William A. Haseltine (born October 17, 1944) is an American scientist, businessman, author, and philanthropist. He is known for his work on HIV/AIDS and the human genome.
Haseltine was a professor at Harvard Medical School, where he founded two research departments on cancer and HIV/AIDS. He is a founder of several biotechnology companies, including Cambridge Biosciences, The Virus Research Institute, ProScript, LeukoSite, Dendreon, Diversa, X-VAX, and Demetrix. He was a founder chairman and CEO of Human Genome Sciences, a company that pioneered the application of genomics to drug discovery.
Biography He was born to a scientific family. His grandfather was an engineer, his father a PhD physicist. He was raised at the Naval Ordnance Test Station at China Lake in the Mojave Desert of California, surrounded by weapons scientists and engineers. His older sister Florence received both a Ph.D. in biophysics and an MD, and his younger brother Eric a PhD in neurobiology. His younger sister Susan became a specialist in computer systems.
Haseltine's early life is described in the book Rapture, by Brian Alexander (1d), and in Gene Masters by Ingrid Winkelgren (3d).
Haseltine graduated from Sherman E. Burroughs High School in 1962. In 1966 he received a BA in chemistry from the University of California, Berkeley, and in 1973 a Ph.D. in biophysics from Harvard University.
Career As a pre-medical undergraduate student majoring in chemistry, he published two scientific papers, one on the composition of the Martian atmosphere in Science and a second on the use of isotope shifted lasers for communication to outer space in Applied Physics Letters. He was elected to Phi Beta Kappa his junior year and graduated at the top of his class. Upon graduation he decided to learn as much about science as possible towards creating new ways to treat and cure disease.
At Harvard University, he worked under the direction of James D. Watson, who shared the Nobel Prize for the discovery of the structure of DNA, and Walter Gilbert, who later received a Nobel Prize for developing a method to determine DNA sequences. He elucidated the means by which bacteria signal the shift from growth when food is abundant to maintenance when food is scarce, the topic of his PhD thesis titled Magic Spot and the Stringent Response.
During his graduate studies, Haseltine was also active in his opposition to the war in Vietnam. He wrote several articles on the use of technology in the Vietnam War and broke the "Agent Orange Defoliation" story in a cover article in the New Republic. He worked with the American Friends Service Committee to create a resource center for those who wished to understand their own communities’ involvement in the war and lectured against the war throughout the country for several years. He was a founder of "Science for the People".
In 1973, Haseltine joined the laboratory of David Baltimore at the Massachusetts Institute of Technology as a post-doctoral fellow. There he began to work on fundamental aspects of how retroviruses known to cause cancer in animals reproduce. His work, in collaboration with several other scientists, provided unexpected insights into the process of retrovirus replication and was recognized as innovative in publication in leading scientific journals. This work prepared him for research on human disease and retroviruses, both important later in his career.
He interrupted his postdoctoral studies at MIT briefly the summer of 1973 to serve as a visiting professor at the University of Copenhagen Faculty of Health and Medical Sciences, where he continued his work on the regulation of gene expression in bacteria.
Research
Cancer research In 1976, he joined the faculty of the new comprehensive cancer center, the Dana Farber Cancer Institute affiliated with Harvard Medical School. He became a professor in the Harvard Medical School Department of Pathology and shortly thereafter a professor in the Cancer Biology Department of the Harvard School of Public Health. He founded the equivalent of two academic departments: the Laboratory of Biochemical Pharmacology devoted to work on cancer cause and treatment, and the Division of Human Retrovirology, dedicated, understanding and finding treatments for HIV/AIDS. As a professor, he published more than two hundred research articles in leading scientific journals and edited several books. He mentored dozens of graduate students and postdoctoral fellows, many of whom have gone on to successful careers of their own at Harvard and elsewhere. He taught advanced level courses in cancer biology and HIV/AIDS to graduate and medical students. For many years he taught a course "Biology and Social Issues" for Harvard non-science undergraduates and was a tutor and thesis advisor for several generations of Harvard undergraduate biochemistry students.
Retrovirus replication continued to be a focus of his early research as a Harvard professor. This research led to fundamental insights including the "end to end jumping" of the initial copy of the genome. He then began to focus on two related issues: how retroviruses induce cancer in animals, and whether or not retroviruses cause cancer and other diseases in humans. His laboratory discovered that the key determinant of the ability of retroviruses, those that do not carry oncogenes, to cause cancer is their ability to rapidly replicate in cells that themselves grow rapidly. This allows the retrovirus to implant nearby a cellular oncogene. Another impact for science was his work on the small genetic elements upstream of the transcription start site, now called enhancers, which determine the rate at which genes are copied into RNA. This work provided a key insight into factors that distinguish one cell type from another. Haseltine's account of having identified transcriptional enhancers has been disputed. In The Exceptions (2023), Kate Zernike writes that the discovery was first published by Nancy Hopkins' laboratory in PNAS in July 1983, and situates the episode within a broader account of the treatment of women scientists at MIT. Zernike gathered statements from individuals from the time that argued Haseltine's professor, David Baltimore, had repeatedly acted against Hopkins' advancement in the field due to his resentment of her success as a woman in science.
In 1978, Haseltine began to focus on improving chemotherapy by exploring how the drugs and radiation used to treat cancer worked, as many anti-cancer treatments killed the rapidly growing cancer cells by damaging DNA. The Haseltine lab was among the first to apply the new techniques of DNA sequencing to this understanding of DNA damage and its repair.
The laboratory extended this work to study the process by which cancer causing chemicals and radiation cause the changes to DNA which can lead to cancer. The work revealed a new and unexpected form of sun-induced DNA damage, called the 6-4 lesion, is responsible for most mutations in sun exposed skin that cause cancers including melanoma.
Human T Cell Leukemia Virus Haseltine was one of the very few scientists in the late 1970s who continued to work on the concept that retroviruses played an important role in human diseases. This idea once popular in the late 1960s and early 1970s was abandoned by many after a decade or more of a futile search for human retroviruses by laboratories around the world. Haseltine, working with a few other scientists, thought that human retroviruses would behave differently from those that affect laboratory animals such as mice and would behave more like those that cause cancer and immunological deficiencies in non-laboratory animals. These viruses seem to disappear after early infection, the disease appearing only after several years. Haseltine devoted part of his laboratory to the study of retroviruses in these animals in the hope that they would provide insight into human disease. In 1978 he helped to design a special containment laboratory at the Dana Farber Cancer Institute to work on these viruses should they be discovered, a step later essential for his work on HIV/AIDS.
In 1979 the first human retrovirus to cause a human disease was discovered, the Human T cell leukemia Virus (HTLV). HTLV is sexually transmitted from men to women, by women to their children and by blood transfusions. The disease, T-cell leukemia, arises decades after infection. Haseltine and his laboratory discovered that HTLV carried a novel gene called the transactivator X (now called tax). Over the next few years, Haseltine and his colleagues showed that tax is the gene responsible for the cancers. Haseltine spent the summer of 1983 as a visiting professor at the University of Kyoto working with Japanese scientists studying the Human T cell Leukemia virus, a virus endemic to Japan.
HIV/AIDS research and public policy The work HTLV prepared Haseltine for work on AIDS. Before the AIDS epidemic was identified, Haseltine already had the expertise and the facilities to study human retroviruses. He first learned of the new disease from colleagues in late 1981. In early 1982 he and a few other scientists who were working on HTLV formed a small working group to identify the cause of the new disease. They met regularly every 4–6 weeks from early 1982 to 1985. With help from the Centers of Disease Control, this group formed the hypothesis that AIDS was caused by a human retrovirus similar to HTLV. They proposed to use methods similar to those used to isolate the HTLV virus to find this new virus. These methods were successfully used to isolate the virus, now called the Human Immunodeficiency Virus (HIV) and to demonstrate that it is the cause of AIDS.
He predicted that drugs that target these proteins will also be effective in treating the infection. A drug that inhibits the rev protein has been approved by the USA Food and Drug administration for treatment of HIV infection. His laboratory went on to describe additional viral genes and proteins – vpr, vpu, vif, and nef required for efficient virus growth in some but not all circumstances.
The discoveries were summarized in an article in 1988 in Scientific American.
Haseltine was appointed to the council of the National Institute of Allergy and Infectious Disease (NIAID) to help direct how these funds were to be used. Over the next few years funding of HIV/AIDS research grew to about $2 billion per year. Haseltine played an important early role in the creation of the International Society for AIDS Research, now the International AIDS Society, and was the Founding editor of the scientific journal AIDS Research and Human Retroviruses..
Haseltine then helped design programs to transfer knowledge from academic laboratories to pharmaceutical and biotechnology companies to develop new anti viral drugs. Early on pharmaceutical companies were reluctant to initiate new research programs on HIV/AIDS. Biotechnology companies lacked the necessary funds and expertise for such work. To address this issue, Haseltine suggested that NIAID create a special grant program to encourage pharmaceutical and biotech companies to work on HIV related problems. Under this program a relatively large amount of money was granted to academic scientists provided that their laboratory have a pharmaceutical or biotechnology partner capable of translating knew knowledge to new drugs. The majority of the funds of these grants went to the industry partner to encourage the development of new drug research activities. These co-operative drug development grants led directly to the discovery of the protease inhibitors that changed the course of HIV/AIDS treatment and later to drugs that effectively target the integrase and envelope proteins.
By 1992, only ten years after the AIDS virus was first recognized, the institutions that today guide HIV/AIDS research were created and still endure.