LONDON — A banned in vitro fertilization technology that uses two women and one man to create embryos could soon be legalized following an endorsement from a group of six British ethicists.

A working group of the London-based Nuffield Council on Bioethics issued a report in June stating that it would be “ethical” for scientists to mingle genetic material from three people in order for some couples to have their own genetic offspring without passing on a rare, heritable form of mitochondrial disease that can be “severe and debilitating.”

Critics of the controversial report call it “Frankenstein” technology that uses “emotional blackmail” — sad but uncommon circumstances — to justify technologies that will inevitably lead to genetic engineering — tampering with the human genome to “enhance” and select for certain characteristics that will be passed from generation to generation.

As well, there is a growing body of evidence that the same IVF technology used to avoid disease is itself a cause: Children born using IVF techniques to have significantly higher rates of birth defects.

The current technological crossroads arises at a condition called mitochondrial disease. Mitochondria are tiny organelles outside of the nucleus of a cell that produce the body’s energy. There are hundreds or even thousands in each cell.

Mitochondrial disease affects about one in every 6,500 people and involves defects in these tiny, vital powerhouses. It can affect multiple systems and present at any age, causing progressive illnesses, including severe muscle weakness, stroke, blindness and organ failure.

Most mitochondrial disease is a result of mutations in the nuclear DNA. Many cases result from non-genetic factors, such as toxin or virus exposure. A subset of the disease is caused by mutations in the tiny amount of DNA that is present in the mitochondria themselves, called mitochondrial DNA.

Mitochondrial DNA is unique because it is transmitted by the mother. It is not believed to affect identifiable traits of a person such as height, hair color or intelligence.

However, just as mutations in nuclear DNA can cause genetic disease such as Down syndrome, mitochondrial DNA mutations are responsible for some mitochondrial disease.


‘Pronuclear Transfer’

The Nuffield Council for Bioethics appointed a working group of six people to consider the two new technologies that would apply to this small subset of cases. “The intention is to allow women carrying disorders of mitochondrial DNA the chance to have healthy children that are genetically related to them but born free of those disorders,” said the report.

The first technology, called “pronuclear transfer,” involves creating two embryos, each fertilized by the sperm of the intended father, but one with an egg from the mother carrying faulty mitochondria and one from an unaffected donor egg. The genetic material of the parents is then transplanted from the faulty embryo into the embryo with healthy mitochondria.

The second technology involves “re-housing” the genetic material of an affected mother in a healthy donor’s egg before fertilization and thus avoids destroying human embryos in the process.

But the killing of human embryos (now a routine feature of many IVF procedures) is not the controversial point in question. What is unique about the new technology is the mixing of DNA from three individuals and stepping into “germ-line modification” of humans, tampering with the genetic material that will be passed on through generations. While somatic gene therapy affects the way genetic material is read, similar to what words in a book are read, germ-line therapy actually changes the DNA, or the writing in the books.

The Nuffield working group of four academics, a clinical geneticist and a journalist, concluded that the technology is morally justified.

“Due to the health and social benefits to individuals and families of living free from mitochondrial disorders, and where potential parents express a preference to have genetically related children, on balance we believe that if these novel techniques are adequately proven to be acceptably safe and effective as treatments, it would be ethical for families to use them, if they wish to do so and have been offered an appropriate level of information and support,” they wrote.

“Our view of the ethical acceptability of replacing mutated human genes with healthy human genes refers to mitochondrial genes and to no others,” journalist Geoff Watts, who chaired the group, said. “No floodgate is being opened.”

“And yet, and yet … we must be realistic,” he added. Watts told a press conference that “sooner or later someone is going to want to do this in nuclear genes.”

“What worries most people about constructing a person in this way is the same thing that worries them about GM [genetically modified] foods or human animal hybrids: the way that scientists treat nature as a set of infinitely exchangeable parts to be mixed and matched as necessary,” said David King, a molecular biologist who is director of Human Genetics Alert, a secular British reproductive technology watchdog group not affiliated with the pro-life movement. 

“Just as Frankenstein’s creation was produced by sticking together bits from many different bodies, it seems that there is no grotesquerie, no violation of the norms of nature or human culture, at which scientists and their bioethical helpers will balk,” said King. “But such concerns cannot be admitted as real within the discourse of bioethics and can certainly never overcome its trump cards of ‘medical progress’ or simply increasing knowledge.”

King referred to the “emotional blackmail” that is used to pressure society to accept dangerous new technologies. “We see this over and over again,” he told the Register. “There’s always some extremely rare, bizarre case to justify crossing an ethical line.”


An Irony

Rebecca Taylor, a molecular biologist who started the website Mary Meets Dolly to provide Catholics with an understanding of Church teaching on genetic-engineering issues and columnist for the Register, said that procedures used on somatic cells for strictly therapeutic purposes are in principle morally licit.

“Such actions seek to restore the normal genetic configuration of the patient or to counter damage caused by genetic anomalies or those related to other pathologies.”
Not so with germ-line cell therapy, she said. “Whatever genetic modifications are effected on the germ cells of a person will be transmitted to any potential offspring,” Taylor said. “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.”

She said the three-parent technique will take this “do it first; ask questions later” approach to a whole new level: “It would engineer a human being in such a way that that engineering will be passed on to future generations — generations that never gave consent. A dangerous precedent, indeed,” she said. “I fear that once a germ-line genetic modification like this is ‘successful,’ and U.K. law is changed to accommodate it, a door will be opened to even more germ-line human genetic engineering, not all of it for therapeutic purposes. And that, in my opinion, may be the ultimate point of this technology.”

Ironically, the enthusiasm of ethicists for new technological advances in IVF comes just as evidence mounts of their danger of producing the very types of birth defects they claim to be striving to prevent. This spring, research led by the Robson Institute at the University of Adelaide and published in The New England Journal of Medicine, examined 309,000 births in South Australia. It found the risk of a serious birth defect affecting major organs, spine or limbs or requiring treatment was 5.8% following natural conception. The incidence rose to 7.2% following conventional IVF and 9.9% with the widely used technique of intra-cytoplasmic sperm injection (ICSI) in which sperm is injected into the egg to facilitate fertilization. Yet no move to repeal ICSI has been presented.

“The nuclear transfer method’s only benefit is that it allows the mother to be a 50% genetic parent,” added King. “It is understandable that people want that, but that benefit does not justify the risks to the child — plus the risks to society — from crossing the ethical line forbidding germ-line engineering. You do not undertake such risks for the sake of more ‘options’ for parents.”

Register correspondent Celeste McGovern writes from Aboyne, Scotland.