Reprogramming Stem Cells – Or Pro-Lifers’ Minds?

Reprogramming Stem Cells – Or Pro-Lifers’ Minds?
By Debi Vinnedge

In November 2007, two scientists Dr. Shinya Yamanaka and Dr James Thomson published their studies describing a new stem cell technique that produced embryonic-like stem cells by simply reprogramming adult skin cells.[1]  Immediately several bioethicists and pro-life leaders touted the iPS – or “induced pluripotent stem” cells to be an ethical alternative to embryonic stem cell research and human cloning.  For if one could produce embryonic stem cells without destroying innocent human beings that would end the ethics debates once and for all. Or would it?

Some have noted that the reprogramming methods were quite simple, but in reality the science is fairly complicated for the average reader to understand.  Perhaps that is just what some of the pundits were counting on, because unless one is skilled at recognizing the red flags raised in this research, they would never discover the dark secrets no one wants the pro-lifer community or politicians to know.  And so we will take you through this gently, in layman’s terms.

Both studies involved introducing genes into adult stem cells through what is known as a “lentivirus”.  A lentivirus in and of itself is a serious safety quagmire since by definition it is a slow moving virus that persistently infects the target cells, often causing fatal diseases years after the initial infection. The HIV virus is an example of a well-known lentivirus that may take several years to progress into AIDS.  However, since the lentivirus, was a highly effective method of delivering the needed DNA to the target adult skin cells for reprogramming them to an embryonic state, scientists figured they would tackle the safety hazards in latter experiments.

So just how did this lentivirus produce the miraculous effect of turning an adult stem cell into an embryonic one?  Now think about it – this isn’t magic, folks: how could a cell that is taken from a 20 year old suddenly return to an embryonic state?  In order to do that, the host adult skin cell would have to receive a huge influx of younger DNA that would cause the aged cells to regress in age.  Sort of like injecting a veritable “fountain of youth” into the cells, because this DNA is normally only active in embryonic or fetal cells.  So, literally, a 20 year-old skin cell was coerced into activating genes not used since fetal life, and it became embryonic again, but not without the same host of problems inherent with all embryonic stem cells as you will shortly discover.

And just where did researchers obtain that DNA?  Why from embryonic and aborted fetal cell lines of course!  Scientists used a technique known as PCR, or Polymerase Chain Reaction.  PCR is 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.

Researchers then claimed that these newly transformed cells would be genetically identical to the patient whose adult skin cell was modified, thereby eliminating problems with immune rejection.  This was in fact, the main purpose of so-called “therapeutic” cloning, whereby scientists claimed to produce genetically identical embryos for the purpose of harvesting patient specific stem cells. However, nothing could be further from the truth in either method.

In human cloning, the nucleus of a donor egg is replaced with the nucleus of an adult stem cell through a method called “somatic cell nuclear transfer”.  But, since only the nucleus of the egg is removed, residual mitochondrial DNA from the donor egg is still present in the newly formed embryo. With the reprogramming method, foreign DNA from both the lentivirus and embryonic or fetal cells are also present in the newly formed iPS cells.  So not only are there still immune rejection problems, scientists noted that just like embryonic stem cells, the iPS cells formed teratomas and cancerous tumors, another “little” annoyance they promised to deal with later.

So exactly where did the researchers get those aborted fetal and embryonic stem cells?  Different scientists used different sources, but the primary aborted fetal material used was HEK-293, that is, Human Embryonic Kidney, specimen number 293, as well as modified versions of this cell line, named PLAT-A, PLAT-E, 293FT and Phoenix cells.

Dr Alex Van der Eb, of the Netherlands obtained HEK from an electively aborted baby and according to Van der Eb during 2001 FDA hearings, the information on the original abortion “was lost” and all he could remember was that it was a healthy fetus. He noted that the lack of family history also made HEK questionable for FDA standards of safety.[2] 

In addition to using the HEK cells, Dr Thomson obtained his DNA sequences from human embryonic stem cells, some of which were part of President Bush’s federally funded stem cell lines. Further, Thomson tested his reprogramming method using IMR-90 aborted fetal cell line, which was taken from the lung tissue of a 16-week gestation female baby. IMR-90 is a designer cell line specially produced by the NIH and Coriell Cell Repository as a future replacement for aborted fetal cell line WI-38, which is currently used in vaccine production.[3]

In February, 2008, two more studies were published on reprogramming adult stem cells: the first by UCLA’s Dr Kathrin Plath using neonatal foreskin cells; the second by Dr Yamanaka, using mouse liver and stomach cells, in which he claimed to overcome the problem of tumor formation. Interestingly enough, while none of his mice developed tumors, he admitted that several of them died for “unknown reasons”.  Once again, both scientists used aborted fetal cell lines as their DNA source and in addition, Plath then cultured her reprogrammed foreskin cells on embryonic stem cells. [4]  Since then several more published studies continue to rely on both aborted fetal and embryonic stem cells in order to accomplish the reprogramming.  Well why not?  After all, no one is complaining!

For despite the fact that the truth about the origins of the DNA has been revealed, many pro-life leaders are still salivating over this research as a means of ending the “need” for human cloning. But their reasoning falls short for several moral reasons.

First, they argue that because the embryos and aborted children have already been destroyed, it is morally acceptable to use those cell lines. While it is quite true that the scientists involved in the reprogramming research may or may not have directly destroyed some of the embryos they used, or participated in the original abortions, they did use cell lines taken from human beings that were deliberately destroyed specifically for research purposes.  And both the Vatican and the United States Catholic Conference of Bishops (USCCB) have condemned such practices:

In their 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” (Libreria Editrice Vaticana, p. 17).

In addition, the USCCB posted their response to President Bush’s August 2001 decision to provide federal funding for only those embryonic stem cells in which the embryos had already been destroyed.  They noted especially both the above citation from the PAFL and the following from Donum Vitae (Instruction on Respect for Human Life In its Origin and on the Dignity of Procreation: Replies to Certain Questions of the Day, Sacred Congregation for the Doctrine of the Faith, 1987):

“To use human embryos or fetuses as the object or instrument of experimentation constitutes a crime against their dignity as human beings having a right to the same respect that is due to the child already born and to every human person…The corpses of human embryos and fetuses, whether they have been deliberately aborted or not, must be respected just as the remains of other human beings...Furthermore, the moral requirements must be safeguarded, that there be no complicity in deliberate abortion and that the risk of scandal be avoided” (I.4). “It is a duty to condemn the particular gravity of the voluntary destruction of human embryos obtained ‘in vitro’ for the sole purpose of research…” (I.5).[5]

Clearly, there is nothing morally permissible in what these scientists have done and thus, one might assume that if our pro-life leaders knew how the reprogramming was accomplished they would not have spoken out in favor of this research.  However, that is not necessarily the case.  Donum Vitae, an official Vatican instruction discussed direct use of the embryo or fetus. For example, taking tissue directly from an aborted baby and transplanting it was clearly defined as illicit. The Pontifical Academy For Life, which is considered a guideline, rather than an instruction, discussed using the cell lines that are produced from embryonic or fetal remains.  Because there was no official teaching on these cell lines some ethicists felt it would be morally permissible to use these cell lines in research since the scientists were not directly involved with the destruction of the embryos or fetuses. In fact, this is exactly what happened when Georgetown University scientists were using existing aborted fetal cell lines in government sponsored research programs.[6]   And it is similar to what happened with arguments about the production of vaccines from aborted fetal remains, where researchers deliberately destroyed unborn children specifically for vaccine development.[7]  

In embryonic stem cell research, the embryo is destroyed when scientists extract the stem cells from the blastocyst.  In aborted fetal research, the abortions are pre-planned and arranged for immediate harvesting and preservation of organs and tissues.  Subsequently, cell lines are produced from the remains.  In both cases, once the cell lines are developed, they are then patented and frozen for future use in the hope of one day producing viable therapies and medical products.  In iPS cell research, in order to prove their findings, scientists must use  embryonic stem cells as a control comparison in order to validate that the newly created iPS cells are indeed embryonic-like. Thus, embryonic stem cells are an inherent part of both the reprogramming and the control studies.

In the April 2008 Ethics and Medics publication, Fr Tadeusz Pacholczyk of the National Catholic Bioethics Center, in commenting on the new iPS experiments pronounced the source of the reprogrammed cells to be “ethically pristine” and that the new reprogrammed stem cells “were produced without destroying or using any human embryos.”

There are two problems with this assertion.  First, the “source” – that is the original adult stem cell – was the only thing that was “ethically pristine” as it came from a living adult donor.  However, the source of the DNA used to reprogram those cells was from immoral sources, as was the finished product since it was dependent on using cells from deliberately destroyed human embryos and aborted fetuses.  The second problem is the assertion that the reprogrammed cell lines “were produced without destroying or using any human embryos.”  In fact, the scientists do not say whether or not they did in fact use new embryos in some parts of the research.  But in any case, they did use existing aborted fetal and embryonic stem cell lines, meaning that someone else conveniently did the killing while these scientists reaped the benefits. And while many would say this was clearly wrong, others still felt it was morally permissible as long as there was sufficient distance between the actual destruction of innocent human beings and the researchers using the cell lines in present day research. Clearly, a definitive Church teaching was needed as confusion abounded.

Finally, in December 2008, the Holy See was about to end all dispute on the matter. In its’ new instruction from the Congregation for the Doctrine of the Faith entitled Dignitas Personae. they emphatically asserted that the use of these “illicit biological materials” is prohibited.

“A different situation is created when researchers use “biological material” of illicit origin which has been produced apart from their research center or which has been obtained commercially…In this regard, the criterion of independence as it has been formulated by some ethics committees is not sufficient. According to this criterion, the use of “biological material” of illicit origin would be ethically permissible provided there is a clear separation between those who, on the one hand, produce, freeze and cause the death of embryos and, on the other, the researchers involved in scientific experimentation. The criterion of independence is not sufficient to avoid a contradiction in the attitude of the person who says that he does not approve of the injustice perpetrated by others, but at the same time accepts for his own work the “biological material” which the others have obtained by means of that injustice…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 …abortion…”

End of discussion, case closed.  Or is it?  In the second article in the same issue of Ethics and Medics noted above, Richard Doerflinger of the USCCB Pro-Life Secretariat provides further insight as to why some may be falling silent on the not so “pristine” methods that were used in the reprogramming, stating that the research “may affect the fortune of several pieces of legislation now before Congress”.  He cited the Human Cloning Prohibition Act and the Human Animal Hybrid Prohibition Act noting that it would be difficult to argue against the passage of these bills when there is now an “ethically sound alternative” in iPS cell research.

And there you have it: Smoke and mirrors.   If attention can be averted toward using reprogrammed stem cells, there will be no need to advance embryonic stem cell research and human cloning. Unfortunately, that argument has already been tested with successful, moral adult stem cell therapies and has failed. Scientists will never agree to abandon immoral research especially if they can have the federal government funding it. Yet what is lurking around the corner may very well end the debate about using iPS cells to pacify those pushing embryonic stem cell research.

Aside from the ethical problems presented here, another glaring concern in reprogramming a stem cell back to the so-called “iPS” or “pluripotent” state, is that those cells are not just “pluripotent”, but in fact, could become or already may be “totipotent”.  To explain: Pluripotent stem cells are those in the early embryonic stage that can form most of the cells, tissues and organs in the human body; totipotent cells can form all cells, tissues and organs – plus, they can form entirely new embryos, something that happens in natural reproduction when twins form.  So what was to stop scientists from reverting the cells a little further back in the development stages of an embryo to the totipotent stage, which could provide them with an unlimited supply of human embryos?  Nothing.

Coincidentally, in April 2008 the UK’s Independent broke the news story: Now we have the technology that can make a cloned child’, by Steve Connor, Science Editor in which he describes how reprogrammed skin cells were used to produce cloned mice, and perhaps in the near future, cloned human beings.[8]

Robert Lanza, of American biotechnology company Advanced Cell Technology admitted the technique was unethical and unsafe but still noted that, “the technology could be used to produce a child.”   The method was touted as extremely desirable for infertile couples since the embryo would be produced with biological material from both parents.

“It raises the same issues as reproductive cloning and although the technology for reproductive cloning in humans doesn’t exist, with this breakthrough we now have a working technology whereby anyone, young or old, fertile or infertile, straight or gay can pass on their genes to a child by using just a few skin cells,” he said.

The article describes the reprogramming method used and goes on to state: “Last year, when the breakthrough was used on human skin cells for the first time, it was lauded by the Catholic Church and President George Bush as a morally acceptable way of producing embryonic stem cells without having to create or destroy human embryos.”

“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 (Lanza) 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.”

So does the Catholic Church really think this is so great?  Hardly, because those in authority have not been informed as to what was really done in these studies. And lest one thinks that this latest rogue research is somehow confined to mad scientists in Great Britain, the National Institutes of Health recently awarded an $8.9 million dollar contract to scientists at the University of Wisconsin School of Medicine, the Genome Center of Wisconsin, the Morgridge Institute for Research and the Medical College of Wisconsin to further both embryonic stem cell and iPS cell research.[9]  It will only be a matter of time before the procedure is used here in the US for full-blown human cloning.

The truth is that if iPS cells are truly embryonic in nature, they will also carry the same dangers and clinical failures that have plagued embryonic stem cell research for years. Without question if unwarranted focus is given to iPS cells, embracing this research as the panacea for the future, it will be utter folly for the pro-life camp. First of all, that’s no better than proponents of embryonic stem cell research and so called “therapeutic cloning” who have given false hope to the weak, the vulnerable and the suffering by promising miraculous cures. And while the debates have, up to this point, focused primarily on the moral aspects, the only argument that can and does win the debate across political or moral or even medical ideology is the safety aspect. Because one can argue ethics until they are blue in the face, but one cannot argue against solid clinical results which only exist in adult stem cell research.

Meanwhile, those who have steered religious and political leaders to support reprogramming in hopes of diverting attention and funding from human cloning, may find that such tactics could backfire. Not only does their silence denote acceptance of immoral and clinically useless research, but also, by omitting the truth, they are hampering funding efforts for actual patient cures in adult stem cell research. That is both a travesty of justice and ironically, a pro-life defeat for those who have worked so hard to promote moral avenues of research. Worst of all, it is a devastating blow to patients awaiting cures.