Wagner-Jauregg J (1931)

Ueber die Infektionsbehandlung der progressiven Paralyse [On infection treatment of progressive paralysis]. Münchener Medizinische Wochenschrift 78:4-7.
The Austrian physician Julius Wagner-Jauregg, a Nobel Prize Winner in 1927, had first reported using alternation to generate treatment comparison groups in 1926. In a further paper in 1931 he named this methodological principle ‘Simultanmethode’.

Key passage(s)




Wagner-Jauregg J (1931). Ueber die Infektionsbehandlung der progressiven Paralyse [On infection treatment of progressive paralysis]. Münchener Medizinische Wochenschrift 78:4-7.

“Malaria treatment is not the only non-specific treatment for progressive paralysis; other non-specific methods have been recommended soon after the onset of treatment with tuberculin and the quest to invent new methods has simply increased since the introduction of malaria therapy. Years ago, on the basis of [personal] experience, I tried to establish a step ladder of effectiveness of these non-specific methods. The least effective seemed to me to be the methods that use any substances not stemming from micro-organisms, for instance, … various proteins, milk, Phlogetan, etc. More effective seemed to me to be products derived from micro-organisms, such as tuberculin, vaccines of all sorts; the most effective [seemed to me to be] the infectious diseases themselves. So far the usable infectious diseases malaria tertiana and quartana have been joined by febris recurrens Africana and related forms and rat bite disease.

It seems to me that one has not always proceeded very critically and systematically with the introduction of other new methods. First one should demonstrate that the method is effective. This was demonstrated with tuberculin in the following way: in a sufficiently large number of unselected paralytics, one was treated alternately with tuberculin, the other was left untreated.

This approach is no longer acceptable today, for one could not take responsibility for leaving a substantial number of paralytics untreated, in order to test the effectiveness of a new procedure, the more so as a quite effective procedure, malaria treatment, already exists. Optimally, one should therefore compare the new procedure that one wishes to test, with malaria, by treating alternately from a large number of untreated paralytics alternately one with malaria and one with the new procedure. I do not consider it appropriate that a researcher treat using one procedure at one place and another [researcher] other patients at another place with another procedure, and that the results be compared afterwards with each other. Simply consider how different the perspectives of cure are according to whether the patients are in an asylum, in a psychiatric clinic, in a general hospital ward, or in a private hospital; furthermore, an important role is played by the selection of the patients to be treated. Furthermore, the results of a treatment can only be reviewed when one has monitored over years the fate of those treated.”



“Therefore I am of the opinion that one can obtain incontestable (unobjectionable) judgements about the effectiveness of two different kinds of treatment only if an researcher treats the patients selected according to the same principles, alternately according to the one and the other way of treatment, and when the successes (results) are evaluated by the same examiner according to the same principles: and furthermore if the constancy of the successes (results) are re-examined after a sufficiently long time.

Using this approach in the Vienna clinic, treatment with malaria was compared both with Saprovitan and with Pyrifer. The number of cases treated with these methods was modest; it amounted to 10 each with [malaria or] Saprovitan, and 11 each with [malaria or] Pyrifer. This number seemed, however, to suffice, because none of the 10 Saprovitan cases showed any remission, and although the Pyrifer treatment was not ineffective, malaria treatment showed an advantage. Apart from this, both [the new] methods of treatment proved, however, not to be far from safe, despite the fact that they had been promoted precisely because of their [supposed] safety in contrast to the allegedly so dangerous malaria cure.

I have been surprised that this method of testing therapeutic procedures has not found any imitation at all. But this may be because the child has not hitherto been given a name. I will therefore christen it ‘ The Simultaneous Method’ and use this term henceforth.”

Translation by Ulrich Tröhler


Julius Wagner-Jauregg (1857-1940)