Three-Parent Embryo: Modifying Future Generations

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In October of 2012, scientists in Oregon announced they had created a dozen human embryos with the genetic material from two women and one man. While these embryos never made it to a womb, these researchers are hopeful that they will be given federal approval to, as USA Today reports, "test the procedure in women." This, of course, means transferring these genetically modified embryos to mothers willing to gestate them.

A few weeks later, in December 2012, scientists from New York proclaimed they have improved upon the technique that created these three-parent embryos and are intent on further developing their breakthrough for use in humans.

Why are scientists creating embryos with three genetic parents? Their intent is to prevent the inheritance of something called mitochondrial disease. Mitochondrial diseases are caused by mutations in mitochondrial DNA, often referred to as mtDNA. Unlike most of our genetic material, mtDNA is not found in the nucleus of the cell; mtDNA is instead found in organelles outside the nucleus called mitochondria. We inherit our mtDNA from our mothers because at fertilization sperm dump their mitochondria. A woman with a deleterious mutation in her mtDNA passes that mutation onto her children.

Therein lies the impetus for creating the three-parent embryo. Scientists have taken the egg from a woman with a mutation in her mtDNA and removed the nucleus. They transplant that nucleus into a donor egg with normal mtDNA. The genetically modified egg is then fertilized with the father’s sperm as in normal in vitro fertilization (IVF). The technical term for the procedure is called "maternal spindle transfer." The resulting embryos have the genetic material of three people: the nuclear DNA from one woman and one man and the mtDNA from the woman who donated the egg.

Morally, there is more at stake with the three-parent embryo than is readily apparent. The ethical issues go beyond the creation of human life in a laboratory. Maternal spindle transfer is not your average gene therapy. To date, gene-therapy trials have focused on introducing a normal copy of a gene into cells where a genetic mutation causes the cells to malfunction. This is called somatic gene therapy. Somatic gene therapy is genetic engineering for one patient in a particular cell of interest. Patients undergoing this kind of gene therapy will not pass these modifications to their children.

In contrast, germ-line gene therapy is genetic modification that will be inherited. This kind of gene therapy modifies egg and sperm so it affects not just the person undergoing the procedure, but every generation after. Maternal spindle transfer is germ-line gene therapy. The embryos created with this technique cannot help but pass their modification on to future generations.

There is real concern that the acceptance of germ-line modifications like maternal spindle transfer, even for therapeutic reasons, opens the door to other kinds of germ-line engineering, including modifications that would enhance already healthy offspring to be "superhuman" in strength or intelligence.

The Catholic Church is clear that somatic gene therapy, non-inheritable genetic engineering in one individual for therapeutic reasons, is a moral good. But the Church draws a clear line between somatic and germ-line gene therapy.

Dignitas Personae, the 2008 instruction on bioethics from the Congregation for the Doctrine of the Faith, states: "Procedures used on somatic cells for strictly therapeutic purposes are in principle morally licit. ... The moral evaluation of germ-line cell therapy is different. Whatever genetic modifications are effected on the germ cells of a person will be transmitted to any potential offspring. Because the risks connected to any genetic manipulation are considerable and as yet not fully controllable in the present state of research, it is not morally permissible to act in a way that may cause possible harm to the resulting progeny. In the hypothesis of gene therapy on the embryo, it needs to be added that this only takes place in the context of in vitro fertilization [IVF] and thus runs up against all the ethical objections to such procedures. For these reasons, therefore, it must be stated that, in its current state, germ-line cell therapy in all its forms is morally illicit."

So even though the intent of creating three-parent embryos is therapeutic in nature, because IVF is required and because this is a germ-line modification, Catholics cannot embrace this procedure.

Looking closer at the passage from Dignitas Personae, the phrases "in the present state of research" and "in its current state" suggest that there may be a time where the Church may support germ-line gene therapy. If the gene therapy could be accomplished by modifying egg or sperm precursors in the body, allowing conception to take place naturally in the marital act, then that would address the problems with the use of IVF.

But there is still the problem of safety. The risks of modifying sperm and egg are indeed "considerable" to the potential offspring, which is why many countries like the United Kingdom, Canada, Australia and France have laws against inheritable genetic modifications.

The United States has no such laws. Most Americans are unaware that this is not the first time scientists have created children with the genetic material of three parents. Back in the 1990s, New Jersey embryologist Dr. Jacques Cohen began using a similar technique called "cytoplasmic transfer" to help infertile couples conceive. Seventeen children were born after this technique, and two were confirmed with genetic testing to have the genetic material of three people.

According to a 2002 report in the Washington Monthly, one of the cytoplasmic-transfer children has been diagnosed with "pervasive developmental disorder." Cohen and his group were quick to dismiss cytoplasmic transfer as the cause. But the Washington Monthly quotes Dr. Jim Cummins, an Australian biologist, who warned, "To deliberately create individuals with multiple mitochondrial genotypes without knowing the consequences is really a step into the dark."

The Food and Drug Administration (FDA) quickly claimed regulatory authority and told IVF clinics to cease offering cytoplasmic transfer. For the new three-parent embryo technique to proceed into the clinic, doctors will have to seek approval from the FDA, which is presumably where the scientists in Oregon are headed next.

So the question remains: Can the safety of germ-line therapy be evaluated in an ethical manner? Right now, the Church is saying, "No." And with the inherent risks to future progeny, this objection may never be sufficiently addressed for the Church to change its stance.

Genetically engineered human embryos are no longer the stuff of science fiction, and germ-line genetic modifications are already a reality. Our faith provides us a clear and concise teaching that such modifications are unethical not only because they currently require IVF techniques, but also because they pose great risk to future generations. We Catholics are charged with educating our families, friends and neighbors about unethical germ-line modifications before they become mainstream. Once the modifying of egg and sperm becomes commonplace with IVF, there is the real possibility that such techniques will no longer be used to simply fix broken genes. They may be used to modify our children, grandchildren and great-grandchildren with whatever enhancements to the human genome we can dream up.

If society embraces germ-line modifications like maternal spindle transfer, the three-parent embryo may be only the beginning.

Rebecca Taylor is a clinical laboratory specialist in molecular biology.

She writes about bioethics on her blog Mary Meets Dolly.