In many ways, Chain was the major driving force of the penicillin “story”. In 1971, he spoke at a symposium on the history of penicillin and related antibiotics. The title of his talk was “Thirty years of penicillin therapy.” The published account (see references below) is of great interest and gives many insights into how this outstanding research developed. Following are several quotations in Chain’s own words.
“In 1935, a few months after his appointment to the Chair of Pathology at Oxford, I was invited by Professor H. W. Florey, as he then was, to join his staff at the Sir William Dunn School of Pathology. Though Florey had no specific biochemical training, he was very conscious of the importance of biochemistry for progress in all the biological sciences, and particularly his own subject, experimental pathology, and he felt that a Department such as the one he intended to build up, could not be fully successful without some internal biochemical support….
I was then a refugee from Hitler’s Germany. I had left my native town, Berlin, on that fateful day, 30 January 1933, when Hitler acceded to power and Europe was temporarily plunged into a darkness in comparison with which the darkest Middle Ages now appear as a blaze of light. After a short interlude in London at University College, I had the great good fortune to be accepted by Hopkins in his Department as a research worker, largely through the good offices of the late Professor J. B. S. Haldane, and spent there two very happy years. One of my main scientific interests at that time was the study of the biochemical mode of action of neurotoxic snake venoms….
When Hopkins asked me whether I would like to go to Oxford to join Florey’s staff, I was at the same time both extremely surprised and delighted, for I never expected such exceptionally good fortune to come my way in my unsettled condition with a very uncertain future in front of me. He introduced me to Florey in his office immediately after our talk and I naturally accepted the offer without any hesitation….
I collected about 200 references on growth inhibitions caused by the action of bacteria, streptomycetes, fungi and yeasts on one another. It was
evident that in many cases the growth inhibition was caused by specific metabolites produced by the various micro-organisms. However, next to nothing was known about the chemical or biological nature of the inhibitory substances, and it seemed an interesting and rewarding field of exploration….
When I saw Fleming’s paper for the first time I thought Fleming had discovered a sort of mould lysozyme, which in contrast to mould lysozyme, acted on a wide range of gram positive pathogenic bacteria….
“In 1943, we proposed the thiazolidine-ββ-lactam structure of penicillin
which is now universally accepted. It was one of the last structural
investigations which was carried out mainly with chemical methods though we received considerable help from X-ray crystallographic analysis carried out by Dorothy Hodgkin. She succeeded in 1945 in obtaining the complete structure of the penicillin molecule by X-ray analysis and in proving
unequivocally the presence of the four membered β-lactam ring which was doubted by many organic chemists. It took Dorothy Hodgkin about two years to calculate the structure of the penicillin molecule, using mechanical
calculators then at her disposal; today, with the modern computers, the job would be completed in two weeks, or maximally a month.”
In 1948, Chain left Oxford to organize the International Centre for
Chemical Microbiology at the Istituto Superiore di Sanita in Rome. There, he and his colleagues pursued research in a number of fields. A new strong
interest was development of industrial-scale fermentation pilot plants as
research tools. This continued when Chain moved back to England in 1964 to become head of the Department of Biochemistry at the Imperial College of
Science and Technology (London); Chain’s activities in Rome and Imperial College are reviewed in a 1991 article in Nature (see ref. to B. Chain). The keynote caption of the latter is “The discovery of penicillin remains one of the greatest advances in medical science. From the success of the discovery the biotechnology industry became established.”
From B. Chain, 1991: “Influenced by his experiences during the first frustrating attempts at scaling-up penicillin production in the Oxford laboratories using antiquated and inappropriate technologies, Chain was convinced that progress in isolation and characterization of biologically active substances (not only antibiotics, but vitamins, hormones, growth factors and other biological molecules active at very low concentrations) absolutely required large scale production of biological material …. Chain’s own career also predisposed him to an interdisciplinary approach to scientific problems. He trained as an organic chemist, turned later to biochemistry, and ultimately became interested in bioengineering …. Both in Rome and later in London, Chain’s ambitions to work on a scale unprecedented within an academic biochemistry department were fulfilled.”
References:
Gest, 2003
MacFarlane, G. Howard Florey/The Making of a Great Scientist. The Scientific Book Club (London), 1979.
Chain, E. Thirty years of penicillin therapy. Proc. Roy. Soc. Lond. B179: 293-319, 1971.