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POST-WAR RESEARCH
171 method employs 18, - and occasionally 24, frames per skin exposure of about 50 rontgen in a seconds. of 6-8 Subsequently, each photograph period is copied up to twenty times, and thus when the film is viewed the whole process is slowed down and can be studied’more closely. Professor Janker uses as a contrast medium 70% or 80% organic iodide of which 30-60 ml. is injected into an arm vein in 1-2 seconds ; so this part of the method is much the same as when cassettes or roll film are used. The illustration accompanying Professor Janker’s article gives some idea of the excellent definition obtained with X-ray cinematography and also of the information which such pictures can offer to the physician in diagnosis and to the surgeon in planning an operation. Indeed, this is the only technique which allows one to see the blood, or rather a radio-opaque substance, actually flowing through the
second with
a
heart. APPROVED SCHOOLS AMONG possible economies being considered in these hard times is, a saving on approved schools. The Select Committee on Estimates have therefore been trying to decide whether such schools are doing their job.l There .are 162 approved schools in England and Wales, 124 of them run by voluntary bodies ; and in Scotland there are 25 schools, all but 1 of them voluntary. There are advantages in both types, the committee think: voluntary societies have a long and good tradition, many of them have a religious background, and their staffs believe that voluntary bodies encourage initiative in headmasters; on the other hand, such schools may be out of the general current of public life, whereas localgovernment schools are not. The record of success is moderately good. In England and Wales 66% of successes are claimed among the boys and 80% among the girls ; in Scotland the figures are rather better-76-3% for boys and 93.6% for girls. The committee were well satisfied, on the whole, with the conditions in the five schools which they visited ; but they describe one unsuitable and gloomy place where the children were poorly dressed, the atmosphere oppressive, and the gymnasium closed to them in their spare time, the only recreation-rooms being the classrooms. They recommend that conditions here should be remedied with the least possible delay. Approved schools are expensive ; the weekly cost for senior boys ranges from E3 17s. 8d. to E9 12s. 7d. ; for girls it ranges from 1:3Os. 3d. to E616s. 9d. This is doubtless partly due to the need for a relatively high ratio of staff to children. Approved schools are open all the year round, and as the children’s leisure, like their school hours, is a learning time, the number of teachers cannot be reduced if results are to be maintained and improved. On the other hand the number of children being admitted has declined year by year since the end of the war-for what reasons we are not told in this report -and it seems that some of the senior girls’ schools are to be closed. The committee advise that the possibility of closing more schools should be kept under review. They suggest no major change in the present dual management of school, by voluntary and statutory bodies, but they think that efficiency would be greater if local government was represented on all voluntary management boards. They also think that fostercare might be used more widely as an alternative to approved-school training. Classifying schools, in which children are studied before being sent to the most appropriate approved schools, have proved very successful. These only cover the needs of half the country at present, and the committee favour the provision of more classifying schools, believing that by 1. Approved Schools. Eighteenth Report from the Select Committee on Estimates : Session 1948-49. H.M. Stationery Office. Pp. 128. 4s.
their use the time some children spend in an approved school might be reduced. They hold that facilities for practical training should be introduced where they do not already exist, and should be related as closely as possible to outside apprenticeship and vocational requirements. Altogether it looks as though wecannot save much here : the money spent on approved is in the main well spent.
schools
POST-WAR RESEARCH IN the years following the end of the war the activities of the Medical Research Council fell broadly into three phases : contraction, reorientation, and expansion. The council’s report on these yearsopens with a brief epitaph on its short-term investigations during the war 2 : ’
,
" It may be said here, in retrospect, that when the fundamental knowledge available was already substantial, investigations of this type generally led to satisfactory solutions of immediate value ; but that when fundamental knowledge was inadequate, as in the case of wound shock, for example, the additional information gained under wartime conditions did not generally provide a basis for complete control, although the results often gave useful practical help of a limited kind. This is a lesson of great significance in planning for the future."
Among the war-time committees which
have been disbanded are those concerned with war wounds, clinical trials and synthesis of penicillin, brain injuries, traumatic shock, malaria, typhus, therapeutic requirements, and military personnel research. Though the brain-injuries committee no longer functions, the cognate committee do the on nerve injuries remains in being, as also and committee food-rationing (special diets) advisory the Royal Naval personnel research committee ; but the largest war-time activity carried over into peace is the operation, on behalf of the Ministry of Health, of the Public Health Laboratory Service. For research-workers the personal reorientation to peace-time conditions was not easy. ’
’
’
" In other cases, especially among the leaders, the change to be faced was even greater, because those who were controll-
and directing other men engaged on wartime problems had little time to engage personally in research. These men have had to re-adapt their lives, and, after working in gregarious conditions while helping others in the practical solution of war problems, have had to settle down again to the laboratory bench with entirely different problems to
ing
study."
. _
...
The council itself has been faced with shortages of accommodation, of equipment, and also of trained men. This last shortage is attributed to the long gap in recruitment, and to a lesser extent to war casualties ; and added to this is the competition of other expanding medical and scientific services for the limited man-power available." Among the main preoccupations of the council, occupational health and nuclear physics have taken an increasingly prominent place ; and new research units have been set up as follows : a pneumoconiosis unit at Cardiff, an industrial-medicine unit at Birmingham, blood-products, blood-group, and bloodtransfusion units in London, a dental unit in London, a clinical chemotherapeutic unit at Glasgow, a clinical endocrinological unit at Edinburgh, an electromedical unit at Stoke Mandeville, a building unit in London, a toxicology unit at Porton, a biophysics unit in London, a radiobiological unit at Harwell, a vision unit in London, a unit on the molecular structure of biological systems at Cambridge, a social-medicine unit in London, and a unit on climate and working efficiency at Oxford. The cost of instituting these units and of expanding the council’s other establishments, including the National "
1. Committee of Privy Council for Medical Research: Report of the Medical Research Council for the Years 1945-48. H.M. Stationery Office. Pp. 283. 5s. 2. Medical Research in War : Report of the Medical Research Council for the Years 1939-45. See Lancet, 1948, i, 718.
172 Institute of Medical Research, is reflected in the growth of grants-in-aid by Parliament for current expenditure from £415,000 in 1946-47, to B618,000 in 1947-48, and £770,000 in 1948-49. To the nation this is a bargain
price. VACCINES AGAIN
IN the heyday of vaccines there was much debate about the best method of rendering the bacteria harmless without impairing their powers to stimulate antibody formation. Heat, phenol, and other bactericidal agents all had their advocates. That we hear less of all this than we did is due, no doubt, to experience, which has shown that vaccine therapy is less effective than some had claimed and that vaccine prophylaxis is applicable to relatively few of the ailments which plague us. Felix’s1 successful substitution of alcohol for heat as a killing agent in making a prophylactic against enteric fever, and Grasset’s2 introduction of endotoxoid vaccine for the same purpose, both indicate that this subject still deserves inquiry ; and a recent paper by Pattison 3 suggests a line of approach which has not, as far as we know, been followed before. He wished to immunise mice against a streptococcus of group B, the group which includes the organisms mostly responsible for bovine mastitis. Having first shown. that the strain he was employing was sensitive to penicillin, he injected a lethal dose intraperitoneally ; and he followed this with injections of penicillin in aqueous solution at intervals of 1/2, 2, and 6 hours. Later the three doses were replaced by a single one of procaine-penicillin half an hour after the injection of the organisms. With each method the injection of organisms, repeated two or three times, protected the animal against a further lethal dose of streptococci given a few days later. The basic idea is so obvious that we are not surprised that no-one has previously called attention to it. There is much more that we would like to know-how long such immunity lasts ; how it compares quantitatively with the immunity produced by the same dose of organisms killed by heat and other methods ; and what happens if the bacteriostatic effect of penicillin wanes, to allow a resurrection of the viable organisms. But the method is of special interest because the time has come, we believe, when the arguments for vaccine therapy might usefully be re-examined in the light of newer knowledge. THE INDEX-CATALOGUE
FOR seventy years the Index-Catalogue of the Army Medical Library at Washington has been an indispensable tool for medical research all over the world. It is the key to the work of our predecessors, buried in the ever-
growing stack of periodical literature. This work is ignored at peril. Pasteur’s revival of Jenner’s work after three-quarters of a century ; Banting’s culmination of earlier attacks on the secret of diabetes ; Florey’s enlargement of Fleming’s discovery of penicillin, which had been anticipated by Lister-all these illustrate the inescapable chain of discovery. When John Shaw Billings built up the Army Medical Library in the ’70s, he saw that an index to journal literature was as essential as a catalogue of his books. He accepted the " decided preference " of a great majority of American physicians against the convenience of librarians, and combined the two.
He foresaw that
Index-Catalogue would be of general usefulness : " an analysis, by subjects, of so large a collection of medical periodicals," Billings wrote in his first preface, " is, necessarily, useful in St. Petersburg, for example, as well as in Washington, its measure of utility in any locality being the extent of the collections of medical periodical literature therein." In Britain, certainly, good use has his
been made of it, for the United States government has 1. Felix, A. Brit. med. J. 1941, i, 391. 2. Grasset, E. C.R. Soc. Biol. Paris, 1931, 106, 810. 3. Pattison, I. H. J. Path. Bact. 1949, 31, 337.
presented the successive volumes widely. We have
come
indeed, that the Index-Catalogue is comprehensive and infallible, and are surprised when American to assume,
critics point out that- it is neither. The truth no doubt is that a machine devised seventy years ago deserves overhaul ; and, observing with admiration the active resurgence of the Army Medical Library from comparative quiescence in the lean ’30s, we have looked forward to the projected correlation of the Index-Catalogue with the Quarterly Cumulative Index ltledicus. The Index-Catalogue has served, not altogether regularly, as, a twenty-year cumulation of the Index Medicus, cutting the labour of search from forty volumes to one. We knew that the Americans, who are past masters of documentary method, could make it a comprehensive cumulation, easy to use. But now a rumour comes that the Index-Catalogue is to be ended. Billings offered his first volume as a proof that " aid and sympathy " received from many physicians both in America and Europe had not been wasted. We must thank his successors for a payment which has far surpassed this debt, and a,ssure them that if the Index-Catalogue ceases to exist, it will have to be invented again. ’
ANTI-HISTAMINE DRUGS AND THE TUBERCULIN REACTION THERE is ample evidence to showthat the anti-histamine drugs can partially or completely inhibit the development of histamine weals, allergic weals, and passive transfer weals. Elias and McGavick,l for example, found that the preliminary administration of ’Benadryl’ by mouth diminished both the weals and the erythema produced by subsequent histamine skin tests. The question therefore arises whether these drugs will interfere with tuberculin tests. In tuberculous guineapigs Boquet2 could not detect any such inhibitory effect. Sarber, on the other hand, says that adequate doses of benadryl can reduce both the skin reaction and the incidence of necrosis in guineapigs injected with
tuberculin. The point has now been investigated by Friedmanand Silverman3 in children aged 5-11’years who were known to be positive reactors to tuberculin. Injections of 1 in 100,000 (0001 mg.) old tuberculin produced definite positive reactions in 48 children.- Several day later 43 of these children were givenPyribenzamine’ in doses of 60 mg. daily for two days and then the tuberculin test was repeated. After the test the pyribenzamine was continued in the same dosage for a further two days. As controls, the remaining 5 children in the group were not given pyribenzamine but were re-tested with tuberculin at the same time. Finally, still later, 10 of the children were re-tested with the same dose of tuberculin after receiving 240 mg. of pyribenzamine daily. In all cases the tuberculin reactions obtained were about the same as in the initial tests. Criep and his colleagues4 in Pittsburgh have tested human adults and tuberculous guineapigs with pyribenzamine and have reached the same conclusion. Various brands of tuberculin and both oral and intradermal routes of administration of the anti-histaminic drug were used without affecting tuberculin sensitivity. The numbers are, of course small, but the findings suggest that the previous administration of anti-histamine drugs will not affect the results of -a tuberculin test. THE death is
reported from Melbourne
of Dr. L. S.
LATHAM, president of the Royal Australasian College of Physicians, and a former deputy chancellor of the
University 1.
bf Melbourne.
Elias, H., McGavick, H. 61, 133.
2. 3. 4.
Ann. Inst.
Proc. Soc. exp.
Biol.,
N.Y. 1946.
Pasteur, 1943, 69, 55. Boquet, Friedman, E., Silverman, I. Amer. Rev. Tuberc. 1949, 60, 354. Criep, L. H., Levine, M. I., Aaron, T. H. Ibid, 59, 701. A.
second with
a
heart. APPROVED SCHOOLS AMONG possible economies being considered in these hard times is, a saving on approved schools. The Select Committee on Estimates have therefore been trying to decide whether such schools are doing their job.l There .are 162 approved schools in England and Wales, 124 of them run by voluntary bodies ; and in Scotland there are 25 schools, all but 1 of them voluntary. There are advantages in both types, the committee think: voluntary societies have a long and good tradition, many of them have a religious background, and their staffs believe that voluntary bodies encourage initiative in headmasters; on the other hand, such schools may be out of the general current of public life, whereas localgovernment schools are not. The record of success is moderately good. In England and Wales 66% of successes are claimed among the boys and 80% among the girls ; in Scotland the figures are rather better-76-3% for boys and 93.6% for girls. The committee were well satisfied, on the whole, with the conditions in the five schools which they visited ; but they describe one unsuitable and gloomy place where the children were poorly dressed, the atmosphere oppressive, and the gymnasium closed to them in their spare time, the only recreation-rooms being the classrooms. They recommend that conditions here should be remedied with the least possible delay. Approved schools are expensive ; the weekly cost for senior boys ranges from E3 17s. 8d. to E9 12s. 7d. ; for girls it ranges from 1:3Os. 3d. to E616s. 9d. This is doubtless partly due to the need for a relatively high ratio of staff to children. Approved schools are open all the year round, and as the children’s leisure, like their school hours, is a learning time, the number of teachers cannot be reduced if results are to be maintained and improved. On the other hand the number of children being admitted has declined year by year since the end of the war-for what reasons we are not told in this report -and it seems that some of the senior girls’ schools are to be closed. The committee advise that the possibility of closing more schools should be kept under review. They suggest no major change in the present dual management of school, by voluntary and statutory bodies, but they think that efficiency would be greater if local government was represented on all voluntary management boards. They also think that fostercare might be used more widely as an alternative to approved-school training. Classifying schools, in which children are studied before being sent to the most appropriate approved schools, have proved very successful. These only cover the needs of half the country at present, and the committee favour the provision of more classifying schools, believing that by 1. Approved Schools. Eighteenth Report from the Select Committee on Estimates : Session 1948-49. H.M. Stationery Office. Pp. 128. 4s.
their use the time some children spend in an approved school might be reduced. They hold that facilities for practical training should be introduced where they do not already exist, and should be related as closely as possible to outside apprenticeship and vocational requirements. Altogether it looks as though wecannot save much here : the money spent on approved is in the main well spent.
schools
POST-WAR RESEARCH IN the years following the end of the war the activities of the Medical Research Council fell broadly into three phases : contraction, reorientation, and expansion. The council’s report on these yearsopens with a brief epitaph on its short-term investigations during the war 2 : ’
,
" It may be said here, in retrospect, that when the fundamental knowledge available was already substantial, investigations of this type generally led to satisfactory solutions of immediate value ; but that when fundamental knowledge was inadequate, as in the case of wound shock, for example, the additional information gained under wartime conditions did not generally provide a basis for complete control, although the results often gave useful practical help of a limited kind. This is a lesson of great significance in planning for the future."
Among the war-time committees which
have been disbanded are those concerned with war wounds, clinical trials and synthesis of penicillin, brain injuries, traumatic shock, malaria, typhus, therapeutic requirements, and military personnel research. Though the brain-injuries committee no longer functions, the cognate committee do the on nerve injuries remains in being, as also and committee food-rationing (special diets) advisory the Royal Naval personnel research committee ; but the largest war-time activity carried over into peace is the operation, on behalf of the Ministry of Health, of the Public Health Laboratory Service. For research-workers the personal reorientation to peace-time conditions was not easy. ’
’
’
" In other cases, especially among the leaders, the change to be faced was even greater, because those who were controll-
and directing other men engaged on wartime problems had little time to engage personally in research. These men have had to re-adapt their lives, and, after working in gregarious conditions while helping others in the practical solution of war problems, have had to settle down again to the laboratory bench with entirely different problems to
ing
study."
. _
...
The council itself has been faced with shortages of accommodation, of equipment, and also of trained men. This last shortage is attributed to the long gap in recruitment, and to a lesser extent to war casualties ; and added to this is the competition of other expanding medical and scientific services for the limited man-power available." Among the main preoccupations of the council, occupational health and nuclear physics have taken an increasingly prominent place ; and new research units have been set up as follows : a pneumoconiosis unit at Cardiff, an industrial-medicine unit at Birmingham, blood-products, blood-group, and bloodtransfusion units in London, a dental unit in London, a clinical chemotherapeutic unit at Glasgow, a clinical endocrinological unit at Edinburgh, an electromedical unit at Stoke Mandeville, a building unit in London, a toxicology unit at Porton, a biophysics unit in London, a radiobiological unit at Harwell, a vision unit in London, a unit on the molecular structure of biological systems at Cambridge, a social-medicine unit in London, and a unit on climate and working efficiency at Oxford. The cost of instituting these units and of expanding the council’s other establishments, including the National "
1. Committee of Privy Council for Medical Research: Report of the Medical Research Council for the Years 1945-48. H.M. Stationery Office. Pp. 283. 5s. 2. Medical Research in War : Report of the Medical Research Council for the Years 1939-45. See Lancet, 1948, i, 718.
172 Institute of Medical Research, is reflected in the growth of grants-in-aid by Parliament for current expenditure from £415,000 in 1946-47, to B618,000 in 1947-48, and £770,000 in 1948-49. To the nation this is a bargain
price. VACCINES AGAIN
IN the heyday of vaccines there was much debate about the best method of rendering the bacteria harmless without impairing their powers to stimulate antibody formation. Heat, phenol, and other bactericidal agents all had their advocates. That we hear less of all this than we did is due, no doubt, to experience, which has shown that vaccine therapy is less effective than some had claimed and that vaccine prophylaxis is applicable to relatively few of the ailments which plague us. Felix’s1 successful substitution of alcohol for heat as a killing agent in making a prophylactic against enteric fever, and Grasset’s2 introduction of endotoxoid vaccine for the same purpose, both indicate that this subject still deserves inquiry ; and a recent paper by Pattison 3 suggests a line of approach which has not, as far as we know, been followed before. He wished to immunise mice against a streptococcus of group B, the group which includes the organisms mostly responsible for bovine mastitis. Having first shown. that the strain he was employing was sensitive to penicillin, he injected a lethal dose intraperitoneally ; and he followed this with injections of penicillin in aqueous solution at intervals of 1/2, 2, and 6 hours. Later the three doses were replaced by a single one of procaine-penicillin half an hour after the injection of the organisms. With each method the injection of organisms, repeated two or three times, protected the animal against a further lethal dose of streptococci given a few days later. The basic idea is so obvious that we are not surprised that no-one has previously called attention to it. There is much more that we would like to know-how long such immunity lasts ; how it compares quantitatively with the immunity produced by the same dose of organisms killed by heat and other methods ; and what happens if the bacteriostatic effect of penicillin wanes, to allow a resurrection of the viable organisms. But the method is of special interest because the time has come, we believe, when the arguments for vaccine therapy might usefully be re-examined in the light of newer knowledge. THE INDEX-CATALOGUE
FOR seventy years the Index-Catalogue of the Army Medical Library at Washington has been an indispensable tool for medical research all over the world. It is the key to the work of our predecessors, buried in the ever-
growing stack of periodical literature. This work is ignored at peril. Pasteur’s revival of Jenner’s work after three-quarters of a century ; Banting’s culmination of earlier attacks on the secret of diabetes ; Florey’s enlargement of Fleming’s discovery of penicillin, which had been anticipated by Lister-all these illustrate the inescapable chain of discovery. When John Shaw Billings built up the Army Medical Library in the ’70s, he saw that an index to journal literature was as essential as a catalogue of his books. He accepted the " decided preference " of a great majority of American physicians against the convenience of librarians, and combined the two.
He foresaw that
Index-Catalogue would be of general usefulness : " an analysis, by subjects, of so large a collection of medical periodicals," Billings wrote in his first preface, " is, necessarily, useful in St. Petersburg, for example, as well as in Washington, its measure of utility in any locality being the extent of the collections of medical periodical literature therein." In Britain, certainly, good use has his
been made of it, for the United States government has 1. Felix, A. Brit. med. J. 1941, i, 391. 2. Grasset, E. C.R. Soc. Biol. Paris, 1931, 106, 810. 3. Pattison, I. H. J. Path. Bact. 1949, 31, 337.
presented the successive volumes widely. We have
come
indeed, that the Index-Catalogue is comprehensive and infallible, and are surprised when American to assume,
critics point out that- it is neither. The truth no doubt is that a machine devised seventy years ago deserves overhaul ; and, observing with admiration the active resurgence of the Army Medical Library from comparative quiescence in the lean ’30s, we have looked forward to the projected correlation of the Index-Catalogue with the Quarterly Cumulative Index ltledicus. The Index-Catalogue has served, not altogether regularly, as, a twenty-year cumulation of the Index Medicus, cutting the labour of search from forty volumes to one. We knew that the Americans, who are past masters of documentary method, could make it a comprehensive cumulation, easy to use. But now a rumour comes that the Index-Catalogue is to be ended. Billings offered his first volume as a proof that " aid and sympathy " received from many physicians both in America and Europe had not been wasted. We must thank his successors for a payment which has far surpassed this debt, and a,ssure them that if the Index-Catalogue ceases to exist, it will have to be invented again. ’
ANTI-HISTAMINE DRUGS AND THE TUBERCULIN REACTION THERE is ample evidence to showthat the anti-histamine drugs can partially or completely inhibit the development of histamine weals, allergic weals, and passive transfer weals. Elias and McGavick,l for example, found that the preliminary administration of ’Benadryl’ by mouth diminished both the weals and the erythema produced by subsequent histamine skin tests. The question therefore arises whether these drugs will interfere with tuberculin tests. In tuberculous guineapigs Boquet2 could not detect any such inhibitory effect. Sarber, on the other hand, says that adequate doses of benadryl can reduce both the skin reaction and the incidence of necrosis in guineapigs injected with
tuberculin. The point has now been investigated by Friedmanand Silverman3 in children aged 5-11’years who were known to be positive reactors to tuberculin. Injections of 1 in 100,000 (0001 mg.) old tuberculin produced definite positive reactions in 48 children.- Several day later 43 of these children were givenPyribenzamine’ in doses of 60 mg. daily for two days and then the tuberculin test was repeated. After the test the pyribenzamine was continued in the same dosage for a further two days. As controls, the remaining 5 children in the group were not given pyribenzamine but were re-tested with tuberculin at the same time. Finally, still later, 10 of the children were re-tested with the same dose of tuberculin after receiving 240 mg. of pyribenzamine daily. In all cases the tuberculin reactions obtained were about the same as in the initial tests. Criep and his colleagues4 in Pittsburgh have tested human adults and tuberculous guineapigs with pyribenzamine and have reached the same conclusion. Various brands of tuberculin and both oral and intradermal routes of administration of the anti-histaminic drug were used without affecting tuberculin sensitivity. The numbers are, of course small, but the findings suggest that the previous administration of anti-histamine drugs will not affect the results of -a tuberculin test. THE death is
reported from Melbourne
of Dr. L. S.
LATHAM, president of the Royal Australasian College of Physicians, and a former deputy chancellor of the
University 1.
bf Melbourne.
Elias, H., McGavick, H. 61, 133.
2. 3. 4.
Ann. Inst.
Proc. Soc. exp.
Biol.,
N.Y. 1946.
Pasteur, 1943, 69, 55. Boquet, Friedman, E., Silverman, I. Amer. Rev. Tuberc. 1949, 60, 354. Criep, L. H., Levine, M. I., Aaron, T. H. Ibid, 59, 701. A.