Harvey F. Lodish

Harvey was born in Cleveland, Ohio on November 16, 1941. His father Nathan was a manager at a small company manufacturing electrical fittings for houses and autos. His mother Sylvia was a teacher before her marriage; after her children were in school she earned her BA degree and taught 3rd grade in Cleveland Heights. Harvey’s first publication was in 1946, a letter published in a children’s’ column in the Cleveland Press. Harvey started at Chesterfield Elementary School in Cleveland but transferred to Taylor Elementary School in Cleveland Heights when his family (in fact his entire neighborhood) moved to the suburbs in 1951. At Taylor Harvey was appointed head of the school crossing guards, giving him authority over about 20 5th and 6th grade students.

After three years at Roosevelt Junior High Harvey entered Cleveland Heights High School, where he distinguished himself keeping time as the bass drummer in a 164- piece marching band. He also participated in a small research project — measuring the levels of various nitrogenous compounds in the blood — directed by Dr. Ethel Laughlin, a chemistry teacher. During the summers of 1958, ’59, and ’60 Harvey worked at Western Reserve (now Case Western Reserve) Medical School with Dr. Robert Eckel studying potassium transport in red blood cells. This led to his first scientific publication in 1960, and he has been studying red blood cells ever since. (And in 1982 he was elected to the Cleveland Heights High School Alumni Hall of Fame, an honor he shares with his two younger brothers Leonard and Richard).

Harvey entered Kenyon College in 1959 and graduated three years later, summa cum laude and with Highest Honors in Chemistry and Mathematics. During the summer of 1960 he worked at Stanford in the chemistry laboratory of Dr. Carl Djerassi, a Kenyon alumnus and "discoverer of the birth control pill." He saw first hand how close contacts between universities and companies (Syntex in this case) can be mutually profitable and result in excellent science. Harvey was awarded an honorary D. Sc. degree from Kenyon in 1982 and since 1989 has served as a member of the Kenyon College Board of Trustees.

Harvey received his Ph.D. degree in genetics with Dr. Norton Zinder from the Rockefeller University in 1966; his thesis focused on a genetic and biochemical analysis of the three genes in the RNA bacteriophage f2. Then followed two years of postdoctoral research at the M.R.C. Laboratory of Molecular Biology with Drs. Sydney Brenner and Francis Crick; there he determined the factors that control initiation of translation of the three f2 genes. He joined the faculty of the MIT Department of Biology in 1968. Harvey was promoted to Professor in 1976, and in 1983 was appointed Member of the new Whitehead Institute for Biomedical Research. His one "real" sabbatical was in 1977- 78 as a Guggenheim Fellow at the Imperial Cancer Research Fund in London with Dr. Robin Weiss.

Initially, his work at MIT focused on translational control of protein synthesis, collaborating with David Baltimore’s lab on translation of poliovirus mRNA. David Housman, one of his first Ph.D. students, showed that mammalian proteins all begin with a methionine residue transferred from a specific met- initiator tRNA.

From 1971 through 1987 parts of his laboratory studied the regulation of gene expression during differentiation of the cellular slime mold Dictyostelium discoideum, focusing on the details of mRNA biogenesis and on identifying proteins and mRNAs expressed at specific times of differentiation and in either prespore or prestalk cells.

Beginning in 1973, his laboratory has concentrated on the biogenesis, structure, and function of several important secreted and plasma membrane glycoproteins. Working with the Baltimore lab his group defined the biosynthesis and maturation of the vesicular stomatitis virus glycoprotein, elucidating the now well-known ER - Golgi - plasma membrane pathway for biogenesis of cell surface proteins. With Blobel they developed the first in vitro system for studying the biosynthesis, membrane insertion, and glycosylation of a membrane protein, and then demonstrated that removal of the signal sequence and addition of the two N-linked carbohydrates occurs cotranslationally. Later work identified the intracellular organelles that mediate recycling of the asialoglycoprotein and transferrin receptors, and clarified the role of pH changes in delivery of iron to cells and recycling of the transferrin receptor. More recently, his group has elucidated steps in folding and oligomerization of several proteins within the endoplasmic reticulum, shown that exit of several newly-made secreted proteins from this organelle requires that they be properly folded, and developed probes for measurement of the redox state within the endoplasmic reticulum.

His group was the first to clone and sequence mRNAs encoding a mammalian glucose transport protein (the red cell glucose transporter, GLUT1), and then they identified and worked out the roles of a family of glucose transporters, including GLUT2 and GLUT4, in liver, muscle, and adipose tissue. After cloning Band III, the red cell anion exchange protein, his group elucidated the role of this protein and its homologs in acid- base balance in the kidney. Other proteins cloned by members of his lab include the first transporter for free fatty acids, the two subunits of the hepatic asialoglycoprotein receptor, intestinal sucrose-isomaltase, the erythropoietin receptor, the calcitonin and endothelin receptors, and (with the Weinberg lab) two subunits of the TGFß receptor. These have been used to define the structure and biosynthesis of these and related proteins and to identify and characterize related genes that encode proteins of related physiological function.

For example, cloning of the erythropoietin receptor made possible a long series of studies on the signal transduction pathways it activates, leading to an understanding of how it prevents apoptosis of erythroid progenitor cells and allows them to undergo a process of terminal proliferation and erythroid differentiation. Cloning of the TGF-ß receptors led to elucidation of the role of the Smad signal transduction proteins in activation of transcription of genes encoding extracellular matrix proteins and inhibitors of the cell cycle, and to an understanding of how loss of these receptors contributes to tumor development. Later work led to the cloning and characterization of other factors in the TGFß signaling pathway including, with the Weinberg lab, several oncogenes that block TGFß signaling pathways.

Besides studying the erythropoietin and TGFß receptors and the family of mammalian fatty acid transport proteins they cloned, his lab has been studying the insulin receptor and determining how it signals fat cells to increase uptake of both sugars and fatty acids. Together with colleagues at Genset Corp. his group studies the mechanism of action of ACRP30, a new adipocyte- produced hormone they cloned that potently enhances fat and glucose metabolism by muscle and prolonged weight loss in mice. Finally his group studies hematopoietic stem cells, cloning and characterizing new growth factors that may allow expansion of these cells without differentiation, and developing transgenic mice that should allow real- time detection and enrichment of these cells.

On a personal level, Harvey married Pamela Chentow in 1963, and they have three married children - Heidi (born in 1966 and a social worker), Martin (1968, a high school physics and chemistry teacher) and Stephanie (1969, a pediatrician). They have four adorable grandchildren — Sophia, (1997) and Joshua (1998) to Martin Lodish and Kristin Schardt, Emma (1999) to Heidi and Eric Steinert, and Isaac (2000) to Stephanie Lodish and Bruce Peabody. Harvey is a member of the Appalachian Mountain Club 4000-foot club, having climbed on foot all 68 New England peaks over 4000 ft. high. He enjoys jogging every morning; reading, writing, thinking, and talking; traveling with his wife Pam; hiking with his children and students; and playing with his grandchildren.

Harvey is on the Editorial Board of the Proceedings of the National Academy of Sciences. He was on the Board of Reviewing Editors of Science from 1991 through 1999 and was Editor of Molecular and Cellular Biology from 1981 to 1987. Harvey has been on the editorial boards of a number of other journals, including the Journal of Cell Biology, the Journal of Biological Chemistry, and Nucleic Acids Research. He has served on advisory panels for the NIH, NSF, and American Cancer Society, and on the advisory boards of several institutions, including the Biozentrum of the University of Basle, the European Molecular Biology Laboratory in Heidelberg, and the PEW Scholars Program in Biomedical Sciences. He is currently a member of the Board of Trustees of the Massachusetts Eye and Ear Infirmary as well of Kenyon College. He is chair of the advisory board of the Division of Basic Sciences of the Fred Hutchinson Cancer Center, and is a member of the advisory boards of the Center for Molecular Biology Heidelberg (ZMBH) in Germany, the Cleveland Clinic Research Institute, and the California Institute of Technology Division of Biology.

Harvey has been the lead author of the textbook Molecular Cell Biology, now in its fourth edition and translated into six languages. Together with five co-authors he is currently planning the 5th edition, due in 2003.

He was elected a Member of the National Academy of Sciences (1987), a Fellow of the American Association for the Advancement of Science (1986), a Fellow of the American Academy of Arts and Sciences (1999), and a Fellow of the American Academy of Microbiology (1992). He is also an Associate (Foreign) Member of the European Molecular Biology Organization (1996). Dr. Lodish received a MERIT award from the National Institute of Diabetes and Digestive and Kidney Diseases. He is also a recipient of the Stadie Award from the American Diabetes Association and is listed in Who’s Who in America (1987).

Harvey has been very active in the biotechnology industry. He is a founding member (1980) and Principal of the consulting company BIA and was a founder and scientific advisory board member of Genzyme, Inc. He was also a scientific founder of Arris (now Axys) Pharmaceuticals, Inc, and Millennium Pharmaceuticals, Inc and of Cogito Learning Media, Inc. Currently he is a scientific advisory board member of AstraZeneca, Genset SA, and Dyax Corporation.