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The field of ethically legitimate stem-cell research got a boost on Oct. 8, when the Nobel Assembly in Sweden announced that its coveted prize in physiology or medicine would go to Japanese researcher Shinya Yamanaka.
Yamanaka transformed the field of stem-cell research and regenerative medicine in 2006-2007, when he published a series of groundbreaking papers demonstrating that mature differentiated (mammalian) cells, such as skin cells, could be “reprogrammed” to become pluripotent stem cells. He first demonstrated the process using mouse cells and later using human cells.
Pluripotency
“Pluripotency” refers to the capacity of an immature cell to develop into specialized cell types. Before it develops into a mature cell, such as a blood cell, cardiac cell or neural cell, a cell exists in an undifferentiated state.
This unspecialized cell is called a “stem cell.” It’s like a blank slate waiting to be drawn upon or a lump of clay awaiting a form.
If the stem cell is capable of taking the form of (or developing into) all cell types in the body, it is called pluripotent. If it is capable of becoming only the kind of cell in a single family of cells (e.g., those found in the heart), it is multipotent. If its capacity is limited to a single cell type, it is unipotent.
A cell’s type (also called its “fate”) is determined by genes. A single gene is like a line out of an instruction manual. The sum total of one’s genes (“genome”) constitutes the whole manual. Genes provide instructions for making, operating and repairing all the parts of the human body, so genes direct the undifferentiated stem cell towards its particular cell fate. Genes are also responsible for preserving the state of pluripotency.
The Era of Stem-Cell Research
The era of stem-cell research was launched in 1981, when pluripotent stem cells were first isolated from mouse embryos and cultivated in the laboratory by British researcher Martin Evans. The scientific community recognized at once the enormous potential that this newfound ability to isolate, multiply and store pluripotent stem cells promised for medicine and research with humans.
But an ethical hurdle stood in the way: To exploit the potential, human embryos — lots of them — would need to be created and lethally experimented upon.
In 1998, the first successful isolation of human embryonic stem cells (hESCs) was reported by a lab at the University of Wisconsin-Madison. The Promethean allure of “miraculous cures” prompted many in the scientific community to become comfortable with the morally repugnant research.
Yamanaka: Trailblazer
Shinya Yamanaka apparently was not one of them. I do not know if he himself ever performed embryo-destructive research. Nor do I know if he ever used tissue cultures derived from aborted babies when other non-tainted tissues were available. Both of these are morally unacceptable. (Editor's note: The Culture of Life Foundation Oct. 25 released "Yamanaka and iPSCs: A reply to some skeptical friends in the pro-life community.")
But Yamanaka certainly made clear to the world that he was resolute on finding an alternative to embryos-destructive research.
He famously told The New York Times in 2007: “When I saw the embryo, I suddenly realized there was such a small difference between it and my daughters. I thought, We can’t keep destroying embryos for our research. There must be another way.”
Yamanaka asked what genes were responsible for preserving the state of pluripotency (i.e., by what genetic mechanism does a pluripotent stem cell remain pluripotent?). If he could identify the genes responsible, he thought, he might be able to introduce the same genes into the genome of a differentiated somatic cell, such as a skin cell, and thus prompt the cell — literally “reprogram” it — to a state of pluripotency.
In 2007, Yamanaka’s dream of producing pluripotent stem cells from mature body cells without the need for human embryos became a reality. The four genes he identified acted as “reprogramming factors” de-differentiating the mature cell back to a condition of developmental immaturity — to a state of pluripotency. These induced pluripotent stem cells (iPSCs) were proof of the principle that cells could be directly reprogrammed.
Yamanaka’s pioneering discovery opened a new branch of stem-cell research almost overnight — just as the scientific community was waking up to the fact that hESCs may never produce the miracle cures that some had hoped for and the media so irresponsibly and uncritically hyped.
Some of the most prominent cell biologists in the world, including Ian Wilmut (who cloned Dolly the sheep) and James Thomson (who first isolated hESCs in 1998 at the University of Wisconsin), have announced they are going over to iPSC research as a preferred method of creating pluripotent stem cells.
Even the California Institute for Regenerative Medicine (CIRM), created in 2004 to funnel $3 billion of taxpayer money into embryo-destructive stem-cell research, has begun awarding grants for iPSC research and the banking of iPS cells.
Future of Stem-Cell Research
The choice for Yamanaka is not, to be sure, the Nobel Foundation’s way of giving a thumbs-up to ethical stem-cell research, at least not intentionally. To ensure that nobody mistook its motivations, Nobel jointly awarded the 2012 prize to an elderly British cloning scientist named John Gurdon, who pioneered the cloning process known as somatic cell nuclear transfer.
Gurdon is a resolute defender of embryo-destructive research (see J. B. Gurdon and J. A. Byrne, “The First Half Century of Nuclear Transplantation,” Proceedings of the National Academy of Sciences, July 8, 2003, Vol. 100, No. 14, 8051).
Nevertheless, Yamanaka’s prestigious award is indeed a triumph for ethical research.
Since 2007, I have been asked many times whether the discovery of induced pluripotent stem cells has spelled the demise of embryonic stem-cell research. After all, if we no longer need to destroy human embryos to create pluripotent stem cells, why keep doing it?
When the question is put to secular scientists, the official reply is: “We need both types of stem cells: induced pluripotent stem cells and embryonic stem cells (ESCs]; both promise benefits.”
And yet, because of the undeniable disappointment of ESC research, fewer scientists are taking it up, and fewer grant dollars are being spent on it. Scientific American, lamenting the “disappointment,” opined in 2009: “Practicable ESC-based therapies are years away.”
Can the Science of iPSCs Be Used Wrongly?
Most any science can be used wrongly, especially if it’s used in ways that harm or destroy human life. But since the production of pluripotent stem cells from somatic cells by reprogramming need not involve bringing into existence, experimenting upon or destroying human embryos, iPSC research in itself seems to me to be morally unproblematic.
Having said this, iPSCs have not yet yielded any clinical benefits. Because of the concern with cancer causation and tumor formation, the cells are not ready to be used to treat human diseases. Using them prematurely, therefore, and subjecting patients to disproportionate risks of harm would be unethical.
Moreover, if researchers tried to use direct cellular reprogramming (the process used to make iPSCs) to produce human embryos, that is, if, rather than create pluripotent cells, they tried to create “totipotent” cells (e.g., cells such as the human zygote with a complete capacity for organismic development), then it would be just another type of unethical embryo-exploitative research.
Reprogramming would also be unethical if it were used to create female or male gametes (eggs or sperm cells) with the intent of using them for assisted reproduction in humans.
In fact, a milestone towards this dubious goal was announced on Oct. 4, when Japanese researchers published an article in the journal Science saying that they’d successfully transformed (mouse) iPSCs into viable mouse oocytes (eggs) and then used the eggs to produce healthy, fertile mouse pups.
Advantages of Adult Stem-Cell Research
Thus far in the field of stem-cell research, only adult stem cells (ASCs) have yielded clinical benefits. The headline of a USA Today article in 2010 read: “Adult stem-cell research far ahead of embryonic.”
This is no exaggeration. Tens of thousands of successful treatments with ASCs are performed each year. To date, none have been performed using ESCs. The Journal of the American Medical Association reported in 2010 that in one year (2006) more than 50,000 transplants were performed around the world using ASCs obtained from bone marrow, peripheral blood and umbilical cord blood.
Catholic News Agency reported recently that since investors are increasingly demanding results and not just hype, they are shifting their money towards ASC research.
E. Christian Brugger, the senior fellow in ethics and director of the fellows’ program
at the Culture of Life Foundation in Washington, holds the
Stafford Chair of Moral Theology at St. John Vianney Theological Seminary in Denver.
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There is some controversy as to the way in which the stem cells were genetically altered. If what I read is accurate, genetic material from the kidneys of an electively aborted child are used for this purpose.
Thank you for the thoughtful article.
You say that “Reprogramming would also be unethical if it was used to create female or male gametes…for assisted reproduction in humans.”
My wife and me went through IVF and are blessed with two beautiful boys. If there was no option but to reprogram my skin cells so that we could have a loving family, and the treatment was safe, how would this be unethical?
In 1962, while studying the process of egg fertilization and the cell division that results in the growth of a new organism, Sir Gurdon “showed that the genetic information inside a cell taken from the intestines of a frog contained all the information needed to create a whole new frog. He took the genetic information and placed it inside a frog egg. The resulting clone developed into a normal tadpole.”
In other words, Gurdon removed the genetic material contained within the nucleus of a somatic (or body) cell (in this case, the intestine) and inserted it into an egg cell replacing the nucleus it originally contained. This process is known as somatic cell nuclear transfer (SCNT)—a method of cloning. Gurdon was the first to clone an animal—albeit a tadpole!
Most people have probably not heard of Gurdon or his research, but it paved the way for the more infamous research of Ian Wilmut, the first to clone a mammal—Dolly, the lamb—in 1996.
Shinya Yamanaka, on the other hand, has studied cell development in the reverse, so to speak. He is credited with figuring out “how to reprogram mature cells so that they revert to their primitive state as ‘induced pluripotent stem cells,’ or iPS cells, capable of developing into any part of the body.”
When Yamanaka’s research was published in 2007, several bioethicists and many pro-life leaders touted iPS cells as the ethical alternative to embryonic stem cell research. Because it was publicized as a method of turning mature, adult stem cells into “embryonic-like” stem cells that could then be further reprogrammed into other stem cells, what was not to like? But, the devil is in the details.
Reprogramming a mature, adult skin cell (technically speaking, it was a fibroblast cell) into an embryonic-like stem cell requires the infusion of the cell with regulator genes (younger DNA) that will cause the cell to regress in age. A team of UCLA researchers confirmed in early 2008 that the “genes used in combination to reprogram the skin cells regulate expression of downstream genes and either activate or silence their expression.”
Where does one obtain youthful DNA of an embryonic nature? They get it from human embryonic stem cell lines and aborted fetal material!
Theresa A. Deisher, PhD, founder of AVM Biotechnology and a world renowned scientist in the field of adult stem cell therapies and regenerative medicine, notes that while iPS cell research could actually be conducted without the use of human fetal material (such as HeLa, COS, or CHO cells, none of which come from electively aborted preborn babies), all such research to date has utilized HEK-293 (human embryonic kidney, specimen number 293), modified versions of the HEK cell line known as PLAT-A, PLAT-E, 293FT, and Phoenix cells. Also used are IMR-90 (page, 447; a future replacement for WI-38 currently used in vaccine production) and MRC-5, both of which are aborted fetal cell lines.
Dr. Yamanaka used PLAT-E cells as well as MEL-1 hES (which is a male embryonic stem cell line derived from donated IVF embryos in Australia) for reprogramming cells. (See Yamanaka’s research, “Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors,” pages 9 and 10.)
Debi Vinnedge, executive director of Children of God for Life and a nationally recognized author and speaker who has provided testimony for congressional hearings on human embryonic stem cell research, explains the process used by Yamanaka:
Scientists used a technique known as PCR, or Polymerase Chain Reaction. PCR is [a] technique that allows production of large quantities of specific DNA using a simple enzyme reaction. The embryonic and/or aborted fetal DNA was “spliced” or added into the lentivirus DNA, which then delivered it to the adult skin cells. As the aged cells’ DNA mingled with the new DNA and continued to replicate in petri dishes in the lab, they literally reversed their aging process to the embryonic state. And voila! Embryonic stem cells developed from the modified adult stem cells.
So, no, Yamanaka did not use eggs or embryos in his research, as many point out, but he and his team did use human embryonic stem cell lines and/or aborted human fetal remains.
While it is true that the scientists involved in the reprogramming research may not have directly destroyed embryos, or participated in the original abortions, they did use cell lines taken from human beings that were deliberately destroyed and then used for research purposes. And both the Vatican and the United States Conference of Catholic Bishops (USCCB) have condemned such practices.
In its statement, Declaration on the Production and the Scientific and Therapeutic Use of Human Embryonic Stem Cells, the Pontifical Academy for Life answers the question:
Is it morally licit to use ES [embryonic stem] cells, and the differentiated cells obtained from them, which are supplied by other researchers or are commercially obtainable?
The answer is negative, since: Prescinding from the participation—formal or otherwise—in the morally illicit intention of the principal agent, the case in question entails a proximate material cooperation in the production and manipulation of human embryos on the part of those producing or supplying them.
Further, the encyclical Dignitas Personae, paragraph 35, also states:
Therefore, it needs to be stated that there is a duty to refuse to use such “biological material” even when there is no close connection between the researcher and the actions of those who performed the artificial fertilization or the abortion, or when there was no prior agreement with the centers in which the artificial fertilization took place. This duty springs from the necessity to remove oneself, within the area of one’s own research, from a gravely unjust legal situation and to affirm with clarity the value of human life. (emphasis added)
In addition to the problem of using human embryonic stem cell lines, it must also be noted that Yamanaka’s research has been used to advance a new technique in cloning. Steve Connor, science editor for the Independent, wrote the following in an April 14, 2008, article entitled “Now We Have the Technology that Can Make a Cloned Child”:
Scientists who used the procedure to create baby mice from the skin cells of adult animals have found it to be far more efficient than the Dolly technique, with fewer side effects, which makes it more acceptable for human use.
The mice were made by inserting skin cells of an adult animal into early embryos produced by in-vitro fertilization (IVF). Some of the resulting offspring were partial clones but some were full clones—just like Dolly.
Unlike the Dolly technique, however, the procedure is so simple and efficient that it has raised fears that it will be seized on by IVF doctors to help infertile couples who are eager to have their own biological children.
In the same article, Robert Lanza, chief scientific officer of the American biotechnology company Advanced Cell Technology, said that, while cloning “isn’t here now” (and that was 2008), “At this point there are no laws or regulations for this kind of thing and the bizarre thing is that the Catholic Church and other traditional stem-cell opponents think this technology is great when in reality it could in the end become one of their biggest nightmares. It is quite possible that the real legacy of this whole new programming technology is that it will be introducing the era of designer babies.”
Cloning, human embryonic stem cell research, the use of illicit biological materials in research, IVF, designer babies—all are immoral, unethical, and certainly not pro-life. Rather than praise and prizes, such research ought rightly be given condemnation.
We should be even more alarmed with this research when reading the following:
Scientists create fertile eggs from mouse stem cells
NPR
Scientists in Japan report they have created eggs from stem cells in a mammal for the first time. And the researchers went on to breed healthy offspring from the eggs they created. While the experiments involved mice, the work is being met with excitement — and questions — about doing the same thing for humans someday. Moreover, [the research] team did something potentially even more astonishing: They bred healthy mice from eggs made from another type of stem cell known as induced pluripotent stem [iPS] cells.
http://www.npr.org/blogs/health/2012/10/04/162263750/scientists-create-fertile-eggs-from-mouse-stem-cells
When I first read about this, I, too, thought this was a triumph. However, I also read this - http://the-american-catholic.com/2012/10/15/why-are-catholics-praising-the-nobel-prize-stem-cell-technology/ which puts things in a totally different perspective. It seems that this is not a triumph, but a tragedy.
Comments by a Ph.D trained scientist on the procedures within Yamanaka’s work that Catholics would probably find offensive.
http://tinyurl.com/d4nvzfd
Excellent article.
And lets hope & pray that the fraud of neo-evolution will someday soon be similarly exposed as embroynic stem cells ‘research’ is now.
LIES.. this has already been refuted way back in 2008! Please correct the story…
http://www.cogforlife.org/2012/09/10/ips-no-pro-life-panacea/
http://www.cogforlife.org/2012/10/11/reprogramming-pro-lifers-minds-part-ii/
http://the-american-catholic.com/2012/10/15/why-are-catholics-praising-the-nobel-prize-stem-cell-technology/
This is not the first time Christian Brugger has gone against Catholic teaching as we reported in Jan 2011 when he dissented from Dignitas Personae. The Holy See was clear that it is illicit for scientists to use these biological materials (from aborted fetal cell lines and embryonic stem cells) Instead of changing methods, scientists continue to use even more heinous methods in order to reprogram adult cells. Last month we reported on the use of 18-22 week gestation aborted fetal liver and lungs in the iPS cell research. By praising those who did immoral research - including Yamanaka and Gurdon - we can be assured they will never change to the moral cell lines readily available and that work every bit as well! Our latest response to similar articles is at: http://www.cogforlife.org/2012/10/11/reprogramming-pro-lifers-minds-part-ii/
Dr. Brugger,
You should respond to the concerns highlighted by Joan and Liz above.
The author of the article at The American Catholic holds a Ph.D. She states in conclusion,
The bottom line: This technique for iPSCs 1) uses cells grown from electively aborted children, 2) has just as many, if not more, health risks for patients hoping for cures derived from them, and 3) still involves the killing of human embryos to complete the research.
It is worth noting that we already have many cures using cord blood, and before closing, it is also worth reading the 2008 prediction of Robert Lanza, chief scientific officer of American biotechnology company Advanced Cell Technology.
“At this point there are no laws or regulations for this kind of thing and the bizarre thing is that the Catholic Church and other traditional stem-cell opponents think this technology is great when in reality it could in the end become one of their biggest nightmares,” he said. “It is quite possible that the real legacy of this whole new programming technology is that it will be introducing the era of designer babies.”
What’s the real motivation for this research? The reader can decide, but if you are Catholic, or at all concerned about the dignity of human life, stop praising this practice as moral, safe, and the heroic end of research that manipulates and destroys human life. It isn’t.
What are you talking about??????? Only a moral theology person who has no IDEA about science can praise IPS cells! I found this article- unfortunately nobody pays attention to what SCIENTISTS are saying
http://scivias-publisher.blogspot.com/2012/10/egg-cells-from-reprogrammed-skin-cells.html
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