An Essay on Prize One in Life Science and Medicine 2004
The discovery of DNA polymorphism has truly revolutionized the entire field of human genetics and was directly responsible for the birth of molecular genetics. Moreover, the knowledge gained on DNA polymorphism was a principal contributing factor to our current understanding of the structure and function of the human genome. This discovery was directly responsible for the development of DNA-based prenatal diagnosis for a variety of genetic disorders in families at risk, and represented the first uses of DNA tests for human disease.
In the late 1960s and early 1970s, Kan published a series of papers on the traits and detection of thalassemia. Then, in 1972, Kan published a seminal paper (N Engl J Med. 287: 1-5, 1972) on the detection of the sickle gene in the human fetus, and provided insights on the potential for intrauterine diagnosis of sickle cell anemia. The principle of DNA polymorphism was also the foundation on which the field of reverse genetics or positional cloning developed. Before the discovery of DNA polymorphism, genes were cloned by forward genetics, which involved the isolation and purification of the respective proteins followed by cloning of the cDNAs and then the chromosomal genes. This process, however, required abundant expression of the genes to be cloned in order to yield the resulting protein products. The identification of polymorphic markers in the human genome has permitted the localization of the disease-causing genes in their respective chromosomes and facilitated their cloning. This new technology permitted the isolation of disease-causing genes without any knowledge of their gene products, and was truly revolutionary in the field of human genetics.
The impact of these discoveries on the betterment of human kind has been astounding. The seminal contributions made by Kan on DNA polymorphism made it possible to trace the transmission of disease-causing genes in families and pedigrees. As a direct result of these discoveries, novel DNA-based diagnostic procedures were developed to detect prenatal genetic disorders such as sickle cell anemia. Moreover, the modern fields of forensic medicine and pharmacogenetics are based on DNA polymorphism.
Life Science and Medicine Selection Committee
The Shaw Prize
7 September 2004, Hong Kong