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Diseases in Search of Viruses

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Diseases in Search of Viruses DISEASES IN SEARCH OF VIRUSES BY C. H. STUART-HARRIS, M.D., F.R.C.P. Professor of Medicine, University of Sheffield* ft f>]/ery?ne agrees that tremendous changes have occurred in the past few years in the ?f the infectious diseases. Formidable have been both for the tt? weapons forged a c atlftent and the prevention of bacterial infections. As result, diphtheria has be- CQ^e almost extinct and the enteric diseases are much reduced, patients with strepto- 1) ^ disease and with pneumonia less often require hospital treatment, and the acute i^ness *n childhood has Virus infections have 1?t K considerably lightened. W Wever> altered in the same way or to the same extent. Some, such as poliomyelitis, a to both children and adults. undescribed S(J ? become threat Previously conditions as myalgic encephalomyelitis or Royal Free disease, aseptic meningitis with an and little known syndromes such as herpangina, pharyngo-conjunctival fever a^hemOrnholm disease have achieved a of interest and even of as cjjj position importance of ,S.es of morbidity. Moreover, the development of new techniques for the cultivation has led to the realization of a method of control of certain diseases and to a H^lr.Usesk 'cia regard to diagnosis. These changes have affected the work of both clin- oUtlns and microbiologists, and yet there has also arisen a considerable divergence of iti h?0^ between these two groups of medical men. One could almost say that they live -j,,0 different worlds. virune virologist, being equipped with new techniques for the laboratory study of CoVeSes> has been more and more excited over the possibility of fundamental dis- w concerning the nature of viruses, of their mode of multiplication and of the Uity restraining their multiplication by chemical substances. Whenever he his time with human specimens he has found less difficulty in recovering vi^upiedes Sp than in classifying the agents thus recovered and in relating their presence in V^ns to the particular phase of illness or health existing in those from whom they ^rived. There has therefore arisen the phrase of "Viruses in search of disease" been to the to the Coxsackie viruses M t applied chiefly poliomyelitis-like viruses, by th? a<ienoviruses. One gets the impression that virologists are at times unmoved Snf C^nical implications of their discoveries and that therefore they are sometimes to % urge the use of prophylactic weapons against viruses before it has even apparent that they are a significant cause of human distress! if ^.clinician's world is of course familiar to most of you. He moves in an atmosphere illnesses or of family outbreaks where diagnosis and treatment are the ^ce ?.unt needs. He looks on viruses as mysterious microbes very similar to bacteria Nat'ln S*ze anc* blames all diseases of unknown aetiology upon their activity. He is \ hlen*to solve clinical problems in the way that so many problems were solved in nainely by first delineating a syndrome sufficiently clearly for it to be called N)V entity and then by seeking investigation from all possible angles in order to the virus lurking in the patients' interior. Unfortunately clinicians do not Ji^derstand the importance of epidemiological studies, the meaning of latent W forms of virus infection and the significance of virus infections in relation ari ecol?gy (in spite of the prevailing influence of rabbit myxomatosis!) Natur- am sympathetic to the clinician's difficulties, and I am equally Si?Lcli"ic.iari1^ S c]US t^ie dangerous Path which virology is tempted to pursue. I therefore feel J to*-\J LI toIU twoIVYU U1 VltW W1 I , uty tryJ bringUlillg togetherlASgt'U.ll'.L these contrastingVUHUaOUHg pUlllCOpoints of view whenever ^ an address to the Bristol Medico 8th V ' Chirurgical Society, January, 1958. V, 3 No. 268. 29 30 PROF. C. H. STUART-HARRIS easy f can. To do this I must attempt to make the virologist's world a little more clinicians to understand. Virus Growth in Tissue Cultures v. intf0' Research on animal viruses has characteristically depended upon the duction of methods of each one of a cultivation, which has yielded certain haI?f ^s. knowledge but which has eventually failed to throw fresh light on existing Pr0. 0f The new look in virus research at the time stems from the introduce present ^ tissue culture methods by the Boston group of workers centring around Enders Boston children's hospital. Helped by the use of antibiotics to control contamin ^ Enders transformed tissue cultures from their previous position of technical in to a method of He was also instrumen.c0in^j ity capable exploration by any laboratory. s so that placing the tissue cultures within reach of the low power of a microscope histological observation of the changes wrought by virus multiplication cou effected. ... , tne c The two chief ways of tissue cultures for virus cultivation are preparing o method where morsels of tissue are embedded in a plasma clot and allowed to a halo of growing cells and the roller-tube technique of cells dispersed by tryp8111*^ in where the wall of the test-tube becomes covered with a sheet of cells. Virus the grC^ce cells may produce disintegration and cell-death as with poliovirus or else ^ cas alter morphologically but remain alive as with the adenoviruses. In both bu changes observed microscopically are termed cytopathogenic alterations occasionally true that viruses may grow in cells without producing any visible tions. Cytopathogenic changes form the basis of methods for the titration 0 of neutralization tests for measuring specific antibodies against the viruses in or animal sera. and hu^11 studies of viruses show a great variation but animal Morphological e viruses are usually composed of small rounded particles as viewed by the e, microscope. Internal complexity of organization of these elementary bodies as action. lSSimilaf times revealed by methods such exposure of the virus to enzyme ^jcfo- internal is revealed the thin tissue-slice method of complexity by e^ect^eI yifuS graphy perfected by Councilman Morgan and his colleagues in New York. toplaS' bodies of vaccinia and herpes are readily seen by this method developing *n n c^^rane' mic granular areas within complete or incomplete shells of a surrounding eeli but in the case of influenza no organized structure is found except at the Here the rounded bodies and filamentous forms can be seen escaping from juto of plasm in great numbers. The development of the virus from the moment be the cell until its release is hidden from view and cannot for some hours its m even by chemical or serological methods. It seems that the virus particletowa with the cell nucleus or and diverts metabolic activity identity cytoplasm ' replication of its own genetic material which resides in its nucleic acid conte tjfjed are the multiplication of viruses is so different from that of bacteria that we in regarding them as a distinct order of organized life, if indeed one can rega as possessing the essential attributes of living matter. SOME COMMON INFECTIONS AND THEIR VIRUSES Now let us turn to the diseases which either have been in search of letv^rU^ns0er us recently or which still are in search of their causative organisms. First the exanthemata?measles, rubella, chickenpox and herpes zoster: The Exanthemata one vvas re^ Measles virus was transmitted to monkeys some years ago but no ulltil ^ convinced that a successful method of laboratory culture had been foun yjfi1 ^g & Boston workers published their study on measles virus in tissue culture. y or fli produces an unusual cytological change?the various cells of a human DISEASES IN SEARCH OF VIRUSES 31 (fUre merge their identity into a syncytium so that large giant cells are produced. (Le ^ight in passing mention that giant cells can readily be demonstrated by swabbing or in children with measles and the cellular exudate 0 !?ares nasopharynx smearing - a for But tissue c slldes: this is useful diagnostic method measles. the culture giant e on from itifeS - permitted the development of work antibodies during convalescence ctl?n and the titration of gamma globulin against measles virus. Moreover, Enders Carried the virus in cultures of human amnion, transferred it to chick embryo (j and is approaching the development of a vaccine against the disease. A more Will line of work is the present suggestion that measles is related to dog distemper s> jj This arose from the demonstration that most children develop antibodies to ^ er)iper virus as they grow up. But the distemper virus produces such distinctive ?es in the ferret that it seems to be that this virus is related to measles ar)(j unlikely ^ore work on this theme is required. Rubella has so far defied attempts to define Ration. Chickenpox and herpes zoster virus have been grown in tissue cultures transfer from one culture to the next can be made intact ie ' only by using cells, y grafting. Grinding up the cells prevents the virus from re-entry into new cells the relation between virus and host cell must be intimate. Glandular feVe r extremely has proved much more baffling. No success has been achieved in growing the associated with mononucleosis accompanied by a positive Paul Bunnell reaction. yjej ,a cases of apparent glandular fever with a negative Paul Bunnell test have pro Toxoplasma on cultivation. This organism is not of course a virus but the tL that it can cause mononucleosis shows that glandular fever is a syndrome rather a disease. ^^tary Diseases o^t the alimentary viruses require consideration. The innocent term "D.
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