236 H. J. MULLER 



directed mutations or segregations, in the genetic material of the somatic cells. 

 Too many cases were fomid of reversible developmental changes of diverse 

 kinds: for example, dedifferentiations both in vitro and iti vivo; the regeneration 

 of tissues and organs from germ layers other than those normally producing 

 them; cases of somatic cells or their nuclei proving their virtual totipotence 

 by serving, in place of germ cells or their nuclei, for the whole of normal 

 development. To be sure, such work still fails to tell us what does cause 

 development, yet it is very important in telling us something that does not 

 cause it: namely, permanent change in the genetic constitution. 



The genetic-change mterpretation has persisted more obdurately in its 

 application to senility than to other stages and features of development. 

 There are at least two reasons for this. The first is that mutations and genetic 

 changes, in general, must to some extent accumulate with time, even though 

 they do not do so steadily (Muller, 1946a,b). The second reason is that 

 ionizing radiation is known to cause not only genetic changes but also a 

 shortening of the life-span that in considerable measure resembles what 

 would be expected of an acceleration of natural agemg (Henshaw, 1944; 

 Boche, 1946, 1948; Lorenz, 1946). To this fact may now be added Oster's 

 finding (1960, 1961a) in Drosoj)hila and Alexander and Connell's (1960) in 

 mice that chemical mutagens likewise cause a life-span shortenmg, resembling 

 that induced by radiation. 



In view of these pertinent-seeming considerations, what is there now to be 

 said for maintaining the view that natural ageing, at any rate, is to be 

 classed with other developmental changes as not being a reflection of true 

 genetic changes? One cogent Ime of evidence consists in the demonstration, 

 in a wide variety of organisms which undergo clonal ageing when carried 

 through a succession of cycles of asexual reproduction, that these lines of 

 descent are subject to rejuvenation. This can be brought about, as the case 

 may be, either by sexual reproduction or by autogamy, or by special types 

 of asexual reproduction, such as the derivation of the offspring in the next 

 cycle from younger individuals (Jennings and Lynch, 1928; Lansing, 1947) or 

 from more apically placed parts (Sonneborn, 1930). Important in this con- 

 nection is the fact that these revivals camiot be explained by any selective 

 mechanism acting against the more drastically affected cells or groups of 

 cells, since the frequencies of failures are far from enough to aUow such an 

 interpretation. Hence the observed ageing here would not have been based in 

 any permanent genetic alterations. The organisms here in question include 

 ciliates, flatworms, rotifers, fungi, and higher j^lants. Moreover, it is weU- 

 known that given types of vertebrate cells, such as heart muscle cells or 

 fibroblasts, have been maintained in successive tissue cultures without signs 

 of senescence for periods many times the fife-spans of the organisms from 

 which they were derived. 



