Science
Yellow peril
Bernard Dixon
As well as illustrating our fecklessness in handling human faeces, the Italian cholera epidemic has focused attention on an intriguing, but unfinished, chapter in medical science. Why, in short, are cholera vaccines so inadequate? Immunisation against Cholera lasts well under a year, and is only 50-75 per cent effective anyway. Why should this be so, When the science of immunology and the technology of vaccine Manufacture have achieved so much more in combating other serious infectious diseases?
Our remarkably slow progress In dealing with cholera is emphasised by a report just Published in the Journal of Medical Microbiology (vol 6, p 363) by Dr J. Holmgren from the University of Goteborg. Though the work described in this paper begins to suggest the feasibility of Cholera vaccines that bestow solid,
long-lasting protection, Dr Holmgren's researeh is actually very similar to comparable work On such diseases as diphtheria and tetanus, completed over half a century ago.
It was in 1884, in fact, that Friedrich Loeffler deduced that diphtheria bacilli produced their ghastly effects on the body by forming a poison that spread via the bloodstream. Four years later this 'toxin' was isolated. Shortly afterwards other bacteriologists Showed that tetanus bacteria too caused severe damage to organs distant from the wound where the bacteria were growing, by Producing a circulating toxin. Then, in 1891, Emil.von Behring and Shibasaburo Kitasato laid the foundations for immunisation against both diseases, by proving t,hat the toxins stimulated the inrMation of antibodies. These antibodies neutralised the corres iding toxins, and thus prevented the grievous bodily effects they 11.°rynally caused. Prepare such a `oxin in a non-offensive form, and you have a specific, highly effective vaccine. The microbe that causes cholera as identified in 1883 by Robert och, who also suggested that it Produced a specific poison which acted upon the epithelium" of the Intestine. (Cholera victims lose so much fluid, in the form of 'rice water' stools, that they can often be observed to shrink visibly.) Yet in contrast to the few years after that date which it took to identify diphtheria and tetanus toxins, three-quarters of a century elapsed before bacteriologists discovered the cholera toxin. Reason for the delay? Largely, it seems, the absurd ease with which the job was accomplished in the case of diphtheria and tetanus. It was enough to grow these bacteria in liquid cultures, filter off the cells, and inject an animal with a small amount of the remaining liquid, to produce a rapid and obvious lethal effect. The toxin was the disease.
Even using massive quantities of culture fluid, this didn't work with cholera. So bacteriologists abandoned Koch's suggestion, and assumed that bits of the actual bacterial cell must be responsible for the appalling effects of cholera on the human gut. This was a mistaken idea, but it determined the pattern of research for decades. Not until 1971 was a toxin, similar to that of diptheria, positively isolated from cultures of cholera bacilli. The technical problems in identifying it had been enormously more difficult than once seemed likely.
Now, as Dr Holmgren reports in his paper, substantial progress is being made in using this toxin as the basis for a vaccine. When available, such a vaccine should be very much more effective than those now available (which are based on whole bacterial cells).
A scientific breakthrough of this sort is not, however, required to prevent cholera outbreaks like the recent Italian epidemic. That is an altogether simpler matter. We have known since the fast century that intestinal diseases such as cholera and typhoid fever flourish under insanitary condi
tions, and that proper water supplies and sewage disposal will largely thwart their spread. In this case we are certainly not awaiting new knowledge; we fail, ludicrously, to apply that which already exists.
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