Gunes Taylor: Genome editing in plants, animals and humans.

Dr Gunes Taylor, image courtesy of The Francis Crick Institute

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One of the scientific advisors working closely on the exhibit is Dr Gunes Taylor, a postdoc in developmental genetics at the Francis Crick Institute. To begin my chat with Gunes, I wanted to know what exactly is genome editing, and how is it different from genetic modification, or GM?

Gunes: Genome editing as a phrase is actually a catchall. So genome editing has actually been going on for quite a long time, like several decades. But we used to call it genetically modified organisms or GM or things like that. And what happened, actually was about 10 years ago when a new sort of flavour of DNA editing tool came out called CRISPR/Cas9 or CRISPR for short. At that point in time, people started talking a lot more about it rather than just about genetic modification. We started calling it genome editing because CRISPR had basically made it way more controllable. It was editing, not just like genetic modification.

Gunes: So the analogy I always use is CRISPR was to the mobile phone revolution, what the iPhone was. It's like mobile phones existed before iPhone One, but when iPhone One came along we were all like, "Oh wow, okay, this is what a smartphone is." And that's what CRISPR is to genome editing tools. This is faster and cheaper, the analogy doesn't hold there because Apple products are very expensive. But anyway...

Sally: We do talk a lot about CRISPR, as we are a Genetics podcast, we say, "Oh yeah, we CRISPR this, CRISPR that." It's been a while since we've actually talked about what CRISPR is and how it works. What is CRISPR/Cas9, where did it come from?

Gunes: So technically it is a bacterial immune system, that was the research that sort of uncovered this thing.

Sally: Which in itself is kind of bonkers that bacteria have their own immune system.

Gunes: I know!

Sally: We have immune systems against bacteria, and then bacteria have their own?

Gunes: Yeah, so that's exactly right. Bacteria have to also defend themselves from even littler critters like viruses for example. And what they do is, like how we have memory in our immune systems, CRISPR technically is the sort of memory immune system of bacteria in the same way.

Gunes: So they basically take the DNA from the invader, they cut it up, and then they hold onto those little bits, like little wanted posters and they go, "Right, I will recognise this thing, if it ever comes back in again."

Gunes: Cas9 is a separate part. So CRISPR/Cas9 genome editing I always say is a two-part molecular system.

Gunes: One part is the CRISPR, one part is the Cas9. Now the CRISPR part is the programmable bit, because as I said, it's those wanted posters, right? So then as a scientist, what you can do is you can artificially create your own wanted poster for whatever gene that you are wanting to hit. And the Cas9 is the doing end of it, as it were. The Cas9 is a protein blob that does cutting, and so when you put them together, it goes, "Okay, this is what I'm looking for, and Cas9, when I find it, you will cut this piece of DNA."

Gunes: And so what we've got here is a tool for deliberately breaking pieces of DNA in locations of interest. And what we then rely upon is the fact that DNA does not like to be broken. It needs to be fixed. Fixing usually works out just fine, but occasionally mistakes get made. And in this context, when you're doing an experiment, say, and you want to know how important a gene is, if you manage to break the DNA and it doesn't get fixed properly and say a mistake gets introduced, and so that gene stops functioning, that allows you, as a scientist to be able to answer the question, "Hey, how important is this gene to this process that I'm studying?" Look, we've broken it effectively, so now let's see what happens.

Sally: So we can use CRISPR to break genes. Do we also use the same technology to insert genes? Because a lot of the history of GM crops, I'm thinking of like Golden Rice, for example, was inserting vitamin A genes if I remember right, beta-carotene genes, into rice. So can we use CRISPR to insert as well as just to cut?

Gunes: Correct, yes, that's exactly right.

Gunes: So the basic mechanism is, by being able to break in a specific location, you have the opportunity to either remove, to insert, and also to just change over. So if you want to just simply swap out one or two bases for something else, that is something that you can do with a lot more precision using CRISPR, for example, right?

Sally: How is CRISPR being used to edit things? So I'm gonna break this into plants, animals, and humans, because I think in terms of the ethics, I think there's very different ethics for each of those three groups.

Sally: So with plants, where are we at now? I've already mentioned Golden Rice back in the olden days, that was what, like the nineties, noughties, Golden Rice?

Gunes: Yes.

Sally: Quite a long time ago. So where are we currently at with genome editing in plants?

Gunes: You know, we're at the stage now where it's not just, "Oh, we can put in a bit more beta-carotene into the rice."

Gunes: It's like, people are discussing, and many companies are investigating the possibilities for using CRISPR in plants to provide more nutrients, to fortify them with different properties, minerals, vitamins, whatever it is that we want to put into them to increase their nutritional value, literal calories.

Gunes: But a big one at the moment is also talking about the impact of climate change on crops and actually using CRISPR to build more resilient crops to be able to equip the literal plants to be able to grow in different climates that they wouldn't otherwise, and pesticide resistance effectively, or resistance to various forms of blight.

Gunes: So you can basically now, theoretically at least, edit the plants so that they aren't so susceptible to destruction effectively. And this is one of the big ethical concerns and it really splits the field, right? Some people are like, "Great, don't have to use pesticides and kill off loads of animals, you just make the crops more resistant!"

Gunes: And malnutrition is a terrible way to suffer and it affects a huge amount of the planet, "Well, look, you can change that in one fell swoop, basically, so why wouldn't we?"

Gunes: Whereas of course, other people are quite concerned about it or suggest that we should use other methods of fixing these problems rather than going straight in at the DNA level and starting to alter things. Why make rice that's extra good when you could fix the political systems that prevent people in certain areas getting the kind of food or the levels of food that they need. And you know, that's a fair enough question, right? Supply chains and provision of resources, it's not a CRISPR-addressable problem, and that's not to say you shouldn't use those things either, right? I think that's basically the umbrella of it. It's like, "Look, we could fix malnutrition without having to use any form of DNA modification. So how about we start there? "

Sally: So that's genome editing in plants. Moving on to animals. What kind of genome editing is happening with animals, non-human animals I should say?

Gunes: Again, the sort of epicentre of the animal genome editing conversation is all about livestock. Basically it's about agriculture, it's about animals that we rely upon in our food chains. So chickens, pigs, cows, you know, those kinds of things.

Gunes: For example, myostatin is one of the ones that I think is being looked at in cattle, for example. So if you knock out genes that regulate muscle growth, you can lead to excessive muscle growth. Excessive muscle growth leads to more meat. So that's one option.

Gunes: Then there's also the possibility of trying to improve the already ethical minefield that's around livestock. So for example, with chickens and with many of these livestock animals, it's single sex, right? It's only female cows that make milk and with chickens, again, the cockerels are all superfluous. So there is already in fact a company that has used genome editing to introduce elements of a system, let's say, into chickens that allows them to screen for females only. And so only the female chicks are hatched...

Sally: As we will be discussing in the next episode of Genetics Unzipped, we will be talking about getting rid of male chicks!

Gunes: Well, exactly. And you know, the use of these CRISPR technologies has made it possible to do even earlier. Obviously doesn't address the problem of should we be doing this at all, but making it more ethical or more palatable in some sense is another way of doing it.

Sally: And then moving on to humans. This is obviously going to be the most controversial. So what currently is allowed to happen when it comes to editing genes in humans? What isn't allowed to happen and what has been done, what hasn't been done?

Gunes: Okay, so there's a difference between human embryos and human babies. So in human embryos in the UK there was only one, as far as I was aware, the Niakan Lab, they were given a licence to use CRISPR/Cas9 genome editing in early human embryos to research how the early decisions get made during an embryo. So there is some provision for that, but it's very tightly regulated.

Sally: But those embryos are never destined to become humans, to be born.

Gunes: That's exactly right. That's exactly what I was gonna say.

Gunes: So the rule is always and is consistently, supposedly across Earth, if you need to use human embryos to address your research question early on, provision can be made for that, but they will not be implanted, and it's completely illegal to do so in most countries.

Sally: You said there was a difference between editing human embryos and editing humans, babies, adults. What's happening with humans after they've been born and genome editing?

Gunes: Yes. So the reason why there's this important distinction is if you edit human embryos early on, it falls under a category called "heritable genome editing", because if you modify an early embryo, it is possible that you might modify the cells that will become the sperm and the egg eventually. And so the modification you introduce might be propagated onto the next generation. Whereas if you edit in a formed body, the future sperm or egg cells have already been put aside and you probably won't be targeting their genomes, and so it's what's called "somatic genome editing".

Gunes: At present, there is far more interest in the somatic gene editing that's going on. So people are more interested in using genome editing to develop cures and treatments, but of a person who's been born with a situation. So one for example, that springs to mind immediately is things like sickle cell disease or one of these blood disorders. You know, sickle cell disease leads to a huge number of health complications and deaths across planet Earth. It is known to have a genetic basis, and so genome editing can be used to correct that and has been, but there was quite a substantial price tag on it. And so therein we come back to the issue of ethics. Right? Who's gonna pay that? Who can pay that?

Sally: Yeah. What sort of price do you put on a healthy life?

Sally: It's very, very difficult to determine. So you've been sharing all of this kind of research with the public through this public exhibit, what would you say are the biggest misconceptions about this sort of research that you've had to try and overcome when creating this exhibit?

Gunes: Honestly, I think the biggest misconception is that bizarrely people will just be like, "Oh, I'm not going to understand this!" So it's actually just overcoming that initial, "Oh, I'm not smart enough, or I'm not going to get this," hurdle that immediately comes up when you say to someone, "We've got an exhibition about genome editing on."

Gunes: And the fascinating thing is the moment you get people over that hurdle, turns out everyone's got loads of opinions. Because of course they have. Who doesn't? Right? But it's just getting them in!

Sally: I think especially because it is such an ethical issue, like you don't even need to know how the Genetics are being edited to be like, "Okay, if there is a million dollar treatment for someone who gets to pay for that?" You need to know very little about the underlying science behind it to be able to really engage with those ethical quandaries.

Gunes: Exactly. For me, at least the whole thing can be summarised very, very simply. It goes like this:

Gunes: DNA contains information that is important for your health and for your body. That is true for both plants, for animals, and for human beings. And so now that we have a technology that allows us to alter DNA, it means that we can have an impact. We have a choice in the matter of health and bodies of plants, animals, and humans. And so now here is the question, think about anything that you want to in the world about health or about bodies, and now know that we can change that should we wish to. What would you do? What do you think is worth doing? What do you think is not worth doing? 

Gunes: That's it. That's literally what the conversation is. And everybody kind of knows that, we all know that somewhere deep down inside that there is this relationship between what human beings do and how things work out and that we have impact beyond just our own bodies on Earth.

Sally: Have any of your opinions changed through the process of talking with the public about this?

Gunes: Yes. If I'm being very honest, this is just a very personal reflection here, but I consider myself to be a very solution oriented person, and so to me, I would always have thought fixing something has always got to be better than not fixing something. And I'm a big believer in human beings being able to have agency and make anything they want to make possible.

Gunes: I think our human world proves that to me, and so I have this incredible faith that if we want to do something, we can do it, and that, you know, things should be fixed and optimised and brought into balance. These are my beliefs.

Gunes: But I think through this exhibition, through talking to more and more people, the big thing that I've had to accept, I guess, is that some people, would genuinely feel more comfortable to not interfere or not take control and let things be for reasons of historical or social values that maybe I don't necessarily share. And just accepting that people can have that position and accepting that I think has been quite a journey in itself.

Gunes: But one of the things that makes the exhibition unique is that we are also inviting people to write down or record their thoughts and their reflections on the exhibition, and we are literally listening and collating this information. Because of course, the Francis Crick Institute is a major stakeholder in the British research landscape, and also therefore, we will be consulted when it comes to big policy decisions like, for example, what should happen with the genetic modification of plants and agriculture, laws that as I said, are already coming up for debate. So this is an opportunity for the public to have their opinions listened to by an institution like ourselves, and then we can collate that information and it genuinely will impact how we communicate going forward.

That was Dr Gunes Taylor from the Francis Crick Institute.