Editing human embryos

At the beginning of August we saw headlines loudly proclaiming that scientists have managed to use precision gene editing technology known as CRISPR-Cas9 (or usually just CRISPR) to fix a faulty gene in early stage human embryos. In fact, this wasn’t the first time that researchers have used CRISPR on human embryos, but it was certainly the most successful attempt to date.

The research team, made up of scientists in the US, South Korea and China, successfully fixed a faulty version of a gene called MYBPC3, which is responsible for the serious heart defect hypertrophic cardiomyopathy, which affects one in 500 people and can be fatal. Although the fix wasn’t perfect, it was more efficient than previous attempts, marking an important step forward for the technology.

To find out more about what’s different this time, Kat Arney spoke with Yalda Jamshidi, who specialises in the genetics of heart disease at St George’s, University of London.

Yalda - So, there's actually been three attempts that have been published in the medical literature before that were all out of China. And in all three cases, they had similar problems. One of them was that they couldn’t get enough of the healthy copies into the embryos so that the correction wasn’t very efficient. And also, they found that there was a mixture of modified and unmodified cells so whilst some cells there was a correction, there wasn’t in others. And they didn’t have very high efficiency rates. So, I think in the first study that was published, out of 68 embryos, they could only correct four of them.

And so the difference between that study and the current published study is that they had tried to edit this after the sperm and the egg fertilized. So it’s a much later stage in development. It was still in the embryo but certainly not as early as the current one which literally was at the time of fertilization, they would put in the CRISPR or the gene editing machinery at the same time.

Kat - Now, I used to study very early development and I know that that time when the sperm goes into the egg, there’s also sorts of unpacking, repacking, rearranging going on. Do you think that might have contributed to the success of the process?

Yalda - Yes. I think actually that probably isn’t too unexpected, because at that time in development the embryo is already trying to deal with a lot of mutations or correcting lots of changes that it finds. And so, perhaps this process already happens to some extent at that early stage and having just an extra mutation to correct wasn’t so difficult for the embryo.

Kat - So this is just one condition. Was there a particular reason why this condition was tried? Could it work with other diseases or even traits, for example like intelligence?

Yalda - So I think that’s an interesting question. Perhaps one of the reasons they focused on this cardiomyopathy is because it’s fairly common - so 1 in 500 adults actually suffer from hypertrophic cardiomyopathy.

It’s also quite severe, so there’s no treatment at present. Anything that they do take is really to try and alleviate symptoms, but there’s no cure. And because it’s highly associated with sudden cardiac arrest, so you might hear about it when you see these athletics who are running around and suddenly suffer cardiac arrest on the pitch, it’s actually quite a shocking condition.

So I think maybe part of the reason was that it is a very severe life threatening condition, so that would be one reason to target it. Whether or not they would apply this to other genes, and other mutations in diseases, we’ll have to wait and see.

But I think when it comes to traits like intelligence or height or eye colour, you hear about all these designer babies and whether we’re going to do that, I think that’s a much more complicated situation because it’s not one gene and one mutation that causes those. It’s actually lots, hundreds and thousands working together. So whether we’re ever going to be able to gene edit 100 at one go is probably fairly unlikely.

And also, the genes we know contribute to many conditions and many traits, so you might target something that is going to affect height but actually end up affecting something else unwanted, so you might end up affecting weight by editing that gene. So I think that’s not going to happen anytime soon.

Kat - In terms of the technical side of this, what actually happened to the embryos? These didn’t grown into babies, did they?

Yalda - No. So like much research that’s carried out on embryos, there’s a limit to how long you can keep them in culture. That’s usually 5 to 7 days maximum. So at that point they would have been destroyed. There was certainly no intention by the researchers to implant these embryos at the end of it.

Kat - Given the kind of techniques we have at the moment for screening for serious genetic diseases at the pre-implantation stage in the IVF process, is this really necessary? How would it work? How would it fit into that?

Yalda - So at that moment, if a couple would opt for preimplantation genetic diagnosis, the laboratory that would deal with it would take the sperm and the egg, and they would be screened for mutations.

And if a parent has a mutation such as the one for the hypertrophic cardiomyopathy, half of the embryos will have a mutation, therefore, half of them would need to be discarded. So, in ethical terms perhaps, if we didn’t need to discard those 50 per cent of embryos and we could correct them and improve the efficiency then I think there might be a place for this kind of treatment.

Kat -所以我们的想法是,如果这个纠正过程dure works when you put the sperm into the egg, you would just correct all of them whether they were faulty or not and then expect that you would have a much higher percentage of fixed embryos that you could choose from.

Yalda: Yes, that’s correct. So, if you could make the efficiency high enough then you wouldn’t need to worry about discarding any unhealthy copies.

Kat - Now we’ve obviously know that probably we can, should we do this?

Yalda - So, it was much more efficient than previous studies. I think it was just over 70 per cent efficient. But what they we're actually doing was enhancing what we already carry out, which is preimplantation genetic diagnosis for families like this.

So whether or not we would want to bolster the current chance of those embryos being healthy by an extra 20 per cent, 25 per cent, is probably not quite there yet. It would need to become much more efficient and much closer to 90 per cent efficiency. Because ideally, you want to have a situation where all of your embryos are corrected and healthy, and able to implant them. So I think there’s still some way to go with efficiency.

The intention wasn’t necessarily to use this to treat. It was more about learning how the process works, and we don’t know lots about how gene editing affects embryos over time. And there would need to be much more research time to study that, probably on non-human primates before anyone started thinking about doing clinical trials and getting this into clinics. So I think we’re quite some way off in that sense.

Whether we should do it or not, I think that’s a highly contentious question and certainly, a lot of the papers and the people are asking that question. And in my own opinion, I would say that, hopefully if we could make the procedure much more efficient, much more safe and there was plenty of evidence that it would work and it would be fine, then in some cases, where there really is no other alternative, no other medical treatment or possibility, then it should be something that could be considered. But only once the public and the scientific community and the legal community have come to a kind of a consensus about what we are going to do with these sorts of techniques and how safe they are, and we really are okay with it happening.

Kat - How would you like to see the discussion about these techniques, about this technology, changing in the media?

Yalda——我认为这将是伟大的如果有be more of a balance with what is being reported and less focus on designer babies and the use of genome editing to try and produce these designer babies. Because much of the research and the researchers who are looking at it, they’re really not looking to and up with the designer baby that they can then go and help a couple improve the child’s intelligence. It’s actually more about trying to help patients who have serious life-threatening conditions now, and they want to alleviate their symptoms where there isn’t a medical cure at present.

Kat - And hopefully, more education and understanding about what this technology actually is and how it works and how genetic works.

Yalda - Definitely. I think genetics is getting even more and more exciting at the moment and it’s definitely starting to get into the media a little bit more. But there’s plenty of room for education and for helping people understand what we mean by all these science fiction-type words and techniques, so that people will understand a little bit better what we are trying to do and why we are trying to do it.

Kat - Yalda Jamshidi from St George’s University of London.