Florey, Howard Walter, Baron Florey
- R. G. Macfarlane
- , revised by E. P. Abraham
Howard Walter Florey, Baron Florey (1898–1968)
Florey, Howard Walter, Baron Florey (1898–1968), experimental pathologist and bacteriologist, was born in Adelaide, Australia, on 24 September 1898, the youngest child and only son of Joseph Florey (d. 1918), an Oxfordshire shoemaker who had emigrated in 1885, and his second wife, Bertha Mary Wadham, an Australian, with whom he had two daughters and a son. Joseph's first wife had died in 1886, leaving two daughters. By 1906 he had built up a shoe manufacturing business with branches throughout Australia. Howard Florey went to Kyre College and St Peter's Collegiate School, Adelaide, where he was nicknamed Floss. He was clever, hard-working, and determined, winning six scholarships and many prizes. He was also good at games, representing his school (and later his university) at tennis, at football, and in athletics. He first wanted to study chemistry at the university but his father had been told that there would be little scope for this subject in Australia and in 1916 he entered Adelaide University medical school. There he was usually first in his class, winning three scholarships. He qualified as MB BS in 1921. In 1918 his father died suddenly, his business was found to be insolvent, and the Florey family was translated from wealth to poverty. Florey's medical studies were secured by his scholarships, but his earlier ambition for research rather than a well-paid clinical post in Adelaide was maintained with some personal misgivings. In 1921 he was awarded a Rhodes scholarship and, having qualified in medicine, he worked his passage to England as a ship's surgeon, arriving on 24 January 1922.
Move to England
In Oxford, Florey enrolled in the department of physiology under Sir Charles Sherrington, and at Magdalen College. Sherrington recognized his drive and creative independence of mind, and became his most influential guide and friend. In 1923 Florey obtained a first class in the honour school of physiology, then stayed on, at Sherrington's invitation, to study the blood flow in the capillaries of the brain. He made some discoveries and devised a method for inserting transparent windows in living tissues which he later used in various parts of the body to answer questions by direct, simple observation. In October 1924 he moved to Cambridge as John Lucas Walker student in the pathology department under Professor H. R. Dean, who, with Sherrington, felt that a more experimental approach to pathology could be achieved by an active young physiologist. Florey had spent the summer vacation with the third Oxford University Arctic expedition as medical officer, and, though it provided no major excitements, he never forgot this experience of human comradeship and of the colourful beauty of the Arctic. In Cambridge he continued his study of blood flow changes in inflammation and thrombosis—problems which remained a major interest for the rest of his career. He submitted this work for an Oxford BSc in 1925, and was congratulated by his examiners. In the same year he was awarded a Rockefeller fellowship to go to the United States to learn microsurgical techniques. He spent three months with Dr A. N. Richards in Philadelphia and then went to Chicago to work out methods for the study of mucus secretion. Since his Arctic expedition Florey had suffered bouts of indigestion. Investigation had revealed a mucous gastritis and, experimenting on himself, he became interested in mucus, the mechanism of its secretion, and its importance in protecting the mucous membranes. It was a line that led by logical stages to his work on penicillin.
Cambridge and early work on lysozyme
While in America, Florey accepted the offer of a Freedom research fellowship at the London Hospital. He took up this post in June 1926, but it proved not entirely congenial since the laboratories were more concerned with routine than research. But he found a collaborator in Paul Fildes, with whom he experimented on a treatment for tetanus, and he often slipped away to work for a few days in Oxford or Cambridge. In 1926 he married Dr Mary Ethel Hayter (d. 1966), a pathologist, the daughter of John Hayter Reed, an Adelaide bank manager, whom he had known as a medical student in Adelaide; they had one son and one daughter. London life suited neither of them, and when Florey was offered the Huddersfield lectureship in pathology at Cambridge he returned eagerly in October 1927 to the same room which he had occupied before going to America. He now had a new laboratory boy—the fourteen-year-old Jim Kent, who was to stay as his indispensable and devoted assistant for the next forty-one years, and who contributed so much to the success of his research projects. Florey had become a fellow of Gonville and Caius College and its director of medical studies, but he had (or made) ample time for research. He had embodied work on the flow of blood and lymph in a thesis for a Cambridge PhD which was conferred in 1927. During the next four years he began several fruitful lines of study and with various collaborators published twenty scientific papers. One of these lines in particular had momentous consequences. In 1922 Alexander Fleming had accidentally discovered an agent in mucoid secretions which dissolved certain bacteria. He called it 'lysozyme' and supposed that it might normally prevent infection. It proved, however, to act on only relatively harmless bacteria, and little further work was done on it. Florey took up lysozyme in 1929 because he thought that its presence in mucus might explain an antibacterial action he had observed and also the natural immunity of some animals. He studied lysozyme in animals, publishing two papers in 1930. Though the results did not suggest that lysozyme was necessary to natural immunity, Florey retained a determination to discover its nature and mode of action.
In 1932 Florey was appointed Joseph Hunter professor of pathology at Sheffield University, a choice which surprised orthodox pathologists who still considered him a physiologist. However, there were experienced pathologists in the department who could maintain the routine work while Florey infused vitality into the teaching and research. One of his projects was on the control of the spasms in tetanus by curare combined with mechanical artificial respiration—the basis of the modern treatment. He made important advances in the field of gastrointestinal function. Lysozyme remained a major interest, although one constantly frustrated by the lack of adequate biochemical collaboration.
Chair of pathology in Oxford and the development of penicillin
In 1934 the chair of pathology in Oxford became vacant on the death of Georges Dreyer. Florey was appointed in 1935, being strongly supported by Edward Mellanby, secretary of the Medical Research Council. The Sir William Dunn School of pathology, designed by Dreyer himself on a grand scale, had become something of a mausoleum. Florey came into this partial vacuum with Beatrice Pullinger (from Sheffield) and Jim Kent. The three of them brought the department to life at all levels—teaching, research, and technical assistance. They were hampered by lack of money and Florey had to spend much time in fund-raising. The Medical Research Council and the Rockefeller Foundation were his main benefactors, but the sums obtained now seem absurdly small. There was little to be had from the university, and Florey was disappointed that pre-clinical departments like his own did not receive any substantial help from the £2 million Nuffield benefaction which was mostly spent on clinical research and teaching at the Radcliffe Infirmary.
Florey brought his department to life largely by attracting young postgraduates who had their own grants. The quality of their research and his own work attracted others and within a few years the Oxford school of pathology was among the best laboratories of its kind in the world. Florey expanded his own lines of research to include these new recruits, forming teams in which each contributed some special expertise, and over which he kept a general but not authoritarian control. One such project was the study of the lymphocyte, another was gastrointestinal function, a third was the study of the micro-circulation by cine-photography. But the most productive of all was the work which established the clinical value of penicillin.
In 1935 Florey finally obtained the help of a chemist, E. A. H. Roberts, who partly purified lysozyme by 1937. He had also engaged a young refugee biochemist, Ernst B. Chain, and asked him to discover how lysozyme dissolved bacteria. Chain found it to be an enzyme which attacks a specific bacterial structure. While reviewing the literature on lysozyme, Chain came across the paper by Fleming, published in 1929, describing the chance discovery of a Penicillium mould that apparently dissolved pathogenic bacteria in its vicinity. Fleming gave the name ‘penicillin’ to filtrates of broth cultures of the mould. Chain also found a culture of Fleming's mould in the school of pathology, with which he did a few tentative experiments in 1938. Florey had been well aware of many cases in which one micro-organism inhibited another. However, he had not been particularly interested in penicillin, even though Dr C. G. Paine at the Jessop Hospital in Sheffield had tried it locally, with some success, on eye infections. Florey noted the fact that Harold Raistrick and his colleagues had abandoned an attempt at the London School of Hygiene to purify this labile substance, but he agreed with Chain that a study of antibacterial substances produced by micro-organisms might widen a research which now seemed to be reaching a dead end in lysozyme as a therapeutic agent, and they decided to work together on three such products, including penicillin. The project was mentioned to the Medical Research Council in January 1939, and again in September, when a request for a special grant yielded £25 and the possibility of £100 later. However, the Rockefeller Foundation granted $5000 (£1200) per annum, for five years, a considerable sum at the time. Experiments showed that penicillin was the most promising of the substances chosen for study, and might have therapeutic as well as scientific importance. Thereafter the project became a team one. N. G. Heatley undertook the production of the mould filtrate; Chain, later joined by E. P. Abraham, worked on the purification and chemistry, while Florey and Margaret Jennings (who later became his second wife) carried out the animal work and, with Professor A. D. Gardner, the bacteriology.
On Saturday 25 May 1940 there was enough penicillin, still less than 1 per cent pure, to discover if it could protect mice from an otherwise lethal infection—a crucial test. Eight mice were injected with virulent streptococci, and an hour later four of these had injections of the crude penicillin. All four untreated mice were dead in a few hours; all the treated mice were alive and well the next day. Florey's remark, 'It looks promising', was a typically laconic assessment of one of the most important experiments in medical history. The results of a large series of such experiments, published in August 1940, completely confirmed the initial promise. Florey tried to persuade British drug firms to produce enough penicillin to treat human cases, but they were already hard-pressed by wartime needs and damage and when he failed he turned his own department into a small factory. All that can be said here of the physical, chemical, biological, and administrative difficulties is that they were overcome by collaborative perseverance and ingenuity, and by Florey's energy, determination, and personal example. Beginning in January 1941, there was a limited trial under his direction by C. M. Fletcher on patients at the Radcliffe Infirmary, Oxford. The cases chosen were mostly those of otherwise hopeless infection. Though only six could be treated systematically, and even these with restricted doses, the results were practically conclusive. Penicillin had been shown to overcome infections which were beyond any other treatment.
In June 1941, with Mellanby's approval, Florey and Heatley went to the United States to try to enlist commercial help. Florey's old friend A. N. Richards promised government support for firms prepared to develop large-scale methods of production, and three accepted. While Heatley remained to assist, Florey returned to Oxford to direct an even greater production effort in his department. This allowed a completely conclusive trial on 187 cases in 1942, largely carried out by Florey's wife. In the summer of 1943 Florey and Hugh Cairns went to north Africa to find out how a small amount of penicillin could be used most efficiently for the treatment of war wounds. Six months later Florey went to Russia with information on the new results. Meanwhile commercial production had, at last, begun in Britain, and this revealed that certain technical methods had been patented in America. Florey was criticized for having given away a valuable commercial asset. The information which Florey gave in America had been freely offered earlier in Britain. But in America he learned that much larger amounts of penicillin might be obtained by deep fermentation in large aerated vessels and this was to change the whole outlook on penicillin production. It was then considered unethical in Britain for those in medical research to patent medical discoveries. Soon after the end of the war the official attitude to patenting changed completely. When, in 1953, G. F. Newton and E. P. Abraham in the school of pathology isolated the first of the therapeutically useful cephalosporin antibiotics Florey gave them strong encouragement and confirmed himself its curative value in mice. This was his last personal involvement in the field of antibiotics. In 1949 a complete account of the Oxford work at that time was published as a two-volume book, Antibiotics, by Florey and six of his collaborators. In all, he was also the author or co-author of thirty-two scientific papers and more than thirty published lectures and reviews on the subject.
Recognition and its rewards
In scientific and medical circles the Oxford achievement had been recognized and applauded. Florey had been elected a fellow of the Royal Society in 1941, before the true value of penicillin had been established. Thereafter many other honours followed. He was knighted in 1944, and in 1945 he shared the Nobel prize for medicine with Chain and Fleming. The general public, however, tended to regard Fleming as the creator of penicillin therapy. He had, of course, discovered by chance the antibacterial power of a Penicillium mould, shown that the ‘mould broth filtrate’ was non-toxic to animals, and had used it, without much success, as a local antiseptic in a few cases. He had also suggested that it might be injected locally. But he had not during the next ten years developed his discovery or aroused interest in it, and, in any case, in the 1930s sulphonamides, which were easy to make, had captured medical interest. Fleming had taken no part at all in the Oxford work, although his cultures had prompted it. When the astonishing success of penicillin therapy became popular news, 'so gratifying as to be at times almost unbelievable', Florey was unwilling to talk to reporters. Fleming had less reserve, and articles appeared in which he was portrayed as the hero of a long struggle to harness his discovery, producing large amounts of penicillin at St Mary's Hospital, London, for use there or at Oxford under his direction. Such distortions, continuing uncorrected for many years, created a general impression that only Fleming's name should be associated with penicillin.
After a period of work on the use of antibiotics in tuberculosis, Florey returned in the mid-1950s to his early research interest. He used electron microscopy and marker techniques in new studies of mucus secretion and of vascular changes which can cause thrombosis. As always, he encouraged young workers to participate, and because his interest in the leucocytes was leading into the wider fields of immunology and cytogenetics, his department was ready to move into another new era. Florey, always the best animal surgeon in the department, regularly did long experiments undistracted by his emergence as a public figure. In this latter role he surprised those who had known him as something of a firebrand, since he accepted high official responsibilities with patience and even pleasure. He was concerned with the foundation of the Australian National University, paid many visits to Canberra, and was personally involved with the design, building, and organization of the John Curtin School of Medical Research. He refused to become the school's director and wrote to the vice-chancellor of the university in 1957: 'I have all my life struggled against becoming merely an administrator because I like doing experiments' and he believed that detailed bureaucratic control could stifle the essential function of an academic institution. However, he retained his association with the university and was its chancellor in 1965. In 1960 Florey was elected president of the Royal Society, and he brought to it a vitality which rejuvenated what was rather a staid organization and made of its officers and staff a team with a new sense of purpose. A major change was the move from the society's elegant but cramped quarters in Burlington House to the far more spacious Carlton House Terrace. He also widened the society's interests to include applied science and demography, and he opened its doors to lively discussion meetings and study groups which extended its already great influence.
In 1962 Florey became provost of Queen's College, Oxford, and relinquished his chair of pathology. The move puzzled some colleagues who thought that, after a life concerned with the clear objectives of science and scientists, he would find it tiresome to preside over a college with a then difficult governing body. For a time, it seems, he did, but mutual adjustments led to a pleasant working relationship and he was able to contribute practical improvements, as he had done before in other appointments. The college gained European studentships and the Florey Building, and something of a new outlook; he received the pleasure of a gracious style of living. He had always appreciated the college system in Oxford and Cambridge, and had much enjoyed the fellowship of Lincoln College which he had held since 1935 (he was made honorary fellow in 1962). In 1965 he was created a life peer as Baron Florey of Adelaide and Marston and a member of the Order of Merit. He had become a commander of the Légion d'honneur, and had received the US medal for merit, the royal and the Copley medals of the Royal Society, honorary degrees from ten British and eighteen foreign universities, and other worldwide honours, medals, and prizes. But he always spoke of his achievements with a modesty that was undoubtedly sincere. He went out of his way to claim that what had been done in Oxford with penicillin was due to the work of a small group of people and to see that they received recognition.
In 1966 Ethel Florey died after some years of disabling ill health. In 1967 Florey married Margaret Augusta Jennings (1904–1994), daughter of Thomas Fremantle, third Baron Cottesloe, and formerly wife of Denys Arthur Jennings. She had worked in fruitful collaboration with Florey at the school of pathology since 1936. For some years Florey had suffered from angina, unknown to his colleagues, and it was from a heart attack that he died suddenly in Oxford on 21 February 1968.
Qualities and personality
As a scientist, Florey had an extraordinary flair for choosing expanding lines of research; the ability to reduce a problem to simple questions answerable by experiment; great industry and determination; and an honesty that allowed of no self-deception. Equally important, he could inspire others to work almost as hard and well as himself. He published more than 150 scientific papers (excluding reviews and lectures) but the vast amount of experimental work entailed is revealed only by his notebooks. General Pathology (1954), the textbook edited by Florey and published in four editions, reflects the progressive teaching at his school. As a person, despite his outward geniality and humour, he was a man of profound reserve. He did not show his deeper feelings and he had few, if any, close friends. Ethel Florey's ill health and, in particular, her progressive deafness, had from the first marred the happy companionship which both had hoped for from their marriage. Yet she had charm, if not tact, and made a supreme effort to overcome these physical handicaps in her work on penicillin. Outside his own laboratory, Florey's main enjoyment was in travel, which in later years became worldwide. From his first arrival in Oxford in 1922 he took every opportunity to go abroad, working in foreign laboratories, learning languages, and, above all, appreciating the history, art, architecture, and music of the countries he visited. His letters to Ethel before their marriage are full of these experiences, and they reveal him as sensitive, lonely, unsure of himself, and deeply concerned for human troubles—a picture of himself very different from the one he presented to the world. 'I don't think it ever crossed our minds about suffering humanity' he said publicly of his reasons for starting work on penicillin. But in 1923, in a letter to Ethel, he wrote of 'the appalling thing of seeing young people maimed and wiped out while one can do nothing'. He was referring to untreatable infections. He, perhaps more than anyone before him, helped to achieve their defeat.
- Australian National University Library, Canberra, Noel Butlin Archives Centre, corresp. and papers
- Harvard U., Countway Library of Medicine, lectures
- Medical Research Council, London, corresp. and papers
- RS, corresp., notebooks, and papers
- Nuffield Oxf., corresp. with Lord Cherwell
- Rice University, Houston, Texas, Woodson Research Center, corresp. with Sir Julian Huxley
- Wellcome L., corresp. with Sir Ernst Chain
- W. Stoneman, photograph, 1943, NPG
- W. Bird, photograph, 1960, NPG [see illus.]
- H. Carr, oils, 1965, RS
- H. Carr, oils, Queen's College, Oxford
- W. Dargie, portrait, St Peter's Collegiate School, Adelaide
- F. Deane, portrait, Sir William Dunn School of Pathology, Oxford
- J. Dowie, bronze head, Prince Henry Gardens, Adelaide
- A. Gwynne-Jones, portrait, University of Adelaide
Wealth at Death
£30,554: probate, 6 June 1968, CGPLA Eng. & Wales