There is now practically complete agreement among bacteriologists that the observations made first by Massini on the change in color of Bacterium coli mutabile grown in Endo's medium, associated with the acquisition of the power to ferment lactose, are perfectly reliable and free from possibilities of mistake. The work has been extended and confirmed by many workers, especially R. Müller, who finds that this bacterium can similarly acquire and maintain the power to ferment other sugars. A careful account of the whole subject written by Müller for the information of biologists will be found in Zts. für Abstammungsl., VIII, 1912. After discussing the biological significance of the facts, he concludes with a caution to the effect that bacteria are so different from all other living things that generalizations from their behavior must not be indiscriminately applied to animals and plants.

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.

Ehrlich has suggested with great probability that the dyes which possess this action owe it to the fact that they have the particular chemical linkage which he calls "ortho-quinoid." In outward respects, such as motility and general appearance, the modified organisms are unchanged, but their virulence is diminished. As regards the possibility of the defective strain reacquiring the kinetonucleus, Werbitzki states that in one case passage through 50 animals and treatment with dyes left the strain unaltered; but that in another case at the sixteenth passage 7 per cent. of the trypanosomes were found to have re-acquired the organ, and in subsequent passages the percentage increased, until at the twenty-seventh passage practically all had re-acquired it. Kudicke, however, in similar experiments did not succeed in causing re-acquisition by transplantation.

By the action of various drugs and anti-bodies races of trypanosomes resistant to those substances have been obtained. These breed true, at least when kept in the same species of animal in which the resistance was acquired. As to whether change of virulence is produced by passage through certain animals or not, there is as yet no general agreement.

Other changes, especially in size and some points of structure, are said to occur when certain trypanosomes proper to mammals are passed through cold-blooded vertebrates (Wendelstadt and Fellmer), and it is stated that these changes persist, but the observations have not yet been confirmed.

Experiments lately conducted by Woltereck with Daphnia are interesting as having given a definite positive result, in so far, at least, as the ova were affected by conditions before leaving the bodies of the parent individuals. The observations relate to the offspring resulting from parthenogenetic eggs. Females bearing ephippia (fertilised eggs) were isolated until the ephippia were dropped, and in this way the offspring of fertilisation were excluded. Males, of course, appeared from time to time in the cultures, but as fertilised eggs were rejected, their presence did not disturb the result. The most remarkable observations related to Daphnia longispina.

This species as found in the lower lake at Lunz had the front end of the body blunt and nearly round in profile; but on being cultivated in a warm temperature and with abundant nourishment the front end of the body became produced into an elongated "helmet," as Woltereck calls it. Experiment showed that the change was primarily due to the abundance of food, and owing to temperature in a subordinate degree.