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Genetic Effects of Atom Bombs
124 It would be idle to lay the blame on any one authority group of persons-producer or--consumer. We are all to blame.
or
Prospects in Poliomyelitis
’
LACK of epidemiological knowledge is not the only obstacle to aneffective control of poliomyelitis. BURNETmaintains that we already know enough about this disease, in which undetectable carriers and mild for the most part undiagnosable infections far outnumber the obvious cases, to see that control is impracticable and that the only useful preventive measure is to prohibit tonsillectomy in times of epidemic prevalence. This is a pessimistic view but it is the carefully considered opinion of an acknowledged authority on virus diseases. It is not customary for doctors openly to admit defeat. The practitioner often prescribes a placebo to give an anxious patient the impression that something useful is being done when in fact nature is being left to take her course. Routine disinfection, admittedly for the sake of appearances, is still an accepted part of public-health practice in dealing with some infectious diseases. DEENY and MACCoRMACK,2 who lately described in these columns the measures employed to deal with outbreaks of poliomyelitis in Eire, disarmingly made no claim that the scheme applied, which included quarantine of contacts, school closure, water chlorination, and destruction of flies, had any effect on the spread of the disease..They merely recorded that in their experience communities rendered anxious by the prevalence of poliomyelitis will submit to any scheme, however troublesome, provided there is a strong suggestion that it will afford protection. They expressed the opinion that the reassuring effect of such control measures " established their psychological worth." If, however, this was all that could be expected of them, their use would be barely
justifiable. Some of the
measures advocated for the control need poliomyelitis very careful consideration before are a on they applied large scale without more justification than that of the placebo. A committee of which advised 3 on experts recently poliomyelitis in
of
boarding-schools
was
noticeably guarded
in
its
attitude to the quarantine of contacts. Except in residential communities like boarding-schools, and in families of easy financial circumstances, quarantine There is no means measures are difficult to apply. of enforcing them and no solution to the problem of compensation for loss of earnings which at once arises when a quarantine of adult contacts is attempted in the ordinary household. Another measure which cannot be lightly undertaken is the closure of dayschools. This is more likely to limit spread in rural than in urban areas, where, unless local housing conditions are well above average, it is almost impossible to prevent the aggregation of children who are not attending school into groups affording excellent opportunities for the spread of a virus which is infective by casual contact. It was found in Australia in 1937 that the decline of an outbreak which began and reached a peak during school holidays was not interrupted when the day-schools reopened. It has Burnet, F. M. State of Victoria. Dept. of Health Bulletin, Jan.June, 1945. 2. Deeny, J., MacCormack, J. D. Lancet, July 6, 1946, p. 8. 3. Ibid, 1946, i, 972. 1.
been shown that the chlorination of water-supplies in a manner effective against bacterial pollution does not destroy the virus of poliomyelitis. The prevalence of poliomyelitis is not therefore of itself a good reason for precautionary chlorination of the water-supply; moreover, to prevent the spread of the virus by house. hold utensils it is more logical to use boiling or steam sterilisation thanchlorinated or other dis. infectant rinses. Regarding the extensive use of D.D.T. for the destruction of flies in an attempt to control poliomyelitis it may be noted that a definite relation between flies infected by excreta or sewage and the spread of the disease among human beings has not yet been established. In this country there is often a high incidence of poliomyelitis during the late autumn and early winter when there are no flies about. So there are grounds for the view that at present the chances of preventing poliomyelitis are remote, and that this tragic disease must be accepted as a risk inseparable from social life in human communities. But even the pessimist would not think it futile to probe still further into the epidemiology-to seek, for instance, a satisfactory explanation of the wellmarked seasonal incidence of poliomyelitis. The the are better field in of prospects perhaps it seems reasonable to and forecast immunology, that the disease will in the end be robbed of its virulence if not of its powers of spread.
Genetic Effects of Atom Bombs IN the atom bombs which exploded a few hundred metres above Hiroshima and Nagasaki, a kilogramme or so of uranium 235 or plutonium 239 underwent fission, with the production of about 1021 ergs of energy. Part of this energy was expended in the blast which caused the material damage to buildings, part was dissipated as hot air, and an appreciable proportion was emitted as radiation. The radiation which reached the ground comprised (a) visible, infra-red, and ultraviolet light, resembling sunlight but of much higher intensity, (b) neutrons, and (c) gamma rays resembling the penetrating rays used in radium therapy or supervoltage X-ray therapy. The visible and near-visible light produced burns on the unprotected skin of people exposed to the flash, but since such radiation is not penetrating it does not directly damage deeper tissues. Neutrons and gamma rays are capable of penetrating to all parts of the body, and substantial thicknesses of building material. are required to protect against them. According to the official report,l injuries due to penetrating radiation should mainly be ascribed to gamma rays rather than The gamma-ray emission from the bomb perhaps equivalent to 1011 curie-hours of radium, and appears to have produced at the ground a dose of the order of 1000 r at one kilometre from the centre of damage, and 10 r at three kilometres. Injuries suffered by people exposed to the .gamma rays, as described in the official report, include neutrons.
t
was
the
haemopoietic system resulting in to reproductive organs shown reduction in counts and miscarriages in sperm by pregnant women. All these types of injury were
damage
to
anaemia, and damage
1. Effects of the Atomic Bombs at Hiroshima and London. 1946. See Lancet, July 6, 1946, p. 14.
Nagasaki.
125
anticipated from existing knowledge of the action of X rays and gamma rays. In addition to these injuries, which became apparent within a few days or at most a few months after the bombing, other harmful effects are to be antici-
to be
pated which will appear only in later generations. These are genetic changes, induced by the radiation
in the germ cells of survivors and handed on to their offspring. A discussion at the British Institute of Radiology in May,2 with Prof. J. B. S. HALDANE, F.R.S., in the chair, made it clear that, while the production of mutations by radiation in man has not been demonstrated, there is no reason to doubt that it can occur. There is evidence that radiation induces mutation in a considerable number of plant and animal- species, including mice. Two principal types are recognised-gene mutation and chromosome mutation. The former involves no detectable change in the microscopical appearance of the chromosomes and is presumed to be due to internal change in a gene ; the latter involves rearrangement of existing genes by, for example, an exchange of segments between two chromosomes, and may be detectable microscopically. The commonest radiation-induced mutations in mice are of the chromosome type and their effect is to cause hereditary partial sterility. When a male or female mouse has been irradiated with neutrons or X rays in a dosage of a few hundred rontgens, some of its offspring will consistently produce small litters. About half the members of these small litters, when reared and mated to normal mice, will in turn give rise to small litters, and so on, the effect being transmitted to about half the offspring in each generation. The small litter size is due to a proportion of the fertilised eggs dying, either before implantation in the uterus or as embryos in the uterus. If this effect exists with human beings, it may show itself as a hereditary
tendency to miscarriage. This hereditary partial sterility
is produced when mature sperm are irradiated, but the effect on immature sperm is much slighter, so the maximum degree of chromosome mutation is obtained only if mating takes place within a few days of irradiation. Gene mutations, on the other hand, are produced about as readily in immature as in mature germ cells ; consequently the offspring conceived of one of the parents at any time after irradiation may be expected to carry mutant genes. Offspring which receive a mutant gene from one parent will usually receive the corresponding gene in the normal form from the other parent, and since mutant genes are often recessive to the normal type the effect of the mutant-gene is concealed. Eventually, after a greater or lesser number of generations (depending on the degree of inbreeding, but possibly of the order of a hundred generations), a conception may occur in which both egg and sperm contribute the same mutant gene, and the mutation will then show itself in the resulting organism. Thus a considerable time is likely to elapse between the production of a recessive mutation and the appearance of a visibly abnormal Mutants which are person. not recessive to the normal type (and this is the case with many of the known human mutants), and mutant genes carried in the sex chromosomes, will show up in the offspring of irradiated people 2. Nature, Lond. 1946, 157, 738.
and will not remain hidden for many generations. The vast majority of mutations are deleterious, and the production of mutations is undoubtedly to be included among the harmful effects of the atom bomb. To assess the magnitude of the effect is, however, only possible if one is prepared to make guesses which while plausible may be wrong. The mutationrate in experimental material is of the order of 3 X 10-8 per gene per rontgen. The spontaneous rate of mutation in man in the case of two known mutations is about 10-per gene per generation, or say 4 X 10-77 per gene per year. Thus a dose of about 10 r probably produces as many mutations as occur spontaneously in a year, and in the germ cells of the survivors of the atom bomb as many mutations were probably produced as would arise spontaneously in several years. Considerations of this kind are also relevant in planning peace-time applications of atomic energy which might involve greater numbers of people than have hitherto run the risk of exposure to radiation.3 It is now thought that X-ray and radium workers can tolerate about 1 r per week without injury to health. So long as only a minute fraction of the whole population is exposed to radiation, doses of this order will not increase the mutation-rate in the population as a whole by any significant proportion. But if developments in nuclear physics lead to a considerable fraction of the population running the risk of exposure to radiation, it will be necessary to reduce the " tolerance " dose much below that figure. If, for example, the whole population were exposed to 1 r per week, then the mutation-rate would probably be increased several fold above the spontaneous rate, resulting eventually in a great increase in hereditary abnormalities. Fortunately the authorities are alive to these dangers and to the necessity for obtaining further information on the production4 of hereditary changes by radiation in mammals. .
B.C.G.
July 17 a deputation from the Tuberculosis Association, the Joint Tuberculosis Council, and the National Association for the Prevention of Tuberculosis went to the Ministry of Health to present the memorandum by Prof. W. H. Tytler, which we summarise on p. 138. They asked that s.c.. vaccine should be made available for trial in this country. Sir Wilson Jameson, chief medical officer of the Ministry, who received the deputation with sympathy, indicated his willingness to To see whether suitable vaccine can be provided. determine its use, and the class of persons to be immunised, it would, he thought, be necessary to appoint an expert committee. ON
3. 4.
Wiesner, B. P. Lancet, 1946, i, 33 ; Walker, K. M. Dale, H. H. Ibid, p. 399.
Ibid, p. 69.
" ... If there is a valid criticism to be made of the Civil Service at the present time, it is that it does not always fully appreciate the point of view of the public and does not always have that sense of urgency which we would wish it to have. The obvious remedy is to recruit civil servants from men who have been at the receiving end of Ministry letters. They will, then, have a different outlook and a greater sense of urgency.... We are no longer under the kind of system in which the Civil Service first developed, in which its chief role was to stop other people from doing things. The Civil Service is increasingly having a planned and positive role to play, and we may need to go much further than we have done during the war in bringing in men of business, scientific, and technical experience of every kind."-Mr. H. D. HUGHES in the House of Commons on June 21.
or
Prospects in Poliomyelitis
’
LACK of epidemiological knowledge is not the only obstacle to aneffective control of poliomyelitis. BURNETmaintains that we already know enough about this disease, in which undetectable carriers and mild for the most part undiagnosable infections far outnumber the obvious cases, to see that control is impracticable and that the only useful preventive measure is to prohibit tonsillectomy in times of epidemic prevalence. This is a pessimistic view but it is the carefully considered opinion of an acknowledged authority on virus diseases. It is not customary for doctors openly to admit defeat. The practitioner often prescribes a placebo to give an anxious patient the impression that something useful is being done when in fact nature is being left to take her course. Routine disinfection, admittedly for the sake of appearances, is still an accepted part of public-health practice in dealing with some infectious diseases. DEENY and MACCoRMACK,2 who lately described in these columns the measures employed to deal with outbreaks of poliomyelitis in Eire, disarmingly made no claim that the scheme applied, which included quarantine of contacts, school closure, water chlorination, and destruction of flies, had any effect on the spread of the disease..They merely recorded that in their experience communities rendered anxious by the prevalence of poliomyelitis will submit to any scheme, however troublesome, provided there is a strong suggestion that it will afford protection. They expressed the opinion that the reassuring effect of such control measures " established their psychological worth." If, however, this was all that could be expected of them, their use would be barely
justifiable. Some of the
measures advocated for the control need poliomyelitis very careful consideration before are a on they applied large scale without more justification than that of the placebo. A committee of which advised 3 on experts recently poliomyelitis in
of
boarding-schools
was
noticeably guarded
in
its
attitude to the quarantine of contacts. Except in residential communities like boarding-schools, and in families of easy financial circumstances, quarantine There is no means measures are difficult to apply. of enforcing them and no solution to the problem of compensation for loss of earnings which at once arises when a quarantine of adult contacts is attempted in the ordinary household. Another measure which cannot be lightly undertaken is the closure of dayschools. This is more likely to limit spread in rural than in urban areas, where, unless local housing conditions are well above average, it is almost impossible to prevent the aggregation of children who are not attending school into groups affording excellent opportunities for the spread of a virus which is infective by casual contact. It was found in Australia in 1937 that the decline of an outbreak which began and reached a peak during school holidays was not interrupted when the day-schools reopened. It has Burnet, F. M. State of Victoria. Dept. of Health Bulletin, Jan.June, 1945. 2. Deeny, J., MacCormack, J. D. Lancet, July 6, 1946, p. 8. 3. Ibid, 1946, i, 972. 1.
been shown that the chlorination of water-supplies in a manner effective against bacterial pollution does not destroy the virus of poliomyelitis. The prevalence of poliomyelitis is not therefore of itself a good reason for precautionary chlorination of the water-supply; moreover, to prevent the spread of the virus by house. hold utensils it is more logical to use boiling or steam sterilisation thanchlorinated or other dis. infectant rinses. Regarding the extensive use of D.D.T. for the destruction of flies in an attempt to control poliomyelitis it may be noted that a definite relation between flies infected by excreta or sewage and the spread of the disease among human beings has not yet been established. In this country there is often a high incidence of poliomyelitis during the late autumn and early winter when there are no flies about. So there are grounds for the view that at present the chances of preventing poliomyelitis are remote, and that this tragic disease must be accepted as a risk inseparable from social life in human communities. But even the pessimist would not think it futile to probe still further into the epidemiology-to seek, for instance, a satisfactory explanation of the wellmarked seasonal incidence of poliomyelitis. The the are better field in of prospects perhaps it seems reasonable to and forecast immunology, that the disease will in the end be robbed of its virulence if not of its powers of spread.
Genetic Effects of Atom Bombs IN the atom bombs which exploded a few hundred metres above Hiroshima and Nagasaki, a kilogramme or so of uranium 235 or plutonium 239 underwent fission, with the production of about 1021 ergs of energy. Part of this energy was expended in the blast which caused the material damage to buildings, part was dissipated as hot air, and an appreciable proportion was emitted as radiation. The radiation which reached the ground comprised (a) visible, infra-red, and ultraviolet light, resembling sunlight but of much higher intensity, (b) neutrons, and (c) gamma rays resembling the penetrating rays used in radium therapy or supervoltage X-ray therapy. The visible and near-visible light produced burns on the unprotected skin of people exposed to the flash, but since such radiation is not penetrating it does not directly damage deeper tissues. Neutrons and gamma rays are capable of penetrating to all parts of the body, and substantial thicknesses of building material. are required to protect against them. According to the official report,l injuries due to penetrating radiation should mainly be ascribed to gamma rays rather than The gamma-ray emission from the bomb perhaps equivalent to 1011 curie-hours of radium, and appears to have produced at the ground a dose of the order of 1000 r at one kilometre from the centre of damage, and 10 r at three kilometres. Injuries suffered by people exposed to the .gamma rays, as described in the official report, include neutrons.
t
was
the
haemopoietic system resulting in to reproductive organs shown reduction in counts and miscarriages in sperm by pregnant women. All these types of injury were
damage
to
anaemia, and damage
1. Effects of the Atomic Bombs at Hiroshima and London. 1946. See Lancet, July 6, 1946, p. 14.
Nagasaki.
125
anticipated from existing knowledge of the action of X rays and gamma rays. In addition to these injuries, which became apparent within a few days or at most a few months after the bombing, other harmful effects are to be antici-
to be
pated which will appear only in later generations. These are genetic changes, induced by the radiation
in the germ cells of survivors and handed on to their offspring. A discussion at the British Institute of Radiology in May,2 with Prof. J. B. S. HALDANE, F.R.S., in the chair, made it clear that, while the production of mutations by radiation in man has not been demonstrated, there is no reason to doubt that it can occur. There is evidence that radiation induces mutation in a considerable number of plant and animal- species, including mice. Two principal types are recognised-gene mutation and chromosome mutation. The former involves no detectable change in the microscopical appearance of the chromosomes and is presumed to be due to internal change in a gene ; the latter involves rearrangement of existing genes by, for example, an exchange of segments between two chromosomes, and may be detectable microscopically. The commonest radiation-induced mutations in mice are of the chromosome type and their effect is to cause hereditary partial sterility. When a male or female mouse has been irradiated with neutrons or X rays in a dosage of a few hundred rontgens, some of its offspring will consistently produce small litters. About half the members of these small litters, when reared and mated to normal mice, will in turn give rise to small litters, and so on, the effect being transmitted to about half the offspring in each generation. The small litter size is due to a proportion of the fertilised eggs dying, either before implantation in the uterus or as embryos in the uterus. If this effect exists with human beings, it may show itself as a hereditary
tendency to miscarriage. This hereditary partial sterility
is produced when mature sperm are irradiated, but the effect on immature sperm is much slighter, so the maximum degree of chromosome mutation is obtained only if mating takes place within a few days of irradiation. Gene mutations, on the other hand, are produced about as readily in immature as in mature germ cells ; consequently the offspring conceived of one of the parents at any time after irradiation may be expected to carry mutant genes. Offspring which receive a mutant gene from one parent will usually receive the corresponding gene in the normal form from the other parent, and since mutant genes are often recessive to the normal type the effect of the mutant-gene is concealed. Eventually, after a greater or lesser number of generations (depending on the degree of inbreeding, but possibly of the order of a hundred generations), a conception may occur in which both egg and sperm contribute the same mutant gene, and the mutation will then show itself in the resulting organism. Thus a considerable time is likely to elapse between the production of a recessive mutation and the appearance of a visibly abnormal Mutants which are person. not recessive to the normal type (and this is the case with many of the known human mutants), and mutant genes carried in the sex chromosomes, will show up in the offspring of irradiated people 2. Nature, Lond. 1946, 157, 738.
and will not remain hidden for many generations. The vast majority of mutations are deleterious, and the production of mutations is undoubtedly to be included among the harmful effects of the atom bomb. To assess the magnitude of the effect is, however, only possible if one is prepared to make guesses which while plausible may be wrong. The mutationrate in experimental material is of the order of 3 X 10-8 per gene per rontgen. The spontaneous rate of mutation in man in the case of two known mutations is about 10-per gene per generation, or say 4 X 10-77 per gene per year. Thus a dose of about 10 r probably produces as many mutations as occur spontaneously in a year, and in the germ cells of the survivors of the atom bomb as many mutations were probably produced as would arise spontaneously in several years. Considerations of this kind are also relevant in planning peace-time applications of atomic energy which might involve greater numbers of people than have hitherto run the risk of exposure to radiation.3 It is now thought that X-ray and radium workers can tolerate about 1 r per week without injury to health. So long as only a minute fraction of the whole population is exposed to radiation, doses of this order will not increase the mutation-rate in the population as a whole by any significant proportion. But if developments in nuclear physics lead to a considerable fraction of the population running the risk of exposure to radiation, it will be necessary to reduce the " tolerance " dose much below that figure. If, for example, the whole population were exposed to 1 r per week, then the mutation-rate would probably be increased several fold above the spontaneous rate, resulting eventually in a great increase in hereditary abnormalities. Fortunately the authorities are alive to these dangers and to the necessity for obtaining further information on the production4 of hereditary changes by radiation in mammals. .
B.C.G.
July 17 a deputation from the Tuberculosis Association, the Joint Tuberculosis Council, and the National Association for the Prevention of Tuberculosis went to the Ministry of Health to present the memorandum by Prof. W. H. Tytler, which we summarise on p. 138. They asked that s.c.. vaccine should be made available for trial in this country. Sir Wilson Jameson, chief medical officer of the Ministry, who received the deputation with sympathy, indicated his willingness to To see whether suitable vaccine can be provided. determine its use, and the class of persons to be immunised, it would, he thought, be necessary to appoint an expert committee. ON
3. 4.
Wiesner, B. P. Lancet, 1946, i, 33 ; Walker, K. M. Dale, H. H. Ibid, p. 399.
Ibid, p. 69.
" ... If there is a valid criticism to be made of the Civil Service at the present time, it is that it does not always fully appreciate the point of view of the public and does not always have that sense of urgency which we would wish it to have. The obvious remedy is to recruit civil servants from men who have been at the receiving end of Ministry letters. They will, then, have a different outlook and a greater sense of urgency.... We are no longer under the kind of system in which the Civil Service first developed, in which its chief role was to stop other people from doing things. The Civil Service is increasingly having a planned and positive role to play, and we may need to go much further than we have done during the war in bringing in men of business, scientific, and technical experience of every kind."-Mr. H. D. HUGHES in the House of Commons on June 21.