Awards & Honors

Lasker Awardee

Hidesaburo Hanafusa

(1929—2009)

1982 Albert Lasker Basic Medical Research Award

Evolution has equipped the human body with innumerable mechanisms to protect it against predatory elements and the ravages of disease. Research into the human genome has furthermore uncovered a panoply of dormant functionality ready to be called into action, potentially providing other lines of defense. In certain situations, however, some of the most innocent genes can become killers. During the 1960s and 1970s, research by Japanese molecular oncologist Hidesaburo Hanafusa evidenced the existence of oncogenes, genes with the ability to induce cancer. The discovery effected a paradigm shift in cancer research and garnered Dr. Hanafusa a share of the 1982 Albert Lasker Basic Medical Research Award.

In 1911, Rockefeller Institute scientist Peyton Rous made the seminal discovery that a virus can cause cancer. Though his finding — the virus is now called Rous sarcoma virus (RSV) — was initially viewed with a debilitating skepticism, the definitive proof achieved by his Rockefeller colleague Richard E. Shope in 1934 opened from Dr. Rous's discovery an entirely new field of research. Three decades later, viral oncologists were still feverishly adding to the impressive list of cancer-causing viruses they had tracked down, but virtually nothing was known about the mechanisms by which the microbes replicate or induce malignancy.

In the early 1960s, during experiments at the University of California, Berkeley, to purify Rous sarcoma virus, Dr. Hanafusa discovered that, though the virus was powerful enough to induce cancer, it had one significant flaw — it could not replicate on its own. Sometime in its recent evolution, RSV had picked up a useful stowaway: a noncancerous version of the Rous virus called RAV, which brought with it the power of replication. In return for this gift, Dr. Hanafusa found, RSV promotes continual proliferation of a host cell (cancer), which then produces an abundance of molecular tools that further aid the stowaway virus in its own replication processes. Dr. Hanafusa's hypothesis from observing the pair of viruses in action was the first to suggest a clear role for an oncogene. Because each virus has something the other doesn't — RSV can transform normal genes into cancerous ones and RAV can replicate — the segment of the viral genome that codes for replication must have been replaced in RSV by a gene or segment of genes that codes for transformation. That region on the RSV genome was mapped a few years later and the transforming gene discovered there was named src, for sarcoma.

Continuing studies with retroviral replication led to the observation that the viral genomes of RSV daughter cells are made of DNA rather than the parent cell's RNA. (Research by David Baltimore would later explain this phenomenon.) Termed "proviruses," the researchers found that these new-and-improved copies contain extra genetic material that has the ability to incorporate itself into the DNA of normal cells.

Dr. Hanafusa's work at The Rockefeller University, which he joined as professor and head of laboratory in 1973, was critical in firmly establishing the fact that potentially cancer-causing oncogenes are present in healthy animal and human cells. In 1976, two researchers at the University of California, San Francisco, J. Michael Bishop and Harold Varmus, reported that the section of the RSV genome that contains src is remarkably similar to a section that exists in healthy animal cells. Dr. Hanafusa and his colleagues discovered in subsequent experiments that mutant versions of RSV that had lost the src gene could regain their cancer-causing ability through growth in normal host cells. An identical but silent gene from the host cells, Dr. Hanafusa found, had been captured by the virus, mutated to activate its transformative property, and used to fill the gap left by the missing viral gene. These findings led to the critical hypothesis, since abundantly confirmed, that viral cancer-causing genes are uncontrolled versions of normal cellular genes.

After Dr. Hanafusa's revelations, several other laboratories identified normal cellular genes that had been co-opted by mutant retroviruses for their transformative potential. The surge of research that followed — now commonly known as the oncogene revolution — fundamentally changed how both basic researchers and physicians viewed the already complex phenomenon of cancer. Dr. Hanafusa shared the 1982 Lasker Award with Dr. Bishop and Dr. Varmus, as well as Raymond Erikson of Harvard University and Robert Gallo of the National Institutes of Health.

CAREER

Born in Nishinomiya, Japan, in 1929, Dr. Hanafusa was educated at Osaka University, where he received his Ph.D. in biochemistry in 1960. The following year, he left Japan to join the laboratory of Harry Rubin at the University of California, Berkeley. From 1964 to 1966, he was a visiting scientist at the Collège de France in Paris, and then he accepted a post as head of a laboratory of viral oncology at the Public Health Research Institute in New York City. Dr. Hanafusa joined The Rockefeller University in 1973, as professor and head of the Laboratory of Molecular Oncology. He retired in 1998 and returned to Japan, where he was director of the Osaka Bioscience Institute until his death in 2009. Dr. Hanafusa was a foreign associate of the United States National Academy of Sciences and a member of the Japan Academy. In addition to the Lasker Award, he received a Howard Taylor Ricketts Award, an Asahi Press Prize, an Alfred P. Sloan Jr. Prize and a Japan Order of Culture.