If we review great cancer science arising in California and the Beach Boys, we should certainly not forget the Little Old Lady From Pasadena (Go granny, go granny, go granny, go), but what makes Pasadena really of interest to us as cancer aficionados is the presence of the California Institute of Technology, or Caltech, from which many Nobel laureates have arisen (including Sheldon of “The Big Bang Theory”). The 1975 Nobel Prize in Medicine was awarded to three Caltech scientists—Renato Dulbecco, Howard Temin and David Baltimore—for their work on tumor viruses.

Renato Dulbecco was born in Italy and entered the University of Turin at age 16 where he studied medicine. In the laboratory where he worked, he became friends with Salvador Luria and Rita Levi-Montalcini, both of whom later won the Nobel Prize. Dulbecco was called to military service during World War II but was wounded. After the war, he returned to doing research in a laboratory in Turin. By this time, Luria was in the U.S., and so Dulbecco and Levi-Montalcini went to to join him at Indiana University. There he studied phages, viruses that infect bacteria, and at least for a while shared an office with James Watson, another future Nobel laureate, and caught the attention of Max Delbruck, himself a later Nobel laureate, and was recruited to Caltech.

Dulbecco started working on how animal viruses functioned, and actually made significant contributions in poliovirus. He went from that to studying animal tumor viruses, starting with polyoma virus and then Rous sarcoma virus. He developed methods for quantifying the presence of virus particles and determining the presence of transformed cells. In the late 1950s, Howard Temin joined him as a student. In 1975, Dulbecco, Temin and David Baltimore would share the 1975 Nobel Prize in Medicine for their contributions to the understanding of how viruses cause cancer, essentially by the discovery of reverse transcriptase and the explanation of how RNA could be integrated into the normal cell’s DNA genome. This was also the basis for our later understanding of human immunodeficiency virus (HIV).

Howard Temin was born and raised in Philadelphia, his father an attorney and his mother a social activist, and so was imbued with values of social justice and independent thinking. The money earmarked for his bar mitzvah party was donated to a local camp for displaced persons. His speech as valedictorian of his high school class was devoted to decrying the recent testing of a hydrogen bomb.

He attended Swarthmore College and then joined Dulbecco’s lab at Caltech to earn his PhD in animal virology. He discovered that the Rous sarcoma virus had “some kind of close relationship” with the genome of the tumor cell—this was in 1960. Temin was recruited to the McArdle Laboratory for Cancer Research at the University of Wisconsin, one of the great centers for cancer research in the U.S., to start a research lab in viral carcinogenesis. In studying RSV, an RNA virus, Temin applied actinomycin D, which inhibits DNA. This blocked the activity of RSV when it was introduced into normal cells, implying that DNA was in the pathway from RSV to the action of RSV. Temin ultimately discovered that RSV contained an enzyme, reverse transcriptase, which generated complementary DNA from the RNA in the virus, and it was this DNA strand that was being inserted into the normal cell to transform it to a cancer cell.

To complete our trio, David Baltimore was raised in Forest Hills and Rego Park until his family moved to Great Neck because his mother felt the schools were better there. His father was Orthodox and his mother an atheist, so he attended
synagogue regularly and observed Jewish holidays with his father until his bar mitzvah. He also went to Swarthmore College, and during a summer program at Cold Spring Harbor Laboratory met Salvador Luria and Cyrus Levinthal who were initiating a program in molecular biology at MIT (this was the late 1950s). He went there and completed his PhD in two years. He got into animal virology as well and spent some time at Rockefeller University, subsequently doing postdoctoral work with James Darnell at MIT and Jerard Hurwitz at Albert Einstein College of Medicine. He spent several years at the Salk Institute in La Jolla before being recruited back to join the faculty at MIT under Luria.

Baltimore discovered that an RNA-containing virus, vesicular stomatitis virus, contained an RNA-dependent polymerase within the virus to replicate its RNA. When this virus would enter a healthy mammalian cell, this was the method it would utilize to replicate itself. He subsequently shifted his work to tumor viruses and investigated our old friend, Rous sarcoma virus, as well as Rauscher murine leukemia virus—these are both RNA-containing tumor viruses. Virtually simultaneously with Temin, he discovered reverse transcriptase and the mechanism of transcription of RNA to DNA, and coined the term “retroviruses.” He was 37 years old when he won the Nobel Prize in 1975.

Baltimore subsequently became a major scientific administrator. In 1990 he became president of Rockefeller University. And for our purposes, he was appointed president of Caltech in 1997, a position he held until 2019.

Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].

This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.