Analogies and Artifacts:
Can Embryonic Stem Cell Research be Morally Acceptable? (Part II)

Hi Joe,

Interesting post. I do have some disagreements with your analysis, though:

Because the BA is “embryo-like”, the natural comparison would be to the normal human embryo (the stage of development between fertilization and the end of the eighth week.). But unlike an embryo, the BA is not, at any stage of the process, a living being. Because of its altered genetic structure, it is incapable of becoming a human embryo.

This is the critical point, and I think it can only be accepted if one plays fast and loose with the definition of embryo. Hurlbut writes:

"There are numerous potential approaches involving alteration of the genes necessary for early intercellular organization, formation of extra-embryonic structures, or the primary patterning of organogenesis."

Hurlbut here is conflating several different sorts of mutation:

1. Disruption of organogenesis. These mutations have their effects relatively late in embryonic development, after the blastocyst stage. It is difficult to argue that an embryo would not be produced.

2. Formation of extra-embryonic tissues. These tissues are critical for early embryonic development but not for the very earliest cell divisions.

3. Genes necessary for early intercellular organization. More promising perhaps, but if they prevent an inner cell mass from forming, they won't be of any use in derivation of ES cells.

The specific mutation described by Hurlbut, loss of Cdx2, would be in class 2 above. This gene is needed for differentiation of the trophectoderm, so the mutant would not develop into a normal blastocyst. It would, however, develop normally through the very earliest pre-blastocyst stages of embryonic development. It is unambiguously a defective embryo, not a pseudo-embryo.

Later in his essay, Hurlbut mentions trisomy of chromosome 1 which causes failure of implantion. If life begins at implantation, then the trisomy 1 blastocyst would be a pseudo-embryo, but if life begins at conception, then a trisomy 1 blastocyst is a doomed embryo, morally no different than an embryo that fails to complete gastrulation or neural tube development.

In "normal" nuclear transfer of mammalian cells, we know that the vast majority of embryos die during devolopment because of defects in genomic imprinting. In humans, we do not yet know whether any of the embryos would survive. This imprinting is derived from the cell used in nuclear transfer, so as Hurlbut says of ANT, it is accomplished ab initio. The embryos are brought into existence with the defect which will prevent their development. So, what is the moral difference between normal nuclear transfer and altered nuclear transfer?

In fact, the entity with which the BA is most similar is the hydatidiform mole. These types of moles are produced by the development of a germ cell that lacks equal contributions of DNA from both the egg and the sperm. A key distinction between the development of hydatidiform moles and embryos is that the moles begin growing without being fertilized.

I'd say the key distinction is not that the hydatidiform mole begins growing without being fertilized, but rather that it begins growing without maternal genetic contribution when sperm fertilizes an egg that lacks a nucleus. The entities created by ANT would be precisely the opposite of a hydatidiform mole. A mole is entirely extraembryonic tissue; in effect, it is all placenta. The entities created by ANT (e.g. by Cdx2 mutation) would lack the extraembryonic tissues. Significantly, Hydatidiform moles are not a source of embryonic stem cells. To get ES cells, you need an embryo, defective or otherwise.

Whether or not ANT is appealing may depend on the reason someone objects to ESCR with normal embryos. If one believes that embryos deserve respect because they will develop into a human being, then ANT may be both acceptable and appealing. If one believes that embryos are human beings from (or before) the first cell division, then ANR isn't much help.

Regards

In order to determine the moral status of the biological artifact (BA) produced by altered nuclear transfer, we need to find an analogically similar entity with a matching "fact pattern".

There's nothing wrong with this as far as it goes, but recognize that we don't "need to" conduct the argument this way. That is, analogical reasoning of this type is not the only way to conduct such arguments, nor, often, is it a very good way.

A better way is simply to ask whether the thing in question meets a clear set of criteria for inclusion in whatever category we are concerned with. That is, the question is not whether it is "like" members of one category or another, but whether it does, in fact, actually pass a specified test for inclusion - in which case it should be included whether or not it is "like" anything else. It is not always easy to specify such criteria or arrive a agreement on them, but when it is possible it allows for much easier and less subjective assessments.

Analogical reasoning is never compelling because an observer is always free to say "but it seems more like this other thing to me". And, since real-world comparisons almost always reveal some ways in which a thing is "like" one possible alternative and some ways in which it is "like" another, such comparisons must always specify what terms of comparison are being used - which is no less controversial than trying to specify objective criteria for inclusion. (Is a giraffe more "like" a gerbil or a telephone pole? It's more like a gerbil if the desired comparison is "living things," but more like a telephone pole if the desired comparison is "tall things.")

This kind of argument just seems to me an extension of the typical conservative subjectivism - "well, it seems bad to me, so it's bad as a universal moral rule." Conservatives will never specify and defend a clear set of criteria defining personhood, but are quick to tell you that moral absolutes flow from how things "seem" to them. I think it underscores the inherent weakness of the argument.

But unlike an embryo, the BA is not, at any stage of the process, a living being. Because of its altered genetic structure, it is incapable of becoming a human embryo.

This is wrong twice over.

Taking them in reverse order, the "embryo" question was settled in your previous post. "Embryo" simply means, in the commonly-accepted definitions, a developing organism between the first cell division and the "fetus" stage. Being an "embryo" has nothing to do with whether it is likely to survive or is even potentially viable. Anything undergoing the process of pre-birth development is (in its early stages) an embryo. It was conservatives who emphasized this definition during the stem cell debate. One of your other commenters even posted a long series of definitions making exactly this point, as an argument against one of your critics.

As for "living being," here you run up against the vagueness of using your preferred term "human being" to mean "moral person." As has been stipulated many times in these discussions, a human embryo is indeed a "human being"; how then is this new form of embryo not one? How is it not even a "living being"? It's clearly "living" - that's the whole point. And it's clearly a "being" ("being" just means "a thing that exists" [a thing that "be"s]). If you want to stretch the point to insist that it's not a "living human being," that's just as obviously false - it's clearly human, since it comes from a human egg cell and has human DNA (minus one gene, but that can't matter - uncountably many human beings are born every day with one or more missing or defective genes). If this entity weren't a "living being" there would be no way to even have this discussion.

To put this in other terms, your statement that it's not a "living being" can only be understood as a moral evaluation - not as a scientific observation. As a scientific point, it's simply, and quite obviously, false. You apparently mean the term "being" to identify not just something that exists, but some category of moral entity - either a "person" or, as you later say, an "organism". But this is not a fact you can observe - it's a conclusion you must argue for.

As for me, I'm glad to find you finally seeing the distinction between mere biological existence and moral personhood - you're now just one step away from the truth. But we have to realize that no conclusion on this subject, one way or the other, is a question of directly observable fact only. Using terms like "living being," "human being," "organism" as if they have moral - not scientific - significance simply confuses the issues.

Which brings us to: As the PCB chairman Leon Kass explains, “what we're talking about here is not an organism and not a being in the same way as a cyst or a mole is not a being. It's not just that it will not develop further. It's not the developing thing. It's a thing - there is growth that takes place here but it is not an organism.”

I refer you again to my previous remark about "shoddy thinking" on the PCB. How is this embryo "not the developing thing"? It has to develop fairly extensively to get to the stage of producing stem cells. (As Kass notes in the immediately following sentence: "It's a thing - there's growth that takes place here . . . ." OK. So . . . it's a "thing" that has "growth," but it's "not the developing thing." Good "thing"king, Leon.) And what does he mean by "it's a thing . . . but it is not an organism"? This seems to be a new use of "organism" in a moral sense, perhaps akin to "human being," that we haven't seen before. I wish conservatives would stop moving the scientific goal posts. At any rate, unless he means that an organism that cannot develop normally, or cannot develop to viability, is not an "organism" at all, this makes no sense. He specifically denies that the question of viability is relevant (and elsewhere he argues against abortion for "defective" fetuses, so that's apparently not the issue). So there seems to be no grounds on which he can distinguish this "non-organism" from the embryonic "organisms" that he does recognize - the only difference between them are genetic defects and viability, which he specifically denies are morally relevant. It's impossible to tell just what makes a thing an "organism" and what not.

Another interesting point is that Hurlbut specifically cites non-viable conceptuses as non-organisms. ("There are natural biological precedents for entities that lack the qualities and characteristics of an organism, yet are capable of generating ES cells. . . . [F]ailures of fertilization due to abnormal complements of chromosomes or improper chromatin configurations (imprinting) may still proceed along partial trajectories of organic growth without being actual organisms. Trisomies of chromosome number one, for example, will grow to the blastocyst stage but will not implant.") This specifically flies in the face of widespread conservative arguments against anti-implantation contraceptives or abortion of defective fetuses. How, on Hurlbut's argument, is an embryo with trisomy-1 morally different from an embryo with the Tay-Sachs gene or severe spina bifida? On the standard conservative line, certain death at any stage does not remove the moral standing of an embryo - how could it in this case?

Over and over, these arguments seem to be nothing more than subjective impressions dressed up in technical-sounding language. What is funny about them is that they contradict the arguments about embryos that both writers had previously made, and actually bring them closer to the position held by most liberals.

In fact, the entity with which the BA is most similar is the hydatidiform mole. These types of moles are produced by the development of a germ cell that lacks equal contributions of DNA from both the egg and the sperm. A key distinction between the development of hydatidiform moles and embryos is that the moles begin growing without being fertilized. Since this type of rare growth is not a living organism, there would be no concerns over using it for research purposes . . .

Ignoring the "living organism" bit (would any of you who are now so indifferent to "organisms" - after having been nearly apoplectic over "human beings" for so long - care to tell us just what distinguishes "organisms" from non-organisms?), what have you got against hydatidifom moles? Apparently, what makes then non-persons is that they are "produced by the development of a germ cell that lacks equal contributions of DNA from both the egg and the sperm" and they "begin growing without being fertilized." Very well, then: what makes a being morally worthy is that it is fertilized with equal contributions of DNA from an egg and sperm.

This means that human clones - of whatever kind - have no moral standing.

We don't need to produce clones with altered genes, harvest their stem cells, and then replace the missing genes. Clones - produced by inserting a full complement of DNA from a somatic cell (neither an egg nor a sperm!) into an egg cell whose DNA has been removed, and then chemically stimulating that egg cell to begin development without fertilization by a sperm - don't meet either of the tests you've laid down for an "organism." That's a relief. By your standards, we still can't do research on embryos left over from IVF experiments (because they were produced by fertilization of an egg by a sperm, with equal complements of DNA from each), but apparently we can do anything at all to cloned embryos! Good news.

Of course, this does put you somewhat at odds with most of the rest of the conservative community, who tend to regard any "living being" of the human type as a "human being" and thus an "organism" and therefore a moral person. It also suggests that many organisms that would normally be considered "human beings" - such as persons with non-disjunction defects such as Down Syndrome or Klinefelter Syndrome (having extra chromosomes - and therefore non-equal contributions of DNA from sperm and egg) - would not be persons. And, of course, there is no good reason to believe that the definition of "person" (er, "organism" . . . I mean "living being" . . . "living human being" . . . uh, whatever it is this week) actually does depend on "fertilization . . . [with] equal contributions of DNA from both the egg and the sperm." You have given us no argument for accepting that definition. Apparently it just "seems" right to you.

(It's interesting to note as well that federal law, explicitly endorsed as good policy in the PCB report on "Monitoring Stem Cell Research", defines cloned haploid parthenogenetic cell masses - genetically identical to hydatidiform moles except they come from the female gamete - as human embryos, in direct contrast to your claim about fertilization and equal genetic complements. As one researcher noted, "They can just make up anything they want, can't they?")

In the end, these arguments are simply assertions of moral intuition surrounded by technical facts that only serve to muddy the issue. The question is not one of diploid or haploid genomes, fertilization or cloning, or any technical issue. It is the familiar, old moral question of when moral personhood obtains. Interestingly, all your old arguments about it ("life begins at conception" where "conception" includes cloning by some sort of dispensational handwaving) would obviously bring these "altered" embryos into the fold of moral persons - along with anything else that had a human genetic complement. Suddenly you, Hurlbut, and the exalted if bumbling Leon Kass - who previously had been insisting on full moral personhood for non-viable fetuses, anencephalics, unimplanted embryos, and anything else - now find amazing moral significance in minor distinctions involving a single gene. Still more amusing, the impact of this gene is to prevent full development of the embryo, but you claim that this makes the embryo a non-person while simultaneously denying that viability has anything to do with it (and, presumably, while still maintaining that all other non-viable embryos are persons)!

I think, as I said before, that you've painted yourself into a very complicated corner. I also think it's one that's unnecessary for you. Obviously, the best thing would be for you to follow your new insights to their conclusion and accept that all embryos are non-persons, because they all lack the necessary factors for personhood. But if you want to retain your conservative inclinations, it's probably best just to drop this "BA" BS and go back to an easier and more consistent position: all embryos are persons and these "altered" embryos are not a way around that. I don't agree with that position, but at least it makes sense. This new plan seems like an attempt to slide through that definition without revising it, and it leads to some contradictory and unworkable claims.

Joe Carter --

Thanks for Part II, which I found as interesting as Part I. I do hope, however, that you'll clarify the following two lines:

But unlike an embryo, the BA is not, at any stage of the process, a living being. Because of its altered genetic structure, it is incapable of becoming a human embryo.

By your definition, however, a "BA" is "a living being" -- at least, as I understand it. A BA consists of living, growing human genetic material. Indeed, it contains the same material that makes up a human embryo. Its DNA is human; its form a human form (albeit at an early stage of development). Accordingly, to the extent that embryonic material is a living being, a BA is a living being.

Indeed, the distinction that you draw between a BA and an embryo is not that one is a living being and one is not; rather, as the second sentence of the above-quoted passage indicates, you distinguish a BA from an embryo based upon their relative potentials. An embryo is a living being and a potential human, and thus deserving of protection; a BA is a living being but not a potential human, and thus not deserving of protection.

It's important to be clear in this debate what is the operative distinction between humanity and non-humanity. Thus, if you are relying on some distinction between BAs and embryos other than their relative potentials, please state it.

One quick further note, as to this:

The technique of IVF allows a medical technician to fertilize an ovum outside the body, creating an embryo that can then be implanted in the mother’s womb. While the practice is not universally accepted, many evangelicals consider it to be a legitimate and ethical means of initiating a pregnancy.

IVF results in embryonic destruction; accordingly, to the extent an evangelical accepts such "killing" to create a new life, he or she would presumably also accept such "killing" to save a life. Or he or she is not thinking things through.

To the extent that I merely repeat Keith's points (I see some -- though not complete -- overlap), my apologies.

Nick: This is the critical point, and I think it can only be accepted if one plays fast and loose with the definition of embryo.

Before we get too deep into hashing out these points it would probably be a good idea to clarify a few definitions. For embryo, I am using the one presented by the NIH:

In humans, the developing organism from the time of fertilization until the end of the eighth week of gestation, when it becomes known as a fetus.

The reason I (so far) see no moral problem with ANT is because it initiates growth without the fertilization of the ovum.

So, what is the moral difference between normal nuclear transfer and altered nuclear transfer?

From my rather limited knowledge of the processes, I would say the difference is that one is the creation of an embryo that will later be destroyed and the other is the creation of a biological artifact, an entity that never becomes an embryo.

To get ES cells, you need an embryo, defective or otherwise.

While you might consider the difference nothing more than semantics, I find that without fertilization taking place, no embryo is created. We wouldn’t normally consider growths of an ovum that has not been fertilized to be an embryo, so I don’t think we should consider the BA to be one either.

Michelle: Is it before or after fertilization?

From my understanding, fertilization never occurs in the creation of this entity.

Kevin: Conservatives will never specify and defend a clear set of criteria defining personhood, but are quick to tell you that moral absolutes flow from how things "seem" to them.

I’ll be glad to specify a (tentative) set of criteria for personhood: (a) the organism must be a member of the human species, (b) it must currently be “alive”, and (c) it is currently existing between the time of conception and the time of legally defined death. If a being meets all three criteria then they are a “person.”

Taking them in reverse order, the "embryo" question was settled in your previous post. "Embryo" simply means, in the commonly-accepted definitions, a developing organism between the first cell division and the "fetus" stage.

The missing component in this definition is “fertilization.” Without that it is not a “developing organism.”

Anything undergoing the process of pre-birth development is (in its early stages) an embryo.

True, if we are talking about genuine development. We wouldn’t consider a cancerous ovum to be an “embroyo” so we should not consider the BA to be one either.

If you want to stretch the point to insist that it's not a "living human being," that's just as obviously false -

I think you are obscuring the common denotation that is derived from the combination of those terms. A cancerous growth could fit that same definition as you are applying it but I don’t think anyone considers a tumor to be a “living human being.”

Using terms like "living being," "human being," "organism" as if they have moral - not scientific - significance simply confuses the issues.

I would say they have both. For me, the moral takes precedence over the scientific anyway. But I wouldn’t make such sharp distinctions when they are not warranted. While it may aid us in the thinking process, the real world application doesn’t allow us to put such issues into distinct boxes labeled “science” and “ethics.”

Von: IVF results in embryonic destruction; accordingly, to the extent an evangelical accepts such "killing" to create a new life, he or she would presumably also accept such "killing" to save a life. Or he or she is not thinking things through.

While I abhor the destruction of embryos that takes place in actual practice, there is no inherent reason that IVF must result in “killing.” We have to distinguish between the practice as it could be done ethically from the way it is commonly abused.

Kevin: Until then, I've got Joe.

I don’t know whether to be flattered or creeped out. ; )

Joe,

Before we get too deep into hashing out these points it would probably be a good idea to clarify a few definitions. For embryo, I am using the one presented by the NIH:

In humans, the developing organism from the time of fertilization until the end of the eighth week of gestation, when it becomes known as a fetus.

But that definition is not terribly useful if we are talking about nuclear transfer, which never involves fertilization. Do you mean to say that Dolly the sheep was never an embryo? If you accept that nuclear transfer of normal nuclei can produce embryos like Dolly, then you can't argue that the nuclear transfer using modified nuclei fails to produce embryos simply because there is no fertilization. The transfer of a diploid nucleus to an enucleated ovum substitutes for fertilization and, if all goes well, initiates embryonic development. The only difference between Dolly and the product of ANT is that the ANT embryo is doomed to die young.

We wouldn’t normally consider growths of an ovum that has not been fertilized to be an embryo, so I don’t think we should consider the BA to be one either.

The product of altered nuclear transfer is not growth from an unfertilized ovum. By definition, nuclear transfer involves adding DNA from another source to the ovum after removing the ovum's own DNA.

Joe,
I'm not up on the technical language. The gist of what your saying as I see it is as follows.

My genetic material (for example) can be used and it can be pushed along a sequence of events which end up in developing ES cells for therapeutic use (perhaps for me) should not a priori wrong. What makes this issue sticky, is with a small alteration in those steps that same cluster of cells could be use to produce a clone, which you, I, and many others think is wrong. Is that it?

Every day we get more proficient in manipulating the stuff of which we are made. It's scary that so many scientists (especially in biology) are such tyros when it comes to ethics.

With that little differnece is where Kevin's confusion with respect to Mr Kass and the PCB arises. That is how just a little change alters the ethics of the situation. By noting that little change, the ethics of the situation changes for you, me, and Mr Kass. But Kevin has just decided that all embryos are just so much meat and washes his hands of the whole affair. Maybe someday he'll notice the gaping barn door of possiblities he's left himself open to with that decision. But on the other hand perhaps he's completely ok with eugenics as long as its performed on embryos.

Perhaps I’m mistaken, but I was under the impression that nuclear transfer fulfilled all of the same functions as fertilization. Obviously, it has a different name and occurs by an alternate process but the essential function is the same.

Yes, we agree here.

Here is where I see the difference: Nuclear transfer substitutes for fertilization, therefore creating an embryo. ANT initiates a process that is not similar to the full range of functions in fertilization, therefore no embryo is created.

Right. This is precisedly where I disagree with Hurlbut. Altered nuclear transfer starts a process that is identical to "normal" nuclear transfer at the earliest stages but goes awry at some later stage. The disrupted stage varies depending on whether it involves genes controlling organogenesis or extraembryonic tissues, but in all cases it occurs after the time that prolife conservatives recognize as the beginning of life.

Certainly, there are entities that grow but are not not embryos. You gave the example of a hydatidiform mole. But I think it is significant that those entities are not and cannot be a source of ES cells.

So are you saying that ANT is the same as fertilization?

Yes. I'm saying that ANT is the same as normal nuclear transfer at the time that normal nuclear transfer is equivalent to fertilization.

Regards.

Analogical reasoning is never compelling because an observer is always free to say "but it seems more like this other thing to me".

A good point, but there's a certain class of analogical reasoning which does produce results that are generally useful: moral and legal reasoning. The guidelines for this reasoning have been developed over the entire life of the human race, and have, in spite of many difficulties, proven both useful and productive.

This kind of argument just seems to me an extension of the typical conservative subjectivism - "well, it seems bad to me, so it's bad as a universal moral rule."

This IS a typical conservative response, although I've usually seen it expressed in a more limited way. Suppose, though, that I tell you my belief: that I feel that ANT is questionable (I feel queasy about it), and therefore I believe that implementing it NOW, without ethical examination, is wrong? This is a conservative response by any definition; is it wrong?

In my opinion, it is not only right, it's necessary. Innovation isn't always bad or good, but it's always new; time is needed to explore the implications before widespread action is taken.

Conservatives will never specify and defend a clear set of criteria defining personhood,

Wow, what an absolute. Haven't there been quite a few attempts at defining personhood? Isn't the definition "every living human is a person" clear? It's not complete, definitely, but it's clear. It may even be inaccurate -- ad argumentum, there may be humans who are not persons -- but it's still a clear definition.

As more borderline cases are explored, this definition has been refined by clarifying what is meant by "living"; this is an ongoing ethical issue.

but are quick to tell you that moral absolutes flow from how things "seem" to them.

Has anyone ever /actually/ told you that? It seems like an inherent contradiction. I'm sure that you meant to say that some people act and speak /as though/ their feelings determine moral absolutes. I suspect that there's a good cause for this behavior: I think most people believe that moral absolutes inform their feelings. If this is true, then a bad feeling is a somewhat reliable indicator that something is morally wrong. Examination and consideration is required to determine whether the feeling actually IS informed by a moral absolute, or whether it's just a leftover feeling caused by improper inculation of a moral absolute.

-Billy