Andrew B. Leiter, MD, PhD, and Charalabos Pothoulakis, MD
Morton Grossman (1919–1981), the father of modern gastrointestinal endocrine physiology, was truly one of the giants of the last century in gastrointestinal research. Dr Grossman’s appointment in 1955 as chief of gastroenterology at the Wadsworth VA Medical Center in Los Angeles was a major turning point in his career. From 1955 until 1962, he ran the section and trained clinical gastroenterologists, all the while continuing his research. He was one of the first scientists appointed to the newly created Senior Medical Investigator program at the VA and was also professor of medicine and physiology at the UCLA School of Medicine.
In 1973, Dr Grossman learned that the National Institutes of Health intended to fund a center for the study of peptic ulcer disease. Almost single-handedly he organized the Wadsworth-UCLA and Dallas GI groups to submit a proposal, which was funded. Thus, in 1974 Dr Grossman became the first director of the Center for Ulcer Research and Education (CURE), which served as a prototype for the Digestive Diseases Research Core Center Program at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
During his life, Dr Grossman authored 400 articles. He trained a generation of fellows and scientists from all parts of the world. Many of them went on to successful research careers and to hold positions of distinction as heads of departments of gastroenterology, surgery, and physiology. His major contributions lay in defining the secretory mechanisms of the stomach and pancreas and the actions of regulatory gastrointestinal peptides. Dr Grossman set uncompromising standards for scientific validity and accuracy of reporting. In 1979 he was presented the Friedenwald Medal from the American Gastroenterological Association in recognition of his accomplishments.
His friends and colleagues will most remember his curiosity, his encyclopedic memory, the breadth of his interests and his energy in pursuing them, his intelligence, his perfectionism, his fairness, his wisdom, his integrity, his devotion, and his kindness.
The Grossman Distinguished Lectureship was established in 1989 to honor the memory and accomplishments of Dr Grossman. Previous speakers have all been distinguished, world-renowned scientists, including eight Nobel laureates. The 2015 Grossman Lecture will be given by Hans Clevers, president of the Royal Netherlands Academy of Arts and Sciences.
Over the last decade, few scientists have had as significant an impact on digestive disease research as Dr Clevers. Over a decade ago, Dr Clevers identified a transcription factor TCF1 as a key transcriptional effector protein of the Wnt signaling pathway. His discovery had a major impact on understanding this important pathway in metazoan development. More importantly his findings identified a missing link toward understanding how adenomatous polyposis coli (APC) mutations and β-catenin give rise to colorectal cancer.
With the tools he developed for studying Wnt signaling, Dr Clevers recognized that self-renewing cells at the base of intestinal crypts showed highly active Wnt signaling. This critical observation lead to the discovery of a seven transmembrane domain receptor, leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), as both a Wnt target gene and a marker of intestinal stem cells (ISC). Although the existence of a pluripotent intestinal stem had been proposed for decades, it remained elusive for study because there were no known markers.
In a series of classic experiments, Clevers and his colleagues established that LGR5-expressing cells fulfilled the properties of the long-postulated self-renewing intestinal stem cell. His discoveries and ongoing work have triggered an avalanche of information from his laboratory and many others about the ISC as an adult stem cell, the biology of the stem cells and their niche, the functional role of LGR5 as an R-spondin receptor, and the ability to propagate stem cells in organoid cultures. As a result of his seminal work, the ability to study stem cells has evolved from experiments that could never be done, to a wellspring of new knowledge that has our advanced understanding of the gastrointestinal tract.