Howard Florey

Background

Before the advent of antibiotics even minor scratches and abrasions could turn into death sentences if they became infected with bacteria. Serious bacterial infections such as puerperal fever, scarlet fever, meningitis, osteomyelitis, rheumatic fever and pneumonia regularly resulted in death.

The Scottish scientist Alexander Fleming discovers the antibiotic properties of the penicillium natartum mould in 1928 but is unable to extract the active component, penicillin, and does not realise its potential. The discovery languishes for a decade until a medical research team headed by Florey decide to investigate.

Mini biography

Born on 24 September 1898 in Adelaide, the capital of South Australia. His father, Joseph, is a British immigrant and prosperous boot and shoe manufacturer. His mother, Bertha, is Australian. Florey is the youngest of five children and the family's only son.

He attends the Kyre College Preparatory School (1908-1910) and then the Saint Peters Collegiate School (1911-1916).

At school Florey is an outstanding scholar and sportsman. He has a special interest in chemistry and an early ambition to pursue a career in scientific research. He passes his public exams with honours, receives numerous scholarships, awards and medals, and becomes head prefect.

Speaking later of his schooling Florey says, "The science teaching at St Peter's was probably quite good. We had a man named Sneaker Thompson. He was called Sneaker because he used to go round in rubber-soled shoes. He used to get some chemistry into us, and at quite an early age I had some idea of doing research. I might have been 12 when this came over.

"I remember my sister saying, 'Oh, you mean you'd like to be a sort of Pasteur,' and I didn't know what that meant. My first interest was chemistry; I was not very good at mathematics, and in those days, for chemistry you didn't have to know much mathematics."

In 1916, after finishing his secondary schooling, Florey contemplates enlisting to fight in the First World War but his parents refuse to give their consent.

1917 - He enrols to study science and medicine at the University of Adelaide. During his final year at the university he meets his first wife, Ethel Hayter Reed, a fellow medical student.

"It was a small medical school in Adelaide in those days, I think 24 or some quite small number in a year, it was quite small," Florey later says.

"According to modern standards the teaching of physiology was hardly worth considering. Anatomy was quite good, biochemistry had hardly started, there was no tremendous pressure on one. No, the Adelaide course in those days was very good, and then I got a Rhodes Scholarship actually before the end of the medical course, and went straight off to Oxford.

"I think even in those days I thought it was highly improbable that I'd ever come back to Australia. And this may sound a very odd thing to say, but I think I left here thinking that there were no opportunities in the sort of things I was beginning to get interested in, physiology for example."

1918 - The Florey family business collapses. In September Florey's father dies from a heart attack. Though the family now faces financial difficulty, Florey is able to complete his science and medical degrees with the aid of scholarships.

1921 - In December, after being awarded the Rhodes Scholarship for South Australia, Florey travels to Britain to attend Oxford University, working as ship's doctor on the voyage out.

At Oxford he studies science and physiology, obtaining a Bachelor of Science degree and First Class Honours in Physiology in 1924.

Florey will spend most of the rest of his life in Britain, although he travels widely and makes regular trips back to Australia.

"I was very well treated in Oxford," Florey says in a recorded interview given to Hazel de Berg in 1967 and now held in National Library of Australia Oral History Collection.

"One could get away with any sort of gaucheries as 'Oh, just one of these rough colonials,' and this was very good line to play. But I fortunately fell in with Sir Charles Sherrington, who was one of the great physiologists, not only in his day but I suppose in all time. But I was doing some research in Sherrington's department, and one day he came along and asked me if I was interested in experimental pathology.

"He said he thought the time was right for somebody with a physiological background to take up some experiments in pathology. He then said, 'Would you like to go to Cambridge?' And he said, 'There is a studentship vacant there, and I've been asked if there's anyone suitable here to put in for it, and I'll put your name in.'"

1924 - Florey is offered a John Lucas Walker Student scholarship at Cambridge University, where he works as a researcher.

During the year he takes a two-month break from his work to join the Oxford University Arctic Expedition as its medical officer.

1925 - Florey wins a Rockefeller Travelling Fellowship to study in the United States for a year. He uses the opportunity to develop his research techniques at Alfred Newton Richards' laboratory at the University of Pennsylvania.

1926 - On his return to Britain, Florey takes up a Fellowship at Gonville and Caius College, Cambridge University, where he receives a PhD in pathology in 1927. At the same time, he holds the Freedom Research Fellowship at the London Hospital.

1927 - Ethel Reed travels to Britain to join Florey. The couple marry on 19 October. They will have two children, a daughter in 1929 and a son in 1934. However, the couple are incompatible and the marriage, while it lasts until Ethel's death, is not a success.

Meanwhile, Florey is appointed Huddersfield Lecturer in Special Pathology at Cambridge.

1930 - Florey is appointed to the Joseph Hunter Chair of Pathology at the University of Sheffield, remaining in the post until 1934.

1935 - He is appointed professor of pathology and director of the Sir William Dunn School of Pathology at Oxford University. It is while holding these positions that he will do his most significant research.

1938 - Florey gathers an interdisciplinary team of scientists to investigate the properties of antibacterial substances. Members of the team include the biochemists Ernst Boris Chain, Edward Penley Abraham and Norman Heatley, the bacteriologist Arthur Duncan Gardner, Jena Orr-Ewing, the gastroenterologist Margaret Jennings and Florey's wife Ethel.

The team's investigations take a fateful turn when Ernst Chain recalls a paper by Alexander Fleming on the penicillium natartum mould, 'Antibacterial Action of Cultures of Penicillium'.

Florey and Chain realise that the antibacterial properties of the penicillium natartum mould deserve greater scrutiny and focus the team on isolating and analysing penicillin, the mould's active constituent.

Norman Heatley investigates ways to extract penicillin from the penicillium natartum mould. Chain and Abraham work on purifying the antibiotic. Gardner and Orr-Ewing study how penicillin affects other organisms. Florey and Jennings look at the impact of penicillin on animals. Ethel Florey later works with her husband on clinical trials.

Talking of Chain's contribution to the team Florey later says, "He came and worked, not on penicillin, but he came and worked on snake venoms. But in the laboratory at that time, we were working on an antibacterial substance named lysozyme and Chain became interested in this substance and eventually he proposed and I agreed to go along with it, that we made a thorough investigation of antibacterial substances. And this was the start of why we looked at penicillin."

However, with the Second World War brewing, Florey is unable to obtain sufficient funds for his research from the British Medical Research Council. He turns to the American Rockefeller Foundation, which grants him almost all he wants.

Speaking of the work of his team Florey later says, "All we did was to do some experiments and have the luck to hit on a substance with astonishing properties."

"There's a terrible lot of luck in this sort of thing. We happened to have hit an antibiotic which worked in man. We could have worked with hundreds of others and they would have been chemical curiosities. So this was a bit of luck. ...

"I get much more credit than I deserve in this matter, because I'm quite clear that nothing would have gone along, except for a group of about five or six people not a big group, with some technicians, and that was sufficient to discover all the essential points about penicillin."

Referring to Fleming, Florey says, "I'd like to emphasise first of all we didn't work with Sir Alexander Fleming, I hardly knew him. Fleming's work was done 10 years before the work in Oxford, but we just happened to work on the substance that he'd discovered."

1939 - The Second World War breaks out on 1 September when German troops invade Poland. Britain and France declare war on Germany two days later.

If Florey's team can show that penicillin can be used to prevent battle wounds from becoming infected and then produce the drug in sufficient quantities the Allied forces will gain a significant advantage over their Axis opponents.

1940 - On 25 May Florey and his team test penicillin on eight mice that have been injected with a lethal dose of streptococci bacteria. Four of the eight mice are treated with penicillin. The others are used as controls. By the next day, all the untreated mice are dead. Those that have received the penicillin remain alive and well.

Further testing on hundreds of mice follows. The findings are reported in the medical journal 'The Lancet' on 24 August.

1941 - Penicillin is given its first human trial in early January when a young woman with terminal cancer agrees to receive an injection to test the drug's toxicity. She exhibits some adverse side-effects but Abraham is able to demonstrate that these have been caused by impurities in the dose and not the penicillin itself.

On 12 February the drug is administered to Albert Alexander, a British policeman dying of septicaemia contracted from a scratch on his face that has become infected. Within a day of receiving the penicillin Alexander begins to recover. However, Florey's team has been unable to prepare enough of the antibiotic for a full course of treatment and Alexander relapses and dies on 15 March.

The hunt for methods to produce penicillin in commercial quantities now begins in earnest. Due to the war drug companies in Britain are unable to assist with large-scale production. Florey and Heatley fly to the US to see if drug companies there can assist. The trip is a success and results in innovations that increase the efficiency of the production process by about 20 times.

The development of penicillin is given extra impetus by the US Government after the Japanese bomb the Pearl Harbour naval base in Hawaii on 7 December and the US enters the war. The US sees the large-scale manufacture of the drug as an important component of the war effort.

Meanwhile, Florey is elected to the Royal Society, Britain's independent scientific academy.

1942 - The British Government agrees to produce penicillin in commercial quantities.

1943 - Florey travels to North Africa to test penicillin on wounded soldiers. The results are outstanding. Lives are saved and amputations prevented.

In March 'The Lancet' publishes an article by Ethel and Howard Florey on the results of a series of 187 cases of sepsis treated with penicillin.

By the end of the year mass production of the drug has commenced. By the D-Day landings on the beaches in Normandy on 6 June 1944 enough penicillin has been manufactured to treat all the Allied casualties.

By the end of the war penicillin is being produced by many laboratories (including the Merck, Squibb and Pfizer companies in the US and the Commonwealth Serum Laboratories in Australia) and the drug is being widely used to treat Allied troops.

1944 - Florey is knighted.

He returns to Australia briefly at the invitation of Prime Minister John Curtin, who is keen to see penicillin manufactured for civilian use. Curtin also asks Florey to help establish the Australian National University (ANU) and a medical research centre, to be called the John Curtin School of Medical Research.

1945 - Florey, Fleming and Chain are awarded the Nobel Prize for Physiology or Medicine.

At the presentation ceremony held in Stockholm on 10 December Professor G. Liljestrand says, "In a time when annihilation and destruction through the inventions of man have been greater than ever before in history, the introduction of penicillin is a brilliant demonstration that human genius is just as well able to save life and combat disease."

Full copy of presentation speech.

Speaking at the Nobel Banquet following the presentation Florey says, "On a personal plane science can act as a force to bring people together but no one can I think be optimistic at the present time about civilisation as we know it.

"During the last few years the demonstration of what the application of scientific methods can achieve has been so striking and of such a magnitude that even those brought up in the classical tradition, who form most of the statesmen and politicians of the world, are at last aware of the tremendous tasks that lie ahead in the utilisation of these forces.

"We have been astonished at the reaction of some of them to this realisation. Apparently their idea is that they will utilise and control scientists but that we are so ignorant and insensitive that our views on policies to be pursued and the use to which our work is to be put are of little or no importance. ...

"Perhaps on those who have today and in former years received the greatest of distinctions in being awarded a Nobel Prize now rests not only the responsibility for furthering the immediate interests of science but also that of ensuring that those who control our destinies are fully informed of the tremendous forces with which they deal. "

Full copy of banquet speech.

In the following years Florey will receive awards from Britain, France, Australia and the US, including the Lister Medal of the Royal College of Surgeons, the Berzelius Medal of the Swedish Medical Society, the Royal and Copley Medals of the Royal Society, the Medal of Merit of the US Army, and appointment to the French Légion d'Honneur and the British Order of Merit.

His face will appear on the Australian $50 note and he will have a suburb in the Australian capital Canberra named after him. His name will also be given to a building in the University of Melbourne, the largest lecture theatre in the University of Adelaide's medical school, a lecture theatre and professorship in the John Curtin School of Medical Research, a joint Royal Society-ANU lecture and travelling fellowship, a fellowship at Lady Margaret Hall, Oxford, and a building belonging to the Queen's College.

1946 - Florey continues working on antibiotics at the Sir William Dunn School of Pathology at Oxford University. One of his group's most famous accomplishments is the development of the broad-spectrum antibiotic cephalosporin C in 1954.

Florey will also study the role of white cells in the fight against viruses and bacteria, laying the foundations for current understanding of the vaccination process.

1950s - When various strains of bacteria begin to become resistant to penicillin the drug is chemically altered to restore its effectiveness. However, developing resistance will be an ongoing problem for penicillin, along with other antibiotics.

Penicillin and other antibiotics will also come to be blamed in part for population growth around the world. Florey will later say, "As we're all glad now that it works, but then you've got the reverse side of the medal, because I'm now accused of being partly responsible for the population explosion which is one of the most devastating things that the world has got to face for the rest of this century."

1958 - Florey opens the John Curtin School of Medical Research in Canberra.

1960 - He becomes the first Australian and first pathologist elected as president of the Royal Society. During his five-year tenure he reorganises the society and greatly expands its research-professorship program.

1962 - Florey resigns from the Sir William Dunn School to take up the post of provost of Queen's College, Oxford University.

1965 - He is made Baron Lord Florey of Adelaide and Marston. The same year he accepts the Chancellorship of the ANU, although he continues to live in Britain.

1966 - Ethel Florey dies on 10 October.

1967 - On 6 June Florey marries Margaret Jennings, a member of the original team that developed penicillin and Florey's colleague and special assistant for more than 30 years.

1968 - Florey dies of a heart attack on 21 February at his Queen's College lodgings in Oxford.

In a memorial service held in Westminster Abbey the Nobel Laureate Edgar Adrian describes Florey as "one of the great leaders of medical science."

"Millions owe their very lives to him and for what he did Florey is to be honoured as were Pasteur, Jenner and Lister," he says.

Postscript

1981 - A commemorative stone to Florey is placed in Westminster Abbey.

2004 - A panel of experts appearing on a TV special produced by the Australian Broadcasting Corporation select Florey as 'The Greatest Australian'.

Comment

It is difficult to say just how many people around the world have had their lives saved by penicillin. One source estimates the number at around 50 million people. It could be less, it could be more, but it is surely in the tens of millions.

Whatever the figure, it is likely that Florey and his team are responsible for saving the lives of more people than any other group of individuals from the 20th Century, and probably from the whole of human history.

Florey, however, was sober about his achievement.

"Well there are a lot of misconceptions about medical research," he told Hazel de Berg in 1967.

"People sometimes think that I and the others worked on penicillin because we were interested in suffering humanity. I don't think it ever crossed our minds about suffering humanity. This was an interesting scientific exercise, and because it was of some use in medicine was very gratifying, but this was not the reason that we started working on it."