1325
EDITORIALS Earth matters Next week tens of thousands of people, from across the globe, will gather in Rio de Janeiro, Brazil, for the United Nations Conference on Environment and Development (UNCED), where three treaties are on the table. Is the medical profession prepared to participate in this important process, with its pressing implications for the public health? Accumulation of greenhouse gases in the troposphere and ozone depletion in the stratosphere are the main threats to our ecosystem. The discovery of Antarctic ozone depletion in 1987 confirmed that human activities were destabilising the global environment, and led to the Montreal Agreement in that year. Although northern hemisphere ozone levels reached record low values in January and February this year, the additional Arctic loss was less than one-fifth of the 50% drop predicted: warming reduced the concentration of nitric acid ice crystals on which chlorine and bromine act to break down ozone.! Treaty number 1: carbon emissions-the chief manmade sources of greenhouse gases are fossil fuel combustion (which contributes close to 6 billion tonnes [gigatons] of carbon annually), and the burning and clearing of forests (another 1-2 gigatons).22 Terrestrial and marine chlorophyllic organisms provide the principal "sinks" for carbon;3 and carbon dioxide and monoxide constitute 70% of the 100-year global warming potential of greenhouse gases.4In 1850, COZ concentration was 280 parts per million by volume, where, on the evidence of ice cores, it had stood for the previous ten centuries. In 1990, it surpassed 350 ppm.5 There is no question that man-made emissions are altering atmospheric as well as soil chemistry, although the sum effect on outcome measures such as global temperature remains in
dispute. Treaty number 2: deforestation-the threat to forests is well documented. About half the forest cover in the developing world has vanished during this century.6
Land and sea plants provide atmospheric oxygen, cool the earth’s surface by removing CO2 and, through evaporation and release of aerosolised sulphurs, help generate rain-producing and sun-reflecting clouds.7 As Fellows notes in this issue (p 1330), forests also give us medicines; and researchers in Belize have shown that harvesting medicinal herbs for the market can be more profitable than removing trees for farming or for
timber.8
Treaty
number 3:
biodiversity-it is estimated that
the earth has 10-100 million species of organisms, in five kingdoms.9 Beyond the irreplaceable losses
occurring and the remedies never to be discovered, "biodiversity is a necessity, not just a luxury", in the words of Prof Lynn Margulis, in an address to Harvard biologists. The biogeochemical cycles on earth and in its biota serve to modulate atmospheric oxygen, temperature, ocean salinity, and ambient pH-ie, the conditions necessary for life as it now exists. Alterations in predator-prey relations and in host and disease agent refuges may create shifts along the commensal-pathogen continuum, and thereby change the distribution and impact of disease. The World Health Organisation predicts changes mainly in water-based and vector-borne diseases.il An interesting account comes from Australia. A "rash of infectious diseases that ... swept northern Australia" in austral summer, 1991, led to speculation that early signs of the process may have appeared. The chairman of the National Health and Medical Research Council’s public health committee reported four epidemics in the Northern Territory (due to water-borne and soil-based bacteria; growth of a water-based amoeba; and the spread south of an arbovirus infection, Ross River fever, usually confmed to the northernmost part of the territory), accompanying a period of exceptionally hot, rainy weather .12 This period coincided with a temperature rise in El Nino, the western Pacific warming centre located on the equator, directly north of Australia. Some people argued that "natural cycles" may explain such coincidences. However, there is now convincing evidence that altered atmospheric chemistry is affecting marine microflora, and that algae and plankton provide a reservoir for cholera.13 Unusually large algal blooms have been reported world wide during the past two years, having been nurtured by increased C02, nitrate deposition (from sewage and pollution), and warming. 14 The epidemiology of the Latin American cholera pandemic, with multiple epicentres along the Pacific accords with this hypothesis. The coast, compensatory growth of marine chlorophyllics, a byproduct of fertilisation and land deforestation, may be an expanded reservoir for cholera and one that is responsive to environmental factors. The medical and scientific professions must begin to influence our course of development. Collaboration can include: (a) studies of the impact of global changes on specific diseases; (b) disease-based geographical information that intercalate with systems and environmental (c) impact climatological models; and cost evaluations conducted in advance of largescale enterprises. We need to put pressure on governments to participate actively in the UNCED treaties, to adopt quickly regulations that implement their aims and targets, and to provide the incentives for research and development. There are numerous directions for such research--eg, greater energy efficiency; use and storage of renewable energy sources; non-chlorofluorocarbon and halon cooling systems; expanded mass transport; and advanced
1326
clean-up technology. Finally,
our
epidemiological
skills can aid communities that have been hard hit by polluting industries, and those developing local ordinances to regulate ozone-depleting and infraredabsorbing emissions. The global economic downturn has already damaged health in the third world. 15 International financial relations (debt and unequal terms of trade) propel environmentally destructive economic activities such as clear-cutting of forests for exportoriented monocropping and lumber, putting immediate needs against long-term survival. The conversion process will require massive debt-fornature swaps, and independent regional funding bodies to provide the necessary "demand-pull" economic forces. Investment in new technologies can play a crucial role in rekindling our faltering global economy.
Medical involvement is in its infancy. The Genevabased International Society of Doctors for the Environment began publishing a journal after its conference in Cortona, Italy, in November, 1990. The US-based Physicians for Social Responsibility will host an international course on the health impact of climatic change this autumn. Much more is needed to influence public opinion and our leadership, with participation from all parts of the globe. UNCED will mark an important milestone in a universal project to achieve a healthy, sustainable future: public health should be firmly on the agenda. 1. Kerr RA. Ozone hole: not over the Arctic-for now. Science 1992; 256: 734. 2. Kerr RA. Fugitive carbon dioxide: it’s not hiding in the ocean. Science
3.
1992; 256: 35. Quay PD, Tillbrook B, Wong OS. Oceanic uptake of fossil fuel CO2:
carbon-13 evidence. Science 1991; 256: 74-79. 4. Subak S, Raskin PD. Greenhouse gas scenario system (G2S2). Stockholm Environment Institute, Boston Office, 1992 (database). 5. Broecker WS. Keeping global change honest. Global Biogeochem Cycles 1991; 5: 191-92. 6. Turner BL, ed. The earth as transformed by human action. Cambridge:
Cambridge University Press, 1990. 7. Bates TS, Charlson RJ, Gammon RH. Evidence for the climate role of marine biogenic sulfa. Nature 1987; 329: 319-20. 8. Dold C. Tropical forests found more valuable for medicine than other uses. New York Times April 28, 1992: C4. 9. Stevens WK. Humanity confronts its handiwork: an altered planet. New York Times May 5, 1992: C1. 10. Margulis L. From Gaia to microcosm. Presentation to the Harvard University Department of Organismic and Evolutionary Biology, April 16, 1992. 11. WHO Task Group. The potential health effects of climatic change. Geneva: WHO, 1990. 12. Lush N. Will greenhouse kill us? Lancet 1991; 338: 500-01. 13. Epstein PR. Cholera and the environment. Lancet 1992; 339: 1167-68. 14. Kauppi PE, Mielikäinen K, Kuusele K. Biomass and carbon budget of European forests 1971 to 1990. Science 1992; 256: 70-74. 15. Summerfield D. Western economics and third world health. Lancet 1989; ii: 551-52.
Microdialysis Biochemical investigation of human beings in health and disease has been constrained by the difficulty of obtaining material for study. In practice, most measurements are made in plasma or serum derived from venous blood, although arterial and
capillary blood, urine, faeces, cerebrospinal fluid,
sweat, amniotic
fluid, breath, and tissue biopsy
also used. Most of these sources are samples impractical for continuous monitoring of acute changes. Another problem is that blood is normally taken from peripheral vessels, so the concentration of the analyte may differ substantially from that in the tissue of interest. Protein-binding interferes with the measurement of many substances in blood. As a result, methods of measuring "free" drugs and hormones have been developed but these techniques are often not straightforward and interpretation of results may be controversial. Plasma proteins can also interfere with the measurement of substances in blood that are not protein bound. Measurement of substances in the low-protein environment of the extracellular fluid (ECF) would have several advantages. An important benefit is that the concentration of the substance measured in the ECF is that to which the cell is directly exposed. Some of the methods for sampling the ECF had the drawback of producing local tissue damage. In 1972, Delgado and colleagues1 described the technique of microdialysis, in which a small probe was inserted with very little tissue disruption. This technique has been continuously developed since then and has been used in many studies, especially for neurological research in animals. Commercial microdialysis probes, pumps, and collecting devices are available, and the technical development of microdialysis is now at a stage where it has the potential for use in human studies. A are
minisymposium on microdialysis was recently published in the Journal of Internal Medicine.2-5 Microdialysis is based on the passive transfer of substances across a dialysis membrane inserted into the tissue of interest. Two types of devices are used: (a) a dual concentric probe with the dialysis tube at the end; and (b) a transversely implanted dialysis tube with separate input and exit sites in the tissues. It is possible to control both composition and flow rate of the dialysis fluid, and dialysis membranes with different molecular weight cut-offs can be used. Apart from gaining information by passive sampling of ECF, one can add drugs, hormones, and other small bioactive molecules to the dialysis fluid and monitor the tissue response. Flow rates in microdialysis are 1-3 nl/min and the concentrations of analytes are often in the picomolar (10-12) or even femtomolar (10-15) range. Consequently, very sensitive detection systems have had to be developed. Many substances can be
measured
by high-performance liquid chromatography with various types of detectors but especially electrochemical methods. Enzymic techniques can be used for more concentrated analytes, and their sensitivity can often be enhanced by fluorescence and luminescence detectors. Small bioactive peptides can also be recovered in the dialysate, but radioimmunoassays with sufficient sensitivity are extremely difficult to do. One
EDITORIALS Earth matters Next week tens of thousands of people, from across the globe, will gather in Rio de Janeiro, Brazil, for the United Nations Conference on Environment and Development (UNCED), where three treaties are on the table. Is the medical profession prepared to participate in this important process, with its pressing implications for the public health? Accumulation of greenhouse gases in the troposphere and ozone depletion in the stratosphere are the main threats to our ecosystem. The discovery of Antarctic ozone depletion in 1987 confirmed that human activities were destabilising the global environment, and led to the Montreal Agreement in that year. Although northern hemisphere ozone levels reached record low values in January and February this year, the additional Arctic loss was less than one-fifth of the 50% drop predicted: warming reduced the concentration of nitric acid ice crystals on which chlorine and bromine act to break down ozone.! Treaty number 1: carbon emissions-the chief manmade sources of greenhouse gases are fossil fuel combustion (which contributes close to 6 billion tonnes [gigatons] of carbon annually), and the burning and clearing of forests (another 1-2 gigatons).22 Terrestrial and marine chlorophyllic organisms provide the principal "sinks" for carbon;3 and carbon dioxide and monoxide constitute 70% of the 100-year global warming potential of greenhouse gases.4In 1850, COZ concentration was 280 parts per million by volume, where, on the evidence of ice cores, it had stood for the previous ten centuries. In 1990, it surpassed 350 ppm.5 There is no question that man-made emissions are altering atmospheric as well as soil chemistry, although the sum effect on outcome measures such as global temperature remains in
dispute. Treaty number 2: deforestation-the threat to forests is well documented. About half the forest cover in the developing world has vanished during this century.6
Land and sea plants provide atmospheric oxygen, cool the earth’s surface by removing CO2 and, through evaporation and release of aerosolised sulphurs, help generate rain-producing and sun-reflecting clouds.7 As Fellows notes in this issue (p 1330), forests also give us medicines; and researchers in Belize have shown that harvesting medicinal herbs for the market can be more profitable than removing trees for farming or for
timber.8
Treaty
number 3:
biodiversity-it is estimated that
the earth has 10-100 million species of organisms, in five kingdoms.9 Beyond the irreplaceable losses
occurring and the remedies never to be discovered, "biodiversity is a necessity, not just a luxury", in the words of Prof Lynn Margulis, in an address to Harvard biologists. The biogeochemical cycles on earth and in its biota serve to modulate atmospheric oxygen, temperature, ocean salinity, and ambient pH-ie, the conditions necessary for life as it now exists. Alterations in predator-prey relations and in host and disease agent refuges may create shifts along the commensal-pathogen continuum, and thereby change the distribution and impact of disease. The World Health Organisation predicts changes mainly in water-based and vector-borne diseases.il An interesting account comes from Australia. A "rash of infectious diseases that ... swept northern Australia" in austral summer, 1991, led to speculation that early signs of the process may have appeared. The chairman of the National Health and Medical Research Council’s public health committee reported four epidemics in the Northern Territory (due to water-borne and soil-based bacteria; growth of a water-based amoeba; and the spread south of an arbovirus infection, Ross River fever, usually confmed to the northernmost part of the territory), accompanying a period of exceptionally hot, rainy weather .12 This period coincided with a temperature rise in El Nino, the western Pacific warming centre located on the equator, directly north of Australia. Some people argued that "natural cycles" may explain such coincidences. However, there is now convincing evidence that altered atmospheric chemistry is affecting marine microflora, and that algae and plankton provide a reservoir for cholera.13 Unusually large algal blooms have been reported world wide during the past two years, having been nurtured by increased C02, nitrate deposition (from sewage and pollution), and warming. 14 The epidemiology of the Latin American cholera pandemic, with multiple epicentres along the Pacific accords with this hypothesis. The coast, compensatory growth of marine chlorophyllics, a byproduct of fertilisation and land deforestation, may be an expanded reservoir for cholera and one that is responsive to environmental factors. The medical and scientific professions must begin to influence our course of development. Collaboration can include: (a) studies of the impact of global changes on specific diseases; (b) disease-based geographical information that intercalate with systems and environmental (c) impact climatological models; and cost evaluations conducted in advance of largescale enterprises. We need to put pressure on governments to participate actively in the UNCED treaties, to adopt quickly regulations that implement their aims and targets, and to provide the incentives for research and development. There are numerous directions for such research--eg, greater energy efficiency; use and storage of renewable energy sources; non-chlorofluorocarbon and halon cooling systems; expanded mass transport; and advanced
1326
clean-up technology. Finally,
our
epidemiological
skills can aid communities that have been hard hit by polluting industries, and those developing local ordinances to regulate ozone-depleting and infraredabsorbing emissions. The global economic downturn has already damaged health in the third world. 15 International financial relations (debt and unequal terms of trade) propel environmentally destructive economic activities such as clear-cutting of forests for exportoriented monocropping and lumber, putting immediate needs against long-term survival. The conversion process will require massive debt-fornature swaps, and independent regional funding bodies to provide the necessary "demand-pull" economic forces. Investment in new technologies can play a crucial role in rekindling our faltering global economy.
Medical involvement is in its infancy. The Genevabased International Society of Doctors for the Environment began publishing a journal after its conference in Cortona, Italy, in November, 1990. The US-based Physicians for Social Responsibility will host an international course on the health impact of climatic change this autumn. Much more is needed to influence public opinion and our leadership, with participation from all parts of the globe. UNCED will mark an important milestone in a universal project to achieve a healthy, sustainable future: public health should be firmly on the agenda. 1. Kerr RA. Ozone hole: not over the Arctic-for now. Science 1992; 256: 734. 2. Kerr RA. Fugitive carbon dioxide: it’s not hiding in the ocean. Science
3.
1992; 256: 35. Quay PD, Tillbrook B, Wong OS. Oceanic uptake of fossil fuel CO2:
carbon-13 evidence. Science 1991; 256: 74-79. 4. Subak S, Raskin PD. Greenhouse gas scenario system (G2S2). Stockholm Environment Institute, Boston Office, 1992 (database). 5. Broecker WS. Keeping global change honest. Global Biogeochem Cycles 1991; 5: 191-92. 6. Turner BL, ed. The earth as transformed by human action. Cambridge:
Cambridge University Press, 1990. 7. Bates TS, Charlson RJ, Gammon RH. Evidence for the climate role of marine biogenic sulfa. Nature 1987; 329: 319-20. 8. Dold C. Tropical forests found more valuable for medicine than other uses. New York Times April 28, 1992: C4. 9. Stevens WK. Humanity confronts its handiwork: an altered planet. New York Times May 5, 1992: C1. 10. Margulis L. From Gaia to microcosm. Presentation to the Harvard University Department of Organismic and Evolutionary Biology, April 16, 1992. 11. WHO Task Group. The potential health effects of climatic change. Geneva: WHO, 1990. 12. Lush N. Will greenhouse kill us? Lancet 1991; 338: 500-01. 13. Epstein PR. Cholera and the environment. Lancet 1992; 339: 1167-68. 14. Kauppi PE, Mielikäinen K, Kuusele K. Biomass and carbon budget of European forests 1971 to 1990. Science 1992; 256: 70-74. 15. Summerfield D. Western economics and third world health. Lancet 1989; ii: 551-52.
Microdialysis Biochemical investigation of human beings in health and disease has been constrained by the difficulty of obtaining material for study. In practice, most measurements are made in plasma or serum derived from venous blood, although arterial and
capillary blood, urine, faeces, cerebrospinal fluid,
sweat, amniotic
fluid, breath, and tissue biopsy
also used. Most of these sources are samples impractical for continuous monitoring of acute changes. Another problem is that blood is normally taken from peripheral vessels, so the concentration of the analyte may differ substantially from that in the tissue of interest. Protein-binding interferes with the measurement of many substances in blood. As a result, methods of measuring "free" drugs and hormones have been developed but these techniques are often not straightforward and interpretation of results may be controversial. Plasma proteins can also interfere with the measurement of substances in blood that are not protein bound. Measurement of substances in the low-protein environment of the extracellular fluid (ECF) would have several advantages. An important benefit is that the concentration of the substance measured in the ECF is that to which the cell is directly exposed. Some of the methods for sampling the ECF had the drawback of producing local tissue damage. In 1972, Delgado and colleagues1 described the technique of microdialysis, in which a small probe was inserted with very little tissue disruption. This technique has been continuously developed since then and has been used in many studies, especially for neurological research in animals. Commercial microdialysis probes, pumps, and collecting devices are available, and the technical development of microdialysis is now at a stage where it has the potential for use in human studies. A are
minisymposium on microdialysis was recently published in the Journal of Internal Medicine.2-5 Microdialysis is based on the passive transfer of substances across a dialysis membrane inserted into the tissue of interest. Two types of devices are used: (a) a dual concentric probe with the dialysis tube at the end; and (b) a transversely implanted dialysis tube with separate input and exit sites in the tissues. It is possible to control both composition and flow rate of the dialysis fluid, and dialysis membranes with different molecular weight cut-offs can be used. Apart from gaining information by passive sampling of ECF, one can add drugs, hormones, and other small bioactive molecules to the dialysis fluid and monitor the tissue response. Flow rates in microdialysis are 1-3 nl/min and the concentrations of analytes are often in the picomolar (10-12) or even femtomolar (10-15) range. Consequently, very sensitive detection systems have had to be developed. Many substances can be
measured
by high-performance liquid chromatography with various types of detectors but especially electrochemical methods. Enzymic techniques can be used for more concentrated analytes, and their sensitivity can often be enhanced by fluorescence and luminescence detectors. Small bioactive peptides can also be recovered in the dialysate, but radioimmunoassays with sufficient sensitivity are extremely difficult to do. One
