Pierre Louis’ 1835, Recherches sur les effets de la saignée dans quelques maladies inflammatoires, et sur l’action de l’émétique et des vésicatoires dans la pneumonie is one of the less impressive looking books in the John Martin Rare Book Room, but it was instrumental in laying the foundation for what we now term, “evidence based medicine.” For over 2000 years the practice of bloodletting (phlebotomy) was a mainstay of therapeutics. In fact it is difficult to identify a disease for which this practice was not recommended at some time. Bleeding had its roots in the classical Hippocratic/Galenic medical paradigm which held that the cause of illness was the result of an imbalance of humors (blood, phlegm, bile, and black bile). Just as important as the volume of blood removed was the site of the bleeding; some of the earliest medical illustrations depict the most appropriate bleeding points for various ailments. When Pierre Louis (1787-1872) placed the practice under statistical scrutiny, using “la methode numerique” he was thus swimming against the tide of centuries of tradition and authority. In Recherches sur les effets de la saignée…, Louis measured the effectiveness of bloodletting in pneumonia in 77 previously healthy patients and came to the general conclusion that bloodletting had no benefit and was even deleterious in certain groups. Just as importantly, Louis lays down in a few simple sentences the rationale large scale evaluation and in so doing paves the way for the modern clinical trial:

“Let us further remark that the objection made to the numerical method, to wit, the difficulty or impossibility of forming classes of similar facts, is alike applicable to all the methods that might be substituted. It is impossible to appreciate each case with mathematical exactness, and it is precisely on this account that enumeration becomes necessary. By so doing, the errors (which are inevitable) being the same in the two groups of patients subjected to different treatments, mutually compensate each other, and they may be disregarded without materially affecting the exactness of the results”

Louis’ methods and conclusions were lambasted by the medical establishment and it was several decades before bloodletting stopped for good and statistical analysis found its way into mainstream medical thinking.