Darwin in Italia

patients. The demonstration led to the realization that an exotoxin was produced in the experimental animal but it took many experiments and much subsequent work to define the conditions whereby such an exotoxin could be isolated and purified under laboratory conditions. The work was slow because there were many who did not believe that such an exotoxin could possibly exist. Simultaneously, particularly under the leadership of William Phillips, a former naval officer, a team began investigations of the physiological consequences of the disease and demonstrated the chemical content of the fluid that was being passed in such huge volumes. That it was essentially a filtrate of plasma, with added bicarbonate, became evident. Research stations began to pour back balanced fluids. Earlier attempts to return electrolyte and fluid to the blood were considered failures. This was because when the patients became somewhat rehydrated, the diarrhoea returned. Soon, however, it was realized that this was to be expected. However, biochemical studies had led some to use hypertonic fluids and others hypotonic fluids with sometimes disastrous results. Finally, came the realization that a balanced mixture of salts could be returned to the body of the affected victim, in volumes equal to those that were being lost and that, almost miraculously, the mortality rate was then reduced to negligible proportions. Not much later, in consequence of the availability of the exotoxin and the intestinal loop of the experimental animal, it could be demonstrated that in the presence of glucose, the electrolytes and the fluids would re-enter the body from the intestinal tract and oral rehydration was instituted. It was not all that simple. Each of the steps was opposed by many, for what seemed to be adequate scientific reasons at the time. Perhaps the most important scientific failing was the absence of carefully controlled clinical trials of the type that would now be considered virtually a necessity before any treatment could be evaluated. This was a time, not yet completely gone, when the laboratory observation reigned supreme and the techniques of large-scale clinical observation through controlled trials had not received widespread acceptance, particularly among those who fancied themselves as "hard" scientists. These are chapters from which all may learn, the most important lesson being that the closed intellect, no matter how skilled and highly trained, will make errors in judgement if the guiding principle is not empirical results of carefully conducted experiments. This is …