Behring EA, Boer NN, Kossel H (1893)
Zur Behandlung diphtheriekranker Menschen mit Diphtherieheilserum [On the treatment of diphtheria patients with curative diphtheria serum]. Deutsche Medicinische Wochenschrift 17:389-39.
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Key passage(s)

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Translation

The innocuousness of a treatment…is one of the preconditions for justifying a recommendation that it be introduced for therapy in humans. The second, even more important precondition, is evidence of the value foreseen by using it. This is the point that I want to raise here in discussing in detail my remedy for diphtheria…

When examining a curative serum, it has emerged that we can proceed in a much more precise and rational way than has hitherto been used by pharmacologists and clinicians evaluating drugs. When, for example, Resorcin, Kairin, Thallin, Antipyrin, Antifebrin and the myriad other chemicals were introduced in the treatment of diseases of man, one proceeded as follows.

The chemists prepared the drug artificially; the physiological chemists elicited particular effects on temperature regulation and neural function, etc, or a physician working with bacteriological methods found bacteriostatic activity in the drug; then clinicians tried it out in many diseases and patients; on the basis of their recommendations, industry became interested, and the new drug became sought after as a commercial commodity: from then on thousands of doctors found opportunities to make their own observations, and according to these, our treasure trove of medicaments has either been enriched – after the commission of the pharmacopeia had passed judgement that a worthwhile medicament had been discovered – or, more frequently, after a short and glamorous life, the new preparations fell into inglorious oblivion…

This formerly-used approach carries too many dangers. In particular, the enthusiasm, I will not suggest – the disingenuousness of many observers, is a constant factor. A doctor or any other person occupied with the business of medicine applies a new or hitherto untried drug, which came into his hands by accident, in only one or a few cases of an…

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Translation

…infectious disease; he sees a rapid cure in these cases and believes that this is a consequence of the said drug. He does not assess in a further thousand cases whether this more rapid cure is really attributable to the drug rather than, for example, to the less severe individual infections in the observed cases, and so this new specific drug is complete and is often being recommended with great enthusiasm. How many drugs have been recommended in the past three years alone against diphtheria! The upshot of all these endorsements has simply been and is, in essence, that doctors have now become unnerved about all newly recommended drugs and have lost all confidence.

We have no need to acquiesce any longer in the desolation expressed in these words written by an eminent representative of pharmacology and internal medicine [Rossbach] since Robert Koch banned direct drug testing in man as a method for finding new specific drugs in the Institute for Infectious Diseases.

We have here adopted a different path from that which I have described above, and which has yielded so few satisfactory results. We make our medicaments ourselves, we test them ourselves, firstly, not in man, but in animals; we determine ourselves the conditions in which they are innocuous, and the limits within which this is the case; we try out their influence on the course of the human diseases produced in animals, using Roberts Koch’s methods, and when we have determined a specifically curative effect, we take pains to perfect these specific drugs until their application in man also promises a totally specific effect; only now will we ourselves assess the innocuousness of these specific drugs in the clinical department of the Institute for Infectious Diseases. Observations in patients are not needed to establish the specificity of these drugs; it is needed only to confirm it. Next decisions are required about whether the new drug is already effective enough to elicit unambiguous curative effects in patients, and, when this has been established, we have finally to answer questions of dosage and the most appropriate route of administration. Only when we have accomplished all this do we dare to give our remedy to those doctors who are not yet trained in this kind of drug evaluation for them to test on their own patients…

So far in the past months 30 cases have been treated with my normal serum (or with the equivalent dog curative diphtheria serum of Medical Officer Wernicke): 14 in Berlin, 3 of whom were in Counsellor Henoch’s children’s department; in all of them the diagnosis ‘diphtheria’ has been reliably established, in particular, in our Institute, every case in which diphtheria bacilli could not be detected bacteriologically were excluded. Out of these 30 cases, 6 died and 24 have been cured; this is a mortality rate of 20%.

These numbers are still much too small to allow a conclusive judgement about serum therapy: but they are nevertheless encouraging and prompt continuation of serum treatment on an extended scale. Only when we have statistics on hundreds and thousands of diphtheria patients treated with serum will it be the time to deduce final conclusions about the effectiveness of the curative diphtheria serum against this so murderous disease, particularly in childhood.