141 
1919-20.] The Harmala Alkaloids in Malaria. 
especially in malaria. It is important that evidence of this kind should be 
put on record, not only with a view to the possible improvement of the 
treatment of known protozoal diseases, but also with the set intention of 
keeping such pharmacological agents in mind for trial in such new diseases 
due to protozoa as are, no doubt, still to be discovered. 
The term “ general protoplasmic poison ” is apt to be misleading, for it 
tends to obscure the fact that the substances included under this designation 
exhibit selective action of a high order. The comparative insusceptibility 
of the salt-water as compared with the fresh-water amoeba is only one well- 
known instance of this. This fact is mentioned merely because it explains 
why the employment of such substances in protozoal diseases, based only 
upon general pharmacological evidence, is within limits empirical. In the 
present stage of knowledge, one cannot, from the fact that a substance is 
highly toxic to one, or even many, species of protozoa, predict that it will 
be comparably toxic to the pathogenic protozoon of a particular disease. 
Generally speaking, different protoplasmic poisons have been found 
necessary for the treatment of different protozoal diseases (malaria, amoebic 
dysentery, syphilis, etc.), although a remedy which is specific for one 
disease may have a slighter effect on another, especially if caused by a 
closely allied type of protozoon. 
The minimum lethal dose of harmaline by subcutaneous injection was 
found to be 0T gramme per kilogramme for the rabbit, guinea-pig, rat, and 
cat. If the whole dose were in the blood at one time, this would give a 
concentration of about 1 in 500 to 800, allowing the blood-volume to 
be somewhere between one-twelfth and one-twentieth of the body-weight. 
Raab showed that a solution of harmaline 1 in 20,000 kills paramoecia in 
8 to 20 minutes. If, therefore, one gave one-fifth of the M.L.D. by subcuta- 
neous injection in a mammal, a concentration sufficient to kill paramoecia 
in 8 to 20 minutes (1 in 20,000) would be found in the blood if only one- 
fifth to one-eighth of this dose were in the blood at one time. 
The use of harmaline in a protozoal disease was therefore well within 
the range of therapeutic possibility, although, as has been explained, such 
experiments can give nothing more than an indication of a possible 
therapeutic value in any particular disease. 
2. Experiments on Trypanosomiasis. 
Professor James Ritchie kindly gave me a strain of “ surra ” for 
investigating the action of harmaline on trypanosomes. It was found 
in twelve control experiments that this strain killed rats by sub- 
