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Home , Anemia, Sickle cell disease

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In 1910, Chicago James B. Herrick published a description of oddly shaped cells taken from dental student Walter The past 100 years of sickle cell research have resulted in landmark discoveries that ushered in the era of molecular . Clement Noel, providing the first detail in Western medical literature of what has come to be known as . The NHLBI continues to look ahead to find new and better treatments. Its revitalized research portfolio of basic, clinical, and One hundred years later we know that the sickle-shaped cells are due to a defect in , the protein in red blood translational research addresses the genetic factors affecting disease manifestations, regulation of hemoglobin synthesis, cells that carries throughout the body. A genetic alteration in the hemoglobin molecule causes the body to produce development of drugs to increase production, and the development of animal models for preclinical studies. misshapen red blood cells, many of which take the characteristic “C”-shape that is the hallmark of sickle cell disease. The Institute supports research on transplantation of blood-forming stem cells, gene , a better understanding of and new treatments for , optimal uses of , and management of overload related to blood transfusions.

What is Sickle Cell Disease? The National , Lung, and Blood Institute The Institute is also leading an effort to develop evidence-based clinical practice guidelines for the care of people who have sickle cell disease, which are expected to be released in 2011. The NHLBI is committed to working with other agencies within Sickle cell disease, also known as sickle cell , is inherited. The National Heart, Lung, and Blood Institute (NHLBI), which the Department of Health and Services to disseminate the clinical guidelines with an emphasis on use by primary care People who have the disease inherit two copies of the sickle is part of the National Institutes of Health, has funded sickle practitioners. To ensure that the new guidelines reach their intended audiences, the NHLBI will launch a public awareness and cell gene—one from each parent. The gene codes for production cell research since 1948, when the NHLBI was founded as the education campaign to focus nationwide attention on sickle cell disease as a serious issue. of an abnormal hemoglobin. If a person inherits only one National Heart Institute. Since 1972, when the National Sickle copy of the sickle cell gene, he or she will have . Cell Disease Program began, the NHLBI has spent more than The NHLBI recognizes that actively engaging patients, families, practitioners, and communities is essential to improving the People who have sickle cell trait do not have the disease, $1 billion on sickle cell research. lives of persons affected by sickle cell disease, and will continue to work with them, community-based groups and scientific but they carry one of the genes that causes it. Similar to organizations to do so. people who have sickle cell disease, people with sickle cell The NHLBI has played a crucial role in not only funding basic trait can pass the gene to their children. research but also devising and implementing large clinical A Century of Progress: trials, and conducting workshops and consensus meetings to In the , sickle cell disease affects an estimated guide the research agenda. Research on sickle cell disease Sickle Cell Disease and Clinical Trials 70,000 to 100,000 people, the majority of whom are African and other diseases that affect hemoglobin has played a The NHLBI sponsors a number of important clinical trials designed to advance the search for better treatments of sickle cell Milestones in Sickle Cell Disease Americans. All states screen newborns for sickle cell disease. central role in the advancement of genetics and molecular disease. These studies would not be possible without the participation of volunteers who help researchers determine which Sickle cell disease occurs in approximately one out of every biology and has sparked innovations in other areas of . treatments work. For information on current clinical trials, please visit: http://www.clinicaltrials.gov/. 500 African American births and one out of every 36,000 Hispanic American births. In addition, about 2 million people More important, the contributions of clinical trial participants Research and Care More information on sickle cell disease is available at http://www.nhlbi.nih.gov/new/sicklecell.htm. in the United States have sickle cell trait. have been essential for the development of new treatments for sickle cell disease. Because of their contributions, we NHLBI Health Information Center The symptoms and complications of sickle cell disease vary have gained an understanding of the molecular causes of the P.O. Box 30105 widely. Some people have mild symptoms while others have disease; developed effective approaches for preventing and Bethesda, MD 20824-0105 very severe symptoms and are hospitalized frequently for treating its complications including infection, , and lung Phone: 301-592-8573 treatment. Normal red cells pass smoothly through the blood disease; and even cured a small number of people using bone TTY: 240-629-3255 vessels, but sickled cells are stiff and sticky. Sickled cells tend marrow transplantation. Fax: 301-592-8563 to form clumps that can block blood flow and to episodes of extreme pain, known as crises, as well as chronic damage Discrimination Prohibited: Under provisions of applicable public laws enacted by Congress since 1964, no person in the United States shall, on the grounds of race, color, national origin, handicap, or age, be excluded from participation in, be denied the benefits of, or be subjected to discrimination under any to vital organs. Persons with sickle cell disease have life-long program or activity (or, on the basis of sex, with respect to any education program or activity) receiving Federal financial assistance. In addition, Executive anemia because their red blood cells survive only about Order 11141 prohibits discrimination on the basis of age by contractors and subcontractors in the performance of Federal contracts, and Executive Order one-tenth as long as cells with normal hemoglobin. 11246 states that no federally funded contractor may discriminate against any employee or applicant for employment because of race, color, religion, sex, or national origin. Therefore, the Heart, Lung, and Blood Institute must be operated in compliance with these laws and Executive Orders.

Bone marrow transplants offer a cure to children and Photo credit for 1910 Herrick paper: Archives of , 1910, VI(5):517-521, Copyright © 1910 American Medical Association. All right reserved. adolescents who have a matched donor. Because of the limited availability of matched bone marrow donors, however, sickle cell disease has no widely available cure. Treatments are available to address symptoms and complications.

People who have sickle cell disease now lead longer, more productive lives. In the early 1970s, the average lifespan was only 14 years. Today, individuals with sickle cell disease are Publication No: 10-7657 living into their forties or fifties, and beyond. September 2010 1910 1945 1949-1950 1957 1971 1972-1973 1978 1987 1996 2001 2006 2009 Chicago physician James B. Herrick “ There are frequent abdominal Inheritance of sickle cell disease Scientists show abnormality of The National Association for Sickle National Sickle Cell Disease Program Prenatal method to diagnose sickle cell NIH Consensus Development Panel Method developed to use maternal Program starts to collect The NHLBI launches Sickle Cell Study in NHLBI laboratory finds first publishes a description of sickled independently described by two sickle hemoglobin due to amino acid Cell Disease founded. It becomes established. The National Heart disease using DNA samples reported. recommends screening all U.S. blood sample for prenatal diagnosis umbilical from sibling Disease Clinical Research Network. modified blood adult stem-cell cells in a blood sample from 20-year-old crises which may mislead the best teams. Sickle cell genes needed from substitution in protein, making sickle the Sickle Cell Disease Association of and Lung Institute begins funding newborns for sickle cell disease of disease. donors in families with children transplant regimen reverses sickle dental student Walter Clement Noel surgeon into operating for some both parents to produce sickle cell cell disease the first America, Inc. in 1994. comprehensive sickle cell centers and The NHLBI launches multicenter study and giving to all affected who have sickle cell disease or NHLBI scientists find that a cell disease in nine of 10 adults from Grenada. Term “sickle cell acute surgical condition when disease. Receiving gene from one whose molecular basis is known. establishes sickle cell branch at Institute. with 4,000-plus individuals from infants by 3 months of age. with the goal of future , brain natriuretic peptide severely affected by disease. anemia” coined based on paper. parent produces sickle cell trait. “ It is a sad and shameful fact newborns to age 70. First study to transplantation. or BNP, detected in a simple blood the real diagnosis is sickle-cell that the causes of this disease document clinical course of disease test can identify people with sickle Clinical trial testing of drug anemia…” from birth to adulthood. Researchers use to cell disease who have developed treatment for pulmonary 1959 have been largely neglected 1973 correct sickle cell disease in mice. pulmonary , a life- hypertension in adults with – Dr. John T. Givens, Journal of Marclan A. Walker, a 21-year-old West throughout our history. Scientists develop neonatal screening threatening . disease stopped early due to the National Medical Association Virginia college student, describes methods using blood spots on 1979 safety concerns. We cannot rewrite this record filter paper. life with sickle cell disease in the Red blood cells from patients with Ebony magazine story, “I’m living of neglect, but we can reverse it. 2002 The NHLBI convenes workshop of sickle cell disease shown to stick more The Health Resources and Services on borrowed time.” Story was later To this end, this administration readily to cells lining blood vessels 2008 researchers, health care providers, picked up by Time magazine. Administration The Newborn Screening Saves 1948 than do normal red blood cells. advocacy organizations, patients, The National Heart Institute established. is increasing its budget for Program starts. Lives Act of 2007 establishes and others to discuss key public Sickled cells from 1910 Herrick paper grants to provide for education and First round of grants includes $8,640 Public Awareness Poster research and treatment of outreach issues. to Dr. James Neel to study inheritance sickle-cell anemia . . .” 1980 Multicenter study of bone marrow outreach on newborn screening and of sickle cell disease. 1963 NIH Consensus Development transplantation in children with coordinated follow-up care. 1951 The three-dimensional structure of – President Richard Nixon, Binding of sickled red blood cells to Panel Report sickle cell disease finds the procedure Scientific American runs story on the hemoglobin protein deciphered in his “Special Message to the inside of blood vessels shown to can cure young sickle cell patients NIH Consensus Development Panel 2010 Pauling’s discovery of molecular using x-ray crystallography. block blood flow. Extent of stickiness Newborn screening for sickle cell finds hydroxyurea treatment Sidney Poitier directs and stars in who have siblings that share a “ I’m only a patient when I’m in nature of sickle cell disease, raising Monumental accomplishment took the Congress Proposing a suggested as possible determinant of disease required in 44 states, the underused and recommends its movie “A Warm December,” which specific protein. the doctor’s office, I’m really a public awareness of the condition. over 20 years to complete. Dr. Max National Health Strategy” disease severity. District of Columbia, Puerto Rico, increased use in adolescents Perutz received the Nobel Prize for has sickle cell disease as a central theme. and the U.S. Virgin Islands. and adults. whole person living an active this work in 1967. 1997 life; I just happen to live with Dr. James Herrick 1982 1972 Periodic blood transfusions in children sickle cell disease.” 1974 The NHLBI first publishes “The with sickle cell disease who are at Dr. James Neel National Sickle Cell Anemia Control 1991 “ The shape of the reds was very Feasibility of newborn screening for Management of Sickle Cell Disease.” high risk for stroke shown to reduce – Tiffany McCoy, a person who 1968 Act provides for establishment First line of mice that have sickle sickle cell disease demonstrated. risk of first stroke by 90 percent. irregular, but what especially Research suggests low concentration Researchers describe red cells from of voluntary sickle cell disease cell disease developed to aid in lives with sickle cell disease The compound 5-azacytidine shown 2003 of sickled cells in blood from newborns individuals with sickle cell disease screening; counseling; public and finding treatments. attracted attention was the large Method for prenatal diagnosis to elevate fetal hemoglobin levels. Hydroxyurea therapy found to with sickle cell disease due to high that remain sickled even when oxygen professional education; and research “W ith the completion of [this number of thin, elongated, sickle- by sampling fetal blood from the improve survival in adults most level of fetal hemoglobin in their red Dr. levels are restored. Cells termed and training in diagnosing, treating, severely affected with disease. umbilical vein developed. study], we now know that we shaped and crescent-shaped forms.” blood cells. “irreversibly sickled.” and controlling disease. Howard 1984 University’s Dr. Roland Scott played can effectively prevent the – Dr. James B. Herrick Several teams independently NIH Consensus Development Panel Report “ There are many things yet to be a leading role in advocating for the act. demonstrate that hydroxyurea two leading causes of death in 2004 learned about sickle cell anemia. 1953 1975 increases fetal hemoglobin levels. Diagnostic tool developed to identify 1969 children with sickle cell disease: Study finds children with sickle “ The compelling benefits of Tiffany McCoy 1933 New York becomes first state to Fame and distinction await the sickle cell disease and other conditions National Heart Institute becomes cell disease at high risk for stroke Scientists test 2,500 African Americans in require newborn screening for sickle Bone marrow transplant performed Study shows even small increases in pneumococcal and stroke.” hydroxyurea warrant increased man who can solve the problems due to defective hemoglobin. National Heart and Lung Institute. who stop receiving periodic blood The NHLBI and the Centers for Disease Memphis; determine sickle cell trait and cell disease. to treat a child with . It also fetal hemoglobin can result in fewer – “S ickle Cell Research for transfusions after 30-month adoption of this drug as a Control and Prevention launch sickle cell disease are separate entities. of this malady.” cures the child’s sickle cell disease. pain crises. Treatment and Cure,” NHLBI minimum return to high risk frontline therapy in adults with program to determine the number – Editorial, Journal of the of stroke. of people diagnosed with inherited National Medical Association 1954 1970 sickle cell disease.” blood disorders, including sickle 1934 Sickle cell trait found to protect “ What has been little appreciated, 1986 1995 1998 U.S. Postal Service issues Sickle Cell – Dr. Otis Brawley, cell disease. Dr. Roland Scott An NHLBI study shows penicillin as Painful sickle cell “crises” suggested against . Finding explains why despite all this study and interest, is Major NHLBI-sponsored study The Food and Drug Administration Disease Awareness postage stamp. conference panel chair the prevalence of the sickle gene in a preventive measure in children NHLBI-supported study shows to result from blockages of small A milder variation of sickle cell shows hydroxyurea reduces number approves hydroxyurea for sickle cell blood vessels. corresponds with regions where the real importance of the disease with sickle cell disease 3 months to 3 of pain crises and related hospital adults with sickle cell disease may 1949 disease found in disease treatment in adults based on The NHLBI realigns Sickle Cell Dr. Linus Pauling and others reveal malaria is a major cause of death. years old can reduce the incidence of visits by 50 percent. Treatment have changes in brain function. as a community health problem.” associated with increased levels of NHLBI-sponsored study. Disease Research Program by that sickle cell disease due to abnormal Streptococcus infection, increases fetal hemoglobin levels fetal hemoglobin. Finding suggested expanding support for basic hemoglobin protein molecule. Term – Dr. Robert B. Scott, a major cause of childhood death, by and is first effective therapy for James B. Herrick Symposium increasing fetal hemoglobin levels research and developing a new 1940 “molecular disease” coined. Journal of the American 84 percent. Practice later becomes severely affected adults with sickle — Sickle Cell Disease Care and could offer treatment target. Clinical Trials Research Network Researchers suggest exchange of 1955 widely adopted. cell disease. Research: Past, Present and Future Medical Association and evidence-based treatment. oxygen for carbon dioxide occurring in developed to identify commemorates 100th anniversary of stars in TV movie “To All Also initiates development small blood vessels may cause red blood abnormal hemoglobin, a method 1976 NHLBI-sponsored study shows once Herrick’s paper that first identified My Friends On Shore,” which addresses of evidence-based clinical cells to sickle and block blood vessels. still used today to confirm sickle cell National Heart and Lung Institute a child with sickle cell disease is 5 sickle cell disease. Symposium sickle cell disease. practice guidelines. disease diagnosis. becomes the National Heart, Lung, years old, penicillin treatment can brings together researchers, health and Blood Institute (NHLBI). be stopped. care providers, advocacy groups, patients, and the public.

For references on studies noted in the timeline, please visit http://www.nhlbi.nih.gov/new/ sicklecell.htm.