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Medical Conferences

THE NATURE OF VIRUS MULTIPLICATIONTHE spring congress of the Society for General Micro-

biology was held at Oxford, the theme for the discussionsbeing the Nature of Virus Multiplication. The sym-posium fell into two main parts, the first being a

discussion of the general principles involved in the

production of virus material, and the second a discussionof the means of reproduction in specific viruses.

FORMATION OF VIRUS MATERIAL

New virus material is nucleoprotein in nature, andH. CHANTRENNE pointed out that the processes of itsformation were intima,tely linked with the ribose-

nucleic acids of the cell cytoplasm and with the high-energy phosphate bonds of adenosine triphosphate.The real difficulty, he said, was to explain how a specificprotein was created : to state that this was due to

enzymic action was begging the question, since each

enzyme would be protein in nature and require anotherset of enzymes to build it up. Two possible mechanismsmight account for protein specificity ; one was the

template theory put forward by Pauling,l and the other(Chantrenne suggested) was that unwanted materialwas broken down by cell proteases, in which case thenucleoproteins produced in a cell might be those thatwere capable of withstanding the intracellular proteo-lytic enzymes. F. C. BAWDEN and N. W. PIRIE

suggested that the specificity of nucleoproteins producedas a result of virus infections in plants was less exactthan many virus workers believe, and that at least99% of the proteins produced as a result of infection wereserologically identical with the virus but were non-infective. The only character which differentiated a

virus from any other nucleoprotein was its ability toinfect a cell, and, this being so, the so-called

" soluble

phases of viruses should be treated with much reserveas many such stages were most probably by-productsof virus multiplication.Both these speakers and those who followed emphasised

that the great difference between viruses and bacterialay in their dependence on the host-cell for multiplica-tion, which implies that it may be much more difficultto find criteria which enable us to differentiate betweenviruses and cell nucleoprotein than it is to find differencesbetween bacteria and virus. Until such charactersare found, many viruses will remain unrecognised ;for all viruses do not possess the essential feature of

pathogenicity which at the present time enables us

to recognise them.Other problems discussed included the part played

by nucleic acids in the synthesis of new virus particles,and it was thought that these compounds have as greata potential specificity as has the protein moiety ofthe virus particle. R. MARKHAM, working with plantviruses, has shown that at least six and possibly thirtynucleic acids may be present in a virus particle, and hesuggested that they may be responsible for the charactersof the virus, the protein portion acting as a carrier forthese nucleic acids.A discussion on the enzymic activity of viruses

showed that there are two schools of thought ; one

believes that the agglutination of erythrocytes byinfluenza virus is enzymic, while the other thinks thatviruses are without enzymes. Whichever view is correctit has been established that viruses are without respiratoryactivity and do not possess enzymes which would enablethem to reproduce.

MULTIPLICATION OF VIRUSES

From the discussion of the general problems of virusmultiplication it could be concluded that the virus

1. Pauling, L. J. Amer. chem. Soc. 1940, 62, 2643.

ilietabolisiii is so iutirrrately linked to the cell that theformation of the fresh virus particles is probably by thesame pathways which the cell uses to reproduce itsown nucleoproteins, and only in the matter of"

specificity " does the virus material diner. How virus

"

specificity " of the protein and nucleic acids is

established ill the cell is as yet unknown, and though thetemplate theory lias great theoretical attractions itsapplication to individual problems is more difficult.

Further discussion took place on the multiplication ofindividual viruses, and the most argument centred aroundinfluenza virus and the bacteriophages, because theseviruses are readily handled and quantitative methodscan be used in their study. In both these types of

organism the most interesting problem is the questionof the changes which occur between the infection of acell and the appearance of fresh virus within the cell,During this latent period no infective virus can befound within the cell. A few years ago Luria z

suggested that the phage breaks up into units whichreproduce individually and then re-aggregate to form theinfective particle, but recently Dulbecco 3 has shown,by radiation studies of infected cells, that this is notthe explanation and Luria has abandoned his earlierviews. At the present time no explanation accounts forall the phenomena observed in the bacterial viruses;this might he due, as Felix 4 believes, to the fact thatbacteriophages are not a virus but are a part of thebacterial cell with a separate existence.Xo discussion of bacteriophage multiplication would

be complete without a consideration of how lysogeniebacterial strains are formed ; and here again there weretwo schools of thought, the one believing in Lwoff’s5theory of the propha,ge, and the other accepting Boyd’,s6view that bacteria are lysogenic because they carrynon-pathogenic or symbiotic bacteriophage particles.The discussion on these lysogenic bacteria suggested thatbacteriophage may infect bacteria and give rise to a

lysogenic strain of organisms in more than one way.The reproduction of influenza virus has been studied

in much detail, and with this and other animal virusesdiscussion turned largely on the nature of the lateat

period after infection and Hoyle’s theory that thevirus is built up in a series of differing units which

aggregate to form the influenza elementary body.Hoyle bases his views on the serological differentiationof the various units of the particle, but this opinionwas strongly criticised. It was suggested that hisresults could be explained if influenza produced non.infective serologically specific material, as has beenfound in plant viruses. In support of the view voil

Magnus 8 has shown that "

incomplete "

or non-infectivematerial can be produced by influenza virus. Those who

disagreed with Hoyle’s theory argued that there is no. need to assume a break-up ’into separate units; ther

thought that the viruses could multiply by each geneticunit of the virus reproducing itself and so .forming anew particle. As in the case of bacteriophages, no theory

, quite explains the facts observed ; ; the objections to

; Hoyle’s theory have already been stated, and any theorywhich insists on a simple replication and fission of virusparticles does not adequately account for the latent

. period or the recombination of viruses observed by: Burnett. 9

While much more information is available for bacterio- ’

phages and influenza viruses, the problem is being,’ investigated with other viruses ; but in many of theseB investigations the results are eomplieated by the fact

2. Luria, S. E. Proc. nat. Acad. Sci., Wash. 1947, 33, 253.3. Dulbecco, R. J. Bact. 1952, 63, 199.4 Felix, A. Proc. 4th International Congress of Microbiology.

1947, p. 355.5. Lwoff, A., Gutmann, A. Ann. Inst. Pasteur, 1950, 78, 711.6. Boyd, J. S. K. J. Path. Bact. 1951, 63, 445.7. Hoyle, L. Brit. J. exp. Path. 1948, 29, 390.8. von Magnus, P. Acta path. microbiol. scand. 1951, 29, 157.9. Burnett, F. M., Lind, P. E. J. gen. Microbiol. 1961, 5, 59.

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that it is necessary to use animal hosts, making it difficultto have a detailed analysis of each step as is possiblewith bacteriophages.

If one may generalise-and in such a diverse group oforganisms it is possibly unwise to do so-it seems thereare three main steps in virus multiplication. Thefirst step is the entry of the virus into a susceptible celland its loss of infectious form ; the second is the periodbetween infection and the appearance of fresh infectivevirus; and the third is the increase in number andmaturation of the virus particles leading to the dis-

organisation of the host cell. In the solution of thesecond of these problems may lie the clue to the natureof life. C. H S.

Parliament

Third Reading of the N.H.S. BillON the motion for the third reading, Miss PATRICIA

HORNSBY-SMITH, parliamentary secretary to the Ministryof Health, said that the Government had not introducedthe Bill for the sheer delight of taking the NationalHealth Service to pieces, but because they had to takea realistic view of the country’s financial difficulties.They regretted the necessity for this Bill, but they werecalled upon to cure the financial fever of their predecessors.Having decided to implement the 1949 Act and imposea shilling prescription charge, the Government hadintroduced this tidying-up measure so that there shouldbe no anomaly between patients obtaining prescriptionsfrom their general medical practitioners and taking themto chemists, and other patients going to the outpatientand dispensing departments of hospitals. Such ananomaly would have increased the pressure on theoutpatient departments.In committee, Miss Hornsby-Smith continued, they

had been pressed to make exemption from these paymentsfor various types of ailment and patient. An amendmenthad been passed exempting patients with venereal disease.This was a clearly defined group of patients who weretreated at special centres. We were also bound by theBrussels Agreement. But this was the only exemptionthey were prepared to make. Exemptions made accordingto the nature of the ailment would make it difficult forthe hospitals to administer the scheme. Exemptions,in the Government’s view, must therefore be on a basisof need. Accordingly people drawing National Assistancebenefit and war pensioners had been exempted. Wherethere was hardship beyond these two groups the NationalAssistance Board was empowered to help.Turning to the charges for appliances, Miss Hornsby-

Smith pointed out that these would be limited to fouritems : surgical boots, surgical belts, wigs, and elasticstockings. No charge would be made for appliances forchildren under 16.She defended the dental charges on the ground that

this was the place in the service where savings could bestbe made. The patients were generally active and inregular employment ; and it was hoped that these chargeswould increase the attention given to the priority classesof children, adolescents, and expectant mothers. Tolessen the effects of the charges where there seemedspecial reason the priority classes had been exempted,and for adolescents the age of exemption extended to 21.It had also been decided not to charge for the initialexamination and report. In conclusion she challengedthe Opposition to say, if they persisted in repudiatingthese charges, how they would make up the deficit onthe Estimates. Or were they prepared to allow theexpenditure on the health service to rise without limit ?Mr. H. A. MARQUAND welcomed the modifications

made in the Bill, but said that it remained thoroughlyobjectionable in principle. In his view it was unnecessaryto have made such generous gifts to those who paidincome-tax and to make savings of this kind at theexpense of -the sick, of chronic sufferers, and of thedisabled and afflicted. The Labour Party had introducedcharges in 1951 during the period of rearmament, butthey were not intended to be permanent and a time-limit was set to them. If the Labour Partv were returnedto power, Mr. Marquand continued, " we shall take steps

as soon as Parliamentary opportunity permits, to bringall these charges ... to an end."The third reading was carried by 284 votes to 266.

Dangers of Toxic Substances in AgricultureIn the House of Lords on April 29, Lord CARRINGTON,

joint parliamentary secretary to the Ministry of Agri-culture, moved the second reading of the Agriculture(Poisonous Substances) Bill, which he said had becomenecessary because of the increasing use in agricultureof poisonous substances as insecticides and weed-killers.The Government believed that enough was now knownto justify regulations. The regulations, for which thisBill accordingly provided, would follow the lines of therecommendations put forward last year by the Zuckermanworking party, which include the provision of protectiveclothing. The Government had at present no power ofenforcement of the precautionary measures, and it wasapparent that voluntary precautions were not enough.There was general agreement that precautions shouldhave statutory backing and that definite obligationsshould be placed on both employer and employed.For some matters, for the time being at any rate, volun-

tary arrangements would continue, either because enoughexperience had not yet been gained, or because therewas insufficient agreement. Medical examination, forexample, was one. But regulations would be madeat once to deal with protective clothing, washing facilities,cleanliness generally so as to avoid contamination,periods of work, supervision and training of workers,the keeping of records, and the notification of sicknessand accidents. In the first instance the Bill wouldapply to two classes of substances-dinitro compounds,such as dinitro-ortho-cresol (D.N.O.C.), used for sprayingas weed-killers ; and organo-phosphorus compounds, usedas insecticides. The Minister would have power toextend the scope of the Bill to other substances by order.Lord DOUGLAS OF BARLOCH regretted that the Bill

did not protect the public generally. Some of thesepoisonous substances, he said, were used in the form ofsprays and it was easy for small drops to be carriedthree or four miles on a breeze. It had already happenedthat innocent passers-by had been poisoned. TheZuckerman report had drawn attention to this. Therewas also the wider problem of the effect of these sub-stances on the people who consumed agricultural pro-ducts. It had been found by experiments upon testanimals that D.D.T., and a number of substances of thatchemical group, produced liver injuries.Lord CARRINGTON, replying to the debate, said the

recommendation of the Zuckerman working party thatthe words " deadly poison

" should be put on containershad been referred to the Poisons Board. The board wasrather against such a step, because they felt it woulddetract from the use of the word " poison " withoutqualification on other poisons which were sold in shops.However, the board recommended that manufacturersmight apply the word " poison " followed by thesewords :

"Caution. This substance is poisonous ; the inhalationof its vapour, mist, spray or dust may have harmful con-sequences. It may be dangerous to let it come into contactwith the skin or clothing."The working party were inquiring into the effect of

these poisons on the consumer, but there was no evidenceto show how they could have any such effect. Certainlyin this country there was no evidence that D.D.T. hadbeen harmful to human beings. He thought that nobleLords had been unnecessarily anxious about the dangerof spraying these substances. These poisons were

cumulative and it took a comparatively long time to getany kind of dangerous dose from these sprays. TheBill was read a second time.

QUESTION TIMERecrtaatrnent of Nurses

Mr. R. W. SORENSEN asked the Minister of Health how farthe supply of trained nurses and probationers in hospitals hadimproved during the past 12 months ; and approximatelythe ratio of patients to nurses in the main London teachinghospitals compared with other hospitals in the London area.-Mr. H: F. C. CROOKSHANK replied : During the twelve months