Although the HbS gene is most common in Africa, sickle cell disease went unreported in African medical literature until the 1870s. This may be because the symptoms were similar to those of other tropical diseases and because blood was not usually examined. In addition, children born with sickle cell disease usually died in infancy and were typically not seen by physicians. Most of the earliest published reports of the disease involved black patients living in the US.
African tribal populations were all too familiar with the disease and created their own names for it. It is interesting to note that the tribal names all carry repeating syllables – possibly to symbolize the repeating painful episodes.
Such names include ahututuo (from the Twi tribe); chwecheechwe (from the Ga tribe); nuidudui (from the Ewe tribe); and nwiiwii (from the Fante tribe). Many tribal names were also imitations of the cries and moans of the sufferers or formed such phrases as “body chewing” or “body biting” which described their terrible torment.
In one West African tribe, children who died soon after birth were called “ogbanjes” meaning children who come and go. The tribespeople believed that an evil spirit was trying to be born into a family with ogbanje children, but the babies bravely died to save the rest of the family from the demon. Some tribes had as many as 40% of the people carry the sickle cell gene.
In the US in 1846, a paper entitled “Case of Absence of the Spleen” (from the Southern Journal of Medical Pharmacology), was probably the first to describe sickle cell disease. It discussed the case of a runaway slave who had been executed. His body was autopsied and found to have “the strange phenomenon of a man having lived without a spleen.”
Although the slave’s condition was typical, the doctor had no way of knowing this as the disease had not yet been “discovered.” The first formal report of sickle cell disease came out of Chicago about 50 years later, in 1910. In 1922, after three more cases were reported, the disease was named “sickle cell anemia.”
In 1904, Dr. James Herrick reported “peculiar elongated and sickle shaped” red blood cells in “an intelligent negro of 20.” These sickled cells were discovered by a hospital intern, Dr. Ernest Irons, who examined the patient’s blood and sketched the strange cells.
The patient had come to Dr. Herrick with complaints of shortness of breath, heart palpitations, abdominal pain, and aches and pains in his muscles. He also felt tired all the time, had headaches, experienced attacks of dizziness, and had ulcers on his legs. After noting these symptoms, the doctor took samples of his blood.
This first sickle cell patient had come to Chicago in 1904 to study dentistry in one of the best schools of the country and was likely the only black student there. He was a wealthy man from the West Indies; and, despite repeated hospitalizations for his illness, Walter Clement Noel completed his training, along with his classmates, three years later. He returned to Grenada and practiced dentistry until he died of pneumonia at the age of 32. Although the disease does not distinguish between the rich and the poor, it does single out those from the tropical and subtropical climates of the Old World.
One long-held theory as to why it was so common in the tropics was its association with malaria. In the 1940s, E.A.Beet, a British medical officer stationed in Northern Rhodesia (now Zimbabwe), observed that blood from malaria patients who had sickle cell trait had fewer malarial parasites than blood from patients without the trait. Following this observation, a physician in Zaire reported that there were fewer cases of severe malaria among people with sickle cell trait than among those without it.
In 1954, Anthony Allison, continued to build on these observations and hypothesized that sickle cell trait offered protection against malaria. He suggested that those with the trait did not succumb to malaria as often as those without it; but, when they did, their disease was less severe.
It is now known that, when invaded by the malarial parasite, normally stable red cells of someone with the sickle cell trait can sickle in a low oxygen environment (like the veins). The sickling process destroys the invading organism and prevents it from spreading through the body. This apparent ability of a genetic condition to protect carriers is particularly important in infants. Thus, in regions repeatedly devastated by malaria, people who carry the sickle cell trait will have a greater chance for survival than other individuals.
In the following years, evidence began to collect in support of this theory as well as some against it. When studies were restricted to young people, the hypothesis held – the sickle cell trait did offer protection to children but not to adults since they were unable to develop antibodies to the malarial parasite. However, even though their immunity was partial, it did help them to survive but offered little additional advantage.
Since the youngsters were not able to produce antibodies to the malarial parasite until their immune systems matured, it was the pre-immune malarial patients whose survival was protected by sickle cell trait. For them as well, although protection was only partial, they did survive longer. Since then, several studies of malarial epidemics have revealed a higher survival rate for sickle cell trait individuals than for those who lack the gene HbS. These study areas included geographical distribution, gene frequency, and transgenic mice (the transportation of genes from one species into another).
An English neurologist, Lord Brain, once suggested that although a double dose of the sickle cell gene could be fatal, a single gene might increase a person’s resistance to a disease. As more research was done, it was discovered that he was right, especially when it came to malaria. However, only those with sickle cell trait, not the disease, are protected against malaria. Those with sickle cell disease would either die from the blood disorder or die after coming into contact with malaria because of their weakened immune systems. But if someone with sickle cell trait contracts malaria, the person’s body is somehow shielded from this potentially fatal disease.
Scientists have found that the red blood cells of people with sickle cell trait break down quickly when the malaria parasite attacks them. Since the parasite must grow inside red blood cells, the disease does not have a chance to become firmly established. However, not everyone with sickle cell trait is protected either. Apparent resistance to the disease occurs only in children between the ages of two and four.
Studies have shown that African Americans, who have lived in malaria-free areas for as long as ten generations, have lower sickle cell gene frequencies than Africans – and the frequencies have dropped more than those of other, less harmful African genes.
Similarly, the sickle cell gene is less common among blacks in Curacao, a malaria-free island in the Caribbean, than in Surinam, a neighboring country where malaria is rampant – even though the ancestors of both populations came from the same region of Africa.
There are several theories as to why people with sickle cell trait have milder cases of malaria. This has to do with their being a host to fewer and weaker parasites.
- The parasite inside the red cell produces acid. In the presence of acid, HbS has a tendency to polymerize which causes the cells to sickle. Since sickled cells are destroyed as the blood circulates through the spleen, the parasites are destroyed as well.
- Malarial parasites do not live long under low oxygen conditions. Since the oxygen concentration is low in the spleen, and since infected red cells tend to get trapped in the spleen, they may be killed there.
- Another thing that happens under low oxygen conditions is that potassium leaks out of HbS-containing cells. The parasite needs high potassium levels to develop. This may be the reason the parasite fails to thrive in red blood containing Hb S.