Former SUNY Downstate Medical Center Faculty Member Receives Lasker Award
Oct 8, 2015
Dr. Evelyn M. Witkin Awarded for Work Conducted At Downstate 1955-1971
Brooklyn, NY – Evelyn M. Witkin, PhD, who served on the SUNY Downstate Medical Center faculty in the Department of Cell Biology from 1955 to 1971, has been awarded the 2015 Albert Lasker Basic Medical Research Award for discoveries concerning the DNA-damage response – a fundamental mechanism that protects the genomes of all living organisms.
Dr. Witkin, who was most recently a faculty member at Rutgers University, shared the prize with Dr. Stephen J. Elledge, Brigham and Women’s Hospital.
Dr. Witkin’s work at SUNY Downstate focused on elucidating mutation frequency decline, or MFD. By analyzing the kinetics of MFD under a variety of conditions, she was able to deduce almost all the features of the mutagenic process. Using bacteria strains that required tryptophan for growth and subjecting them to doses of ultraviolet (UV) light, Dr. Witkin concluded that MFD is due to the rapid enzymatic repair of the potentially mutagenic UV photoproducts when protein synthesis is inhibited or delayed.
In the early 1960s, Dr. Witkin wrote that MFD is repair before replication; mutation fixation is replication without repair. She concluded that an unrepaired UV product in DNA is lethal, because DNA polymerase, the normal DNA copying enzyme, stalled at these lesions. She proposed that the bacterium survives, albeit as a mutant, only if it has another DNA polymerase that is able to replicate past the lesion, even if there is a high probability of error in DNA synthesis.
Dr. Witkin was the first to reveal the action of an anti-mutagenic repair process, later identified as excision repair, which is found in humans and most other organisms. She found that bacterial mutants lacking excision repair are exceedingly sensitive to radiation, and that the survivors of exposure are riddled with radiation-induced mutations.
Towards the end of her stay at Downstate, Dr. Witkin showed that UV damage of DNA leads to a number of effects in E. coli, including the induction of a latent bacteriophage and a delay in cell division leading to filamentous growth. She proposed that UV-damaged DNA generates a regulatory signal that activates a large number of genes. This was the first step towards her major discovery that became known as the SOS response.
The term “SOS” was borrowed from the international danger signal because the SOS response in E. coli is activated only when the bacteria are under stress. When DNA is severely damaged, the DNA genes go into action until the damage is repaired; only then does DNA replicate and the cell divide, and the expression of the SOS genes return to their normal state. Dr. Witkin continued to study the SOS response until her retirement in 1991.
Dr. Witkin did most of her work before the molecular tools that are routinely used in labs today were even invented. Her experimental approach was to let the bacteria perform the relevant biochemistry, which is very different than what most biological investigators use today. She would perform very simple experiments with very intricate thinking behind them, using mainly Petri dishes, pipettes, and bacterial culture. The last laboratory step was counting the number of bacterial colonies found on plates.
By the time she left Downstate in 1971, Dr. Witkin achieved a detailed understanding of how UV photoproducts in DNA lead to mutations by interpreting curves on a graph. She showed that most UV-induced mutations are mistakes in replication caused by unrepaired photoproducts in DNA passing though the replication fork. Only very recently has this process been demonstrated using purified proteins in vitro.
The Lasker Awards are among the most respected science prizes in the world. Lasker Awards often presage future recognition by the Nobel committee, so they have become popularly known as "America's Nobels." Eighty-six Lasker laureates have received the Nobel Prize, including 44 in the last three decades. The prize that Dr. Witkin received, the Albert Lasker Basic Medical Research Award, honors scientists whose fundamental investigations have provided techniques, information, or concepts contributing to the elimination of major causes of disability and death.
Dr. Witkin has been recognized with numerous other awards, including election to the National Academy of Sciences in 1977; the Thomas Hunt Morgan medal by the Genetics Society of America in 2000; and the President’s National Medal of Science in 2002.
More information on Dr. Witkin can be found in an excellent monograph written by Miriam H. Feuerman, PhD, associate professor of cell biology at Downstate, in Downstate at 150: A Celebration of Achievement, Martin J. Salwen, editor. A full copy of Dr. Feurerman’s monograph can be found at: https://www.downstate.edu/sesquicentennial/.
###
About SUNY Downstate Medical Center
SUNY Downstate Medical Center, founded in 1860, was the first medical school in the United States to bring teaching out of the lecture hall and to the patient’s bedside. A center of innovation and excellence in research and clinical service delivery, SUNY Downstate Medical Center comprises a College of Medicine, College of Nursing, School of Health Professions, a School of Graduate Studies, School of Public Health, University Hospital of Brooklyn, and a multifaceted biotechnology initiative including the Downstate Biotechnology Incubator and BioBAT for early-stage and more mature companies, respectively.
SUNY Downstate ranks twelfth nationally in the number of alumni who are on the faculty of American medical schools. More physicians practicing in New York City have graduated from SUNY Downstate than from any other medical school.