The End of the Stem Cell Wars
ANDERSON, RYAN T.
The End of the Stem Cell Wars A victory for science, for the pro-life movement, and for President Bush RYAN T. ANDERSON The stem cell wars are over. Leading scientists are telling us that they...
...Work still needs to be done to ensure that viral vectors do not introduce dangerous mutations, but the scientists I spoke with thought this would be achievable with minimal delay...
...However, there are concerns regarding the safety of iPS cells for human therapies, due to the use of viral vectors that integrate into the cell’s DNA, potentially causing dangerous mutations, and to the use of c-Myc, a gene that is associated with some forms of human cancer...
...And no one has yet fi gured out how to convert these stem cells into transplantable cells usable for therapies...
...The Thomson approach described in Science avoided some of these drawbacks by using no cMyc and optimizing the safety of the induced pluripotent stem cells from the start...
...The ethicists I spoke with had only praise for the new developments...
...In fact, the new method may actually prove superior to embryo-destructive alternatives...
...Thomson notes, “For drug development, human iPS cells should make it easier to generate panels of cell lines that more closely refl ect the genetic diversity of a population, and should make it possible to generate cell lines from individuals predisposed to specifi c diseases...
...He was right...
...This approach holds tremendous promise for advancing our scientifi c understanding of stem cells and for advancing the study of regenerative medicine...
...Nonetheless, there are serious challenges to overcome before pluripotent stem cells—whatever their source—will be ready for clinical therapies...
...Some ethicists weren’t fully sold, fearing that the tumor-like entities might be deformed embryos...
...Of all the many people I have talked with about stem cells, none has ever expressed any antiscience or antimedicine inclinations...
...His approval ratings were in the cellar, and the general public largely supported the bill...
...Direct reprogramming of adult cells to pluripotent stem cells is one of the most signifi cant scientifi c fi ndings of the last quarter century,” she said...
...For the petition-signers and the direct-mail organizers, the philosophers and the scientists who have defended the sanctity of human life, the Cell and Science stories come as a reward...
...These kinds of experiments are now immediately possible and will likely be the fi rst application of iPS cells...
...Markus Grompe, professor in the department of molecular and medical genetics at the Oregon Health and Science University, director of the Oregon Stem Cell Center, and a board member of the International Society for Stem Cell Research, told me that “the therapeutic potential of all human pluripotent stem cells, including those generated by direct reprogramming, remains uncertain...
...To be an embryo requires not only a particular nuclear state, but also certain organizational factors that the oocyte cytoplasm provides...
...In addition, human cloning would require an enormous number of human eggs—which could be obtained only by subjecting donors to painful and potentially dangerous hormonal-stimulation procedures...
...Amid this controversy, a number of scientists discussed possible alternative sources of embryonic stem cells...
...His team used a different group of genes—Oct4, Sox2, Nanog, and Lin28—to achieve the same end: direct reprogramming of adult human cells to the pluripotent state...
...James Thomson explains it best in his Science paper: The human iPS cells described here meet the defi ning criteria we originally proposed for human embryonic stem cells, with the signifi cant exception that the iPS cells are not derived from embryos...
...Kass who said that reprogramming methods would, if pursued vigorously, enable us to realize the full benefi ts of stem cell science while respecting human dignity...
...Conference of Catholic Bishops pointed out the happy irony: “The scientist who gave us human embryonic stem cell research has helped fi nd the way to go beyond embryodestructive research, and in response to these new fi ndings, the scientist who gave us cloning tells us that the cloning agenda is on the way to being obsolete...
...Their expression in reprogramming precludes totipotency...
...And Congress was wrong...
...The fear was that likely “donors” would be poor women undergoing a distasteful procedure solely for the fee...
...All pluripotent stem cells carry a risk of tumor formation...
...The new technique is so promising that on November 16, Ian Wilmut announced that he would no longer seek to clone humans...
...Wilmut, of Dolly the sheep fame, agrees...
...That’s the story coming out of Cell and Science...
...Had a President Gore or a President Kerry allowed the science to go forward without regard for moral principle, it would have set a terrible precedent...
...All along,” George reports, “it was Dr...
...Another example, favored by Ian Wilmut, is motor neuron disease (Lou Gehrig’s disease...
...Indeed, it is not Bush alone, but the entire pro-life movement, that has been vindicated...
...And they should be able to do so at last without controversy...
...They’re a media-conjured fantasy...
...Stem cell research wasn’t a prime issue during the 2000 campaign...
...Wilmut, you may remember, is the scientist who cloned Dolly the sheep...
...As it turns out, the breakthrough Thomson study was partially funded by NIH...
...Richard Doerfl inger of the U.S...
...President Bush then issued another executive order, this one instructing the National Institutes of Health to promote reprogramming research...
...entities that could then be harvested for the equivalent of embryonic stem cells...
...The difference is simply in the method of their production...
...Furthermore, two of the genes used for reprogramming—Nanog and Sox2—are never found in embryos, only in stem cells...
...What about all of those antiscience religious fanatics who used to scold about “playing God...
...Comparing his cloning methods with Yamanaka’s, he said, “The work which was described from Japan of using a technique to change cells from a patient directly into stem cells without making an embryo has got so much more potential...
...Cloning, it was said, would also provide an unlimited supply of human embryos...
...Still, some critics were unconvinced...
...It also is illustrative of the politics of science...
...Had Bush lost either election, or had he caved to pressure from those who slandered him as “antiscience,” it is very possible that the new method of stem cell production—the new gold standard, in all likelihood— would never have been found...
...On August 9, 2001, President Bush waded into this morass...
...I asked Maureen Condic, professor of neurobiology and anatomy at the University of Utah School of Medicine, about these cells...
...Grompe points out that stem cells have important uses beyond therapy, and for these uses, too, iPS cells are clearly superior to embryo-derived stem cells...
...This breakthrough enables researchers to create human embryonic stem cells directly from adult cells...
...When I asked Father Thomas Berg, the executive director of the Westchester Institute for Ethics and the Human Person, about this concern, he replied, “From a Catholic perspective, reprogramming clears the bar in terms of reasonable concern for human dignity in biotech research: Never at any point in the process of reprogramming is there ever a danger of involving—even accidentally we might say—techniques that could bring about a human embryo, as would happen in cloning...
...Or so the story went...
...But many people thought human cloning with the sole intention to kill crossed an ethical line...
...The order also restricted that funding, however, to research using existing embryonic stem cell lines: No more embryos would be created and destroyed for taxpayerfunded research...
...But outside the scientific community, conventional wisdom held that these alternative sources, while interesting, were being proposed only to provide Bush with political cover during the waning years of his presidency...
...But because President Bush stood his ground, we have avoided that moral catastrophe...
...Shortly before announcing his response to the legislation, the president invited George and Grompe to the Oval Offi ce to discuss it with him...
...Accounts of independent research by two separate teams of scientists were published on November 20—one in the journal Cell and one in the journal Science—documenting the production of pluri potent human stem cells without using embryos or eggs or cloning or any morally questionable method at all...
...Here it will be of interest to examine the formation of nerves and motor neurons from patients with the actual disease, in an attempt to discover ways to help the cells survive and function better...
...In short: The new technique produces patient-specifi c stem cells with all the benefi ts of stem cells from embryos, but without the production and destruction of human embryos or the use of human eggs...
...Yamanaka himself notes these pitfalls, but indicates that they should be surmountable: His technique works even when you take c-Myc out of the mix and use only the other three genes (though it achieves its results at a less effi cient rate...
...Whether or not the next president shares Bush’s pro-life convictions, it is highly unlikely that taxpayer funds will go to support embryo destruction, which has become not only unnecessary but also less effi - cient than the alternatives...
...Politically, the controversy wasn’t yet ripe, though it became so just months into Bush’s fi rst term...
...The promise of cloning was that therapies could be produced using human embryos cloned directly from the patient— thus resulting in a genetic match...
...Thomson’s technique is also noteworthy because it uses a lentivirus to introduce the gene group, which is the safest of retroviral integration methods...
...The resulting cells—called induced pluripotent stem cells, or iPS cells—are functionally identical to human embryonic stem cells: They possess all of the same properties...
...He recently sought and received a license from the British government to attempt to clone human embryos for research purposes...
...George downplays his own role in shaping the president’s thinking...
...Contrary to popular belief, Bush’s order did not ban anything...
...It is a new study by Thomson himself that has caused the present stir, but this time Thomson is not alone...
...They were “pluripotent”—capable, in theory, of developing into any type of body tissue—whereas so-called adult stem cells were thought to be useful for forming a narrower range of tissue types...
...So scientists had been searching for a way to remodel the gene expression of adult cells to transform them into stem cells...
...Thus, iPS cells may very well help us discover therapies for some of the most daunting genetic diseases...
...Different cells have the same genes, expressed differently...
...When I spoke with Robert George, he praised Leon Kass, the former chairman of the President’s Council, together with William Hurlbut, as the driving intellectual force against embryo-killing and in favor of fi nding alternative methods of obtaining pluripotent stem cells...
...That expectation has now been shattered...
...For transplantation therapies based on these cells, with the exception of autoimmune diseases, patient-specifi c iPS cell lines should largely eliminate the concern of immune rejection...
...The president agreed and announced his veto...
...As soon as a new president was inaugurated, federal funds would fl ow into human cloning and embryo-destructive research...
...As anyone familiar with reparative medicine knows, immune rejection is one of the tallest hurdles to clear...
...They don’t exist...
...Moreover, Yamanaka notes that integration of the virus into the DNA will not reduce the usefulness of induced pluripotent stem cells for study of human diseases in the laboratory, and that other nonviral means of introducing the reprogramming factors into cells are likely to be suffi cient to generate iPS cells...
...Princeton’s legal philosopher Robert P. George, who also serves on the President’s Council on Bioethics, told me, “From the beginning we have been arguing that we must do everything we can to advance the cause of stem cell science but without sacrificing our respect for nascent human life and the principle of the inherent and equal dignity of each and every member of the human family...
...This reputation persists even though adult stem cells are already used in therapies to treat several diseases and are being tested in hundreds of clinical trials, while not a single embryonic stem cell therapy exists, even in trials...
...But no egg or cytoplasm is used in this method...
...When introduced into adult cells, these genes directly reprogram the cells to a pluripotent state...
...Yamanaka went to work to make it happen with human cells...
...And the insights gained are likely to lead to the development of new drugs and strategies to benefi t human health...
...Similar to human embryonic stem cells, human iPS cells should prove useful for studying the development and function of human tissues, for discovering and testing new drugs, and for transplantation medicine...
...The recent news gives scientists a better method of producing embryonic stem cells while retaining our nation’s commitment to the equal and inherent dignity of all human beings...
...A Gore or Kerry presidency would have bestowed federal blessing and taxpayer funds on laboratory work predicated on the assumption that embryonic human beings can be treated as spare parts and that cloning to kill is acceptable...
...Even now, nine years later, embryonic stem cells are thought by many scientists to have greater potential than other types...
...What does all of this mean...
...William Hurlbut, a professor at Stanford and a member of the President’s Council on Bioethics, proposed Altered Nuclear Transfer, a process that produced nonembryonic tumor-like Ryan T. Anderson is an assistant editor at First Things...
...Finally, using mice, a Japanese scientist, Shinya Yamanaka, showed that he could create embryonic stem cells directly from adult cells, and within less than a year his study was replicated and signifi cantly expanded by two separate research groups...
...Yamanaka’s team discovered a collection of four genes—Oct3/4, Sox2, Klf4, and c-Myc—that does precisely this...
...Direct reprogramming techniques make it possible to generate pluripotent cells from specifi c individuals with particular diseases...
...Having political leaders of principle who insist on ethical standards in scientifi c research, then, is always of the utmost importance...
...George presented the scientifi c and philosophical case for respecting the human embryo, while Grompe assured the president that alternatives such as reprogramming, if given time, would win the day...
...This latest news just goes to show that it really is possible...
...Considering the realities of Washington, it is no surprise that the pro-embryodestruction forces in the House of Representatives actually teamed up to defeat a bill that would have funded research on reprogramming, which they dismissed as a distraction...
...Now, citing the new technique, he has abandoned his plans...
...Because induced pluripotent stem cells, created from a patient’s own body, are a perfect genetic match, they should prove especially useful for both the study of diseases and the development of treatments...
...This new production technique is possible because the difference between a stem cell and an adult cell is not a matter of genetics but of epigenetics: which genes are expressed, how, and to what degree...
...While some Catholic moral theologians had previously worried that reprogramming methods “mimicked conception” and might produce disabled embryos, the new technique should alleviate all fears...
...Hurlbut’s proposal was then modifi ed, using oocyte cytoplasm to directly reprogram a cell’s nucleus to make it pluripotent...
...It was only in 1998 that Thomson succeeded in isolating human embryonic stem cells...
...Though other types of human stem cells were known at the time (some were even in clinical trials), embryonic stem cells were thought to be the holy grail because they were believed to be more fl exible...
...Leading scientists are telling us that they can pursue the most promising stem cell research without using—much less killing—human embryos...
...Opposition was fi erce, but Bush stood fi rm...
...No immediate cures should be expected from human pluripotent stem cell-based therapy, either embryo-derived or iPSC...
...After Congress passed a bill funding embryo-destructive stem cell research, Bush sought counsel...
...In Cell, Yamanaka announces that the pluripotent stem cell-producing technique he used on mouse cells works with human cells...
...This is the biggest stem cell advance since James Thomson became the fi rst scientist to isolate embryonic stem cells, less than a decade ago...
...At present, people on all sides of the old stem cell debate should be able to celebrate...
...But scientists are hopeful that these hurdles will be overcome...
...Similarly, now, we don’t know what the next biotech breakthrough will be...
...Whatever it is, we can be certain that some people will demand we pursue it...
...A Phillips Foundation fellow, he is the assistant director of the Program in Bioethics at the Witherspoon Institute of Princeton, N.J...
...They can be used to study how human organs and tissues form...
...The science of pluripotent stem cell research can move forward toward therapies and cures in a manner that is free of any ethical concerns...
...Concerns that scientists might “go too far back” and reprogram a cell to a totipotent stage—making an actual embryo, not a stem cell—are quickly settled once one understands the science...
...He issued an executive order that opened human embryonic stem cell research to federal funding for the fi rst time ever...
...First, the tumor risk of such cells must be harnessed, and second, the effi cient conversion to transplantable cells must be mastered...
...For example, it will be possible to make pluripotent stem cells from children with Fanconi’s anemia, a devastating genetic disease, and study the effects of candidate drugs on the formation of human blood...
...The problem with producing embryonic stem cells was that human embryos—nascent human beings—had to be destroyed in the process...
...Most likely, science and the public would have accommodated themselves to the mass production and mass killing of human embryos...
Vol. 13 • December 2007 • No. 12
