- Email: [email protected]
PIECEMEAL GENETICAL ENGINEERING
257
Erythema nodosum is the vivid clinical manifestation of a hypersensitivity state brought about by one or more precipitants. Whether the provocation be sulphathiazole, streptococci, the tubercle bacillus, or sarcoidosis, the ultimate development of erythema nodosum depends also on racial or constitutional predisposition, the hormonal background, and even geographical factors. It is common in women of childbearing years and in association with pregnancy and lactation. It is particularly evident among Irish women in London 16 and Puerto Rican immigrants in New York 17; and it has been found to be associated with coccidioidomycosis in the San Joachim valley of California, with histoplasmosis in Ohio, and with leprosy in Africa. In adults in Great Britain and Scandinavia, sarcoidosis is undoubtedly the commonest associated disorder. There being such a tangle of contributory factors, our ignorance of its pathogenesis is hardly surprising. In his pioneer studies L6FGREN 18 emphasised the interplay of factors-including pelvic inflammation, gallbladder disease, pregnancy, lactation, and the combination of streptococcal and tuberculous infectionwhich may lead to erythema nodosum. In any attempt to isolate one of the various known causes account must be taken of clinical associations, histological and bacteriological findings, chest radiography, and the results of Mantoux and Kveim skin tests. Thus, the presence of iritis, parotitis, facial palsy, or hypercalcaemia and hypercalciuria points to an association with sarcoidosis, just as recurrence after further provocative doses of sulphathiazole would suggest a pharmacological cause. The isolation of streptococci from the throat may be insufficient evidence, but a fourfold rise in the antistreptolysin titre between acute-phase and convalescentphase specimens of serum is highly suggestive of streptococcal infection as the cause. The main value of the Mantoux test is to detect conversion from a negative to a positive reaction to tuberculin. This would point strongly to primary tuberculosis as the cause, just as this would be virtually excluded by a persistently negative reaction. No categorical assumptions can be made from varying degrees of tuberculin hypersensitivity; most patients with Mantoux-positive sarcoidosis react only to 10 or 100 tuberculin units (r.u.), and in the few who are positive to 1 T.u. onset of tuberculosis is a more likely cause. Bilateral hilar lymphadenopathy, revealed by a chest radiograph, suggests sarcoidosis, whereas unilateral hilar lymphadenopathy may be part of a tuberculous Ghon focus. In the absence of histological confirmation by skin biopsy, it is difficult to obtain convincing proof of sarcoidosis by other means. The miliary granulomas observed in sections prepared from material obtained by aspiration of the liver are identical in sarcoidosis and tuberculosis; hence this blind biopsy technique is unhelpful in distinguishing between these two causes of erythema nodosum. On the other hand, the Kveim test has been shown to be specific and reliable in identifying cases of erythema nodosum due to sarcoidosis.19 The composition of any reported series of cases of 17. 18. 19.
Siltzbach, L. E. Amer. Rev. resp. Dis. 1961, 84, 22. Lofgren, S. Acta med. scand. 1946, 124, suppl. 174. James, D. G., Thomson, A. D., Willcox, A. Lancet, 1956, ii,
218.
erythema nodosum will reflect the discipline and personal interest of the author. Erythema nodosum was thought to be a manifestation of streptococcal infection in half and of sarcoidosis in a third of 70 cases observed by dermatologists,2O who concluded that the Kveim test would be helpful in cases of erythema nodosum of doubtful origin. The frequency of tuberculosis as a cause seems to be on the wane in children 21 and negligible in adults 16; instead, the predominant factors are streptococcal infection in all but the youngest children and sarcoidosis in adults. A follow-up postal questionary 21 suggested that, of 115 instances of erythema nodosum during 1948-58 in the Liverpool area, a fifth were due to tuberculosis; in 13% there was bilateral hilar lymphadenopathy, and in 8% a probable association with streptococcal infection. It is disconcerting to note that most large series include a high proportion of cases in which the cause has not been established. Routine radiographic examination of the chest, the Kveim test, and serial antistreptolysin titres should help to reveal the aetiology in some of these
..
"
cases, but a more imaginative approach be needed to shed light on the remaining hard core. may It would be uncharitable not to grant erythema nodosum some footing, at least temporarily, among the autoimmune disorders, particularly since it is commonly associated with many of the features regarded as markers of an autoimmunopathy —namely, raised and distorted serum-globulin levels, a prompt response to corticosteroids, immunological abnormalities involving cellular antibodies, false-positive serological reactions, and the occasional coexistence of Sjogren’s disease, Hashimoto’s thyroiditis, and hsemolytic anasmia. Perhaps circulating autoantibodies will be found in at least occasional cases of erythema nodosum.
idiopathic "
Annotations PIECEMEAL GENETICAL ENGINEERING
Family Planning-always a remarkably interesting journal-has just produced a tenth anniversary issue 24 in which Prof. P. B. Medawar says some important things very simply. Many medical readers will be helped by his distinction between " heroic eugenics ", whose ultimate purpose is to reshape the genetic constitution of mankind, and the less ambitious policy which he calls " piecemeal genetical engineering ", dedicated to the welfare of individual men and women and content to do good (as William Blake put it) in minute particulars ". The older eugenists hoped that, by one means or another, we might someday arrive at a population of uniformly excellent individuals who would breed true. But the conditions of man’s life are always changing, and a free-living population must always contain at least some members that can cope with new environments, new climates, and new enemies and infections. There is no one best genetic solution to the problem of remaining alive "
20. Vesey, C. M. R., Wilkinson, D. S. Brit. J. Derm. 1959, 71, 139. 21. A Group of Pædiatricians. Lancet, 1961, ii, 14. 22. Gordon, H. Brit. J. Derm. 1961, 71, 393. 23. Mackay, J. R. Gastroenterology, 1961, 40, 617. 24. Family Planning, January, 1962. Edited by Dr. David Pyke and Mrs. Medawar. From the Family Planning Association, 64, Sloane Square, London, S.W.1.
258
and perpetuating our kind; and, just as some livestock breeders are now returning to cross-breeding, eugenists are pointing to the importance of genetic diversity. Some regard the greater fertility shown by predominantly hybrid (or rather heterozygous) animals as an inbuilt genetic device which enforces genetic diversity.
All
welfare of human
beings are not binding on us in perirreversible, and if they turn out to be
petuity ; they faulty they can be revised ". are not
VACUUM EXTRACTION IN OBSTETRICS
FOR the mother
vacuum
extraction of the foetus is
geneticists agree that " fitness " in its most general apparently safe and effective, but according to mounting sense depends on a nicely balanced coordination and evidence the risk to the foetus is greater than was susinteraction of particular genetic factors; and breakdowns pected.l Many workers concede that foetal damage is or ineptitudes of the genetic apparatus, such as lead to possible,2-8 but some hold that scalp abrasion, skin necrodisease, are adventitious or accidental. But many genetic sis, or cephalhaematoma do not seriously threaten the life or defects are in principle manageable; and even when the health of the baby. Intracranial haemorrhage has been somatic consequences of a particular defect are manifold 59-11 but most workers hesitate to blame the described,3 and widespread, we can still, Professor Medawar says, instrument for this injury.6 indeed Snoeckand Rosa 12 in principle entertain the possibility of prevention or of calculate that intracranial stress and the risk of cerebral cure ". It is quite untrue to say that the congenital diseases are much less with vacuum extraction than haemorrhage cannot be cured: phenylketonuria and galactosaemia will with forceps delivery, but this view is challenged by be cured in the foreseeable future. Admittedly the patients de Boer. 13 will be left with a disability that debars them from eating Huntingford,8 who has used the extractor in the what they choose; and this is worse than the sort of management of delay in the first stage of labour, reports disability which obliges so many of us to wear spectacles; evidence of high foetal mortality and morbidity when the but it is not so much worse that we should be content to instrument is applied before the cervix is fully dilated. Of see its victims die. There are some inborn genetical dis11 babies 4 were severely asphyxiated at birth and required orders for which it is very difficult to envisage the intratracheal oxygen before respiration was established possibility of cure, and of these the most important is satisfactorily. 2 of the asphyxiated babies died shortly mongolism. But here one may take comfort from certain after birth, and 1 of the deaths was clearly due to intrademographic tendencies which will reduce the incidence of cranial haemorrhage. Of the 9 surviving babies 4 showed mongolism—one being the trend towards earlier marriage. evidence of cerebral irritation (irritability, photophobia, On the ways in which a policy of piecemeal genetical a high-pitched cry, neck stiffness, and a positive Moro’s engineering would work out, Professor Medawar thinks sign). These symptoms cleared within a few days, and that a great measure of agreement would be found among at early follow-up there was no indication of permanent geneticists. As regards the dominant " inborn diseases, neurological damage; the late results remain to be assessed. These findings, even though the numbers are small, throw some, such as achondroplasic dwarfism, cause great damage short of death, while others, such as Huntington’s grave doubt on the safety of vacuum extraction before the chorea and familial intestinal polyposis, become manifest cervix is fully dilated. Boon 14 15 reports significant foetal complications in a relatively late in life. Here the humane and rational policy is to warn the future victims of the disease (if they can be series of 160 cases delivered in the Kandang Kerbau identified) about the consequences of having children- Hospital, Singapore. 10% of the babies had severe half of whom are likely to be as much afflicted as themcephalhsematoma. The collection of blood in these cases selves. People who have sex-linked recessive diseases, crossed the suture-lines and was often associated with such as haemophilia, should be similarly warned of the severe jaundice and ansemia, 1 baby had to have a bloodto The hardest risks their descendants. transfusion. grave problems, Cephalhxmatoma was commoner and more however, arise from the many other recessive diseases, severe in this series than in others.10 16-19 15 babies had which remain latent unless one carrier marries another. signs of neurological involvement such as generalised To sterilise the afflicted would be useless, for they are stiffness, poor sucking reflex, hypotonia, or fits; they are of those who the and a small still being followed up, but already 2 apparently have proportion carry gene; only to discourage childbearing by all carriers would be to permanent brain damage. X-ray examination of the skulls commit racial suicide. But if it were possible to recognise of these 15 babies revealed diverse radiographic signs. the carriers of each recessive gene (perhaps because they Depressed fracture of the skull-bones at the site of applihave some trivial disorder biochemically akin to the full cation of the extractor was found in 4 of the 15; and recessive form) they could be discouraged from marrying erosion of the parietal bones, in the presence of severe each other; for, on the average, a quarter of their children cephalhaematoma, was noted in a further 6. In 1 case will have the disease and half will be carriers. This policy there was a quantity of air under the frontal bone besides would not contraindicate any large proportion of a depressed fracture and erosion of a parietal bone. Boon marriages, but it " would reduce the overt incidence of 1. See Lancet, 1961, ii, 189. 2. Rosa, P., Piraux, P. Bull. Soc. belge. Gynéc. Obstét. 1957, 27, 30. particular recessive diseases to a very low level indeed ". 3. Berggren, O. G. A. Acta obstet. gynec. scand. 1959, 38, 315. For the moment at least, Professor Medawar is inclined to 4. Evelbauer, K. Geburtsh. Frauenheilk. 1959, 19, 188. 5. Chalmers, J. A., Fothergill, R. J. Brit. med. J. 1960, i, 1684. dismiss the theoretical objection-namely, that, by deny6. Snoeck, J. Proc. R. Soc. Med. 1960, 53, 749. 7. Lauridsen, L. J. Obstet. Gynaec. Brit. Commonw. 1961, 68, 139. ing carriers a chance to marry one another, we should be 8. Huntingford, P. J. Lancet, 1961, ii, 1054. of lethal destruction the recessive gene by 9. Furstenberg, N., Soderhjelm, L. Nord. med. 1960, 64, 843. preventing 10. Hockuli, E., Stöckli, A. Geburtsh. Frauenheilk. 1960, 20, 346. disease or incapacity for reproduction. " The gene will 11. Smedley, G. T. Proc. R. Soc. Med. 1960, 53, 756. 12. Rosa, P. Bull. Soc. beige. Gynéc. Obstét. 1955, 25, 142. therefore be propagated in the population " and in the 13. de Boer, C. H. Lancet, 1961, ii, 875. 14. Boon, W. H. ibid. p. 662. very long run the carriers must have children by each 15. Boon, W. H. J. Singapore pœdiat. Soc. 1961, 3, 56. other if they are to have children at all. But, as he remarks, 16. Fothergill, R. J., Chalmers, J. A. Practitioner, 1961, 186, 559. 17. Barben, H. P. Schweiz. med. Wschr. 1958, 88, 1155. on the time scale of human evolution " the proposals that 18. Amosy, G., Ahlander, K. Nord. med. 1960, 64, 839. we may make today about safeguarding the genetic 19. de Azevedo, G. Portug. med. 1959, 43, 75. "
"
u.
u.
Erythema nodosum is the vivid clinical manifestation of a hypersensitivity state brought about by one or more precipitants. Whether the provocation be sulphathiazole, streptococci, the tubercle bacillus, or sarcoidosis, the ultimate development of erythema nodosum depends also on racial or constitutional predisposition, the hormonal background, and even geographical factors. It is common in women of childbearing years and in association with pregnancy and lactation. It is particularly evident among Irish women in London 16 and Puerto Rican immigrants in New York 17; and it has been found to be associated with coccidioidomycosis in the San Joachim valley of California, with histoplasmosis in Ohio, and with leprosy in Africa. In adults in Great Britain and Scandinavia, sarcoidosis is undoubtedly the commonest associated disorder. There being such a tangle of contributory factors, our ignorance of its pathogenesis is hardly surprising. In his pioneer studies L6FGREN 18 emphasised the interplay of factors-including pelvic inflammation, gallbladder disease, pregnancy, lactation, and the combination of streptococcal and tuberculous infectionwhich may lead to erythema nodosum. In any attempt to isolate one of the various known causes account must be taken of clinical associations, histological and bacteriological findings, chest radiography, and the results of Mantoux and Kveim skin tests. Thus, the presence of iritis, parotitis, facial palsy, or hypercalcaemia and hypercalciuria points to an association with sarcoidosis, just as recurrence after further provocative doses of sulphathiazole would suggest a pharmacological cause. The isolation of streptococci from the throat may be insufficient evidence, but a fourfold rise in the antistreptolysin titre between acute-phase and convalescentphase specimens of serum is highly suggestive of streptococcal infection as the cause. The main value of the Mantoux test is to detect conversion from a negative to a positive reaction to tuberculin. This would point strongly to primary tuberculosis as the cause, just as this would be virtually excluded by a persistently negative reaction. No categorical assumptions can be made from varying degrees of tuberculin hypersensitivity; most patients with Mantoux-positive sarcoidosis react only to 10 or 100 tuberculin units (r.u.), and in the few who are positive to 1 T.u. onset of tuberculosis is a more likely cause. Bilateral hilar lymphadenopathy, revealed by a chest radiograph, suggests sarcoidosis, whereas unilateral hilar lymphadenopathy may be part of a tuberculous Ghon focus. In the absence of histological confirmation by skin biopsy, it is difficult to obtain convincing proof of sarcoidosis by other means. The miliary granulomas observed in sections prepared from material obtained by aspiration of the liver are identical in sarcoidosis and tuberculosis; hence this blind biopsy technique is unhelpful in distinguishing between these two causes of erythema nodosum. On the other hand, the Kveim test has been shown to be specific and reliable in identifying cases of erythema nodosum due to sarcoidosis.19 The composition of any reported series of cases of 17. 18. 19.
Siltzbach, L. E. Amer. Rev. resp. Dis. 1961, 84, 22. Lofgren, S. Acta med. scand. 1946, 124, suppl. 174. James, D. G., Thomson, A. D., Willcox, A. Lancet, 1956, ii,
218.
erythema nodosum will reflect the discipline and personal interest of the author. Erythema nodosum was thought to be a manifestation of streptococcal infection in half and of sarcoidosis in a third of 70 cases observed by dermatologists,2O who concluded that the Kveim test would be helpful in cases of erythema nodosum of doubtful origin. The frequency of tuberculosis as a cause seems to be on the wane in children 21 and negligible in adults 16; instead, the predominant factors are streptococcal infection in all but the youngest children and sarcoidosis in adults. A follow-up postal questionary 21 suggested that, of 115 instances of erythema nodosum during 1948-58 in the Liverpool area, a fifth were due to tuberculosis; in 13% there was bilateral hilar lymphadenopathy, and in 8% a probable association with streptococcal infection. It is disconcerting to note that most large series include a high proportion of cases in which the cause has not been established. Routine radiographic examination of the chest, the Kveim test, and serial antistreptolysin titres should help to reveal the aetiology in some of these
..
"
cases, but a more imaginative approach be needed to shed light on the remaining hard core. may It would be uncharitable not to grant erythema nodosum some footing, at least temporarily, among the autoimmune disorders, particularly since it is commonly associated with many of the features regarded as markers of an autoimmunopathy —namely, raised and distorted serum-globulin levels, a prompt response to corticosteroids, immunological abnormalities involving cellular antibodies, false-positive serological reactions, and the occasional coexistence of Sjogren’s disease, Hashimoto’s thyroiditis, and hsemolytic anasmia. Perhaps circulating autoantibodies will be found in at least occasional cases of erythema nodosum.
idiopathic "
Annotations PIECEMEAL GENETICAL ENGINEERING
Family Planning-always a remarkably interesting journal-has just produced a tenth anniversary issue 24 in which Prof. P. B. Medawar says some important things very simply. Many medical readers will be helped by his distinction between " heroic eugenics ", whose ultimate purpose is to reshape the genetic constitution of mankind, and the less ambitious policy which he calls " piecemeal genetical engineering ", dedicated to the welfare of individual men and women and content to do good (as William Blake put it) in minute particulars ". The older eugenists hoped that, by one means or another, we might someday arrive at a population of uniformly excellent individuals who would breed true. But the conditions of man’s life are always changing, and a free-living population must always contain at least some members that can cope with new environments, new climates, and new enemies and infections. There is no one best genetic solution to the problem of remaining alive "
20. Vesey, C. M. R., Wilkinson, D. S. Brit. J. Derm. 1959, 71, 139. 21. A Group of Pædiatricians. Lancet, 1961, ii, 14. 22. Gordon, H. Brit. J. Derm. 1961, 71, 393. 23. Mackay, J. R. Gastroenterology, 1961, 40, 617. 24. Family Planning, January, 1962. Edited by Dr. David Pyke and Mrs. Medawar. From the Family Planning Association, 64, Sloane Square, London, S.W.1.
258
and perpetuating our kind; and, just as some livestock breeders are now returning to cross-breeding, eugenists are pointing to the importance of genetic diversity. Some regard the greater fertility shown by predominantly hybrid (or rather heterozygous) animals as an inbuilt genetic device which enforces genetic diversity.
All
welfare of human
beings are not binding on us in perirreversible, and if they turn out to be
petuity ; they faulty they can be revised ". are not
VACUUM EXTRACTION IN OBSTETRICS
FOR the mother
vacuum
extraction of the foetus is
geneticists agree that " fitness " in its most general apparently safe and effective, but according to mounting sense depends on a nicely balanced coordination and evidence the risk to the foetus is greater than was susinteraction of particular genetic factors; and breakdowns pected.l Many workers concede that foetal damage is or ineptitudes of the genetic apparatus, such as lead to possible,2-8 but some hold that scalp abrasion, skin necrodisease, are adventitious or accidental. But many genetic sis, or cephalhaematoma do not seriously threaten the life or defects are in principle manageable; and even when the health of the baby. Intracranial haemorrhage has been somatic consequences of a particular defect are manifold 59-11 but most workers hesitate to blame the described,3 and widespread, we can still, Professor Medawar says, instrument for this injury.6 indeed Snoeckand Rosa 12 in principle entertain the possibility of prevention or of calculate that intracranial stress and the risk of cerebral cure ". It is quite untrue to say that the congenital diseases are much less with vacuum extraction than haemorrhage cannot be cured: phenylketonuria and galactosaemia will with forceps delivery, but this view is challenged by be cured in the foreseeable future. Admittedly the patients de Boer. 13 will be left with a disability that debars them from eating Huntingford,8 who has used the extractor in the what they choose; and this is worse than the sort of management of delay in the first stage of labour, reports disability which obliges so many of us to wear spectacles; evidence of high foetal mortality and morbidity when the but it is not so much worse that we should be content to instrument is applied before the cervix is fully dilated. Of see its victims die. There are some inborn genetical dis11 babies 4 were severely asphyxiated at birth and required orders for which it is very difficult to envisage the intratracheal oxygen before respiration was established possibility of cure, and of these the most important is satisfactorily. 2 of the asphyxiated babies died shortly mongolism. But here one may take comfort from certain after birth, and 1 of the deaths was clearly due to intrademographic tendencies which will reduce the incidence of cranial haemorrhage. Of the 9 surviving babies 4 showed mongolism—one being the trend towards earlier marriage. evidence of cerebral irritation (irritability, photophobia, On the ways in which a policy of piecemeal genetical a high-pitched cry, neck stiffness, and a positive Moro’s engineering would work out, Professor Medawar thinks sign). These symptoms cleared within a few days, and that a great measure of agreement would be found among at early follow-up there was no indication of permanent geneticists. As regards the dominant " inborn diseases, neurological damage; the late results remain to be assessed. These findings, even though the numbers are small, throw some, such as achondroplasic dwarfism, cause great damage short of death, while others, such as Huntington’s grave doubt on the safety of vacuum extraction before the chorea and familial intestinal polyposis, become manifest cervix is fully dilated. Boon 14 15 reports significant foetal complications in a relatively late in life. Here the humane and rational policy is to warn the future victims of the disease (if they can be series of 160 cases delivered in the Kandang Kerbau identified) about the consequences of having children- Hospital, Singapore. 10% of the babies had severe half of whom are likely to be as much afflicted as themcephalhsematoma. The collection of blood in these cases selves. People who have sex-linked recessive diseases, crossed the suture-lines and was often associated with such as haemophilia, should be similarly warned of the severe jaundice and ansemia, 1 baby had to have a bloodto The hardest risks their descendants. transfusion. grave problems, Cephalhxmatoma was commoner and more however, arise from the many other recessive diseases, severe in this series than in others.10 16-19 15 babies had which remain latent unless one carrier marries another. signs of neurological involvement such as generalised To sterilise the afflicted would be useless, for they are stiffness, poor sucking reflex, hypotonia, or fits; they are of those who the and a small still being followed up, but already 2 apparently have proportion carry gene; only to discourage childbearing by all carriers would be to permanent brain damage. X-ray examination of the skulls commit racial suicide. But if it were possible to recognise of these 15 babies revealed diverse radiographic signs. the carriers of each recessive gene (perhaps because they Depressed fracture of the skull-bones at the site of applihave some trivial disorder biochemically akin to the full cation of the extractor was found in 4 of the 15; and recessive form) they could be discouraged from marrying erosion of the parietal bones, in the presence of severe each other; for, on the average, a quarter of their children cephalhaematoma, was noted in a further 6. In 1 case will have the disease and half will be carriers. This policy there was a quantity of air under the frontal bone besides would not contraindicate any large proportion of a depressed fracture and erosion of a parietal bone. Boon marriages, but it " would reduce the overt incidence of 1. See Lancet, 1961, ii, 189. 2. Rosa, P., Piraux, P. Bull. Soc. belge. Gynéc. Obstét. 1957, 27, 30. particular recessive diseases to a very low level indeed ". 3. Berggren, O. G. A. Acta obstet. gynec. scand. 1959, 38, 315. For the moment at least, Professor Medawar is inclined to 4. Evelbauer, K. Geburtsh. Frauenheilk. 1959, 19, 188. 5. Chalmers, J. A., Fothergill, R. J. Brit. med. J. 1960, i, 1684. dismiss the theoretical objection-namely, that, by deny6. Snoeck, J. Proc. R. Soc. Med. 1960, 53, 749. 7. Lauridsen, L. J. Obstet. Gynaec. Brit. Commonw. 1961, 68, 139. ing carriers a chance to marry one another, we should be 8. Huntingford, P. J. Lancet, 1961, ii, 1054. of lethal destruction the recessive gene by 9. Furstenberg, N., Soderhjelm, L. Nord. med. 1960, 64, 843. preventing 10. Hockuli, E., Stöckli, A. Geburtsh. Frauenheilk. 1960, 20, 346. disease or incapacity for reproduction. " The gene will 11. Smedley, G. T. Proc. R. Soc. Med. 1960, 53, 756. 12. Rosa, P. Bull. Soc. beige. Gynéc. Obstét. 1955, 25, 142. therefore be propagated in the population " and in the 13. de Boer, C. H. Lancet, 1961, ii, 875. 14. Boon, W. H. ibid. p. 662. very long run the carriers must have children by each 15. Boon, W. H. J. Singapore pœdiat. Soc. 1961, 3, 56. other if they are to have children at all. But, as he remarks, 16. Fothergill, R. J., Chalmers, J. A. Practitioner, 1961, 186, 559. 17. Barben, H. P. Schweiz. med. Wschr. 1958, 88, 1155. on the time scale of human evolution " the proposals that 18. Amosy, G., Ahlander, K. Nord. med. 1960, 64, 839. we may make today about safeguarding the genetic 19. de Azevedo, G. Portug. med. 1959, 43, 75. "
"
u.
u.