With the ever-increasing potential of new technology and the exponential growth of the life sciences field, researchers are always running into new problems to solve. In this interview series, we get scientists’ opinions on the ‘Big Challenge’ in their field and the steps being taken to address it. From new and unique hurdles to fresh takes on common problems, we dive into the complexities of the research landscape.
In this interview, we chat to James Davies (Clinical Scientist, University of Oxford) about the technical, clinical and ethical challenges associated with genome editing.
FLG: What is your background and role?
James: I’m a Clinician Scientist at the University of Oxford and I have a clinical background in haematology. In particular, I’m interested in cell therapy and bone marrow transplantation and I’m also a qualified intensive care physician. In terms of my academic profile, my lab is interested in two things. The first is trying to understand how the genome functions, and particularly the non-coding genome, which accounts more than 95% of the genome sequence and is involved in controlling when genes are turned on and off. We’re trying to understand how that leads to genes being expressed in different cell types and to understand how variation in the code leads disease. That’s currently one of the big questions in genomics.
The second thing is genome editing. We’re trying to develop new treatments to change the genome of cells. Combining that with my clinical interest in bone marrow transplantation, we like to edit blood-derived cells, and particularly blood-derived stem cells. Part of that, of course, is having a good understanding of how the genome works. Then, we can use that knowledge to work out whether these treatments are going to be safe and effective.
FLG: What is the ‘big challenge’ in your field?
James: There are several challenges, particularly on the genome editing side. The first is a technical one, which a lot of people are working on. It’s how to make the editors better – how to make them more accurate, to allow you to make the changes more efficiently and make the changes in cells without causing toxicity.
Then there’s the challenge of implementing it in the clinic. The first trials of patients being treated with edited hemopoietic stem cells have been undertaken, and it looks very promising. So, it’s an incredibly exciting time to be involved in this field. But there are several challenges in that area as well. The first of those is to try to guarantee that they’re going to be safe, and to match that against the risks that the patients have. If someone’s got a disease that’s life threatening, then it is reasonable to take on greater risk than if it’s something that’s purely a quality-of-life issue.
The other really big challenge is trying to get these therapies approved by the regulators. That’s one of the things that’s coming through and hopefully some of the early treatments will be approved in the next few months. Off the back of that, one of the key things is going to be accessibility to these treatments. At the moment, people are talking about incredibly high price tags – in the millions of dollars per patient. So, one of the challenges here is to try and ensure that all the people who can potentially benefit from these treatments have access to them. That’s something that’s going to pan out over the next 10 to 20 years.
The next big challenge is that we’re obviously working on common diseases at the moment – things like sickle cell disease and thalassemia – but can we then convert these gains from common disease into rare disease? One of the things that’s really exciting and interesting, at least to me, is this idea of completely personalised therapy. So, designing a treatment for a single person with a single mutation.
FLG: Why should people care about this challenge?
James: It’s hard to overstate how important genome editing potentially will be as a treatment. This is the first time that we as a species have been able to sequence our own genome and then change it at will. That’s incredibly powerful, and it leads to the prospect that we will be able to cure diseases indefinitely.
The other side of the coin is that there are potential ethical problems, particularly if you end up manipulating the genome in egg and sperm cells so that the edits get passed down into future generations.
So, people should be mindful about the negative aspects as well as being excited about the huge potential positives.
FLG: What is being done to tackle the issue, or what should be done to tackle the issue?
James: In terms of the work to get this into the clinic, this is being taken forward by both academia and industry. There are large numbers of scientists who are trying to improve genome editing technology and trying to use it to develop new treatments.
Very rapid progress is being made here, and I would imagine that within the next few years we will have cures for many of the really important common genetic diseases. I’m talking about sickle cell disease, thalassemia, Duchenne muscular dystrophy, and inherited diseases of the liver and eye, which are relatively amenable to treatment with genome editing. There is even exciting progress being made on genome editing inside the brain. The data from ex-vivo editing of haemopoietic stem cells for sickle cell disease (CRISPR therapeutics / Vertex) and the in vivo editing of the liver for rare genetic disorders (Intellia Therapeutics) is really exciting. So, there are a number of areas in which really rapid and important progress is being made.
In terms of the ethical side of things, that’s something that’s still being worked on. But generally, most people, I think at this point, are happy with an embargo on intentional germline genome editing, which I think is a really good thing.
FLG: What is your advice to people breaking into the field?
James: That’s a difficult one to answer. It’s incredibly exciting and I’d encourage anybody to try and get involved in it, if they’re looking for an area of science to become fascinated by. There’s a very rapid pace of development at present, so it’s not for the faint hearted. Frequently, the field is moving around you so fast that by the time you finish an experiment it’s almost immediately out of date. So, you have to be very nimble to survive in this field, I think!
Enjoyed this interview? James Davies is one of 250+ speakers joining us at The Festival of Genomics & Biodata in January. Here’s what he had to say about the event.
FLG: Finally, could you tell us what you’re looking forward to about the Festival and why you chose to speak?
James: I think it’s the scope. There’s a huge number of different speakers and topics that will be covered. I think it should be a really exciting Festival, and I’m really keen to be involved. I’m very much looking forward to it.
Register here to hear more from James and the rest of our expert speaker faculty in January.