Neal Young received a A.B. cum laude from Harvard College in 1967 and his M.D. in 1971 from the Johns Hopkins School of Medicine. He did post-graduate medical training at Massachusetts General Hospital and Barnes Hospital at Washington University in St. Louis before joining the NHLBI in 1981. He is a Master of the American College of Physicians and the recipient of more than 30 awards and honors, including most recently the 2012 Samuel J. Heyman Service to America Medal (Sammie) for Science and the Environment. Dr. Young has authored 270 original scientific and medical articles in peer reviewed journals and more than 120 reviews and book chapters. He also is author or editor of 10 medical and scientific books, including a new textbook of hematology. Dr. Young is a member of the American Society for Clinical Investigation, American Association of Physicians, American Federation for Clinical Research, American Society of Hematology, and International Society for Experimental Hematology. He is co-inventor on 7 patents concerning B19 parvovirus.
Dr. Young’s research is focused on bone marrow failure—human diseases that result in a failure to produce blood cells, i.e. aplastic anemia. His comprehensive bedside-to-bench approach begins with enrolling hundreds of patients per year in the largest bone marrow failure clinic in the world. His laboratory uses a variety of approaches to analyze these patient samples for clues to disease etiology, which then inform work in animal models. His research has taken several directions including immune-mediated pathology, the genetics of bone marrow failure, and viruses that provoke the abnormal immune response or directly kill hematopoietic stem cells.
In severe acquired aplastic anemia, the bone marrow is entirely devoid of hematopoietic stem and progenitor cells as a result of immune-mediated destruction. The disease is incurable, but therapeutic immunosuppression through the infusion of antithymocyte globulin (ATG)—polyclonal antibodies generated in animals by inoculation with human thymocytes—has proven beneficial. Dr. Young studies the immunological and cell biological mechanisms that contribute to stem cell destruction and uses the resulting data to inform therapeutic approaches. He has recently published the first prospective study demonstrating the superior effectiveness of horse ATG as compared to the current standard of care, rabbit ATG. In addition to redefining the most effective immune-directed therapy, the finding raises questions about therapeutic mechanisms that may translate into even more effective strategies.
After screening blood or marrow cells from patients with apparently acquired aplastic anemia, Dr. Young and his colleagues described the first mutations in TERT, the gene for telomerase reverse transcriptase. They found correspondingly low telomerase enzymatic activity and shortened telomeres in white blood cells from these patients. Following up on these observations, Dr. Young has shown that shortened telomeres result in chromosomal instability in hematopoietic cells and precede malignant evolution in human aplastic anemia, providing insight into some potential origins of this disease.
Dr. Young also focuses on the pathogenic mechanisms of the human parvovirus B19, which targets human bone marrow erythroid progenitor cells. In individuals with underlying hemolytic disorders, parvovirus B19 infection results in transient aplastic crisis (TAC), a temporary cessation of red blood cell production with severe worsening of anemia, which is occasionally fatal. In immunosuppressed individuals, parvovirus B19 can persist and cause severe anemia and pure red cell aplasia. Upon maternal infection, B19 can be particularly dangerous to a developing fetus. The major capsid protein of parvovirus B19, VP2, constitutes about 95% of the capsid structure. The minor capsid protein, VP1, is identical except for an additional 227 amino acids at the amino terminus. Dr. Young has studied the immunogenicity of these capsid proteins to determine the critical components required to elicit a neutralizing antibody response. As a result of this research, a candidate parvovirus B19 vaccine has recently entered early human trials.
If successful, this vaccine could benefit countless at-risk people, and would represent another research success that has made Dr. Young’s research clinic an international referral center for people with aplastic anemia and other bone marrow failure syndromes.