La naissance des biotechnologies pharmaceutiques en France (1887-1914)

International audience; The successful results of the treatment of diphtheria by serum taken fromhorses immunized against the diphtheria toxin, were disclosed by Émile Roux atthe International Congress of Hygiene held in Budapest on September 5, 1894.The Behring’s-Roux’ method (it would be unfair to attribute serotherapy to theFrench, since the German contribution has been decisive) resulted in a 2 to 3fold decrease of the lethality among the sick children included in the clinicaltrials. Actually the series of tests of anti-diphtheria sera certainly constitutes thefirst set of random human clinical trial of a drug.The production of serum followed simple and easily reproducible procedures.In about a year, serotherapy had become the dominant treatment of diphtheria,and death toll was reduced from about 50% to 10-15 % and even less in mostcountries in Europe and out of Europe. Diphtheria serotherapy had become “theherald of modern medicine”, i. e. a medical approach to a disease exclusivelybased on the development of the scientific programme of microbiology.Serotherapy introduced decisive changes in the manner infectious diseaseswere considered. Everyone now expected that they will, sooner or later, bedefeated by the same or similar scientific strategies. It did not matter much thatsera against other microbes did not keep their promises: the belief in theefficiency of sera did not fade out in the public.The production of anti-diphtheria sera could be taken as the birth ofpharmaceutical biotechnologies, more than the production of anti-anthrax vaccines and of vaccine itself. It anyway imposed the fast passage fromlaboratory to industry. The entirely novel drug introduced to a series of problemswhich had not previously been imagined. In Germany, the production of antidiphtheriaserum was, from its very beginning, the result of a close collaborationbetween laboratories, industry and the relevant Imperial Health Services, thusjoining already existing administrative and technical structures. In France,pharmaceutical industry merely did not exist and had to be built up. The InstitutPasteur was cleaver enough to retain the monopoly of production and qualitycontrol of anti-diphtheria serum, actually of all sera to be later produced.However, well controlled norms of quality were not part of the culture of thenew-born Institut Pasteur. The production of sera and their trade by the InstitutPasteur forced the latter to introduce German-derived procedures and normsconcerning the standardization of sera. The Institut also had to develop theproduction of sera under highly controlled conditions in continuously adaptedand improved facilities located in Marnes-la-Coquette, a small town in thevicinity of Paris.The production and trade of anti-diphtheria serum clearly is at the origin ofboth the international reputation and of the wealth of Institut Pasteur whichguaranteed its independence with respect to French universities. Not only did itcontribute to firmly establish the institution in the French medical and scientificlandscape, but it also permitted Émile Roux to implement his long term project:physically couple the laboratories to a production center and to a hospital wherenew drugs, whatever of biological or chemical origin, would be tested onpatients. Indeed, the budgetary surplus left by the sales of anti-diphteria serumpermitted the the building of a private hospital primarily devoted to infectiousdiseases, a kind of model hospital, and the creation of laboratories of chemistryincluding a fast growing laboratory of therapeutic chemistry, itself largelyinspired by German chemistry. The project of Émile Roux was fulfilled a fewyears before WWI and was taken as a model by several foreign countries such asBrazil.