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THE NOBEL PRIZEWINNER

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773 special schools to meet the needs of George and his like, and the second is to arrange that any authority charged with the care of a child or young person should be able to represent to the juvenile court that some particular form of treatment is desirable in his interests. Subject to the approval of the court, all forms of treatment (except, of course, the punitive measures reserved for offenders) should be readily available for all such children. He also thinks it wrong that the parents of a child who has been ascertained to be maladjusted or educationally subnormal, and whom the education authority propose to send to a special school, should be able to appeal to no-one but the Minister ; and that they should have no appeal, except to the Home Secretary himself, against a proposal-originating in his own department-to license a child from an approved school and place him with foster-parents or in some other institution. Such appeals, he thinks, should be made to the juvenile court. For what, he says, do these children need ? They need to be helped, and in many cases the court can help them, through the magistrates’ knowledge of their background, and of the conditions encouraging the attitude of mind or weakness of character which is responsible for their behaviour. The magistrates, the probation officer, the teacher, the children’s officer, the psychiatrist, and above all the child, should combine into a team ; and their job is not merely to modify the environment to suit George but to consider the extent to which the George may be expected to modify himself to suit the environ- ment. For success in the second part of this programme the one essential member of the team is George. ELECTRON MICROSCOPY OF VIRUS-INFECTED TISSUES THE earliest electron. microscopic studies of viruses were directed to the virus rather than to the infected tissue cells. This entailed the isolation of virus in a concentrated and purified state, with the risk that the rough methods of handling (including repeated high-speed centrifugation) might produce distortions in the shape and size of the virus particles. A great advance in technique came from the use of red-cell " ghosts " which can adsorb influenza and related viruses. The beautiful pictures by Chu, Dawson, and -Elford were obtained with only the gentlest handling of the virus ; and with the help of simple biological techniques it was possible to identify the virus particles with confidence. The study of virus-infected tissues was an obvious, although difficult, line of inquiry which gave promise of throwing some light on the problem of virus multiplication. Among the first reported studies of this kind were those of Claude et al.,2 Bang and Gey,3 and Wirth and Athanasui 4 working with fowl tumour viruses, eastern equine encephalomyelitis, and vaccinia viruses respec- tively. Later work has been reported from America with influenza, tobacco mosaic, fowl pox, herpes simplex, and vaccinia viruses ; and in this country Flewett and Challice 5 have described studies made with tissue cultures infected with fowl plague virus. Wyckoff now describes the results of electron microscopic studies of chick embryo tissues infected with influenza virus. Masses of filaments and spheres of the same diameter as the virus were found at the surface of infected cells. Wyckoff suggests that the filaments are fragments peeling off from the surface of infected cells, and that these filaments then segment into the spherical forms. The photographs which illustrate his paper are similar 1. Chu, C. M., Dawson, I. M., Elford, W. J. Lancet, 1949, i, 602 ; J. gen. Microbiol. 1949, 3, 298. 2. Claude, A., Porter, K. R., Pickels, E. G. Cancer Res. 1947, 7, 421. 3. Bang, E. B., Gey, G. O. Proc. Soc. exp. Biol., N.Y. 1949, 71, 78. 4. Wirth, J., Athanasui, P. Ibid, 70, 59. 5. Flewett, T. H., Challice, C. E. J. gen. Microbiol. 1951, 5, 279. 6. Wyckoff, R. W. G. Nature, Lond. 1951, 168, 651. to those shown by Flewett and Challice at the July meeting of the Pathological Society of Great Britain. There are two difficulties in any study of this type. The first is that although great advances have recently been made the techniques of preparing and cutting tissue I sections for electron microscopy are still in their youth. Secondly comes the difficulty in interpreting results, particularly in -view of the deeply rooted tendencies to believe what one sees and to see what one believes. The possibilities of error and misinterpretation in work of this kind are so many that it is not surprising that while the microbiologist has been able to dig deep into the ground of new knowledge with his bare hands, the elec- tron microscopist, with all his paraphernalia, is still only scraping the surface. But new and important advances will come from the association of developments of technique in electron microscopy with the experimental approach of the biologist. When the " stills " which the electron microscopist has photographed are replaced by a cinematographic record of virus-infected tissues we shall be nearer to understanding the methods of virus multiplication. EXTENSION OF A LONDON SCHOOL AN extension of the Royal’Free Hospital School of Medicine is being opened by the Queen this week. Thepreclinical departments of the school have for many years been seriously overcrowded, and research work has been sorely hampered by lack of space. The new building houses on successive floors extensions of the departments of chemistry, physiology, and anatomy, and the departments of biology and pharmacology, with a well-equipped workshop in the basement, and an animal- house, cold room, and conservatory on the top noor. For equipment wood has had to be used sparingly ; but the standard-and interchangeable-underbench steel fittings in the research laboratories and private rooms have already proved a useful innovation. The steel shortage is, in its turn, evident in the pillars which are to be found throughout the building. In the single lecture- theatre, however, the " dead-space " from this cause comprises only three or four seats. The floors are of cork, which has already proved pleasantly silent, easy on the foot, and resistant to accidental assault by strong acid. THE NOBEL PRIZEWINNER THE Nobel prize for physiology and medicine is to be awarded this year to Dr. Max Theiler " for his discoveries. concerning yellow fever and how to combat it." The first firm step against this disease was taken at the start of this century when Walter Reed and his fellow workers. established its association with mosquitoes, and notably Aedes egypti. This mosquito, with its domesticated ways, is eradicated fairly easily ; and in Central and South America the eradication campaign which followed Reed’s discovery seemed at first to have also eliminated yellow- fever infection. It emerged, however, that only the urban type had been controlled, whereas the jungle type, due to tree-dwelling mosquitoes, continued unabated. It is against this type, where mosquito control is often impracticable, that the vaccine developed by Theiler and his associates has the greatest value. In 1927 Adrian Stokes and his colleagues, working in Nigeria, found that Asiatic monkeys could be infected with the virus. Sub- sequent work with a killed vaccine proved unsuccessful, and vaccination with virus attenuated by passage through mice by Theiler himself proved unsatisfactory. In 1937 he and his colleagues obtained a variant strain (17D) grown in tissue cultures containing chick embryo from which the brain and cord had been removed. The efficacy of the resulting vaccine was proved in the late war ; between 1940 and 1947 more than 28 million doses were prepared by the Rockefeller Foundation alone, for distribution among the Allies. In 1934 Theiler discovered
Transcript
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773

special schools to meet the needs of George and his like,and the second is to arrange that any authority chargedwith the care of a child or young person should be ableto represent to the juvenile court that some particularform of treatment is desirable in his interests. Subjectto the approval of the court, all forms of treatment

(except, of course, the punitive measures reserved foroffenders) should be readily available for all suchchildren. He also thinks it wrong that the parents ofa child who has been ascertained to be maladjustedor educationally subnormal, and whom the educationauthority propose to send to a special school, shouldbe able to appeal to no-one but the Minister ; and that

they should have no appeal, except to the HomeSecretary himself, against a proposal-originating inhis own department-to license a child from an approvedschool and place him with foster-parents or in someother institution. Such appeals, he thinks, should bemade to the juvenile court.For what, he says, do these children need ? They need

to be helped, and in many cases the court can help them,through the magistrates’ knowledge of their background,and of the conditions encouraging the attitude of mindor weakness of character which is responsible for theirbehaviour. The magistrates, the probation officer, theteacher, the children’s officer, the psychiatrist, and aboveall the child, should combine into a team ; and their

job is not merely to modify the environment to suit

George but to consider the extent to which the Georgemay be expected to modify himself to suit the environ-ment. For success in the second part of this programmethe one essential member of the team is George.

ELECTRON MICROSCOPY OF VIRUS-INFECTED

TISSUES

THE earliest electron. microscopic studies of viruseswere directed to the virus rather than to the infectedtissue cells. This entailed the isolation of virus in aconcentrated and purified state, with the risk that therough methods of handling (including repeated high-speedcentrifugation) might produce distortions in the shapeand size of the virus particles. A great advance intechnique came from the use of red-cell " ghosts " whichcan adsorb influenza and related viruses. The beautiful

pictures by Chu, Dawson, and -Elford were obtainedwith only the gentlest handling of the virus ; and withthe help of simple biological techniques it was possibleto identify the virus particles with confidence. The

study of virus-infected tissues was an obvious, althoughdifficult, line of inquiry which gave promise of throwingsome light on the problem of virus multiplication.Among the first reported studies of this kind were

those of Claude et al.,2 Bang and Gey,3 and Wirth andAthanasui 4 working with fowl tumour viruses, easternequine encephalomyelitis, and vaccinia viruses respec-tively. Later work has been reported from Americawith influenza, tobacco mosaic, fowl pox, herpes simplex,and vaccinia viruses ; and in this country Flewett andChallice 5 have described studies made with tissuecultures infected with fowl plague virus. Wyckoff nowdescribes the results of electron microscopic studies ofchick embryo tissues infected with influenza virus.Masses of filaments and spheres of the same diameter asthe virus were found at the surface of infected cells.Wyckoff suggests that the filaments are fragmentspeeling off from the surface of infected cells, and thatthese filaments then segment into the spherical forms.The photographs which illustrate his paper are similar

1. Chu, C. M., Dawson, I. M., Elford, W. J. Lancet, 1949, i, 602 ;J. gen. Microbiol. 1949, 3, 298.

2. Claude, A., Porter, K. R., Pickels, E. G. Cancer Res. 1947, 7, 421.3. Bang, E. B., Gey, G. O. Proc. Soc. exp. Biol., N.Y. 1949, 71, 78.4. Wirth, J., Athanasui, P. Ibid, 70, 59.5. Flewett, T. H., Challice, C. E. J. gen. Microbiol. 1951, 5, 279.6. Wyckoff, R. W. G. Nature, Lond. 1951, 168, 651.

to those shown by Flewett and Challice at the Julymeeting of the Pathological Society of Great Britain.There are two difficulties in any study of this type.

The first is that although great advances have recentlybeen made the techniques of preparing and cutting tissue

I

sections for electron microscopy are still in their youth.Secondly comes the difficulty in interpreting results,particularly in -view of the deeply rooted tendencies tobelieve what one sees and to see what one believes. The

possibilities of error and misinterpretation in work ofthis kind are so many that it is not surprising that whilethe microbiologist has been able to dig deep into theground of new knowledge with his bare hands, the elec-tron microscopist, with all his paraphernalia, is still onlyscraping the surface. But new and important advanceswill come from the association of developments of

technique in electron microscopy with the experimentalapproach of the biologist. When the " stills " which theelectron microscopist has photographed are replaced bya cinematographic record of virus-infected tissues weshall be nearer to understanding the methods of virusmultiplication.

EXTENSION OF A LONDON SCHOOL

AN extension of the Royal’Free Hospital School ofMedicine is being opened by the Queen this week.

Thepreclinical departments of the school have for manyyears been seriously overcrowded, and research work hasbeen sorely hampered by lack of space. The new

building houses on successive floors extensions of the

departments of chemistry, physiology, and anatomy, andthe departments of biology and pharmacology, with awell-equipped workshop in the basement, and an animal-house, cold room, and conservatory on the top noor.For equipment wood has had to be used sparingly ; butthe standard-and interchangeable-underbench steel

fittings in the research laboratories and private roomshave already proved a useful innovation. The steel

shortage is, in its turn, evident in the pillars which are tobe found throughout the building. In the single lecture-theatre, however, the " dead-space " from this cause

comprises only three or four seats. The floors are of cork,which has already proved pleasantly silent, easy on thefoot, and resistant to accidental assault by strong acid.

THE NOBEL PRIZEWINNER

THE Nobel prize for physiology and medicine is to beawarded this year to Dr. Max Theiler " for his discoveries.

concerning yellow fever and how to combat it." The firstfirm step against this disease was taken at the start ofthis century when Walter Reed and his fellow workers.established its association with mosquitoes, and notablyAedes egypti. This mosquito, with its domesticated ways,is eradicated fairly easily ; and in Central and SouthAmerica the eradication campaign which followed Reed’sdiscovery seemed at first to have also eliminated yellow-fever infection. It emerged, however, that only the urbantype had been controlled, whereas the jungle type, dueto tree-dwelling mosquitoes, continued unabated. It is

against this type, where mosquito control is often

impracticable, that the vaccine developed by Theiler andhis associates has the greatest value. In 1927 AdrianStokes and his colleagues, working in Nigeria, found thatAsiatic monkeys could be infected with the virus. Sub-

sequent work with a killed vaccine proved unsuccessful,and vaccination with virus attenuated by passage throughmice by Theiler himself proved unsatisfactory. In 1937he and his colleagues obtained a variant strain (17D)grown in tissue cultures containing chick embryo fromwhich the brain and cord had been removed. The efficacyof the resulting vaccine was proved in the late war ;between 1940 and 1947 more than 28 million doses wereprepared by the Rockefeller Foundation alone, fordistribution among the Allies. In 1934 Theiler discovered

Page 2: THE NOBEL PRIZEWINNER

774

the encephalomyelitis virus of mice, which has manysimilarities in its behaviour to human poliomyelitis andhas been extensively studied for this reason.

Dr. Theiler was born in Pretoria on Jan. 30, 1899,and studied at Rhodes University College and the

University of Cape Town before coming to London in1919. In 1922 he qualified here, and subsequently heheld an appointment at Harvard University before

joining the Rockefeller Foundation, with which he hassince remained. He is due to receive the prize fromKing Gustaf Adolf in Stockholm on Dec. 10-the

anniversary of Alfred Nobel’s death.

HIGH-RESOLUTION RADIOAUTOGRAPHY

THE introduction of radioactive isotopes has placeda whole host of new methods in the hands of the biologicalinvestigator. Among the most striking of these is radio-autography. The principle, which is extremely simple,may be illustrated by taking as an example the distri-bution of radioactive iodine in the thyroid gland.Radioactive iodine, like its non-radioactive counterpart,is rapidly concentrated in the thyroid gland. This

gross concentration is detectable by means of anyinstrument, such as a Geiger counter, which is sensitiveto ionising radiations in its vicinity. The radioautographis a more precise means of detecting the localisation ofthe radioactive iodine. Histological sections are preparedin the usual way and laid on a photographic platecontaining a sensitive silver emulsion. After an

appropriate time, depending on the radioactivity inthe specimen, the plate is developed. Blackeningof the plate indicates the presence of radioactivity in thecorresponding area of the section. With sufficientlyfine-grain plates further photographic enlargement ofthe autograph is possible ; but when enlargement beyonda few diameters is attempted, serious limitations becomeapparent. The difficulties are well discussed, and anentirely novel method’of overcoming them is described,by Fink,! of the University of California.The most important bar to obtaining radioautographs

capable of useful magnification is the failure of a pointsource of radioactivity to produce only a point of

blackening in the underlying film. This is due to the

quite random emanation of the a and particles in alldirections from any point source of activity. The

blackening of the silver in the emulsion from the actionof these particles therefore occurs in the form of a discwith intensity maximal in the centre and falling to zeroat the periphery ; the actual diameter of the disc dependson the intensity of the radiation and the duration ofthe exposure. If, in a given radioautograph, the radiusof the disc of blackening corresponding to a point sourcein the section is 50 u., then points less than 100 tJ. apartcould not be distinguished in the autograph owing tooverlap of the areas of blackening. Since the resolutionof two points 100 Ex, apart is almost within the powerof the unaided eye, photographic enlargement beyondtwo or three diameters could contribute little of value.The problem of improving resolution, therefore, may beexpressed quite simply. It consists of devising methodsfor reducing the size of the area of blackening in theplate corresponding to a point source of activity in the’section. The smaller the area of blackening the greateris the useful magnification which the autograph willstand.Methods used up to now to limit the area of blackening

depend on eliminating the obliquely directed particles byan absorbing layer between the section and the plate,the particles moving at right-angles to the surface beingmore likely to penetrate the absorbing layer than themore obliquely directed particles with their longer pathin the absorbing layer. Assuming, however, that theproblem of the random direction of emitted particles

1. Fink, R. M. Science, 1951, 114, 143.

were overcome, there would still be a further difficulty- tamely, the limitation of the number of radioactiveatoms that can be packed into any given submicroscopicstructure, especially under physiological conditions. Anymethod that by absorbing the obliquely directed particlesreduces the amount of energy available for action onthe photographic plate is equivalent to a further reductionin the number of radioactive particles in the givensubmicroscopic structure.Fink has attempted to avoid all these difficulties by

the entirely novel method of mechanically enlarging thesection itself before the autograph is made. The processis comparable, as he says, to the enlargement of a figurepainted on a toy balloon, when the balloon is inflated.To achieve this mechanical enlargement, the pyroxylin-embedded section was placed upon a thin block of leadand covered with lead foil. By a combination of pressureand expansion in a rolling mill a mechanical enlargementof 20 diameters was achieved. Radioautographs werethen obtained by placing the photographic plate againstthe lead-foil-covered surface of the specimen. Further

photographic enlargement gave a final picture with amagnification of 48 diameters. Comparison of this picturewith that of the straight autograph similarly magnifiedrevealed a greatly improved picture, in every waycomparable with an ordinary photomicrograph of thesame magnification. Some artefacts are of course

produced during mechanical enlargement, but these a-e eslight compared with the undoubted improvement inthe final picture. A further advantage of this ingeniousmethod is the accuracy with which micro-dissection canbe carried out ; otherwise difficult feats are done withthe ease of " cutting out of paper dolls."

EIGHTIETH BIRTHDAY

H. M. Turnbull recalls a time when Robert Hutchison,in his deerstalker cap and long ulster, attracted people’sattention because he looked like Sherlock Holmes.! Butin the past few decades he has attracted their attentionmore because he looks like Robert Hutchison. Eversince he joined the staffs of the London Hospital andGreat Ormond Street in 1900, he has been slightly legen-dary ; for his quality as a clinician is only one aspect ofhis quality as a person, which has been evident in manyindividual ways. As a teacher he has displayed what canbe done with intelligence by common sense-and whatcannot be done. Skilled in reducing mental fevers bycool (even chilly) applications, he has carried pessimismto a length that suggests its origin in idealism ; and it is

partly because of his kindliness, and his strong (ifeclectic) sympathy, that so many ot his former studentsquote him affectionately as they sit in their igloos orunderneath their palm-trees. By demonstration andpersuasive speech and writing he has in fact done a greatdeal to raise the standards of practice, and the tributespaid him in the October issue of the Archives of Diseasein Childhood show why this is so. As one contri-butor says : " it is perhaps his wisdom, intellectualhonesty, absolute integrity, and sound clinical judgmentmore than any other qualities which have impressedthemselves upon all who have known him, compellingtheir admiration and respect." Another speaks discern-ingly of his mind being intellectually gay : and thosewhose dullness has often been lessened by Sir Robert’scompany will prescribe for his 80th birthday on Oct. 28a little of the " judicious levity " of which he is a master.

THE INDEX and title-page to Vol. I, 1951, which wascompleted with THE LANCET of June 30, is now inpreparation. A copy will be sent gratis to subscriberson receipt of a postcard addressed to the Manager ofTHE LANCET, 7, Adam Street, Adelphi, W.C.2. Sub-scribers who have not already indicated their desire toreceive indexes regularly as published should do so now.

1. Hunter, D. Lond. Hosp. Gaz. October, 1951.


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