Stem Cell Research
Madam Speaker, there have been a number of articles in the recent press relative to stem cell research, with particular reference to embryonic stem cell research. I thought it might be well in starting this little discussion to take a look…
Madam Speaker, there have been a number of articles in the recent press relative to stem cell research, with particular reference to embryonic stem cell research. I thought it might be well in starting this little discussion to take a look at what we mean by stem cells.
I have here a chart which shows in very abbreviated form the development of an early embryo. It starts out with the zygote, which is the fertilized egg; and then it skips a couple of stages of development, and it goes through the blastocyst, and then it goes to the gastrula. By the time the embryo gets to the gastrula stage, the cells have already differentiated to the place that we have three different kinds of somatic stem cells. This is the ectoderm, and the mesoderm, and the endoderm, and then those very specialized cells, which in the female will be the germ cells in the ovary, the ova, and in the male will be the millions and millions of sperm that are in the gonads of the male.
If we look back, Madam Speaker, at these stem cells that are present here in the gastrula, where we have these three, as we call germ layers, we see the ectoderm can further differentiate into skin and nervous system and some of the pigment cells in our body; and then the mesoderm, the middle layer, that differentiates into what is most of us by mass and weight, cardiac muscle, our big skeletal muscles, the bone, the smooth muscle, all of our blood, and the blood is an organ, it happens to be a liquid organ that is dispersed through the body; and then the endoderm. This is much more limited in volume and in variety, but still very important. The pancreatic cells, the thyroid cells, the lining of the gut, the lining of the lung and so forth.
It might be worth just a moment, Madam Speaker, to take a look at our next chart, which kind of puts this in context. We started out with the zygote, which is the fertilized egg here, and we ended up with the inner cell mass with these three germ layers. What we show here are all the stages that were omitted in that first chart. This is one-half, as the little diagram here in the upper left shows, of the reproductive tract of a female. It shows the ovary on one side and the fallopian tube, with the funnel-like opening here called the infundibulum. Then it shows the fallopian tube on down to the uterus itself.
What it shows, Madam Speaker, is that fertilization takes place well up in the fallopian tube, and that begins day one. And then as the egg slowly moves down the tube, it splits first into two cells, then four cells, and then eight cells, and then the larger variety of cells, and finally where you have the inner cell mass and then to the gastrula.
There are two kinds of stem cells, adult stem cells, and those are derivatives of the cells that we showed in the previous chart. For instance, in the humans we have adult stem cells in our bone marrow. These are cells which are differentiated to the point that they will produce a limited variety of cells, but still undifferentiated to an extent because these stem cells in the bone marrow can produce red blood cells and polymorphonuclear leukocytes, part of the white blood cells, and the thrombocytes, those are the cells, the platelets as we call them, that are associated with clotting. And there are a number of adult stem cells similar to that that still retain some of the capability for producing more than just one kind of cell.
We have been working with adult stem cells medically now for more than 3 decades, and there have been a number of medical applications, treatment of humans that have been made with adult stem cells. But just because they are what they are, Madam Speaker, a great number of people believe that there should be more potential from the embryonic stem cells simply because they can produce any and all of the tissues of the body.
Since we have been working with embryonic stem cells for now just a little over 6 years, we have not had the opportunities for medical applications we have had in adult stem cells, but this does not dim the hopes of the scientific community and the medical community that ultimately there may be more and better applications of embryonic stem cells to treatment of diseases than adult stem cells, simply because of what they are, puripotent cells retaining the ability to produce any and all of the tissues of the body.
It is possible, Madam Speaker, that this characteristic, which makes them so potentially attractive and exciting, may be uncontrollable. They may be so bent on dividing that we cannot control their division. They may end up producing tumors and cancer-like growths in the organism in which you put them.
But if that can be controlled, the medical community and the researchers associated with it believe there is potential for enormous applications to medicine of embryonic stem cell research. We have now had 58 applications of adult stem cells in helping to treat some of the diseases.
What are the diseases that could be treated with stem cells? Ordinarily, one thinks that the greatest potential for the use of stem cells would result from use in diseases from tissue deficiency rather than diseases that result from some organism, although if there is an infection in the body and a tissue is damaged, there is the hope that it might be replaced with stem cell application. There are a number of diseases that the scientific community and the general public believe might be amenable to treatment with stem cells, particularly embryonic stem cells.
Diabetes is one of those. This is the most costly disease in our country. It costs more to treat the diabetics in our country than any other single disease. I have these come through my office. Particularly heartrending are the little children that come there, 5 and 6 years old some of them, such brittle juvenile diabetics that they have an implanted pump and they have to prick their finger or some part of their body a number of times a day to monitor the glucose level so that just the right amount of insulin can be injected to control this.
This insulin is produced by cells called island of Langerhan cells. Dr. Langerhan was the German scientist that described them. And they look like little eyelets because they are simply distributed through the tissue of the pancreas. The pancreas is a very large gland at the very beginning of the small intestine that secretes all of the different kinds of digestive enzymes so that fats, carbohydrates, and proteins all are digested using the enzymes secreted by the pancreas.
I have no idea why nature placed the islets of Langerhans in the pancreas. They could be placed anywhere. With these stem cell applications if we could create islet tissue, they could be placed in the person. It could be placed in the groin, under their arm, under the skin, anywhere. It does not have to be in the pancreas. This islet tissue could then make insulin which would cure diabetes. When you give insulin to the diabetic, it delays progression of the disease, but it does not cure it. A person with juvenile diabetes faces the prospect that they probably will have a shortened life, problems with their vision as the vascular bed in the back of the eye breaks down, and they may
have problems with circulation in their extremities, particularly in the feet where there is some difficulty getting blood back uphill to the heart.
As many people in this country know through relatives and friends, this results frequently in sores that do not heal and results in gangrene, so the toes or a foot may need to be taken off. Diabetes is one of the diseases that is very attractive as a potential for use of stem cells, because if we could just produce islet tissue, we could cure diabetes, the most expensive disease that we have.
Another disease is multiple sclerosis, and if impaired cells could be replaced through stem cell therapy, then the person could walk again.
Lou Gehrig's disease, I remember my grandmother was tripping and falling, and they did not know why. It took them quite awhile back, this was a number of years ago, to determine she had Lou Gehrig's disease. I remember as a teenager going to her bedside. She was maintained in the home. She slowly deteriorated, losing first one muscle function and then another. Finally, at the end, the only muscle function she had remaining was the ability to blink her eyes. It was once for yes and two for no, as I remember. She could not swallow and had indicated she did not want to be force fed and ultimately she died from starvation with this disease.
Well, anybody who has a friend or a relative that has gone through that kind of experience has to be enthusiastic about the potential for stem cell therapy. This was a number of years ago, but if it were tomorrow or the day after tomorrow figuratively, maybe there could be stem cell therapy for my grandmother, and she would not have to have died at the relatively young age she died at.
Alzheimer's disease is another one. President Reagan died from Alzheimer's disease. Victims do not even recognize their favorite loved ones, have no memory and may wander outside and wander off.
There is a whole category of autoimmune diseases. I have a paper which lists 63 of the autoimmune diseases. By that, I mean a disease where the body gets confused as to what is the body and what is not the body.
When we are developing as embryos in our mother's womb, there are certain cells in our circulatory system called T-cells located in the lymphatic tissue, and the T-cells are imprinted with who we are because once we get out of the mother's womb, we are going to be in a hostile environment, exposed to bacteria and viruses, and so it is important that the body knows what it is so the defense mechanisms in the body can be marshaled to eject the intruder.
These T-cells identify what is you and what is not you, and they alert some of the specialized cells in our white blood cell system so they are attracted to the site, and they eject, they may consume, they eject the intruder.
There are 63 distinct autoimmune diseases. For some reason, the body gets confused and the autoimmune system gets confused and starts attacking your joints, for instance. We know that disease as arthritis.
I remember my first real introduction to this big list of autoimmune diseases was a secretary I had, a very vibrant young lady whose life was really, really changed because she had lupus. There are many Americans who have family or friends who have lupus, and lupus was one of the first autoimmune diseases that was discovered.
There is a controversy going on over the potential for embryonic stem cell medical applications and adult stem cell medical applications. We have been working for more than 3 decades with adult stem cells, and our very able medical scientific community has been able to develop a number of applications that can cure or at least lessen the severity of disease using adult stem cells.
Since we have been working with embryonic stem cells for only a brief period of time, we do not have any direct applications to medicine of embryonic stem cell therapy, but that does not dim the enthusiasm of the medical community because they believe that the potential there ought to be greater.
But the real problem here is that up until this time the only way that we can get embryonic stem cells is to destroy the embryo. The scientists go into the inner cell mass stage. That is this stage here, day five. Of course, what we are doing now in the laboratory is not done in the uterus. All of this is done in a petri dish. The in vitro is in glass. In vivo means life. The embryo is destroyed at the inner cell mass stage, and cells are taken to produce a stem cell line.
About 4 years ago, this produced a real dilemma for the President who, like all of us, has family and friends who have one or more of these diseases that could be potentially ameliorated or cured by embryonic stem cell application. Yet the President knew the only way we were presently getting embryonic stem cell lines was by destroying embryos. He, as I am, is a strong pro-life advocate and the President had a problem with taking one life because that embryo produced in the laboratory in surplus and in vitro fertilization had the potential when implanted in a receptive mother to become a baby and the President's problem was that he had a moral problem with taking one life with the hope of helping another.
While the President was wrestling with this problem and what to do about it, there was a briefing at the National Institutes of Health for Members of the Congress and for their staff. I went out there to that briefing.
As the next chart shows, when we were talking about the potential for embryonic stem cell lines, I remembered my training of more than 50 years ago when I got my doctorate at the University of Maryland and had a course in advanced embryology and then went on to teach medical school for 4 years and postgraduate medicine doing basic research at the National Institutes of Health. I remembered what everybody knows, because they had the course in advanced embryology it was in my mind, that whenever we have identical twins what has really happened is that half of the cells have been taken from the early embryo. The half that is taken becomes a perfectly normal baby, and the half that is left becomes a perfectly normal baby.
Madam Speaker, one is a clone. When one thinks about cloning, remember that Mother Nature or God, to whomever you want to subscribe it, has been cloning for a very long time. Now these early embryos can split either at the two-cell stage or at the inner cell mass stage or anywhere in between, presumably.
We know at least at those two extremes because we can tell by how they present at birth when they split. If they share an amnion, they split at the two cell stage. If they have separate amnions, they probably split at the inner cell mass stage.
So knowing that half of the cells could be taken away from an early embryo without harming the embryo, unless you think identical twins are somehow deficient, and I have talked with a number of identical twins, and I have not talked with any of them who thought they were less a person or deficient because half of the cells were taken away to produce the other identical twin.
It occurred to me that you ought to be able to take cells from an early embryo without hurting the embryo to develop a stem cell line from that early embryo. I mentioned this to the researchers at NIH, and they said, yes, that is theoretically possible to do that.
Just after that, I was at an event and the President was there and when I went through the line, I mentioned my visit at NIH and the response that they had given to my question. A few days later, I had a call from Carl Rove and the President had turned the pursuit of this suggestion over to Carl Rove. Carl told me that he talked to the people at NIH, and they tell me what you have suggested is not possible.
Carl, I said either they are funning you or they misunderstand you, because these are the same people that can take a single cell and take the nucleus out of that cell and put another nucleus in it. That is what they did with Dolly the sheep and the large number of clones that have been produced since then.
I said, of course, if they can take the nucleus out of a cell and put another nucleus in it, they can certainly take a cell or two out of what is a relatively big embryo. So he went back and asked them again and then called back and said they are still telling me they cannot do that. So a few days later, the President came out with his executive order.
Madam Speaker, you may remember this was kind of a decision like Solomon might have made. Obviously, from the potential efficacy of embryonic stem cell research and medical applications, it is very desirable that we do that.
On the other hand, if the only way to get embryonic stem cells is by destroying an embryo, then you are left with the quandary of, is it really acceptable to destroy one life with the hope that you are going to help another?
So the President came to a decision that I think represented great wisdom. He recognized that a number of embryos had already been killed, destroyed to establish stem cell lines, and since you cannot turn back the hands of time to change that, these embryos were gone, the stem cell lines were there, and so the President, recognizing the potential for embryonic stem cell research, and being concerned that you should not take one life with the hope of helping another, wisely I think, said we could spend Federal dollars on any exploration we chose with the existing stem cells lines, and he thought there were about 60. There have never been 60, but he was told there were something like 60 stem cell lines, and Federal dollars could be used for research on those lines, but no Federal dollars could be used for developing or destroying any additional embryos for stem cell lines.
This was about 4 years ago, and as we knew, the scientific community knew, as I knew because of my background, these stem cell lines would eventually run out. Stem cell lines, like people, age. For reasons that we may not understand, they do not last forever. Those stem cell lines, Madam Speaker, are running out. We now have, I think the accepted figure is 22 stem cell lines left, and all of these are contaminated with mouse feeder cells. This is the result of a technique which is used to facilitate the replication of these cells in the tissue culture, and they are now all contaminated with mouse feeder cells so that although they are perfectly good for research and a lot of research is being done, they are not good for medical application because you would not want to put the cells contaminated with mouse feeder cells in a human.
So what now? One of the potential solutions to this problem is included in H.R. 810, the Castle-DeGette bill; and the argument made in this bill is that there are about 400,000 surplus embryos out there from in vitro fertilization. You see, to make sure that the doctor is going to have a good embryo or two or three to implant in a mother, because they do not all take, he will produce more embryos than he will probably need. Then he will look at them under the microscope and pick the strongest looking of those embryos and may put two or three or so in the mother.
One of our Members, the Rohrabachers, are now the proud parents of triplets from in vitro fertilization. All of them grew and so they are now the proud parents of these very happy and healthy little babies. Since there are 400,000 surplus embryos out there that are frozen, the argument is, and this is the argument of the bill, that since these embryos, at least many of these embryos, realistically most of these embryos will ultimately be discarded, they will not stay frozen for 49 years there, they will not last forever, and by and by they will be discarded, and so the argument is, why should medicine not benefit from cells, from embryos that are going to be discarded anyhow? That to many people is a compelling argument. It was a compelling argument to a majority of people in the House, and now they are considering this bill in the Senate.
But to those in the pro-life community, there is another way of looking at these embryos. I am at the microscope and there is an embryo under the microscope there. That embryo could become a snowflake baby. More than 100 times parents who do not have an ovum, cannot get pregnant any other way, have adopted these surplus embryos and we have more than 100 of what we call snowflake babies. The embryo that I am looking at under the microscope might be adopted and that could be any one of the 400,000 embryos, and it might be the next Albert Einstein. How could I destroy an embryo that might be adopted and might be the next Albert Einstein? So this is the argument on the other side, which is why the great debate over H.R. 810.
As a result of a series of discussions with the White House and with a number of the interested groups, we have developed a bill which is called H.R. 3144, the Respect for Life Pluripotent Stem Cell Act of 2005.
Madam Speaker, I will make this short bill a part of the Record.
Madam Speaker, the gentleman from Georgia (Mr. Gingrey) has joined us. I would like to yield to him before I go through the history of how we got to this bill and the people we talked to
and exactly what is in the bill. I thank the gentleman for joining us.
Madam Speaker, reclaiming my time, I want to thank my colleague very much for his comments. He is very generous. I did not come to the Congress, and that was 13 years ago, until I was 66 years old; and I am very fortunate to have some prior life experiences that have permitted me to understand some opportunities here in the Congress that might not have been so obvious to others who did not have this background.
After the President came down with his executive order, I continued to meet with the folks at NIH, and I subsequently learned, by the way, I need to come back to that problem with Karl Rove and his discussion with the NIH people, and this was a typical example of failed communications. And so often we think that we are carrying on a dialogue and we are really carrying on simultaneous monologues.
However it happened, what the NIH people were telling Karl Rove was that they were not sure that they could make a stem cell line from an embryo that early. That is true. That is why in our bill we advocate animal model research rather than beginning with humans. But there is no reason we should not be able to do that.
Now, as a matter of fact, a Russian scientist working in this country, Verlinsky, says he has, in fact, done that. I have met a number of times with people from NIH. On July 20 of last year, for instance, we had an extended meeting in my office with representatives from NIH, with representatives from Health and Human Services, and with representatives from the White House.
And then, Madam Speaker, a very interesting thing happened while we were having this series of meetings with the NIH and HHS and the White House and with the outside groups. There appeared in the literature a paper, a very interesting paper, on preimplantation genetic diagnosis. And what these medical people were doing, and this was in England, the first paper came from a clinic in England, what they were doing was going into the eight-cell stage and taking a cell or two out to do a preimplantation genetic diagnosis to see if the baby would have a genetic defect. And if there was no genetic defect, they implanted the remaining seven cells, sometimes six cells. And more than 600 times that went on to produce a perfectly normal baby. That is now being done in this country just outside Washington, in Virginia. A few weeks ago I spent probably a half hour or more on the phone with two of the medical scientists there who were involved in this research.
There is one potential ethical problem here, although the President's Council on Bioethics thinks it is not a problem. I would like to avoid, Madam Speaker, even the possibility of a problem. And that problem is that the cell that we take from that embryo might, under the right circumstances, become an embryo itself. The members of the President's, and I have the white paper here I am going to refer to in just a moment, Council on Bioethics think that that is not feasible. But, Madam Speaker, if we were to wait just a little later to take the cell to the inner cell mass, and I probably ought to put that chart of the uterus back up here so that I can point to what I am referring to here, in the laboratory they are going at the eight-cell stage and taking a cell or two out and doing a preimplantation genetic diagnosis.
If there is no genetic defect, they implant the remaining cells, and more than 1,000 times worldwide now, they have had a normal baby born. The argument is that that cell they take out under the right circumstances is pluripotent, totipotent at that stage probably, and could produce another embryo. To avoid that, if we just wait until the inner cell mass stage, which is the stage from which the embryonic stem cell lines are now developed when they destroy the embryo, there is no reason they cannot go into this inner cell mass and through the trophoblast and they could take out several cells then because there are a lot of cells there.
By that time we already have some differentiation. The cells in the inner cell mass are going to produce the baby. The three germ layers that we talked about at the very beginning and the cells in the trophoblast are going to produce the decidua. The decidua is the amnion and chorion, the tissues that support the baby, and we can see those starting to develop down here in day 8 and 9 when the embryo has attached itself to the wall of the uterus and the uterus grows and produces some tissues and there is a growth of this decidua here and we have the placenta, these big opposing vascular bags through which food and oxygen and CO2 and hormones and so forth are exchanged between the baby and the mother.
By the way, Madam Speaker, this is a pretty hazardous journey; and we do not know the exact percentage, but maybe less than half of all of the ova here that get fertilized actually implant in the uterus. As a matter of fact, one of the techniques for preventing conception is an IUD. They simply place a foreign object here in the uterus, and the uterus reacts to the presence of that foreign by not permitting the fertilized egg, the embryo, to implant there.
I yield to the gentleman from Georgia.
Madam Speaker, reclaiming my time, I thank the gentleman very much for that contribution.
While we are carrying on these discussions with the White House and NIH and HHS and with the outside groups, the President's Council on Bioethics submits a white paper; and in this white paper they go over four potential techniques that might produce pluripotent stem cells, which is another way of saying the equivalent of embryonic stem cells, without destroying or harming an embryo. And what our bill does, Madam Speaker, is simply ask NIH to please explore these potentials, first of all, in animal models; and the bill gives them $15 million to begin this exploration.
I just wanted to spend just a moment talking about the four things that are in here because it may be of interest to a number of people. The first is called pluripotent stem cells derived from organismically dead embryos. Well, this says that all these embryos I had mentioned earlier, all these embryos will not live. And when an embryo is moribund, it is not going to divide anymore, then it is the equivalent of a brain dead person and there should be no problem taking cells from it like they would take organs from a brain dead person.
One might have a little question about the vitality of the cell they take from that embryo, but at least ethically if the embryo is dead or moribund, the equivalent of a brain dead person, they could take an embryo from it. The second procedure, and the next chart shows a little clip from that, is one in which, down at the bottom here, it says ``a similar idea was proposed by Representative Roscoe Bartlett.'' This was my recommendation in 2001. And this simply says they go into an early embryo, as I have mentioned, and take out a cell without hurting the embryo because mother nature or God, whoever people think makes identical twins, has been doing this for a very long time.
Our bill simply asks the NIH to do this in animal models to make sure that it is safe and efficacious.
A third technique is called pluripotent stem cells derived from biological artifacts. This is an interesting one. And what the proposal there is that they take an ovum and they take the nucleus out of the ovum and then they take an altered nucleus out of a somatic cell.
You alter the nucleus so that you have turned off some of the genes, and then you put that nucleus inside the egg. Now, why would you do that? Because in the cytoplasm of the egg outside the nucleus of the egg, there are some factors which turn on and turn off genes and kind of control what happens inside the nucleus. So now they have turned off some genes so this thing will divide; that will never be a baby because they have kind of messed up the genetics. Well, if they can never be a baby, then maybe ethically you can take stem cells from it, and this is something that really needs to be explored.
These several techniques are all open for investigation. Oh, the fourth one of these is pluripotent stem cells by differentiation. I mentioned the differentiation of cells. That is when they decide that they are going to be just this or that, and all the cells they produce after that are just that kind of cell. Now, sometimes, you can take a cell and kind of put it in an environment where you have confused it, you have shocked it, you have done something to it, so it forgets what it was supposed to be, and it starts making cells, tissues that it would not ordinarily make in that stage of differentiation. So what our bill does is to permit the research, particularly on two of these, the nucleus transfer and the taking of cells from the early blastomere.
Our bill has received input from the White House, from the Conference of Catholic Bishops, from Right the Life communities, so there is a broad spectrum of individuals and organizations out there that are supportive of what we are doing.
In the few moments left, Madam Speaker, I would like to note that there have been a plethora of articles very recently about this, and I would like to submit these for the Record. They are not very long, and I will insert them into the Record. Here is National Geographic, July 2005. Stem cells, a big article, very good article on stem cells there. Here is a letter of May of this year from Dr. Battey who is the chief spokesman for stem cell research at the National Institutes of Health who is quite supportive of our bill and what we propose to do, and here is a very interesting op-ed piece written by Richard Doerflinger who represents the Catholic Bishops.
By the way, I need to give credit where credit is due. It was Richard Doerflinger who made the great suggestion that the first thing you do with that cell you take from the early embryo is to create a repair kit so that all during the life of that person, they will have frozen the ability to produce a new liver if they need it, islets of Langerhans, spinal cord cells, whatever they need. There is a great op-ed piece by Richard Doerflinger who explains his support for our bill. He says, Representative Bartlett and his colleagues are helping to demonstrate what has always been true: science and ethics were meant to be allies, not enemies, and this is certainly true.
Tuesday, July 12, Associated Press, Lawmakers Wary of Backup Stem Cell Bill. For those who would like to see just the Castle-DeGette bill passed, our bill, and the President, by the way, says that if that other bill gets to his desk, he will veto it. For those of us who believe that we really ought to research stem cells, we really look forward to a bill which the President can support.
Stem Cell Legislation is At Risk, July 9, Washington Post. GOP Probes Nondestructive Cell Research, Washington AP, June 29. And then just today, in Congressional Quarterly, Congress Considers Numerous Stem Cell Bills. It mentions our bill in the House, and that Bill Frist is expected to draft a related bill in the Senate.
I am very pleased, Madam Speaker, that my background has permitted me to understand some of the potential here, my experience with my grandmother, with these little diabetic kids, my profound pro-life commitment. I am very pleased that I was able to propose a potential solution that I think meets the morals and the demands of both sides of this issue.
Madam Speaker, I ask unanimous consent to insert the following articles:
Department of Health
and Human Services,
Bethesda, Maryland, May 23, 2005.
Hon. Roscoe G. Bartlett,
House of Representatives,
Washington, DC.
Dear Mr. Bartlett: I am pleased that Drs. Allen Spiegel and
Story Landis were able to meet with you, Mr. Otis and Mr.
Aitken during your visit to the National Institutes of Health
(NIH) last month to discuss ways to derive human embryonic
stem cells (hESCs). Drs. Spiegel and Landis were serving as
Acting Co-Chairs of the NIH Stem Cell Task Force during my
leave of absence from this position. Earlier this month, I
returned to chair the Task Force. NIH shares your enthusiasm
on the therapeutic potentials of hESC research and thank you
for your continued support of this field.
Drs. Spiegel and Landis briefed me about your April 26th
meeting. I am also aware that you have had previous meetings
with NIH officials, including myself, Lana Skirboll and
Richard Tasca, on this topic. You propose the possibility of
using a cell (or two) removed from the 8-cell stage human
embryo undergoing preimplantation genetic diagnosis (PGD) to:
(1) create a ``personal repair kit'' made up of cells removed
from the embryo and stored for future use; and (2) for
deriving human embryonic stem cell lines.
You suggested that creating hESC lines in this manner would
avoid ethical questions surrounding the fate of a human
embryo. Live births resulting from embryos which undergo PGD
and are subsequently implanted seem to suggest that this
procedure does not harm the embryo, however, there are some
reports that a percentage of embryos do not survive this
procedure. In addition, long-term studies would be needed to
determine whether this procedure produces subtle or later-
developing injury to children
born following PGD. Also, it is not known if the single cell
removed from the 8-cell stage human embryo has the capacity
to become an embryo if cultured in the appropriate
environment.
NIH is not aware of any published scientific data that has
confirmed the establishment of hESC lines from a single cell
removed from an 8-cell stage embryo. We are aware of the
published research of Dr. Yury Verlinsky in the Reproductive
Genetics Institute in Chicago that showed that a hESC line
can be derived by culturing a human morula-staged embryo
(Reproductive BioMedicine Online, 2004 Vo. 9, No. 6, 623-629,
Verlinsky, Strelchenko, et al). It is also worth noting,
however, that in these experiments, the entire morula was
plated and used to derive the hESC lines. The human morula is
generally composed of 10-30 cells and is the stage that
immediately precedes the formation of the blastocyst.
At the April 26th meeting, NIH agreed that such experiments
might be pursued in animals, including non-human primates.
That is, animal experiments could be conducted to determine
whether it is possible to derive hESCs from a single cell of
the 8-cell or morula stage embryo. To date, to the best of
our knowledge no such derivations have been successful. NIH
also does not know whether these experiments have been tried
and failed in animals and/or humans and, therefore, have not
been reported in the literature. NIH agreed to explore
whether there have been any attempts to use single cells from
the 8-cell or morula stage of an animal embryo to start
embryonic stem cell lines by consulting with scientists that
are currently conducting embryo research. From these
discussions, these scientists believe it is worth attempting
experiments using a single cell from an early stage embryo or
cells from a morula of a non-human primate to establish an
embryonic stem cell line.
Of note, a recent 2003 paper from Canada shows that when
single human blastomeres are cultured from early cleavage
stage embryos, before the morula stage, that there is an
increased incidence of chromosomal abnormalities. Even with
hESCs derived from the inner cell mass of the human
blastocyst, the odds of starting a hESC line from a single
cell are long, perhaps one in 20 tries. Thus, the odds of
being able to start with a single cell from an 8-celled or
morula staged embryo are equally challenging. This would make
it difficult to accomplish the goal of establishing ``repair
kits'' and hESC lines from any single PGD embryo. (Fertil
Steril, 2003 June, 79(6):1304-11, Bielanska, et al). It is
possible, however, that improvements in technologies for
deriving and culturing hESCs may improve these odds.
NIH concludes that the possibility of establishing a stem
cell line from an 8-cell or morula stage embryo can only be
determined with additional research. NIH would welcome
receiving an investigator-initiated grant application on this
topic using animal embryos. The Human Embryo Research Ban
would preclude the use of funds appropriated under the Labor/
HHS Appropriations Act for pursuing this research with human
embryos. As with all grant applications, the proposal must be
deemed meritorious for funding by peer review and then will
be awarded research funds if sufficient funds are available.
It also bears keeping in mind that it may take years to
determine the answer.
At the April 26th meeting, you had mentioned that twins can
develop when the inner cell mass splits in the blastocyst and
forms two embryos enclosed in a common trophoblast. You asked
if cells from the inner cell mass could be safely removed
without harming the embryo. In animal studies, it has been
shown that the blastocyst can be pierced to remove cells of
the inner cell mass and the embryo appears to retain its
original form but it is not known whether the embryo will
result in the birth of a healthy baby. Since this experiment
in human embryos at either the morula or the blastocyst stage
would require evaluations of not only normal birth but also
unknown long term risks to the person even into adulthood, it
would have to be considered a very high risk and ethically
questionable endeavor. Because of the risk of harm, this
research would also be ineligible for Federal funding.
You had also asked NIH about the latest stage in
development that an embryo can be artificially implanted into
the womb. We know that infertility clinics transfer embryos
at the blastocyst stage (approximately Day 5 in human embryo
development) as well as at earlier stages.
Finally, I am providing an additional resource that was
discussed at the April meeting. I have enclosed a copy of a
recently released white paper developed by the President's
Council on Bioethics (PCB) on Alternative Sources of Human
Pluripotent Stem Cells. In this white paper, the PCB raised
many ethical, scientific and practical concerns about
alternate sources for deriving human pluripotent stem cells
without harming the embryo. Your proposal is specifically
discussed in this report.
I hope this information is helpful.
Sincerely,
James F. Battey, Jr., M.D., Ph.D.,
Chairman, NIH Stem Cell Task Force and Director, National
Institute on Deafness and Other Communication Disorders.