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develops, it must do so within the established plan. Weagree with every word of this but hope the plans will notbe too rigid. A new laboratory, shiny with plate glassand stainless steel, is persuasive evidence of progress todisplay to the sympathetic visitor. A tousled pathologist,with blood on his coat and gentian-violet in his nails, isless impressive; but on him and his kind, and not onbuildings and organisation, the future of pathologydepends-everywhere.

Annotations

GENES ON THE MONGOL CHROMOSOME?

DESPITE great advances in knowledge of human chromo-somes and their disorders, we are still far from beingable to relate the nndings to those of classical genetics.Except for the X chromosome, whose genes are relativelyeasy to identify because of the phenomena of sex-linkage(and would be, even if no-one had ever seen a human Xchromosome), no genes have yet been.certainly locatedin any chromosome.There are several ways in which study of a chromo-

somal abnormality might lead to identification of a genecarried by the chromosome concerned.! Because mon-

golism is by far the commonest recognisable autosomelesion, chromosome 21 is by far the most hopeful subjectfor such studies, and two recent communications in thisjournal suggest possibilities in this direction.

Dr. Margery Shaw,2 describing a translocation mongolfamily (one, incidentally, of a number suggesting that thebizarre mode of transmission in Hamerton’s family 3 wasnot altogether typical), found evidence of an ABO linkage,though none with six other blood-groups. This couldwell mean that the ABO group is carried in one of thechromosomes concerned in the translocation. One ofthose concerned belonged to the 13-15 group, and if thisis responsible it may be a long time before much use canbe made of the information. If, however, it should bethe 21, this would mean, as Bateman 4 pointed out, adetectable change in the frequency of the ABO blood-groups in mongols. Given a large enough survey, thispoint should not be difficult to prove one way or the other,and it is believed that the results of at least one such

survey will soon be available.

Today’s article by Dr. Trubowitz and his colleagues(p. 486) may represent a successful application of a differentapproach. The amounts of at least some enzymes are

quantitatively related to the number of chromosomes

carrying the appropriate gene. If both chromosomes ofa pair carry the defective gene, none of the normal enzymeis produced: if only one of the pair is normal, half thenormal amount is produced. It should then follow thatif three chromosomes are carrying the gene, the enzymeshould be present in just one and a half times the normalconcentration. It is thus at least a reasonable first assump-tion that an enzyme found to be present in about 150%of the normal concentration in mongols is likely to becontrolled by a gene on pair 21. Which is just what1. Renwick, J. in Recent Advances in Human Genetics (edited by L. S.

Penrose); p. 120. London, 1961.2. Shaw, M. Lancet, 1962, i, 1407.3. Hamerton, J. L., Cowie, V. A., Giannelli, F., Briggs, S. M., Polani, P. E.

ibid. 1961, ii, 956. Hamerton, J. L., Steinberg, A. G. ibid. 1962, i, 1408.4. Bateman, A. J. ibid. 1960, i, 1293.5. ibid. July 7, 1962, p. 29.

Trubowitz et al. seem to have found in the alkaline

phosphates of leucocytes.These workers were led to make this investigation by

the known facts of the frequency of leukxmia in mongols,of the loss of part of a chromosome 21 in chronic myeloidleukaemia, and of the low alkaline phosphatase in myeloidcells in chronic myeloid leukaemia. They are properlycautious in interpreting their results, pointing out thatthe prevalence of infection among mongols might affectthe results.

Their suggestion that they can divide their mongolsinto two classes-one with normal and one with raised

phosphatase-receives little support for their figures,which suggest rather a single population with a widescatter about a raised mean; and their further suggestionthat one of the classes might be the translocation mongolswould demand an inordinately high proportion oftranslocation mongols in their group.There are, indeed, many possibilities of error; but it is

not too unreasonable to hope that we are witnessing herethe first step towards a gene map of the autosomes.

GROUNDNUTS

DURING 1960 young turkeys all over England died intheir thousands from hepatitis. Other poultry and somelarger animals suffered to a lesser extent. Epidemiologicalinquiry showed that the common factor was a diet con-taining certain batches of groundnut meal from Brazil,Experimental feeding of this meal showed that younganimals were more susceptible than adults; ducklings thanturkey poults and chicks; and piglets and calves thanlambs. The chemists soon demonstrated that the mealwas not contaminated by castor-oil bean or insecticides,and it did not contain any toxic alkaloid such as that

responsible for ragwort poisoning-to which this newdisease bore some resemblance. The next step was todevise a reliable test for the presence of the toxic factor,and here fortune was kind : close correlation was foundbetween the results of a biological test using ducklingsand those of an in-vitro test which depends upon thefluorescence of the toxin in ultraviolet light. Use of thesetechniques revealed that almost every country which

exports groundnuts sends us a few samples containing thetoxin, and that many of the Brazilian batches are toxin-free. This wide distribution of the poison suggested thatthe cause might lie in some natural parasite of the nut,and indeed, before long, the poisonous property wasshown to be associated with the presence of the common

mould, Aspergillus flavus. Sterile samples of nuts andmeal, when artificially infected with some (but not all)strains of A. flavus and incubated in a humid atmosphere,produced the toxin in abundance. With little regard toeuphony, the toxic principle has since been named" aflatoxin ".

A. flavus has a worldwide distribution, but for freemultiplication needs a relative humidity approaching 80%.The nuts grow underground, and conditions are suited tofungal infection before they are harvested and afterwardswhile they are drying in the fields. Luckily, most of theinfected nuts show a brown discoloration which is plainio see. Man has probably escaped serious illness becausethese brown and withered nuts are excluded from thehand-picked grade which is reserved for humans at

cocktail parties and monkeys in the zoo. Peanut butteris made from the same grade of nut. The greater part of

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the crop is pressed for oil, and the residue from thepresses is destined for animal foodstuffs as meal or cake.Traces of aflatoxin can be found in the oil (which is one

of the main constituents of margarine), but these areremoved during the refining process. There were traces,too, in the milk of some cows fed experimentally on toxicmeal ; but all tests of bulked milk from normal sourceshave been negative. No human disease attributable tothis toxin has yet been detected; but inquiry is still in

progress. An undertaking by the compounders of feedingstuffs to test all groundnut meal before use has reducedthe risk to birds and beasts. Unfortunately, no method ofdetoxifying the affected meal has yet been devised.Groundnut growers hope that more careful harvestingand quicker drying will reduce fungal infection; but boththe nuts and A. flavus flourish under similar atmosphericconditions.The elucidation of this agricultural epidemic of hepatitis

has been an elegant demonstration of epidemiologicalmethod, and that the working party 1 has made its reportwithin two years of the first signs of the illness is a creditto all who have taken part in the inquiry. We took a greatdeal longer to unravel the not dissimilar problem ofberiberi.

NEUROGENIC BASIS OF RAYNAUD’SPHENOMENON

THE triphasic colour changes described by Raynaudare best regarded as a symptom complex common tomany different disorders. Since the concept of a singleRaynaud’s " disease " was abandoned, the underlyingconditions with which white fingers may be associatedhave multiplied. In cold damp climates, many peoplehave an inherited " local fault " first manifest around

adolescence, which consists in an over-reaction of theirdigital vessels to cooling. Most of those so afflicted readilybear with the condition once they have been reassuredthat it is benign. Much more important is the group inwhich the colour changes in the fingers are an indicationof general systemic disease-commonly, rheumatoid

arthritis, scleroderma, or disseminated lupus erythema-tosus. In young men, thromboangiitis obliterans maywell be responsible, whereas, in the elderly, the under-lying cause may be atherosclerosis in the large or smallvessels supplying the extremities. Many of the associatedclinical patterns have still to be worked out. Among themost puzzling is the youngish or middle-aged woman whodevelops, without any previous or family history, occlusivedigital-artery disease leading to pulp atrophy and ulcera-tion. Only in the occasional case does the small-vesseldisease also involve other organs such as the lungs orbrain: in the majority it remains restricted to the fingers.The microscopic appearance of the vessels is not veryinformative, the most striking feature being endothelialhyperplasia.De Takats and Fowler have investigated the neuro-

genic factor in Raynaud’s phenomenon. That vaso-constrictor impulses can be a dominant or accessorypartner in the production of vasospasm has long beenrecognised. In the days of extensive thoracolumbar

sympathectomy for hypertension, hyperhidrosis andphasic colour changes in the hands developed in manypatients after the autonomic ablation. Blanching of the1. Report of the interdepartmental working party on Groundnut Toxicity

Research. Department of Scientific and Industrial Research. 1962.Pp. 61. 6s. 6d.

2 De Takats, G., Fowler, E. F. Surgery, 1962, 51, 9.

fingers may clearly be linked with anger or emotionaloutbursts, and peripheral neuritis has been suggested asthe cause of " vibrating-tool

"

Raynaud’s. De Takats andFowler investigated seven patients in whom the attackswere associated with abnormal electroencephalograms(E.E.G.S). All were women. Four below the age of thirty-six were hyperhidrotic; their E.E.G.S showed positivespikes at frequencies of 6 and/or 14 per second; no otherabnormality could be found. The remaining three womenhad scleroderma or disseminated lupus. About 50% ofpatients with scleroderma are said to have abnormalE.E.G.S. De Takats and Fowler do not say clearly howthey selected these seven patients, how severely theirhands were affected, or how commonly the electro-

encephalographic technique would pick up abnormalitiesin healthy women of the same age-group. But pursuit ofthis type of investigation would be interesting-particu-larly in the rather inadequate individual with dampsweaty hands, high peripheral vascular tone, and phasiccolour changes in the fingers.De Takats and Fowler emphasise that the treatment of

Raynaud’s phenomenon should begin with recognitionof the broad diagnostic problem involved. They claimthat the results of sympathectomy depend more on theshrewdness with which patients are selected for the opera-tion than on the type of sympathectomy performed. Themilder the case and the larger the neurogenic component,the better the result. Patients with severe " local faults "or with systemic disease do badly. Paradoxically, occlusivedisease (e.g., thromboangiitis obliterans or athero-

sclerosis) is often benefited, sympathectomy clearing upor ameliorating local ulceration or pulp necrosis.De Takats and Fowler reported that the results of

sympathetic denervation were excellent in their patientswith abnormal E.E.G.S.

RUBELLA IN PREGNANCY

THE Swedish National Board of Health instructed

hospitals to find out from women, admitted between July,1951, and June, 1952, for delivery or abortion, whether(1) they had had contact with any person infected withrubella, and (2) they had contracted rubella during theirpregnancy. Women with the immediately precedinghospital-registration numbers served as controls. The

survey had much in common with that carried out in this

country in 1952,1 though the inquiry was made later in thepregnancy. In no case of rubella had an attempt beenmade to confirm the diagnosis at the time of infection.The findings of the survey have been collated by

Lundstrom.2 In general, they are very similar to those ofthe British survey, but they provide some useful additionalinformation, particularly about chorioretinitis, micro-

cephaly, and immaturity. At follow-up examination atthree years of age, the overall frequency of malformationfound in children born after first-trimester rubella was 58in 425, or 14%-almost exactly the same as in the Britishseries. In the British series audiometric examination of57 such children revealed that 30% had some hearing loss;this was found in a similar proportion (8 out of 27) in theSwedish series. In addition, an ophthalmoscopic examina-tion was made of 60 of the Swedish children; 12

(20%) were found to have some chorioretinitis, but nodetails are given of the extent to which sight was affected.As in the British series, there was no clear indication

1. Manson, M. M., Logan, W. P. D., Loy, R. M. Rep. publ. Hlth.med. Subj., Lond. 1960, no. 101.

2. Lundström, R., Acta pœdiat., Stockh. 1962. suppl. 133.