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.Theysuggested that the effect was due to antitoxic substances capable of neutral-izing the toxins produced by the diphtheria or the tetanus germs.3 Behringwas confident that serotherapy could be applied to a variety of infectious54 From Diphtheria to Tetanusdiseases, but according to his own account he concentrated on tetanus firstbecause Kitasato had already done a lot of work in this field.4 Moreover, teta-nus was ideal for study in the laboratory: the symptoms were easy to recog-nize, the tetanus toxin was more accessible and potent than the diphtheriatoxin, experiments on the white mice used for tetanus research were cheaperthan diphtheria experiments on guinea pigs, and finally Behring was moresuccessful in immunizing animals against tetanus than against diphtheria.5This is why between 1890 and 1893 most research was done on tetanus.Another important aspect was funding.Behring quickly recognized thatto extend his therapy to humans he needed large quantities of serum, butKoch s Institut für Infektionskrankheiten could not afford to keep large ani-mals capable of producing serum in sufficient quantities.In August 1891,Behring s assistant Erich Wernicke bought several sheep on his own accountand started keeping them at his home near Berlin.6 With these animals,Behring and Wernicke made their first attempts to immunize larger animalsagainst diphtheria, but they soon had to face the fact that their privatemeans were insufficient for the larger scale experiments they wanted toundertake.The first opportunity to work with a larger group of horses wasoffered to Behring a few months later, when the veterinary school of thePrussian state, directed by Professor Schütz, took an interest in serotherapy.The Ministry for Agriculture had given 10,000 Marks for research on teta-nus because it frequently affected domesticated animals.7 It was agreed thatBehring should provide the tetanus toxins and Schütz the horses.After along and laborious process and more than 100 bleedings, Behring succeededin obtaining serum whose immunizing power he estimated to be 1:106.8This initial work with horses represented a partial success for Behring,which he needed badly after having suffered an embarrassing setback withthe public demonstration of his anti-diphtheria serum in December 1891.Inorder to persuade a larger circle of practitioners, he had infected guinea pigswith diphtheria cultures under the eyes of Professor von Bergmann and hisstaff in the surgical department of the university hospital in Berlin.Half ofthe guinea pigs were also given anti-diphtheria serum, but in the followingdays not one animal showed any symptoms of diphtheria.Although Kochcame to Behring s aid by explaining that the cultures had probably sufferedfrom the low winter temperatures during the transport from his instituteto the hospital, the clinicians had lost confidence in serotherapy.9 It wasmore than a year later that Behring made another such attempt this timewith tetanus-infected mice which he presented in Emil du Bois-Reymond sInstitute for Physiology.10 This time, he succeeded in demonstrating thetherapeutic effect of the serum.In the same month, Behring reported onextensive experiments on the evaluation of the curative qualities of theserum he had undertaken with his co-worker Angelo Knorr.As it was verydifficult to obtain reproducible results in animal experiments,11 they choseone particular serum as a standard and attributed it the value of 1.ConsciousAnne I.Hardy 55of the fact that results from different laboratories were only comparable withreference to a fixed standard, Behring suggested that other laboratories sendhim their sera for evaluation.12 At the same time, he tried to define a stand-ard for the anti-diphtheria serum as well.13Behring was keen to establish his claims to priority in the area of sera,since he was not the only one working in the field.Paul Ehrlich, who hadjoined Koch s research team at the Institut für Infektionskrankheiten in 1891,had carried out a very significant study on the reaction of mice with respectto the vegetable poisons Abrin and Ricin.14 Ehrlich worked with these toxinsrather than those produced by bacteria because they were easier to dose withprecision, and his aim was to describe the immune reaction of the body ina more mathematical way.15 In the beginning, Behring happily acknowl-edged this work because it supported his own hypothesis of specific immunereactions, but Ehrlich soon turned into a serious competitor.Shifting hisattention to tetanus, Ehrlich had begun to study the transmission of anti-bodies to maternal milk first in mice16 and then goats.17 Because milk wasmore accessible than blood, Ehrlich could determine the antitoxin concen-tration frequently every second day or even daily.In detailed graphicalrepresentations, he demonstrated, together with Ludwig Brieger, that thenumber of antitoxins in maternal milk dropped shortly after the injection oftetanus-toxin only to increase dramatically a few days later
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