Dr. M.R.C. Greenwood
Associate Director for Science
Office of Science and Technology Policy
Testimony before the Committee on Science, Space, and Technology
U.S. House of Representatives
September 28, 1994
For decades we have known that height, hair and eye color are all
traits that people inherit from their forebears. We also know
that some dreadful diseases come about as a consequence of having
inherited a gene from one or both parents. Some of the worst of
these devastate the lives of young children and their families
and cost hundreds of thousands of dollars, if not more, simply to
relieve the pain and suffering in less than satisfactory ways.
For the families of those afflicted, any approach that could
prevent or cure such conditions would be worth any cost and many
would welcome information that would predict whether they or a
child would be affected by a genetic disease.
However, in addition to these traumatic and still rather rare
inherited conditions affecting only a small group of patients, we
now know that a huge proportion of the population carries not a
certain commitment, but a predisposition to chronic disabling
conditions which take a lifetime to develop such as diabetes and
some forms of cancer and heart disease. When put together, then,
the impact of genes and our ability to modulate or change their
function is relevant to virtually everybody in this country.
Before I go on and talk about gene therapy specifically, I want
to point out that "fixing" genes and improving health and quality
of life is completely consistent with our long term goals of
providing preventative and corrective medicine targeted to the
known individual needs of our citizens. In the past, we have had
to focus only on relieving the symptoms of genetically determined
disease. The future offers the opportunity to diagnose, cure and
alter the course of disease.
There is a degree of public interest in the nature and philosophy
of gene therapy, and its potential problems. This is not a new
response to the advent of innovative therapeutic agents. For
example, in 1802 when Edward Jenner proposed injecting humans
with material from cows to vaccinate against smallpox, there was
a great outcry illustrated by cartoons depicting people sprouting
horns and tails. It is overwhelmingly important for Congress to
help the American people to understand the scientists and also to
help the scientists understand the public's concerns. We believe
the Nation cannot afford to lose this opportunity to improve the
lives of patients and cure these diseases. It also cannot afford
to ignore the misunderstandings or mistakes that could develop
and which thoughtful debate can prevent.
As a life sciences researcher, I spent 25 years before coming to
Washington trying to understand the genes that predispose or
cause diabetes and obesity; two diseases which, if you look
around this room, are of great personal interest to at least some
of us. Today, we know on which chromosomes the genes that cause
these diseases reside in some animals, and have learned in the
past month that insulin dependent diabetes mellitus, the form
that so often and tragically afflicts young people, is regulated
in part by genes on chromosomes 6 and 11, but that as many as 18
other chromosome regions may also be associated. So, to be sure,
these issues are not simple. In other words, some genetic
diseases can be traced to a single simple problem in one
individual gene, while numerous other familial conditions are
linked to a highly complex set of coding faults. We have to
understand that the situations our biomedical investigators face
today are as complex as they are heartbreaking.
Although there has been a resurgence of antibiotic-resistant
strains, e.g., tuberculosis, antibiotics are largely adequate to
manage many previously fatal bacterial infections and great
strides have been made in curbing certain viral diseases.
Vaccines are our most powerful weapon against the common
infectious diseases of childhood--measles, mumps, rubella, and
now Haemophilus influenza, as well as others such as hepatitis B.
I characterize vaccines in this way because they actually prevent
the occurrence of infection which is the most cost-effective
approach to illness.
However, the medical armamentarium is still limited with respect
to the prevention or treatment of many common chronic or long-
term disabling diseases including arthritis, diabetes, heart
disease, cancer, and mental illness. The most highly desired
goal, from the perspective of the patient and the country's
health care system, is to prevent the occurrence of disease. The
bulk of our treatment strategies for such conditions rely on
ameliorating symptoms but fall short of actually curing patients.
For those situations in which genetic elements are the causative
agents, it stands to reason that the route to prevention and cure
is through molecular biology and gene therapy. I think the
promise is real, but we have a long way to go before genetic
medicine is a common practice.
Almost all inherited metabolic disorders are the result of
improperly functioning proteins, especially enzymes. Enzymes are
the catalysts that permit us to extract nutrients from the food
we eat, to transfer energy enabling us to perform tasks, to send
signals from one cell to another, and to detoxify and excrete the
endproducts of these life processes. Enzymes are essential to
life and a defect in the gene coding for these compounds would be
lethal to the developing fetus. Every living organism relies on
the appropriate enzymes being present at the right time and in
the right amounts. Therefore, the simple replacement of a
defective gene may not be sufficient to improve the condition of
the patient. Exquisitely fine regulation of production of the
enzyme at the molecular level is also crucial in some cases.
Another example of how complicated genetic intervention can be is
the fact that we may need to reach the genes in a specific organ
like the islets of Langerhans in the case of patients with
diabetes. It may not be feasible or practical to rely on
surgically removing the target cells, altering them in a petri
dish in the laboratory and returning them to the patient. Other
options include creating methods that will enable the replacement
genetic material to home in on the target cells or tissues, such
as using viral delivery systems that are already accustomed to
reaching the desired cells, or selecting for treatment those
conditions that can be remedied without need for such
specificity. Both of these options are under study.
The early candidates for gene therapy therefore, are those
defects that may be remedied in a fairly simple fashion by
introducing a gene that codes for a product that does not require
careful regulation but can be functional and useful in any amount
while present in the general circulation. Other candidates fall
in the second category that I mentioned, as treatments for
diseases such as cancer and AIDS that work by boosting the
patient's internal defense systems. For now, the selection of
disease targets is limited by the available science and
technology. As we learn more and more about regulation of gene
expression in the normal organism, we will be able to apply this
to our understanding of disease processes.
I think it is fair to say that today's biomedical investigator
has , for the first time, the scientific knowledge and
technological tools to begin addressing questions that have
eluded us in the past. The answers open doors to additional
avenues of investigation, bringing us closer to understanding the
fundamental biological processes underlying normal and disease
states. This knowledge, in turn, points toward means to
diagnose, treat and, ultimately, cure or prevent disease.
I think it is worth paraphrasing a statement made by one of the
scientists that locating the BRCA-1 gene creates more questions
than it answers. With this key gene in hand, we can begin to
examine the entire cascade of events that lead up to the
development of breast cancer, including, perhaps, the 95 percent
of cases that are not hereditary. We also expect that this
discovery may be extended to helping to understand the normal
forces that regulate cell growth and cell division and how
disruption of this function leads to cancer. Of course there is
immediate interest in using the gene to develop a screening test
to identify women at increased risk of inherited breast cancer
and ovarian cancer. This will take some time -- time we will
need to identify and establish procedures under which such tests
would be helpful.
I will return to the issue of ethics and genetic information in a
moment. The point I want to underscore is that a great deal of
fundamental scientific research must be done in order to put the
results of genetic studies to use in the diagnosis and treatment
of disease. Continued support for the science that offers such
tremendous promise will result ultimately in better quality, more
cost-effective health care than we can provide today with our
still rudimentary understanding of the genetic basis of disease.
Research in molecular biology and genetics is supported not only
through the Human Genome Project, but also by virtually all NIH
components, the National Science Foundation and many other
agencies. I believe you will hear more about this work from Dr.
Wivel. We must not lose sight of the long-term value of this
commitment.
The discovery of the breast cancer susceptibility gene and the
attention it generated in the press offers a useful opportunity
to educate the public about the power and limitations of
biomedical science. Dr. Varmus and the NIH scientists deserve
the credit for explaining what this discovery means for women at
risk of breast cancer and for the public at large. When this
announcement was made, we were gratified to see that the press
showed great sensitivity in explaining that a screening test
would not be forthcoming immediately. But questions about who
should be screened and under what conditions have been raised and
should be fully aired, even before such a test becomes available.
To help inform the public discussion, we will have to
continuously explain the scientific and ethical issues. That is
one of the reasons that in its position paper on research,
Science in the National Interest, the Administration has pushed
for more programs to enhance public scientific literacy.
Enhancing our scientific literacy empowers our populace,
providing the means for informed decisionmaking. Providing a
forum for airing tough issues and exposing them to the scrutiny
of experts and interested individuals is also important. This
hearing makes an important contribution to increasing awareness
of issues related to gene therapy. I think the early public
interest in human gene therapy protocols, before the technology
was in hand, also played a role in resolving some reservations
and permitting approval of this work.
OSTP began developing this proposal at the request of the
Departments of Energy and Health and Human Services, in October
1993. These agencies had been considering establishment of a
joint advisory panel to examine issues related to maintaining the
confidentiality of genetic information resulting from the Human
Genome Project. It became clear that there were a number of
other bioethical issues that would benefit from consideration by
an expert, standing advisory body. Thus, the informal
interagency working group was expanded to include representatives
of DOD, NASA, VA, NSF and Justice. Discussions also took place
with members of Congress including Representative Markey and
Senators Kennedy, Glenn and Hatfield. With their interest and
encouragement, several improvements were made in early drafts.
The products of these discussions are the draft charter and
preamble which have been recently published in the Federal
Register.
The key points of the charter are:
You may recall the groundbreaking work of the National Commission
for the Protection of Human Subjects of Biomedical and Behavioral
Research and the President's Commission for the Study of Ethical
Problems in Medicine and Biomedical and Behavioral Research;
reports such as Defining Death, Splicing Life and Research
Involving Children. It is our hope that this new group would
build upon the impressive body of collective wisdom generated by
earlier commissions. We believe that the Commission would be
useful in considering some of the difficult issues that will be
discussed today.
I thank you for your attention and offer to answer any questions
you might have.