A Philadelphia family
Howard Martin Temin was born on December 10, 1934, in Philadelphia, the second of three sons of Henry Temin, an attorney, and Annette Lehman Temin, who was active all her life in civic affairs, especially education. The family was Jewish. His older brother, Michael, became a Philadelphia lawyer, and his younger brother, Peter, became a well-known economist at the Massachusetts Institute of Technology.
Howard went to Philadelphia’s public schools and graduated from Central High School. His interest in biological research was set early: for four summers, from 1949 to 1952, he took part in a programme for high school students at the Jackson Laboratory in Bar Harbor, Maine. Its director, C. C. Little, told his parents that Howard was unquestionably the finest scientist of the fifty-seven students there.
Education and a chance turn
Temin studied biology in the honours programme at Swarthmore College, graduating in 1955, and went on to graduate school at the California Institute of Technology, intending to study embryology. After a year and a half he switched to animal virology and joined the laboratory of Renato Dulbecco. Working closely with Harry Rubin, a postdoctoral fellow there, he studied Rous sarcoma virus, which causes cancer in chickens. He was also strongly influenced by Max Delbrück and Matthew Meselson.
Rous sarcoma virus carries its genes as RNA, not DNA. Yet the cells it turned cancerous passed the change on to their daughter cells, generation after generation, as if the virus’s genes had become a permanent part of the cell. In his doctoral thesis, completed in 1959, Temin wrote that the virus had some kind of close relationship with the genome of the infected cell. In the following year, as a postdoctoral fellow, he formulated what he called the provirus hypothesis.
Science filled his summers. Besides the Jackson Laboratory programme, he spent the summer of 1953 at the Institute for Cancer Research in Philadelphia and returned to the Jackson Laboratory in 1955 before starting graduate school. At Central High School he graduated as valedictorian, and in his speech he spoke about the hydrogen bomb and the prospect of a moon landing.
A heresy in the basement
In 1960 Temin moved to the McArdle Laboratory for Cancer Research at the University of Wisconsin in Madison. His first laboratory was in a basement, with a sump in the tissue culture room and the building’s steam pipes running through his biochemistry lab. There, by 1964, he had sharpened his idea into the DNA provirus hypothesis. Using actinomycin D, a drug that stops cells reading their DNA, he showed that the virus’s survival depended on DNA. He concluded that when the virus infects a cell, its RNA genes are copied into DNA, which then sits in the cell’s chromosomes as a provirus.
This was close to heresy. The central dogma of molecular biology, as most scientists understood it, said that genetic information flows one way only: from DNA to RNA to protein. For six years many leading scientists dismissed Temin’s idea. He kept working, with a small group, convinced that the evidence was on his side.
The McArdle Laboratory had found the post hard to fill, because at the time virology was widely seen as irrelevant to cancer research. Temin worked with only two technicians at first; his first postdoctoral fellow arrived in 1963 and his first graduate student in 1965. Alongside his virus work he studied what controls the multiplication of cells in culture, and showed that a growth-stimulating factor in calf serum was the same as somatomedin, a hormone that mediates the effects of growth hormone.
Reverse transcriptase
To prove his case, Temin needed the enzyme that would do the copying. In 1969 he and his postdoctoral fellow Satoshi Mizutani began searching for it inside virus particles. They found it: an enzyme carried by the virus that builds DNA using RNA as a template, reversing the usual direction of genetic information. At the Massachusetts Institute of Technology, David Baltimore independently found the same enzyme in a mouse leukaemia virus. Both papers were published in the same issue of Nature on June 27, 1970.
The enzyme became known as reverse transcriptase, and viruses that use it as retroviruses. The discovery forced a revision of molecular biology’s central dogma and won general acceptance for Temin’s provirus hypothesis. In 1975 Temin, Baltimore and Dulbecco shared the Nobel Prize in Physiology or Medicine for discoveries concerning the interaction between tumour viruses and the genetic material of the cell.
Recognition followed quickly. Before the Nobel Prize, Temin received the Warren Triennial Prize and the Gairdner International Award, both shared with Baltimore, and the Albert Lasker Award for Basic Medical Research. He was elected to the National Academy of Sciences in 1974 and later became a Foreign Member of the Royal Society of London.
From cancer viruses to HIV
Little more than a decade later, the importance of Temin’s discovery became tragically clear. The virus that causes AIDS, identified in the early 1980s, is a retrovirus. It survives by using reverse transcriptase to write its genes into the DNA of human immune cells. Because scientists already understood the enzyme, it became the first target for AIDS drugs. Zidovudine, also called AZT, a reverse transcriptase inhibitor, was approved in the United States in March 1987 as the first antiretroviral medicine; from 1994 to 1999 it was the main way to stop mothers passing HIV to their babies at birth.
Reverse transcriptase inhibitors remain a cornerstone of the drug combinations that have turned HIV from a death sentence into a manageable condition for millions of people, and they are also used against hepatitis B, which copies itself in a similar way. Reverse transcriptase also became one of the most important tools in biology. Scientists use it to turn the RNA messages of a cell into DNA that can be studied, cloned and measured. It is the basis of many laboratory techniques and diagnostic tests, including the RT-PCR tests used to detect RNA viruses such as the one that causes COVID-19, and engineered retroviruses are used to deliver genes in gene therapy.
A conscience in science
Temin did not keep his views to himself. At the Nobel Banquet in Stockholm in December 1975, with the Queen of Denmark among the audience, he spoke on behalf of the three laureates and said they were outraged that stopping cigarette smoking, the one major measure available to prevent much cancer, had not been more widely adopted. He had the ashtray removed from the laureates’ table. In the same speech he thanked the American taxpayers who had funded their work and hoped that science would be used only for peaceful purposes.
He also used his fame to help persecuted colleagues. In October 1976 he visited Jewish scientists in the Soviet Union who had lost their jobs after applying to emigrate to Israel. He brought gifts they could sell to survive and scientific journals they were not allowed to receive. When a lecture he gave to these scientists was followed by arrests, he recorded one scientist’s account and passed the tape to American newspapers.
Jewish identity
Temin was born to a Jewish family in Philadelphia and is counted by the Jewish Virtual Library among the Jewish Nobel laureates in medicine. His commitment to the refuseniks, Soviet Jews punished for seeking to emigrate, shows a sense of solidarity that he backed with action, visiting them in person and making their plight known in the West.
In 1962 he married Rayla Greenberg of Brooklyn, a population geneticist who also worked at the University of Wisconsin. In his Nobel autobiography he called her a constant source of support and warmth. They had two daughters, Sarah Beth and Miriam.
Later work and service
Temin spent his whole independent career at Wisconsin, where he became American Cancer Society Professor of Viral Oncology and Cell Biology. After the Nobel Prize he studied how retroviruses package their genes, how they vary and evolve, and how a vaccine against HIV might be made. He advised the National Institutes of Health, including on gene therapy, served on the National Cancer Advisory Board and on AIDS and vaccine panels, and sat on the World Health Organization’s advisory council. He received the National Medal of Science in 1992.
He also trained many scientists. One of his doctoral students, Edward Fritsch, co-wrote Molecular Cloning: A Laboratory Manual, for decades the standard handbook of genetic engineering laboratories.
Temin served on the editorial boards of the Journal of Virology and the Proceedings of the National Academy of Sciences and was a founding member of the World Cultural Council in 1981. He thought hard about the uses of science; in his Nobel Banquet speech he reminded the audience that the U.S. government supports productive projects as well as, unfortunately, some destructive ones.
Death and legacy
In a bitter irony, Temin, a lifelong non-smoker and campaigner against smoking, developed lung cancer. He died in Madison on February 9, 1994, aged 59.
His career is a lesson in scientific courage. For years he held to an idea most of his field thought impossible, because his experiments told him it was true. The enzyme he predicted and found has given the world drugs that keep millions of people with HIV alive, tests that detect dangerous viruses, and tools used in laboratories everywhere.
Sources & further reading
Howard M. Temin, Biographical, NobelPrize.org · Howard M. Temin, Banquet speech, NobelPrize.org · Scientist of the Day: Howard Temin, Linda Hall Library · Howard Temin, Jewish Virtual Library · Howard Martin Temin, Wikipedia · Zidovudine, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
A life of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.