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Notes and News

ROYAL SOCIETY OF TROPICALMEDICINE AND HYGIENE

AT a meeting on April 22, Brigadier T. P. H. MCKELVEYpresented a paper by himself and his colleagues on chloro-quine-resistant falciparum malaria among British servicepersonnel in west Malaysia and Singapore. Resistance to

chloroquine was considered to be present if after thestandard course of the drug there was failure to respondwithin 7 days or recrudescence within 28 days. To sub-stantiate resistance demonstrated clinically, chloroquinedeterminations were carried out on the blood along withparasite studies. Of 71 patients accepted into the study 36did not respond to the standard course of chloroquine orrecrudesced later under supervision in conditions in whichreinfection could not have taken place. No evidence offailure to absorb chloroquine was obtained in these patients.Further treatment of recrudescences was carried out usingstandard or high dosage chloroquine regimens. Furtherrecrudescences occurred in half of those who had standarddoses and in 5 of 14 patients who had 2400 mg. over 4 days,but in none of 8 patients who had more than this amount.The majority of these with resistance had acquired theirinfection in Johore State. Proportionally more Britishthan Gurkha or Malayan personnel exhibited resistanceprobably because in the Gurkhas and Malayans partialimmunity assists in eradicating parasites. It was alsoconsidered probable that the reason underlying the effec-tiveness of repeated courses of chloroquine was that theselater courses were given where the earlier infection orinfections had produced some acquired immunity. In theensuing discussion the point was made that this carefulwork had emphasised the need for new antimalarial drugsand for constant alertness for patients presenting withchloroquine-resistant malaria in areas where malaria is notendemic. Fortunately chloroquine-resistant malaria hashitherto been found to respond to treatment with a com-bination of 1 g. sulformetoxine and 50 mg. pyrimethamine.

Mr. P. G. Shute has been elected an honorary fellow of thesociety in recognition of his contributions to malariology. TheManson medal for 1971 has been awarded to Major-GeneralSir Gordon Lovell for his work on the epidemiology of malaria.The Chalmers medal for 1971 has been awarded to Dr. RalphLainson for his work in medical protozoology.

FLEXIBLE STRUCTURES

OF his elucidation of the tertiary structure of myoglobin,Nobel laureate J. C. Kendrew remarked that " he wouldnot care to have to undertake the task a second time ".

Judging from the instruments on display at an open dayof the M.R.C. Laboratory of Molecular Biology, in Cam-bridge, last week, he need not worry. The analysis ofX-ray crystallographic pictures and the conversion of theresulting data into an electron-density map and, ulti-mately, a large-scale atomic model are tasks greatly suitedfor computers and other automated assistance. Today’smolecular biologists have a much easier task in unravellingthe shapes of proteins: where in the 1960s a full structurewas the result of years of painstaking effort, it seems pos-sible that before long the job will take months or evenweeks. But why make models ? There must be some-

thing more to the laboratory’s programme than a ratherelegant union between craftsmanship and pure science.The object is to give the research-worker something tospeculate with, and nowhere has this been done more

profitably than with the delicate tracery of M. F. Perutz’smodels of haemoglobin. The abnormal Hb of sickle-celldisease has shown how a very small error in a protein chain

can make a world of difference to the shape of the redblood-cell. With the normal haemoglobin Perutz and hiscolleagues have explained how oxygen avidity of Hb changesas more and more of the four binding sites are filled or vaca-ted. The crucial factor is the volume of the iron atom. Inarterial blood it fits snugly in the centre of the porphyrinring, but in deoxyhaemoglobin the spin state alters and theatom swells and protrudes about 0-75A beyond the planeof the ring. Interaction between protein chains allows thistiny distortion to affect other sites in the molecule eventhough, in atomic terms, they are a long way away. Themolecule’s structure can be locked in place by an unfamiliarthree-carbon molecule 2,3-disphosphoglycerate, the fournegative charges of which complement four positive chargesheld out at a certain point in the protein chains. Theavailability of this ligand can thus control the availabilityof oxygen to the tissues-a property of practical importancein the rapid adjustments that take place after a few hours’exposure to the low oxygen tension of an aeroplane flight.The basic science of the M.R.C. Laboratory provides

understanding of the function of physiologically importantmolecules but it still seems far removed from the day-to-day clinical problems of the teaching hospital whose siteit shares. Just as it could be argued that no patient beingtreated in Addenbrooke’s Hospital today would have beena whit the worse if the helical nature of D.N.A. had neverbeen described, so too the second generation of molecularbiologists have few illusions about the direct applicationof their work in the near future. But there are occasional

pointers: the possibility of altering pathologically import-ant abnormal hxmoglobins is one, another is the findingof vulnerable areas in virus growth. One of the othermore complete stories on display was the growth of thehelical R.N.A. virus that causes tobacco mosaic disease,the possibility here being that, by finding how virusesreproduce and grow, weak points suitable for outside

interference, might be identified-a reasoning analogousto that of determining the detailed life-cycle of parasitesand their carriers before setting out to eradicate tropicaldiseases. Klug and his colleagues published earlier thisyear 1 their interpretation of how T.M.v. starts out on itshelical structure. The first twist in a helix is, on energygrounds, rather unfavourable. This group has shown thatthe basic unit in the helical development of the proteinwhich encases R.N.A. is not a single protein unit or even asimple ring but a disc of two 17-unit rings one on top ofthe other. Somehow the polar features of the disc recog-nise the fifty or so 5’-terminal bases of R.N.A. thus ensuringthat it wraps up the correct polynucleotide. As a responseto this R.N.A.’S tight binding to the protein units the discdislocates, allowing the beginnings of a helix to develop.From then on growth is by successive addition of morediscs-not, as had been expected, by addition of singleunits once the initial difficulty had been overcome.

MACROMOLECULES AND MEMORY

Prof. Holger Hyden’s sophisticated techniques for

isolating neurons and glia and their use in studying theuptake of labelled aminoacids by discrete parts of thebrain have attracted much attention. As first ArthurThomson visiting professor at Birmingham University,he gave the opening lecture at a meeting in Birmingham,on March 18 and 19, on Macromolecules and Behaviour.Having taught rats to use a paw, other than the one ofchoice, to obtain food, he has found that there is initiallya stimulation of 3H-leucine uptake into the hippocampalregion of the trained rat. As training proceeds, the area

1. Durham, A. C. H., Finch, J. T., Klug, A. Nature New Biol. 1971,229, 37; Durham, A. C. H., Klug, A. ibid. p. 42; Butler, P. J. G.,Klug, A. ibid. p. 47.

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of labelling shifts, the cortex becoming highly labelledwhile the hippocampus returns to normal levels of 3H-leucine incorporation. The S100 protein is also changedand appears as a double band on electrophoresis.A similar pattern of increased uptake of labelled uridine

into R.N.A. was described by E. Glassman (Chapel Hill).After subjecting the mouse to a short training period, an in-crease in uptake was found in the R.N.A. of the diencephalon,but not in the cortex or parietal region of the brain.

Steven Rose (Bletchley) and his co-workers in Cam-

bridge have used an elegant system of control animals intheir studies. They split the brain of young chicks longi-tudinally and used a light source to one eye to study thecorrelation between imprinting and protein synthesis.One half of the brain thus became the " yoked " controlof the other. The R.N.A.-polymerase was elevated 30minutes after exposure to light, and after 60 minutes thelevel of R.N.A. was raised. After a further 60 minutes, anincrease in protein synthesis was evident. The questionwas, of course, what stimulated the R.N.A.-polymerase ?D. A. Booth (Brighton) investigated the effect of block-

ing protein synthesis after the establishment of a patternof learning. Cycloheximide was found to block long-termmemory but to have no effect upon short-term memory.E. Glassman described long-term memory as a structuralchange and short-term memory as merely a modificationof existing molecules.

Discussing the technicalities of experimental procedure,J. T. Rick (Birmingham) pointed out that most studiesconcerned with the biochemical correlates of behaviourmade use of aversive conditioning stimuli to obtain rapidoverlearning. Stimulation by electric shock has a significanteffect on brain chemistry which is complicated by learning,and Rick argued that studies based on the extinction,rather than the acquisition, of a learned response mightbe a more useful technique.

Studies on invertebrates by Gerald Kerkut (Southamp-ton) and G.W. 0. Oliver (Portsmouth) showed some interest-ing variations in biochemical effects. In snails, cholinesteraseactivity in the ganglia increased during learning, whereasthe opposite reaction was found in cockroaches. In snailsincreased enzyme activity was not associated with a risein concentration. Kerkut described how snails could beinduced to learn faster after treatment with amphetamineand pemoline and more slowly after cycloheximide,congo-red, and acridine-orange.John Dobbing (Manchester) presented some pertinent

facts about the effect of very early malnutrition on braindevelopment. Anxiety for food and general fearfulnesscontinued long after the period of malnutrition had beenreversed. G. Ungar (Houston) described learning as atransferable phenomenon-an actual polypeptide-whichcould be extracted from the brain of a trained mouseand injected into a naive animal to facilitate learning.The aminoacid sequence of such a molecule is now known.

B. W. Agranoff (Ann Arbor) described the disruption oflearned behaviour in goldfish by blockers of D.N.A., R.N.A.,and protein synthesis. Puromycin, for example, did notprevent learning, but it effectively blocked long-termmemory.

ATTENDANCE ALLOWANCE

REGULATIONS were published on April 20 by Sir KeithJoseph, Secretary of State for Social Services, setting outconditions for entitlement to the new attendance allowance,which will become payable on Dec. 6. About 50,000severely disabled people are expected to qualify for theallowance, which has been increased to E4-80 a week fromthe original figure of E4. Under the regulations, all adultsand children aged 2 or over who satisfy the medical con-ditions will be entitled to the allowance. Conditions about

residence and presence in Great Britain will operate. For

people who are drawing the allowance but who enterhospital, or certain other (mainly local-authority) resi-dential accommodation, the allowance will continue to bepaid for the first 4 weeks after admission, to meet continu-ing liabilities incurred while living at home. Where aclaim for attendance allowance is made on behalf of a

child, it must be shown that the child needs attention andsupervision substantially in excess of that normally requiredby a child of the same age, or sex; the person entitled tothe allowance will generally be the child’s mother, or,where the child is not living with her, the father or otherperson who is caring for the child. The allowance will notbe payable for children in residential accommodationexcept, for example, where parents are paying for a childto stay in a home or hospital under privately made arrange-ments. All decisions on claims will be made by theAttendance Allowance Board; the claimant will be able toask the Board to review their decision, and followingreview, appeals against the Board’s decisions on questionsof law may be made to a National Insurance Commissioner.The new allowance will not affect the basic amount of

supplementary benefit a person may already be receiving.Under further regulations, yet to be made, the require-ments of a person entitled to attendance allowance will beraised by the amount of the allowance when calculatingbasic scale-rate entitlement to supplementary benefit.

EDUCATING MENTALLY HANDICAPPEDCHILDREN

IN transferring existing services for the education ofmentally handicapped children from the Department ofHealth and Social Security to the Department of Educationand Science (in accordance with the Act of 1970), over400 new special schools have been formed out of trainingcentres and hospital provision. This represents the additionof about two-fifths to the total of 1000 existing specialschools, and of nearly one-third to the number of 100,000handicapped children already in special schools. The

Department of Education and Science intends to improvethe quality of the education provided for the children inthese schools, and to secure educational facilities for childrenin hospitals, in other residential care, and at home for thosewho are not at present receiving any education. The

Secretary of State for Education, Mrs. Margaret Thatcher,has decided that there will be no separate category for theseverely mentally handicapped; all mentally handicappedchildren, regardless of the kind or degree of their handicap,will be categorised as educationally subnormal, though, ofcourse, it is recognised that their educational needs will bedifferent. It is hoped that this will secure parity of esteemfor the severely handicapped and their teachers, and alsoflexibility of transfer between the new special schools andthose existing before the new Act came into force.

In a speech given in Bristol, Mrs. Thatcher said that,as the Act provided, the responsibilities of the Departmentof Education and Science and the local education authoritieswould extend to all children of school age, however severelyhandicapped. However, it was only to be expected thatsome of these children would go through periods whenthey were unresponsive; thorough assessment over a lengthof time, and in an educational setting, would establishwhether a child was capable of responding to education,and where he was not, someone should be appointed togive educational advice to those caring for the child andto arrange for his periodic reassessment. The Departmentwas reviewing the whole question of nursery provision,and was well aware of the importance of the early yearsin a child’s development, whether he was handicappedor not. It had been estimated that less than half of the8000 children in hospitals for the mentally handicapped

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had been attending anything that could be called a school,and not many more had been receiving any systematictraining or education. A great deal would have to be doneto improve this situation, and would depend on the degreeof cooperation achieved between hospital staff and theeducation authorities. In future the teachers of mentallyhandicapped children would be trained in colleges ofeducation alongside teachers of other children. Theircourse would last a full 3 years, instead of 1 or 2 years asin the past, and courses might in future be extended tocover the problems of children with less severe learningdifficulties.

University of CambridgeThe following degrees have been conferred:M.D.-C. R. M. Prentice.M.Chir.-J. D. Jenkins.M.B.-V. S. Blanchette, R. J. Barnes, R. J. R. Dunstan, D. N.

Faithfull-Davies, N. R. Fieldman, P. G. Frost, W. J. Grange, R. St. J.Harold, M. R. Hulton, A. A. Jackson, H. M. Mather, J. D. Pickard,J. S. Watson, R. M. Weatherstone.

University of LondonA course on teaching methods, mainly for new university

lecturers, will be held at the University of London Instituteof Education on Sept. 13-17. Details may be had from the

University Teaching Methods Unit, 55 Gordon Square,London WC1H ONT (01-580 6451, ext. 11).

University of BirminghamDr. J. E. Fox has been appointed lecturer in physiology.

Dr. J. H. Marston and Dr. B. Weatherhead have beenappointed lecturers in anatomy.

University of Newcastle upon TyneDr. J. N. Walton, professor of neurology in the depart-

ment of medicine, has been appointed dean of medicine.

University College Hospital Medical SchoolThe Max Rayne Foundation is to contribute E750,000

for the construction of a new research institute adjoiningthe hospital and medical school. On April 21, LordRosenheim launched a public appeal for funds to developthe possibilities of this new institute and modernise theold school buildings. The appeal is, in fact, already two-thirds of the way to its E750.000 target: S250.000 has comefrom the Clore Foundation; staff and former studentshave raised nearly E100,000; and about E150.000 has beenreceived or promised from elsewhere. Lord Rosenheimsaid that in the new institute high priority would be givento collaborative work on birth defects and genetic disorders,and that the school hoped to establish the first academicand research department of geriatrics in London.

Vertebrate and Insect HaemoglobinThis is the subject of a European Molecular Biology

Organisation lecture, to be given by Dr. G. Braunitzer(Munich) at 5 P.M. on Thursday, May 20, in the AnatomyTheatre, University College, Gower Street, LondonWC1E 6BT.

International Cancer FellowshipsThe International Union Against Cancer, with funds

provided by the American Cancer Society, is to awardfellowships for cancer research in 1972 to experiencedinvestigators on the staff of universities, teaching hospitals,research laboratories, or similar institutions. The awardswill be made for work on the experimental or clinical

aspects of cancer research. Application forms (which mustbe returned by Sept. 1) may be had from the InternationalUnion Against Cancer, P.O. Box 400, 1211 Geneva 2,Switzerland.

Society for the Study of International Medical CareAt the next meeting of the society, to be held at 6.30 P.M.

on May 12, at 14 Princes Gate, Hyde Park, London S.W.7,Sir Desmond Bonham-Carter will speak on the develop-ment of effective management in a non-producing serviceorganisation. Visitors wishing to attend should notifyDr. G. E. Ffrench, Occupational Health Unit, CentralMiddlesex Hospital, Park Royal, London N.W.10, byMay 5.

CORRIGENDUM: Prevalence of Glycosuria in Normal Pregnancy.-In the article by Dr. N. G. Soler and Prof. J. M. Malins (March27, p. 619) the penultimate sentence of the second paragraph ofthe discussion should have read: " Whilst the carbohydratecontent of breakfasts was meagre, averaging 29 g., the carbo-hydrate contents of midday and evening meals averaged 65 g."

AppointmentsFLOOD, C. M., M.D.Lond., F.R.C.O.G. : consultant gynxcologist, St.

Anthony’s Hospital, Cheam.JAMES, D. C., M.B.Birm., M.R.C.P.E.: consultant psychiatrist, the

London Hospital, Whitechapel.MURPHY, W. M., M.B., N.U.I., F.R.C.S.I.: consultant orthopaedic surgeon,

St. Anthony’s Hospital, Cheam.PARRISH, J. A., M.D.Lond., M.R.C.P.: consultant in general medicine,

St. Anthony’s Hospital, Cheam.PARSONS, D. W., M.B.Lond., F.R.C.S. : consultant orthopaedic surgeon,

St. Anthony’s Hospital, Cheam.PiTT, B. M. N., M.D.Lond., D.P.M.: consultant psychiatrist, the London

Hospital, Whitechapel.RIDLEY, ALAN, M.D.Newcastle, M.R.C.P.: consultant neurologist, theLondon Hospital, Whitechapel.

North East Metropolitan Regional Hospital Board:BEYNON, D. G., M.B.Cantab., F.F.A. R.c.s., D.A.: consultant anxs-

thetist, Southend-on-Sea hospital group.BiRT, R. C., M.B.Lond., F.F.A. R.C.S. : consultant anxsthetist, South-

end-on-Sea hospital group.KEANE, BRIGID, M.B.Lond., D.M.R.D.: consultant radiologist, Forest

hospital group.LESSOF, LEILA, M.B.Lond., D.R.M.D.: consultant radiologist, Hackney

hospital group.NAYLOR, ANN F., M.B.Lond., F.F.A. R.C.S., D.A.: consultant anoes-

thetist, Forest hospital group.NAYLOR, H. G., M.B.Lond., F.R.c.s.: consultant surgeon, South

Essex hospital group.OAKEY, J. S., M.B.Sydney, M.R.C.PATH., D.P.M., D.T.M.&H.: consultant

hmmatologist, South Essex hospital group.ORBLOWITZ, S. M., M.B.Wsrand., D.P.M.: consultant psychiatrist,

Warley Hospital.THOMAS, D. A., M.R.C.S., F.F.A. R.C.S., D.A. : consultant ana.athetist,

Brentwood hospital group.

South Western Regional Hospital Board:BIRD, M. C. C., M.B.Birm., D.P.M. : consultant psychiatrist, Hortham

and Brentry hospital group.BuRNs-Cox, C. J., M.B.Lond., M.R.C.P.: consultant in general

medicine, Frenchay hospital group.HILLS, M. M., M.B.Birm., F.F.A. R.c.s.: consultant anassthetist,

North Gloucestershire clinical area.HUNT, A. C., M.D.Lond., F.R.C.PATH. : consultant in morbid anatomy,

Plymouth clinical area.KILBY, J. 0., M.s.Lond., F.R.C.S. : consultant general surgeon,

North Gloucestershire clinical area.

WINDSOR, A. C. M., M.B.Wales, M.R.C.P., M.R.C.P.G.: consultant in

geriatric medicine, Bristol clinical area.WRIGHT, D. G., M.B.Lond., M.R.C.P. : consultant in geriatric medi-

cine, Bath clinical area.

Western Regional Hospital Board:BROWN, D. M., M.B.Birm., F.F.A. R.C.S. : consultant anaesthetist,

Glasgow Royal Infirmary.Dow, G. R., M.B.Glasg., D.A.: consultant anoesthetist, Stobhill

General Hospital, Glasgow.FOLLETT, G. F., M.B.Sheff., M.R.C.PATH.: consultant biochemist,

Stirlingshire and Falkirk Royal Infirmaries.GRAY, ANNE M., M.B.Glasg., D.P.M.: consultant psychiatrist, Levem-

dale Hospital, Glasgow.McNAIR, MARGARET M., M.B.Glasg., F.F.R., D.M.R.D.: consultant

radiologist, Royal Hospital for Sick Children, Yorkhill.O’GORMAN, MARGARET E. N., M.B.Glasg., D.P.M.: consultant child

psychiatrist, Stirlingshire area.Ross, R. M., M.B.Glasg., F.R.C.S.E. : consultant general surgeon,

Royal Alexandra Infirmary, Paisley.