role for DNA in its replication cycle. Since the genome of RSV was RNA, Temin’s interpretation was met with significant skepticism. In 1959, he suggested that given the radiation sensitivity of the virus, it likely replicated through a DNA intermediate, which integrated into the infected host genome. This argument was later termed the provirus hypothesis.
In 1959, Temin received his PhD from Caltech but remained there another year while pursuing further genetic studies of RSV. He became increasingly convinced that his provirus hypothesis was correct. The following year, he moved to the University of Wisconsin’s McArdle Laboratory for Cancer Research, where he remained for the duration of his career.
In 1962, Temin married Rayna Greenberg. The couple had two daughters. During the next several years, Temin observed that inhibitors, which act at the level of DNA, would also inhibit the activity of RSV, while having no effect on growth of other RNA viruses. These results fit well with the provirus hypothesis.
At the time, viruses were not thought to incorporate enzymes within their structure. The idea that an enzyme could copy RNA into DNA was even more novel. In 1967, when biologist Joseph Kates demonstrated that poxvirus carried an enzyme for transcribing DNA into RNA as part of its structure. Other scientists began discovering similar results with other viruses. In addition, it was discovered that certain DNA transforming viruses did so through integration into host cell genomes.
In 1970, Satoshi Mizutani, a postdoctoral fellow in Temin’s laboratory, developed an assay method for measuring the activity of an enzyme capable of transcribing RNA into DNA, an enzyme referred to as the reverse transcriptase. Temin announced the results at a cancer conference in Houston, Texas in May 1970. An article was published shortly afterwards in the journal Nature, along with an identical discovery reported by biologist David Baltimore using a murine (mouse) RNA tumor virus. The presence of the enzyme was subsequently reported in a large number of other RNA tumor viruses. In 1975, on his forty-first birthday, Temin was awarded the Nobel Prize in Physiology or Medicine.
Temin spent much of his career studying the genetics of avian tumor viruses such as RSV, now placed in the viral category of retroviruses—RNA viruses that utilize a DNA intermediate. Though internationally renowned for his work, he remained dedicated to the working in the laboratory. In 1992, he was diagnosed with cancer. Although his cancer proved fatal, Temin still managed to produce fifteen publications while battling the disease. He also applied for a patent for an AIDS vaccine. Late in his career, Temin received an honorary degree from his alma mater Swarthmore, as well as honorary degrees from numerous other universities.
Temin died on February 9, 1994, from a rare form of lung cancer, adenocarcinoma. Temin never smoked cigarettes and was a vociferous advocate of antismoking campaigns throughout his life.
Impact
Beginning with the work of pathologist Peyton Rous early in the twentieth century, it became apparent that the class of infectious agents known as RNA tumor viruses could transform normal cells into malignant ones. Temin’s work in the 1960s suggested that these viruses replicate using a DNA intermediate. Since the cell was not known to encode an enzyme that copies RNA into DNA, Temin’s hypothesis was initially ignored by the scientific establishment. Geneticist Francis Crick had posited in the 1950s that the flow of information in the cell went from DNA to RNA to protein, a flow known as the “central dogma of molecular biology.” Temin’s hypothesis seemed to contradict what had become the consensus among biologists pertaining to Crick’s hypothesis, despite the fact that Crick did not actually rule out the possibility of RNA to DNA transfer.
In 1970, Temin and Baltimore, working independently, demonstrated the presence of reverse transcriptase as part of the structure of viruses. The discovery explained how RNA tumor viruses could integrate into the host in a form known as a provirus. The existence of the reverse transcriptase was found to be integral to the replication of a larger class of viruses now called retroviruses.
Retrovirologists quickly attempted to apply Temin’s work to explain how viruses might cause cancer. Their hypotheses regarding the provirus theory of cancer were subsequently shown to be premature, as it became increasingly that clear viruses were not associated with most human cancers. However, the reverse transcriptase was shown to play a major role in replication of other human retroviruses as well, most notably the human immunodeficiency virus (HIV). The first generation of anti-HIV drugs specifically targeted the viral reverse transcriptase. A cellular reverse transcriptase was also identified by molecular biologist Carol Greider in the 1980s as the enzyme that synthesizes telomeres on the tips of chromosomes. Temin’s discovery opened the way for scientific acceptance of such an enzyme.
Bibliography
Crotty, Shane. Ahead of the Curve: David Baltimore’s Life in Science. Berkeley: U of California P, 2001. Print. Biography of Baltimore, codiscoverer of the reverse transcriptase. The role played by Temin in the discovery of reverse transcriptase is also highlighted.
Mukherjee, Siddhartha. The Emperor of All Maladies: A Biography of Cancer. New York: Scribner, 2010. Print. Pulitzer Prize–winning book about cancer, from its earliest descriptions to modern discoveries and treatments. Temin’s contributions are discussed.
Varmus, Harold. The Art and Politics of Science. New York: Norton, 2009. Print. Autobiography of one of the men who discovered the significance of cellular oncogenes. Discusses the role played by Temin and others in discovery and significance of the reverse transcriptase.