In Focus
Penicillin: World War II infections and Howard
Florey
The results were dramatic – the control mice rapidly succumbed,
while all of the treated mice survived. These results attracted great
interest from the scientific and military communities because, if
Ian Gust
replicated in humans, the drug had the potential to influence the
Department of Microbiology and
Immunology
University of Melbourne
Parkville, Vic. 3010, Australia
Tel: +61 3 8344 3963
Fax: +61 3 8344 6552
Email: [email protected]
outcome of WWII.
It took Florey and 16 colleagues several months to produce sufficient material to treat a handful of patients. The team worked under
difficult circumstances with a lack of funding and equipment; at first
penicillin was made using old dairy equipment. Hospital bedpans
were later used to grow the mould and the liquid containing
Howard Florey is celebrated for his major contributions to
penicillin drained from beneath the growing mould and filtered
the large-scale production of the fungal product, penicillin,
through parachute silk.
during World War II (WWII), leading to life-saving outcomes
for many more than those with war wounds.
The first patient they treated was a policeman, in whom an infected
scratch had developed into a life threatening infection. He was given
Howard Florey was born in South Australia in 1898. After studying
penicillin, and within a day began to recover. Unfortunately Florey’s
medicine at the University of Adelaide he was awarded a Rhodes
team only had sufficient drug for 5 days of treatment and when
Scholarship to work in Oxford under Sir Charles Sherrington. After
their efforts to recycle penicillin from the patient’s urine failed,
subsequently undertaking a PhD at Cambridge and a brief period
he relapsed and died. Because of this experience, the team then
as Professor of Physiology at The University of Sheffield, he was
concentrated their effects on sick children, who did not require such
appointed to a chair in the Sir William Dunn School of Pathology at
large quantitates of the drug, demonstrating its value in a child with
Oxford, where he remained until his retirement.
septicaemia and another with meningitis.
In the 1930s bacterial infections were an unimportant cause of illness
By mid-1941 the drug’s potential was widely recognised and it was
and death in civilian populations were untreatable. In civilian life,
clear that the team needed the help of industry to produce it at large
diseases such as meningitis and pneumonia were frequently fatal,
scale. Companies in Britain were unable to help out because of the
minor wounds could result in cellulitis or life threatening septicae-
war, so later that year Florey and Heatley took a dangerous flight
mia and sexually transmitted diseases such as syphilis and gonor-
to the United States in a blacked-out plane. Penicillin production
rhoea were serious conditions. On the battlefield it is estimated that
was declared a war project and given high priority. Florey convinced
up to one-third of lives lost were due to secondary infections.
four major pharmaceutical companies (Pfizer, Abbott, Merck and
Florey became interested in the use of natural substances to combat
Lederle) and many smaller players to become involved.
infections and in 1938, with biochemist Ernst Chain, began a
systematic study of the antibacterial properties of substances produced by bacteria and fungi. They selected penicillin, a substance
produced by the fungus Penicillium notatum, which had been
described by Alexander Fleming almost a decade earlier, for further
study. Chain and his colleague Norman Heatley were able to devise
extraction and purification techniques which enabled them to
obtain sufficient penicillin to test its efficacy in laboratory animals.
During these meetings Florey encountered a scientist from the
Department of Agriculture who was searching for a new use for a
thick liquid that was a by product from the milling of corn. When this
liquid was used, as a substrate the yield of penicillin was increased
10-fold. A further boost was given when Mary Hunt (known as
Mouldy Mary) found a species of penicillin growing on a moulding
cantaloupe (P. chrysogenum) was almost 200 times as successful
again in producing penicillin as P. notatum. Further modifications
On 25 May 1940, a batch of laboratory mice were injected with
resulted in strains almost 1000 times as productive as Fleming’s
a lethal dose of streptococci and half then treated with penicillin.
original cultures.
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In Focus
By late 1943 mass production of the drug had commenced in 25,000
A paper that he wrote played a seminal role in the decision to
gallon aerated metal tanks, a process that Pfizer devised and made
establish the Australian National University and during 1947–1958
available to its rivals and later that year Florey was able to test the
he was closely associated with development of the John Curtin
drug in soldiers in North Africa, with dramatic results especially in
School of Medical Research, effectively acting as its non-resident
the treatment of gonorrhoea. Production continued to rise so that
head and declining several offers of the Directorship.
some 2 million doses were available for the D-day landings in June
1944. The results were dramatic, the survival rate for wounded
soldiers rising from 4 per 100 (WWI) to around 50 per 100 and the
death rate from pneumonia, falling from 18% to less than 1%. By the
end of the war, many laboratories were manufacturing the drug,
including Australia’s Commonwealth Serum Laboratories.
Florey was an excellent experimentalist, a gifted writer and a strong
and effective administrator who had the knack of getting things
done. His last major role, that of President of the Royal Society was
outstandingly successful, resulting in major reforms.
Florey was an excellent sportsman, who excelled at tennis. He loved
In 1943, the public health worker, Bill Keogh, convinced the war
cabinet that Australia needed to be self-sufficient in penicillin and
to travel, was an enthusiastic photographer and found pleasure in
gardening.
identified a young vet, Val Bazely, who was serving in an armoured
Once the importance of penicillin was recognised, Florey received
regiment in New Guinea, as the man for the job. Bazely was ordered
many honours. He became a member of the Royal Society in 1941,
back to Melbourne and almost immediately sent to the US. He spent
was knighted in 1944, received the Nobel Prize in 1945, the French
three months visiting major manufacturers and returned in Decem-
Legion d’honneur in 1946 and the US Medal of Merit in 1948. In 1965
ber with a great deal of new knowledge, most of it in his head.
he was created Baron Florey of Adelaide and later appointed to the
Bazely set himself the heroic target of producing penicillin within
Order of Merit.
six weeks and worked day and night to achieve it. He produced
As one of Australia’s greatest scientists, Florey has been rightly
specifications and working drawings, designed purification process-
celebrated. His likeness adorns Australia’s $50 note, and his name
es, identified suppliers and fabricators, commandeered equipment
lives on – both a suburb in Canberra and a major research institute in
and scrounged for scarce raw material. To obtain efficient staff, he
Melbourne are named after him.
persuaded soldiers who were awaiting discharge to assist him. By
February, 1944, 10 weeks after his return, a sizable quantity of
material had been produced and, by April, CSL became the first
company in the world able to provide penicillin to both soldiers
and civilians.
Biography
Professor Ian Gust A.O., is a medical virologist with advanced
training in pathology and infectious diseases. In 1986 he established
the Burnet Institute (1986) and became its founding director. In
Despite living in Britain for all his working life, Florey took a great
1990 he became the R&D Director at CSL Ltd. More recently he has
interest in Australia, hosting many young post-docs in his labora-
assisted public and private sector organisations, either as a board
tories and visiting regularly.
member or scientific advisor.
International Symposium on the Biology of Actinomycetes
Kusadasi, Aydin - Turkey
8–12 October 2014
Register at
www.isba17.com
17 8
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