Denham Harman, M.D., Ph.D., 98, a legendary figure in science for his 1954 proposal of the Free Radical Theory of Aging, died Tuesday at Lakeside Hospital in Omaha after a brief illness. He served on the faculty of the University of Nebraska Medical Center in Omaha for 52 years (1958 to 2010).
Dr. Harman, who was nominated six times for the Nobel Prize, theorized that free radicals - highly reactive molecules freed in the normal chemical processes - cause aging and disease through their destructive actions in cells and tissues. The theory was first ridiculed and dismissed by many in the scientific community, but gained support in the 1960s with other scientists.
He added further support to the theory by conducting pioneering research on the role of antioxidants - vitamins C, E and beta-carotene - and how they can reduce the cancer-causing and atherosclerosis-causing effects of free radicals.
“If we are able to extend human lifespan it is only by standing on the shoulders of giants like Dr. Harman,” said David Sinclair, Ph.D., professor at Harvard Medical School and a leading expert in aging who gained notoriety for his discovery that resveratrol, a compound in red wine, activates a protein that promotes health and longevity in animal models. “Dr. Harman embodies the best of American scientific pursuit, having made seminal contributions to knowledge and giving generously to students and to the wider community.
"Dr. Harman is one of the most influential scientists of the past 50 years, bringing world-class science to what was once a backwater of biology. His Free Radical Theory of Aging is a cornerstone of the aging field. He has inspired thousands of young scientists to work on aging, including myself.”
Last April, Dr. Sinclair came to UNMC to deliver the Denham Harman, M.D., Ph.D., Lectureship in Biomedical Gerontology, which was established in 2002 by the University of Nebraska Foundation to honor Dr. Harman.
A San Francisco native, Dr. Harman earned his undergraduate (1940) and doctorate (1943) degrees in chemistry from the University of California at Berkeley and his medical degree (1954) from Stanford University. At the time he developed his aging theory, Dr. Harman was serving as a research fellow in the Donner Laboratory of Medical Physics at UC-Berkeley.
His interest in aging was sparked by an article titled “Tomorrow You May Be Younger.” It appeared in The Ladies Home Journal and was written by William Laurence, science editor of the New York Times.
From 1943 to 1949, Dr. Harman worked as a research chemist for Shell Development Company in Emeryville, Calif. While working at Shell, his research produced 35 basic patents, including the compound for the Shell No Pest Strip.
Dr. Harman joined the UNMC faculty in 1958 when he was named the Nebraska Heart Association Chair of Cardiovascular Research with appointments in biochemistry and internal medicine. He was promoted to professor of medicine and biochemistry in 1968 and was honored in 1973 by being designated the Millard Professor of Medicine.
Because elderly patients had special needs, Dr. Harman believed geriatrics, or care of the elderly, should be a separate subsection of internal medicine. In 1973, UNMC established the first section of biomedical gerontology with Dr. Harman serving as section head. It was the first such program in the country. Today, it is commonplace for academic health science centers to have gerontology sections.
Dr. Harman retired in 1986 and was named an emeritus professor, but he never relented in his quest to better understand aging. “His work became his hobby,” said Helen Harman, his wife of 71 years.
Dr. Harman continued to work at his office from 9 a.m. to 4 p.m., four days per week until 2010 - at the age of 94 - when his health deteriorated following surgeries and he moved to an assisted living facility.
In 1970, Dr. Harman helped establish the American Aging Association (AGE), a national lay-scientific health organization patterned after the American Heart Association. Its main purpose is to promote biomedical aging research directed towards slowing the aging process. He served as AGE’s first president and as executive director of the organization from 1972 to 1992. In 1985, he founded the International Association of Biomedical Gerontology.
In addition to serving on the UNMC faculty, Dr. Harman served as chief of the Nebraska Geriatric Service for Douglas County Hospital from 1971 to 1986.
His numerous awards include: the 1999 Distinguished Alumni Award from the Stanford Medical Alumni Association; being recognized in 2000 as one of the 40 outstanding Stanford medical graduates during the past century; the Distinguished Achievement Award from AGE in 2002; and the 2003 Dean’s Award for Outstanding Contributions to the UNMC College of Medicine. In 1981, he was appointed chairman of one of the committees of the White House Conference on Aging.
Earlier this year, Dr. Harman was nominated by UNMC for the prestigious National Medal of Science Award. Winners from this year’s nominees have yet to be announced.
Dr. Harman traveled extensively around the world speaking on aging. He spent a month in Japan lecturing to students and professionals around the country. He was named an honorary member of the Japan Society for Biomedical Gerontology and the South Korean National Aging Institute.
He was a fellow in the American College of Physicians, the American College of Nutrition, the American Geriatric Society, the Gerontological Society of America, the American Heart Association Council on Atherosclerosis, and the Radiation Research Society.
A memorial service will be held at 10 a.m. Saturday at Dundee Presbyterian Church, 5312 Underwood Ave. with a reception following. Memorials should be made to the Harman Lectureship Fund through the University of Nebraska Foundation.
In addition to his wife, Helen, survivors include a sister, Marjorie Harman, Omaha; three sons - Doug (Pamela), Winnetka, Ill., David, Omaha, and Mark, a physician in Tulsa, Okla. - one daughter, Robin Harman, and her husband, William Alexander, Plano, Texas; and four grandchildren, Lesley and Meredith Harman, Winnetka, Ill. and Andrew and McKenna Alexander, Plano, Texas.
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What others are saying about Denham Harman:
“Dr. Harman created a paradigm shift not only in how we think about aging, but also in the understanding of several chronic diseases. It is not possible to pick up any major text on aging or on chronic disease without reading about free radicals. He was among the most influential scientists of his generation and had a major impact on research in aging, cardiovascular disease and cancer. All of us at UNMC should feel honored to have been associated with him. As a scientist and as a wonderful person, he will be greatly missed.”
Jane Potter, M.D., Neumann and Mildred Harris Geriatrics Professor and division chief of geriatrics at UNMC
“Denham made landmark contributions to science and humanity with his introduction of the Free Radical Theory of Aging. We were fortunate to have such an accomplished scientist in our midst for so long. He was nominated for the Nobel Prize! UNMC and the world at large are better off because of Denham Harman.”
Harold M. Maurer, M.D., chancellor emeritus, UNMC
“Dr. Harman was an anti-aging pioneer. The free radical theory of aging was quite controversial when he first proposed it, and he carried out the landmark experiments that showed that antioxidants can slow the aging process. Here at UNMC, he helped develop and grow the geriatrics and gerontology programs and remained actively engaged long after he became an emeritus faculty. He leaves behind an incredible legacy. He truly made a difference.”
Jennifer Larsen, M.D., vice chancellor for research, UNMC
“Dr. Harman held a very unique role on the internal medicine faculty at UNMC. He developed an innovative hypothesis regarding one mechanism of aging and saw his theory accepted by aging experts around the world and extended into the areas of chronic degenerative diseases and malignant transformation of tissues. Dr. Harman brought great academic recognition to both himself and the medical center through his scientific understanding that translated into practical clinical approaches in geriatric care.”
Lynell W. Klassen, M.D., Robert L. Grissom Professor of Internal Medicine and former chair, UNMC Department of Internal Medicine
“Although I never had the honor of meeting Dr. Harman personally, I’m very familiar with his contributions to the field of aging. He is - without question - a historic figure in the world of science. We lost a great man, but he leaves behind a rich legacy that will never be forgotten. My condolences to his family and friends on the passing of this scientific icon.”
Jeffrey P. Gold, M.D., UNMC chancellor
“Dr. Harman’s Free Radical Theory brought needed perspective to the differences in species’ lifespan regarding protection against these processes, and it offered testable hypotheses regarding interventions. As my career in aging expanded past my graduate training, it was most gratifying to finally meet Dr. Harman in person at various scientific meetings. It was even more delightful to discover the warm and inviting person behind this great intellect. He was so supportive and encouraging of young investigators and would gladly discuss issues in the biology of aging. Through the force of his science and his leadership of the American Aging Association, Dr. Harman created an enduring legacy which will stand strongly through the years.”
Donald Ingram, Ph.D., professor, Nutritional Neuroscience and Aging Laboratory, Pennington Biomedical Research Center, Louisiana State University System
“Dr. Denham Harman is one of the true pioneers of aging research. The free radical hypothesis has been a central element of the field ever since Dr. Harman's landmark paper. Beyond his own work and continued exploration of the free radical hypothesis, Dr. Harman's contribution to science has helped lay the foundation for important, related areas of inquiry such as the mitochondrial and DNA damage hypotheses. We can trace the field of stress response, its role in aging and the significant inroads provided in understanding metabolic syndrome back, in significant measure, to Dr. Harman's work as well.”
Richard J. Hodes, M.D., director of the National Institute on Aging, National Institutes of Health
“I entered the scientific world of aging shortly after I saw the name Denham Harman and never imagined that I would meet him for the first time in San Antonio in 1995. Since then, I never stopped working on the subject and with the help of his seminal ideas. In 2007, we made a major symposium in Porto, Portugal, ‘The Free Radical Theory of Aging - 50 years and beyond - A Tribute to Denham Harman.’ It was attended by 180 people from 15 countries. Dr. Harman could not come, but in fact, especially for this event, he recorded a live intervention which was broadcast in the lecture hall. It was unforgettable.”
Henrique Almeida, M.D., Ph.D., Faculdade de Medicina do Porto, IBMC - Instituto de Biologia Molecular e Celular, Porto, Portugal
"Denham’s contribution to both the understanding and the eventual medical control of aging cannot be overstated. His original free radical theory of 1954 and his incredibly prescient extension of it to mitochondria in 1972 were among the foremost theoretical contributions to our field in its century-long history. Equally momentous has been his stout defense of the view that biogerontology’s ultimate goal is the elimination of age-related physical and mental decline, even in the decades when such a position was viewed as politically suicidal. Without him as a role model, I seriously doubt that I would have had half the success in this field that I have.”
Aubrey de Grey Ph.D., biomedical gerontologist, chief science officer of SENS Research Foundation, Mountain View, Calif.
“As a scientist who has been going to meetings on the biology of aging all over the world for many decades, I am hard put to think of a single meeting at which the name ‘Denham Harman’ and his famous free radical theory of aging has not been discussed! We are all inspired by his pioneering research and by his organizational skills in the founding of the American Aging Association.”
George Martin, M.D., professor of pathology emeritus, University of Washington, Seattle
“I have respected Dr. Harman’s foresighted thinking of free radicals being the basis of biological aging since I started to work on aging seriously more than 30 years ago. The originality of his idea certainly deserves a Nobel Prize. It was a great pleasure when he and his wife, Helen, kindly visited our country to receive the Honorary Membership of the Japan Society for Biomedical Gerontology at the age of 87, an age that one might hesitate to travel such a long distance.”
Sataro Goto, Ph.D., Juntendo University Graduate School, Institute of Health and Sports Science & Medicine, Japan
“Denham Harman is the visionary who saw the connection between radiation-causing free radical oxidative damage and premature aging, and free radical by-products of mitochondria in normal metabolism contributing to the aging process. I am one of the many scientists who have followed in his footsteps. We celebrate his pioneering vision.”
Bruce Ames, Ph.D., professor of molecular and cell biology at the University of California, Berkeley, and senior research scientist at the Children's Hospital Oakland Research Institute
“The original free radical theory aging proposed by Denham Harman was the most novel aging hypothesis and played the pivotal role in the understanding of possible mechanisms underlying the aging process and age-related disease process. Although the original theory needed modifications as the free radical science progressed, the important involvement of free radicals as the most potent factors in modulating various aspects of the aging process is undeniable.”
Byung Pal Yu, Ph.D., professor emeritus, University of Texas Health Science Center, San Antonio
“Dr. Harman was one of the pioneers who elaborated translational scientific research, antioxidative medicine and therapies such as antioxidant orthomolecular, scavenger, anti-oxidative stress. His findings generated an important development in gerontology and geriatrics, anti-aging medicine, longevity sciences and in bio-medicine in general. He is a remarkable figure in the field of science of the 20th and 21st centuries.”
Dan Riga, M.D., Ph.D. and Sorin Riga, M.D., Ph.D., directors of the Department of Stress Research & Prophylaxis, Bucharest, Romania