Madame Chairman and members of the Committee, we are pleased
to appear before you today to discuss advances in genetic
technology and the resultant challenges for public policy. The
Human Genome Project is an historic 15-year international
research endeavor with the goal of producing detailed maps of the
23 pairs of human chromosomes and sequencing the 3 billion
nucleotide bases that make up the human genome. Launched in
1990, the project is supported in the United States by the
National Center for Human Genome Research (NCHGR) at the National
Institutes of Health (NIH) and the Department of Energy (DOE).
The primary mission of the project is to develop research
tools--genetic and physical maps, DNA sequence information, and
new technology--to allow researchers to find and analyze genes
quickly and efficiently. The project thus far has been
successful in meeting or exceeding the goals outlined in its
original plan.
In October 1995 the Human Genome Project completed its fifth
year with a record of excellent progress toward its goals. The
first goal of the Human Genome Project, creating a detailed
genetic map for the human genome, has been accomplished.
Recently, a team of U.S. investigators published a physical map
of the human genome composed of over 15,000 well-ordered markers;
this represents a major milestone on the way to the next goal--a
comprehensive physical map of the human genome. Though original
projections were that this map would not be finished until the
end of 1998, completion is now expected in 1997. These
accomplishments have set the stage for the project's ultimate
goal, sequencing all the DNA in the human genome by 2005.
In 1996, the NCHGR has increased its investment in two areas
of DNA sequencing research. Pilot projects were initiated to
address and resolve issues that will be confronted in large-scale
sequencing of human DNA. These pilot projects are expected to
generate between 50 and 100 million base pairs of human DNA
sequence by 1998 and, in doing so, develop the methods that will
be used in the determination of the complete human DNA sequence.
The NCHGR has also increased its investment in the
development of new technology for DNA sequencing, concentrating
on miniaturization and automation of current techniques. This
approach has focused on improving speed and lowering cost.
Progress in these projects has been remarkable as several
laboratories have obtained at least 1 million base pairs of DNA
sequence at a cost of about 50 cents per base pair. This
represents It dramatic reduction in the cost of DNA sequencing
from $5-$10 per base pair when the Human Genome Project began.
We do not have to wait for the first complete human genome
sequence however, to begin to reap the benefits. New genetic
information has already enormously increased the number and kind
of disease genes being isolated. Not only are the so-called
"single- gene" disorders giving up their secrets, but we are
beginning to see the same discoveries for complex disorders, such
as diabetes, schizophrenia, and breast cancer--disorders that are
quite common in this country and in almost every corner of the
globe.
In NCHGR's Division of Intramural Research (DIR) and in many
institutions around the country, scientists are already using
large- scale genome-based approaches to study human genetic
diseases. DIR investigators utilize cutting-edge genome science
to develop streamlined techniques to rapidly isolate and analyze
disease-linked genes, generate improved methods to diagnose
inherited and acquired genetic disease, and investigate treatment
strategies. Animal models with disease that mimic genetic human
disorders are being developed to aid in understanding causes and
possible treatments of several diseases. For example, earlier
this month researchers at NCHGR and their collaborators reported
the development of a laboratory mouse with a disease which has
virtually all the characteristics of Ataxia- Telangiectasia (A-T)
observed in people, including neurologic problems, cancers of the
immune system, slow growth, radiation sensitivity, and abnormal
development of sperm and eggs. A-T is of particular importance
since carriers are estimated to represent 1% of the population
and are apparently at increased risk of a variety of cancers,
including breast cancer. Although scientists have gleaned clues
about the function of the human A-T gene from similar genes in
single-celled yeast, the new mouse model gives them the first
opportunity to study the disease in a controlled way in
multi-celled animals other than humans.
THE ETHICAL, LEGAL, AND SOCIAL IMPLICATIONS PROGRAM
As an integral part of the Human Genome Project, the NCHGR
and the DOE have each set aside a portion of their funding to
anticipate, analyze, and address the ethical, legal, and social
implications (ELSI) of the new advances in human genetics that
have resulted from the HGP. The current goals of the ELSI
program are to improve the understanding of these issues through
research and education, to stimulate informed public discussion,
and to develop policy options intended to ensure that genetic
information is used for the benefit of individuals and society.
The NCHGR ELSI program is focusing on several high-priority areas
raised by the most immediate potential applications of new
genetic technologies; privacy and fair use of genetic
information; responsible clinical integration of new genetic
technologies ethical issues surrounding the conduct of genetics
research; and, professional and public education about these
issues. The ELSI program is now positioning itself to address the
issues which will arise once the complete sequence is known.
Privacy and fair use of genetic information
As our knowledge grows about the genetic basis of disease, so
too does the potential for discrimination and stigmatization
based on the information contained in our genes. Of particular
concern is the fear of losing jobs or health insurance because of
a genetic predisposition to a particular disease. A woman with a
positive family history who tests positive for BRCA1 has an
estimated 85 percent likelihood of developing breast cancer, and
a 50% risk of ovarian cancer. Fighting those risks with
intensive surveillance or surgery, without health insurance,
would for many individuals result in economic ruin and probable
tragedy.
Last year, the NIH-DOE Joint Working Group On Ethical, Legal,
and Social Implications of Human Genome Research (ELSI Working
Group) and the National Action Plan on Breast Cancer (NAPBC)
developed and published recommendations for state and federal
policy makers to protect against genetic discrimination:
Definitions "Genetic information" is information about genes,
gene products or inherited characteristics, that may derive from
the individual or a family member. "Insurance provider" means an
insurance company, employer, or any other entity providing a plan
of health insurance or health benefits including group and
individual health plans whether fully insured or self-funded.
Health Insurance Access Renewability, and Portability
- Insurance providers should be prohibited from using genetic
information, or an individual's request for genetic services, to
deny or limit any coverage or establish eligibility,
continuation, enrollment or contribution requirements.
- Health Insurance Affordability
Insurance providers should be prohibited from establishing
differential rates or premium payments based on genetic
information, or an individual's request for genetic services.
- Genetic Privacy
Insurance providers should be prohibited from requesting or
requiring collection or disclosure of genetic information.
Insurance providers and other holders of genetic information
should be prohibited from releasing genetic information without
prior written authorization of the individual. Written
authorization should be required for each disclosure and include
to whom the disclosure would be made.
In order to assure that the Nation benefits from the fruits
of genetic research, safeguards must be in place to protect
individual privacy and prevent insurance and employment
discrimination. Despite the initiatives of various states
including New Hampshire, Ohio, Minnesota, Maryland and most
recently New Jersey to pass legislation aimed at protecting
individuals from being denied health insurance based on their
genetic status, we have at best a patchwork of privacy and
anti-discrimination proposals. In addition, state laws do not
provide protection for the many Americans who obtain their health
insurance coverage through self-funded employer-based plans,
because the federal Employee Retirement Income Security Act
(ERISA) exempts self-funded plans from state oversight.
Therefore, to provide minimum protection nationwide, these issues
must be addressed at the federal level.
Currently, the NAPBC and the ELSI Working Group are
collaborating on the next area of potential discriminatory use of
genetic information: the employment arena. A workshop on the use
of genetic information in the workplace will be held this fall to
delineate potential policy options.
Responsible clinical integration of new genetic technologies:
As a result of the Human Genome Project, new disease genes
are discovered almost weekly. Once a disease gene is identified
it is virtually only a matter of months before a diagnostic test
can be made available. Developing effective treatment and
preventive measures is a much more prolonged endeavor. These new
diagnostic technologies are moving quickly from research into
clinical practice, which raises concerns about the impact of
these findings on people's lives and health.
This year, tests became available in the research arena for
identifying mutations in the BRCA1 gene that predisposes
individuals to breast cancer, the HNPCC genes that predispose
individuals to colon cancer, and the apolipoprotein E gene that
plays a role in the inherited form of Alzheimer's disease.
Predictive genetic testing in the face of poor or uncertain
preventative or therapeutic interventions raises many concerns
regarding, benefits and risks. The safety and effectiveness of
these new predictive tests must be addressed to ensure a level of
quality and reliability.
Three key initiatives are underway to address crucial
questions surrounding genetic testing, especially for cancer
susceptibility. NCHGR and several other NIH Institutes are
co-sponsoring a Cancer Genetics Studies Consortium, focusing on
the psychological and social impact of cancer testing on
individuals and their family members. Recommendations for
approaches to genetic testing and counseling for cancer risk are
being developed. The studies are well underway, and the
investigators have developed draft recommendations for the
optimal medical management of patients and families who carry
mutations in the major gene for heritable breast cancer, BRCA1,
and the HNPCC colon cancer genes.
A second initiative proposed by the National Cancer Institute
(NCI) is the National Cancer Genetics Network. The Network as
currently envisioned would consist of a consortia of
organizations whose members are physicians in practice
individuals interested in undergoing testing will be enrolled by
physicians who are participating in the Network. Those
physicians would receive educational materials to facilitate
their ability to deliver these complex genetic services, which is
essential because most physicians have not received this type of
training. Patients would follow a uniform informed consent
process and would be provided with up-to-date and validated
educational information about the benefits and risks of testing.
This would enable them to make an informed decision about whether
or not to proceed. All patients, regardless of mutation status,
would be enrolled in a confidential registry, so that the
consequences of deciding whether or not to be tested and the
effectiveness of various follow-up interventions can be
evaluated. The network is critical because the premature
introduction of cancer susceptibility testing into general
clinical practice in the absence of large-scale follow-up studies
may prevent our ability to answer crucial management questions.
The final NCHGR initiative on testing, the Task Force on
Genetic Testing (TFGT), was established by the ELSI Working Group
to examine the Development and delivery of safe and effective
genetic tests and the quality of the laboratories providing the
tests. The Task Force includes representatives from the
biotechnology industry, professional medical and genetics
societies, the insurance industry, consumers, and federal
agencies. In light of the rapid pace of disease-gene discovery
and genetic test development, the findings of the TFGT will be
crucial to the development of sound policies and practices for
the introduction of new genetic tests. The group has now issued
draft principles and expects to complete its work in early 1997.
Ethical issues surrounding the conduct of genetic research:
Genetic research may result in the discovery of information
that is powerful and potentially predictive. In addition, such
information may have familial implications. While in some cases
such information may be beneficial to research subjects and their
families, there is also potential for misinterpretation or
misuse. Special concerns have arisen about the process of
informed consent, particularly when the risks and benefits of
research participation may not be fully known. Concerns have
also arisen about how best to prevent the preliminary or
premature release of research results and to protect individual
privacy rights for genetic research participants. Examination of
existing research guidelines and recommendations over the past
five years has revealed that current guidance and protections
need to be enhanced in order to deal with the special
considerations related to genetics research.
Stored tissue samples are valuable resources for genetics
research. Due to increasing concerns about the adequacy of
informed consent and privacy protections when stored tissue
samples are used in genetics research, the Centers for Disease
Control and Prevention (CDC) and the ELSI program supported a
meeting to explore these issues. After intensive deliberations,
recommendations were developed and published in December, 1995 in
the Journal of the American Medical Association. As a direct
result of these deliberations, a number of other groups have now
taken up this issue including the American Society of Human
Genetics and the American College of Medical Genetics, the
College of American Pathologists and numerous other organizations
which represent the pathology community.
Professional and public education:
As more genetic tests become available to the public, the use
and interpretation of those tests and the information they
generate will no longer be managed by genetic specialists alone.
There will be too few professionals with the advanced training in
genetics to meet the expected demand for genetic testing and
services. As patients ask more questions about genetic tests and
disease risk, responsibility for the use and interpretation of
tests and genetic information will increasingly fall to primary
care physicians, nurses, physician assistants, and public health
professionals who are not specialized or trained in genetics.
Therefore, it is imperative that all of our Nation's health
care professionals have the knowledge, attitudes, skills and
resources they need to effectively integrate genetics into the
diagnosis, prevention, and treatment of disease, and to address
the related ethical, legal, and social issues. In 1995, NCHGR
held a meeting of health professionals and education experts to
define education priorities for the ELSI grant program. These
experts concluded that while public education is important,
professional education is of the highest priority, because most
individuals will seek genetic information from medical
professionals. To this end, NCHGR is now working with
professional organizations and consumer groups on a proposal to
establish a National Coalition for Health Professional Education
in Genetics. Yesterday, we concluded the first planning meeting
of the Coalition and I believe these successful discussions will
provide the necessary direction for our health professionals in
this important area.
Conclusion
Congress, and particularly this Committee, has long been the
leader in supporting genetic research and the Human Genome
Project. Therefore, it is fitting that this Committee is now
taking the lead in addressing the important policy issues raised
by this research. Protecting privacy and preventing the misuse
of genetic information is essential not only for us to reap the
benefits of this research but indeed, in order to carry or the
research at all. Increasingly we hear of people unwilling to
participate in genetic research out of fear that information
about their genes might be used against them by insurers or
employers. Genetic discrimination has been hailed as the "civil
rights" issue of this decade. We have the unique opportunity to
address genetic privacy and discrimination issues now as the
scientific information unfolds, before we find ourselves in a
full- fledged crisis. I look forward to continuing to work
closely with the Congress to develop sound policies to ensure
that the Human Genome Project and new genetic information is used
to benefit, not harm, the American people.
This concludes my remarks. I would be pleased to answer any
questions you may have.
