1243 ous devices to keep particular muscle-groups exercised, or to the warm plunge-bath, where physiotherapists exhort and persuade the gaily clad bathers to achieve the next stage of activity, or to the gymnasium, where the instructor notes with pride the gain in power of limbs impaired by poliomyelitis or other disorder. From 4.30 to 9.30 P.M. the patients are off duty. They can have tea in the handsome lounge, rest and read in the quiet room, chat or play games in the common-room, walk in the grounds, go out and visit friends, or join in the programme arranged by their own entertainments com- mittee. On three evenings a week the education and recreation department provides programmes of docu- mentary and instructional films, or arranges discussions, games, or plays by local amateur dramatic societies or by the patients themselves. All the patients have physical disabilities. Treatment for industrial patients with neuroses is, of course, available at Roffey Park, near Horsham. The average stay at Farnham Park is four weeks-the longest ten weeks. The food is very good, and so is the morale of the patients ; perhaps the two are linked. The Slough Industrial Health Service is thus a compre- hensive scheme for the welfare of workers in industry, and has already shown its member firms a good return in the saving of working-time. The workers themselves at first regarded it with the customary scepticism of the British working man, who is always wary of institu- tions outspokenly designed to do him good. Gradually, however, they have come to recognise the value of the service, and now make full use of it. 1. Lancet, May 16, 1953, p. 988. SCURVY The Edinburgh Meeting As already recorded in these pages, the Royal College of Physicians of Edinburgh and the Nutrition Society combined during the weekend of May 22 to celebrate in Edinburgh the bicentenary of the publication of Lind’s Treatise of the Scurvy.’ The proceedings opened with a " special graduation ceremonial " at which the Vice-Chancellor (Sir Edward Appleton, F.R.S.) conferred the honorary degree of doctor of laws upon Surgeon Vice-Admiral Sir SHELDON DUDLEY, F.R.s. In a fighting speech Sir Sheldon said that the medical officer in the Royal Navy must educate his executive superior in practical hygiene, and that the importance of this subject was so great that there should be a health officer on the Board of Admiralty. There was, he declared, no such entity as subclinical scurvy, and he believed that less than 15 mg. daily of ascorbic acid was a maintenance dose although during the war dietitians had tried to persuade him that the figure was 300 mg. At the conclusion of the ceremony a bronze plaque commemorating Lind was unveiled, the gift of the Sunkist Growers of Citrus Fruit in California and Arizona. Later in the day another formal speech was made-this time by Prof. V. P. SYDENSTRICKER (Augusta, Georgia), who gave the Sydney Watson Smith lecture in the Royal College of Physicians on the Impact of Vitamin Research on the Practice of Medicine. * * * The scientific meetings of the Nutrition Society were opened by Sir EDWARD MELLANBY, F.R.S., who stated that Lind was the first to introduce the experimental method into medicine. He cruised in safer waters when he came to contemporary history and reminded us of the service Sir Sheldon Dudley had performed in estab- lishing the Royal Naval Personnel Research Committee, and of the careful researches on nutrition of Dame Harriette Chick over many years ; he and she were the only two surviving members of the original Accessory Food Factors Committee set up jointly in 1917 by the Medical Research Committee and the Lister Institute. Dame HABBiETTE CHICK then reviewed the early investi- gations of scurvy and incidentally differed from Sir Sheldon in affirming the existence of the prescorbutic state. Later in the symposium a paper on authors on scurvy before Lind was read on behalf of Mr. A. J. LORENZ. Perhaps the most important contribution of the session was given by Mr. C. G. KING, PH.D. (Nutrition Foundation, New York City), who by labelling com- pounds with 14C has indicated how L-ascorbic acid is formed in the body of the rat from D-glucose, D-glucu- ronic acid being an intermediate. He has also made the interesting observation that with deficiency of ascorbic acid there is an increased formation of cholesterol from acetate ; but, although he is a champion of high human allowances of ascorbic acid, he was careful not to claim that ingestion of the vitamin would decrease athero- sclerosis. This relation to cholesterol metabolism is possibly related to one of the most interesting aspects of ascorbic acid, its connection with the adrenal cortex. Ascorbic acid may form as much as 4 % of the dry weight of the adrenal cortex, and the vitamin was of course initially isolated from adrenals by Szent-Gy6rgyi in 1927. Sayers 2 and his colleagues have shown that adrenal ascorbate is reduced by corticotrophin (A.C.T.H.) or by various stresses. It is possible that an oxidation product of ascorbic acid is required for the synthesis of adrenal cortical hormone from cholesterol, and it may be that corticotrophin promotes the oxidation of ascorbic acid ; Cornforth and Long have suggested that cortisone promotes the peripheral oxidation of ascorbic acid. Prof. R. M. KARK (Chicago) reviewed the relation of ascorbic acid to scurvy, corticotrophin, and surgery ;. he claimed that there was no evidence that cold or adrenal cortical activity increases the human requirement of ascorbic acid, and he did not believe that ascorbic acid or a derivative of it is used in synthesising adrenal hormones. The Lind tradition of experimental work on man was upheld by papers from Dr. J. H. CRANDON (Boston) and Prof. H. A. KREBS, F.R.S. Dr. Crandon described the now classical experiment 4 in which he subsisted for six months on a diet containing no vitamin C ; subsequently he has investigated the relation of ascorbic acid to surgery. Professor Krebs described the similar experiment later conducted in Sheffield on conscientious objectors.5 In the latter experiment a supplement of 10 mg. of ascorbic acid daily was found to cure clinical scurvy in all six volunteers and protected three volunteers from scurvy for 424 days ; this figure of 10 mg. was somewhat arbitrarily trebled to arrive at a figure which would satisfy " ill-defined additional needs and to allow a margin of safety." Even this figure of 30 mg. is of course very much lower than that required for saturation : in a delightful paper Prof. GOUNELLE, of Paris, informed the meeting that he had found that tuberculous prisoners-of-war did not become saturated until they were given 300 mg. daily. The question whether saturation is desirable or necessary was taken up by Dr. King in the discussion at the end of the sessions when he defended the daily allowance of 75 mg. of ascorbic acid recommended by the National Research Council. Mr. L. J. HARRIS, sc.D., had suggested that the question of requirement was one that needed discussion, and, after pronouncing himself in favour of saturation, he called on Dr. King. Dr. KING said that 75 mg. gave only half-saturation ; the guineapig allowed to choose its diet kept itself saturated, and animals that synthesised their own ascorbic acid were saturated ; it could be shown that guineapigs survived diphtheria toxin better on high levels (5-10 mg. daily) than on lower levels (2-5 mg.), even though these lower levels completely protected 2. Sayers, G. Physiol. Rev. 1950, 30, 241. 3. Cornforth, J. W., Long, D. A. Lancet, Jan. 24, 1953, p. 160. 4. Crandon, J. H., Lund, C. C., Dill, D. B. New Engl. J. Med. 1940, 223, 353. 5. Lancet, 1948, i, 853.
Transcript
1243
ous devices to keep particular muscle-groups exercised,or to the warm plunge-bath, where physiotherapistsexhort and persuade the gaily clad bathers to achieve thenext stage of activity, or to the gymnasium, where theinstructor notes with pride the gain in power of limbsimpaired by poliomyelitis or other disorder. From 4.30to 9.30 P.M. the patients are off duty. They can havetea in the handsome lounge, rest and read in the quietroom, chat or play games in the common-room, walkin the grounds, go out and visit friends, or join in theprogramme arranged by their own entertainments com-mittee. On three evenings a week the education andrecreation department provides programmes of docu-
mentary and instructional films, or arranges discussions,games, or plays by local amateur dramatic societiesor by the patients themselves. All the patients havephysical disabilities. Treatment for industrial patientswith neuroses is, of course, available at Roffey Park,near Horsham. The average stay at Farnham Park isfour weeks-the longest ten weeks. The food is verygood, and so is the morale of the patients ; perhaps thetwo are linked.The Slough Industrial Health Service is thus a compre-
hensive scheme for the welfare of workers in industry,and has already shown its member firms a good returnin the saving of working-time. The workers themselvesat first regarded it with the customary scepticism ofthe British working man, who is always wary of institu-tions outspokenly designed to do him good. Gradually,however, they have come to recognise the value of theservice, and now make full use of it.
1. Lancet, May 16, 1953, p. 988.
SCURVYThe Edinburgh Meeting
As already recorded in these pages, the Royal Collegeof Physicians of Edinburgh and the Nutrition Societycombined during the weekend of May 22 to celebrate inEdinburgh the bicentenary of the publication of Lind’sTreatise of the Scurvy.’The proceedings opened with a " special graduation
ceremonial " at which the Vice-Chancellor (Sir EdwardAppleton, F.R.S.) conferred the honorary degree of doctorof laws upon Surgeon Vice-Admiral Sir SHELDON DUDLEY,F.R.s. In a fighting speech Sir Sheldon said that themedical officer in the Royal Navy must educate hisexecutive superior in practical hygiene, and that theimportance of this subject was so great that there shouldbe a health officer on the Board of Admiralty. Therewas, he declared, no such entity as subclinical scurvy,and he believed that less than 15 mg. daily of ascorbicacid was a maintenance dose although during the wardietitians had tried to persuade him that the figure was300 mg. At the conclusion of the ceremony a bronzeplaque commemorating Lind was unveiled, the gift of theSunkist Growers of Citrus Fruit in California andArizona. Later in the day another formal speech wasmade-this time by Prof. V. P. SYDENSTRICKER (Augusta,Georgia), who gave the Sydney Watson Smith lecture inthe Royal College of Physicians on the Impact of VitaminResearch on the Practice of Medicine.
* * *
The scientific meetings of the Nutrition Society wereopened by Sir EDWARD MELLANBY, F.R.S., who statedthat Lind was the first to introduce the experimentalmethod into medicine. He cruised in safer waters whenhe came to contemporary history and reminded us ofthe service Sir Sheldon Dudley had performed in estab-lishing the Royal Naval Personnel Research Committee,and of the careful researches on nutrition of DameHarriette Chick over many years ; he and she were theonly two surviving members of the original AccessoryFood Factors Committee set up jointly in 1917 by theMedical Research Committee and the Lister Institute.
Dame HABBiETTE CHICK then reviewed the early investi-gations of scurvy and incidentally differed from SirSheldon in affirming the existence of the prescorbuticstate. Later in the symposium a paper on authors onscurvy before Lind was read on behalf of Mr. A. J. LORENZ.Perhaps the most important contribution of the
session was given by Mr. C. G. KING, PH.D. (NutritionFoundation, New York City), who by labelling com-pounds with 14C has indicated how L-ascorbic acid isformed in the body of the rat from D-glucose, D-glucu-ronic acid being an intermediate. He has also made theinteresting observation that with deficiency of ascorbicacid there is an increased formation of cholesterol fromacetate ; but, although he is a champion of high humanallowances of ascorbic acid, he was careful not to claimthat ingestion of the vitamin would decrease athero-sclerosis.
This relation to cholesterol metabolism is possiblyrelated to one of the most interesting aspects of ascorbicacid, its connection with the adrenal cortex. Ascorbicacid may form as much as 4 % of the dry weight of theadrenal cortex, and the vitamin was of course initiallyisolated from adrenals by Szent-Gy6rgyi in 1927. Sayers 2and his colleagues have shown that adrenal ascorbate isreduced by corticotrophin (A.C.T.H.) or by variousstresses. It is possible that an oxidation product ofascorbic acid is required for the synthesis of adrenalcortical hormone from cholesterol, and it may be thatcorticotrophin promotes the oxidation of ascorbic acid ;Cornforth and Long have suggested that cortisonepromotes the peripheral oxidation of ascorbic acid.
Prof. R. M. KARK (Chicago) reviewed the relationof ascorbic acid to scurvy, corticotrophin, and surgery ;.he claimed that there was no evidence that cold or adrenalcortical activity increases the human requirement ofascorbic acid, and he did not believe that ascorbic acidor a derivative of it is used in synthesising adrenal
.
hormones.The Lind tradition of experimental work on man was
upheld by papers from Dr. J. H. CRANDON (Boston)and Prof. H. A. KREBS, F.R.S. Dr. Crandon describedthe now classical experiment 4 in which he subsistedfor six months on a diet containing no vitamin C ;subsequently he has investigated the relation ofascorbic acid to surgery. Professor Krebs describedthe similar experiment later conducted in Sheffield onconscientious objectors.5 In the latter experiment a
supplement of 10 mg. of ascorbic acid daily was found tocure clinical scurvy in all six volunteers and protectedthree volunteers from scurvy for 424 days ; this figureof 10 mg. was somewhat arbitrarily trebled to arrive at afigure which would satisfy " ill-defined additional needsand to allow a margin of safety." Even this figure of30 mg. is of course very much lower than that requiredfor saturation : in a delightful paper Prof. GOUNELLE,of Paris, informed the meeting that he had found thattuberculous prisoners-of-war did not become saturateduntil they were given 300 mg. daily. The questionwhether saturation is desirable or necessary was taken
up by Dr. King in the discussion at the end of the sessionswhen he defended the daily allowance of 75 mg. ofascorbic acid recommended by the National ResearchCouncil. Mr. L. J. HARRIS, sc.D., had suggested that thequestion of requirement was one that needed discussion,and, after pronouncing himself in favour of saturation,he called on Dr. King. Dr. KING said that 75 mg. gave onlyhalf-saturation ; the guineapig allowed to choose its dietkept itself saturated, and animals that synthesised theirown ascorbic acid were saturated ; it could be shownthat guineapigs survived diphtheria toxin better on highlevels (5-10 mg. daily) than on lower levels (2-5 mg.),even though these lower levels completely protected2. Sayers, G. Physiol. Rev. 1950, 30, 241.3. Cornforth, J. W., Long, D. A. Lancet, Jan. 24, 1953, p. 160.4. Crandon, J. H., Lund, C. C., Dill, D. B. New Engl. J. Med.
1940, 223, 353.5. Lancet, 1948, i, 853.
1244
against scurvy. After Professor KARK had made theobservation that Gurkhas with low dietary levels ofascorbic acid had better physical achievements than aHarvard crew, Dr. KING emphasised that the NationalResearch Council allowance should not be regarded as a" requirement " ; Prof. E. J. BIGWOOD (Brussels),however, equated " requirements " with
" allowances."Mr. A. L. BACHARACH thought that the National ResearchCouncil figure ought to be high, because if it applied tofoods as purchased there could be losses in cooking, andif it applied to the average person there would be afrequency distribution about the mean and thereforeabout half the population would need more than themean. Dr. HARRIS closed the discussion with theremark that we must agree to differ on the question ofrequirements.
It may be noted, however, that the National ResearchCouncil figures are specifically stated to refer to the" content of foods as eaten and [they] do not allow forlosses in storage, cooking, and serving " ; further theyare " levels enough higher to cover substantially allindividual variations in the requirements of normalpeople."
Lack of time for full discussion immediately after
papers was the obvious defect of the symposium whichhad been otherwise excellently arranged by Mr. C. P.STEWART, PH.D., and Dr. A. P. MEIKLEJOHN. This lackwas most obvious in the case of a paper from Dr. S. B.WOLBACH (Boston, Mass.) on the histology of scurvy,extracts of which were read in his absence.
Wolbach’s views are controversial, but could not becontroverted. The controversy concerns the nature ofthe defect in connective tissue in scurvy. In the scorbuticanimal fibroblasts produce a metachromatic-stainingmaterial containing polysaccharides, and collagen is notformed ; it is not certain whether the defect is in extra-cellular gelation or in the production of a precursor orfactor by connective tissue cells. There seems littledoubt that collagen can be maintained but not adequatelyformed in the scorbutic animal, and King 6 has shownthat ascorbic acid is not part of the chondroitin sulphateor collagen molecule. Wolbach believes the defect isnot in the production of the precursor of collagen, but inthe extracellular conversion of the precursor into collagen;he thinks 7 that the pink-staining amorphous extra-cellular material in scorbutic tissues is the precursor ofcollagen. Follis,8 however, showed that this materialwas not produced in the bone of scorbutic animals unlessthose bones are subjected to stress ; he regards Wolbach’sgelation theory as unproved. Both schools regard thechanges in bone, teeth, and gums in scurvy as secondaryto the failure to form connective tissue. This has beensummarised by Meiklejohn, Passmore, and Stewart :" Wolbach showed a loss of collagen from connective tissues
and a disappearance of intercellular cement. As a result thecells forming the walls of the capillary blood vessels fail tostick together and this gives rise to the characteristic hæmor-rhages.... There is also defective formation of dentine in theteeth and of the special tissue (osteoid) responsible for thegrowth and repair of bones.... Thus the three outstandinganatomical lesions of scurvy—the hæmorrhages, the looseningof teeth, and the bony deformities—can be traced to a singlecause : the failure in the supply of collagen for maintenanceof connective tissue and intercellular cement." 1
Here we can see that the controversy is even broaderthan the precise defect in production of collagen ; for,first, it is generally believed that in scurvy there is noloss of collagen but a failure to form it (once formed itcan be maintained) ; secondly, capillary permeability isprobably a function of the intercellular cement and isindependent of ascorbic acid, whereas capillary strengthis often but not always decreased in scurvy since there isweakening of the collagen surrounding the capillary walland no weakening of the wall itself, the endothelial inter-
6. Burns, J. J., Burch, H. B., King, C. G. J. biol. Chem. 1951,191, 501.
7. Wolbach, S. B., Bessey, O. A. Physiol. Rev. 1942, 22, 233.8. Follis, R. H. jun. Pathology of Nutritional Disease. Oxford,
1948.
cellular cement being normal in scurvy 9 ; thirdly, thedefective formation of dentine has no causative relationwith the loosening and shedding of the teeth in scurvywhich Lind so graphically described.The biochemical lesion underlying these histolqgical
changes is not ’known. Possibly ascorbic acid or itsoxidation products are concerned in setting up -S-S-bonds that link the protein chains in collagen. A mostimportant metabolic defect in scurvy concerns theoxidation of tyrosine. Sealock 10 showed in 1940 thatthe metabolism of this amino-acid was defective inscurvy ; next year Levine 11 and his colleagues reportedthat premature infants fed on cow’s milk, a diet high inprotein and low in ascorbic acid, excreted large amounts ofderivatives of tyrosine in the urine unless ascorbic acidwas given.
Dr. W. J. DARBY (Tennessee) discussed the relation ofascorbic acid to tyrosine and hsemopoietic ’vitamins. He
supported the view that both ascorbic acid and folic orfolinic acid are concerned in the oxidation of p-hydroxy-phenylpyruvic acid to 2, 5 : dihydroxyphenylpyruvic acidwhich is then decarboxylated to give homogentisic acid ;he also supported the need of ascorbic acid for theconversion of folic to folinic acid.
In the last year or two the stages in the oxidation oftyrosine through the compounds just mentioned havebeen elucidated and, although it is not certain that folicacid plays any part in them, ascorbic acid or its oxidationproducts are known to be concerned in the oxidation ofp-hydroxyphenylpyruvic acid and possibly in the lateroxidation of homogentisic acid. These biochemicalaspects should have been discussed and it was a pitythat there was no time for discussing each paper after itwas presented ; the short and somewhat desultorydiscussion at the end of the sessions achieved little.
* * *
But the meeting closed in the evening with an excellentdinner that included scurvy-grass, adrenal cortices, andpaprika ; a dietitian expressed herself satisfied that thevitamin-C content of the meal reached at least the 75 mg.recommended by the National Research Council. Herethere was some confusion of sex, for the figure of 75 mg.relates to men ; but this confusion was perhaps startedby Sir Edward Appleton who at the opening ceremonyspoke of " the dietitian himself " ; and a few minuteslater one wondered whether the dietitians who had
pressed 300 mg. daily on Sir Sheldon Dudley were maleand if so were in fact dietitians. But the presence of oneof the four honorary members of the Nutrition Societyat the dinner (Dame Harriette Chick) reminded us thatexcellent experimental work on vitamin C had during thepast years been contributed by men and women workingpartly on guineapigs and partly on man. This new
knowledge is today applied in the prevention of scurvyin a way that would have satisfied Lind.
H. M. S.
9. Lee, R. E., Lee, N. Z. Amer. J. Physiol. 1947, 149, 465.10. Sealock, R. R., Silberstein, H. E. J. biol. Chem. 1940, 135, 251.11. Levine, S. Z., Gordon, H. H., Marples, E. J. clin. Invest.
1941, 20, 209.12. Child Health: Report of the Committee on Child Health of the
Scottish Health Services Council. H.M. Stationery Office.Pp. 21. 9d.
CHILD HEALTH IN SCOTLANDIN 1949 a committee of the Scottish Health Services
Council was set up, under the chairmanship of Mr.Alexander Cunningham, to review provision for childhealth in the country. The committee has now reported,’2and it suggests that the position should again be surveyedat the end of the first decade of the National HealthService.The committee urges the need for bringing together
prevention and cure in all aspects of child care. Otherrecommendations include the following :
Antenatal period.-In domiciliary practice there shouldbe close cooperation between doctor and midwife and health
