Stanley J. Korsmeyer

The scientific community has been saddened and diminished by the loss of Stanley J. Korsmeyer, M.D., who died of lung cancer last month at the age of 54. Over the last 25 years, Korsmeyer had been an international leader in the fields of cancer biology and programmed cell death (apoptosis). Through his studies of apoptosis, Korsmeyer helped revolutionize our concepts of carcinogenesis. Korsmeyer, a medical oncologist by training, also helped translate this knowledge into the development of novel cancer therapeutics that are just now entering into human clinical trials. Stan didn’t start out to be a research scientist. He grew up the oldest of four on a livestock farm in southern Illinois. It was his involvement in the 4-H club that spawned his interest in science. From the beginning, his scientific experiments met with success. The pair of Hampshire Hogs he raised at age 14 were named Grand Champion at the Illinois State Fair, and Stan went off to the University of Illinois determined to become a veterinarian. However, on the advice of one of his veterinary mentors, he switched to pre-med. Following receipt of an M.D. degree from the University of Illinois and an internship and residency at UCSF, he arrived at the NIH as a Research Fellow at a time when molecular biology was just beginning to revolutionize the study of human disease. There, under the tutelage of scientists like Tom Waldmann and Phil Leder, Stan soon joined the vanguard of research scientists characterizing the molecular features of the chromosomal translocations that had been observed in patients with leukemia/lymphoma. Over his career, Stan contributed to the characterization of a variety of chromosomal translocations and identified several widely studied oncogenes including MLL, AF-4, and Ttg-1 (rhombotin). Although he had many accomplishments, Stan will be best known for his contributions to the discovery and characterization of the role that programmed cell death plays in the pathogenesis of cancer. In 1985, the Korsmeyer laboratory was one of three laboratories to describe the molecular aspects of a chromosomal translocation between chromosomes 14 and 18 observed in the majority of patients with follicular lymphoma. This translocation placed the immunoglobulin gene enhancer from chromosome 14 in close proximity to a previously uncharacterized gene on chromosome 18 that was given the name Bcl-2. From the beginning, Bcl-2 was a problem. It didn’t score easily in any of the assays usually used to characterize oncogenes. In 1988, a group from The Walter and Eliza Hall Institute reported that Bcl-2 could promote the survival of hematopoietic cells in culture. Shortly thereafter, Korsmeyer, who had been pursuing an independent investigation to determine whether Bcl-2 overexpression could alter B cell development and/or transformation in vivo, confirmed and extended this observation. Korsmeyer demonstrated that a Bcl-2 transgene expressed under the control of an immunoglobulin enhancer led to the progressive accumulation of B cells in vivo. The Stanley J. Korsmeyer