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Vol. 12 Issue 3, Summer 2007

Biomonitoring and Biomarkers Update
The Ribbon 

By Suzanne Snedeker, Ph. D., BCERF Associate Director for Translational Research

It has been five years since the Centers for Disease Control and Prevention (CDC) received funding to launch its Environmental Public Health Tracking Program, which includes the biomonitoring of blood and urine levels of environmental chemicals in the general US population. Recently the CDC released a report on the history of the tracking program and progress they have made toward making linkages between the environment and human health. Canada has recently announced the launching of a new biomonitoring program as part of a larger health survey being conducted from 2007-09. Researchers and medical professionals have projected new directions that can be taken in future to develop biomarkers of diseases, including cancer biomarkers and environmental biosensors. Summaries and commentary on all three of these areas are provided, plus an update by Sandra Steingraber on the new biomonitoring legislation in California.

Biomonitoring and Environmental Health Tracking in the US

The CDC has recently released a new report, Keeping Track, Promoting Health (hereafter Keeping Track), which highlights the history of the CDC’s tracking program, as well as the successes and challenges of the first four years (2002-2006). This includes efforts devoted to designing, improving, and formulating the many components and infrastructure needed for the tracking program’s operation and long-term sustainability. An executive summary of this report is available at http://www.cdc.gov/nceh/tracking/keepingtrack.htm, and the 53-page report is downloadable as a pdf file. Major elements of the report are outlined below.

The Gap. The concept of identifying chemical hazards and assessing impact on the health of both wildlife and humans was a relatively new idea when the Environmental Protection Agency (EPA) was created in 1970. However, creation of the EPA resulted in moving some of the responsibilities for monitoring public health as impacted by environmental factors from other federal public health agencies to the EPA. The CDC report, in summarizing the history of the tracking program, notes that by 1988 the Institute of Medicine of the National Academies issued a report stating that the public health system in the US had a poor infrastructure. One of its weaknesses was a “fragmented responsibility for environmental health” (page 12, as cited in Keeping Track). This was echoed in the Pew Environmental Health Commission’s report issued in 2000. The Pew report documented an “environmental health gap” (page 13, as cited in Keeping Track). The US lacked basic information to link environmental hazards with chronic diseases. The Pew report’s recommendation for an environmental public health tracking system ultimately lead to congressional funding for the CDC to establish such a program starting in 2002. The accomplishments of the CDC program fall into several categories.

Update on California’s Environmental Contamination Biomonitoring Program
By Sandra Steingraber, Ph.D.

Suppose evidence emerges from studies of laboratory animals for a link between a particular chemical and early sexual maturation. Suppose this chemical is found in popular consumer products like, say, cosmetics. Or suppose it is a pesticide in widespread use. Could exposure to this chemical be playing a role in the falling age of puberty in US girls?

Without a biomonitoring program, there is no good way to answer that question. Evaluating the influence of chemical exposures on endpoints like pubertal timing is nearly impossible in the absence of a baseline for chemical exposure in infants and children. The US Centers for Disease Control (CDC) does monitor chemical contaminants in a representative sample of the US population, but the CDC’s program collects very little data on infants and young children. And it does not target highly exposed populations for testing.

Enter the California Environmental Contamination Biomonitoring Program. In September 2006, California became the first state to mandate a statewide biomonitoring program. When fully implemented, it will test for the presence of environmental chemicals in the bodies of a representative sample of Californians throughout the state as well as initiate localized studies in communities of concern. Children of farm workers and nail salon workers could, for example, be identified as a subpopulation that could potentially benefit from biomonitoring.

Although late, the state’s FY 08 budget did recently pass, containing a full $5.2 million for the program.

Governor Schwarzenegger had requested only $1.5 million for the first year. Most observers felt this was a paltry sum because it would only allow planning in Year One of the program. Subsequently, the Senate pro Tem Don Perata, who was the lead author on the bill creating the program, has been able to raise the proposed budget to $5 million. The $5.2 million which has been allocated should enable a good launch for the program, including the purchase of laboratory equipment.

The program is to be guided by a nine-member Scientific Guidance Panel, with four appointments from the Legislature and five from the Governor. The Senate Rules Committee has already named two appointments. They are Dr. Richard Jackson, former Director of the National Center for Environmental Health at CDC and currently Adjunct Professor at UC Berkeley's School of Public Health, and Dr. Gina Solomon, Assistant Clinical Professor of Medicine at UC San Francisco and Senior Scientist at the Natural Resources Defense Council.

Davis Baltz, the director of the Precautionary Principle Project at Commonweal in Bolinas, California and longtime watchdog of the biomonitoring legislative process, feels optimistic. “The program is an important milestone – it is the first statewide biomonitoring program in the country. It will generate important exposure information on environmental chemicals that we need but don't have, and it will likely spur legislative initiatives in other states.”

Here are some key aspects of the program:

* The program does not restrict chemicals that can enter the program. There are permissive criteria that will allow the inclusion of chemicals of concern to the state. There is no requirement for a risk assessment to be performed before chemicals can enter the program.

* There is a right-to-know provision. The program will allow contributors (those providing their blood or urine) to receive results if they want them.

* The program's first priority will be to generate a statewide "snapshot" of environmental chemical exposure among Californians. In addition, the program will begin to plan for and then conduct smaller, localized community-based studies. Thus, California will be able to track statewide exposure trends over time, as well as investigate at highly exposed communities.

* The program represents a collaboration of three agencies. The lead is the California Department of Public Health, and the two others are both within the California Environmental Protection Agency: the Department of Toxic Substances Control (DTSC) and the Office of Environmental Health Hazard Assessment (OEHHA).

The new law's language can be found at:

http://www.leginfo.ca.gov/pub/05-06/bill/sen/ sb_1351-1400/sb_1379_bill_ 20060929_chaptered.html

Sandra Steingraber, Ph.D., is a Distinguished Visiting Scholar at Ithaca College and former scholar in residence at BCERF. Her new monograph, The Falling Age of Puberty in U.S. Girls: What We Know, What We Need to Know, is available free of charge from The Breast Cancer Fund (www.breastcancerfund.org) and is available for electronic download at www.breastcancerfund.org/puberty/.

Biomonitoring Program. The CDC wisely used an established survey, the National Health and Nutrition Examination Survey, to monitor the levels of environmental chemicals in a cross section of the general population every two years. The biomonitoring program has been expanded from monitoring 25 chemicals in the first biomonitoring report to 135 chemicals in the 2005 report. The 2007 report (not yet published) will provide data on monitoring 148 chemicals in blood and urine in the general US population. Age groups monitored range from young children to seniors, with additional data collection to determine levels of chemicals among certain racial/ethnic groups (Mexican-Americans, Non-Hispanic blacks, Non-Hispanic whites).

State and City Pilot Projects. Keeping Track states the premise that has driven early phases of the tracking program: local agencies understand local problems best, and can be the most efficient at monitoring and taking action on local environmental health concerns. But the CDC realized that states and cities needed resources to establish better ways to collect environmental data, and to make linkages with existing state databases that contain health and environmental endpoints. Hence the CDC funded a pilot study conducted in New York City that enabled investigators to link 15 different sources of information to track whether the misuse of pesticides could be linked to illness in children, as well as effects on fetal health. The CDC grant also supported programs to allow residents to report illegal use of certain pesticides, and to learn more about appropriate methods for pest control. According to the study’s chief investigator Daniel Kaas, the study was an amazing success. “We were phenomenally successful in making a difference at the local level, increasing awareness, reducing hazards, and improving health” (page 2 of Prologue, Keeping Track). Other such pilot projects provided many states and several cities with resources to both improve their capacity to monitor environmental and health endpoints, and more importantly, provided funding to make connections between levels of chemicals in the environment and people, with actual health effects.

“Connecting the Dots” at the National Level. Keeping Track emphasizes that making connections is vital to understanding the total picture of how our environment may affect our health. Many times we don’t make optimal use of existing data because of a failure to “connect the dots.” Many federal agencies are already responsible for monitoring levels of chemicals in the environment: the EPA monitors air quality; the U.S. Geological Survey (USGS) monitors chemicals in waterways and wells, and the National Aeronautics and Space Administration (NASA) tracks geographic information on a spatial basis (called GIS). While much of this federal environmental data is public information, all of the different databases need to be looked at together to get a better picture of which chemicals are in the environment and what is the potential for exposure. And in order to interpret the data, levels in the environment and biomonitoring data in people need to be linked to existing health databases. The CDC discovered that linking environmental levels of chemicals to existing health data was, and remains, a real challenge. This is partly because health endpoint data (e.g. cancer diagnosis or mortality data, birth outcomes, poisoning data) is collected by cities, counties and/or states, or is a part of individual research projects. Confidentiality issues affect both access to data and to what extent health endpoint data is used. Different databases maintained by different states and municipalities may code information differently. Keeping Track relates the fundamental challenges of sharing data when one locale records information by street, and another by zip code. Current legal structures protect privacy, but can also restrict the accessing and sharing of information necessary to developing a national network of health-endpoint information. Despite these obstacles to connecting the dots, making strides toward bringing together existing data is crucial; CDC efforts to do so are described below.

Information Technology (the Sticky Web). One of the challenges being tackled by the CDC is how to best improve the ability to share health information across small networks (that will make up the larger network) while also protecting privacy. Developing methods to share, analyze, and interpret the data are hurdles that must be overcome in order to provide a usable system to track environmentally-related health outcomes. Such a networked system would work at the local and national levels to allow cities, states and federal agencies to quickly access information that can be used in real time, so community members and policy makers can be made aware of hazards, take preventative actions, and ultimately improve health. Many of the 2006 state grants have been awarded to improve information technology, laboratory capacity, and methods of communication so those who need the data can access it, interpret it, and take action. The report projects the ambitious plan that the Environmental Public Health Network will be ready to launch in 2008.

One More Step. We at BCERF strongly support the concept and share the common philosophy of providing sound information on the health risks of environmental factors so individuals, groups and policy makers can take action in their personal lives, workplaces, and communities to reduce the incidence of disease, including cancer. Yet one of the most difficult aspects of this work is tracking how people and organizations use cancer risk information we provide. The CDC faces a similar challenge in assessing the impact of the Environmental Public Health Network. Not only does the Network need to be carefully constructed, accessible, and well used, there needs to be a way to record what types of decisions are made as a result of accessing and using the information. Beyond communicating risk information, better methods are needed to capture how the information is used, and if the use of the network at the individual, city, state, and national level ultimately results in improved health over the short and long term.

Biomontoring in Canada

Health Canada has recently announced that they will conduct a national health survey in 2007-2009, The Canadian Health Measures Survey, which will include measuring environmental chemicals in blood and urine from a sample that represents the general Canadian population. It is anticipated that 5,000 male and female Canadians from ages 6 to 79 will participate in the survey, and a smaller subset will be monitored for levels of environmental chemicals. Questionnaires will also be used to provide information on environmental risk factors. The purpose of the biomonitoring component is to establish a baseline of the levels of chemicals in the bodies of Canadians, as well as providing data to allow comparison of levels with other countries, and in future to follow trends in the levels of the chemicals over time. Classes of chemicals that will be monitored include: metals, phthalates, polychlorinated biphenyls (PCBs), brominated flame retardants, organochlorine pesticides, organophosphate insecticide metabolites, phenoxy herbicides, continine, perfluorinated compounds, and bisphenol-A. The results of this study should greatly complement the existing CDC biomonitoring program, and will allow a greater ability to determine chemical levels in people living in North America. The study is described at: http://www.chemicalsubstanceschimiques.gc.ca/bio_e.html.

Cancer Biomarkers

Efforts to develop cancer biomarkers have been heralded as the new wave of research needed to facilitate cancer treatment as well as to predict how the environment may affect cancer risk. In an article written by William Dalton and Stephen Friend that appeared in the May 2006 issue of Science, the authors state that biomarkers provide a measurable reference for what is ‘normal’ and allow a frame of reference for predicting or detecting what is ‘abnormal.’ Genetic alterations in mutations, such as the BRCA mutations for breast cancer, specific proteins (prostate-specific antigens-PSA), as well as markers of circulating tumor cells have all been used in predicting cancer risk, while others like images (mammograms) are biomarkers used in detecting tumors. In their commentary, Dalton and Friend predict that new molecular technologies that will greatly expand the range of cancer biomarkers available may revolutionize cancer care in several ways: 1) detection of cancer at an early stage, especially in high risk individuals, 2) guide individual treatments based on the characteristics of that person’s tumor, and 3) refinement of the genetic markers may facilitate the development of new drugs to treat cancer. Research to identify markers that can truly predict a patient’s treatment response and identify those who will respond favorably to treatments has proven to be a challenge.

The original hope that scientists would find a single treatment response marker for a disease, they conclude, was at best naïve. It was found that early efforts to come up with biomarkers for the progression of diseases like breast and other cancers instead needed to looked at sets of genes, and carefully follow how up- and down-regulation of these genes changed as the disease progressed. Various research groups started to report on ‘gene signatures’ that predicted very aggressive types of tumors. But, wide variations in the sets of genes associated with these signatures were reported by different research groups. Hence, the scientific community is back at the drawing board trying to figure out why such variation occurred. The article mentions part of the variation may be due to different methods used to recruit subjects (enrolling all available versus specific age groups) and the methods different laboratories used collect and analyze the tumors.

According to Dalton and Friend, researchers have learned several lessons. One is the danger of oversimplification. Complex cancer biology can’t be ignored; it has to be embraced. Biomarkers that can be applied to predict effectiveness of patient treatment will only be successful if markers are identified that include the wide molecular diversity of the disease and acknowledge that the biomarkers may change depending on the stage of the disease.

The other issue being faced is how to build full partnerships to share information while tackling issues of privacy and the pressures of intellectual property rights, both in academia and in industry. While this new frontier of molecular imaging holds great promise in detection, treatment, and ultimately understanding the basic biology of how cancer arises, a collaborative approach will be needed if the science is to be translated into practice.

Environmental Biomarkers (and beyond)

In a second commentary written by David Schwartz and Francis Collins (May 4, 2007 in Science), the authors envision a time when people may wear personal monitors with sensors that would collect information on exposure to chemicals, and provide information to your doctor on why you are sick and how you should be treated. Such sensors would integrate information on what you are exposed to, when you are exposed (in ‘real time’), and your individual biological response. However, lessons can be learned from researchers in the cancer biomarker field. Complexity, biological diversity, wide variation in individual responses, and difficulties in sharing information will likely affect the field of environmental biomarkers in similar ways these components have affected advances in the cancer biomarker field.

While it is true that we are on the edge of a new type of science that may be able to determine and record how a chemical exposure affects a biological response and disease risk, is likely that we will not be able to interpret such data without conducting a number of similarly designed studies that document baseline responses, and the likely wide variation in responses between individuals exposed to the very same chemical. Schwartz and Collins acknowledge that there will be gene-related changes that occur after exposure to a chemical that the biosensor may record that have nothing to do with increased disease risk. There is likely to be considerable ‘noise,’ and research will be needed to characterize the sets of gene-related biological changes that predict disease risk. There will need to be considerable analysis of data to separate the wheat from the chaff, sharing of data across many disciplines, and monitoring of different at-risk populations over time in order to make sense of the data.

Those in the biosensing field can learn from those in the cancer biomarker field, that there will need to be standardization of methods, data collection, and data pooling, and new methods in computational biology to sift through results. The immediate goal of developing panels of biomarkers for priority chemicals with known disease outcomes, and the future goal to develop sensors of emerging chemicals of concern should both be supported. I agree with the authors that if biosensing is to be validated to predict how environmental stressors affect or predict disease states, significant resources will have to be committed to this effort. However, a strategic plan to develop the framework needed to interpret the wealth of data that will come out of these studies also needs to be a priority.

Steps have been taken to support a multi-disciplinary approach. Schwartz and Collins describe a new effort they will co-chair, called the Genes, Environment, and Health Initiative (GEI). They discuss the training of scientists to think across disciplines and the creation of training opportunities in a new field, environmental genomics. The technology to achieve biosensing is fast approaching. The ability to translate the data into cancer prevention and public policy may be the larger challenge.

The Challenge: Understanding and Acting on Environmental Health Information

Our analytical and molecular genomic methods to collect biomonitoring and biomarker data have improved, but our ability to interpret data and relate it to predicting disease has lagged behind. While we have heavily invested in the technology to detect chemicals, biological responses, and genomic endpoints, similar resources on how to best interpret the data, how the data can and should be used for setting public health policy, and how to communicate results to the general public have not been allocated. The resources needed for interpretation, risk communication, dissemination, and documenting impact will be considerable. That is probably the lesson to be learned by all three approaches, from environmental health tracking, to cancer biomarker development, to environmental biosensors: we need better frameworks to interpret and communicate the data for using it to improve public health, and we need to commit the resources to do so.

In a recent analysis of the successes, challenges, and future efforts needed to sustain and extend the Environmental Public Health Tracking Program that appeared in the March 2007 issue of the American Journal of Public Health, study authors came to similar conclusions. They state that the “…ultimate measure of success in regard to the EPHT (Environmental Public Health Tracking) will be the translation of the data into effective prevention strategies. Ongoing evaluation of the ways in which surveillance and research results are being applied to prevent exposures, reduce adverse health risks, and improve environmental public health policies will be essential in providing the evidence base necessary to assess the impact and efficacy of EPHT.”

References

CHMS (2007). Human biomonitoring of environmental chemical substances; biomonitoring in the Canadian Health Measures Survey (http://www.chemicalsubstanceschimiques.gc.ca/bio_e.html, cited 8/10/07) (Health Canada).

Dalton, W.S., and Friend, S.H. (2006). Cancer biomarkers – an invitation to the table. Science 312, 1165-1168.

Levin, A. (2007). Keeping Track, Promoting Health (pdf downloaded at: http://www.cdc.gov/nceh/tracking/keepingtrack.htm, cited 8/10/07) (Atlanta, GA, Centers for Disease Control and Prevention).

Litt, J.S., Wismann, A., Resnick, B., Smullin Dawson, R., Hano, M., and Burke, T.A. (2007). Advancing health and environmental disease tracking: a 5-year follow-up study. American Journal of Public Health 97, 456-463.

Schwartz, D., and Collins, F. (2007). Environmental biology and human disease. Science 316, 695-696.

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Last Update 09.17.07