621

SPECIAL ARTICLES

MEDICAL RESEARCH COUNCIL

ANNUAL REPORT FOR 1934-35

THE Introduction to the report of the MedicalResearch Council provides year by year in 30 briefpages an index, a record, and a forecast: an indexto the trend of medical research during the periodunder review; a record of results achieved to thedate of its close; and a forecast, often alreadyconfirmed in the intervening six months, of theconclusions reached as the outcome of work essentiallycomplete but not yet published. It is a peculiarmerit of this annual report to steer between the

policy, unfair to other workers in the same field,of staking out claims for discoveries of which fulldetails are not available and that of supplying amere summary of communications already familiarto the readers of scientific periodicals.This year a dozen subjects from among those on

which work has been actively pursued are selectedfor review. Pride of place is given to

Nutrition: Application of Modern KnowledgeThere have been many recent indications of greater

public interest in nutrition. Though this interestmay have been aroused not solely nor even primarilybecause of the intrinsic practical importance of

proper feeding in its relation to health, but largelybecause of the probable economic effects on agricultureand industry, the Council express satisfaction thatthe discoveries of their own and other investigatorsof nutritional problems are likely in the near futureto play their due part in advancing human welfare.

HISTORICAL SURVEY

In view of this change in attitude they enumeratesome of the more practical discoveries which theyhave assisted during the 20 years of their existence.In the first year of their work they initiated research

on rickets which led to the elucidation of its nutritionalaetiology, and in particular to the discovery of a calcifyingvitamin (vitamin D), a substance which was ultimatelyprepared in its pure form by workers at the NationalInstitute for Medical Research. They also promoted, inassociation with the Lister Institute, clinical investigationson rachitic children at Vienna, which confirmed the

laboratory investigations and placed the methods for theprevention and cure of the disease on a firm basis. Later

they supported work, arising from the rickets investiga-tions, as a result of which it is now practicable to improvegreatly the structure of the teeth of the rising generationby proper feeding in infancy and childhood. They arealso responsible for the clinical investigations whichdemonstrated that, apart from dental structure, decay ofthe teeth can be slowed down by diet. This work has ledto a new outlook on what is probably the commonestdisability of civilised man-namely, dental decay--andhas supplied facts ready and feasible for widespreadtranslation into practice.One of the most important practical investigations

initiated by the Council demonstrated the effects ofsupplementing the diet of growing children with milk andother substances. Through their Accessory Food FactorsCommittee the Council have initiated and financiallysupported investigations made with the object of stan-dardising the different vitamins. Vitamin D was firststandardised in this country, and the whole series ofinvestigations later made it possible for internationalconferences, convened by the Health Organisation of theLeague of Nations in 1931 and 1934, to establish inter-national standards and units for vitamins A, B1, C, and D.Thus people throughout the world can now discuss these

vitamins in terms of units, in the same way as they candiscuss time and distance in units of hours and metres.

Other inquiries supported by the Council calledattention to the high incidence and significance of anaemiaboth in pregnant and lactating women and in their infantsin this country, and showed how the condition could beavoided or mitigated. Certain nutritional investigationshave been directed to the study of goitre, and othershave had as their object the determination and closeanalysis of the usual dietaries of different sections of thecommunity.These are only a few of the more important

contributions to knowledge in nutrition for whichthe Council have been responsible. Throughouttheir existence they have realised the fundamentalimportance of this rapidly developing subject, andhave placed it in the foreground of their programme.

THE NEW TEACHINGS

It is fortunate that the essential teachings can bereduced to a few simple statements. The first isthat the younger the child the more essential iscorrect feeding for proper growth and health. Itis thus necessary to apply the new teachings ofnutrition to the case of the pregnant and lactatingmother; and, despite the great importance of

improvement in the dietary of school-children, properfeeding of the infant and child of pre-school age isan even greater need. Breast feeding is of even highervalue than has been previously believed, and oughtto be more extensively adopted and continued forlonger periods.On the dietary side, the broad requirements can

be simply stated to the public-without mentionof calories, vitamins, or other technicalities necessaryto the investigator-by saying that much more milk(" safe" milk), cheese, butter, eggs (especially egg-yolk), and vegetables (especially green vegetables)ought to be consumed. In particular, milk oughtto be the chief drink for children, and especiallyin the first years, while bread and other cereals shouldin these early years be greatly reduced.

CURRENT WORK

Prof. E. P. Cathcart and Mrs. A. M. T. Murrayhave completed the analysis of data on family dietscollected from various towns in Great Britain overa period of years, particular attention being given tothe iron, calcium, and phosphorus contents of thediets. A quantitative survey of the diets of croftersand others in remote Highland areas is contemplatedfor purposes of comparison.A quantitative study of the ordinary diets of

120 men and women has been completed by Miss E. M.Widdowson, working under Dr. R. A. McCance, whowith Dr. L. R. B. Shackleton has also continuedhis observations on the chemical composition offruits and vegetables and their losses in cooking.It appears that most of the iron of vegetables andbread, and little of the iron of meat are utilised inhuman nutrition, and that about half the phosphorusof cereals, nuts, and pulses is in a form which cannotbe absorbed.

Prof. S. J. Cowell has done further experiments on thefactors controlling the excretion of calcium in the intestine.It appears that the rate of excretion depends on thedegree of saturation of the tissues generally with calcium,but that it is not much affected by sudden variations inthe calcium content of the blood. Miss E. M. Hume,assisted by Mrs. I. Smedley MacLean, D.Sc., have madefurther observations on the effects of fat deficiency whichwere noted by Burr and Burr in rats. Experiments are

622 MEDICAL RESEARCH COUNCIL REPORT

in progress to determine what substances in lard andlinseed oil are responsible for curing the lesions producedand for restoring the rate of growth to normal. An

inquiry is also being made into the influence of the fatsin the diet on reproduction. Under the general directionof Prof. W. W. C. Topley and Prof. Cathcart, Dr. MarionWatson has obtained preliminary results which indicatethat diet and various environmental factors have specificeffects on the fertility, growth, and survival-rates of youngmice. Attempts are now being made to determine whetherit is possible by dietetic means to increase the resistanceto Bact. aertrycke.

Dr. Helen Mackay is examining the value of a soyabean preparation as a supplement to milk in the diet ofinfants. The iron content of the bean is comparativelyhigh, and it is thought that it may possibly replaceinorganic iron salts for the prevention and treatment ofnutritional ansemia. An inquiry at the North EasternHospital, Tottenham, showed that the addition of extrarations of vitamins A and D to the diets of children withmeasles was without effect on the course of this disease oron the incidence of the minor skin infections.

The method devised by Mr. C. 0. Harvey to measureminute quantities of iodine in biological substanceshas been used by Miss M. G. Crabtree to study theiodine content of samples of milk, pasture, and

drinking water from different parts of Englandwith the idea of obtaining definite proof whether theincidence of goitre in certain districts is actuallyrelated to the iodine-content of the local milk andwater supplies. The findings so far indicate that theiodine-content of milk from the non-goitrous districtsof Suffolk is higher than of that from the goitrousdistricts of Somerset.

VITAMIN STUDIES

The seven pages devoted to vitamin studies inthis year’s report record much work on various

components of the vitamin-B complex, and on

vitamin C (ascorbic acid) with short sections on thechemistry of vitamin E and notes on the storage andon the standardisation of vitamin A.

As part of an inquiry into the vitamin Bl content ofhuman diets Mr. P. C. Leong has measured the amountsof this vitamin present in genuine wholemeal wheat andin ordinary brown bread and has found the differencebetween them to be surprisingly small. By arrangementwith physicians at several hospitals trials are being madeof the therapeutic effects of vitamin-B concentrates in" pink disease " in children ; encouraging results havebeen obtained in a few cases, although caution is requiredin their interpretation.Application of the work of Mr. L. J. Harris, Sc.D., and Mr.

S. N. Ray, Ph.D., on the diagnosis of vitamin-C deficiency tochildren under the care of Prof. L. G. Parsons and of Dr.E. Pritchard suggests that a suboptimal intake of vita-min C is common in artificially fed infants but not inbreast-fed ones, human milk being three or four timesricher in this vitamin than cow’s milk. Observations onadults by Dr. M. A. Abbasy and Dr. Harris indicate thatone or two oranges a day suffice rapidly to bring reservesof vitamin C up to normal in persons whose diet has beendeficient in this respect, but there is evidence that mothersoften disobey instructions to give orange juice regularlyto their infants.

The only mention of work on vitamin D in thissection of the report is on that of Miss Fischmann,who is studying its influence on ossification in tissuecultures. Elsewhere (p. 137) reference is made to theobservations of Prof. J. B. Duguid, assisted byDr. M. R. P. Williams, on the experimental productionof a form of nephritis by giving large quantitiesof orthophosphates by mouth, in the presence of

hypervitaminosis D ; and (p. 110) to the study byDr. Dorothy Russell of the vascular, renal, and

pituitary changes found in this condition.

Examples of Combined Clinical andLaboratory Research

Ergot in childbirth : isolation of ergometrine.-The end of the fascinating story, extending over

30 years, of the struggle to reconcile clinical andpharmacological experience in respect to the activityof various preparations and derivatives of ergot ishere recalled.

Again and again, during this period, new constituentshave been isolated from ergot which, although of greatphysiological interest, failed to replace in the confidenceof the practising doctor the watery extracts of the wholedrug. He continued to rely, for the purpose of stimulatingcontractions of the uterus, on these extracts given by themouth, though he was assured that they contained noneof the alkaloids found to be pharmacologically activewhen injected. This discrepancy between clinical practiceand pharmacological evidence lasted till 1932 when Dr.Chassar Moir was able to demonstrate by objectiverecords the powerful contractions of the human uterusinduced by the popular watery extract of ergot. Closecooperation between the late Mr. W. H. Dudley, D.Sc.,working on the chemical side, and Dr. Moir enabled themjointly to announce in March, 1935, the discovery of

ergometrine as the substance in ergot responsible for the emost familiar of the actions of ergot.The Council point out that these researches,

while illustrating how results of equal or even greaterimportance may be attained by the laboratory asby-products of the chase, also illustrate how vital tothe solution of a problem, originating in and concern.ing clinical practice, may be the guidance providedby continued investigation upon the clinical materialitself.

The curative agent of pernicious (MKpmm.—Anotherexample of the need for continuous clinical guidanceis in the testing of the therapeutic activity of prepara-tions derived from liver. It is as yet impossible toforetell whether any particular preparation willbe active until it has been tested on patients sufferingfrom pernicious anaemia. No effective laboratorytest of activity has yet been established, in spite ofworld-wide endeavours, while the chemical complexityof the liver principle has prevented the discovery ofany chemical or physical property which can be

regarded as a measure of its therapeutic influence.The Council were able to organise last year clinicaltrials by Prof. Stanley Davidson, Prof. E. J. Wayne,and Dr. C. C. Ungley of a preparation of liver extractmade by a British firm according to the methodof Dakin and West, published in America ; the resultof these trials (published in THE LANCET, Feb. 15th,1936, p. 349) demonstrated the extremely high degreeof potency of this preparation. Injections of from0.1 to 0-2 gramme of it once weekly, brought about alarge increase in the red blood corpuscles of the

patients tested and in the course of a few weeksrestored them to health.

Prevention of child-bed fever.-Here also thecombination of clinical and laboratory research hasbeen effective.

The fact that the morbid agent known to be responsiblefor puerperal sepsis is a streptococcus characterised byability to hsemolyse red blood corpuscles has of recentyears been supplemented by the knowledge that thecocci having this property comprise several groups andsub-groups, of which only certain members are harmfulto human beings. It emerges moreover that the hsemo-lytic streptococci occasionally found in the genital tractof healthy parturient women are not, as was formerlysupposed, identical with those causing puerperal fever,which latter come from some outside source. Dr. Dova Cole-brooke has recently tracked down the probable sourcesof infection. She has confirmed the view that the strep-

623MEDICINE AND THE LAW

tococci of the respiratory tract bear an intimate relationto puerperal fever ; and her results suggest that therespiratory tract of the mother must be taken into accountas well as that of her attendants, and that familial sourcesof infection may also be looked for.

Arising from her work is the lesson that it is

dangerous for any person suffering from an acuteinfection of this tract to engage in maternity work,and that maternity and surgical cases should not betreated under the same roof unless the nursing staffscan be kept separate.

Standards for sex hormones.-Under this heading theCouncil urge medical men using sex hormones in theirwork to insist on knowing the exact nature and

strength of the preparations supplied. The marketis flooded with different preparations, and each

manufacturing firm has given a proprietary nameto its own particular product. While some of theseproprietary preparations are good, both their composi-tion and activity being controlled, others are of asemi-bogus nature. The situation lent itself both toquackery and to ignorant treatment of diseaseuntil last year a conference, convened by thePermanent Standards Committee of the HealthSection of the League of Nations, met in Londonunder the chairmanship of Sir Henry Dale, and madeimportant decisions in respect of nomenclature andstandardisation.

A uniform scientific nomenclature and standard unitshave been adopted for three important natural substancesof which therapeutic preparations are now available.These are : (1) "oeatrone," " " cestriol, and " cestradiol, "the oestrus-producing hormones (the alternative names

applying to hydroxy-ketonic, trihydroxy and dihydroxypreparations, respectively) ; (2)

"

progesterone," thehormone of the corpus luteum which produces in the femalethe changes associated with pregnancy and pseudo-pregnancy ; and (3)

" androsterone," a chemical sub-stance closely related to that responsible for the develop-ment of the secondary sex characteristics in the male.

The effectiveness of the proposals must ultimatelydepend on the attitude of. those who use the substances.The Council point out that clinical knowledge ofthe actions of these sex hormones is still veryelementary, and it is certain that they are physio-logically potent, often in unexpected directions.

Miscellaneous Inquiries.-TravellingFellowships

Other studies reviewed editorially by the Councilare the researches into the value, effects, and possibledangers of different methods of producing anaesthesia ;the artificial cultivation of living tissues ; iodine and

thyroid disease ; industrial pulmonary disease;bed-bug infestation and the toxicity of industrialsolvents. We shall have occasion from time to timeto comment on some of these and on work in progressat the National Institute for Medical Research, at theclinical research units, and under the external researchschemes subsidised by the Council.

Regret is expressed that in consequence of a changein policy of the Rockefeller Foundation, the systemof international fellowships is being abandoned infavour of concentration upon a more restricted

programme for the promotion of research. TheCouncil had been privileged to award five or sixwhole-time fellowships every year, of the valueof between f350 and f450 each ; analyses showedthat of the 70 men and women who had completedtheir tenure of these fellowships 12 are professors,36 others are engaged full-time, and a further 16half-time in higher teaching and research. Theorganisation of a new scheme of the same kind is thus

considered highly desirable. A start has been madein the establishment of one such fellowship by thetrustees of the late Lord Leverhulme, and the Councilsuggest that other potential benefactors have herea great opportunity of performing an importantnational service.

Mr. Ramsay MacDonald, who as Lord Presidentintroduces this year the report of the Committee forMedical Research of the Privy Council, announces .,that the grant-in-aid provided by Parliament for theexpenditure of the Medical Research Council last yearamounted to 165,000, compared with 139,000 ineach of the three previous years. The increase hasmade it possible to proceed with plans for new .

research work which had been temporarily in

abeyance and to undertake additional investigationsrequired for the purposes of administrative depart-ments. Prof. J. A. Ryle and Prof. Matthew Stewarthave replaced respectively Lord Dawson of Penn andProf. A. E. Boycott as members of the Council,and the impending retirement of the chairman, LordLinlithgow on his appointment as Viceroy of Indiais announced with warm appreciation of his services.

MEDICINE AND THE LAW

A Fatal Dose of ParaldehydeIN Strangways-Lesmere ’. Clayton and others

Mr. Justice Horridge has refused to hold a districthospital at Weymouth liable for the negligence ofits nurses. The negligence consisted of administering6 ounces of paraldehyde to the plaintiff’s wife beforean operation in mistake for 6 drachms. The honorarysurgeon to the hospital gave instructions to the housesurgeon for the patient to have per rectum 6 drachmsin 9 ounces of water. The night nurse made a

pencilled note of the instructions on the bed-boardand handed it to Nurse A when the latter came on

duty. The judge accepted the evidence of the daysister and the night sister that this pencilled note,thrown away after the operation, specified 6 drachmsand not 6 ounces. It was the duty of Nurse A toadminister the drug and of Nurse B to check thequantity. The bottle of paraldehyde was taken froma locked cupboard ; the label stated that the dosewas to 2 fluid drachms. Nurse A poured out6 ounces (half the bottle) and mixed it with 9 ouncesof water ; Nurse B watched her do so. The patientdied of heart failure due to an overdose of paral-dehyde. Mr. Strangways-Lesmere sued the generalcommittee and trustees of the Weymouth DistrictHospital and also Nurses A and B. He contendedthat a hospital was, like any other employer, liablefor the negligence of its servants. The test was thepower of the governors of the hospital to control thenurses’ work. A hospital authority was, he con-

tended, protected in respect of the negligence of itsnurses only where the negligence occurred in thecourse of work demanding professional nursing skillover the performance of which the governing bodycould have no control whatever. Here, said the

plaintiff, the hospital authority had clearly assumedcontrol over the measuring and checking of dangerousdrugs by nurses because a hospital regulation had beenmade which required the sister on duty to check thedose. This regulation appeared not to have been

properly published to the staff ; it was not known toNurse A or Nurse B ; no precautions had been takento see that the rule was carried out. On the otherhand the hospital authorities argued that their