Sickle Cell Secrets
In 1907, a surgeon and an intern discovered why cells sickle after
they noticed something odd.
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Centuries ago African tribes chose names for sickle cell anemia to express the misery the disease inflicts: chwechweechwe (relentless, gnawing pains in the bones and joints), hemkom (body-biting), and nuidudim (body-chewing).
The illness was not discovered in the West until 1904. That year, a dental student from Grenada came to a Chicago hospital complaining of muscle pain, headaches and heart palpitations. Physician James Herrick examined a sample of his blood and saw “peculiar, elongated and sickle-shaped red blood corpuscles” among the usual round variety. It was 1927 before researchers were able to show what triggered that sickling.
While preparing to test the effect of formaldehyde on sickle cells, Indiana University School of Medicine surgeon E. Vernon Hahn and intern Elizabeth Gillespie noticed something odd. When they shook a tube of solution containing distorted red blood cells, the cells regained their disc shape. Hypothesizing that a lack of oxygen encouraged sickling, they exposed the cells to gases that did not contain free-ranging oxygen. In nearly every case, the cells sickled.
A few years later, researchers in Canada took a simpler approach: They tightened a rubber band around a finger to cut off the flow of oxygenated blood, punctured it and examined the blood that dripped out. These observations led chemist Linus Pauling to identify hemoglobin—an oxygen-carrying protein within the red blood cell—as the culprit.
A single inherited mutation prevents sickle cell hemoglobin from carrying sufficient oxygen. After defective hemoglobin molecules release their oxygen, they cluster into rodlike structures that push against the cell’s membrane, bending it into a sickle shape. Because sickle cells have a much shorter life span than normal cells, anemia results. The more severe symptoms (crippling pain, strokes and early death) come when sickle cells, which are rigid, clog vessel openings, blocking the flow of blood to vital organs and extremities.
Today, sickle cell anemia remains particularly common in sub-Saharan Africa and among people of African descent. (It is also regularly found in other malaria-stricken regions; the sickle cell trait confers some resistance to malaria.)
Therapies such as blood transfusions have increased life expectancy. But the first preventive medicine wasn’t discovered until 1995: Hydroxyurea, an anticancer drug, seems to prompt production of fetal hemoglobin, which is less apt to sickle.
“It was the most important therapeutic discovery in many decades,” says Martin Steinberg, director of the Center for Excellence in Sickle Cell Disease at Boston Medical Center.
In 2001 scientists at MIT and Harvard cured the disease in mice with an antisickling gene. Steinberg cautions: “Gene therapy is a goal to pursue but may be a long way off.”