What follows is a discussion of an issue with many empirical aspects to it. Because pro-lifers have been urged to get on board with the proposal in question, I think it's important for us to have an informed opinion. The empirical statements in what follows all have evidence for them, but I am interested in and open to corrections of any of them, the more so as I am not an embryologist and have studied these matters only as an amateur.
The procedure in question is called ANT-OAR: Altered nuclear transfer oocyte assisted reproduction. My position is that ANT-OAR is wrong, not primarily because the entities it would produce would be human embryos (in one current versions of the proposal, I'm presently inclined to think that they would not be), but even if the entities it produces are not human embryos. My position against ANT-OAR is thus, as far as I know, original in the debate.
ANT-OAR has been held up as a method by which embryonic stem cells can be produced without producing human embryos at all. A number of sincere and ethically careful people, most notably William Hurlbut, have been assiduously working on the concept of ANT-OAR in the hopes that it will provide a place where pro-lifers and proponents of embryo-destroying research can agree. Their hope is that this will free pro-lifers from the accusation that they are holding up scientific progress and foreclosing on the possibility (still only theoretical) of disease cures from embryonic stem cells. (See the statement on ANT here, with as endorsers not only Dr. Hurlbut but also such pro-life luminaries as Robert P. George and Hadley Arkes.)
Wesley J. Smith has recently linked an article in Nature Reports Stem Cells in which Marcus Grompe, a scientist at the Oregon Stem Cell Center, advocates ANT. To his credit, Grompe says outright that research that involves destroying IVF embryos should not be done, and he even goes so far as to say that such embryos have souls, which is an astonishing statement to see published in such a journal. But he believes that ANT is a project that we can all get behind.
There is a great deal to be said here, and this post will already be long enough, but at the outset I should say that even aside from the serious ethical issues, scientifically, pragmatically, and sociologically, ANT-OAR proponents are on the wrong track. Adult stem-cell research has proven very promising. Embryonic stem-cell research is not only unproven as far as curative potential, there is also the serious question of tumor causation as a result of the very pluripotency that is so coveted in embryonic stem cells. Moreover, no pro-lifer is going to get any credit whatsoever from a committed embryonic stem cell proponent for urging ANT-OAR. To those who believe in the human sacrifice that is embryo-destroying research, nothing less than full freedom, with federal tax funding, to pursue that avenue is acceptable. So I'm inclined to think there is little point from any angle in pursuing ANT-OAR.
But the more serious question is whether ANT-OAR is morally wrong. To understand all of this, a little background, which may be redundant for some readers: Cloning involves producing a mammalian zygote by taking a somatic cell nucleus and transfering it into an enucleated egg. In the process of the fusion of the egg with the genetic information in the somatic cell nucleus, a totipotent cell--a zygote--comes into existence and the egg and somatic cell nucleus cease to exist as separate entities. The genetic information in the somatic nucleus is thrown into a different epigenetic state so that it isn't "the nucleus of a skin cell" but rather the nucleus of a totipotent cell. From there on, the development of the embryo continues normally, assuming that it is successfully implanted within the requisite window of time. At about five days along (in the case of humans) the first level of cell differentiation takes place when the embryo comes to be called a blastocyst. Instead of all the cells being the same, there are now two levels--an inner cell mass, composed of pluripotent cells, and a trophectoderm layer which will in the continued development of the embryo "turn into" the placenta, an essential organ of the embryo's (and later the fetus's) own body, carried outside the body. The inner cell mass will, in the continued course of normal development, differentiate into everything else--in other words, it will develop into the embryo proper.
Standard embryo-destroying research usually begins with IVF embryos which have been conceived not by cloning but by the mixing of egg and sperm in the lab. Scientists strip the trophectoderm layer off, harvest the inner cell mass, and then culture the inner cell mass, using it to develop stem-cell lines.
With all this in place, here we go: Earlier proposals for ANT (known simply as ANT without the OAR) were in my opinion quite clearly wrong as it was plausible that what those procedures would make in the lab would simply be damaged human embryos. The earlier ANT proposal involved simply knocking out a gene in the somatic cell nucleus before implantation, a gene necessary for the later development of the trophectoderm layer. The concern there was that what would be brought into existence when the altered somatic nucleus was placed into the enucleated egg would appear at first to be a normal human zygote but would simply fail properly to develop a trophectoderm at the blastocyst stage and hence would die. In other words, it looked like this proposal would merely produce an embryo with a fatal flaw.
The more recent proposal involves doing more than merely the negative step of knocking out the gene in the somatic cell but also encouraging (I don't know how, but I assume they do) the production of what is known as a "transcription factor" called nanog in the somatic nucleus. The theory is that this forced expression of nanog and perhaps also the introduction of nanog separately into the enucleated egg would guarantee that when the egg and somatic nucleus fuse the result will be, from the beginning, a pluripotent cell like that of the later inner cell mass. Hence--so runs the theory--the desired ICM cells could be produced without the entity's ever having passed through a totipotent zygote stage in the first place.
As far as I know, this method has not yet been tried, not even in mice. The only thing that appears to have been tried in mice is the gene knock-out procedure. So it isn't clear if this would all go the way ANT-OAR proponents are speculating, even in animal studies.
Grompe apparently sees no significant moral difference between the gene-knocking and the positive-factor versions of ANT. He implies that both are morally acceptable, but Hurlbut et. al. appear to be leaning rather heavily on the distinction between them.
Some critics of ANT-OAR argue that in the very nature of the case, there must a moment, however brief, when the cell formed in the nuclear transfer process is a human zygote. (See Adrian J. Walker, p. 774, footnote 10, here. Links to the rest of the articles in the Communio exchange can be found here.) But as far as I can see, this position is purely a priori. What Walker does not appear to be considering is the possibility--which apparently is what the ANT-OAR proponents are counting on--that it is the process of fusion with the egg itself that produces the type of cell in question. This appears to be what happens in ordinary cloning. It is apparently the process of the somatic nucleus's fusion with the enucleated egg that does the "reprograming" of the genetic information to produce a new cell which, from the time it first exists as a complete cell, is neither a skin cell nor an egg but a mammalian zygote. Similarly, the claim in ANT-OAR appears to be that it is the very process of fusing the altered somatic nucleus with the enucleated egg that does the reprograming so that the new cell produced is from the outset neither a skin cell nor an egg cell nor a zygote but rather a pluripotent cell like those of the blastocyst inner cell mass. That this will happen I don't know. That it is impossible in principle is far more than I can say.
Suppose that we grant for the sake of argument that the process of ANT-OAR goes the way its proponents say and that it produces from the first moment nothing but pluripotent cells like those of the inner cell mass of a blastocyst. The first question, then, is whether such a pluripotent ICM cell would be a human embryo. The argument for this proposition is simply that, after the blastocyst differentiation takes place in the course of normal development, it is the pluripotent cells of the inner cell mass that later do turn into all of the human embryo except for the placenta. And, so this argument runs, just as we would not say that a later fetus without his placenta is not a human being, so we should not say that a pluripotent ICM cell without the trophectoderm is not a human being.
I'm presently not convinced by this argument. Going back to the process of embryo destructive research, it seems to be generally agreed that the harvesting step in which scientists strip the trophectoderm layer and take the ICM for culturing does indeed kill the embryo. Given that this is the case, it appears that the ICM without the trophectoderm should be regarded not as a complete and living embryo but rather as the dead body of an embryo, or nearly all of the dead body, the part wanted by scientists for research. This is why the cultured ICM cells, even though they are receiving sustenance, do not continue to differentiate and develop as embryos. A parenthetical note on this reasoning is that it therefore looks to me as though the trophectoderm has a more important role than merely turning into the placenta later on. The trophectoderm is not yet the placenta at the blastocyst stage, and its presence as an outer layer appears to be necessary in some way beyong the roles assigned later to the placenta (providing a means for the provision of oxygen and nutrition) for the further differentiation and organization of the inner cell mass into the visible embryonic body. There may well be people out there who know how and why the trophectoderm is necessary for this process, but I am not one of them.
Now suppose that the inner cell mass of the blastocyst after harvesting in embryo-destroying stem cell research should be regarded not as a living embryo but as the dead body of an embryo. In that case, what ANT-OAR proposes to produce, by producing ICM cells immediately, is something just like the dead body of an embryo.
It seems to me that producing such an entity is morally wrong, even if ANT-OAR goes just the way its proponents want it to go. Proponents of ANT-OAR often analogize the process to producing some sort of obviously non-embryonic tissue. One early analogy was to a teratoma--a form of cancer. Grompe compares ANT-OAR to producing muscle cells. But of course pluripotent ICM cells aren't muscle cells and they aren't cancer. If they were either of these, they wouldn't be useful for the work that scientists hope to do with them. The reason they are desired is precisely because they are just like the part of a blastocyst that will later develop into the whole visible body of the embryo. It is precisely because they have the capacity to turn into all the organs and tissues of the embryo other than the placenta that researchers want them. In other words, it's precisely because they are just like the dead body of the embryo harvested when an IVF embryo is killed that they are the goal of ANT-OAR.
So I propose a different analogy: Suppose that in some sci-fi scenario a scientist (I'm inclined to call him a mad scientist) could build an exact physical duplicate of your body from the feet up, stopping before making the head. This built, decapitated body would not have developed from anything that ever was or ever looked like a human embryo, zygote, or baby. The scientist built it, let's say, in his lab. He doesn't put a head on it, either because he can't or because if he did it might come to life, and then you'd have ethical problems. So he's succeeded in building something that is just like your decapitated body, without its ever having been alive in the first place. Neat trick! Now it can be used for spare parts for you if you need an organ transplant.
Doesn't this raise ethical concerns in itself?
I propose a principle. You might think it's just obviously wrong or obviously right, but I propose it for your consideration:
A whole human body or nearly-whole human body, even if not living, should not be an object of manufacture.
I have to admit that this principle seems to me self-evidently true on its face. This is despite the fact that it goes farther than the usual objection to cloning--that a living human person should not be an object of manufacture.
I think that those who recognize the exceptional nature of human beings and an important connection between this exceptional nature and the human body should accept the principle for that reason: Human beings are special. Human beings are in their natural and normal state embodied agents. Human specialness confers specialness on the human body, which should therefore be treated with particular respect. It is not respectful in the relevant sense to build a whole or nearly-whole human body. Hence, etc. Christians recognize the specialness of the human body because they accept that man is made in the image of God. The implications of the specialness of the human body are, of course, highly controversial even among Christians. But I believe that the sense of revulsion at the sci-fi scenario sketched above (the Faceless Frankenstein scenario, we might call it) is evidence that a violation of the special nature of the human body is taking place in that scenario. If the analogy holds to making pluripotent cells, then the wrongness transfers to that process as well.
One argument against the principle I'm promoting is that there seem to be morally unproblematic acts in which scientists do "build" parts of human bodies. Adult stem-cell work itself is like this: Multipotent cells are encouraged to change their epigenetic state so that they turn into nerve cells and other cellular types needed for disease treatment. Is there a principled line that is crossed when we are not merely making muscle cells, nerve cells, or blood cells directly from already-differentiated cells but rather are first making pluripotent cells? I believe that there is. It seems to me morally significantly different if the process involved never passes through a stage that is anything like making a complete or near-complete human body. Hence I don't think my argument also rules out adult stem-cell research.
Unfortunately, though, if indeed pluripotent cells exactly like those of the ICM are wrong to make for the reason I've given, we should not be pursuing any avenues for making them and should rather be relying only on cells that are differentiated to a further level than pluripotency, and trying to turn them directly into the tissue types needed, as is done presently in adult stem cell research. But we should not be pursuing research (mentioned by Grompe) to try to take adult cells and "turn the clock back" on them so as to turn them back into fully pluripotent cells, from which they would then be redifferentiated later into cell types needed for treatment. This might itself seem to be a counterintuitive result of my position. Surely, it might seem, if we can coax adult cells into turning back into something just like ICM cells without even using a somatic nuclear transfer technique that looks like cloning, we haven't done anything wrong. Why, in that case, all we worked with to begin with were your own adult cells.
But these days, we have to admit that we are already to some extent living in a world of science fiction. Who would have believed, three hundred years ago or even fifty years ago, that a sheep could be made by cloning itself? And cloning starts with what appear on the face of it to be unpromising materials--an enucleated egg, an ordinary cell from an adult body. In fact, if we were cloning a female, both of these could come from the same person in the first place. If scientists can make an entire baby sheep starting with a somatic cell and an enucleated egg, it shouldn't be all that surprising if they eventually find a way to make something just like the dead body of a mammalian embryo without bothering with the egg. Grompe points out that in any event the "turn back the clock" sort of research appears to have great practical obstacles in its way, but if it happens, we should be willing to face the fact that doing so might be immoral for Faceless Frankenstein reasons. So I'm willing, for the time being anyway, to bite that particular bullet.
Readers will have to draw their own conclusions. My strongest advice would be that we not be hasty. There is no moral imperative upon us to approve something that will allow pluripotent stem cell research, and there is no reason for the almost agonized eagerness I sense among Hurlbut and his allies to find ethical routes to such research. I think that it will be much harder--both psychologically and sociologically--for pro-lifers to withdraw their approval once given to some procedure than to decide later that some research procedure they had questioned is in fact morally acceptable. I hope, in any event, to have provided sufficient information and framework for a consideration of ANT-OAR from a scientifically informed pro-life perspective.
Comments (25)
Lydia--Thanks for delving into this. My feeling, since reading several positive-spinning pro-life pieces on ANT-OAR, has been that there's something very questionable in ANT-OAR, even if it's not murder. Isn't there something about the components of human life that deserve respect? Shouldn't we be very hesitant to manipulate them?
Arguably, it's hard to distinguish ANT-OAR from other forms of medical technology that use human cells to supplement our natural deficiencies. But this isn't the same as a skin graft or something. Besides your point about manufacture and (I would extend it) commoditization, I find myself extremely wary of intentionally forcing a defective process of human life to occur. This is different than growing useful cells in a petrie dish or something. There's certainly manipulation there, but the cells are following their inherent purpose according to normal mechanisms.
In ANT-OAR, inasmuch as I understand it, we are subverting those mechanisms and purposes. I suppose it's my sympathies to natural law and teleological reasoning speaking.
One warning I would give to you and other anti-ESC folks is not to think that the apparent problems with ESC approaches and the promises of adult stem cells are convincing reasons to oppose embryonic approaches. It's dangerous to presume a limit on scientific advancement and pin an argument on that. What we ought to do is focus on the ethics, not the efficacy, of the approaches we know of. Science could very well make embryo-destructive approaches work, sooner or later. Presuming it won't is stalling because the ethical arguments (which, of course, you clearly aren't evading) are hard to make and harder to build consensus around.
Posted by Chris Floyd | October 20, 2007 12:10 PM
I certainly agree that even if ESC had all the promise its proponents claim it would be immoral and that we shd. focus on the ethical arguments.
The only reason I bring up the practical point is because from a prudential point of view I suppose there could be more legitimate motivation for trying to find out if we could make pluripotent cells ethically if pluripotent cells really do carry the promise claimed for them. This, I think, is the source of Hurlbut's continual attempts to find _some way_ to do it ethically. By pointing out that it probably won't work, I'm trying in a sense to put a damper on the sense of urgency here. Why are we trying so hard on this front? It's always been a bit of a puzzle to me.
Posted by Lydia | October 20, 2007 12:33 PM
Lydia,
A whole human body or nearly-whole human body, even if not living, should not be an object of manufacture. I would say this is wrong on three counts. First, at least part of it has to be living since necrotic tissue is fairly toxic, but perhaps you mean something more like stasis. Second, your example of nearly-whole human bodies have no agency, so I have trouble figuring out what is supposed to be special about the Faceless Frankenstein. I will quickly reiterate a previous argument which notes that the Headless Horseman has agency, so he is entitled to human dignity. Third, it is less natural to have a mechanical manufactured device implanted to keep us healthy, like a pacemaker, which does not raise ethical concerns from anybody. Building an organ that is uniquely tuned to a person's biochemistry is much more natural in the sense of healing an unhealthy part with a healthy part.
Posted by Step2 | October 20, 2007 8:08 PM
Step2, when I say "not living" I mean "not physically functioning as a whole living body." You are of course correct that the individual cells must be non-necrotic for it to be useful. We could build that into the Faceless Frankenstein scenario. Perhaps a machine pumps oxygenated blood through the headless trunk and limbs.
I have no problem with what we might call a "starfish scenario" where one simply makes new organs from further differentiated (e.g. multipotent) cells without first undifferentiating back to a state identical to the ICM.
Posted by Lydia | October 20, 2007 8:22 PM
Many of the concerns raised by this blog are dealt with in the following writings by Dr. William Hurlbut: please go to www.alterednucleartransfer.com and click 'resources' then click 'publications' and select number 7 for the science and number 6 for philosophical arguments.
Posted by live4 | October 22, 2007 1:42 AM
I don't have anything to say about the substance of this, except that I agree; and thanks for all the effort, Lydia.
Posted by Paul J Cella | October 22, 2007 10:17 AM
Thanks, Paul.
Live4, I am quite familiar with the kinds of responses, both scientific and philosophical, that Hurlbut and other proponents of ANT-OAR give to their critics. Since as far as I know no one has ever made the specific criticism I make above (regarding making bodies), I doubt very much that he has answered it. I have read several pieces both by him and by other advocates of the procedure and have linked to them above--the joint statement, and the responses in the Communio exchange. I have probably not read the specific parts of his web site to which you refer but will do so. I have begun #6 and see nothing that addresses my specific criticism here.
Posted by Lydia | October 22, 2007 12:02 PM
Well, I've been incognito since reading this Friday evening, and I have to state that, while I would posit that ANT-OAR is wrong because it involves the deliberate creation of defective human beings, I haven't the slightest objection to this argument; indeed, this argument may actually be stronger. One of the finest things to appear here on W4, for which congratulations are in order.
Posted by Maximos | October 22, 2007 1:17 PM
Thanks, Maximos.
I've now read the two pieces recommended by live4. Neither addresses my principle, and this isn't surprising, since all the ethical concern has focused on whether or not an embyro is produced.
One thing I find disturbing in all of these documents is the strange ambivalence about the difference between gene knock-out techniques and forced positive-expression techniques. In 2005 we find Dr. Hurlbut acknowledging (footnote 9 of publication 6 mentioned by live4) some understandable ethical concern about the mere knock-out of Cdx4--a gene necessary for differentiation at the blastocyst stage. He is there obviously looking for the "nanog" factor. His acknowledgement of these concerns in footnote 9 is only partial. It isn't clear to what extent he shares them, but he doesn't dismiss them. The joint statement (which I linked) was also published in 2005, but I'm guessing was perhaps written later, after the nanog expression idea was available. The 2006 document (publication 7 on the ANT web site) discusses _both_ techniques without _any_ acknowledgement of legitimate concerns that the mere gene knock-out technique might be producing merely damaged embryos. In fact, on p. 46 of that document we find a chart that clearly implies that if the product of the nuclear transfer technique cannot form a trophectoderm, it *is not an embryo*. By the end of that document, a combination of cdx4 knock-out _and_ forced nanog expression is what is in view, but again, there is no implication that this is necessary to insure that what is formed is not an embryo. And as I pointed out in the main post, Grompe is writing right now implying that the two techniques are morally equivalent.
So what gives? All of this gives me the impression that, to speak frankly, these guys really don't have a very definite grip themselves on whether these techniques are or aren't producing embryos. Sometimes they imply that the mere inability to produce a trophectoderm layer later on is enough to mean, by definition, that the entity isn't an embryo. Other times they seem to imply that there is a definite and scientifically detectible difference between a totipotent and a pluripotent cell and that the forced nanog expression technique will guarantee, verifiably, that what is formed is a pluripotent cell ab initio. Does this mean that they couldn't tell this with the cdx4 knock-out products? Why are they adding these bells and whistles? Do they really know what they are doing? The shifts in emphasis, etc., raise some doubts.
All this, of course, though disturbing, is merely when we're concerned about producing embryos and is to some degree moot if it is also wrong to produce the ICM, because it is identical to a near-complete human body.
Posted by Lydia | October 22, 2007 4:27 PM
I find myself sympathetic to Chris Floyd's criticism regarding tinkering with the "components of human life." And it's not just the components that deserve respect but the process that brings them into being, which in a sane world is sexual intercourse. Cloning is a perversion of that normal way of coming into being. These techniques you discuss seem like further perversions of the 'normal' cloning procedure. They remind me of contraceptive techniques, in which the chemicals in a pill are designed to prevent human conception; here, the ANT-OAR techniques are intended to accomplish the same. Yet these fellows want to mimic the cloning procedure (conception) without having to call it that; they want that result to behave in certain embryonic ways, but without passing through the embryonic stage; in short, to manufacture the components of an embryo while remaining confident that it's not one. They achieve this by purposely inducing congenital defects; in effect, they sabotage the process of conception, such that we are left with what appear to be living but badly mutilated embryos. This seems to me nothing less than diabolical.
Posted by William Luse | October 23, 2007 5:13 AM
There is indeed something eerie, and to me more eerie the more material I read by ANT-OAR proponents, about their cool and unruffled talk of deliberately sabotaging the cloning procedure so that it's just like cloning only not really. Moreover, this is what they take, in all sincerity, for exercise of virtue, since it is the way they hope to make sure they are not destroying human life.
I want to recognize that some of these men may have paid a price in their careers for their unwillingness to get on the ordinary embryonic stem-cell bandwagon. I don't want to downplay their genuine concern to do what's right. But I think their immersion in a certain niche of the scientific community, even their fighting against it, has had an unfortunate effect on them. Several. For one thing, there is this extreme urgency to find _some way_ to derive pluripotent cells. They just can't bring themselves to say, "This is all pointless and silly. Adult stem-cells are providing cures already. Let's pursue that angle full-bore and leave the ideologues to insist on embryonic stem-cell research." No, they feel they _must_ find some way to walk this unpleasantly fine ethical line and to get "embryonic stem-cells without embryos."
Second, there is I think a feeling that no one could possibly object to this research if it isn't producing embryos, that there could be no other objection. This arises, I think, from Leon Katz's statements (I've heard about them but am reporting them second-hand) to the effect that "the yuck factor" isn't s sufficient reason not to pursue research. But why not? If you sense danger in the physical sense, don't you take that for evidence? You can sense these guys' impatience with people who demand a guarantee that what is being produced is not an embryo. Their feeling is that if they've shown it beyond reasonable doubt everyone should be satisfied. Well, on _that_ score, perhaps so, though with all the waffling I discussed in the previous comment, I'm not sure they _have_ shown it beyond reasonable doubt. But how about the wider question of whether this is wrong? Have they shown that it isn't wrong beyond reasonable doubt? Not even close. And I would say, as a curmudgeonly rationalist, that the distaste one feels reading about "failed conceptions" (Hurlbut's word) and how they are now going to try deliberately in this technique to bring about "failed conceptions" so that they just have a "disorganized cell mass" instead of an embryo, _is evidence_ that something is wrong. (The distaste, that is.) But in the milieu they are in, I think they have come to feel they aren't allowed to say that.
Posted by Lydia | October 23, 2007 9:27 AM
Excellent discussion, spreading some light on a "hazy" subject. Keep up the commentary. nancy
Posted by nancy mac | October 23, 2007 1:57 PM
I am desperately trying to avoid commenting until I understand the technical details a bit better. But if what they are doing is, as it appears to be, akin to what we do with "knockout mice" and other creatures subject to genetic experimentation then I will end up coming down where Maximos is on it: that we don't even have to assent to Lydia's proposed principles to conclude that what is being engineered is not "not embryos" but rather "intentionally defective embryos".
Posted by Zippy | October 23, 2007 9:32 PM
Lydia,
In an article entitled "The Middle Way" in the March/April 2007 issue of the journal Science & Spirit, Dr. Hurlbut wrote, "On two occasions, however, a group of distinguished scientists, moral philosophers, and religious leaders met to analyze rigorously the ANT proposal, and they endorsed pursuing it in animal studies. Cardinal William Levada, then the archbishop of San Francisco, also wrote a letter to President George W. Bush, encouraging him to support further investigation of the proposal."
As you know, Cardinal Levada is Prefect of the Congregation for the Doctrine of the Faith in the Roman Curia. I mention this not to make an argument from authority, for ANT must be evaluated on its merits, but simply to caution you that there are serious Catholic thinkers who have supported ANT, lest you dismiss it too lightly. I would assume that Cardinal Levada would be able to discern whether ANT was "diabolical", as one of the previous posts here thinks it is.
I appreciated your thoughtful blog on ANT, and I have been preparing some substantive comments in response, which I hope to post in a day or so as I find time to finish them.
Posted by live4 | October 24, 2007 1:32 AM
...and they endorsed pursuing it in animal studies.
I'm not sure that really tells us anything other than "sure, go ahead and find out more about this in animal experiments." Saying that it is fine to think about something and find out more about what it entails isn't quite the same thing as endorsing doing it.
Posted by Zippy | October 24, 2007 1:51 AM
As I understand it, they are doing the knock-out mouse thing already (or have done it), but Hurlbut et. al. are now proposing that in addition they force expression of nanog in the somatic cell and also insert it into the enucleated egg. This is supposed to provide further insurance that what is produced is not a living human embryo but a cell like those of the inner cell mass. As I've commented, I detect an ambivalence as to whether the mere knock-out approach is wrong or perfectly fine, and this itself worries me as to how clearly the scientists themselves are able to tell if what they are producing is a living embryo. But I've tried to see if I can grant that the additional nanog stimulation would have the effect hoped for (it evidently hasn't been tried) while arguing that the activity is still wrong.
Posted by Lydia | October 24, 2007 9:23 AM
There were four transcription factors (one of them nanog) that, when activated, turned a normal mouse cell into an embryonic mouse cell. This was done fairly recently, but you could see that this approach had promise from papers that have come out over the last few years. They are now trying to do this in human cells--to the best of my knowledge, this will not produce anything resembling a human body, but I admit I'm not up on it.
Posted by W.E.D. Godbold | October 24, 2007 5:55 PM
There's a brief review (By Howard Chang and Ceorge Cotsarelis) of the experiment and its antecedents in Nature Medicine (Vol 3, No. 7 July 2007, p. 783-784). The originals were published in three places: Nature in June (Okita et al. and Wernig et al.) and in Cell Stem Cell (Maherali et al., 2007).
Posted by W.E.D. Godbold | October 24, 2007 6:06 PM
I should have been clearer: I know nanog expression has been tested in mice in some ways. What I meant was that as far as I know they have never tried forcing nanog expression in a nucleus of a somatic cell before doing nuclear transfer, as in the present ANT-OAR proposal. But if they have, I'd be very interested to know just what happened.
What I mean by "resemble a human body" is that the cells in question would be identical to the cells of the inner cell mass. I've discussed above in the main post why I believe that making an inner cell mass is plausibly analogous to making a human body--at a very early stage, of course. The reason is that the inner cell mass goes on to become "the embryo proper," as one article says--all of the embryo except the placenta. That's why ICM cells are pluripotent. While I'm willing for now to grant that making the cells of the ICM isn't tantamount to making a living embryo, it sure looks to me like making a dead one.
Posted by Lydia | October 24, 2007 6:51 PM
I've just looked up the abstracts and such on several of those papers on mouse cell reprograming. It looks to me like this is the same type of thing that Grompe is referring to when he says this:
"Several papers published this summer demonstrated that these cells are truly equivalent to ES cells and can even be used for germline transmission —that is, to produce a new generation of animals. Direct reprogramming has not yet been demonstrated for human cells, however, and the requirement for retroviral integration of the reprogramming genes would pose a significant problem for any clinical use of such cells. Thus, direct reprogramming of human cells may become a true alternative only in the future."
But Grompe didn't mention the same papers but rather a different one. But it sounds similar, including the infection with retroviruses to make the changes. Can someone explain to me what he means (there was a mention of something like this in the other papers, too) when he says "can even be used for germline transmission —that is, to produce a new generation of animals"?
This would be covered by the section of my post regarding the theoretical possibility of reprograming adult cells back to an ICM-like state.
Posted by Lydia | October 24, 2007 8:28 PM
Lydia, Grompe's statement that the reprogrammed adult cells "can even be used for germline transmission —that is, to produce a new generation of animals"means that they were shown to produce the gametes (eggs or sperm), as well as all the other tissue types of the animal body, and that the gametes so produced were successfully used for reproduction. This is considered the most stringent test for pluripotency.
I'm still working on a response to your blog as time permits.
Posted by live4 | October 25, 2007 9:20 AM
Thanks, Live4. I thought that might be what it meant but was confused by a part of one of the other papers where it talked about injecting the ES cells into "tetraploid blastocysts" and thereby producing "late-term embryos." I didn't get that, at all, and was wondering if it were in any way related to the sentence in Grompe's article.
Posted by Lydia | October 25, 2007 3:44 PM
Hello Lydia et. al.,
I have just written an article that appeared in the journal Life and Learning which relates directly to your discussion here. It is accessible to non-scientists, and I offer three reasons (some theological, some philosophical) explaining why I think ANT-OAR is not morally acceptable. Here is the link to the article, and if anyone has any comments or thoughts feel free to e-mail me! Thank you for your discussion here. pjc
http://www.uffl.org/vol17/COLOSI07.pdf
Home page: www.uffl.org
Posted by Pete Colosi | August 16, 2008 1:50 PM
Lydia,
Fabulous post. Very thoughtful and a penetrating analysis.
I have some questions. I am coming at this issue from the other side - as an embryologist.
You have characterized isolated inner cell mass cells as the corpse left over when an embryo is subjected to immunosurgery to isolate embryonic stem cells. Given your principle - A whole human body or nearly-whole human body, even if not living, should not be an object of manufacture - making inner cell mass cells is therefore immoral.
Here is the point where I am having trouble. Inner cell mass cells can, in the proper developmental context, form a body, head, liver, lungs, stomach and so on. However, they must be in the right developmental context to do that. If injected under the skin of a congenic mouse, they will form teratomas that are tumors with a pastiche of tissues. If left to themselves, they will form embryoid bodies, which harbor a whole host of cell types, but the embryoid bodies are disorganized conglomerations of different cell types. It seems to me that inner cell mass cells are not equivalent to bodies, but can forms parts of bodies under the right conditions. Instead inner cell mass cells are, well, inner cell mass cells and are not equivalent to anything in our own bodies. They can form the tissues and cells or our bodies, but only do so under specific conditions whereby they are exquisitely instructed and induced to make one thing and then another at just the right time and just the right place.
What you do think?
Posted by Michael Buratovich | March 11, 2009 6:37 PM
Michael,
Thanks for your comment. I'm always happy to hear from someone who may have more information.
Se here
http://whatswrongwrongwiththeworld.net/2007/11/new_information_requires_rethi.html
for my follow-up post in which I reconsider my view on ICM cells in the light of further info. Perhaps you will be able to shed some light on some of the questions I raise in that post.
My remaining concern with ANT-OAR is now centered on the fact that, to be frank, it seems to me that people promoting ANT-OAR are not able to be nearly as certain as they talk like they are (sorry for the convolution) that they are not making a damaged embryo in the process. I _have_ been able to gather some further info. on that subject in the intervening time which has just convinced me more strongly than I was convinced before that in all these cloning techniques scientists are more or less flailing about without any very clear idea of _what_ they are making. Indeed, I was told by one embryologist that the way they know in a Dolly-type case that they have made an embryo by SCNT is...if it implants and turns into Dolly. But that test, of course, utterly fails to distinguish damaged embryos from non-embryos.
Posted by Lydia | March 11, 2009 9:03 PM