In memoriam: Bernard G. Forget
Authors: Ronald P. McCaffrey, Bertil E. Glader
Journal: American Journal of Hematology (2016)

Bernard G. Forget, MD, one of the most important figures in American hematology, died on November 6, 2015, at the age of 76. He was educated at the University of Montreal, receiving a B.A. in 1959, and, in 1963, he received his M.D. from McGill University, where he was class valedictorian. His medical internship and residency were completed at Massachusetts General Hospital. This was followed by a resident year in Pathology at the same institution. He was a Clinical Associate at the NIH for two years and spent a year as a Visiting Fellow in the Biochemistry Laboratory of Professor R. Monier in Marseille, France. Upon his return to the US, he completed a clinical and research fellowship in Pediatric Hematology, in David Nathan's Hematology Division at Boston Children's Hospital, Harvard Medical School. Following the fellowship he joined the faculty, advancing to the rank of Associate Professor of Pediatrics in 1975. He moved to the Yale School of Medicine in 1976, to head up the Division of Hematology, becoming Professor of Medicine and Genetics in 1978. He spent the remainder of his career at Yale, where he was renowned as a researcher, clinician, and teacher. His early scientific work focused on the purification and characterization of human globin mRNA, and working with Edward Benz, he soon demonstrated the functional properties of their mRNA preparations. Techniques were later developed in partnership with David Houseman to establish a cDNA–mRNA hybridization assay to accurately measure the relative abundance of alpha and beta mRNAs in RNA preparations. This collaboration demonstrated quantitative deficiency of beta-globin mRNA in beta-thalassemia and quantitative deficiency of alpha-globin mRNA in alpha-thalassemia. Later, they demonstrated the deletion of beta-globin gene sequences in the syndrome of hereditary persistence of fetal hemoglobin. The Forget laboratory also carried out detailed mapping, cloning, and characterization of the beta-gene cluster in deletion forms of hereditary persistence of fetal hemoglobin and delta-beta-thalassemia. Another important collaborator of Dr. Forget was his Yale colleague, Sherwin Weissman. A major accomplishment was their demonstration that one of the common forms of beta-thalassemia is due to a substitution in an intron of the beta-globin gene that causes alternative splicing of the precursor globin mRNA, one of the first descriptions of this mechanism as the molecular basis of a human genetic disease. Later, the emphasis in the Forget laboratory shifted to the molecular analysis of genes encoding the erythrocyte membrane skeleton proteins such as spectrin and ankyrin, elucidating the molecular basis of hereditary hemolytic anemias due to abnormalities of the red cell membrane. The cDNAs and genes for alpha spectrin, beta spectrin, and ankyrin were cloned and their structures determined. In addition, specific point mutations of these genes were identified in association with clinical cases of hereditary spherocytosis. More recently, Forget studied the gene expression profile of hematopoietic stem/progenitor cells with the goal to elucidate transcriptional regulatory circuits during hematopoiesis. He was the author of over 280 scientific publications. The textbook, Hemoglobin: Molecular Genetic and Clinical Aspects, which he co-authored with Frank Bunn in 1986 remains a classic hemoglobinopathy reference text. His numerous awards included the Henry M. Stratton Medal of the American Society of Hematology in 1996 for distinguished research in hematology, and in 2007, he was elected to membership in the American Academy of Arts and Sciences. In 2013, he received the Yale Cancer Center Lifetime Achievement Award. He was beloved by his colleagues, all of whom counted him as a friend. He influenced the lives of generations of young scientists at Yale, at Harvard, and throughout the world, and was famous for his quiet, insightful, courteous style of discourse. He was always fun to be with in social situations, especially at the annual meeting of the American Society of Hematology (ASH), where for many years an after-hours, salon-like gathering, referred to as The Chateau Forget, was a fixture. Over the years hundreds of colleagues would be welcomed for late-night, wonderfully relaxed, discussion and socialization. Bernadette, his wife of more than 50 years, and their children and grandchildren, were the loves of his life. They anchored him, they brought him joy, and they made him the happy, fulfilled person he was. He and Bernadette loved France, and those friends who were able to be with them on their frequent visits to France fondly recall the intensely happy experience of being with them in Paris and Provence.