2 Laws of Mutation

Law 1: Mutation Is A Single Event

The laws governing the induced mutation rate are extremely simple.

Law 1: The increase is exactly proportional to the dosage of rays, leading to a coefficient of increase.

We are so used to simple proportionality that we are liable to underrate the far-reaching consequences of this simple law.

To grasp them, we may remember that the price of a commodity, for example, is not always proportional to its amount.

In ordinary times a shopkeeper may be so much impressed by your having bought six oranges from him, that, on your deciding to take after all a whole dozen, he may give it to you for less than double the price of the six. In times of scarcity the opposite may happen.

In the present case, we conclude that the first half-dosage of radiation, while causing, say, one out of a thousand descendants to mutate, has not influenced the rest at all, either in the way of predisposing them for, or of immunizing them against, mutation.

For otherwise the second half-dosage would not cause again just one out of a thousand to mutate. Mutation is thus not an accumulated effect, brought about by consecutive small por- tions of radiation reinforcing each other. I t must consist in some single event occurring in one chromosome during irradiation. What kind of event?

Law 2: Localization Of The Event

(2) If you vary the quality of the rays (wave-length) within wide limits, from soft X-rays to fairly hard y-rays, the coefficient remains constant.

This is provided you give the same dosage in so-called r-units – you measure the dosage by the total amount of ions produced per unit volume in a suitably chosen standard substance during the time and at the place where the parents are exposed to the rays.

As standard substance one chooses air not only for convenience, but also for the reason that organic tissues are composed of elements of the same atomic weight as air.

A lower limit for the amount of ionizations or allied processes I (excitations) in the tissue is obtained simply by multiplying the number of ionizations in air by the ratio of the densities.

It is thus fairly obvious, and is confirmed by a more critical investigation, that the single event, causing a mutation, is just an ionization (or similar process) occurring within some ‘critical’ volume of the germ cell.

What is the size of this critical volume? I t can be estimated from the observed mutation rate by a consideration of this kind: if a dosage of 50,000 ions per cm 3 produces a chance of only I: 1000 for any particular gamete (that finds itself in the irradiated district) to mutate in that particular way, we conclude that the critical volume, the ’target’ which has to be ‘hit’ by an ionization for that mutation to occur, is only lloo of 5oAoo of a cm 3 , that is to say, one fifty-millionth of a cm 3 .

The numbers are not the right ones, but are used only by way of illustration.

In the actual estimate we follow M. Delbriick, in a paper by Delbriick, N.W. Timofeeffand K.G. Zimmer,2 which will also be the principal source of the theory to be expounded in the following two chapters.

He arrives there at a size of only about ten average atomic distances cubed, containing thus only about 10 3 == a thousand atoms. The simplest interpretation of this result is that there is a fair chance of producing that mutation when an ionization (or excitation) occurs not more than about’ 10 atoms away’ from some particular spot in the chromosome.

We shall discuss this in more detail presently. The Timofeeff report contains a practical hint which I cannot refrain from mentioning here, though it has, of course, no bearing on our present investigation.

There are plenty of occasions in modern life when a human being has to be exposed to X-rays. The direct dangers involved, as burns, X-ray cancer, sterilization, are well known, and protection by lead screens, lead-loaded aprons, etc., is provided, especially for nurses and doctors who have to handle the rays regularly.

The point is, that even when these imminent dangers to the individual are successfully warded off, there appears to be the indirect danger of small detrimental mutations being pro- duced in the germ cells - mutations of the kind envisaged when we spoke of the unfavourable results of close-breeding.

To put it drastically, though perhaps a little naIvely, the injuriousness of a marriage between first cousins might very well be increased by the fact that their grandmother had served for a long period as an X-ray nurse.

It is not a point that need worry any individual personally. But any possibility of gradually infecting the human race with unwanted latent mutations ought to be a matter of concern to the community.