Principles for drug treatment
The pioneering drug developments made by Sir James W. Black, Gertude B. Elion and George H. Hitchings have led to treatments for many disorders, such as hypertension, herpes and cancer, and earned them the 1988 Nobel Prize for physiology and medicine.
Smooth muscle cells have alpha- and beta-receptors that respond to chemicals such as epinephrine. In the 1960s, Sir James W. Black worked to develop a chemical that would bind to the beta-receptors, cause heart muscles to relax, and reduce the workload of the heart in those suffering heart problems. Such chemicals had been shown to work in a range of animal models, which provided the foundation for Black’s discovery of pronethalol and propranolol, the first beta-blockers to work in humans. Beta-blockers are now used to successfully treat hypertension, hyperthyroidism, migraines and a range of heart problems. Black was also interested in histamine, a molecule that stimulates the immune response. There are two types of histamine receptor, and using similar methods to those used in the development of beta-blockers, Black developed an antagonist molecule for the second type of histamine receptor. This dulled the immune response and proved clinically useful in the treatment of peptic ulcers.
Gertude B. Elion and George H. Hitchings began their long collaboration in the 1940s, where they set about investigating the differences in nucleic acid metabolism between normal human cells and the organisms that can harm them: cancer cells, protozoa, bacteria and viruses. They attempted to exploit these differences by creating drugs that specifically target the copying of genetic material by infectious agents or cancer, without harming human cells. The pair’s work often utilised animal models before moving on to clinical trials in humans, and resulted in the discovery of effective treatments for leukemia, autoimmune diseases, malaria, herpes and bacterial infections.