Research on Human Nutrition

382 LEADING ARTICLES

BENEDICT et al.10 concluded that in gouty subjectsthere may be a more rapid mechanism for transformingglycine into uric acid than is normally the case, andthey suggested that this transformation may be

accomplished by a different metabolic route.

Research on Human NutritionIN the 19th century, nutritional research was

concentrated on energy requirements and the inter-relations of the three basic foodstuffs-proteins, fats,and carbohydrates. In the first half of the 20th

century the predominant interest was in the vitamins.After their discovery by HopKiNs and FuNK, know-ledge of their properties accumulated rapidly, andconsequently we now know enough to prevent thefive major vitamin-deficiency diseases-beriberi, pell-agra, scurvy, rickets, and keratomalacia. That thesefive diseases can still be seen here on occasion, andremain prevalent in some other parts of the world,is due to the great difficulty of applying new nutri-tional knowledge and in particular the need for moreinstruction on the subject. Today, in the second half,of the 20th century, the principal problems in humannutrition about which the general public, the clinician,and the research-worker would all like more informa-tion include : (1) the relation of dietary habits todegenerative processes of ageing, and particularly toatheroma and the growth-rates of tumours ; (2) theeffects on health of the manifold chemical and physicaltreatments involved in the processing of all thecommon foods, which is inevitable in an industrial

community ; (3) the effects of various foods anddietary habits on the efficiency and working capacityof the industrial population ; (4) the effects of dieton resistance to infectious disease, especially thecommon respiratory infections ; and (5) the constitu-tion of the diets most favourable to human growthand development at all stages from prenatal life toadolescence. The importance of this last problemwas emphasised in the latest annual report of theMedical Research Council," in which a section on theinvestigation of human nutrition is almost whollydevoted to kwashiorkor and the supply of suitableproteins for the young. In most of Africa, and insome other countries, probably nothing else is so

important for the improvement of health.A research nutritionist, if asked to tackle any of

these problems, might well reply that this would beeasy provided he had a suitable supply of volunteers,prepared to live on controlled diets for months oryears. He might.add that if he was expected to relyon the excellent equipment for housing and feedingsmall rodents, which he had inherited from his pre-decessors of the " vitamin era," he would have littlehope of doing much towards their solution. In facthe can contribute new knowledge only by carefulfield observations, when circumstances permit, and byseizing the rare opportunity that may arise for acontrolled experiment. Nevertheless, valuable con-tributions have been made in the last decade, includingthe field studies of SMITH and WOODRUFF 12 in a

Japanese prisoner-of-war camp, of the Cambridge10. Benedict, J. D., Roche, M., Yü, T. F., Bien, E. J., Gutman,

A. B., Stetten, DeW. jun. Metabolism, 1952, 1, 3.11. Report of the Medical Research Council for the year 1953-54.

H.M. Stationery Office.12. Smith, D. A., Woodruff, M. F. A. Spec. Rep. Ser. med. Res.

Coun., Land. no. 274, 1951.

school of experimental medicine in Western Germany,13and of BROCK and AUTRET 14 and others in Africa.A good example of a careful attempt to correlate dietwith morbidity and mortality is the study by KEY&and his colleagues 15 of the association between theincidence of coronary-artery disease and a high nationalconsumption of fats in many countries. Controlled

experiments, however, have been few and far between.The most comprehensive has been the Minnesotaexperiment 16 on human starvation, but chances oftests on such a scale rarely arise, though groups ofvolunteers have been collected among conscientiousobjectors in war-time. WIDDOWSON and MCCANCE’s 17controlled trial of the nutritive value of breads madefrom various flours, carried out in orphanages in

post-war Germany, were excellent attempts to eluci-date a most difficult problem ; but, as we pointedout the other day,18 their results are none too easy tointerpret and certainly give no clear-cut guidance tothose responsible for the regulation of milling processes.

This week we publish a paper, by Professor BROCKand his colleagues from three centres in South Africa,on the treatment of kwashiorkor. For the last five

years there has been no doubt that dry skimmed-milkpowder is an effective remedy for kwashiorkor; butskimmed milk is a complex chemical mixture, and thenature of the active therapeutic agent has beenuncertain. In this latest work a good series of con-trolled trials have shown. that casein is the factor thatinitiates the cure, and in this respect its action hasproved to be independent of the addition of a generalvitamin mixture. A few further trials have indicatedthat an amino-acid mixture alone can be equallyeffective in causing immediate improvement in childrenwith kwashiorkor. These findings will be valuable tophysicians responsible for the treatment of the manycases of kwashiorkor in Africa, but they should bestill- more useful in planning preventive measures.

Milk is certainly an excellent prophylactic againstthe disease ; but in Africa, as in many other places,it is impracticable to wait and hope for the develop-ment of dairy-herds capable of supplying the needs ofthe children, especially in their critical second year.When we can define accurately in chemical terms theproperty of the substance or substances in the milkthat is so critical for child development, then it shouldbecome possible to find alternative sources, perhaps-from vegetable products, and to plan agriculture soas to enable prophylaxis to be carried out on thescale required. The investigations of BROCK and hiscolleagues are a promising start in the task of findingout what the critical chemical agents are. Theirtrials have been on a large scale in three separatecities. Good central organisation and a sufficiency ofskilled staff-chemists, doctors, and nurses-havebeen the factors responsible for the success alreadyachieved.

Opportunity to elucidate the nutritional problemsof our day is not easily found ; ; and we must hope13. Members of the Department of Experimental Medicine, Cam-

bridge. Spec. Rep. Ser. med. Res. Coun., Lond. no. 275, 1951.See Lancet, 1951, ii, 390.

14. Brock, J. F., Autret, M. F.A.O. Nutritional Studies no. 8.Rome, 1952. See Lancet, 1952, ii, 1070.

15. Keys, A. Circulation, 1952, 5, 115.16. Keys, A., Brozek, J., Henschel, A., Michelsen, O., Taylor, H. L.

Biology of Human Starvation. Minneapolis, 1950. SeeLancet, 1951, i, 95.

17. Widdowson, E. M., McCance, R. A. Spec. Rep. Ser. med. Res.Coun., Lond. no. 287, 1954. See Lancet, 1954, ii, 1006.

18. See Lancet, July 30, 1955, p. 235.

383ANNOTATIONS

all the more that those who control grants will

appreciate the necessity for financial assistance andstaff on a liberal scale and that they will not expectresults to be produced rapidly. In this country, weare indeed fortunate in that the Medical ResearchCouncil has already done so much to support basicresearch on human nutrition.

Annotations

PLOUGHSHARES AT GENEVA

THE International Conference on the Peaceful Usesof Atomic Energy, organised by the United Nations atGeneva, is now drawing to a close after nearly two weeks’deliberation in which about a thousand scientific papershave been read or tabled. For the first time a gooddeal about the design of nuclear reactors and atomic

power stations has been made public, and the machineryused in this work offered for international sale. Eco-

nomically and industrially atomic energy has becomeimportant for national prestige, and it seems that at

present Britain leads in the export of radio-isotopes.Part of the interest of the conference was to learn whatRussia, the United States, and Canada were offering.Some of the medical papers, naturally enough, were

on the health risks of radioactivity, which is where

radiotherapy, genetics, and physics join hands. Othersdealt with the biochemical and physiological results ofusing radio-isotopes in the investigation of intermediarymetabolism, usually mammalian : a very great deal hasalready been published on such subjects as diabetes, thesynthesis of hsemoglobin, and the metabolism of steroidhormones and proteins. In a third group of papersatomic energy was applied in medical practice-forexample, to the detection of cerebral tumours, theinvention of a highly portable X-ray apparatus requiringno electricity, the examination of thyroid activity, thespread of communicable diseases in the field-a miscel-laneous and ingenious group of fruitful applications. Itis evident that many clinicians can hardly be aware ofthe enormous quantity of work that has been done, andmostly published, in the past ten years. Some of it isready to affect clinical practice and research, but it isdifficult for the medical worker to know what oppor-tunities atomic energy offers him, not because of anysecrecy but because of the specialised language andspecialist journals in which the work often appears.There is a need for simple reviews which explain thesituation to the non-physicist, and perhaps for some kindof medical advisory service like that already offeredto industry.At Geneva Dr. E. E. Pochin gave an excellent brief

review of iodine metabolism. For examination of thyroidfunction he recommended a simple test in which an

inoffensively small dose of radioactive iodide is injected,and two hours later the degree of absorption by thethyroid is estimated by a five-minute count at thepatient’s neck and thigh. Normally the kidney clearsthe plasma of iodide at the rate of 2 litres per hour, whilethe thyroid works at only 1 litre per hour ; but the thyro-toxic thyroid clears at 15 litres per hour. The normalhuman thyroid (unlike that of rat and rabbit) dischargesits iodine slowly, over six weeks or more. But thethyrotoxic gland discharges quickly (about four days),and so does carcinomatous thyroid, which has a pooruptake, however. A similar method for assay of thyroidfunction is in use in the U.S.S.R., according to Dr. M. N.Fateyeva ; but in Russia the chief interest has been tostudy thyroid activity in non-thyroid diseases. Forinstance, increased thyroid activity has been noted instage-1 essential hypertension, in 50% of patients with

rheumatic carditis at the height of the disease, and inacromegaly. The test is useful in the differential diagnosisof anxiety state from thyrotoxicosis, since functionremains normal in the neurosis. Canadian workersadvocated the measurement of radio-iodine in the salivatwenty-four hours after a test dose as a good guide tothyroid function.

Urinary excretion of creatine in considerable amountsis one of the laboratory signs of thyrotoxicosis. Dr.DeWitt Stetten, jun., explained that creatine is normallymade in the liver and taken up by the muscles, whereas creatine phosphate it takes part in muscular con-traction. A fraction of it is converted there to creatinineand excreted constantly in the urine. Using isotopemethods it has been possible to show that the creatinuriaof thyrotoxicosis is due to overproduction by the liverunder thyroid stimulation. In muscular dystrophies, onthe other hand, liver production is normal but thediseased muscle does not take up its creatine ration,which consequently appears in the urine. In anotherillustration of isotope work Prof. A. B. Hastings describedresults in diabetic rats partly confirmed for humandiabetics, which show that in dia-betes there is both aninability of muscles to use glucose and an overproductionof glucose by the liver, which contains twice the normalamount of the enzyme glucose-6-phosphatase. Wheninsulin is given, the muscle failure is corrected almost atonce whereas the liver abnormality takes some hours toput right.

In an equally interesting report, Dr. Dale W. Jenkinsdescribed the labelling of mosquitoes and flies to determinetheir spread from a release point, their life-span, theirpredators (which also become radioactive), and the totalnatural population (by dilution). In the same way,many viruses and bacteria can be made radioactive, andtheir survival in and dissemination by their hosts followed.And in man erythrocytes can be labelled by contact withsodium chromate (Cr51), and serum-albumin with radio-active iodine, as Prof. W. V. Mayneord mentioned in auseful review of other isotope methods. He describedhow xenon 133 can be adsorbed on carbon and used totake radiographs without any source of electricity orlarge apparatus : a radiograph of the ankle needed aten-second exposure. Professor Mayneord also referredto the use of radioactive isotopes selectively absorbedby cerebral tumours, as did Dr. G. L. Brownell andDr. W. H. Sweet, who have devised an ingenious wayof displaying the tumours without opening the skull.

They inject arsenic 74 intravenously, and this concen-trates about ten times more in tumour tissue thanin normal cerebrum.The many papers on the health effects of radiation

combined to emphasise the impossibility of being surethat so-called safe exposure limits are neither too highnor too low. Dr. D. E. Clark reported 15 cases ofcarcinoma of thyroid in children under 16, all of whomhad at some time had X-ray treatment for benign con-ditions of the head, neck, or chest. Dr. R. J. Hasterlikand Dr. L. D. Marinelli described 4 patients who gotneutron and gamma-ray overdoses from an accident atwork. None of them had symptoms of radiation sickness,and only 1 showed a (transient) skin erythema. Haemato-logical investigation did not show a great deal either,

but there was a high and abnormal urinary amino-acidexcretion within twelve hours of exposure and thiscontinued for five months ; and sperm counts on themen showed diminution or aspermia maximal at thetenth month, with subsequent recovery. As for genetic

. effects produced by the increased rate of mutation, we, really know nothing good or ill. As Dr. J. F. Loutit

said, " New mutations are merely repetitions of the oldv which Nature has tried before. When the environmentL changes, a mutation once deleterious may in fact beL favourable."