PRONTOSIL AND ITS SUCCESSORS
By OUR MEDICAL CORRESPONDENT
THE medical profession as a whole, both at home and abroad, has always, and rightly, been cautious in accepting any new advance either in technique or therapy as one of major importance. In medicine, as in most other fields of human experiment and endeavour, fashions have come and gone, hopes have been raised and dashed ; and more and more increasingly, in the last generation or two, insistence has been laid on the testing of every new claim by independent observers under the strictest conditions of control. This has no doubt led, from time to time, to undue delay and prejudice in recognising the validity and full significance of some genuine pioneer work ; and the battles that had to be fought by the sponsors of anaesthesia and antiseptics may well appear to later generations hard to understand. But it is probably, on balance, and considering the issues at stake, all to the good that the path of proof and conversion should not be too easy.
There seems little doubt, however, that the discovery of the sulphonamide group of drugs does mark a very real and proved advance in the treatment of certain dangerous and often fatal bacterial diseases ; and that it has also opened up a new and most promising avenue of research. As in the case of so many previous discoveries, including those of Lister and Pasteur, it has a curiously indirect history. The chemical forerunners of the group were originally studied in connexion not with medicine at all but with the dyeing of textiles ; and it was found by some German chemists that certain dyes containing sulphonamide groups had an especial fastness. Later it was found that some of these dyes were destructive to bacteria though not apparently in the living subject.
It remained for Professor Gerhard Domagk, who has just been awarded the Cameron Prize of Edinburgh University, to demonstrate, in conjunction with his fellow-workers Mictzch and Klarer of the I.G. Farbenindustrie (Bayer) at Elberfeld, the practical effectiveness in medicine of an azo- dye containing a sulphonamide group, to which the name Prontosil was given. It was not, however, until he and other German observers had done a further three years' intensive work on the action of the drug and its results that he pub- lished any conclusions. And by then an impressive series of laboratory and clinical observations had gone far enough to establish Prontosil as an altogether exceptionally powerful agent in respect of various diseases due to the streptococcal group of bacteria.
That was in 193s, and it was principally as the result of the adoption of Prontosil and its subsequent successors and modifications by Dr. Colebrook and his colleagues at Queen Charlotte's Hospital that the new discovery first became appreciated in this country. Here it was found that its effect in reducing the mortality from puerperal fever after childbirth was little short of dramatic. The case-mortality rate which, prior to 1935, had been 25 per cent., dropped abruptly to below 5 per cent.
Later it was discovered that Prontosil, which was not without certain dangers, owed its chief effectiveness to a somewhat simpler basic constituent, now known as sulpha- nilamide ; and this has since been extensively used, in one form and another, all over the world. As it was at first in connexion with the streptococcal infections that the sulpho- namide drugs had come into prominence, it was chiefly in the combating of such diseases as puerperal fever, septic- aemia, or blood-poisoning, erysipelas and streptococcal meningitis that it was used ; and it was also adopted not only for curative purposes in many cases of middle-ear inflammation, but as a preventive against the not uncommon sequel to this of acute mastoiditis. The results reported were almost unanimously striking ; and it was quickly clear that, in these particular fields, a new and major form of treatment had definitely arrived.
Meanwhile, however, clinical trials were being made of sulphanilamide and allied preparations in cases of other forms of bacterial infection, such as that due to the gonococcus, in which, in an early series of 47 cases reported from America, 36 were cured in less than five days. Equally impressive figures were also being recorded in Germany with the use of a modification of the same drug, known as Uleron ; and promising results were at the same time being obtained in another group of cases of meningitis.
Perhaps the most striking of these successors of the original Prontosil has been the substance now known as M and B 693, which has been mainly associated with the name of Dr. Lionel Whitby in this country, working in relation with the English chemical firm of May and Baker. This particular sulphonamide product is not only extremely effective in the case of certain most dangerous streptococcal infections, but has an especially destructive action against several types of the organism responsible for pneumonia in some of its acutest and most fatal forms. It has already proved itself, in considerable series of such cases, a definitely life-saving remedy of the most positive order.
As regards the exact process by which this new group of drugs exert their influence, our knowledge is not yet com- plete. That an actual destruction of the capsules of the organisms takes place appears to have been demonstrated in the case of pneumococci in the presence of M and B 693. Researches up to date, however, would seem to show that this is rather an indirect than a direct result of the drug's action, and that what probably takes place is some chemical change either in the environment of the hostile organisms or their own metabolism, depriving them of some necessary nutritional or reproductive factor. The drugs, as a group. seem to act quite independently of the body's own immunity reactions and to have no effect upon these ; although, in some cases, the stimulation of the body's own anti-bodie, by an appropriate vaccine may be a most valuable re- inforcement to the bactericidal action of the drugs.
Finally, it may be repeated that the triumphs alread achieved by these drugs—yet another instance of inter- national laboratory and clinical teamwork—have opened ul avenues of possible extension that are already being vigor- ously explored both by bio-chemists and .clinicians in almost every civilised country.
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