Guest post by Rowena Fletcher-Wood
Excited, Mary Hunt tipped out the produce of her shopping: a large moulded cantaloupe. She had come across the cantaloupe by chance, and the ‘pretty, golden mould’ had proved irresistible. She had discovered the Penicillium chrysogeum fungus, a species that turned out to produce 200 times the volume of penicillin as Fleming’s variety. It was a serendipitous discovery, and vital at a time when the greatest challenge facing medicine was producing enough of the antibiotic to treat all of the people who needed it.
Hunt’s finding has been barely noticed beside the original accidental discovery: Fleming’s return from holiday to find a ‘fluffy white mass’ on one of his staphylococcus culture petri dishes. Fleming was often scorned as a careless lab technician, so perhaps the contamination of one of his dishes – which had been balanced in a teetering microbial tower in order to free up bench space – was not that unexpected. But Fleming had the presence of mind to not simply dispose of the petri dish, but to first stick it beneath a microscope, where he observed how the mould inhibited the staphylococcus bacteria. Competition between bacteria and fungi was well known and, in fact, when Fleming published in the British Journal of Experimental Pathology in June 1929, the potential medical applications of penicillin were only speculative.
In 1897, a 23 year old French scientist, Ernest Duchesne, published his doctoral thesis on antagonism between moulds and microbes – specifically, Penicillium glaucum versus Escherichia coli. His insight into the healing power of penicillin extended as far as curing guinea pigs of typhoid, but his research was never recognised.
Fleming lacked the resources and chemical training to isolate and test the active ingredient in penicillin, so he handed his research over to pathologist Howard Florey in 1938. Florey quickly transformed his Oxford lab into a penicillin factory. However, even with the discovery of Penicillium chrysogeum, production was slow.
The first patients to formally trial penicillin were a cluster of 25 streptococcus-infected mice. Unlike their 25 less fortunate friends who were not given the new medicine, they made a full and swift recovery. In 1940, Oxford policeman Albert Alexander became the first human to take penicillin. Alexander was suffering from fatal septicaemia, but within 5 days of treatment he began to recover. Sadly, the penicillin ran out and as techniques at the time were unable to produce enough, Alexander died. Although it was widely administered amongst the troops during World War II, once again, production was limiting.
The real breakthroughs in penicillin production began shortly after the establishment of a new American lab; in particular, the casual introduction of corn-steep liquor, a by-product of the corn wet milling process. This was being mixed with a wide variety of substances in an effort to find a use for it, and was seen to significantly increase penicillin yields.
In 1942, Anne Miller, suffering blood poisoning after a miscarriage, became the first successful civilian recipient, but further tests were still needed to explore the range of diseases treatable by penicillin.
Horrifically, in 1946-8, the Public Health Service, Guatemalan government, National Institutes of Health and the Pan American Health Sanitary Bureau approved a study to infect prison inmates, asylum patients, and Guatemalan soldiers with STDs and treat them with penicillin. Over 1300 people were infected, and 83 died.
Today, penicillin is the most used antibiotic in the world, treating large numbers of dangerous diseases. It also has many derivatives, the discovery of which began in 1957, when John Sheehan developed the first total synthesis. Although the synthesis proved difficult to upscale, it nevertheless produced a 6-aminopenicillanic acid intermediate – the starting material for a whole new class of antibiotics. Although the penicillin you and I take is manufactured in a lab, the battle between fungi and bacteria continues, and you can still come across this world-changing substance naturally growing in its parent mould.
