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for torture, so for capital punishment, and medicalorganisations should leave no room for ambiguity.

The Lancet

1. Amnesty International. The role of the doctor in executions. In: Healthprofessionals and the death penalty. London: AI, 1989.

2. Anon. Medical participation in capital punishment. In: Medicine

betrayed: the participation of doctors in human rights abuses. London:Zed Books/BMA, 1992: 102-17.

3. The Execution Protocol. By Stephen Trombley. London: Century. 1993.Pp 342. £9.99. ISBN 0-517-59113-8.

4. Amnesty International. The death penalty: list of abolitionist andretentionist countries (June 1992). London: AI, 1992.

5. Guttmann RD. On the use of organs from executed prisoners. TransplantRev 1992; 6: 189-93.

6. Jones GRN. Judicial execution and the prison doctor. Lancet 1990; 335:713-14.

7. Canan RF. Burning at the wire: the execution of John Evans. In: RadeletM, ed. Facing the death penalty. Philadelphia: Temple UniversityPress, 1989: 60-80.

Health sector reform in the formerSoviet Union

The Soviet Union vanished at the end of 1991.Much Communist tradition vanished with it. In the

republics of the former USSR centrally plannedsocialist policies have been cast aside as governmentsmove swiftly towards free markets.1,2 The effects ofradical economic reform on the prices of everydaycommodities are widely known (when Russiaabolished price controls on 90 % of goods on January 2last year, prices rose by an average of 250% the nextday),3 but what about the implications for healthand health services? The market approach to

improvements in the macroeconomy means that

policies aiming to redistribute wealth will be weaker,and increasing poverty and unemployment will lead todeterioration in health status. In health care, the focuson new mechanisms of finance is leading countriestowards adoption of social insurance systems.Consequently the traditional function of healthministries as providers is being taken over byinsurance organisations and by private or local

government agencies.4,5How should the new health ministries respond to

these changes? One option is to do nothing and toaccept that their role will steadily diminish until theyare left with only those tasks that no-one else

wants-eg, inspection of water supplies and sewagedisposal systems. The alternative is to seize the

opportunity to redefine their role as ministries ofhealth rather than of health care and ensure that the

public health is pushed up the agenda. If they choosethe latter course, what should they be doing?Experience in other countries suggests that healthministries have at least three important functions:(a) to monitor the health of their population;(b) constantly to remind and advise senior policymakers on the implications to people’s health ofgovernment policies; and (c) to develop, with otherministries, a national health strategy. The second stepis to look at the changes required to enable ministries

to fulfil these roles. With respect to monitoring healthstatus, most countries have in place some form ofcentralised collation of national morbidity and

mortality data. However, the Soviet model of

epidemiology has been largely confined to the study ofinfectious diseases. Health ministries and centralstatistical offices will have to develop skills in non.communicable-disease epidemiology to assess thehealth problems facing their population and to

monitor the results of policies to reduce them.Armed with information on the health of the

population and knowledge of the multiple causes of illhealth, ministries of health can act as advocates ofhealthy policies at national level. This role will be vitalas other ministries come under pressure to adoptpolicies with important consequences for health. Forexample, a department of industry may be attractedby the economic benefits of a large chemical plant andmay not consider the effect of the resulting toxic waste,Nevertheless, advocacy in these situations is nevereasy: other ministries, with their own priorities andobjectives, may be much stronger. True intersectoralaction in health requires commitment from the mostsenior policy makers within a country. Given thiscommitment, the various government departmentsmay be asked to examine their role in promotinghealth and preventing disease, and to participate indeveloping a national health strategy. Ministries ofhealth should have a major input, but to do so theymust ensure that they have staff who are highly trainedin multisectoral approaches to improving health andwho have the necessary economic and epidemiologicalskills to compare the costs and potential benefits ofvarious interventions.

Meanwhile, health ministries must not neglect theirrole with respect to health services. Withdecentralisation and privatisation they will cease to beproviders of health care. This will enable them todevelop new roles-setting standards; ensuringquality of care; and promoting equity of distributionof health service resources. These changes requirenew legislation, alteration of the organisationalstructure and attitudes within ministries, and effectiveinformation systems.

In the immediate post-reform period, healthministries in some central and eastern Europeancountries were deluged with visitors bringing offers ofall kinds of assistance.6 Apart from the time that iswasted in meeting visiting "experts", many of theprojects on offer were of little long-term value. Hightechnology equipment has been provided with nothought about how spare parts and consumablesmight be paid for or who might operate it.Uncoordinated courses in management, withdifferent groups flying in for a few days to promotetheir own philosophy, led to confusion and cynicismNational policy makers in the former Soviet Unionshould learn from this experience and work withinternational donors to consider first, whether theappropriate institutional development of public health

211

within countries is being supported;7 and second, thepossible adverse health consequences of any proposeddevelopment projects. Only then can steps be taken toavoid or mitigate possible adverse effects on the

country’s health of the prevailing winds of change.

The Lancet

1. Chen LC, Rohde JE, Jolly R. A looming crisis: health in the Central AsianRepublics. Lancet 1992; 339: 1465-67.

2. Sheiman I. Health care reform in the Russian Federation. Health Policy1991; 19: 45-54.

3. Anon. Reaping the whirlwind. In: Russia reborn. Economist, Dec 5, 1992:5.

4. McKee CM. Health services in central and eastern Europe: past problemsand future prospects. J Epidemiol Commun Health 1991; 45: 260-65.

5. Deacon B, Castle-Kanerova M, Manning N, et al. The new easternEurope: social policy past, present and future. London: Sage, 1992.

6. Chopin K. Too many advisers, not enough aid. BMJ 1992; 304: 1429-32.7. Normand C. Romania: health service management training. Lancet 1992;

340: 1153-54.

HLA AND DISEASE

Non-inherited maternal HLA antigens

The HLA system was discovered by researchers studyingtransplantation rejection. However, transplantation is a

non-physiological process-the raison d’etre of the HLAsystem is not to constitute a frustration barrier for surgeons.Studies over the past twenty years have indicated that HLAmolecules are facilitators that assist an individual’s immune

system to distinguish self from non-self. This recognition isachieved by the interactions of HLA molecules with specificreceptors on the surface of T lymphocytes (TCRs).Essentially all antigenic peptides-non-self and

"pathological self" in the context of autoimmunity-arerecognised in association with HLA molecules by TCRs.CD4 T cells see the antigenic peptides associated with HLAclass II molecules (HLA-DR, DR, and DQ)1 of antigen-presenting cells such as macrophages, dendritic cells, and Blymphocytes. CD8 T cells see antigenic peptides complexedwith HLA class I molecules. Molecular studies have

provided crystallographic evidence of HLA molecules withbound peptides in their groove2 and have led to the

isolation/characterisation by aminoacid sequence of suchpeptides.3These advances hold more than a passing interest for

clinicians and immunologists since they could illuminateour understanding of observations, dating from populationstudies of the 1970s, of the association of HLA types withdiseased4—eg, the HLA-B27 with ankylosing spondylitis,Reiter’s syndrome, and acute anterior uveitis. Strongcorrelations were subsequently noted between HLA class I Imolecules and certain autoimmune diseases such as Graves’disease (HLA-DR3), insulin-dependent diabetes mellitus(DR3/DR4), and rheumatoid arthritis (DR4). Theseinteresting associations pose several problems. Thus,population studies determine statistical associations, butsuch associations cannot be regarded as proof of geneticlinkage between a disease susceptibility gene and the HLAmarker gene and tell us nothing of disease processes. Thisdifficulty can be partly overcome by HLA diseaseassociation family studies, by use of affected sibling pairs,

and latterly by molecular approaches based on sequencing ofDNA or proteins associated with indexed HLA genes andglycoproteins. Such techniques have amply confirmed theassociation of DR4 with rheumatoid arthritis. Furthermore,they have revealed subtleties not evident from the use ofserological and cellular methods of HLA typing. For

example, the &bgr; chains of HLA-D1 14 subtypes of HLA-DR4and DR1 show identical aminoacid sequences in some

regions of their polymorphic domains-the regions expectedto bind antigenic peptides. Sequence data of HLA moleculesassociated with insulin-dependent diabetes reveal that a

single aminoacid can distinguish a disease susceptible orresistant HLA molecule among serologically identical types .5

These molecular advances have nevertheless not

overcome the second major problem of HLA and diseaseassociation-ie, the conundrum whereby many diseases(including rheumatoid arthritis) occur in patients who donot possess the indexed HLA type. Various explanationshave already been forwarded; another is presented in thisissue (p 200) by ten Wolde and colleagues. They show thatthe presence of HLA-DR4 in the mothers of children who

subsequently manifest rheumatoid arthritis (without havinginherited DR4) correlates with disease inheritance. Theinfluence of non-inherited maternal antigens (NIMA) mayhave several explanations. At parturition, maternal cellsexpressing DR4 (eg, blood monocytes, dendritic cells, Bcells) may gain access to the neonatal immune system. Suchmaternal DR4 cells containing a culpable peptide in theirgroove may adversely affect the function of specific clones ofneonatal T cells. If the T cells were to become "tolerised/anergised" by such an encounter this would represent ahuman analogue of classic Medawarian acquiredimmunological tolerance as defined in mice.6 Suchmodulated T cells, upon encounter months to years laterwith an altered self-antigen or environmental antigencross-reacting with peptides as originally present in thegroove of maternal DR4 molecules, may show maladaptiveresponses that permit the development of rheumatoidarthritis.

Prospective experiments could be designed to isolatematernal DR4 cells from neonatal blood and to characterisethe peptides in their groove. By a process of reverseimmunogenetics,7,8 the sequence of such molecules could becompared with data bank sequences of environmentalantigens purported to be associated aetiologically withrheumatoid arthritis. NIMA provides us with a workinghypothesis, the very cornerstone of research, to challenge orsupport the current models of HLA and disease association.

Herb Sewell

1. Germain RN. Antigen presentation. The second class story. Nature 1991;353: 605-07.

2. Bjorkman PJ, Saper MA, Samraoui B, et al. The foreign antigen bindingsite of T cell recognition regions of class I histocompatibility antigens.Nature 1987; 329: 512-18.

3. Falk K, Rotzschka O, Stevanovic S, et al. Allele specific motifs revealedby sequencing of self peptides eluted from MHC molecules. Nature1991; 351: 290-96.

4. Sewell HF. Basic immunology. In: Eremin O, Sewell HF, eds.

Immunological basis of surgical science and practice. Oxford: OxfordUniversity Press, 1992: 1-74.

5. Todd JA, Bell JI, McDevitt HO. HLA-DQ beta gene contributes tosusceptibility and resistance to insulin-dependent diabetes mellitus.Nature 1987; 329: 599-604.

6. Billingham RE, Brent L, Medawar PB. Actively acquired tolerance offoreign cells. Nature 1953; 172: 603-06.

7. Hill AVS, Elvin J, Willis AC, et al. Molecular analysis of the association ofHLA-B53 and resistance to severe malaria. Nature 1992; 360: 434-39.

8. Anon. Molecular basis of resistance to malaria. Lancet 1992; 340: 1404.