February, 1931 



EVOLUTION 



Page thirteen 



pened? The roots of life — the genes — had indeed been struck, 

 and had yielded. 



It must not be supposed that all the above types appeared 

 congregated together in one family. The vast majority of the 

 offspring that hatched still appeared quite normal, and it was 

 only by raking through our thousands of cultures that all these 

 types were found. But what a difference from the normal fre- 

 quency of mutation, which is so painfully low! By checking up 

 with the small numbers of mutants found in the numerous un- 

 treated or control cultures, which were bred in parallel, it was 

 found that the heaviest treatment had increased the frequency 

 of mutation about 150 times — that is, an increase of 15,000 

 per cent. 



VI. SIMILARITY OF THE X-RAY TO THE 

 NATURAL MUTATIONS 



Yet these mutations were obviously of the same general 

 nature as the spontaneous mutations that occur without X-ray 

 treatment. This was shown by the fact that in many cases 

 changes had been produced which were undoubtedly identical 

 with spontaneous variations which had been found in the pre- 

 vious history of the Drosophila work; the effects in these cases 

 appeared identical in every particular, and the method of in- 

 heritance, the position of the gene concerned in the chromo- 

 some, was found to be the same. 



The new types of mutations, like the old, conformed in their 

 general expression and mode of inheritance to certain general 

 principles which I have previously observed to hold in the case 

 of the mutations occurring in untreated material. One of these 

 principles was that the great majority of the mutations — of 

 X-ray as well as of natural origin — are recessive to the normal 

 type, despite the presence of a rather small minority of domin- 

 ants. Thus the technique of breeding out through a number of 

 generations in order to find the mutations was found to be justi- 

 fied. And it may be remarked here that if human beings are 

 affected by X-rays in the same way as flies, we can not expect 

 to find much evidence of a mutational effect of X-rays on them 

 from data derived only from the first, or even the first, second 

 and third human generations, and such a negative result will 

 therefore by no means indicate a lack of significant genetic 

 effect. 



The second principle observed was that the X-ray mutations, 

 like the natural ones, included both inconspicuous as well as 

 conspicuous changes, changes of slight or almost imperceptible 

 degree as well as striking changes of structure or quality, and 

 changes that registered their effect, so far as could be deter- 

 mined, only in slight lowerings of the general vitality, as well 

 as those that were more graphically describable. If anything, 

 the more easily overlooked effects were the more frequent. 



A third principle noted was thnt moslTof the X-ray muta- 

 tions were in some way detrimental to the animal in living its 

 life — they were steps in the wrong directions in the struggle for 

 existence. This finding has already been discussed in the case of 

 the natural mutations, and it has been explained that this is 

 just what is to be expected, on the whole, of changes that occur 

 * at random, accidentally, "by chance" — I care not what term vou 

 wish to use to describe the idea that they occur without refer- 

 ence to their consequences, unadaptively, and hence are more 

 likely to be "wrong" than "right" changes, just because there 

 are more wrong roads than right roads to follow, and because. 



as is well known, the right road is apt to be the narrower. In 

 the case of the X-ray mutations it is easily seen that, if the 

 change occurs as I have pictured it, it must occur accidentally, 

 without reference to the possible advantage or disadvantage it 

 would confer, since the shooting electrons let loose by the 

 X-rays are coursing helter-skelter through the cell, quite blindly, 

 and are just as apt to hit one gene as another, to strike it either 

 on its left or its right side, through its heart or its appendix, 

 so to speak, and so will cause one change or another indiscrim- 

 inately. We have in the X-ray mutations, then, a group of 

 variations which seem necessarily to be random, and hence 

 would necessarily be mostly detrimental. In view of this, it is 

 interesting to compare with them in this respect the natural 

 mutations, and to note that, so far as our evidence goes, the 

 natural mutations have, on the average, every bit as much ten- 

 dency to be detrimental as the X-ray mutations have. The ob- 

 vious conclusion is that the natural mutations too must be ran- 

 dom changes, in the same sense that the X-ray mutations are. 



Most Mutations Kill 



As in the studies on natural mutations, so too among our 

 artificial ones, the great majority were lethal — they killed the 

 fly before it ever hatched, except where there was a normal 

 gene from the other parent to dominate over the lethal and 

 save the fly's life, so that it could be bred and the method of 

 transmission of the lethal studied. The changes in wings, eyes, 

 etc., previously mentioned were only the exceptional visible 

 changes, culled from out of a great mass of lethals. Thus, 

 although the great majority of the descendants of X-rayed flies 

 that lived looked normal, many of them carried, hidden by the 

 dominant normal gene, a recessive lethal gene. And if we 

 count up all these lethals we find that the majority of the 

 offspring of heavily X-rayed flies are not really normal in their 

 genes after all, for something over 50 per cent, of them contain 

 some kind of lethal mutation that will not work its destruction 

 until a still later generation. This too deserves being considered 

 iu its bearing on X-ray effects in the case of human beings. 

 Now previous studies of Altenburg and myself on natural 

 mutations have shown that among them too, although the 

 total frequency of mutations is so much smaller, nevertheless 

 the number of lethals is just as large, relatively to the number 

 of other, visible mutations which occur naturally, as it is 

 among the X-ray mutations. As the lethals differ from the 

 others, after all, merely in being more detrimental, this result 

 simply means that natural mutations are just apt to be very 

 detrimental, i.e., lethal, as are X-ray mutations, thus confirm- 

 ing what I have called the "accidental" character of the natural 

 mutations. 



The descendants of the X-rayed flies have been bred through 

 many subsequent generations. It is found that, where a gene 

 was not caused to mutate in the first place, it will not show a 

 subsequent tendency to mutate, without further treatment, i.e., 

 there is no perceptible after-effect on the genes that escaped an 

 immediate hit. On the other hand, those genes that were hit 

 and mutated now breed true to their new type,' which in the 

 great majority of cases gives evidence of being as stable as the 

 original type was before treatment. We now have in the labor- 

 atory various mutant races of flies, derived from our earlier 

 X-ray experiments, which have passed through something like 

 fifty or more generations since the time the mutation took 



