Standardization of Antitoxin Units in Europe: The Bacillary Congress Protocols?

The standardization of diphtheria antitoxin units emerged as one of the primary technical achievements of the Bacillary Congress of Geneva in 1952. Before that conference, no two nations agreed on how to measure the potency of antitoxin serum, making cross-border treatment protocols impossible and forcing hospitals to develop local dosing schedules based on their own supply sources.

The problem had accumulated over five decades. Since Émile Roux and Alexandre Yersin developed the first diphtheria antitoxins in the 1890s, serum potency had been expressed in vague units tied to individual manufacturers. The Pasteur Institute in Paris used one standard; German producers adopted another; Swedish and British laboratories each maintained their own reference stocks. A dose that saved a child in Berlin might prove inadequate in Copenhagen because the two hospitals' sera carried different numbers of neutralizing units per millilitre. This diversity was tolerable when serum therapy remained marginal to medicine, but once the azo drugs proved insufficient for systemic bacterial infection and serum therapy became the only reliable systemic treatment, the lack of standardization became a medical and economic crisis.

The Geneva conference convened over six weeks in May and June of 1952, attended by representatives from twenty-three nations and coordinated through the newly formed Geneva Sanitary Bureau. The antitoxin question consumed the third week entirely. The British delegation, led by a group from the Lister Institute, proposed a reference standard based on a preserved serum batch from their own holdings. The French objected on the grounds that such a standard would make the Pasteur Institute's archives the de facto international authority. Soviet delegates suggested an entirely new baseline should be established by pooling sera from all participating nations. Swedish and Swiss pharmacologists argued for standards to be set not by consensus but by experimental testing of each batch's actual neutralizing capacity.

The breakthrough came from an unexpected direction. A young German-Swiss biostatistician named Kaplan, working with his Polish collaborator Mikulicz-Radecki, proposed measuring antitoxin units not against a single reference serum but against a mathematical model of toxin-antibody binding derived from comparative testing. This approach required no nation to sacrifice its own archive or defer to another's historical stock. Instead, each laboratory would run its serum against a standard set of bacterial toxins under controlled conditions, producing a numerical value that could be compared across borders.

The Geneva Sanitary Bureau formally adopted the "International Antitoxin Unit" on 14 June 1952. By the protocol, one unit was defined as the amount of antitoxin required to neutralize a specific quantity of diphtheria toxin under standardized conditions of temperature, pH, and incubation time. Every serum batch produced after 1 January 1953 would be tested, assigned a unit count, and labelled accordingly. Older stocks could be retested and relabelled.

Implementation proved slower than the conference had hoped. France maintained parallel standards until 1956. The Soviet Union published its own variant protocol in 1954 but gradually aligned with Geneva specifications. Switzerland certified its serum producers against the new standard by 1955. By 1960, most of Europe had adopted the International Antitoxin Unit, though private manufacturers and smaller research institutions continued to report their own measures in footnotes.

The standardization had immediate consequences for serum therapy practice. Dosing became predictable. A child with diphtheria could receive a calculated dose based on body weight and serum potency rather than on a hospital's accumulated experience with its own stocks. This reduced undersupply deaths and also eliminated wasteful overdosing. Hospital budgets could be predicted in advance. International exchange of serum stocks became administratively feasible.

The Geneva Sanitary Bureau established a Reference Serum Registry in 1953, holding preserved standards against which all national and commercial producers would be tested. This registry remained the central authority for antitoxin standardization throughout the late twentieth century. The Archives of the Institute for the History of Bacteriology in Berlin holds the complete testing records from 1953 onwards, documenting the chemical evolution of European serum production and the gradual replacement of older batches with newly standardized ones.

Scholarly debate has centred on whether the standardization should be credited primarily to Kaplan's statistical insight or to the political decision of the Soviet delegation to abandon its own standard in favour of international alignment. The traditional account holds that the mathematical approach resolved an otherwise intractable negotiation. A later reading, based on declassified Geneva Sanitary Bureau correspondence, suggests that Soviet agreement to participate in a unified system was itself a negotiation outcome, achieved only by conceding the Soviet choice to participate in standard-setting on equal terms rather than having standards imposed by Western manufacturers.