Sunday, January 10, 2021

Purifying penicillin

‘Down to the lab where I saw the Professor [Florey]. He asked me if I would like to help him design apparatus. Naturally I jumped at the opportunity, and he said that he could probably get me a Nuffield grant at £300 p.a. for six months.’ This is from the diary of the British biochemist Norman Heatley on the very day he joined the Oxford University team of scientists who would soon develop a technique for purifying penicillin in large volumes. Heatley, born 110 years ago today, was not among the Nobel prize winners in 1945 for the discovery and development of penicillin, but his diaries testify to the crucial part he played.

Heatley was born in Woodbridge, Suffolk, where, as a boy, he developed a passion for sailing on the local river. At Tonbridge School, he was inspired towards an interest in chemistry, and then biochemistry. After graduating in natural sciences at St John’s College, Cambridge, in 1933 he went on to attain his PhD in 1936. That same year he moved to the University of Oxford, where he became a fellow of Lincoln College and joined a team of scientists tackling the problem of how to manufacture penicillin in usable quantities. The team was led by the Australian pathologist Howard Florey and included Ernst Chain. Heatley, although the junior member, had a gift for ingenuity and invention, and it was he that suggested transferring the active ingredient of penicillin back into water by changing its acidity, thus purifying the penicillin.

In early 1941, the team treated their first patient, a policeman at the Radcliffe Infirmary. His condition improved, but, for lack of enough penicillin, he eventually died. The new drug was then successfully given to children as they required smaller amounts. After failing to get backing from any British pharmaceutical companies, Florey and Heatley flew to the US where a laboratory in Peoria, Illinois, had agreed to work on production of much large volumes of penicillin. Florey soon returned to Oxford but Heatley stayed on as an advisor for another year. Before the end of the war, soldiers were being treated by the new antibiotic, reducing significantly the number of deaths and amputations resulting from infected wounds. 

Heatley returned to Oxford where, in 1944, he married Mercy Bing. They had three sons and two daughters (though one son died in a road crash). He was elected to a newly endowed research fellowship at Lincoln College where he remained for many years. In 1945, Alexander Fleming, Chain and Florey were all awarded the Nobel Prize in Physiology or Medicine ’for the discovery of penicillin and its curative effect in various infectious diseases.’ Heatley’s contribution was not fully recognised for another 45 years, until 1990 when Oxford University awarded him the rare distinction of an honorary Doctorate of Medicine. He died in 2004. Further information is available from Wikipedia, the BBC or obituaries in The Guardian, or The Lancet

Heatley’s role in the penicillin story has been described in some detail in two modern books partly thanks to a diary he kept at the time. In 2004, Henry Holt published The Mold in Dr. Florey’s Coat: the story of the penicillin miracle by Eric Lax. Lax says, for example, that ‘Heatley’s diary for October 1939 details his many ideas for and success in assaying penicillin, which was not yet a catchword and whose spelling varied. “Quite encouraging results from the penecillin [sic] testing technique”.’ See also a review of the book in Nature. And in 2012 Viviane Quirke’s Collaboration in the Pharmaceutical Industry - Changing Relationships in Britain and France, 1935–1965 was published by Routledge. A few extracts from Heatley’s diary can be found in both books. 

30 September 1939
‘Down to the lab where I saw the Professor. He asked me if I would like to help him design apparatus. Naturally I jumped at the opportunity, and he said that he could probably get me a Nuffield grant at £300 p.a. for six months.’

31 December 1939
‘What a year! .  . . The latter part of the year I have left research entirely, and have been concentrating on the production of P on a large scale. Now, with the help of George Glister, Ruth Callow, and Claire Inayat we are beginning to grow P nearly one thousand times the scale on which I was growing it a year ago.’

15 June 1940
‘I went to register for National Service after lunch, then worked in the lab until 7 o’clock. Collected a pass from the military authorities in the Old Clarendon, for our lab is to be guarded by the Army after 7.0 pm.’

27 June 1940
‘George and I collected about 40 litres of P solution, and filtered it. In the afternoon tried the dustbin still I had designed, and it worked perfectly, although the cooling condenser was not quite efficient enough.’

7 July 1940
‘Spent the evening making masks of silk, for handling cultures in a sterile way.’

8 July 1940
‘Tried out the first complete apparatus for extraction of P, but it did not seem to work well at all. Began to scheme out of a new idea for suspending wicks or thread in ether, and running aqueous solution down them.’

9 July 1940
‘Spent all day making a new P extractor, on the wick principle. Seemed to work fairly well, but the wicks soon became clogged with mess from the P.’

17 July 1940
‘The whole of one batch of 30 tins was infected, so we discarded it. Set up a new batch of tins. Began to make a new P extracting device. The Professor showed me how to inject mice - he will be away tomorrow and wants me to do it for him then.’

25 July 1940
‘Spent all day playing with the P-extracting apparatus. Gained several useful experiences, and I think it will work quite well eventually.’

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