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Monday, May 14, 2012

Genetically modified humans: Here and more coming soon

CHILDREN with three parents might sound like monstrous chimeras, but they are among us already. In the late 1990s, an American team created the first genetically engineered humans by adding part of the egg of one woman to the egg of another, to treat infertility. When the US Food and Drug Administration got wind of the technique it was promptly banned, though related methods have been used in other countries.
Now a research team in the UK is experimenting with creating three-parent embryos. This time, the goal is to prevent children inheriting a rare group of serious diseases caused by faulty mitochondria, the powerhouses in our cells. Mitochondrial diseases affect at least 1 in 8000 people, probably more, and there are no treatments.
Mitochondria are always inherited from the mother, so for women in whom they are faulty, replacing the mitochondria in their eggs with healthy ones from a donor would help ensure their children are healthy. What makes the idea controversial is that mitochondria contain DNA of their own, meaning babies created this way will have genes from a "second mother".
Supporters of this approach point out that mitochondria contain a mere 37 of the 20,000 or so human genes. Changing them is akin to changing a battery, they argue. Yet it is becoming increasingly clear that the influence of mitochondrial genes extends far further: different variants can affect our energy, athleticism, health, ageing, fertility, perhaps even our intelligence, all of which help make us who we are as individuals.
The prospect of trying to prevent mitochondrial diseases by creating babies with two mothers raises a host of issues. On the one hand, if the Food and Drug Administration felt that three-parent embryos were unsafe, what's changed? On the other hand, if this approach really is safe, wouldn't it make sense to equip our children to live longer, healthier and more active lives by giving them the best possible mitochondria? The answers to these questions offer insights into some of the most intriguing aspects of sex, health, disease and longevity - and even into the origin of species.
Mixed up
Male mitochondria are an evolutionary dead end. While there are 100 or so in the tail of every sperm, powering its motility, they are destroyed when the winning sperm gets inside the egg, which is stocked with 100,000 or more mitochondria of its own. As a result, mitochondrial DNA almost always passes from egg to egg, mother to daughter.
This is the deepest distinction between the sexes. Forget the Y chromosome, which is a genetic johnny-come-lately, restricted to mammals: reptiles, insects and plants all have different systems of sex determination. Even many simple algae and fungi have two sexes, but the only thing their sexes have in common with ours is the passage of mitochondria down the "maternal" line.
How this came about is still hotly debated. The leading hypothesis, proposed in 1992, is that if mitochondria from the father and mother had to compete with each other for survival, "selfish" mitochondria would evolve to the detriment of the entire organism: the mitochondria that are best at proliferating are not necessarily best at providing a cell with the right amount of energy. Whatever the reason, all the mitochondria in our cells are normally identical.
In the 1990s, however, the fertility technique pioneered by Jacques Cohen at the Institute for Reproductive Medicine and Science of St Barnabas in Livingston, New Jersey, resulted in children with cells containing a mixture of mitochondria from different individuals - something that almost never happens naturally. The technique, known as ooplasmic transfer, involves transferring tiny extracts of healthy donor eggs into the eggs of infertile women, with the vague aim of "pepping them up" a little. It boiled down to injecting a bit of good egg into a bad egg, and hoping for the best. Surprisingly, it seemed to help, although no controlled trials were done to show this for sure.
Unanticipated consequences
The group suspected it was transferring mitochondria, but didn't anticipate the consequences. Despite injecting less than 5 per cent of the egg-cell volume, when blood cells were taken from two of the 30 babies born this way, about a third of the mitochondria were found to come from the donor egg.
While there is no evidence that these children will suffer from diseases as a result of their cells having a mixture of mitochondria from two different women, there is no guarantee that they won't, either. This is why most researchers think the FDA was right to ban ooplasmic transfer until its effects are understood. However, Jonathan Van Blerkom, a developmental biologist at the University of Colorado in Boulder, who sat on that FDA committee, sees the work now taking place in the UK in a different light. The approach holds enormous promise, he says, and it would be "criminal" to ban it.

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