In all work with this class of material there is obviously danger of error through foreign infection of the cultures, but there can be no doubt that though some of the "mutations" recorded may be due to this cause, the majority of the instances observed under stringent conditions are genuine. Another and equally serious difficulty besetting work with bacteria and fungi cultivated from spores is that the appearance of variation may in reality be due to the selection of a special strain previously living masked among other strains. This possibility must be remembered especially in those instances which are claimed as exemplifying the effects of acclimatisation. Manifestly this consideration can be urged with most force when the strain which gave rise to the novelty was not raised from a single individual spore. Moreover, when once the possibility of spontaneous variation is admitted, it must be difficult to be quite confident that any given variation observed is in reality due to the novel conditions applied, and as I understand the evidence, the appearance of the mutational forms does not with any regularity follow upon the application of the changed conditions. Researches into the variation of these lower forms will, no doubt, be continued on a comprehensive scale. So long as the instances recorded are each isolated examples it is impossible to know what value they possess. If they could be coordinated in such a way as to provide some general conception of the types of variation in properties to which bacteria, or any considerable group of them, are habitually liable, the knowledge might greatly advance the elucidation of genetic problems. Of mutational changes directly produced with regularity in micro-organisms by treatment, the experiments with trypanosomes provide some of the clearest examples. A summary of the evidence was lately published by Dobell,[4] from which the present account is taken. The most definite fact of this kind established is that certain dyes introduced into the blood of the host have the effect of destroying the small organ known as the "kinetonucleus" in the trypanosomes. The trypanosomes thus altered continue to breed, and give rise to races destitute of kinetonuclei. This observation was originally made by Werbitzki and has been confirmed by several observers. The exact way in which this alteration is effected in the trypanosomes is not quite definitely made out, but there is good reason for supposing that the dyes have a direct and specific action upon the kinetonucleus itself, and circumstances make it improbable that in some division a daughter-organism without that body is produced, or that any selection of a pre-existing defective variety occurs.