849
only 0-8%. Although the fact that this statistic is based on only 263 patients suggests the need for caution in interpretation, this rate does not differ significantly from the corresponding rate of 0-4% achieved by the Shouldice Clinic, a Canadian hospital which specialises in elective herniorrhaphy.1-3 Moreover, our results are strikingly better than the 3-year recurrence-rate of 7-0% reported by Marsdenand the temporally less-welldefined rate of 14.3% reported from St. Thomas’s Hospital (Both these papers were concerned with a variety of operations and with traditional lengths of stay but differed in their definitions of a recurrence: we adopted Marsden’s criterion.) In contrast, the 86 cases in which a polyester suture material was used showed an estimated 2-year recurrence-rate of 8.1 1%-far worse than the Shouldice Clinic results but comparable to those of rate is
Marsden.5 We have previously concluded that, although day-case surgery has no early clinical, social, or financial disadvantages for the hernia patient, its major advantage
Occasional
Survey
THE INCIDENCE OF HEREDITARY DISEASE IN MAN
GENE mutations, chromosome aberrations, and changes in the chromosome number occur spontaneously, and some result in abnormalities in the offspring, ranging from mildly detrimental to severely disabling or lethal. Such effects can also be induced by environmental mutagens, including ionising radiations. There is particular concern at the present time about the possible effects of ionising radiations arising from the generation of nuclear power. When estimates of the frequency of radiation-induced hereditary defects in human populations are provided for purposes of radiological protection they are ordinarily based on what is known about the spontaneous incidence of hereditary disease. The Medical Research Council’s Committee on Protection against Ionising Radiations last year organised a forum meeting, at which were discussed the frequencies of hereditary diseases, their severity, the extent to which they are maintained by new mutation, and their transmissibility. The topics discussed at the forum, which will also be of interest to those concerned with environmental mutagens other than ionising radiations, are presented below. CHROMOSOME ANOMALIES IN LIVE BIRTHS
Chromosome anomalies in the newborn are a consequence of constitutional changes in the germ cells and zygote. Broadly, these fall into two categories-changes in numbers of chromosomes and changes in the structure of individual chromosomes. A recent large survey showed the incidence of chromosome anomalies in live births in Edinburgh to be 6.67/1000, and similar values have been found in Canada, the U.S.A., and Denmark. Common number anomalies include trisomy-21 (causing Down syndrome) and an extra sex chromosome (giving XXY, XYY, or XXX). The somewhat rarer loss of one sex chromosome results in Turner syndrome. All of these ’The forum took place on March 16, 1976, under the chairmanship of Prof. E. Potam, F.R.S. A full report of the proceedings will be published m the October, 1977, issue of thelournal of Medical Genetics. P
takes the form of potential economic benefits for the N.H.S. It now appears that, given the right operation and, in particular, the right suturing material, shortstay surgery can also achieve impressively low recurrence-rates.
We are grateful to the patients and doctors who contributed to this research, to Mrs Elizabeth Murphy and Mrs Janet Cranage for dataprocessing, to the Northern Regional Health Authority for computing, and to the Department of Health and Social Security which supports
one of us (I.T.R.). Requests for reprints
should be sent to I.T.R., Medical Care Research Unit, University of Newcastle upon Tyne, 21 Claremont Place, Newcastle upon Tyne, NE2 4AA. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8.
Iles, J. D. H. Lancet, 1965, i, 751. Glassow, F. Can. med. Ass. J. 1973, 108, 308. Glassow, F. Ann. R. Coll. Surg. 1976, 58, 133. Devlin, H. B., Evans, D. S., Birkhead, J. S. Br. J. Surg. 1969, 56, 466. Marsden, A. J. ibid. 1958, 46, 234. Shuttleworth, K. E. D., Davis, W. H. Lancet, 1960, i, 126. Bradford Hill, A. Principles of Medical Statistics. London, 1971. Morris, D., Ward, A. W. M., Handyside, A. J. Lancet, 1968, i, 681.
usually the result of new mutation and are seldom transmitted. The overall frequency in human populations is about 5 per 1000. Structural rearrangements include deletions, ring formation, inversions, and translocations. Translocations can be balanced (with no loss of genetic information) or unbalanced (with loss or gain). In a normal population, balanced translocations occur at a frequency of 1-9/1000 and unbalanced translocations at 05/1000. Unbalanced translocations usually cause serious handicap and are seldom transmitted. Balanced translocations are transmissible as such or may result in chromosomally unbalanced children. Fertility is reduced by about 15% in people with balanced translocations. are
CHROMOSOME ANOMALIES IN MISCARRIAGES AND
STILLBIRTHS
The numbers of chromosome anomalies reported in spontaneous abortions vary considerably. The major factor influencing the proportion of abnormalities is the gestational age of the abortions. An estimated 50% of all recognised spontaneous abortions are chromosomally abnormal. Chromosome aberrations are also found in about 8/1000 stillbirths and about 6/1000 neonatal deaths. If it is assumed that in 1000 pregnancies there are 150 spontaneous abortions, 10 stillbirths, and 840 live births (of which 10 are neonatal deaths), the total frequency of fetal and neonatal deaths from chromosome anomalies is about 75 per 1000 pregnancies, the great majority of which arise as new mutations. MONOGENIC DISORDERS
Monogenic disorders include those caused by dominant genes and those caused by recessive genes. There are very many of these conditions, most of which are individually rare. The overall incidence of monogenic disorders is about 10/1000 live births, comprising about 7/1000 dominants, about 25/1000 recessives, and about 0-4/1000 X-linked conditions. Common dominant conditions are polycystic kidney disease and monogenic hypercholesterolsemia. Examples of common recessive conditions are cystic fibrosis and sickle-cell ansemia. The commonest X-linked condition is Duchenne muscular
850
The reason for the relatively high frequency of some dominant conditions is probably largely a reflection of their relatively late clinical onset and hence small effect on reproductive fitness. There is no need to postulate an improbably high mutation-rate for them. Estimated mutation-rates in man for dominant and X-linked conditions lie between 10-5 and 10-6, with greater values only for neurofibromatosis, polycystic disease of the kidneys, haemophilia, and Duchenne muscular dys-
dystrophy.
trophy. CONGENITAL MALFORMATIONS AND CHILDHOOD NEOPLASMS
The total incidence of potentially handicapping or lethal congenital malformations is about 2.4%. Overall, about two-thirds of affected children survive to 5 years. The percentage of brothers and sisters affected by the same malformation as the patient lies between 2% and 5%. In pyloric stenosis and hip dislocation, which are very much commoner in one sex than the other, the risk of a younger sibling having the condition seems to be rather higher when the patient is of the sex less often affected. These and other findings indicate that each common defect involves a mul:iplicity of factors, some genetic and others environmental. The risks of recurrence in a family-i.e., in a brother or sister-are all much lower than would be expected if single genes of major effect were involved, and this suggests that the part played by new mutation in causing cases is small. It has been estimated that 1-36/1000 children born alive present with a malignant neoplasm before they are 15 years old. About one-thirtieth of these have retinoblastoma, of which nearly half the cases are thought to be due to an autosomal dominant gene. None of the commoner childhood cancers occurs more than 10 times as often in siblings as in the general population. The familial concentration of these other childhood cancers is even smaller than for the more common malformations, which suggests that the role of the genotype in aetiology may also be smaller. THE
MAJOR
PSYCHOSES
Schizophrenia and manic-depressive illness are the major mental disorders of adult life in which genetic factors have been established as playing an important part. The life-time expectancy for someone from the general population developing schizophrenia is probably about 1%. The total expectancy for schizophrenia and affective psychoses is about 5% and for senile dementia about 2-5%, given survival to age 80. Most current theories do not assume that disorders like schizophrenia are maintained in the population by new mutations. The genes involved probably have multiple alleles. If the aetiology of psychoses is multifactorial, their frequency may be relatively insensitive to changes in mutation-rate. ISCHAEMIC HEART-DISEASE
Ischaemic heart-disease kills 1 in 4 of the population, and 1 man in 10 dies from this disease before the age of 65. The disease has a large genetic component, probably involving multiple genes. The genetic component in the aetiology of ischaemic heart-disease certainly interacts with environmental factors. Radiation therefore may affect the incidence, but since the disease is common it is difficult to say in what manner or to what degree.
RADIOLOGICAL PROTECTION AND ASSESSMENT OF HEREDITARY DAMAGE
One method used to assess radiation-induced hereditary damage is based in the concept of the "doubling dose"-i.e., the radiation dose which doubles the natural mutation frequency. This can be determined in controlled experiments on animals, especially mice. The value is then applied directly to data on the frequencies of various hereditary diseases in man. The assumption that doubling doses determined for different gene mutations and chromosome changes in mice can be applied across the whole range of human genetic disease requires further validation. However, the use of a single doubling dose for several mutation end-points does have some experimental support. Values commonly used for doubling doses for X rays and gamma rays are 30 rad for acute exposures and 100 rad for chronic irradiation of mice of either sex. Surveys of survivors of the atomicbomb explosions at Hiroshima and Nagasaki suggest that doubling doses are at least as great as these values. However, there is some evidence that much smaller doses can double the number of chromosome aberrations in conceptuses. DISCUSSION
To estimate the risk of hereditary damage from ionisthe genetically determined diseases to be
ing radiation, considered
are those whose frequency is closely linked to the mutation-rate as estimated from the incidence in live births. These disorders, most of which are serious, include those arising from numerical chromosome anomalies (about 5/1000), the dominant monogenic disorders (about 7/1000), and some disorders resulting from structural chromosomal rearrangements (about 2/1000), giving a total frequency of about 14 per thousand live births. The doubling-dose concept might be applied to such disorders. If, for chronic irradiations with X or gamma rays, the doubling-dose is 100 rad, a total of 140 cases of these hereditary diseases would occur in one million people of child-bearing age exposed to 1 rad. The question of whether multifactorial disorders should be considered in assessing the risks of ionising radiations is one of semantics, for if multifactorial dis-
maintained
by mutations, they are essentially example, there are genetic and environmonogenic. mental components in the aetiology of ischaemic heartdisease, and a fraction of the total incidence is actually maintained by new mutation, because this fraction is a monogenic disease-for example, so-called essential familial hypercholesterolsemia. With regard to polygenic conditions in general, there is still dispute over the eases are
For
increased mutation-rate would affect If they are largely maintained by frequency. new mutation it would not be unrealistic to employ the doubling-dose concept. The dominant monogenic conditions have special importance in assessing radiation effects. The relationship between mutation-rate and birth frequency is relatively direct, the theoretical equilibrium birth frequency being the product of twice the mutation-rate and the mean persistence (in terms of generations) of each mutant gene. Any increase in mutation-rate will be reflected at once by an increase in the birth frequency of fresh cases of such dominant conditions born to unaffected parents. Recessive monogenic conditions must also be considered. extent to
their
which
an
851
However, many believe that the
more common of these diseases are (or were recently) maintained at their frequency level by heterozygous advantage rather than by new mutations. Moreover, the interval between the occurrence of a recessive mutation in a gene and the birth of the affected subject may be long-centuries or even millenia. It is now becoming possible to visualise ways of controlling the frequency of recessive gene disorders-i.e., the future carriers will be identified and, where appropriate, offered prenatal screening. Therefore, in the future the incidence of recessive gene disorders is likely to change. Requests for reprints should be addressed to J.V. M.R.C.
Radiobiology Unit,
Harwell, Didcot,
PATRICIA ASH
Oxon. OX11 0RD
J. VENNART
M.R.C. Clinical Genetics Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH
Commentary
C. O. CARTER
from Westminster
Preventive Medicine FROM A CORRESPONDENT
WHEN the Department of Health and Social Security published its discussion document, Prevention and Health: Everybody’s Business, last year it did not get the attention it deserved. This was hardly surprising since it was published on the day Sir Harold Wilson announced his resignation as Prime Minister. No such ill luck befell the Commons Expenditure Committee last week when it produced its report on preventive medicine which, with its two volumes of evidence, ran to almost 1000 pages. After an investigation lasting sixteen months, during which it took oral evidence from 30 groups and individuals and written evidence from many more, the committee has come up with 58 recommendations dealing with issues varying from smoking, drinking, diet, and exercise, to reorganising the National Health Service, building more health centres, and improving the career structure for doctors in community medicine. The conclusions are as wide-ranging as the subject of the committee’s inquiry. But what, if any will be the effect of the report on Government policy or public opinion? In many respects the Government is ahead of public opinion, and in pressing Ministers to support preventive medicine the committee is largely preaching to the converted. Under Dr David Owen’s guiding hand as Minister of State for Health the D.H.S.S. committed itself to prevention, issuing its little red book, holding a symposium last summer and publishing a series of discussion documents on separate issues. So what the committee has attempted to do is to concentrate on areas where a small diversion of resources might have an impact in the short term. The report considers the various strategies open to Government and suggests that although compulsion by legislation and by selective pricing policies have their part to play, education is the preferable way forward. "Getting the message through to the people most at risk" was one of the main problems which the committee encountered. To those who doubt the value of this approach, it points to a gleam of hope: health education appears to be having an impact in socioeconomic
groupsand n, many of whom, for up
instance, have given
smoking.
One of the committee’s first recommendations, therefore, is that the Government give increasing support to the Health Education Council, which in recent years has tended to feel ignored. Now, after its recent additional grant of [,1 million, its annual budget is around ,3 million. Great stress is also laid on the part radio and television can play, and one suggestion is the resurrection of programmes like the Radio Doctor. Relatively few general practitioners, says the committee, are interested in health education. The professional bodies should take steps to improve this situation; and the report points out that the Health Education Council now has a joint working-party with the British Medical Association to consider a system which would give G.P.S some financial incentive to do preventive work. Another proposal is for the establishment of more health centres. But public attention will be focused more on the committee’s consideration of specific topics. The M.p.s reserve their harshest action for cigarette smoking, which both the Health Education Council and the B.M.A. indicate as their first priority targets. The B.M.A. declared in its evidence: "The encouragement of a non-smoking community is probably the single most urgent task now facing preventive medicine and the community which it serves". The committee responds with a battery of proposals on which it appears to have been greatly influenced by what has happened in Scandinavian countries. Although to some extent they have been pipped at the post by the action announced by Mr David Ennals, Secretary of State for Social Services, the M.p.s are demanding much tougher measures. They want to see legislation to ban all tobacco advertising except at the point of sale, an increase in the price of cigarettes each year, the abolition of cigarette coupons, stronger health warnings on packets, and an end to cigarette machines on the streets. Significantly this part of the report caused the most dissension in committee and indeed the proposal for an annual increase in duty was approved only on the casting vote of the chairman of the full committee. Cigarette smoking, the M.p.s contend, is a greater evil than alcohol, whose consumption in moderation, they agree, is harmless and even beneficial-at least sufficiently so to persuade one committee member to switch from total abstinence to a brandy a night. The committee’s recommendations are a mixed bag of educative measures, such as using television more extensively and spending more on educating children and other young people, and the price mechanism, with the plea that prices should remain at the same level relative to average incomes as they are now. Elsewhere in its report the committee supports the further development of day-care abortion units, measures to improve dental health, better diet, more exercise, and the early introduction of a national screening service for women most at risk from breast cancer. On the thorny question of finance, the committee says that any increased expenditure on prevention must be at the expense of some other programme and it recommends that more of the State resources at present going to high-technology medicine should be reallocated. When it comes to priorities the M.p.s considered smoking and the need for research, but finally decided that concentration of resources on children would bring the most reward.
only 0-8%. Although the fact that this statistic is based on only 263 patients suggests the need for caution in interpretation, this rate does not differ significantly from the corresponding rate of 0-4% achieved by the Shouldice Clinic, a Canadian hospital which specialises in elective herniorrhaphy.1-3 Moreover, our results are strikingly better than the 3-year recurrence-rate of 7-0% reported by Marsdenand the temporally less-welldefined rate of 14.3% reported from St. Thomas’s Hospital (Both these papers were concerned with a variety of operations and with traditional lengths of stay but differed in their definitions of a recurrence: we adopted Marsden’s criterion.) In contrast, the 86 cases in which a polyester suture material was used showed an estimated 2-year recurrence-rate of 8.1 1%-far worse than the Shouldice Clinic results but comparable to those of rate is
Marsden.5 We have previously concluded that, although day-case surgery has no early clinical, social, or financial disadvantages for the hernia patient, its major advantage
Occasional
Survey
THE INCIDENCE OF HEREDITARY DISEASE IN MAN
GENE mutations, chromosome aberrations, and changes in the chromosome number occur spontaneously, and some result in abnormalities in the offspring, ranging from mildly detrimental to severely disabling or lethal. Such effects can also be induced by environmental mutagens, including ionising radiations. There is particular concern at the present time about the possible effects of ionising radiations arising from the generation of nuclear power. When estimates of the frequency of radiation-induced hereditary defects in human populations are provided for purposes of radiological protection they are ordinarily based on what is known about the spontaneous incidence of hereditary disease. The Medical Research Council’s Committee on Protection against Ionising Radiations last year organised a forum meeting, at which were discussed the frequencies of hereditary diseases, their severity, the extent to which they are maintained by new mutation, and their transmissibility. The topics discussed at the forum, which will also be of interest to those concerned with environmental mutagens other than ionising radiations, are presented below. CHROMOSOME ANOMALIES IN LIVE BIRTHS
Chromosome anomalies in the newborn are a consequence of constitutional changes in the germ cells and zygote. Broadly, these fall into two categories-changes in numbers of chromosomes and changes in the structure of individual chromosomes. A recent large survey showed the incidence of chromosome anomalies in live births in Edinburgh to be 6.67/1000, and similar values have been found in Canada, the U.S.A., and Denmark. Common number anomalies include trisomy-21 (causing Down syndrome) and an extra sex chromosome (giving XXY, XYY, or XXX). The somewhat rarer loss of one sex chromosome results in Turner syndrome. All of these ’The forum took place on March 16, 1976, under the chairmanship of Prof. E. Potam, F.R.S. A full report of the proceedings will be published m the October, 1977, issue of thelournal of Medical Genetics. P
takes the form of potential economic benefits for the N.H.S. It now appears that, given the right operation and, in particular, the right suturing material, shortstay surgery can also achieve impressively low recurrence-rates.
We are grateful to the patients and doctors who contributed to this research, to Mrs Elizabeth Murphy and Mrs Janet Cranage for dataprocessing, to the Northern Regional Health Authority for computing, and to the Department of Health and Social Security which supports
one of us (I.T.R.). Requests for reprints
should be sent to I.T.R., Medical Care Research Unit, University of Newcastle upon Tyne, 21 Claremont Place, Newcastle upon Tyne, NE2 4AA. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8.
Iles, J. D. H. Lancet, 1965, i, 751. Glassow, F. Can. med. Ass. J. 1973, 108, 308. Glassow, F. Ann. R. Coll. Surg. 1976, 58, 133. Devlin, H. B., Evans, D. S., Birkhead, J. S. Br. J. Surg. 1969, 56, 466. Marsden, A. J. ibid. 1958, 46, 234. Shuttleworth, K. E. D., Davis, W. H. Lancet, 1960, i, 126. Bradford Hill, A. Principles of Medical Statistics. London, 1971. Morris, D., Ward, A. W. M., Handyside, A. J. Lancet, 1968, i, 681.
usually the result of new mutation and are seldom transmitted. The overall frequency in human populations is about 5 per 1000. Structural rearrangements include deletions, ring formation, inversions, and translocations. Translocations can be balanced (with no loss of genetic information) or unbalanced (with loss or gain). In a normal population, balanced translocations occur at a frequency of 1-9/1000 and unbalanced translocations at 05/1000. Unbalanced translocations usually cause serious handicap and are seldom transmitted. Balanced translocations are transmissible as such or may result in chromosomally unbalanced children. Fertility is reduced by about 15% in people with balanced translocations. are
CHROMOSOME ANOMALIES IN MISCARRIAGES AND
STILLBIRTHS
The numbers of chromosome anomalies reported in spontaneous abortions vary considerably. The major factor influencing the proportion of abnormalities is the gestational age of the abortions. An estimated 50% of all recognised spontaneous abortions are chromosomally abnormal. Chromosome aberrations are also found in about 8/1000 stillbirths and about 6/1000 neonatal deaths. If it is assumed that in 1000 pregnancies there are 150 spontaneous abortions, 10 stillbirths, and 840 live births (of which 10 are neonatal deaths), the total frequency of fetal and neonatal deaths from chromosome anomalies is about 75 per 1000 pregnancies, the great majority of which arise as new mutations. MONOGENIC DISORDERS
Monogenic disorders include those caused by dominant genes and those caused by recessive genes. There are very many of these conditions, most of which are individually rare. The overall incidence of monogenic disorders is about 10/1000 live births, comprising about 7/1000 dominants, about 25/1000 recessives, and about 0-4/1000 X-linked conditions. Common dominant conditions are polycystic kidney disease and monogenic hypercholesterolsemia. Examples of common recessive conditions are cystic fibrosis and sickle-cell ansemia. The commonest X-linked condition is Duchenne muscular
850
The reason for the relatively high frequency of some dominant conditions is probably largely a reflection of their relatively late clinical onset and hence small effect on reproductive fitness. There is no need to postulate an improbably high mutation-rate for them. Estimated mutation-rates in man for dominant and X-linked conditions lie between 10-5 and 10-6, with greater values only for neurofibromatosis, polycystic disease of the kidneys, haemophilia, and Duchenne muscular dys-
dystrophy.
trophy. CONGENITAL MALFORMATIONS AND CHILDHOOD NEOPLASMS
The total incidence of potentially handicapping or lethal congenital malformations is about 2.4%. Overall, about two-thirds of affected children survive to 5 years. The percentage of brothers and sisters affected by the same malformation as the patient lies between 2% and 5%. In pyloric stenosis and hip dislocation, which are very much commoner in one sex than the other, the risk of a younger sibling having the condition seems to be rather higher when the patient is of the sex less often affected. These and other findings indicate that each common defect involves a mul:iplicity of factors, some genetic and others environmental. The risks of recurrence in a family-i.e., in a brother or sister-are all much lower than would be expected if single genes of major effect were involved, and this suggests that the part played by new mutation in causing cases is small. It has been estimated that 1-36/1000 children born alive present with a malignant neoplasm before they are 15 years old. About one-thirtieth of these have retinoblastoma, of which nearly half the cases are thought to be due to an autosomal dominant gene. None of the commoner childhood cancers occurs more than 10 times as often in siblings as in the general population. The familial concentration of these other childhood cancers is even smaller than for the more common malformations, which suggests that the role of the genotype in aetiology may also be smaller. THE
MAJOR
PSYCHOSES
Schizophrenia and manic-depressive illness are the major mental disorders of adult life in which genetic factors have been established as playing an important part. The life-time expectancy for someone from the general population developing schizophrenia is probably about 1%. The total expectancy for schizophrenia and affective psychoses is about 5% and for senile dementia about 2-5%, given survival to age 80. Most current theories do not assume that disorders like schizophrenia are maintained in the population by new mutations. The genes involved probably have multiple alleles. If the aetiology of psychoses is multifactorial, their frequency may be relatively insensitive to changes in mutation-rate. ISCHAEMIC HEART-DISEASE
Ischaemic heart-disease kills 1 in 4 of the population, and 1 man in 10 dies from this disease before the age of 65. The disease has a large genetic component, probably involving multiple genes. The genetic component in the aetiology of ischaemic heart-disease certainly interacts with environmental factors. Radiation therefore may affect the incidence, but since the disease is common it is difficult to say in what manner or to what degree.
RADIOLOGICAL PROTECTION AND ASSESSMENT OF HEREDITARY DAMAGE
One method used to assess radiation-induced hereditary damage is based in the concept of the "doubling dose"-i.e., the radiation dose which doubles the natural mutation frequency. This can be determined in controlled experiments on animals, especially mice. The value is then applied directly to data on the frequencies of various hereditary diseases in man. The assumption that doubling doses determined for different gene mutations and chromosome changes in mice can be applied across the whole range of human genetic disease requires further validation. However, the use of a single doubling dose for several mutation end-points does have some experimental support. Values commonly used for doubling doses for X rays and gamma rays are 30 rad for acute exposures and 100 rad for chronic irradiation of mice of either sex. Surveys of survivors of the atomicbomb explosions at Hiroshima and Nagasaki suggest that doubling doses are at least as great as these values. However, there is some evidence that much smaller doses can double the number of chromosome aberrations in conceptuses. DISCUSSION
To estimate the risk of hereditary damage from ionisthe genetically determined diseases to be
ing radiation, considered
are those whose frequency is closely linked to the mutation-rate as estimated from the incidence in live births. These disorders, most of which are serious, include those arising from numerical chromosome anomalies (about 5/1000), the dominant monogenic disorders (about 7/1000), and some disorders resulting from structural chromosomal rearrangements (about 2/1000), giving a total frequency of about 14 per thousand live births. The doubling-dose concept might be applied to such disorders. If, for chronic irradiations with X or gamma rays, the doubling-dose is 100 rad, a total of 140 cases of these hereditary diseases would occur in one million people of child-bearing age exposed to 1 rad. The question of whether multifactorial disorders should be considered in assessing the risks of ionising radiations is one of semantics, for if multifactorial dis-
maintained
by mutations, they are essentially example, there are genetic and environmonogenic. mental components in the aetiology of ischaemic heartdisease, and a fraction of the total incidence is actually maintained by new mutation, because this fraction is a monogenic disease-for example, so-called essential familial hypercholesterolsemia. With regard to polygenic conditions in general, there is still dispute over the eases are
For
increased mutation-rate would affect If they are largely maintained by frequency. new mutation it would not be unrealistic to employ the doubling-dose concept. The dominant monogenic conditions have special importance in assessing radiation effects. The relationship between mutation-rate and birth frequency is relatively direct, the theoretical equilibrium birth frequency being the product of twice the mutation-rate and the mean persistence (in terms of generations) of each mutant gene. Any increase in mutation-rate will be reflected at once by an increase in the birth frequency of fresh cases of such dominant conditions born to unaffected parents. Recessive monogenic conditions must also be considered. extent to
their
which
an
851
However, many believe that the
more common of these diseases are (or were recently) maintained at their frequency level by heterozygous advantage rather than by new mutations. Moreover, the interval between the occurrence of a recessive mutation in a gene and the birth of the affected subject may be long-centuries or even millenia. It is now becoming possible to visualise ways of controlling the frequency of recessive gene disorders-i.e., the future carriers will be identified and, where appropriate, offered prenatal screening. Therefore, in the future the incidence of recessive gene disorders is likely to change. Requests for reprints should be addressed to J.V. M.R.C.
Radiobiology Unit,
Harwell, Didcot,
PATRICIA ASH
Oxon. OX11 0RD
J. VENNART
M.R.C. Clinical Genetics Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH
Commentary
C. O. CARTER
from Westminster
Preventive Medicine FROM A CORRESPONDENT
WHEN the Department of Health and Social Security published its discussion document, Prevention and Health: Everybody’s Business, last year it did not get the attention it deserved. This was hardly surprising since it was published on the day Sir Harold Wilson announced his resignation as Prime Minister. No such ill luck befell the Commons Expenditure Committee last week when it produced its report on preventive medicine which, with its two volumes of evidence, ran to almost 1000 pages. After an investigation lasting sixteen months, during which it took oral evidence from 30 groups and individuals and written evidence from many more, the committee has come up with 58 recommendations dealing with issues varying from smoking, drinking, diet, and exercise, to reorganising the National Health Service, building more health centres, and improving the career structure for doctors in community medicine. The conclusions are as wide-ranging as the subject of the committee’s inquiry. But what, if any will be the effect of the report on Government policy or public opinion? In many respects the Government is ahead of public opinion, and in pressing Ministers to support preventive medicine the committee is largely preaching to the converted. Under Dr David Owen’s guiding hand as Minister of State for Health the D.H.S.S. committed itself to prevention, issuing its little red book, holding a symposium last summer and publishing a series of discussion documents on separate issues. So what the committee has attempted to do is to concentrate on areas where a small diversion of resources might have an impact in the short term. The report considers the various strategies open to Government and suggests that although compulsion by legislation and by selective pricing policies have their part to play, education is the preferable way forward. "Getting the message through to the people most at risk" was one of the main problems which the committee encountered. To those who doubt the value of this approach, it points to a gleam of hope: health education appears to be having an impact in socioeconomic
groupsand n, many of whom, for up
instance, have given
smoking.
One of the committee’s first recommendations, therefore, is that the Government give increasing support to the Health Education Council, which in recent years has tended to feel ignored. Now, after its recent additional grant of [,1 million, its annual budget is around ,3 million. Great stress is also laid on the part radio and television can play, and one suggestion is the resurrection of programmes like the Radio Doctor. Relatively few general practitioners, says the committee, are interested in health education. The professional bodies should take steps to improve this situation; and the report points out that the Health Education Council now has a joint working-party with the British Medical Association to consider a system which would give G.P.S some financial incentive to do preventive work. Another proposal is for the establishment of more health centres. But public attention will be focused more on the committee’s consideration of specific topics. The M.p.s reserve their harshest action for cigarette smoking, which both the Health Education Council and the B.M.A. indicate as their first priority targets. The B.M.A. declared in its evidence: "The encouragement of a non-smoking community is probably the single most urgent task now facing preventive medicine and the community which it serves". The committee responds with a battery of proposals on which it appears to have been greatly influenced by what has happened in Scandinavian countries. Although to some extent they have been pipped at the post by the action announced by Mr David Ennals, Secretary of State for Social Services, the M.p.s are demanding much tougher measures. They want to see legislation to ban all tobacco advertising except at the point of sale, an increase in the price of cigarettes each year, the abolition of cigarette coupons, stronger health warnings on packets, and an end to cigarette machines on the streets. Significantly this part of the report caused the most dissension in committee and indeed the proposal for an annual increase in duty was approved only on the casting vote of the chairman of the full committee. Cigarette smoking, the M.p.s contend, is a greater evil than alcohol, whose consumption in moderation, they agree, is harmless and even beneficial-at least sufficiently so to persuade one committee member to switch from total abstinence to a brandy a night. The committee’s recommendations are a mixed bag of educative measures, such as using television more extensively and spending more on educating children and other young people, and the price mechanism, with the plea that prices should remain at the same level relative to average incomes as they are now. Elsewhere in its report the committee supports the further development of day-care abortion units, measures to improve dental health, better diet, more exercise, and the early introduction of a national screening service for women most at risk from breast cancer. On the thorny question of finance, the committee says that any increased expenditure on prevention must be at the expense of some other programme and it recommends that more of the State resources at present going to high-technology medicine should be reallocated. When it comes to priorities the M.p.s considered smoking and the need for research, but finally decided that concentration of resources on children would bring the most reward.
