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A CHALLENGE TO HEALTH-CARE PROVIDERS -- CHANGING PATTERNS OF DISEASE: HUMAN HEALTH AND THE ENVIRONMENT
[This essay first appeared in SAN FRANCISCO MEDICINE November- December 2002, Volume 75, No. 9. See https://www.sfms.org/sfm/sfm1102b.htm .]
by Ted Schettler, MD, MPH*
For most of us, genetic inheritance plays a limited role in determining our health. More important is where and how we live, work, and play -- the quality of what we drink, eat, and breathe. >From the time of conception, throughout development, and into early and late adulthood, environmental factors either directly impact biological tissues or influence gene expression and shape subsequent disease risks.
Although links between exposures to environmental contaminants and health impacts have been known for centuries, recent research documents an expanding list of previously unrecognized effects after fetal or infant exposures. The developing fetus and child are particularly vulnerable to toxic insults. During this time cells are rapidly dividing, and growth is dramatic. Various events, including development of the brain and endocrine, reproductive, and immune systems, are uniquely susceptible to disruption that is often permanent. To compound the problem, pound for pound, children are often disproportionately exposed to toxic environmental agents because of the way they breathe, eat, drink, and play. Moreover, immature detoxification pathways in children frequently result in increased impacts of toxic exposures when compared to adults.
Small exposures to substances like lead, mercury, or polychlorinated biphenyls (PCBs), which have no discernible impact on adults, can permanently damage the developing brain of a child, if the exposure occurs during a window of vulnerability. Early exposures to dioxin or polychlorinated biphenyls (PCBs), chemicals from industrial activities that bioaccumulate in dietary fat, damage the developing immune system, making the child more prone to infections. Risks of asthma and high blood pressure are increased by early environmental exposures.[3,4] Recent research from Sweden concludes not only that environmental factors play a more important role than genetic inheritance in the origin of most cancers, but also that cancer risk is largely established during the first 20 years of life.
Technological developments have dramatically reduced mortality resulting from many diseases. In many instances, however, disease incidence is increasing, although for some conditions without standardized tracking mechanisms, trends are difficult to determine accurately. The burden from current patterns of disease and disability is enormous and extracts a terrible toll from individuals, families, and communities. Nearly 12 million children in the U.S (17 percent) suffer from one or more developmental disabilities, including deafness, blindness, epilepsy, speech defects, cerebral palsy, delays in growth and development, behavioral problems, or learning disabilities. Learning disabilities alone affect 5 to 10 percent of children in public schools, and these numbers appear to be increasing.
Attention deficit hyperactivity disorder conservatively affects 3 to 6 percent of all school children, and the numbers may be considerably higher. The incidence of autism seems to be increasing, though much of this apparent increase may be due to increased reporting. The age-adjusted incidence of melanoma, lung (female), prostate, liver, non-Hodgkin's lymphoma, testis, thyroid, kidney, breast, brain, esophagus, and bladder cancers has steadily increased over the past 25 years. Some birth defects, including disorders of the male reproductive system and some forms of congenital heart disease, are increasingly common. Sperm counts and fertility are in decline in some areas of the U.S. and other parts of the world. Asthma is more common and more severe than ever before. Genetic factors explain far less than half of the population variance for most of these conditions. Although smoking and sun exposure are well-recognized risk factors for some conditions, improved understanding of development of the brain and the immune, reproductive, respiratory, and cardiovascular systems leads to the conclusion that other environmental factors play a major role in determining current patterns of disease.
To the limited degree that health care providers address environmental factors at all, most focus nearly all of their attention on personal behaviors, like smoking, substance abuse, or use of sunscreens. These are more easily addressed by individuals than more complex problems like air and water pollution, hazardous waste sites, agricultural systems that inevitably result in farmworker pesticide exposures, and mercury contamination of dietary fish. Global environmental conditions, however, are changing, along with the changing pattern of disease and disability, and our increasing understanding of the importance of environmental factors in determining the health of individuals and populations places a new and special responsibility on the medical profession.
Consider that:
** Over 6 billion people inhabit the planet, and reasonable mid-level estimates predict 9 to 10 billion by mid-century. Two-and-a-half more "earths" would be needed to support today's population if everyone were to use as many resources as Americans do on a per capita basis.
** The release of ozone-depleting chemicals used for industrial and agricultural purposes has depleted the stratospheric ozone layer and is likely a major contributor to the increased incidence of malignant melanoma.
** Carbon dioxide concentration in the atmosphere has increased by nearly 30 percent in the last 150 years. Carbon dioxide is a greenhouse gas that contributes to global warming. Hazardous air pollution, in general, is the norm in most parts of the U.S. and elsewhere in the world.
** Humans are responsible for more atmospheric nitrogen fixation than all other sources combined. Nitrates contaminate groundwater, surface water, and air at toxic concentrations.
** Humans are responsible for most of the mercury deposition on the surface of the earth. Mercury makes its way into the food chain, where it bioconcentrates. In most states, freshwater and marine fish are sufficiently contaminated with mercury to require warnings to women of reproductive age to limit consumption because of risks to fetal brain development.
** Large numbers of plant and animal species have been driven to extinction, and most marine fisheries are severely depleted. More than half the world's coral reefs are threatened by human activities.
** In addition to naturally occurring products like lead and mercury that are mined from the earth, novel synthetic industrial chemicals contaminate the world's ecosystems, its human and non-human inhabitants, their breast milk and egg yolk, ovarian follicles, amniotic fluid, and meconium. The toxicity of most is little known.
** Of the approximately 85,000 chemicals on the federal inventory, nearly 3,000 are produced in excess of 1 million pounds annually. For these high-production volume (HPV) chemicals, toxicity data are surprisingly sparse. Even basic toxicity testing results are not publicly available for 75 percent of them. In the U.S., according to the 2000 Toxics Release Inventory, over 6.2 billion pounds of the listed toxic chemicals, including 2 billion pounds of known or suspected neurotoxicants, were released into the environment by major emitters required by federal law to file reports. Emissions from small industries and neighborhood shops are unquantified. The extent of exposure from these releases and from the use of various consumer products that contain them is also largely unknown, but population-based surveys give an indication of the ubiquity of exposures.
As the industrial revolution has continued to unfold over the last century, humans have fundamentally altered the local and global environment. We see signals and changing patterns in the development of children and subsequent occurrence and distribution of disease that deserve serious attention. The medical community is challenged to widen its scope of responsibility to embrace a more ecological assessment and response to the emerging pattern of disease and disability.
Early in their training, health care providers are taught to inquire into the family and social history of their patients or clients. This is not enough. Specific knowledge of the home, community, workplace, and school environment is essential for identifying risks and mapping preventive strategies. Medical education needs to incorporate into the curriculum new understanding of the role of the environment in the development of disease and disability. Health clinicians can also play important roles in policy debates at the community, state, or national level. The division between medical practice and public health practice that began in the early 20th century has not narrowed nearly enough. Health care providers can become strong advocates for clear air and water, for communities free of hazardous waste sites, and schools free of toxic chemicals and mold.
The public supports a large medical-industrial complex, but that support is not limitless. It is time for the medical community to re-examine its priorities and social contract with the public, and to integrate fully and creatively into routine medical care what we know about the causes of the changing pattern of diseases and disabilities.
* Dr. Schettler is on the medical staff of Boston Medical Center and has a clinical practice at the East Boston Neighborhood Health Center. He is science director of the Science and Environmental Health Network (https://www.sehn.org). Dr. Schettler is co-author of GENERATIONS AT RISK: REPRODUCTIVE HEALTH AND THE ENVIRONMENT, which examines reproductive and developmental health effects of exposure to a variety of environmental toxicants. He is also co-author of IN HARM'S WAY: TOXIC THREATS TO CHILD DEVELOPMENT, which discusses the impact of environmental exposures on neurological development in children.
FROM SILENT SPRING TO SCIENTIFIC REVOLUTION, PT. 2
by John Peterson Myers*
We are exploring the shifts in scientific thinking about chemicals and health that have occurred since the publication of Rachel Carson's SILENT SPRING in 1962 -- shifts resulting from the discovery that some industrial chemicals in the environment can interfere with hormones and growth factors in plants and animals, including humans. This essay first appeared in SAN FRANCISCO MEDICINE, November 2002. See https://www.sfms.org/sfm/. For more documents related to these topics, see https://www.OurStolenFuture.org and https://www.ProtectingOurHealth.org. --Peter Montague, editor]
Low Doses May Be More Potent than High Doses
Another key shift [in scientific thinking] is the acknowledgement that the assumption that the dose makes the poison can be misleadingly simplistic, if it is used to imply that only high dose exposures induce effects. In fact, low exposure levels sometimes cause effects not seen at higher levels [for example, see 12,13,14]. Researchers are now intensely pursuing these non-monotonic dose response curves and the uncertainty about their underlying mechanisms, which likely vary from case to case. [A "non-monotonic dose response curve" means that as the dose of a chemical is raised or lowered, the effect does not necessarily rise or fall in lock step with the dose. In some cases, low doses may cause greater effects than high doses.] One plausible hypothesis [to explain why dose and response do not always move together in lock step] is that at low, physiological levels, the contaminant interferes with developmental signaling but does not activate biochemical defenses against impacts that would be caused by higher exposures. At somewhat higher levels, these defenses are activated and the contaminant is successfully detoxified. At even higher levels, the defense mechanisms are overwhelmed by the toxicant and more traditional toxicological effects are induced.
Common Chemicals Can Disrupt Hormone Signals
As scientific research has focused on mechanisms of message disruption, it has implicated a wide array of chemicals. This expansion has involved both ongoing identification of compounds capable of interfering with estrogen, which was the initial focus, as well as research broadening the range of message systems studied. Some of the most troubling discoveries about new actors is that they involve compounds in widespread use in consumer products, including plastic additives like phthalates and plastic monomers like bisphenol A, which leaches from polycarbonate products. [Polycarbonates are strong plastics, such as Lexan, used in drink bottles, eyeglass lenses and shatterproof windows.]
New Studies Reveal Unsuspected Health Effects
That is not to say that we have complete understanding of even the best known contaminants. This reality was highlighted by a study published in 2001 about DDT, in which Longnecker and others report a highly significant association between DDT in maternal serum [blood] and the likelihood of preterm [premature] birth. Their study used birth records and stored serum from the mid 1950s-60s. They concluded that the U.S. had experienced a hitherto undetected epidemic of preterm birth during this period because of DDT use. Longnecker (personal communication) went further to estimate that because of the close association between preterm birth and infant mortality, up to 15% of infant mortality during that period may have been attributable to DDT use.
Chemicals Interfere with Hormones in Unsuspected Ways
Disrupting chemicals have been identified that interfere with [many hormone systems, such as] estrogen, androgen, progesterone, thyroid, insulin and glucocorticoid signaling, among others. The mechanism does not always involve mimicking (or inhibiting) ligand-receptor binding. [Many hormones work like a key fitting into a lock and the scientific name for this is ligand-receptor binding.] For example, as noted above, atrazine appears to enhance aromatase conversion of testosterone to estrogen.
Chemicals Can Disrupt Hormones in Several Ways
Signal disruption may also intercede in steps leading to gene activation after ligand-receptor binding. [In other words, after the hormone key fits into one of the cell's locks, other things should happen, but some chemicals disrupt normal events at this stage.] This was established by in vitro [test tube] experiments showing that arsenic selectively inhibits gene activation by the glucocorticoid-receptor complex after normal ligand-receptor binding and subsequent entry into the cell nucleus, at arsenic concentrations far beneath cytotoxic [toxic to cells] levels. While human health impacts have yet to be demonstrated via this mechanism, dysfunctions [interferences] in glucocorticoid action have been linked to weight gain/loss, protein wasting, immunosuppression, insulin resistance, osteoporosis, growth retardation, and hypertension.
Mixtures are Important but Not Often Studied
Another important issue raised by emerging science is the powerful interactions that can occur within mixtures of chemicals, even though regulatory toxicology is conducted virtually exclusively on pure single compounds. Two results published in 2002 emphasize the importance of considering mixtures: In the first, Rajapakse and others demonstrated that a mixture of estrogenic compounds, each present at a level beneath that capable of producing a statistically detectable estrogenic response in an in vitro [test tube] system, combined to more than double the response of the system to 17-estradiol [the commonest form of female sex hormone]. In the second, Cavieres and others found that a common off-the-shelf dandelion herbicide mixture strongly reduced fetal implantation [successful pregnancy] rates in mice at one-seventh the concentration considered safe for its principal herbicidal component, 2,4-D, by the U.S. Environmental Protection Agency.
Chemicals and Germs Together Increase Disease Risks
The issue of mixtures is complicated further by interactions now known to occur between contaminants and infectious agents [bacteria and viruses]. Large increases in disease risk can be associated with simultaneous exposure to contaminants and infectious agents. For example, Rothman and others reported a greater than 20-fold increase in relative risk to non-Hodgkins Lymphoma with combined exposure to elevated (but still background) PCBs and Epstein-Barr virus. The mechanism underlying this result is unknown, but is possibly due to well-established immune system impairment by PCBs. If this mechanism is widespread, then current estimates of morbidity and mortality due to contamination are likely to be unrealistically low. Immune system interference by a variety of contaminants is widely reported.
Traditional Regulatory Science May Not Protect Us
Together these conceptual shifts are also challenging the adequacy of current epidemiology to guide regulatory standards. The patterns underlying these conceptual shifts -- including (1) non-monotonic dose response curves; (2) windows of vulnerability during development; (3) the ubiquity of mixtures; (4) the likelihood that multiple chemicals can induce similar impacts via disruption of developmental processes; (5) the same chemical can cause different impacts depending upon when exposure occurs; (6) long latencies [delays] between exposure and manifestation of impact in a mobile population, etc. -- all increase the likelihood of false negatives [falsely concluding that no harm is occurring] in epidemiology as it is currently practiced.
Thus the revolution in science that Rachel Carson stimulated raises today a series of troubling questions about whether current health standards truly protect public health. Effects of low level, background exposures are likely to be far more widespread than acknowledged, and involve many more health endpoints [health effects] than traditionally considered, yet these new mechanisms of toxicity thwart the epidemiological tools now available to establish human harm.
Important Role for Health Professionals
We are confronting an enormous gap between what science now tells us about the links between contamination and health, and the antiquated approaches still used to safeguard public health. Health professionals will be important contributors to narrowing that gap, first by informing themselves about the underlying science, and then by helping to advance public understanding of the emerging evidence. Carson's scientific revolution can drive a transformation in public health that reinvigorates investments in prevention through exposure reduction.
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