The Cause of Sickle-Cell Anemia 1949 – The First Identified Genetic Disorder

African tribal populations often have their own names for sickle-cell anemia (SCA), a painful blood disorder that can be fatal. In one West African tribe, such children are often called “children who come and go” —the meaning of the name ogbanjes. According to some legends, these children died to free their families from demons.

SCA is notable for being the first disease conclusively shown to be caused by a specific protein abnormality and the first genetic disorder whose molecular basis was fully understood. 

People with SCA have red blood cells with abnormal hemoglobin proteins, which normally carry oxygen to tissues through the bloodstream. The condition occurs when a child inherits a ‘defective hemoglobin gene’ from both parents. If a normal and a defective gene are inherited, the person has sickle-cell trait (SCT), but no symptoms. In malaria-affected regions, SCA also becomes an evolutionary advantage. People with SCA are resistant to malaria infection. 

In SCA, red blood cells (RBCs) can take on an inflexible sickle (crescent) shape that can block capillaries and restrict blood flow. Symptoms include:

• Pain
• Increased blood pressure in the pulmonary artery
• Stroke 
• Kidney failure

Anemia (a low RBC count) results from the destruction of sickled cells in the spleen. However, if a malaria parasite enters an RBC in a person with SCT, the RBC may break down more quickly than in a person without the trait. This makes it harder for the parasite to reproduce.

In 1910, the American physician James Herrick and his intern Ernest Irons published a report on a patient's sickle-shaped blood cells. In 1949, the American chemist Linus Pauling and his colleagues showed that SCA results from an abnormal hemoglobin molecule. SCA can be treated with blood transfusions, bone marrow transplants and treatments such as hydroxyurea, which reactivates the production of beneficial fetal hemoglobin.

About the Article Image: Normal and sickle-shaped red blood cells.

Historical Figures Mentioned in the Article: James Bryan Herrick (1861–1954), Ernest Edward Irons (1877– 1959), Linus Carl Pauling (1901–1994)

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