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Multiple testing with new tuberculins has revealedgenetically determined differences in skin reactivity.’6Some individuals react to shared mycobacterialantigens, some to species-specific antigens, and othersto neither when tested with the reagents at routineconcentrations. These patterns of reactivity are linkedto HLA-DR histocompatibility types and may prove tobe of great relevance to an understanding of thegenetics of resistance to mycobacterial disease. Newtuberculins have also been used to investigatesuppressor or regulatory mechanisms in mycobacterialinfections. It has thus been possible to demonstrate thespecificity of such mechanisms and, by mixing of thetuberculins, to show whether antigens of one speciescan suppress responses to those of another species. 17New tuberculins are therefore important new tools

for the study of mycobacterial diseases and some veryexciting and promising lines of investigation havealready been followed. Other studies suggestthemselves, including an investigation of the use ofthese reagents for the diagnosis of disease caused by theso-called atypical mycobacteria. The use of newtuberculins has already led to a renaissance of interestin skin testing in mycobacterial disease - a subjectregarded by many authorities as dead, or almost so.More importantly, it has been shown that a simple testused imaginatively in the field may yield as muchvaluable information as the costly paraphernalia of amodern immunology laboratory. Let us hope that thenew tuberculins will soon be made commercially sothat their potential can be widely evaluated.

Inequalities RevisitedTHE intelligence quotient (IQ) is still one of the most

useful measures of mental performance though it is

being increasingly recognised as only one componentof a complex matrix of human skills that determine anindividual’s mental ability. An IQ of 50 has beenarbitrarily designated as the cut-off point below whicha child is classed as educationally subnormal (severe)(ESN[S]) and the prevalence of such an abnormalityduring childhood is about 3-4 per z Theaetiology is usually a pathologically defined entity,

16. van Eden E, Vries RRP, Stanford JL, Rook GAW HLA-DR associated genetic controlof responses to multiple skin-tests with new tuberculins. Clin Exp Immunol 1983;52: 287-92.

17. Nye PM, Price JE, Ravankar CR, Rook GAW, Stanford JL. The demonstration oftwotypes of suppressor mechanism in leprosy patients and their contacts by quadrupleskin-testing with mycobacterial reagent mixtures. Lepr Rev 1983, 54: 9-18

1 Lewis EO. The report of the mental deficiency committee, Part IV. An investigationinto the incidence of mental deficiency Joint Committee of Board of Education andBoard of Control. London: HMSO, 1929.

2 Goodman N, Tizard J. Prevalence of imbecility and idiocy among children Br Med J1962, i: 216-19.

3 Birch HG, Richardson SA, Baird D, Horobin G, Illsley R A clinical and

epidemiological study-mental subnormality in the community. Baltimore:Williams and Wilkins, 1970.

4 Frew R, Peckham C Mental retardation: a national study. Br Hosp J Soc Serv Rev 1972;82: 2070-72

5. Gustavson KH, Holmgren G, Jonsell R, Son Blomquist HK. Severe mental retardationin children in a northern Swedish county. J Ment Defic Res 1977, 21: 161-80.

with trisomy 21 being the commonest recognised.These children generally require lifelong care andattention and were once regarded as ineducable. InBritain the recognition that, with appropriate training,their functional ability could be improved led to achange in approach culminating in the Education(Handicapped Children) Act of 1970, which placed theonus of their education on the Department ofEducation and Science.Mild educational subnormality (ESN with an

IQ between 50 and 70 is much more common, beingfour or five times more prevalent than ESN(S), and isgenerally believed to be predominantly sociocultural inorigin. Such children are disproportionatelyconcentrated among the lower socioeconomic groups,the retardation being linked to material deprivation,poor educational facilities, family instability, and lackof mental stimulation. 1,4,1,7 An Israeli report has

challenged this conventional view and claims that themain cause of mild retardation may be brain damage asa result of biological disturbances during pregnancy,delivery, or infancy rather than polygenic heredity ornon-biological social deprivation.8 There are seriousmethodological deficiencies in the work; nevertheless,it does raise the issue of what could be done by way ofprevention-whether the approach should be medicalor social. Though both are important their relativemerits can be almost impossible to disentangle becauseof the complex interaction.Probably the largest and most expensive social

experiment undertaken with the aim of amelioratingeducational disadvantage and preventing mild mentalimpairment was the preschool Head Start interventionprogramme in the USA, part of the Johnsonadministration’s declaration of unconditional war on

poverty in 1964. By 1967, about 215 000 children wereenrolled in more than thirteen thousand centres, butthe initial enthusiasm for the project gave way todisillusionment with the publication of the

Westinghouse Report,9 which found only short-termgains with no measurable long-term effects. This

reopened the debate on the relative importance ofgenetic versus environmental influences on

intelligence However, the conclusion that the HeadStart programme was unsuccessful has since beencriticised on the grounds that too much was beingexpected of too little-that preschool intervention wasexpected to compensate for the whole panoply of socialdisadvantage; that the intervention was too limited,akin to admitting a severely malnourished child tohospital for a week or two and expecting the weightgains to be maintained several years after returning to

6. Wedge P, Prosser H. Born to fail. London: Arrow Books, 19737 Fogelman K Britain’s sixteen-year-olds. London: National Children’s Bureau, 19748 Costeff H, Cohen BE, Weller LE Biological factors in mild mental retardation. Develop

Med Child Neurol 1983; 25: 580-879. Westinghouse Learning Corporation. The impact of Head Start: An explanation of the

effect of Head Start on children’s cognitive and affective development SpringfieldVA: US Department of Commerce, Clearing House for Federal Scientific andTechnical Information, 1969.

10. Jensen AR How much can we boost IQ and scholastic achievement. Harvard Educ Ret1969; 39: 1-123

201

the original environment; that there was an enormousvariation in the quality of individual Head Start

projects. Nevertheless, within the Head Start

programme there have been isolated successes,

particularly if the education process has extended intothe home, has been focused on essential verbal andconceptual skills, and has involved the parents.’ 1-’4After the 1967 Plowden Repore5 and in the light of theAmerican experience a similar social experiment wasset up with the development of four educationalpriority areas in England, and one in Scotland; theeffects of this are yet to be fully evaluated.Coincident with the educational initiatives of Head

Start, and as part of the federal programme againstpoverty, were several initiatives in the health spheresuch as the Children and Youth Projects and Maternaland Infant Care programmes. Here, as with HeadStart, there was disappointment in the measuredachievements though there were several isolatedinstances where favourable effects were reported.16-19 Itis also noteworthy that, after the antipovertyprogrammes of the 1960s, the post-neonatal mortalityrate, a sensitive social indicator, showed a narrowing ofthe differential between Whites and "others" in theUS.2oIn the UK the public debate on inequalities and

health began much more recently with the publicationof the Black Report.21 One of its conclusions was thatabolition of child poverty should be among the nationalgoals for the 1980s and it made recommendations

concerning child benefits that were recognised as beingcostly. In the event it was the costliness that led to theshelving of several of the recommendations, yet thiswas an attempt at a strategic rather than a tacticalapproach to the problem, at holistic rather than

piecemeal reform. The consequences of poverty areenormous and amelioration of its effects will be

correspondingly difficult. The disappointments ofsocial experiments to date can be said to be due to theconfused contradiction between astronomical ends andminuscule means. As G. K. Chesterton observed inanother context, "the ideal has not been tried and found

wanting. It has been found difficult and left untried".22

11. Bereiter C, Englemann S. Teaching disadvantaged children in the preschool. NewJersey: Prentice Hall, 1966.

12. Radin R. Three degrees of maternal involvement in a preschool programme: impact onmothers and children. Child Develop 1972, 42: 1355-64.

13. Darlington RB, Royce JM, Snipper AS, Murray HW, Lazar I. Preschool programs andlater school competence of children from low-income families. Science 1980; 208:202-04.

14. Gray SW, Wandersman LP. The methodology of home based intervention studies:problems and promising strategies. Child Develop 1980; 51: 993-1009.

15 Central Advisory Council for Education. Children and their primary schools. London:HMSO, 1967.

16 McNamara JJ, Blumenthal S, Landers C. Trends in infant mortality in New York Cityhealth areas served by Children and Youth Projects. Bull NY Acad Med 1978; 54:484-98.

17 Gold EM. Total maternal and infant care. an evaluation. Am J Publ Health 1969; 59:1851-56.

18. Chabot A. Improved infant mortality rates in a population served by a comprehensiveneighborhood health program Pediatrics 1971; 47: 989-94.

19. Komaroff AL, Duffell PJ. An evaluation of selected federal categorical health programsfor the poor. Am J Publ Health 1976; 66: 255-61

20. Pharoah POD, Morris JN. Postneonatal mortality. Epidemol Rev 1979; 1: 170-83.21 Report of the Working Group on Inequalities in Health. London: DHSS, 1980.22 Chesterton GK. The unfinished temple. In: What’s Wrong with the World. London:

Cassell, 1910.

PYRROLIZIDINE ALKALOIDS

THE plants that are the source of esterified pyrrolizidinesbelong to several families, but have in common that they aretemporarily abundant in disturbed habitats such as

unweeded or abandoned cultivation, especially in aridclimates. Plants of this kind commonly synthesise verypoisonous substances, which are thought to have evolvedwith them as a defence against predators, and particularlyagainst insects. The present enormous variety of floweringplants and their associated, and often dependent, specialisedinsects is in large part due to a hundred million years of suchcoevolution, producing what now amounts to a chemicallove-hate relationship between them.The clergyman naturalist John Ray, a correspondent of

Linnaeus at the end of the seventeenth century, is creditedwith first having recognised that the linking of an insect witha plant might have a chemical basis.2 The Cinnabar moth(Tyria jacobaeae, L), the example he cited, maintains a nearmonopoly on ragwort (Senecio jacobaea, L, Compositae),since it is able with impunity to metabolise the pyrrolizidineesters that the plant contains. It also retains them in theirtoxic state in glands in the hairs of the caterpillar and in thehaematocoele of the adult. As a result both. stages are

distasteful and poisonous to most birds, the cuckoo being anexception. In 1939 the Cinnabar was the subject of the firstquantitative demonstration of the protective value and

symbolic quality of warning coloration. Pyrrolizidines,obtained from the nectar of flowers of the familyApocynaceae, have recently also been shown to be an

obligatory substrate for the male mating pheromones of someDanaid butterflies-posing in the process an intriguingevolutionary puzzle.4No herbivorous mammals are known to have evolved

tolerance, and horses and cows are poisoned world-wide. 5The resulting liver failure received many, and often

picturesque, names before its cause was generally recognisedat the end of the last century. In Britain ragwort ranks with

yew as the commonest cause of poisoning of grazing animals. 6The plant often dominates overgrazed pasture. When

growing, it is avoided short of starvation; when dried, itsdeterrent smell and colour are lost, but its toxicity remains.Sheep are believed to be relatively resistant, and have in theirrumen anaerobic bacteria that obtain energy by the reductionof pyrrolizidine esters to methylated derivatives of theircomponent alkaloids, so detoxifying them.7In man, as in domestic animals, pyrrolizidines cause

centrilobular haemorrhagic necrosis of the liver at the site oftheir oxidative metabolism, with occlusion of hepatic venulesand the clinical picture of the Budd-Chiari syndrome.8People are poisoned either by eating flour that has beenmilled from grain contaminated by the seeds of species ofSenecio, Heliotropium (Boraginaceae), or Crotalaria

(Leguminosae) or, as in the cases lately reported from HongKong,9 by taking parts of the plants in herbal remedies. An

1. Culvenor CCJ. Pyrrolizidine alkaloids-occurrence and systematic importance in

angiosperms. Bot Notiser 1978; 131: 473-86.2. Ray J. Historia insectorum. London: A and J Churchill, 1710.3. Windecker W. Euchelia (Hypocrita) Jacobaeae L. und das Schutztrachtenproblem. Z

Morph Ökol 1939; 35: 84-138.4. Edgar JA, Culvenor CCJ, Pliske TE Coevolution of Danaid butterflies with their host

plants. Nature 1974, 250: 646-48.5. Hill KR, Markson LM, Schoental R. Discussion on Seneciosis in man and animals.

Proc Roy Soc Med 1960, 63: 281-88.6. Forsyth AA. British poisonous plants. London: HMSO, 1968: 98-102.7. Lanigan GW. Peptococcus heliotrinreducans sp. nov., a cytochrome-producing

anaerobe which metabolises pyrrolizidine alkaloids J Gen Microbiol 1976, 94: 1-10.8. Stuart KL, Bras G Veno-occlusive disease of the liver. Quart J Med 1957; 26: 291-317.9. Kumana CR, Ng M, Hsiang UL, Ko W, Wu PC, Tod D. Hepatic veno-occlusive

disease due to toxic alkaloid in herbal tea. Lancet 1983, ii. 1360