Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
It often seems like only yesterday that I was growing up in New Orleans, where I witnessed the interaction of genetics and the environment around the city’s diverse neighborhoods. I saw a range of people suffering from obesity, diabetes, and other ailments resulting from a poor diet and lack of exercise.
These experiences pointed me toward science as a career, but something else stoked my passion for hematology: I saw three of my close friends suffer unbearable, unimaginable pain from sickle cell disease. And I was helpless to do anything about it. Then, two of them died while I was still in high school. The third died several years later. When you’re a teenager, you’re not supposed to bury your friends. But that’s what sickle cell does. That’s the toll it takes. And that’s how I was drawn into hematology.
During medical school at Brown University and beyond, I pursued my passion for hematology research. Eventually, I was fortunate to be part of the team that contributed to the development of the first and only FDA-approved therapy for sickle cell disease, hydroxyurea. More recently, colleagues in my lab reported on a modified blood stem cell transplant regimen that has reversed sickle cell disease in adults and is associated with relatively low toxicity. Mere words cannot describe how good it feels to see people live longer and better lives.
And now, as director of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), I’m privileged to work with an extraordinarily talented team of scientific and administrative managers who work tirelessly to support our own scientists and grantees and who are searching for cures and better methods for preventing and managing illnesses that rank among America’s greatest public health challenges.
I’m often asked how NIDDK, with its broad scope of seemingly unrelated interests, happened to get into the hematology business. It dates back to 1950, when NIH Institutes were fewer and further between. What is now NIDDK was established as the National Institute of Arthritis and Metabolic Diseases (NIAMD) by the Omnibus Medical Research Act. The newly created NIAMD incorporated and expanded the laboratories of the preexisting Experimental Biology and Medicine Institute, which had been handling nearly all internal medicine research outside of cardiology — a de facto “Institute of Internal Medicine,” although not in name. The NIAMD’s mission included clinical investigation in rheumatic diseases, diabetes, anemias, and various metabolic and gastrointestinal diseases. This was logical at the time, as hematology was considered an integral component of internal medicine rather than its own specialty as we know it today.
Also in the early 1950s, NIAMD started to award hematology research grants, focused on the following general areas within the field: erythrocyte production, turnover, aging, and metabolism; erythropoietic regulation and erythropoietin; hemolytic anemias; hemoglobin; B12 and folate; iron metabolism; hematopoiesis and bone marrow grafts; transplant immunology; immunohematology; and leukocyte cell biology.
As part of one of those very first NIDDK research grants — number 0002 to be exact — NIH-supported researchers, led by legendary hematologist the late Dr. Max Wintrobe, helped to pioneer many ground-breaking discoveries that resulted in a clearer understanding of red cell metabolism and how hereditary disorders can lead to several debilitating diseases.
In the 1960s, the discovery and characterization of the human leukocyte antigen (HLA) system shed important light on the immune response and molecular differentiation between “self” and “non-self” cells and tissues.
In the 1980s, our scientists helped to develop techniques for cloning of genes for human hematopoietic cytokines, for expression of these cytokines as recombinant proteins, and for successful introduction of these biological therapies — EPO and G-CSF — into clinical practice. The clinical availability of EPO, now in various forms, has had a major impact on the management of anemia associated with renal failure. G-CSF is now widely used to hasten the recovery of circulating neutrophils following myelosuppressive chemotherapy, and equally important, to release hematopoietic stem and progenitor cells from the bone marrow into the circulation where they can be harvested by apheresis for use in autologous and allogeneic transplantation. These so-called “G-CSF mobilized” hematopoietic stem cells (HSC) support much more rapid hematopoietic recovery in transplant recipients than that achieved by HSC harvested directly from the marrow, greatly reducing the early toxicity and risks of these transplants.
As the 1990s approached and throughout that decade, we contributed to detailing immunophenotyping of human blood cell subtypes with murine monoclonal antibodies specific for cell surface molecules. This procedure has allowed for major advances in understanding cellular immune responses, in diagnosing and classifying leukemias and lymphomas, and in isolating, through immunophenotypic recognition, transplantable HSCs. Further, this research has led to the production of various recombinant “humanized” murine monoclonal antibody preparations that are now widely used clinically both to prevent platelet aggregation and restenosis following cardiac bypass surgery or arterial stenting and to treat B-cell malignancies.
Scientists have made many other remarkable discoveries revealing genetic associations with diseases. Pertaining to hematology, understanding these genes is important in at least the following three areas of research:
The basic mechanisms involved in hematopoiesis and in regulating the expression of genes relevant to normal blood cell maturation and function
The metabolism, storage, and transport of iron and disorders resulting from disturbances in these processes, including hemochromatosis and ironrestricted anemias
The basis of acquired and congenital disorders of erythropoiesis, including anemias, thalassemias, and sickle cell disease resulting from disturbances in the production or function of hemoglobin
As NIDDK reflects on the past 60 years of supporting and conducting research, it is clear that the scientific progress achieved during that time period has been remarkable. Looking to the future, NIDDK will continue to build on the landmark scientific discoveries of the past to foster new research breakthroughs. Paramount to this effort is the continued vigorous support of basic, pre-clinical, and clinical research, as well as the development of educational materials to disseminate important new research findings to patients, their families, and health-care providers. To inform research directions in hematology, NIDDK will continue to solicit input from the broad scientific community through forums such as scientific workshops and conferences. In addition, strategic planning, with broad external input, will continue to guide future research directions. To view a poster that illustrates the long, productive research experience that NIDDK’s hematology grantees have had, visit www2.niddk.nih.gov/Funding/OnTheRoad/OnTheRoad_2011_ASHematology.htm.
Moving forward, NIDDK is hopeful that its research portfolio will continue to provide scientific insights and improvements in patient care. As always, an important component of the Institute’s support for biomedical research is its strategic planning. Often, initiatives and funding solicitations emerge from opportunities identified through this planning process, which reflect both broad scientific review and input from key stakeholders. Planning may occur in an ad hoc process or may be organized under the auspices of the Kidney, Urologic, and Hematologic Diseases Interagency Coordinating Committee, and sometimes involves partnering with professional and/or patient advocacy groups. Through these efforts, NIDDK seeks to steer the research enterprise in a way that follows science while maximizing the return on the Institute’s investment in order to improve the lives of patients and their families.
