What are environmental diseases?

Causes and Symptoms

The modern word “miasma” comes from the Greek miasma or miainein, meaning “pollution” or “to pollute.” Before scientific theories of disease became entrenched in medical practice, miasma was used to connote bad environments in which human exposure led to various diseases. Even today, one of the most devastating human diseases, malaria, draws its name from references to “bad air.” There is clearly a rich historical record of human recognition of the intimate connection between environmental quality and diseases. It is now known that serious human diseases are caused by numerous chemical, physical, and biological agents (risk factors) that occur naturally or as a result of human actions that modify the environment. In fact, the more that is learned about disease etiology, the more the complex interplay between environmental conditions and root causes of diseases within the body are recognized. Furthermore, some people are more sensitive to environmental risk factors because of their age, sex, occupation, culture, or genetic characteristics.

Environmental diseases are those illnesses for which cause and effect can be reasonably associated through epidemiological studies, preferably verified through laboratory experiments. Therefore, the recognition of environmental diseases draws upon two traditional postulates regarding causation in the study of human diseases, one ascribed to Robert Koch
(1843–1910) and the other ascribed to Austin Bradford Hill (1897–1991). The more important set of guidelines for environmental diseases is generally known in epidemiology as Hill’s criteria of causation, based on his landmark 1965 publication entitled “The Environment and Disease: Association or Causation?” Hill warned that cause-effect decisions should not be based on a set of rules. Instead, he supported the view that cost-benefit analysis is essential for policy decisions on controlling environmental quality in order to avoid diseases. It is arguable that Hill’s treatise initiated current trends characterized by the precautionary principle in environmental health
science. Nevertheless, Hill’s nine viewpoints for exploring the relationship between environment and disease are worth emphasizing. They are precedence, correlation, dose-response relationship, consistency, plausibility, alternatives, empiricism, specificity, and coherence.

According to the precedence viewpoint, exposure must always precede the outcome in every case of the environmental disease. One of the most famous examples here is the classic epidemiological study of John Snow (1813–58) on the spread of cholera
and its association with exposure to contaminated water in the densely populated city of London.

According to the correlation viewpoint, a strong association or correlation should exist between the exposure and the incidence of the environmental disease. The clustering of diseases within neighborhoods or among workers at a specific occupation is frequently the beginning of investigations into environmental diseases. Clusters can provide strong evidence of correlations. Bernardino Ramazinni (1633–1714), considered by many to be one of the founders of the discipline of occupational and environmental health sciences, published his treatise De Morbis Artificum in 1700 following critical observations regarding the correlation between environmental exposures of and diseases in workers.

According to the dose-response viewpoint, the relationship between exposure and the severity of environmental disease should be characterized by a dose-response relationship, in which an increase in the intensity and/or duration of exposure produces a more severe disease outcome. “The dose makes the poison” is one of the central tenets of environmental toxicology. This phrase is attributed to Paracelsus (1493–1541). This tenet has proven difficult to interpret for formulating health policy in the case of environmental diseases because the variation in human genetics and physiology means that, in many situations, a single threshold of toxicity cannot be established as safe for every person. Exposure to ionizing radiation
is an example of a situation in which it is difficult to establish dose-response relationships that are useful for setting uniformly applicable preventive health policy.

According to the consistency viewpoint, there should be consistent findings in different populations, across different studies, and at different times regarding the association between exposure and environmental disease. This means that the relationship should be reproducible. For example, exposure of people to mercury across civilizations, occupations, and age groups has been consistently associated with certain health effects that allowed the recognition of the special hazards posed by this toxic metal. Mercury was used in various manufacturing processes for several centuries, and where precautions are not taken to prevent human exposure, disease invariably results.

Consistency should cut across not only generations but also occupations and different doses of exposure. For example, “mad hatter’s” disease was associated with the use of mercury in the production of fur felt, in which mercurous nitrate was used to add texture to smooth fibers such as rabbit fur to facilitate matting (the process is called "carroting" because of the resulting orange color). More recently, the exposure of pregnant women to fish contaminated with methyl mercury from industrial sources in Japan produced developmental diseases in fetuses. The societal repercussions of the so-called Minamata Bay disease are still not completely settled after more than fifty years. Mercury is now widely recognized as a cumulative toxicant with systemic effects and organ damage, with symptoms including trembling, dental problems, blindness, ataxia, depression, and anxiety.

According to the plausibility viewpoint, compelling evidence of “biological plausibility” should exist that a physiological pathway leads from exposure to a specific environmental risk factor to the development of a specific environmental disease. This does not exclude the possibility of multiple causes, some acquired through environmental exposures and others through genetic processes. For example, lead poisoning
has been recognized since the 1950s as a pervasive and devastating environmental disease. The symptoms of lead poisoning vary, from specific organ effects, such as kidney disease, to systemic effects, such as anemia, and to cognitive effects, such as intelligence quotient (IQ) deficiency. How a single environmental toxicant can produce such wide-ranging diseases was a puzzle until the molecular mechanisms underpinning lead poisoning and the pharmacokinetic distribution of lead in the human body was understood. Lead is temporarily stored in the blood, where it binds to a key
enzyme, aminolevulinate dehydratase, which participates in the synthesis of heme. The by-products of that reaction produce anemia and organ effects, including kidney and brain diseases. Long-term storage of lead in the body occurs in bony tissue, where other effects are possible. These biological understandings have helped activists and scientists agitate for environmental policy to reduce lead exposure worldwide.

According to the alternatives viewpoint, alternative explanations for the development of diseases should be considered alongside the plausible environmental causes. These alternative explanations should be ruled out before conclusions are reached about causal relationships between environmental exposures and disease. For example, the typically low doses to which populations are exposed to pesticides and the long time period between exposure and the typical chronic disease outcomes, such as cancers and neurodegenerative disorders, make it difficult to reconstruct the disease pathways and pinpoint causative agents. This is where it is important to consider all alternatives and to eliminate them before compelling arguments can be made about the effects of pesticide toxicity. Sometimes observing wildlife response to environmental risk factors help narrow down alternative explanations, as Rachel Carson taught in her timeless book
Silent Spring
(1962).

According to the empiricism viewpoint, the course of environmental disease should be alterable by appropriate intervention strategies verifiable through experimentation. In other words, the disease can be preventable or curable following manipulation of the environment and/or human physiology. For acute exposures, the emergency response is to eliminate the source of exposure. However, this is not always possible in cases where patients are unconscious or otherwise unable to articulate clearly the source of exposure, as is the case for many children. Nevertheless, standardized procedures exist for responding to environmental exposure beyond eliminating the source. For example, therapy based on chelation (from the Greek chele, meaning “claw”) works for toxic metal
exposure because the mode of action of the therapeutic agent, ethylene diamine tetra-acetic acid (EDTA), is well understood. It is possible to establish empirically the relative effectiveness of EDTA in dealing with various forms of toxic metal exposures. For example, under normal physiological conditions, EDTA binds metals in the following order: iron (ferric ion), mercury, copper, aluminum, nickel, lead, cobalt, zinc, iron (ferrous ion), cadmium, manganese, magnesium, and calcium. Based on this information, it is possible to design therapeutic processes that minimize adverse side effects.

According to the specificity viewpoint, when an environmental disease is associated with only one environmental agent, the relationship between exposure and environmental disease is said to be specific. This strengthens the argument for causality, but this situation is extremely rare. For example, the rarity of mesothelioma, a lung disease that afflicts people who have been exposed to asbestos fibers, made it possible to use epidemiological evidence quickly to support policy in restricting the use of asbestos in commercial products and to protect employees from occupational exposures.

The recognition of new diseases often leads to speculation about causative agents or conditions. Occasionally, new ideas about causation challenge orthodox theories. According to the coherence viewpoint, it is important to conduct a rigorous assessment of coherence with existing information and scientific ideas before such causes are accepted in the case of environmental diseases. For example, the origin of neurodegenerative diseases associated with exposure to prion
protein remains mysterious, and some environmental causes have been proposed, including exposure to toxic metal ions. Another example is the current concern with the introduction of nanoparticles into commercial products, with concomitant environmental dissemination. Although much has been learned from an understanding of the human health effects of respirable particulate matter, researchers should be sufficiently open-minded to the possibility that nanoparticles will behave differently in the environment and in the human body.

Hill’s nine viewpoints were presented in the context of pitfalls associated with overreliance on statistical tests of “significance” as a justification to base health policy on epidemiological observations. Hill’s viewpoints have been debated extensively, and it is worth noting the following caveats presented in the 2004 article “The Missed Lessons of Sir Austin Bradford Hill,” by Carl V. Phillips and Karen J. Goodman: statistical significance should not be mistaken for evidence of substantial association; association does not prove causation; precision should not be mistaken for validity; evidence that a causal relationship exists is not sufficient to suggest that action should be taken; and uncertainty about causation or association is not sufficient to suggest that action should not be taken.

The second set of guidelines regarding causality derives from what is generally known as Koch’s postulates, but it is perhaps only useful for precautionary approaches to proactive assessment of potential health impacts of new agents about to be introduced into the environment. This approach complements the epidemiology-based inferences described by Hill, but further refinement is warranted to deal with complicated issues such as interactions between multiple environmental agents, which could have additive, neutral, or canceling effects. The question of dose is also difficult to subject to simple conclusions because of phenomena such as hormesis, in which small doses may show beneficial effects.

For environmental diseases, a modified version of Koch’s postulates can be expressed as follows. First, exposure to an environmental agent must be demonstrable in all organisms suffering from the disease but not in healthy organisms (assuming predisposition factors). Second, the identity, concentrations in different environmental and physiological compartments, and transformation pathways of the agent must be known as much as possible. Third, the agent should cause disease when introduced into healthy organisms. Fourth, biomarkers showing modification of the physiological target affected by the environmental agent must be observable in experimentally exposed organisms.

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