[Congressional Record Volume 152, Number 23 (Tuesday, February 28, 2006)]
[House]
[Pages H426-H432]
From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]
EMBRYONIC STEM CELL RESEARCH
The SPEAKER pro tempore. Under the Speaker's announced policy of
January 4, 2005, the gentleman from Maryland (Mr. Bartlett) is
recognized for 60 minutes as the designee of the majority leader.
Mr. BARTLETT of Maryland. Mr. Speaker, very shortly now the juvenile
diabetes people will be coming through the Congress. They do this every
year, I believe.
I look forward to this visit with really mixed emotions. These
children come in with this disease that has and will change their
lives. Many of them are so brittle that they have to have a pump
embedded under their skin that pumps insulin, because the sugar may go
violently up or down with potentially disastrous effects on the person.
Many times a day they may have to get a droplet of blood to determine
the sugar level.
They will appeal to us, as they have every year for the past 5 years,
please vote for Federal funds for embryonic stem cell research because
they believe, like the loved ones of many other types of patients, that
there could truly be miracle cures from embryonic stem cells. They will
tell us that there are several hundred thousand embryos out there that
are frozen in fertility clinics.
I have a daughter-in-law who is going through that process now. They
harvest eggs. They fertilize the eggs. First, they have to give a
hormone treatment to the prospective mother so that there will be the
production of more than just the one egg that is produced normally per
month. They will harvest a number of eggs, 8, 10, 12 eggs. Then they
will fertilize those eggs, and they will watch their growth in the
laboratory, and they will choose two or three of what look like the
strongest fertilized eggs, and then they will implant those in the
prospective mother.
The remaining eggs are frozen. It costs money to keep them there. The
family may pay for that process because these little embryos that are
implanted may not take, and they may need to do it again, and frozen,
they could last quite a while, and they may want to have another child.
So they will pay to keep them frozen for a while; but by and by, time
and changes in the family, they will see no further need to keep them
frozen. When they cease doing that, then the laboratory must either
dispose of the embryos or bear the expense of keeping them frozen.
So each year a number of these embryos are discarded, and there has
been an appeal, which has been bought into by some of my very good
friends in the Congress, that from a ethical perspective, why should we
not get some medical use from these embryos that are going to be
discarded anyhow.
That is a tough position to put pro-life people in, and the reason
that most, but not all, pro-life advocates are opposed to this is
because they view this as the beginning of a slippery slope. Today, you
are permitting the use of surplus embryos that are going to be
discarded anyhow; tomorrow, you might be producing embryos. They may be
stronger, younger. You may be producing embryos just so you can discard
them so you could use them for medical research.
I remembered the juvenile diabetes groups that come through, the
children and their parents when, in 2000, I went to the National
Institutes of Health when they had a briefing for Members of Congress
and staff on embryonic stem cell research, the potentials and the
challenge. There were a number of staff there. I think that I was the
only Member of Congress who was there.
I went there from a somewhat unusual background, a different
background than the average Member of Congress, because in a former
life, I went to school and got a doctorate in human physiology. I got
it not in a medical school but at an arts and sciences campus, and so
we had to take a great variety of courses.
{time} 2045
Things like limnology and ichthyology and cytology and protozoology
and advanced genetics. And one of the courses I took was advanced
embryology. And in that course I had an opportunity to study and learn
something about the process which is so familiar to anybody who has
studied biology in life, that is, the development of the embryo and how
this process goes.
I recognized that occasionally in humans in the early embryo,
sometimes at the two-cell stage and sometimes later, and you can tell
by how the babies present whether they share an amnion or simply share
the chorion; how they present at birth you can tell at roughly what
time in the development of the embryo did it split. And each of those
halves of the original embryo, either one cell if it was a two-cell
stage, or multiple cells if it was further along in the development
before it split, each half produces what appears to be a perfectly
normal baby. We call them identical twins. And there are tens of
thousands of them out there and a great deal of scientific interest is
in these twins.
And a lot of research has been done, because when you are looking at
two genetically identical people, you have an opportunity to make some
studies and observations that you would have to use a great many more
subjects to make using the usual genetic different subjects.
And so recognizing that you could take half of the cells away from
the original embryo and each half produced a perfectly normal baby, I
rationalized, gee, it ought to be possible to take a cell from the
early embryo and it would not even know it. And that is because all the
cells in the early embryo are what we call totipotent or at least
pluripotent. Totipotent means they can produce another embryo if you
take the cell out, and pluripotent means they can produce all of the
cell types that make up the body. By the time they are pluripotent,
they have lost the ability to coordinate all of the different kind of
cells into an integrated individual, so they could not produce an
embryo.
I asked the researchers at NIH, should it not be possible to take a
cell from an early embryo without killing the embryo, probably without
hurting the embryo, since in every set of identical twins half of the
cells have been taken away from the embryo.
And by the way, Mr. Speaker, one of those is a clone. I guess you can
decide which one of those identical twins you would identify as the
clone, but clearly one of them is a clone, and both of them develop
into what appears to be, by observations over hundreds of years and
more recently many years of intensive physiological and medical
observation, what appear to be perfectly normal human beings.
And so I asked the researcher at NIH, shouldn't it be possible to
take a cell from an early embryo without killing the embryo, probably
without hurting it? And they said, yes, they thought that should be
possible. So a few days after that I happened to be at an event when
the President was there, and I knew that he was laboring with a
decision, a very difficult decision, of whether he was going to permit
Federal dollars to be used in embryonic stem cell research when
presently at that time the only source of embryonic stem cells resulted
from the destruction of an embryo.
So I told the President about the meeting at NIH and about my
discussion with the researchers there, and a few days later I got a
call from Karl Rove. The President had remembered that conversation and
turned the follow-up over to Karl Rove, and Mr. Rove told me that he
had gone to NIH and had spoken with the investigators there, and they
had told him that that was not possible. I said, Karl, either they are
funning you or they misunderstood your question, because these are the
same people that can go into an individual cell and take out the
nucleus and put another nucleus in that cell. And they are telling you
they cannot take a cell or two out of a big embryo?
So he went back and asked them again and came back and called me a
second time and said, Roscoe, they tell me that they cannot do that. I
wondered at the time what had happened. And a couple of years later,
when the researchers at NIH were in my office, they somewhat sheepishly
admitted that they had permitted Mr. Rove to believe something that
wasn't quite true. Because what they had told him
[[Page H427]]
was that they weren't sure that they could produce a stem cell line
from a single cell taken from an early embryo.
That is exactly what my bill had proposed to do, was to determine,
with animals, whether in fact that was possible or not. They had not
meant for him to believe that it was not possible to take a cell from
an early embryo.
Now, I cannot get inside their head to tell you, Mr. Speaker, why
they permitted Mr. Rove to go away with this misconception, I can only
tell you that I think that if I were in their place, I would have
judged that the President might very well make the decision that it was
okay to use these discarded embryos. Because, after all, they were
going to be discarded anyhow, and the potential for life-saving medical
applications was so great that I think that they may have rationalized
that the President was going to issue an executive order which would
make possible the use of Federal funds in the study of embryonic stem
cells taken from these surplus embryos. That, of course, is not what
the President did.
I am happy to be joined this evening by Dr. Gingrey, and I wanted to
engage him in a dialogue, because I think that the same kind of an
emotional response that might have permitted the researchers at NIH to
permit this discussion to result in a misconception by Mr. Rove, that
an analogous emotional response on the part of many pro-life advocates
makes it very difficult for them to even talk about the potential of
any form of embryonic stem cell research because they are so
conditioned that the only way in the past that we have been able to get
embryonic stem cells was by destroying an embryo, and so they equate
any discussion of embryonic stem cell research as requiring the
destruction of an embryo.
The President has a bioethics council that published a white paper in
which they talked about four different techniques, potentially
bioethically acceptable that could produce embryonic stem cells without
destroying an embryo. And I wonder what is the best approach, because
we want to carry everybody along with us. I want no one to be offended
that what we are proposing, what has been proposed as a matter of fact
by the President's council on bioethics is a violation of our
fundamental belief that life is sacred. Every life is sacred, and
particularly the least of these, this totally defenseless embryo. Their
life is sacred, and we must protect that.
So the research that I am proposing, that my colleague has been
supporting, does exactly that. And I am wondering what is the best way
to bring this community along with us so that they understand that
there are potential techniques that could be used for producing
embryonic stem cells that will not consist of destroying or even
hurting the embryo. What do you think is the best way to approach this?
Mr. GINGREY. Well, first of all, let me thank the gentleman from
Maryland for his legislation, H.R. 3144, and for allowing me to spend a
little time with him this evening as we try to explain to our
colleagues what we are talking about here and what is the essence of
the Bartlett bill.
I think the gentleman is correct that the perception among those of
us who are strongly pro-life, and I think most of my colleagues on both
sides of the aisle sort of know each other's former profession before
we came to this august body, and I practiced medicine, not just an
M.D., but specializing in obstetrics and gynecology; and so over a 26-
year period, doing the average number of deliveries a doctor would do
in a year, that amounts to over 5,000; and very proudly I can stand
here tonight and say that I am pro-life and have never performed an
abortion.
But I think that in response to the gentleman's question, people that
are pro-life know that embryonic stem cell research that was ongoing
before President Bush made his decision 2 or 3 years ago, that those
stem cell lines were indeed obtained from this so-called excess. Really
not excess. Cannot tell that to the Snowflake babies that have been
adopted, those embryos, and there are close to 100 of those precious
children alive today, but the pro-life community, indeed, everybody
understood that the stem cell lines that were created were created from
the destruction of embryos that were produced utilizing artificial
reproductive technology that the gentleman from Maryland so adequately
explained.
And of course those children, and I say children, they are embryos,
but they certainly become children. They become fetuses, and they
become children, and they become young adults, and they become middle-
aged and senior citizens. They are human life. And, basically, what the
President said is those that have already been destroyed to create
these cell lines, we will allow researchers, our scientists, to apply
for grants to conduct the research on those cell lines, those embryonic
stem cells, but not to destroy any more life; to put a moratorium on
that and to absolutely not continue to destroy life.
In fact, in 1999, President Clinton's National Bioethics Advisory
Commission, NBAC, acknowledged broad agreement in our society that
early human embryos ``deserve respect as a form of human life.'' They
recommended funding of embryonic stem cell research only if there were
no alternatives. But what Congressman Bartlett is talking about
tonight, of course, is an alternative, a viable, if I can use that
term, a viable alternative. And that is what he has outlined for us in
this legislation, and I know he will talk about that.
But the important point is that people who are pro-life understand
this, that taking a cell or two from an embryo, once it has gotten to
the point where those cells are not totipotent, that you are not
literally taking maybe something that in itself could divide and become
an embryo; you get beyond that stage to what he describes as
pluripotent.
And the difference in those two capabilities in those embryonic cells
is hugely important to the pro-life community. And he, of course, has
done such a great job tonight, and I commend him for that, of
explaining how in nature this occurs with the division of a multi-cell
embryo to become identical twins; and it is, I think, a good
explanation. And I think that is probably what is important, in
response to your question, my good friend from Maryland, is this
educational process.
And I know you have worked on this. I do not know how many times you
have done this Special Order, but you have honored me in giving me an
opportunity to participate with you and get into a colloquy and discuss
some of these issues. This is the way to do it. This is the seed corn.
This is what gets it started. It is a matter of understanding that
there is an alternative to destruction of human life for the betterment
of other lives.
{time} 2100
Mr. BARTLETT of Maryland. Dr. Gingrey, thank you very much.
There is another consequence of this understandable emotional
reaction on the part of the pro-life community, and that is the
statement that is made over and over again that we have, I think it is
up to 70-some now, treatments or cures from adult stem cells and none
from embryonic stem cells; therefore, why would you want to bother
looking at embryonic stem cells?
The reason we have 70-some treatments from adult stem cells is we
have been working with them for about 3 decades and we have been
working with embryonic stem cells for just a little over 6 years. A
newborn baby cannot run a marathon, and there just has not been time
for the medical community to develop the potential from embryonic stem
cells.
I will be the first to tell you that this research may be very
disappointing. I hope that it will not be, because these cells really
want to divide, and like an obstreperous teenager, they may be very
difficult to control. But the hope is that since embryonic stem cells
can certainly make any and every tissue and, potentially, organ in the
body, they ought to have the greatest potential.
And I wonder what we need to do so that the statement is not repeated
that it is really silly to talk about embryonic stem cell research
because we have 70-some treatments or cures from adult stem cells and
none yet from embryonic stem cells. That is, of course, a true
statement, but you need to put it in context. The reason for it is we
have been working for more than 3 decades with adult stem cells and
just a little over 6 years with embryonic stem cells. And I want our
community to have credibility at the end of the day.
How do we meet this emotional challenge?
[[Page H428]]
Mr. GINGREY. Mr. Speaker, if the gentleman will yield, I think it
really is a good point that you are making that we have been utilizing
adult stem cells for a long time, for many years, and whether we are
talking about cells that are obtained from bone marrow or from blood,
even, of course, some umbilical cells. But as the gentleman points out,
there have been some real great success stories reported: cancers,
including ovarian and testicular cancer; leukemia; Hodgkin's disease;
stroke; heart disease; Parkinson's disease; as the gentleman mentioned,
juvenile diabetes; Crohn's disease, an inflammatory disease of the
bowel which can be so devastating.
And I think Roscoe Bartlett, the gentleman from Maryland, mentioned
maybe 58, in total, success stories. But the earliest cell, I think,
has the greatest potential, and that is basically the point that the
congressman is making and why his bill, H.R. 3144, to provide funding,
very necessary funding, to do the basic and applied research starting
in animal models to show that you indeed can take these, again, not
totipotential but pluripotential, so not another embryo, but something
that has gone beyond that stage that does not have the capability in
and of itself of becoming a human being. That is what we want to say to
the pro-life community.
So we are taking, though, the very earliest beyond that stage cell,
and there is no telling what tissue it can develop into, whether we are
talking about brain tissue and trying to treat people, God rest his
soul, like Christopher Reeves or other people with spinal cord
injuries, or someone with severe Parkinson's disease or Alzheimer's or
juvenile diabetes where you create islet cells that you can transplant
into a person's pancreas that, because of a genetic defect, has no
islet cells.
So that is really, I think, the answer, to say why it is worth the
effort, why it is absolutely worth the effort. First and foremost, you
do not have to take human life for the betterment of other human lives,
and we want to build on the success of utilization of adult stem cells
and go that extra mile, and this is what this bill will do, allow us to
do the basic research, fund it with Federal dollars so we can get to
that point.
Mr. BARTLETT of Maryland. Thank you very much. I appreciate your
mentioning the diabetes, particularly juvenile diabetes.
The deficiency, of course, is in the Islet of Langerhan cells, named
after the German scientist who first saw them. They are like little
islands scattered through the pancreas. I have no idea why they are in
the pancreas. They have no relationship to the physiology of the
pancreas; they just happen to be there, and they are not producing
enough insulin. But replacing the insulin does not cure diabetes
because the person who has diabetes will end up with eye problems,
circulatory problems, toes that they lose, gangrene, and so forth.
And these children now are starting out with the absolute certainty
that they are not going to have the quality of life of other children
because just replacing the insulin does not cure diabetes. It controls
many of the effects, but there will still be consequences to the
diabetic.
And as you mentioned, there is the hope that with embryonic stem
cells we could grow Islet of Langerhan tissues. And you would not have
to put those back into the pancreas. You could, as a matter of fact,
put them in the groin or under the arm or under the skin, anywhere.
They just have to have access to circulation. They will produce the
insulin. The circulation will pick up the insulin, and then it flows to
the liver and the cells of the body where it does its miracle work.
But this is the reason that they are so enthusiastic about embryonic
stem cell research, because of all of the diseases out there. And we
spend more money on diabetes than any other disease in the country, and
there is probably more debility and suffering from diabetes than any
other disease in the country. And that is why they are so adamant in
their desire that we permit Federal dollars to be spent, because with
the power of NIH and the peer review, and they have created miracles in
the past, they hope they can do another one.
I would like to just look for a moment at the physiology, and the
chart, boy, this is really abbreviated. I will show you a little more
expanded one in a moment.
But the two gametes come together and produce what is called a
zygote, and this is the fertilized cell. It now has half the genes from
the mother and half the genes from the father. And then that fertilized
cell grows through several stages, and they have skipped the morula
stage here and they go right to the blastula and then to the gastrula.
And here you start the differentiation into the three germ layers.
Every tissue of our body develops from one of the three germ layers:
the endoderm, that is what is inside; and the mesoderm, that is what is
in the middle; and the ectoderm. Very interestingly, the parts of the
adult body that develop from ectoderm is our skin and our nervous
tissue. Most of this, by weight, develops from mesoderm. All the
muscles, all the bones develop from mesoderm. And here you see at the
bottom are derivatives of the ectoderm and the mesoderm and the
endoderm, and then the unique cells, the germ cells, the sperm in the
male and the egg in the female.
Now, adult stem cells, when you hear people talk about adult stem
cells, what they are talking about is a cell down here, and one of the
easiest ones to talk about are adult stem cells that have to do with
making blood, and these stem cells found in the bone marrow primarily
can produce a variety of cells. The polymorpho-nuclear leukocytes, the
erythrocytes, the thrombocytes, all of those can be produced.
Now, you can take an adult stem cell and trick it into believing that
it has not gone through all of this differentiation, that it is
somewhere back here so that it can now make tissues other than just the
ones that it was destined to make and the organ from which you took it.
And these are the techniques that are used in adult stem cell research
and treatment.
The next chart shows a little more detail in this development
process, and this shows it in the reproductive tract of the female.
Here is the ovary from which the egg is released. And the egg now
starts a long journey down through the fallopian tube. It will be 7 to
10 days before it finally implants in the uterus. The sperm, of course,
makes its way from the vagina up through the uterus and through the
fallopian tube, and it fertilizes the egg. It shows it very correctly
here. Fertilization occurs well up in the fallopian tube. A little
later down and it cannot be fertilized.
And this shows the production of the zygote. It shows the first
cleavage to produce a two-cell mass. At this point these two cells
could separate to produce two embryos, two babies. We know them as
identical twins. Or it can go on to split into four cells and eight
cells, and I will come back to the eight cell in just a moment because
that is the one medically that is of considerable interest.
Then it becomes a morula. You see it there, the compacted morula. And
then you get the inner-cell mass, which you saw a pretty good picture
of in the previous slide. And, of course, what we are talking about is
what goes on in the laboratory now in a petri dish. You fertilize it
there rather than in the reproductive tract, but the same sequence of
development occurs. And they simply take the inner-cell mass out of the
embryo and squash it and kill it and take the cells out to produce a
stem cell line.
In the laboratory, in in vitro fertilization, they grow the embryos
up to the eight-cell stage, and it is at that stage that they have the
most luck in implanting them in the uterus of the female. Several years
ago in England, a clinic there began taking a cell, and sometimes they
got two, from the eight-cell stage, and they did a preimplantation
genetic diagnosis on it because if you had the option of making sure
that your baby was not going to have a genetic defect like trisomy 21,
mongolism, for instance, you certainly would want to avoid that if you
could.
They do a preimplantation genetic diagnosis, and if there is no
genetic defect, they then take the remaining six or seven cells and
implant them, and now worldwide I suspect there have been more than
2,000 babies born.
There is a clinic just outside Washington, in Virginia, and a year
ago I spent more than a half hour talking
[[Page H429]]
with two of the physicians there who have been doing this technique. So
we now are producing babies with this technique, with the assurance
that there will not be any genetic defects.
Another really good use of that cell that you take from that, and I
have to credit Mr. Dorflinger with this, the spokesman for the
Conference of Catholic Bishops, and he suggested that the most ethical
reason for taking a cell from the early embryo, even more ethically
defensible than doing a preimplantation genetic diagnosis, would be
making a repair kit. That is sort of the goal when you freeze the cord
blood, and we had a bill that everybody but one voted for that gave
Federal dollars for freezing cord blood.
Those will not be embryonic stem cells. They will be adult stem
cells, but at least they are closer to the genetic identity of that
person than other cells would be. And more than 2,000 times worldwide
now we have had a perfectly normal baby from that process.
So what I had proposed to the people has, in fact, been done. And
what I envision at the end of the day in our bill, H.R. 3144, does not
support experimentation in humans. It is only animal experimentations
to verify that these procedures are, in fact, doable and efficacious
and that the embryo is not harmed.
{time} 2115
This technique and three other techniques are included in the white
paper prepared by the President's council on bioethics, alternative
sources of human pluripotent stem cells.
Dr. Gingrey mentioned totipotent and pluripotent, and I would like to
spend a moment talking about that. Totipotent means that the cell you
take could produce another embryo. Pluripotent means that it could
produce all the cells, tissues, organs of the body; but it does not
have the capability to organize them into a person. Ethically, if you
took a cell that was totipotent, you would simply be creating a new
embryo, and so the argument starts all over again. So you need to take
a cell from a stage where it is just pluripotent, not totipotent.
I am assured by the research community that no one has ever been
successful in developing an embryo with a cell taken from the eighth
stage. You see, these cells know, and I use that term advisedly, know
that ultimately they are going to differentiate, and apparently that
differentiation problem has started well before you see the three germ
layers developing, because between the fourth stage and the eight-cell
stage, they have lost their ability to be totipotent. They can now only
be pluripotent. As Dr. Gingrey pointed out, it is very essential that
ethically you take cells that could only be pluripotent.
I have two quick slides here that look at the development of twins.
This is the two intercell masses. These are when the twins develop, the
identical twins develop later, when it splits later. You can see that
because they each have their own amnion. They share a chorion, of
course, but they each have their own amnion.
Let me see the next one, which shows how you have what are called
fraternal twins. Here you have two eggs produced by the mother,
ordinarily only one, sometimes two, sometimes three, but ordinarily
only one egg, unless you are giving some hormone treatment. Then those
are now presented in separate chorions. They, of course, have their own
amnion, which is the tissues around the baby which contains the fluid
in which the baby floats, and the tissue around that is called the
amnion.
There are four techniques in the white paper. I would like to look at
the technique that I have been looking about. Number two in the white
paper.
They credit me with suggesting that. There is a little footnote: ``A
similar idea was proposed by Representative Roscoe Bartlett of Maryland
as far back as 2001,'' and I think I actually talked to the President
before that. They say it may be some time before stem cell lines can be
reliably derived from single cells. We have two investigators, Landry
and Verlinsky, who claim that they have done that.
You see, these cells love company, and they don't behave well if they
are alone and they don't have company, so that is why there was the
concern that maybe you could not develop an embryonic stem cell line
from a single cell. But these two investigators have done it in a very
clever way. They provide company for the cells, and then they separate
the company, these are other types of cells, they separate the
embryonic cells from the other cells that provided company for them to
encourage them to continue the division process.
A second technique, as a matter of fact it was number one, mine was
number two, the first technique that they talked about is a really
interesting one. What this does is to propose the use of cells from an
embryo much like we use organs from a cadaver. Everybody is familiar
with that, and there are many people that have a will that say you can
harvest their organs to benefit somebody if that would be useful.
When you create these embryos in the laboratory, not all of them are
robust. A fair percentage of them never make it. They divide through a
few stages for a few days and then just die. This proposal is if you
determine that the embryo is moribund, and there is pretty good
scientific evidence that you can do that with quite some certainty,
kind of equivalent to determining a person is brain dead and therefore
there is no chance that they can go on with life as we know it, and his
proposal is that if you determine that the embryo is not going to make
it, that it will die, but before it dies, you then take a cell or cells
from the embryo to create an embryonic stem cell line. This is very
equivalent to taking organs from a cadaver.
There may be some question as to whether you can get a really good
strong cell from an embryo that is in a day or two going to be dead,
but it is possible that you could do that. My bill actually asks for
Federal dollars to explore all of these techniques with animal models.
I was talking to one of the researchers, Dr. Hurlbut, the other day.
This is Dr. Landry's proposal. I noted that I would be enormously
surprised if what we found in the great apes was not going to be what
we found in humans, and he agreed that he too would be enormously
surprised.
It may be somewhat humbling, but we share a vast majority of our
organs with the great apes, the chimpanzees and orangutans and
gorillas. You have to look to see genetic differences. They have the
same number of chromosomes, and we share many, many, most, 90-odd
percent of all the chromosomes. So it would be very unlikely that what
we found in animals would not occur in humans.
We have a couple more charts that address this. There has been a lot
of thought given to this, and I think that we have one; let's look at
the one that actually shows the depiction, yes, that one. Let us look
at that one.
That shows what happens in these cells, these embryos, in just a
couple of days. They go from a perfectly normal looking embryo to a
dead embryo, but there are clues that that is a certain result that the
experts can see in these cells.
So this is a potentially viable, I believe ethically acceptable
technique, very analogous to taking organs from a cadaver. This is
simply taking cells from what would be the equivalent in an embryo of a
cadaver, an embryo that will not live, that will die.
There is another technique, and I would like to submit two papers
here for the Record, and these are papers describing another technique,
a very interesting one. This is Dr. Hurlbut's contribution.
Researchers can take an oocyte, that is the egg from a mother, and
they can take the nucleus out of that oocyte and place a nucleus from
an ordinary cell, like a skin cell, inside the cell, and then with a
little shock treatment you can trick the cell into believing that it
was fertilized, and it will go on to develop into an individual. That
is how we got Dolly the Sheep. It is called cloning.
Dr. Hurlbut's suggestion is, and this is called epigenetic nuclear
transfer, that he alters that. The nucleus that you place in the cell
has an induced genetic defect. They alter one of the genes so that the
result cannot produce an embryo.
There are things that happen in some mothers where you have growths
and they will have teeth and hair, but it certainly is not a baby. It
is not coordinated. You can turn off this gene so
[[Page H430]]
that what you have produced is not an embryo, could not be a baby.
It is very interesting that the way you turn that off is by RNA,
ribonucleic acid, rather than deoxy ribonucleic acid, which is what is
in the nucleus and what makes up the genes and chromosomes. The RNA is
out in the cytoplasm, and I am not so sure that a clone is going to be
that identical to the original because the RNA, the cytoplasmic RNA, is
going to be different; and the cytoplasmic RNA has a big influence
because it can turn on and turn off genes. This is the technique used
for doing this.
This, I think, is from Nature Magazine, one of the premier scientific
journals. It is the British equivalent to our Science Magazine. It is
really multi-disciplinary and very discriminating in the articles that
it prints.
The bottom sequence here shows what he would do. He is producing
something that cannot be a baby because the gene that is responsible
for the organization of these various types of cells into a coherent
human being is turned off. By the way, whether he turns that off in the
cymatic nucleus before he puts it in the cell so you avoid the argument
that you are altering an embryo, because it is not an embryo, it is
just a nucleus from a skin cell and he turns off the gene there, and
then he takes the cell out of an oocyte and places this nucleus from
the skin cell with the genetic alteration, places it in there. This is
also a potentially viable technique.
All of these, by the way, you can argue that you may have some
ethical problem with it. You may argue that you are intentionally
creating a freak here just so you can harvest the cells from it. But
since you are doing this before you place the nucleus in the oocyte,
you are simply altering the nucleus in a skin cell, I think you can get
by the ethical arguments.
Let us go back for a moment to the ethical arguments, because they
are very important. I want to make sure that sensitivities of nobody in
the pro-life community are violated.
The technique that I suggested to the President and the one that is
described in our bill, we would not get the stem cells until several
things had happened over which we have no control and no influence. The
first thing is that a couple has decided that they are going to do in
vitro fertilization. In addition, they have decided that they want to
create a repair kit for their baby. They may or may not decide that
they want to do a pre-implantation genetic diagnosis.
By the way, you can do both of those in the same cell. You simply
culture the cell and you have now more than one, ultimately many, so
you can take a cell for pre-implantation genetic diagnosis. They will
have made the decision they want a repair kit. All we are asking for is
a few surplus cells, one will do, a few would be better, a few surplus
cells from their repair kit.
What this would do is provide for that baby, then a child, then an
adult, throughout its life the potential that if it had diabetes, you
could develop other Langerhans cells from its repair kit that are
genetically absolutely identical to the person so there would now be no
threat of rejection. This would clearly, clearly be miracle medicine.
I think we have gotten by the ethical objections, because whether or
not you believe that parents ought to use in vitro fertilization, these
parents have decided to do that. Whether or not you believe they should
take a cell to produce a repair kit, these parents have decided to do
that. So they have already made those two decisions, both of which I
think are ethical.
{time} 2130
Parents really want a child when they will go to the extent of in
vitro fertilization. As I mentioned, my daughter-in-law is going
through that. And after the surgery for harvesting of the cells, she
cannot even drive a car for quite a while. This is not a casual
procedure.
So these are loving parents who want a child. And I think it would be
very rational that they would want that child to have a repair kit if
they could, and we are simply asking for a few surplus cells from the
repair kit.
I should mention the fourth procedure that is in this white paper,
and that is the dedifferentiation of the adult cells. This
dedifferentiation is a play on differentiation, and what happens is
that the single cell produced by the union of two gametes, called the
zygote, this cell now differentiates. It produces tissues that are
endoderm, from which the lining of your intestinal tract and lungs and
the lining of your blood vessels will come, the mesoderm and so forth.
So they have differentiated.
You can now potentially get the equivalent of an embryonic stem cell
if you can simply take one of these adult cells and trick it into
believing that it has not differentiated. What you will do is
dedifferentiate it.
I do not know how consistently you can do that, but that is why we
need to do the research. On occasion you can do that, and I do not know
how consistently you can do it. I do not know how viable the tissues
will be once you have done it, but that is the reason that you do
research.
I would just like to again mention that our bill, 3144, does not
provide any Federal funds for any work on humans. It is only animal
experimentation. And it would provide Federal money for working on all
of the techniques that the President's Council on Bioethics indicated
might be ethically acceptable under the right circumstances.
Of course, one of the things that is very much involved in whether it
is ethical or not is, does it do harm to the baby? And that is why the
animal experimentation first. We want to make sure that in fact these
techniques can occur. We want to make sure that there is no negative
effect on the embryo.
There should not be, Mr. Speaker, unless you think that identical
twins are somehow deficient, there should not be any medical effect,
because we have, over hundreds of years, tens of thousands of identical
twins, all of which appear to be perfectly normal human beings.
The potential for healing, medical applications in embryonic stem
cells is just incredibly great, which is why the big interest in this.
It is why the people at NIH would really like funding for this. It is
why the groups that will come to see us, the juvenile diabetic groups
that come to see us, will be advocating so strongly for research with
embryonic stem cells, because this really could be a big, big
breakthrough.
It could provide miracle cures that we can only dream of today. We
need to make very sure that we are not crossing ethical bounds, that we
are purely ethical.
Mr. Speaker, I am very concerned that none of my friends in the pro-
life community be offended by any of this research, which is why the
animal experimentation first, with a clear bioethical look at this.
I appreciate very much this opportunity to discuss this. Mr. Speaker,
I include for the Record the articles I referenced earlier.
Production of Pluripotent Stem Cells by Oocyte Assisted Reprogramming
As described in the President's Council on Bioethics'
recent White Paper, altered nuclear transfer (ANT) is a broad
conceptual proposal for producing pluripotent stem cells
without creating and destroying embryos. In the description
set forth below, we outline a research program for a form of
ANT that should allow us to produce pluripotent stem cells
without creating or destroying human embryos and without
producing an entity that undergoes or mimics embryonic
development. The method of alteration here proposed (oocyte
assisted reprogramming) would immediately produce a cell with
positive characteristics and a type of organization that from
the beginning would be clearly and unambiguously distinct
from, and incompatible with, those of an embryo. Incapable of
being or becoming an embryo, the cell produced would itself
be a pluripotent cell that could be cultured to establish a
pluripotent stem cell line. Significantly, this cell would
not be totipotent, as a zygote is.
Our proposal is for initial research using only nonhuman
animal cells. If, but only if, such research establishes
beyond a reasonable doubt that oocyte assisted reprogramming
can reliably be used to produce pluripotent stem cells
without creating embryos, would we support research on human
cells.
With few exceptions all human cells contain a complete
human genome, i.e. the complete DNA sequence characteristic
of the human species. Specifically, one-celled human embryos,
pluripotent human embryonic stem (or ES) cells, multipotent
human adult stem cells, and differentiated (specialized)
adult human cells such as neurons all contain a complete
human genome. Thus, possession of a human genome is a
necessary but not sufficient condition for defining a
[[Page H431]]
human embryo with its inherent dignity. Rather the nature of
each cell depends on its epigenetic state, i.e. which subset
of the approximately thirty thousand human genes is switched
on or off and, if on, at what level. For example, the gene
for albumin, a liver specific protein, is found both in human
embryos and in adult human liver cells called hepatocytes.
However, neither the messenger RNA (mRNA) for albumin nor the
protein itself is found in single-celled embryos because in
them the gene is silenced.
This fundamental observation has given rise to the concepts
of cell fate plasticity and epigenetic ``reprogramming.'' If
successful, reprogramming converts a cell from one kind to
another by changing its epigenetic state. The ability to
clone animals, such as Dolly the sheep, by transfer of a
specialized adult nucleus to an enucleated oocyte
demonstrates the power of epigenetic reprogramming: the
oocyte cytoplasm is sufficient to reprogram the somatic
nucleus to a totipotent state. Human cloning has been
proposed as a means of generating human embryos whose
pluripotent stem cells would be used in scientific and
medical research. Here, through a form of altered nuclear
transfer, we propose to utilize the power of epigenetic
reprogramming in combination with controlled alterations in
gene expression to directly produce pluripotent cells using
adult somatic nuclei, without generating and subsequently
destroying embryos.
How do pluripotent stem cells differ from totipotent
single-celled embryos? Several key transcription factors
essential for establishing and maintaining the pluripotent
behavior of ES cells have been identified. Importantly, some
of these are specifically expressed only in pluripotent
cells, such as embryonic stem cells or the cells found in the
inner-cell-mass (ICM) of the week-old embryo or blastocyst.
They are not expressed in oocytes or single-celled embryos.
Expression of these factors therefore positively defines and
distinguishes mere pluripotent cells from embryos. These
factors instruct a cell to have the identity of a pluripotent
cell. Currently, the best studied example is the homeodomain
transcription factor called nanog (Mitsui, Tokuzawa et al.
2003*). Nanog is not present in oocytes or single-celled
embryos, but first becomes expressed weakly in the morula
and then highly in the ICM (Mitsui, Tokuzawa et al. 2003;
Hatano, Tada et al. 2005). Deletion of nanog does not
prevent early cleavage stages of embryogenesis including
formation of the ICM but does prevent the formation of an
epiblast (Mitsui, Tokuzawa et al. 2003). ES cells in which
nanog is blocked lose their pluripotency--which clearly
shows that nanog is a positive factor instructing cells to
be pluripotent, i.e. to behave like an ES cell.
Furthermore, ES cells which constitutively express nanog
can no longer be differentiated, i.e. are forced to remain
in their undifferentiated state (Mitsui, Tokuzawa et al.
2003).
We propose a procedure that combines epigenetic
reprogramming of a somatic nucleus with forced expression of
transcription factors characteristic of embryonic stem cells,
to produce a pluripotent stem cell. As a result of this
procedure, nanog and/or other, similar factors, would be
expressed at high levels in somatic cells prior to nuclear
transfer, to bias the somatic nucleus towards a pluripotent
stem cell state. Such altered nuclei would then be
epigenetically reprogrammed by transplantation into
enucleated oocytes. Alternatively or concomitantly, the mRNA
for these same factors could be introduced into the oocyte
prior to nuclear transfer. This procedure could ensure that
the epigenetic state of the resulting single cell would
immediately be different from that of an embryo and like that
of a pluripotent stem cell: the somatic-cell nucleus would be
formed into a pluripotent stem-cell nucleus and never pass
through an embryonic stage. Therefore, unlike some other
proposed methods of ANT, this method would achieve its
objective not by a gene deletion that precludes embryonic
organization in the cell produced, but rather by a positive
transformation that generates, ab initio, a cell with the
distinctive molecular characteristics and developmental
behavior of a pluripotent cell, not a totipotent embryo. This
should allow us to produce a pluripotent stem cell line with
controlled genetic characteristics.
ENDORSERS
Institutional affiliations are provided for purposes of
identification only and do not necessarily represent the
views of organizations with which endorsers are affiliated.
Endorsers who are not themselves specialists in biomedical
science do not put themselves forward as experts in that
field. Their endorsement of the proposal pertains to the
ethics of ANT-OAR, assuming its technical feasibility.
Hadley Arkes, Ph.D., Edward N. Ney Professor of
Jurisprudence and American Institutions, Amherst College,
Amherst, Massachusetts.
Rev. Nicanor Pier Giorgio Austriaco, O.P., Ph.D., Assistant
Professor of Biology, Providence College, Providence, Rhode
Island.
Rev. Thomas Berg, L.C., Ph.D., Executive Director, The
Westchester Institute for Ethics and the Human Person,
Thornwood, New York.
E. Christian Brugger, D. Phil., Assistant Professor of
Theology, Institute for Psychological Sciences, Arlington,
Virginia.
Nigel M. de S. Cameron, Ph.D., President, Institute on
Biotechnology and the Human Future, Research Professor of
Bioethics, Chicago-Kent College of Law, Illinois Institute of
Technology, Chicago, Illinois.
Joseph Capizzi, Ph.D., Catholic University of America,
Fellow, Culture of Life Foundation, Washington, D.C.
Maureen L. Condic, Ph.D., Associate Professor of
Neurobiology, University of Utah, School of Medicine, Salt
Lake City, Utah.
Samuel B. Condic, M.A., Department of Social Sciences,
University of Houston--Downtown, Houston, Texas.
Rev. Kevin T. FitzGerald, S.J., Ph.D., Dr. David P. Lauler
Chair in Catholic Health Care Ethics, Center for Clinical
Bioethics Research, Associate Professor Department of
Oncology, Georgetown University Medical Center, Washington,
D.C.
Rev. Kevin Flannery, S.J., D.Phil., Dean of the Philosophy
Faculty, Pontifical Gregorian University, Rome, Italy.
Edward J. Furton, Ph.D., Ethicist, The National Catholic
Bioethics Center, Philadelphia, Pennsylvania.
Robert P. George, J.D., D.Phil., McCormick Professor of
Jurisprudence, Princeton University, Princeton, New Jersey.
Timothy George, Th.D., Dean, Beeson Divinity School,
Samford University, Birmingham, Alabama.
Alfonso Gomez-Lobo, Dr. phil., Ryan Professor of
Metaphysics and Moral Philosophy, Georgetown University,
Washington, D.C.
Germain Grisez, Ph.D., Flynn Professor of Christian Ethics,
Mount Saint Mary's University, Emmitsburg, Maryland.
Markus Grompe, M.D., Director, Oregon Stem Cell Center,
Portland, Oregon.
John M. Haas, Ph.D., President, The National Catholic
Bioethics Center, Philadelphia, Pennsylvania.
Robert Hamerton-Kelly, Th.D., Dean of the Chapel (Retired),
Stanford University, Palo Alto, California.
John Collins Harvey, M.D., Ph.D., Senior Research Scholar
and Professor Emeritus of Medicine, Center for Clinical
Bioethics, Georgetown University Medical Center, Washington,
D.C.
Paul J. Hoehner, M.D., M.A., FAHA, Harvey Fellow in
Theology, Ethics and Culture, The University of Virginia
Graduate School of Arts and Sciences, Associate Professor of
Anesthesiology, The University of Virginia Health Sciences
Center, Charlottesville, Virginia.
William B. Hurlbut, M.D., Consulting Professor in the
Program in Human Biology, Stanford University, Palo Alto,
California.
John F. Kilner, Ph.D., President, The Center for Bioethics
and Human Dignity, 2065 Half Day Road, Bannockburn, Illinois.
Patrick Lee, Ph.D., Professor of Philosophy, Franciscan
University of Steubenville, Steubenville, Ohio.
William E. May, Ph.D., Michael J. McGivney Professor of
Moral Theology, John Paul II Institute for Studies on
Marriage and Family at The Catholic University of America,
Washington, D.C.
Rev. Gonzalo Miranda, L.C., Ph.L., S.T.D., Dean of
Bioethics, Regina Apostolorum Pontifical Athenaeum, Rome,
Italy.
C. Ben Mitchell, Ph.D., Associate Professor of Bioethics &
Contemporary Culture, Trinity International University,
Bannockburn, Illinois.
Most Reverend John J. Myers, J.C.D., D.D., Roman Catholic
Archbishop of Newark, New Jersey.
Chris Oleson, Ph.D., Associate Professor of Philosophy,
Center for Higher Studies, Thornwood, New York.
Rev. Tad Pacholczyk, Ph.D., Director of Education, The
National Catholic Bioethics Center, Philadelphia,
Pennsylvania.
Rev. Peter F. Ryan, S.J., S.T.D., Associate Professor of
Moral Theology, Mount St. Mary's University, Emmitsburg,
Maryland.
William L. Saunders, J.D., Senior Fellow and Director, The
Center for Human Life & Bioethics, The Family Research
Council, Washington, DC.
David Stevens, M.D., M.A., Executive Director, Christian
Medical & Dental Associations, Bristol, Tennessee.
Rev. Msgr. Stuart W. Swetland, S.T.D., Director, The Newman
Foundation, Adjunct Associate Professor, University of
Illinois at Urbana-Champaign, Urbana, Illinois.
M. Edward Whelan III, J.D., President, Ethics and Public
Policy Center, Washington, DC.
Rev. Thomas Williams, L.C., Ph.L., S.T.D., Dean of
Theology, Regina Apostolorum Pontifical Athenaeum, Rome,
Italy.
____
Researchers Offer Proof-of-Concept for Altered Nuclear Transfer
Cambridge, MA, Oct. 17, 2005.--Scientists at Whitehead
Institute for Biomedical Research have successfully
demonstrated that a theoretical--and controversial--technique
for generating embryonic stem cells is indeed possible, at
least in mice.
The theory, called altered nuclear transfer (ANT), proposes
that researchers first create genetically altered embryos
that are unable to implant in a uterus, and then extract stem
cells from these embryos. Because the embryos cannot implant,
they are by definition not ``potential'' human lives. Some
suggest that this would quell the protests of critics who
claim that embryonic stem cell research necessitates the
destruction of human life. Scientists and ethicists have
debated the merits of this approach, but so far it has not
been achieved.
``The purpose of our study was to provide a scientific
basis for the ethical debate,'' says Whitehead Member Rudolf
Jaenisch, lead author on the paper that will be published in
the October 16 online edition of the journal
[[Page H432]]
Nature. ``Our work is the first proof-of-principle study to
show that altered nuclear transfer not only works but is
extremely efficient.''
First proposed by William Hurlbut, Stanford University
professor and member of the President's Council on Bioethics,
ANT has been described as an ethical alternative to somatic
cell nuclear transfer (SCNT), also known as therapeutic
cloning.
For SCNT, a donor nucleus, for example one taken from a
skin cell, is implanted into a donor egg cell from which the
nucleus had been removed. This egg cell is then tricked into
thinking it has been fertilized. That causes it to grow into
a blastocyst--a mass of about 100 cells--from which stem
cells are removed. These embryonic stem cells can divide and
replicate themselves indefinitely, and they can also form any
type of tissue in the human body. However, to cull these stem
cells, the blastocyst must be destroyed, which some critics
insist is tantamount to destroying a human life.
The procedure theorized by Hurlbut is similar to SCNT, but
with one crucial twist: Before the donor nucleus is
transferred into the egg cell, its DNA is altered so that the
resulting blastocyst has no chance of ever becoming a viable
embryo. As a result, a ``potential human being'' is not
destroyed once stem cells have been extracted.
Jaenisch--a firm supporter of all forms of human embryonic
stem cell research--has shown that technical concerns about
this approach can be overcome.
Jaenisch and Alexander Meissner, a graduate student in his
lab, focused on a gene called Cdx2, which enables an embryo
to grow a placenta. In order to create a blastocyst that
cannot implant in a uterus, the researchers disabled Cdx2 in
mouse cells.
They accomplished this with a technique called RNA
interference, or RNAi. Here, short interfering RNA (siRNA)
molecules are designed to target an individual gene and
disrupt its ability to produce protein. In effect, the gene
is shut off. Jaenisch and Meissner designed a particular form
of siRNA that shut off this gene in the donor nucleus and
then incorporated itself into all the cells comprising the
blastocyst. As a result, all of the resulting mouse
blastocysts were incapable of implantation.
However, once the stem cells had been extracted from the
blastocysts, Cdx2 was still disabled in each of these new
cells, something that needed to be repaired in order for
these cells to be useful. To correct this, Meissner deleted
the siRNA molecule by transferring a plasmid into each cell.
(A plasmid is a unit of DNA that can replicate in a cell
apart from the nucleus. Plasmids are usually found in
bacteria, and they are a staple for recombinant DNA
techniques.) The stem cells resulting from this procedure
proved to be just as robust and versatile as stem cells
procured in the more traditional fashion.
``The success of this procedure in no way precludes the
need to pursue all forms of human embryonic stem cell
research,'' says Jaenisch, who is also a professor of biology
at MIT. ``Human embryonic stem cells are extraordinarily
complicated. If we are ever to realize their therapeutic
potential, we must use all known tools and techniques in
order to explore the mechanisms that give these cells such
startling characteristics. ``
ANT, Jaenisch emphasizes, is a modification, but not an
alternative, to nuclear transfer, since the approach requires
additional manipulations of the donor cells. He hopes that
this modification may help resolve some of the issues
surrounding work with embryonic stem cells and allow federal
funding.
This research was supported by the National Institutes of
Health/National Cancer Institute.
____________________