StemCellResearch

Life at Four Cells Old
Authors Mount a Philosophical Defense of Human Life in Earliest Stages

By Father John Flynn, LC

ROME, APRIL 13, 2008 - Stem cell research using material taken from human embryos continues to be hotly debated. Advocates of using embryos maintain that at such early stages, the cells cannot be considered a human person. However, a recent book by two philosophers argues the contrary.

Robert P. George, who is also a member of the President's Council on Bioethics, and Christopher Tollefsen, avoid religious-based arguments and lay out a series of scientific and philosophical principles in favor of the human status of the embryo. In "Embryo: A Defense of Human Life" (Doubleday), they maintain that the status of a human being commences at the moment of conception.

The book starts by recounting the history of a boy named Noah, born in January 2007. He was rescued, along with other frozen embryos, from the disaster that struck New Orleans in 2005. It was Noah's life -- a human life -- that was saved, George and Tollefsen point out, the same life that was later implanted in a womb and was subsequently born.

A human embryo, they continue, is a living member of the human species even at the earliest stage of development. It is not some type of other animal organism, or some kind of a clump of cells that later undergoes a radical transformation. Barring some kind of tragic accident, a being in the embryonic stage will proceed to the fetal stage and continue to progress in this development.

The point at issue, according to the authors, is at what stage we can identify a single biological system that has started on the process to being a mature human being. This decisive moment, they argue, comes with conception. Some medical experts believe it happens slightly after, with the formation of the united chromosomes of the sperm and egg. In any case, continue George and Tollefsen, there is widespread agreement among embryologists that at the latest, a new human individual comes into existence once the chromosomal structure is formed.

They argue that there are three key points to keep in mind regarding the human status of the embryo.

-- From the start, it is distinct from any cell of the mother or the father.

-- It is human in its genetic makeup.

-- It is a complete organism, though immature, and unless prevented by disease or violence, will develop into the mature stage of a human being.

Consequently, destroying human embryos, even at an early stage, in order to obtain stem cells for research or medical treatment is giving a license to kill a certain class of human beings in order to benefit others.

Not just science

Faced with such a situation, George and Tollefsen reject the position that it should be scientists who alone determine what they do in their research activities. The problem with the embryonic stem cell issue is that the pace of technology has run ahead of a discussion about the nature and value of human embryos, the authors contend.

Opposing such research does not place us in a classic sort of science versus religion situation, they affirm. Opposing the destruction of human life in its initial stages does not have to rely on religious principles, or on believing that such a life has been endowed with a soul, the book adds.

Purely philosophical reason is sufficient to guide us in determining what is ethically licit to do with human embryos. In this sense, defending the rights of an embryo is similar to defending people against unjust discrimination, argue George and Tollefsen.

They admit there are differing moral philosophies. One theory to discard is that of consequentialism, which leads us to the position that there are some human beings who must be sacrificed for the greater good.

George and Tollefsen found their ethical position on natural law theory, which leads to the conclusuion that it is morally wrong to damage or destroy a basic human good. If, therefore, a scientist were to seek a cure for some disease, but the method involved deliberately destroys human life, then it is not licit.

The one basic human right, in fact, that almost all natural law theorists agree upon is that of an innocent person not to be directly killed or maimed. The capacity of the human being to reason and choose freely sets us apart and gives us a dignity higher than other living beings. An assault on human life is, consequently, an assault on human dignity, no matter the victim's age or stage of development, the authors conclude.

Persons

One of the book's chapters deals with the objection that while an embryo may be human it is, nonetheless, not a person and does not have the same dignity or rights. George and Tollefsen reply that such a view is mistaken, as it falls into the error of considering that some human beings are inferior to others on the basis of accidental characteristics.

In fact, they continue, denying the status of personhood based on a capacity for mental capacities or other parameters of functionality poses many problems. Are we to be allowed to kill newborn babies, given that they too are unable to carry out basic human functions?

Rather, we should realize that a mere quantitative difference in capacity is not the correct criterion for determining rights, as it is only a difference of degree. The real difference is between human beings and all other non-human animals, which is a radical difference of kind. Thus, the embryo is a potential adult in the same way that infants, children and adolescents are potential adults.

Embryos are, they insist, already human beings, and are not merely potentially human. Moreover, the right to life of a human does not vary according to the stage of its development because it is the foundational right for persons. "It is the right on which all other rights are predicated, and marks whether a being is a being of moral standing at all," continue George and Tollefsen.

Fallacy

Another fallacious argument is that which maintains that embryos are not worthy of a full moral status because a high percentage of them fail to implant in the mother's womb or spontaneously abort. The authors point out that this is a naturalistic fallacy, supposing that what happens in nature must be morally acceptable when caused by human action.

The falsity of this reasoning is also evident, George and Tollefsen point out, when you consider that historically, infant mortality has been very high. In such a situation just because many young babies died does not make it ethically licit for them to be killed to benefit others.

Another line of reasoning used to defend research with embryonic cells is that there are many thousands of frozen embryos who remain unwanted following artificial fertilization treatments, and who will never have a chance to be implanted and grow to maturity. A scientist could use these cells for the good of research.

George and Tollefsen reply, saying that this it is manifestly unfair to demand that a person -- in this case the embryo -- sacrifice his life in this manner. "Human beings have a moral right not to be intentionally killed to benefit others," they declare.

They also argue that it is an error to condemn hundreds of thousands of human lives to a sort of frozen limbo. Thus the process of creating and freezing such embryos needs to questioned, state the authors.

We need to turn our attention to their fate, George and Tollesen recommend, not by using embryos as if they were some kind of biological material, but by acknowledging their humanity. These and other persuasive arguments in the book make it valuable reading at a time when science is at danger of running ahead of our ethical reasoning.

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Of Cybrids, Hybrids, & Chimeras
Learning from the U.K. battle over human-animal hybrids.

By Father Thomas Berg October 23, 2007 4:00 AM

In September, Britain’s Human Fertilization and Embryology Authority (HFEA) approved the concept of creating hybrid embryos by merging human cells with animal eggs for research purposes. Essentially a form of cloning, the procedure requires scientists to fuse a normal human body cell with a non-human animal egg — of a cow or a rabbit for instance — stripped of its own nucleus. Once fused, factors remaining in the non-human egg would initiate processes by which an embryonic organism would develop. Whether the non-human source of eggs are remotely genetically related (cow eggs) or proximately related (monkey eggs), the resulting product (called by some a “cybrid”) would, in the opinion of leading experts in mammalian cloning, be essentially human, save for the negligible influence of the non-human genetic material (the mitochondria) found afloat in the enucleated egg.

From such embryos, British researchers want to extract embryonic stem cells. By creating clones from the cells of patients suffering from incurable genetic diseases such as ALS (Lou Gherig’s disease), researchers hope to develop matching lines of stem cells that carry the disease, and to use them to develop therapies. Ian Wilmut, creator of Dolly the Sheep, believes that studying cells derived by the hybrid method cannot be matched by doing similar studies in merely animal models. He points out that these cells could also be used for testing drugs, and for perfecting the cloning technique. Using animal eggs would allow researchers to by-pass ethical concerns regarding the use of human eggs. And under current law in the U.K., the hybrid embryos would be destroyed after 14 days.

As might be expected, the idea of creating human-animal hybrids provoked repugnance in the general public. In response, the HFEA conducted a three month long “consultation,” a mix of polling, town hall style meetings, and debates. This was coupled with months of heavy lobbying by proponents of the technique who claimed at one point that a ban on hybrid cloning “would cost patients’ lives.” According to the HFEA report, once the public was presented with “factual information” most of the respondents “became more at ease with the idea.”

The U.K. human hybrid debate should supply us with several insights about how to revitalize our own intractable national debate over ethical stem cell research. Here are just a few.

Let’s be honest about the ethical limitations of the “yuck factor.”
The first thing the HFEA had to deal with was the generalized public revulsion at the idea of crossing human DNA with animal eggs. While the yuck factor is at times a useful rule of thumb in moral matters and deserves our careful attention, one must admit that it fails to constitute a sufficient basis for reasonable ethical judgments. Centuries ago, the novel prospect of cutting open and studying human cadavers was met with repugnance and deep moral suspicion; in more recent times, the idea of organ donation met with similar reactions in some quarters. Both were eventually accepted. How many long-accepted medical interventions still cause repugnance? And recent biomedical advances such as the use of porcine heart valves in cardiac patients, the growing of human livers in laboratory animals for study as disease models, or the fusing of non-reproductive cells from human and non-human tissues to study chromosomal behavior — all forms of human-animal chimera formation — while perhaps causing some emotional discomfort are surely morally licit.

On the other hand, if arguably a majority of Americans rejects outright other kinds of human-animal hybrid formation, it is for reasons that go well beyond emotional repugnance. The cross-fertilization of human and non-human egg and sperm, (i.e., the creation of “humanzees”); the grafting of non-human animal stem cells into a human embryo or fetus or vice versa; or bringing about the gestation of a human fetus within a non-human animal womb — all such proposals normally provoke disgust; but if they garner our moral opprobrium, surely it is out of respect for human dignity and not simply because the “yuck” factor has collectively kicked in.

Let’s debate issues of substance free of scientific disingenuousness.
Why, we should ask, do more than a few researchers hold out so remarkably little hope of success for the experiments currently under consideration by the HFEA — to use rabbit or cow eggs to clone human cells? Sir John Gurdon, a pioneer of cloning at Cambridge University, fears these experiments will yield “a lot of genetic abnormality that won't lead to good quality stem cells". Neville Cobbe, a geneticist and cell biologist at the University of Edinburgh, writing in the journal Zygon this month, questions the feasibility of modeling these diseases — many of which are late on-set conditions — in embryos when we have only fleeting knowledge of the genes and proteins that cause those diseases. These problems would be further exacerbated by using bovine or murine eggs so distantly related to the human genome. Another leading expert on mammalian cloning, Shoukhrat Mitalipov of Oregon Health and Science University, agrees that “interspecies cloning only works with very close species.” He describes as “very slim” the chances that bovine eggs would reprogram human cells into embryonic stem cells, and points out that several labs have tried these experiments for almost a decade with no success.

This suggests that these scientific proposals are mere test cases to measure the social acceptability of controversial science. But rather than engaging these questions openly, some scientists prefer to do an end-run around public deliberation and force the issue in the laboratory.

The real issue here is the social acceptability of allowing science to cross heretofore inviolable moral boundaries. The British human-animal hybrid debate is a poor proxy for robust moral discussion of the two issues it conceals: the moral licitness of human cloning for research purposes, and the further issue of mingling human and non-human cells in a reproductive manner.

In the U.S., we would do well to continue this debate in earnest, keeping it in the public square where it belongs, while avoiding the pitfalls of investing time, energy and public resources in junk science as a substitute for substantive public moral discourse. While respecting contrary views, I personally believe that as a nation we should reject any form of human-non-human hybrid formation on the same grounds for which I and millions of Americans reject human cloning: human embryos have a privileged moral status and should not be treated as raw material for medical research. There is also a reasonable resistance to creating a market for human eggs and the likely exploitation of women to obtain the eggs.

Let’s invest in research that shows greatest potential for near-term scientific and clinical benefits while bridging the moral divide.
If cures and therapies are really the name of the game, let’s invest in research that is scientifically promising while purporting to avoid the ethically charged issue of destroying human embryos, such as: the reprogramming of ordinary somatic (body) cells, the procurement of embryonic stem cells from already dead embryos, ways of altering the cloning process so as to avoid the production of human embryos altogether (“altered nuclear transfer”), the derivation of stem cells from umbilical cord blood, and the use of a patient’s own adult stem cells.

I myself believe that embryo-destructive research cannot be morally justified, even if it were to become the source of cures for dreaded diseases. Yes, once upon a time, the ideas of studying human cadavers, and donating organs were deemed an affront to human dignity. And with time this moral objection was judged as groundless. Some today believe opposition to using human embryos for research is another cultural taboo which will also pass with time. I disagree. Neither the carving of cadavers nor the transfer of viable organs requires a willingness to kill a living human individual. Embryo destructive research does just that. It takes the life of a human individual in his or her earliest stage of development. Biomedical science fails humanity when it deliberately destroys human life in the pursuit of trying to cure it.

— Rev. Thomas Berg is executive director of the Westchester Institute for Ethics and the Human Person, and member of the ethics committee of New York’s Empire State Stem Cell Board.

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Is therapeutic cloning obsolete?
After years of urging the public and governments to support the destruction of embryos, scientists may have led them up a blind alley.
Michael Cook | Saturday, 16 June 2007

Next week the international grandees of therapeutic cloning gather in Cairns, Australia, the sun-soaked gateway to the Great Barrier Reef, for their annual conference. They have serious strategic issues to deal with along with their scientific papers and posters: persuading governments to open their wallets, ensuring that the Bush Administrations restrictions on their work are lifted, allaying the public's qualms about creating embryos solely for research.

But one issue will dominate: ten years after Dolly the sheep was cloned, is therapeutic cloning ready to be mothballed?

Only a few days ago an article in the leading journal Nature brought amazing news. (1) A Japanese team at Kyoto University has discovered how to reprogram skin cells so that they "dedifferentiate" into the equivalent of an embryonic stem cell. From this they can be morphed, theoretically, into any cell in the body, a property called pluripotency. It could be the Holy Grail of stem cell science: a technique which is both feasible and ethical.

"Neither eggs nor embryos are necessary. I've never worked with either," says Shinya Yamanaka. (2) The first instalment of his research appeared a year ago -- and was greeted with polite scepticism by his colleagues. At the time they were mesmerised by dreams of cloning embryos and dissecting them for their stem cells.

The previous head of the International Society for Stem Cell Research, Lawrence S. B. Goldstein, had even dismissed reprogramming as quixotic. "If there are scientists who morally oppose [embryonic] stem cell research and want to devote their energies to uncovering alternatives, that’s fine," said Goldstein. "But in no way, shape, or form should we ask the scientific community and patient community to wait to see if these new alternatives will work." (3) Now, however, ten years after Dolly, not one scientist anywhere using a cloned human embryo has created a stem cell line. Not one. And a Japanese Don Quixote has.

This is mainstream research, not an eccentric theory from wild-eyed pro-lifers. Yamanaka's work has been confirmed by two other teams affiliated with the Massachusetts Institute of Technology, Harvard University and the University of California, Los Angeles -- both of them headed by ardent supporters of embryonic stem cell research.

They say that the reprogrammed cells meet all the tests of pluripotent cells -- they form colonies, propagate continuously and form cancerous growths called teratomas, as well as producing chimaeras. "Its unbelievable, just amazing," says Hans Schöler, a German stem cell expert. "For me, it's like Dolly. It's that type of an accomplishment." (4)

What Yamanaka did was to take a mouse skin cell and introduce into it four proteins which trigger the expression of other genes to make it pluripotent. "It's easy. There's no trick, no magic," he says. Naturally, it's easy only for experts at the moment. There are some worrying issues to contend with: one of the proteins seems to contribute to cancers in 20% of the mice. But since cancers are the Number One problem with embryonic stem cells as well, it is not surprising that stem cells induced to an embryonic state share this embryonic flaw.

Harvard researcher Chad Cowan says that it will change the field: "The most amazing thing about these papers is you now take this whole idea of reprogramming out of the hands of cloning specialists and put it into the hands of anyone who can do molecular and cell biology." (5)

Now the race is on to apply the technique to human cells. "We are working very hard -- day and night," says Yamanaka.

Will this disruptive technology open up ethical avenues in the promising field of stem cell research which do not involve turning women into battery hens for their eggs and destroying embryos?

At the moment, the stem cell grandees, like all establishment figures, have no plans to change their tune. One of the stars of Cairns, MIT's Rudolph Jaenisch, told Nature that therapeutic cloning remains "absolutely necessary".

And executives from embryonic stem cell companies were not optimistic about the new technique either. Because it involves tinkering with the genome, it could be dangerous, warned Thomas B. Okarma, of Geron, the leading private company in the field. Getting approval from regulatory authorities would therefore become far more complicated. (6) What else could he say? No doubt manufacturers of video tapes muttered about serious flaws in DVDs when they first appeared on the market.

With an ethical solution looking quite plausible, the pressure will be on scientists to justify embryonic stem cell research. Two years ago, Dr Janet D. Rowley, an Australian working in the US who is an implacable foe of the Bush Administration's policy, dismissed ethical solutions. "We have extremely limited research dollars, and to use them to study these alternatives is wrong," she declared. "That money should be available for actual research." (7) But now stem cells derived from embryos are starting to look like dead-end "alternatives".

Don't expect supporters of embryonic stem cell research to respond rationally, not in the short term, at least. The other day, Democratic Caucus Chairman Rahm Emanuel told the US House of Representatives as he voted to overturn the Bush policy: "It is ironic that every time we vote on this legislation, all of a sudden there is a major scientific discovery that basically says, 'You don't have to do [embryonic] stem cell research.' " (8)

Connect the dots, Mr Emanuel. Maybe you don't have to.

Michael Cook is editor of MercatorNet.

Notes

(1) "Simple switch turns cells embryonic". NewsNature. 7 June 2007.

(2) "Simple switch turns cells embryonic". NewsNature. 7 June 2007.

(3) "Scenarios for stem cell creation debated". JAMA. 22/29 June 2005.

(4) "Simple switch turns cells embryonic". NewsNature. 7 June 2007.

(5) "Teams Reprogram Differentiated Cells -- Without Eggs." Science. 8 June 2007.

(6) "A Long, Uncertain Path for New Cell Technique." New York Times, 7 June 2007.

(7) "Scenarios for stem cell creation debated". JAMA. 22/29 June 2005.

(8) "Darn Cells. Dividing Yet Again!" Washington Post. 10 June 2007

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Real Stem-Cell News
New developments point toward a consensus solution and away from the Democrats' bill.
By Yuval Levin June 6, 2007

ARTICLE
National Review Online
Publication Date: June 6, 2007

The politics of stem cells are stuck in a repeating loop. This week, the House of Representatives will again take up a bill to overturn President Bush's embryonic-stem-cell-funding policy, and to use taxpayer dollars to encourage the destruction of human embryos for research. The Congress already passed such a bill last year, and the president vetoed it. In fact, the House already passed that bill again just this January, the Senate passed a slightly altered version in April, and now the House is passing that Senate version to send it to the president. The replay will continue next week, too, when President Bush again vetoes the bill, and the Congress once more fails to come up with the votes to override the veto.

And yet on the ground stem-cell science is hardly in a state of déjà vu. While opponents of the Bush policy again and again trot out their tired arguments in Washington, scientific developments continue to point in a different direction -- away from the false opposition of science and ethics and toward a potential consensus solution.

That solution, if it pans out, would involve the production of cells with the characteristics and abilities of embryonic stem cells, but without requiring the destruction of embryos. The President's Council on Bioethics examined a few possible ways of doing this in a brief paper two years ago, and since that time just about all the possibilities they examined have seen some real-world progress. The most appealing of the techniques they looked at involves chemically reprogramming adult cells to function like embryonic stem cells -- essentially producing the kind of cells researchers want but without the need for an embryo.

In its 2005 report, the bioethics council considered such "somatic cell reprogramming" the most ethically attractive but least scientifically feasible of the alternatives they examined. But they were wrong on the latter point. Within months of their report, studies began to emerge showing real progress toward such reprogramming. A team at Harvard took one key step in August of 2005, another in Japan published an impressive advance last summer, and word has trickled out from several labs of similar efforts underway.

Today, that trickle has turned into a serious flow. The coming week's issue of the journal Nature, made available online this morning, contains several extensive reports of surprisingly significant advances toward full-blown somatic-cell reprogramming.

The key publication comes from a team at MIT led by the prominent stem-cell scientist Rudolph Jaenisch. Working in mouse cells, they took the results of the 2006 Japanese effort, corrected some key flaws, introduced several improvements, and produced cells that appeared to pass all the critical tests of so-called "pluripotency" -- the ability to be transformed into a large variety of cell types, which scientists so value about embryonic stem cells.

The team states its startling conclusion in the usual mild-mannered scientific deadpan: "Our results show that the biological potency and epigenetic state of in-vitro-reprogrammed induced pluripotent cells are indistinguishable from those of embryonic stem cells." They assert with confidence that their findings "establish that somatic cells can be reprogrammed to a pluripotent state that is similar, if not identical, to that of normal embryonic stem cells." In other words a regular adult cell, like one of your skin cells, can be turned into the equivalent or near-equivalent of an embryonic stem cell, and without the need for any embryos. These are truly astonishing findings, unimaginable just a few years ago.

This is just one study, to be sure. But it is one of several published just this week, and one of a growing number over the past two years that begin to establish more firmly the principle that embryo-destruction may simply not be necessary for the benefits that scientists have found in embryonic stem cells. The Jaenisch paper, and the others published this week, seem likely to become lasting landmarks on the path toward ethically uncontroversial stem-cell science.

But the Democrats in Congress have barely noticed any of this. The latest iteration of their stem-cell funding bill does include some language offering support to the development of these alternatives, but it comes joined to language that would use taxpayer dollars to encourage embryo destruction. Even as they gesture toward the possibility of common ground, they push it away and turn their backs. Indeed, today, in advance of tomorrow's stem-cell funding vote, the Democratic leadership reportedly plans a vote on a bill to protect the practice of producing human embryos by cloning and then destroying them for research (and in the usual Orwellian fashion the bill presents itself as a ban on human cloning).

Now more than ever, the premise behind President Bush's stem-cell funding policy -- that science and ethics can be championed together, rather than set in opposition to each other -- seems supported by the latest stem-cell science. And now more than ever, the course chosen by the leaders of Congress seems like pure political cynicism.

-- Yuval Levin is a fellow at the Ethics and Public Policy Center and senior editor of The New Atlantis magazine.

Father Thomas Berg: Stem Cell research

iPSCs: What the Scientists are Saying November 27, 2007

Allegory of the Seven Liberal Arts by Marten de Vos

The News last week that separate teams of scientists had managed to reprogram
human skin cells to be the virtual functional equivalent of human embryonic stem cells, sent a shock wave through the scientific world. The reprogrammed cells-called induced pluripotent state cells (iPSCs)-are produced without damaging, destroying or even involving human embryos.

After the Japanese team led by Dr. Shinya Yamanaka reported further successes in reprogramming mouse skin cells last June, no one expected that only five months later he would already be reporting on successes with human cells.

But what has been perhaps most surprising, not to say amazing, is what stem cells scientists themselves-many, ardent advocates of embryonic stem cell research-have been saying about this new alternative to embryo-destructive stem cell research.

Ian Wilmut and Dolly the Sheep

First there was Dr. Ian Wilmut, the creator of Dolly the sheep, who, foreseeing the successes that were coming in reprogramming (which renders the cloning of embryos for their stem cells obsolete) announced two weeks ago that he was abandoning cloning. "Reprogramming," he was reported to have said in the London Telegraph, "is the future of stem cell research" possessing as it does "so much more potential" than standard ESC research.

Allegory of the Seven Liberal Arts by Marten de Vos
Dr. Yamanaka affirmed that "Any scientist with basic technology in molecular and cell biology can do reprogramming." Dr. Doug Melton, a stalwart advocate of ESC research and of human "therapeutic" cloning affirmed in the New York Times that "anyone who is going to suggest that [reprogramming] is just a side show and that it won't work is wrong." And Alta Charo, a UW-Madison professor of law and bioethics, and popular secular voice on the ethics of stem cell research said the discovery "could be a game-changing event."

James ThomsonThen, of course, to top these and many other declarations, there was an interview last Wednesday in the New York Timeswith Dr. James Thomson of the University of Wisconsin at Madison, who lead the other team that reported successful reprogramming and who is himself the first scientist to isolate human embryonic stem cells, the feat that initiated the great stem cell controversy in the U.S. "Now with the new technique, which involves adding just four genes to ordinary adult skin cells," affirmed Thomson, "it will not be long...before the stem cell wars are a distant memory." "A decade from now," he said, "this will be just a funny historical footnote."

Affirmations like these have led many of us to ponder whether or not we now indeed find ourselves-happily-at the end of the stem cell wars. Only time will tell. Voices to the contrary have certainly not been lacking. A chorus of voices have also been insisting that all avenues of research need to go forward, including embryo-destructive research. The reasonableness of such claims, however, has been dealt a serious blow. To the general public, the concept of ethically uncontroversial research which now holds out the same promise as human ESC research and can be used immediately in the laboratory, is not a difficult sell. As Institute senior Markus GrompeMaureen Condicfellows Maureen Condic and Markus Grompe affirmed in a TheWall Street Journal op-ed last Friday:

iPSCs are clearly superior to embryo-derived ESCs. Pluripotent stem cells can be used to study "developmental biology in a dish." They enable researchers to observe how human organs and tissues form. The insights garnered from such studies are likely to lead to the development of new drugs and strategies which can benefit human health.

Direct reprogramming techniques make it possible to generate pluripotent cells from specific individuals, including those with particular diseases. It will be possible to make iPSCs from children with Fanconi's anemia, a devastating genetic disease, and to study the effects of candidate drugs on the formation of human blood. These kinds of experiments are now immediately possible and likely will be the first practical application of iPSCs. (Emphasis added).

Not a hard sell to a nation that is by and large exhausted-or simply fed up-with the controversy surrounding the use of embryos for research. Add to all this the technical ease and cost-effectiveness of somatic cell reprogramming, and one cannot help but imagine a noclick heret-so-distant future in which the sad spectacle of embryo-destructive research has become for the most part-as Dr. Thomson says-a footnote in the history of science. Let's hope so.

NOTE: More information about iPSCs, including background, papers and commentary, is available at our website: www.westchesterinstitute.net.

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THE FUTURE IS NOW: Stem Cell Debate Changes
by Father Thomas Berg, LC

Father Thomas Berg - Director
It's called 'reprogramming'.

Another technical term for it is 'somatic cell dedifferentiation.' Just get those terms into your vocabulary because they'll be around for the foreseeable future. As reported in two scientific papers published today, reprogramming is now the future of stem cell research and renders ethically controversial therapeutic cloning obsolete.

Ever since the debate of embryo-destructive stem cell research began in earnest in 1998 when researchers at the University of Wisconsin first isolated human embryonic stem cells, we've known that the best overall answer to the ethical impasse would be a solution that both allows the search for stem-cell related cures to go foreword, while doing so without harming or destroying embryonic human life in the process.

We now have that solution.

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Altered Nuclear Transfer
Date: April 12, 2007

In the search for scientifically and ethically acceptable alternatives to embryo-destructive stem cell research, altered nuclear transfer (ANT) requires particularly close analysis, due both to its complexity, and to its potential as a scientifically acceptable substitute source of embryonic-like stem cells, and substitute platform for the kinds of research otherwise afforded by actual living human embryos.

ANT is the conceptual proposal advocated by Dr. William Hurlbut of Stanford University and member of the President's Council on Bioethics. In ANT, a normal adult body cell is genetically modified. In its nucleus, genes essential for normal embryo formation are drastically altered. This cell is then implanted in an egg with its nucleus removed—the same technical procedure used in cloning. Theoretically, however, the resultant product of the procedure would not be an embryo, but a disordered biological artifact, capable of yielding embryonic-like stem cells, but otherwise more akin to very unusual tumors called teratomas which can, although rarely, form spontaneously for example in female ovaries.

In October, 2005, the journal Nature reported that MIT researchers Alexander Meissner and Rudolf Jaenisch had, for the first time, used ANT in laboratory mice to derive a line of “fully competent” mouse embryonic stem cells. Their use of the procedure produced what were arguably not mouse embryos, but rather disorganized masses of cells that appeared to lack the organization necessary to be considered genuine mouse embryos. The Meissner/Jaenisch research constituted proof of principle that ANT works scientifically—at least in mice.

Since December of 2004, I have been working extensively with a group of scientists and moral theologians in the on-going moral evaluation of ANT, beginning with a Scholars Forum dedicated to this question in April of 2005. The continuing point of moral concern (because of its conceptual proximity to human cloning) is whether it can be shown with moral certainty that this procedure would not give rise to a human embryo if done with human cells. Of course, even if that could be shown, we would require further assurances that its broad application could be pursued in a manner that would not involve the use of human eggs (thus avoiding the further ethical pitfall of creating yet another venue for the potential exploitation of women for their eggs in the name of scientific research).

Out of that April 2005 gathering emerged a joint statement signed by more than 30 leading moral philosophers and theologians. We wrote at the time:

Our proposal is for initial research using only nonhuman animal cells. If, but only if, such research establishes beyond a reasonable doubt that oocyte assisted reprogramming [ANT] can reliably be used to produce pluripotent stem cells without creating embryos, would we support research on human cells

Our work on this issue has generated both hope and controversy—a good deal of which was chronicled in an article in the January 2006 issue of Crisis magazine.

We will rightly remain cautious on ANT until further research on animals (particularly on primates) can give us greater assurance that the product of ANT would not be an embryo—that, of course, remains the crucial moral question. Only further animal research, coupled with continued philosophical and theological reflection, could potentially afford us a reasonable degree of moral certainty that ANT pursued with human cells would not render a human embryo.

The value of ANT, if it can be shown to be ethically acceptable, lies in what it offers science: (1) a reliable source of stem cells (essentially equivalent to normal human embryonic stem cells); (2) a reliable method for generating patient-matched cells for growing replacement tissues (in other words, an acceptable substitute for so-called ‘therapeutic cloning'); and (3) a workable platform (the ANT product) for pursuing other kinds of research not immediately related to the search for cures.

Over the past two years, I have seen growing indications that not a few scientists, preferring to avoid the moral controversies entailed by embryo-destructive research, would be satisfied with just such an alternative.

So, here at the Institute, our moral analysis of ANT is on-going. The prospect of a future in which the human embryo constitutes the research platform of choice for the biotech industry compels us to consider ANT and all the proposed alternatives with principled and rigorous moral analysis. We sustain the hope that our on-going analysis of these alternatives, coupled with absolute respect for human life, will lead us to clear determinations about morally acceptable solutions.

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This post is part of short series of posts I am dedicating to explore in greater detail a couple of these alternatives. I've already written about one of these, namely, direct cell reprogramming. Today I want to explore the concept of removing single cells from “naturally dead” embryos obtained from in vitro fertilization (IVF) clinics.

This method was first proposed by Drs. Donald Landry and Howard Zucker (both of Columbia University ) in a paper in the Journal of Clinical Investigation.

Their proposal rests on the scientific possibility of deriving new lines of human embryonic stem cells from just a few cells extracted from these “dead” embryos. The proposal also hinges on the close association of the concept of removing cells from “naturally dead” embryonic human beings, and the concept of organ donation from deceased, fully developed human beings.

But how would we determine whether left-over IVF embryos have, in fact, expired, and how would we distinguish them from those embryos that are simply doomed or already in a process of dying? The Landry/Zucker proposal formulates a notion of embryonic (natural) death drawing on the criteria for assessing death of a developed human. Fully developed human beings are normally considered dead when they have irreversibly lost the capacity for integrated organic body function. The commonly accepted indicator of this loss is “brain death” or the complete cessation of all spontaneous brain activity. And while brain death may come about (marking the consequent loss of a capacity for integrated body function), millions of cells and any number of whole organs remain alive.

Landry and Zucker's proposal is that an embryo is naturally dead when the embryo has irreversibly lost the capacity for integrated cell division, even if some of the individual cells are alive.

Dr. Landry spoke to Senate staff last week as part of a briefing sponsored by the Westechester Institute. He noted in his presentation that current research has shown that no embryo that has been arrested (ceased cell division) for more than 48 hours ever recovered. Concluding that such arrest is irreversible , Landry posited that this marks the threshold for meeting the criteria for natural embryonic death: irreversible loss of integrated organic function, indicated by a 48-hour period of cessation of cell division.

Notwithstanding some ethical concerns that still require further reflection, along with many other Catholic ethicists I am hopeful that those concerns can be allayed, and that the Landry/Zucker proposal will quickly move into the mainstream as an ethically and scientifically viable alternative to embryo-destructive research.

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Embryo-friendly Stem Cell Research
Date: April 02, 2007

Upon their return after Easter recess, United States Senators are expected to take up debate on two stem cell bills. They've been through this same exercise before—last July, to be precise. One bill, S.5 , which already passed the House in January, proposes to broaden federal funding for embryonic stem cell (ESC) research. It is identical to the legislation passed in House and Senate last July, championed in the House by representatives Mike Castle (R-Del) and Diane DeGette (D-Colorado), and in the Senate by Arlen Specter (R- Penn), and which became the object of President Bush's first-ever veto. If approved in the Senate, the rehashed legislation is destined for yet another presidential veto, without—it would seem—enough votes (67 would be needed) for the Senate to override the veto.

Of interest here, however, is a second bill the Senate will debate. S.30 , sponsored by Sens. Johnny Isakson (R-Ga.) and Norm Coleman (R-Minn.), seeks to direct federal funding to research on alternative sources of embryonic-like stem cells, alternatives that do not involve the creation, damaging or destruction of human embryos (something necessarily involved in standard embryonic stem cell research.) A very similar bill passed the Senate unanimously last July, but was stalled in the House .

I want to take advantage of this development to dedicate a brief series of posts on my blog to explore several issues related to these alternative sources. First of all, as Dr. Robert George and I asserted in The Wall Street Journal two weeks ago, it is increasingly clear that ethically and scientifically acceptable alternatives to embryo-destructive research may well be within reach. These alternatives would appear to hold out the promise of providing stem cells with properties equivalent to, or nearly equivalent to, embryonic cells, but without involving the use (and destruction) of human embryos as a means to an end.

In recent posts I have already explored one such alternative, direct cell reprogramming. In future posts, I want to explore two others that have made significant headway in the past two years, but which also still require careful moral analysis.

But prior to that, I want to return to a key presupposition of our pursuit of alternatives. The pursuit of scientifically acceptable alternatives to ESC research presupposes that the whole ESC research project is scientifically legitimate. It presupposes that ESC research can one day proffer valuable scientific knowledge and even lead to therapeutic applications in a way that adult stem cell research cannot.

My experience over the past five years working closely with both pro-life and secular scientists and experts in the field of stem cell biology tells me that this presupposition is correct. Here's why.

Adult stem cell research has proffered hundreds of positive and promising clinical trials on human subjects (something embryonic stem cell research is years from commencing). In fact, there are over 1200 human trials involving cells derived from ASCs currently underway around the globe. That is all wonderful.

Notwithstanding those inroads, however, ASC research is still at a very early stage. Most treatments derived so far from ASC research apply to blood-related diseases. A broader application of ASC-derived therapies is also likely many years away. Will ESC research come up with cures that cannot be found by cells derived from ASCs? That remains within the realm of possibility.

More importantly, however, as Dr. George and I were at pains to state in the WSJ piece, the search for cures is only one motive behind ESC research and it is clearly not the only motive:

Most scientists acknowledge that ESCs will not provide therapies for many years, if ever. Their therapeutic potential is, at best, speculative. They cannot be used now, even in clinical trials, because of their tendency to produce tumors. So it comes as no surprise that many scientists now admit that their primary interest in pursuing ESC research lies not in the hope for direct cell transplant therapies, but in the desire to enhance basic scientific knowledge of such things as cell signaling, tissue growth and early human development.

We must remember that we are now entering the era of developmental biology. In that realm, biologists want to do basic scientific research on human embryos and the cells that compose them at very early stages so as to harness the science of cell differentiation—the science of how stem cells generate more specialized tissues. It may be true that precisely from such knowledge there can arise potential therapeutic applications, but such scientific knowledge is of value regardless of whether there are ever cures or not. For many of these researchers, the whole project of seeking therapeutic advances using human adult stem cells, noble enough in itself, is largely a side show, having little or no impact on their endeavors.

Again, we are talking about a kind of scientific knowledge that the study of ASCs cannot deliver. To get what they are looking for, scientists want human embryonic stem cells or their functional equivalent. Human adult stem cells will simply not fit the bill. In this sense, adult stem cell research will never assuage the scientific interest in human embryos or their stem cells.

Hence it is incumbent upon us, now more than ever, to seek out ethically acceptable alternatives that can give scientists what they want, but which avoid the destruction of embryonic human life. And these I hope to explore with you in up-coming posts.

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Direct Cell Reprogramming: Hitting Rewind II
Date: March 26, 2007

A couple weeks ago I was talking about one of the most promising alternative sources of human “pluripotent” stem cells called direct cell reprogramming. It holds out the possibility of producing embryonic-like stem cells, but without destroying, harming, or even involving human embryos in the process.

Reprogramming (also called de-differentiation) proposes to take adult cells from the human body and send each cell's nucleus back to a pluripotent state, meaning that each of these cells would then be capable of producing any tissue type in the human body—virtually equivalent in versatility to human embryonic stem cells.

Direct cell reprogramming offers the possibility of turning a normal adult body cell into a cell with the properties of an embryonic stem cell, but without involving human embryos in the process.

Furthermore, these stem cells would be genetically matched to the person who donated the body cells. They could then be used to grow tissues for future use in tissue replacement therapies (everything from regeneration of damaged heart tissue to Parkinson's to spinal chord injury). A perfect genetic match, these tissues would not be rejected by the donor's immune system. Most importantly, there would be no embryo created, destroyed, damaged or used in any way at any point in the process.

As I mentioned in the previous blog on this topic, in August 2006, the journal Cell published research by a Japanese team of researchers lead by Shinya Yamanaka. In that research, Yamanaka reported successes in reprogramming mouse cells by altering just four genetic factors in those cells. In so doing, the team was able to demonstrate that the new cells had pluripotent-like qualities.

I recently asked Westchester Institute senior fellow Dr. Markus Grompe to comment on the significance of Yamanaka's work and whether anyone has yet replicated it? Here's what Markus had to say:

Nobody has yet published a replication of this work, although I have not yet heard anyone cast serious doubt on it either. Yamanaka is making all of his protocols and reagents available. The work is highly significant, because it suggests that pluripotent cells can be made from adult cells without using oocytes, embryonic stem cells or any other fetal/embryonic material. The method involves direct genetic manipulation of the adult cells with the goal of reprogramming its epigenetic state. It is also significant, because it implies that tissue-matched pluripotent cells can be generated for individual patients.

Markus further confirmed that perhaps as many as 50 labs around the world, and upwards of 200 stem cell researchers, are currently pursuing cell reprogramming. He also confirmed that, if successful, cell reprogramming holds out the same promise as so called “therapeutic cloning”, meaning that the end product—patient-specific, genetically matched tissue—would be similar if not identical to what scientists would hope to achieve through cloning. When I asked him how long it would likely take before we see published research on successful attempts to do this with human cells, he prognosticated 2008 or 2009 at the latest—but was quick to add: “Success is in the eye of the beholder, however.”

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An Unreal Debate: Stem-cell ideologues vs. the facts       by Yuval Levin
Posted: Wednesday, January 10, 2007

ARTICLE: National Review Online    Publication Date: January 10, 2007

This week offers a perfect snapshot of the sorry state of the embryonic-stem-cell-research debate. On Monday, the newspapers were full of headlines about a new scientific paper showing that stem cells derived from amniotic fluid appear to have many of the same capabilities as embryonic stem cells, but without the ethical pitfalls of embryo destruction. But on Thursday, the House of Representatives plans to take up once again a bill that would overturn President Bush’s stem-cell-research-funding policy, and have the government use taxpayer money to encourage the destruction of embryos for their cells.

That disconnect mirrors the larger detachment of the political push for embryonic-stem-cell funding from the actual facts on the ground. Again and again, advocates for relaxing the ethical standards on funding make assertions and arguments with no basis in fact. Again and again they refuse to acknowledge the increasing evidence that genuine alternatives to embryo-destructive research may be possible.

The false claims are familiar by now. We continue to hear there is a “ban” on federal funding of embryonic-stem-cell research. But in fact, the Bush administration was the first to fund the research, and has devoted well over $100 million to it since 2001, though only in ways that do not encourage the further destruction of embryos.

We continue to hear that 100 million Americans are sick and could be cured by stem-cell research, but it is hard to imagine what that claim might be based on. In March of last year, Rep. Mark Souder (R., Ind.) had the following exchange in writing with Dr. James Battey, director of the NIH Stem Cell Task Force:

    Souder: A common figure tossed around regarding the “promise” of embryonic stem cell research is that it can provide cures for 100 million people. Is there any scientific evidence to actually support that claim?

    Battey: It is unclear where this statistic came from. Human embryonic stem cell (hESC) research is a relatively new field of science, having been first reported by James Thomson at the University of Wisconsin in 1998. More basic research needs to be conducted in the laboratory before the full potential for treating diseases is clear.

No one has since come forward to justify the figure, yet the stem-cell campaigners, including members of Congress, continue to use it.

We continue to hear that the stem-cell lines eligible for funding under the Bush policy are contaminated by exposure to animal cells, and therefore useless for any future therapeutic applications. But the FDA has plainly said that past exposure to animal products need not make a cell line ineligible for future use, and in any case a series of papers in the past year (most notably this one by stem-cell pioneer James Thomson) has shown animal materials can be removed from the existing lines. The most recent global survey of stem-cell work also shows that the Bush-approved lines continue to be used in a majority of embryonic-stem-cell projects worldwide — so researchers hardly consider them useless.

We continue to hear that the Bush-approved lines lack genetic diversity, or are not matched to patients with specific diseases. But the bill before the House this week would not address either point, since it would only make available more lines of cells derived from embryos created for in vitro fertilization. To match cell lines to patients using existing techniques, researchers would have to employ human cloning; and to derive a line with a genetic heritage not commonly represented by IVF patients, they would have to create embryos specifically to destroy them for research. Advocates of embryo-destructive research will likely move to endorse these radical steps next, but for the moment they claim they do not support the creation of embryos specifically for research, and in any case their bill would not fund it.

We continue to hear that American scientists are falling behind in embryonic-stem-cell research because federal support is lacking. But the latest numbers clearly demonstrate a large and stable American lead in the field. No other country even comes close to matching the output of American embryonic-stem-cell researchers.

We continue to hear that the American public passionately supports embryonic-stem-cell research and demands the loosening of the ethical boundaries imposed by President Bush. But actual surveys of public opinion suggest views are divided and not firmly held.

Strangely, though, for all this talk, the opponents of President Bush’s stem-cell-funding policy have not had much to say about the real news in the field over the past two years. That news has been almost exclusively about the emerging possibility of developing cells with the abilities of those derived from embryos, but without the need to harm human embryos.

A number of possible avenues have presented themselves. One would involve reprogramming adult cells to function like embryonic stem cells, whether by fusing them with existing stem-cell lines or by injecting them with the right combination of chemical factors. Another study has shown that such “pluripotent” cells could be derived from testes. And yet other researchers have begun to find cells with such capabilities in the placenta collected after birth, in human cord blood, and, as we saw earlier this week, also in amniotic fluid. Numerous labs around the world are now working to develop these techniques further, and to pursue more of them.

What we’re seeing is not exactly a search for one particular magic bullet to end the stem-cell debate. Rather, these studies show that the capacity to differentiate into a great many different cell types may not be exclusive to embryonic stem cells or any other one particular type of cell, and that the debate we have had now for the better part of a decade may have been based on a faulty premise to begin with.

All of this suggests the divisive fight over embryonic-stem-cell research might just be amenable to a consensus solution: a way to get the type of cells the scientists seek while avoiding any harm to nascent human life.

But advocates of looser funding rules will not take “yes” for an answer. Rather than jump at the chance to promote a common-ground way forward on stem cells, they have chosen to ignore the emerging alternatives, and insist that embryo-destructive research must be funded.

Last year, when the Congress passed the very same bill the House will consider this week, several members of both houses proposed an additional bill that would have encouraged research into new ethical methods of deriving embryonic-like cells. The Senate passed the bill unanimously. But in the House, most of the Democrats and a few Republican opponents of the president’s policy decided they could not support the search for a solution. They opposed the bill, and prevented its passage. Their intransigence sent a very strange message: They would have the federal government fund the exploration of pluripotent stem cells only if it involved destroying human embryos. Otherwise, they were not interested. They would only back the science if it were controversial. These opponents of the stem-cell-alternatives bill included the entire Democratic House leadership, and this year they have prevented the same bill from even coming to a vote.

Step by step these past few years, the public arguments for overturning the Bush funding policy and using taxpayer dollars to encourage embryo destruction have fallen apart, and the possibility of a consensus solution to this divisive battle has emerged. But the leaders of the effort to overturn the president’s policy have opted to ignore the facts and turn down a potential solution. They would prefer a political rallying point over a scientific way forward. Let us hope the Congress as a whole does not make the same choice.

— Yuval Levin is a fellow at the Ethics and Public Policy Center and senior editor of The New Atlantis magazine.

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Author

Why the controversy?

A brief introduction to stem cells

The potential benefits of stem cell treatment

Obtaining stem cells from embryos

Adult stem cells and regenerative medicine

Stem cells and cloning

The ethics of stem cell science

Embryo research and human dignity