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Cornforth, Sir John Warcupfree

(1917–2013)
  • J. Clifford Jones

Sir John Warcup Cornforth (1917–2013)

by unknown photographer, c.1975

Alamy

Cornforth, Sir John Warcup (1917–2013), chemist, was born in Sydney, Australia, on 7 September 1917, the second of four children of John William Cornforth, a teacher of English and classics, and his wife, Hilda, née Eipper (1887–1969), a nurse. His father had emigrated to Australia from England, and his mother was Australian-born, of part German and part Irish descent. He spent his first five years in Armidale, in northern New South Wales, before the family returned to Sydney.

Sydney, Oxford, and penicillin

Just as it is sometimes difficult to imagine Paris without the Eiffel Tower, so it can be difficult to imagine Sydney without the Harbour Bridge. Cornforth was a boy of fourteen when the Sydney Harbour Bridge was opened in March 1932. By that time he was a pupil at Sydney Boys' High School, and was third year dux for that year. There were awards from the school prior to that and after it, notably a prize for Greek in 1930. He continued to earn prizes from Sydney Boys' High School up to and including the year in which he left to go to the University of Sydney to study chemistry.

By the time Cornforth went to university he was totally and irreversibly deaf, as a result of otosclerosis. Hearing problems had begun when he was about ten years old, and had intensified to the degree of complete deafness by the time he went to university. He could not hear the lectures, but took down notes and immensely benefited from the laboratory classes. He graduated with first-class honours and the university medal. It was while an undergraduate at Sydney that he acquired his nickname, ‘Kappa’ Cornforth. At that time chemistry students had to purchase at least some of their laboratory requisites. A student needed to be able to identify his or her own flasks, beakers, and so on, and therefore scratched initials onto them. Cornforth departed from this convention by marking his glassware with the Greek letter kappa (κ). It was through his self-taught proficiency at glass-blowing that he met Rita Harriet Harradence [Rita Cornforth]Lady Cornforth (1915–2012), a fellow chemistry student (born on 16 September 1915 in Sydney, daughter of Walter Charles Harradence, who ran a general store), who asked him to fix one of her flasks. They did their honours projects on similar topics under the same supervisor, and the work was published with the supervisor as a further author, the first of many publications together (but the only one in which her name was given as R. Harradence).

After graduating Cornforth travelled to England to undertake DPhil work at Oxford, and was accompanied by Rita, who was also heading for Oxford as a research student in organic chemistry. They were married at Oxford register office on 27 September 1941 and had three children.

Cornforth's DPhil supervisor at Oxford was Sir Robert Robinson, an Englishman who, by coincidence, had been the first professor of organic chemistry at the University of Sydney from 1912 to 1915, and was to become a Nobel laureate. He was also Rita Cornforth's supervisor. There began an association between Cornforth and Robinson which was to culminate in Cornforth's authorship of Robinson's biographical memoir for the Royal Society of London jointly with Alexander Todd. The memoir concludes, as is standard practice, with a list of Robinson's publications, and for 1942 there are two authored by Robinson and the two Cornforths, one authored by Robinson and R. Cornforth, and one authored by Robinson and J. W. Cornforth, all published in the Journal of the Chemical Society. The venue of this shared work was the Dyson-Perrins Laboratory at Oxford. The first of the papers by Robinson and the ‘Cornforth duo’ ('Nuclear methylation of phenols by means of methanolic sodium methoxide') was concerned with sodium methoxide as a methylating agent. This had previously proved its worth in the methylation of pyrroles, and the paper demonstrated how substituted phenols will also respond to sodium methoxide as a methylating agent. The second of the triply authored papers ('The preparation of β-Tetralone from β-Naphthol and some analogous transformations') was concerned with reduction of a substituted naphthalene by sodium and alcohol and subsequent hydrolysis to give a well characterized product. The paper authored by Robinson and J. W. Cornforth only ('Experiments on the synthesis of substances related to the Xterols, part XL') was one part of a long series written by Robinson and a succession of co-workers. A simple organic compound had been tested for certain reactions, and positive results indicated promise for the same reactions by the same approach with more complicated organic structures. The paper authored by Robinson and R. Cornforth was on 'Preparation of certain 3-substituted indoles'.

After his doctoral studies Cornforth remained with Robinson for a period and they studied penicillin together. This was during the Second World War and was the primary activity in Robinson's research portfolio at that time. The Nobel prize in physiology or medicine in 1945 went to Alexander Fleming, Ernst Boris Chain, and Howard Walter Florey (also Australian) for 'the discovery of penicillin and its curative effect in various infectious diseases'. Once the biological activity of penicillin was characterized it was important for it to be studied as an organic substance, and this was the contribution made by Robinson and Cornforth. In 1949, by which time Cornforth had left Oxford, they published together The Chemistry of Penicillin, a Princeton University Press title which became the standard textbook on penicillin for many years.

Among those Cornforth worked with at Oxford was the future Nobel laureate Dorothy Hodgkin. They held discussions on the structure of penicillin and it is recorded that the young Cornforth said to Hodgkin that if his view of one feature of the structure of penicillin turned out to be incorrect he would 'give up chemistry and take up croquet instead' (Ferry, 199). (Hodgkin's biographer goes on to say that, far from giving up chemistry to play croquet, Cornforth obtained a Nobel prize in chemistry and was knighted.)

The National Institute for Medical Research and Shell: cholesterol and enzyme catalysis

In 1946 Cornforth moved from Oxford to the Medical Research Council's National Institute for Medical Research (NIMR) in Mill Hill, Middlesex. His collaboration with Robinson did not stop then, and they continued to publish jointly until 1949. Cornforth's move from Oxford to the NIMR (at a time when universities in England were set to expand, and someone of his background ought to have experienced no difficulty at all in obtaining an academic post and ascending rapidly the ladder to a chair) was perhaps in part explained by his deafness, which would have made lecturing and tutoring difficult. The NIMR was a much more suitable venue, and provided the opportunities for Cornforth's immense capabilities to be utilized without the degree of oral communication that a university setting would have demanded.

Over part of his time at the NIMR Cornforth collaborated with R. B. Woodward, an organic chemist at Harvard University (later also to become a Nobel laureate), in the synthesis of steroids. Woodward later made use of the technique for methylation with sodium methoxide as a reagent, developed by the two Cornforths in collaboration with Robinson, in his synthesis of quinine. The paper on sodium methoxide as a methylating agent was one of Cornforth's earliest published works, yet its contents were to be of the utmost value to leaders in organic synthesis.

Cornforth shared an interest in cholesterol with a distinguished Hungarian organic chemist, George Popjak, who was also in the service of the NIMR. Cholesterol was one of the most studied natural products of that time and any discovery leading to elucidation of its structure was seen as being ‘newsworthy’. Accordingly, in 1953 (the year he was elected a fellow of the Royal Society; his election was proposed by Robinson, and supported by Florey and Hodgkin among others) Cornforth, with Popjak and another collaborator, G. D. Hunter, published a short piece ('Letter to the editors', in Archives of Biochemistry and Biophysics, 1953) in which they reported degradation of part of the cholesterol organic structure with isotopically labelled simple organic reagents. Work on cholesterol continued at the NIMR and was published as a succession of papers. Rita Cornforth, also having a role at the NIMR, was among the authors of some of the subsequent work on cholesterol. She did, however, take time out to raise the family and later said that 'I found it easier to put chemistry out of my mind when I was at home than to put the children out of my mind when I was in the lab' (Hargittai, Women Scientists, 25).

In 1962 Cornforth and Popjak became co-directors of the Milstead Laboratory of Chemical Enzymology, a Shell facility near Sittingbourne in Kent. (The presence there of Popjak and of Cornforth led to its being known as the ‘Popcorn laboratory’, though Popjak left to take up a post at the University of California, Los Angeles, in 1968, after which Cornforth was sole director.) At Milstead, Cornforth focused his efforts on enzyme-catalysed organic reactions and it was this that was to become the work for which he was perhaps most noted. Enzymes are high molecular weight substances, and in their functioning the space they occupy and possible hindrance to and by nearby structures is important. Cornforth's research accordingly was into the stereochemistry of enzyme-catalysed reactions. The raison d'être for the Milstead Laboratory was the need for Shell to stay competitive in petrochemical manufacture in which, since it began in the early twentieth century, close attention has had to be paid to catalyst development. Cornforth wrote a review on the topic ('Enzymes and stereochemistry', published in Tetrahedron in 1974), which made two particularly interesting points. One was that the catalytic function of enzymes is due solely to the linkages of their amino acids. The other was that enzymic catalysis research owed its advance to isotopic labelling, which came into being in the 1930s.

Later years, and wider interests

It was inevitable that the universities, especially the new ones, would be wanting an association with a scholar of Cornforth's stature even though his appointment to a conventional professorial post was not feasible. While at Milstead he undertook some part-time academic work at the new University of Warwick (1965–71) then as a visiting professor at the University of Sussex (1971–5). In 1975 he left Milstead to become a Royal Society research professor at the University of Sussex. Being an externally supported professorship, this did not involve major responsibilities for university administration. At Sussex he built on his earlier work by embarking on a research project to develop synthetic compounds that would perform catalytic reactions in the laboratory. He also provided a new, elegant synthesis of the terpenoid abscisic acid, and continued his work in heterocyclic chemistry. He remained active in research until his ninetieth year.

It was also in 1975 that Cornforth was awarded the Nobel prize in chemistry on a fifty-fifty basis with Vladimir Prelog. Cornforth's prize was for 'his work on the stereochemistry of enzyme-catalyzed reactions', though the Nobel committee's press release noted that, 'This subject is difficult to explain to the layman, as it is a question of geometry in three dimensions' (www.nobelprize.org). Enzyme catalysts were found to be applicable to a very broad range of organic reactions and were widely applied industrially, for example in the production of pharmaceuticals. In particular, Cornforth's work on how enzymes create cholesterol led to the development of new drugs to slow the formation of cholesterol, and therefore to slow the development of cardiovascular disease. Among many other honours, he was knighted in 1977.

It was not possible to study for a PhD degree in Australia until after the Second World War: the first Australian PhD graduated in 1949. People like Cornforth who went to the UK to pursue PhD work because of the impossibility of doing it in Australia often stayed in the UK, and although their Australian identity was rarely lost its significance tended to diminish with the years. This was less true of Cornforth than of most of the other ‘former Australians’ of his generation who became science professors in the UK. In 1975 he was proud to be chosen as ‘Australian of the year’. In turn Australians took great pride in Cornforth, one of ten Australians to have been Nobel laureates.

Those who knew Cornforth socially recalled his approachability and his friendliness towards the families of colleagues. He played Scrabble and chess (he won the Hampstead championship trophy in 1953, 1956, and 1957) as well as being a tennis enthusiast, and would enjoy a glass of beer at a rural pub. He always acknowledged the role played by his wife, Rita, in his life and work, in particular in preventing his deafness from restricting his professional advancement. Indeed, many wondered whether, had Rita had a major role in his later work, the Cornforths might have emulated the Curies in becoming husband-and-wife joint recipients of a Nobel prize.

Rita Cornforth died on 6 November 2012 at their home, Saxon Down, Cuilfail, near Lewes, east Sussex, of pneumonia following a stroke. John Cornforth died thirteen months later, on 8 December 2013, at the Princess Royal Hospital, Haywards Heath, west Sussex, of an ischaemic stroke. They were survived by their three children, Brenda, a general practitioner, John, an engineer, and Philippa, a teacher of communication skills to adults with hearing loss.

Sources

  • The Independent (1 Feb 2014)
  • obituary, University of Sussex website, 4 Feb 2014, www.sussex.ac.uk/broadcast/read/22455, 21 Aug 2016
  • Nature (6 Feb 2014)
  • Angewandte Chemie, 53 (2014), 2–3
  • R. Purchase and J. R. Hanson, eds., ‘Special feature on Sir John Cornforth’, Science Progress, 98/3 (Sept 2015), 211–43
  • D. Ridley, ‘Reflections on the life and works of Sir John W. (‘Kappa’) Cornforth’, Australian Journal of Chemistry, 68 (2015), 538–42
  • M. Hargittai, Women scientists: reflections, challenges, and breaking boundaries (2015), 22–5
  • WW (2013)
  • private information (2017) [J. E. Saxton; archivist, Sydney Boys' High School]
  • m. cert.
  • d. cert.
  • d. cert. [R. Cornforth]

Archives

  • RS

Film

  • BFI NFTVA, interview footage
  • Vega Science Trust, interview footage, 2002, vega.org.uk/video/programme/19

Sound

  • NL Aus., A. Turner, interview, 20 May 1995, catalogue.nla.gov.au/Record/2170078

Likenesses

  • Bettmann, photograph, 1975, Bettmann / Getty Images
  • photograph, 1975, Alamy [see illus.]
  • N. Sinclair, bromide print, 1993, NPG
  • obituary photographs
  • photograph (with R. Cornforth), repro. in Hargittai, Women scientists, 22
Biographical Memoirs of Fellows of the Royal Society
(1849–)