Volume 172 Issue 4

Editorial Genetically modified food: consternation, confusion, and crack-up The controversy over genetically modified food exposes larger issues about public trust in science and the role of science in policymaking MJA 2000; 172: 148-149 "The great pioneers of our subject were tormented by crises of belief and uncertainty, which we need to understand in facing our own problems today. It is only today, after 70 years, that such understanding is coming within our reach -- and may soon slip out of our reach."1 Did this desperate plea come recently from a scientist in defensive retreat? A scientist, perhaps, embroiled in the debate about genetically modified food, who flinched on reading that Stanley Ewen and Arpad Pusztai had found an "unexpected proliferative effect" of genetically modified potatoes on rat gut?2Not, thankfully, on this occasion. These were the opening remarks of a respected senior botanist, C D Darlington, in an issue of the Philosophical Transactions of the Royal Society of London devoted entirely to the manipulation of genetic systems in plant breeding. He was writing over 20 years ago. Interference with our systems of food production has always aroused public alarm, occasionally with justification. From soaking crops with pesticides to taking short cuts in the feeding of cattle (bovine revenge being wreaked on Britain with variant Creutzfeldt-Jakob disease), food is a lightning-rod for public fears about scientists' allegedly reckless indifference to safety. But, even by these high standards of public sensitivity, the debate surrounding genetically modified organisms became the scientific controversy of 1999,3 a debate that is summarised in this issue of the Journal, with restrained good temper, by Huppatz and Fitzgerald on one side 4 and Leeder on the other.5 Four larger issues have been exposed by these kinds of exchange in the last months of the 20th century, and the arguments they incite threaten the fragile remnant of trust that remains between the public and scientists. First, how can two (reasonably) well-regarded organisations peer review the same work -- Ewen and Pusztai's research on the effects of feeding genetically modified potatoes to rats -- and yet come to such radically opposite conclusions about its validity, as did the Royal Society and The Lancet? All six Royal Society reviewers pronounced the research "flawed", while five out of six of The Lancet's reviewers judged that Ewen and Pusztai's work should be published.6 Peer review as a reliable technique for assessing the validity of scientific data is surely discredited. The mistake, of course, is to have thought that peer review was any more than a crude means of discovering the acceptability -- not the validity -- of a new finding. Editors and scientists alike insist on the pivotal importance of peer review. We portray peer review to the public as a quasi-sacred process that helps to make science our most objective truth teller. But we know that the system of peer review is biased, unjust, unaccountable, incomplete, easily fixed, often insulting, usually ignorant, occasionally foolish, and frequently wrong. A recent editorial in Nature was right to conclude that an over-reliance on peer-reviewed publication "has disadvantages that should be countered by adequate provision of time and resources for independent assessment and, in the midst of controversies, publicly funded agencies providing comprehensive, reliable and prompt complementary information".7 Second, given each outrageously overblown claim and counterclaim about the safety of genetically modified foods, how can the public ever begin to reach a balanced opinion about this important new technology? British -- but hopefully not Australian -- doctors, scientists, politicians, and even journalists, treat the public with little more than patronising contempt when a compelling scientific issue surfaces. According to research published by the United Kingdom's Economic and Science Research Council,8 "the public are not stupid and ignorant about their approach to [genetically modified food] risks but have a sophisticated grasp of the main issues". In the United States, the culture is, as so often, entirely different. Faced with growing public anxiety about genetically modified foods, the Food and Drug Administration (FDA) called three open meetings to discuss the widespread concerns. The FDA plans to channel this public point of view into its own food-labelling and safety policies. Here is a model that other countries might adopt to their advantage. Third, after the latest storm has calmed, how much more do we really know about the safety of genetically modified foods? Regrettably, very little. Considered opinions have been traded,9,10 but few new insights have been gained. The insipid but correct conclusion is that more research -- notably to confirm or refute Ewen and Pusztai's preliminary findings -- is needed. But perhaps the terms of the debate could be refined. Mark Tester, for example, has argued against discussing genetically modified plants as a homogeneous group. Instead, he proposes a classification of such foods based on the type of gene transfer used -- between kingdoms, between plant species, or between genes in a single type of plant genome.11 Each category of transfer carries a diminishing theoretical risk. Careful thinking, and not brutish restatements of old positions, is now required. Finally, this and other recent public health scares have focused attention on the validity of the precautionary principle. This principle states that, where there are significant risks of damage to the public health, we should be prepared to take action to limit those risks, even when scientific knowledge is not conclusive, if the balance of likely costs and benefits justifies it. I have argued that the precautionary principle "offers one useful means to inform decision making".12 By contrast, Aaron Klug, President of the Royal Society, noted in his 1999 anniversary address that the precautionary principle "is no way to deal with uncertainty -- it is a recipe for [scientific] stagnation".13 Therefore, the question remains unresolved: how do policymakers make policy on controversial matters of public health when the scientific evidence is inconclusive? In some ways, this bitter debate is spurious. Huppatz and Fitzgerald repeat a familiar argument -- namely, that "gene technology offers enormous potential for world agriculture". The Royal Society went further, claiming that "we cannot assume that current practices will feed the population of 8 billion expected by 2020";7 hence, genetically modified food offers one solution to a projected global famine. Is this the problem we are trying to solve with genetic modification? If not, then what is? And if so, we may be missing a simpler, but far more profound, answer. The little research that has been conducted about the origins of famine reveals that the solution of "more food" may be no solution at all. There is no direct relation, Amartya Sen concludes in his study of poverty and famine,14 between food availability and starvation. Access to food depends far more on a complex mix of economic, social and political factors -- eg, without an income and a stable environment to exchange money for food, a person may starve in the face of plenty. If Sen's argument is correct, and the evidence he cites is persuasive, seeking a technological food fix for world hunger may be not only the biggest scientific controversy of 1999, but also the most commercially malevolent wild goose chase of the new century. Richard Horton Editor, The Lancet London, UK Reprints: Dr R Horton, The Lancet, 84 Theobald's Road, London, WCIX 8RR, UK. Darlington CD. Genetics and plant breeding, 1910-80. Philos Trans R Soc Lond 1981; B 292: 401-405. Ewen SWB, Pusztai A. Effects of diets containing genetically modified potatoes expressing Galanthus nivalis lectin on rat small intestine. Lancet 1999; 354: 1353-1354. Controversy of the year: GM foods under attack. Science 1999; 280: 2243. Huppatz JL, Fitzgerald PA. Genetically modified foods -- safety and regulatory issues. Med J Aust 2000; 172: 170-173. Leeder SR. Genetically modified food -- food for thought. Med J Aust 2000; 172: 173-174. Horton R. Genetically modified foods: "absurd" concern or welcome dialogue? Lancet 1999; 354: 1314-1315. Dangers of over-dependence on peer-reviewed publication [editorial]. Nature 1999; 401: 727. The politics of GM food: risk, science, and public trust. London: Economic and Science Research Council, 1999. The Royal Society Statement, 1998. Genetically modified plants for food use. London: The Royal Society, 1998. Millstone E, Brunner E, Mayer S. Beyond "substantial equivalence". Nature 1999; 401: 525-526. Tester M. Seeking clarity in the debate over the safety of GM foods. Nature 1999; 402: 575. Horton R. The new new public health of risk and radical engagement. Lancet 1998; 352: 251-252. Klug A. Anniversary address 1999. London: The Royal Society, 1999. Sen A. Poverty and famines. Oxford: Oxford University Press, 1981. Make a comment

Richard Horton

Editorial The health of young Australians Mental disorders account for the major burden of disease in young people MJA 2000; 172: 150-151 Community views on youth health tend to be polarised and contradictory. On the one hand, adolescents are seen as having few overt health needs: mortality is low by comparison to that in older groups, and most young people, and their parents, rate their health as good. On the other hand, the emergence in recent decades of youth suicide, drug abuse and new infectious diseases (eg, HIV) has elicited strong and sometimes conflicting opinions about moral and social threats to young people's health. Individualism, a growth in permissiveness, and a decline in religious affiliations have all attracted debate. The recent report Australia's young people: their health and well-being 1999,1 from the Australian Institute of Health and Welfare (AIHW), provides some clarity. It follows an earlier report on child health2 and gives the first comprehensive national picture of the health of young Australians (see Box for key points). In general, Australian youth remain healthy, and retain a positive view of their health. Some health trends are positive: overall mortality in young people in the 1990s was at historically low levels (mostly due to the substantial reductions in motor vehicle deaths in the previous two decades); and rates of teenage pregnancy were low compared with those of other First World countries. However, new threats to youth health have emerged: Mental and behavioural disorders are increasingly recognised as affecting youth disproportionately and account for over half their disease burden. With the changing profile of infectious disease, newer bloodborne and sexually transmitted diseases have become prominent, with threefold higher notifications of both chlamydia and hepatitis C. The prevalence of syphilis has declined further, but gonorrhoea notifications have doubled. Shifts in young people's lifestyle carry implications for health later in life. Tobacco use remains obstinately high, with 40% of young adults continuing to smoke. Physical activity declines across the teens, so that fewer than a third of women aged 20-24 years take part in regular, moderate to vigorous physical exercise. Moreover, 22% of 15-24 year olds already have a body mass index in the overweight or obese range for adults. Some groups have disproportionately high levels of health problems. Low socioeconomic status is linked to higher death and hospitalisation rates, as well as to lower self-rating of health. Recent death rates for young Aboriginal and Torres Strait Islanders are close to three times higher in males and twice as high in females compared with rates for non-Indigenous youth. High levels of mental disorders and substance abuse are major contributors at one level, but the fundamental causes are more likely to be found in social and economic conditions, the loss of cultural identity and the disaffection of youth in many of these communities. The report's findings will inevitably prompt questions about current health provision for young Australians. At present, young people's primary care attendances, for example, are mostly for relatively minor respiratory conditions, musculoskeletal problems or acne. The conditions contributing to the disease burden in young people are less common reasons for general practice presentations, suggesting scope for the development of "youth-friendly" primary-care services capable of responding to youth health problems. With training in adolescent health care, general practitioners can both learn and retain the skills for responding to youth health needs,3 and such training could be linked to health education for young people about access, availability and use of health services. Health promotion has an even greater role. Health problems cluster not only in particular groups but also in individuals. For example, the young regular tobacco user is more likely to engage in heavy alcohol consumption and illicit drug use, have poorer mental health and an overall less healthy lifestyle.4 The clustering can mostly be traced back to common determinants of health in family, community, school and developmental backgrounds. Recent North American research has emphasised the protective influence of family and school attachment on problems ranging from deliberate self-harm and emotional distress to tobacco and illicit substance use, violence and early sexual activity.5 Such findings have been mirrored in recent Australian research.6,7 More importantly, preventive intervention targeting these social risk and protective factors is feasible and can be effective.8,9 Family and school-based interventions, both in adolescence and during childhood, have been shown to reduce adolescent problems as diverse as antisocial behaviour, substance abuse and sexually risky behaviour.9 Similarly, strategies based on community mobilisation, peer support, mentoring and legislative enforcement show promise in specific areas. Many gaps in our knowledge remain. Mental health problems loom large, but available data provide an incomplete picture of current need, changes over time and effectiveness of current health provision. Health profiles of groups with the greatest needs -- the young, the homeless and the disabled -- are incomplete, as are those of Aboriginal and Torres Strait Islanders. Much remains to be learned about health interventions and their effectiveness. Most importantly, data on the psychosocial processes that underpin youth health are not available. Health promotion should be guided not only by knowledge of the health problems of young people, but also by an understanding of relevant risk and protective factors. For mental health problems, these are likely to include parental care, the experience of psychosocial adversity, trauma and violence, victimisation, school failure and underemployment. This understanding is of value, not only in selecting the focus of health promotion, but in helping to ensure its continued relevance and sustainability. A recent report from the World Health Organization noted that most investment has gone into innovation rather than continuing programs, with only one in five youth health programs extending beyond five years.10 Sustainable preventive health programs for youth necessarily depend on effective cooperation with government sectors such as education, justice and employment, as well as non-governmental organisations involved with youth, younger children and their families. As the most comprehensive available account of the health of young Australians, the AIHW report will do much to inform the intersectoral dialogue that must underpin the setting of priorities and, in turn, the development of a rational advocacy. However, implementing effective responses to these priorities will require further work to build a more complete picture of the psychosocial determinants of the major health problems of young people. George C Patton Professor of Adolescent Health, Department of Paediatrics University of Melbourne Centre for Adolescent Health, Melbourne, VIC pattonATcryptic.rch.unimelb.edu.au Lynelle J Moon Senior Analyst, Population Health Unit Australian Institute of Health and Welfare, Canberra, ACT Reprints: Professor G C Patton, Department of Paediatrics, University of Melbourne, Centre for Adolescent Health, 2 Gatehouse Street, Parkville, VIC 3052. Moon L, Meyer P, Grau J. Australia's young people: their health and well-being. PHE19. Canberra: Australian Institute of Health and Welfare, 1999. Moon L, Rahman N, Bhatia K. Australia's children: their health and well-being. PHE7. Canberra: Australian Institute of Health and Welfare, 1998. Sanci LA, Coffey C, Veit FCM, et al. Evaluation of an educational intervention for general practitioners in adolescent health care: randomised controlled study. BMJ 2000; 320: 224-230. Hibbert M, Caust J, Patton G, et al. The health of young people in Victoria. Melbourne: Centre for Adolescent Health, 1996. Resnick MD, Bearman PS, Blum RW, et al. Protecting adolescents from harm: findings from the National Longitudinal Study on Adolescent Health. JAMA 1997; 278: 823-832. Glover S, Burns JBH, Patton GC. The Gatehouse Project: the scope of school based intervention for the prevention of adolescent depression. Family Matters 1998; 49: 11-16. Silburn SR, Zubrick SR, Garton AF, et al. Western Australian Child Health Survey: Family and Community Health. Perth: Australian Bureau of Statistics, 1996. (Catalogue No. 4304.5) National Crime Strategy (Homel R, editor). Pathways to prevention. Canberra: Attorney General's Department, 1999. Toumbourou JW, Patton GC, Sawyer S, et al. Guidelines to inform planning and purchasing of evidence-based practice: interventions for promoting health in the adolescent population. Melbourne: Department of Human Services, 1999. WHO/UNFPA/UNICEF Study Group. Programming for adolescent health and development. Geneva: World Health Organization, 1999. Make a comment Key points from the report Australia's young people: their health and well-being 19991 Young Australians remain in good health... Two-thirds of young people rated their own health as "excellent" or "very good" and getting better. Overall death rates for 12-24 year olds declined by 29% over the period 1979-1992 to 60/100000 (partly due to a 60% decline in motor vehicle accident deaths, 1979-1997), and have remained stable since then. but there are areas of concern... The major burden of disease (combined effect of mortality and disability) for this age group is from mental disorders. Injury is the leading cause of death for 12-24 year olds (40/100000 per year in 1997), with two-thirds of all deaths attributed to some form of injury, including accidents and suicide. Suicide (15.1/100000 per year) and drug-related deaths (4.2/100000 per year) have not followed the declines in most other causes of death, particularly for young men. In 1998, 25% of young people aged 14-19 years and 40% of those aged 20-24 years were regular or occasional smokers. While 54% of 15-24 year olds in 1995 were of acceptable weight, 22% were overweight or obese. The proportions of young people reporting exercising at a "vigorous" or "moderate" level for sport or recreation declined with age. and some groups are worse off. Recent death rates (1995-1997) for Aboriginal and Torres Strait Islander youth were 2.8 times higher for males (278/100000 per year) and 2.0 times higher for females (70/100000 per year) than those of their non-Indigenous counterparts (males, 101/100000 per year; females, 35/100000 per year). The 20% of males in the lowest socioeconomic group were 1.7 times more likely to die and 1.4 times more likely to be hospitalised than males in the highest group; for females, these ratios were 1.4 and 1.2, respectively. Twenty per cent of unemployed youth in 1995 assessed their health status as being fair or poor, compared with 9% of employed youth and 8% of students. Back to text

George C Patton · Lynelle J Moon

Editorial Mood disturbances and coronary heart disease: progress in the past decade Psychological factors are increasingly being identified as important contributors to the onset and course of coronary heart disease MJA 2000; 172: 151-152 Psychological conditions, such as life event stress, mood disturbance and personality disorders, are believed to be important risk factors for coronary heart disease (CHD).1-3 Building on the work of the past decade, growing evidence is emerging that mood disturbances can contribute substantially to CHD. This work has studied the effect of a range of emotional conditions, including hostility and anger, but we will focus here on anxiety and depressed mood. Anxiety Studies of patients with pre-existing CHD show that anxiety, independently of conventional risk factors, can be predictive of recurrent acute CHD events.4 Moreover, prospective studies of anxiety in normal populations show that there is an association between anxiety assessed at enlistment and subsequent CHD mortality over many years, even when conventional risk factors are controlled for -- the relative risks are significant, being of the order of 5-6 for sudden death and 2-3 for fatal acute myocardial infarction (AMI).5 Impressive data also come from prospective studies of panic disorder, which show that CHD mortality risk may be doubled in people with the disorder.6,7 There has been strong supportive psychophysiological evidence -- for example, in patients with pre-existing CHD undergoing ventriculography and exposed to trivial experimental stressful tasks, a significant but transient reduction (of up to 50%) in coronary muscle perfusion can occur.2,8 At the other end of the evidence hierarchy are the clinical case reports of patients with panic disorder, found to be free of CHD at angiography, who have had an acute AMI or ongoing angina following panic attacks.9 It has furthermore been shown that patients with panic disorder, while lacking any demonstrable peripheral elevation in serum catecholamine levels, nonetheless have significant release of adrenaline from the coronary sinus during panic attacks.10 This may in turn adversely affect coronary perfusion, cardiac rhythm, shear forces on atheromatous plaques, and platelet function.11 States of severe emotional arousal can also affect underlying pathophysiological risk factors for CHD, including platelet function and haemostasis.12,13 Longer-term effects of anxiety on cardiovascular pathophysiology are also possible; it has been shown that subjects with an exaggerated blood pressure response to mental stress may experience more rapid progression of carotid atherosclerosis.14 Depressed mood Depressed mood is emerging as an important risk factor for CHD. Depressed mood in CHD patients is associated with increased mortality.15 The increased risk is not trivial (relative risk > 3), being of the same order as other risk factors such as prior AMI and impaired left ventricular function after infarction. Even in long-term studies of normal CHD-free populations, depression at enlistment doubles the risk of subsequent acute coronary events16 and increases mortality risk.17 States resembling depression, such as "vital exhaustion" (characterised by fatigue, irritability and demoralisation),18 have been shown to be associated with acute myocardial events in normal populations even when conventional risk factors are controlled. Unlike the more acute effects of anxiety, the effects of depression are not immediate. Indeed, in one prospective study, mortality rates in women with depression did not begin to increase until after 16 months of follow-up.19 Thus, depression may well have a prolonged mode of action on CHD risk. One study found that one component of depression (ie, hopelessness) was associated with more rapid progression of atherosclerosis.20 The CHD risk of a person with chronic depression or dysphoric mood, either as an induced state or an enduring trait of "depressive" personality, needs further study. Personality Recently the "type D ('distressed') personality" has been described by Denollet et al as a result of finding significant differences in CHD outcome in those with certain personality traits. The type D personality is identified by two components: the continual experience of negative emotions, including depression, and the inhibition of social expression of these emotions. In a sample of patients undergoing cardiac rehabilitation, deaths from cardiac causes were increased fourfold in those with type D personality even after controlling for conventional risk factors.21 This suggests that type D personality (whether as a biological construct of temperament or a constellation of habitual behaviours) is a risk factor at least equivalent in importance to the other, "conventional" coronary heart disease prognostic factors. Implications It is possible that the association between mood and CHD risk is not causal, but that the two are linked by some common underlying genetic factor, perhaps associated with vascular disease in general. Weighted against this interpretation are the experimental findings showing the effect of emotions on cardiovascular pathophysiology. To explore the possibility of covariance, prospective aetiological and interventional studies are necessary to examine both mood state (which is episodic) and the personality-based predisposition (trait) to depression. Intervention studies are now in progress to assess whether antidepressants may reduce CHD events in those with depression following AMI.22 In the meantime, in patients with pre-existing CHD or those at increased risk of CHD, the identification and treatment of mood disorders, including anxiety and depression, is important for improving quality of life and for reducing the risk of CHD events and mortality. Christopher C Tennant Professor, Department of Academic Psychiatry Loyola McLean Lilly Psychiatry Research Training Fellow Department of Academic Psychiatry Royal North Shore Hospital, St Leonards, NSW tennantATmed.usyd.edu.au Hemingway H, Marmot M. Evidence-based cardiology: psychosocial factors in the aetiology and prognosis of coronary heart disease. Systematic review of prospective cohort studies. BMJ 1999; 318: 1460-1467. Rozanski A, Blumenthal JA, Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation 1999; 99: 2192-2217. Tennant CC, Palmer KJ, Langeluddecke PM, et al. Life event stress and myocardial reinfarction: a prospective study. Eur Heart J 1994; 15: 472-478. Moser DK, Dracup K. Is anxiety early after myocardial infarction associated with subsequent ischemic and arrhythmic events? Psychosom Med 1996; 58: 395-401. Kawachi I, Gollditz G, Ascherio A, et al. Prospective study of phobic anxiety and risk of coronary heart disease in men. Circulation 1994; 89: 1992-1997. Coryell W, Noyes R, House JD. Mortality among outpatients with anxiety disorder. Am J Psychiatry 1986; 143: 508-510. Weissman MM, Markowitz JS, Ouellette R, et al. Panic disorder and cardiovascular/cerebrovascular problems: results from a community survey. Am J Psychiatry 1990; 147: 1504-1508. Tennant C. Experimental stress and cardiac function. J Psychosom Res 1996; 40(6): 569-583. Mansour VM, Wilkinson DJ, Jennings GL, et al. Panic disorder: coronary spasm as a basis for cardiac risk? Med J Aust 1998; 168: 390-392. Wilkinson DJ, Thompson JM, Lambert GW, et al. Sympathetic activity in patients with panic disorder at rest, under laboratory mental stress, and during panic attacks. Arch Gen Psychiatry 1998; 55: 511-520. Deedwania PC. Hemodynamic changes as triggers of cardiovascular events. Cardiol Clin 1996; 14: 229-238. Grignani G, Pacchiarini L, Zucchella M, et al. Effect of mental stress on platelet function in normal subjects and in patients with coronary artery disease. Haemostasis 1992; 22: 138-146. Malkoff SB, Muldoon MF, Zeigler ZR, Manuck SB. Blood platelet responsivity to acute mental stress. Psychosom Med 1993; 55: 477-482. Kamarck TW, Everson SA, Kaplan GA, et al. Exaggerated blood pressure responses during mental stress are associated with enhanced carotid atherosclerosis in middle-aged Finnish men: findings from the Kuopio Ischaemic Heart Disease Study. Circulation 1997; 96: 3842-3848. Frasure-Smith N, Lesperance F, Talajic M. Depression and 18-month prognosis after myocardial infarction. Circulation 1995; 91: 999-1005. Ford DE, Mead LA, Chang PP, et al. Depression is a risk factor for coronary artery diease in men: the precursors study. Arch Intern Med 1998; 158: 1422-1426. Simonsick EM, Wallace RB, Blazer DG, Berkman LF. Depressive symptomatology and hypertension-associated morbidity and mortality in older adults. Psychosom Med 1995; 57: 427-435. Appels A, Otten F. Exhaustion as precursor of cardiac death. Br J Clin Psychol 1992; 31: 351-356. Whooley MA, Browner WS. Association between depressive symptoms and mortality in older women. Arch Intern Med 1998; 158: 2129-2135. Everson SA, Kaplan GA, Goldberg DE, et al. Hopelessness and 4-year progression of carotid atherosclerosis. The Kuopio Ischaemic Heart Disease Risk Factor Study. Arterioscler Thromb Vasc Biol 1997; 17: 1490-1495. Denollet J, Stanislas US, Stroobant N, et al. Personality as independent predictor of long-term mortality in patients with coronary heart disease. Lancet 1996; 347: 417-421. Shapiro PA, Lesperance F, Frasure-Smith N, et al. An open-label preliminary trial of sertraline for treatment of major depression after acute myocardial infarction (the SADHAT Trial). Sertraline Anti-Depressant Heart Attack Trial. Am Heart J 1999; 137: 1100-1106. Make a comment

Christopher C Tennant · Loyola McLean