Editing Howard Florey (section)

== Early career ==
=== London Hospital ===
Florey was unhappy working at London Hospital; he disliked the long daily commute from [[Chobham]] that put his experimental work at the mercy of the railway timetable. In the summer Howard and Ethel lived in a flat in [[Belsize Park]] so he could devote more time to his work. He wrote up the results of the research he had done in New York on [[lacteal]]s and [[lymphatic capillaries]], which was published in the ''[[Journal of Physiology]]'' in 1927.{{sfn|Macfarlane|1979|pp=146–150}}<ref>{{cite journal |first=Howard |last=Florey |title=Observations on the Contractility of Lacteals – Part I |journal=The Journal of Physiology |issn=0022-3751 |date=12 January 1927 |volume=62 |issue=3 |pages=267–272 |doi=10.1113/jphysiol.1927.sp002357 |pmid=16993848 |pmc=1514841 }}</ref><ref>{{cite journal |first=Howard |last=Florey |title=Observations on the Contractility of Lacteals - Part II |journal=The Journal of Physiology |issn=0022-3751 |date=7 June 1927 |volume=63 |issue=1 |pages=1–18 |doi=10.1113/jphysiol.1927.sp002375 |pmid=16993861 |pmc=1514918 }}</ref>

Florey then embarked on writing a thesis for a fellowship at [[Gonville and Caius College, Cambridge]], where he became an unofficial fellow in 1926.{{sfn|Macfarlane|1979|pp=146-150}} His thesis on "Physiology and pathology of the circulation of the blood and lymph" was accepted, and his fellowship awarded in 1927.{{sfn|Abraham|1971|p=259}} He also continued his work on the secretion of [[mucus]]. London Hospital's facilities for the laboratory animals he needed for his research were unsatisfactory, so these experiments were carried out at Oxford and Cambridge. However, he was able to study the lacteals in patients undergoing abdominal surgery.{{sfn|Macfarlane|1979|pp=146–150}}

=== University of Cambridge ===
The sudden death of British pathologist [[Thomas Strangeways]] on 23 December 1926 created a vacancy in the Huddersfield Lectureship in Special Pathology at Cambridge,<ref>{{cite journal |title=Mr. T. S. P. Strangeways |journal=Nature |issn=0028-0836 |volume=119 |issue=92 |date=15 January 1927 |doi=10.1038/119092a0 |last1=R |first1=H. |page=92 |bibcode=1927Natur.119...92R |s2cid=4072016 |doi-access=free }}</ref> and it was offered to Florey.{{sfn|Macfarlane|1979|pp=151-153}} At Cambridge, Florey had a secure appointment and fine laboratory facilities, although the salary of £900  ({{Inflation|UK|900|1926|fmt=eq|r=-3|cursign=£}}) was only slightly higher. He had to teach, which he disliked, preferring research, but there was satisfaction that the new [[tripos]] course was largely designed by himself and [[Alan Nigel Drury]].{{sfn|Macfarlane|1979|p=199}} He recruited fourteen-year-old Jim Kent as his assistant. It was the practice at Cambridge that laboratory technicians would rotate through the various laboratory departments, which provided them with thorough training, but was frustrating to the researcher, who had to break in a new assistant every few months. Finding a good one was difficult for Florey; his reputation for hard work, long hours and exacting standards preceded him. He arranged for Kent to be permanently assigned as his assistant, and Kent would remain in the role for the next forty years.{{sfn|Macfarlane|1979|pp=151–152}}

The Floreys bought a house in Cambridge, and Florey cycled to work every day, including Sundays, arriving at 10:00, except on class days when he had to be there earlier.{{sfn|Macfarlane|1979|pp=155–156}} Ethel collaborated on two papers, co-written with Drury and [[Albert Szent-Györgyi]] respectively,{{sfn|Williams|1984|pp=33–34}}<ref>{{cite journal |last1=Drury |first1=A. N. |last2=Florey |first2=H. |last3=Florey |first3=M. E. |author-link3=Mary Ethel Florey |title=The vascular reactions of the colonic mucosa of the dog to fright |journal=The Journal of Physiology |issn=0022-3751 |date=23 October 1929 |volume=68 |issue=2 |pages=173–180 |doi=10.1113/jphysiol.1929.sp002604 |pmid=16994058 |pmc=1402856 }}</ref><ref>{{cite journal |last1=Florey |first1=H. |last2=Szent-Györgyi |first2=A. |author-link2=Albert Szent-Györgyi |last3=Florey |first3=M. E. |author-link3=Mary Ethel Florey |title=Methods for testing for the presence of adrenal cortex hormone  |journal=The Journal of Physiology |issn=0022-3751 |date=25 July 1929 |volume=67 |issue=4 |pages=343–348 |doi=10.1113/jphysiol.1929.sp002574 |pmid=16994036  |pmc=1402838 }}</ref> but stopped coming to the laboratory after she became pregnant. Nonetheless, during the summer break in 1929, she accompanied Florey to Spain, where Sherrington had arranged for him to study methods of nerve staining under [[Santiago Ramón y Cajal]]. They decided to commemorate this trip by naming their daughter, who was born on 26 September 1929, Paquita Mary Joanna.{{sfn|Abraham|1971|p=258}}{{sfn|Williams|1984|pp=34–35}} Two years later they spent the summer with the French histologist and endocrinologist [[Pol Bouin]] at the [[University of Strasbourg]], where Florey studied mucinogen, the chemical precursor to [[mucin]].{{sfn|Macfarlane|1979|p=205}}{{sfn|Williams|1984|pp=35–36}}<ref>{{cite journal |title= Pol André Bouin, MD (1870-1962). Bouin's fixative and other contributions to medicine |year=1992 |journal=Archives of Pathology & Laboratory Medicine |issn=0003-9985 |volume=116 |issue=8 |pages=882–884 |last=Ortiz-Hidalgo |first=Carlos |pmid=1497471}}</ref>

In January 1929, Florey began a study of [[lysozyme]],{{sfn|Macfarlane|1979|p=171}} an enzyme that forms part of the immune system in animals. For Florey this was a natural extension of his work with mucus. Lysozyme occurs in secretions containing mucus, and Florey wondered if it was a property of mucus. He mastered lysozyme [[assay]], and chemically identified it. He tested various animals for its presence; dogs, rabbits and guinea pigs all had it in their secretions, but cats had very little, and goats had none, except in their tears. In a paper published in 1930, Florey concluded that lysozyme played little part in natural immunity.{{sfn|Macfarlane|1979|pp=178–182}}

=== University of Sheffield ===
There was little prospect for promotion at Cambridge; Florey hoped that a chair of experimental medicine would be created, but this did not occur until 1945. He collaborated with biochemist [[Marjory Stephenson]] on his lysozyme project, but she did not have enough time to spare for a researcher in another department, and their results were not published. He yearned to have an interdisciplinary team and funds for work other than his own.{{sfn|Macfarlane|1979|pp=202–203}} The death of James Sholto Cameron Douglas on 30 October 1931 created a vacancy in the Joseph Hunter chair of pathology at the [[University of Sheffield]], and Florey decided to apply.<ref>{{cite journal |title=J. S. C. DOUGLAS, M.A., D.M., M.Sc. |journal=[[The BMJ|British Medical Journal]] |issn=0959-8138 |date=14 November 1931 |volume=2 |issue=3,697 |page=923 |doi=10.1136/bmj.2.3697.923-a |pmid=20776506 |pmc=2315164 }}</ref>{{sfn|Macfarlane|1979|p=205}}

[[File:Florey Lodge, Sheffield.jpg|thumb|Florey Lodge, Sheffield]]

That Florey was not a pathologist was not overlooked; the Scottish pathologist [[Robert Muir (pathologist)|Robert Muir]] declared: "There is no pathologist named Florey."{{sfn|Williams|1984|p=36}}  The faculty board decided to take a chance on Florey, and he was appointed on 9 December. He took up the appointment in March 1932. The Floreys moved for the fourth time in five years, this time to a Victorian manor on  {{convert|1|acre}} of ground about {{convert|1|mi}} from the university, which later became student accommodation with the name "Florey Lodge". The chair came with a salary of £1,000  ({{Inflation|UK|1,000|1930|fmt=eq|r=-3|cursign=£}}) per annum, but there was no provision for an assistant. He took Kent with him anyway, eventually securing 50 shillings a week ({{Inflation|UK|2.5|1930|fmt=eq|cursign=£}}) for him from the [[Medical Research Council (United Kingdom)|Medical Research Council]] (MRC). [[Guy's Hospital]] in London offered Florey a chair in pathology in February 1933. This caused alarm at the university, for it had recently lost two of its senior professors through the retirement of [[John Beresford Leathes]] and the departure of [[Edward Mellanby]] to become the secretary of the MRC. The university officials did not wish to lose Florey as well, and they raised his salary to £1,200 per annum to induce him to stay.{{sfn|Macfarlane|1979|pp=208–214}}{{sfn|Williams|1984|pp=36–41}}

The [[Sheffield Medical School]] was small, with only about fourteen students each year. The lack of a first-rate pathologist was remedied when Beatrice Pullinger joined the staff in January 1934, and she became Florey's ally in successfully lifting the standard of research and teaching in the department.{{sfn|Macfarlane|1979|pp=208–214}}{{sfn|Williams|1984|pp=36–41}} While Florey's main interest was lysozyme, he pursued other lines of research as well. The death of his brother-in-law,  John Gardner, from [[tetanus]] led to an interest in treating the disease, which he pursued in collaboration with [[Paul Fildes]] and H. E. Harding.{{sfn|Macfarlane|1979|pp=221–225}}{{sfn|Abraham|1971|pp=259–261}}<ref>{{cite journal |journal=[[The Lancet]] |issn=0140-6736 |volume=224 |issue=5,802 |pages=1036–1041 |date=10 November 1934 |title=The Treatment of Tetanus |first1=H. W. |last1=Florey |first2=H. E. |last2=Harding |first3=Paul |last3=Fildes |author-link3=Paul Fildes  |doi=10.1016/S0140-6736(00)56616-1 }}</ref> He also researched the structure and function of the [[lymphatic system]] with Pullinger,{{sfn|Abraham|1971|pp=259-261}}<ref>{{cite journal |last1=Pullinger |first1=B. D. |last2=Florey |first2=H. W. |title=Some Observations on the Structure and Functions of Lymphatics: Their Behaviour in Local Œdema. |journal= British Journal of Experimental Pathology |issn=0958-4625 |date=February 1935 |volume=16 |issue=1 |pages=49–61 |pmc=2065093 }}</ref> and continued his studies of [[contraception]] with Harry Carleton that had begun at London Hospital.{{sfn|Macfarlane|1979|pp=221–225}}{{sfn|Abraham|1971|pp=259–261}}

Florey's son [[Charles du Vé Florey|Charles du Vé]] was born in Sheffield on 11 September 1934, but for a time Florey's relationship with Ethel had deteriorated to the point where they were communicating in writing and contemplating a legal separation.{{sfn|Macfarlane|1979|pp=221–225}}{{sfn|Abraham|1971|pp=259–261}}<ref>{{cite interview |first=Charles du Vé |last=Florey |interviewer-last=Blythe |interviewer-first=Max |title=Professor Charles du Vé Florey in interview with Dr Max Blythe |publisher=Oxford Brookes University |location=Edinburgh |date=17 February 1998 |url=https://radar.brookes.ac.uk/radar/items/7ea51825-d26c-4575-8973-985d58aec234/1/Florey,C.pdf |access-date=3 February 2023 |archive-date=25 October 2023 |archive-url=https://web.archive.org/web/20231025104256/https://radar.brookes.ac.uk/radar/file/7ea51825-d26c-4575-8973-985d58aec234/1/Florey%2CC.pdf |url-status=live }}</ref> This was regarded as a serious matter; no Oxford fellow divorced without resigning his fellowship until the 1950s.{{sfn|Williams|1984|p=41}}

=== University of Oxford ===
Despite his success in revitalising the pathology department at Sheffield, Florey had grander ambitions than following the example of Douglas and dying in office. An opportunity arose with the death of [[Georges Dreyer]] on 17 August 1934, the holder of the chair of pathology in the [[Sir William Dunn School of Pathology]] at Oxford. Dreyer had overseen the construction of a palatial new laboratory, but by 1934 it had attracted few students and researchers. While Florey had reservations about leaving Sheffield for Guy's, he had none about Oxford.<ref>{{Cite journal |title=Georges Dreyer, C.B.E., M.D., F.R.S. |journal=[[British Medical Journal]] |issn=0959-8138 |volume=2 |page=376 |doi=10.1136/bmj.2.3842.376-a |date= 25 August 1934 |s2cid=45000548 }}</ref>{{sfn|Macfarlane|1979|pp=226-233}} The electoral board met on 22 January 1935, and Florey was appointed Professor of Pathology and Fellow of [[Lincoln College, Oxford]], which controlled the chair, effective 1 May 1935. The chair came with an annual salary of £1,700 ({{Inflation|UK|1,700|1935|fmt=eq|r=-3|cursign=£}}).{{sfn|Macfarlane|1979|pp=234–239}}{{sfn|Williams|1984|pp=42–43}} The school's budget was  £3,432 a year ({{Inflation|UK|3,432|1935|fmt=eq|r=-3|cursign=£}}) for all equipment and salaries except Florey's. He enforced strict economy measures such as forbidding the use of the [[elevator|lift]], which saved £25 a year.{{sfn|Macfarlane|1979|p=243}}

[[File:Sir William Dunn School of Pathology.jpg|thumb|left|The [[Sir William Dunn School of Pathology]] in Oxford]]
While the building could accommodate a staff of thirty researchers, twenty-five technicians and forty to fifty students, there was only a fraction of that number, and morale was low. Florey retained [[Jean Orr-Ewing]] and Margaret Campbell-Renton, who had been working with Dreyer, and brought Kent with him. Pullinger joined them soon after as demonstrator of pathology.{{sfn|Macfarlane|1979|pp=240–243}} Florey and Pullinger restructured the pathology course.{{sfn|Williams|1984|pp=47–48}} He hired [[Margaret Jennings (scientist)|Margaret Jennings]] as a gastroenterologist in October 1936,{{sfn|Macfarlane|1979|pp=240–243}} and she worked with him on his studies of mucus secretion.{{sfn|Macfarlane|1979|pp=240–243}} She became Florey's mistress in 1940; their affair was a poorly-kept secret.{{sfn|Lax|2015|pp=128–130}} He appointed P. J. Smart as the office administrator, and she remained in the role until she retired in 1976.{{sfn|Williams|1984|pp=47–48}} He attracted Rhodes Scholars such as Australian [[Brian Gilmore Maegraith|Brian Maegraith]] and Americans [[Robert H. Ebert]] and Leslie Epstein to the Sir William Dunn School of Pathology;{{sfn|Macfarlane|1979|pp=261–263}}{{sfn|Williams|1984|p=55}} other doctoral students included [[Peter Medawar]], Gordon Sanders and [[Jean Medawar|Jean Taylor]].{{sfn|Macfarlane|1979|p=266}}

[[Arthur Duncan Gardner]] headed the MRC's Standards Laboratory, which was located on the premises, and Gardner expected that his unit would have to move out, but Florey moved to keep him, as he needed a good bacteriologist.{{sfn|Macfarlane|1979|pp=240–243}} He arranged for Gardner to become head of his bacteriological section, with the title of reader of bacteriology in 1936. The Standards Laboratory eventually moved to the MRC's laboratories at [[Colindale]], but not until 1946.{{sfn|Macfarlane|1979|p=260}}

Florey also wanted a biochemist on his staff, but this proved difficult. He acquired the services of E. A. H. Roberts with a £300 MRC grant in July 1935, and for the next two years Roberts worked with Florey and Maegraith on Florey's lysozyme project. Still, Florey wanted a biochemist on his own staff. He tried to get [[Hugh Macdonald Sinclair]], but Sinclair declined the offer. [[Norman Pirie]] asked Florey if he could assume the role, but when Florey approached Sir [[Frederick Gowland Hopkins]], Pirie's boss, Hopkins refused to release Pirie. He tempered this refusal by recommending [[Ernst Boris Chain]], one of many Jewish refugees from [[Nazi Germany]] who had found sanctuary in the UK. Chain had recently completed his PhD thesis under Hopkins's supervision. He gratefully accepted Florey's offer of an appointment although it was initially for one year only, and with an annual salary of £200 ({{Inflation|UK|200|1935|fmt=eq|r=-3|cursign=£}}).{{sfn|Macfarlane|1979|pp=252–257}}{{sfn|Williams|1984|pp=52–53}} In turn, Chain felt that he needed a collaborator, and he had one in mind: [[Norman Heatley]], who was finishing his PhD in Hopkins's department. Heatley was happy to come, and Florey was able to arrange for the MRC to fund the position.{{sfn|Macfarlane|1979|p=274}}

[[File:Penicillin Past, Present and Future- the Development and Production of Penicillin, England, 1944 D17803.jpg|thumb|right|upright|Florey in his office in 1944]]
In 1936, Florey received a letter from Hilda stating that their mother Bertha had terminal cancer, so he arranged to travel to Australia with Ethel, Paquita and Charles during the summer break. They travelled on the {{SS|Orsova|1908|6}} to Melbourne, where they were met by Bertha, Charlotte, Hilda, Valetta and Hilda's daughter [[Joan Gardner (microbiologist)|Joan Gardner]]. In addition to spending time with his family, he visited [[Peter MacCallum]] at his laboratory. MacCallum introduced Florey to [[Roy Wright (physiologist)|Roy Douglas (Pansy) Wright]], an experimental physiologist, and they arranged for Wright to come to Oxford the following year to assist Florey and Jennings with their work on mucus secretion. Florey then joined Ethel and the children in Adelaide. The family returned to Oxford in October. Bertha died on 27 November.{{sfn|Macfarlane|1979|pp=268–271}}

Henceforth, Florey would lead an interdisciplinary team in an attack on a particular problem. Each member of the team tackled a particular aspect in their own way, with simultaneous research along different lines building up a complete picture. This was a manner of collaboration that was practically unknown in the UK at the time. However, the team members, including Florey, all worked on multiple projects at the same time. Florey was strict with his own collaborators, but gave considerable latitude to those working on other aspects of a project. He did not hold team meetings, although he encouraged team members to discuss issues with himself and each other, and he dropped by each laboratory nearly every day to view progress and provide suggestions.{{sfn|Macfarlane|1979|pp=266–267, 274–275, 305}}

The first such project was an investigation of [[lymphocytes]]. Florey developed a detailed project plan and deployed eight graduate researchers on it, including Sanders, Medawar and Taylor. Florey performed delicate surgery on rabbits to examine the effects of lymphocyte deprivation. The project, not completed for many years, resulted in several papers and advances in the understanding of the [[immune system]].{{sfn|Macfarlane|1979|pp=266–267, 274–275, 305}}

Florey continued with his lysozyme project. Although the MRC had agreed to pay Roberts's salary, it baulked at providing money for a piece of apparatus that he required. Florey then turned to the Rockefeller Foundation for assistance, and was provided with US$1,250 (about £320)({{Inflation|US|1250|1936|fmt=eq|r=-3}}). Florey and Maegraith harvested lysozyme from animals, and Roberts was able to purify it. [[Edward Abraham]] then managed to [[crystallization|crystallize]] it in 1937. Chain and Epstein then studied it and determined that it was a [[:wikt:polysaccharidase|polysaccharidase]] and, with Gardner's help, were able to determine its structure, and how it acted on [[polysaccharide]]s.{{sfn|Macfarlane|1979|pp=276–278}}<ref>{{cite journal |last1=Epstein |first1=L. A. |last2= Chain |first2=E. |author-link=Ernst Chain |title=Some Observations on the Preparation and Properties of the Substrate of Lysozyme |journal=British Journal of Experimental Pathology |issn=0958-4625 |volume=21 |issue=6 |pages=339–355 |date=December 1940 |pmc=2065383 }}</ref> The lysozyme research was successful, but while it was lethal to [[micrococcus|micrococci]], these bacteria are not usually [[pathogenic bacteria|pathogenic]], and were of little concern to medicine.{{sfn|Williams|1984|pp=60–62}}