[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.

                          ____________________