977

On the other hand, in Wilson’s disease this transferof copper from albumin to globulin does not, take

place: the radioactive copper remains associatedwith the albumin fraction. These findings accordwith the observation by SCHEINBERG and GITLINthat in this disease the plasma level of caoruloplasminis low. It seems that the low level is due to defective

synthesis in the body, which leads to the presencein the serum of large amounts of copper bound toprotein but not so firmly as it is in the c2eriiloplasmiiimolecule ; and is presumably this copper which is

deposited in the brain and liver and results in theclinical manifestations of the disease. Why the copperis deposited in the brain and particularly in the basalganglia is uncertain, but normally basal gangliacontain a large amount of copper and possibly thereis a protein there with a high affinity for themetal. PORTER and FOLCH 8 examined the form inwhich copper is laid down in the brain and havefound notable differences between healthy subjectsand patients with hepatolenticular degeneration.CHALMERS et awl.9 have now put forward the hypo-thesis, backed by some experimental observations,that liver-protein from patients with this disease

has a greater affinity for copper than has protein fromnormal liver. They feel that the excessive depositionof copper may be related to this rather than to theabnormal circulating copper.Treatment of the condition with dimercaprol

(BAL) was first reported in 1951.210 This drug forms,a stable non-toxic complex with copper and causesit to be excreted in the urine in even larger amounts.In some cases this drug improves the clinical state-which stren.gthens the supposition that excessive

deposition of copper is the immediate cause of thedisease. Lately other methods of treatment havebeen used. Oral administration of potassium sulphideregularly with meals diminishes the alimentaryabsorption of copper by forming insoluble coppersulphide. WALSHE11 has found that penicillamineincreases the excretion of copper. Calcium disodium

ethylenediamine tetra-acetate has also been used,but has the disadvantage that it must be givenintravenously.The diagnosis of Wilson’s disease by chemical

methods depends on demonstrating excessive copperin the urine or a low serum level of cseruloplasmin.Small amounts of copper are not easily estimated,and there is always a possibility of error from con-tamination of the specimen with extraneous copper.For this reason the estimation of cæruloplasmin,particularly by the simplified method of RAVIN,12is probably to be preferred. Serum-cæruloplasmincan be estimated indirectly by measuring the rate ofoxidation of paraphenylene diamine in the presenceof the serum ; the rate of oxidation is proportionalto the level of caeruloplasmin. From DENNY-BROWN’swork it is apparent that the success of treatmentwith dimercaprol depends a good deal on earlydiagnosis. Clinically the diagnosis in the early stagesmay be extremely difficult or impossible; so such

helpful chemical methods are highly important.8. Porter, H., Folch, J. Arch. Neurol. Psychiat. 1957, 77, 8.9. Chalmers, T. C., Iber, F. L., Uzman, L. L. New Engl. J. Med.

1957, 256, 235.10. Denny-Brown, D., Porter, H. Ibid, 1951, 245, 917.11. Walshe, J. M. Lancet, 1956, i, 25.12. Ravin, H. A. Ibid. p. 726.

Long-term Studies in ManATHEROMA is perhaps the most important unsolved

problem in human pathology and certainly the mostdiscussed. In the welter of observations and specula-tions on the relation between coronary-artery diseaseand dietary fat, three facts now stand out beyonddispute. First, coronary-artery disease is closelyassociated with a disturbance of blood-lipids and inparticular with high levels of cholesterol in the serum.Secondly, in countries and communities with a highprevalence of coronary-artery disease, the susceptiblepopulation have levels of serum-cholesterol and intakesof dietary fat higher than are found in countries wherethe disease is less common. (In these epidemiologicalstudies ANCEL KEYS and his colleagues at the Univer-sity of Minnesota have been pioneers.) Thirdly, inpeople whose level of serum-cholesterol is high itcan be lowered by altering the quality of the fat inthe diet. The study of the effects of different dietaryfats on serum-cholesterol levels which Dr. AHRENSand his colleagues present at the front of this issueconfirms and amplifies earlier reports from themselvesand others. The most sceptical critic cannot now

dispute the fact that the quality of the dietary fatinfluences the levels of serum-lipids. He must be

strongly impressed, too, by the evidence that the

ability of the fat to lower the level of serum-cholesterol is associated with its degree of unsaturation,though, as AHRENS points out, other chemical pro-perties of the fat have not been completely ruled out.Of course other factors besides diet-e.g., the constitu-tional make-up of the individual, hormonal activity,and perhaps the extent of physical activity-alsodetermine in part the levels of serum-lipids. Nor is it

satisfactorily established that patients are clinicallyimproved, and the risk of cardiac infarction reduced,when the serum-lipids are held continuously atlow levels by a dietary regime. All this obviouslyneeds further study. Unfortunately few medicalcentres in the world have, as yet, the organis-ation necessary for experiments on man on the scalerequired.Mankind owes a great debt to laboratory animals,

and much help has been obtained from them in

acquiring an understanding of the nature of diseasesarising as a result of acute infections and dietarydeficiencies. But, whereas there is much pathology incommon between a guineapig and a man sufferingfrom generalised tuberculosis, and also between arabbit and a child blinded by keratomalacia, theanimal counterparts of the chronic degenerativediseases of man either do not exist or have little relationto human disease. Hence it is important to be able toexamine the progress of diseases in man under experi-mentally controlled conditions. AHRENS and his

colleagues say that " the unique design " of theirstudies " was based on the belief that nutritionalexperiments can be carried out as precisely in manas in animals." In this belief they were justified bythe fortitude of the 37 citizens of New York, who wereprepared to live for periods ranging from two to fortymonths without eating any natural food and subsistingentirely on synthetic diets. That these people wereable to do so, and for the most part appeared toimprove in health on these artificial regimes, is a greattribute to the skill and sympathy of the staff at the

978

Rockefeller Institute and also to the administrativearrangements.Advancement of our understanding of several

important pathological processes would be muchaccelerated by the study of patients under similarlycontrolled conditions for periods to be measured inmonths. But although some teaching hospitals inBritain have small metabolic wards, none are providedwith the staff or equipment required for studies onsuch a scale over so long a time. To ensure both the

physical and social well-being of experimental patientsand the accurate collection and analyses of data a verylarge staff is needed, as well as floor space for labora-tories and social amenities : to care for and investigatethoroughly 5 patients, a staff of 25 to 50 persons maybe necessary. But the setting up of one or more suchresearch centres in this country would have immensepractical value. Properly safeguarded, Homo sapienscan be a very useful laboratory animal.

Annotations

RACIAL DISCRIMINATION IN MEDICINE

THE Natal Provincial Administration, noting that thesalary scales in their hospitals have always distinguishedbetween nurses and teachers of different races, decided

recently to extend this principle to the eight non-

European doctors working as interns at EdendaleHospital, Pietermaritzburg. These doctors have resignedin protest.

Since 1950 in South Africa graduates in medicine havehad to hold house-appointments for a year in an approvedhospital before registering with the South African Medicaland Dental Council. In 1950, though no Transvaal

provincial hospitals would employ iioii-Eurol)eiii doctors,the number of non-European medical graduates fromJohannesburg was small enough for all to find posts inmission hospitals or in the British Protectorates. III

July, 1951, however, three Indian graduates could notfind a place ; and apparently no-one was responsible forfinding them one. For several months they searched invain for appointments ; and it was not until their plighthad been given publicity by various student and pro-fessional bodies that arrangements were made for themin a provincial hospital serving non-Europeans. The

practical difficulty that had to be overcome was thatwhite nursing sisters in South Africa could not be

expected to " take orders " from non-white interns.

(The seriousness of this difficulty is emphasised by theprovision of the present Nursing Bill, which imposes afine of up to :E200 on anyone allowing a white nurse towork under a non-white person.) This obstacle wascircumvented in the Transvaal provincial hospital byemploying non-white sisters in units where non-whiteinterns were placed. Like all other Transvaal provincialemployees, however, these interns in Transvaal hospitalswere paid at a lower rate because of their race-a stateof affairs accepted by the profession, no doubt becauseof the urgent need to enable them to serve their statutoryyear. At that time the Natal Provincial Administrationwas not prepared to give appointments to non-Europeaninterns in any of its hospitals : even the 1500-bed non-

European hospital in Durban did not have non-Europeaninterns, though its present connection with the medicalschool for non-Europeans has obviously changed theposition. Influenced probably by a serions shortage ofjunior doctors, it later decided to appoint non-Europeaninterns at Edendale Hospital ; and these are the appoint-ments now made vacant by resignation.

In South African society, different rates of pay for

European and non-Kuropean doctors will be regarded byma.uy as logical and consistent. It is entrenched national

policy in industry anti agriculture, and in other pro-fessions suelt as nursing and teaching (although not inuniversity lecturing). To the South African doctor,however, it does raise a new issue, since differential ratesaffect not only the economic but inevitably the profes-sional status of all his colleagues. The events of recent

years are a challenge o the standing of the South Africanmedical profession of which it is well aware. The BritishMedical Association’s cancellation of its proposed con-ference in South Africa, because satisfactory arrauge-ments could not be made for all delegates regardless ofrace, was a, gra.ve blow. When the South African gov-ernment decided that only white donors might give bloodto white recipients and that blood bottles were to belabelled accordingly, many South African doctors felt thisas a slur on the scientific reputation of their country—though the Medical Council thought it could not actin this " political " issue. The recent decision to imposeapartheid in all universities and medical schools is con-sidered a threat to the maintenance of equal professionalstandards for all graduates. Different status and differenttraining for non-European nurses, now to be added tothe already existing lower salary scales, will also haverepercussions for the medical profession. Not long agoa South African local authority advertised in the SouthAfrican Medical Journal for 15 "European" generalpractitioners to attend to its employees. The local branchof the Medical Association have published their emphaticopposition to tlie racial discrimination implied in theadvertisement and have approached the authority witha view to its revision. They recognise the duty to resistdiscrimination against colleagues.At its March meeting the South African Medical and

Dental Council decided after debate that non-Europeaninterns, in accepting posts at different pay-rates fromEuropean interns, did not contravene its ethical rules.The executive regarded the matter of differential ratesas one of public policy in which it was inappropriateto intervene. On the other hand, many members of theprofession hold that, though the rules of the SouthAfrican Medical and Dental Council may not have beencontravened, such discrimination does not conform withHippocratic ethics. The professional interests of SouthAfrican doctors are threatened in many ways by this andthe other developments in the medical schools and thenursing profession. Consistent ethical and professionalstandards, scientific freedom, and a ready exchangebetween nations are essential to the advance of modernmedicine in all countries.

1. Bright, R. Guy’s Hosp. Rep. 1836, 1, 388.2. Hansborg, H. Acta. med. scand. 1925, 61, 576.3. Rammelkamp, C. H., Weaver, R. S., Dingle, J. H. Trans. Ass.

Amer. Phyens, 1952, 65, 168.

NEPHRITOGENIC STREPTOCOCCI

ALTHOUGH Bright 1 observed over a hundred years agothat renal disease with albuminuria may follow scarlatina,the significance of haemolytic streptococcal infections inthe pathogenesis of acute glomerulonephritis has beenslow to emerge. Nowadays it is believed that infectionwith group-A streptococci may result in at least twonon-suppurative complications-rheumatic fever andacute nephritis-but while the link with rheumaticsequelae is well substantiated, until recently the evidencefor the link with glomerulonephritis has been patchy.Much of the earlier work establishing the streptococcalassociation of acute rheumatism was epidemiological, butwith glomerulonephritis epidemiology reveals no dis-cernible pattern. In patients with scarlet fever (whenthis disease was very common) the incidence of nephritisvaried very widely,2 both between epidemics and fromyear to year. Rammelkamp and his colleagues,3 using