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SPECIAL ARTICLES

MEDICAL RESEARCH COUNCILANNUAL REPORT 1936-36

THE report of the Medical Research Council for1935-361 begins on a note of welcome to LordBalfour of Burleigh as the new chairman, succeedingLord Linlithgow, and of congratulation to Sir HenryDale, F.R.S., director of the National Institute forMedical Research, on the award of the Nobel prizefor medicine jointly with Prof. Otto Loewi of Graz.

This award recognises their work on the nature of thechemical mechanism involved in the transmission of nerveimpulses. Sir Henry Dale and his co-workers showed thatacetylcholine is the chemical transmitter not only of thevagal impulse to the heart muscle but of other parasym-pathetic nerve activities, and also of some sympatheticactions. They have now established that acetylcholineis also the medium through which motor nerve impulsesactivate voluntary muscle ; probably, indeed, the trans-mission of the effects of most efferent impulses throughoutthe peripheral nervous system is dependent at some

stage or other on this chemical action.

The physiological and clinical implications of thisbrilliant work are not yet explored. Already, how-ever, it has provided a scientific basis for Dr.Mary Walker’s discovery that prostigmin alleviatescases of myasthenia gravis ; and there are indica-tions that some compounds closely allied to acetyl-choline, but more stable, may have therapeutic value.

It is customary for the council to select for com-ment in an introductory survey some dozen from thevarious schemes of research in progress. This yearincreased space has been allocated to this survey,which deals with clinical research ; influenza ; nutri-tion ; the prevention and treatment of childbedfever; deafness; the experimental study of epi-demics ; cotton-dust " asthma " ; tuberculosis :treatment by artificial pneumothorax; and medicalresearch in the tropics.

Clinical Research

Lord Nuffield’s gift to Oxford is welcomed as beingfully in accord with the policy of the council, parti-cularly in its establishment of senior clinical postson a nearly whole-time basis. Reference is made tothe handicapping effect on research in clinical medi-cine and surgery of the claims of private professionalpractice and to the tendency for promising clinicalinvestigators either to become increasingly absorbedby their patients or to transfer their interests toresearch in other fields. The increase in the numberof substantially whole-time clinical posts, candidatesfor which are expected to have had experience inresearch, makes the opportunities at Oxford, andon a smaller scale at Cambridge under the directionof Prof. J. A. Ryle, of special importance. Thecouncil’s contribution to the training of investigators inclinical science and experimental pathology during theyear under review has been the establishment of six post-graduate studentships and four research fellowships.. Influenza

The investigations on influenza at the NationalInstitute for Medical Research by Sir Patrick Laidlaw,F.R.S., Dr. C. H. Andrewes, Dr. Wilson Smith, andDr. Stuart-Harris (holding a Royce fellowship) have

1 Report of the Medical Research Council for the year1935-36. London: H.M. Stationery Office. 1937. Pp.172. 3s.

made substantial progress. Attention is here drawnto three aspects of it.

(1) World-wide diffusion of the virus originally isolatedand identified at the Institute.2-Filtered nasal washingsfrom patients suffering from typical influenza in widelydistant parts of the world (as England, Porto Rico,Philadelphia, Alaska, Australia, Holland, EuropeanRussia) when inoculated into ferrets causes the appear-ance of the same virus in their respiratory passages ; thisvirus will then infect other ferrets and can be transmittedto mice. This evidence suggests strongly that the virusthus propagated in the ferret is the primary infectiveagent of epidemic influenza in man.

(2) Transmission of ferret influenza to man.-The acci-dental infection of one of the team of workers from aferret, and the subsequent demonstration of antibodies inhis blood-serum, which had previously been negative,provided the important link completing the chain ofevidence for the identity of the virus maintained andstudied for over two years in ferrets, as the cause of humaninfluenza ; it also provided additional evidence of a con-nexion between the virus-neutralising antibody in theblood-serum and resistance to infection. Negative evidencepointing in the same direction has been obtained by Dr.Stuart-Harris, who found that blood-sera of inhabitantsof St. Helena, which escaped the pandemic of influenzain 1918, had no neutralising antibody for the virus. Theseislanders have since suffered from an epidemic diseaseresembling influenza, and samples of sera from personsaffected are being examined.

(3) Possibility of immunising man against influenza.-Substantial progress has been made by Dr. Andrewes andDr. Smith towards the production, from the virus, of a vaccinepotent and pure enough to be worth testing for its valuein immunising the human subject. A virus of such potencyhas been obtained that the filtrate from the lungs ofinfected mice is able to infect a mouse in a dilution of onein ten million ; and this virus can be made completelynon-infective, without appreciable loss of antigenic value,by treatment with very weak formaldehyde. The virusin the living state is apparently innocuous when given byhypodermic injection, and is being used in that way forimmunisation trials in the United States.A vaccine purified by ultrafiltration has been found,

in the mouse, to confer a substantial degree of resistanceto infection by the respiratory passages, and trials of itsimmunising effect on man are in progress.

It would be premature to attempt to estimate theprobability of practical success with such methods.Though a virus extracted from the infected mouselung, or from a culture on chicken embryo, will

newly evoke the specific neutralising antibody in theblood of a human subject, or produce an increase ofthis antibody if it is already present, it remainsuncertain whether the amount of circulating anti-

body thus produced will confer a significant degreeof resistance to naturally acquired infection, or if itdoes, how long such resistance would last. But thereis ample justification for hope.

Nutrition

The relative importance of nutrition and exercisein the promotion of bodily and mental fitness isdiscussed ; physical development and health are

primarily dependent on proper feeding, and exercises,whether as games or drill, are subsidiary to this, andtheir full benefits can be obtained only in thosewhose bodily and mental qualities have been developedto their innate maximum by proper feeding.Among the investigations of nutritional factors sup-

ported by the council, those deemed worthy of specialremark are the studies by Prof. E. P. Cathcart and Mrs.A. T. M. Murray of the ordinary diet of families in various

2 Lancet, 1933, 2, 66.

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towns, notably in St. Andrews, Cardiff, Reading, andGlasgow. Though the types of foodstuffs eaten variedwithin wide limits the distribution of calories between

protein, fat, and carbohydrate eaten by people indifferent towns was found to be remarkably constant.

According to these workers the daily diet of 109 womenstudents (average age 21), whose general physique andhealth was reported to be very good, contained 2035calories per person.

Doubt is expressed whether much misplaced trustis not being put on the 3000 calorie intake as a stan-dard figure. The council point out that the TechnicalCommission on Nutrition, appointed by the HealthSection of the League of Nations, decided that adaily allowance of 2400 calories net is adequate tomeet the energy requirements of an adult, male orfemale, living an ordinary everyday life in a temperateclimate and not engaged in manual work.

Steps designed to improve the physical fitness ofthe community must take account of both the educa-tional and economic aspects of this problem. Evenif there were abundant money for food expenditurein every household, ignorance and stupidity wouldoften prevent the maximum nutritional benefitsfrom being obtained ; but the limiting factor in alarge section of the community remains the food-purchasing power.

Dr. R. A. McCance has analysed, for some fifteen dif-ferent constituents, the chemical composition of someBritish foods, and the losses which they undergo duringcooking : 87 kinds of fish, 45 cuts of meat, 12 differentbirds, 65 fruits, and 67 vegetables were studied, withoutignoring the limitations of direct chemical analysis offood as a guide to its nutritional value. Many acceptedtheories about cooking were not supported by the experi-mental evidence-e.g., it makes no difference to the losseswhether meat is plunged into boiling water at the startor placed in cold water and slowly brought to the boil ;and although vegetables lose nutrients rapidly when theyare cooked in water, they may be soaked and washedin cold water in the raw state without loss.

Since diets can seldom be weighed or measured untilafter they have been prepared and cooked, the valueof having reliable figures for the chemical compositionof cooked foods should be appreciated not only byphysicians but by those in charge of the dietetic

departments of hospitals.

Influence of Diet on Decay of Children’s TeethThe council observes that the theory advanced by

Mrs. M. Mellanby on dental decay-that a dominantfactor in determining the structure of the teeth andtheir resistance to decay is the nutritional conditionof the body, and more particularly the supply of

specific food elements provided to the teeth in earlylife-is based on experimental and clinical evidencewhich has been generally accepted by scientificworkers ; but it has met with criticism and evendenial from some dentists. It is almost impossiblein a field experiment with children to secure con-trolled conditions in which all factors can be stabilisedexcept the one under test, especially when this is abiological agent applied over a long period. How-ever, the results of a trial over a restricted period andsubject to inevitable limitations which was under-taken at Birmingham on children living in institu-tions support convincingly the previous findings ofMrs. Mellanby. They are in agreement with her view,so far as vitamin D is concerned, that the teeth-likeother organs of the body-are strongly influenced bynutritional factors brought to bear upon them,either through their blood-supply or indirectlythrough the saliva. The dental decay that developedin the children receiving vitamin D was definitely

less than in the control children not receiving theadditional amount of this substance.

In one other important respect confirmation ofearlier work by this report is deemed worthy of men-tion. The less obvious forms of imperfect dentalstructure (hypoplasia), described by Mrs. Mellanbyin 1923 as not only widespread among children inthis country but also directly related to liability todecay, were seen to be present in a large proportionof these children, whereas gross defects of structure(the " hypoplasia " of the text-books) were compara-tively rare. A direct relationship between thestructure of the teeth and decay was also found.

These sample tests of Mrs. Mellanby’s thesis supportthe view that the most promising method, according topresent knowledge, of improving the dental conditionof this country is to increase consumption of milk andother dairy and market-gardening produce whichbenefit dental structure and resistance, and especially inthe earlier years of life to reduce the consumption ofbread and other cereals which either actively or passivelyresult in the developmnt of defective teeth. By thismeans it may be expected at least that the teeth ofthe next generation will be greatly improved.

Prevention and Treatment of Childbed Fever

After Dr. Dora Colebrook’s demonstration thathsemolytic streptococci, the micro-organisms respon-sible for puerperal sepsis, are not present in the birthcanal of normal women, but are conveyed thereto fromthe respiratory tract or skin of medical attendants, orof friends, or of the patients themselves, came thecheering news of the remarkable success apparentlyachieved at Queen Charlotte’s Hospital by Dr.Leonard Colebrook and his colleagues in combatingthis infection even when it is well established.They used the German dye Red Prontosil andProntosil Soluble, and are now making clinicaltests of the colourless substance para-aminobenzene-sulphonamide, which is allied in composition to redprontosil, since experiments in progress suggest that itgives even better results. During the years 1931to 1935, 495 cases of puerperal sepsis entered QueenCharlotte’s Hospital, and of these 112 died, giving afatality of 22-7 per cent. In part of the year 1936,64 cases of puerperal sepsis were treated by redprontosil and prontosil soluble in the same

hospital; of these cases only 3 have died, giving afatality of 4-7 per cent. Moreover, there has been asudden reduction in the severity of peritonitis asso-ciated with puerperal sepsis in cases treated withprontosil, and none of these patients developed apalpable pelvic or abdomino-pelvic inflammatorymass or abscess after the beginning of treatment,although this is ordinarily one of the commonestcomplications of puerperal infections by hsemolytiostreptococci. If caution is still necessary in claim-ing success for this treatment it is because ofthe signs of a general diminution in the severity ofpuerperal sepsis in this country during the pastfive years ; but a change in fatality-rate from 22-7to 4-7 per cent. is at least strongly suggestive of thevalue of these new drugs, quite apart from thepublished records of surprising recoveries in indi-vidual cases. Reliance on curative drugs must inany case be the third line of defence in the fightagainst puerperal sepsis. The first line must be theconduct of childbirth in such a way as to prevent(a) access of pathogenic organisms, especially strepto-cocci associated with sore-throat, to the birth canalof women, and (b) transport of these organisms from

3 See Lancet, 1936, 2, 1319 and 1323.

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the skin and other parts of the body. Secondly, theresistance of pregnant women should be raised tothe highest possible level by an ample supply ofmilk, green vegetable, and other protective foods.

Deafness

The aspects of deafness which have been studiedare: (1) the actual range of defect in hearing, as

regards frequency and amplitude of sound in indi-vidual people, and the amount of improvementthat can be produced by mechanical means on thebasis of this detailed knowledge ; (2) the degree towhich deafness gives the clue to apparent mentalretardation; (3) prevention of acquired deafness.

Dr. and Mrs. A. W. G. Ewing and Dr. T. S. Littler havefound that the results obtained by testing patients for aseries of pure tones by means of the audiometer providea reliable index of the intelligibility of speech to the deaflistener, and, in teaching, that the class amplifier has anumber of definite advantages over individual aids.

Dr. Phyllis Kerridge has concluded from the resultsof careful study that nearly all " partially deaf " childrenwould benefit greatly by hearing-aids ; whereas amongthe deaf children-i.e., those who cannot hear the con-versational voice as far as two feet away-more than halfwould derive considerable benefit from sound-magnifica-tion instruments.

As to prevention, the reports by Dr. T. E. Banksand Dr. Parkes of a lower incidence of inflam-mation of the middle ear and other sequelae ofscarlet fever and measles following the use of serain London County Council hospitals are noted withsatisfaction, and the extension of such forms oftreatment in these and other directions is anticipated.

Experimental Study of EpidemicsThere have been many productive clinical investi-

gations into epidemic diseases but certain funda-mental problems of epidemiology have resisted fieldinvestigation. On the other hand a close experi-mental study of animals in a herd exposed to infectionhas already answered certain questions relative tohuman epidemics, and may be expected to answermore in the future. For the last 18 years a teamnow working at the London School of Hygiene andTropical Medicine have exposed large numbers ofmice to different infective agents and have studiedtheir mortality-rates and possible methods of alteringthese rates.

It appears that in large herds or groups living underconditions favourable to the spread of epidemic disease,and receiving regular additions of healthy animals, thedisease will persist indefinitely. It also appears that,under such conditions, the form of the mortality curveand the size of the herd is determined in the main bythe rate of immigration. In certain epidemics the rateof mortality during the early days of herd life is veryhigh, approximately half the entrants being dead after25 days, and three-quarters to four-fifths after 50 days.Between the 40th and 60th days of cage life, the mortality-rate reaches a low level. The expectation of life from the20th to the 30th day rises continuously, but never reachesthe expectation of normal mice living in the same environ-ment but not in contact with an infective disease. It isconsidered that these events show that both selection(by death of the more susceptible) and natural immunisa-tion play a part in the increased average resistance dis-played by surviving mice, and that natural immunisationis more important than selection.

As regards possible methods of interfering with thenormal course of infected herds, three of these havebeen studied-artificial immunisation, changes indiet, and bacteriophage. The best results were

obtained with artificial immunisation, but a completeimmunity was never obtained : the dietary experi-

ments were negative, but recently Dr. Marion Watson,working in association with Prof. W. W. C. Topley,F.R.S., has obtained results which suggest that diethas a powerful influence on the mortality-rates ofmice infected artificially with Bacillus aertrycke.Similarly, the negative results obtained with bacterio-phage are regarded as by no means conclusive.Active immunisation, though it has failed in theseexperiments to give results as successful as thosereported from the field, has significantly increasedthe expectation of life, particularly in ectromeliaepidemics. It seems probable that the experimentalmethod will make it possible to define more clearlythe factors that determine the successful exploitationof this method of prophylaxis.

Cotton-Dust 11 Asthma "

The disabling chest trouble due to the inhalationof cotton dust by certain workers in the cotton

industry takes the form of attacks of cough or

breathlessness, occurring particularly on Mondaymorning after the week-end break. Gradually thesymptoms spread over the ensuing days of the weekand clinical examination of patients with establishedsymptoms reveals the signs of chronic bronchitis andemphysema. The death-rate from bronchitis amongmale cotton strippers between the ages of 20 and 60is five and a half times greater than that for all

occupied and retired males, and ten times greaterthan that in such dusty occupations as cementworkers and lime burners. Prof. Carl Prausnitz,working in Maitland’s department in the Universityof Manchester, has investigated this problem. Hewas able to show that although much has been doneby mill-owners to reduce the dust in card-rooms, themost dangerous fraction of cotton dust, consistingof the particles under two microns in diameter, stillobtains access to the workers’ lungs ; the proteinfraction of this dust contains some toxic factorwhich is probably responsible for the respiratorytrouble. Prof. Prausnitz is not hopeful that desensi-tisation will improve the condition ; and since the

present methods of ventilation and exhaust do notentirely exclude these minute particles, the solutionprobably depends either on the adoption by the workersof suitable respirators, of which a more satisfac-tory form is being sought, or on the application of newmeans of preventing the particles from entering the air.

Tuberculosis : Treatment by ArtificialPneumothorax

The fate of patients receiving artificial pneumo-thorax treatment under the tuberculosis scheme ofthe London County Council between the years 1920and 1930 has been reviewed by Dr. F. J. Bentley.As a result of this study it emerged that those patients

in whom complete collapse had been produced had amuch higher rate of survival than those whose affectedlung was only partially collapsed ; also that success ismore likely in the early stages of disease and where onlyone lung is affected. It is interesting that favourableresults in both sexes were found in the age-group 25-30,while the age-group 20-25 is peculiar in showing the bestresult in males and disappointing results in females.Dr. Bentley suggests that the treatment might well beused more extensively in young male adults.

Artificial pneumothorax treatment is of limited

application but in properly selected individualsufferers it sensibly increases the expectation of lifeand working capacity.

Tropical MedicineThe concluding paragraphs of the introduction to

this report record the formation and proposed

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activities of the new tropical medical research com-mittee. This committee has already made recom-mendations, on which the council have begun totake action, for the recruitment of able younginvestigators willing to work in the tropics and forthe eventual establishment of permanent posts forresearch in tropical medicine, to which workersengaged at first on a temporary basis may reasonablyaspire.

In addition to launching this main scheme of

fellowships and appointments, the council are

prepared to assist research in tropical medicine inother ways as opportunity may offer. In particular,grants will be available to enable workers in establishedpositions at home, particularly those not having thefacilities already possessed by the staffs of schoolsof tropical medicine, to make short visits to thetropics for the purposes of research or the collectionof material.

AIR-RAID WARDENS

THE Air-Raid Precautions Department of the HomeOffice issued last week a memorandum explaining theneed for an organisation of citizen volunteers to

perform a number of important duties in time of airattack, thereby augmenting and relieving the normalresources of the civil authorities and safeguardingthe general public. These volunteers, to be entitledAir-Raid Wardens, would work in contiguity totheir homes and places of business, their chief dutiesbeing to advise their fellow citizens on the pre-cautions against air raids as officially recommended ;in time of war they would know how to start reliefmeasures and where to apply for appropriate help.

THE DUTIES OF THE WARDENS

The wardens will require organisation and trainingand it is proposed that their work would always bedone in consultation with the police. It is expresslystated that they would be males, and that no directresponsibility for fire fighting will be laid upon them,as an auxiliary fire service will be formed by thefire brigade.The qualities and functions of a warden are

set out succinctly in the memorandum. He shouldbe a responsible member of the public, wellknown and respected in his area, and his dutywill be to supplement the resources of the police andfire brigade by rapid information as to the detailsof the fall of bombs, and by giving immediate warningof the suspected presence of gas. It would be hisduty to shepherd the public to shelter when anair-raid warning has been received, and to deal withcasualties or damage until skilled help arrives.Lastly and most importantly, the wardens are urgedto set an example of coolness and steadiness amongtheir neighbours. In each borough or district theyshould form a service of their own under a chiefwarden assisted by head wardens acting as groupleaders.The distribution of civilian respirators will be in

the hands of the wardens acting in collaboration withthe local authorities. It is recognised that the servicesof a considerable number of trained men intimatelyacquainted with the particular locality will be

required, for in any immediate preparations forwar members of existing public services might not beavailable. Although the war duties of the wardensdo not commence until the actual air attacks, therespirators should by that time be already distributed.

THE WARDENS IN TIME OF WAR

It is proposed that the wardens should operateErom fixed posts, each man being responsible for adefined group of streets, or

" sector," and each postshould be manned during a raid by two or threewardens. The duties of the wardens, as set out,may be more particularly summarised thus: Toknow the organisation in their locality, to advisepersons in the street when an air-raid warning hasbeen given, and to report at prescribed places thepresence of gas or fires and the falling of bombsin their sector. Other duties are to estimate theextent of damage done and to be ready to reportupon it, to assist occupants of damaged buildings tofind new shelter; to guide the police, fire brigade,first-aid parties, and rescue parties on arrival uponthe scene of damage ; to convey messages or render

any other assistance required by police or fire brigadeofficers ; and to help householders or the personnel offire posts to fight incipient fires, pending the arrivalof the fire brigade. And to assist in every possible wayto prevent panic. The Government will be responsiblefor equipment, and wardens, after training, will beeligible for the Air-Raid Precautions badge.

ORGANISATION OF AIR-RAID WARDENS

There are many points yet to be determinedbefore the Home Office plans can be regarded as

complete, but alternative schemes of organisation areput forward. Every scheme of organisation shouldprovide for a chief warden in executive control,assisted by head wardens in charge of groups of posts.These leaders will be required whether the control ofthe wardens is placed in the hands of the chiefconstable or of some other local official. Subject tothis general principle, the scheme of organisationof air-raid wardens can take one of several forms, ofwhich the following are the main types :—

SCHEME A

Air-raid wardens may be organised independently ofthe police, under the control of some local official otherthan the chief officer of police. They would work underthe chief warden, who would be in executive charge ofthe service in the local air-raid precautions organisation,but responsible to the permanent official deputed to exer-cise supervision and control. If this scheme is adopted,it is nevertheless recommended that the police should beconsulted before the actual enrolment of wardens, toensure that only suitable men are chosen. This schemewill be adopted in the metropolitan police district becauseit is felt that the size of the district and the large numberof important local authorities which it contains make itpreferable to decentralise the air-raid wardens’ organisa-tion. It does not follow that it would be the most suitablescheme outside the metropolitan police district. Wherethis scheme is adopted, it would be possible to employsome existing body or association as the agent for organis.ing and training the air-raid wardens, the chief wardenbeing a responsible official of that body or association.

SCHEME B

An alternative scheme would be for local authorities toarrange the framework of the wardens’ organisation,particularly as regards the numbers of wardens requiredand the location of their posts, on the basis that in timeof war they would operate under the control of the chiefconstable. Each area would have its chief warden,appointed by the local authority or authorities concernedin consultation with the chief constable, and the chiefwarden would be responsible for the recruitment andtraining of wardens with such assistance from the policeas might be arranged. This scheme is of a hybrid charac-ter, but it is not considered that there need be any difficultyin its working smoothly, provided that close cooperationwas maintained with the chief constable from the outset,