Environmental Causes Of Disease Research Articles

Blaming the southern victim: Cancer and the Italian ‘Southern Question’ in Terra dei fuochi and Taranto

In this article, the author addresses two critical environmental situations in southern Italy: the Terra dei fuochi (Land of fires) near Naples, characterized by a history of illegal disposal of toxic waste, and Taranto, where the Ilva steel plants have a record of exceeding the legal emission limits for several pollutants. Despite a recognition of these situations, public political discourse in Italy still tends to link the higher than average incidence of cancer in the two areas to lifestyles rather than to environmental factors. The author locates this phenomenon within the larger context of the ‘Southern Question’ – the historical stigmatization of southern Italy as backwards and uncivilized. She argues that this same stereotype not only stigmatizes a geographical region, but also facilitates the stigmatization of the people who become ill in Taranto and Terra dei fuochi as the result of lifestyle rather than environmental factors. Furthermore, this same stereotype also stigmatizes social movements against the pollution as irrational and uncivilized. Previous studies have linked situations of environmental injustice to the Global South or to specific areas with racialized stereotypes; here it is argued that the whole southern half of Italy can be considered a new geographic scale in which phenomena of environmental injustice, denial of environmental causes of disease, and geographic stigmas, intersect.

Increased Minimum Mortality Temperature in France: Data Suggest Humans Are Adapting to Climate Change.

Outdoor temperatures can influence population mortality rates, with the mortality–temperature relationship typically depicted as a U- or J-shaped curve.1 The lowest point of this curve defines the minimum mortality temperature (MMT)—that is, the temperature with the lowest mortality rate—while the raised ends represent increased deaths at both lower and higher temperatures. A new study in this issue of EHP that’s based on 42 years’ worth of climatic and mortality data shows that the MMT in France has increased over time, suggesting some measure of adaptation to warming during that period.1 Climate change models predict higher average temperatures and more frequent and intense heat waves in the coming decades.2,3 Hot weather contributes to potentially deadly heat exhaustion and heat stroke, and can exacerbate preexisting medical conditions. This is particularly true for populations that are vulnerable due to age, socioeconomic factors, limited social support, geographic isolation (for instance, rural areas where air conditioning may be less common), and poor access to health care.2,3,4,5 Higher rates of heat-related deaths tend to occur with heat waves earlier in the summer, before people have acclimatized to the season’s hotter temperatures.6 Improvements in social, environmental, behavioral, and health care factors can reduce a population’s vulnerability,7 and acclimatization to warmer temperatures may also reduce heat-related impacts on human health.2,5 As mean summer temperatures in France increased over time (right), so did the temperatures associated with the lowest mortality rates (left). The current study demonstrates how statistical modeling paired with the increasing availability of enormous data sets might predict the extent to which humans can adapt to climate change. Unlike previous work exploring the temperature–mortality relationship, this study included small towns and rural settings as well as urban centers. The researchers used high-resolution climate data to superimpose a grid of 30×30-km squares over continental France. The resultant 295 squares encompassed 36,000 communes, the smallest administrative unit for which sociodemographic data were available. The researchers obtained death certificates for all people aged 65 and older who died of natural causes within continental France during 1968–2009, a total of 16,487,668 deaths. “Temperature influences many causes of deaths,” explains coauthor Alain-Jacques Valleron, emeritus professor at Universite Pierre et Marie Curie. “We would have lost much of what we wanted to study—the impact of temperature on mortality—if we had only focused on deaths that were registered as directly related to temperature.” Analyses of the temperature–mortality relationship focused on grid squares with more than 22,500 deaths during the entire 42-year period (228 squares). The researchers also divided the study period into three 14-year periods (1968–1981, 1982–1995, and 1996–2009), focusing on squares with more than 7,500 deaths during each period (224 squares). Nearly all squares had U- or J-shaped temperature–mortality curves. The MMT was found to shift upward over time, from 17.5°C (63.5°F) in the first period, to 17.8°C (64.0°F) in the second period, to 18.2°C (64.8°F) in the third period. Mean summer and winter temperatures also increased over time, by 1.6°C (2.9°F) for summer and 0.8°C (1.4°F) for winter. Subsequent sensitivity analyses corroborated these results. The authors concluded that adaptation to higher temperature had occurred during the 42-year period of the study.1 “I was interested in their conclusions about the MMT shift in time,” says Matthew Heaton, an assistant professor of statistics at Brigham Young University who was not involved in the study. “I think it’s a nice conclusion, but I’d like to see more to justify their conclusions—for example, confidence intervals or hypothesis testing.” Heaton also praises the length of time covered by the study, “the longest that I’ve seen,” and the fact that it covers rural areas. He points out that some of the analyses focused on locations that had more than 15,000 deaths, which cuts out the least populated areas. However, those analyses did not change the overall conclusions. The researchers are planning to expand on their findings, says Valleron, particularly with regard to the causes of mortality and in light of temperatures plateauing in some places within France. As the authors note, their study considered only one aspect of climate change that could affect health—temperature. Temperature-related impacts may coexist with other factors affecting mortality rates.2 However, these factors can also be examined using models similar to those in the current study. Says Valleron, “The approach can be extended to many environmental databases to try to find environmental causes of disease.”

New developments in the genetics of borderline personality disorder

ContextThe etiology of borderline personality disorder (BPD) is complex. Patients with BPD report many negative events during childhood, such as neglect, sexual abuse, and physical abuse. However, none of these antecedents is considered specific to BPD. Interestingly, a genetic vulnerability has been identified in patients with BPD, and there is a recent interest in the potential interaction between genetic and psychosocial factors (e.g., childhood abuse) in BPD.ObjectiveWe propose here a review of the current literature concerning the genetics of BPD and recommendations for future research.DiscussionHere are several explanations that may account for this lack of results. One of them may be due to the choice of candidate genes. Indeed, there is a tendency to look for genetic effects on disease rather than genetic effects on vulnerability to environmental causes of disease. We believe that such a conceptual shift may affect the choice of new candidate genes in BPD. Genes associated with the physiological response to stress in the hypothalamic–pituitary–adrenal axis are then natural candidates for gene–environment interactions research in BPD. Finally, we propose a paradigm shift, in which “plasticity” genes (rather than “vulnerability” genes) would be involved in the pathogenesis of BPD.ConclusionFamilial and twin studies largely support the potential role of a genetic vulnerability at the root of BPD, with an estimated heritability of approximately 40%. Moreover, there is evidence for both gene–environment interactions and correlations. However, association studies for BPD are sparse, making it difficult to draw clear conclusions. According to our meta-analysis, no significant associations were found.

Potential Input From Metabolomics for Exploring and Understanding the Links Between Environment and Health

Humans may be exposed via their environment to multiple chemicals as a consequence of human activities and use of synthetic products. Little knowledge is routinely generated on the hazards of these chemical mixtures. The metabolomic approach is widely used to identify metabolic pathways modified by diseases, drugs, or exposures to toxicants. This review, based on the state of the art of the current applications of metabolomics in environmental health, attempts to determine whether metabolomics might constitute an original approach to the study of associations between multiple, low-dose environmental exposures in humans. Studying the biochemical consequences of complex environmental exposures is a challenge demanding the development of careful experimental and epidemiological designs, in order to take into account possible confounders associated with the high level of interindividual variability induced by different lifestyles. The choices of populations studied, sampling and storage procedures, statistical tools used, and system biology need to be considered. Suggestions for improved experimental and epidemiological designs are described. Evidence indicates that metabolomics may be a powerful tool in environmental health in the identification of both complex exposure biomarkers directly in human populations and modified metabolic pathways, in an attempt to improve understanding the underlying environmental causes of diseases. Nevertheless, the validity of biomarkers and relevancy of animal-to-human extrapolation remain key challenges that need to be properly explored.

Using existing cohorts in research on environmental causes of diseases – pros and cons from a European Perspective

Cohorts are an excellent method to study the role of environmental factors in causing chronic diseases, but usually takes decades of data collection. Further studying environmental causes of diseases requires assessment of environmental exposures. However many environmental exposures can be assessed independently from study subjects by retrospective characterization using existing monitoring data and modeling. Therefore it is tempting to add retrospective and prospective environmental exposure assessment to existing cohorts for studying the role of such factors in causation of chronic diseases. An example of such studies is the ESCAPE (European Study of Cohorts for Air Pollution Effects) which is a large inter-disciplinary collaboration of 25 European partners in 17 countries linking 32 existing cohort studies including the SAPALDIA cohort in Switzerland. It aims to characterize long term exposure to traffic related pollution and its association with chronic pathologies with particular reference to pregnancy & birth outcomes, respiratory diseases, cardiovascular diseases and cancer. The work package for respiratory health in adults aims to investigate the effect of ambient air pollution on the level and change of lung function (FVC and FEV1), prevalence and incidence of COPD, prevalence of chronic bronchitis symptoms and incidence of asthma. Such studies using existing cohorts are faster, cheaper and efficient due to availability of long term health information including early life time covariates, socio-economic information, past changes in health and known co-factors. Availability of different phenotypes and biobanks are also advantageous. If environmental monitoring data are available it is easy to link with existing cohort data. However the major disadvantage will be the heterogeneity of study designs with respect to population selection, sampling, age structure etc. Large heterogeneity can occur with the questionnaires used, the health assessment methods, phenotype definitions, biobank markers, and quality of retrospective exposure assessment. Therefore “other-purpose” existing cohorts are complementary but not an alternative to establishing fully standardized cohorts, biobanks and enviro-banks. Large scale new mega cohorts with biobanks and enviro-banks have major scientific advantages that cannot be accomplished with uncoordinated smaller cohorts.

A Resolution for Physicians: Time to Focus on the Public Health Threat of Gun Violence

The Editors discuss how physicians, who have long been powerful voices in discussions of issues that threaten public health, should draw on similar motivations and strategies to promote sensible, e...

Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis

Epigenetic mechanisms integrate genetic and environmental causes of disease. Comprehensive genome-wide analyses of epigenetic modifications have not demonstrated robust association with common diseases. Using Illumina HumanMethylation450 arrays on 354 ACPA positive rheumatoid arthritis (RA) cases and 337 controls, we identified two clusters within the MHC region whose differential methylation potentially mediates genetic risk for RA. To reduce confounding hampering previous epigenome-wide studies, we corrected for cellular heterogeneity by estimating and adjusting for cell-type proportions and used mediation analysis to filter out associations likely consequential to disease. Four CpGs also showed association between genotype and variance of methylation in addition to mean. The associations for both clusters replicated at least one CpG (p<0.01), with the rest showing suggestive association, in monocytes in an independent 12 cases and 12 controls. Thus, DNA methylation is a potential mediator of genetic risk.

An Integrated Approach to the Exposome

The editorial by Lioy and Rappaport (2011) provides a timely addition to the discussion about the exposome and exposure science. We are encouraged by the recognition of the importance of combining measurements of personal exposure with measurements of biological markers of exposure. However, rather than focusing on two approaches (i.e., top-down vs. bottom-up), we advocate a fully integrated approach to measurement of the exposome. There are currently serious limitations in measuring internal and external exposure. It may be feasible to measure biological markers in blood or other media periodically, but such measures are not without difficulties. Recent developments in omics technology are very promising, but many of these techniques have low reproducibility between laboratories, show high intraindividual variability, and are still expensive; in addition, uncertainties remain in biological interpretation of these markers (Vineis et al. 2009). It is still often impractical to prospectively measure personal inhalation, dermal, and ingestion exposure. Such information could be collected periodically, but the scientific effort would be great and the intrusion into the subjects’ lives would probably be unacceptable. Increased research effort will undoubtedly help improve measurement of both internal and external exposure. However, other sources of information exist that could contribute to constructing the exposome. We all routinely leave traces of our exposome in everyday electronic databases or databases that could be easily constructed. For example, the goods we purchase in a supermarket are often tracked by loyalty cards, which may provide a rich source of information on food consumption and the consumer products we use. Consumption of electricity and natural gas is increasingly being logged electronically by utility companies to assist billing. These data could be used to determine use of electrical items (informative about exposure to electric and magnetic fields) and activity patterns. It is relatively straightforward to track movements of individuals using mobile phones, and these data can be used, for example, to help estimate exposure to air pollutants. Within the next few years we will see an explosion in availability of sensors for many environmental contaminants that will be relatively cheap and easy to use and that could provide a more or less continuous log of information that can be related to exposure. These include simple sensors in the homes of subjects that continuously record information on air temperature, airborne contaminants, and other environmental factors. These sensors may provide personal exposure data or could, in combination with activity patterns and behavior, be used to reconstruct exposure profiles. The availability of data on use and activity patterns, as well as developments in sensor and omics technology, suggests that the dichotomy in top-down and bottom-up approaches may not be appropriate, as there are other strategies that could be used to determine the exposome. In addition, the terms “top-down” and “bottom-up” may be interpreted differently, with consequent confusion of terminology. Instead, we should aim to develop a concept of the exposome that takes into account all sources of available exposure information. The key factor in developing an integrated approach will be the articulation of clear theoretical paradigms linking exposures with disease. All of the exposure and contextual data could be used to reconstruct the exposome of individuals in an epidemiological study using appropriate models to link the data to parameters of interest in the exposome. Data on internal and external exposures, data on personal behavior, and environmental information from sensors could be used to triangulate on the exposome. This is an extremely exciting time in exposure science, and we believe that the coming years will provide a great opportunity to make a significant leap forward in understanding the relationship between environmental exposure and disease. Maximizing the opportunities provided by various developments requires a fully integrated approach to the exposome. This approach must be based on a clear theoretical framework that incorporates measurement and modeling of external exposure, databanks on patterns of behaviors, and markers of internal exposure.

Discovering environmental causes of disease

Although chronic diseases are primarily environmental (ie, not genetic) in origin, the particular environmental causes of these diseases are poorly understood. A WHO study of worldwide cancer mortality identified nine...

A Study in Balance: How Microbiomes Are Changing the Shape of Environmental Health

The agents we now know as bacteria have been known for centuries to play a key role in certain kinds of illnesses and ailments. But aside from infectious diseases, the communities of microbes we carry in specific parts of our bodies—our microbiomes—are a relatively new topic in human health. Now this field of study has taken an evolutionary leap forward with new research showing human microbiomes may play a far greater role in environ-mental health than ever imagined. The excitement around this field was obvious at a National Academy of Sciences (NAS) workshop on the interplay of the microbiomes, environ-mental agents, and human health held 27–28 April 2011,1 where talks by researchers working in this area inspired numerous “eureka!” moments. New findings about the ways in which human microbiomes transform arsenic and mercury—two of our most prevalent and well-defined external human health hazards—suggest the role of commensal bacteria may equal or exceed that of genetic polymorphisms that regulate metal transformations within the body, says Ellen Silbergeld, a professor of environmental health sciences at the Johns Hopkins University Bloomberg School of Public Health. The implications of these new insights are staggering. Environmental health scientists may need to expand the toxicokinetics of metals and other environmental agents, as well as associated biomarkers, to include the microbial component. “This is a huge thing that has never been thought of before in environmental health sciences,” Silbergeld told workshop attendees. Emerging findings also demand a re-examination of what it means to be exposed to environmental agents, Silbergeld says. To a toxicologist, she explains, a contaminant is only “in the body” once it has crossed from the external environment into circulating blood, or a cell, or an organ. But new findings suggest biologically relevant transformations may take place prior to absorption, when contaminants interact with the microbiome in the mouth, intestines, or other tissues. Because of the metabolic processes mediated by microbiomes, a great deal of what toxicologists attribute to human metabolism—such as methylation of arsenic—may actually take place at least in part before contaminants cross into the internal environment of our bodies.

Assessing causal relationships in genomics: From Bradford-Hill criteria to complex gene-environment interactions and directed acyclic graphs

Observational studies of human health and disease (basic, clinical and epidemiological) are vulnerable to methodological problems -such as selection bias and confounding- that make causal inferences problematic. Gene-disease associations are no exception, as they are commonly investigated using observational designs. A rich body of knowledge exists in medicine and epidemiology on the assessment of causal relationships involving personal and environmental causes of disease; it includes seminal causal criteria developed by Austin Bradford Hill and more recently applied directed acyclic graphs (DAGs). However, such knowledge has seldom been applied to assess causal relationships in clinical genetics and genomics, even in studies aimed at making inferences relevant for human health. Conversely, incorporating genetic causal knowledge into clinical and epidemiological causal reasoning is still a largely unexplored area.As the contribution of genetics to the understanding of disease aetiology becomes more important, causal assessment of genetic and genomic evidence becomes fundamental. The method we develop in this paper provides a simple and rigorous first step towards this goal. The present paper is an example of integrative research, i.e., research that integrates knowledge, data, methods, techniques, and reasoning from multiple disciplines, approaches and levels of analysis to generate knowledge that no discipline alone may achieve.

Adductomics: Characterizing exposures to reactive electrophiles

To understand environmental causes of disease, unbiased methods are needed to characterize the human exposome, which represents all toxicants to which people are exposed from both exogenous and endogenous sources. Because they directly modify DNA and important proteins, reactive electrophiles are probably the most important constituents of the exposome. Exposures to reactive electrophiles can be characterized by measuring adducts from reactions between circulating electrophiles and blood nucleophiles. We define an ‘adductome’ as the totality of such adducts with a given nucleophilic target. Because of their greater abundance and residence times in human blood, adducts of hemoglobin (Hb) and human serum albumin (HSA) are preferable to those of DNA and glutathione for characterizing adductomes. In fact, the nucleophilic hotspot represented by the only free sulfhydryl group in HSA (HSA-Cys34) offers particular advantages for adductomic experiments. Although targeted adducts of HSA-Cys34 have been monitored for decades, an unbiased method has only recently been reported for visualizing the HSA-Cys34 ‘subadductome’. The method relies upon a novel mass spectrometry application, termed fixed-step selected reaction monitoring (FS-SRM), to profile Cys34 adducts in tryptic digests of HSA. Here, we selectively review the literature regarding the potential of adductomics to partially elucidate the human exposome, with particular attention to the HSA-Cys34 subadductome.

Environmental Pollution and Human Health: Estimation and Action, From Local to Global and Back

Environmental Pollution and Human Health: Estimation and Action, From Local to Global and Back

Children's Health and the Environment: An Overview

Environmental pediatrics, the branch of pediatric medicine that studies the influence of the environment on children's health, has in the past decade grown exponentially. Rising rates of pediatric chronic disease and growing recognition of children's extensive exposures and great vulnerabilities to toxic hazards in the environment have catalyzed this expansion. New scientific initiatives have resulted. They include 14 Centers for Children's Environmental Health and Disease Prevention Research supported by the US National Institutes of Health and the US Environmental Protection Agency; a global network of Pediatric Environmental Health Specialty Units supported by the US Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry; new postdoctoral training programs in pediatric environmental medicine; and the National Children's Study, the largest prospective epidemiological study of children's health ever undertaken in the United States, which launched in 2009 and will follow 100,000 children from conception to age 21 to assess environmental influences on health and development. These research initiatives have delineated the exquisite vulnerability of fetuses, infants, and children to toxic hazards in the environment. They have led to discovery of new environmental causes of disease and disability in children. This issue of The Mount Sinai Journal of Medicine focuses on children's health and the environment. We have brought together thought leaders in children's environmental health to critically examine new research findings, to explore new opportunities for translating research to treatment and prevention, and to offer a vision for the future of this rapidly expanding field.

The impact of new research technologies on our understanding of environmental causes of disease: the concept of clinical vulnerability

In spite of decades of epidemiological research, the etiology and causal patterns for many common diseases, such as breast and colon cancer or neurodegenerative diseases, are still largely unknown. Such chronic diseases are likely to have an environmental origin. However, "environmental" risks have been often elusive in epidemiological studies. This is a conundrum for current epidemiological research. On the other side, the relative contribution of genes to chronic diseases, as emerging from GWAS, seems to be modest (15-50% increase in disease risk). What is yet to be explored extensively is a model of disease based on long-term effects of low doses of environmental exposures, incorporating both genetic and acquired susceptibility ("clinical vulnerability"), and the cumulative effects of different exposures. Such a disease model would be compatible with the weak associations found by GWAS and the still elusive role of many (low-level) environmental exposures. We also propose that the introduction of "-omic" high-throughput technologies, such as transcriptomics, proteomics and metabolomics, may provide, in the next years, powerful tools to investigate early effects of environmental exposures and understand the etiology of common diseases better, according to the "clinical vulnerability model". The development of "-omics", in spite of current limitations and lack of sound validation, could greatly contribute to the elucidation of the disease model we propose.

NIEHS Supports Partnerships in Environmental Public Health

NIEHS Supports Partnerships in Environmental Public Health Linda S. Birnbaum, PhD I would like to start by thanking the journal for inviting me to write an editorial to accompany Dr. Juliana van Olphen and her colleagues’ thoughtful evaluation that focuses on the important topic of community health partnerships.1 As the new director of the National Institute of Environmental Health Sciences (NIEHS) and the National Toxicology Program, I am pleased to take on this role during a time when both the environment and health are top priorities for our country. I am a big supporter of community-based participatory research (CBPR) that ensures community members have an active role in planning, implementing, translating and disseminating research that addresses local environmental health concerns. NIEHS has been a long-standing leader in fostering partnerships between community groups and researchers to better understand environmental causes of disease. Our commitment is demonstrated in a number of ways. For example, NIEHS, in cooperation with the National Cancer Institute, requires that a Community Outreach and Translation Core (COTC) is established in each of our four Breast Cancer and the Environment Research Centers—one of which was the subject of Dr. van Olphen’s independent analysis published in this issue. COTCs conduct essential work to ensure that the views and concerns of the breast cancer advocacy community are heard and that the research findings are disseminated to the public. Developing educational materials for children and adults about breast cancer and the environment, holding public awareness forums and town meetings, and exploring areas of concern or interest to the community are all essential activities led by the COTC to create community participation in environmental health issues such as breast cancer. What van Olphen’s article demonstrates is that COTCs can further advance and promote CBPR principles within research-intensive Centers. NIEHS grantees employing CBPR approaches are contributing to our understanding about breast cancer and the environment. There is a growing body of literature showing that early-life exposures to endocrine disruptors—particularly during gestation and childhood, but also continuing through puberty, first childbirth, and breastfeeding—are critical to later-life breast cancer risk. As researchers learn more about what causes and how to prevent breast cancer, grantees such as those we support through our environmental justice program are spreading the word and empowering communities to take action. Breast cancer advocates in two communities that differ in racial/ethnic and economic character are working in partnership with researchers to assess household exposures to endocrine disrupting compounds, and to develop communication tools for reporting results to affected individuals and communities.2 These research findings are being used by community groups and advocates to affect public health and lead to policy changes. Congress recently recognized the contributions of NIEHS and the National Institutes of Health as a whole for their outstanding work in the breast cancer and environment area, when it passed the “Breast Cancer and Environment Research Act of 2008.”3 The Act looks to NIH to take a lead role in defining the future research agenda for collaborative research efforts related to breast cancer and the environment. NIEHS’ leadership role in translating research on breast cancer and the environment is the outgrowth of the Institute’s commitment to CBPR approaches that promote having the community actively involved in shaping and conducting research and intervention strategies. Since 1995, through its CBPR activities, the Institute has supported principles that have been developed and shared by leaders in the field such as those developed by Barbara Israel et al. 4 and Lawrence Green et al.5 Principles that call for building on the strengths and resources within the community; focusing on the local relevance of public health problems; and disseminating results to all partners are endorsed by NIEHS and are evident in work supported by NIEHS. Recognizing the [End Page 195] continuum of CBPR, the Institute promotes these principles throughout a variety of programs from traditional outreach and education efforts to more complex biomedical, hypothesis-driven research questions that address environmental justice and health disparities issues. To build upon our past accomplishments and to progress our research agenda in this area, we recently sought input from research grantees and members of advocacy...

Regulation and regulatory effectiveness in public health

Regulation for health in the modern era has its foundations in the English Public Health Act of 1848. Early legislation was concerned with controlling environmental causes of disease. However, the focus on regulation today within health departments has diminished, displaced by a focus on services and related programs. The regulatory debate is now centred on what degree of protection, or safety margin, is required, and how regulatory efficiency may be improved. The example of tobacco control is reviewed to show how regulation can play a large role in chronic disease control, and consideration given to how regulatory tools could be further diversified and regulatory effectiveness improved. Andrew Penman The Cancer Council NSW Email: andrewp@nswcc.org.au Population health goals in the early 21st century mostly focus on reducing mortality from chronic disease and the compression of associated morbidity.1 These conditions share common proximate risk factors rooted in lifestyle. Health promotion developed largely to change lifestyle behaviours through education and social change – a change mediated though information, services, the built environment and organisational practice. In this paradigm, the role of health protection, or health regulation, has been minimised, and the title given to the frontline warrior of the first public health act – Inspector of Public Nuisances – seems out of place in these more egalitarian times. Developments in health regulation Health promotion has resulted in a more explicit understanding of the diversity of the health environment and recognition that individual behaviour is profoundly affected by social context. Human behaviour and the environment interact, and environmental regulation can play an important role in chronic disease control. This understanding has required an evolution in the philosophy and practice of health regulation. The story of tobacco control illustrates the role that regulation can play in modifying behaviours and lifestyles. One development is in our understanding of chronic disease. Traditional health protection excelled at elimination of a hazardous agent at source. In chronic disease, specific regulatory measures are crafted to eliminate not the proximate cause of disease, but any of a number of contributory causes. Taken as a whole, these measures may be demonstrably effective in reducing risk, but the contribution of any single measure may be moderate to minor. Advertising bans, tax increases, smoke-free public places, on-pack warnings and point-of-sale restrictions have all contributed to smoking abatement. Although evidence can be adduced to demonstrate short-term impact on behaviour, it is more difficult to isolate the impact of each measure on smoking prevalence, and especially to predict this in advance of a regulatory decision.2 The statement, “Why don’t you just ban the stuff?”, heard in popular discourse on tobacco illustrates the public expectation that our measures should be more decisively effective. Another development has been to recruit regulatory instruments from outside the health sector, appropriate to the environmental–behavioural goals. In tobacco control, taxing 10.1071/NB08055 PERSPECTIVE

Regulation for chronic disease control: the pathfinder role of tobacco

Regulation for health in the modern era has its foundations in the English Public Health Act of 1848. Early legislation was concerned with controlling environmental causes of disease. However, the focus on regulation today within health departments has diminished, displaced by a focus on services and related programs. The regulatory debate is now centred on what degree of protection, or safety margin, is required, and how regulatory efficiency may be improved. The example of tobacco control is reviewed to show how regulation can play a large role in chronic disease control, and consideration given to how regulatory tools could be further diversified and regulatory effectiveness improved.

Managing risk: identifying environmental causes of disease

In most areas of science, non-experimental evidence does not command a great deal of public attention. In health, it frequently becomes a matter of urgent public concern. From the safety of vaccination to the risks of passive smoking, the validity of non-experimental research has often been a flashpoint of political as well as scientific debate. Yet observational research underpins a vast amount of clinical and public-health knowledge that is fundamental to daily medical practice and to policymaking. High-profile reversals of a few flawed or over-interpreted research studies should not be allowed to damage the overall credibility of non-experimental methods in medicine.

Mendelian randomization: can genetic epidemiology help redress the failures of observational epidemiology?

Establishing causal relationships between environmental exposures and common diseases is beset with problems of unresolved confounding, reverse causation and selection bias that may result in spurious inferences. Mendelian randomization, in which a functional genetic variant acts as a proxy for an environmental exposure, provides a means of overcoming these problems as the inheritance of genetic variants is independent of-that is randomized with respect to-the inheritance of other traits, according to Mendel's law of independent assortment. Examples drawn from exposures and outcomes as diverse as milk and osteoporosis, alcohol and coronary heart disease, sheep dip and farm workers' compensation neurosis, folate and neural tube defects are used to illustrate the applications of Mendelian randomization approaches in assessing potential environmental causes of disease. As with all genetic epidemiology studies there are problems associated with the need for large sample sizes, the non-replication of findings, and the lack of relevant functional genetic variants. In addition to these problems, Mendelian randomization findings may be confounded by other genetic variants in linkage disequilibrium with the variant under study, or by population stratification. Furthermore, pleiotropy of effect of a genetic variant may result in null associations, as may canalisation of genetic effects. If correctly conducted and carefully interpreted, Mendelian randomization studies can provide useful evidence to support or reject causal hypotheses linking environmental exposures to common diseases.