1066

Letters to the Editor

RADIATION HAZARDS

J. B. S. HALDANE.University College,London.

Sm,-The Medical Research Council report is of greatinterest, and many of its results must be accepted. In

particular it seems that the genetic damage caused byexperimental nuclear explosions so far is much less thanthat caused by diagnostic radiology in economicallyadvanced countries. This is probably so for the worldas a whole, since the British figures are fairly typical forsome 400 millions of human beings ; though in theabsence of protection from houses the danger from fall-out in the tropics may often exceed that in Britain,sometimes by a factor as high as 7, the value given onp. 57 of the report.But the report seems to suffer from two defects, one of

presentation and one of calculation. In its table 1 D

(p. 93) the extra births of phenylketonurics among ageneration of 20 million due to a doubling of the mutation-rate are given as 5. But the total in all subsequentgenerations, supposing the population of England toremain steady, would be 500 ; and the total for theworld, on the same assumption, would be about 60times this figure, or 30,000. Phenylketonuria accountsfor about 1% of severe mental defect, but not all mentaldefect is genetically determined. If two-thirds were

genetically determined, a doubling of the mutation-ratefor one generation would probably lead to the birth ofabout 2 million mental defectives, and also, in myopinion, of a somewhat larger number of physicallydefective children and a good many more abortions andstillbirths.The report estimates the increase of radiation to

human gonads from test explosions as less than 1%(p. 59), or less than 0.03r per generation, and the doublingdose as 30 to 80r (p. 45) or 10 to 27 times the naturaldose. So if tests continue at the present level during onegeneration, their total effect would be to produce onlyabout 2000 mental defectives or less. However this maybe, I think that a figure of 5 might prove unduly reassuringto a casual reader, even if a figure of 2 million is regardedas too alarming.But I believe that these figures are too low, for the

following reason.12 2 Before any atomic bombs had beenexploded, I calculated the probable mutation-rates

corresponding to existing frequencies of congenitalabnormalities. The calculation was therefore unaffected

by any emotions concerning nuclear warfare. If a

recessive gene for a character such as phenylketonuriahas a frequency of 0.5% in gametes (as assumed in thereport) and no phenylketonurics breed, this means that,apart from inbreeding, 0.5% of such genes meet withother similar genes per generation, so such a gene has anaverage " life " of 200 generations between its appearanceby mutation and its elimination by natural selection.But inbreeding accounts for a good many cases. OfMunro’s 3 47 families containing phenylketonurics threeparental pairs were first cousins, two were more distantrelatives, and very likely another five or more were stillmore distantly related, the two genes which cooperatedto produce an idiot or imbecile being due to the sameoriginal mutation.

If, in fact, 11 or 12 of Munro’s families (say, 25%)were from consanguineous parents the mean " life " ofsuch a recessive gene is reduced to 160 generations. Butin the middle ages and earlier, inbreeding was far moreprevalent than today. Most people lived in .villages andmarried neighbours. Thus recessive genes were eliminatedmuch more rapidly than today, and a higher mutation-rate was needed to balance this elimination. Owing to

1. Haldane, J. B. S. Ann. Eugen. 1939, 9, 232.2. Haldane, J. B. S. Ibid, 1940, 10, 417.3. Munro, T. A. Ibid, 1947, 14, 60.

the long " life " of these genes the present gene frequencywas effectively determined many centuries ago. It i8difficult to guess at the intensity of inbreeding in mediaevalEngland. I have assumed a figure well below that foundfor a Jewish community in South Germany, but abovethat of nineteenth-century European peasantries. Onthis basis one can very roughly calculate the mutation-rate, and it turns out to be about 2.6 times that given inthe report, perhaps more. For rarer genes the correctionis greater. Thus I think that the total number of mentaldefectives produced by a doubling of the mutation-rateduring one generation would be nearer 8 million than 2million, and might well exceed 10 million. Since it isstated in the M.R.C. report (p. 90) that the principles onwhich mutation-rates can be indirectly estimated werelaid down by myself in 1932, I think that my own sub-sequent work, which increased the estimates by a con-siderable factor, might have been taken into considera-tion. I am aware that they were stated in a ratherabstract and mathematical form. For this reason I havegiven them here in as simple words as I could achieve.I may add that when the correction is made, the doublingdose for the gene for phenylketonuria, if it is as sensitiveas the average of 7 genes investigated by Russell 4 inmice, becomes about 36r, which is in accordance withthe findings of the report (p. 45). The detailed calcu-lations will be published elsewhere.

I wish to emphasise the importance of human inbreed-ing for another reason. It is proposed to compare thefrequencies of several abnormalities in different areas,in the hope of discovering or disproving a mutageniceffect of radioactive substances in the soil. In the case ofrare recessive conditions inbreeding in some rural areasmay be expected to have a very large effect. Since, onthe whole, inbreeding may be expected to be higher inthe more radioactive areas of Britain (e.g., West Cornwalland Aberdeen) than in the country as a whole, rarerecessive conditions will also be common. And this

might well lead to an overestimation of the mutageniceffect of radioactive minerals. For this reason it is myconviction that such a survey would be a waste of publicmoney, and what is even more serious, of the skill of themen and women who undertake it.

It must also be remembered that the human doublingdoses of radiation may be higher than for most otheranimals, on account of the great length of human

generations. Thus a human generation is about sixtytimes as long as a mouse generation, and a man receives60 times as much radiation per generation. But thenumber of nuclear divisions per generation, which mayalso provoke mutation, is not much greater in men thanmice. Hence radiation may be a relatively more

important mutagenic agent in men than mice, and thedoubling dose correspondingly lower. If so the calculatedeffects must be multiplied by a further factor.

4. Russell, W. L. Radiation Biol. 1954, 1, 825.5. Bull, F. P., Jackson, D. M., Lowbury, E. J. C., Topley, E. Lancet,

1951, i, 161.

BURNS AND SCALDS

SiR,ŇYour leader of May 19 and the letters from*Dr. Hall-Smith (May 26) and Dr. Leonard Colebrook(June 2) discuss the treatment to be carried out-inthe home or in the surgery-of burns and scalds whichare sufficiently superficial to justify non-hospital treat-ment. Dr. Hall-Smith protests that your advocacyof an anti-histamine ointment encourages the develop-ment of sensitisation eczemas. Dr. Colebrook upbraidsyou for neglecting the advice of Bull et a1.5 to use topicalpenicillin. Dr. Hall-Smith remarks that anti-histamineointment is fast replacing the topical antibiotics as themost potent cause of iatrogenic dermatitis. Dr. Cole-brook denies that topical penicillin is likely to produce