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INTERNATIONAL STREPTOCOCCI
1075 INTERNATIONAL STREPTOCOCCI
ATTITUDES to international research vary from a frank disbelief that it is profitable or possible to a rosy hope that it may solve all our problems. The truth is probably somewhere in between, and those who have such a project in mind will do well to read an account1 of a survey of the serological types of hsemolytic streptococci found in twelve countries and the diseases with which they are associated. The inquiry would seem a relatively simple one. The participants were all experts in this subject. Politicians may be unaware of the genuine good will which develops between the men of all races who worry over the same problems: the exchange of technical know-how is soon followed by an exchange of Christmas
cards.
,
Streptococcus pyogenes is an organism easy to recognise and isolate, it is found almost everywhere, and it is still a potent cause of human ill-health. It may be divided into " types " by agglutination and precipitation reactions which are within the competence of any good technician. What could be simpler than a collaborative study on a random sample of a few hundred strains from each country ? Because it is common experience in any one country that the strains from cases of scarlatina are not the same as those found in infections of the skin, it was decided that each national expert should collect about equal numbers from patients with sore throats, scarlatina, and extra-respiratory infections. These were to be typed by both T-agglutination and M-precipitation and, because accidents happen in the best-regulated institutions, 5% of all strains were to be cross-checked by another laboratory and, in event of , disagreement, by a third. Not all laboratories found it possible to adhere to the original plan of sampling. Neither Genoa nor Yokohama could produce many strains from extra-respiratory sources. Not every laboratory used a full set of 21 agglutinating sera, and some lacked some or all of the M sera. Agreement between the -laboratories was, however, fairly good: material concord on 86% of specimens and disagreement on only 5%. The main area of contradiction was in the make-up of the T-agglutination complexes, and there were grounds for thinking that many of these arose from minor differences in technique. In general, the survey showed convincingly that, while some streptococcal types are found almost universally, the pattern varies considerably from country to country. Scarlatina everywhere seems to be caused by a very limited selection of serotypes, and these are seldom those which are common in extra-respiratory infections. " Time spent in reconnaissance is seldom if ever wasted." Looking back it is easy to say that this survey would have been more informative had all the laboratories used complete sets of sera from a single source and if their methods had been identical in every detail. A greater uniformity in sampling might have been an advantage. Although the alternatives present very real difficulties the use of routine " material in this sort of "
inquiry
is not entirely satisfactory. The specimens may random sample of those received by the laboratory but, because they are sent by physicians of various habits and interests, they are not a true mirror of the infections at large in the community. The commoner the infection the more serious this source of error: it is unlikely
be
a
1.
Parker, M.
T. Bull. Wld Hlth
Org. 1967, 37,
513.
that many cases of rabies escape investigation. In this survey the collection of the specimens was spread over several months because differences in seasonal occurrence might be of interest. Limiting the inquiry to one month - say, February, since all the laboratories were in the northern hemisphere-might have given different results. Lastly, someone may object that the total number of strains examined (5912) was too small in view of the multiplicity of types, but there is a limit to all things and those who took part had other duties. Both in its methods and its results this is a very interesting report and, as it says, it operis the door on many other problems. The wider use of precipitation methods of typing has suggested that the host-parasite relationship of some strains of streptococci is more specialised than had been thought, and it will be of interest to see these methods pursued on a wider scale. In this inquiry no laboratory within the tropics was included. S. pyogenes used to be thought a rare organism in India: perhaps it was looked for in the wrong places.
ASPARAGINASE AND LEUKÆMIA
IT has long been known that cancers are rare in guineaIn 1953 Kidd2 found that the serum of guineapigs inhibited certain mouse and rat lymphomas; and Broome3 showed that L-asparaginase in the serum was responsible for this action. The inhibiting effect is a direct one and does not involve an immune response.4 The cells of sensitive tumours (including lymphosarcoma in the dog5 and various transplantable rat tumours, including a carcinosarcoma 6) are dependent on an external source of the aminoacid, L-asparagine, while the insensitive tumour cells can do without it. Dolowy et al. showed that i-asparaginase-containing fractions of guineapig serum caused a fall in the white-cell count and a shrinkage of enlarged organs in a child with acute lymphoblastic leukaemia; and others have noted complete temporary remissions.8 Since L-asparaginase does not affect normal cells, it could be a valuable means of treating cancers whose cells require L-asparagine.
pigs.
Oettgen et al. demonstrated that L-asparaginase will induce remissions in some cases of acute lymphoblastic and acute myeloblastic leukaemia and they observed a positive correlation between the in-vivo response and the demonstrable in-vitro requirement for L-asparagine of the leukaemia cells. Patients likely to respond could therefore be picked out by laboratory tests (which is a distinct advantage because of the extreme scarcity of L-asparaginase). Two sources of the enzyme at present exist-the guineapig serum and Escherichia coli,9 which produces two L-asparaginases, only one of which is effective against 1. Twort, C. C., Twort, J. M. J. Path. Bact. 1932, 35, 976. 2. Kidd, J. G. J. exp. Med. 1953, 98, 565. 3. Broome, J. D. Nature, Lond. 1961, 191, 1114. 4. Boyse, E. A., Old, L. J., Campbell, H. A., Mashburn, L. T. J. exp. Med. 1967, 125, 17. 5. Old, L. J., Boyse, E. A., Campbell, H. A., Brodey, R. S., Fidler, J., Teller, J. D. Cancer, N.Y. 1967, 20, 1066. See also Lancet, 1967, i, 431 448. 6. Kwak, K. S., Jameson, E., Ryan, R. M., Kurtz, H. M. Cancer Res. 1961, 21, 44. 7. Dolowy, W. C., Henson, D., Cornet, J., Sellin, H. Cancer, N.Y. 1966,
19, 1813. Oettgen, H. F., Old, L. J., Boyse, E. A., Campbell, H. A., Philips, F. S., Clarkson, B. D., Tallal, L., Leeper, R. D., Schwartz, M. K., Kim, J. H. Cancer Res. 1967, 27, 2619. 9. Mashburn, L. T., Wriston, J. C. Archs Biochem. Biophys. 1964, 105,
8.
450.
ATTITUDES to international research vary from a frank disbelief that it is profitable or possible to a rosy hope that it may solve all our problems. The truth is probably somewhere in between, and those who have such a project in mind will do well to read an account1 of a survey of the serological types of hsemolytic streptococci found in twelve countries and the diseases with which they are associated. The inquiry would seem a relatively simple one. The participants were all experts in this subject. Politicians may be unaware of the genuine good will which develops between the men of all races who worry over the same problems: the exchange of technical know-how is soon followed by an exchange of Christmas
cards.
,
Streptococcus pyogenes is an organism easy to recognise and isolate, it is found almost everywhere, and it is still a potent cause of human ill-health. It may be divided into " types " by agglutination and precipitation reactions which are within the competence of any good technician. What could be simpler than a collaborative study on a random sample of a few hundred strains from each country ? Because it is common experience in any one country that the strains from cases of scarlatina are not the same as those found in infections of the skin, it was decided that each national expert should collect about equal numbers from patients with sore throats, scarlatina, and extra-respiratory infections. These were to be typed by both T-agglutination and M-precipitation and, because accidents happen in the best-regulated institutions, 5% of all strains were to be cross-checked by another laboratory and, in event of , disagreement, by a third. Not all laboratories found it possible to adhere to the original plan of sampling. Neither Genoa nor Yokohama could produce many strains from extra-respiratory sources. Not every laboratory used a full set of 21 agglutinating sera, and some lacked some or all of the M sera. Agreement between the -laboratories was, however, fairly good: material concord on 86% of specimens and disagreement on only 5%. The main area of contradiction was in the make-up of the T-agglutination complexes, and there were grounds for thinking that many of these arose from minor differences in technique. In general, the survey showed convincingly that, while some streptococcal types are found almost universally, the pattern varies considerably from country to country. Scarlatina everywhere seems to be caused by a very limited selection of serotypes, and these are seldom those which are common in extra-respiratory infections. " Time spent in reconnaissance is seldom if ever wasted." Looking back it is easy to say that this survey would have been more informative had all the laboratories used complete sets of sera from a single source and if their methods had been identical in every detail. A greater uniformity in sampling might have been an advantage. Although the alternatives present very real difficulties the use of routine " material in this sort of "
inquiry
is not entirely satisfactory. The specimens may random sample of those received by the laboratory but, because they are sent by physicians of various habits and interests, they are not a true mirror of the infections at large in the community. The commoner the infection the more serious this source of error: it is unlikely
be
a
1.
Parker, M.
T. Bull. Wld Hlth
Org. 1967, 37,
513.
that many cases of rabies escape investigation. In this survey the collection of the specimens was spread over several months because differences in seasonal occurrence might be of interest. Limiting the inquiry to one month - say, February, since all the laboratories were in the northern hemisphere-might have given different results. Lastly, someone may object that the total number of strains examined (5912) was too small in view of the multiplicity of types, but there is a limit to all things and those who took part had other duties. Both in its methods and its results this is a very interesting report and, as it says, it operis the door on many other problems. The wider use of precipitation methods of typing has suggested that the host-parasite relationship of some strains of streptococci is more specialised than had been thought, and it will be of interest to see these methods pursued on a wider scale. In this inquiry no laboratory within the tropics was included. S. pyogenes used to be thought a rare organism in India: perhaps it was looked for in the wrong places.
ASPARAGINASE AND LEUKÆMIA
IT has long been known that cancers are rare in guineaIn 1953 Kidd2 found that the serum of guineapigs inhibited certain mouse and rat lymphomas; and Broome3 showed that L-asparaginase in the serum was responsible for this action. The inhibiting effect is a direct one and does not involve an immune response.4 The cells of sensitive tumours (including lymphosarcoma in the dog5 and various transplantable rat tumours, including a carcinosarcoma 6) are dependent on an external source of the aminoacid, L-asparagine, while the insensitive tumour cells can do without it. Dolowy et al. showed that i-asparaginase-containing fractions of guineapig serum caused a fall in the white-cell count and a shrinkage of enlarged organs in a child with acute lymphoblastic leukaemia; and others have noted complete temporary remissions.8 Since L-asparaginase does not affect normal cells, it could be a valuable means of treating cancers whose cells require L-asparagine.
pigs.
Oettgen et al. demonstrated that L-asparaginase will induce remissions in some cases of acute lymphoblastic and acute myeloblastic leukaemia and they observed a positive correlation between the in-vivo response and the demonstrable in-vitro requirement for L-asparagine of the leukaemia cells. Patients likely to respond could therefore be picked out by laboratory tests (which is a distinct advantage because of the extreme scarcity of L-asparaginase). Two sources of the enzyme at present exist-the guineapig serum and Escherichia coli,9 which produces two L-asparaginases, only one of which is effective against 1. Twort, C. C., Twort, J. M. J. Path. Bact. 1932, 35, 976. 2. Kidd, J. G. J. exp. Med. 1953, 98, 565. 3. Broome, J. D. Nature, Lond. 1961, 191, 1114. 4. Boyse, E. A., Old, L. J., Campbell, H. A., Mashburn, L. T. J. exp. Med. 1967, 125, 17. 5. Old, L. J., Boyse, E. A., Campbell, H. A., Brodey, R. S., Fidler, J., Teller, J. D. Cancer, N.Y. 1967, 20, 1066. See also Lancet, 1967, i, 431 448. 6. Kwak, K. S., Jameson, E., Ryan, R. M., Kurtz, H. M. Cancer Res. 1961, 21, 44. 7. Dolowy, W. C., Henson, D., Cornet, J., Sellin, H. Cancer, N.Y. 1966,
19, 1813. Oettgen, H. F., Old, L. J., Boyse, E. A., Campbell, H. A., Philips, F. S., Clarkson, B. D., Tallal, L., Leeper, R. D., Schwartz, M. K., Kim, J. H. Cancer Res. 1967, 27, 2619. 9. Mashburn, L. T., Wriston, J. C. Archs Biochem. Biophys. 1964, 105,
8.
450.