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Quest for ethical stem cells prompts moral questions

Embryonic Stem Cells. / Nissim Benvenisty (CC by 2.5).

The first human trials for the treatment of blindness using induced pluripotent stem cells has brought the hope of creating stem cell therapies that do not rely upon destroyed embryos back in the public eye.

However, moral and medical questions surrounding the research on "iPSCs" have raised questions about whether the process is living up to its hopes of providing an innovative advance in biotechnology without relying on the destruction of embryos.

"Morally, there is no doubt that iPSC technology is a huge improvement over destroying IVF embryos or cloning embryos to gain pluripotent stem cells," Rebecca H. Taylor, a clinical lab specialist in molecular biology and author of the Catholic bioethics website "Mary Meets Dolly," told CNA, "but they are not totally free from ethical issues."

Taylor pointed to the widespread use of some "morally tainted" cell lines – that is, cells taken from aborted human beings – in various branches of scientific research, including in the creation of induced pluripotent stem cells.

The upcoming medical trial, approved by the Japanese government in late July, will be the first human trials using induced pluripotent stem cells.

To treat the patients' macular degeneration, scientists will take cells from tissue elsewhere in the patients' bodies and introduce genetic factors that allow the adult cells to become pluripotent stem cells: a type of cell capable of turning into a wide variety of tissues.

Having converted the cells into stem cells, the scientists will program the cells to grow new retinal material which can then be transferred back into the patients' eyes. Since the tissue comes from the patient's own body, scientists expect that there will be little or no chance of rejection of the new retina pieces.

The scientists anticipate that this therapy will be able to stop damage and vision loss caused by macular degeneration, while current drug therapies can only slow the disease's progress.

The technique used in these human trials differs greatly from other stem cell techniques used in the past. Unlike adult stem cells, which are already coded to make only certain kinds of cells, the induced pluripotent cells can be harvested from a number of tissue sources, and turned into almost any other kind of tissue in the body.

The only other kind of tissue with such diverse potential is embryonic stem cells, which have been the subject of research hopes for decades.

Since embryonic stem cells come from "a human organism that is genetically different" than the subject who will be treated with them, Taylor explained, they are more likely to be rejected by the subject than are tissues grown from induced pluripotent stem cells.

"If proven safe to use in patients, iPSC technology may mean genetically-matched stem cell therapy for a variety of diseases," she added.

The creation of induced pluripotent stem cells also offers the hope of a morally superior means of advancing stem cell research. Embryonic stem cells have been the subject of controversy for nearly two decades because the harvesting of embryonic stem cells requires the controlled creation and subsequent destruction of human life in its earliest stages.

Since induced pluripotent stem cells offer "patient-specific pluripotent stem cells without creating and destroying a cloned embryo," Taylor said, they offer a "huge improvement over destroying" human embryos for stem cell research.

However, norms surrounding the way scientists induce a pluripotent state introduce moral concerns to induced pluripotent stem cell research.

In order to induce a pluripotent state in adult cells, two things must typically happen: genetic factors must be introduced into the cell, and the factors must be activated. However, the current standard processes to achieve both of these steps involve the use and destruction of human embryos.

Dr. Mahendra Rao, director of the Center for Regenerative Medicine at the National Institutes of Health, explained to CNA that "the Yamanaka protocol is routine" in the medical community.

This process, created by Nobel laureate Shinya Yamanaka, was used as a means of limiting the creation and destruction of embryos for research. His technique calls for the growth of factors in a human cell line, Hek293, and  the activation of those factors by a virus in order to induce a pluripotent state. This process will be used in the Japanese human trials.

However, the Hek293 cell line was begun with tissue taken from the kidney of a human person who was aborted in the Netherlands during the early 1970s.

"The fact that a cell line of illicit origin was used as a tool in this technique does morally taint the research," Taylor explained.

She added that this cell line is "ubiquitous in labs all over the world," and that it and other "cell lines derived from abortions that occurred decades ago are common tools in biotechnology." Taylor added that it is so common, that she was "sure many researchers have no idea where these cell lines originated or that they are morally tainted."

The use of this cell line and other research derived from aborted subjects has been addressed by Vatican theologians. In its 2005 "Moral Reflections on Vaccines Prepared from Cells Derived from Aborted Human Foetuses," the Pontifical Academy for Life noted that even though the abortions occurred over 40 years ago, "they do not cease to pose ethical problems."

They concluded that "vaccines with moral problems pertaining to them may also be used on a temporary basis" if it is a life-threatening disease and there are no alternative vaccines.

Otherwise, Catholics and others who wish to respect life at all stages ought to abstain from their use, as well as further research using that technique.

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The Pontifical Academy for Life emphasized, "there remains a moral duty to continue to fight and to employ every lawful means in order to make life difficult for the pharmaceutical industries which act unscrupulously and unethically," and encouraged the creation and investigation of morally sound research alternatives.

In the years since the creation of induced pluripotent stem cells, there has been the creation of morally sound research alternatives, and new techniques that do not depend upon the destruction of embryos are in development.

The genetic factors used in the Yamanaka process can be cultured in "other cell lines, that were obtained morally," Taylor clarified.

Brendan Foht, assistant editor of the bioethics journal The New Atlantis, explained to CNA that "there are other ways of getting those genes expressed and reprogrammed" that avoid the use of genetic factors and proteins altogether.

He noted that research has been done on moving past the Yamanaka process because of the virus' tendency to mutate cells during the activation of the genetic factors, thus potentially creating cancers.

In 2008 Yamanaka discovered that pluripotent stem cells could be created through the introduction of plasmids – a ring of genetic material – into an adult cell. These rings of genetic code are easily grown in bacterial cells, and would not rely upon embryo destruction at all.

Scientists are also looking now to replace the use of the genetic factors with drug-like chemicals, which are created in a lab and do not depend upon growth in the objectionable embryonic cell line or any other living cell.

Given the forward steps toward creating ethically-produced induced pluripotent stem cells, the moral standing of the induced pluripotent stem cell trial in Japan is thrown into serious doubt.

Pointing to the Vatican's statements on the use of vaccines relying on embryo-destructive research and their permissibility only in in life-threatening cases with no other moral alternatives, Foht suggested that the Japanese trial is immoral.

Even with the alternatives and breakthroughs present, however, Foht said pro-life advocates "need to persuade the scientific community to do ethical research," and continue to speak against unethical and objectionable research.

Taylor echoed the need to speak out against induced pluripotent stem cell research that uses embryonic cells.

"We need to make sure that we object to cell lines of illicit origin whenever we hear of their use in science or medicine," so that investigation of moral research will be continued and that "iPSC technology may soon be free of that particular moral stain."

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