Howard Florey

In the 1930s, penicillin was known only as an interesting curiosity. The few scientists who had heard of it knew it as an unusual bacteria-killing substance produced by a microscopic fungus. Nobody had found an effective way to produce penicillin or use it in medical treatments.

In the early 1940s, Howard Florey and his scientific team transformed penicillin into a potent antibiotic. In doing so, they revolutionized medical science, helped the Allies win World War 2, and went on to save countless millions of lives.

Howard Florey, Ernst Chain, and Alexander Fleming shared the 1945 Nobel Prize in Medicine – Fleming for penicillin’s original discovery in 1928 and Florey & Chain for transforming it into a bacteria-killing magic bullet.

Beginnings

Howard Walter Florey was born on September 24, 1898 in the city of Adelaide, South Australia. His father, Joseph Florey, was a shoemaker, and his mother Bertha Mary Wadham was a housewife. The family was prosperous – Joseph’s shoemaking business was expanding, opening new branches.

Howard grew up with four older sisters – he had two half-sisters from Joseph’s first marriage and two elder sisters. Joseph’s first wife died of tuberculosis.

At school (Kyre College Preparatory, then St Peter’s Collegiate) Howard excelled at sport and academically.

He won a number of university scholarships and represented his school in tennis, athletics, gymnastics and football competitions. His favorite subject was chemistry, but his headmaster told his father there was no demand for chemists in Australia.

Medical Degree & Ship’s Doctor

In 1916, age 18, Howard Florey began a medical degree at the University of Adelaide. Highly disciplined and hard working, he came first in most exams.

His father died in 1918, and it turned out that his shoemaking business was insolvent.

Howard Florey continued his medical studies thanks to scholarships. In 1921, he graduated as top student and was awarded a Rhodes Scholarship for the University of Oxford. He served as the ship’s doctor on the long voyage to the UK.

A Decade of Learning: UK and USA

Having voyaged to the other side of the world, Florey immediately embarked on another major journey, an intellectual one, working in various locations, studying several disciplines, and carrying out increasingly sophisticated research work.

• In 1923, he gained a first class degree in Physiology from Oxford and developed a new method to place transparent windows in living tissues. He traveled as medical officer on an expedition to the Arctic.
• In 1924, at Cambridge, he researched blood flow changes taking place in thrombosis.
• In 1925, he was awarded a Rockefeller fellowship taking him to Philadelphia to learn microsurgical methods and to Chicago to study mucus secretion.
• In 1926, he became a research fellow at the London Hospital. The work failed to excite him – he felt it was too routine. He found he did not enjoy living in London.
• In October 1927, age 29, he returned to Cambridge as a Pathology lecturer. Cambridge awarded him a PhD for his earlier research on blood flow.
• In 1932, he accepted an offer to become Professor of Pathology at the University of Sheffield.

The Discovery of Penicillin

Lysozyme

After three years at Sheffield, in 1935, age 37, Florey returned to Oxford as Chair of Pathology. He attracted a number of highly talented graduate students to work in his department.

Also in 1935, a 28-year-old refugee from Nazi Germany, Ernst Chain, began lecturing at Oxford. Chain was a biochemist, and in 1939 Florey recruited him to his lysozyme research project.

Lysozyme was a substance discovered in human body fluids and egg whites by Alexander Fleming in 1922. His research identified lysozyme as a microbe killer.

From Lysozyme to Penicillin

Florey, the pathologist, asked Chain, the biochemist, to discover the mechanism involved when lysozyme dissolved bacteria.

Chain began a literature search and came across Fleming’s 1929 paper describing his discovery that Penicillium fungus produces a bacteria-killing substance.

Fleming named the substance penicillin and attempted to produce it on a larger scale, but failed. Assistance from a skilled chemist or biochemist would have been a huge benefit in terms of isolating, purifying and concentrating penicillin as an antibiotic drug. However, Fleming’s boss, Almroth Wright, disliked chemists and refused to allow them in his laboratory!

Fleming gave a culture of his original Penicillium to Oxford’s School of Pathology where it had been kept alive. In 1938, Chain began some exploratory experiments with it. The results were interesting.

Florey, helped by a generous grant from the Rockefeller Foundation, decided to abandon lysozyme and study penicillin.

A Penicillin Team

Florey built a penicillin research team. Its principle members were:

• Norman Heatley: Penicillium fungus growth.
• Arthur Sanders: Penicillin extraction.
• Ernst Chain, later with Edward Abraham: Penicillin purification and chemistry.
• Arthur Gardner and Jena Orr-Ewing: Penicillin testing on selected harmful bacteria.
• Howard Florey and Margaret Jennings: Penicillin testing on infected animals.

Penicillin Saves Mice

In May 1940, Florey tested penicillin at a purity level of just 1 percent on mice infected with deadly streptococci. The four mice he treated survived, while four untreated mice died. Florey’s team published their results in The Lancet in August 1940 with the title: Penicillin as a chemotherapeutic agent.

Penicillin Saves People

In the fall of 1940, the Battle of Britain was raging: Britain was fighting for its existence against Nazi Germany.

Florey failed to persuade British drug companies to produce penicillin. They were already running flat out on other war work. His response, working with amazing intensity, was to turn his laboratories into a miniature penicillin factory.

By January 1941, he and his team had produced enough penicillin to begin clinical trials on six patients dying of bacterial infections in Oxford’s Radcliffe Infirmary.
The infirmary’s Dr. Charles Fletcher supervised the trials, giving penicillin to all six dying patients. Five survived. One died after the penicillin supply ran out.

Everyone in Florey’s team was thrilled. Penicillin had saved five people from certain death. Increasingly, the drug looked like the long-dreamed-of magic bullet – a bacteria killer with no toxicity to humans.

Scaling Up

In June 1941, Florey and Heatley travelled to America to describe their penicillin production process. The U.S. government offered money to any American company willing to produce penicillin on a large scale. The money was needed because, although Florey’s method was suitable for small-scale production, it was not suitable for industrial-scale production.

Meanwhile Florey’s own lab-factory continued operating. By 1942, he had enough penicillin for a larger-scale clinical trial on 187 patients at the Radcliffe Infirmary, which was again successful.

Robert Gwyn Macfarlane was a clinical pathologist who helped with the clinical trials at the Radcliffe Infirmary. He became a great admirer of Florey, writing a biography in 1979: Howard Florey, The Making of a Great Scientist.

Penicillin Helps the War Effort

In 1943, Florey travelled to North Africa to carry out penicillin trials on war wounds. By the war’s end, penicillin had saved the lives of tens of thousands of allied soldiers.

Florey did not patent penicillin or any aspect of its production, believing it would be unethical.

Nobel Prizes

Florey, Alexander Fleming, and Ernst Chain were awarded equal shares of the 1945 Nobel Prize in Physiology or Medicine:

“for the discovery of penicillin and its curative effect in various infectious diseases.”

Penicillin – Who to Thank?

When it became apparent that penicillin was a wonder drug, Alexander Fleming’s employer, London’s St Mary’s Hospital, made sure its link to penicillin was highly publicized – good publicity helped bring in donations from the public.

In its pursuit of publicity, the hospital received valuable help from one of its benefactors, Lord Beaverbrook, the owner of several major British newspapers.

Fleming was more than happy to speak to the press about his work.

Florey, however, instructed his team members not to speak to the press under any circumstances. He knew that only tiny amounts of penicillin were available and he did not want to raise the public’s expectations of a miracle cure.

In the world’s eyes, Fleming became the big name associated with penicillin. Florey and Chain’s crucial roles in turning Fleming’s discovery into an antibiotic drug were understated – a situation that did not change when the Nobel Prize was shared between the three scientists.

In 1998, Professor Sir Henry Harris, who succeeded Florey as Oxford’s Chair of Pathology captured the situation in a nutshell, also praising the often unsung Norman Heatley:

“…without Fleming, no Florey or Chain, without Chain no Florey, without Florey no Heatley, without Heatley no penicillin.”

Honors

Florey received a large number of honors, including:

• 1941: Elected as fellow of the Royal Society
• 1944: Knighted, becoming Sir Howard Florey
• 1945: Lister Medal
• 1945: Nobel Prize in Physiology or Medicine
• 1945: Berzelius Medal (Sweden)
• 1946: Légion d’honneur (France)
• 1947: Medal of Merit (USA)
• 1946: Albert Medal
• 1948: British Medical Association Gold Medal
• 1951: Royal Medal
• 1957: Copley Medal
• 1960: Elected as president of the Royal Society
• 1960: Wilhelm Exner Medal (Austria)
• 1965: Lomonosov Gold Medal (USSR)
• 1965: Life Peerage, becoming Baron Florey of Adelaide and Marston

Further Information and The End

In October 1926, Florey married Dr. Mary Ethel Hayter Reed. They had met as students in Australia and she joined him in London. They had a daughter and a son: Paquita and Charles.

Mary, a pathologist, played a major role in the first big clinical trial of penicillin in 1942. In 1952, she began publishing her book The Clinical Application of Antibiotics, in four volumes.

Florey enjoyed classical music, gardening, photography and shooting home movies. In his late 50s he took up oil painting.

In 1962, age 64, Florey retired from scientific research, becoming Provost of Queen’s College, Oxford.

In 1966, his wife Mary died.

In 1967, Florey married Margaret Jennings, a member of his original penicillin team.

Howard Florey died at age 69 of a heart attack on February 21, 1968 in Oxford – he had suffered from angina for a number of years. Survived by his children and second wife, he was buried in Oxford’s St. Nicholas Churchyard. A month after his death, a memorial service was held for him in Westminster Abbey.

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Further Reading
W. E. Herrel
Further Observations on the Clinical Use of Penicillin
Proc. Staff Meet., Mayo Clin. Vol. 18: pp 65-76, March 10, 1943

R. G. Macfarlane, revised by E. P. Abraham
Florey, Howard Walter, Baron Florey (1898–1968)
Oxford Dictionary of National Biography, May 2008
https://doi.org/10.1093/ref:odnb/33182

E. P. Abraham
Howard Walter Florey, Baron Florey of Adelaide and Marston, 1898-1968
Biogr. Mems Fell. R. Soc. 1971 Vol. 17, pp. 255-302, 1 November

David Greenwood
Antimicrobial Drugs: Chronicle of a Twentieth Century Medical Triumph
OUP Oxford, February 2008

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