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THE BORDERLAND OF LIFE
1339
living and non-living agents ? There is a third possibility-to make more liberal our views on what
THE LANCET LONDON:SATURDAY, JUNE 11, 1938
THE BORDERLAND OF LIFE FouR years ago most workers on viruses when as to the probable nature of the filtrable agents they were studying would have replied with little hesitation that they were minute living micro-organisms. To-day this question would not perhaps be answered so confidently, though workers in this country at any rate still largely subscribe to the " living " theory. Their faith in it, however, has been a little shaken by the recent demonstration that certain plant viruses, more particularly the virus of tobacco mosaic and its variants, are peculiar proteins of very high molecular weight. Though before 1935 various investigators held that tobacco mosaic virus was probably a simple protein, it was W. M. STANLEY in America who in that year provided the first really solid evidence in support of this contention. And although the observations made at Cambridge by BAWDEN, PiBIE, BERNAL, and FANTCUOHEN are in disagreement with STANLEY’S findings on one point-the possibility of obtaining the tobacco mosaic virus in the form of true crystals-in all other respects they are in full accord ; tobacco mosaic virus seems to be a heavy protein of very large molecular size which can be obtained in a high state of purity without any loss of virulence. Both in America and this country rapid strides have been made in this aspect of plant virus research. The variants to which tobacco mosaic virus gives rise, as well as several other plant viruses, have been identified with heavy proteins, each virusprotein being clearly distinguishable from the rest ; the protein of one virus, that of bushy stunt, has been obtained by the Cambridge workers in the form of true crystals. Although there is still just a possibility that these proteins are not the viruses themselves, but an impurity in the form of pathological proteins resulting from the disease process with which the virus is associated, the available evidence strongly supports the view that the proteins are in fact the viruses. Some viruses, then, seem to be nucleo-proteins that can be obtained in paracrystalline or crystalline form and, according to accepted view as to what constitutes life, are non-living agents. And it is the bearing of this astounding new knowledge on the problem of the nature of viruses in general that is engaging the attention of virus workers throughout the world to-day. Are we to abandon the idea that any of the viruses, even the largest animal ones, are living organised things and conclude that all viruses are non-living ? Or must we assume that the big group of disease agents which we call viruses is really a heterogeneous collection comprising both
questioned
constitutes life and to admit that as the result of adaptation to a parasitic existence a microorganism may eventually lose all enzyme activity and become completely dependent on the cells it parasitises for all the factors necessary for its existence-a form of life without an independent It is this conception which Sir metabolism. PATRICK LAiDLAW puts forward in the Rede lecture for 1938 which he delivered recently at Cambridge.1 He accepts the large viruses as minute bacteria. They have definite shape and size ; they can reproduce themselves and retain their individuality irrespective of the cellular environment in which this multiplication takes place ; and some of them have an antigenic complexity similar to that of bacteria. The only thing which they have not been shown to possess is an independent metabolism and it is not, as Sir PATRICK points out, their size which would prevent this, since the organism of bovine pleuro-pneumonia and the minute organisms which he and W. J. ELFORD isolated from sewage are of the same order of size as the large viruses and yet have demonstrable metabolic activities. Sir PATRICK is not prepared to accept the view put forward by STANLEY and others that those plant viruses which are simple proteins are autocatalysts. His objection is that this hypothesis presupposes the existence of a precursor substance in the susceptible cells from which the autocatalytic virus manufactures itself. A virus with a wide host range would require the presence of the specific precursor in the cells of quite unrelated species. The cells of the chorioallantoic membrane of the developing hen’s egg, susceptible to many viruses, would have to possess a whole range of precursor substances, which is hardly credible. Another objection to the autocatalytic hypothesis is that if the formation of a virus from its precursor were such a simple matter one would expect viruses to arise spontaneously in isolated communities from time to time and there is no evidence that this occurs. Further, if one accepts the large viruses like vaccinia and psittacosis’as living micro-organisms and the plant virus proteins and possibly the very small animal viruses as non-living autocatalysts, where, Sir PATRICK asks, is one to draw the line ?1 If, for instance, the virus of foot-and-mouth disease is to be placed in the non-living group, where is one to classify the virus of vesicular stomatitis which, though considerably larger, produces an identical clinical condition ?1 As Sir HENRY DALE concluded in his Huxley lecture three years ago, the virus group has to be considered as a whole. Either viruses are all living things or they are all non-living agents ; to draw a line dividing the group into two classes of agent of such diverse character appears almost impossible. Finding himself in agreement with this conclusion, Sir PATRICK LAIDLAW puts forward the view that in the group of viruses we 1 Virus
Disease and Viruses. By Sir Patrick Laidlaw, London : Cambridge University Press. 1938.
F.R.C.P., F.R.S. Pp. 52. 2s. 6d.
1340 have a collection of micro-organisms which have traversed the path of evolution towards the goal of complete parasitism to varying degrees. The large viruses would thus be those which had lost the power to synthesise one or two essential factors necessary for their life and had so become dependent on that cellular environment where these particular factors were to be found. And passing down the virus scale there would be the loss of more and more metabolic activities until one reached the smallest viruses bereft of all ferment activity, the " " ultra-parasites resigned to living a borrowed life. The very simplest form of virus would thus be micro-organisms which had lost everything except the ability to transmit the character of the species. It is, assuredly, a most attractive hypothesis but it leaves one point unexplained. If the very simplest form of virus which is represented by a simple nucleo-protein in molecular dispersion does not reproduce itself by autocatalysis, then how does it multiply ? Does it do this by fission ? If so, this is something quite foreign to our conception of the behaviour of molecules.
GENERAL OR SPECIAL HOSPITAL FOR MATERNITY?
,
CONCERN for the hard core of the maternal death-rate is leading, rightly or wrongly, to a great increase in the demand for institutional care. In three districts of New York City 80 to 90 per cent. of deliveries take place in hospital, and there is evidence that this figure may yet be equalled in this country. If Prof. MUNRO KERR had his way it would be exceeded. The discussion over which he recently presided1 at the Royal Sanitary Institute, and a rather earlier (March 25th) discussion from a slightly different standpoint at the Royal Academy of Medicine in Ireland, show that informed opinion is exercised by the main problem, can the obstetric art be better practised at home, in a special hospital, or in a unit of a general hospital where its force is joined by other departments which assume for its purpose, and in the best sense, an auxiliary role ? The function of the maternity hospital is not simply the conduct of normal labour in healthy women. Were it so, separate housing would be the evident course to protect against infection. Ante natal and postnatal care and paediatrics are obvious extensions of its responsibility. The system the must for climax the confinement of responsible also supervise events leading up to it and the subsequent rehabilitation ; and this calls for the knowledge and practice of every improvement in the prevention and treatment of disease and disability in mother and child. These considerations led the Departmental Committee on Maternal Mortality and Morbidity (1932) to recommend the inclusion, wherever possible, of maternity units within general hospitals. Throughout his period of responsibility the obstetrician is called upon to deal not only with the " unruly waywardness " that pregnancy may cause in the organism, but also with the imperfections of long ingrafted con=
"
1
See Lancet, April 30th, p. 1000.
dition."
Hence
departments of medicine, surgery, orthopaedics, pathology, dietetics, and radiology all form part of the ideal maternity service. Their lack cannot be compensated by the most devoted obstetric skill. The maternity unit of the general hospital has all these needs fulfilled under the one roof. Medical or surgical complications can be
treated
in
convenient
collaboration
with
specialists but with the obstetric significance of each development understood, and the ultimate decision governed by the department undertaking the final test, the actual delivery. The need for easily available specialist advice extends even into the labour theatre.
logical department
Close contact with a radiois essential to the nice conduct
of difficult cases and emergencies whose previous history is unknown. Our knowledge of the sources of hsemolytic streptococcus infections and the new chemotherapy have gone far to solve one problem of puerperal sepsis. There remains the other great cause of death and disability, the anaerobic streptococci. It may be that better understanding of the mechanism of labour will lessen this danger also. Radiography, by showing the available room in each type of pelvis, may to some extent prevent the trauma from blind manipulations which predisposes to infection. In particular a pathological department should be at the service of a maternity unit, and this is the strongest argument for its association with a general hospital. The advantages that its bacteriological research department gives such a special hospital as Queen Charlotte’s may well be unrivalled. For the average maternity service, even the faint shadow of such resources would be unobtainable unless it were incorporated with other departments to justify the appointment of a full-time pathologist. In the puerperium the obstetrician has to depend almost completely on the bacteriologist’s report for the appropriate segregation of the emergency admission, the unbooked, the suspect, and the infected cases. The protagonist of the special hospital may protest that contact between the nursing staff of the maternity and other units of the general hospital will increase the risk of infection reaching the parturient or puerperal woman. It should be possible to ensure, however, that the staff of each unit have no contact while in uniform. The case for separate housing requires more study. While R. CRUICKSHANK has demonstrated that nurses in contact with cases of streptococcal infection in surgical wards show a considerable percentage of carriers, experience at Queen Charlotte’s has been different. Investigations there have shown no significant difference in the incidence of carriers among the nurses of the entirely separate main and isolation blocks. Perhaps the difference lies in the care taken in the isolation block, by adequate masking of the nose and mouth, to guard against the development of carriers. At the British Postgraduate Medical School, among other similar institutions, it has been shown that the same principles are feasible in the maternity unit of a general hospital with an enthusiastic and instructed staff.
living and non-living agents ? There is a third possibility-to make more liberal our views on what
THE LANCET LONDON:SATURDAY, JUNE 11, 1938
THE BORDERLAND OF LIFE FouR years ago most workers on viruses when as to the probable nature of the filtrable agents they were studying would have replied with little hesitation that they were minute living micro-organisms. To-day this question would not perhaps be answered so confidently, though workers in this country at any rate still largely subscribe to the " living " theory. Their faith in it, however, has been a little shaken by the recent demonstration that certain plant viruses, more particularly the virus of tobacco mosaic and its variants, are peculiar proteins of very high molecular weight. Though before 1935 various investigators held that tobacco mosaic virus was probably a simple protein, it was W. M. STANLEY in America who in that year provided the first really solid evidence in support of this contention. And although the observations made at Cambridge by BAWDEN, PiBIE, BERNAL, and FANTCUOHEN are in disagreement with STANLEY’S findings on one point-the possibility of obtaining the tobacco mosaic virus in the form of true crystals-in all other respects they are in full accord ; tobacco mosaic virus seems to be a heavy protein of very large molecular size which can be obtained in a high state of purity without any loss of virulence. Both in America and this country rapid strides have been made in this aspect of plant virus research. The variants to which tobacco mosaic virus gives rise, as well as several other plant viruses, have been identified with heavy proteins, each virusprotein being clearly distinguishable from the rest ; the protein of one virus, that of bushy stunt, has been obtained by the Cambridge workers in the form of true crystals. Although there is still just a possibility that these proteins are not the viruses themselves, but an impurity in the form of pathological proteins resulting from the disease process with which the virus is associated, the available evidence strongly supports the view that the proteins are in fact the viruses. Some viruses, then, seem to be nucleo-proteins that can be obtained in paracrystalline or crystalline form and, according to accepted view as to what constitutes life, are non-living agents. And it is the bearing of this astounding new knowledge on the problem of the nature of viruses in general that is engaging the attention of virus workers throughout the world to-day. Are we to abandon the idea that any of the viruses, even the largest animal ones, are living organised things and conclude that all viruses are non-living ? Or must we assume that the big group of disease agents which we call viruses is really a heterogeneous collection comprising both
questioned
constitutes life and to admit that as the result of adaptation to a parasitic existence a microorganism may eventually lose all enzyme activity and become completely dependent on the cells it parasitises for all the factors necessary for its existence-a form of life without an independent It is this conception which Sir metabolism. PATRICK LAiDLAW puts forward in the Rede lecture for 1938 which he delivered recently at Cambridge.1 He accepts the large viruses as minute bacteria. They have definite shape and size ; they can reproduce themselves and retain their individuality irrespective of the cellular environment in which this multiplication takes place ; and some of them have an antigenic complexity similar to that of bacteria. The only thing which they have not been shown to possess is an independent metabolism and it is not, as Sir PATRICK points out, their size which would prevent this, since the organism of bovine pleuro-pneumonia and the minute organisms which he and W. J. ELFORD isolated from sewage are of the same order of size as the large viruses and yet have demonstrable metabolic activities. Sir PATRICK is not prepared to accept the view put forward by STANLEY and others that those plant viruses which are simple proteins are autocatalysts. His objection is that this hypothesis presupposes the existence of a precursor substance in the susceptible cells from which the autocatalytic virus manufactures itself. A virus with a wide host range would require the presence of the specific precursor in the cells of quite unrelated species. The cells of the chorioallantoic membrane of the developing hen’s egg, susceptible to many viruses, would have to possess a whole range of precursor substances, which is hardly credible. Another objection to the autocatalytic hypothesis is that if the formation of a virus from its precursor were such a simple matter one would expect viruses to arise spontaneously in isolated communities from time to time and there is no evidence that this occurs. Further, if one accepts the large viruses like vaccinia and psittacosis’as living micro-organisms and the plant virus proteins and possibly the very small animal viruses as non-living autocatalysts, where, Sir PATRICK asks, is one to draw the line ?1 If, for instance, the virus of foot-and-mouth disease is to be placed in the non-living group, where is one to classify the virus of vesicular stomatitis which, though considerably larger, produces an identical clinical condition ?1 As Sir HENRY DALE concluded in his Huxley lecture three years ago, the virus group has to be considered as a whole. Either viruses are all living things or they are all non-living agents ; to draw a line dividing the group into two classes of agent of such diverse character appears almost impossible. Finding himself in agreement with this conclusion, Sir PATRICK LAIDLAW puts forward the view that in the group of viruses we 1 Virus
Disease and Viruses. By Sir Patrick Laidlaw, London : Cambridge University Press. 1938.
F.R.C.P., F.R.S. Pp. 52. 2s. 6d.
1340 have a collection of micro-organisms which have traversed the path of evolution towards the goal of complete parasitism to varying degrees. The large viruses would thus be those which had lost the power to synthesise one or two essential factors necessary for their life and had so become dependent on that cellular environment where these particular factors were to be found. And passing down the virus scale there would be the loss of more and more metabolic activities until one reached the smallest viruses bereft of all ferment activity, the " " ultra-parasites resigned to living a borrowed life. The very simplest form of virus would thus be micro-organisms which had lost everything except the ability to transmit the character of the species. It is, assuredly, a most attractive hypothesis but it leaves one point unexplained. If the very simplest form of virus which is represented by a simple nucleo-protein in molecular dispersion does not reproduce itself by autocatalysis, then how does it multiply ? Does it do this by fission ? If so, this is something quite foreign to our conception of the behaviour of molecules.
GENERAL OR SPECIAL HOSPITAL FOR MATERNITY?
,
CONCERN for the hard core of the maternal death-rate is leading, rightly or wrongly, to a great increase in the demand for institutional care. In three districts of New York City 80 to 90 per cent. of deliveries take place in hospital, and there is evidence that this figure may yet be equalled in this country. If Prof. MUNRO KERR had his way it would be exceeded. The discussion over which he recently presided1 at the Royal Sanitary Institute, and a rather earlier (March 25th) discussion from a slightly different standpoint at the Royal Academy of Medicine in Ireland, show that informed opinion is exercised by the main problem, can the obstetric art be better practised at home, in a special hospital, or in a unit of a general hospital where its force is joined by other departments which assume for its purpose, and in the best sense, an auxiliary role ? The function of the maternity hospital is not simply the conduct of normal labour in healthy women. Were it so, separate housing would be the evident course to protect against infection. Ante natal and postnatal care and paediatrics are obvious extensions of its responsibility. The system the must for climax the confinement of responsible also supervise events leading up to it and the subsequent rehabilitation ; and this calls for the knowledge and practice of every improvement in the prevention and treatment of disease and disability in mother and child. These considerations led the Departmental Committee on Maternal Mortality and Morbidity (1932) to recommend the inclusion, wherever possible, of maternity units within general hospitals. Throughout his period of responsibility the obstetrician is called upon to deal not only with the " unruly waywardness " that pregnancy may cause in the organism, but also with the imperfections of long ingrafted con=
"
1
See Lancet, April 30th, p. 1000.
dition."
Hence
departments of medicine, surgery, orthopaedics, pathology, dietetics, and radiology all form part of the ideal maternity service. Their lack cannot be compensated by the most devoted obstetric skill. The maternity unit of the general hospital has all these needs fulfilled under the one roof. Medical or surgical complications can be
treated
in
convenient
collaboration
with
specialists but with the obstetric significance of each development understood, and the ultimate decision governed by the department undertaking the final test, the actual delivery. The need for easily available specialist advice extends even into the labour theatre.
logical department
Close contact with a radiois essential to the nice conduct
of difficult cases and emergencies whose previous history is unknown. Our knowledge of the sources of hsemolytic streptococcus infections and the new chemotherapy have gone far to solve one problem of puerperal sepsis. There remains the other great cause of death and disability, the anaerobic streptococci. It may be that better understanding of the mechanism of labour will lessen this danger also. Radiography, by showing the available room in each type of pelvis, may to some extent prevent the trauma from blind manipulations which predisposes to infection. In particular a pathological department should be at the service of a maternity unit, and this is the strongest argument for its association with a general hospital. The advantages that its bacteriological research department gives such a special hospital as Queen Charlotte’s may well be unrivalled. For the average maternity service, even the faint shadow of such resources would be unobtainable unless it were incorporated with other departments to justify the appointment of a full-time pathologist. In the puerperium the obstetrician has to depend almost completely on the bacteriologist’s report for the appropriate segregation of the emergency admission, the unbooked, the suspect, and the infected cases. The protagonist of the special hospital may protest that contact between the nursing staff of the maternity and other units of the general hospital will increase the risk of infection reaching the parturient or puerperal woman. It should be possible to ensure, however, that the staff of each unit have no contact while in uniform. The case for separate housing requires more study. While R. CRUICKSHANK has demonstrated that nurses in contact with cases of streptococcal infection in surgical wards show a considerable percentage of carriers, experience at Queen Charlotte’s has been different. Investigations there have shown no significant difference in the incidence of carriers among the nurses of the entirely separate main and isolation blocks. Perhaps the difference lies in the care taken in the isolation block, by adequate masking of the nose and mouth, to guard against the development of carriers. At the British Postgraduate Medical School, among other similar institutions, it has been shown that the same principles are feasible in the maternity unit of a general hospital with an enthusiastic and instructed staff.