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A Survey of Genetics
1023
retention of useful vision indicate that much more is to be expected from irradiation with cobalt than has so far been realised; and a more extensive trial of this form of treatment in preference to enucleation seems to be indicated. Histological examination of the 11 enucleated eyes has not so far revealed a firm correlation between the structure of the growth and its degree of radiosensitivity; but possibly more information on this aspect may be forthcoming when a larger series can be examined. A
Survey of Genetics
looking for a long-term research investment growth prospects, and prepared to accept immediate yields that may be interesting rather than practically profitable, should consider human genetics very closely. The discovery and control of environmental factors in disease is becoming-to exaggerate only a little-more and more a matter of assembly-line research. The builtin tendencies to disease must be tackled more deviously, and they will be longer with us. Growing realisation of this prospect, coupled with encouragement from some major advances in the past decade, has led the subject ANYONE
with
out of the somewhat musty back-rooms where it has lurked into something much more like the light of day. Young physicians attend conferences on genetics; primary membership examiners expect candidates to have heard of chromosomes; and an issue of the British Medical Bulletinis devoted to British work on the subject. The extent to which research workers in various fields are being driven to grapple with the genetic background is admirably illustrated by the fact that, of nineteen contributors to the Bulletin, only three are primarily geneticists. Even this issue’s editor, Dr. A. C. STEVENSON, came into genetics via public health, a chair of social medicine in Belfast, an interest in population studies, and so finally population genetics.
His own contribution2 is an apposite survey of the size of the problem-of the frequency of disease of genetic origin. So far as prenatal loss is concerned, about 30 out of every 100 conceptions fail to produce a live child (about half early losses, about half evident abortions, and about 2% stillbirths), and of these failures at least half are due to congenital malformations or other readily demonstrable defects of the ovum or foetus. Thus apparently at least 15% of all conceptions have inherent defects incompatible with live birth. Of liveborn infants, STEVENSON estimates that some 50 per 1000 have disabling congenital defects. Of these 50, 25 will have actual malformations, of which 15 will be recognised at birth and the majority by 5 years (though some malformations which are undeniably congenital and cause serious disease may go unrecognised till middle life-some cases of congenital cystic kidneys, for instance). Of these 25 cases of actual malformations, only 5 are due to recognised single-gene disordersconditions such as achondroplasia, microphthalmos, ichthyosis, and Marfan’s syndrome-while 20 must be regarded as unexplained " congenital deformities. "
1. British Medical 2. ibid. p. 254.
Bulletin, 1961, 17, no. 3. 20s.
Recognised maternal disease such as rubella is responsible for only a very small fraction of these. Of the remaining half of the 50-those without deformities8 are due to single-gene disorders which do not cause actual deformity (rather an artificial distinction in many cases): this group consists chiefly of a very large number of rare disorders, but includes such conditions as mucoviscidosis, the muscular dystrophies, phenylketonuria, and the abnormal haemoglobins. 4 are rhesus incompatibilities; another 4 (almost certainly an underestimate) are chromosomal anomalies. The remaining 9 are the severe disorders with important genetic components, such as diabetes, schizophrenia, and pernicious anaemia. The estimate of this rather nebulous category
might perhaps be expanded. But we must remember that STEVENSON is concerned only with defects that directly cause significant disease. Genetically definable deviations from the theoretical norm multiply so fast, and genetic factors in diseases not generally regarded as genetic (such as the influence of blood-groups in peptic ulcer) are emerging so frequently, that it is becoming defend the extreme view that no-one is congenitally normal, and no disease is altogether devoid of genetic basis. But 1 in 5 conceptions and 1 in 20 live births with genetic defects are high enough estimates to stomach for the present. ever
easier
to
Genetic advances recently have proceeded in three almost independent main directions, each of which is well represented in the Bulletin. Six papers on chromosome anomalies between them cover the ground very thoroughly, and are written by pioneers all of whose names will be very familiar to readers of The Lancet, where much of their original work has appeared in the past three years. Five papers on biochemical abnormalities represent a much more eclectic survey, but they are a good selection: papers on galactosaemia and pseudocholinesterase give representative accounts of two
elegant
recent
one-gene one-enzyme
demonstrations,
while broader surveys of plasma-proteins, aminoaciduria, and " pharmacogenetics " (i.e., inherited abnormalities in response to drugs) cover between them a great deal of ground. Prof. H. HARRis’3paper on plasma-proteins, though limited to those variations which can readily be demonstrated by electrophoresis, is an especially useful demonstration of the proliferation of differences between individuals even within a relatively small field, showing how near we are to proving a man’s biochemistry to be as individual as his fingerprints.
Fingerprints, reduced to mathematically amenable and demonstrating with most admirable precision the modes of inheritance expected of a simple multifactorial system,4 are an example of the third thread in terms
this Bulletin-the modern refinement of Galtonian mathematical techniques in the study of genetics. Most useful of these probably is Dr. J. A. FRASER ROBERTS’ account 5 of multifactorial inheritance, which makes this difficult and profoundly important subject seem almost
simple. 3. ibid. p. 217. 4. Holt, S. B. ibid. 5. ibid. p. 241.
p. 247.
retention of useful vision indicate that much more is to be expected from irradiation with cobalt than has so far been realised; and a more extensive trial of this form of treatment in preference to enucleation seems to be indicated. Histological examination of the 11 enucleated eyes has not so far revealed a firm correlation between the structure of the growth and its degree of radiosensitivity; but possibly more information on this aspect may be forthcoming when a larger series can be examined. A
Survey of Genetics
looking for a long-term research investment growth prospects, and prepared to accept immediate yields that may be interesting rather than practically profitable, should consider human genetics very closely. The discovery and control of environmental factors in disease is becoming-to exaggerate only a little-more and more a matter of assembly-line research. The builtin tendencies to disease must be tackled more deviously, and they will be longer with us. Growing realisation of this prospect, coupled with encouragement from some major advances in the past decade, has led the subject ANYONE
with
out of the somewhat musty back-rooms where it has lurked into something much more like the light of day. Young physicians attend conferences on genetics; primary membership examiners expect candidates to have heard of chromosomes; and an issue of the British Medical Bulletinis devoted to British work on the subject. The extent to which research workers in various fields are being driven to grapple with the genetic background is admirably illustrated by the fact that, of nineteen contributors to the Bulletin, only three are primarily geneticists. Even this issue’s editor, Dr. A. C. STEVENSON, came into genetics via public health, a chair of social medicine in Belfast, an interest in population studies, and so finally population genetics.
His own contribution2 is an apposite survey of the size of the problem-of the frequency of disease of genetic origin. So far as prenatal loss is concerned, about 30 out of every 100 conceptions fail to produce a live child (about half early losses, about half evident abortions, and about 2% stillbirths), and of these failures at least half are due to congenital malformations or other readily demonstrable defects of the ovum or foetus. Thus apparently at least 15% of all conceptions have inherent defects incompatible with live birth. Of liveborn infants, STEVENSON estimates that some 50 per 1000 have disabling congenital defects. Of these 50, 25 will have actual malformations, of which 15 will be recognised at birth and the majority by 5 years (though some malformations which are undeniably congenital and cause serious disease may go unrecognised till middle life-some cases of congenital cystic kidneys, for instance). Of these 25 cases of actual malformations, only 5 are due to recognised single-gene disordersconditions such as achondroplasia, microphthalmos, ichthyosis, and Marfan’s syndrome-while 20 must be regarded as unexplained " congenital deformities. "
1. British Medical 2. ibid. p. 254.
Bulletin, 1961, 17, no. 3. 20s.
Recognised maternal disease such as rubella is responsible for only a very small fraction of these. Of the remaining half of the 50-those without deformities8 are due to single-gene disorders which do not cause actual deformity (rather an artificial distinction in many cases): this group consists chiefly of a very large number of rare disorders, but includes such conditions as mucoviscidosis, the muscular dystrophies, phenylketonuria, and the abnormal haemoglobins. 4 are rhesus incompatibilities; another 4 (almost certainly an underestimate) are chromosomal anomalies. The remaining 9 are the severe disorders with important genetic components, such as diabetes, schizophrenia, and pernicious anaemia. The estimate of this rather nebulous category
might perhaps be expanded. But we must remember that STEVENSON is concerned only with defects that directly cause significant disease. Genetically definable deviations from the theoretical norm multiply so fast, and genetic factors in diseases not generally regarded as genetic (such as the influence of blood-groups in peptic ulcer) are emerging so frequently, that it is becoming defend the extreme view that no-one is congenitally normal, and no disease is altogether devoid of genetic basis. But 1 in 5 conceptions and 1 in 20 live births with genetic defects are high enough estimates to stomach for the present. ever
easier
to
Genetic advances recently have proceeded in three almost independent main directions, each of which is well represented in the Bulletin. Six papers on chromosome anomalies between them cover the ground very thoroughly, and are written by pioneers all of whose names will be very familiar to readers of The Lancet, where much of their original work has appeared in the past three years. Five papers on biochemical abnormalities represent a much more eclectic survey, but they are a good selection: papers on galactosaemia and pseudocholinesterase give representative accounts of two
elegant
recent
one-gene one-enzyme
demonstrations,
while broader surveys of plasma-proteins, aminoaciduria, and " pharmacogenetics " (i.e., inherited abnormalities in response to drugs) cover between them a great deal of ground. Prof. H. HARRis’3paper on plasma-proteins, though limited to those variations which can readily be demonstrated by electrophoresis, is an especially useful demonstration of the proliferation of differences between individuals even within a relatively small field, showing how near we are to proving a man’s biochemistry to be as individual as his fingerprints.
Fingerprints, reduced to mathematically amenable and demonstrating with most admirable precision the modes of inheritance expected of a simple multifactorial system,4 are an example of the third thread in terms
this Bulletin-the modern refinement of Galtonian mathematical techniques in the study of genetics. Most useful of these probably is Dr. J. A. FRASER ROBERTS’ account 5 of multifactorial inheritance, which makes this difficult and profoundly important subject seem almost
simple. 3. ibid. p. 217. 4. Holt, S. B. ibid. 5. ibid. p. 241.
p. 247.