Research in clinical medicine

637

RESEARCH IN CLINICAL MEDICINE2

By HE,my MOORE.

The honour of being elected as Chairman of the Section of Medicine of the Royal Academy of Medicine in Ireland is one to which I am fully sensible, both by reason of the duties which the office entails and my own .shortcomings. I cannot hope to occupy this position with the skill in debate or the tact in discussion displayed by my predecessor, Professor Rowlctte, who has made a mark upon and given a tone to the Dublin School of Medicine by his work inside and outside this Academy. At the coming meetin, gs, therefore, I ask you to balance my will to be helpful against the deficiencies which I shall surely show. I thank the Section for their confidence.

The subject I have chosen for my opening address is Research in Clinical Medicine. It is, I think, a suitable time to review the present position of clinical research in relation to both past and future, for we who actively deal with disease seem to have entered upon one of those critical periods which not infrequently occur in the progressive sciences, and which involve a change of methods and outlook. The subject under discussion is one to which I have given some thought from time to time, partly because I had a laboratory training in Dublin and Germany before I took up clinical work, but mainly because of experiences during my three years as a full-time worker on t~e staff of the Hospital of the Rockefeller Institute ~or Medical Research in New York, whichinsti tution, under the leadership of Dr. Rufus Cole, has to a certain extent inspired the ideas underlying the organisation of clinical research in the United States to-day.

In preparing this address I first set down my own views in the form .of notes, and this done, I read up the more recent writings on the subject. I found that my views were not new or origina], but were in substantial agreement with those expressed during the last few years by Dr. Rufus ~Cole i of New York and this month by Lord Moynihan; ~ they seem to be not very dissimilar from those of Sir Thomas Lewis, 3 except that my respect for the importance of the pure clinician in research is apparently greater than his. The recent paper by Trotter4 is an admirable presentation of the philosophical aspect of the subject. I then debated with myself as to whether I should deal with the subject at all, having nothing new to say, but I eventually decided in the affirmative, for it seemed that it was not originality that was wanted so much as interchange of views with other speakers. What I have to say has, I fear, little ~ap- plicability to the situation in the Irish Free State, because no

* Being the Inaugural Address to the Section of Medicine, read o~ October 17th, 1930.

638 IRISH JOURNAL OF MEDICAL SCIENCE

money seems to be available for clinical research in ~his country to-day, and, indeed, little interest, alas, is displayed in it by public bodies or private philanthropists.

Up to comparatively recent times clinical investigation of disease consisted, in the main, of bedside observation aided by relatively simple tests and quantitative measurements, with an attempt at the correlation of symptoms and faul ty function with the structural post-mortem and post-operative changes found in organs and tissues--the observational method, we may call it. I t was, is, and always will be a productive method of research, and it has a most important function as the testing ground of discovery. During the past two decades there has been a progressive increase of interest on the part of clinicians in the functional as well as in the structural aspects of disease, with the result that, not only have pathology and physiology become en- riched, but a better and more fundamental understanding of disease processes is being gradually, if slowly, obtained. In other words, we have come to regard disease in terms of physiology, that is, in terms of the living organism. The study of these more detailed and intricate aspects of disease necessitated methods more searching than mere bed-side observation alone; thus, the more precise and quantitative methods of the laboratory and the experimental method for the testing of hypothesis, involving the use of animals if necessary, came to be made use of in the clinic. This resulted in the necessity for clinical investigators to train themselves in the use and the in- Lerpretation of the more advanced methods of the laboratory in order to employ them in their quest of the elucidation of disease problems in the clinic. The clinicians themselves transported the technical methods and procedures of the laboratories to the clinic and used them as important adjuncts, wherever necessary, for the active study of disease as it occurred in the victim himself, that is, in its natural environment. This is one of the keynotes of organised modern clinical research; the method continues and is likely to yield progressively rich results. As a consequence of the wealth of information thus accumulated and of the t ruly enormous literature which resulted (not .all of it, I fear, quite sound) modern medicine has become one of the most complicated and difficult of the sciences, while still retaining its old character as an art. I t is a healthy sign of clinical medicine that those who practise it have become dissatisfied with the explanation of disease processes offered from laboratories which themselves have only the most indirect contact with disease as it naturally occurs. Who is more fitted to study disease than the clinician, the man who observes and handles it all his days, provided that he is able to use all the available weapons of attack, that is, both laboratory and clinical? Where should it be studied other than as it naturally occurs, in the patient? No one, certainly, who has frequent contact with disease will deny that the study of the patient is, as always, important .and fundamental, and that it will, tin-

RESEARCH IN CLINICAL MEDICINE 639

doubtedly, yield much useful information in the future as it has done in the past; but, as our knowledge progresses, or as our lack of it is revealed, problems more complicated than can be solved by mere clinical observation alone manifest themselves, and thus the more precise .and complicated aids and instruments of precision of the laboratories, including animal experiment, become necessary as important adjuncts in the clinic for their solution.

By way of illustration, let us briefly consider some of the more important advances of recent years in clinical medicine. Recall to mind the complicated combined biochemical and bedside studies which gave us our present understanding of acidosis, ketosis, diabetic coma and the principles underlying the dietetic treatment of diabetes mellitus. Insulin, which probably has saved more lives and given more comfort to the human race since its introduction than almost any other drug in the same period, was discovered, it is true, in the laboratory, but it had to be subjected to an intensive co-.ordinated study in the clinic and laboratory before it could be intelligently used in the treatment of diabetes and diabetic coma. The discovery of the extraordinary property of liver enabling the erythroblasts of patients suffering from pernicious anmmia to maturate, based admittedly on the laboratory work of Whipple on dogs rendered chronically .anmmic from repeated hmmorrhages, was made in the clinic and was elaborated in a careful, scientific, laboratory-clinical study which may well be pointed out as a classical example of how clinical research should be done. T~e same close co-operation between bedside and laboratory work is seen in the discovery of the pre-operativc use of iodine in toxic goitre, and in much of our recently acquired knowledge of diseases of the heart, certain diseases of infants and children, some diseases of the g'astro-intestinal tract, our partial understanding of certain aspects of immunology and the treatment of certain infections, the differentiation of certain types of nephritis, in the discovery that the secretion of the normal stomach can form from its action on meat a substance as potent as liver in inducing a remission in pernicious anaemia, and in other branches of progressive clinical medicine too numerous to mention. Indeed, one may say that the first harvest of the results of the method have scarcely yet been fully garnered, so fruitful has been the sowing. Not unimportant, also, is it that the co-operative clinical and laboratory method has frequently disproved false claims and saved us from wasting valuable time and effort in following inefficient and unscientific procedures. Thus, we see that a considerable proportion of the advances made in clinical medicine in recent years--discoveries of such importance that they have profoundly changed t~he practice of medicine in the last two decades--have resulted from the co-operative working of the clinic and laboratory as .one unit. In fact, the majori ty of the clinical investigators of to-day must be trained, not only for work in the wards, but must be prepared to perform,

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supervise, or advise upon the procedures of the laboratory in relation to the solution of their clinical problems. This is the main and the significant fact to which we must give recognition in our discussion to-night on research in clinical medicine. Of course, it is not suggested that every clinical investigator must necessarily work in the laboratory nor that every laboratory worker must actively participate in bedside observation; but, i f the signs of the times are correctly interpreted in this matter, there seems to be no doubt that the closest co-operation is necessary between the laboratory and clinic, and that, in clinical research, those who work mainly in the one should be, in some degree at least, familiar with the methods used and problems under investigation in the other. No one will deny that many of the important practical discoveries of recent years were elaborated in the laboratory, but the ideas underlying many even of these were born in the clinic, and the laboratory results had to be further studied in the clinic before being successfully used with patients. Such work can be done most efficiently where there is a co-operative clinical-laboratory unit, rather than in a ward with an indirect laboratory connection.

We may conclude, then, in general, that research in clinical medicine will be most productive when carried out on disease as it naturally occurs, that is, in the patient, by men who .are fitted to study it from all angles by whatever means available, and that the clinic and laboratory where such investigations are conducted should function, if possible, as one synergic unit. Many important indications as to the nature of disease and methods for investigating it will ever be furnished by bedside study; these will have their use in guiding, initiating and controlling the work of the laboratory, but the effectiveness of the relatively simple observational mode of reproach alone is, in general, diminishing because of the complexity of modern medicine.

The fact that this discussion is taking place to-night suggests that we are not altogether satisfied with the present organisation of clinical research. The reason, I think, is that there is not sufficient opportunity for the conduct of investigation in accord- ance with the principles just outlined. I t is curious to reflect that the clinical study of disease, as it occurs in the sufferer, is less well organised and endowed, in these islands, than is investigation in almost any other branch of science; this is .all the more remarkable because disease is accountable for the greater part of the suffering and unhappiness of the human race. More- over, it is well known that in communities where disease is being actively investigated by the synergic working of the clinic and laboratory, bedside observation is most careful and accurate, and therapeutic aid is in general most efficient, because of the stimulus of productive clinical research on both teachers and practitioners.

The question we might now put to ourselves is: How are we to organise our clinical researches? If our public hospitals were acquired by some wealthy Croesus and if we were to be furnished

RESEARCH IN CLINICAL MEDICINE 641

in return with funds to build up and equip .a new hospital organisation, I think we should set about our task actuated by somewhat different principles to those that stimulated the comparatively haphazard growth of the present hospital organisation. We should design our hospitals with four principles, at least, in ~rlew : ~

(1) The efficient care of the sick. (2) The study of disease, as it naturally occurs in patients, by

all co-ordinated available means, that is, clinical and laboratory, observatior~al, functional and experimental (by the latter I mean the formulation and testing of hypothesis), as well as from the minute examinagon of necropsy and bi.opsy material.

(3) The teaching and training of students, post-graduates, research workers and nurses.

(4) The institution of hospital social service for after-care and after-study, as well as for sociological reasons.

But, as such ideals are at present unattainable on a large scale in a world more or less impoverished, one can only keep them in mind in an endeavour partially to remedy an imperfect situation.

The time at our disposal is not sufficiently great to enable us to discuss the position exhaustively, but there is one aspect of it that should repay consideration: Should our research workers be whole-time or part-time, and should the man in practice, with a sound hypothesis or a reasonable tentative solution of a practical problem in disease, be afforded an opportunity for working out his idea?

There is much to be said in favour of the whole-time investigator in receipt of a salary stff~icient to enable him to live in the degree of comfort adequate to his scientific and professional status, with reasonable security of tenure; he will be able to devote his whole time to his studies without the distractions of routine teaching, ordinary private practice or consulting work; he will have leisure for thought, and the circumstances under which he works will permit him to view his problems with a logical, critical and scientific eye. His teaching should be con- fined mainly to demonstrations and lectures bearing on his own particular line of work. In order that he may not become too absorbed in his own comparatively restricted field, and, becoming narrowed in outlook, lose a balanced perspective on medicine as a whole, he should attend the staff meetings of the whole unit, so that he may learn as well as teach; he should keep in close touch with the learned medical societies, and maintain intercourse with outside teachers and practitioners. By such contacts he will foster broadmindedness in outlook as well as productivity in work, and his problems will be ventilated with reference to what Lewis calls " curative medicine." Above all, he should g~l~rc]. against arrogance and preserve the spirit of scientific humility in


his mental receptiveness. There is, no doubt, some danger--I have seen it happen--that the whole-time worker, if he omits such safeguards, will neglect the art of medicine for the science, will become disdainful of the psychological aids and kindncsses to patients (considering them wasteful of time and "1m- scientific ") upon which their successful handling so much de- pends. The pendulum is now too far on the side of curative medicine--we must see to it that it does not, with the develop- ment of the whole-time investigator, swing too far to the scientific side and make the means the end; the investigator must keep in mind that the cure of disease is the objective to be reached and scientific accuracy the sign-post on the road. In many cases it may be desirable that the full-time worker be an official of the university or medical school as well as of the hospital; this idea is in practice in many places in the United States. Finally, it may be said that such whole-time investigators have contributed so much to progressive clinical medicine in recent years that their numbers and their facilities must increase rather than diminish.

The part-time worker cannot be said to be such a success. Admittedly, this statement is not universally true, but, on the whole, it is difficult to sustain interest in research and at the same time to have one's mind disturbed by the calls of practice; the psychological atmosphere of investigation is so different from that of practice that the mind does not usually give of its best to either when it is engaged with the problems of both. The only justification for the part-time worker in organised clinical research is either want of funds to equip and pay him for his full time, or, in certain cases, the advisability of giving a man in practice the opportunity to test a promising hypothesis. Un- doubtedly, there are men in practice who have important ideas which they wish to elaborate, who are willing .and able partially to sacrifice the rewards of practice therefor, and who are so mentally endowed that they can readily change from the psychological atmosphere of practice to that of research; such men are not common, but those in authority should be able to recognise them and should afford them the necessary opportunity of part- time clinical research. As an example of clinical research of the highest order, carried on for years in the course of a busy practice, one recalls the work of the late Sir James Mackenzie. It is not always that ability can conquer lack of opportunity as his did-- we should see that opportunity is always present, otherwise some day we may fail to facilitate fruition of some important and far-reaching hypothesis.

I t may not be always advisable, however, for a worker to make his enquiries in a research clinic. If his material can be assembled there, then, his studies being centralised and his equipment being at his hand, his efforts will probably be economical both in time and in money and his results more .accurate. But such central- isation is not always possible, because, for example, of symptom- atological diversity or chronicity of the diseases under investi-

RESEARCH IN CLINICAL ]~IEDICINE 643

gation. Then he may be compelled to do his work in the field or in the general hospitals. This, however, does not detract from the main thesis of this communication.

I t would lead us too far afield to enter into a discussion of how the clinical research worker, who takes investigation as a career, should be trained. Suffice it to say that, having had a year or two of sound clinical experience and a period of general laboratory work, he should study, under direction, some comparatively simple clinical problems, doing both the bedside and laboratory work himself; the supervision of his early research should not be dictatorial but rather suggestive, and the exercise of his native logic should be unhampered; he shotdd gain experience of experimental work with animals so *,hat he m~y be prepared later on to use this method whenever necessary in his more advanced clinical investigations; then, when he undertakes subsequently more difficult clinical research, he will usually be in a position to acquire, devise or advise upon such methods and technique as may be necessary for the elucidation of his problems. Sometimes complicated and intricate methods are necessary for the solution of clinical questions, procedures involving special knowledge of a particular branch of science and too technical for the worker to master within .a reasonable length of t ime-- here co-operation with another investigator who possesses the requisite skill and judgment in the particular subject is frequently productive of success.

I t seems to me that there is needed at present some organlsa- tion to promote research in clinical medicine; some definite plan is advisable, rather than the pious hope that the good will of the leaders of our profession wilt stimulate ,a co-ordinated attack on the problems of disease. Why should there not be formed a Society of Hospital Teachers and Consultants, or even a Federa- tion of Hospitals, for the advancement of research in clinical medicine ? Such a body might be able to collect some funds and allocate them for organised research, and even might allocate the problems themselves, in order to avoid unnecessary duplica- tion of effort and to ensure that work might be undertaken under more favourable conditions. Scientific meetings of such a Society might have an important influence on productivity.

I t is, I think, generally true that a period of investigation makes one a better teacher and a better practitioner of medicine, because it makes one think of disease in terms of physiology.

I f some full-time research positions, tenable for a limited period of years, say five, were established in our hospitals, they should form a good recruiting ground for at least some of the higher clinical teaching positions. This would also mean that because a man had once ~oined the ranks of the researchers he need not be compelled to remain there always--the advisability of providing a method of escape from work that might eventually prove un~eongenial or unfruitful is obvious enough. There can bc little doubt that .a "period spent in investigating little anJerstood fields


in disease should enhance rather than diminish ability to diagnose and treat disease.

We must keep clearly in mind that however research in clinical medicine is conducted, and however noteworthy are its re,~ults, the final tests of reliability must be made in the clinic and in tbe practice of medicine outside its walls. For us, successful investigations which do not lead to results applicable to disease in man are either of academic interest or the starting point of further researches. Moreover, we must not lose sight of the important fact that the clinical study of disease as it actually occurs in patients will not only suggest problems and initiate attempts at their solution, but can often furnish guidance and give directional indications of great importance to the co-operative laboratory investigations which may make all the difference between partial and complete success.

Finally, then, we may say that organised research in clinical medicine should be carried out whenever possible in a special department of the hospital or in a clinic specially designed for that purpose. This department or clinic should be well equipped with all the necessary laboratory and library facilities and staffed by individuals who, in general, devote their whole time to clinical investigation, their teaching being comparatively limited and specialised. The laboratories and wards should act as a unit for the purposes of research, the workers for the greater part being familiar with the methods of both bedside and laboratory. I t must be recognised, however, that in clinical medicine there frequently become manifest problems the s tudy of which may be impossible in a clinical-laboratory unit ; in such cases the research necessary may have to be undertaken in the field by the observational or experimental method or by both combined; it is here that discretion and understanding on the part of those in authority are especially needed, not alone in the organisation of the work, but in the choosing of suitable workers and in providing opportunity, equipment and material. Such concepts as these should not interfere with the provision of aid to men engaged in practice who have the requisite qualities and ideas for carrying out investigation in disease problems.

I f there is one lesson that can be learned from the material aspect of the age we live in, it is that research pays. In clinical research the return will be bet ter .medicine, greater and more prompt relief of suffering, improved teaching, diminished morta- lity-rates and increased longevity, not to speak of the increased confidence and satisfaction which will accrue to the whole medics! profession from work well done.

When one deals with a subject such as this, one naturally desires to order one's thoughts not only in relation to the recorded opinions of others, but also with regard to one's own experiences. I hope I shall be pardoned, therefore, if I become personal in applying the present thesis to my own occasional excursions into clinical investigation; these cannot be called im-

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portant, but they may not be completely devoid of interest in relation to the matter under discussion.

For part of the time spent in the R, ockefeller Hospital, I was engaged in a study of the chemotherapeutic action of ethylhydro- euprein in pneumonia, s The work began in the laboratory with experimental animals, and during the last two years was con- tinued out in the clinic with laboratory co-operation, my collaborator and myself doing both clinical and laboratory work. I t was a laborious work, but was productive only in a negative sense, ~amely, that it disproved the claims that the routine use of optochin in pneumonia was curative. I mention it now as it was an example of the clinical-laboratory method of investigation advocated above. It also illustrated the important fact that results obtained by animal experiment cannot always be wholly applied to disease in man.

My investigative interests of late years in Dublin have been mainly clinical and observational with laboratory aid, the latter being done by a collaborator or by myself. In order to do the "work (such as it was) at all, the rewards of practice had in some degree to be sacrificed, and as the results were not very productive from the scientific point of view, it is doubtful whether it was worth while except for the personal discipline and experience ~nvolved.

We have been interested in the cardiac arrythmias, and were able to describe and study two cases of paroxysmal ventricular tachycardia ~ when less than 40 cases of the condition had been recorded in th~ literature; both cases were successfully treated. We witnessed 19 attacks of auricular flutter in 6 patients and devised a successful method of treating them by digitalis and quinidine ~ which had not been previously described ; recent writings have confirmed the views we expressed at the time of this publication. This work was clinical with the laboratory aid of the electro-cardiograph.

We have followed over 200 cases of diabetes under treatment and over 100 cases of vascular hypertension for several years without being able to add anything new to current clinical knowledge. We have formed the opinion, however, that salt-poor dietetic treatment is of use in the vascular hypertension cases. This work was clinical with laboratory aid.

I have also made some studies on hypocalc~emia with the collaboration of Dr. J. M. Hayden which we hope to publish in the near future; they were profitable more by giving order to our own ideas on the subject than by contributing new knowledge, but the results of treatment were, on the whole, gratifying.

I have been particularly interested in achlorhydria, and the results of a clinical study of this condition have been recently presented to this section. 8 In brief, we found, up to date, that in 933 fractional test-meals done on patients 21.8 per cent. showed achlorhydria, and this condition was found in 79 per cent. of 29 cases of Graves' disease, 43 per cent. of ,60 cases of diabetes


mellitus and in many cases of gastro-intestinal diseases, most numerous amongst which were cholecystitis and visceroptosis with gastric hypotonia. The interesting fact came to light that there is a definite type of secondary anmmia in which, apparently, achlorhydria is a pre-requisite condition and that this achlorhydric anaemia, as we call it, is a very common condition--we have studied 28 cases collected over a period of 3�89 years. We were able to restore the blood picture to practically normal in almost all cases by suitable doses of iron, to show that the ad- ministration of dilute hydrochloric acid in suitable dosage by mouth, while desirable and helpful, was not necessary for the restoration of the blood picture to normal, and that even when the anaemia had disappeared the fractional test-meal still showed achlorhydria. We were also able to show that the clinical ~'eatures of achlorhydric anaemia are comparatively definite. It is interesting to note that, almost simultaneously, Witts, 9 of London, published a similar study of this condition, calling it by the same name, and that his description and results almost entirely coincided with ours, although we were unaware of each other's work.

We have had some interesting experiences with toxic goitre. For example, amongst about seventy cases of undoubted hyperthyroidism, we have seen seven without any obvious thyroid enlargement and with basal metabolic rates above ~- 40 per cent. In five of these we made a therapeutic-diagnostic test with Lugol's solution and all reacted positively, that is, by reduction of the basal metabolic rate to normal. Four of the seven had achlorhydri~a (three were not tested for this condition), all but one had tachycardia and all had tremor. In four of them it was the combination of tachycardia, tremor and achlorhydria that suggested a basal metabolic rate estimation. In one case of tachy- eardia following an acute infection of obscure etiology we actually witnessed the disappearance of HC1 from the stomach secretion as the basal metabolic rate rose from normal to -~ 65 per cent., exophthalmos and tremor meantime appearing. In two cases of hyperthyroidism without detectable goitre, and in two with obvious thyroid enlargement, sub-total thyroidectomy resulted in symptomatic cure although the thyroid tissue removed showed no pathological changes. This suggested that, when one performs a therapeutically successful sub-total thyroidectomy in cases of toxic goitre, one simply breaks a vicious circle, that one leaves the cause of the hyper- secretion of the thyroid untouched, and that one simply leaves so little thyroid tissue in situ that the remnant cannot be forced to over-secrete by the unknown and untreated cause. Further, one might believe it possible that the accepted histological changes seen in Graves' goitre might develop only after these glands had been over-secreting for a considerable length of time, in other words, that the histological changes might be an expression of work hypertrophy and that in the early stages

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~]~e o v e r - s e c r e t i o n m i g h t be f u n c t i o n a l only, w i th no co r r e spond- ing c e l l u l a r h y p e r p l a s i a . H o w e v e r , we have h a d no o p p o r t u n i t y of t e s t i n g th i s h y p o t h e s i s , n o r a r e we l i k e l y to have one.

W e have h a d two cases of p o l y c y t h e m i a vera r u b r a in which, w h e n t h e use of p h e n y l h y d r a z i n e h y d r o c h l o r i d e f a i l ed to reduce the b l o o d c o u n t a n d h~emoglobin p e r c e n t a g e to normal , p r ev ious r a d i a t i o n of the bones r e n d e r e d the subsequent use of the d r u g e m i n e n t l y s a t i s f a c t o r y . I have no t seen this combined m e t h o d m e n t i o n e d in t h e l i t e r a t u r e . One case of th is disease r e a c t e d f a v o u r a b l y to t h e d r u g a f t e r i r r a d i a t i o n h a d fa i led , and a f o u r t h case is n o w r e c e i v i n g x - r a y t r e a t m e n t a f t e r a p r o l o n g e d a n d u n s u c c e s s f u l cour se of p h e n y l h y d r a z i n e w i th the idea tha t , i f t h e r a y t r e a t m e n t fa i l s , t h e s u b s e q u e n t use of t h e d r u g m a y g ive f a v o u r a b l e r e su l t s .

W e have , a lso , p u b l i s h e d some s t u d i e s on the t y p e s of pneu- mococci c aus ing l o b a r p n e u m o n i a in D u b l i n l~ pern ic ious ~nmmia it, t h e b a s a l m e t a b o l i c r a t e ~2 a n d n e p h r o s i s ~3.

F i n a l l y , I w o u l d l i ke to m e n t i o n a r a t h e r r e m a r k a b l e exper i ence w i th a r a r e c o n d i t i o n w h i c h m a y be c a l l e d acu te spon taneous h y p o g l y c m m i a ; on ly seven such cases have been r e p o r t e d in the l i t e r a t u r e .

A woman, aged 27 years, was brought into the hospital in an unconscious condition on June 4th, 1930; there was a peculiar r igidi ty of the somatio musculature so tha t the tendon reflexes could not be obtained ; the conjunc- tival reflex was present, and there was a bilateral Babinski sign. She was frothing at the mouth and h~d been unconscious for some hours. The urine, obtained by catheter, contained ~ trace of albumen, no glucose and no diacetie acid. We were told tha t she did not have diabetes and never had insulin. Her blood sugar was only 35 rag. per cent. Evidently, we were dealing with one of those rare cases of acute spontaneous hypoglyo- mmia, of which only seven are reported in the l i terature; they have been called hyperinsulinism, but I do not think this name a good one. The diagnosis was tested by the intravenous injection of 10 grammes of gluceso, and this procedure resulted in immediate and complete return of oonsciousness and disappearance of the r ig idi ty and of the Babinski sign. The blood-sugar three hours after the iniection was 111 rag. per cent. We have kept this pat ient under observation for several months in an endeavour to trace the cause of the attack. In brief, we found that she had achlorhydria and tha t her stools were rich in undigested starch granules. Apparently, her hypoglycsemia was in some way connected with imperfect digestion of starch and possibly with imperfect regula- tion of her formation of insulin. At any rate, taka-diastase, when given by mouth, corrected the amylaceons dyspepsia, for starch disappeared from the stools after three days of treatment, the blood-sugar was main- tained at 78 to 85 mg. per cent. and she got no more attacks of uncon- ,ciousness. 'The amylaceeus dyspepsia was apparently temporary, for we ~-ere able to discontinue the ~al~a-diastase after some weeks without starch ~ppearing in the stools. Finally, after several weeks' treatment with hydrochloric acid by mouth this substance was again formed in adequate amount by the stomach.

M a n y i n t e r e s t i n g q u e s t i o n s a r i s e f r o m such an exper ience , not o n l y in r e l a t i o n to s t a r c h d ige s t i on , b u t also as to w h e t h e r some so -ca l l ed h y s t e r i c a l o r c p i l e p t i f o r m a t t a c k s m a y no t be due to a c u t e s p o n t a n e o u s h y p o g l y c s e m i a . Th is is, I th ink , the first case r e c o r d e d w h e r e t he c o n d i t i o n w a s a s soc i a t e d w i t h amylaeeous d y s p e p s i a . W e hope to p u b l i s h t h e d e t a i l s l a t e r . Unfor tu -

648 I R I S H J O U R N A L O F M E D I C A L S C I E N C E

na t e ly , l a c k of t i m e a n d e q u i p m e n t p r e v e n t e d a f u l l p h y s i o l o g i c a l i n v e s t i g a t i o n of th i s case.

I have m e n t i o n e d these l a t e r o b s e r v a t i o n s , n o t b e c a u s e t h e y a r e of a n y i m p o r t a n c e in t h e m s e l v e s , b u t to show t h a t , e v e n i n one clinic, the p r o b l e m s a re legion. I feel conv inced t h a t we have in D u b l i n the m e n c a p a b l e of success fu l ly a t t a c k i n g c l in ica l r e s e a r c h p r o b l e m s a n d t h a t a l l we n e e d is the w h e r e w i t h a l to f inance the w o r k . P e r h a p s i t is n o t too m u c h to hope t h a t b e f o r e t he end of o n e ' s d a y s one m a y see t h i s c i ty , as in t h e d a y s o f C o r r i g a n a n d G r a v e s a n d S tokes , a c t i ve once a g a i n in r e s e a r c h in c l i n i ca l med ic ine .

l~eferences. 1. Cole Rufus: Science, ]970, vol. li, p. ~29.

tAddress delivered before the General Hospital Society of Connecticut, May 29, 1926.

Scie~ce, 1927, vol. lxvi, p. 545. Science, 1928, vol. lxvii, p. 47. Science, 1930, vol. lxxi, p. 617.

2. Lord Moynihan: Lancet, ii, 1930, p. 778. 3. Lewis, Sir Thomas: Brit. Med. J., 1930, March 15, p. 479. 4. Trotter , W. : Brit. Med. J., 1930, July 26. 5. Moore, H. and Chesney, A. : Arch. Int. Med., 1917, xix, 611, and

1918, xxi, 659. 6. Moore, H. : IRISH Jo. ME~. SCI., 1928, Dec. 7. Moore, H. IRIs~ Jo. MED. SoI., 1928, February. 8. Moore, H. : IlCISH Jo. MEI). ScI., 1930, Sept., 589. 9. Witts , L. J . : Guy's Hospital Reports, 1930, July, 253.

10. Moore, H. : IRISH Jo. MED. ScI., 1923, March. 11. Moore, H. and Dungan, A. : IRISH Jo. MED. ScI., 1927, Aug. 12. Moore, H. : Lancet, 1925, Jan. 31. 13. Moore, H. and O'Farre l l , W. R. : Brit. Med. J., 1930, Aug. 16.

THE LANCET COMMISSION ON NURSING. Lord Crawford and Balcarres has consented to preside over The Lance~

Commission on the position of nursing. The terms of reference of the Commission are to inquire into the reasons lor the shortage of c a n d i d a ~ , t rained and untrained, for nursing the sick in general and special hospitals throughout the country, and to ot~er suggestions for making the service more at t ract ive to women suitable for this necessary work. The members of the Commission a r e : - -

The Earl of Crawford and Balcarres, P.C., K.T., F.R.S. Prof. Henry Clay, M.A., D.Sc., late Professor of Social Economics in

the University of Manchester. Miss R. E. Darbyshire, R.R.C., Matron, University College Hospital . Miss L. Clark, M.B.E., R.R.C., Matron, Whipps Cross Hospital. Dr. Robert Hutchison, F .R.C.P. , Physician to the London Hospital

and to the Hospital for Sick Children, Great Ormond Street. Prof. F. R. Fraser , M.D., F.R.C.P. , Professor of Medicine in the

University of London, Physician to St. Bartholomew's Hospital. Mr. A. Lister Harrison, J .P . , Chairman, Committee of Management,

Metropoli tan Hospital. Miss M. D. Brock, D.Lit t . , Headmistress, the Mary Datchelor Girls'

School. Mrs. Oliver Strachey, Chairman, Employments Committee, London

Society for Women's Service. Miss Edith Thompson, C.B.E., Member of Council, Bedford College,

University of London. Sir Squire Sprigge, M.D,, F .R.C.P. , the Editor of The Lancet, with

Dr. M. H. Kettle, an assistant editor, as honorary secretary. Any organisation or individual wishin~ to provide evidence for the

Commission to consider, or to make proposals relating to the improve- ment of conditions of service of the nursing profession, is asked to com- municate with the hen. secretary at The Lancet Offices, 7 Adam Street , Adelphi, London, W.C.

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