As Wesley J. Smith reminds us here, it looked like the embryonic stem-cell wars might be close to being over beginning in 2007, not because of any ethical conversion on the part of advocates of ESCR, but because of a scientific breakthrough in making pluripotent cells without any damage or harm to embryos. The new technique produces cells known as induced pluripotent stem cells, or iPSCs. Since then, research using them has simply flown. See here for a wealth of articles about iPSC successes in producing various types of cell groups all through reprogramming adult cells. In one experiment, scientists introduced iPSCs directly into a mouse's heart, without reprogramming them, and allowed the surrounding heart cells to do the reprogramming and turn them into heart cells. It worked. Here is a story about producing nerve cells from the skin cells of a patient with Lou Gehrig's Disease (ALS). ALS is a subject about which we have heard a lot from the ESCR crowd; iPSCs have given us what they were hoping for, without destroying embryos. Browse around in the articles to learn more about iPSC research.
The scientific excitement surrounding iPSCs was very well justified. Because they were pluripotent, they had the potential to give us everything that embryonic stem cells were supposed to give us. Pluripotency was exactly what was desired from ESCs, only the ESC research required tearing a tiny embryo to pieces in order to obtain the pluripotent cells of the inner cell mass. Nor does the iPSC creation technique involve cloning. iPSCs could be made from a creature's own adult cells, which would mean that if treatments can be developed using pluripotent cells, there would be no risk of tissue rejection as there would be if the cells were obtained from a non-cloned embryo. Previously, scientists' hope for obtaining such a perfect match came from clone-and-kill.
Now, right at the outset it needs to be said, loud and clear, that both iPSCs and ESCs carry a great big problem that arises from the very feature that makes them so desired--namely, pluripotency. Pluripotent cells obtained from either source have the serious potential to form cancers in the body of mammals into which they are injected. However, insofar as ESCR was hyped as possibly providing a route to treatment for illnesses, iPSCR deserves equal hype, with the additional utilitarian advantages of no tissue rejection risk and no need to work out the remaining practical kinks in cloning.
Moreover, when it comes to plain research on specific diseases (such as this), without re-injecting the cells into a patient's body, iPSCs give us the pluripotency that is desired from ESCs for creating cell lines of various tissue types.
No wonder Smith repeatedly used the headline "lead into gold" when describing iPSC research.
However, while many (and not by any means only conservatives) were rejoicing, there were also sour grapes from others who just couldn't stand the thought that a true substitute, and, practically speaking, an even better substitute, for ESCs (and for human cloning) might have been found. The sour grapes sometimes took the form of distraction or misleading statements, sometimes of vague statements that somehow embryo-destructive research might still be necessary and that the darned conservatives were still trying to stifle something or other, sometimes of misleading on-going hype about ESCs.
Unfortunately, we have also seen some extremely confused reporting about iPSCs themselves which could cause unnecessary ethical worries about iPSC research. A recent example is this article in Forbes's on-line science column by science writer John Farrell. Farrell is apparently getting his information from this article by Paul Krzyzanowski. Entitled "The Line Between Embryonic and Pluripotent Stem Cell Research Is Blurring," Farrell's article reports, following Krzyzanowski, that scientists have used a technique called tetraploid complementation whereby they can take some iPSCs, do some things with them (I shall discuss below what the technique involves and what other entities it involves), and bring an embryo into existence which did not previously exist. That embryo could, of course, then itself be used for research or destroyed. In fact, the scientists made live mice out of the embryos they created. Farrell, again following Krzyzanowski, concludes from this that
iPS cells are very much more like hES than was previously appreciated, so that favoring iPS cell research because because they don’t have the same origin as hES cells may not be a safe solution to the ethical issue for conservatives anymore.
Let's see some other things Krzyzanowski himself has to say about the matter. Well, inter alia, he says this,
“Does this research suggest that every somatic cell in our body holds the potential to become another human?” Krzyzanowski said. “It’s a very deep question about ourselves.”
Golly, very deep. Where have we heard that before? Oh, yes, in the cloning discussion. Raise your hands, class, if anyone else here has ever heard someone on the left try to tell you that, since the DNA of a somatic cell could be injected into a denucleated egg, the whole thing zapped with electricity, and an embryo produced thereby (a cloning technique), this raises "deep questions" about whether all our cells are really potential humans, so maybe conception isn't so special after all, maybe embryos aren't so special after all, etc.? Yes, I figured I wasn't the only one. And it's baloney sausage here, just as it's baloney sausage there. (Spoiler alert: Krzyzanowski is trying to get us confused about whether making iPSCs is somehow ethically or scientifically "really like" making embryos. Don't let him succeed.) Oddly, this obvious red flag about Krzyzanowski's scientific clarity and reliability doesn't seem to have made Farrell suspicious. What else do we get from Krzyzanowski's own article? This:
Thus far, iPS cells have been a less controversial and more acceptable source of stem cells for conservative politicians to promote. While iPS cells have a perfect niche in the stem cell research field, Romney has specifically stated that he “cannot condone the creation of human life for the purpose of destroying it”, which presumes that the creation of human life is a property that iPS cells do not have.
How will Romney’s opinion change in light of these papers, which describe healthy mice being created from iPS cells? The authors of the PLoS Biology report claimed that iPS cell lines can create live, iPS derived mice that survive into adulthood. One iPS cell line was particularily effective: 20 out of 151 embryos yielded adult mice, which were fully composed of iPS derived cells over 90% of the time.
Scientific advances such as these put human iPS cells into the same spotlight that embryo-derived hES cells have been under since 2001. Do these discoveries now mean that in 2012 human iPS cells similarly fall under the “creation of human life” category and that they’re a target for future research prohibition? This is a critical question and researchers and the public need to know what society will do.
Those scary conservatives, always looking to "prohibit" something. Heaven only knows what they are going to go after next! Another couple of hints that Krzyzanowski might not be just exactly the most reliable or politically unbiased reporter on these issues: His implication that the current debate is actually over "prohibiting" research as opposed to not funding it, and his fear-mongering that conservatives, including Romney, who is hardly a firebrand, might be suddenly about to up and "prohibit" iPSC creation, which they previously supported. The political capital Krzyzanowski is trying to make here is fairly evident.
Let's try to get ourselves out of the fog created by these statements from Krzyzanowski (and Farrell). Krzyzanowski is trying to get us to think that maybe, somehow, creating iPSCs is something like making embryos and that making them somehow should now be thought of as "falling under the category of creating human life" because some researchers did something or other with them that ended up resulting in the existence of mouse embryos and eventually mature mice. Farrell tells us that this means that the "line is blurring" between iPS research and ESC research and that some brand-new discovery means that iPS cells are more like ESCs "than was previously appreciated," which has some vaguely ominous ethical implications (to conservatives) for iPS research.
Now, what sounds a little bit "off" right away about that last claim? Oh, yes, maybe it's this: The whole point of iPSCs is that they are supposed to be like ESCs, only not derived by embryo destruction! So how can it be that we somehow "never appreciated" before that they are just like cells derived from embryo destruction, though they weren't derived from embryo destruction? Didn't we know that already? Didn't we, in fact, hope that that was the case? So what's the problem here?
Well, evidently the problem is supposed to have something to do with the fact that researchers made embryos "using" iPSCs. Krzyzanowski manages to give the vague impression that somehow, voila, iPSCs turned into mice. This is also consonant with Krzyzanowski's nonsense about how maybe every somatic cell in our body is a potential human being. Since we know that that is nonsense, that should give us a clue that this is nonsense as well. And as it turns out, it is nonsense for very much the same reason.
Here's what this tetraploid complementation thing is all about: It is a test for pluripotency. Bear that in mind. It is not a way of producing pluripotent cells. Rather, it is one (of several) methods for testing to see if the cells are truly pluripotent. Now, let's review as well what pluripotency means. Pluripotency, as opposed to totipotency, means that a cell is not an embryo and (crucially) has no innate capacity for forming an embryo. Got that? There is nothing about iPSCs that just turns into an embryo. Pluripotent cells lack the potential for forming various structures such as the placenta. Pluripotent cells, whether derived by killing an embryo or by the iPSC reprogramming technique, are (or are just like) the cells of the early embryo's inner cell mass. In order to turn around and get an embryo from them, if for some reason one wants to do so, one has to do either cloning or another technique, tetraploid complementation, that bears some resemblances to cloning.
Here is how tetraploid complementation works (see here, here, and here): Get hold of another embryo from somewhere, at an extremely early stage stage. Fatally damage it by running an electrical current through it, making it tetraploid rather than diploid. This is now your shell, which will make things like the placenta for the embryo you want to manufacture. It will fulfill approximately the same role that an enucleated egg fulfills in cloning. Please note that none of this has anything to do with iPSC research thus far. You can't make a tetraploid fused embryo solely from iPSCs. You actually have to get hold of an embryo. This is just a separate, embryo-destructive step in the process of a test for whether some cells you have on hand (wherever you got them from) are pluripotent. (By the way, for whatever importance this has, not only is tetraploid complementation not something that can be done entirely with iPSC cells, the technique also far predates the iPSC discovery. It's not anything new. It was used for a long time with ESCs. I've traced its use back as far as 1993, and that's just as far as I've been able to trace it so far.)
Once you've manufactured your fused, tetraploid embryo from a normal embryo, inject the cells you want to test for pluripotency, which you might have gotten by destroying another embryo to harvest its inner cell mass or from the iPSC reprogramming technique, into the maimed tetraploid embryo shell. If the cells you inject are truly pluripotent, the shell and the injected pluripotent cells will begin to interact, and you will get a viable embryo of the relevant mammalian type. If you implant that embryo and all else goes well, you will get a mature, furry mouse, or whatever else you were trying to make.
Notice that the iPSCs in this assay are serving something like the role that somatic cell DNA serves in a cloning technique. There, as here, the injected material cannot produce an embryo on its own and has no natural tendency to become an embryo. Rather, it is injected into a shell, and it is the interaction between them that produces an embryo. In other words, in the tetraploid complementation assay, which can be done with either ESCs or iPSCs, the pluripotent inner cells are simply material that is being used in an elaborate process, for which entirely different structures are also necessary, to manufacture an embryo.
Obviously, if this were done with human embryos, it would be unethical from start to finish. The creation of the tetraploid embryo (which is destructive of a living embryo) would be unethical to begin with. The creation of a new embryo by a cloning-like technique would be unethical as a way of producing a human being. And of course if the embryo were then destroyed, this would also be unethical.
However, this is a test for pluripotency, not a means of bringing about pluripotent cells. It is something that some scientists have chosen to do with some iPSCs, just as scientists sometimes do it with ESCs. It is in no way essential to the production of iPSCs nor to their use for producing cell lines or new tissues. What it shows us is that at least some iPSCs really are P, that is, really are pluripotent, but so far from being the bombshell, "previously unappreciated" discovery about iPSCs that we are being told that it is, it merely confirms what was hoped and suspected all along (based on other evidence)--that at least some iPSCs are in fact pluripotent. The fact that they can be used as raw materials in this particular, cloning-like technique, which would be unethical to do with humans, demonstrates their pluripotency in one, particularly stringent, scientific way. Big deal.
Farrell's column indicates that he sent a question by e-mail to Krzyzanowski, though he doesn't say what the question was. In response, Krzyzanowski momentarily moved away from complete scientific obscurantism and admitted that none of this actually is essential to iPSC research:
I don’t think the technique is strictly necessary for generating new stem cell lines[.]... The iPS cells can already maintain growth on their own.
Mr. Krzyzanowski, I wouldn't be surprised if you know quite well that it isn't necessary at all, not just not "strictly" necessary. In fact, we have plenty of iPS cell lines that were produced by reprogramming, which is the whole point of iPSC, not by round-the-barn tetraploid complementation. In some of the research you cite, some scientists took some iPS cells they already had and said, "Hey, let's try this tetraploid complementation assay with a mouse tetraploid embryo and these allegedly pluripotent cells and see what happens." In other words, all this stuff about how maybe making iPS cells is the same thing as the "creation of life" (so the Big Bad Conservatives might want to "prohibit" it) and how maybe every somatic cell in our body has the potential to become a human is junk science. Not to mention political hackery masquerading as science reporting.
Now, someone might say that if scientists were to choose to do the tetraploid complementation assay with human iPSCs, this could be called a type of human "iPSC research," and it would be unethical. Farrell for some reason raises the idea that scientists might make a human embryo by this tetraploid complementation technique, using iPSCs as the inner material, and then destroy that embryo and make cell lines from it. Well, scientists might do all kinds of things. But that certainly wouldn't be the iPSC research that has already created such a stir and so much excitement, it wouldn't be necessary for it, and it isn't what any pro-lifer or politician means if he says that he supports iPSC research. This last point is, please note, one of several things Paul Krzyzanowski is deliberately obscuring. It's also extremely difficult to see what advantage such a roundabout procedure would have over the iPSC research done so far for possible treatment or for producing new tissues genetically identical to the patient. Why first make the iPSCs, then make an embryo through an elaborate process that requires you to find and destroy yet another embryo, then destroy the newly manufactured embryo, then get its ESCs, then make cell lines out of those? You already had embryonic-like cells with which to make cell lines when you had the iPSCs in the first place! (If they hadn't in fact been reprogrammed sufficiently to a pluripotent state to make the tissue you wanted, you would find that out when you tried. The elaborate test of the tetraploid complementation technique for pluripotency doesn't seem to have any practical advantage over simply attempting to induce the cells to make the desired tissue. In fact, far from it.)
I won't lay bets that some scientist wouldn't do this with human iPSCs, out of curiosity if nothing else, but there is certainly no reason to identify it with iPSC research generally nor to say that, because of this sheer possibility, the "line is blurring" between iPSC research and ESC research. Do we say that the "line is blurring" between ethical and unethical drug research simply because some scientist could do research using some drug unethically? The universe would suffer heat death before we finished listing all the things that exist that can be used immorally, but it is merely darkening counsel to say that "lines are blurring" between moral and immoral uses of things just because immoral uses are possible.
Unfortunately, this isn't the first time that Forbes has published an article that made confusing or false statements about iPSCs. About a year ago, Farrell published a column there which was meant to be some sort of criticism of an article by Wesley J. Smith in the Weekly Standard. As Smith pointed out, it missed the mark in that respect, by the odd method of simply not addressing what Smith was actually saying. The 2011 post by Farrell had many problems, but I will not go into them all here because my own post is already quite long thus far. Several of the problems concerned iPSCs: To begin with, it was odd that at no point in the article did Farrell mention iPSCs by name, nor (though he was allegedly talking about alternatives to ESCR) did he acknowledge their potential. Considering that iPSCs have been such a major breakthrough as an alternative to ESCs, this was a truly misleading omission. But worse, Farrell actually said,
For diseases like diabetes, for example, and Amyotrophic lateral sclerosis, the absence of endogenous stem cells requires researchers to look at embryonic stem cells, as these are the only ones that can potentially replace the cells lost or destroyed by those conditions.
This is flatly false and has been already shown to be false regarding ALS. This article by Farrell was posted in 2011. Already in 2008 neurons had been made from an ALS patient using iPSCs! One could have learned about this research by reading Smith, but Farrell disdains Smith as "a typical example of a social conservative who can only view science through an ideological lens," so maybe he wasn't reading him in 2008 and hence missed some facts that could have enabled him to avoid making an error as a science writer in 2011.
But it gets even worse yet. Farrell does appear to allude to iPSCs, though without naming them, at just one point in his article, where he says,
[Weekly Standard readers] should also be aware that even reprogrammed differentiated cells, which social conservatives have also applauded as an alternative to embryonic stem cells, can be derived from both embryos and adults. And in order to be of any real use, they must be introduced into de-nucleated eggs in order to generate cell lines.
Those dumb social conservatives! Some of them might not know the (irrelevant) fact that one could derive iPSCs from differentiated cells in embryos rather than deriving them from differentiated cells in adults. Er, wait a minute: Who cares? Are we trying to treat embryos? Are we looking for DNA-matched tissues for embryos? Is there some special importance to iPSC research about taking differentiated cells from embryos rather than adults? (Answer to that: No.)
But then we come to the real jaw-dropper: Assuming that Farrell is here talking about iPSCs, and it doesn't seem that he can be talking about anything else, he states that they must be introduced into denucleated eggs in order to "be of any use" for generating cell lines. What??? This is a howler of epic proportions for a science writer to make. iPSCs have always been understood to be an alternative to techniques that involve the use of denucleated eggs (in other words, cloning techniques) for generating cell lines. Here is just one of many articles that makes that clear. Here is another, which says,
This new procedure circumvented the need for an oocyte, which is required by an earlier method of generating customized pluripotent stem cells termed somatic cell nuclear transfer (SCNT)-mediated nuclear reprogramming.
For the record, anyone who has been a regular, careful reader of Smith would have known that and would not have made that blunder. Yet according to Farrell it is Smith who views science through an ideological lens. Something is very odd here. Perhaps Farrell should instead consider Smith to be a more reliable source as a starter for his science writing than whatever sources he is presently using. Naturally, further research is always possible and desirable, and Smith always provides links to facilitate that process.
Let there be no misunderstanding: If iPSC research were unethical, then the chips would have to fall where they may. Back when we were being told, with a suspicious amount of hype and violin playing, that ESCR would provide CURES and was the only thing that would provide CURES, we pro-lifers rightly stood firm and said, "It's never right to do wrong to do right. Killing innocent human beings at any stage of development is never justified as a means to an end, even if that end is healing other human beings." And if there were something intrinsically immoral about iPSC research as well, we would have to oppose it, regardless of its potential. At one time I was worried myself that there might be something immoral about it (for a rather esoteric reason), but I changed my mind on the basis of additional information. Moreover, it should go without saying that, if scientists without a good moral compass do start doing unethical things with iPSCs (like using them in embryo-destructive research), pro-lifers should and presumably will condemn that specific research.
But it will not help us in our moral reasoning to have scientific information presented obscurely and vaguely, not to mention misleadingly. At this point, I would be willing to go out on a limb and predict that, if you see someone saying that "the line is blurring" between different forms of stem-cell research, further investigation will show that there is no blurred line at all but only blurred thinking. Let's put our glasses on and keep our vision clear.