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Americans in Vietnam, though this is disputed on theground that the agents employed are not lethal. As forbiological agents, there is no firm proof that they haveever been used.
Though the 1925 Geneva Protocol banned the first useof both chemical and bacteriological weapons, it did notforbid retaliatory use nor did it preclude research or actualproduction. In the past decade in some fifteen or morecountries much research has been done; and in a fewproduction has risen steeply. Details of the known agentsand their application in war are given in two recent books-one British,! one American.2 Neither makes comfortable
reading. Among the new generation of chemical weaponsis a nerve gas reputed to be 2000 times as toxic by cutaneousabsorption as mustard gas; a dose so small (2-10 mg.) asto be invisible on the skin would be fatal. Deliverysystems have also been improved, and aerosol sprays,bomb clusters, and guided missiles are among the meansnow available for disseminating both chemical and
biological agents. Nerve agents are said to be stored atthe Rocky Mountain Arsenal in Denver in quantitiescapable of killing hundreds of millions of people. Theurge to stockpile biological weapons is less keen,but preparations for large-scale rapid production are
known to have been made, for example, at Pine BluffArsenal in Arkansas. Little is known about the
position in Communist countries, but it is probablysimilar.
Science, medicine, and industry are becoming in-
creasingly concerned in this situation. Hersh 2 cites over50 American universities engaged in CBW projects; and,despite the fact that the information was supplied by thePentagon, " almost without exception the universities-once queried-denied they were conducting such re-
search ". Some of the heads of these institutions seemed
genuinely unsure of what was going on in this subjectwithin their own campus. U.S. contracts for work onCBW projects have also been given to a number ofuniversities in other countries, including Japan, France,West Germany, Holland, Belgium, Sweden, Ireland, andGreat Britain. Of these some are engaged in similarresearch projects for their own Governments. A list of 28CBW research contracts let to British universities was
given in Hansard on May 29, 1968. Much of the work,of course, is basic research not necessarily directly relatedto CBW. Although most is published, a small part remainssecret: at present about 80-90% of the work at the
Ministry of Defence’s Microbiological Research Establish-ment is published.3 In the U.S.A. the classified sectoris larger.The work undertaken by any one research team may
seem and indeed be innocent enough and be directed purelytowards defence. But much of the knowledge could con-ceivably be used in the reverse direction. The issues to befaced are fundamental and, for doctors in particular 4
inescapable. What is the purpose of science-and ofmedicine ? Must what the State asserts to be in thenational interest always be accepted as paramount ?Should doctors and other scientists ensase in nrenarations
1. CBW. Chemical and Biological Warfare: its scope, implicationsand future development. Report of the London Conference onCBW. Edited by STEVEN ROSE. London: George Harrap. 1968.Pp. 209. 30s.
2. Chemical and Biological Warfare. America’s Hidden Arsenal. BySEYMOUR M. HERSH. London: MacGibbon & Kee. 1968. Pp. 354.50s.
3. See Lancet, 1968, ii, 959.4. ibid. p. 391.
which could be used to spread poisons and disease ? Whateffect has secrecy on professional and on internationalrelations ? These two books on CBW may help to focusattention on the need for reappraisal of ethical values in aworld that seems increasingly to be losing its way.
HISTOCOMPATIBILITY DIFFERENCESAND CANCER
THE rapid growth of Australia’s contribution to thescience of medicine and the formation in 1956 of theCollege of Pathologists of Australia-seven years beforeits British counterpart-have led to the emergence of anew quarterly journal entitled, simply, Pathology.1 Thefirst issue is largely devoted to aspects of immunology andcancer research, but the editors indicate that papers con-cerned with all branches of clinical and experimentalpathology will be considered for publication.
Observations by Stanley and his colleagues on murineinfection with reovirus 3 culminated in 1966 in findingswhich linked the induction of runting with lymphoma.2 3After exposure to the virus during the neonatal period,only 1 % of mice of the Prince Henry (PH) strain survivedthe acute effects of the infection. In the survivors achronic progressive disease developed, the features ofwhich included lymphopenia, monocytosis, the presenceof a thermolabile antibody, and histopathological changesin the liver and other tissues suggestive of autoimmunedisease. The virus could not be recovered from animals
during the later stages of the disease. In 1 out of 26 long-term survivors malignant lymphoma (2731/L) developed.Transfer to newborn PH mice either of lymphoma cellsfrom this 1 mouse or of spleen cells from mice thatexhibited only runting gave rise first to runting (intwenty to thirty days) and later in some animals (after thethirty-first day) to massive lymphomas.
These findings were consistent with observations madein other species 4 and with previous observations inmice.5 Sinkovics 6 suggested that the association betweenrunt disease and lymphoma might come about in one ofthree different ways: (1) a passenger virus such as reovirus3 (or other microorganism) might give rise to both auto-immune disease and runting; (2) cell-induced runt
disease might escalate into malignant lymphoma; or (3) aspecific leukaemia virus carried by PH mice might cause theemergence of both autoimmune reactive and malignantlymphocytes. Sinkovics favoured the third explanation.Keast and Papadimitriou,7 however, found no evidenceof the presence of any of the common murine leukxmiaviruses in 2731/L lymphoma cells.The second of Sinkovics’ choices was originally pro-
posed by Schwartz and Beldotti,8 who reported that theinjection of parental spleen cells into Fi hybrid mice
1. The official journal of the College of Pathologists of Australia. Fourissues a year. Annual subscription A$15, U.S.$20, £8. SydneyUniversity Press, Press Building, University of Sydney, N.S.W.,Australia 2006. Manuscripts may be sent to the Editor, Prof. FrankMargarey, Department of Pathology, University of Sydney, N.S.W.,Australia 2006.
2. Joske, R. A., Leak, P. J., Papadimitriou, J. M., Stanley, N. F., Walters,M. N.-I. Br. J. exp. Path. 1966, 47, 337.
3. Stanley, N. F., Walters, M. N.-I. Lancet, 1966, i, 962.4. Dameshek, W. ibid. p. 1268.5. Sinkovics, J. G. Arch. Virusforsch. 1962, 12, 143.6. Sinkovics, J. G. Lancet, 1966, ii, 229.7. Keast, D., Papadimitriou, J. M. ibid. p. 589.8. Schwartz, R. S., Beldotti, L. Science, N.Y., 1965, 149, 1511.
195
(C57BL x DBA/2) gave rise to graft-versus-host disease,and that in the long-term survivors of this reaction
lymphoid neoplasms resembling Hodgkin’s disease or
lymphosarcoma developed. The mice that bore thetumours were chimaeras, but the tumours themselves wereof host origin and did not grow in the mice of the donorparent strain.
A paper in the new Australian journal by Keast andStanley 9 examines the hypotheses that a chronic form ofthe graft-versus-host (G.v.H.) reaction or minor histo-
compatibility differences in lymphoid cells are sufficientto produce neoplasms in PH mice. The experimentswere conducted in newborn mice of the PH strain, whichhas a low natural incidence of leuksemia. Chronic G.v.H.disease was induced by the intraperitoneal inoculation ofspleen cells from mice of another strain in numbers suchthat 65 out of 120 survived runting disease longer thanthirty-five days. The effect of minor histocompatibilitydifferences was explored by the inoculation of spleen cellsfrom adult PH mice of both sexes into newborn PH mice.In neither experiment did the long-term survivors withG.v.H. disease get leukaemias or neoplasms of other typesin higher incidence than untreated PH mice. Keast and
Stanley conclude that the results provide no supportfor the Schwartz-Beldotti theory. The findings favourthe view that, in PH mice, lymphocytes altered byreovirus-3 infection may react against the host to giveeither auto-immune disease or malignant lymphoma.Whether the same type of change produces both effectsis not clear, but, according to Stanley,lo two types ofabnormal cell are present in the 2731/L lymphoma.
It would be unwise to extrapolate the negative findingsof Keast and Stanley 9 to other biological systems in whichevidence of autoimmune disease is associated with theinduction of cancer. Both the autoimmune disease andthe reticulum-cell neoplasms to which mice of the NZBstrain are subject are probably due to a leuksemicvirus."-13 If so, here is an example of Sincovics’ thirdpossibility.
HUNTING THE CARRIER
MOST bacteriologists concerned with public health havemade use of the Moore swab, but outside their circle thissimple device seems little known. The original purposewas to trace carriers of Salmonella paratyphi B.14 It isno more than a bundle of sterile gauze on a long stringwhich can be lowered into a sewer and left there for a few
days to collect a sample of sewage for bacteriologicalexamination. Some of the liquid sewage is held in thesubstance of the fabric by capillary action, and a certainamount of solid matter accumulates on the outside of thebundle. It is, in fact, a crude sort of filter, costing almostnothing, which can be left in a stream of sewage indefinite-ly without getting clogged. When the swab has beenremoved from the sewer the fluid which drips from itmay be cultured directly and, in addition, the whole swabmay be immersed in an enrichment medium with further9. Keast, D., Stanley, N. F. Pathology, 1969, 1, 19.
10. Stanley, N. F. Lancet, 1966, ii, 589.11. Mellors, R. C., Huang, C. Y. J. exp. Med. 1966, 124, 1031.12. Mellors, R. C., Huang, C. Y. ibid. 1967, 126, 53.13. East, J., de Sousa, M. A. B., Prosser, P. R., Jaquet, H. Clin. exp.
Immun. 1967, 2, 427.14. Moore, B. Mon. Bull. Min. Hlth, 1948, 7, 241.
subculture. The choice of culture media will dependon the whim of the bacteriologist and on the organismwhich is sought: Moore found that media suitablefor the detection of S. paratyphi B were useless forS. typhi.I5There may be sound epidemiological reasons for
believing that there is a carrier of some specific intestinalinfection at large in a community. Finding him is anothermatter. The first stage in Moore’s method is to confirmthe suspicion by the isolation of organisms from one of themajor sewers, preferably not once but several times. Thesewer is followed back to the first junction and the choicebetween the two feeding sewers made by putting a swabin each. And so on at every division until the trail leadsto the street and even to the house where the carrier lives.It is not, of course, all plain sailing. It may be that atone junction neither branch yields a positive and theprocess must be repeated. Many carriers excrete theirorganisms intermittently and some go on holiday or movehouse. Several carriers may exist, so that at one junctionboth swabs yield positives and both must be followed up.The shifting of manhole covers and the laying of swabsinterrupts the quiet routine of municipal life and someobjections are not unusual. In spite of these difficulties,the Moore swab has usually allowed the medical officer ofhealth to get his man, and at far less expenditure of timeand effort than any possible alternative. The use of theswabs has been extended to other purposes. So long asthe streams are not too broad, they work equally well innatural water courses. Placed in the drain serving anabattoir they give a fair sample of the salmonellas har-boured by the animals which have been slaughtered there(and this is probably an indicator of the organismspresent in the community). For still waters they areobviously unsuitable.
In the epidemic in Aberdeen in 1964 something over400 persons were infected with S. typhi. 16 Very probably,there were a few others who escaped detection or wereinfected at second hand. Some argument has arisen onthe proportion of those who, having had typhoid, remaincarriers: it probably varies much from epidemic to
epidemic. But, since most of those infected in Aberdeenwere treated in hospital, few undetected carriers werelikely to be loose in the community. Only one, however,might have been a danger and it was clearly desirable tocomb the city thoroughly. Moore swabs had never beenused in a city of this size, but they seemed to be themethod of choice. 17 The existence of known carriersenabled some controlled observations to be made on theefficacy of the method and on the choice of culture media.Four schedules for culturing the swabs were tried, ofwhich one was a good deal better than the others, but it isfair to add that it required the use of 22 plates for eachspecimen. (Some senior bacteriologists have held thatthe number of plates inoculated is more important thanany refinements of the medium.) By the best methods ofculture, S. typhi could usually be isolated from thedomestic sewers serving the houses where the carrierslived, but when the sampling was extended downwardthe number of isolations fell off steadily: the larger thesewer the fewer the isolations. The reason for this isobscure. Both carriers had been treated with anti-
15. Moore, B. ibid. 1950, 9, 72.16. The Aberdeen Typhoid Outbreak 1964. Scottish Home and Health
Department. H.M. Stationery Office, 1964.17. Callaghan, P., Brodie, J. J. Hyg., Camb. 1968, 66, 489.