“Nature is always a step or two ahead of us,” he explained. “In my world, we can hunt for a gene with a particular function for 10 years, and once we find it, it’s just the beginning. We always know we have much more to learn about it.”
An esteemed Finnish scientist who was recruited to Ohio State from the University of Helsinki in 1997, de la Chapelle devoted himself to lifelong learning until he died at age 87 in December 2020 after a 23-year tenure in which he developed and led the university’s human cancer genetics program to prominence. His death came just nine months after the passing of his wife, Clara D. Bloomfield, MD. Both were Distinguished University Professors at Ohio State.
De la Chapelle was internationally renowned as a pioneer in the study of human cancer genetics. His research, which included more than 800 publications in scientific journals over nearly half a century, led to important seminal discoveries about the molecular and genetic nature of cancer, setting the stage for innovative treatments.
De la Chapelle received numerous accolades during his career, including his election to the National Academy of Medicine and a lifetime achievement award from the Collaborative Group of the Americas on Inherited Colorectal Cancer (CGA-ICC). The CGA president at that time described de la Chapelle as “a giant in the field of genetics and specifically in colorectal cancer genetics” whose discoveries “paved the way for identification, diagnosis and cancer prevention in patients with mismatch repair mutations.”
De la Chapelle began his career at the University of Helsinki. His early work on the analysis of human X and Y sex-determining chromosomes identified the region of the Y chromosome responsible for maleness. He co-initiated the International Workshops on Chromosomes in Leukemia, which resulted in a series of discoveries. With the use of linkage disequilibrium to find genes responsible for hereditary diseases in isolated populations, his laboratory discovered the region of chromosomes responsible for 14 human diseases. For seven of those, he found the gene responsible for the disease.
One of de la Chapelle’s most important achievements was helping to identify and map four mismatch repair genes that cause Lynch syndrome (LS), an inherited disorder that makes certain families susceptible to colorectal cancer. By discerning that this susceptibility results from a damaged cell’s inability to repair its DNA, he discovered a cancer-causing mechanism.
At Ohio State, de la Chapelle not only led the human cancer genetics program for the OSUCCC – James but also mentored students and continued his groundbreaking research on molecular causes of cancer. His focus was on the mapping, cloning and characterization of high-and-low-penetrance genes for cancer predisposition.
He emphasized applying laboratory discoveries to the development of diagnostic procedures and treatments, including a test to screen people for LS, and studies that led to recommendations for the universal screening of patients with colorectal cancer for LS so that, if they tested positive, their relatives could be screened for LS as well. His work led to the Ohio Colorectal Cancer Prevention Initiative, which involved 50 hospitals throughout Ohio.
He also contributed to the study of papillary thyroid cancer (PTC), acute myeloid leukemia and endometrial cancer.
“The OSUCCC – James benefited for nearly a quarter century from Dr. de la Chapelle’s expertise as a researcher, educator, administrator and friend to all who worked with him or were mentored by him,” says OSUCCC director Raphael E. Pollock, MD, PhD, FACS. “His 1997 recruitment to Ohio State with Dr. Bloomfield was a momentous occasion for our program.”
Despite his many achievements, de la Chapelle once said he had no high aspirations for being remembered.
“I did not win the Nobel Prize, I did not detect the structure of DNA like (James) Watson and (Francis) Crick — those are the sorts of highly visible things that people remember,” he said. “But there will always be those who want to know how things evolved in certain academic disciplines, and there I hope I’ll have my little slot.”
Mission accomplished.