Res Medica, Autumn 1969, Volume VI, Number 4 Page 1 of 6 Mutation Research and Human Welfare Professor Charlotte AuerBach F.R.S. The Institute of Animal Genetics, Edinburgh Abstract From an address to the Society in November 1968. GENETICAL RADIATION DAMAGE Knowledge gained from mutation research can be put to various uses for the benefit of mankind. One of them is assessment of genetical hazards from ionizing radiations. Before the war, this meant almost exclusively X-rays used in diagnosis and therapy. H. J. Muller, who in 1927 discovered the mutagenic action of X-rays, almost at once entered upon a campaign against the reckless use of radiation in medical practice. Especially in the USA , it was fashionable for the G.P. to have in his surgery a fluoroscope with, usually, an unknown and, often, a very high output of radiation and to use it indiscriminately even where less dangerous methods of diagnosis were available. There was also a practice of temporarily sterilizing men by radiation; when these men later on became fertile again they produced children from sperm that had been heavily irradiated as spermatogonia. In women, similarly high X-ray doses were used to produce fertility by follicle rupture. Until the war, the medical profession took very little notice of Muller. This careless attitude changed when fall-out and nuclear accidents became a major concern. Nowadays many national and international organisations, in all of which geneticists play an important role, are engaged in monitoring the amount of radiation to which we are exposed, in assessing its genetical consequences and in fixing “permissible” levels of radiation. Copyright Royal Medical Society. All rights reserved. The copyright is retained by the author and the Royal Medical Society, except where explicitly otherwise stated. Scans have been produced by the Digital Imaging Unit at Edinburgh University Library. Res Medica is supported by the University of Edinburgh’s Journal Hosting Service: http://journals.ed.ac.uk ISSN: 2051-7580 (Online) ISSN: 0482-3206 (Print) Res Medica is published by the Royal Medical Society, 5/5 Bristo Square, Edinburgh, EH8 9AL Res Medica, Autumn 1969, 6(4): 8-12 doi: 10.2218/resmedica.v6i4.861 AuerBach, C. Mutation Research and Human Welfare, Res Medica 1969, 6(4), pp. 8-12 doi: 10.2218/resmedica.v6i4.861 MUTATION RESEARCH AND HUMAN WELFARE Professor Charlotte AuerBach, F.R.S. The Institute of Animal Genetics, Edinburgh. From an address to the Society in November 1968 GENETICAL RADIATION DAMAGE radiation to which we are exposed, in assessing its genetical consequences and in fixing “per­ missible” levels of radiation. Knowledge gained from mutation research can be put to various uses for the benefit of mankind. One of them is assessment of DOMINANT MUTATIONS genetical hazards from ionizing radiations. Before the war, this meant almost exclusively So much has been said and written about X-rays used in diagnosis and therapy. II. J. genetical risks from radiation that I can be Muller, who in 1927 discovered the mutagenic brief. My main concern is to put them into action of X-rays, almost at once entered upon perspective. They certainly should not be a campaign against the reckless use of radiation played down but they should also not be exag­ in medical practice. Especially in the USA, it gerated. There is, for example, a widespread was fashionable for the G.P. to have in his belief that children born to irradiated men or surgery a fluoroscope with, usually, an un­ women are likely to be in some way abnormal. known and, often, a very high output of radi­ This is not borne out by observation nor is it ation and to use it indiscriminately even where expected on theoretical grounds. There are less dangerous methods of diagnosis were very few abnormal young among the progeny available. There was also a practice of tem­ of heavily irradiated mice, and none were porarily sterilizing men by radiation; when found among the children of Japanese parents these men later on became fertile again they that had survived exposure to the atom bombs. produced children from sperm that had been Theoretically, the type of mutation that would heavily irradiated as spermatogonia. In women, become manifest already in a child of the similarly high X-ray doses were used to pro­ irradiated person would be a dominant mut­ duce fertility by follicle rupture. Until the ation, and such mutations are known to be war, the medical profession took very little very rare. It is true that some Japanese women notice of Muller. This careless attitude who had been pregnant at the time of the changed when fall-out and nuclear accidents explosions had abnormal children, but these became a major concern. Nowadays many abnormalities were due to direct radiation national and international organisations, in all effects on the foetus, not to effects on the of which geneticists play an important role, germ cells of the parents. They do not con­ are engaged in monitoring the amount of stitute a risk for future generations for, like the effects of thalidomide or German measles together of two gametes with the same mut­ on the embryo, they are not inherited. If, as ated gene. Moreover, it will almost always has been claimed, radiation of the embryo in be impossible to pinpoint a particular case of, utero increases the risk of infantile leukaemia, say, phenylketonuria or recessive blindness as this too would not be a genetical damage. being due to a radiation-induced mutation, for radiation does not create new harmful CHROMOSOME BREAKAGE AND NON-DISJUNCTION genes, it only increases the frequency of the already known ones. Finally, not all recessive mutations have such drastic effects as blind­ What, then, are the risks of radiation that ness or idiocy. Many, probably the majority, causes so much worry to the geneticist? arc harmful only because they lower some Chromosome breaks are one of them, although component of fitness, e.g. resistance to infec­ not the most important one. The reason is tion or degree of intelligence. This can be that chromosome breakage has serious conse­ concluded with a high degree of certainty quences only when it results in a type of from experiments on lower organisms, although translocation that can be inherited and may it would be difficult to prove it for man. result in the repeated births of children suffer­ There can be little doubt that any increase in ing from a “chromosome disease” like Down’s mutation frequency will eventually lead to an syndrome. However, since a translocation re­ impairment of human health and happiness. quires the presence of two broken chromo­ It is our responsibility, especially that of the somes in the same cell, it is not often produced geneticists and politicians, to see that future by the low radiation doses from fall-out. Much generations will not have to pay too heavy a greater is the risk that even these low doses price for the security, health and comfort of will produce chromosomal disease through the present one. non-disjunction, and this has been taken into account in the most recent assessments of radiation hazards. IRRADIATED FOODSTUFFS RECESSIVE MUTATIONS Although it is not easy to arrive at good quantitative estimates of genetical radiation The most serious radiation damage is due damage, there can be no doubt that such to recessive mutations, i.e. to mutations that damage exists in all organisms and at all doses. become apparent only in homozygous indiv­ The situation is quite different for another iduals that have inherited the same mutated possible type of radiation damage which has gene from both parents. Recessive mutations recently become a subject of discussion. This are not only the most frequent ones; they are is the possibility that foodstuffs may become also produced in direct proportion to the mutagenic when they have been sterilized by magnitude of the dose, so that there is no the very high X-ray doses required for this lower threshold below which they do not occur. purpose. Already seven years ago, Indian Moreover, the vast majority of them are harm­ cytologists found chromosome breaks in the ful or even lethal. This is not due to some cells of plants that had been grown in heavily special malice of Nature. It is simply a con­ irradiated fruit juice, sugar solution or potato sequence of evolution which, in every organ­ mash. More recently, the journal “Nature” ism, has selected an array of genes that act created quite a stir among the circles con­ together harmoniously in development and cerned by publishing the results of an experi­ that make the organism fit well into its ment in which a high frequency of mutations environmental niche. New mutations are was found in Drosophila flies that had been much more likely than not to disrupt this reared on X-rayed medium. However, repet­ nicely adjusted interplay between the genes ition of this experiment in many laboratories with each other and with environment. Al­ both here and abroad did not confirm these though mankind certainly could be improved data : the results were either wholly negative genetically, this cannot be achieved by radi­ or the increase in mutation frequency was only ation. For the non-geneticist, it is not easy marginal. There the matter rests at the to grasp the danger of recessive mutations for, moment. The whole situation is typical for by their very nature, these will remain hidden the uncertainties that beset attempts to gener­ for several and, often, for many generations alize findings obtained with chemical muta­ until affected individuals arise from the coming gens; for it must be realized that, if heavily 9 irradiated medium should produce mutations, to have genetical consequences, but it is quite it would do so not through direct transfer of possible that this may be different in germ radiation energy but through the production cells.