- Person
- Ernst Chain
- Lived
- 1906–1979
- Field
- Biochemistry
- From
- German-British
The story
Knowing that penicillin worked was not the same as knowing what it was. By the early 1940s the Oxford team led by Howard Florey had shown that purified penicillin could cure infections, but supplies were tiny. Some chemists were confident they could soon make the drug from simple chemicals, and the Science History Institute describes a major effort on both sides of the Atlantic to work out its molecular structure as the first step toward synthesis.
At Oxford the problem was given to Ernst Chain, the chemist Edward Abraham and the senior organic chemist Robert Robinson, already famous for solving the structures of complex natural substances. In 1942 Chain and Abraham proposed that the heart of the penicillin molecule was a beta-lactam ring, a small, strained ring of four atoms. Robert Burns Woodward at Harvard reached the same view. Robinson, however, favoured a different structure based on an oxazolone, and by the autumn of 1943 groups at Oxford and at the drug company Merck had proposed competing answers.
The question was settled by a new technique. Dorothy Crowfoot Hodgkin, an Oxford neighbour of the chemists, used X-ray crystallography to map the positions of the atoms in penicillin crystals. In 1945 her results confirmed Chain and Abraham's beta-lactam structure and ruled out Robinson's. Her work came too late to help with a wartime synthesis, but it gave chemists a reliable picture of the molecule. On 20 March 1946 Chain gave his Nobel lecture on exactly this subject, under the title "The Chemical Structure of the Penicillins".
A full chemical synthesis was achieved only in 1957, and fermentation remained the basis of commercial production. Yet the Science History Institute notes that the structural knowledge gained during the war proved invaluable for developing later penicillin-like antibiotics that were easier to give, more effective and had fewer side effects.
Chain himself helped turn that knowledge into new medicines. In Rome in 1957, scientists from the Beecham Group working with him isolated the central "nucleus" of the penicillin molecule. Being able to produce it allowed researchers to build semisynthetic penicillins such as ampicillin, and Chain's later research included penicillins resistant to the bacterial enzyme penicillinase. The beta-lactam ring remains the core of a large family of antibiotics used in hospitals and clinics every day.
Why it matters
Identifying the beta-lactam ring guided the design of later antibiotics, including many still used every day in hospitals and clinics.
About Ernst Chain
Berlin-born Jewish refugee biochemist who purified penicillin with Howard Florey at Oxford, turning Fleming’s curiosity into a life-saving drug, and shared the 1945 Nobel Prize.
More about Ernst Chain
- Ernst Chain founded biochemistry at Imperial CollegeAfter building a research centre in Rome, Ernst Chain returned to Britain in 1964 to found Imperial College London's biochemistry department, specialising in fermentation technology.
- Ernst Chain's 1940 Lancet paper electrified medicineOn August 24, 1940, Florey, Chain and their Oxford colleagues reported penicillin's curative power in The Lancet, a paper that electrified researchers around the world.
- Four mice that launched the antibiotic ageOn May 25, 1940, the Oxford team infected eight mice with streptococci and treated four with penicillin. Sixteen and a half hours later only the treated mice were alive.
- Ernst Chain worked out how to purify penicillinAt Oxford, Ernst Chain and Edward Abraham found a way to purify and concentrate penicillin, turning Fleming's fragile mould juice into a usable drug.
Sources
- Ernst Boris Chain Wikipedia
- Howard Walter Florey and Ernst Boris Chain Science History Institute
- Ernst B. Chain: Nobel Lecture NobelPrize.org
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