Voiceover: In February of 2023, the Francis Crick Institute opened Cut and Paste, the first UK exhibition dedicated to exploring public attitudes towards genome editing. 80% of the researchers at the Crick use genome editing technologies every day to study health and diseases, including fertility, brain development, cancer, tuberculosis, malaria, COVID-19, and many others.
The Cut and Paste exhibit was commissioned as part of the Crick’s ongoing work to support public dialogue about the research conducted within the institute. Over recent years, new genome editing tools have been developed, which allow scientists to alter DNA, our body's instruction manual, more quickly, easily, and accurately.
These technologies hold vast potential to improve human health and the world around us. But they also raise all sorts of ethical questions.
You're about to hear audio from an event recorded in front of a live audience at the Crick earlier this year. We begin with Christophe Galichet, a scientist at the Crick working on adult brain stem cells, who was asked to answer a fundamental but very important question - what exactly is genome editing?
Cristophe: So genome editing, it's basically within you, within each of your cells, you will have DNA, which is your instruction book, A book that will say, you will have blue eyes, you will be that tall, and so on and so forth.
And genome editing is just using a tool. So CRISPR-Cas9 is a tool to go to a part of, of the DNA and change slightly the word. So before the new tool, before CRISPR-Cas9, we were doing it very crudely. We were going there, saying, okay, we think that this word is wrong. Let's try to force another word.
I'm pretty sure you've all, um, experienced auto correcting your phone. You try to send a message and then decide to use another word. And the first CRISPR-Cas9 was that. We were thinking, okay, we know where to change. We asked the cell to do it for us, and the cell were changing from time to time the right correction, the one we wanted to achieve, from time to time, the cell decided, no, actually, you mean that word, and it's not what we wanted.
But this system has evolved along the years, and now we can be very more precise, saying, okay, instead of having this word, uh, finishing with a Z, for example, we wanted to finish with an X, and we know we have tools. And genome editing is about that. It's, it's changing a few words in a book and those few words because the book, it's our instruction manual means that we are instructing the cells and therefore the body to do something different.
The Crick is a multidisciplinary institute. We are doing a variety of research trying to understand how the body works and how does the body work when it's being attacked through disease or through infection. So we have teams working on infection and immunity, on the brain, on different parts of the body, and we are using genome editing to try to answer different biological questions.
The last survey that we did, which was around 2020, showed that shy of 80% of the groups within Crick were using genome editing in some sort to answer biological questions. But we were using genome editing mostly with animal models, because it's what we have mostly at the Crick. But we did have a group that was working on human, human embryos, trying to understand how early human embryos develop.
And this is very informative to understand how pregnancy can then carry on and when things go wrong. And they were using genome editing to kind of perturb slightly some genes, some genome, to see how the human embryo will develop if you perturb such and such genes. On the side also, we do have a lot of colleagues at the Crick that are working with clinicians and so we have access to human samples and, and we can therefore understand on the petri dish what is going on and then use genome editing to kind of perturb and see how cells in a petri dish, not in human, but in a petri dish, will, will respond by different changes.
So, human is there at the Crick, very often in a petri dish
Voiceover: In July of 2019, scientists used CRISPR to treat a patient with the world's most common genetic disease. It was a world first. Christophe was asked to briefly tell the story of what happened.
[00:04:58] Cristophe: So this person's name is Victoria Gray. She's an American woman who was diagnosed, uh, from a very young age with sickle cell disease, which is a disease that will affect your blood, and your blood will not carry the oxygen the way, the way it should be.
And so what happened is her suffering was so much that they selected her to this new treatment whereby they took the blood stem cells from her, put them in a petri dish, and knowing which gene was the one that was defective in the sense for sickle cell disease, repaired it. So now they had this new blood stem cell in the petri dish that was repaired.
Then Victoria Gray, unfortunately, had to go through a round of chemotherapy to remove her own blood stem cell. And those blood stem cells that were repaired in a petri dish were then put back onto her. She has been cured entirely from sickle cell disease. She doesn't have any pain anymore. And I'm lucky enough to have met her a few months ago.
Her story is wonderful. And so now we have this kind of story and we have more people coming with sickle cell disease to be cured using genome editing and something that is happening at least in the U.S. and will come to, uh, the world in, in the future.
Voiceover: Suffering and pain are words that are frequently used when discussing genetic conditions, but defining them in biological terms can be challenging.
To help us unpack that, we invited clinical psychologist and research lead at the INPUT Pain Unit, Whitney Scott to speak.
Whitney: I've been for a number of years quite interested in how the experience of ongoing or persistent pain impacts on people's lives, including things like their mental health and their social well being. And in a way, another disclaimer, um, I don't have expertise in genetics or genome editing, and I guess I was quite interested and intrigued when I was invited to, to join this conversation in the sense of if the goal of this work is to relieve suffering, it's probably good that we have a sense of what suffering is and the many things that potentially contribute to human suffering.
So I guess I've been interested in pain, kind of professionally for 16 years now. And I guess my interest in pursuing this as a field, particularly as a psychologist, is that I grew up with a mum that lived with persistent pain and saw the massive impact that had on her physical and, you know, mental health, well being, and as well as on us as a family.
So that really got me thinking that this is probably a quite complex problem because my mom is quite a smart woman, and if she could figure it out, she probably would. And in fact, she spent a long time trying to figure it out. So that kind of set me off on a path of saying, you know, I think there's something for how we support the whole person in pain and how it impacts on them as a human being and the people around them.
That's probably quite important. We know that a whole host of biological processes influence the pain experience, but also a whole host of psychological and social processes impact. So how people think and feel about their experience of pain, their early life experiences, including with pain, how other people treat them when they're in pain, those all impact on the pain experience.
Voiceover: We asked Whitney to give her perspective on the case of Victoria Gray, the woman who was cured of sickle cell anaemia, and on what it might mean for other people living with chronic pain.
Whitney: This case provides quite an, I guess, thought provoking illustration of in some cases, you know, when there is a very direct kind of biological target and it does have this really big impact on a person's pain and quality of life.
You know, it does sound like it has quite a profound impact, and that is perhaps something to explore. But then when we think about the context of other pain conditions, it may be further down the line where we see that application because it's not this kind of single cell or single gene condition as such.
And I think the really intriguing thing that sparked an interest for me was this idea of who even gets selected for that kind of trial in the first place. And I think because by its nature suffering is subjective so we can't, we can't say there's an objective marker of suffering. It depends on the person, it depends on their, you know, their thoughts and their feelings and their social circumstances.
That then becomes a question of who decides how much suffering is enough and what biases might go into how we detect suffering in others and particularly in the sickle cell case I think it's really important to acknowledge that the majority of people that live with sickle cell disease are of African or Afro Caribbean heritage and we know particularly in the detection of pain and suffering there are huge biases that influence that detection, and we always have to be quite conscious of those influences.
So it's not sort of simple, objective manner of saying, this person has met this threshold. There's lots that go into that.
Voiceover: Whitney was then asked to talk about the kind of help that can be offered to patients when neither pharmaceutical nor genome editing interventions are available to them.
Whitney: From my side of things, I very much deal with the suffering that can come with pain. So as I said before, it's those thoughts and feelings that quite naturally show up around pain.
So as human beings, from an evolutionary perspective, it makes a lot of sense for us to experience pain in the short term. So it motivates us to escape situations where our bodily integrity might be in threat, um, you know, effectively it keeps us safe. But what happens when pain lasts a long time is those same sort of thoughts and feelings and evolutionary mechanisms are kind of yelling at us to keep ourselves safe, but we're no longer in danger and so what we support people with is to recognise that pain is complex. It is, of course, a physical experience in the body. And it is also connected with how we think and feel about our bodies. So that first awareness is quite a crucial piece. And then we help people to reconnect with areas of their lives that maybe pain has gotten in the way of. Maybe it's about finding different ways of approaching areas of their life that they care about.
And getting different strategies to, yeah, I guess reconnect with maybe situations or context where they may have avoided because of the pain because of that very natural sort of threat or fear response that is so connected to how we've evolved as humans.
Cristophe: Pain is learning. When you're in pain, you're learning about something.
If you're eating a sandwich and then you're in pain after that, you're learning not to eat that sandwich, because it makes you in pain. It's when pain is no longer a learning process. When pain is not teaching you anything, that is where you need treatment. However, even though we know a lot about genomes and the genes that is implicated in two different conditions, what we know is gene A, for example, would be implicated in obesity.
But gene A might be implicated also in other systems, like brain function, like the way you walk, like the way your heart is beating. Are we prepared to mutate or to repair or to change gene A to treat obesity, given that we might change something else that we haven't thought? So it's a question that we need to also have in our mind that touching one system might have implication on other systems.
Whitney: We need pain to tell us that we're going to harm our body. If we didn't, I might, you know, run into the road and not be all that concerned that I might get hit by a car. Also, the fear connected with that pain, that keeps, keeps us safe. Unfortunately, when some of these mechanisms, you know, generalise in situations when they, they don't need to or they go a little bit haywire, that's when we get challenges like persistent pain that no longer gives us useful information.
That's a really hard pill to swallow because so much of our, how we're socialised, particularly in Western cultures, is to say, you know, this pursuit of happiness, and, you know, we want to be happy. And I guess I would flip it, maybe there's different versions of happiness, and it's not happiness in the sense of we feel positive all the time, but how can we create rich and meaningful and satisfying lives in the presence of the real challenges that it is to be human. And I think I would add to that definition of medicine, it's not just about survival or reducing suffering, but what about thriving in the presence of the challenges that people experience. And I think there's real examples from various spheres of health conditions or, you know, human experience where people have thrived in the face of real adversity. You know, they've learned something from that. It has enabled them to adapt in different ways to move forward.
Voiceover: At the end of the event, we opened up to questions from the audience. One member asked Christophe to explain the scale of what is being done with CRISPR. With many trillions of individual cells in the human body, isn't the task of editing them all an impossible one?
Cristophe: It's true that one could think of changing or editing the genome everywhere. And you cannot touch one trillion ells, it's impossible. But what you can do is touch one cell. One cell will be able to change all one trillion whatever cells in your body.
And this cell is your egg and sperm, the original cell. Because these original cells will give rise to you as a person. So if you edit genome, these cells, you will have genome edited the entire body. So in mice, for example, we do a lot of genome editing that is inherited from generation to generation.
Then this is very informative for us scientists to understand the biology. In human, we are not there yet because we have to think of when you talk about. genetic disorder or a genetic disease or whatever it may be, you're thinking of something that affects the adult life often. But this gene could have a profound effect in the development of the embryo.
And so we have to understand the entirety of the gene's function from the very early stage, through the embryo, through life, up until almost death, to try to really understand that if you were to change one gene that will cure a disease, these genes or this cure or these changes will not have a knock-on effect in either your later life or the earlier life of your next generation, something to consider.
I think this is an area that needs a lot of discussion. A lot of discussion from politicians to have a strong possible understanding from the scientists of what is possible and you know, what we can do, but also to draw a line in the sand of what is acceptable, what is not. We can provide with the tools and I think it's the public that should provide the question. This is my view.
Whitney: Increasingly in healthcare researchers, a focus on involving people with lived experience of the condition under study, not only to interpret study results, but to really, you know, ask the questions, what should we be studying? How should we be studying it? What methods do we use? How do we disseminate it? And I think that is part of democratising science. So rather than saying, scientists do this over here, and then we present it to the public and hope democracy does its thing and works. It's bringing the public into science at the earliest stages and saying what's important to you. And through those conversations, you lead to different avenues and you may, what you initially set out to study may look quite different.
And I think some of these ethical issues often come from people with lived experience, and then you can be thinking about that very reflectively in the early stages. And I think there's even a role for that in biomedical basic sciences, and certainly in the pain field, there's an increasing push towards that at all levels of science, whether it's applied clinical science to basic science as well.
And I think related to that, so who gets to decide and who's making that decision will inform what that decision looks like. And I think one of my concerns in this space kind of related to the example I said before, what about the role of diversity in this and, you know, is that not something that has also driven human development.
So again, we think about neurodevelopmental disorders - autism. For many, many years, it was something that, you know, we 'have to' treat. We have to, you know, 'improve their suffering'. But now many people in the autistic community says 'this is part of who I am. And actually, it's a huge source of strength for me'.
So I think my concern, and it's a political one as well, like, how do we decide what is superhuman and how does that do away with potential diversity? And the political aspect of this is, you know, are we focusing on things that make us productive and that's a very capitalist thing? Or are we focusing on things that make us more connected as human beings and that's a different thing?
