Dr. Ajit Varki
The Rosalind Kornfeld Award for Lifetime Achievement in Glycobiology was established in 2008 to honor Dr. Rosalind Kornfeld’s distinguished scientific career and service to the Society. The Society bestows this prestigious award to scientists who, throughout their professional careers, have made outstanding contributions to Glycobiology.
The 2020 Award recipient is Dr. Ajit Varki, Distinguished Professor of Medicine and Cellular & Molecular Medicine at the University of California San Diego. Dr. Varki has many accolades and titles, but is perhaps known to the greatest number of people as the Executive Editor of the first textbook in the field, Essentials of Glycobiology, now in its 3rd Edition, and the first online open-access textbook at NCBI. His 280 research articles, 200 invited articles and commentaries, and >450 invited presentations span a 43-year career and form an impressive body of work. But it does not begin to tell the life story of this extraordinary physician-scientist.
Ajit was born in India, in the state of Kerala. His youth at Bishop Cotton Boys High School was filled with athletic trophies and top academic accomplishments that led him to the equally prestigious Christian Medical College in Vellore. It was here at age 16, that he met his future wife and scientific partner, Nissi. At CMC, Ajit won numerous gold medals and, as a reference once wrote, “every conceivable award.” 1975 marked a turning point in his life. He left India with his MD for the US in pursuit of “R&R (Research and Rock ‘n Roll).” With just a few dollars in his pocket, he power-walked through the racism of the mid-1970’s, did short residencies at Temple and University of Nebraska and three years later was accepted to Stuart Kornfeld’s lab at Washington University in St. Louis. Rosalind’s lab was next door and Ajit credits her advice and support as being crucial to his success. He became part of the team that worked out the basic science of lysosomal enzyme targeting through mannose-6-phosphate and its receptors. Not one to forget his MD roots, he also helped solve the first congenital disorder of glycosylation, I-cell disease. He recorded ten papers in the Kornfeld years, which brought him to UCSD in 1982, where his first boss, John Mendelsohn, confidently stated, “Ajit is going to be a superstar.”
Ajit quickly rose through the academic ranks through early promotions to Professor and became Editor-in-Chief of the prestigious Journal of Clinical Investigation. He then turned JCI into the first open access journal, realizing many researchers in countries like India could not afford subscriptions. He knew they would benefit greatly from access to the JCI’s contents, like he had a decade earlier. He was then the first foreign medical graduate to be elected President of The American Society of Clinical Investigation.
Early on, Ajit was fascinated by the complexity of modifications of sialic acids, their chemistry, biology and medical importance. He made quantum jumps in the biology and chemistry of O-acetylation. One modification especially caught his attention: N-glycolylneuraminic acid (Neu5Gc). While other Old World primates have generous amounts of it, he found that humans had inactivated the gene that converts Neu5Ac to Neu5Gc. Is it the absence of Neu5Gc that defines us as human? In his final bio-mystery novel, Next, Michael Crichton seemed to think so, as he identified it as a key biomarker used to distinguish humans from chimps. Humans can also incorporate diet-derived Neu5Gc into glycans, but then make antibodies against this “xenoautoantigen”. Perhaps, as Dr. Varki postulates, some human disorders like cancer and heart attacks are aggravated by consuming Neu5Gc-rich red meat diets leading to “xenoautoimmune” inflammation?
Curiosity about evolutionary differences of humans and chimps spawned in the mid 1980’s, coupled with his fascination with sialic acids lead him to create two San Diego Consortia. One was the Glycobiology Training and Research Center, leading to the recruitment of many practicing glycobiology faculty members to UCSD and the other was the Center for Academic Research and Training in Anthropogeny (CARTA), which introduced anthropologists and evolutionary biologists to glycobiology.
Ajit continued to explore the question, “What makes us human?” His book, Denial, proposes that while fear of death risk is critical for survival of other animals, selective “Reality Denial” produces a fearlessness that ultimately powers human optimism and accomplishments, even while increasing the risk of unrealistic beliefs and behaviors that are so rampant today. Is this proposition correct? Hard to say, but it reveals the inventive mind of this physician-scientist who combines his work in glycobiology and evolution with his medical training to ask unique, wide-ranging questions.
Gazing through evolutionary binoculars with his colleague Pascal Gagneux, Ajit envisioned glycosylation to be the battlefield in “Glyco-Wars,” where microbes continually exploit and attack the host’s glycan forest. In response, the host fends them off by creating new layers of increasingly complex, defensive glycans. They captured this battle elegantly in the “Red Queen Hypothesis” that one must run as hard and fast as possible just to stay even. The battle continues.
Ajit served as Associate Dean of Physician-Scientist training at UCSD, training MD-PhD’s, a vital, but now rare group of scientists. He is the Co-Director of the Glycobiology Research and Training Center with Jeff Esko, and, most recently, National Coordinator of the NHBLI Consortium for Career Development in Glycosciences (K-12), designed to train MD’s and PhDs for a future in the spectrum of glycosciences.
Dr. Varki was elected to the American Academy of Art and Sciences, National Academy of Medicine, American Society for Clinical Investigation, and Association of American Physicians. He was recipient of the degree Doctor Honoris Causa from the University of San Martin, Argentina. He won both an NIH MERIT award, an American Cancer Society Faculty Research Award and, within our field, the Karl Meyer Award and IGO Award. Dr. Varki was President of our society in 1996. In 1993, while recovering from the flu and unable to go to the lab, Ajit took time to write what is probably the most-cited review article in the field, “Biological Roles of Oligosaccharides: All the theories are correct (>6000 citations), recently updated in 2017.
Ajit credits much of his success to support and collaborations with Nissi, a Board-certified pathologist, resulting in more than 70 co-publications since the mid-1990’s. Their partnership has been invaluable for the field and both have advocated for increased and balanced roles for women in science. They know first-hand how important gender equity is in science.
Ajit Varki is a physician-scientist, who, for more than 4 decades, has amalgamated his medical training and rigorous science with an expansive, out of the box imagination to expand and integrate glycan research into biology and medicine. He has raised the profile of Glycobiology world-wide and fused medical and basic science with benefits for each discipline. His expansive thinking, determination, creativity and aggregated accomplishments make him the ideal recipient of the Rosalind Kornfeld Lifetime Achievement award.