Medical research [full issue]

WORLD HEALTH THE MAGAZINE OF THE WORLD HEALTH ORGANIZATION • DECEMBER 1983 ADVISORY COMMITTEE ON MEDICAL RESEARCH The first major landmark by T. Adeoye Lambo Deputy Director-General of the World Health Organization n the occasion of the 25th Anniversary of the Advisory Committee on Medical Research (ACMR), to take stock of what has been achieved and what remains to be achieved is an enormous task. Re- search, both fundamental and applied, is one of the most important elements' in our drive to improve the health of every nation. In essence, research is the systematic and rational approach to identifying and solving medical and health problems. These are the prob- lems to which WHO irrevocably commit- ted itself when it announced, through the World Health Assembly, the goal of Health for All by the Year 2000—a goal which, writing in World Health in April 1980 "A Revolution in Research ", I termed : "An irresistible logical process and a passionate protest against the doctrine of inequity and want." One of the great policy changes of the Organization is the emphasis it has put in recent years on research and research training, and on the creation of collaborating centres and other oppor- tunities for full participation of research scientists "across the board ". This move is a manifestation of an absolute need ; it constitutes one of WHO's chal- lenges to the problem of health and disease, and at the same time repre- sents a commitment to itself and to its Member States. During the first two decades of the life of this Organization, serious research efforts were insignificant as compared with the exciting and dynamic advances now in progress. Many members of our ACMR understand that a new world is in the making, a world shaped by that spirit that lives in communion with all men and women of science. It has now become virtually impossible for a scien- tist, a centre or a country, isolated from associates, from other centres or from other parts of the world, to contribute significantly to the progress of re- search. The history of scientific discov- ery has clearly shown that it has almost always been due to the labour of teams, working in centres scattered all over the globe and exchanging the results of their scientific work. Political leaders and policy makers are becoming aware that political action for deyelopment must go hand in hand with political action for health. Without health, economic and social develop- ment has little meaning. Medical re- search without social relevance is of little or no benefit to mankind, nor can medical science be detached from hu- man affairs in general and especially from social and economic influences. Disease or ill-health, including the ef- fects of alterations in the environment, results to a large extent from the life- styles of individuals and communities ; it can also be due to, or associated with, adverse social, economic and other influences. As a result, one significant thrust of the past few years has been towards disease prevention, disease control, and health promotion, using the methods of science, political action and social action. The role of medical re- search in achieving some major succes- ses in preventing and/or controlling dis- ease has been of inestimable worth. This has been due to the social con- sciousness and moral commitment of many distinguished groups of experts and scientists, especially Members of the ACMR who have helped oms to establish research priorities, create new goals, evaluate our projects, and formu- late guidelines for medical and health scientific policy, taking into consider- ation different social and political systems. For 25 years, oms has had the benefit of the contributions of this Committee, through which some of the most able scientists have given much of their creativity to the research efforts of the Organization. Its subjects have ranged from nuclear physics and engineering to biology and its recent revolutionary discoveries, from behavioural science (especially modification of human be- haviour) to human affairs, from the social implications of the by-products and side-effects of medical progress (for instance, genetic engineering, population increase, decline in mortali- ty) to the quality of our life, work and leisure and its relationship to human values. With the help of these men and women of great intellectual gifts, WHO has been able—with very limited re- sources—to have far-reaching catalytic effects in many Member States, es- pecially in creating and/or raising the level of their scientific manpower, tech- nology transfer, interdisciplinary training in health, better ways of identifying priority health problems. It has been possible to mobilise the world's scien- tific community in the Organization's search for new methods, new mechan- isms, new tools and new strategies for meeting diverse health problems, and in our efforts to select and apply scien- tific knowledge from the world's gigan- tic store. It is gratifying to know that these great scientists have also bene- fited from fundamental lessons in "Humanities for the Scientist", being brought face to face with stark realities of the staggering health and socio- economic problems of the Third World. "Of all the communities available to us, there is not one I would want to devote myself to, except for the society of true searchers, which has very few living members at any time ; " these were the Hunting the tsetse fly, carrier of sleeping sickness. Scientific discoveries almost al- ways result from teams working in different centres and exchanging the results of their research. Photo WHO/FAO 2 WORLD HEALTH, Dec. 1983 WORLD HEALTH, Dec. 1983 Cover : Medical Research Cover design by Peter Davies IX ISSN 0043-8502 World Health is the official illustrated magazine of the World Health Organization. Editor : John Bland Deputy Editor : Christiane Viedma Art Editor : Peter Davies News Page Editor: Peter Ozorio World Health appears ten times a year in English, French, German, Portuguese, Rus- sian and Spanish, and four times a year in Arabic and Farsi. Articles and photographs not copyrighted may be reproduced provided credit is given to the World Health Organization. Signed articles do not necessarily reflect WHO's views. World Health, WHO, Av. Appia, 1211 Geneva 27, Switzerland. Contents ACMR: The first major landmark by T Adeoye Lambo 2 Silver anniversary by Martin M. Kaplan 5 Trail blazing by Tabitha Standley and Alexander Kessler 8 Medical research strategy by Christian de Duve 11 WHO•s first research unit : Immunology by Howard Goodman 14 Schistosomiasis: from research to control 16 Genetics and medicine by N. P. Bochkov 18 The seat of pleasure and pain by B. 0. Osuntokun 20 The burden of tropical diseases by E. A. Gregory 24 Behaviour and health by David A. Hamburg and Avery Russell 27 News Page 30 3 Research scientists today are brought face to face with the staggering health and socio-economic problems of the Third World. Photo WHO words of Albert Einstein in one of his letters to Max Born in 1924. The problem of health has become enormous and complex, affecting mil- lions of individuals and society itself. That WHO should now put greater em- phasis on scientific research and tech- nology for health in our search for practical solutions is inescapable. Sci- ence and scientific research in the con- text of our modern society—developing and developed—may well mean the knowledge of our destiny and of the means of fulfilling it. The great scientific revolution, which was destined to transform men's ways of living, thinking and working, was accomplished towards the end of the seventeenth century. If we wish to fix a date for its triumphant consummation, we may take the year 1687, which saw the publication of Isaac Newton's Prin- cipia, as marking the triumph of the new physics. Nothing could more clear- ly emphasise the importance of the social impetus at work behind that re- volution than the fact that the great scientists and those who prepared the thinking world for their discoveries —Galileo, Bacon, Kepler, Descartes, Boyle and Newton himself—were men of deep social and human commitment, dedicated to the task of finding the true relation of nature to man and to the philosophy of science in a broad sense. They saw in their science a logical and single manner of approach to nature, encompassing man and society. Thus, Francis Bacon gave the title "Ad- vancement of Learning" to that book in which he not merely explained the methods by which the increase of knowledge was possible, but also advo- cated the promotion of knowledge to a new and influential position in the or- ganization of human society. His pur- pose, says Dean Church, was to "make knowledge really and intelligently the interest, not of the school or the study or the laboratory only, but of society at large". Again Bacon observed with penetrating insight, "that many excel- lent and useful matters are yet laid up in the bosom of nature ... waiting to be discovered : but they too will doubtless be brought to light in the course and revolution of years." Great advances will no doubt be made, and accelerated progress will give us better knowledge of diseases ; but to prevent and control them will call for a combination of attack, the applica- tion of the methods of biomedical and bio-behavioural sciences, sociology, an- thropology, economics and so on. The health consequences of poverty, such as malnutrition, obesity, smoking, drug abuse, apartheid, crime, suicide, are more likely to be controlled or even prevented by behavioural and environ- mental modification than by our knowl- edge of clinical science. Nevertheless our empirical investigations into disease mechanism must continue ; we need more sophisticated, more realisable, and less expensive technology to cope with the myriads of human diseases in general and health promotion in particular. A quarter of century of inter-discipli- nary and international cooperation in the field of medical research has yielded great benefits in helping to solve human health problems. WHO will continue to look across the frontiers of nations, across the disciplines of sciences, poli- tics, economics and sociology, as it mobilises the intellectual and scientific capacities of men and women from diverse origins to achieve even greater solutions for these crippling health problems and to promote human creativity and freedom. ■ 4 WORLD HEALTH, Dec. 1983 Silver anniversary WHO's Advisory Committee on Medical Research (ACMR) was first conceived in 1958, when a special WHO study was ordered to examine how best to stimulate and coordinate research. The ACMR's first session came into being in the following year by Martin V. Kaplan edical research has become a part of the daily fare for the public at large. Cancer " cures " are touted weekly in the newspapers, television glamorises the surgical and engineering skills involved in replacing hearts, genetic engineering is trans- formed into science fiction. Yet people are much more know- ledgeable—both in fact and fiction—ab- out the progress of medical science than was the case in former years. This is due to an explosive growth in knowledge about biomedicine since World War II and its exploitation by the media. This contrasts strikingly with the situation 50 years ago, when significant dis- coveries in biomedical sciences were the province of a relatively small group of specialists in a particular field. This was generally true at the time just after World War II, when the founders of wHo had the foresight to include in WHO's Constitution a provision for the Organization "to promote and conduct research in the field of health. " We are celebrating in 1983 the silver anniversary of the conception, in 1958, of WHO's Advisory Committee on Medi- cal Research (ACMR). This was a land- mark in the development of WHO's re- search programme. It would be a serious oversight, however, to ignore the first decade of WHO's research efforts (1948- 1958) when funds were scarce and even non-existent for some fields of work. This situation required innovative ap- proaches to international medical re- search efforts, notably through stimulat- ing and coordinating activities in various fields within and between already exis- ting laboratories and institutes through- out the world—a pattern which laid a solid foundation for WHO's research efforts. The most obvious needs for research in that first decade lay in the field of communicable diseases ; they remain of prime importance today for most of the world's population who live in developing countries. Rabies provides a good illustration of a problem requiring early attention by wHo, and how efforts were undertaken to deal with it through research on an international scale—with only token fi- nancial assistance provided by WHO. Ini- tially, it was not clear if the classical treatment with the Pasteur vaccine as used in various countries was at all effective. A resolution adopted at the second session of the wHo Executive Board in November 1948 called for an assessment of anti-rabies vaccination and rabies prophylaxis. So an Expert Committee on Rabies met in April 1950 to assess methods for preventing and controlling the disease in man and lower animals. Since Louis Pasteur's studies some 70 years before, relatively little progress had been made. Diagnostic procedures had slightly improved since his time, but experiments were poorly designed and inconclusive. Extravagant and unsub- stantiated claims were being made for many aspects of the disease, including the use of vaccines and antiserum in humans. The main task of the Expert Commit- tee was to try to separate fact from fiction, and to formulate clear guidelines for action by physicians, veterinarians and health authorities. As a conse- quence of the many uncertainties, the Committee designed a series of col- laborative efforts between laboratories in France, Islamic Republic of Iran, Israel, Spain, USA and USSR. Very important contributions to knowledge in these subjects resulted from these collaborative efforts during the next sev- eral years. Analogous problems were faced, and partially solved, during the first decade of WHO's existence with respect to such other important communicable diseases as poliomyelitis, tuberculosis, and brucellosis, thanks to the same principle of stimulating and coordinating interna- tional research. A watershed in the development of WHO's research activities occurred in 1958 at the Eleventh World Health Assembly (WHA) held in Minneapolis, Minnesota, USA. The Assembly adop- ted a resolution requesting the then Director-General, Dr Marcolino G. Candau, "to organize and arrange for a special study of the role of wHo in research and the ways in which the Organization might assist more ad- equately in stimulating and coordinating research and developing research per- sonnel". The study was made possible by a special financial contribution of the USA. Two meetings of internationally recognised leaders in medical research took place later that year, and their recommendations were adopted in prin- ciple by the Twelfth WHA, in 1959. One of these recommendations was a proposal to set up an Advisory Commit- tee on Medical Research to provide the Director-General with the necessary sci- entific advice. Thus was the first ACMR born. The First Ten Years Now a vigorous expansion of the research programme took place. wHo was required to concern itself primarily with solving "those problems which are better resolved by world cooperative endeavour and by local groups, " and WORLD HEALTH, Dec. 1983 5 Silver anniversary Left : The humble armadillo, a native of the Americas, proved to be the first viable source of large quantities of the leprosy bacillus. In turn, this has opened the way to promising developments in the quest for a simple vaccine against leprosy. Drawing WHO/S. Clerget-Vaucouleurs Right : Foodstuff analysis in the Philippines. Besides pushing outward the furthest frontiers of medical research, the A CMR seeks to apply the most advanced research information to solving practical problems in developing countries. Photo WHO/C. Stauffer "major problems when local effort is inadequate, either because the research potential of the area is limited or be- cause of the nature of the problem. " These guiding principles were applied to a wide variety of subjects, including communicable diseases and environ- mental health, which accounted for over one-half of the total expenditure of some US $20 million devoted to medi- cal research during the first decade. (Today, much more than that sum is spent by WHO in one year on the Special Programme for Research and Training in Tropical Diseases alone.) The re- maining half was devoted to research in non-communicable diseases (mainly cancer and cardiovascular disease), nut- rition, public health practice, biological sciences (immunology, genetics and hu- man reproduction), and pharmacology. But the relatively modest funds avail- able during the first decade were stretched considerably by the device of coordinating research in existing laboratories. Research was targeted on priority problems faced by wHo in the various subjects mentioned. Some 740 investigators in 430 institutions in 77 countries involved themselves in these activities. A network of WHO reference centres, international and regional—of which there were 168 by the end of 1968—started work in the fields of viral, bacterial and parasitic diseases, environ- mental health, mental health, radiation health, nutrition, vector biology and control, and vital and health statistics. Some 50 distinguished scientists, in- cluding many Nobel laureates, served on the ACMR during its first ten years. Their prestige lent considerable weight to the recommendations of the ACMR, which were endorsed by successive World Health Assemblies and implemented by WHO's technical secretariat. By 1968, it had become evident to the ACMR that new approaches were needed to meet serious mortality and morbidity problems affecting most peoples of the world who live in developing countries. A preliminary survey had shown that the global expenditure on research into such parasitic diseases as schis- tosomiasis, onchocerciasis and malaria amounted only to some $25 million. The paucity of results was in stark contrast to the needs of hundreds of millions of people affected by these disorders which resulted in ill health, disabling illnesses and a high death rate. Many other urgent problems apart from communic- able diseases and parasitic infections, such as malnutrition, mental health and family planning, cried out for action. The major problem for the ACMR was how to harness the research potentials in both developed and developing coun- tries so as to undertake collaborative research and at the same time to train scientists of developing countries. Studies made within the WHO sec- retariat into the status of tropical dis- eases on a global scale ultimately led to the establishment of the Special Pro- gramme for Research and Training in Tropical Diseases (TDR), in co-sponsor- ship with UNDP and the World Bank. A consortium of donor agencies helped to raise extra-budgetary funds—an ap- proach which had earlier produced good results for the Special Programme of Research, Development and Research Training in Human Reproduction. Crucial to the efforts on tropical dis- eases and human reproduction was the creation of separate task force groups to tackle each of the technical problems. These task forces consisted of leading scientists in respective fields, charged with determining research approaches which could be followed through in various collaborating laboratories. An important component of this scheme was the use of scientists and existing laboratories in developing countries, and the creation of new units in these countries wherever possible. One exam- ple is the tropical diseases research centre created in Ndola, Zambia. In 1981, this became a national and regional research and training centre 6 WORLD HEALTH, Dec. 1983 within the Zambian government's pro- gramme of health research. The TDR programme concentrating on malaria, schistosomiasis, leishmaniasis, filariasis, trypanosomiasis and leprosy has been one of WHO's most successful research undertakings. Significant ben- efits have accrued from its efforts, particularly in developing a promising vaccine for leprosy, improving diagnos- tic and chemotherapeutic procedures for the parasitic infections and ob- taining much deeper insights into the fundamental biology of the causative agents. At the 17th session of the ACMR in June 1975 the present Director-Gen- eral, Dr Halfdan Mahler, called for a switch of research emphasis into new directions to meet the problems of a rapidly changing world, and especially those faced by developing countries. Manpower resources for research had to be developed for these countries and financial means outside the regular budget had to be harnessed. Dr Mahler also proposed a decentralisation of re- search activities to the wHo regions. In succeeding years, the Global ACMR in Geneva encouraged and guided the development of regional ACMRs, so that in effect decentralisation has been achieved. The ACMR has continued to review the activities of the technical units and their programmes, as well as work in such fields as influenza, small- pox eradication, immunology, mental health, and health services research. The problem of health services re- search has plagued the ACMR almost since its inception. Everyone seems to recognise its importance, but no com- mon methodology has emerged and dis- cussions have floundered in generalities. What seems to be required is to apply health services research on an individual national basis, since each country differs in its needs, resources, cultural habits and other factors. The encouragement of research in mental health has also significantly evolved over time. In the early years of its existence, the ACMR sporadically undertook reviews of mental health re- search. More recently, impressed by the magnitude of mental health problems and significant progress of knowledge in bio-behavioural sciences and mental health, a special subcommittee of the ACMR was established to study this area systematically. The findings of this sub- committee and of a scientific planning group persuaded the ACMR to recom- mend to the Director-General that WHO should have an expanded programme of research and training in bio-behavioural sciences and mental health. The priorities of this programme include research on mental health and bio- behavioural science issues in primary health care, the psychosocial aspects of rapid social and technical change, and health-promoting behaviour (for exam- ple, preventing alcohol abuse in adolesc- ence). The strengthening of institutions, particularly in developing countries, re- search training and coordination are particularly important aspects of this effort of the Organization. The ACMR also did valuable work in guiding WHO's policy on such difficult problems as the uncertain perils and the certain promise of recombinant DNA research, and the safety requirements for laboratories handling dangerous micro-organisms. Thus, over the years, the ACMR has covered a wide span of research subjects at the frontiers of biology. That span has ranged from the advancing edge of fun- damental biological research, to the ap- plication of the most advanced research information to practical problems in developing countries, where there is a crippling lack of all resources for com- bating diseases and environmental threats. Twenty-five years on, the ACMR has established itself as one of the pillars of WHO, ensuring for its activ- ities the technical excellence which the world recognises and expects of the Organization. ■ WORLD HEALTH, Dec. 1983 7 Trail blazing by Tabitha Standley and Alexander Kessler Trail One : Putting family planning back on the WHO map Trail blazing is seldom associated with the work of committees. They often take the least controversial line, particularly in matters of policy, as the easiest way of attaining consensus among their members. A committee has been defined as " a cul-de-sac, down which ideas are lured and then quickly strangled. " Yet a trail was blazed by the WHO Advisory Commit- tee on Medical Research (ACMR) at its sixth session in 1964 when it laid the basis for a wHo programme of research in fertility regulation. Seen from our present-day perspec- tive this may not appear a very daring initiative. It is now generally accepted that family planning is an essential component of health, and that it is a human right ; there is widespread awareness of population problems. As former West German Chancellor Hel- mut Schmidt wrote earlier this year : " When I was at school, there were 2 billion people in the world ; when I was Chancellor, there were 4 billion ; by the year 2000 there will be more than 6 billion. Demographers say that between the year 2020 and 2040 the figure could rise to between 8 billion and 10 billion. " In 1964, however, when the ACMR took this step, the situation was differ- ent : apart from a few exceptions, family planning as a social policy was virtually taboo. After a timid attempt, in the very first years of its existence, at responding to a request from the Government of India for assistance in promoting the rhythm method, WHO was specifically prohibited by the As- sembly of its Member States from engaging in any family planning ac- tivities. Nevertheless, by the early six- ties, the time was ripe for a change. The question was how to pave the way in \\riff) for resuming activity in family planning without raising what were still sensitive and controversial issues. The answer was through research, which was politically acceptable, and much needed from the scientific point of view. This initiative of the ACMR was endorsed by the World Health Assembly and led to the setting up of WHO's research programme on human reproduction, fertility control, sterility and the health aspects of population dynamics. The specific components of this programme, within these topics, were further elaborated by the ACMR at its 1965, 1966 and 1967 meetings. By 1968, research had indeed un- locked the door to a much broader range of WHO projects in family plan- ning services and the training of health workers in this area. In 1983, WHO was collaborating in the national family planning programmes of 80 countries. Trail Two: A new concept of participatory re- search But this was not the only trail blazed by the ACMR. The small initial research programme on fertility regulation met with an enthusiastic response. WHO was urged to take a world leadership role in developing new contraceptives, assessing in developing countries the safety of existing methods of fertility control, devising new ways of provid- ing family planning care and promot- ing a more scientific approach to the study of infertility. At the same time it was asked to help build up in develop- ing countries the capabilities of such research. For such a programme, a number of governments and agencies indicated that they would be prepared to make additional financial con- tributions. This expanded effort required wHo to create new structures to ensure the intimate involvement of scientists and administrators from many countries in the running of the Programme. The aim was to get away from traditional mechanisms, such as those of most Medical Research Councils, in which the bureaucracy plays a preponderant role. Structures were set up that would allow policy-makers and researchers to have a major say on priorities and strategy, and that would make avail- able the best technical expertise for the conduct of studies, and the review- ing and monitoring of research. Through these mechanisms, over 70 countries, of which nearly 50 were developing countries, are currently in- volved in what has become known as the WHO Special Programme of Re- search, Development and Research Training in Human Reproduction. These innovations all received the support of the ACMR and, moreover, were adopted and adapted when the second of WHO's Special Programmes of Research was set up, that relating to tropical diseases. A similar structure has been used for the programme on diarrhoea) diseases, which includes both service and research activities. The Indian Council of Medical Re- search, recognising the value of this participatory approach, has also adopted, for its research activities in family planning, maternal and child health, and nutrition, the very same mechanisms as those of the WHO Special Programme of Research in Human Reproduction. Trail Three: Drug development outside industry One of the major objectives of the Programme is to develop new methods of fertility regulation suited to the 8 WORLD HEALTH, Dec. 1983 Women waiting outside a family planning clinic in Kenya. Research in family planning, through the ACMR, proved politically accept- able at a time when WHO was banned from engaging in any activities related to this still sensitive issue. Photo WHO needs of developing country popula- tions. A method for which there is great demand in these countries is injectable contraception. The two cur- rently available injectables give rise to disturbances of the menstrual cycle, unacceptable to many women, for in- stance spotting or complete cessation of menstrual bleeding. Clearly new compounds are needed, but the phar- maceutical industry is not particularly interested as there is little demand for such products in developed countries. The Programme therefore turned to scientists in academic institutions and challenged them with this high tech- nology task. About 300 new com- pounds have been prepared in univer- sity laboratories in Australia, Brazil, Bulgaria, Islamic Republic of Iran, Israel, Mexico, Nigeria, Poland, Singapore, Spain and Sri Lanka. These compounds have been tested in animals and two have been selec- ted for study in humans. An article in " Science " stated that : "This is probably the first instance in which an international public sector agency has launched successfully a programme of this nature ... the WHO programme illustrates how a multinational cooperative project in drug chemical synthesis can be established outside the traditional pharmaceutical channels—a model that is of particular relevance to lesser developed nations. The programme is an impressive example of an interdisciplinary and fruitful cooperation between an interna- tional organization, such as weo, university or government laboratories from countries all over the world, and a prominent national public institution, such as the National Insti- tutes of Health in the United States. " Trail Four : WHO becomes a patent holder What should WHO do with such compounds and other inventions com- ing from research it sponsors ? Its policy in the past has been not to take out patents but to make knowledge as widely available as possible. On the other hand, no firm would be in- terested in collaborating with WHO in developing a product from the initial testing phase mentioned above to the marketing stage, unless it were pro- tected by a patent. At the same time, however, it seems inappropriate to allow a firm to take out a patent, from which it might derive great profits, on a product in which large investment of public funds has been made by WHO. The Programme pioneered a change in WHO policy, endorsed in 1982 by the World Health Assembly in a resol- ution stating that "It shall be the policy of WHO to obtain patents, inven- tors' certificates or interests in pa- tents ... where such rights and interests are necessary to ensure development of the new technology ". The Pro- gramme at present holds five patents and several are pending. Trail Five : How research affects policy There is, in some quarters, scepti- cism as to the extent to which the results of research influence policy- makers, either because they are not made aware of the findings, or else because the findings are not presented in a form intelligible to them, or be- cause the research was irrelevant to the concerns of administrators. WORLD HEALTH, Dec. 1983 9 MIXING/METERING CONTROL UNIT TURRET MIXER MOULDS TRICAL CONTROL BOX AIR CIRCUIT CONTROL The participatory approach taken in the WHO Special Programme of Re- search in Human Reproduction has served to guard against these dangers and make certain that research is loc- ally relevant and that its results are employed. Thus in Thailand, a bottle- neck occurred in providing post- partum sterilisation, owing to the shortage of physicians. Women were being kept in hospital up to an extra five days after delivery to wait for their operation. The Ministry of Public Health sought the Programme's col- laboration in determining whether it would be safe to use operating room nurses to do these tubal ligations. A training programme was devised and tested, the performance of the nurses was rigorously compared to that of physicians, first on a one-centre basis, then nationwide. The study showed that adequately trained nurses could indeed perform this operation as safe- ly as physicians. They are now cer- tified to do so in Thailand. Another project, in Turkey, ex- plored the possibility of using labour union shop stewardesses for family planning education and motivation. Their impact was so great, among both the women workers and, indirectly, on the wives of men workers, that the Confederation of Labour Unions has convinced the Social Security Admin- istration to open family planning clinics in several SSA hospitals. The research centre at Hacettepe Universi- ty in Turkey, which has collaborated with the Programme in these studies, works closely with the Ministry, and there is a constant flow of ideas and information between the two. This year, five staff members of the Centre served on committees preparing legis- lation on abortion, sterilisation, family planning training and education. Trail Six: The multiplier effect The Centre is also reinforcing re- search capabilities in Turkey and in other developing countries by provid- ing consultants and conducting train- ing courses. Many of the centres in This science fiction monster is WHO's proto- type injection moulding machine for manu- facturing vaginal rings—the successful outcome of collaboration between WHO and industry. Photo WHO developing countries that have been strengthened by the Programme in the past ten years in basic and clinical research are now building up research institutions in their own or other coun- tries : this is the case for example in Cuba, India, Mexico, the People's Republic of China, the Philippines, Singapore and Thailand. Perhaps of all the trails blazed by the ACMR in the area of family plan- ning research—and there are many more which came out of its 1964 decision—this is the one that will have the longest lasting effect. An ever- growing body of scientists all over the world has been constituted with a commitment to research in repro- duction and family planning. In their hands lie certain key aspects of the health of present and future generations. ■ 10 WORLD HEALTH, Dec. 1983 Medical research strategy by Christian de Duve eople are talking more and more nowadays about biomedi- cal research. This neologism re ects the close ties between fun- damental biological and medical research, to which we would add pharmaceutical research. Medical and pharmaceutical research in fact leans ever more heavily on the basic sci- ences, not only biology but also chemistry and physics, and ever grea- ter efforts are being made to derive the best advantage from their knowl- edge and methods. Nevertheless, this "loan" is being repaid with interest by providing biology with a starting point for new investigations as well as an invaluable set of tools. Consider what our present understanding of the phenomena of life owes to the discov- ery of microbes, viruses, antibodies, vitamins, antibiotics and other myco- toxins, hormones and numerous medicines. Yet despite these close links, both types of research have quite different objectives and strategies. Whereas fundamental biological research is aimed at understanding the vital mech- anisms, medical research is trying above all to master them so as to prevent or cure disease, and it tries to do so in a rational way, through a thorough understanding of the prob- lems. But it does not wait for that understanding to come along. Sticking to its pragmatic approach, it does not hesitate to tackle areas that are still unexplored, and to adopt an empirical strategy. The empirical method is more deep- ly rooted in history than the rational approach. This is why even the most primitive peoples have their own phar- macopoeia in which highly effective remedies are found alongside various kinds of " magic " potions. Such collec- tions, brought back by travellers and explorers, until recently provided pharmaceutical chemistry with most of its research material. The result of observations made throughout the world by generations of unknown sor- cerers and magicians (not to mention poisoners), they are no doubt mostly the outcome of random findings. Nevertheless, true research methods have often been at work, involving a fairly systematic procedure of trial and error. Whether pursued consciously or not, this primitive process has given us opium, curare, quinine, digitalis and many other precious natural preparations. It would be a distortion to compare the ultra-modern equipment of to- day's big pharmaceutical research laboratories with the blind fumblings of ancient healers. But while the means may have changed, the strategy differs little. Even today the search for a new medicine usually entails the synthesis and assessment of thousands, tens of thousands or even hundreds of thousands of different compounds. The recent history of Mefloquin is a striking illustration of the randomness of the "mass screening" method, and of the tremendous costs involved. Mefloquin is a new active anti-mala- rial preparation against plasmodium falciparum, developed by the Walter Reed Army Institute of Research after more than 15 years of research and the testing of some 350,000 derivatives, at an estimated cost of more than US$ 200 million. Yet this strategy has largely proved its worth in pharma- ceutical research, and often there is no other way. Sometimes research is guided by simple analogical reasoning. The whole range of natural antibiotics available today and the even fuller range of the mycins (generally avoided on account of their toxicity) have ad- ded immeasurably to biochemistry and molecular biology ; and these are the fruit of a systematic examination of hundreds of thousands of mould stocks gathered all over the world. One simple observation (by Alexander Fleming) lay behind this tremendous "miraculous harvest ", and it was a matter of luck. A particular variety of fungus, penicillium notatum, produced a non-toxic anti-bacterial substance — penicillin . Primitive man could have taken a similar approach. Perhaps he did. In medicine too, the empirical method has had its successes. The great discoveries which have revo- lutionised our means of preventing and sometimes treating diseases which decimated our ancestors were made at a time when our knowledge of living mechanisms was embryonic, when the living cell was a "black box ". The empirical strategy is still with us today in that especially valued form of re- search known as epidemiological in- vestigation, based on an amazingly simple but highly logical method of reasoning. "Find the cause of the disease ", it says " and you have the means of prevention, even if you do not understand what happens. " It is true that epidemiological investigation usually establishes only correlations, and these are not necessarily causal relations ; it identifies "risk factors" rather than agents. But it requires no complex technology except in the field of data processing. And it is accessible to the layman, including the politician and the journalist, which may go some way towards explaining its success. Clinical research too may adopt an empirical approach, imposed to some extent by the restrictions inherent in the manipulations to which patients must be subjected. This limitation may well be offset by the genuineness of the result. As Lucien Israel, the fa- mous French cancer specialist, said : " I am very much in favour of developing and supporting to the hilt that research which is carried out by doctors at their own operational level. " He added : "Empiricism lies at the origin of most medical progress where Fleming-type chance has not been involved. " Israel was right. This is why the medical revolution took place nearly a century before the biological revolu- tion. Many medical discoveries could have been made even earlier than they were, and some were—but sporadically WORLD HEALTH, Dec. 1983 11 Villagers in India line up for sputum ex- amination—a test for tuberculosis. This is an example of the empirical strategy still used in medicine—that valuable form of research known as epidemiological investigation. Photo WHO/P. Almasy and in isolation. The nutritional origin of scurvy, for instance, was well known to the ancient deep-sea navigators. It was not the knowledge or methods which were lacking, but an approach, for which we had to await Francis Bacon, Rene Descartes and, above all, Claude Bernard. While the recipe may have given ample proof of its worth, there could be doubts whether it should still be the preferred one for the future. Even backed by all the facilities of science and of engineering, the empirical strategy retains its random features. In order to succeed, it still needs luck at the right time. Perhaps because so many applications have been made to her, Lady Luck needs more and more coaxing these days, and more atten- tion has to be paid to the cost-benefit ratio. In the case of Mefloquin men- tioned above, only an American milit- ary institute could have afforded such a burdensome research programme. I do not know what all the clinical and epidemiological investigations into ar- teriosclerosis have cost so far, but feel sure that the figure must be in the thousand-million-dollar range. All this for what? We are still not sure of the precise importance of cholesterol in food, and the dispute about un- saturated fatty acids has still not been settled. Even when research yields an unde- niable concrete result, its success in practice is still not assured. Cigarette smoking is a case in point. That it contributes to lung cancers is in virtu- ally no doubt, but the relationship is not as clear as that linking, for instance, Koch's vibrion to cholera. Cigarette smoke is only one factor among others, and is not decisive in itself. When it does act, it does so only after 25 years or more. For many smokers the danger is too far off and vague for them to give up a pleasant habit. Giving up smoking in order to guard against the risk of contracting cancer in 25 or 30 years' time is quite different from refusing to drink pol- luted water—which in any event is hardly attractive—in order not to fall ill tomorrow. So, even though the cause is identified, the mechanism of prevention remains grounded. These drawbacks would be accept- able if there were no other alterna- tive. While our knowledge of the vital mechanisms was rudimentary, there was some justification for going straight for the goal without going by way of understanding. Patients cannot wait and, in any case, events have largely sanctioned the empiricists. As I have already stressed, their strategy has proved remarkably fruitful, not only in medicine and pharmaceutics, but also in other fields of human effort in which living organisms are manipu- lated in some way, such as agriculture, stockbreeding, the food industry and brewing. But today there is a new factor of prime importance : our knowledge is no longer rudimentary. The "black box" has been opened and dismantled, and we are already fam- iliar with its gearing mechanism. It would be pointless here to cavil at what is often and quite rightly called the biological revolution. Since the end of the Second World War, our understanding of the fundamental 12 WORLD HEALTH, Dec. 1983 High-technology word-processors at work in the field of traditional medicine; technicians analysing herbal remedies at the Biomedical Research Unit on Traditional and Herbal Medicine in Mexico City. Photo WHO/J. Bland mechanisms of life has made and con- tinues to make huge strides forward. The consequences and possible appli- cations of new knowledge is very much on our minds. Concerning medical and pharmaceutical research, the message is clear : from now on we can, with increasing confidence, adopt a rational strategy making use of modern bio- logical knowledge and instruments to reach its aim. In the case of diseases, this means examining pathogenic mechanisms and trying to explain them in terms of the cellular and molecular degeneration to which they give rise. For medicines, we shall be able to provide " tailor-made " molecules modelled to suit what is known of the cellular and molecular natures of their targets. This strategy is nothing new, of course. It was vividly described and eloquently defended by Claude Bernard in his famous Introduction to the Study of Experimental Medicine. In this book, which should be bedside reading for every bio-medical researcher, Claude Bernard recom- mends an analytical and critical ap- proach which, he says, should be the same for normal and pathological phe- nomena. On the subject of empiricism, he writes : "Medicine is bound gradu- ally to abandon empiricism and it will do so, like all the other sciences, through the experimental method. " Claude Bernard and many of his successors are dedicated to making this prediction come true, but for long they have come up against a lack of knowledge and means. The ancient experimenters had the advantage of being able easily to move between the laboratory and the patient's bed, but this is no longer so. Today doctors, chemists, pharmacologists and " fun- damentalist " biologists are all locked away within their own disciplines, and often within their own sub-disci- plines, by the increasing specialisation and improvement of their knowledge, their instruments, their methods and their jargon. This isolation, the pen- alty of progress, too easily becomes isolationism. For myself, having spent 25 years in the ivory tower of fundamental biochemistry and having, from its heights, watched the extraordinary de- velopment of modern cellular and molecular biology, I felt that we are not entitled to wrap ourselves up in our isolation and be satisfied merely to contemplate, selfishly and narcissisti- cally, the new and beautiful vision of life which has been revealed to us. This view, I thought, should not only be shared but also translated into practical results which can serve hu- manity's health and welfare. A few of my colleagues share my opinion. For- tunately, this happened a dozen years ago, when it was easier than it is now to dream, to create, and to take risks. The result is the ICP, the International Institute for Cellular and Molecular Pathology, a multi-disciplinary centre in Brussels where fundamental re- search is performed partly for its own sake and partly to further plans for practical applications carried out in collaboration with clinicians and the chemical and pharmaceutical industry. The setting up of the ICP is part of a trend which now has an increasing number of followers, not only in medicine but also in many other fields of human effort. Virtually unknown five years ago, the word " bio-technol- ogy" is now on every lip. It appears on the agendas of numberless national and international meetings, and one could almost say that it is quoted on the stock exchange. This is all well and good, but we must be on our guard against two hazards. The first is the old " hubris "—that arrogance which can bring us to promise more than we can deliver. The discoveries just made are undoubtedly decisive, but our ignor- ance is still immense, and let us not forget that. Moreover, it is not enough just to understand in order to be able to overcome. Take the huge field of hereditary and congenital conditions. In many instances we can describe them with almost molecular precision, but our means of action remain very limited. The other hazard is that of becom- ing drunk with our power to manipu- late the living organism, to the extent of exceeding the limits set by pru- dence, law or morals. I do not feel that this hazard is very great, firstly be- cause I tend to trust my colleagues' sense of responsibility and the solidity of our institutions. Secondly, and perhaps principally, because the hazard is not new. Humanity's entire history is marked by scientific and technical progress, every stage of which could be and often was used for evil as well as good. Nevertheless, the overall balance sheet is heavier on the credit side and may be summarised as nothing less than the gradual freeing of man from his subservience to the blind forces of nature. This liberation, it must be said, has not been achieved smoothly. At every stage it has been accompanied by often profound changes in the structure of society. The bio-technological revolution which we are now experiencing will probably be the same. It is up to us to guide it without excessive conserva- tism, but with an eye to ensuring that true values are safeguarded. ■ WORLD HEALTH, Dec. 1983 13 WHO's first research unit: immunology by Howard Goodman he wisdom of WHO's member countries in deciding, in 1959, that WHO should develop an intensified research programme, has been amply confirmed by the sub- sequent explosive expansion of new knowledge in the biomedical sciences. This research programme has enabled WHO to call upon the world's leading biomedical scientists to help apply this new knowledge towards the develop- ment of methods to control or prevent diseases of major public health concern. The story of how wHo created its first research unit in 1963—for im- munology research—provides an ex- cellent example of the foresight of the ACMR. Immunology has undergone a rapid growth into a scientific discipline in its own right from its historical roots in microbiology. As we increased our understanding of how the immune system functions, immunologists have learned how to prevent infant disability or death from the sensitisation of Rh negative mothers with Rh positive spouses ; how to prevent rejection of kidney and other organ transplants ; how to treat auto-immune diseases ; and how to diagnose and treat some of the dis- eases due to malfunctioning of the immune system. Recent research ad- vances in immunology have led to today's exciting prospects for new vac- cines to protect against parasitic and diarrhoeal diseases. Immunological tests are now an in- tegral part of all branches of medicine : diagnosing thyroid and other endo- crinological diseases by radio-immune assays, detecting drugs, typing tissue antigens for organ transplants, defin- ing allergic sensitivities, detecting auto-immune diseases, and beginning to fill the long-felt need for simplified immuno-diagnostic tests in tropical diseases. (Some of these developments were explained in the November issue of World Health.) WHO's intensified research pro- gramme began in 1959 with the finan- cial support of US$ 1.25 million in its regular budget, a $500,000 gift from the USA, and an offer of a research fellowship from Sweden. Included among the members of the newly established ACMR was Sir McFarlane Burnet, later to be awarded a Nobel prize in Immunology. In the report of the second meeting of the ACMR, the committee stated that research in immunology was of interest to WHO not only because in specialised aspects it entered into many of the research programmes of the Organization, but also because 1 "this field may be expected to expand greatly in importance and have in- creasing influence both on medical thought and practice. " After consider- ing the reports of five Scientific Group Meetings surveying the field, or- ganized by Niels Jerne, then Chief of WHO's Biological Standardization unit, the ACMR supported the creation of the wHo Immunology Unit in 1963. One of the first concerns was to train immunologists, especially in Africa, Asia and Latin America. The first of six regional WHO Research and Training Centres was designated in Ibadan, Nigeria in 1965. The prin- 14 WORLD HEALTH, Dec. 1983 Malaria victim in Latin America. Today, WHO can rely on a generation of newly trained immunologists to apply the flood of new knowledge towards research—research which will eventually lead to the control of such diseases. Photo WHO/P. Larsen ciples of undertaking initial training of immunologists in their own country or region, and of concentrating the train- ing on disease problems peculiar to that region, especially tropical dis- eases, have now been widely applied to other programmes. In 1969, ad- vanced training in immunology was undertaken by the WHO Immunology Research and Training Centre which is now based at the Universities of Lausanne and Geneva, and which serves as a "base unit" for contact with former students in 57 countries. A scientific group on the Teaching of Immunology in the Medical Cur- riculum gave authoritative guidance for countries concerned with finding ways of fitting this new scientific disci- pline into existing medical curricula. WORLD HEALTH, Dec. 1983 Immunology and parasitic diseases formed the subject of the first WHO Immunology Expert Committee in 1965, and brought new knowledge in immunology to bear on the problems of parasitic diseases. In any science, a common language is important for teaching and for com- municating research results. Im- munologists in the early 1960s were discovering new antibody globulin molecules, and each discoverer ap- plied a different name to each new antibody molecule. WHO's pioneering Immunology Nomenclature meeting held in Prague in 1964, led to the publication, in the WHO Bulletin, of the Nomenclature for Human Immunoglobulins. The scientific com- munity of the world welcomed this and subsequent nomenclature proposals in related fields, with consequent ben- efits for students, researchers and medical and veterinary practitioners alike. With no international association of their own to facilitate international communication aimed at standardising nomenclature and sharing research re- sults, immunologists welcomed WHO's help in filling this need. As the fields of immunology expanded, the Organi- zation helped to set up the Inter- national Union of Immunological Societies, which this year spon- sored the Fifth Triennial International Congress of Immunology in Kyoto, Japan. WHO's decision to establish its first research unit in 1963 in General and Applied Immunology brought the Or- ganization the ready collaboration of the world's best technical experts in immunology over the past 20 years, six of whom have been awarded Nobel prizes during that period : McFarlane Burnet, Peter Medawar, Gerald Edelman, Rodney Porter, Baruch Benaceref, and Jean Dausset. wHo can now call upon them, and the help of a generation of newly trained im- munologists in the developing coun- tries, in applying the flood of new knowledge towards research into the control of diseases of public health importance. ■ 15 SCHISTOSOMIASIS From research to control Schistosomiasis, or bilharziasis, affects the poor agricultural populations of 74 tropical and sub- tropical countries, where it is second only to malaria in socioeconomic and public health impact Target and techniques Schistosomiasis, basically a disease of childhood (right), calls for early diag- nosis and treatment. The eggs of the urinary schistosomiasis parasite can be detected with a simple, reusable urine filtration device (below, left and right). With this technique, several hundred people can be examined and treated in a few hours. Eggs of the intestinal schistosomiasis parasite and other in- testinal parasites can be detected in faeces by a simple, low-cost micro- scopic technique, widely used in Latin America and Africa. Primary health workers can identify children needing treatment either by direct observation of blood in the urine or by using reagent strips to detect microscopic levels of urinary blood. Photos WHO/K. Mott. Inset photo H. Feldmeier 0 '3=74,3111111.--** DEVELOPMENT: SMALL AGRICULTURAL DAMS one dot=one small darn N=129 darns 50 100 Km DISEASE: URINARY SCHISTOSOMIASIS Urinary schistosomiasis in Africa (shaded areas). Intestinal schistosomiasis is present in Latin America and Africa, and Asiatic intestinal schistosomiasis in the Western Pacific area. Water is essential- schistosomiasis is not! With rapid urban development in the endemic countries, the risk of schis- tosomiasis is too easily overlooked, although adequate sanitation and water supply would consolidate the effect of the new, safe drugs. New dams (left), artificial lakes and irrigation schemes proliferate, but few steps are taken to prevent the introduction or spread of schistosomiasis. Sao Tome and Prin- cipe recently became the 74th country endemic for schistosomiasis. These problems can be avoided by the appli- cation of modern control techniques. Maps WHO/Geojournal WORLD HEALTH, Dec. 1983 17 Effective treatment Recent research has provided three well tolerated, safe and highly effective drugs for schistosomiasis, all taken by mouth (left). WHO coordinated the pre- clinical and clinical evaluation of prazi- quantel, effective against all forms of schistosomiasis. Oxamniquine is effec- tive against intestinal schistosomiasis in Latin America and Africa. Metrifonate is given, usually in three doses, to treat urinary schistosomiasis. Treatment of children is recommended to reduce the risk of disease caused by heavy infections. Photo WHO/K. Mott Map WHO Cancer prevention WHO seeks to identify preventable causes of cancer. A form of bladder cancer occurs frequently in agricultural workers under 50 with urinary schis- tosomiasis, so early schistosomiasis treatment should curb this cancer. X-rays show the urinary tract of a nor- mal child (left) and a child with urinary schistosomiasis (right). X-ray photos Cantonal Hospital, Geneva and WHO/A. Davis Health education People need to understand how their actions sustain the threat of schis- tosomiasis (left). Egg-laden urine or faeces which contaminate bodies of water will be transformed inside fresh- water snails, and can then penetrate the skin of other water users. BETTER BEST Design L. Chitsulo Percent Prevalence I Less than 10 10-29 rib 9 70 or more distribution of agricultural dams (upper map) corresponds closely with The i tri N=38 survey areas 50-69 30-49 very high prevalences of schistosomiasis (lower map). NEVER Genetics and medicine by N. P. Bochkov he development of human gen- etics has always been closely linked with the progress of biolo- gy and medicine as a whole. During its short history, human genetics has fre- quently been a focus of attention for the bio-medical sciences, and some- times for the social sciences. It has undergone periods of intensive devel- opment, when exciting ideas have emerged and unexpected discoveries have fundamentally influenced the de- velopment of biological science. At the same time, there have been at- tempts to use its concepts to justify racism, genocide, or political persecu- tion, and these have markedly im- peded its growth. Today, human genetics has a bear- ing on theoretical aspects of modern medicine, as well as on such clinical disciplines as paediatrics, obstetrics, neurology, psychiatry and preventive medicine. This extensive and profound in- volvement of human genetics with medicine has resulted from the pro- gress made in the study of human heredity from the level of the molecule up to the investigation of whole popu- lations. And this in turn is due to the increased interest of clinicians and health service organizers in hereditary pathology. Genetic diseases represent a consid- erable proportion of the total morbid- ity and mortality in any population. So the practical requirements of medicine still determine the aims and directions of human genetics, and are based on clinical observations, medical statistics and demographic data. Patients with hereditary diseases are patients suffering from chronic dis- ease, and are five or six times more likely to attend out-patient clinics than others. The proportion of children suffering from hereditary pathology in hospitals is not less than 20 per cent ; many of them will come from families in which all the children are ill. In the developed countries, heredi- tary pathology causes some 30 per cent of child mortality and about half of child blindness and deafness. Chromosome changes are responsible for spontaneous abortions, congenital malformations and other anomalies. And about seven per cent of all pre- gnancies are spontaneously aborted because of some genetic abnormality of the fetus. These figures underline the urgent need for the fundamental problems of human genetics to be resolved. Two positive breakthroughs have been made as a result of fundamental genetic research in the field of disease diagnosis. Firstly, medical genetics has made possible the accurate diagnosis of hundreds of metabolic diseases— variants of chromosome diseases and many other ailments caused by certain genetic conditions. Secondly, it has enabled an early diagnosis to be made. The earlier the disease is detected, the more complete and efficient the treatment can be. Advances in human genetics have made it possible to diagnose diseases even before the manifestation of a clinical picture, that is, immediately after birth or even in the prenatal period. Simple methods of early diag- nosis have been devised for a number of diseases, and are now avail- able throughout the whole network of the health system. There can be few doubts about the impact of intro- ducing into basic medical care these new methods of diagnosing phenyl- ketonuria, cystic fibrosis, haemoglobi- nop athies , erythrocytic enzymop a- thies , and chromosome anomalies. Particular success has been achieved in the prenatal diagnosis of hereditary diseases, making it possible to avoid the birth of an ailing child and bringing about a new approach to the manage- ment of these conditions. Prenatal diagnostics can now be done by means of ultra-sound scan- ning, direct observation by fetoscopy and amniocentesis. The latter method has so far given the best results. Cells obtained from the fetus are cultivated, and after one to three weeks it is possible to diagnose all chromosome diseases and about 100 gene abnor- malities. As evidence of the need for such prenatal diagnosis, it is worth mentioning that at least 50 abnormal fetuses are diagnosed for each 1,000 pregnancies selected for diagnosis. Hundreds of thousands of amniocen- tesis tests have been performed around the world, and there can be no doubt about the safety of this proce- dure for woman and child. Human genetics and developmental biology have greatly improved the treatment of hereditary diseases. Now that the biochemical pathways are much better understood—from the in- itial production of a mutant gene up to the manifestation of a clinical pic- ture—it has become possible to re- medy the course of disease patho- genesis at different stages. In a number of cases it is possible to under- take preventive dietary treatment, re- placement of defective biological en- tities, such as hormones and enzymes, clotting factors or red blood cells, and elimination of toxic products from the organism ; all of these are promising approaches based on understanding the genetic nature of diseases. Early detection, and the possibility of treatment, elimination of environ- mental factors which interact with the genotype to produce pathological con- ditions, and genetic counselling—these are the tools for solving the problem of 18 WORLD HEALTH, Dec. 1983 preventing hereditary diseases. Not only the patient but also the patient's family becomes the object of medical intervention. Geneticists and physi- cians are developing preventive meas- ures which will make this type of specialised medical service more effec- tive. These include new methods of heterozygote screening, better ways of calculating recurrent risk, and im- provements in prenatal diagnosis. Among many examples one could cite of the social impact of prevention and treatment in this field is the work undertaken by WHO's Hereditary Dis- eases Programme on the community control of hereditary anaemias. Some 200,000 lethally affected homozygotes are born each year, about half of them with thalassaemia and half with sickle- cell anaemia. Throughout the world there are at least 240 million hetero- zygotes. These diseases make big de- mands on the health resources of de- veloping countries and, as further pro- gress is made in primary health care, they will become a major public health problem. This has already happened in the Mediterranean areas, where tha- lassaemias are predominant, and it is becoming more evident in parts of South-East Asia. Community control by prospective heterozygote detection, education, and fetal diagnosis has al- ready been successfully applied in some European and Mediterranean areas. Within three years of these programmes starting, the birth rate of infants with thalassaemia major had fallen by 50 to 80 per cent. The relatively low cost of setting up and running the control programmes has already been greatly outweighed by the financial benefits resulting from the reduced thalassaemia birth rate. Another important approach to pre- venting hereditary diseases is ensuring protection from harmful factors in the environment. The efforts of geneticists are directed towards developing new ways of detecting genetic processes in man, and also towards devising new techniques of genetic monitoring. In the broad sense, this means not only biosphere protection but also the elimination of mutagenic drugs, harm- ful food additives, and unjustified X-ray or radiological investigations. The most dangerous factor affecting heredity is ionizing radiation, espec- ially if large human populations were irradiated, as might be expected in the case of nuclear war. The genetic effect of radiation has no threshold, and the mutation frequency depends on the radiation dose. Hence, from a genetic point of view, there is no such thing as a harmless dose ; each dose results in a number of mutations proportional to itself. Since the genetic "efficiency" of neutron irradiation is on average five times that of gamma-irradiation, the most serious biological and genetic consequences are to be expected from neutron bombs. The genetic effect of radiation can be observed in somatic cells, which results in their death or in a changed function. This may bring about prema- ture aging and the development of malignant neoplasms. Genetic effects of radiation of germ cells are responsible for spontaneous abortions, still-births, the birth of chil- dren with congenital malformations, and other diseases. These effects are not limited to one generation, but will be passed down from generation to generation. Mutations practically always exert a negative influence upon such a highly adapted organism as a human being. Though it is not yet possible to evaluate all the consequences of radia- Scientist at work in the USSR. Preventive strategies in the field of public health provide many measures for preserving and improving human health. Photo WHO/ILO tion damage for human heredity, from what is known certain conclusions can be drawn. Whatever genetic effects may result from the use of nuclear weapons, they must inevitably have serious consequences not only for the generation that suffers directly but also for many future generations. Our present generation has all the potential at our disposal not to pass any additional load of hereditary pathology to our descendants. Indeed, the achievements of modern genetics offer us the tools with which we may gradually rid humanity of the heavy burden of hereditary diseases. Pre ventive strategies in the field of public health provide many measures for controlling diseases, and for pre- serving and improving human health. This is why genetics is becoming more and more a fundamental basis of mod- ern medicine. Its findings make it possible to unite the wide social aims of public health with an individual approach to the patient, and that— after all—is the supreme goal of both geneticists and physicians. ■ WORLD HEALTH, Dec. 1983 19 The seat of pleasure and pain Mental and neurological disorders are common in all communities and cultures. Over the last twenty-five years, advances made in biomedical research have contributed enormously to our knowledge of the causes, prevention and management of these disorders by B. 0. Osuntokun he nervous system, particularly the brain which contains ten thousand million cells and is of unequalled complexity in its 100 mil- lion million cellular interconnections, is the supreme organ of the body, and the seat of the mind and soul. Hippo- crates, the father of medicine, wrote 23 centuries ago, "The source of our pleasure, merriment, laughter, amuse- ment, grief, pain, anxiety and tears is none other than the brain, which en- ables us to think, see and hear, and to distinguish the ugly and the beautiful, the bad and the good, the unpleasant and the pleasant. The brain is the seat of madness and delirium, of the fears and frights which assail us often by night and sometimes by day ; it is where lies the cause of insomnia and sleep-walking, of thoughts that will not come, of forgotten duties and of eccentricities." Biomedical research has contri- buted enormously in the last 25 years to our knowledge of the causes, pre- vention and management of many mental and neurological disorders. However as John Donne puts it, the greater the island of knowledge, the longer the shoreline of the unknown : there are still enormous gaps in our knowledge about many of these disor- ders, indicating the need for continu- ing research. Mental and neurological disorders are common in all communities and cultures. From community-based studies carried out in the last 25 years, of the population at risk, it is known that on average five to ten per cent suffer from various mental disorders. Schizophrenia, an illness characterised by fundamental disturbances in per- sonality, thinking, emotions, be- haviour, interests and relationship with people, occurs in about one per cent of the population. Depression in varying severity may afflict about two per cent or even more. At least five per cent suffer from other forms of psychoses (severe mental derange- ment involving the whole personality) or intellectual deterioration due to structural changes in the brain, and mental subnormality (arrested mental development), whose many causes in- clude inherited abnormalities. Ten to fifteen per cent of the popu- lation suffer at one time or the other from neuroses which manifest them- selves commonly as abnormal anxiety states, phobias, morbid irresistible ob- sessions and the mental dissociation syndromes of the hysterical. The an- nual incidence of suicide and attemp- ted suicide ranges from one to four per 10,000 in various communities, but it is commoner in some Western coun- tries and in people in higher social classes above the age of 60 years. Psychosomatic (bodily) diseases in which emotional factors have a de- monstrable role in aetiology (bron- chial asthma, peptic ulcer, irritable co- lon syndrome, essential hypertension, migraine, menstrual disorders and so on) are also very common. Epilepsy, characterised by recurrent loss of consciousness, convulsions and other involuntary movements, abnor- mal sensations or perceptions, and alteration of behaviour, affects as many as two to five per cent of the population in developing countries, and is four to six times more common in those countries than in developed countries. Stroke, or apoplexy, pro- duced mainly by diseases affecting arteries supplying blood to the brain, is among the three commonest cause of death (together with heart diseases and cancer) in developed countries ; it is becoming increasingly common or recognised in developing countries. In the last decade the frequency of stroke has declined in some developed coun- tries, notably the United States of America and Japan. Stroke may affect as many as five per cent or those above the age of 65 years, among whom it is most common, although no age group is immune. Migrainous headaches occur in five to ten per cent of people in both "sophisticated" and "unsophisti- cated " communities. Infectious dis- eases such as meningitis (one type due to meningococcus often occurs in viol- ent epidemics especially in sub-Saha- ran Sahelian countries of Africa), the encephalitides (due to viruses), poliomyelitis, trypanosomiasis, cere- bral malaria, leprosy and many other diseases which also attack the nervous system still afflict millions of people especially in developing countries. Nutritional neurological disorders (in- cluding malnutrition which is mainly due to lack of food, poverty and the associated psycho-sensory depriva- tion) may occur in 10 to 40 per cent of some communities, especially in chil- dren of pre-school age in developing countries. Degenerative diseases (including damage to certain specific parts of the nervous system, as occurs in such conditions as multiple sclerosis), and congenital diseases of the nervous system—in many the cause is obscure and some are inherited—constitute 20 WORLD HEALTH, Dec. 1983 common causes of disability and premature deaths. Trauma-induced diseases (especially head injuries) are also common. Pain, a concomitant of many diseases, is a common cause of misery, vitiating the quality of life. And dementia, characterised by progressive intellectual deterioration, impairment of memory, reasoning, judgment, comprehension, conceptual thinking and behaviour is a common disease of elderly people, but may occur in middle age and often lead to premature death. Basic biomedical research Some regard the brain as more than an organ, rather a series of organs with differences in structure, functions and biochemical composition. We now know that the cells and functional parts of the brain communicate with one another and transmit messages within the brain and to other parts of the body through chemicals called neurotransmitters, of which more than 40 have been identified. These neuro- transmitters, which include acetyl- choline, catecholamines, amino-acids, peptides (simple chains of amino-acids or their derivatives), endorphins and opiods (innately produced substances involved in pain perception and other neurophysiological activities), to- gether with the neuroendocrine sys- tem, closely interact to ensure the normal functioning of the brain, the body, the defence system against dis- eases and also the adaptive system against stress. We now understand better the memory processes, pain perception, the basis of emotions and certain fun- damental drives. This has stimulated the development of valuable hypoth- eses about the underlying biochemical mechanisms in mental and neurologi- cal disorders. For instance, memory loss in Alzheimer's disease and senile dementia is associated, inter alia, with loss or reduction of neurones in the cerebral cortex which contain acetyl- choline ; Parkinson's disease is predo- minantly due to loss of basal ganglia neurones which contain dopamine. Excitatory and inhibitory chemical substances have been identified in the hypothalamus, which constitutes an important part of the brain system, responsible for basic drives such as emotions, hunger, sex, thirst, and in turn influenced by higher brain centres. These substances stimulate or inhibit release of trophic hormones by About five per cent of the population, any- where in the world, suffer at one time or another from abnormal anxiety states or other neuroses. Photo WHO/P. Almasy the pituitary gland (at the base of the brain), which in turn governs the nor- mal functioning of a large number of organs, such as the thyroid, pancreas, adrenals, kidneys, and the sex glands (testes and ovaries). The functional unity of the mind and the body is now better understood. One of the greatest contributions of biomedical research in the last 25 years to the management of mental and neurological disorders has been in developing drugs for effective treat- ment of psychoses, anxiety disorders, epilepsy and Parkinson's disease. Schizophrenia is treated with neuroleptics such as chlorpromazine, haloperidol and other drugs which antagonise or inhibit dopamine recep- tors. Patients with anxiety neuroses benefit from treatment with tranquil- lisers or tranquillo-sedatives such as diazepam (a benzodiazepine) ; the benzodiazepines are now known to bind to specific naturally occurring receptors in the brain and exert part of their beneficial action through this mechanism. A recent development in the treatment of epilepsy is the use of drugs such as sodium valproate which mimics the action of a natural in- hibitor. Parkinson's disease is now more efficaciously treated than before with laevodopa, usually combined with an inhibitor of the enzyme which, outside the nervous system, breaks down dopamine. Through basic biomedical research, we now have a better understanding than before of the neurophysiology of pain. Pain perception involves the modulatory role of neurotransmitters WORLD HEALTH, Dec. 1983 21 such as endorphins, opiods, enkepha- lins, catecholamines and substance P. The gate-control theory of pain, first enunciated in the 1950s, postulated that there is control, at the level of the spinal cord, of transmission of stimuli which convey pain sensations into con- sciousness. Stimulation of fine small nerve fibres in the peripheral nerves opens the gate ; stimulation of large fibres (as may be induced by rubbing the skin) closes the gate, which of course is also subject to the influence of parts of the brain, including those involved in emotions, and of neuro- transmitters. The development of per- cutaneous stimulation, which prefe- rentially stimulates the large fibres, to obtain pain relief was based on this theory. Acupuncture anaesthesia may also be related to the gate-control theory and to the demonstrated re- lease of endogenous suppressors of pain, such as opiods and endorphins. The new technique of using mono- clonal antibodies has helped to eluci- date and identify the antigenic structure of the brain. This is likely to lead to the discovery of various other Locating a suspected brain tumour by mod- ern clinical technology at a hospital in Sao Paulo, Brazil. Photo WHO/PAHO substances, which may further en- lighten us about functions of the brain in health and disease. There are excit- ing therapeutic possibilities and hopes of being able in the future to restore the normal functions of the nervous system, for instance, in patients who are paralysed by stroke and trauma. Clinical research The epidemiology of stroke has in many communities identified the ma- jor risk factors ; the main treatable or preventable ones are hypertension, heart disease and transient ischaemic attacks (TIAs). The frequency of TIA evolving into a major stroke is reduced significantly by treatment with aspirin (in men, but not in women) and less so by other drugs, such as sulphin- pyrazone and dipyridamole which have now replaced anticoagulants such as warfarin. New methods of improving the ac- curacy of diagnosis, especially electro- encephalography (EEG) telemetry combined with videotape recording, have contributed to the management of epilepsy. More importantly, drug treatment has been made more ration- al through the monitoring of blood drug levels with the aim of achieving the maximum beneficial therapeutic level in each individual patient, thus avoiding overdosage, which in itself may account for poor control of seizures. Leprosy, a bacterial infection of peripheral nerves and skin, afflicts 12 million people, mainly in the develop- ing countries. In the mid-1970s, the mycobacterium leprae, the causative organism, began to show resistance to dapsone, which had been the sheet- anchor of treatment. Multiple drug therapy, combining dapsone, rifampi- cin, clofazimine, ethionamide or pro- tionamide, has now become the stan- dard effective regime. An efficient health service delivery system is needed in developing coun- tries to combat the scourge still consti- tuted by such almost totally prevent- able diseases as poliomyelitis and tetanus, effective vaccines for which have been shown recently in Mali and Nigeria to contain, terminate and pre- vent epidemics of meningococcal meningitis. The aetiology of the commonest demyelinating disease of the nervous system, multiple sclerosis (MS), con- tinues to elude us and has been a graveyard of many hypotheses. One recent plausible hypothesis suggests that MS is due to abnormal responses of the " mature " immune system of the adult to such agents as measles virus, Epstein-Barr virus and others. In areas of Africa where MS is ex- tremely rare or unknown, for instance, these agents infect nearly 100 per cent of the population of children, mostly before the age of seven years, while the immune system is relatively imma- ture. Those who survive subsequently become immune to such agents. No effective specific treatment of MS is available, although recent trials of in- tensive immunosuppression with drugs (including azathioprine and steroids) and treatment with hyperbaric oxygen have shown marginal benefits. In the last decade, new imaging techniques such as computerised to- mography have improved the accuracy of diagnosis in neurology. The useful- ness of these new but expensive tech- 22 WORLD HEALTH, Dec. 1983 A mentally retarded girl in Ecuador. Re- search into the functions of the brain in health and disease offers us exciting therapeutic possibilities and new hopes in the future. Photo WHO/L. Solmssen nologies in investigation and diagnosis is undoubted, especially in accurately diagnosing types of stroke, intracranial tumours, cerebral atrophy, hydro- cephalus, demyelinating diseases, epilepsy and diseases of muscles. It is, however, unlikely that they will be available for use in the near future in many developing countries, where priorities in health care delivery are of a different nature. Psychiatric research Psychiatry, arguably the most dif- ficult branch of medicine, deals with the study, recognition, treatment and prevention of mental abnormalities and disorders—all types and degrees of mental ill-health, however caused, and those in which psychological phenomena are important as causes, symptoms, signs or curative agents. Classification is difficult, objective physical signs and laboratory tests are virtually absent, and considerable con- fusion has ensued from attempts to divorce psychiatry from the parent science of medicine and to link it exclusively to sociology, cultural an- thropology and psychology. wHo in recent times has been particularly ef- fective, in collaboration with other organizations, in stimulating the psychiatrists to agree on classifications and definitions of terms. This has restored some order in a previously chaotic and confusing situation, and has encouraged meaningful research and comparability of findings in the aetiology, treatment and natural his- tory of psychiatric disorders. Research has further elucidated the interrelationship of social factors and psychiatric disorders. Recent studies have focussed on the influence of variables such as social isolation, mo- bility, emigration, urbanisation, socio- economic factors, family structures, social disintegration, and changes in culture, on the prevalence of psychiat- ric disorders. No culture or community investigated has been found to be free of the common psychiatric disorders. There is a wealth of information about the impact on health and disease of psychosocial factors linked to smok- ing, abuse of alcohol, drug addiction and other harmful habits, including reckless driving of motor-cars. How to change or modify people's attitudes so as to reduce these apparent self- destructive tendencies is a major challenge to modern medicine and psychiatry. In developing countries, there is a great shortage of personnel trained in delivering health care and undertaking research in neurology and mental health. But lay people and non-doctor personnel can be trained in short periods to provide satisfactory health care, and to take part in meaningful research to determine risk factors in neurological disorders. It has been shown that psychiatric patients can be successfully treated within, and dis- charged to, the community. Commun- ity services are being developed which will ensure that psychiatry and neurol- ogy units based in hospitals and health centres will serve defined catchment areas, to supplement the contribution of primary health care workers trained to provide first-contact service and care to patients. The days are long gone when neurology was said to be directed chiefly to fruitless differentiation be- tween obscure and untreatable de- generative diseases, and the main role of psychiatry was concerned with act- ing as society's custodian of its degen- erate and dangerous members. The advances reviewed above have, by any standard, been considerable and of direct benefit to millions of people. woo, on the advice of its ACMR, has contributed in no small way to these advances. This has been done directly or indirectly through its ex- pert committees and study groups, by fostering technical cooperation among nations, collaborating with institutions including those designated as special centres, or by promoting and develop- ing international multicentric studies and special programmes such as that on Tropical Diseases Research (TDR). Specifically, WHO's Mental Health Programme has been productive and catalytic in stimulating research into mental health and diseases and neurological disorders, especially in developing countries. ■ WORLD HEALTH, Dec. 1983 23 Strengthening of national institu- tions, including training, to increase the research capabilities of the tropical countries affected by these diseases. billion people living in the tropical regions of the world are cut off from the benefits of social and economic progress, and the diseases of the tropics are responsible in large part for their plight. When not suffering from one of these dis- eases—and often from several at once—the people of these regions are constantly threatened by them. Death comes early to many and, among those who do survive to become adults, millions are never healthy enough to be able to achieve social and economic self-reliance. In parts of tropical Africa, the sight of a child leading a line of men blinded by the parasitic disease called on- chocerciasis, or river blindness, is a common one. In fact, in some villages, this disease has brought total blindness to as many as 15 per cent of the adults. Some parasitic diseases, such as malaria, are not only evading control but also spreading to hitherto unaf- fected communities. The struggle to control malaria is being defeated by rapidly increasing resistance of the parasites to available drugs and resistance of the mosquito vectors to insecticides. New and improved tools to control disease, and a solid foundation of scientific and technical manpower in the tropical countries to apply them effectively, are critical to the task of easing the immense burden of disease borne by people who live in the tropics. In response to this need and in recognition of the primary roles of research and training in solving the problems, who, the United Nations Development Programme (uNDP) and the World Bank have joined forces in a unique venture in international tech- nical cooperation. This Special Pro- gramme for Research and Training in Tropical Diseases (TDR) has two in- terdependent objectives : Research and development of new and improved tools to control six major tropical diseases—malaria, schistosomiasis, filariasis, trypano- somiasis (both African sleeping sickness and Chagas' disease), leish- maniasis and leprosy ; and Research activities of the Special Programme focus upon clear and prac- tical goals, and the strategies for at- taining them are worked out with the technicians and scientists in the tropics who actually face the problems. Early results of Special Programme re- search, which started in 1977, include progress in : drug treatment for malaria, schis- tosomiasis and filariasis ; control of the disease vectors of onchocerciasis and malaria, through biological rather than chemical means ; developing and testing of a possible vaccine against leprosy ; identification and production of the antigens required to develop a vac- cine against malaria ; and simple and accurate field tests for the diagnosis of malaria, leprosy and African trypanosomiasis. Until quite recently, nearly all such research took place in developed countries, or was carried out by the nationals of those countries. However, the Special Programme is changing that. A deliberate effort is made to have research carried out in the coun- tries which face the problems of tropi- cal diseases, and by their own scien- tists. This is done by working with those countries in the context of their national programmes of research and development. Thus the percentage of TDR project support going to tropical developing countries rose from 29 per cent in 1977 to 54 per cent in 1982. This has come about primarily through institution strengthening and training support, awarded exclusively to in- stitutions and scientists of developing endemic countries. Over 450 individ- ual training grants have been awarded and 76 national institutions are being strengthened. The Special Programme also recog- nises that there is no substitute for the expertise and facilities of industry in the search for and the production of The burden of tropical diseases by E. A. Gregory 24 WORLD HEALTH, Dec. 1983 A laboratory technician at work in a malaria research centre in Nigeria. Photo WHO/R. da Silva new drugs and vaccines. Full use is made of this expertise and, to comple- ment it, the Special Programme and wHo coordinate and catalyse the rapid pharmacological and clinical evalua- tion of new agents throughout the world. This minimises the delay be- tween pre-clinical screening and clini- cal use and reveals the potential mar- kets for such products. To date, such collaborative endeavours have been productive in the fields of chemo- therapy for malaria, filariasis (oncho- cerciasis) and schistosomiasis, as well as in biological control of the vectors of malaria and onchocerciasis. From the beginning of technical ac- tivities in 1977 until 31 August, 1983, the Programme supported 1,887 pro- jects in 95 WHO member countries ; and some 3,000 scientists from 122 WHO member countries participated in the planning, implementation, opera- tion and evaluation of the Programme. The cost thus far, in direct support to WORLD HEALTH, Dec. 1983 national scientists and institutions, is US$ 98 million. During its six years of operation, the Programme has received remarkable support from scientists and institutions throughout the world, and has created unprecedented expectations in the de- veloping countries. Now, increased and sustained financial support is vital, if the scientific opportunities which have come about as a result of re- search progress are to be exploited and the goals of tropical disease con- trol realised. The Programme's research and de- velopment efforts concentrate on the most promising results to date, and scientists from all over the world will exploit the new opportunities to bring better tools for disease control to the point of practical application in the field. Here is an overview of a few of the opportunities before the Programme : Malaria : The main thrusts of malaria research are in drug and vac- cine development. The rapid spread of drug-resistant parasites has created an emergency need for new drugs and TDR-supported scientists are moving forward at four levels : field ap- plication—the clinical testing of a new and effective drug, mefloquine, will be completed in late 1983 or early 1984 ; development—mefloquine in combi- nation with other drugs (to delay the onset of parasite resistance) will undergo clinical testing ; chemical synthesis—compounds based on totally different chemical formulations, in particular the traditional Chinese medicine, quinghaosu, and its ana- logues, will be synthesised and tested for effectiveness ; and monitoring for resistance—new micro-kits for moni- toring parasite resistance to drugs will undergo field evaluation. During the past five years, there has been more progress towards a vaccine against malaria than during the pre- vious fifty, and the possibility of an effective vaccine has moved from a concept viewed with scepticism to a real possibility. Genetic engineering and hybridoma technology have pro- vided the means through which the antigens responsible for stimulating 25 immunity can now be isolated and produced on a large enough scale to enable scientists to move ahead rap- idly towards the actual development of possible vaccines. Many questions re- main, but preliminary trials in animals are foreseen in the near future, and trials in humans are a possibility within the next few years. These oppor- tunities must be followed through as quickly as possible. Schistosomiasis : The tools available for the control of this disease have changed dramatically over the past five years. A number of new, effective drugs developed by the pharmaceut- ical industry are now at the stage of application, and their effectiveness at the level of village health services must be assessed. New immuno-diagnostic tests are being developed to comple- ment this work, and research on the development of a possible vaccine will be pursued. Filariasis : The most urgent need in this family of diseases is for new drugs to treat river blindness (onchocer- ciasis). Through an international net- work of collaborating laboratories, the possibilities of developing such drugs have increased over the past five years. The discovery of effective ani- mal screens revealed a number of promising new groups of chemical compounds. This, along with the ac- tive collaboration of the Onchocer- ciasis Control Programme and the re- surgence of interest by pharmaceutical companies in developing drugs against this disease, has created the oppor- tunities and the environment for suc- cess. These must now be followed up. Leprosy : Leprosy continues to be a major public health problem in most developing countries, where health services are facing increasing resist- ance of the leprosy bacillus against dapsone, the most commonly used drug. Through major support from TDR, scientists have developed a poss- ible vaccine against this dreaded dis- ease. However, due to the very long period of time before the disease reveals itself in man, trials of a poss- ible vaccine will take at least five and probably closer to 10 years to com- plete. And to obtain significant and valid results, such trials must be plan- ned with great care. The first phase of testing is already under way, but the answer to whether the vaccine does indeed prevent leprosy will come only after years of sustained scientific work. Other opportunities : The several thousand publications on the scientific work supported by TDR reveal a host of opportunities which may lead to new tools for disease control. To take advantage of this new knowledge, the scientific community planned the Spe- cial Programme with great care. All components are linked together so that progress in one part of the Pro- gramme can be transferred to others wherever applicable. Progress of wide applicability frequently comes from the common areas of epidemiology, the social and economic sciences, the basic biomedical sciences and the biological control of vectors. Air view of the Ndola hospital complex, the Zambian Tropical Diseases Research Centre, which collaborates closely whit TDR. Photo WHO TDR-supported efforts in vector con- trol research have resulted in the large-scale field application of Bacillus thuringiensis, serotype H-14, to con- trol the vector of onchocerciasis. This agent will continue to be improved and readied for large-scale production and widespread application in many tropical countries. Other biological agents, especially those which recycle themselves in their natural environ- ment, will also be evaluated. A five- minute diagnostic test for African sleeping sickness (trypanosomiasis) has been developed and is ready for wide application in the field. In concert with the above efforts, the Programme will continue to stimu- late the tropical countries afflicted by these diseases to assume a leading role in the research required to identify and solve their health problems. This is being done together with national authorities, through the training of nationals and the strengthening of nat- ional institutions, according to nat- ional plans. For it is only through national efforts that the new tools will be applied to the task for which they are designated, the prevention of dis- ease and the healing of the sick. While the development of individ- ual institutions remains a major focus, activities will be expanded to stimulate even greater collaboration between institutions, to create a network of research and research training institu- tions in the countries where the dis- eases are endemic. More than 140 scientists have already returned to their home institutions in tropical countries after training. Interaction between Research Capability Strengthening and Re- search and Development is vital to the success of the Special Programme. Many research projects provide im- portant training opportunities for sci- entists and technicians from develop- ing countries. Conversely, group train- ing activities involving scientists from a number of countries, grants to visit- ing scientists, and support to institu- tions all enhance the opportunities for research. This coordination, especially in epidemiology and field trials, pre- pares scientists, technicians and in- stitutions for the final but most impor- tant step — use of the new tools to improve health and life among the peoples of the tropical countries. The Special Programme depends entirely upon voluntary contributions. From 1975 until 30 June 1983, 27 governments (including those of 11 developing countries) and eight other organizations, together with UNDP, the World Bank and WHO, contributed over US$ 133 million to the Pro- gramme. However, TDR is a long-term endeavour since it takes many years to bring a drug or vaccine from the laboratory to the village family which requires it. Long-term endeavours re- quire long-term support. Such support must come both from the tropical developing countries struggling to control the diseases and from others dedicated to the welfare of mankind. ■ 26 WORLD HEALTH, Dec. 1983 Behaviour and health by David A. Hamburg and Avery Russell 3 f we are to improve the health of the world over the remainder of this century, we must accord high priority to the relationship between health and behaviour. Historically, be- haviour has been one of the most neglected areas of inquiry in the life sciences. This changed during the twentieth century as the methods of science increased our understanding of why we act the way we do. Behaviour plays a crucial role in the survival and reproduction of the more complex organisms such as primates—above all in the human primates. It has evolved as the principal means of relating the organism to its surroundings, dealing with vital matters such as food, water, shelter, sex, defence, and child- rearing. Behaviour, we are coming to under- stand, profoundly influences our health, for better or for worse ; and the society we live in can make it easier or harder for us to change behaviour for better health. The world's future turns out to be far more heavily behaviour-related than we understood even a decade ago. Modern science and technology have made powerful contributions to our knowledge on how to meet the basic adaptive needs of food, water, shelter and other factors essential for our survival and reproduction. Yet we have been killing ourselves : inadver- tently for the most part, knowingly to some extent, and regretfully ; but kill- ing ourselves nonetheless. The heaviest burden of illness in the technically advanced countries today is related to individual behaviour, especially the long-term patterns of behaviour often referred to as "life- styles." In the United States, it is estimated that 50 per cent of mortality from the ten leading causes of death can be traced to health-damaging be- haviours like smoking, drinking, eat- ing too many calories and too much fat, and inactivity. Other behaviours highly relevant to health and disease —both mental and physical— are re- sponses to the stresses of life events. The health problems of the develop- ing world are no less related to be- haviour, which is involved not only in mental illness but also in nutrition and A makeshift shower-bath in a crowded street of South-East Asia. Attitudes to hygiene have a direct bearing on health. Photo WHO/P. Almasy sanitation and family planning as well as alcohol and smoking and vehicle use. Thus the lifestyle factors iden- tified as relevant to developed coun- tries are also relevant to developing countries. Smoking, for example, a major cause of both cardiovascular disease and cancer and a contributor to many other chronic illness condi- tions, is on the rise in developing countries. Alcohol use is also on the increase. Diet, in the form of malnutri- tion, probably has its major impact in contributing to the most common form of illness in developing countries : in- fectious disease. The problem of mal- nutrition is of course directly related to the availability of food and to the political and social factors which pro- duce food shortage, but even when food is available it may not be used in the diet in ways appropriate to pre- venting malnutrition. Can developing and developed countries alike, through research and community-based education, learn to adopt health-promoting behaviour and avoid health-damaging be- haviour? This is one of the frontiers of world health today. The experience of several countries gives reason for hope in this regard. Especially in the last decade, a major effort has been made to address the relationship between health and behaviour. In part, this has been done through informal educa- tion, through the media and through free institutions with their openness to new evidence. But this effort has also been carried forward by vigorous scientific inquiry. One important ap- proach has used information on risk factors in the population to prevent cardiovascular and other diseases. The ability to change risk factor be- haviour in favour of health-promoting practices has been clearly demon- strated. Health promotion research is con- cerned with the education of individ- uals, communities, and governments. It involves the search for ways to increase self-reliance and mutual aid in fostering health. Cardiovascular risk factor research in several countries provides one useful model in health education, since it started with a care- ful survey of beliefs and knowledge, used a variety of known behavioural science principles and techniques, and was able to show visible improvements in health. There is a great need to strengthen the capabilities for research on health and behaviour in the developing world— research that is relevant to the characteristics of the countries, with special emphasis on making public education effective in fostering pat- terns of living that protect against major risk factors. During the past several years, WHO's WORLD HEALTH, Dec. 1983 27 Advisory Committee on Medical Re- search has been working toward an expanded programme of research in biobehavioural sciences and mental health. The strengthening of know- ledge in this area is viewed as a fundamental underpinning for medi- cine and public health—physical as well as mental. The work begun by a sub-committee of the ACMR in 1979 has been carried forward by a Scien- tific Planning Group in collaboration with the secretariat of the Division of Mental Health, WHO. A series of three workshops to plan a research agenda is now under way. These workshops deal with critical issues for the future of world health : psychosocial aspects of primary care, with special reference to maternal and child health ; adaptation to rapid socio-technological change ; alcohol problems. In addition, a monograph is being prepared on Health and Behaviour in Developing Countries, delineating major problems and scientific approaches to those problems. These steps logically lead The hardships of urban poverty are reflected in the faces of this mother and her child in a Latin American city. Rapid social change, migration, disturbances in family life all take their toll. Photo WHO/PAHO/J. Vizcarra toward the building of new research capability in developing countries to tackle these important and neglected problems. A few resource centres in develop- ing countries would provide a useful focus for biobehavioural science perti- nent to disease prevention and health promotion. Ideally, efforts should be made to build on existing institutions in developing countries, but it may be necessary to establish new ones if an expanded programme in mental health and biobehavioural sciences is to emerge. Such centres would involve the training of indigenous health pro- fessionals and behavioural scientists to work with their own populations and to carry out rapid, culturally-sensitive studies of communities as needed. Ad- ditionally, the centres would be inti- mately coordinated with the public health structure of the country or region. Besides building an infrastructure for research, it is important to estab- lish exchange programmes and col- laborative relationships that not only allow local research workers to de- velop their skills but also to keep them in touch with advances in health re- search in technically advanced societies (while not encouraging a "brain drain" !). Collaborative re- search across national boundaries is especially needed in this regard, and will be mutually beneficial for de- veloping and technically advanced countries. An important precursor for an ex- panded research programme in de- veloping countries is systematic assess- ment of the burden of illness that is directly related to behaviour. This burden can be measured in a variety of ways including human suffering, dis- ability and losses to the economy. A major category of this behaviour- relevant burden of illness is mental illness. Preventable childhood infec- tions may have severe after-effects on the brain, especially in the context of malnutrition in developing coun- tries. Common and serious disorders such as epilepsy and stroke require attention, and the latter will increase with the expected aging of the population of the world. Another behaviour-related category in de- veloping countries involves emotional stress syndromes associated with the severe dislocation of family life result- ing from rapid socio-technological changes, rapid urbanisation, migra- tion, and other factors. Since about half the population of developing countries consists of chil- dren and adolescents, those countries would benefit from research into the prevention of early damage to the brain, and into behaviour and health generally. Rapid social change and its effects on family disruption and social disorganization can strongly affect de- velopmental processes. Other prob- lems calling for attention include nu- trition (including the effects of changes in breastfeeding customs) ; child neglect, abuse and understimu- lation ; effects on mental and physical health of changes in family structure that occur with increased industrialisa- tion, migration and uprooting ; at- titudes to hygiene in the context of 28 WORLD HEALTH, Dec. 1983 A victim of malnutrition in the Caribbean area. Nutrition (including changes in breast- feeding customs), child neglect and child abuse—these are among the subjects that cry out for further research. Photo WHO/PAHO/J. Vizcarra drinking-water supply and sanitation ; attitudes to family planning ; and the effects of mass migration (both within countries and across countries). How can such issues be presented in a way which arouses and sustains the motivation of individuals and com- munities to adopt health-promoting behaviours ? It is important to identify programmes and practitioners which have succeeded, and to analyse ele- ments of that success which may be transferable, with appropriate modifi- cation, to other situations and cul- tures. Community-based efforts to change behaviour for health are rapidly elicit- ing worldwide interest, and more at- tention is finally being paid to building a scientific basis to enhance their ef- fectiveness. How is it possible to change behaviour for health without coercion ? This involves analysing cul- tural values, and determining the specific knowledge deficits in a com- munity with respect to health. It in- volves social learning, including the skills necessary to maintain health- promoting behaviour. It involves learning how to " exploit" motivations— for example, those of pregnant women to provide the best protection and care for their babies. It involves finding the channels through which members of a particular population may understand, and take seriously, information perti- nent to their own health. These com- munity-based efforts promote major lifestyle changes that are difficult to achieve, and research is necessary to clarify the conditions under which the changes actually occur, for example in preventing heavy smoking or heavy alcohol use, and in improving nutri- tional, family planning and sanitation practices. Several key elements have been identified in research into major be- havioural changes affecting health : Getting the facts straight : accurate biomedical and behavioural informa- tion about risk factors in a community. Clarifying the psychosocial obsta- cles to health-promoting behaviour change. Using modern behavioural and so- cial sciences, including communica- tions research, to learn how to reach a given population in a meaningful way, so that opportunities for promoting health may be fully understood by the population. Employing the social sciences and media strategies in fostering commun- ity-based participation conducive to changing behaviour for health. Evidence accumulating in technical- ly advanced countries demonstrates that carefully conceived and de- veloped media programmes, particu- larly when tied to community pro- grammes, can have an effect in alter- ing health-damaging behaviour. We know too that education programmes can have a major impact on nutrition practices, decreasing malnutrition and thereby increasing resistance to infec- tions. Education can play a role in helping to reduce problems associated with mental disorders, by teaching people to understand mental illness and providing guidelines for action. Media programmes are already being used to help individuals to learn how to cope with stressful situations and life-management skills. A major thrust of enquiry in de- veloping countries therefore should be to assess which principles and techni- ques of conveying health information in the developed world are applicable to their own conditions, and how they can be adapted to specific cultures. If carefully designed, controlled and evaluated, these programmes could serve as models to help to stimulate interest in community-based educa- tion and promote our understanding of how such studies can be conducted and applied in still other developing countries. We are experiencing a revolution in information. It is now possible for even the most remote village in any part of the world to receive informa- tion relevant to health. This revolution can have a great impact on health in developing countries. We must bring the strengths of modern science to bear on finding ways of making such information useful to all mankind. ■ WORLD HEALTH, Dec. 1983 29 'Here Comes the Breakaway Generation' This symbol of a little human figure breaking a cigarette in two is aimed at persuading Canadians to say: " Here com- es the breakaway generation." That is the goal of a newly launched programme to en- courage people (primarily but not exclusively young people) to break away—not only from the smoking habits of older generations, but also from the pressure exerted on them by their peers to light up. The "ultimate aim is to pro- duce a generation of non- smokers," according to R. A. Draper, Director-General, Health and Welfare, Canada. Already two-thirds of Canadians do not smoke. Overall, they are smoking less than before—the figure is down to 10 per cent since 1965—with one notable exception. The rate for females aged from 15 to 19 is up, from 20 to 26 per cent. The campaign, based on a successful Swedish precedent, is scheduled to last up to 20 years. Says Monique Begin, Health and Welfare Minister: "We want to speed up this trend towards freedom from tobacco". Educational material is available in a kit from Lysane Ouimet, Tobacco Programs Officer, Health Promotion, Jeanne Mance Bldg., Ottawa, K1A 1 B4. ■ 0410 04141 00 0 000 000 0.0 *50 000 0000041 0041 000 000 ...... 000 04o* 000 0410 0041 000 0410 0041 000 000 000 41 00 0041 000 000 000 000 000 000 000 000 41410 0410 0041 0041 000 000 000 OOOOOO 000 000 000 000 See 0•0 000 000 000 000 4100 000 000 000.00 004/ ••• 000 0000041 ••• ••• evening. Dispensing Medicines, Artfully A part of the booklet "How to Store Supplies" instructs the primary health care worker how to dispense medicines to those who cannot read. It is done through illustrations such as these : 1 tablet four times daily: at morning, 1/4 tablet twice daily: morning, noon, sunset, evening. I , %MI6 0 0 1 capsule three times daily: morn- 2 teaspoons twice daily: morning, ing, noon, evening. evening. Artwork: The Handbook for Drug Retailers and Wholesalers, Nepal/UNICEF 0 0 ■ :0 1 ) 411111■ '. CC) 'How-To' Booklets Show How to Keep 'Cold Chain' Cold This is, of course, no way to run a store. But, while not typical, the mess shown here is found often enough in developing countries to be worrying. It represents, for WHO's Expanded Programme on Immunization, a fail- ure in the "cold chain" system, the name given to the long line of checks, during storage and distribu- tion, of vaccines from manufacturer to health centre. The failure may be technical or logistical — a badly-maintained re- frigerator, out-of-date vaccines, or simply a shortage of supplies—but here it is, plainly, the collapse of store-keeping. Whatever the reasons, they adversely affect the efficacy and safety of vaccines and ultimately health. Such situations led WHO to set-up courses aimed at training workers in "how-to" techniques—how to cope with breakdowns or, better still, how to prevent them. As the goal of the immunization programme is the protection of children against six diseases— measles, polio, tuberculosis, diph- theria, whooping cough and teta- nus—by 1990, training began with how to estimate monthly require- ments, logicallyenough, of vaccines. But officials conducting the course were so often questioned about the care and handling of other things besides vaccines that, virtually by popular request, they decided to offer more by way of training. After all, the principles are similar, they reasoned, for ordering chloroquine tablets against malaria, oral rehydration salt packets against diarrhoeal diseases, or contracep- Photo: WHO/James Cheyne tives, such as the pill, injedables, intra-uterine devices and condoms. Everything is essentially predicated on the population served at a health centre, generally figured at 50,000. Whether for vaccines or for es- sential drugs, the principles of good store-keeping are basically identical ; namely that store-keep- ers should avoid sudden shortages, or overstocking, and that they should keep supplies away from damaging light, heat, or air. They should also pay heed to instructions on labels, for example the expiry date of drugs. In short, there was enough in common to expand the training courses. Out of the experience gained have come two dozen " how- to" booklets—how-to store and dis- tribute supplies ; how-to maintain kerosene, gas and compression re- frigerators, with tender loving care, and in good repair; and so on. They appear in a series entitled " Logis- tics and the Cold Chain for Primary Health Care" (see below). Jargon- free, and averaging some 15 to 20 pages, they are available at no cost. With the range of choice consid- erably widened, it is now possible for participants at workshops to select for themselves, a la carte, what skills they would like to brush up on, or to acquire, during training. ■ Donors Needed for Materials, Machines in Radiation Medicine Radiologists in industrialised countries please contact WHO's Radiation Medicine unit if able to donate teaching materials, equip- ment, and machines. That appeal was made during the European Congress of Radiology held re- cently in Bordeaux, and spelled out these requirements : Needed : Slides, video-tapes, films, viewing boxes, darkroom ac- cessories, teaching files, journals, textbooks. Intended recipient : a diagnostic radiology centre to open in 1984 in Nairobi, Kenya, established by the government, WHO and the Interna- tional Society of Radiology, Berne. To be used to train students from English-speaking African countries, so teaching materials sought must be recent, and equipment in good working order. At present there are only 17 diag- nostic radiologists in all of Africa south of the Sahara (not counting South Africa). The new centre plans to train from 10 to 15 each year. Under consideration, a similar centre for French-speaking Africa. Needed : Used cobalt therapy machines "with a lease of working life" still left in them. Intended recipients : radiothe- rapy departments in Africa, South- East Asia and the Western Pacific. To be used to treat cancer pa- tients. Because of the acute shor- tage of such machines, there is, thus far, little chance of therapy in most developing nations. At present there is only one cobalt machine for an estimated five million to twenty million people in the Third World. The figure for Europe, by way of comparison, is one for every 200,000 to 300,000. The first machine shipped under this programme, sponsored by WHO and the International Atomic Ener- gy Agency, Vienna, is a Theratron 78. It has been donated by the 30 WORLD HEALTH, Dec. 1983 University of Texas, Galveston, to the Tanzanian Tumour Centre in Dar es Salaam, which is being re- furbished to become an oncology- radiotherapy centre for English- speaking Africa. More such centres are needed. ■ 'If Denmark Forgot To Develop Its Drug Industry...' Their nation would be in the same position as many developing countries are in today "if Denmark had 'forgotten' to develop its phar- maceutical sector," Dr Ernst Lauridsen, Director of WHO's Action Programme on Essential Drugs, suggested to participants at a re- cent meeting of the Danish Medical Association. The consequences of such a lapse of memory, as seen by him would be : That 95 per cent of all their drugs would be procured from abroad, and that from 30 to 40 per cent of the country's health budget would be spent on them. Yet there would be a "chronic shortage of essential drugs." That all drugs would be brand- name drugs and, as a conse- quence, more expensive, with some 400 substances sold under 6,000 names. That drugs would be, on the one hand, obtainable without pre- scription but, on the other hand, would be beyond the means of "possibly up to a half of the popula- tion." That at least 25 pharmaceuti- cal houses would have offices in the country, giving it a ratio of one sales representative for every five physicians. That "physicians would be lav- ishly entertained." That "plenty of free samples would be supplied everywhere– even to medical students" and that "the more entrepreneurial doctors would collect a kick-back from the pharmacy." That it would have a "British- inspired Drugs and Cosmetics Act adopted in 1940" but not updated since then. " In Denmark this would be clear- ly an intolerable situation," said Dr Lauridsen, a Dane himself. "But many developing countries have tolerated the situation for a long time and continue to do so." It was against this background that WHO set up, in 1981, a pro- gramme to provide "safe and ef- fective drugs of acceptable quality at lowest possible cost" to coun- tries. In January 1982, the Interna- tional Federation of Pharmaceutical Manufacturers' Associations indi- cated the willingness of some 50 drug companies to supply 140 es- sential drugs under "favourable conditions." ■ Newsbriefs IMPACT. Under this logo, India opened a two- week-long camp on 2 October, in rural Rhotak, Jaipur and Agra, treating visual, hearing and orthopaedic disabilities. Not only did that date mark the 124th anniver- sary of Mahatma Gandhi's birth, but it also highlighted a recently-launched initiative supported by WHO, UNDP, and UNICEF that focused on "avoidable disablement"–defined, in the larger sense, as including the disability that results from diseases, such as cataract, otitis media (middle ear infection), polio, leprosy and tuber- culosis. India pioneered the use of low-cost techniques for both prevention and treatment of disabilities, and hopes to include such measures in its five-year development plan beginning in 1985. Officials from the three agencies are urging that the country's example be followed by other developing nations. Jobs for the Disabled. At the recently-concluded annual confer- ence of the International Labour Organization, delegates put the finishing touches to a convention on the employment of the disabled, that is intended to benefit those "whose prospects of acquiring, retaining and advancing in suitable employment are substantially reduced as a result of a duly recognised physical or mental impair- ment." A key part of the convention, which now needs to be ratified by countries, provides for incentives to employers hiring the disabled, whose numbers are estimated at some 500 million throughout the world. Malaria Returns to Mauritius. In 1975, malaria came back to Mauritius, just two years after the country was declared free of the disease. Now, seven years later, the number of cases reported has risen eleven-fold, jumping from 55 that year to over 650 in 1982. The resurgence, which finds Mauritian health officials battling an old enemy in a new control programme, is attributed in part to an increase in air and sea traffic, and in part to Cyclone Gervaise, according to WHO's regional office for Africa. 'Store at Room Temperature'. While well-intended, this warning often placed on packets of drugs for export is nonetheless confusing. What exactly is room temperature? The temperature referred to is that of industrialised countries, where drugs come from, that is from 15° to 25° Celsius (60° to 75° Fahrenheit). In developing countries, temperature at home is higher: in the tropics, for instance, from 30° to 35° Celsius (85° to 95° F). Storing drugs at the higher temperature could easily result in spoilage, so storekeepers should pay heed, say officials from WHO's Expanded Programme on Immunization. (See opposite page for related story.) What's Cooking. An issue of WHO's Appropriate Technology for Health Newsletter, just published, is devoted to ways–from compost heap to cooking pot–of increasing the use and improving the nutritional quality of home-grown foods, and thus of bettering health. "Our planetary cooking pot," the editors proclaim as the issue's theme. "The more mixed the better." An article on how to make a compost heap is titled "Heap, heap, hurrah ! " Another recounts the experience of • the Philippines in raising rabbits and growing mush- rooms for profit and for food. Brightly illustrated, the 24-page publication is available, at no cost, in English, French and Spanish. The first Arabic edition is now being prepared. In the next issue The January-February issue of World Health will mark World Health Day 1984–which as usual falls on 7 April. The theme for the Day is Children and Health, and the slogan chosen is : "Children's health : tomorrow's wealth." (As a natural sequel, the World Health Day theme in 1985 will be Adoles- cents and Health.) Authors of the Month Dr T. Adeoye LAMBO is the Deputy Director-General, WHO. Dr Martin KAPLAN, formerly Direc- tor, WHO's Office of Research Prom- otion and Development, is Director, Pugwash Conferences on Science and World Affairs, Geneva. Mrs Tabitha STANDLEY is Senior Sci- entist and Dr Alexander KESSLER is Director, WHO'S Special Programme of Research, Development and Re- search Training in Human Repro- duction, Geneva. Professor Christian DE DUVE is Director, International Institute of Cellular and Molecular Pathology, Brussels. Dr Howard GOODMAN, formerly Di- rector, WHO'S Special Programme for Research and Training in Tropical Diseases, is Director, Tropical Medicine Centre, Johns Hopkins University, Baltimore, Maryland, USA. Professor N. P. BOCHKOV is Direc- tor, Institute of Medical Genetics, the Soviet Academy of Medical Sci- ence, Moscow. Professor B. 0. OSUNTOKUN is Pro- fessor of Medicine (Neurology), University of Ibadan, Nigeria and chaired the 25th Session of the Ad- visory Committee on Medical Re- search held at wit) headquarters in Geneva. Mrs E. A. GREGORY is Communi- cations Officer whith the UNDP/ World Bank/wHo Special Pro- gramme for Research and Training in Tropical Diseases, Geneva. Professor David HAMBURG is Presi- dent of the Carnegie Corporation, New York, and Ms Avery RUSSELL is Director of Publications for the same Corporation. WORLD HEALTH For readers everywhere 1983 Subscription Rates One year Two years Three years US$ 15.— 27. 36. Sw. fr. 25.— 45.— 60.— ORDER FORM Please enter my subscription to "World Health" as follows : One year Two years Three years I enclose cheque/international postal order in the amount of • Name • Street • City • Country • World Health, WHO, Avenue Appia, 1211 Geneva 27, Switzerland World Health is also distributed through the network of international bookstores and sub- scription agencies. For payment in national cur- rencies, please contact your usual bookseller. WORLD HEALTH, Dec. 1983 31 0) 0 -- (I) 0 0 CC —0 Cu sti U) V C C. A new world is in the making, thanks to the efforts of medical research teams working in collaboration all over the globe. Photo WHO/T. Farkas