Sickle Cell Disease Research

Sickle Cell anemia is a group of inherited red blood cell disorders. Normal red blood cells are round like doughnuts, and they move through small blood tubes in the body to deliver oxygen. Sickle red blood cellsbecome hard, sticky and shaped like sickles used to cut wheat. When these hard and pointed red cells go through the small blood tube, they clog the flow and break apart. This can cause pain, damage and a low blood count, or anemia. There is a substance in the red cell called hemoglobin that carries oxygen inside the cell. One little change in this substance causes the hemoglobin to form long rods in the red cell when it gives away oxygen. These rigid rods change the red cell into a sickle shapeinstead of the round shape.

Sickle cell is in many nationalities including African Americans, Arabs, Greeks, Italians, Latin Americans and those from India. You can be Caucasian and have sickle cell disease or trait. All races should be screened for this hemoglobin at birth.

In western literature, the first description of sickle cell disease was by a Chicago physician, James B. Herrick, who noted in 1910 that a patient of his from the West Indies had an anemia characterized by unusual red cells that were “sickle shaped.” In 1927, 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) noted findings that suggested that low oxygen altered the structure of the hemoglobin in the molecule. Janet Watson, a pediatric hematolist in New York, suggested in 1948 that the paucity 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. Using the new technique of protein electrophoresis, Linus Pauling and Harvey Itano showed in 1948 that the hemoglobin from patients with sickle cell disease is different than that of people who did not have sickle cell disease. This made sickle cell disease the first disorder in which an abnormality in a protein was known to be at fault.

In 1956, Vernon Ingram then at the MRC in England, 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 disease the first genetic disorder whose molecular basis was known.

In 1984, bone marrow transplantation in a child with sickle cell disease produced the first reported cure of the disease. 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.

Sickle cell disease is an inherited condition. Two genes for the sickle hemoglobin must be inherited from one's parents in order to have the disease. A person who receives a gene for sickle cell disease from one parent and a normal gene from the other has a condition called "sickle cell trait". Sickle cell trait produces no symptoms or problems for most people. Sickle cell disease can neither be contracted nor passed on to another person. The severity of sickle cell disease varies tremendously. Some people with sickle cell disease lead lives that are nearly normal. Others are less fortunate, and can suffer from a variety of complications. Sickle cell disease is extremely varied in its manifestations. This includes both the organ systems that are affected as well as the severity of the affliction. A study of the natural history of sickle cell disease indicated that about 5% of patients account for nearly one-third of hospital admissions (Platt et al., 1991). A significant number of patients with the disease have few admissions and live productive and relatively healthy lives. The average life-span of people with sickle cell disease is shorter than normal, however, reflecting increased mortality due to the complications of the disease.

Complications from the sickle cells blocking blood flow and early breaking apart include:

pain episodes
strokes
increased infections
leg ulcers
bone damage
yellow eyes or jaundice
early gallstones
lung blockage
kidney damage and loss of body water in urine
painful erections in men (priapism)
blood blockage in the spleen or liver (sequestration)
eye damage
low red blood cell counts (anemia)
delayed growth

The Dream Foundation has recognized that we must continue to explore the biological basis of sickle cell disease and its severity and through the proceeds from the ‘Live the Dream’ specialty license plate, is providing funding for such research efforts.

Forty-one states and the District of Columbia provide universal screening for sickle cell disease. Three states target screening to infants of high-risk ethnic groups. The primary purpose of screening is to identify infants with sickle cell disease, the most prevalent disorder included in neonatal screening panels. Screening also identifies infants with other hemoglobinopathies, hemoglobinopathy carriers, and in some states, infants with alpha-thalassemia syndromes. The majority of screening programs use isoelectric focusing (IEF) of an eluate from the dried blood spots also used to screen for hypothyroidism, phenylketonuria, and other disorders. A few programs use high performance liquid chromatography (HPLC) or cellulose acetate electrophoresis as the initial screening method. Most programs retest abnormal screening specimens using a second complimentary electrophoretic technique, HPLC, immunologic tests, or DNA-based assays.