5961

[Nov. 27, 1937

ADDRESSES AND ORIGINAL ARTICLES

HUXLEY: THE BRAIN AND THE MIND*

BY E. D. ADRIAN, M.D. Camb., F.R.C.P. Lond., F.R.S.PROFESSOR OF PHYSIOLOGY IN THE UNIVERSITY

OF CAMBRIDGE

NINETY-FIVE years ago Thomas Henry Huxleyentered Charing Cross Hospital as a medical studentafter serving for a year as an assistant to Dr. Chandlerin Rotherhithe. In those days medical studies weretaken in an inverted order, or in no order at all, forHuxley began in the surgery of a slum practice andthen went on to chemistry, physiology, and anatomyat this hospital. He took his M.B. after three years,became a surgeon in the navy, and was soon appointedto the frigate Rattlesnake which was to survey EastIndian and Australian waters. Macgillivray was theofficial naturalist to the ship and Huxley the assistantsurgeon, but it was understood that he would do hisshare of the scientific work. He went out fully pre-pared to collect and study marine animals and on theRattlesnake he found his abiding interest in zoologyand was lost to medicine.A man with his eager curiosity and great driving

power would never have kept away from scientificresearch of some kind-he published a paper on thestructure of the hair when he was a medical studentand managed to interview Faraday (" a little man in abrown coat") on a project for a perpetual motionmachine-but the complete abandonment of medicineis interesting in a man of such humane interests.It was not from any lack of acquaintance with sicknessand misery. He records how he saw patients in theEast End " who were really suffering from nothingbut slow starvation and men who did not revoltbecause drink and disease had left nothing in them."But he had the faith of his era in the achievementsof natural science, in the absolute value of the truthswhich it revealed as well as in their practical use in theworld. At Charing Cross his teacher, Wharton Jones,showed him that physiology could be treated on thesame high level as physics and chemistry. Huxleywith his " ineradicable tendency to try to make thingsclear " must have had very little sympathy with thetraditions and ritual of the medicine of those days,and it must have been an unequal contest for hisinterest between the art which dealt ineffectivelywith such distressing material and the new scienceof physiology, interesting in itself and obviouslyan essential background for scientific medicine.

Though Huxley did not stay a physiologist, the manyeditions of his text-book survive to show that it wasone of his abiding interests. This was not merelyfor its own sake or for its connexion with medicine ;he believed a training in biology to be an essentialpart of education and he believed that education wasthe best physic for a contented social order and againstpoverty and disease. As biologist, educationalreformer, philosopher and great man of his time,he probably did far more for the progress of medicinethan if he had been on the staff of his hospital.

HOW THE BALANCE SHOULD BE STRUCK

A lecture which commemorates Huxley the medicalstudent can hardly avoid reviewing the advanceswhich have been made since he studied here, and as

* Biennial Huxley lecture given at Charing Cross Hospitalmedical school on Nov. 18th, 1937.

5961

a physiologist I ought to begin by celebrating thesuccessful invasion of this science into medical

teaching and practice. But I am not sure that theinvasion has not been almost too successful, forthere is some danger that physiology having pene-trated into the realm of zoology on the one side andof medicine on the other will become absorbed in thevast territories it has conquered and will cease toexist as an independent science. For its offspring,biochemistry, the danger is not so immediate, thoughthe biochemist has already made himself so indispens-able to medicine that it may soon become difficultfor him to follow his own devices. How this situa-tion will develop no one can foretell, and we do notreally know how it ought to develop, how the balanceshould be struck between the academic and the

practical. But there is one branch of medical sciencein which the two fields of interest have alwaysblended. In neurology true clinical research from

Huxley’s time onward has had the closest possiblerelation with experimental physiology, and progresshas been due to hospital wards and laboratories

alternately. For this reason and because the subjectmade a special appeal to his philosophical interestsI shall try to consider a few of the present lines ofadvance in our knowledge of the nervous system.For Huxley neurology was an essential part of thescience of the human mind and of human behaviour.Though he maintained that he was no materialist,in his " Life of Hume " he says :

" The roots of psychology lie in the physiology of thecentral nervous system. What we call the operations ofthe mind are functions of the brain and the materials ofconsciousness are products of cerebral activity."This was written 50 years ago and since then we havefound out many things about the brain and the mindwhich were unknown to Huxley. Has our outlookbeen greatly changed by increasing knowledge ?Have we lost the certainty of the Victorian scientists 1Are we in any better position to understand normaland abnormal behaviour, how much, in fact, have wereally advanced since Huxley’s time ? .

The answer must be that Huxley’s position remainsthe only possible one for the biologist in spite of someunforeseen difficulties which have appeared; andthat the science of human behaviour has indeed

progressed in spite of the fact that we have still almostas much reason to fear its aberrations.Those who are preoccupied with the body and its

disorders will have a natural bias towards Huxley’sconclusion, that the brain determines the mind, butits general acceptance is also due to the continuedadvance of the physiology of the living cell. Thishas been greatly influenced by an important branchof neurology which began just 150 years ago and hasgone steadily on its academic way ever since. Fromthe time of Galvani’s observations on animal electricity,celebrated last month in Bologna, nerve-fibres andmuscle-fibres have been experimented upon byphysiologists in every country. Their aim has beento explain the mechanism of nervous conduction andmuscular contraction in terms of molecules and

physico-chemical forces and they have been encouragedby the mechanical precision with which nerves

conduct and muscles contract. Progress has beenslow having regard to the vast amount of researchdone in the field of muscle and nerve physiology.Perhaps it has been no slower than might have beenexpected, for the cell physiologist can advance nofaster than the physical chemist who supplies him

1234 PROF. E. D. ADRIAN : HUXLEY-THE BRAIN AND THE MIND

with the conceptions he must use, the ions, orientedmolecules, and polarised membranes. None the lessthe hope of explaining the living in terms of the non-living has attracted and continues to attract someof the ablest investigators. At the present time,for instance, we are in the middle of a boom period,thanks to developments in electrical technique.A recent discussion of nerve problems at the RoyalSociety attracted physiologists from the ends ofEurope and showed most clearly that real advanceshad been made. One chapter is, in fact, almostcomplete; now that the nervous signals can bestudied by direct electrical observation we mightvery well write off from various physiological journalsthe thousand or more pages which discussed suchpoints as the form and frequency of impulses in theperiod before the advent of the valve amplifier.The interest has now shifted again to the fields ofcell or molecular physiology, the mechanism ofelectrical excitation and of the conducted wave.

It matters little that the mechanistic plan of atomsand electrons has ceased to be the ultimate realityof theoretical physics. After all the plan is stillgood enough for the main structure of physics andchemistry, and if the direction of advance has to bechanged, physiology is so far in the rear that it shouldbe easy to bring its theories into the new alignment.

Progress has been equally encouraging in a relatedbut more obscure field. Within the central nervoussystem the most important cellular activities are

not those relating to transmission along the axons,but to transmission from one cell to another across the

region of dendrites and synapses. This is a harderfield to explore and until the present century all thatwas known of the junctional region was its struc-ture. The functional problems were defined whenSherrington compared the response to stimulationin the nerve-fibre and the reflex arc. Since thenconduction in the spinal cord has been studied ingreat detail and we are now in a fresh period of

activity with two entirely new methods. One is the

analysis of the electric changes which take place inthe regions where there are synapses, in nerve gangliaor in the spinal cord, and the other is the search forthe specific chemical substances which may beconcerned in transmission from cell to cell. WithDale and Loewi’s evidence for acetyl-choline as thestimulant liberated by nerve-endings no one wouldbe surprised to hear that the same kind of humeraltransmission had been found in the brain. The

suggestion opens up the most alluring prospects andthere is already evidence enough to raise our hopes.

ORGANISATION OF CELL UNITS

I have mentioned these more academic branches of

neurology because in them there has been a steadyprogress with no sign of unusual difficulties ahead.From all the evidence there is no reason to supposethat the cell units of the nervous system differ greatlyfrom excitable cells elsewhere. They are less stable,no doubt, and their reactions are less stereotyped,but the mechanism of excitation and conductionis the same in them as in the muscle-fibre. Thespecial properties of the central nervous system mustbe due to the special way in which its units are

organised.Up to a point the organisation of the units is no more

difficult to understand than their individual reactions,thanks to Sherrington’s analysis of the spinal reflexes.In a famous book, now 30 years old, he pointed outthat the function of the central nervous system isto produce an integrated behaviour, to weld cells

and tissues into a single organism. The higher thedegree of synthesis the harder it will be to discernthe components, the machinery which builds up thesmoothly changing patterns of activity. By remov-ing the brain, however, the unifying control is

destroyed and the different parts of the machineryare more in evidence. " Spinal " or " decerebrate "behaviour is a collection of separate activities, eachcoordinated but on much simpler lines, and withthem it is possible to study the ebb and flow of excita-tion and inhibition, the factors on which integrationdepends.

INTEGRATION AT VARIOUS LEVELS

But the difficulties of analysis are of a differentorder when we pass to higher levels of the nervoussystem and more fully integrated behaviour. Atfirst there are merely anatomical complexities tocontend with. Even in the spinal scratch reflex

Sherrington finds that 27 different muscles comeinto play and in the postural reactions managedby the brain stem there is scarcely any part of thebody that does not. It is a triumph of analyticalneurology to have dealt with such elaboratelyorganised activities, but the work of Magnus andRademakers on the postural reactions seems to havereached the high-water-mark for this method ofapproach. Rademakers has now listed most of thereactions involved in standing and his descriptionfills a large book which could scarcely be shortened,yet the standing posture exists merely as a back.ground to the dominant behaviour dictated by thecerebrum. This seems to demand integrations of anentirely different order of complexity and it becomesquestionable whether anything which we can call

intelligent behaviour could be analysed, like standing,into a reasonable number of simple reactions.

Naturally this has been attempted many times,from Gall and the phrenologists onwards. Thecortex has been mapped out into areas speciallyconcerned with particular fractions of intelligentbehaviour and the synthesis has been supposed tofollow from an interaction of the different centres.Broca’s finding of the motor speech centre showedthat definite localisations of this kind were certainlypossible and at one period the cerebral mechanismfor speech seemed to be satisfactorily representedby diagrams of the centres for reading, writing," internal speech," &c., linked by associationtracts in the left hemisphere. Even if the existenceof these centres had been proved it is doubtful if weshould have been much nearer to an understandingof speech in terms of nervous activities, but it wasonly by judicious selection of the facts that actualcases of aphasia could be made to agree with thediagrams ; no one now tries to make them. The factis the cerebrum has not justified the expectationthat it could be analysed as a simple mosaic of cellgroups each dealing with a particular kind of mentalactivity and storing a particular set of memorytraces. Certainly the projection areas are essentialfor different functions, e.g., the striate area forvision and the temporal for hearing, but beyondthis there is little evidence for a detailed correlationbetween particular operations of the mind andparticular parts of the brain.

Lashley has often pointed out that in almost anykind of learning it is quite unnecessary for the samereceptors to be used repeatedly. We can learn thelook of the letter A by contemplating an A of anysize or colour. Somehow the cerebrum becomes tunedto the particular shape, but it cannot be because thesame nervous pathways have been excited when-

1235PROF. E. D. ADRIAN : HUXLEY-THE BRAIN AND THE MIND

ever the shape is seen. The same kind of difficultyarises from the effects of damage to the brain, exceptin the projection areas, for small lesions rarely producean isolated destruction of individual memories or

abilities. A lesion must be large if it is to be effectiveat all, and then it leads to a general weakening of anentire department of intellectual activity, the produc-tion or comprehension of speech for instance, or thediscrimination of visual patterns. The weakening isroughly proportional to the extent of the damage :thus in Head’s studies of sensory defects and of

aphasia it is the complex activities which suffer most,judgments of spatial localisation being disturbed bylesions too small to affect the mere recognition of

similarity and difference. And in the solving ofmaze problems by rats Lashley has found a similarmass effect of the cortex, a loss of efficiency pro-portional to the amount destroyed but not varying inquality with the position of the lesion.As usual, any general statement which we can

make about the cerebrum can be countered by a longlist of exceptions. Now that the neuro-surgeonmust so often explore the surface of the brain withelectrical stimuli there has been a fresh crop ofevidence of localised activities. Stimulating a

particular region may produce a particular mentalpicture-e.g., the complex aura of an epileptic fit,or a particular set of skilled movements ; and smallinjuries in certain positions may cause specific defects.We may expect that such evidence of localisationwill accumulate ; nevertheless it is unlikely to affectthe general conclusion that there is no anatomical

point-to-point relation between the brain and themind. This is illustrated by the recent evidence asto the activity of the frontal lobes. Being associa-tion areas, specially developed in man, the frontallobes might well be concerned with the more elaborateintellectual processes. Bilateral removal (Brickner’scase) certainly causes a decided change for the worsein the personality, but Jefferson describes eightunilateral cases where there was no change at all,at least no general defect and no loss of any specificaspect of mental activity.

A HIGH DEGREE OF’ELASTICITY

Thus we have no detailed anatomical basis formemories and intelligent actions. The factory whichproduces the materials of consciousness is not madeup of a vast number of independent sections eachturning out a particular product. There is a highdegree of organisation and a high degree of elasticity,so that minor accidents have little effect ; on the otherhand, a major breakdown in any department mayaffect the efficiency of the whole concern.The elaborate organisation of the brain is shown

by another set of facts relating to changes in thegeneral level of cerebral and mental activity. AsHead has pointed out, a loss of function due todestruction of the cortex is not a constant quantitybut depends on factors which can change rapidly andare related to emotional tension and alertness. Thenormal fluctuations in the efficiency of our behaviourseem to depend on general factors of the same kind.A new method of research has been introduced byBerger’s discovery that it is possible to record theelectrical activity of the brain with the skull unopened,and records made during sleep and waking, with theattention fixed or wandering have supplemented thedata from patients and anaesthetised animals. Fromthese it appears that the level of nervous activitydepends on widespread interactions between differentparts-e.g., the cortex and the thalamus, or the

brain stein and the ductless glands. Thus the centreof interest in cerebral physiology has now shifted fromthe motor cortex to the diencephalon. This is theregion which seems to have the most direct influenceon the general level of activity, for interferencewith it may induce either sleep or manic excitement,and Cannon and Bard have shown that it is closelyconnected with the bodily expression of anger.We are very far from understanding the parts s

played by cortex, thalamus, and hypothalamus inthe change from sleep to waking or from anger tohappiness, and this is not the occasion for consideringthe various schemes of cerebral machinery whichhave been proposed to account for such things as thetransfer of learning or the mass effect of lesions.Both Pavlov’s work and Lashley’s contain sug.gestions which may resolve the difficulty, but at

present we do not know what kind of change takesplace in the brain when something is learnt and it isimportant to realise our ignorance. All that canbe said is that the cerebral cortex does not make upthe whole of the mechanism for intelligent behaviourand that the level of activity in any region maydepend on interactions which include the more

primitive regions as well. Indeed, everything pointsaway from the analysis of behaviour in terms ofisolated reflexes and association systems and wemust face the idea that the whole brain cooperatesin any of its activities, although we do not know whatkind of mechanism is involved.

THE WHOLE BRAIN COOPERATES

Far from being a confession of failure this meansthat cerebral physiology is now facing its most

important problem. It is facing it armed with newmethods of all kinds, maze learning in animals,biochemical and pharmacological tests, records ofelectric changes in the cortex, and observations onpatients deprived of various parts of their nervoussystem. But the change in physiological outlookis noteworthy for another reason-because it corre-sponds in a measure with the change in psychologicaloutlook which has come since Huxley’s death. The

change can be seen most clearly by comparing amodern text-book of psychiatry with one written50 years ago. In those days, as Bernard Hart pointsout, psychiatry tried to advance much as neurologywas trying, by setting up hypothetical schemes ofmental disorder and then forcing the symptoms tofit. The key points of the scheme were not differentcortical centres, but the faculties of cognition, emotion,and volition ; it seemed reasonable to analyse dis-orders of the mind in terms of these faculties muchas disorders of speech were to be analysed in termsof word centres in the cerebrum. The attemptbroke down in face of the bewildering variety ofmental symptoms, and Kraepelin, using the propermethod of clinical research, found that there weretwo main groupings which had very little relationwith these faculties of the mind. Kraepelin’s dementiapraecox and manic-depressive insanity have nowbecome tendencies rather than diseases, and the

particular mental reaction type has been found to bearsome relation to the type of body. On the theoreticalside, however, the greatest change has come with thegeneral acceptance of the idea that conscious behaviouris guided by a balance of unconscious forces andwould be impossible without them. For this Freudis mainly responsible. His forces are conceived inpsychological terms-hopes and fears in an unconsciousmind-and for most of us it is very difficult to decidehow much is essential and how much merely dependent

1236 PROF. E. D. ADRIAN : HUXLBY—THE BRAIN AND THE MIND

on a particular way of stating the case. It would beabsurd, too, to pretend that amongst Huxley’s teachersand contemporaries there were not some who couldpredict a man’s behaviour as shrewdly as anyone cannowadays, and there are phrases in the writings ofSir James Paget, of Weir Mitchell, and of Gowerswhich show their understanding of the hystericaltemperament. Yet their generation had not Freud’sconception of unconscious drives moulding the

personality and colouring every thought. For themthe will held the balance between conflicting impulsesand was a superior power guided by reason : for usreason is less in control, since the organisation of themind seems to be not unlike the organisation of thebrain with a conflict of drivingforces in the background,though the final product may appear as a smoothlyintegrated activity.

I have a vivid recollection of the puzzled excite-ment with which we discussed Freud’s theories whenwe were medical students in Cambridge before thewar. The central idea then seemed as unlikely aswas the detailed analysis of dreams and trains of

thought ; but nowadays the central idea seems tooobvious to discuss, and, whatever we may thinkof the details of psycho-analysis, we can scarcelyconsider disorders of the mind without making someuse of the Freudian conception.No doubt the change has been assisted by the

natural shift of emphasis when one generationsucceeds another. There have been other formula-tions of the same position, less challenging thanFreud’s, and Pavlov’s work on conditioned reflexes,though it has little to do with psychology, has beenfar more important in one country in changing thepopular conception of the mind. Whatever itscauses, the change has had far-reaching effects: moreon social behaviour generally than on the specialisedactivities of neurologists and psychiatrists, for therewas more to change in the layman’s point of view.It has altered the relation between parents andchildren and made us less sure of ourselves. Weare less shocked than we might have been at theidea of developing beliefs and loyalties by state

propaganda, more ready to accept the challenge thatour scientific deductions will depend on whether wewere bred capitalist or communist, Aryan or non-Aryan. There is nothing new in the idea that reasonis not the main guide of human activities, but

nowadays we have to consider it as a scientificstatement, not merely as a satirist’s invention toshame us into good behaviour.

This change of outlook favours Huxley’s generalconception of brain and mind. It is true that theFreudian mechanism is a psychologic affair and nota neural, but advancing knowledge of cerebral andmental organisation seems to be leading neurologistsand psychologists towards a common ground. Bothare concerned with the driving forces, whether theyare the incentives to intelligent action or the physicaland chemical factors which control the level of

activity in the cortical networks, and both have newmethods of attack of great promise. Although weare not yet sure of the neural basis for the simplestintelligent action we are probably at the beginningof a period of rapid progress in cerebral physiology,and we are certainly nearer to an understanding of thepsychological factors which control behaviour.

PRACTICAL RESULTS ? °

Meanwhile, someone will ask, what practical resultshave followed from this increasing knowledge, whatadvances have there been in the control of abnormality

or disease I No one doubts that disorders of thenervous system are better understood and treatedthan in Huxley’s time, though there has been nosuccess as yet with disseminated sclerosis and someof the slow degenerations. With the psychoneurosesthere is certainly more understanding, though it ishard to avoid the impression that there is also moredisease. It is with the major disorders of the mindthat there has been a relative failure. There are

some new empirical treatments with a limited successand in some cases the prognosis can be given withgreater certainty, but it has to be owned that anincreased understanding of the insane personalityhas not yet done much to restore it to sanity. Soat least it appears to an onlooker. This failureis to be regretted but it is not surprising. Theadvance has been mainly on the psychological sideand can only suggest psychological lines of treatment.For the psychoneuroses these may be enough, butin the psychoses the patient has become inaccessibleto such treatment because his thought has ceased torun along the customary lines. To restore it wouldseem to involve treating the bodily changes whichmust certainly occur when the mind becomes incapableof bearing its normal burdens, and until we have moreknowledge of them there can be no rational treatmentof the disorder.

An advance in the treatment of disease has oftencome from a direct attack with a limited objective,but sometimes the position is turned by a movementon another front. Direct research in psychiatry isessential and may hope, with reasonable luck, to

produce the most immediate results-for instancethere are various problems as to the inheritance ofmental disorder which can only be solved by specificclinical investigation. Yet the general advance of

psychology and neurology has already had an indirectinfluence on psychiatric treatment. It has had amore important influence on the treatment of minordisorders, psychoneuroses, or the disorders of conductwhich infringe the rules of society. In this fieldthe practical results are clear.We need not hope for the time when the medical

experts will be required to deal with all conductwhich is thought by the ruling class to be antisocial.There will be quite enough to decide if we are calledon to breed out abnormalities and produce a

standardised race. But it is none the less the logicaloutcome of Huxley’s creed that the biologist shouldbecome the expert on human as well as on animalbehaviour. We are still too ignorant to suggestmany improvements in the accepted methods bywhich a society controls its members, though latelywe have been bold enough to assert that hungry menare often discontented and that prison does not alwaysinduce repentance. This is perhaps enough at thepresent stage. Huxley speaks somewhere of biologicalscience as providing an antidote to " that phase ofdespair through which the student, if he takes anearnest interest in social problems, will assuredlysooner or later pass." I suppose an occasional

phase of despair for the pains of mankind is still avaluable part of our medical training. We cannotnowadays extract so much comfort from the doctrinesof evolution or of the survival of the fittest, but weare not without compensations. One is the knowledgethat medical and biological research since Huxley’stime has greatly lessened pain and disease ; the otheris the more ambitious belief that by research on thebrain and on the mind we shall come to understandand control the forces which determine humanbehaviour.

1237DR. L. COLEBROOK & OTHERS : SULPHANILAMIDE IN PUERPERAL FEVER

TREATMENT OF

106 CASES OF PUERPERAL FEVER BY

SULPHANILAMIDE

(STREPTOCIDE)*

BY LEONARD COLEBROOK, M.B., B.S. Lond.MEMBER OF THE SCIENTIFIC STAFF, MEDICAL RESEARCH

COUNCIL

ANTHONY W. PURDIE, M.B., F.R.F.P.S. Glasg.,M.C.O.G.

FIRST ASSISTANT IN THE DEPARTMENT OF OBSTETRICS AND

GYNÆCOLOGY, BRITISH POSTGRADUATE MEDICAL SCHOOL;LATE RESIDENT MEDICAL OFFICER AT THE ISOLATION

BLOCK, QUEEN CHARLOTTE’S HOSPITAL, LONDON

And the Members of theHONORARY STAFF OF QUEEN CHARLOTTE’S HOSPITAL

STRIKING results have followed the treatment of

streptococcal puerperal sepsis by the two diazo com-pounds, (1) the hydrochloride of 4’-sulphamido-2 :4-diaminoazobenzol (=Red Prontosil) and (2) thedisodium salt of 4’-sulphamidophenyl-2-azo-7-acetyl-.amino-1-hydroxynaphthalene 3 : 6-disulphonic acid(=Prontosil Soluble) (Colebrook, Kenny et al. 1936a and b). There were however several reasons fordetermining whether similar or even better results

could be obtained with the colourless compound,para-aminobenzenesulphonamide, the remarkableantistreptococcal properties of which were firstdescribed by Trefouel, Nitti, and Bovet (1935).In experimental infections of mice this latter com-

pound is somewhat more effective than the red dyesnamed above, in similar doses ; it is formed in vivowhen these doses are administered to man andanimals (Fuller 1937) ; it confers considerable bac-tericidal power for hsemolytic streptococci uponhuman blood when added to it in vitro (whereasthe soluble red dye does not). All these facts taken

together made it seem probable that the simplersubstance para-aminobenzenesulphonamide wouldprove to be the active principle in treatment by thered dyes. It had also the advantage that it couldbe given by mouth to the great majority of patients ;and does not cause any discoloration of the skin.In view of the confusion which has already arisen

from the introduction of registered trade namesfor the diazo compounds and para-aminobenzene-sulphonamide-in particular from the application ofthe name " prontosil " to all these different sub-stances-it seems very desirable to get rid of allsuch trade names in the ever-increasing literature onthe subject and, in accordance with the usual scientificpractice, to employ the appropriate chemical termswhenever possible, or an arbitrarily chosen symbolwhen the chemical formula does not lend itself toa suitable abbreviation.

Nomenclature

In accordance with this policy we shall adopt thefollowing nomenclature in this report:

(a) The term sulphamido-chrysoidine will be used forthe substance originally designated streptozon by Domagk(1935), now sold under the registered name of " prontosilred " in this country, and " prontosil flavum " in othercountries.

(b) The term P.S’. (because no suitable abbreviation isavailable) will be used for the soluble diazo compoundintroduced by Messrs. Bayer Products Ltd. under thename of Prontosil soluble.

* A report to the Therapeutic Trials Committee of the MedicalResearch Council.

(c) The term sulphanilamide will be used for para-amino-benzenesulphonamide, as first suggested by our colleagueFuller (1937) and adopted by the American Council onPharmacy and Chemistry.The preparation of sulphanilamide used in this ,

clinical trial was that sold under the name Strepto-cide by Messrs. Evans Sons Lescher and WebbLtd., by whom it was supplied in generous quantitiesto the Therapeutic Trials Committee. It may be

regarded as probable, however, that the curativeeffects of sulphanilamide described in this , reportwould have been obtained with any preparation of asimilar degree of purity.

In the present paper we record our experience of106 cases of puerperal fever treated at the isolationblock of Queen Charlotte’s Hospital by sulphanilamideand contrast this experience with that previouslyobtained in the same hospital with sulphamido-chrysoidine and P.S. (Colebrook, Kenny et al. 1936

TABLE I

INFECTIONS BY ILMMOLYTIC STREPTOCOCCI ORIGINATING

IN THE GENITAL TRACT, POST PARTUM OR POST ABORTUM

Comprising Cases. Deaths.(1) Infections by hcemolytic streptococcus Group -4

(.LeMM’e/M’M)—(a) Limitedtouterus.vagina.and perineum 67 .. 0(b) Involving pelvic cellular tissues, fal-

lopian tubes, pelvic peritoneum, or

veins .......... 10 .. 1(c) Certainly associated with generalised

peritonitis .. 4 .. 2Probably associated with generalisedperitonitis ........ 2 .. 1

(d) Associated with septicaemia :Haemolyticstreptococcus only present

in blood culture 10 .. 3Haemolytic streptococcus plus B. coli

present in blood culture .. 1 .. 1Anaerobic streptococcus and entero-

coccus present in blood culture .. 1 .. 0

(2) Infections by hcemolytic streptococcus Group B(Lancefield)-

(b) Involving pelvic cellular tissues, &c.,as (6) above ........ 1 .. 0

(d) Associated with septicaemia (endo-carditis) .......... 1 .. 1

(3) Infections by haemolytic streptococcus Group C(Lancefield)-

(a) Limited to uterus,vagina, and perineum 2 .. 0(4) Infections by haemollltic streptococcus Group G

(NKCe./MM )——(a) Limited to uterus, vagina, and perineum 2 .. 0(d) Associated with septicaemia :

Haemolytic streptococcus only presentin blood culture .... 1 .. 1

Haemolytic streptococcus and otherorganisms present in blood culture 1 .. 1

Total-all infections by heemolytic streptococcus(Groups A, B, C, and G) ...... 100 t .. 8

POST-PARTUM INFECTIONS BY HJEMOLYTIC STREPTOCOCCI

NOT ORIGINATING IN THE GENITAL TRACT

Mastitis with abscess 2 .. 0

CHRONIC INFECTION BY HIEMOLYTIC STREPTOCOCCI tSkin and subcutaneous tissues ...... 1 .. 0

POST-PARTUM INFECTIONS BY ANAEROBIC STREPTOCOCCI

Septiecemic infections-Amaerobic only in blood cultures 1 .. 0plus other organisms in bloodstreptococci cultures ...... 2 1 1

INFECTIONS BY STAPHYLOCOCCI

All septicsemic infections (2 post abortum, 1 postpartum, see notes) ........ 3 .. 1

Total ........ 9 .. 2

* The other organisms were anaerobic streptococci andanaerobic Gram-negative bacilli which we were unable toidentify.

t Three of the 100 cases ( 1 (c) and 1 (d)) appear in two ofthe above categories since they had both septicaemia andperitonitis.$This case was one of post-partum sepsis originating in the

genital tract,with continuous wound infection (pure culture ofhsemolytio screptococcus) for three years until sulphanilamidetreatment was instituted. It has been separately reported byPurdie and Fry (1937) and will not be dealt with here.