Editing human embryos is genetics' new battleground

by jeeg 16. March 2015 21:04


Replacing faulty genes in early human embryos and germ cells is within our grasp. Such changes affect DNA in the nucleus and so would be heritable; ultimately, they could be used to make a genetically modified baby.

There are already reports that groups in China, the US and the biotech industry have done this kind of genetic engineering in the lab, prompting some scientists to call for a moratorium on this work. But the underlying technology is potentially hugely disruptive, offering easier and more precise ways to manipulate genes. Here's what you need to know about this new frontier in genetics.

What's behind the current controversy over human genetic engineering?
Several teams have tried modifying the genome of a human embryo and submitted their results for publication, according to an article published in Technology Review on 5 March. This kind of research is already illegal in some countries.

What exactly has been done?
We don't know the details yet. But based on what's been done in monkeys, the work probably involved fertilising donated human eggs by injecting a sperm and then, while the fertilised eggs were still at the one-cell stage, injecting various RNAs. These RNAs cut DNA at specific sites, tricking our natural DNA repair system into destroying or replacing one or more genes – a technique known as gene editing. The embryos would then have been allowed to develop for a few days until they reached the blastocyst stage – containing a few hundred cells – before being destroyed. The embryos' DNA would have been sequenced to see whether the gene editing had been successful.

So it's now possible to genetically engineer humans?
It was already possible. The hard part is doing it safely and efficiently. Gene editing was first developed decades ago, but it was very difficult and expensive, and often didn't work very well. To create just one genetically modified animal this way typically required hundreds of attempts. But editing genes has become a lot easier, cheaper and more efficient thanks to the CRISPR system, developed just a couple of years ago. This was the method used to modify the human embryos.

Why are some scientists calling for a moratorium?
They argue that human germline gene editing is dangerous, unnecessary and would lead to designer babies. They also claim it could lead to a backlash that would impede the use of gene editing for making non-heritable changes to our bodies. A wide range of diseases, from HIV to cancer, could potentially be treated this way.

So is germline gene editing dangerous?
We don't know yet. One of the points of trying it with human embryos is to find out. The main worry is so-called off-target mutations, that is, unintended changes to the genome. The monkey studies suggest the risk is low. The risk also has to be viewed in context: the DNA in our cells naturally mutates. Each of us is born with around 50 new mutations, the vast majority of which have no known effect.

Is germline gene editing the only way to prevent some heritable diseases?
Severe disorders caused by a single faulty gene, such as cystic fibrosis, can usually be prevented by screening. Parents can opt for IVF, for instance, with preimplantation genetic diagnosis – that is, testing the embryos before they are implanted to ensure they don't have the faulty gene. But when children are at risk of inheriting several faulty genes, screening usually isn't feasible.

Serious genetic disorders that strike early in life are, fortunately, rare. But we probably all inherit dozens if not hundreds of gene variants that increase our risk of common diseases such as cancer, dementia, depression and so on.

Will gene editing lead to designer babies?
Possibly. But it's not clear that many, or any, parents, would want to pay large sums and undergo a risky process – IVF has its dangers – just to ensure their child is blue-eyed. And it is of course possible to allow germline editing for disease prevention while banning it for other purposes. It would be hard for anyone who broke the ban to get away with it, given that genetic tests could reveal whether a child's DNA has been altered. Some argue, though, that parents should be free to choose their child's characteristics if they want.

But wouldn't allowing designer babies lead to the creation of supersmart superhumans?
Actually, no. We could probably modify people to make them resistant to all kinds of infections and diseases, and stronger and fitter. But when it comes to the brain, it is hard to see how we could go beyond what evolution has created. We're nowhere near to being able to predict how tweaking various genes would affect intelligence – in fact, the brain is so complex that this may never be possible. And it would obviously be totally unethical to experiment by creating mutants.

There has, of course, been a lot of interest in finding natural genetic variants that affect intelligence. But despite much effort, we've yet to find any that make much difference.

Michael Le Page, New Scientist



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