COLUMBUS, Ohio - Dr. Albert de la Chapelle, an Ohio State University scientist who has spent 40 years studying the labyrinthine complexity of human genetics, has won the 2002 William Allan Award, the highest honor bestowed by the American Society of Human Genetics (ASHG). De la Chapelle, director of the Human Cancer Genetics Program in The Ohio State University Comprehensive Cancer Center and holder of the Charlotte and Leonard Immke Chair of Cancer Genetics, accepted the award at the annual ASHG meeting in Baltimore.
This is the second award this year recognizing de la Chapelle's four decades of research and discovery; just five months ago, he received the Mauro Baschirotto Award for research achievement from the European Society of Human Genetics.
"This is an outstanding tribute, and a clear reflection of our threefold mission of excellence in research, education, and patient care," says Dr. Fred Sanfilippo, senior vice president for health sciences and dean of the College of Medicine and Public Health at Ohio State. "The university is very proud of Dr. de la Chapelle."
The Allan Award, established in 1961, is named after William Allan (1881-1943), one of the first American physicians to conduct extensive research in human genetics. The award is presented annually to recognize outstanding contribution and achievement in human genetics. The recipient receives a medal and a $10,000 personal prize, and gives a plenary address to the ASHG annual meeting. De la Chapelle's keynote address will be, "Inherited Diseases: Challenges, Victories and Disappointments."
"I am really quite honored, and very surprised," says de la Chapelle. "There are so many others who have made substantial contributions to the field."
De la Chapelle, a member of the U.S. National Academy of Sciences, has devoted most of his life researching the relationship between genetic mutation and disease. He says the pace of discovery in the field is astounding.
"I initially became intrigued with genetics in 1958 under the tutelage of Dr. Herman Hortling, an endocrinologist who was interested in Turner's Syndrome. At that time, genetics had virtually no impact upon human beings and their health, but today we see it infiltrating all of medicine, and really making a difference in how people are treated."
Trained as a medical doctor at the University of Helsinki, Finland, de la Chapelle was board certified in internal medicine in 1965, but moved quickly into the field of genetics, having earned a Ph.D. in human genetics three years earlier. He received postdoctoral training in biochemistry at Columbia University, studied biochemical genetics at the MRC Biochemical Genetics Unit in London and molecular genetics at the University of Paris. He was the first professor of medical genetics in Finland, and chairman of the Department of Medical Genetics at the University of Helsinki from 1974 to1997.
Much of de la Chapelle's early work focused on the genetics of human sex differentiation and determination; he was the first to describe a human male with an entirely normal-looking female XX karyotype, the reverse of the usual situation. This finding illustrated that XX males may actually need only a small amount of genetic material, possibly a single gene, to determine maleness. Today, scientists know the SRY gene is the key factor in this process.
A pioneer in the genetics of leukemia and lymphoma, de la Chapelle discovered various genetic mutations present in acute myeloid leukemia (AML) that signal poorer prognosis. Much of his early work in AML was conducted through the International Workshops on Chromosomes in Leukemia, which he co-founded in 1978, and which continue today as a forum for international collaboration in cancer research.
More recently, de la Chapelle has worked with colleagues worldwide in identifying the genetic footprint behind a number of disorders that are disproportionately represented in the Finnish population. The Finnish population is a prototypical founder population, displaying many characteristics and genetic bottlenecks that make it fertile ground for genetics research. Over the years, approximately 34 hereditary disorders have been identified in the Finnish population, with de la Chapelle's research group responsible for molecularly characterizing many of them. These include diastrophic dysplasia, hereditary hypogonadotropic gonadal failure, progressive epilepsy with mental retardation, and, recently, cartilage hair hypoplasia and Usher syndrome type 3.
A major finding in the early 1990s was the first demonstration that hereditary nonpolyposis colorectal cancer (HNPCC) was a regularly inherited predisposition to cancer caused by mutations in the mismatch repair genes, and that microsatellite instability (MSI) or how DNA replication errors are repaired, is a hallmark of these tumors. This opened the study of a new category of cancer predisposition and progression that is caused by mismatch repair deficiency.
Since joining the faculty at Ohio State, de la Chapelle has continued his work in the genetics of colon cancer. He and his research team have identified many of the molecular changes involved in HNPCC. He demonstrated that HNPCC may account for 2 percent to 5 percent of all colon cancers and that microsatellite instability can be used as a relatively easy and highly powerful tool to screen for these cancers.
Currently, de la Chapelle and his research team at Ohio State are conducting a prospective clinical trial designed to determine the incidence of HNPCC in all newly diagnosed colorectal and endometrial cancer patients in the Columbus area over a three-year period. Preliminary data suggest MSI may be an appropriate means to screen for both hereditary colon and endometrial cancer in the general patient population, a move that could help reduce the incidence and mortality of those cancers by identifying individuals having an exceptionally high-risk.