Environmental Health Perspectives Volume
103, Supplement 3, April 1995
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in PubMed] [Related
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Banking of Human Tissue for Biomonitoring and Exposure Assessment: Utility
for Environmental Epidemiology and Surveillance
Lynn R. Goldman,1 Hoda Anton-Culver,1,2 Martin
Kharrazi,1 and Elinor Blake1
1California Department of Health Services, Emeryville, California;
2University of California, Irvine, California
Abstract
Human tissue banking could provide a tool to address a number of public
health concerns. We can potentially use it to monitor trends in human exposures,
serve as an early warning system for new environmental exposures, assess
low-level exposures around hazardous waste and other point sources of pollutants,
evaluate the effectiveness of regulatory programs, and study etiologies
of diseases (e.g., childhood cancer and birth defects) that are likely to
be related to the environment. This article discusses opportunities to establish
human tissue banks in connection with preexisting public health surveillance
programs for cancer and adverse reproductive outcomes. This is a cost-effective
way to conduct surveillance and enhances the ability to carry out epidemiologic
studies. The article also discusses ethical issues that are particularly
important for public health practice. One is the issue of risk communication
and the need to explain risks in a way that provides people with the information
they need to determine appropriate action on the individual and community
levels. Second is the issue of environmental justice. We recommend early
involvement of communities that are likely to be involved in tissue-banking
projects and full explanation of individual and group social risks from
their participation. -- Environ Health Perspect 103(Suppl 3):31-34
(1995)
Key words: surveillance, environmental health, human tissue banking,
reproductive outcomes, childhood cancer
This paper was presented at the Conference on Human Tissue
Monitoring and Specimen Banking: Opportunities for Exposure Assessment,
Risk Assessment, and Epidemiologic Research held 30 March-1 April 1993
in Research Triangle Park, North Carolina.
Address correspondence to Dr. Lynn R. Goldman, U.S. Environmental
Protection Agency, 401 M Street, S.W. (TS-788), Washington, DC 20460. Telephone
(202) 260-2902. Fax (202) 260-1847.
Introduction
Some environmental epidemiologic and health surveillance needs can be
addressed by using human tissue banking. There are opportunities for developing
tissue banks in the context of existing public health studies and health
surveillance systems. This not only offers possible cost savings but also
the opportunity to provide data for future epidemiologic studies. However,
human tissue banking raises specific ethical concerns on a community level.
This article discusses these issues and gives examples of potential applications.
Uses of Human Tissue Banks in Public Health Surveillance
and Epidemiology
Human tissue banking holds great promise for improving epidemiologic
surveillance of environmental exposures. Surveillance is defined as "the
ongoing systematic collection, analysis, and interpretation of health data
essential to the planning, implementation, and evaluation of public health
practice, closely integrated with the timely dissemination of these data
to those who need to know. The final link in the surveillance chain is the
application of these data to prevention and control" (1). At
a minimum, a surveillance system should allow examination of trends over
time and comparison of data between representative subgroups or geographic
areas.
Public health surveillance for environmental health is limited to blood
lead reporting (2), diseases believed to be possibly of environmental
origin such as birth defects (3), and environmental databases designed
primarily for other purposes (4,5). Blood lead reporting is usually
carried out by states, using requirements of clinical laboratories to report
all or elevated blood lead levels. Birth defects registries exist in only
a few states. Some use passive surveillance methods, obtaining data from
vital records or hospital discharges only, while others use active surveillance
methods involving abstraction of full hospital records. Environmental databases
are usually developed by regulatory programs to track the results of monitoring
and compliance activities, and are of varying usefulness in conduct of environmental
surveillance (5). No longer in existence is the National Human Monitoring
Program (NHMP). The purpose of the NHMP, established in 1967, was to monitor
chemical exposures in the population. It included the National Human Adipose
Tissue Survey (NHATS), which collected adipose tissues from metropolitan
areas in the United States from 1970 to 1990 and monitored chlorinated organic
compounds, such as the organochlorine pesticides and the polychlorinated
biphenyls (6). The National Health and Nutrition Examination survey
(NHANES), a periodic, population-based survey carried out by the National
Center for Health Statistics, has been useful for monitoring trends in blood
lead levels (7) and special studies of pesticides and volatile organic
compounds. A number of reviews have been conducted of these surveillance
systems; these have concluded that at present environmental health surveillance
is fragmentary and in an early stage of development (4-6). Human
tissue banking-- collection and storage of tissues or blood samples from
special groups or the general population--would enhance this current environmental
health surveillance system.
What would be wanted for environmental surveillance of human exposures?
An environmental health surveillance system should:
- integrate with other data sources that contain information on disease
or disability;
- identify pollutants and populations of exposed individuals that require
more urgent public health intervention;
- be useful for planning and evaluation of intervention programs;
- provide "early warning" of new environmental problems;
- provide data for analytic epidemiologic studies; and
- contribute to the knowledge base of "background" levels of
contaminants in the population to help interpret findings from specific
population studies.
Integration with Health Surveillance Systems
Any system of environmental exposure surveillance, including a tissue
bank, should collect data in a manner that will allow integration of information
with information in health surveillance systems, e.g., vital records, registries
of cancers and birth defects, and hospital discharge data. Such data integration
allows for population- based, hypothesis-generating studies, and for linkages
for performing epidemiologic studies (5).
Priority Setting
Knowledge about exposures should help establish relative priorities to
be addressed by public health and environmental regulatory programs. Current
environmental surveillance programs do not give sufficient information about
individual exposures, particularly exposures to population subgroups of
special concern like children, pregnant women, and ethnic minorities.
Program Evaluation
There is very little basis for evaluating the efficacy of environmental
health and regulatory programs. Insofar as efficacy can be measured by decreases
in human exposure, tissue banks can be a useful resource for this purpose
in much the same way that reporting of measles cases is used to monitor
the success of measles immunization programs.
Early Warning
Public health agencies are expected not only to provide surveillance
of known hazards but also to identify newly emerging hazards to assure that
society can promptly and rapidly address them. A tissue bank can be a very
useful resource for this purpose if the tissue banking activities are linked
to the capability to use analytic techniques, not only for identifying known
compounds and indicators of exposure, but also for broadly screening for
new exposures. The finding of new chemicals or indicators of exposure, either
emerging over time or at a higher level in individual population groups,
may warrant further study.
Epidemiologic Studies
Tissue banks can potentially be useful for the conduct of epidemiologic
studies. Little is known about the etiology of a number of diseases that
are believed possibly to be caused by environmental exposures, for example
birth defects and childhood cancer. The public expects that public health
agencies can explain the causes of community outbreaks, or "clusters"
of such diseases; but in many cases too little is known about etiology to
even allow formation of specific hypotheses. At the same time, there are
a number of exposures that convey "theoretical" risks but for
which we have very little human epidemiologic evidence. While we would attempt
to reduce the exposures based on the theoretical risks, a human tissue bank
would increase the opportunities available to learn more about their effects
in humans.
Background Population Exposure Levels
We lack adequate information about "background" levels of exposure
in the population. By background, we mean what a statistician would call
"normal," that is, the expected range of the exposures in the
general population. Public health agencies often encounter situations in
which measurements were taken by others and an interpretation is needed.
For example, in 1990 a biological monitoring technique for urinary malathion
metabolites was used to assess exposures of toddlers in a day care center
in an area in Los Angeles County that was being treated with aerial applications
of malathion. All existing information on urinary malathion metabolites
was for pesticide workers. No data were available for the general population
or for toddlers. There was no information on how to extrapolate from higher
to lower exposures, nor on how malathion metabolism might differ in toddlers
than in adults. Toxicologists who evaluated the data used a number of assumptions
about malathion elimination in toddlers that resulted in extrapolated exposures
that differed by more than an order of magnitude.
Examples of other types of situations for which "background"
data on exposures are needed are hazardous chemical spills, chemical fires,
pesticide drift exposures and other incidents of pesticide misuse, hazardous
waste site exposure assessment and consumer product contamination episodes.
Using Existing Surveillance Systems
As mentioned above, linkage of environmental with health surveillance
offers a number of important advantages in terms of allowing assessment
of health outcomes and in maximizing resources by using established population-based
monitoring systems rather than creating new ones. Opportunities for human
tissue banking exist in several areas using established public health surveillance
programs. Two pilot studies have been conducted by the California Department
of Health Services to take advantage of disease registries and genetic disease
screening programs. By using pre-existing surveillance systems as a base,
one can ensure that the sample is
representative with respect to the general population of persons with diseases
such as cancer or birth defects.
In planning any human tissue banking effort, one should consider what
tissues might already or potentially be available, and their utility for
tissue banking. There is much "throwaway" tissue that may be usable,
such as discarded tissue blocks and serum samples. There are also diagnostic
specimens from surgery that may require obtaining informed consent. Some
of this tissue cannot be used for specific purposes. For example, formalin-preserved
samples have altered chemical constituencies. However, with development
of new analytical techniques, new uses may be found for any tissues that
might be available. For example, the California Department of Health Services
obtains a capillary blood spot on a piece of blotter paper for almost 100%
of births; these blood spots have been retained and archived for years.
Recently, methods have been developed to use them for DNA amplification
studies. When linked with our birth defects surveillance program, this should
prove to be a very valuable resource. Usability involves not only the ability
to analyze the specimen but also the ability to secure, archive, and document
the tissue.
Population-based birth defects and cancer registries are potentially
of great usefulness. An enormous amount of effort is already expended to
collect large amounts of data on persons with these diseases. Since 3% of
births involve a birth defect and 25 to 30% of persons are expected to develop
cancer, these registries cover a large number of people in the areas they
serve. Childhood cancer has been a particular issue of concern in California,
where childhood cancer "clusters" in the agricultural Central
Valley have led to concerns about pesticides and other environmental exposures.
There are a wealth of epidemiologic studies that suggest potential roles
for parental occupational exposures to solvents and pesticides for a number
of specific cancer types, but most of these studies suffer from poor exposure
assessments. Typically, exposures are based on paternal and maternal occupational
codes; a few studies have used questionnaires and there are rarely measurements
of chemicals or biologic markers of exposure. Birth defects are a major
cause of infant mortality and account for many of total potential years
of life lost. Although a number of chemicals can be shown to cause malformations
in laboratory animals, there may not be concordance between the type of
malformation caused in animals and the type caused in humans, so that we
cannot rely solely on animal studies to identify human teratogens. Only
a small fraction of childhood cancers and birth defects, less than 10%,
can be attributed to known environmental and genetic etiologies.
California conducted a pilot study with the University of California
at Irvine (UCI) Cancer Surveillance Program of Orange County (CSPOC) and
the Children's Hospital of Orange County, to set up a tissue bank for childhood
cancer cases for Orange County. We rapidly ascertained new cases of cancer
at the childhood cancer center at UCI, which diagnoses and treats virtually
all childhood cancer cases in Orange County. Ascertainment included identifying
new cases and obtaining blood samples and tumor tissue from the patient
before initiation of treatment. This was important because we wanted to
avoid the biologic changes caused by chemotherapy and radiation treatment,
which might be similar to markers of environmental exposures. We also obtained
blood samples from parents and siblings and interviewed parents, not only
because other family members might be expected to share environmental exposures,
but also to look for genetic traits. UCI separated the lymphocytes and preserved
them in a viable state. Later, chromosome breakage studies were undertaken.
In the pilot study, it was possible to obtain comparable information from
both hospital-based and "friend" controls and we suspect that
it would also be possible to obtain population-based controls as well. Although
we piloted this technique for childhood cancers, it would be a reasonable
approach for birth defects as well. In that case, one would be less concerned
about the timing of case ascertainment. Over time, such a resource would
be useful for conducting population-based environmental and genetic etiologic
studies.
Another area of much environmental epidemiologic interest is in looking
at other reproductive outcomes. Vital records systems contain valuable information
about birthweight; gestational age; fetal and neonatal death, age, ethnicity,
and education of parents; and use of prenatal care. They also contain information
about the mother's residence. However, they contain very little information
about exposure. Increasingly, states carry out prenatal genetic disease
screening programs. In California we conduct serum alpha fetoprotein (AFP)
testing for about 60% of births. This test is performed at 15 to 19 weeks
of gestation and is used to screen for neural tube defects and other disorders.
All tests are carried out in large regional contract laboratories under
supervision of the state laboratory. Typically, samples are discarded after
confirmatory analyses are carried out.
Rather than discarding prenatal AFP samples, we banked all serum specimens
from an 11-county area for a month (3699 samples). The area chosen was in
the Central Valley of California which is ethnically diverse with an especially
large Hispanic population. After linking these specimens with live birth
or fetal death records, there are a number of analyses that are feasible.
At present, we are using the specimens to study the relationship of birthweight
and gestational age to mid-pregnancy cotinine and caffeine levels. It will
be possible to look at not only active smoking but also environmental tobacco-smoke
exposure. With very little extra cost, programs such as the genetic disease
screening program could be modified to archive specimens on a routine basis.
This could be useful not only for studies of reproductive outcomes but also
for a number of other developmental outcomes that may be related to prenatal
exposures. There are a number of chemicals that can be measured in serum,
including some metals and a number of pesticides; and new methods are under
development to measure other substances and to find better markers of exposure.
Cluster Investigations
We also conduct studies of space-time clusters of diseases such as childhood
cancer and birth defects. These studies usually result in inconclusive results.
Tissue banking holds the promise of being able to look later for markers
of exposure or pre-disease conditions that might help elucidate the cause
of at least some of these space-time clusters. The experience with studying
genetic etiologies of cancer can serve as an example of the potential of
this method.
Ethical Concerns
Two interrelated ethical issues are particularly important for public
health practice. One is the issue of risk communication and the need to
explain risks in a way that provides people with the information they need
to determine appropriate action on the individual and community level. Second
is the issue of environmental justice, often referred to as environmental
equity. Environmental justice advocates dislike the term "environmental
equity" because, as Charles Lee of the United Church of Christ has
said, "It sounds as if we all share the problem, it's OK" (8).
It will be very important for any national program of adipose tissue banking,
like any program of environmental surveillance, to over-sample in low income
and various racial and ethnic communities. If past studies can serve as
a guide, we can expect that we will be more likely to find higher exposures
in these communities (9,10). Researchers, who rarely are from these
areas, should not assume that they understand the needs for these communities
or the consequences of their findings for the residents. Certainly, there
is likely to be less access to education, poorer nutrition in low income
areas, and cultural differences in understanding of health and disease.
Such communities are also less likely than a white suburban community to
have resident experts such as scientists, physicians, attorneys, and other
trained professionals who can interpret the data for neighbors; and they
have less access to such expertise overall. In consequence, these communities
may have more difficulty in taking steps needed to deal with any problems
that might be identified, or compelling the government to do so. In low-income
communities, food, housing and child care may take precedence over the environmental
problems. Moreover, identification of specific environmental exposures could
worsen discriminatory practices, such has been seen in "redlining"
practices in neighborhoods with lead contamination. Early involvement and
participation of members of these communities in any monitoring effort are
essential to ensure sensitivity to cultural issues and the barriers to addressing
any problems that may exist, and to identify ways to overcome those barriers.
Informed consent needs to include not only information about individual
medical and privacy risks but also about social risks for both the individual
and the group as a whole. Although involving communities in this way may
delay or even make it impossible to do studies that we would like to do,
this is the only way to proceed ethically if the ultimate goal is the protection
of public health. We have found that involving communities at the outset
saves time in explaining study results and provides for a better ultimate
outcome.
In conclusion, human tissue banking will help address a number of public
health concerns. We can potentially use it to
a) monitor trends in human exposures;
b) serve as an early warning system for new environmental exposures;
c) assess low level exposures around hazardous waste and other point
sources of pollutants; d) evaluate the effectiveness of regulatory
programs; and e) study etiologies of diseases (e.g., childhood cancer
and birth defects) that are likely to be related to the environment.
REFERENCES
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2. CDC. Surveillance of elevated blood lead levels among
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and sufficient? Arch Environ Health 47:398-407 (1992).
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W, Lybarger J, McKenzie D, Murphy R, Wellington D, Woodruff T. Use of exposure
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6. National Research Council. Monitoring Human Tissues
for Toxic Substances. Washington:National Academies Press, 1991.
7. Annest JL, Pirkle D, Makuc D, Neese JW, Bayse DD, Kover
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8. Lavelle M. Residents want justice. The EPA offers equity.
Natl Law J. September 21,1992;S12.
9. Bullard RD. The threat of environmental racism. Natl
Res Environ 7(3):23 (1993).
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Fall 1991/Winter 1992:3.
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