History & Timeline of Sickle Cell Disease

Sickle Cell Disease is the most common inherited blood disorder in the United States and is estimated to affect more than 100,000 Americans. Every year, more than 2,000 babies are born with this disease. That’s nearly 1 in 365 Black or African-American births.

Worldwide, it is estimated that over 300,000 babies are born with sickle cell disease every single year. Sadly, in some parts of the world, many do not live to see their 5th birthdays. The majority of these births are in low and middle income countries.

Discovery of Sickle Cell Disease in the US

“Peculiar elongated and sickle-shaped” is how sickle cells were first described in 1904 by intern Ernest Edward Irons when examining the blood of Walter Clement Noel, a 20-year-old first-year dental student from a wealthy Black family in Grenada. Noel had been admitted to the Chicago Presbyterian Hospital suffering from anemia and was readmitted several times over the next three years before completing his studies and returning to Grenada to successfully practice dentistry. He died of pneumonia in 1916.

Iron’s supervising physician, James B. Herrick, wrote a paper published in 1910 in the Archives of Internal Medicine documenting the first known case of sickle cell disease in the United States.

Although this was the first known US case, elements of the disease had been recognized earlier: African medical literature reported this condition in the 1870s, when it was known in some areas as ”ogbanjes” (“children who come and go”) because of the very high infant mortality rate caused by this condition. There are reports of the condition tracking back to 1670 in one Ghanaian family.

While sickle cell disease primarily affects persons of African descent, it is also present in Portuguese, Spanish, French Corsicans, Sardinians, Sicilians, mainland Italians, Greeks, Turks and Cypriots. Sickle cell disease also appears in Middle Eastern countries and Asia.

Linus Pauling and colleagues were the first, in 1949, to demonstrate that sickle cell disease occurs as a result of an abnormality in the red blood cell. This historical finding was the first time a genetic disease was linked to a mutation of a specific protein.

The origin of the mutation that led to the sickle-cell gene derives from at least four independent mutational events, three in Africa and a fourth in either Saudi Arabia or central India. These independent events occurred between 3,000 and 6,000 generations ago, approximately 70-150,000 years.

A significant figure in Sickle Cell history is Dr. Charles F. Whitten. He was a trailblazer in medical education and sickle cell disease awareness. During the early 1970s, he realized that services for people with sickle cell disease and their families were sorely lacking. Out of his pioneering efforts to advocate for the needs of people with sickle cell disease, the Sickle Cell Disease Association of America (SCDAA) was born.

In 1960 Dr. Whitten started a fund to help minority medical students with financial and academic assistance. He wrote many educational materials and was the recipient of many honors and awards. His papers are archived in the National Institutes of Health Library of Medicine. He was received in the Oval office by three sitting U.S. presidents.

Dr. Whitten died in 2008. He is survived by his wife, Eloise (Culmer) Whitten; his daughters Lisa Whitten, PhD and Wanda Whitten Shurney, MD.

Sickle Cell Timeline (U.S.)

1904 – An unknown (and unnamed) blood disorder was informally described by a medical intern named Ernest Edwards Irons when examining the blood of Walter Clement, a 20 year old dental student from Grenada, West Indies.
1910 – Dr. James Herrick provides the first formal description of sickle cell anemia when he reports that the blood smear of a dental student, Walter Clement, at the Chicago College of Dental Surgery contains “pear-shaped and elongated forms”.
1927 – Hahn and Gillespie associate the sickling of red blood cells with low oxygen conditions.
1940 – Sherman reports that the sickling of red blood cells in the absence of oxygen is caused by a change in the hemoglobin molecule structure.
1948 – Watson suggests that the presence of fetal hemoglobin in the red blood cells of sickle cell newborns is the reason they do not show disease symptoms.
1949 – Noted physical chemist Linus Pauling and associates publish “Sickle Cell Anemia, a Molecular Disease” in Science. This paper explains how protein electrophoresis was used to show that sickle cell hemoglobin differed in structure from normal hemoglobin. This was the first time that the cause of a disease was linked to a change in protein structure.
1956 – Vernon Ingram and J.A. Hunt sequence hemoglobin and discover that the change of a single amino acid in the protein sequence is the cause of sickle cell anemia.
1968 – Although the Black Panther Party for Self Defense (BPP) was founded in 1966, in 1968 the BPP began establishing People’s Free Medical Clinics (PFMC) because of systemic discrimination against Blacks in hospitals and private medical practices and offered everything from free breakfasts for school children to free sickle cell testing. By 1970 all BPP chapters were required to establish PFMC’s.
1971 – The BPP established the Sickle Cell Anemia Research Foundation with efforts to eradicate the disease. Along with already established educational and medical campaigning, the BPP also continued their community screening for Sickle Cell Disease and trait.
1972 – The U.S. Congress passes the National Sickle Cell Anemia Control Act of 1972 as a direct result of the BPP’s relentless advocacy and widespread community education about sickle cell anemia and the government’s neglect of the disease. The Act created national genetic counseling, testing, and research to diagnose and treat sickle cell anemia.
1975 – The state of New York becomes the first state to add Sickle Cell Anemia to it’s panel of newborn screening tests.
1978 – Flavell prepares maps of the human beta and delta globin genes.
1984 – Bone Marrow Transplantation in a child with sickle cell disease produced the first reported cure of the disease. Although the transplantation was done to treat acute leukemia, the child’s sickle cell disease was cured as a side-event. The procedure nonetheless set the precedence for later transplantation efforts directed specifically at sickle cell disease
1988 – Minnesota begins testing all newborns for sickle cell anemia through it’s newborn screening program.
1995 – Upon the completion of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia, Charache reports that the anticancer drug hydroxyurea is the first to reduce the frequent, painful complications that characterize sickle cell disease.
1997 – Periodic blood transfusions in children with sickle cell disease who are at risk for stroke shown to reduce risk of stroke by 90%.
1998 – Under the “Orphan Drug Act of 1983”, the Food and Drug Administration approves hydroxyurea for sickle cell disease. treatment in adults based on the NHLBI sponsored study.
2002 – The Health Resources and Services Administration Newborn Screening Program starts
2004 – Study finds children with sickle cell disease at high risk for stroke who stop receiving blood transfusions after 30 month minimum return to high risk of stroke.
2004 – US Postal Service issues Sickle Cell Disease Awareness Stamp
2005 – South Dakota becomes the last and final state to add sickle cell disease to it’s Newborn Screening Program
2006 – NHLBI launches Sickle Cell Disease Clinical Research Networ
2008 – United Nations passes a resolution declaring World Sickle Cell Disease Day
2009 – Study in NHLBI laboratory finds modified blood adult stem cell transplant regimen reverses sickle cell disease in nine of 10 adults severely affected by disease.
2010 – 100th Anniversary of Herricks’ paper that first identified sickle cell disease.
2015 – Thanks to the hard work and advocacy of Genetic Counselor, Maggie Dreon and others in the sickle cell community, Minnesota Department of Health officially began their sickle cell trait notification program.
2015 – Sickle Cell Support Services (dba Sickle Cell Foundation of Minnesota) is founded.
The Sickle Cell Foundation of Minnesota (SickleCellMN), a 501c3 non profit community based agency was founded on January 1, 2015 to provide much needed advocacy and education support to the sickle cell community. This organization exists to improve the lives of individuals and communities affected by sickle cell disease.
SickleCellMN works in partnership with health care professionals and is open to individuals, sickle cell clinics and treatment centers, health care providers, state and local government agencies, and other organizations that support improved health outcomes in the State of Minnesota.
2017 – 100th Anniversary of Herricks’ research paper that first identified sickle cell disease.
2017 – Although given approval for adult use in 1998, the Food and Drug Administration (FDA) gave full and final approval for use of Hydroxyurea in children. Between 1998 and 2017, the drug had only been given a “special use” approval for use in children.
2017 – Under the “Orphan Drug Act of 1983”, the FDA approves Endari (medical grade L-Glutamine) to treat sickle cell in patients as young as 5 years old, making it only the 2nd approved drug for treating sickle cell disease in the U.S.
2019 – The FDA approved Voxelotor (Oxbryta, Global Blood Therapeutics) for adults and children ages 12 and older with sickle cell disease, becoming the very first drug to treat sickle cell disease by targeting hemoglobin S.
2019 – The FDA approved Crizanlizumab (Adakveo, Novartis) to reduce the frequency of vaso-occlusive crisis (VOC’s) in adults and children aged 16 years and older with sickle cell disease.