Dr. Kohn received an A.B. degree from Harvard in 1952 with majors in Chemistry and Physics,
an M.D. degree from Columbia College of Physicians and Surgeons in 1956, and a Ph.D. in Biochemistry
and Molecular Biology from Harvard in 1965. After internship at Mount Sinai Hospital in New York,
Kohn came to the National Cancer Institute and served as Clinical Associate in the Clinical Pharmacology Service
(headed by Paul Condit) 1957-1960. He then spent 2 years as a graduate student and post-doctoral fellow
in Paul Doty's laboratory at Harvard, returning to the NCI in 1962 as a member of the Laboratory of Chemical Pharmacology
headed by David P. Rall (this Laboratory was a transformation of the earlier Clinical Pharmacology Service).
In 1968, Kohn founded the Laboratory of Molecular Pharmacology (now the DTP) and served as its Chief until 1997.
During this time (1961-1997), Kohn's major area of investigation concerned the mechanisms of action of DNA-targeted
anticancer drugs. He demonstrated that bifunctional alkylating agents produce DNA interstrand crosslinks
and that this is their major cytotoxic action. He elucidated a new mechanism of drug action on DNA,
based on the anthramycin group of antibiotics.
In 1974, he discovered the DNA filter elution phenomenon
in which DNA molecules pass through micropore filters at a rate dependent on DNA strand length.
Based on these observations, he developed methodology to measure several types of DNA damage in mammalian cells.
This methodology was widely used for more than 20 years in many laboratories to study DNA damage and repair
in mammalian cells. By DNA filter elution studies, Kohn and his colleagues in 1979-1982 showed that DNA
topoisomerases are targets of action of several clinical anticancer drugs. This led to worldwide interest
in topoisomerase-targeted drugs that has continued to the present time.
In the 1990's, Kohn and his colleagues began to apply the emerging knowledge of cell cycle checkpoints to study
the responses of cancer cells to DNA damage. As an aid to this end, Kohn developed a notation for molecular
interaction maps that has recently received considerable interest. In 2015, Dr. Kohn became Scientist Emeritus
and continues to collaborate and consult on various DTP projects and with other laboratories.
Drugs Against Cancer: Stories of Discovery and the Quest for a Cure
This book may be viewed as a combination of science, history, medicine, and memoir, and hopefully could mostly be understood without a great deal of prerequisite knowledge. Dr. Kohn has tried to give an account of the earliest published work leading to the anti-cancer drug discovery stories that he will relate. The aim of the book was to explain how the knowledge and application of cancer chemotherapy drugs developed. It is in large part a historical account.