3 Parent Embryos and Designer Babies

The following article and excerpt at the end highlight the very real problems of producing designer babies and genetic engineering…

http://www.wired.com/wiredscience/2010/04/mitochondria-engineering/

3-Parent Embryos Could Prevent Disease, But Raise Ethical Issues

Researchers have produced human embryos containing DNA from three people, a biotechnological proof-of-principle with profound medical and ethical implications.

To accomplish this, chromosomes were taken from one zygote — the single cell formed when sperm and egg fuse — and put into a zygote stripped of its original chromosomes, but left with its original mitochondria, which provide each human cell with energy.

As they grew, the resulting embryos contained so-called nuclear DNA — the 25,000 genes responsible for physical and developmental traits — from two traditional parents, and mitochondrial DNA from a third.

The technique is a subtle form of genetic engineering, which many people consider taboo, and raises other ethical dilemmas. It could also allow parents whose progeny would otherwise suffer from deadly mitochondrial diseases to have healthy children. It’s been done in mice and monkeys, but not in people.

“Previous work showed that these manipulations were possible. This showed that we can get the development of these embryos up to the blastocyst stage,” said Doug Turnbull, a Newcastle University neurologist and co-author of the study, published April 14 in Nature.

Thousands of mitochondria float freely in each human cell, using 17 genes to convert oxygen and nutrients into chemical energy. During reproduction, mitochondria in sperm are destroyed. Only the mitochondria in a mother’s egg are passed on.

Malfunctions in aging mitochondria have been linked to a variety of common diseases, including Alzheimer’s and cancer, but researchers like Turnbull focus on a subset of rare conditions caused early in life by defective mitochondria. About one in 4,000 children develops a mitochondrial disease by age 10. Such diseases are often debilitating, sometimes fatal and presently incurable.

In recent decades, doctors wondered whether defective mitochondria might be swapped for healthy ones in an embryo. In the last few years, sophisticated reproductive technologies and cell-manipulating tools have made that possible — first with mice, and then with more complex creatures.

Two years ago, Turnbull performed the basic steps of the technique with embryos left over from in vitro fertilization. Last August, other researchers performed a variation of the technique, starting with unfertilized eggs rather than zygotes, on rhesus macaque monkeys.

Of 80 embryos in the the Nature study, again taken from IVF leftovers, eight were sustained for six days, long enough to become blastocysts with about 100 cells.

The technique “introduces some inefficiencies because it’s more complicated” to use a zygote, said Shoukhrat Mitalipov, an Oregon Health & Science University reproductive biologist who led the rhesus macaque experiment. Both techniques may ultimately be used, depending on circumstance, he said. But the new results are still powerful.

“This is great. We’ve been thinking about this for years,” said Eric Schon, a Columbia University mitochhondrial geneticist. “That possibility is now closer.”

Many steps remain before mitochondria swapping could be considered for humans. Though engineered mice have matured and reproduced normally, the monkeys are just a year old. But while safety is yet to be determined, ethical questions are emerging.

One issue involves the nature of parenthood: Would a mitochondrial donor be a parent? Turnbull compared mitochondria to the power source for a laptop. “All the characteristics of the computer are stored on the computer. We’re just changing the battery,” he said.

Potentially more tricky is the healthy mitochondria’s source. While leftover embryos used in Turnbull’s approach are plentiful, eggs used by Mitalipov’s technique would need to be donated. Egg donation involves a series of grueling and potentially risky hormone treatments.

Marcy Darnovsky, executive director of the Center for Genetics and Society, worried that the risks of mitochondrial swapping might not be immediately evident. She mentioned intracytoplasmic sperm injection, in which sperm is injected directly into an egg. It’s an approved workaround for male fertility, but some studies now suggest an increased risk of birth defects (pdf). “Observers have said that human beings were the guinea pigs,” Darnovsky said.

Because mitochondria are inherited, both Turnbull’s and Mitalipov’s techniques are a type of germline, or heritable, genetic engineering. Many people think altering DNA is fine when changes aren’t inherited, as with gene therapy to repair eyes, but troubling when traits are passed on. Fearful of designer babies and long-term health uncertainties, countries like France and Germany have banned germline genetic engineering.

Mitochondrial swapping might seem less controversial than regular genetic engineering, because it involves metabolism rather than obvious physical traits. “On the other hand, when embryo manipulations for heritable changes start being done, even with the best intentions, we’re on slippery ground,” said Darnovsky.

“I think this strategy for handling mitochondrial disease is fascinating, important and ethical, but it certainly crosses the line of engineering genes,” said Art Caplan, director of the University of Pennsylvania’s Center for Bioethics. “It’s a quiet intrusion, but it crosses a line that a lot of people said shouldn’t be crossed.”

Doug Wallace, a mitochondrial geneticist at the University of California, Irvine, framed the ethics differently. “Is it fair for society to make it impossible for a woman who has a high percentage of mutant mitochondrial issues to have a healthy baby? That’s what I’m confronted with in my clinic,” he said. “There’s an ethic of what’s best for the patient.”

“For these families, there isn’t a cure,” said Turnbull. “That’s our motivation.”

Following is an excerpt from designer babies a right to choose?: http://www.wired.com/wiredscience/2009/03/designerdebate/

When a Los Angeles fertility clinic offered last month to let parents choose their kids’ hair and eye color, public outrage followed. On March 2, the clinic shut the program down — and that, says transhumanist author James Hughes, is a shame.

According to Hughes, using reproductive technologies — in this case, pre-implantation genetic diagnosis (PGD), in which doctors screen embryos before implanting them — for cosmetic purposes is just an old-fashioned parental impulse, translated into 21st century technology.

If nobody gets hurt and everybody has access, says Hughes, then genetic modification is perfectly fine, and restricting it is an assault on reproductive freedom. “It’s in the same category as abortion. If you think women have the right to control their own bodies, then they should be able to make this choice,” he said. “There should be no law restricting the kind of kids people have, unless there’s gross evidence that they’re going to harm that kid, or harm society.”

Hughes’ views are hardly universal. “I’m totally against this,” said William Kearns, the medical geneticist who developed the techniques used by the Fertility Institutes for cosmetic purposes, in a newspaper interview. In the same article, Mark Hughes, one of the inventors of pre-implantation genetic diagnosis, called its non-therapeutic use “ridiculous and irresponsible.”