JMS Pearce
Hull, England

Hartnup disease, Christmas disease, and Lou Gehrig’s disease are instances of the rare naming of diseases after the patients so afflicted. There are other medical discoveries, disorders, or treatments in which the crucial part played by the patient is unattributed. One example relates to the early days of penicillin.

The story of Alexander Fleming’s accidental discovery in 1928 of the inhibition of bacterial (Staphylococcus aureus) growth by the penicillium notatum mold needs no repetition.^1,2 It took ten years until Howard Florey, Ernst Chain, and Norman Heatley in Oxford began the laborious extraction of penicillin from a mold and its purification as a therapeutic agent. In 1940, they showed that four mice infected with streptococci died, but four other mice, identically infected but given penicillin, survived unharmed.³

Next, they needed to show it might be effective and safe in humans, and here a tragic but unsung war hero emerged.

Albert Alexander (1897–1941)

Albert Alexander, a policeman of the Berkshire Constabulary, had been called to assist the Southampton police in German air raid attacks. At 5:50 pm on 30 November 1940, a devastating Blitz hit the police station, killing a sergeant and injuring two constables, one of whom was Albert Alexander. Treated in Abingdon Cottage Hospital he developed pyemic abscesses on his face, humerus, lungs, and orbit—for which one eye was removed. (The much-publicized story of a scratch from a rose thorn proved false.)

He was transferred to Oxford where Charles Fletcher, a Nuffield research student working with Professor Howard Florey, on 12 February 1941, injected Albert Alexander with the tiny 200 mg dose (10,000 units) of available penicillin. He improved dramatically. But sadly, by the fifth day they had no more penicillin despite adding small amounts extracted from his urine. The unfortunate Albert died on 15 March 1941.⁴ Fletcher recalled, “He was in great pain and was desperately and pathetically ill. There was all to gain for him in a trial of penicillin and nothing to lose… after five days the patient was vastly better, afebrile, and eating well, and there was obvious resolution of the abscesses… importantly, there had been no sort of toxic effect during the five days of continuous administration of penicillin.”^5,6 One year later, in March 1942, penicillin was used in Connecticut to treat Anne Miller, who was dying of streptococcal septicemia. She recovered⁷—the first patient cured with penicillin.

The importance of Albert Alexander’s and Anne Miller’s cases cannot be overestimated. They showed for the first time that the drug could be effective in humans. It also emphasized the necessity for production of penicillin in quantities sufficient to treat human infections on a large scale, since gallons of mold broth were needed to produce minute quantities of penicillin. Prompted by thousands of infected war-injured patients, in 1941 Florey with Heatley traveled to the US to secure support from the Rockefeller Institute, the US Department of Agriculture in Peoria, Illinois, and major pharmaceutical firms. Eventually they produced 2.3 million doses of penicillin in preparation for the D-Day invasion of Normandy. Penicillin became available to British civilians as a prescription drug in June 1946.

Using x-ray crystallography, Dorothy Crowfoot Hodgkin FRS (1910–1994), on Victory in Europe Day, 8 May 1945, demonstrated the molecular structure of penicillin and its four-membered β-lactam ring, essential for antibacterial activity. Her vital discovery paved the way for creating semi-synthetic derivatives of penicillin such as the cephalosporins, which heralded the development of other antibiotics. Belatedly, she was awarded the Nobel Prize in Chemistry in 1964.⁸ The Nobel Prize in Physiology or Medicine 1945 was awarded jointly to Sir Alexander Fleming, Ernst Boris Chain, and Sir Howard Walter Florey (but not to Heatley) “for the discovery of penicillin and its curative effect in various infectious diseases.”⁹

The vital role of Albert Alexander was soon forgotten until eighty years later when the Newbury Council in 2021 erected a memorial plaque. (Fig 2)

References

1. Fleming A. On the antibacterial action of cultures of a Penicillium with special reference to their use in the isolation of B. influenza. Br J Exp Pathol. 1929;10:226-36.
2. Alexander Fleming. Penicillin Nobel Lecture, December 11, 1945. https://www.nobelprize.org/uploads/2018/06/fleming-lecture.pdf
3. Chain E, Florey HW, Gardner NG, Heatley NG, Jennings MA, Orr-Ewing J, et al. Penicillin as a chemotherapeutic agent. Lancet. 1940;236:226-8.
4. Abraham EP, Gardner AD, Chain E, Fletcher CM, Gardner AD, Heatley NG, et al. Further observations on penicillin. Lancet. 1941;238:177-88.
5. Fletcher C. First clinical use of penicillin. British Medical Journal 1984;289:1721-3.
6. Professor Charles Fletcher CBE FRCP in interview with Max Blythe Oxford, June 1984. https://radar.brookes.ac.uk/radar/file/01524f66-5f7a-40c1-a0bc-2cf8f24ae19f/1/Fletcher%2CC_1.pdf
7. Fulton, penicillin and chance. Yale Medicine Magazine, 1999 – Fall / 2000 – Winter.
8. Pearce JMS. Dorothy Crowfoot Hodgkin OM, FRS (1910-1994). Hektoen Int Fall 2020.
9. Howard W. Florey. Penicillin. Nobel Lecture, December 11, 1945. https://www.nobelprize.org/uploads/2018/06/florey-lecture.pdf