History Of Sickle Cell Disease
Sickle Cell Disease : A Brief History
The first report of sickle cell anaemia may have been in 1846 where the autopsy of an executed runaway slave was discussed.[76] The author noted the curious absence of a spleen in this case.
In 1910 a Chicago physician, James B. Herrick, reported the presence of sickle cells in the blood of an anaemic dental student, Walter Clement Noel.[77] These cells had first been observed by his intern Ernest Irons while they were treating Noel in 1904.
An association with pigmented gall stones was noted in 1911 by Washborn. A genetic basis for this disease was proposed in 1915 by Cook and Meyer. The disease was named sickle cell anaemia in 1922 by Verne Mason after several additional cases were reported. All the known cases had been reported in blacks and he concluded that this disease was confined to those of black African descent. The heterozygous condition was independently recognised in 1923 by Huck and Syndestrickler. Syndestrickler also was the first to note the splenic atrophy that occurs in this condition. It was recognised as a Mendelian autosomal characteristic by Taliaffero and Huck also in 1923.[78] A predisposition to pneumonia was noted in 1924 by Graham. The concept of progressive splenic atrophy was proposed by Hahn and Gilespie in 1927. Pneumococcal meningitis in this condition was first reported in 1928 by Wollstein and Kriedel but it was not until 1966 that the association between splenic atrophy and infection was made by Robinson and Watson.
The first report of sickle cell anaemia may have been in 1846 where the autopsy of an executed runaway slave was discussed.[76] The author noted the curious absence of a spleen in this case.
In 1910 a Chicago physician, James B. Herrick, reported the presence of sickle cells in the blood of an anaemic dental student, Walter Clement Noel.[77] These cells had first been observed by his intern Ernest Irons while they were treating Noel in 1904.
An association with pigmented gall stones was noted in 1911 by Washborn. A genetic basis for this disease was proposed in 1915 by Cook and Meyer. The disease was named sickle cell anaemia in 1922 by Verne Mason after several additional cases were reported. All the known cases had been reported in blacks and he concluded that this disease was confined to those of black African descent. The heterozygous condition was independently recognised in 1923 by Huck and Syndestrickler. Syndestrickler also was the first to note the splenic atrophy that occurs in this condition. It was recognised as a Mendelian autosomal characteristic by Taliaffero and Huck also in 1923.[78] A predisposition to pneumonia was noted in 1924 by Graham. The concept of progressive splenic atrophy was proposed by Hahn and Gilespie in 1927. Pneumococcal meningitis in this condition was first reported in 1928 by Wollstein and Kriedel but it was not until 1966 that the association between splenic atrophy and infection was made by Robinson and Watson.
In 1927 Vernon Hahn and Elizabeth Biermann Gillespie showed that sickling of the red cells was related to low oxygen.[79] In some individuals this change occurs at partial pressures of O2 prevalent in the body, and produces anemia and other disorders, termed sickle-cell disease. In other persons sickling occurs only at very low O2 partial pressures; these are asymptomatic sickle-cell trait carriers.
The association with kidney and lung infarcts was noted in 1931 by Yater and Mollari and Baird in 1934 respectively. The term sickle cell trait was coined by Samuel Diggs in Memphis in 1933 to distinguish heterozygotes from those with sickle cell anaemia. Diggs also reported the association with splenic fibrosis in 1935. The pathological mechanism of vaso-occlusion was proposed by Ham and Castle in 1940.
In 1946, E A Beet, a British medical officer stationed in Southern Rhodesia (Zimbabwe), observed that blood from malaria patients who had sickle cell trait had fewer malarial parasites than blood from patients without the trait and suggested that this might be a protective feature. In 1947 Beet published that the incidence of enlarged spleens in sickle cell patients was much lower than in non sickle cell and suggested that this was due to recurrent thromboses which resulted in fibrosis and shrinkage of the spleen. In 1949 Lehmann and Raper published a map of Uganda and showed that the presence of sickle cell anaemia correlated with the presence of malaria.[80] In 1950 Singer et al. noted the abrupt cessation of marrow activity that may occur and coined the term aplastic crisis. The role of parvovirus in aetiology of this condition was not recognised until 1981. P. Brain also while working inNorthern Rhodesia confirmed the lower incidence of splenomegaly and suggested that while homozygotes for the sickle cell gene suffered from several problems heterozygotes might be protected against malaria.[81]
The association with kidney and lung infarcts was noted in 1931 by Yater and Mollari and Baird in 1934 respectively. The term sickle cell trait was coined by Samuel Diggs in Memphis in 1933 to distinguish heterozygotes from those with sickle cell anaemia. Diggs also reported the association with splenic fibrosis in 1935. The pathological mechanism of vaso-occlusion was proposed by Ham and Castle in 1940.
In 1946, E A Beet, a British medical officer stationed in Southern Rhodesia (Zimbabwe), observed that blood from malaria patients who had sickle cell trait had fewer malarial parasites than blood from patients without the trait and suggested that this might be a protective feature. In 1947 Beet published that the incidence of enlarged spleens in sickle cell patients was much lower than in non sickle cell and suggested that this was due to recurrent thromboses which resulted in fibrosis and shrinkage of the spleen. In 1949 Lehmann and Raper published a map of Uganda and showed that the presence of sickle cell anaemia correlated with the presence of malaria.[80] In 1950 Singer et al. noted the abrupt cessation of marrow activity that may occur and coined the term aplastic crisis. The role of parvovirus in aetiology of this condition was not recognised until 1981. P. Brain also while working inNorthern Rhodesia confirmed the lower incidence of splenomegaly and suggested that while homozygotes for the sickle cell gene suffered from several problems heterozygotes might be protected against malaria.[81]
The modern phase of research on this disorder was initiated by the famous chemist Linus Pauling in 1949. Pauling postulated that the hemoglobin (Hb) in sickle-cell disease is abnormal; when deoxygenated it polymerizes into long, thin, helical rods that distort the red cell into a sickle shape. In his laboratory, electrophoretic studies showed that sickle-cell Hb (S) is indeed abnormal, having at physiological pH a lower negative charge than normal adult human Hb (A).[82] In sickle-cell trait carriers there is a nearly equal amount of HbA and HbS, whereas in persons with sickle-cell disease nearly all the Hb is of the S type, apart from a small amount of fetal Hb. These observations showed that most patients with sickle-cell disease are homozygous for the gene encoding HbS, while trait carriers are heterozygous for this gene. Persons inheriting a sickle-cell gene and another mutant at the same locus, e.g. a thalassemia gene, can also have a variant form of sickle-cell disease. Pauling also introduced the term "molecular disease", which, together with molecular medicine, has become widely used.
The next major advance was the discovery by Vernon Ingram in 1959 that HbS differs from HbA by only a single amino-acid substitution in the β-polypeptide chain (β6Glu → Val).[83] It was later established that this results from a substitution of thymine for adenine in the DNA codon (GAG → GTG). This was the first example in any species of the effects of a mutation on a protein.
This collection of clinical findings was unknown until the explanation of the sickle cells in 1910 by a Chicago cardiologist and professor of medicine James B. Herrick (1861–1954), whose intern Ernest Edward Irons (1877–1959) found "peculiar elongated and sickle-shaped" cells in the blood of Walter Clement Noel, a 20-year-old first-year dental student from Grenada, after Noel was admitted to the Chicago Presbyterian Hospital in December 1904 suffering from anaemia.[84]
The next major advance was the discovery by Vernon Ingram in 1959 that HbS differs from HbA by only a single amino-acid substitution in the β-polypeptide chain (β6Glu → Val).[83] It was later established that this results from a substitution of thymine for adenine in the DNA codon (GAG → GTG). This was the first example in any species of the effects of a mutation on a protein.
This collection of clinical findings was unknown until the explanation of the sickle cells in 1910 by a Chicago cardiologist and professor of medicine James B. Herrick (1861–1954), whose intern Ernest Edward Irons (1877–1959) found "peculiar elongated and sickle-shaped" cells in the blood of Walter Clement Noel, a 20-year-old first-year dental student from Grenada, after Noel was admitted to the Chicago Presbyterian Hospital in December 1904 suffering from anaemia.[84]
Noel was readmitted several times over the next three years for "muscular rheumatism" and "bilious attacks". Noel completed his studies and returned to the capital of Grenada (St. George's) to practice dentistry. He died ofpneumonia in 1916 and is buried in the Catholic cemetery at Sauteurs in the north of Grenada.[85] Herrick's published account included illustrations, but the earliest available slide showing sickle cells is that of a 1918 autopsy from a soldier with sickle trait, initially reviewed only 92 years later.[86]
The disease was named "sickle-cell anemia" by Verne Mason in 1922, then a medical resident at Johns Hopkins Hospital.[87] However, some elements of the disease had been recognized earlier: A paper in the Southern Journal of Medical Pharmacology in 1846 described the absence of a spleen in the autopsy of a runaway slave. The African medical literature reported this condition in the 1870s, when it was known locally as ogbanjes ("children who come and go") because of the very high infant mortality rate caused by this condition. A history of the condition tracked reports back to 1670 in one Ghanaian family.[88]
Linus Pauling and colleagues were the first, in 1949, to demonstrate that sickle-cell disease occurs as a result of an abnormality in the haemoglobin molecule. This was the first time a genetic disease was linked to a mutation of a specific protein, a milestone in the history of molecular biology, and it was published in their paper "Sickle Cell Anemia, a Molecular Disease".
The disease was named "sickle-cell anemia" by Verne Mason in 1922, then a medical resident at Johns Hopkins Hospital.[87] However, some elements of the disease had been recognized earlier: A paper in the Southern Journal of Medical Pharmacology in 1846 described the absence of a spleen in the autopsy of a runaway slave. The African medical literature reported this condition in the 1870s, when it was known locally as ogbanjes ("children who come and go") because of the very high infant mortality rate caused by this condition. A history of the condition tracked reports back to 1670 in one Ghanaian family.[88]
Linus Pauling and colleagues were the first, in 1949, to demonstrate that sickle-cell disease occurs as a result of an abnormality in the haemoglobin molecule. This was the first time a genetic disease was linked to a mutation of a specific protein, a milestone in the history of molecular biology, and it was published in their paper "Sickle Cell Anemia, a Molecular Disease".
