- Email: [email protected]
Biology of the Trachoma Agent
30
beautifully with the sex-chromatin findings; and, indeed, the hypothesis is derived directly from It all fits
OHNo’s views of the sex chromatin.2 All active chromosomal material in the nucleus, including the working X, is extended during the so-called " resting phase " of the nucleus to form the indistinct background chromatin. Unemployed Xs condense to form sex-chromatin masses. Hence the number of the bodies is always just one less than the number of X chromosomes present, except in polyploid cells, where each extra autosome set calls for an extra working X chromosome.13 The sex chromosome acts as a unique marker for the X chromosome simply because the whole mechanism is unique to the X chromosome. LYON has suggested that the inactivation of surplus X chromosomes occurs about the 12th day, when sexchromatin bodies become visible,144 and is purely random. At this time the precursor cells of many tissues are not very numerous: this could readily account for such phenomena as the patchiness of skin colour in mice heterozygotes, each patch representing the progeny of a single cell with an active X of one or other type. Moreover, if the definitive cells are few, random allocation to two classes may give rise to many cases where the distribution is far from the expected 50 : 50, which may explain the variations in expression in female heterozygotes. It must be supposed, for instance, that in the average female carrier of colour blindness half the cones are normal and half colour-blind, and that this suffices for almost normal colour vision: but that wide variation can occur in the proportion of cells of the two types, which may account for the great range of colour vision found in such carriers. There is another respect in which this is a very satisfying explanation. The differences between male and female in man (as in most species), however conspicuous or however important in practice, are not really profound. A simple yes-no decision, some time before the 40th day, as to whether the germ cells are to develop in the cortex or the medulla of the primitive gonad, is all that is necessary: everything important follows from it. It has always seemed altogether out of proportion that this small difference should be represented by a whole chromosome. The Y, small and the carrier of little if anything beyond its testicular organiser, is precisely adapted to its function. The large X, packed with active genes, should give rise to enormous differences between the sexes. At least we know now why it does not produce them: it is simply rendered inactive. What we do not know is why the second X need be there at all. In man its absence gives rise to Turner’s syndrome, but this is not a general phenomenon, for the XO mouse is a normal fertile female. A function for the second X might be regarded as the next major problem in this field. GRUMBACH et al. believe, with OHNO,2 that the inactivation of the surplus X chromosome may be only the most conspicuous example of a more general phenomenon. They refer to unpublished work, using 13. Lennox, B. Brit. med. Bull. 1961, 17, 196. 14. Park, W. W. J. Anat. 1957, 91, 369.
tritiated thymidine, which indicates that D.N.A. synthesis in the inactive X chromosome is notably out of step with the remainder, but that lesser differences occur among the autosomes. It may be that such lesser differences, probably reversible in part, and associated with intermitotic condensation of the chromosomes concerned, may result in blocking off of parts of chromosomes from normal activity and hence in differentiation between cells. This is a fascinating possibility, though it cannot be regarded as more than
speculation at present. One final point from a recent contribution: MACLEAN’S review 15 from Edinburgh of the behaviour of the polymorph drumsticks in various X-chromosome disorders can be said finally to have disposed of any doubt that these bodies are simply a variant of the sex chromatin.
Biology of the
Trachoma
Agent
resembling morphology the virus-like microorganisms of the psittacosis-lymphogranuloma (P.-L.) group, which can be grown in embryonate eggs in
ALTHOUGH
and cell cultures, the agents of trachoma and of the closely allied inclusion-blennorrhoea syndrome for long resisted attempts at cultivation in the laboratory. Indeed, half a century was to elapse between the original description of trachoma inclusion bodies,16 and isolation of a virus in the chick embryo yolk sac by T’ANG and others 17 in 1957. As soon as this had been accomplished, however, progress was rapid; so much so that last year the New York Academy of Sciences convened a conference on the biology of the trachoma agent, with the object of summarising and coordinating the considerable information gained by many workers in various countries. The published proceedings,18 which include papers from laboratories in the United States, the United Kingdom, Gambia, Israel, South Africa, Japan, Formosa, and Saudi Arabia, reflect the general quickening of interest in this area of research. From the opening session on isolation methods, it transpired that trachoma viruses have now been isolated in many countries where the disease is endemic; apparently identical viruses have been isolated in England and America from patients with inclusion blennorrhoea. These agents closely resemble each other in morphology and staining characteristics, in their ability to grow in the chick-embryo yolk sac, and in their resistance to streptomycin. Furthermore, they contain the heatstable complement-fixing antigen common to the P.-L. group, of which they appear to be typical members. Despite its title, the conference did not therefore concern itself exclusively with the trachoma agent, but considered related microorganisms when necessary for comparison or contrast.
It has
been
suspected that the P.-L. agents do behave as typical viruses, and this supposition is amply conformed by studies on the trachoma/inclusionlong
not
15. 16. 17. 18.
Maclean, N. Lancet. 1962, i, 1154. Halberstaedter, L., von Prowazek, S. Arb. GesundhAmt., Berlin, 1907, 26, 44. T’ang, F. F., Chang, H. L., Huang, Y. T., Wang, K. C. Chin. med. J. 1957, 75, 429. Ann. N.Y. Acad. Sci. 1962, 98, 1-382.
31
blennorrhoea microorganisms. Many techniques have been used to investigate their mode 0 reproduction in cultured cells and in chick embryos, including infectivity measurements, light and electron microscopy, and
cytochemical procedures .19-2.1
It
seems
generally agreed
that the infecting particle is an " elementary body ", rich in deoxyribonucleic acid (D.N.A.); under the electron microscope it appears as a dense-centred particle about 0,3 !k in diameter. After entering the host cell it loses infectivity. Some hours later, a larger " initial body " appears within the cytoplasm. This form gives the staining reaction for ribonucleic acid (R.N.A.) and has little or no infectivity; by a process that is not clearly understood, the initial body gives rise to a further generation of elementary bodies which form the mature cytoplasmic inclusion and which are capable of initiating a further cycle of infection on release from the cell. Although several aspects of this complex series of events have still to be elucidated, enough has been learned to make it clear that the P.-L. agents occupy a special taxonomic position. In their obligate intracellular habitat and loss of infectivity in the early stages of replication, they resemble the viruses; whereas closer affinity with the bacteria is suggested by the presence of both forms of nucleic acid, a cell wall containing muramic acid and various aminoacids, the possible occurrence of fission in the later stage of multiplication, and susceptibility to sulphonamides and some antibiotics. Nevertheless, for want of a better term, it is still customary to call these infective agents viruses. Investigations of the action of various anti-metabolites hold particular interest for the clinician. In general, the testing of antibiotics for anti-trachoma activity in vitro or in ovo gives the results to be expected from knowledge of their therapeutic efficacy in man; thus, the tetracycline compounds inhibit the later stages of replication in cell cultures,20 whereas penicillin merely delays tnattIration.20 21 On the other hand, the laboratory evidence for the antiviral activity of streptomycin 26 or the sulphonamides 20 27 is conflicting and seems to be influenced by the particular host/virus system employed. Two new substances were reported to have antitrachoma activity in laboratory tests. Tylosin tartrate acts like the tetracyclines in infected cell cultures 20; Nitractin,’ although weight for weight less active than several other therapeutic substances, is virtually nontoxic for labotatory animals, and has the advantage of acting as a repository drug,27 a useful attribute for treating trachoma in the field. Apart from their value for exploring the complicated chemical events in viral synthesis, these investigations already give promise of more effective drugs for the treatment of trachoma. As far as is known, conjunctival infection with trachoma and inclusion blennorrhoea can be induced 19. Collier, L. H. ibid. p. 42. 20. Pollard, M., Tanami, Y. ibid. p. 50. 21. Bernkopf, H., Mashiah, P., Becker, Y. ibid. p. 62. 22. Moulder, J. W. ibid. p. 92. 23. Higashi, N., Tamura, A., Iwanaga, M. ibid. p. 100. 24. Mitsui, Y., Kajima, M., Nishimura, A., Konishi, K. ibid. 25. Litwin, J. ibid. p. 145. 26. Gordon, F. B., Quan, A. L. ibid. p. 261. 27. Hurst, E. W. ibid. p. 275.
p. 131.
only in primates, and many eye-to-eye inoculations were made in monkeys, apes, and baboons before these viruses were isolated in the laboratory. Recent investigations with cultured virus confirm earlier reports that inclusionblennorrhoea virus is more pathogenic than trachoma in apes and monkeys; unfortunately, however, the difference in the experimental syndromes is not sufficiently constant to make this a useful criterion for distinguishing these agents.28 29 Furthermore, pathogenicity of a given strain may be attenuated by repeated passage in chick embryos,29 and this must be borne in mind when appraising the results of primate inoculation. Since experiments in simian species cannot help in distinguishing between trachoma and inclusion-blennorrhoea viruses, inoculation of volunteers is necessary. One school, championed by THYGESON,30 concludes from clinical and experimental findings that these syndromes are quite distinct: trachoma is spread from eye to eye, and is characterised by corneal lesions, cicatrisation, and a long course; inclusion blennorrhoea (or conjunctivitis) is primarily a genital infection which may be transmitted to the adult eye, or to the infant eye at birth. In contrast totrachoma, the ophthalrriic infection resolves spontaneously in a comparatively short time without corneal lesions or scarring. Nevertheless, some workers maintain that there is no sharp line between these syndromes. Further evidence for this supposition, fully documented by photographs, was presented by JONES and COLLIER,31 who isolated an agent of the P.-i.. group from the eye of an English baby with typical inclusion blennorrhoea of the newborn; on inoculation into the eye of a blind adult volunteer, it induced follicular conjunctivitis with corneal lesions indistinguishable from trachoma. A fascinating aspect of recent researches, and one potentially important in the control of the disease, is the immunology of trachoma. The isolation of the causal agent aroused hopes of serological methods for use in diagnosis, and of preventive vaccines; and several communications to the conference bore directly on these problems. Although the complement-fixation test with heated group antigen seems of little use in diagnosis,32 one group of workers described the preparation of specific antigens that do not cross-react with sera from cases of lymphogranuloma venereum or of psittacosis, and which are more sensitive than group antigen for detecting antibodies in trachoma patients.33 In two laboratories, various strains of trachoma, when injected intravenously, were found to be toxic and lethal for mice; and this effect could be offset by prior immunisation of the mice with a suitable antigen.34 35 Crossprotection tests showed that most of the strains tested fell into two immunologically distinct groups; those examined by BELL and THEOBALD 34 were isolated in several countries, but there was no relation between the results of these tests and geographical distribution. It 28. 29. 30. 31. 32. 33. 34. 35.
Dawson, C. R., Mordhorst, C. H., Thygeson, P. ibid. p. 167. Collier, L. H. ibid. p. 188. Thygeson, P. ibid. p. 201. Jones, B. R., Collier, L. H. ibid. p. 212. Collier, L. H. ibid. p. 324. Woolridge, R. L., Grayston, J. T. ibid. p. 314. Bell, S. D., Theobald, B. ibid. p. 337. Chang, I., Wang, S., Grayston, J. T. ibid. p. 347.
32
yet known whether the existence of different serotypes, as revealed by the mouse toxicity test, is relevant to vaccine prevention of conjunctival infection in man. More direct approaches include study of the therapeutic effect of vaccines on experimental trachoma in primate hosts 36; tests of efficacy in preventing experimentally induced trachoma 36 37 or inclusion blennorrhaea 38 ; and field trials in trachoma endemic areas. The results reported at this meeting were all preliminary, and, although by and large they are encouraging, much more work is clearly necessary before the prospects for vaccine prophylaxis can be properly assessed. is
not
Annotations BROADCASTING IN BRITAIN
A POPULAR programme on television may win the attention of rather more than half of Britain’s entire population-man, woman, and child. Certainly, as a means of spreading information, the radio wave has for many years left every other medium far behind, and its pace is still accelerating. It can make people drink beer, eat eggs, commit crimes, win elections, and start wars. It can also make them paint in oils, read Tolstoy, employ discharged mental patients, and love their neighbours. The control of the radio wave is therefore one of the big issues of the generation, and it is more than a national one: it involves every country with a broadcasting system. Every day two new television stations open somewhere in the world,39 and developing countries look to those with longer experience to guide their use. The patterns vary greatly. In some countries, the services are left, unsupervised, in the hands of commercial firms with the main aim of advertising. In others they are a monopoly of the State and may be used to secure political conformity. In at least one country they are run by religious bodies along sectarian lines. New services in new countries usually lean heavily on cheap imported film, which carries the cultural hazard of painting strange stereotypes of Western civilisation in terms of cowboys, gangsters, and sudden death. Television is difficult and expensive to start, and UNESCO in Paris gives special priority to advising such countries on technical and financial matters. In Britain we have not only the longest experience (our television service was the first in the world) but also the gift of compromise, and other nations consult us. Radio NHK in Japan, for example, is a direct copy of the British Broadcasting Corporation. The Pilkington report on broadcasting 40 is, therefore, much more than a document of national importance: it may help to shape mass communication in Dunedin or New Delhi. It is the most careful appraisal of this complex and immensely important subject that has yet appeared (its members read 636 memoranda submitted to it, and a further 216 committee papers). The report does not describe the quite substantial researches already carried out into the effects of these mass media on attitude and conduct; but valuable memoranda on this work are published separately. The 36. 37.
Grayston, J. T., Woolridge, R. L., Wang, S. ibid. p. 352. Snyder, J. C., Bell, S. D., Murray, E. S., Thygeson, P., Haddad, ibid. p. 368. Collier, L. H. ibid. p. 375.
38. 39. Television and the World. B.B.C. Film. 40. Report of the Committee on Broadcasting, 1962. Stationery Office. Pp. 342. 18s.
N.
Cmnd 1753. H.M.
committee accept the view that repeated violence shown the screen may have a harmful cumulative influence on later conduct, and they criticise the amount of time given to such programmes. On the more strictly medical side, the committee has not appraised the B.M.A. memorandum, with its proposal of a " medical editor " to give expert advice, nor has it examined the positive uses and ethical problems of programmes designed to inform the public about physical and mental disease. on
FLUORINE AND BETTER TEETH
FIVE years ago the water-supplies of Watford, Kilmarnock, and part of the county of Anglesey were modified by the addition of fluoride to a level of 1 part per million. In these three -areas the teeth of young children have been examined regularly since then, and their dental state has been compared with children in three control areas (Sutton, Ayr, and the rest of Anglesey). The results, published1 this week, indicate a substantial improvement in the teeth of the children drinking fluoridated water, and the findings so far are in line with American experience. No evidence of any harmful action of fluoride has been observed; and there have been no technical difficulties in adding fluoride to the water at the chosen concentration. For the few years that fluoridation has been in operation in the study areas, its full effect can now be observed only in children up to the age of 5, who have had fluoride all their lives. Thus, although the dental condition of children aged 3 to 14 years has been recorded, the report presents only the findings for the deciduous teeth of children aged 3 to 7. The findings have been assessed on the full deciduous dentition (20 teeth) for 3-4-year-olds, and on deciduous canines and molars only (12 teeth) for 5-7-year-olds, to eliminate uncertainty caused by natural shedding of incisor teeth. In the study areas the extent of dental decay, as measured by the average number of carious (decayed, missing, or filled) teeth, has been much reduced in the younger age-groups both absolutely and by comparison with the control areas. The proportion of children free from caries has been substantially increased and the proportion of children with 10 or more carious teeth has been greatly reduced. In the combined study areas in 1955-56 (before fluoridation) children aged 3 years had on average 3-80 carious teeth: in 1961 the figure for this age was 1-29. For 4-year-olds the reduction was from 5-39 to 231; and for 5-year-olds from 5-81 to 2-91. Among children of 6 and 7, some of whose teeth were calcified before fluoridation began, caries was not reduced to the same extent. For the 6-year-olds the average fell from 6-49 carious teeth to 481; and for the 7-year-olds from 7-06 to 6-05. There were also reductions in caries in the control areas but only of between 2% and 7%, compared with a reduction range of 66% to 14% in the study areas. Moreover, caking into account changes in the control areas, the proportion of children in the study areas free from caries has been increased by about three-quarters. No harmful effects from the addition of 1 p.p.m of fluoride to drinking-water have been demonstrated in any of the extensive medical evidence that has been collected and reviewed during these trials. The report declares: "... the raising of the fluoride content of drinking water to a level of 1 p.p.m. is safe." 1.
Rep. publ. Hlth med. Subj. Lond. 1962, no. 105. H.M. Stationery Office. Pp. 50. 4s.
beautifully with the sex-chromatin findings; and, indeed, the hypothesis is derived directly from It all fits
OHNo’s views of the sex chromatin.2 All active chromosomal material in the nucleus, including the working X, is extended during the so-called " resting phase " of the nucleus to form the indistinct background chromatin. Unemployed Xs condense to form sex-chromatin masses. Hence the number of the bodies is always just one less than the number of X chromosomes present, except in polyploid cells, where each extra autosome set calls for an extra working X chromosome.13 The sex chromosome acts as a unique marker for the X chromosome simply because the whole mechanism is unique to the X chromosome. LYON has suggested that the inactivation of surplus X chromosomes occurs about the 12th day, when sexchromatin bodies become visible,144 and is purely random. At this time the precursor cells of many tissues are not very numerous: this could readily account for such phenomena as the patchiness of skin colour in mice heterozygotes, each patch representing the progeny of a single cell with an active X of one or other type. Moreover, if the definitive cells are few, random allocation to two classes may give rise to many cases where the distribution is far from the expected 50 : 50, which may explain the variations in expression in female heterozygotes. It must be supposed, for instance, that in the average female carrier of colour blindness half the cones are normal and half colour-blind, and that this suffices for almost normal colour vision: but that wide variation can occur in the proportion of cells of the two types, which may account for the great range of colour vision found in such carriers. There is another respect in which this is a very satisfying explanation. The differences between male and female in man (as in most species), however conspicuous or however important in practice, are not really profound. A simple yes-no decision, some time before the 40th day, as to whether the germ cells are to develop in the cortex or the medulla of the primitive gonad, is all that is necessary: everything important follows from it. It has always seemed altogether out of proportion that this small difference should be represented by a whole chromosome. The Y, small and the carrier of little if anything beyond its testicular organiser, is precisely adapted to its function. The large X, packed with active genes, should give rise to enormous differences between the sexes. At least we know now why it does not produce them: it is simply rendered inactive. What we do not know is why the second X need be there at all. In man its absence gives rise to Turner’s syndrome, but this is not a general phenomenon, for the XO mouse is a normal fertile female. A function for the second X might be regarded as the next major problem in this field. GRUMBACH et al. believe, with OHNO,2 that the inactivation of the surplus X chromosome may be only the most conspicuous example of a more general phenomenon. They refer to unpublished work, using 13. Lennox, B. Brit. med. Bull. 1961, 17, 196. 14. Park, W. W. J. Anat. 1957, 91, 369.
tritiated thymidine, which indicates that D.N.A. synthesis in the inactive X chromosome is notably out of step with the remainder, but that lesser differences occur among the autosomes. It may be that such lesser differences, probably reversible in part, and associated with intermitotic condensation of the chromosomes concerned, may result in blocking off of parts of chromosomes from normal activity and hence in differentiation between cells. This is a fascinating possibility, though it cannot be regarded as more than
speculation at present. One final point from a recent contribution: MACLEAN’S review 15 from Edinburgh of the behaviour of the polymorph drumsticks in various X-chromosome disorders can be said finally to have disposed of any doubt that these bodies are simply a variant of the sex chromatin.
Biology of the
Trachoma
Agent
resembling morphology the virus-like microorganisms of the psittacosis-lymphogranuloma (P.-L.) group, which can be grown in embryonate eggs in
ALTHOUGH
and cell cultures, the agents of trachoma and of the closely allied inclusion-blennorrhoea syndrome for long resisted attempts at cultivation in the laboratory. Indeed, half a century was to elapse between the original description of trachoma inclusion bodies,16 and isolation of a virus in the chick embryo yolk sac by T’ANG and others 17 in 1957. As soon as this had been accomplished, however, progress was rapid; so much so that last year the New York Academy of Sciences convened a conference on the biology of the trachoma agent, with the object of summarising and coordinating the considerable information gained by many workers in various countries. The published proceedings,18 which include papers from laboratories in the United States, the United Kingdom, Gambia, Israel, South Africa, Japan, Formosa, and Saudi Arabia, reflect the general quickening of interest in this area of research. From the opening session on isolation methods, it transpired that trachoma viruses have now been isolated in many countries where the disease is endemic; apparently identical viruses have been isolated in England and America from patients with inclusion blennorrhoea. These agents closely resemble each other in morphology and staining characteristics, in their ability to grow in the chick-embryo yolk sac, and in their resistance to streptomycin. Furthermore, they contain the heatstable complement-fixing antigen common to the P.-L. group, of which they appear to be typical members. Despite its title, the conference did not therefore concern itself exclusively with the trachoma agent, but considered related microorganisms when necessary for comparison or contrast.
It has
been
suspected that the P.-L. agents do behave as typical viruses, and this supposition is amply conformed by studies on the trachoma/inclusionlong
not
15. 16. 17. 18.
Maclean, N. Lancet. 1962, i, 1154. Halberstaedter, L., von Prowazek, S. Arb. GesundhAmt., Berlin, 1907, 26, 44. T’ang, F. F., Chang, H. L., Huang, Y. T., Wang, K. C. Chin. med. J. 1957, 75, 429. Ann. N.Y. Acad. Sci. 1962, 98, 1-382.
31
blennorrhoea microorganisms. Many techniques have been used to investigate their mode 0 reproduction in cultured cells and in chick embryos, including infectivity measurements, light and electron microscopy, and
cytochemical procedures .19-2.1
It
seems
generally agreed
that the infecting particle is an " elementary body ", rich in deoxyribonucleic acid (D.N.A.); under the electron microscope it appears as a dense-centred particle about 0,3 !k in diameter. After entering the host cell it loses infectivity. Some hours later, a larger " initial body " appears within the cytoplasm. This form gives the staining reaction for ribonucleic acid (R.N.A.) and has little or no infectivity; by a process that is not clearly understood, the initial body gives rise to a further generation of elementary bodies which form the mature cytoplasmic inclusion and which are capable of initiating a further cycle of infection on release from the cell. Although several aspects of this complex series of events have still to be elucidated, enough has been learned to make it clear that the P.-L. agents occupy a special taxonomic position. In their obligate intracellular habitat and loss of infectivity in the early stages of replication, they resemble the viruses; whereas closer affinity with the bacteria is suggested by the presence of both forms of nucleic acid, a cell wall containing muramic acid and various aminoacids, the possible occurrence of fission in the later stage of multiplication, and susceptibility to sulphonamides and some antibiotics. Nevertheless, for want of a better term, it is still customary to call these infective agents viruses. Investigations of the action of various anti-metabolites hold particular interest for the clinician. In general, the testing of antibiotics for anti-trachoma activity in vitro or in ovo gives the results to be expected from knowledge of their therapeutic efficacy in man; thus, the tetracycline compounds inhibit the later stages of replication in cell cultures,20 whereas penicillin merely delays tnattIration.20 21 On the other hand, the laboratory evidence for the antiviral activity of streptomycin 26 or the sulphonamides 20 27 is conflicting and seems to be influenced by the particular host/virus system employed. Two new substances were reported to have antitrachoma activity in laboratory tests. Tylosin tartrate acts like the tetracyclines in infected cell cultures 20; Nitractin,’ although weight for weight less active than several other therapeutic substances, is virtually nontoxic for labotatory animals, and has the advantage of acting as a repository drug,27 a useful attribute for treating trachoma in the field. Apart from their value for exploring the complicated chemical events in viral synthesis, these investigations already give promise of more effective drugs for the treatment of trachoma. As far as is known, conjunctival infection with trachoma and inclusion blennorrhoea can be induced 19. Collier, L. H. ibid. p. 42. 20. Pollard, M., Tanami, Y. ibid. p. 50. 21. Bernkopf, H., Mashiah, P., Becker, Y. ibid. p. 62. 22. Moulder, J. W. ibid. p. 92. 23. Higashi, N., Tamura, A., Iwanaga, M. ibid. p. 100. 24. Mitsui, Y., Kajima, M., Nishimura, A., Konishi, K. ibid. 25. Litwin, J. ibid. p. 145. 26. Gordon, F. B., Quan, A. L. ibid. p. 261. 27. Hurst, E. W. ibid. p. 275.
p. 131.
only in primates, and many eye-to-eye inoculations were made in monkeys, apes, and baboons before these viruses were isolated in the laboratory. Recent investigations with cultured virus confirm earlier reports that inclusionblennorrhoea virus is more pathogenic than trachoma in apes and monkeys; unfortunately, however, the difference in the experimental syndromes is not sufficiently constant to make this a useful criterion for distinguishing these agents.28 29 Furthermore, pathogenicity of a given strain may be attenuated by repeated passage in chick embryos,29 and this must be borne in mind when appraising the results of primate inoculation. Since experiments in simian species cannot help in distinguishing between trachoma and inclusion-blennorrhoea viruses, inoculation of volunteers is necessary. One school, championed by THYGESON,30 concludes from clinical and experimental findings that these syndromes are quite distinct: trachoma is spread from eye to eye, and is characterised by corneal lesions, cicatrisation, and a long course; inclusion blennorrhoea (or conjunctivitis) is primarily a genital infection which may be transmitted to the adult eye, or to the infant eye at birth. In contrast totrachoma, the ophthalrriic infection resolves spontaneously in a comparatively short time without corneal lesions or scarring. Nevertheless, some workers maintain that there is no sharp line between these syndromes. Further evidence for this supposition, fully documented by photographs, was presented by JONES and COLLIER,31 who isolated an agent of the P.-i.. group from the eye of an English baby with typical inclusion blennorrhoea of the newborn; on inoculation into the eye of a blind adult volunteer, it induced follicular conjunctivitis with corneal lesions indistinguishable from trachoma. A fascinating aspect of recent researches, and one potentially important in the control of the disease, is the immunology of trachoma. The isolation of the causal agent aroused hopes of serological methods for use in diagnosis, and of preventive vaccines; and several communications to the conference bore directly on these problems. Although the complement-fixation test with heated group antigen seems of little use in diagnosis,32 one group of workers described the preparation of specific antigens that do not cross-react with sera from cases of lymphogranuloma venereum or of psittacosis, and which are more sensitive than group antigen for detecting antibodies in trachoma patients.33 In two laboratories, various strains of trachoma, when injected intravenously, were found to be toxic and lethal for mice; and this effect could be offset by prior immunisation of the mice with a suitable antigen.34 35 Crossprotection tests showed that most of the strains tested fell into two immunologically distinct groups; those examined by BELL and THEOBALD 34 were isolated in several countries, but there was no relation between the results of these tests and geographical distribution. It 28. 29. 30. 31. 32. 33. 34. 35.
Dawson, C. R., Mordhorst, C. H., Thygeson, P. ibid. p. 167. Collier, L. H. ibid. p. 188. Thygeson, P. ibid. p. 201. Jones, B. R., Collier, L. H. ibid. p. 212. Collier, L. H. ibid. p. 324. Woolridge, R. L., Grayston, J. T. ibid. p. 314. Bell, S. D., Theobald, B. ibid. p. 337. Chang, I., Wang, S., Grayston, J. T. ibid. p. 347.
32
yet known whether the existence of different serotypes, as revealed by the mouse toxicity test, is relevant to vaccine prevention of conjunctival infection in man. More direct approaches include study of the therapeutic effect of vaccines on experimental trachoma in primate hosts 36; tests of efficacy in preventing experimentally induced trachoma 36 37 or inclusion blennorrhaea 38 ; and field trials in trachoma endemic areas. The results reported at this meeting were all preliminary, and, although by and large they are encouraging, much more work is clearly necessary before the prospects for vaccine prophylaxis can be properly assessed. is
not
Annotations BROADCASTING IN BRITAIN
A POPULAR programme on television may win the attention of rather more than half of Britain’s entire population-man, woman, and child. Certainly, as a means of spreading information, the radio wave has for many years left every other medium far behind, and its pace is still accelerating. It can make people drink beer, eat eggs, commit crimes, win elections, and start wars. It can also make them paint in oils, read Tolstoy, employ discharged mental patients, and love their neighbours. The control of the radio wave is therefore one of the big issues of the generation, and it is more than a national one: it involves every country with a broadcasting system. Every day two new television stations open somewhere in the world,39 and developing countries look to those with longer experience to guide their use. The patterns vary greatly. In some countries, the services are left, unsupervised, in the hands of commercial firms with the main aim of advertising. In others they are a monopoly of the State and may be used to secure political conformity. In at least one country they are run by religious bodies along sectarian lines. New services in new countries usually lean heavily on cheap imported film, which carries the cultural hazard of painting strange stereotypes of Western civilisation in terms of cowboys, gangsters, and sudden death. Television is difficult and expensive to start, and UNESCO in Paris gives special priority to advising such countries on technical and financial matters. In Britain we have not only the longest experience (our television service was the first in the world) but also the gift of compromise, and other nations consult us. Radio NHK in Japan, for example, is a direct copy of the British Broadcasting Corporation. The Pilkington report on broadcasting 40 is, therefore, much more than a document of national importance: it may help to shape mass communication in Dunedin or New Delhi. It is the most careful appraisal of this complex and immensely important subject that has yet appeared (its members read 636 memoranda submitted to it, and a further 216 committee papers). The report does not describe the quite substantial researches already carried out into the effects of these mass media on attitude and conduct; but valuable memoranda on this work are published separately. The 36. 37.
Grayston, J. T., Woolridge, R. L., Wang, S. ibid. p. 352. Snyder, J. C., Bell, S. D., Murray, E. S., Thygeson, P., Haddad, ibid. p. 368. Collier, L. H. ibid. p. 375.
38. 39. Television and the World. B.B.C. Film. 40. Report of the Committee on Broadcasting, 1962. Stationery Office. Pp. 342. 18s.
N.
Cmnd 1753. H.M.
committee accept the view that repeated violence shown the screen may have a harmful cumulative influence on later conduct, and they criticise the amount of time given to such programmes. On the more strictly medical side, the committee has not appraised the B.M.A. memorandum, with its proposal of a " medical editor " to give expert advice, nor has it examined the positive uses and ethical problems of programmes designed to inform the public about physical and mental disease. on
FLUORINE AND BETTER TEETH
FIVE years ago the water-supplies of Watford, Kilmarnock, and part of the county of Anglesey were modified by the addition of fluoride to a level of 1 part per million. In these three -areas the teeth of young children have been examined regularly since then, and their dental state has been compared with children in three control areas (Sutton, Ayr, and the rest of Anglesey). The results, published1 this week, indicate a substantial improvement in the teeth of the children drinking fluoridated water, and the findings so far are in line with American experience. No evidence of any harmful action of fluoride has been observed; and there have been no technical difficulties in adding fluoride to the water at the chosen concentration. For the few years that fluoridation has been in operation in the study areas, its full effect can now be observed only in children up to the age of 5, who have had fluoride all their lives. Thus, although the dental condition of children aged 3 to 14 years has been recorded, the report presents only the findings for the deciduous teeth of children aged 3 to 7. The findings have been assessed on the full deciduous dentition (20 teeth) for 3-4-year-olds, and on deciduous canines and molars only (12 teeth) for 5-7-year-olds, to eliminate uncertainty caused by natural shedding of incisor teeth. In the study areas the extent of dental decay, as measured by the average number of carious (decayed, missing, or filled) teeth, has been much reduced in the younger age-groups both absolutely and by comparison with the control areas. The proportion of children free from caries has been substantially increased and the proportion of children with 10 or more carious teeth has been greatly reduced. In the combined study areas in 1955-56 (before fluoridation) children aged 3 years had on average 3-80 carious teeth: in 1961 the figure for this age was 1-29. For 4-year-olds the reduction was from 5-39 to 231; and for 5-year-olds from 5-81 to 2-91. Among children of 6 and 7, some of whose teeth were calcified before fluoridation began, caries was not reduced to the same extent. For the 6-year-olds the average fell from 6-49 carious teeth to 481; and for the 7-year-olds from 7-06 to 6-05. There were also reductions in caries in the control areas but only of between 2% and 7%, compared with a reduction range of 66% to 14% in the study areas. Moreover, caking into account changes in the control areas, the proportion of children in the study areas free from caries has been increased by about three-quarters. No harmful effects from the addition of 1 p.p.m of fluoride to drinking-water have been demonstrated in any of the extensive medical evidence that has been collected and reviewed during these trials. The report declares: "... the raising of the fluoride content of drinking water to a level of 1 p.p.m. is safe." 1.
Rep. publ. Hlth med. Subj. Lond. 1962, no. 105. H.M. Stationery Office. Pp. 50. 4s.