The sub-title of the book is “The Remarkable True Story of the Penicillin Miracle”. The author had the full cooperation of Florey's family and the widow of the third member of the Oxford team, Dr Norman Heatley. It gives a very readable account of the discovery of penicillin by Fleming and its development in Oxford by Florey, Chain and Heatley. Also for the first time, in an easily accessible manner, it records the work done by the biochemist Heatley, for many years the unsung hero of the miracle.
The first chapter has the heading “The Quiet Scot” and records Fleming's discovery of lysozyme the “antibiotic” that occurs widely throughout nature. The bacteria that it does not destroy are, of course, the pathogens. Dr VD Allison was a research student with Fleming when lysozyme was discovered and while working with Fleming, he made lysozyme the subject of his MD thesis. He came to Belfast as a Bacteriologist and ended his career as Director of Laboratory Services for the Northern Ireland Hospitals Authority.
Lax deals briefly with Fleming's war work in a makeshift laboratory near Boulogne where he worked with Thomson, later Sir William, Professor of Medicine, Queen's University, Belfast. However most of the chapter describes the discovery of penicillin and Fleming's attempt to isolate it and how his papers and lectures were completely ignored.
The book is particularly good at describing the very different personalities of the main collaborators: Florey, the bluff, taciturn, irascible Australian who was always “The Professor” who, frequently was unable to praise a junior to his face but was fulsome in his praise to other people. Lax calls him “The Rough Colonial Genius”. He was the clinical physiologist who had the brain wave to look for a biological drug better than the recently introduced sulphonamides. Chain, “The Temperamental Continental” – a refugee, some of whose family were eventually murdered in the holocaust. He anticipated criticism where none was intended and reacted over sensitively to any disagreement. He thought the laboratory should be run on the same lines as in Germany – a strict hierarchy with everyone doing what the chief wanted without discussion or demur. Before starting any research he explored the literature and found the long-forgotten paper on penicillin by Fleming.
The third member of the triumvirate was Heatley the diffident English gentleman easy to work with and respected and beloved by the technical staff. The contrast with Chain could not be more marked – “…. he and Chain were opposites in temperament, in personality, in scientific approach … Heatley was reticent and shy, Chain was voluble and demonstrative; Heatley was reluctant to seek credit, Chain was quick to claim his due.”
Chain was a very difficult colleague. Sometimes when he and Florey were arguing the very walls of the room seemed to vibrate. Although Heatley worked with Chain he collaborated with Florey.
Heatley, a biochemist was also an expert in the recently introduced technique of micro-assay and developed a technique of measuring the potency of any sample of penicillin in what became internationally known as Oxford units. His first task was to culture sufficient penicillium from which Chain was to extract the active principle – penicillin and determine its formula. However penicillin proved to be highly unstable and Chain was making very little headway in isolating it. That problem was not solved until after Heatley joined the team.
Vast quantities of culture medium were required for the isolation of a minute quantity of the active principle. All sorts of containers were used – bedpans were the best but took up too much room in a steriliser. Heatley devised and had made rectangular “bedpans” that proved eminently suitable. He also invented and built an apparatus from bits and pieces and glassware that he made himself for the continuous extraction of what at first was thought to be pure penicillin. The first isolated powder was yellow and later shown to be only 1 percent pure. When Heatley suggested that the yellow colour was not the active principle he was shouted down by Chain but went on to prove that he was right.
“Without Heatley, No Penicillin” is the heading of one chapter. The phrase was coined by Professor Sir Henry Harris, a successor to Florey as head of the Sir William Dunn School of Pathology where the “miracle” happened.
Three very different men, each a genius in his own field, fortuitously came together and isolated penicillin, a task that Fleming had been unable to accomplish. Its wonderful power in killing staphylococci in vitro and in vivo in mice was soon proven. And it was not long before an expanded team demonstrated its life-saving power in humans.
All the pharmaceutical firms in Britain were too fully committed to war work to undertake the commercial production of penicillin. Florey and Heatley went to the United States of America to get that started. Fortunately, using apparatus unavailable in England, a method of deep culture of the penicillium was discovered. Also a different strain of the fungus was isolated that gave a much increased yield of penicillin.
Lords Beaverbrook and Moran ensured that Fleming's discovery was well publicised, thereby getting funds for St Mary's Hospital. Fleming was by no means averse to basking in the spotlight but he did occasionally refer to the work done in Oxford. He shared the Nobel Prize with Florey and Chain, was knighted, elected to the Royal Society and received a multitude of other awards. In 1941 Florey was elected to the Royal Society mainly for work before his quest for penicillin commenced. He also received many awards, was knighted and later received a Life Peerage. Chain also was elected to the Royal Society, received many awards and was knighted. Heatley whose work had been essential received no recognition during his working life. However his widow says that he was never embittered by this oversight. He was appointed to the Order of the British Empire in 1978 and 12 years later Oxford University repented of its neglect and awarded him the first Penicillin Fellowship at Lincoln College, named the lab in which he worked for 42 years The Heatley Laboratory and instituted an annual lecture and a lectureship in his honour. Thirty years after the penicillin work was completed Oxford made him its first non-medical Honorary Doctor of Medicine.
Heatley married Mercy Bing, a medical graduate of Oxford and the daughter of the founder and first Headmaster of Rockport School Holywood, Co. Down which has honoured Heatley by naming their Science Laboratory “The Heatley Laboratory”. Rockport School is celebrating its centenary this year.
There is another connection to Northern Ireland. The War Office sent Florey and Lieutenant Colonel Ian Fraser, RAMC (later Sir Ian) of the Royal Group of Hospitals, Belfast to North Africa to test penicillin in the treatment of war casualties. The taciturn Florey did not enjoy the company of the ebullient Fraser!
The Mould in Dr Florey's Coat was no accident. The three collaborators and the pathologist Sanders had penicillium spores rubbed into clothing so that, if in the war the laboratory were destroyed or three of them killed, or if the country were invaded, the research could start again elsewhere.