Parent and Caregiver Handbook for Sickle Cell
Appendix: History of sickle cell disease
Below is a quick summary of the history of sickle cell disease, including some of its high and low points.
4950 BC: Sickle cell disease is known to have existed 7,000 years ago. Genetic studies suggest that the Egyptian King Tut may have had sickle cell disease. It is found in African tribal records dating back to at least 1670 in Ghana. Following the slave trade to the United States, characteristics of sickle cell disease were described in enslaved persons throughout the 1800s.
1600s – 1800s: Shamans (early medicine men) from different tribes in Africa discovered sickle cell disease long before the 1900s, realized that it passed from parents to children, and gave it names in their tribal languages.
1910: Sickled red blood cells were first described by Ernest E. Irons and James B. Herrick in 1910. Irons saw “peculiar elongated and sickle-shaped” cells in the blood of a man named Walter Clement Noel, a 20-year-old, first-year dental student from Grenada. These observations led to the name “sickle cell disease.”
1931: Dr. Lemuel Whitley Diggs noted that pain in sickle cell disease occurred because of clogging of small blood vessels.
1949: Linus Pauling, a great chemist, discovered that sickle cell disease was caused by a mutation in the hemoglobin within the red cell. This led to the announcement that sickle cell disease was the first molecular disease. Pauling went on to promote a campaign to keep people with sickle cell trait from having children in the 1960s but dropped it amid heavy criticism in the 1970s.
1957: The Sickle Cell Disease Foundation, the first and oldest non-profit, social service, sickle cell disease organization was founded in California.
1960s and 1970s: Sickle cell became a lightning rod for the civil rights movement. At the time, the average patient died before age 20 years.
1970: Dr. Roland B. Scott published a series of important articles calling sickle cell disease, “high prevalence, low priority.” Dr. Scott described how sickle cell disease, despite being common, received very little financial support compared to other diseases that are less common but occur in non-Blacks. Despite scientific discoveries, little investment was made to improve the lives of people with sickle cell disease.
1970: In Oakland, the Black Panthers screened thousands for sickle cell disease as part of their nutrition and health programs. Black universities, the Black Panther Party, and Martin Luther King, Jr. took up sickle cell disease as a cause, publicizing it as a neglected health problem and civil rights issue as never before.
1971: Dr. Charles Whitten founded the Sickle Cell Disease Association of America, the largest community-based organization for sickle cell disease in the world, dedicated to improving the lives of people with sickle cell disease.
1972: After years of pressure from leaders in the civil rights movement, the U.S. government passed the Sickle Cell Anemia Control Act, which established government funding for screening, research, and treatment of sickle cell disease.
1973: Positive effects of screening newborns and individuals for sickle cell trait led to discrimination against healthy people with sickle cell trait.
1976: Dr. WY Kahn developed a method to diagnose sickle cell disease prenatally.
1980: Dr. Robert P. Hebbel discovered that sickle cells are very sticky, and that they clog the blood vessels because of this. This laid the groundwork for approval of the drugs that prevent sickle cells from sticking to the blood vessels.
1982: Dr. Joseph DeSimone showed that people living with sickle cell disease had the ability to activate a dormant gene that produced fetal hemoglobin. Fetal hemoglobin is normally produced in the babies in the womb and very young babies, even in sickle cell disease. It does not sickle. That same year, it was found that drugs (hydroxyurea) could increase the level of fetal hemoglobin after birth in people with sickle cell disease and thalassemia.
1985: Dr. Howard Pearson discovered that people with sickle cell lose the function of their spleen as babies. The loss of normal spleen function is the major cause of life-threatening infections in people with sickle cell disorders.
1986: Dr. Marilyn Gaston led the Prophylactic Penicillin Study that demonstrated that prophylactic (daily, even if a person is not sick) penicillin taken by healthy children living with sickle cell disease prevented most life-threatening infections.
1988: Dr. Elliott Vichinsky showed that newborn screening for sickle cell disease dramatically lowered the infant death rate. This was followed by universal screening of all newborns in California.
1990s: Newborn screening took hold and life expectancy had doubled, with people with sickle cell disease living into their 40s.
1994: The Cooperative Study of Sickle Cell Disease demonstrated that comprehensive care for sickle cell disease helped those with the disease live into their 50s and 60s.
1995: The Multicenter Study of Hydroxyurea, led by Dr. Samuel Charache, was completed. It showed that the use of hydroxyurea in people with severe sickle cell disease resulted in fewer hospitalizations and painful events, and less need for blood transfusions. The drug raised fetal hemoglobin and lowered inflammation.
1996: Dr. Mark Walters found in a large multicenter trial that bone marrow transplant can cure children with sickle cell disease.
1998: Hydroxyurea became the first drug approved by the U.S. Food and Drug Administration (FDA) for the prevention of sickle cell disease complications in adults.
1998: The Stroke Prevention Study in Sickle Cell Disease showed that transcranial doppler – a way of looking at blood flow in the brain – could identify children at risk for a stroke. This was followed by a study that showed that regular blood transfusions could help prevent strokes for these children.
2000: Dr. Elliott Vichinsky found that acute chest syndrome was a leading cause of death for those with sickle cell disease. Acute chest syndrome is an infection of the lungs that can happen in children and adults living with sickle cell disease. He found it could be prevented with early diagnosis and transfusion.
2001: Dr. Samuel Ballas found that people with sickle cell disease were not receiving standard-of-care treatment, and that an ethical crisis existed in the medical world. This ethical crisis was most apparent in the treatment of adults with sickle cell disease who were discriminated against by health institutions and providers.
2004: Dr. Darlene R. Powars looked at sickle cell disease in over 1,000 people and found that as they aged, organ failure caused about half of the deaths in the group. This led to finding that early detection of organ injury could prevent or lessen organ damage.
2004: Dr. Mark T. Gladwin found that pulmonary hypertension (high blood pressure in the lungs) is a serious problem for people living with sickle cell disease and may lead to death. Often this condition is not screened for, although it can be diagnosed by a simple test. Once diagnosed, pulmonary hypertension can be treated.
2009: Dr. Labouch was responsible for curing sickle cell disease in a patient using gene therapy. This was followed by research trials with multiple patients receiving gene therapy. While gene therapy is still being studied for its safety and long-term success, the studies have shown that people with sickle cell disease who do not have a matching bone marrow transplant donor may be cured by using their own stem cells.
2014: Dr. Michael R. DeBaun and others found that silent cerebral infarction (blood not flowing in the brain) is the most common neurologic problem in children with sickle cell disease. Cerebral infarction causes learning disabilities and increased risk of a clinical stroke. Regular screening of children at risk with MRI can find early infarctions, which can be corrected with transfusions and new drug therapies. This and other studies showed the need to monitor children with sickle cell disease for subtle signs of learning deficits so that these problems can be improved or corrected.
2015: Dr. Russell Ware and others in the international TWITCH trial found that hydroxyurea can replace the need for chronic transfusions in many children with sickle cell disease who are at risk for stroke. This study was followed by others around the world that found that hydroxyurea is safe and effective for prevention of stroke and other sickle cell complications in countries with limited resources.
2017: The FDA approved L-glutamine (Endari) for the treatment of sickle cell disease. This oral supplement lowers the number of painful events and the need for hospitalizations.
2019: The FDA approved crizanlizumab (Adakveo), an IV medication that blocks the sticking of sickled cells to blood vessels. This study showed that patients taking this medication had fewer hospitalizations for pain.
2019: The FDA approved oral voxelotor (Oxbryta). This drug reduces sickling by improving the health of the red blood cells, resulting in increased hemoglobin and less anemia.
2019: Governor Gavin Newsom signed the Budget Act of 2019 approving $15 million in sickle cell disease funding to expand access to services and better understand long-term trends in diagnosis, treatment, and healthcare access for people with sickle cell disease in California. Efforts by the Pacific Sickle Cell Regional Collaborative (PSCRC) and the Sickle Cell Disease Foundation led to this funding and the creation of the Networking California for Sickle Cell Care Initiative (NCSCC).
2020s: New gene therapies hold great promise for finding a cure for sickle cell disease. Research involving stem cell or bone marrow transplants and CRISPR gene-editing therapy is advancing quickly, raising questions about safety, cost, and access.
This information is provided courtesy of the University of San Francisco, Benioff Children’s Hospital Oakland Sickle Cell Center.