Page 11 - Haematologica Vol. 107 - September 2022

LANDMARK PAPER IN HEMATOLOGY
David C. Rees
standing of its pathophysiology, including an appreciation of ineffective erythropoiesis, and that the cellular patho- logy resulted from an excess of the unaffected globin chain rather than a deficiency of the protein from the mutated gene. This technique of globin chain synthesis was refined slightly over the years, but remained essen- tially the same. It was central to many of the discoveries concerning transcriptional and translational control of the globin genes, which in turn acted as paradigms for mo- lecular biology in general. In particular, globin chain syn- thesis was used to identify the significance of many variants identified in the globin genes, and was only really replaced when quantitation of messenger RNA became routine in the 1990s. Similarly, it was used in the routine diagnosis of hemoglobinopathies until the 1980s, and in particular was used in the early prenatal diagnosis of he-
moglobinopathies from fetal blood samples.3
This landmark paper arose primarily from the interaction between a very astute hematologist, David Weatherall, who had identified an important question, and a very skilled protein chemist, John Clegg, who knew how to an- swer it. Together they went on to write 200 papers toge- ther, including more than 20 published in Nature. This interaction was one of the driving forces behind the de- velopment of molecular medicine, with the establishment of the Institute of Molecular Medicine (later the Weather- all Institute of Molecular Medicine) in Oxford, and the spawning of numerous clinical and laboratory scientists across the world.
Disclosures
No conflicts of interest to disclose.
References
1. Cooley TB, Lee P. A series of cases of splenomegaly in children with anemia and peculiar bone changes. Trans Am Pediatr Soc. 1925;37:29-30.
2. Weatherall DJ, Clegg JB, Naughton MA. Globin synthesis in
thalassaemia: an in vitro study. Nature. 1965;208(5015):1061-
1065.
3. Fairweather DV, Modell B, Berdoukas V, et al. Antenatal diagnosis
of thalassaemia major. Br Med J. 1978;1(6109):350-353.
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