La naissance des biotechnologies pharmaceutiques en France (1887-1914) (2013)

The successful results of the treatment of diphtheria by serum taken from
horses immunized against the diphtheria toxin, were disclosed by Emile Roux at
the International Congress of Hygiene held in Budapest on September 5, 1894.
The Behring’s-Roux’ method (it would be unfair to attribute serotherapy to the
French, since the German contribution has been decisive) resulted in a 2 to 3
fold decrease of the lethality among the sick children included in the clinical
trials. Actually the series of tests of anti-diphtheria sera certainly constitutes the
first 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 most
countries in Europe and out of Europe. Diphtheria serotherapy had become “the
herald of modern medicine”, i. e. a medical approach to a disease exclusively
based on the development of the scientific programme of microbiology.
Serotherapy introduced decisive changes in the manner infectious diseases
were considered. Everyone now expected that they will, sooner or later, be
defeated by the same or similar scientific strategies. It did not matter much that
sera against other microbes did not keep their promises: the belief in the
efficiency of sera did not fade out in the public.
The production of anti-diphtheria sera could be taken as the birth of
pharmaceutical biotechnologies, more than the production of anti-anthrax vaccines and of vaccine itself. It anyway imposed the fast passage from
laboratory to industry. The entirely novel drug introduced to a series of problems
which had not previously been imagined. In Germany, the production of antidiphtheria
serum was, from its very beginning, the result of a close collaboration
between laboratories, industry and the relevant Imperial Health Services, thus
joining already existing administrative and technical structures. In France,
pharmaceutical industry merely did not exist and had to be built up. The Institut
Pasteur was cleaver enough to retain the monopoly of production and quality
control 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 the
new-born Institut Pasteur. The production of sera and their trade by the Institut
Pasteur forced the latter to introduce German-derived procedures and norms
concerning the standardization of sera. The Institut also had to develop the
production of sera under highly controlled conditions in continuously adapted
and improved facilities located in Marnes-la-Coquette, a small town in the
vicinity of Paris.
The production and trade of anti-diphtheria serum clearly is at the origin of
both the international reputation and of the wealth of Institut Pasteur which
guaranteed its independence with respect to French universities. Not only did it
contribute to firmly establish the institution in the French medical and scientific
landscape, but it also permitted Emile Roux to implement his long term project:
physically couple the laboratories to a production center and to a hospital where
new drugs, whatever of biological or chemical origin, would be tested on
patients. Indeed, the budgetary surplus left by the sales of anti-diphteria serum
permitted the the building of a private hospital primarily devoted to infectious
diseases, a kind of model hospital, and the creation of laboratories of chemistry
including a fast growing laboratory of therapeutic chemistry, itself largely
inspired by German chemistry. The project of Emile Roux was fulfilled a few
years before WWI and was taken as a model by several foreign countries such as
Brazil.