William E. Connor, MD
Bill Connor, a pioneer in lipid and atherosclerosis research, passed away in Portland, Oregon, on October 25 at the age of 88. This gracious and unassuming man was an innovative biomedical investigator, stimulating teacher, and compassionate physician. His scientific curiosity and courage to challenge existing concepts enabled him to make seminal contributions to lipid metabolism and its role in cardiovascular health and disease.
Bill completed undergraduate studies at the University of Iowa in 1942 and served in the United States Army Signal Corps during World War II. After receiving his MD degree from the University in 1950, he began postgraduate training, spent 2 years in private practice, and then completed a medical residency at the Iowa City Veterans Administration Medical Center. He was appointed to the University of Iowa faculty in 1956 as an Instructor in Internal Medicine and rapidly rose to the rank of Professor. Bill was a pioneer in the treatment of hyperlipidemia and achieved national recognition while at Iowa for his studies in lipid nutrition, cholesterol metabolism, and atherosclerosis. In 1975 he moved to the Oregon Health and Science University, where he maintained a vigorous and productive research program in lipids and nutrition until the time of his death.
During his tenure at Iowa, Bill was Principal Investigator of a Program Project in Lipids and Thrombosis and the Arteriosclerosis Specialized Center of Research. In addition, he served as Director of the Lipid Research Clinics Program and the Clinical Research Center. Because of his widespread medical interests, infectious enthusiasm for research, and collegial manner, he attracted many faculty collaborators and was a superb role model for trainees and junior investigators.
The remarkable breadth of Bill’s research is documented in his nearly 400 publications, beginning in 1956 with a study of hyperlipidemia in patients with coronary disease and concluding with 2 papers that will be published posthumously in 2010: one describing the effects of lutein on macular degeneration and the other describing a diagnostic test for cerebrotendinous xanthomatosis. His level of productivity is amazing considering that much of his work involved clinical investigation in a metabolic ward setting that required time-consuming procedures like sterol balance. Among his many important research contributions, 4 deserve special mention.
Bill first achieved national acclaim for his studies of human cholesterol metabolism. When he entered the field, dietary cholesterol was not considered to be an important factor in determining the plasma cholesterol concentration. Through carefully controlled metabolic studies, Bill proved that this widely held view was incorrect. He showed that plasma cholesterol was influenced by dietary cholesterol intake and determined the threshold level and range over which this occurred in humans. As a member of 2 key National Heart, Lung, and Blood Institute advisory groups, the Diet Heart Study Committee and the Lipid Metabolism Advisory Committee, which he chaired, Bill played an important role in implementing these findings for public health policy. He also coauthored several popular cookbooks, including The New American Diet with Sonja Connor, his wife and scientific colleague, to provide the public with a practical means for applying these heart-healthy recommendations.
Bill firmly believed in dietary cholesterol restriction and followed a low-cholesterol diet himself. Furthermore, he had the dietary staff prepare a low-cholesterol, high-fiber lunch for visiting colleagues to illustrate that such food was palatable and nutritious. At the end of a National Institutes of Health site visit held soon after he left Iowa, a senior committee member who had participated in several previous site visits took me aside and said that the group was very happy that Bill was no longer the Director of our Center. I was stunned and said, “Why, didn’t you like his work?” He replied, “No, we always thought that Bill’s research was great, but now we don’t have to eat those awful soybean and onion sandwiches for lunch.”
What probably was Bill’s most notable research accomplishment is a study performed in collaboration with Mark Armstrong and Emory Warner, which showed that cholesterol reduction caused regression of coronary atherosclerosis in a nonhuman primate. Their 1970 Circulation Research article was the first evidence that challenged the existing paradigm that atherosclerosis was an irreversible process. Bill followed this with evidence for cholesterol turnover in human atherosclerotic arteries, suggesting that regression also might be possible in humans. These seminal findings formed part of the growing scientific justification for the landmark Lipid Research Clinics multicenter trial demonstrating that low-density lipoprotein cholesterol reduction can produce regression of human coronary atherosclerosis.
Bill Connor’s discovery of the genetic disease sitosterolemia, published in 1974, is a clear indication of his scientific intuition. Two sisters were referred to him for treatment of large tendon xanthomas. He unexpectedly found that their plasma cholesterol concentrations were within normal limits and reasoned that the problem probably was caused by a cholesterol-like substance. Through detailed chromatographic analysis, he found abnormally high levels of β-sitosterol and campesterol in the patients’ plasma and tissues and showed that this was attributable to increased absorption of dietary plant sterols. He also tested both parents, found that they were unaffected, and concluded that the disease resulted from an inherited recessive trait.
After moving to Oregon, Bill continued his research on dietary fat and cholesterol-related metabolic diseases, especially the Smith-Lemli-Opitz syndrome. In addition, much of his effort was focused on the role of omega-3 (fish oil) fatty acids in the prevention of coronary disease and in facilitating central nervous system development. He performed the first metabolically controlled fish oil feeding studies with William Harris and showed that fish oil has a hypotriglyceridemic effect in human adults. Other studies with Martha Neuringer in developing rhesus monkey demonstrated the importance of omega-3 fatty acid in primate retinal and neural function. This was followed by dietary studies in human infants that established the amount of omega-3 fatty acid needed to produce an adequate blood level of docosahexaenoic acid, the omega-3 fatty acid necessary for optimum retinal and brain development. These findings contributed to the growing consensus that ultimately resulted in supplementation of infant formulas with omega-3 fatty acids.
Among Bill Connor’s numerous professional honors were election to the American Society for Clinical Investigation and Association of American Physicians. He also was elected Chairman of the American Heart Association Council of Arteriosclerosis (a forerunner of the Arteriosclerosis, Thrombosis, and Vascular Biology Council), was chosen to give the 1989 Duff lecture of the Council, and was an Arteriosclerosis, Thrombosis, and Vascular Biology Editorial Board member for many years. His notable national appointments included Chairman of the National Heart, Lung, and Blood Institute Program Projects Committee and Cochair of the United States Senate Select Committee Panel on Nutrition and Health. In addition, he was awarded honorary memberships in the American Dietetic Association and the American Board of Clinical Lipidology.
Bill loved the outdoors and was a strong advocate for the environment. He encouraged physical exercise and enjoyed cycling, hiking, gardening, and camping with his wife, 5 children, and 8 grandchildren. He also worked tirelessly for social justice and world peace. Bill was a patient teacher, very supportive mentor, and warm friend. He will be missed by his many scientific colleagues, especially by those of us who had the privilege of working with him.