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Aversion treatment with tetraethylthiuram disulphide is

similarly contraindicated.The most important therapy is social. These elderly

alcoholics (once they are sober and circulation andmetabolism have been suitably propped up) respondimmediately to the company of their contemporaries andpurposeful rehabilitation. This should be arranged as atraining programme with physiotherapists and occupationaltherapists.Once the patients have been physically and mentally

restored, they should be prevailed on not to return to theirown homes but to live in some form of a community.Occasionally the patient can be discharged to the home ofone of the family. But in this event one must be convincedthat the family can cope with the situation and assume apaternal rather than a merely protective role. In most

cases, residence in an old people’s home, away from butnear the family, should be advised. The social pressuresof outsiders and the friction of living in the companyof others seem to be the best protection against a

relapse.Although all these patients recovered physically, 2 had

to be retained in hospital on account of increasing dementia,and the 2 who were discharged to relatives are undersurveillance and have so far not relapsed. The strain onthe relatives is great, and admission to some form ofcommunal care is being contemplated.

DISCUSSION

Chronic alcoholism is said to begin in the first threedecades of life in 75 % of all cases.3 In this series only2 started drinking so early; 5 took to alcohol after increas-ing isolation, grief, and the other erosions of life

inseparable from old age.Once the patients found themselves discovered by their

families as drinkers, a new set of circumstances arose. Thefamilies were scandalised and afraid of gossip; they feltthat no-one should know about their mother’s failings;hence they gave money and often brought drink themselvesto the house. This accounted for the expensive tipplechosen. To keep up appearances one would be told " sheonly drinks for medicinal purposes ", " she is a total

abstainer, but she needs brandy for her heart ", and so on.From this stage to that of blackmail was only a little step.As consumption rose, so did threats to tell the neighbours,to go about undressed, playing on the guilty feelings ofthe family; the result was more drink brought into thehouse and less food consumed, until some minor illnessor accident in the end made the family send for thedoctor. In 5 out of the 7 patients, the doctor did not realisewhat had been happening. 7 patients of 404 consecutivedomiciliary and assessment visits were addicted to alcoholto such an extent that they presented as difficult diagnosticproblems.

If the present series is representative, 1-7% of elderlypatients who seek admission to hospital seem to bealcoholic addicts on comparatively small doses, and witha low tolerance. The price they pay may not be heavyin terms of damage to their cardiovascular system, but ofthe present series practically all showed some abnormalityof liver function. The sustained misery which suchpatients spread among those around them, and theblackmail which they exert on their families, posedifficult sociomedical problems.3. Mayer-Gross, W., Slater, E., Roth, M. Clinical Psychiatry. London,

1960.

MEDICAL RESEARCH

THE year 1913 saw the beginning of formal Governmentsupport for medical research in this country and the birthof what is now the Medical Research Council. TheCouncil’s report for 1962-63 reflects the types of prob-lem-not all of them scientific-which, fifty years later,confront its research-workers. Prominent among themare the ethical considerations arising from experimentationon human subjects.Investigations on Human Subjects

Since there is no experimental animal quite like man,the advancement of medical knowledge sooner or laterrequires that unproved or frankly experimental proceduresshall be carried out on human subjects. Increasingly, thisnecessity is involving investigators in ethical and even

legal dilemmas. The Council, asked to advise, felt that norigid code of rules could be devised which would beuniformly applicable. It has, nevertheless, prepared astatement giving general guidance on the conduct of theseprojects.The Council distinguishes between procedures which are to

be embarked upon in the hope of benefiting a patient and thosewhich are irrelevant to the subject’s well-being or state of health.The decision to undertake those in the first category is made, itsays, in the context of the doctor-patient relationship. The doctoruses his clinical judgment (fortified, if he is wise, by advicefrom experienced colleagues), and the patient presumably truststhat judgment and abides by it. He agrees to undergo the newprocedure, be it diagnostic, therapeutic, or prophylactic, as hewould more conventional forms of treatment. The Councilconsiders a parent or guardian clearly competent to give per-mission for such a beneficial procedure to be carried out in achild too young to give his own valid consent.More difficult is the correct conduct of investigations from

which the subject is not intended to benefit. Understanding thenature and consequences of what is proposed, the subjectshould, says the Council, explicitly consent to participate. Theinvestigator should try to arrange to receive this consent verballyin front of a witness; and if he stands in any special relation tothe subject (e.g., doctor to patient, teacher to student) he shouldmake sure it is indeed voluntarily given. Parents cannot, in law,give consent on behalf of their children for this type of proce-dure ; and no court would recognise a child of less than 12-14years of age as able to give valid consent on his own account.Similarly, if a mentally disordered person is incapable of givinghis true consent, none can do it for him. Consequently, youngchildren and the severely deranged should not be subjected tothis type of experiment.The controlled clinical trial presents problems all its own. In

general, such trials are permissible only where there is genuinedoubt as to which of two regimens is the better. Where the onlyform of treatment is that being investigated, this should beexplained to the participants and their true consent obtained.On occasion, however, such full explanation would be irijudi-cious-for example, when the element of suggestion is to beassessed. The Council feels that, in view of such inherentdifficulties, controlled trials should be conducted by groups ofworkers rather than individuals; and a doctor should be atliberty to withdraw his patient from the trial and institutealternative treatment should this seem in the patient’s interest.The Council suggests, finally, that any account of investiga-

tions on human subjects should be accepted for publicationonly if it includes a clear statement that proper consent wasobtained. The ethical standards laid down by law are not, itbelieves, sufficient of themselves to maintain the position oftrust which the medical investigator still holds in the com-

munity. The progress of much future research will depend onthat public confidence. Its preservation is therefore worth alittle care.

1. Medical Research Council: Report for 1962-63. Cmnd 2382. H.M.Stationery Office. Pp. 257. 16s. 6d.

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Some Aspects of ResearchHow basic are the gene and the chromosome to current

research is apparent from the choice of subjects for reviewin the report.Chromosome damage induced by radiation is under investiga-

tion at the Council’s unit for the study of the clinical effects ofradiation. Accidental or therapeutic irradiation, whether localor general, has been shown to be followed by the appearance inthe peripheral blood of lymphocytes with abnormal chromo-some complements. The abnormalities are of two types-stableaberrations in which each chromosome retains its centromereand in which the cell is therefore theoretically capable of con-tinuing division, and unstable aberrations in which the presenceof acentric fragments or ring forms implies that cellular divisioncannot proceed without the elimination of chromosomalmaterial and eventual cell death. Cells with abnormalities ofeither type have been found in the peripheral blood as long astwenty years after exposure. Detailed study of those with theunstable configurations has provided indirect evidence of thepresence in the body of lymphocytes with a remarkable poten-tial for survival without division. Some such cell is sorelyneeded to provide a basis for the " immunological memory

"

which allows the antibody-producing system to react to a

second encounter with a given antigen by vigorous antibodyproduction.The role of the gene in protein synthesis has formed

a basis for work on penicillinases under way at Mill Hill.According to the French workers, Jacob and Monod, protein

synthesis is governed by two types of gene-a structural genedetermining the configuration of the product, and a controlgene controlling its rate of production. This control is mediatedby a repressor substance which inhibits activity at the structural

gene. Enzyme production by bacteria, and in particular thesynthesis of penicillinase, has been interpreted in terms of thishypothesis. Bacterial synthesis of the enzyme is normally of nobiological use and is kept at a negligible level by the suppressorsubstance. The presence of penicillin, however, inhibits thesuppressor and penicillinase production is released. In threebacterial species studied at Mill Hill, the synthesis of penicillinhas been found to increase a hundredfold after an hour’scontact with traces of penicillin.The gene obtrudes besides on practical medicine.

Thanks to studies in clinical genetics, many patients inneed of improved genetic counsel can now find it. The

early diagnosis and prevention of some hereditary diseasehave also been rendered practicable.A family study of glaucoma simplex, for instance, has revealed

that, in almost half the collaterals and descendants of affectedpersons, the outflow of aqueous humour from the anteriorchamber of the eye is abnormal. In few with this latentabnormality will glaucoma subsequently appear. Nevertheless,their continuing observation and, where necessary, prompttreatment should be rewarding.

Genetic problems in orthopaedic disease are to betackled by one of the seven new research groups set upby the Council during the year. The remainder are tostudy abnormal haemoglobins, the megaloblastic anaemias,respiration and energy metabolism in the newborn, themechanical properties of human tissues, the psychologicalaspects of speech and language, and immunologicalmechanisms in skin disease. These additions, whichreflect the range of the Council’s interests, bring thenumber of its research establishments to eighty-six.

Conferences

COMPUTERS IN BIOLOGY AND MEDICINE

THE conference gathered by the Medical ResearchCouncil in Oxford last week really began in Cambridge.Charles Babbage, of Peterhouse, Lucasian professor ofmathematics at Cambridge from 1828 to 1839, spentthirty-seven years and much of his fortune in the pursuitof the great calculating engine-which, though it nevercame off, was the undoubted ancestor of today’s computingmachines. The applications of computers in biology andmedicine gave the conference plenty to absorb and discuss;and the M.R.C. did splendidly to organise this meeting atjust the time when interest in computers is quickening 1(" at last ", some would say) and to secure contributionsfrom so many of the leading thinkers on this subject.

RECORD LINKAGE

" Record linkage " is the bringing together of separatelyrecorded facts about health events in the same individualor family. The idea and advantages of doing this for awhole population were first suggested by Farr 2 in 1874;but little was accomplished until a national index of birth,marriage, and death certificates was constructed in Canadasoon after the 1939-45 war. This alphabetical list of thethree events for the whole country was extracted fromcards punched from microfilm copies of the certificates.Subsequently H. B. Newcombe and his colleagues linkedstillbirth and birth certificates with marriage certificatesfor the population of British Columbia; and they showedhow a computer could be programmed to link data fromvital certificates into family groups. The conference

1. See Lancet, 1964, i, 1171.2. Farr, W. Supplement to 35th Annual Report of the Registrar General,

1875; p. 110.

agreed that the efficient use of the great mass of recordedinformation about health and disease would depend onthe organisation of files in this and other ways to facilitaterecord linkage and the development of appropriatecomputer techniques.

Dr. E. D. ACHESON explained what had been done inthe Oxford Record Linkage Study.3 3 From the pilotpopulation of 325,000, there are four ways of entering thefile : birth, confinement, death, and discharge from hos-pital. When more than one of these events has involvedan individual since Jan. 1, 1962, the records concerningthem have been brought together. And the health recordsof babies born since that date have been linked withthose of their mothers to form the nucleus of a file of

family records. The results so far have demonstrated theflexibility of the data for use in different kinds of researchproblem; and if the links can be extended to other sourcesof information-educational attainments, for example-valuable correlations may be established. The costs ofthe study’s first two years (using only manual recordmatching) show that 77% of the expense is incurred intranscribing, photocopying, coding, and punching, andonly 23% is for the additional process of manual linking.

Prof. J. N. MoRRIs declared that very little of the healthinformation recorded was actually used-or usable. Heand his colleagues had wanted to examine the suggestionthat duodenal ulcer was becoming less common; but ithad proved technically impossible to extract the detailsthey wanted from the files of the Ministry of Pensionsand National Insurance. Many people looked hopefullyto the computers to order and control this mass of facts.Moreover, as Payne 4 has observed, annual health reportscould be computed within days of the period to whichthey refer; and the computer could report significant

3. Acheson, E. D. Brit. J. prev. soc. Med. 1964, 18, 8.4. Payne, L. C. Lancet, July 4, 1964, p. 32.