The selection of drugs for chemotherapy research in leprosy.

Unlike the problem in the chemotherapy of most infectious diseases, and even of tuberculosis, that of the selection of drugs for clinical work in leprosy is beset with numerous difficulties of diverse nature. The first difficulty arises from the inability of Mycobacterium lepme to grow on any artificial medium, and from the impossibility, at the present stage of research, of transmitting leprosy to any laboratory animal. This precludes both in vitro and in vivo direct screening tests such as those which culminated in the introduction of isonicotinic acid hydrazide in the domain of tuberculosis. Recourse to experimental infections by means of M. lepme murium has proved quite unreliable, as is shown by the contrast between, on the one hand, numerous clinical observations of the low degree of efficacy in human leprosy of isonicotinic hydrazide as compared with the sulfones and thiosemicarbazones (1, 2, 15), and, on the other hand, reports upon the outstanding activity of isonicotinic hydrazide in murine leprosy (6, 8, 14). Using the intracorneal inoculation test, Goulding, Robson, and Rees (10) found from a comparative study of therapeutic effects in mice of 4,4'-diaminodiphenylsulfone, thiosemicarbazones, and isonicotinic hydrazide that the last-named substance was the only one to display activity. A similar discrepancy exists between the good therapeutic effects in animals (13) and the far less satisfactory clinical results obtained with streptomycin (7). The second difficulty encountered arises from the unusual length of the treatment periods inherent in leprosy, which virtually precludes the use of drugs like streptomycin, with pronounced side-effects, or those which would rapidly bring about bacterial resistance. Nothing of course is known about the conditions under which the Hansen bacillus might develop drug-resistant strains, but judging from the speedy appearance of Koch bacilli resistant to isonicotinic hydrazide in the treatment of tuberculosis, this might well account for the poor activity of this drug in human leprosy. A third difficulty is of an ethical and even economic nature. Results of the many large-scale investigations reported in recent years, and the