A baby boy has been born using DNA from three people – the first ever birth resulting from a new technique that helps people with rare genetic diseases have healthy children. The achievement is being hailed as a milestone in fertility medicine, up there with the first IVF baby. But why is it such a big deal? How controversial is the technique? And is it safe? Here you can find some answers for your burning questions.
Who are the boy’s three “parents”?
The boy’s mother and father are a Jordanian couple who have already lost two children to a genetic disease called Leigh syndrome. The mother carries genes for this disease in her mitochondrial DNA, which is found in the cell’s energy-generating mitochondria. While we inherit the bulk of our DNA from both parents, mitochondrial DNA is only passed down from our mothers. To avoid passing on the disease-causing mitochondrial DNA, John Zhang and his colleagues at the New Hope Fertility Center in New York City used mitochondria from an egg belonging to another woman – an anonymous donor.
How much DNA comes from each person?
Almost all of the boy’s DNA will come from his mother and father. That’s because most of our genes – around 20,000 in total – are found in the cell’s nucleus; just 37 are found in the mitochondria. In the new procedure, Zhang’s team removed the nucleus from one of the mother’s eggs and inserted it into a donor egg, which had its own nucleus removed. This egg was then fertilised with the father’s sperm. The resulting embryo therefore had nuclear DNA from its parents and mitochondrial DNA from the donor.
What do these 37 mitochondrial genes do?
These mainly code for enzymes that keep the mitochondria themselves functioning. While a malfunction can trigger a devastating disease, the genes are unlikely to code for the more obvious traits people inherit from their parents.
But because they power cells, mitochondria could indirectly affect other things by altering the way cells function. A few studies have suggested that mitochondrial DNA might influence a person’s athletic ability, how long they will live and even their IQ. The exact mechanisms aren’t clear.
Haven’t “three parent” babies been born before?
Yes, although using a different technique. Back in the 1990s, Jacques Cohen and his colleagues at the Institute for Reproductive Medicine and Science at Saint Barnabas in New Jersey were the first to inject fluid from healthy eggs – including their mitochondria – into eggs from women who had been through several rounds of failed IVF. The hope was that the donated mitochondria would boost the flagging eggs.
The team tried their technique 30 times in 27 people, and 17 babies were born. But two fetuses developed a genetic disorder, in which they lacked an X chromosome. One of these pregnancies resulted in a miscarriage, the other was aborted. This led to safety concerns. In 2001, the US Food and Drug Administration wrote to fertility clinics in the US, asking them to stop using the method, and to instead apply for approval from the FDA itself in all cases. The method, called ooplasmic transfer, fell out of favour at that point.
Is the new method safe?
As far as safety is concerned, it is too soon to know. The baby boy is the first to be born with the new method, so we have too few births to draw conclusions from. For now, though, it seems that the boy – now 5 months old – is healthy.
The primary concerns are that some faulty mitochondria could have slipped through the net. It is virtually impossible to leave behind all the mitochondria from the mother’s egg when removing the nucleus, even with the steadiest hand. And the level of mutated mitochondria that can cause symptoms varies by disease. One concern is that “bad” mitochondria, even in tiny amounts, could be better at replicating than “good” mitochondria – eventually tipping the balance and causing disease further down the line.
A second concern is that having mitochondria from two sources could disturb the normal relationship between the nucleus and mitochondria, although it is unclear if this is the case. It is a good sign that the boy is healthy, but he will need to be carefully monitored over the coming years.
Is the procedure legal?
It depends on where you want to do it. A similar technique was approved in the UK last year, although, as far as we know, no one in the country has tried it yet. Embryologists who want to carry out the procedure in the UK first have to apply for a licence, and then must follow a legal and ethical framework. They must also closely follow the development of any babies that are born.
In the US, it is up to the FDA to approve the procedure before it can be legally carried out. The country’s Institute of Medicine recommended that they do this back in February, at least for sons, who won’t be able to pass on any of the mitochondrial DNA they receive from the donor. The FDA has yet to make a decision. Zhang says that he tried to apply for FDA approval, but that the organisation told him there was no department set up that could review his application. So he performed the treatment in Mexico, where, as he puts it “there are no rules”. He hopes to continue his work in Mexico, China and the UK.
Why is it so controversial?
Some people don’t like the idea of a baby having three biological parents, and argue that mitochondrial DNA goes some way to shaping important characteristics, such as personality. But the scientific consensus is that swapping mitochondria is similar to changing a battery – it’s unlikely to have much, if any, influence over a person’s behaviour.
Others have argued that the technique is unnecessary. After all, it won’t help those who have already been born with mitochondrial diseases. Parents often don’t find out they are carriers of these diseases until they give birth to sick children. And those who do know they could pass on a disease have other options, such as using a donor egg. The technique is specifically for people who carry genes for the disease, but want to have a child genetically related to them.
Another concern is that, by creating a new mix of genetic material, embryologists are creating lasting genetic changes that will be passed down through generations, before we have a chance to find out if they are dangerous. Some argue that this starts us on a slippery slope of germ-line editing – one that could eventually lead to “designer babies”.
Could it have other uses?
Potentially. Some embryologists believe that ineffective mitochondria could be the cause of age-related infertility, and that eggs of older women fail to form viable embryos because they essentially lack energy. That’s the idea behind Augment – a treatment that uses mitochondria from a woman’s own ovarian stem cells to rejuvenate her egg cells. The team behind this project announced their first birth last year. However, many in the field remain sceptical – doubting that ovarian stem cells actually exist.
If ovarian stem cells don’t exist, but the theory behind the rejuvenation idea stacks up, then mitochondria taken from the eggs of young women could be used as an alternative.