Philip John Ryan
The University of Washington, Seattle, Washington, United States
|Howard Walter Florey|
One of the most remarkable medical breakthroughs of all times occurred during the darkest days of World War II:1 the rediscovery of penicillin, which was mass-produced and disseminated to Allied troops, substantially reducing the number of deaths and amputations from infected wounds, and ushering in the dawn of the antibiotic era.
The initial discovery of penicillin has attained almost mythological status in the history of science. On 3rdSeptember 1928, Alexander Fleming, a Scottish scientist, returned from his family holiday to a cluttered laboratory, serendipitously noticing one of his culture plates had been contaminated by a blue-green mold encircled by a distinct halo of inhibition of bacterial growth. He identified the fungus as a Penicillium species and assigned the name penicillin to the substance released, which also inhibited the growth of several other bacterial species. He duly published these observations,2 but abandoned further investigations following several unsuccessful attempts to isolate a purified sample.
The less well-known but manifestly more significant story occurred about a decade later. Howard Florey, a pragmatic, industrious and somewhat reserved Australian scientist, headed a research team at the University of Oxford, including the enthusiastic and sometimes volatile biochemist Ernst Chain, a refugee from Hitler’s Germany. Their scientific brief was to research antibacterial substances produced by microscopic organisms. In 1938, Chain undertook an extensive survey of the literature, unearthing Fleming’s previously overlooked article on penicillin, whose unusual biological properties presented a complex challenge for purification. By March 1940, Chain had established a method for extracting and purifying small quantities of penicillin, paving the way for a series of remarkable experiments.3
On Saturday 25 May 1940, Florey infected eight mice with a lethal dose of the bacterium Streptococcus pyogenes, then either injected them with penicillin or left them untreated. The following day, the four mice treated with penicillin remained well; the untreated controls had died. Although generally understated in demeanor, Florey is reported to have telephoned his colleague, Margaret Jennings, exclaiming, “It looks like a miracle.”4
The ever-encroaching war on the home front hampered attempts by Florey to engage pharmaceutical companies in producing penicillin for human clinical trials; and the production of even minute quantities of penicillin necessary for treating a single patient was still a vast undertaking. An innovative junior member of the team, Norman Heatley, observed that the growth of the Penicillium mold flourished in porcelain hospital bedpans; however, these were in short supply because of war, so a pottery company was commissioned to manufacture 1000 square bedpans, and six ‘Oxford Penicillin Girls’ employed to cultivate the mold.5
On 12 February 1941, at the Radcliffe Infirmary, Oxford, a 43-year-old constable, Albert Alexander, became the first patient treated with penicillin. He had suffered an innocuous scratch from a rose-thorn in the mouth, which had subsequently become infected, disseminating into multiple suppurating facial abscesses. Within just several days of treatment, he exhibited an astounding improvement in his condition; sadly, however, the supply of penicillin rapidly dwindled, even after recycling by extracting it from urine, and within a month, he relapsed and died. Five more patients were treated over the next three months, several of them children, who required smaller doses. Of these, four recovered; the other, a child of four, was cured of his infection but tragically died of a brain hemorrhage.3
A sense of urgency pervaded the team: lab members smeared Penicillium mold on the inside of their coats as a contingency in case of invasion. The war prevented British companies from large-scale production, so in June 1942, Florey and Heatley embarked on a covert night flight with blacked-out plane windows across the Atlantic, transporting their precious cargo of penicillin. After a series of high-level discussions, they convinced several American companies, aided by government support, to begin immediate production on a vast scale. Penicillin provided crucial treatment to severe casualties of D-day in Normandy in 1944 and several other major battles, affording a key advantage to the Allies at a critical juncture of the war.3 Following the war, a wide range of antibiotics were developed, revolutionizing the treatment of infectious diseases and continuing to save innumerable lives today.
Florey, Chain, and Fleming were awarded the Nobel Prize in 1945 for their roles in this incredible discovery, and Florey was created a Life Peer in 1965. Lord Florey’s breakthrough not only provided lifesaving treatment during one of the most horrific chapters of the twentieth century, but created a vital new weapon for that ancient and deadliest of battlegrounds, the war against bacteria.
- Ekins, A. & Stewart, E. War Wounds, Medicine and the Trauma of Conflict (Exisle Publishing Ltd, Auckland, New Zealand, 2011).
- Fleming, A. “On the antibacterial action of cultures of a Penicillium, with special reference to their use in the isolation of B. influenzae.” British Journal of Experimental Pathology 10, 226-236 (1929).
- Abraham, E.P. Howard Walter Florey. “Baron Florey of Adelaide and Marston. 1898-1968.” Biographical Memoirs of Fellows of the Royal Society 17, 255-302 (1971).
- Lax, E. The Mold in Dr. Florey’s Coat: The Story of the Pencillin Miracle (Henry Holt and Company, New York, 2005).
- Bickel, L. Florey: The Man Who Made Penicillin (Melbourne University Press, Melbourne, Australia, 1995).
PHILIP JOHN RYAN, MBBS(Hons), BMedSc, PhD is currently undertaking postdoctoral studies in the Department of Biochemistry at the University of Washington, Seattle, in the laboratory of Professor Richard Palmiter, HHMI, after being awarded the American Australian Association’s Sir Keith Murdoch Fellowship. His project involves mapping the neural circuits of appetite and feeding behavior. He recently completed his PhD in neuroscience at The Florey Institute of Neuroscience and Mental Health in Melbourne, Victoria, Australia, where he studied the effects of the neuropeptide, relaxin-3, on feeding, anxiety, depression and addiction.