Charles S. Lieber, M.D. (1931-2009)
Authors: Steven Schenker
Journal: Hepatology (2009)

Dr. Charles S. Lieber, a distinguished scientist and pioneer in the field of alcohol effects on the liver and the gastrointestinal tract, died in early March, 2009 at his home in New Jersey, surrounded by his loving family. He was 78 years old. Dr. Lieber was born in Belgium in 1931, and as a youngster of Jewish faith, he experienced poignantly the horrors and persecution of Nazi invasion. Indeed, he was forced to wear a yellow star on his chest and witnessed the burning of his local synagogue. In his interview in the journal Addiction in 2001, he vividly described the bombing of Dunkirk, where he sought temporary refuge, his flight on foot to southern France (Vichy), and escape into Switzerland into an internment camp. These very traumatic events were positively balanced by his "adoption" by an elderly Swiss couple who altruistically provided him with an expensive education. This permitted a return to Belgium after the war, where he obtained his undergraduate and medical degrees, both summa cum laude, from the University of Brussels. Even these successful accomplishments were marred by the development of a bleeding gastric ulcer requiring surgery. Based on my conversation with him, I feel convinced that these composite experiences were largely responsible for his dedication and interest in medicine, and possibly even in gastroenterology. After graduating as the top-ranking medical student, and obtaining training in internal medicine, gastroenterology, and pharmacology at the University of Brussels, Dr. Lieber obtained fellowship funds to study in the United States. This started in the area of liver disease and nutrition at the famous Thorndike Memorial Laboratory (Harvard Unit) of the Boston City Hospital with Charles S. Davidson (1958–1963). He then moved to Cornell University Medical College as Associate Professor of Medicine and Director of the Liver Disease and Nutrition Unit at Bellevue Hospital in New York City. In 1968 he joined Mount Sinai School of Medicine as Professor of Medicine and Pathology, and Chief of Liver Disease and Nutrition at the Bronx Veterans Affairs Medical Center. There, he also directed the Alcohol Dependence Treatment Program and Alcohol Research Center. Dr. Lieber's scientific productivity over the last 50 years has been prodigious, both in quantity and quality. He has authored or coauthored some 1023 scientific publications and 12 books. A survey of citations by the Institute for Scientific Information reveals that he is one of the most cited scientists in the world, and some of his articles have been selected as "Citation Classics" by Current Contents and have received other accolades. It is impossible to do full justice to his seminal research contributions in this brief tribute, but this is a list of some key ones. In 1945, it was a prevailing view from studies in rats that poor nutrition and not excess alcohol was responsible for alcoholic liver damage. In elegant studies done in rodent, baboon, and human, this notion was overturned, and the toxic effects of excess alcohol on the liver were verified. He then documented some of these toxic metabolic effects of alcohol on the liver. He pioneered the importance of a new, alcohol-inducible cytochrome P450 pathway for alcohol metabolism in liver microsomes (now called CYP2E1). This was shown to be important in alcohol metabolism at higher ethanol levels, and to interact with the detoxification of other agents, such as acetaminophen. Perivenular fibrosis was identified as an important precirrhotic lesion. He investigated gastric alcohol dehydrogenase enzymes and cloned sigma alcohol dehydrogenase. He showed the importance of excess alcohol in inactivating intestinal lactase (as one mechanism of diarrhea in such patients) and produced evidence for increased serum uric acid in patients with gout due to indirect alcohol effects on renal tubules. Although noted last here among his list of achievements, he was one of the first to investigate the role of gastric bacteria in generating ammonia production from gastric urea, and the reversal of this by antibiotic treatment. Much later, this evolved into the discovery by Drs. Marshall and Warren of Helicobacter pylori and its role in stomach ulcers and cancer, and the award of the Nobel Prize presented to them in 2005. As one can imagine, Charles was the recipient of numerous awards (key ones are given in Table 1), was a member of the most prestigious honorary societies, has been editor or member of the editorial boards of 34 professional publications, and has held some 39 visiting professorships worldwide. He was an honorary member of various foreign scientific associations. He founded and has been president of the Research Society on Alcoholism, and was president of the American Society for Clinical Nutrition and the New York Gastroenterological Association. Dr. Lieber has attracted numerous coworkers and trainees to his laboratory. Many of these are now eminent scientists and directors of their own unit. At last count (likely incomplete), some 154 fellows had trained with Dr. Lieber including 36 from the United States, 36 from Europe, and 62 from Southeast Asia. Dr. Lieber considered these individuals his extended family and kept in touch with them. In turn, they maintained their long-term interest and loyalty to him, as shown to me during my travels. A few key collaborators do deserve special mention. Ms. Lee DeCarli helped run his laboratory for many years and was considered by Charles as absolutely indispensible. Drs. Fiorenzo Paronetto and Emanuel Rubin, as pathologists, and Dr. Arthur Cederbaum in biochemistry, were key colleagues at various points in his career. However, clearly the most important ingredient in his life was his prior fellow, his research collaborator, and his partner, Dr. Maria Leo-Lieber. From personal observations at times of success and stress, this was a marriage of mutual love, respect, and devotion. Despite his incredibly busy academic life, Charles remained very close to his older children, Colette and Daniel, from his first marriage, and especially his three younger ones, Leah, Samuel, and Sarah. When Leah was asked in her kindergarten class what kind of physician Charles was, she replied, "I am not sure exactly, but I think he is a Paper Doctor". This was in obvious reference to the articles and grants that were such a large part of his life. Charles was devoted to his five children, helping them with homework when they were younger, and then with personal decisions later in life. All three daughters chose a career in medicine, Colette as a dermatologist, Leah as a gastroenterologist, and Sarah, the youngest one, entering medical school this year. Of the two boys, Daniel is a successful businessman and Samuel is a Ph.D. in mechanical engineering involved in the medical field. To accommodate his extensive commitments, Charles would wake up at 4:00 AM, dictate numerous articles and grant proposals, go for a swim (allegedly to help his back) and then would start the full day. One example of timesaving is that I understand he proposed to Dr. Leo during a flight on medical business. Perhaps this is because he had a captive audience! He maintained his Jewish religious affiliation to the end and shared it with his children in their upbringing. Charles Lieber was an extraordinary man. He was intense, obviously brilliant, and dedicated to science. He pursued knowledge in depth, defended his views brilliantly, and yet gentlemanly, and lived with a passion for discovery. He had little tolerance for incompetence, but truly appreciated good work. He had an engaging smile and was fiercely loyal to his friends. I am proud to call myself one of them. For me, he was an academic role model to emulate. He will be sorely missed by many, including me, but his contributions and legacy will live on, making this a better world for all of us. Dr. Charles S. Lieber