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NEW
BIOLOGY & PUBLIC POLICY SEMINARS
 A
series cosponsored by
CSIS and the Whitehead Institute
for Biomedical Research
April
2001
The
Interface of Biomedical
Research and Public Policy in
the Genomic Revolution
Lightning
advances in deciphering the human genetic code are propelling
our society into uncharted waters and raising profound
issues at the juncture of science and policy-issues
that must be addressed soon,
according to speakers at a seminar sponsored
by the Center for Strategic and International Studies
(CSIS)
and the Whitehead Institute for Biomedical Research.
Illustrating this point, scientists posed questions
that go to the heart of the social contract between
citizens and their government, from privacy rights to
public trust. This issue brief presents highlights of
the New Biology: Challenges and Opportunities, the first
in a series of briefings convened in Washington, D.C.,on
March 29, 2001 to stimulate dialogue between leaders
in science, medicine, law, and biotechnology and senior
government policymakers on matters that will shape much
of the genomic revolution's impact on individuals and
institutions in this country for the next 10-15 years.
From
Mendel's Laws to Modern Lawmakers
"We
are living through the most remarkable revolution in
scientific history," according to Dr. Eric Lander, director
of the Whitehead Institute's Center for Genome Research.
Although people have noticed resemblances between parents
and offspring throughout human history, our understanding
of an informational basis to life remained vague until
1865, when Gregor Mendel reported the results of his
breeding experiments with pea plants. Those landmark
findings languished for 35 years. The twentieth century
began with publication of three papers on Mendel's laws
of heredity and closed with a rough draft of the human
genome. "It's not a bad story for a century," Lander
said.
A sea change in biomedical research took place around
1980, when genetic knowledge made possible a systematic
approach to disease. For diseases known to transmit
in families, for example, scientists "examined random
bits of DNA up and down the chromosomes" until they
found one whose inheritance pattern correlated with
the disease. (See Genetics Glossary.) "It became possible
to find where causes are without knowing what the causes
are," Lander said. From that point, scientists could
move along the chromosome from nearby markers to isolate
the gene itself. This laborious process, which took
five years and hundreds of people at a cost of $50 million,
was used to isolate the gene for cystic fibrosis in
1989. Today a scientist can type the sequence for a
protein into a computer and have the machine identify
similar proteins and their functions, shaving five years
off a genetic research project. More than 1,000 diseases
have been mapped to chromosomal regions this way.
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"You
and the person sitting next to you are 99.9% identical
at the genetic level," said Lander.
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"It
was tedious to do this for every disease, and so was
born one of the first great infrastructure-building
programs in biology," according to Lander. The National
Human Genome Research Institute and the U.S. Department
of Energy launched the Human Genome Project in 1990
as a 15-year effort to find and sequence all the genes
in the human body. Thanks to rapid technological advances,
that work will be completed in 2003, two years ahead
of schedule. When the human genome sequence is complete,
it will be like a parts list-a finite number of building
blocks, in this case, some 30,000 genes. Lander explained
the value of having such a list of all the variations.
"The amount of variation between any two people in this
room is only about 1 letter in 1,300. You and the person
sitting next to you are 99.99 percent identical at the
genetic level," he said.
To
illustrate the potential importance of this small degree
of variation to individuals and to research, he used
apolipoprotein E (apoE) on chromosome 19. ApoE has its
own variants of E2, E3, and E4. Any person who is homozygous
for E4-that is, has a double dose of it genetically-has
a 60-70 percent lifetime risk of developing Alzheimer's
disease. With DNA amplification technology, that genetic
information can be gleaned easily from a drop of saliva.
Pinpointing apoE's link to Alzheimer's disease has directed
the pharmaceutical industry to study this protein's
activity and develop drugs that may substantially delay
the devastating effects of the disease. Lander predicted
that variations in the genome will one day be correlated
with specific diseases, from asthma to stroke.
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Eric
Lander, director of the Whitehead Center for Genome
Research |
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At
the same time, Lander said that the central challenge
of our time may well be how we as a society acknowledge
both our fundamental sameness and our genetic differences,
while avoiding the pitfalls of genetic determinism.
Expressing concern thatpeople will see themselves as
limited by their genes, Lander said, "This would be
a terrible mistake. There is no genetic evidence whatsoever
to support this kind of genetic determinism."
Changing
the Basis of Biomedical Research and Treatment
What
is the medical promise of the new biology? At a fundamental
level, it will help us understand the molecular mechanisms
of disease. "It would be immoral not to undertake research
that gives us a chance of understanding what the basis
of human medical suffering is about," said Lander. "We
owe it to our children." The result will be better therapies
because we will be able to target treatment to underlying
causes of disease rather than symptoms, classify diseases
by distinct subtypes that respond to different treatments,
and classify side effects.
Preventive
therapies are another potential benefit, he said. Some
drugs may be developed to slow a process decades before
the disease becomes symptomatic, posing an interesting
challenge for the pharmaceutical industry: How can a
clinical trial be designed to demonstrate a drug's effect
on something that has not developed?
Preventive
therapies are another potential benefit, he said. Some
drugs may be developed to slow a process decades before
the disease becomes symptomatic, posing an interesting
challenge for the pharmaceutical industry: How can a
clinical trial be designed to demonstrate a drug's effect
on something that has not developed?
The
ultimate result of this knowledge, he commented, will
be a much more systematic approach to biomedical and
pharmaceutical research that will not only improve treatment
but lower the cost of drug development by boosting the
industry's success rate, which is now only 1-2 percent.
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"How
fast we go will be determined by how well organized
we are, how much we fund science, and importantly,
how we deal with the social issues," noted Lander.
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Speculating
on a timeline for these advances, Lander said, "I feel
confident that we will have largely dealt with cancer
by the end of this century. How fast we go will be determined
by how well organized we are, how much we fund science,
and importantly, how we deal with the social issues."
He raised a critical issue about moving too fast. Some
people will be pressing to attempt improvements on the
human genome "long before we can do them safely," Lander
warned. "And even if we do ever have the base of knowledge
to do it responsibly, do we wish to regard human beings
as products of manufacture?" he asked. "Tinkering with
a system we barely understand-the hubris in that is
truly spectacular." Dr. Gerald R. Fink, director of
the Whitehead Institute, emphasized the importance of
distinguishing the cloning of humans from stem cell
research: "They are two very different issues scientifically."
The
Balancing Act: Scientific Progress and Social Protections
In
just a decade, the Human Genome Project has given scientists
the tools to understand all the information encoded
in the DNA molecule. These tools have raised a wide
range of pressing questions about genetics and public
policy, said Dr. Philip R. Reilly, chief executive officer
of Interleukin Genetics, Inc.
Doctor/Patient
Confidentiality.
Consider how the genomic revolution is challenging the
inviolate nature of doctor/patient confidentiality.
What if a patient is diagnosed with a genetically linked
form of colon cancer, and his brother has a 50 percent
chance of having inherited that gene. If the patient
chooses not to tell his brother, does the doctor have
an obligation to share that genetic information with
the man's blood relatives, and if so, how does he reconcile
that with patient confidentiality?
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Phillip
Reilly, CEO of Interleukin Genetics
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Today
there are no rules or guidelines for the sharing of
genetic information across families. Over the next 20
years, Reilly expects a move toward a more family-centered
notion of confidentiality-"a world in which physicians
have the right, but not the obligation, to make limited
disclosures to third parties about DNA information."
"In
the area of health and insurance discrimination, we
do not have a federal law that protects genetic information,"
Reilly noted.
Health Insurance Discrimination and Coverage.
In the area of health insurance and discrimination,
Reilly noted that, with the exception of one section
of the Health Insurance Portability and Accountability
Act of 1996, "we do not have a federal law that protects
genetic information." About 39 states have enacted such
laws. Reilly favors broad antidiscrimination laws that
apply to all medical information, "to protect against
the use of medical information to keep people out of
the health insurance system or to charge them much higher
rates."
Looking
ahead, some day a more reliable genetic test for Alzheimer's
disease will be available. "Can insurers demand that
you have a test you don't want? Can they demand access
to tests you've already had?" Lander queried. The risks
of disclosure may deter people from having a test that
may be medically beneficial. What if the long-term care
insurance industry requires genetic screening and refuses
to sell insurance to applicants whose genetic tests
show a high risk for the disease, Reilly queried.
Do the new genetics change the very concept of disease,
and what is covered under insurance? Consider the case
of a Nebraska woman with a strong family history of
ovarian cancer who had her ovaries removed prophylactically.
When her insurance company refused to approve the procedure,
she had it done outside the plan and sued to recover
the cost of the surgery. At issue was a single question:
Did this woman meet the insurance contract's criteria
for "disease or disability"? She was healthy at the
time of surgery, and the pathologist found no evidence
of disease in the ovaries. By a vote of 4-3, the state
Supreme Court held that, under the contract provisions,
she qualified for coverage. Clearly, Reilly commented,
this is a matter of public policy.
Workplace Issues. In the arena of genetic
information and employment, "we are at the very outset
of an important public policy debate, and so far, I
think it's not gone very well," according to Reilly.
A few states have enacted laws that prohibit genetic
testing for any reason in the workplace, but that approach
does not adequately address the complexity of the issues.
For example, he asked, what if some people's genotype
put them at very high risk for a disease if they're
exposed to a certain chemical in the workplace, and
it's possible to ascertain that risk? "We want to be
able to use the information to protect individuals,
not to just prohibit the exposure," he said.
Public Trust. Understanding the molecular
mechanisms of disease and their variations requires
sizeable study populations. Recruiting and funding for
such studies, Lander said, is less a scientific or technical
problem than a social problem. Finland, for example,
has a national health care system, a population that
has "extraordinary trust in its government," and very
high rates of participation in large population studies.
"We will not be able to pull this off without a trusting
population, and we're going to have to earn that trust,"
he said, by developing protections for genetic information.
Issues
of both privacy and public trust come into play in genetic
research involving human subjects. In the United States,
most such research is conducted through institutional
review boards, a local system of oversight that is being
attacked as overburdened and underfunded, with attendant
risks for participating patients. In fact, Reilly pointed
out, there are no rules governing human subject research
that is conducted without federal funds, and he expects
Congress to address this topic in the coming years.
Even the existing federal rules were created long before
the genetic revolution, when the primary concern was
physical harm. In the era of genetics, however, the
overriding concern is informational harm-the inadvertent
or deliberate sharing of genetic information that can
affect employment or insurance.
Another matter of public trust involves genetically
modified food. In the United States, "we have been spared
the bitter and economically dangerous debate that is
occurring in Europe," Reilly said. The public trust
in Europe has been lost, Lander added, "because government
and scientists together failed to deliver thoughtful,
careful, trustworthy analysis." In the early 1990s,
the Food and Drug Administration issued a proposal not
to disclose on food labels any genetically modified
contents. Reilly questioned the wisdom of that policy
decision: "Why not, if it's safe, label it?" he asked.
"Sure, there's some cost associated with labeling it,
but I think there's a greater cost associated with not
labeling it if it breeds suspicion."
Patents. Genetic research is rapidly changing
patent law. Genes are already patentable by their discoverers,
but patent lawyers are exploring technologies that will
allow them to file patents on all molecules affecting
a particular receptor for a specific disease. "We are
now granting, without anybody paying attention to it,
patents on all possible molecules, including ones that
haven't been invented." This policy will block all "me-too"
drugs, derivative products such as different molecules
against the same receptor, Lander cautioned. He sees
danger in this direction, because historically, such
drugs have driven down the cost of pharmaceuticals through
competition. "There's clearly a role for private industry,"
Lander added, "but as a society, we have an obligation
over the course of the next 20-30 years to lay a foundation
which is not patentable."
Reexamining
the Criminal Justice System
From
his work with the Justice Department's Commission on
the Future of DNA Evidence, Reilly has seen how rapidly
genetic information is changing the criminal justice
system. In just 10 years, all 50 states have enacted
laws for DNA felon data banks that can communicate through
a common language. Now, a sample from a crime scene
can be run through a very large, national database,
making it possible to exonerate the wrongfully accused
quickly, focus prosecution on those who were at the
crime scene, and aid those who have been wrongfully
convicted. In the last three years, 100 people convicted
of felonies have been released from prison because their
DNA did not match evidence from the victim.
Money is one of the biggest problems plaguing DNA forensics
in the United States today, he said. Few states that
have enacted the laws have appropriated funds, and the
federal government has made "only a small financial
gesture toward dealing with the backlog problem-the
half a million samples collected pursuant to these laws
that have not been analyzed."
The use of DNA to identify possible criminals raises
other thorny issues. As an example, authorities in Florida
suspected a man for a violent crime, but they did not
have adequate probable cause to obtain a blood sample
to compare with their forensic DNA evidence. They trailed
him, and eventually saw the suspect spit in a parking
lot. They collected that sample, analyzed it, found
that it matched with evidence, and arrested him. However,
Lander pointed out that simply by wiping their mouths
with a napkin, people usually leave enough cells for
DNA typing. "In Washington, how long will it be before
an enterprising reporter does this for a presidential
candidate? And what about each member of Congress? Does
the public have a right to know your full genotype?"
he asked. At present, no laws prevent anyone from collecting
napkins and revealing genetic information about any
of us.
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DNA
information is forcing the criminal justice system
to reexamine some of its most basic rules, according
to Reilly.
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DNA
information is forcing the criminal justice system to
reexamine some
of its most basic rules, according to Reilly. One example
is the statute of limitations. Some states have a seven-year
limit for bringing to trial a person accused of rape.
With DNA evidence, however, it is now possible to "identify
who an individual must be without knowing his name"
and to prosecute him years later. In Wisconsin, a prosecuting
attorney has filed a case against John Doe and defined
him by his DNA. "Is that a good thing or a bad thing?"
he asked. "Do we want to revamp the statute of limitations?"
A related legal issue is the principle of finality-that
when a case has been appealed and decided, it's over.
DNA evidence showing that innocent people have been
convicted of felonies suspends that basic legal tenet.
Another
basic tenet of the legal system is the presumption that
children born within a marriage are the offspring of
the husband and wife. Population genetic studies show,
however, that 2-5 percent of "presumed paternal biological
relationships are not, in fact, true." Men have already
filed actions claiming they should not have to pay support
for a child raised as theirs but proven by DNA technology
to be unrelated. In theory, he said, more than 100,000
children per year could be denied child support on these
grounds, raising other issues for our society.
"Should there be a universal DNA data bank covering
everyone from birth?" Reilly asked. (This topic will
be addressed at the next CSIS/Whitehead breakfast seminar,
DNA Forensics: Should the United States Establish a
Forensics Data Bank? on May 2, 2001.) The United States
already has the makings of a universal DNA bank, he
noted. Since 1962, most children born here have had
blood drawn at birth for genetic tests; many states
have kept the dried blood samples, which are a rich
source of DNA. The DNA data banks are proliferating,
and there is a paucity of rules to guide them.
Given the range of social and legal issues raised by
the genomic revolution, "a challenge to policymakers
and members of Congress is to make sure that genetics
brings us together rather than separates us," said Reilly.
This
issue brief was written by The Stein Group.
The
New Biology and Public Policy is published by the
Center for Strategic and International Studies (CSIS),
a private, tax-exempt institution focusing on international
public policy issues. Its research is nonpartisan and
nonproprietary.
CSIS does not take specific public policy positions.
Accordingly, all views, opinions, and conclusions expressed
in this publication should be understood to be solely
those of the authors.
Funding for this series has been provided to CSIS and
the Whitehead Institute from The W.M. Keck Foundation,
The Richard Loundsbery Foundation, and the U.S. Department
of Energy Office of Biological and Environmental Research.
© 2001 by the Center for Strategic and International
Studies
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