[Congressional Record Volume 140, Number 56 (Tuesday, May 10, 1994)]
[Senate]
[Page S]
From the Congressional Record Online through the Government Printing Office [www.gpo.gov]
[Congressional Record: May 10, 1994]
From the Congressional Record Online via GPO Access [wais.access.gpo.gov]
SCIENTIFIC RESEARCH AT THE UNIVERSITY OF PENNSYLVANIA
Mr. SPECTER. Mr. President, I had the occasion yesterday to visit the
University of Pennsylvania and to observe the results of scientific
research, which are very heartening and which show the value of
appropriations by the Congress of the United States for the National
Institutes of Health. Those funds have been not only maintained but
increased over the course of the past 14 years in the face of very
substantial budget cuts and in the face of consistent recommendations
by the administration, whether it is a Republican administration or
Democratic administration, to cut that funding.
Ten years ago, those appropriations were in the range of $5 billion.
For fiscal year 1994, the appropriation is almost $11 billion--it is
$10.9 billion.
Among the very difficult decisions which we have to make, the
Subcommittee on Labor, Health, and Human Services, and Education,
chaired by the distinguished Senator from Iowa, Senator Harkin, where I
am the ranking Republican, are those appropriations by some $6 billion
last year.
Yesterday, I had the opportunity to meet with Dr. James Wilson, who
is a brilliant, young research physician having both an M.D. and Ph.D.
He is head of the human gene therapy program at the University of
Pennsylvania Medical Center. In commending Dr. Wilson for his work, I
want to add that he has had very considerable help, and that there are
many who are jointly responsible for the enormous achievements which
have been made there. What happened, essentially, is that there has
been gene therapy which has already had very marked, wondrous results
on reducing the cholesterol level of a patient to stop the hardening of
the arteries and in providing relief from the dreaded disease of cystic
fibrosis.
These breakthroughs on gene therapy are wondrous results which
alleviate human suffering, which will prolong life, and which will have
the potential for enormous savings in medical costs in the United
States. One of the concerns which I have is the proposals on medical
matters which are now pending in the Senate and in the House which
would reduce the kind of funding for medical institutions like the
University of Pennsylvania and like many others around the country
which are finding really phenomenal results to alleviate human
suffering, prolong life, and very markedly bring down the costs of
medical care.
Dr. Wilson outlines that on cystic fibrosis, which strikes children,
the cost ranges into $1 million in the course of some 30 years of
treatment at a cost of about $35,000 a year, and the prospects are
present to have a single year's treatment alleviate the problem of
cystic fibrosis.
When I speak of these matters, I want to emphasize that the
achievements are just in their beginning stages, and they have made
this progress in the course of the last 5 years since 1989. The
opportunities for the future are really boundless.
I also want to comment on a visit which I paid to another
distinguished researcher, Dr. Ralph Brinster, a world renowned genetic
expert at the University of Pennsylvania veterinary school where there
has been research done on ways of changing the composition of the genes
of animals from one generation to the next. There is the process of
genetically altering sperm cells in animals so the traits passed down
from one generation to the next could be changed. The work of Dr.
Brinster has resulted in the application for a patent.
There has been some concern that his work might be applicable to
humans as well. There is no indication of that at the present time, and
the aspects of the ethical considerations in alteration of genes is
under very intense scrutiny by the officials at the University of
Pennsylvania both as to the work which is being done by Dr. Ralph
Brinster and also the work by Dr. James Wilson. The work of Dr.
Brinster has applicability already beyond the changing of the cells of
animals to application in plants where there is an opportunity for
tremendous increase in quality and quantity of plant growth.
Having met these two distinguished doctors yesterday, I wanted to
share with my colleagues and also with those who may be watching on C-
SPAN II the kinds of dramatic results which are in the works with their
scientific research.
Dr. Wilson comments, and I think it is appropriate to pass on his
comments, that there is very intensive research being done as to cancer
and as to AIDS on the changing of the cell dynamism which have great
potential promise for the future.
Mr. President, I ask unanimous consent that the full text of an
article from the New York Times, dated April 1, 1994, be printed in the
Record at the conclusion of my statement.
The PRESIDING OFFICER (Mr. Ford). Without objection, it is so
ordered.
(See exhibit 1.)
Mr. SPECTER. I thank the Chair.
That statement refers to the work of Dr. Wilson and Dr. Mariann
Grossman at the University of Pennsylvania Medical Center.
I further ask unanimous consent that the full text of an article in
the Philadelphia Inquirer, dated April 8, 1994, concerning the work of
Dr. Ralph Brinster be printed in the Record at the conclusion of my
remarks.
The PRESIDING OFFICER. Without objection, it is so ordered.
(See exhibit 2.)
Mr. SPECTER. Mr. President, these articles give a fuller picture of
the achievements already made and of the potential for the future.
I can assure those who are concerned about this kind of research that
the Subcommittee of Appropriations on Labor, Health, Human Services and
Education will be giving very serious consideration to the
appropriations for NIH which will enable these research experts and
others to carry on the very important work of this field.
I thank the Chair and yield the floor.
Exhibit 1
[From the New York Times, Apr. 1, 1994]
Gene Experiment to Reverse Inherited Disease Is Working
(By Natalie Angier)
Philadelphia, March 31--The first effort to reverse an
inherited disease permanently by altering the genetic makeup
of a patient's cells so far shows all the signs of a real, if
modest, triumph.
In results to be published on Friday in the journal Nature
Genetics, researchers said they had partly corrected a
devastating cholesterol disorder called familial
hypercholesterolemia by supplying the patient, a
30-year-old woman from Quebec, with copies of an essential
gene she lacks.
The new paper is the first to report any therapeutic
benefits of human gene therapy, a radical approach to
treating disease that has been rich in publicity but, until
now, quite thin on hard data. Now, scientists and others have
their first opportunity to scrutinize the real merits of gene
therapy and decide what its benefits and limitations may be.
Announcing the results of their first patient's outcome
almost two years after the woman received gene therapy, Dr.
James M. Wilson and Mariann Grossman of the University of
Pennsylvania Medical Center and their colleagues said at a
news conference that they had cut the woman's harmful
cholesterol levels by almost 20 percent and raised her
concentration of so-called good cholesterol significantly.
Recent scans of her arteries showed no evidence of
progressive clogging, a problem that had caused the woman to
suffer a heart attack at the age of 16 and require coronary
bypass surgery at 26. Familial cholesterolemia, an extremely
rare condition, causes such severe buildup of cholesterol
throughout the body that many people with the disorder die of
heart attacks in childhood or adolescence.
The researchers emphasized, however, that the woman's
cholesterol level remained quite high--more than twice the
normal range--and that they had no idea whether their
intervention would end up prolonging her life.
``We've achieved a partial correction of a metabolic
defect,'' Dr. Wilson said in an interview. ``This shows that
the principle of gene therapy is sound, and that it can work.
We have high hopes for this patient, but what will happen to
her in the long run, there is no way of predicting now.''
The gene therapy procedure is a physically grinding ordeal,
requiring major surgery. In it, the researchers remove about
15 percent of the liver, separate and grow the cells in
plastic dishes and supply the cells with copies of the gene
they need, using a harmless virus as a delivery shuttle. The
crucial gene dictates the production of the so-called low-
density lipoprotein receptor, the body's sponge for harmful
cholesterol. A billion of those manipulated cells are then
reinfused into the patient through the portal vein that feeds
the liver, where at least some of them resettle into their
home base and begin producing the needed cholesterol
receptor.
Dr. Wilson has estimated that about 3 to 5 percent of the
woman's liver cells are now behaving as vigorous liver cells
do, generating the receptors and pulling cholesterol from the
bloodstream.
Appearing at the news conference, the woman, who has asked
that her name and picture not be used, appeared to be as
healthy--and as shy--as a teenager. Her blond hair swept back
and her prim white blouse buttoned up to the collar, she said
she had felt ``very well'' since the operation in 1992.
Speaking through an interpreter in her native French, she
said: ``I feel very well physically and morally. I feel I can
do more physical activity, like skiing, dancing and other
social activities.''
2 brothers died
Two of her brothers died of heart attacks in their early
20's as a result of familial hypercholesterolemia, but she
sounded an optimistic note: ``I'm certainly going to live
until 90 years of age.'' The woman, a seamstress and part-
time bank teller, is also benefiting from cholesterol-
lowering drugs, which had no effect on her before the gene
therapy intervention. The researchers have also been pleased
to see that the therapy has raised her levels of high-density
lipoprotein, or good, cholesterol, for reasons that remain
mysterious. This could further cut down on her risk of future
heart attacks.
Hearing of the new results, other researchers were at once
heartened and cautious. ``These are early days, and it's
exciting that it works,'' said Dr. Dusty Miller, a gene
therapy expert at the Fred Hutchinson Cancer Research Center
in Seattle. ``The problem is, of course, that the liver
technique is very cumbersome and difficult to do.''
Dr. John Kane, director of the Lipid Clinic at the
University of California at San Francisco, said, ``This is
far from a complete correction, but the fact that they have
stable engraftment of the cells over all these months is
encouraging.'' He added: ``This is a landmark experiment.
It's the Kitty Hawk of gene therapy.''
4 Others in Experiment
The severe form of familial hyper-cholesterolemia is
exceedingly rare, afflicting about one in a million people in
the United States, although about one in 500 have a milder
form of the disorder. Since the Quebec woman, four other
hypercholesterolemia sufferers have undergone the liver
redesign experiment, the youngest of them a 7-year-old girl
from Philadelphia.
Dr. Wilson said a similar gene therapy protocol might soon
prove useful for treating other metabolic disorders, like
phenylketonuria and a hereditary inability to break down
ammonia in the body. ``Individually these disorders are
relatively rare, but collectively they're relatively
common,'' he said. He and others also hope to find less
invasive ways of delivering new genes to liver tissue,
perhaps packaging them into carrier bubbles of fat, or into
cold viruses that can directly infect liver cells.
Many other gene modifying experiments are at various stages
of clinical trials, among them treatments for severe combined
immune deficiency disorder, cystic fibrosis and a number of
types of cancer. Dr. Wilson had the great good fortune, Dr.
Miller said, to be the first to reach the publication finish
line.
Repairing Liver Cells
People with familial hypercholesterolemia have liver cells
that lack receptors to mop up circulation-clogging LDL
cholesterol. In an experimental therapy, part of the liver is
removed and some liver cells are given the missing gene. When
the altered cells are restored to the liver, they seem to
help it handle cholesterol.
____
Exhibit 2
[From the Philadelphia Inquirer, Apr. 8, 1994]
Penn's Bid for a Patent May Spur Genetic Debate
(By Huntly Collins)
The University of Pennsylvania has applied to patent a
technique to genetically alter sperm cells in animals so
traits passed down from one generation to the next could be
changed.
Although the application focuses on experiments with
animals, it suggests that the technique might be used in
humans as well.
The patent application, reported yesterday by The New
Scientist, a British journal, raises fundamental issues that
have been debated for years but that have always seemed too
theoretical to be taken seriously.
Now, the debate may begin in earnest.
Critics contend that so-called germ-line gene therapy,
which would alter the DNA in nascent sperm cells, raises the
specter of eugenics--using science to create a superior human
race.
They fear that parents could use the technique for
frivolous purposes, such as determining the color of a
child's eyes, or for other ends, such as screening out
children who might be homosexual.
But others think the technique might work medical miracles,
allowing families plagued by catastrophic genetic illnesses--
such as hemophilia, sickle cell anemia, or cystic fibrosis--
to be rid of them once and for.
Attacking such diseases through genetic engineering of
sperm cells might also be more efficient--and save more
money--than the gene therapy techniques now being developed,
which would change the genes in individuals but not in
succeeding generations.
``For many years, a lot of people * * * thought that
modifying germ lines was unethical,'' said Arthur Kaplan, a
medical ethicist at the University of Minnesota. ``From my
own point of view, that doesn't make sense. If you can get
rid of diseases, why wouldn't you do it?''
The patent application filed with the U.S. Patent and
Trademark Office on Dec. 6, 1991, seeks to patent a technique
developed by Dr. Ralph Brinster, a world-renowned researcher
at the Penn veterinary school.
Although the patent application seeks to use the technique
in animals, it makes passing reference to the fact that the
same procedure might be used in humans.
It is the reference to humans that has provoked concern on
both sides of the Atlantic as scientists grapple with the
far-reaching implications.
The head of the European Patent Office in Munich told The
New Scientist that the patent application raised serious
ethical issues.
The journal quoted Christian Gugerell as saying it was
``highly doubtful'' that his agency could approve the patent.
Gugerell revealed the existence of the patent application
at a recent meeting in London, the journal said.
Officials of the U.S. patent office could not be reached
for comment yesterday.
But Nelson Wivel, director of the Office of Recombinant DNA
Activities at the National Institutes of Health, said the
agency's advisory committee, which must approve experimental
gene therapy treatments in humans, ``will not even review''
germ-line therapy at the present time.
He said scientists have not yet perfected ways of targeting
genes at specific places on chromosomes. Such imprecision
could lead to calamitous mistakes. For instance, a gene that
is necessary for normal development might be turned off, or a
gene that can cause certain types of cancers might be turned
on.
But Wivel, who reviewed Penn's patent application
yesterday, said the document focuses largely on animals--
primarily mice--rather than people. He said the reference to
the potential use in humans appeared to reflect the
university's desire to cover all its legal bases.
``If you read the patient, it's not as daunting as it might
seem.'' Wivel said. ``The document is simply a lawyer doing
his or her job.''
Penn officials refused to make a copy of the patent
application available, saying it was proprietary information.
Under an international patent treaty, such applications fall
in the public domain 18 months after they are filed.
``I thought my patent application would be recognized as
just an exploration of basic science,'' he said.
Brinster emphasized that he did not believe germ-line gene
therapy was technically feasible in humans at present, ``nor
should it be considered now.''
He said when the technology is perfected, its use in humans
should be decided by the federal government only after
considerable public debate.
``There should be a lively debate. The public should be
thinking about it. But I'm not the person to be at the center
of the debate,'' Brinster said.
He said he had no strong views about the ethics of altering
human sperm cells. ``I'm just one person,'' he said. ``I'd
have to hear everybody else's view about it.''
Brinster, a professor of reproductive physiology who holds
the Richard King Mellon chair at the Penn vet school, was one
of the first scientists to develop transgenic mice, which
carry some human genes.
In his pathbreaking experiments, he transplanted genes for
human growth hormone into a fertilized egg of a mouse. The
egg was inserted into the reproductive tract of a female
mouse and she gave birth to a mouse twice the size of a
normal mouse.
In recent years, Brinster has turned his attention to the
spermatogonia of male mice. These primitive cells are
fascinating because they keep duplicating themselves and they
can develop into any type of cell in the body.
Brinster, who is a member of the National Academy of
Sciences, said his research was aimed at learning how these
cells eventually differentiate.
He said that if his gene therapy technique works; it might
be used to improve the sperm output of certain animals. He is
conducting his federally funded research with a graduate
student, Jim Zimmerman, whose name is also on the patent
application.
Mr. PELL. Mr. President, I suggest the absence of a quorum.
The PRESIDING OFFICER. The clerk will call the roll.
The legislative clerk proceeded to call the roll.
Mr. DeCONCINI. Mr. President, I ask unanimous consent that the order
for the quorum call be rescinded.
The PRESIDING OFFICER. Without objection, it is so ordered.
____________________