Howard Florey and Ernst Chain: Lives and Careers

Penicillin is often told as the story of one man and one mouldy culture plate. The medicine that reached patients in the 1940s, however, came out of a laboratory in Oxford led by two very different people: Howard Florey (1898–1968), an Australian physiologist and pathologist who ran the Sir William Dunn School of Pathology, and Ernst Chain (1906–1979), a Berlin-born biochemist who had arrived in England as a refugee. In 1945 they shared the Nobel Prize in Physiology or Medicine with Alexander Fleming “for the discovery of penicillin and its curative effect in various infectious diseases.”

This page follows the two men side by side: where they came from, how their training led each of them to Oxford in 1935, how they came to work together, and what each did in the decades after the war. The laboratory story itself — the mould broth, the mouse experiment of May 1940 and the first patients — is told only in outline here; it has its own page in this wing, as do the science of the Penicillium mould and the wartime mass production that followed.

Table of Contents

  1. A Boot Manufacturer’s Son from Adelaide
  2. Rhodes Scholar: Oxford, Cambridge and America
  3. Sheffield and the Oxford Chair of Pathology
  4. A Chemist and Pianist from Berlin
  5. Leaving Germany in 1933
  6. Cambridge, Hopkins and the Move to Oxford
  7. Two Temperaments in One Laboratory
  8. Florey After the War: The Royal Society, Queen’s College and Canberra
  9. Chain After the War: Rome, London and Mayo
  10. Timeline of Two Lives
  11. Key Research Papers
  12. Connections

1. A Boot Manufacturer’s Son from Adelaide

Howard Walter Florey was born on 24 September 1898 at Malvern, a suburb of Adelaide in South Australia. He was the youngest child and only son of Joseph Florey, a boot manufacturer who had emigrated from England, and Joseph’s second wife, Bertha Mary, née Wadham. The Australian Dictionary of Biography, in its entry on him by the virologist Frank Fenner, and his official Nobel biography both record this family background; counts of his siblings differ between sources because his father had daughters from an earlier marriage.

Florey went to the Collegiate School of St Peter in Adelaide and then studied medicine at the University of Adelaide, graduating M.B., B.S. in 1921 (the Science History Institute gives 1922; the Dictionary of Biography and the Nobel biography both give 1921). He was awarded the M.D. much later, in 1944. Among his fellow medical students in Adelaide was Mary Ethel Hayter Reed (1900–1966), whom he would later marry.

The Adelaide years matter to the later story for one reason above all: Florey arrived in England already trained as a doctor, and his interest lay in how the living body works — such as the flow of blood and lymph — rather than in chemistry. That background shaped the kind of laboratory he would later build.

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2. Rhodes Scholar: Oxford, Cambridge and America

In 1921 Florey sailed for England as a Rhodes Scholar to Magdalen College, Oxford. There he read the honour school of physiology under Sir Charles Sherrington, the physiologist of the nervous system who later shared the 1932 Nobel Prize. Florey’s Nobel biography describes Sherrington as an “influential guide and friend” to the young Australian. Florey took the Oxford B.A. and B.Sc. in 1924.

The same year he moved to Cambridge as a John Lucas Walker Student. In 1925–26 a Rockefeller Travelling Fellowship took him to the United States for about ten months. The Science History Institute’s biography notes that part of this time was spent in the laboratory of the pharmacologist Alfred Newton Richards at the University of Pennsylvania — a connection that mattered greatly in 1941, when Richards was in a position to help bring penicillin production to America. The same biography records that Florey also spent a summer as the physician on an Arctic expedition.

On 19 October 1926 Florey married Mary Ethel Reed in Paddington, London. They had two children, Paquita and Charles. Back at Cambridge, Florey completed a Ph.D. in 1927 on the flow of blood and lymph, and in the same year became Huddersfield Lecturer in Special Pathology. Through these posts he moved steadily from physiology into experimental pathology — the study of disease processes in living tissue.

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3. Sheffield and the Oxford Chair of Pathology

In 1931 Florey was appointed to the Joseph Hunter Chair of Pathology at the University of Sheffield, his first professorship. Four years later, in 1935, he returned to Oxford as Professor of Pathology and head of the Sir William Dunn School of Pathology, with a fellowship at Lincoln College. (The Science History Institute gives 1936; the Dictionary of Biography and the Nobel biography give 1935.) He held the Oxford chair until 1962.

The Dunn School gave Florey a large, well-equipped building and the freedom to choose his own problems. One of the problems he brought with him was lysozyme, an antibacterial enzyme found in tears and other body fluids, which Fleming had described in the early 1920s. Florey had been studying how the body defends its surfaces, and lysozyme fitted that interest. To understand how such a substance worked, he needed a chemist — and the person he recruited was Ernst Chain.

The Oxford appointment also brought Florey into the circle of people who would later work on penicillin with him, including Margaret Jennings, a long-time colleague in his laboratory who appears as a co-author on the 1940 and 1941 penicillin papers in the Lancet.

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4. A Chemist and Pianist from Berlin

Ernst Boris Chain was born in Berlin on 19 June 1906. His father, Dr Michael Chain, was a chemist and industrialist; the Science History Institute describes the family as being of Russian-German-Jewish descent. His father died when Ernst was 13, and the family’s circumstances declined afterwards.

Chain attended the Luisengymnasium in Berlin and then the Friedrich-Wilhelm University, where he graduated in chemistry in 1930. He went on to three years of research on enzymes at the Charité Hospital in Berlin, where, according to the Science History Institute, he also obtained his doctorate. Enzymes — the proteins that speed up the body’s chemical reactions — were the subject that would bring him to Oxford.

Alongside chemistry ran music. The Science History Institute records that Chain seriously considered a career as a concert pianist, and his Nobel biography lists music as one of his recreations. He chose science, but the piano stayed with him throughout his life.

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5. Leaving Germany in 1933

In 1933, after the National Socialists came to power in Germany, Chain left for England. Kardos and Demain, in their 2013 profile of him, describe him as having fled in 1933 as a Jewish refugee from Nazism.

His mother and sister stayed in Germany. According to the Science History Institute, both died in the Holocaust.

Chain arrived in England as one of many German Jewish scientists who left in the 1930s. The Science History Institute records that he worked briefly at University College Hospital Medical School in London before moving on to Cambridge.

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6. Cambridge, Hopkins and the Move to Oxford

From 1933 to 1935 Chain worked at the School of Biochemistry in Cambridge under Sir Frederick Gowland Hopkins, the biochemist who had shared the 1929 Nobel Prize for work on the “accessory food factors” later called vitamins. Chain’s research there was on phospholipids, the fatty molecules that form cell membranes.

In 1935 Chain was invited to join Florey at the Sir William Dunn School in Oxford, and in 1936 he became demonstrator and lecturer in chemical pathology. His Nobel biography lists his work between 1935 and 1939: snake venoms, the metabolism of tumours, the way lysozyme acts on bacteria, and methods of microanalysis. The lysozyme work — working out what the enzyme actually attacks in the bacterial cell — led directly to a wider question: what other natural substances made by microbes could kill bacteria?

So in 1935 both men arrived in Oxford: Florey as head of the department; Chain as a young refugee chemist on his staff.

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7. Two Temperaments in One Laboratory

Florey and Chain brought different training to the same problem. Florey was a doctor, physiologist and experimental pathologist, used to working with living animals and tissues; Chain was a chemist trained in German enzyme laboratories. Their joint work is a well-known example of a physiologist-pathologist and a biochemist working on one question from two directions.

The penicillin years in outline

In 1938–39 (Florey’s Nobel biography gives 1938; Chain’s gives 1939) the two began a systematic investigation of antibacterial substances made by bacteria and fungi. The Science History Institute notes that they first thought such substances might be enzymes like lysozyme. One of the substances they chose was the “penicillin” that Fleming had described in 1929 but never isolated. A grant from the Rockefeller Foundation funded the team. On 25 May 1940 a protection experiment in mice gave the first clear result; the team reported it in the Lancet in August 1940, and the first patients were treated at Oxford’s Radcliffe Infirmary in 1941, reported in the Lancet in August 1941. That summer Florey flew to the United States to seek large-scale production. The whole laboratory story is told on The Oxford Penicillin Work, 1938–1941.

The two published papers list a team, not a pair: Edward Abraham, Norman Heatley, Arthur Gardner, Margaret Jennings, Jean Orr-Ewing, Gordon Sanders and, in 1941, the physician Charles Fletcher wrote alongside Florey and Chain. Florey and Abraham later wrote their own history of the Oxford work (1951), and Heatley left a memorial account of an episode of his work with Florey (1970).

The disagreement over patenting

One difference between the two men is well documented. According to the Science History Institute, Chain urged that penicillin be patented, as was usual in German research institutes, and Florey refused; the Institute writes that this decision “long rankled” with Chain. The Australian Dictionary of Biography explains Florey’s side: in the 1940s, patenting a medical discovery was regarded as against medical ethics, and Florey made no fortune from penicillin. The Science History Institute adds that when the Dunn School later worked on the cephalosporins in the 1950s, Florey urged patenting.

In 1945 Fleming, Chain and Florey shared the Nobel Prize. Florey had been elected a Fellow of the Royal Society in 1941 and knighted in 1944; Chain was elected a Fellow of the Royal Society in 1949.

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8. Florey After the War: The Royal Society, Queen’s College and Canberra

Honours followed the Nobel Prize. Florey was made a member of the French Légion d’honneur in 1946 and received the United States Medal of Merit in 1948. With colleagues he wrote the two-volume work Antibiotics (1949), and he edited Lectures on General Pathology (1954). Mary Ethel Florey, his wife, worked on clinical trials of penicillin at the Radcliffe Infirmary, in military hospitals and at the Birmingham Accident Hospital, and later wrote the four-volume The Clinical Application of Antibiotics (1952–61).

Australia and the National University

Florey never lost his ties to Australia. In 1944 he visited as Nuffield Visiting Professor, to discuss penicillin production there and report on medical research. According to the Dictionary of Biography, his report played a major part in the founding of the Australian National University in Canberra. He was an adviser to its John Curtin School of Medical Research from 1948 to 1955, and from 1965 he was the university’s Chancellor.

The Royal Society and Queen’s College

From 1960 to 1965 Florey was President of the Royal Society. In 1962 he left the Dunn School chair to become Provost of The Queen’s College, Oxford. In 1965 he was created a life peer as Baron Florey of Adelaide and Marston and appointed to the Order of Merit.

Last years

Mary Ethel Florey died on 10 October 1966. On 6 June 1967 Florey married Margaret Jennings, née Fremantle, his long-time laboratory colleague. He died of a heart attack (myocardial infarction) on 21 February 1968 in his lodgings at Queen’s College, aged 69. The Dictionary of Biography records that his estate was valued at £29,786. His likeness later appeared on the Australian fifty-dollar note; a Canberra suburb and the Florey Institute in Melbourne bear his name; and a commemorative stone was placed in Westminster Abbey in 1981. His Royal Society biographical memoir was written by Edward Abraham (1971).

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9. Chain After the War: Rome, London and Mayo

Chain’s own post-war honours included the Berzelius Medal (silver) and the Pasteur Medal in 1946, the Paul Ehrlich Centenary Prize in 1954, and the rank of Commander of the Légion d’honneur. In 1948 he married the biochemist Dr Anne Beloff; they had two sons and a daughter.

Rome, 1948

The same year Chain left Oxford for Rome, as Scientific Director of the International Research Centre for Chemical Microbiology at the Istituto Superiore di Sanità, Italy’s national public-health institute, which had a fermentation pilot plant. There, in collaboration with a British pharmaceutical company’s research group, work on penicillin produced its “nucleus”, 6-aminopenicillanic acid, from which new semisynthetic penicillins could be made; a 1960 paper in Nature, with Chain as last author, reported forming it from penicillin with an enzyme. Kardos and Demain write that Chain also helped several countries start penicillin industries after the war, including the Soviet Union and China. The science of this work is covered on Wartime Mass Production and the Antibiotic Era.

Imperial College, London

Chain returned to Britain as Professor of Biochemistry at Imperial College London, where he again set up an industrial-scale fermentation pilot plant. His Nobel biography gives the year as 1961; the Science History Institute and Kardos and Demain give 1964. A 2017 profile in an Irish newspaper, the Connaught Telegraph, records that he was knighted in 1969. In 1971 he published a long review in the Proceedings of the Royal Society, “Thirty years of penicillin therapy”.

Mulranny, County Mayo

Chain built a house at Mulranny in County Mayo, on the west coast of Ireland, and, according to the Connaught Telegraph, moved there in the winter of 1970. He died on 12 August 1979 at Mayo General Hospital in Castlebar, aged 73. Edward Abraham, who had also written Florey’s memoir, wrote Chain’s Royal Society biographical memoir (1983).

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10. Timeline of Two Lives

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Key Research Papers

  1. Abraham EP. Howard Walter Florey, Baron Florey of Adelaide and Marston 1898-1968. Biogr Mem Fellows R Soc. 1971;17:255-302. PubMed PMID: 11615426
  2. Abraham EP. Ernst Boris Chain, 19 June 1906 - 12 August 1979. Biographical Memoirs of Fellows of the Royal Society. 1983;29:42-91. DOI: 10.1098/rsbm.1983.0003
  3. Kardos N, Demain AL. Ernst Chain: a great man of science. Appl Microbiol Biotechnol. 2013;97(15):6613-22. PubMed PMID: 23793259
  4. Ligon BL. Sir Howard Walter Florey--the force behind the development of penicillin. Semin Pediatr Infect Dis. 2004;15(2):109-14. PubMed PMID: 15185195
  5. Raju TN. The Nobel chronicles. 1945: Sir Alexander Fleming (1881-1955); Sir Ernst Boris Chain (1906-79); and Baron Howard Walter Florey (1898-1968). Lancet. 1999;353(9156):936. PubMed PMID: 10094026
  6. Chain E, Florey HW, Gardner AD, Heatley NG, Jennings MA, Orr-Ewing J, Sanders AG. Penicillin as a chemotherapeutic agent. The Lancet. 1940;236(6104):226-228. DOI: 10.1016/S0140-6736(01)08728-1
  7. Abraham EP, Chain E, Fletcher CM, Gardner AD, Heatley NG, Jennings MA, Florey HW. Further observations on penicillin. The Lancet. 1941;238(6155):177-189. DOI: 10.1016/S0140-6736(00)72122-2
  8. Florey HW, Abraham EP. The work on penicillin at Oxford. J Hist Med Allied Sci. 1951;6(3):302-17. PubMed PMID: 14873930
  9. Heatley NG. In memoriam, H.W. Florey: an episode. J Gen Microbiol. 1970;61(3):289-99. PubMed PMID: 4922763
  10. Rolinson GN, Batchelor FR, Butterworth D, Cameron-Wood J, Cole M, Eustace GC, Hart MV, Richards M, Chain EB. Formation of 6-aminopenicillanic acid from penicillin by enzymatic hydrolysis. Nature. 1960;187:236-7. PubMed PMID: 14438509
  11. Chain E. Thirty years of penicillin therapy. Proc R Soc Lond B Biol Sci. 1971;179(1057):293-319. PubMed PMID: 4401412

PubMed Topic Searches

  1. Papers by H. W. Florey
  2. Papers by E. B. Chain on penicillin
  3. History of penicillin at Oxford
  4. Biographies of Howard Florey

Further Reading

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Connections

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