Science Interviews

Interview

Fri, 11th Mar 2016

Tony Perry - Engineering humans

Tony Perry, University of Bath

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Kat - It’s time to hear again from one of last month’s guests - Professor Tony Perry from the University of Bath, who I spoke to at a conference on human genome editing organised by the Progress Educational Trust. Following on from our previous conversation about some of the ways scientists are hoping to use CRISPR to treat diseases within the body, I wanted to find out how the technology might be used to engineer humans free from genetic conditions, such as cystic fibrosis, which is caused by inheriting two faulty copies of the CFTR gene. And just because we can - does that mean that we should?

Tony - Using CRISPR/Cas9, we could edit a one-cell embryo so that its genome doesn’t any longer have that deletion. It has what everybody else has. Because we make the edit in a one-cell embryo, when the one-cell embryo divides, the genomes of those two cells will also inherit the edit that we’ve made. When they divide, and so on and so forth, so that when the child is born, all of the cells in the child will now contain the repaired version of the cystic fibrosis gene, so they won't get cystic fibrosis. So the reason is very useful, is that we could – or potentially, this is what excites people is that we can have anticipated this disease by repairing the predisposing genetic change that causes it.

So people are obviously very excited by that, not just because of cystic fibrosis although that’s very important, but because there are many other conditions. And so, cystic fibrosis as an example of what's called a monogenic disorder where it’s thought that a single gene can give rise to the condition. It’s thought that between perhaps 3,000 and 5,000 of these conditions exists - up to 6,000. And so, although individually, they're extremely rare many of them, collectively, they really add up to something, hundreds of thousands or millions even in the UK.

Kat - Those are conditions that seem to be linked to one particular gene fault, but the more we learn about diseases like diabetes, heart disease, the common things that tend to plague us, it seems from the genetic research that it’s due to lots and lots of gene, or lots of more subtle variations and certainly, many types of cancer as well. There aren't many like the cancers that are linked to specific faults in the BRCA genes like breast and ovarian cancers. How can we possibly go in and tinker with all of those variations? How is that going to work for these more common diseases that are linked to lots and lots of gene faults?

Tony - Well, these are very good questions and so, we don’t know. But certainly at the moment, there is every prospect that yes, we will be able to go one day in the future and edit the predisposing alleles for multiple genes. At the moment, the record is 62 in one swing of the bat. And so, it may be more and there are going to be issues and life is never that simple is it? But what we have to remember in all of these I think is that there are two things. One is that the CRISPR/Cas9 technology is not the only technology. There's DNA sequencing technology which is also marching ahead of the furious pace and which will feed into this discussion. But the second thing is that the CRISPR technology was first applied and reported in February 2013. So, this is fewer than 3 years ago. It’s remarkably soon after that first report in mammalian cells of CRISPR/Cas9. And already, we’re talking about these incredibly ambitious goals. So, I think if it continues to make the progress that its made so far, we should have every hope that CRISPR/Cas9 technology will be made safe enough for multiple human applications if we decide to apply it in that way.

Kat - What are some of the questions that people have raised about the safety, the accuracy of this kind of technology when it comes to editing humans?

Tony - Well, I think you raised a good point and it’s clearly a major bug bear. What is the specificity of this system? So, we have a system that’s highly accurate, but from time to time, it makes a cut where we don’t intend it to make a cut. So, we can now use whole genome sequencing to find out or learn more about that off-target cutting. And that means that we can design, we can engineer improved scissors, improved satnav so that the off-target cutting becomes less and less frequent. This is already very soon after that first since the advent really of CRISPR/Cas9 in mammalian cells. So, I think that we should be very optimistic that we can – scientists, scientific community can present the rest of society with the tools that are safe enough for these human applications, should they decide to use them.

Kat - It seems fairly obvious to me that there's going to be a point where we can do this and the big question is, should we do this? How is that discussion playing out, not just here in the UK, but around the world?

Tony - It’s interesting. The main centres of the discussion that I'm aware of are of course in the US where most of the technological advances have been made. They’ve done a fantastic job there and in the UK, where there's been a great deal of discussion about this. There's also, we shouldn’t forget China where the only report so far to be published of a human embryo genome editing using CRISPR/Cas9 appeared in April 2015, this year. So, these are the main places. The dichotomy really seems to be between people who say, we should at least explore the possibility of using this for medical applications. By this, I mean the CRISPR/Cas9 editing, and those who say, “No, just no. It’s crossing a line” and that’s the phrase that Francis Collins, the director of the National Institute of Health in the US used at the end of April in 2015 when he came out and made a statement as a director. He and others think this is just crossing a line which is never justifiable and the line is one where are now doing as you suggested, we are editing the human genetic contribution to our makeup and that’s something we just don’t get to do.

My view is that actually, these considerations must be heard and respected – all of them – those pro and those anti. At this stage, because the discussion, although it’s raging at the moment and I'm glad it is, it’s still quite young. It will be altered as technological advances get rolled out and continue to come at us – as I said that they're not just in the editing but also in the whole genome sequencing field. We shouldn’t rush to conclusions. So, my hope at the moment is that the discussion is as informed as possible about the science of what's going on rather than being utterly speculative and based on things which are a little bit sometimes fanciful.

Kat - We’ve talked about using this kind of technology for curing or preventing the development of diseases, but what about say, I have a friend who has a yearning to have a fish’s tail or something like that or maybe if I wanted super senses or something like that? Are people interested in editing maybe non-human characteristics into ourselves or enhanced human characteristics?

Tony - This is very interesting and it’s really in the realms of speculation. But yes, certainly, people are interested whether it be – maybe not so much although I don’t know people who want to become or for their children to be like mermaids - but certainly, yeah, combat troops of the next generation who have infrared vision for example or can smell certain odorants that other people can't detect. These are the kind of things that the kind of applications that some people might consider, and there are many, many others and it’s quite good fun – I don’t want to trivialise it - but to make lists of these things, the attributes that aren't directly disease-related but you might introduce it into the human germline.

The thing about this and that the problem with this is that it’s not really in my view an issue particularly for the editing technology. Once we have the tools for the editing and the vision for what we want to do, we still have to know how to apply these tools to get to that vision. This is what I call process. Unless we have the process right, we’ll never get to the vision. By process in this case, I mean, what genes are you going to edit and exactly how? Maybe which regions of the genes? So, you could take a very simple one. I don’t know if it’s important but it’s simple to describe because – and you did so of adding a fish’s tail onto a person so that they're like a mermaid perhaps or merman. Well, just where do you start? We’re nowhere near knowing how you would do that. In terms of the Hox gene expression, this is the days of the segmentation gene, the Homeobox gene transcription factors that control limb development. We’re just in the tall grass, still in the basic biology.

And people talk about IQ. I want my kids have an IQ of 300. Well okay, tell us which genes to edit and we’ll see what we can do. We just have no idea at the moment for many of these things. And so, a lot of this talk of these extra traits is utterly fanciful. It really belongs to the realms of genetics. It doesn’t have all that much to do with CRISPR/Cas9 per se, even if that’s your vision. And until people can tell you, “Look, we have now a very good idea that this gene, this gene, this gene, expressed at these different levels” and there might be hundreds different splice variants, different variants of the genes at different levels at certain combinations might give you an IQ of this.” Then we might think about, “Well, do we want to do that and how we want to do that using the CRISPR/Cas9 technology?” but for most of these, we’re nowhere near getting there.

Kat - Tony Perry from the University of Bath.

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