Gil Ashwell, 1916–2014

On June 27, 2014, George Gilbert “Gil” Ashwell, a pioneer in the field of glycobiology and a constant presence on the campus of the National Institutes of Health (NIH) for more than 50 years, died at age 97. Gil was world renowned as codiscoverer of the asialoglycoprotein receptor in the liver. He was a recipient of the prestigious Gairdner Foundation Prize and a member of the National Academy of Sciences, and he continued to make valuable research contributions far past his retirement, into his 90s, joking in a 2008 Nature interview that he just couldn’t stay away from the laboratory (1).

G. Gilbert Ashwell (1916–2014). Image courtesy of John Hanover (National Institutes of Health, Bethesda).

Gil will be sorely missed, not only by his NIH family but by the innumerable researchers around the world he has mentored and collaborated with during his long and rewarding career. Every element of his career—from the thoroughness of his research approach, to his pure love of conducting science and sharing his ideas—made Gil the quintessential NIH scientist many of us aspired to be.

However, Gil shunned the limelight, nearly to the point to which many young researchers today do not know the legacy that is his. Allow us, then, to share how Gil came to the NIH Intramural Research Program and influenced the field of glycobiology so greatly.

Gil attended Worcester Polytechnic Institute in Massachusetts as an undergraduate, but his intellectual interests were much broader than the relatively limited science and chemistry courses offered there, so he transferred to the University of Illinois in Urbana, from which he graduated with a major in chemistry and a minor in philosophy. Gil’s interest in philosophy led him to travel to the Sorbonne, but on the ocean voyage over he met his future wife, Edna Fleischmann, and they both ended up together in Vienna. The deteriorating conditions in Europe forced a move to Switzerland, where Gil studied philosophy at Erasmus University. Subsequently, Gil worked as a chemist at Merck, where he worked on the isolation of penicillin and subsequenty pursued more advanced studies with Louis Fieser at Harvard. Gil continued at Merck until 1944, when he entered medical school at Columbia University in New York, followed by a two-year research fellowship there in the laboratory of Zacharias Dische, of the “Dische reaction” fame. Gil joined the NIH National Institute of Arthritis and Metabolic Diseases (NIAMD) in 1950. He became chief of NIAMD’s Laboratory of Biochemistry and Metabolism in 1967 and held that position (through the institute’s name changes) through most of his NIH career.

In his early days at the NIH, Gil studied the effects of radiation on biological systems. He soon switched to studying carbohydrates, which became the focal point of his career. Gil’s initial work focused on intermediary metabolism, and among his accomplishments were the discoveries of d-xylulose phosphate as an intermediate in the pentose cycle, several intermediates in the catabolism of vitamin C, and β-ketogulonic acid as an intermediate in the synthesis of l-xylulose, the key sugar in pentosuria, a carbohydrate metabolism disorder.

Gil is best known for his work with Anatol G. Morell, a researcher and old friend whom he reconnected with while on sabbatical at Columbia University in 1965. Together, they perfected an enzymatic method for radiolabeling serum glycoproteins by removing the terminal sialic acid and labeling the underlying galactose residue. Building on this technique and applying it to the study of lectins and Wilson’s disease, the two researchers serendipitously discovered the asialoglycoprotein receptor, now also known as the Ashwell–Morell receptor. This was perhaps the first receptor ever described. Researchers worldwide use the basis of Gil’s work with Morell to deliver drugs specifically to the liver. This receptor also plays a key role in limiting the aggregation of platelets in life-threatening complications of infection.

A few years after this, Gil and a visiting fellow in his laboratory, Toshisuke Kawasaki, now a prominent scientist in Japan, isolated an avian hepatic binding protein that was specific for terminal N-acetylglucosamine residues on glycoproteins, another discovery of profound biological importance. Several other important discoveries followed.

Aside from National Academy of Science membership in 1979 and the Gairdner Prize in 1982, Gil also received the American Society of Biological Chemists (ASBC)-Merck Prize in 1984, an honorary doctoral degree from the University of Paris in 1988, the Alexander von Humboldt Foundation Senior Scientist Award in 1989, and the Society for Glycobiology’s Karl Meyer Award (with Dr. Saul Roseman) in 1993. Gil was named NIH Institute Scholar in 1984. This was a special title created specifically to recognize Gil’s distinguished scientific achievements.

After his formal retirement in 1997, Gil continued studying glycoprotein metabolism in the National Institute of Diabetes and Digestive and Kidney Disease Laboratory of Cell and Molecular Biology, working closely with J.A.H. For more about Gil’s scientific work, please consider the following: Gil’s landmark 1974 paper in the Journal of Biological Chemistry, “The Isolation and Properties of a Rabbit Liver Binding Protein Specific for Asialoglycoproteins” (2), Gil’s short interview with Nature in 2008 (1), and a Journal of Biological Chemistry “Centennial Issue” tribute to Gil (3).

Outside the laboratory, Gil was no less brilliant. He spoke several languages and he read classic literature in French and German. His oldest friends speak of Gil’s efforts to secure passage of many Jews from Europe to America to escape Nazi persecution, something Gil rarely discussed. As noted, Gil was studying in Switzerland at the outbreak of World War II. From wartime Basel, he helped Jewish refugees write letters to their American relatives in the hope of being sponsored for immigration.

Gil’s wife, Edna Fleischmann, died in 2004. Gil’s son, Jonathan Ashwell, is chief of the National Cancer Institute Laboratory of Immune Cell Biology. Gil is also survived by his daughter, Ariel, and two grandchildren.

We are proud of and indebted to Gil for making the NIH his scientific home.