Sickle Cell was the first disease understood at the molecular level, but we’ll get to that awesome story later. The story of Sickle Cell is a study in how a good thing can come with bad consequences.

Once upon a time in the Green Sahara (this part of Africa was wet and rainy and covered with forest 7,300 years ago) a child was born with heightened immunity to malaria.

It was a great habitat for mosquitoes, which carry malaria, a disease that these days kills one child every two minutes.

This child would have been born with a genetic mutation in one chromosome, affecting the shape of the blood’s hemoglobin. The child wouldn’t have suffered because the other gene would have been perfectly normal.

With a better chance against an illness that was a major killer, then as now, this child with the genetic mutation lived and had children, and those children spread out. The mutation would have endured, passing on for hundreds of years before one unfortunate child would have been born with two copies of the mutation and would have developed Sickle Cell Anemia.

The first recorded cases in history occurred in Egypt during the predynastic period (3200 BCE)

During the Bantu migrations and, later, the slave trade, Sickle Cell would have travelled to other parts of Africa and on to other parts of the world, including the Near East, India, and Southern Europe, developing into different sub-types along the way.

The first modern report of sickle cell disease may have been in 1846 where the autopsy of an executed runaway slave was discussed; the key finding was the absence of the spleen. Reportedly, African slaves in the United States exhibited resistance to malaria, but were prone to leg ulcers.

The abnormal characteristics of the red blood cells, which later lent their name to the condition, were first described by Ernest E. Irons who was an intern to Chicago cardiologist and professor of medicine 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. Noel had been admitted to the Chicago Presbyterian Hospital in December 1904 suffering from anaemia.

Shortly after the report by Herrick, another case appeared in the Virginia Medical Semi-Monthly with the same title, “Peculiar Elongated and Sickle-Shaped Red Blood Corpuscles in a Case of Severe Anemia.” This article is based on a patient admitted to the University of Virginia Hospital on November 15, 1910.

In 1922, the name “Sickle Cell Anemia” is first used in a description by Verne Mason.

In 1927, scientists Hahn and Gillespie showed that sickling of the red cells was related to low oxygen.

In 1940, Sherman (a student at Johns Hopkins Medical School) noticed a difference between the way light passed through sickled blood cells compared to normal cells.

In 1948 Janet Watson, a pediatric hematologist in New York, suggested that the scarcity of sickle cells in the peripheral blood of newborns was due to the presence of fetal hemoglobin in the red cells, which consequently did not have the abnormal sickle hemoglobin seen in adults.

In 1949, chemist Linus Pauling, who would go on to win two Nobel Prizes, co-authored a paper in Science offering the first-ever proof that a human disease was caused by an abnormal protein. A genetic mutation inherited from both parents caused defects in the hemoglobin protein found in red blood cells. Using the new technique of protein electrophoresis, Linus Pauling and Harvey Itano showed that the hemoglobin from patients with sickle cell disease is different than that of regular people. This made Sickle Cell the first disorder in which an abnormality in a protein was known to be at fault.

In 1956 Vernon Ingram and J.A. Hunt sequenced sickle hemoglobin and showed that a glutamic acid at position 6 was replaced by a valine in sickle cell disease. Using the known information about amino acids and the codons that coded for them, he was able to predict the mutation in sickle cell disease. This made Sickle Cell the first genetic disorder whose molecular basis was known.

In 1977 the development of DNA sequencing by Walter Gilbert and Frederick Sanger allowed the mapping of the Sickle Cell gene.

In 1984 a bone marrow transplantion in a child with Sickle Cell produced the first reported cure of the disease. The transplantation was done to treat acute leukemia. The child’s Sickle Cell was cured as a side-event. The procedure nonetheless set the precedence for later transplanting efforts directed specifically at Sickle Cell.

In 1995 Hydroxyurea became the first drug proven to help prevent complications of Sickle Cell.

In July 2019, a team edited the DNA of an American woman with Sickle Cell. Doctors first removed stem cells from the woman’s bone marrow. Then, they genetically modified them using CRISPR to make them produce a protein that makes healthy red blood cells but whose production is typically shut down shortly after birth. The procedure was successful, but researchers need time—at least two years—to know how it will hold up in the long run.

In November 2019 the U.S. Food and Drug Administration approved Adakveo, a treatment to reduce the frequency of vaso-occlusive crisis for patients age 16 years and older.

This month a trial investigating the safety, feasibility and efficacy of a form of gene therapy (ARU-1801) for children and adults with Sickle Cell is underway in the U.S. and Jamaica.