World-Renowned Geneticist at UCSF Dies

By Jennifer O'Brien

Ira Herskowitz, PhD, one of the country’s leading geneticists, whose studies on the yeast Saccharomyces cerevisiae yielded major insights into the fundamental aspects of cells and who was a pioneer in pharmacogenetics—the study of the way natural variations in individuals’ genes affect their response to drugs - has died.

Herskowitz, 56, was Hertzstein Professor of Genetics in the Department of Biochemistry and Biophysics at the University of California, San Francisco and co-director of the UCSF Program in Human Genetics.

The cause of death was pancreatic cancer.

“Ira was a brilliant, internationally renowned scientist, an inspired mentor and lecturer, and a remarkable colleague who in many ways defined the essence of UCSF.  He was a dear friend to many in the School of Medicine and across the campus, and we shall all miss him,” said Haile T. Debas, MD, Dean of the UCSF School of Medicine.

“Ira was legendary, both at UCSF and in the worldwide biomedical research community. Not only was he a pioneer in genetics but also a great educator and an irrepressible, exuberant spirit. He dedicated much time to his graduate students and to illuminating the wonders of science to the greater public. As such, he was an enormously important member of the UCSF community and the world. His death is a great loss for the University of California, San Francisco community and the field of biomedical research,” said UCSF Vice Chancellor Regis Kelly, PhD.

His death has been felt nationwide. “Ira was one of the great romantics in science: his love of biological problems was infectious, and it affected his students, his colleagues, and his readers throughout the world. He had a knack for seeing the universal lesson in the specific experiment—-for drawing the larger implication for all of biology and medicine from a result with a bacterial virus or a single yeast cell.  Because he wrote and spoke—and even sang—about these things so well, his voice influenced us all,” said Harold Varmus MD, president and chief executive officer of Memorial Sloan-Kettering Cancer Center.

“Ira loved science and he never tired of demonstrating to me just what yeast genetics could do for cell biology. He was trying to impress me not with his cleverness but with the cleverness of science itself.  He would as happily tell me about another’s work as his own,” said Marc W. Kirschner, PhD, Carl W. Walter Professor of Cell Biology at Harvard Medical School.

Earlier this month, Herskowitz received the 2003 Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research. This internationally recognized honor, considered on par with the Lasker award, is given annually to scientists for recent discoveries of particular originality and importance to basic medical research. It is presented by Brandeis University.

Herskowitz’s pioneering genetic studies on the yeast Saccharomyces cerevisiae yielded major insights into the fundamental aspects of cell biology in all organisms, including humans. He discovered the molecular basis for cellular differentiation, or specialization, in yeast and the molecular mechanisms that control yeast cell division. He also pioneered studies of gene expression, cell signaling, cell formation and growth control in the yeast.

The discoveries have provided major insights into how changes within DNA contribute to inherited diseases, and thus have tremendous implications for the treatment and prevention of such diseases. More broadly, the research has contributed to the understanding of the way in which organisms develop.

“Ira pioneered the use of yeast to discover several of the fundamental principles of eukaryotic cell biology. I know of no one with a greater love and devotion to the practice of science and a greater dedication and interest in teaching. Those who knew him were the fortunate ones,” said Tom Kornberg, PhD, UCSF professor and vice chair of biochemistry and biophysics.

“Ira inspired a generation of students and even faculty colleagues to follow his lead in applying ‘the awesome power of yeast genetics,’ in his widely quoted words, to solve their experimental problems. He also symbolized to us all what a well-rounded scientist should aspire to,” said Kelly.

Herskowitz also was a leader in the new field of pharmacogenetics, the study of the way in which natural variations in individuals’ genes can affect their response to drugs. He was co-leader of a novel UCSF National Institutes of Health-funded study aimed at determining how human genetic variation affects the performance of cellular gatekeepers known as membrane transporters, which control whether drugs enter the blood stream. The research has not only led to revelations about the range and pattern of transporter variation in humans, but also has revealed evolutionary and functional constraints on that variation.

In this endeavor, his collaborator was Kathy Giacomini, PhD, UCSF chair of pharmaceutical sciences and co-leader of the NIH funded study. Together, they forged a strong intellectual partnership. “Ira knew nothing about pharmaceutical sciences, and I knew nothing about genetics,” said Giacomini. Together they created the burgeoning pharmacogenetics program.

“Ira was dedicated to bringing together the basic sciences and disease-related research and clinical care. This is why he loved pharmacogenetics. It was a handle for him to bring genetics to therapy. Before he died, he told me to think big - to continue to work to bring together basic science, molecular medicine and clinical care. He believed UCSF was the kind of institution that could carry out such an effort,” said Giacomini.

In other research relevant to pharmaceutical sciences, Herskowitz’s team recently reported the way in which yeast cells, and perhaps cancer cells, become resistant to the potent anti-cancer drug cisplatin.
As co-director of the UCSF Program in Human Genetics, Herskowitz helped provide a unified framework for all human genetics teaching and research activities at UCSF.
But Herskowitz’s passions extended beyond the lab. He was an avid ping pong player and an ardent supporter of the San Francisco Bay Area’s professional sports teams. His sense of humor was apparent in his scientific talks.

He was also an enthusiastic folk and blues singer, well known for such songs as “I’ve Been Working on the Genome” and “Nights in the Cold Room.”

“Even those with little knowledge of his science knew of his reputation for guitar playing and singing, with a repertoire ranging from the standards to witty and satirical songs of his own composition,” said Kelly.

Herskowitz came from a scientific and medical family. His father, Irwin H. Herskowitz, PhD, a drosophila geneticist, is Professor Emeritus of Biology at Hunter College of the City University of New York. His brother Joel Herskowitz, MD, a pediatric neurologist in Boston, is author of the “Double Talking Helix Blues,” a song about DNA that Ira performed all over the world. His sister, Mara Herskowitz, RN, is a psychiatric nurse from New York.

A member of the UCSF Comprehensive Cancer Center and the Herbert Boyer Program in Biological Sciences, Herskowitz received his bachelor’s degree from the California Institute of Technology in Pasadena and his doctorate from Massachusetts Institute of Technology in Cambridge, where he also conducted postdoctoral research and was a long-standing member of the Visiting Committee.
Herskowitz was elected to the Institute of Medicine in 2002, a rare honor for a basic scientist.

He was elected a member of the National Academy of Sciences in 1986, and a fellow of the American Academy of Arts and Sciences in 1998. He is a longstanding member of the American Association for the Advancement of Science and the American Academy of Microbiology. He also is a former MacArthur Foundation Fellow,1987-92. His many awards and offices include the Eli Lilly Award in Microbiology and Immunology, 1983; president, Genetics Society of America, 1985; Genetics Society of America Medal, 1988; Mendel Lecturer, Genetics Society of Great Britain, 1991; Distinguished Alumni Award, California Institute of Technology, 1994; Honorary Doctor of Science Degree, St. Louis University, 1997; Yanofsky Lecturer, Stanford University, 2001; and the Genetics Society of America Thomas Hunt Morgan Award, 2002.

The Rosenstiel Award was established in 1971 as an expression of the conviction that educational institutions have an important role to play in the encouragement and development of basic science as it applies to medicine. The recipient receives a $10,000 prize and a medallion acknowledging receipt of the award.
Herskowitz is survived by his parents, Reida and Irwin, his sister, Mara, and his two brothers, Joel and Alan.

A funeral will be held on Sunday, May 4, 11:45 a.m., Riverside Memorial Chapel, 180 West 76th St., (at Amsterdam Ave.), New York, New York. 212/362-6600.

A memorial service is planned for June at the Legion of Honor in San Francisco.  Details will be posted on the UCSF Biochemistry Department home page,

Donations in Herskowitz’s name can be made to two funds—the Graduate Program in Genetics and the Graduate Program in Biopharmaceutical Chemistry. Donations for both should be made to the Regents of the University of California and sent to the UCSF Department of Biochemistry & Biophysics, Genentech Hall, 600 16th Street, San Francisco, CA 94143-2140.