published Thursday, June 12th, 2014

Cleaveland: Scientific discovery and chance

By Dr. Clif Cleaveland

Unexpected observations can play a significant role in scientific advances. An unprepared mind dismisses the occurrence or considers it a bother. A prepared mind asks, "What does this mean?"

In 1928, British research physician Alexander Fleming observed that a contaminating speck of material prevented growth of bacteria on a culture medium. The speck turned out to be bread mold from the genus Penicillium. Fleming identified the mold and began a series of studies on its properties. Subsequent experiments showed that a filtrate of broth containing the mold could kill a variety of bacteria involved in human disease.

Fleming named the filtrate "penicillin," a name that has stuck. Eventually, problems with purifying penicillin frustrated Fleming, and he returned to his previous work. He summarized his penicillin experiments in a report published in The British Journal of Experimental Pathology in 1929.

Nine years later, a trio of scientists at Oxford University -- Howard Florey, Ernst Chain and Norman Heatley -- focused their attention on the discovery of antibacterial chemicals. With war clouds building over Europe, they realized the need to develop medications to treat wound infections. Scouring earlier literature, Chain found the report by Fleming. A sample of bread mold was obtained from an adjacent lab and an amazing race to develop a miracle drug was underway.

The group appropriated every vessel they could locate for growing mold in a variety of broths. Pie pans, large milk cans and metal containers of every description were used for culturing the mold. Young women, "penicillin girls," were hired to tend to the smelly mixtures. While Florey and Chain worked on the chemistry of penicillin, Heatley steadily improved methods for growth, purification and eventual mass production of the agent.

In mid-1940, enough penicillin had been created to carry out an experiment with mice; it showed that penicillin protected the animals from streptococcal infection and the treated mice suffered no apparent ill effects from penicillin. In January 1941, the first dose of penicillin was administered to a woman who was dying of cancer. She gave her consent to the experiment. No ill effects were observed. In February, enough penicillin had been manufactured to treat for several days an Oxford policeman suffering from a severe streptococcal and staphylococcal infection of head and neck. His response was dramatic. Each day his urine was collected so that excreted penicillin could be isolated and readministered the following day. Eventually, there was no more penicillin. The infection recurred and the patient died.

Production problems and the strains of war made further work on penicillin in England impractical. Florey and Heatley traveled to America, where they convinced American pharmaceutical companies to take on the challenge. While in the U.S., they discovered a more effective species of Penicillium growing on cantaloupe.

Florey felt strongly that discoveries such as penicillin belonged appropriately to mankind and that individuals should not profit from them. Consequently, the Oxford team derived no financial reward for their work. American companies profited greatly from patents related to their work with penicillin.

The first doses of penicillin reached North Africa in late 1942 for use in wounded soldiers. By war's end, countless doses had been administered, substantially reducing deaths from infection among Allied warriors. The subsequent impact of penicillin and its derivatives in the treatment of a wide variety of bacterial infections has been enormous.

Fleming and Florey were knighted in 1944. Fleming, Florey and Chain received the Nobel Prize for Medicine and Physiology in 1945, despite a vigorous press campaign to limit the award to Fleming. The invaluable work of Heatley was belatedly acknowledged with the conferring in 1990 of an honorary doctorate of medicine by Oxford University.

And all because Fleming asked "What does this mean?" in 1928.

Contact Clif Cleaveland at cleaveland1000@comcast.net.

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