C. Robin Ganellin - Scientific Work

Scientific Work

In 1958, shortly after his Ph.D. studies at Queen Mary College, Ganellin joined Smith Kline and French Laboratories in the UK where he began research in medicinal chemistry. Two years after starting at SK&F, he went to the Massachusetts Institute of Technology where he performed his postdoctoral work with Arthur C. Cope. At MIT he devised the first direct optical resolution of a chiral olefin using platinum complex chemistry. After a year at MIT, he returned to the United Kingdom to resume his work at SK&F. In 1966 he headed a landmark research team at SK&F, collaborating with Sir James Black researching histamine H2-receptor antagonists. This research eventually led to the discovery of cimetidine, also known by its trademark name Tagamet which is currently produced by GlaxoSmith Kline.

Cimetidine was a revolutionary drug at the time of its creation. Peptic ulcers, or stomach ulcers, used to be a very serious medical condition. Stomach ulcers were very difficult to treat and caused a great deal of pain. If left untreated, they could even be life threatening. In some cases, surgery was required to remove the ulcer. Because of these factors, cimetidine was an incredibly popular drug after it was approved for prescription. Cimetidine first entered the market in the United Kingdom in 1976, and was received extremely well. Cimetidine quickly garnered over one billion dollars in annual sales, making it the first blockbuster drug, and it is currently listed by the World Health Organization as one of the most essential drugs.

Ganellin’s contribution to this research was integral to its success. His adeptness at physical organic chemistry enabled him to understand the individual H2-receptor antagonist drugs they developed. Initially, the team developed burimamide as a potential H2-receptor antagonist for medicinal use. However, it was soon realized that burimamide was not an appropriate oral medicine. They quickly identified a similar drug, metiamide, which appeared to have clinical potential. However, metiamide also had a shortcoming – its safety was uncertain. The end result of their trials was cimetidine, an H2-receptor antagonist superior to both burimamide and metiamide. The precursor drugs which marked the progress of their research are termed prototypes. These prototype drugs helped them understand the mechanisms that described how the drugs function. Ganellin’s input was vital to the progression of their research along the sequence of prototypes to final product.

Although Ganellin’s contribution to the discovery of cimetidine was immeasurable, he was not alone. He collaborated with many other scientists at SmithKline and French, including fellow medicinal chemist Graham J. Durant. Durant was able to provide his expertise on guanidine chemistry to further the progress of the research. Sir James Whyte Black, a biologist from Scotland, was also instrumental in their research. He identified the role of the H2-receptor in the production of stomach acid. This discovery was crucial to their research, providing the impetus to search for a suitable H2-receptor antagonist to affect production of stomach acid. John C. Emmett, another medicinal chemist, is also credited as a co-discoverer of cimetidine. In addition to these key players, many others contributed to the research, such as William Duncan, the director of research at SK&F, as well as Michael Parsons, whose pharmacological experience was greatly beneficial.