1515
Consequently there is much to commend a simple, non-invasive, cheap test such as conjunctival impression cytology (CIC), which is rapidly gaining wide acceptance.7-9 There is lack of agreement on several technical details, perhaps the most important being how to interpret as normal or abnormal the
10. Carlier C, Coste J, Etchepare M, et al. Conjunctival impression cytology with transfer as a field-applicable indicator of vitamin A status for mass screening. Int J Epidemiol 1992; 21: 373-80. 11. World Health Organisation. Control of vitamin A deficiency and xerophthalmia. Tech Rep Ser no 672, 1982. 12. Sommer A. Vitamin A deficiency and childhood mortality. Lancet 1992;
339: 864.
appearances of the cellular elements of the bulbar
epithelium. Accompanying eye infections such as trachoma, or irritation due to smoke or dust, may sometimes give false-positive results. The importance of the quality of the cytological preparations has not been thoroughly assessed. Carlier and colleagues1o in France, one of the foremost groups in the use of CIC, have lately proposed a formula for a prevalence criterion for subclinical vitamin A deficiency. As they point out, this was done by WHO for clinical xerophthalmia and the WHO recommendations have been widely adopted.l1 From a meta-analysis of six controlled community-based prophylaxis-mortality trials,
Horse
conjunctival
Sommer12 reports
an
overall reduction in child
mortality of 34%. This meta-analysis has not been published, but even if the percentage is an overestimate it is difficult to escape the conclusion that
marginal or subclinical deficiency of vitamin A is an important determinant of deaths in young children throughout the world. 12 years have now passed since WHO expert group met to consider the control of vitamin A deficiency and xerophthalmia. The grave consequences of the new dimension that has been unearthed mean that another meeting is overdue. High on its agenda should be achievement of a consensus on the detailed technique of CIC and all aspects of its application and interpretation, together with recommendations concerning the control of the marginal deficiency of vitamin A it is designed to detect. Until then, the deceptive simplicity of CIC lays it wide open to abuse. a
1. Sommer A, Tarwotjo I, Hussaini G, Susanto D. Increased mortality in children with mild vitamin A deficiency. Lancet 1983; ii: 585-88. 2. Sommer A, Tarwotjo I, Djunaedi E, et al. Impact of vitamin A supplementation on childhood mortality: a randomised controlled community trial. Lancet 1986; i: 1169-73. 3. Rahmathullah L, Underwood BA, Thulasiraj RD, et al. Reduced mortality among children in southern India receiving a small weekly dose of vitamin A. N Engl J Med 1990; 323: 929-35. 4. Flores H, Campos FACS, Araujo CRC, et al. Assessment of marginal vitamin A deficiency in Brazilian children using the relative dose response procedure. Am J Clin Nutr 1984; 40: 1281-89. 5. Tanumihardjo SA, Muhilal, Yuniar Y, et al. Assessment of vitamin A status in preschool-age Indonesian children by the modified relative dose response (MRDR) assay. Am J Clin Nutr 1990; 52: 1064-67. 6. Blomhoff R, Green MH, Green JB, et al. Vitamin A metabolism: new perspective on absorption, transport, and storage. PhysiolRev 1991;71: 951-90. 7. Natadisastra G, Wittpenn JR, West KP, et al. Impression cytology for detection of vitamin A deficiency. Arch Ophthalmol 1987; 105: 1224-28. 8. Gadomski AM, Kjolhede CL, Wittpenn J, et al. Field trial of conjunctival impression cytology (CIC) to detect subclinical vitamin A deficiency, part II: comparison of CIC with biochemical assessments. Am J Clin Nutr 1988; 48: 695-701. 9. Carlier C, Moulia-Pelat JP, Ceccon JF, et al. Prevalence of malnutrition and vitamin A deficiency in the Diourbel, Fatick and Kaolack regions of Senegal: feasibility of impression cytology with transfer. Am J Clin
Nutr 1991; 53: 66-69.
manure
after Rio
When Malthus painted his dismal population scenario he was not to know how birth control, technology, and education would come to the rescue. But relief proved only temporary. Today we have the "demographic trap"1 and technological fixes for that are nowhere in sight. It is the same with horse droppings. If horse-drawn transport had continued to grow from the rate of, say, 1792 the streets of our cities would now be deep in manure. Along came the horseless carriage and once more we were freed by the ingenuity of scientists and engineers-yet within less than a century cities such as Athens and Los Angeles are deep in a different sort of ordure, one to which the internal combustion engine contributes heavily. There are things that can be done with technology, often low technology but at the Rio de Janeiro environmental summit that finished last weekend little was heard of the notion that technological solutions to the world’s environmental problems are just around the comer. So, the two weeks that were the "last chance to save our planet" are over. The earth is still there, just. So are the politicians, full of sound and even fury sometimes, but with no vision and signifying nothing because they suspect that those who put them into office back home are not yet persuaded of the need for sacrifice. Sustaining the environmental debate after Rio is the challenge that faces those who found the Earth Summit a crashing disappointment (but see p 1529 for a view from someone who was there). That task will have to be shared by the projected
Sustainable Development Commission, The Lancet has argued that there is a substantial medical dimension to the current destruction of the environment.2That case is well made in the World Health Organisation’s excellent contribution to the Rio jamboree. In her foreword to the reportSimone Veil wrote that "the kind of development needed to safeguard health and welfare will depend on many
conditions, including respect for the environment,
development without regard for the environment would inevitably result in impairment of human health". WHO did not neglect population. How sad, then, that population per se got so little publicity in Brazil. It is there in Agenda 21, one of the products of the UN Conference on Environment and Development, but separated from "protection and promoting human health" (with its obvious WHO input). Some argue that poverty must first be corrected, and limitation on family size will follow. It while
is
too
more
late. On the road to that destination how many nations in Africa and elsewhere will fall into the
1516
downward spiral on which the demographic trap closes? Neither an expanding population nor everexpanding aspirations are tolerable and the two in harness will be fatal. It is no good levelling off carbon dioxide emissions, saving rain forests, guarding the diversity of species-or even donating 0-7% of the gross national product of a developed world that has wreaked most of the environmental havoc so farunless there is a commitment on population in the developing world. Such an undertaking from, say, the Group of 77 countries would put to shame the posturing and wriggling of the leaders of some wealthy nations. 1. Editorial. Pressure on the eco-seams. Lancet 1992; 339: 1265-67. 2. Editorial. Earth matters. Lancet 1992; 339: 1325-26. 3. Our planet, our health: report of the WHO Commission on Health and Environment. Geneva: WHO, 1992.
Pandolfi’s box: research in
Europe
There was a crisis in Brussels last week-not about Maastricht or Viking voters but on the future of the European Community’s small medical research programme. The EC spends huge sums on research and development, but of the total expenditure of 5700 million ecu planned for 1990-94, biomedicine and health gets just 2-3%. This is 87 million or so, less than the allocation to biotechnology or to testing industrial materials, and about one-quarter of the sum given to fusion energy. The EC commissioner in charge is Felippo Pandolfi. He would prefer a larger treasure chest, recognising that Brussels-controlled R & D pales into insignificance beside the amounts spent by individual member states.1 Medicine is no exception: the current EC programme, known as BIOMED 1, will spend over five years less than half the annual budget of the UK’s Medical Research Council. BIOMED, as with the 1987-91 Fourth Medical and Health Research Programme (MHR4), will mainly be used to lubricate the wheels of collaborative research in Europe. "Subsidiarity" is EC-speak for doing nothing from Brussels that can be done just as well in and by member states individually. In BIOMED, which rolls on from MHR4, this is translated as "concerted actions".2 More than one country must be involved, of course; the project has to fit in with EC priorities (AID S, cancer, cardiovascular disease, and ageing, for example); and there must be a perceived, if not always provable, add-on benefit to warrant EC participation. Even with these restraints, and with many leading groups not knowing of or not wishing to take advantage of the offer, applications have swamped the funds available. The job of handling Pandolfi’s box falls to advisers and to a secretariat which is overstretched and understaffed. Such an excess of demand over supply-and we are talking in BIOMED of about 20 to 13---demands a well-oiled selection procedure that wins the respect of research-workers. Once the priorities have been
declared, scientific quality should be the main, some would say the only, consideration. In other words, peer review of applications and of supported projects in progress. The medical research community in Europe thought it had won that argument but now fears that the process has become too politicised. However, the EC is a political animal, and even in the US, where peer review has a bureaucracy all of its
"pork barrel" has not disappeared.4 There are legitimate political pressures: the encouragement of science in less well endowed EC states is surely justifiable (opportunities for training grants were advertised in last week’s Lancet). Three times the EC Commission has appointed panels to look at its medical research programmes (Wolstenhoime, Hunter, and Maynard, to name the chairmen), and these have been critical. The latest of these reports appeared in July, 1990,5 and its comments on MHR4 were not kindly received in Brussels. It questioned whether concerted actions were the right way to go and it found the review system imperfect. Some useful work has resulted: contributions from EURODIAB, from the Parisbased AIDS centre, and from a Dutch team looking at inequalities in health and UK-based projects on asthma and avoidable deaths come to mind. The yield elsewhere is less impressive but even there the building of bridges has been a significant own, the
achievement. Those attending last week’s meeting of the BIOMED management committee were expecting a lively gathering. They were not disappointed. After painstaking scientific appraisal 1900 "declarations of intent" had already been whittled down to just over 300, and those applicants had been invited to submit in greater detail. The prospect remains that no more than 100 can be funded of this first wave of proposals. The management committee-three representatives of all twelve EC members and of six associated countries-has this year been downgraded to a committee "advisory in nature", and they were horrified to learn that the Commission had written to all applicants, leaving the impression that everything might yet be reassessed. As a result 725 (not 313) detailed proposals have been received. The meeting on June 11, chaired by Hendrik Tent, came near to collapse. On Friday came compromise. The scientific rankings stand but it looks as if the remaining selection procedures will have to be applied to the 725. Time is running out. BIOMED must allocate 42 million ecu by the end of the year, leaving only three summer months for the detailed scrutiny before decision time in October. 1. Mundell I. Maastricht drives R & D to the market. Nature 1992; 356:650. 2. European Community. Biomedical and health research programme
(1990-1994). Biomed HealthRes Newsl 1991, no S/91. 3. Dyer M. Biomed I programme. Lancet 1992; 339:1221. 4. Greenberg DS. When science and politics collide. Lancet1992;339:1469. 5. Commission of the European Communities. Evaluation of the fourth Medical and Health Research Programme (1987-1991). Luxembourg: Office for Official Publications of the EC, 1990.
Consequently there is much to commend a simple, non-invasive, cheap test such as conjunctival impression cytology (CIC), which is rapidly gaining wide acceptance.7-9 There is lack of agreement on several technical details, perhaps the most important being how to interpret as normal or abnormal the
10. Carlier C, Coste J, Etchepare M, et al. Conjunctival impression cytology with transfer as a field-applicable indicator of vitamin A status for mass screening. Int J Epidemiol 1992; 21: 373-80. 11. World Health Organisation. Control of vitamin A deficiency and xerophthalmia. Tech Rep Ser no 672, 1982. 12. Sommer A. Vitamin A deficiency and childhood mortality. Lancet 1992;
339: 864.
appearances of the cellular elements of the bulbar
epithelium. Accompanying eye infections such as trachoma, or irritation due to smoke or dust, may sometimes give false-positive results. The importance of the quality of the cytological preparations has not been thoroughly assessed. Carlier and colleagues1o in France, one of the foremost groups in the use of CIC, have lately proposed a formula for a prevalence criterion for subclinical vitamin A deficiency. As they point out, this was done by WHO for clinical xerophthalmia and the WHO recommendations have been widely adopted.l1 From a meta-analysis of six controlled community-based prophylaxis-mortality trials,
Horse
conjunctival
Sommer12 reports
an
overall reduction in child
mortality of 34%. This meta-analysis has not been published, but even if the percentage is an overestimate it is difficult to escape the conclusion that
marginal or subclinical deficiency of vitamin A is an important determinant of deaths in young children throughout the world. 12 years have now passed since WHO expert group met to consider the control of vitamin A deficiency and xerophthalmia. The grave consequences of the new dimension that has been unearthed mean that another meeting is overdue. High on its agenda should be achievement of a consensus on the detailed technique of CIC and all aspects of its application and interpretation, together with recommendations concerning the control of the marginal deficiency of vitamin A it is designed to detect. Until then, the deceptive simplicity of CIC lays it wide open to abuse. a
1. Sommer A, Tarwotjo I, Hussaini G, Susanto D. Increased mortality in children with mild vitamin A deficiency. Lancet 1983; ii: 585-88. 2. Sommer A, Tarwotjo I, Djunaedi E, et al. Impact of vitamin A supplementation on childhood mortality: a randomised controlled community trial. Lancet 1986; i: 1169-73. 3. Rahmathullah L, Underwood BA, Thulasiraj RD, et al. Reduced mortality among children in southern India receiving a small weekly dose of vitamin A. N Engl J Med 1990; 323: 929-35. 4. Flores H, Campos FACS, Araujo CRC, et al. Assessment of marginal vitamin A deficiency in Brazilian children using the relative dose response procedure. Am J Clin Nutr 1984; 40: 1281-89. 5. Tanumihardjo SA, Muhilal, Yuniar Y, et al. Assessment of vitamin A status in preschool-age Indonesian children by the modified relative dose response (MRDR) assay. Am J Clin Nutr 1990; 52: 1064-67. 6. Blomhoff R, Green MH, Green JB, et al. Vitamin A metabolism: new perspective on absorption, transport, and storage. PhysiolRev 1991;71: 951-90. 7. Natadisastra G, Wittpenn JR, West KP, et al. Impression cytology for detection of vitamin A deficiency. Arch Ophthalmol 1987; 105: 1224-28. 8. Gadomski AM, Kjolhede CL, Wittpenn J, et al. Field trial of conjunctival impression cytology (CIC) to detect subclinical vitamin A deficiency, part II: comparison of CIC with biochemical assessments. Am J Clin Nutr 1988; 48: 695-701. 9. Carlier C, Moulia-Pelat JP, Ceccon JF, et al. Prevalence of malnutrition and vitamin A deficiency in the Diourbel, Fatick and Kaolack regions of Senegal: feasibility of impression cytology with transfer. Am J Clin
Nutr 1991; 53: 66-69.
manure
after Rio
When Malthus painted his dismal population scenario he was not to know how birth control, technology, and education would come to the rescue. But relief proved only temporary. Today we have the "demographic trap"1 and technological fixes for that are nowhere in sight. It is the same with horse droppings. If horse-drawn transport had continued to grow from the rate of, say, 1792 the streets of our cities would now be deep in manure. Along came the horseless carriage and once more we were freed by the ingenuity of scientists and engineers-yet within less than a century cities such as Athens and Los Angeles are deep in a different sort of ordure, one to which the internal combustion engine contributes heavily. There are things that can be done with technology, often low technology but at the Rio de Janeiro environmental summit that finished last weekend little was heard of the notion that technological solutions to the world’s environmental problems are just around the comer. So, the two weeks that were the "last chance to save our planet" are over. The earth is still there, just. So are the politicians, full of sound and even fury sometimes, but with no vision and signifying nothing because they suspect that those who put them into office back home are not yet persuaded of the need for sacrifice. Sustaining the environmental debate after Rio is the challenge that faces those who found the Earth Summit a crashing disappointment (but see p 1529 for a view from someone who was there). That task will have to be shared by the projected
Sustainable Development Commission, The Lancet has argued that there is a substantial medical dimension to the current destruction of the environment.2That case is well made in the World Health Organisation’s excellent contribution to the Rio jamboree. In her foreword to the reportSimone Veil wrote that "the kind of development needed to safeguard health and welfare will depend on many
conditions, including respect for the environment,
development without regard for the environment would inevitably result in impairment of human health". WHO did not neglect population. How sad, then, that population per se got so little publicity in Brazil. It is there in Agenda 21, one of the products of the UN Conference on Environment and Development, but separated from "protection and promoting human health" (with its obvious WHO input). Some argue that poverty must first be corrected, and limitation on family size will follow. It while
is
too
more
late. On the road to that destination how many nations in Africa and elsewhere will fall into the
1516
downward spiral on which the demographic trap closes? Neither an expanding population nor everexpanding aspirations are tolerable and the two in harness will be fatal. It is no good levelling off carbon dioxide emissions, saving rain forests, guarding the diversity of species-or even donating 0-7% of the gross national product of a developed world that has wreaked most of the environmental havoc so farunless there is a commitment on population in the developing world. Such an undertaking from, say, the Group of 77 countries would put to shame the posturing and wriggling of the leaders of some wealthy nations. 1. Editorial. Pressure on the eco-seams. Lancet 1992; 339: 1265-67. 2. Editorial. Earth matters. Lancet 1992; 339: 1325-26. 3. Our planet, our health: report of the WHO Commission on Health and Environment. Geneva: WHO, 1992.
Pandolfi’s box: research in
Europe
There was a crisis in Brussels last week-not about Maastricht or Viking voters but on the future of the European Community’s small medical research programme. The EC spends huge sums on research and development, but of the total expenditure of 5700 million ecu planned for 1990-94, biomedicine and health gets just 2-3%. This is 87 million or so, less than the allocation to biotechnology or to testing industrial materials, and about one-quarter of the sum given to fusion energy. The EC commissioner in charge is Felippo Pandolfi. He would prefer a larger treasure chest, recognising that Brussels-controlled R & D pales into insignificance beside the amounts spent by individual member states.1 Medicine is no exception: the current EC programme, known as BIOMED 1, will spend over five years less than half the annual budget of the UK’s Medical Research Council. BIOMED, as with the 1987-91 Fourth Medical and Health Research Programme (MHR4), will mainly be used to lubricate the wheels of collaborative research in Europe. "Subsidiarity" is EC-speak for doing nothing from Brussels that can be done just as well in and by member states individually. In BIOMED, which rolls on from MHR4, this is translated as "concerted actions".2 More than one country must be involved, of course; the project has to fit in with EC priorities (AID S, cancer, cardiovascular disease, and ageing, for example); and there must be a perceived, if not always provable, add-on benefit to warrant EC participation. Even with these restraints, and with many leading groups not knowing of or not wishing to take advantage of the offer, applications have swamped the funds available. The job of handling Pandolfi’s box falls to advisers and to a secretariat which is overstretched and understaffed. Such an excess of demand over supply-and we are talking in BIOMED of about 20 to 13---demands a well-oiled selection procedure that wins the respect of research-workers. Once the priorities have been
declared, scientific quality should be the main, some would say the only, consideration. In other words, peer review of applications and of supported projects in progress. The medical research community in Europe thought it had won that argument but now fears that the process has become too politicised. However, the EC is a political animal, and even in the US, where peer review has a bureaucracy all of its
"pork barrel" has not disappeared.4 There are legitimate political pressures: the encouragement of science in less well endowed EC states is surely justifiable (opportunities for training grants were advertised in last week’s Lancet). Three times the EC Commission has appointed panels to look at its medical research programmes (Wolstenhoime, Hunter, and Maynard, to name the chairmen), and these have been critical. The latest of these reports appeared in July, 1990,5 and its comments on MHR4 were not kindly received in Brussels. It questioned whether concerted actions were the right way to go and it found the review system imperfect. Some useful work has resulted: contributions from EURODIAB, from the Parisbased AIDS centre, and from a Dutch team looking at inequalities in health and UK-based projects on asthma and avoidable deaths come to mind. The yield elsewhere is less impressive but even there the building of bridges has been a significant own, the
achievement. Those attending last week’s meeting of the BIOMED management committee were expecting a lively gathering. They were not disappointed. After painstaking scientific appraisal 1900 "declarations of intent" had already been whittled down to just over 300, and those applicants had been invited to submit in greater detail. The prospect remains that no more than 100 can be funded of this first wave of proposals. The management committee-three representatives of all twelve EC members and of six associated countries-has this year been downgraded to a committee "advisory in nature", and they were horrified to learn that the Commission had written to all applicants, leaving the impression that everything might yet be reassessed. As a result 725 (not 313) detailed proposals have been received. The meeting on June 11, chaired by Hendrik Tent, came near to collapse. On Friday came compromise. The scientific rankings stand but it looks as if the remaining selection procedures will have to be applied to the 725. Time is running out. BIOMED must allocate 42 million ecu by the end of the year, leaving only three summer months for the detailed scrutiny before decision time in October. 1. Mundell I. Maastricht drives R & D to the market. Nature 1992; 356:650. 2. European Community. Biomedical and health research programme
(1990-1994). Biomed HealthRes Newsl 1991, no S/91. 3. Dyer M. Biomed I programme. Lancet 1992; 339:1221. 4. Greenberg DS. When science and politics collide. Lancet1992;339:1469. 5. Commission of the European Communities. Evaluation of the fourth Medical and Health Research Programme (1987-1991). Luxembourg: Office for Official Publications of the EC, 1990.
