The history of the therapeutic use of crude penicillin.

The antibacterial properties of culture filtrates of Penicillium notatum were discovered in 1928 by Alexander Fleming,' but the realization of penicillin's full therapeutic potential had to await the contributions of Florey and Chain some twelve years later.2 Although early samples of the penicillin salts produced at Oxford were remarkably potent, they were not very pure,3 and difficulties with large-scale production meant that even these partially purified products were not initially widely available. This led a number of workers to re-examine the therapeutic properties of crude penicillin filtrates. Since their aim was to produce large amounts ofcrude filtrate for direct use on patients, complex purification procedures were purposely avoided. In this way, it was hoped that crude penicillin might be produced and used in hospitals, or even by general practitioners; as a result the crude product become known as "home-made penicillin".4 These culture filtrates were quite distinct from the partially purified penicillin salts produced by the Oxford workers and are referred to in this essay as crude penicillin. Essentially, three methods were developed for the topical application of crude penicillin. These were (1) use of liquid filtrates which were usually applied using lint or other absorbent material; (2) the use of dressings inoculated with P. notatum often in conjunction with liquid filtrates; and (3) the application ofcrude penicillin in agar, the so-called pen-agar method. In addition, crude filtrates were also occasionally administered by injection. A number of remarkable cures were achieved using crude penicillin, but fears concerning its uncontrolled production and purity eventually limited its use. At the same time, however, the partially purified product was becoming more widely available, making the use of crude filtration obsolete. As a result, the relatively large-scale production and use of crude penicillin covered only a short period from * Milton Wainwright, BSc, PhD, Lecturer in Microbiology, Department of Microbiology, University of Sheffield, Sheffield S10 2TN. l A. Fleming, 'On the antibacterial action of cultures of a Penicillium with special reference to their use in the isolation of B. influen-ae', Br. J. exper. Path., 1929, 10: 226-236. 2 E. Chain, H. W. Florey, A. D. Gardner, N. G. Heatley, M. A. Jennings, J. Orr-Ewing, and A. G. Sanders, 'Penicillin as a chemotherapeutic agent', Lancet, 1940, ii: 226-228. 3 D. Masters, Miracle drug, London, Eyre & Spottiswoode, 1946, p. 102. 4 A. J. Hobson and L. D. Galloway, 'Home-made penicilin', Lancet, 1944, i: 230-231.