Science for Health
07 January 2014
Sir John ‘Kappa’ Cornforth died on 8 December 2013, aged 96. He worked at NIMR for 16 years (1946-62) and won the 1975 Nobel Prize for Chemistry for his work on the stereochemistry of enzyme-catalysed reactions.
John Cornforth was born on 7 September 1917 in Sydney, Australia. He attended Sydney High School and entered the University of Sydney at the age of 16. He graduated in 1937 with first-class honours and a University medal. In childhood he showed the first signs of deafness, due to otosclerosis, and gradually lost his hearing completely. After a year of postgraduate research in Australia, Cornforth was awarded one of two 1851 Exhibition scholarships in 1939 to study at Oxford with the renowned chemist Robert Robinson. The other winner of the scholarship that year was Rita Harradence, also an organic chemist, who Cornforth knew already. They married in 1941 and worked closely together throughout their careers. He said later:
Throughout my scientific career my wife has been my most constant collaborator. Her experimental skill made major contributions to the work; she has eased for me beyond measure the difficulties of communication that accompany deafness; her encouragement and fortitude have been my strongest supports.
After completing their PhD work on steroid synthesis the Cornforths worked with Robinson on penicillin, which was the major chemical project in his laboratory at Oxford during the war. Cornforth had earlier discovered what was to prove a key reaction for the synthesis of the sterols and after the war he returned to this pursuit.
John and Rita Cornforth moved to NIMR in 1946, working there until 1962. John Cornforth collaborated with George Popjak, in NIMR’s Division of Biochemistry, and they began an extensive series of studies using radioisotopes to determine how cholesterol is made in the body. They found that the carbon skeleton of cholesterol is built up in a complex series of enzyme-regulated stages, entirely from two-carbon (acetyl) fragments. The work is directly relevant to understanding the action of modern cholesterol-reducing statin drugs. Cornforth said:
At NIMR I came into contact with biological scientists and formed collaborative projects with several of them. In particular George Popják and I shared an interest in cholesterol. Popják and I began to concert experiments in which the disciplines of chemistry and biochemistry could be applied to this subject. We were led to devise a complete carbon-by-carbon degradation of the ring structure of cholesterol and to identify, by means of radioactive tracers, the arrangement of the acetic acid molecules from which the system is built.
Amongst his many investigations into natural products and their biosynthesis and possible manufacture was the successful search to find a natural starting material for the manufacture of cortisone. Later work included new techniques for isotopic labelling and extensions of the stereochemistry of enzymes.
The NIMR Director at the time, Charles Harington, regarded Cornforth as “being unquestionably in the first rank of organic chemists in this country”. In 1954 Cornforth seriously considered returning to Australia to work in a proposed new research institute in Melbourne but eventually decided against it, much to Harington’s relief.
In 1962 Cornforth left NIMR to become joint director, with George Popjak, of the Shell Research Milstead Laboratory at Sittingbourne. This lab was created by Shell at the urging of Robert Robinson, to foster work at the interface of chemistry and biology. In 1975 Cornforth moved to the University of Sussex as Royal Society Research Professor in the Department of Applied Science, retiring in 1982.
Cornforth was a modest and unassuming man. While he had hoped that his work would turn out to be important, he refrained from expecting such a grand Prize as the Nobel. “You could say it was original enough and useful enough to be considered for the Prize. But my own approach at the time was to put this resolutely out of my mind.”
John Cornforth received many awards throughout his career, becoming FRS in 1953 and receiving the Royal Society’s Royal Medal (1976) and Copley Medal (1982), as well as the 1975 Nobel Prize for Chemistry, for his work on the stereochemistry of enzyme-catalysed reactions, shared with Professor V. Prelog. He was made a Knight Bachelor in 1977.
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