CRISPR Interview with Rice Professor Isaac Hilton
Oct 2, 2022 | Video Transcript by Sophia Mai
Transcript:
Sophia: Hello! Welcome to the first STEMATA interview over CRISPR and cell therapies. My name is Sophia Mai, and I am joined today by Professor Hilton. To begin, could you please introduce yourself, and what you specialize in?
Isaac Hilton: Yes. First, thank you, Sophia, for the opportunity today. This is a really great forum, and I’m really excited to be here. I’m also very grateful to you for reaching out and making this possible. So my name is Isaac Hilton. I’m an assistant professor of bioengineering at Rice University here in Houston, Texas, and my lab works on understanding how the basic mechanisms of human cells work so that in the longer term we can actually control those mechanisms to make cells better as genetic medicines and cell therapies.
Sophia: Thank you! To begin, I wanted to ask what your definition of CRISPR was or a possible analogy to explain how CRISPR works to someone without any previous knowledge.
Isaac Hilton: That’s a great question. So really what CRISPR is is an immune system for bacteria and other prokaryotes called archaea. And so what this allows these microbes to do is basically target foreign pieces of DNA. And so they use these CRISPR systems to basically seek and destroy DNA that doesn’t match their genomes so they can recognize the difference between foreign DNA that comes in viruses that can infect bacteria and their own DNA, and when they find that foreign DNA, they chew it up and they chop it up, and they do that in sort of a scissor mechanism. They cut up the invading DNA, and so these CRISPR systems are always surveilling looking for foreign DNA to cut up to protect the bacteria that get infected. Now what engineers have done, bioengineers and other synthetic biologists is basically repurpose that system for use in mammalian cells. And there’s not a really great analogy other than these technologies are essentially ways that we can, in human cells, instead of recognizing foreign DNA, which we sometimes do, but we can use these systems to fix DNA that’s hazardous or dangerous to human cells or human beings. And so, when you think about the human immune system, it is to protect the bacteria from invading pathogens, like viruses. Just like us, bacteria can be invaded by viruses, but in the human cells, the engineered versions of the CRISPR-Cas systems we can use these technologies to basically target DNA that we want to fix or that we want to change to make the cells do a particular function or to correct a disease. And there are some other more nuanced uses of the tools to really control how genes are turned on or off too and those have, in human cells, application for cell circuits, controlling better gene therapies and having cells perform functions that they might not naturally be able to do.
Sophia: What are some of your biggest concerns about gene editing and cell therapies?
Isaac Hilton: So this is a great question, and there are three things I’d say about this. The first is knowledge is power, and so we have to get everyone able to understand how these tools work and that’s why I’m so excited for these types of opportunities that young, talented, smart people like you are creating because this allows us to start to communicate and have a dialogue with the public because if the public understands these technologies, first that just raises awareness and creates more opportunities and helps create a better more informed public on the importance of science and the importance of how science can actually improve human life and the human condition. And so I think educating the public on how these technologies work is really important so that’s one of my biggest concerns. The second concern for CRISPR technologies and cell therapies is that I think we need to be continually interested and motivated to make these things as safe and effective as possible. And so safety is a high priority. So just to recap those two, knowledge to the public and safety in patients and so that those are both huge concerns and the third concern is just as important and that as these medicines progress past the clinical trials and into the clinical space proper, we want to make sure that they are equitable. You don’t want to have a therapy that can only be used by people who have the money to access them. I think it’s very important that we make sure that all of these technologies and medicines that are created from them are available to everybody. And so the three things are increasing public knowledge, making sure these things are safe and effective, and making sure that everybody has equal access to the technologies.
Sophia: Being such a new innovation, what difficulties do you face when discovering ways for CRISPR to be used or developing a stronger understanding of cell therapies?
Isaac Hilton: That’s another great question. So I think the first thing is, to do science well you have to work hard and it’s costly. It has a fiscal cost. And we as researchers in the biomedical space, in the bioengineering space, we rely on the public to support science because we go to the government for much of our funding. So that funding is very competitive, and it takes a lot of time to secure funding, and we work hard to do so, and we want to make sure that we are doing science right and that is costly. And so one of the difficulties, if you can call it that, is that we really need the public to support science better. And so this is basically my pitch to say get out there and vote for the public and vote for science because we need, as researchers, the public to help us enable science. The more public support we can get, the more science we can do, and the better we can make our world for everybody. The second challenge that we face is a little more technical. So the first is a little bit more enabling from the cost side, and the second is more technical in the sense that at current levels we really need to make sure that the tools are working as we expect every single time. And that goes back to point one. How do we make sure that these tools are safe and effective and so when we think about that it’s in the space or in the context of what’s the best technology for a particular application or indication and how do we make sure that it’s gonna be robust across all conditions that that technology might encounter.
Sophia: What do you find most rewarding about doing research, and what drew you to doing studies in this field?
Isaac Hilton: So, I’ll start with what makes it as rewarding for me. I love the idea of knowledge for knowledge’s sake. And there are so many discoveries in this field yet to be made. And so in my lab and on my team, we’re really interested in making these discoveries, but we want to do so in the sense that we can help the world. And we can help people have better lives and we can help people have more equitable lives so that everyone can be healthier and ideally happier. And be able to spend time on things other than worrying about their health. Now we also love the idea of, or I do anyways, and almost everyone on my team I think if you were to ask them would echo this is that I sort of science as being like a science detective. So you know, oftentimes there are these really interesting puzzles to solve in the cell and in cell therapy and in the CRISPR and in the biotechnological development arena. And so, we love designing experiments to really correctly understand and solve those puzzles. And so we have a lot of fun doing that but we also use that to make these therapeutics in the longer term better. The third thing I’ll say is this is such a great opportunity and it’s sort of my dream job because the other thing that I get to do that is so meaningful to me is that I get to one, engage with young, smart people like you but also I have the opportunity to train the next generation of scientists. And in my perspective, I want them to be the best in the world and I also see that as a force multiplier because that allows me to basically help the world even beyond my time on this planet. So I can hopefully train people to be the best they can be and then they can go train others and they can make their own discoveries. And so become this amplification of knowledge and opportunity and discovery for the world. And what drew me to this is that I always loved science even from a youngster. And I’ve also just loved the sort of search for the truth and really the truth is always in the data. It’s just how interpret it and how you communicate it is where you constantly need to be refining your expertise.
Sophia: Finally, what advice do you have for aspiring scientists seeking to go deeper into gene editing or molecular biology?
Isaac Hilton: That’s a really good question. So my advice is it’s a good rule for everyone, be nice. Try to understand where other people are coming from, and two is to be proactive. Information is often time, at least the foundational information is often times out there. This is why as scientists we publish papers and you know publish comes from “pub” meaning “public.” That data should be communicated to the masses and it should be available, at least in the distilled format, to everybody. And so if you think about being proactive and learning about gene editing, in this case, to the extent that the information is out there, constantly be learning and constantly be thinking about where are the bottlenecks because those bottlenecks are where solutions are needed. But more importantly, in the context of proactivity, developing that independence, the functional independence of being able to search out the literature and search out the information will really help anyone become an expert quickly, more quickly than they would without that dive into the publicly available information. And also the final thing is, doing exactly what you’re doing. Reaching out to people because almost every professor and academic that I know is happy to talk to folks like you and make sure that we’re doing our best to encourage the next generation of smart people to come along and fill these holes, to keep this sort of force amplification of knowledge and new discoveries and new therapies alive.
Sophia: That's all I have for you today. Thank you so much for your time and responses! It was great talking to you about CRISPR, and I hope people found value in this interview.
Isaac Hilton: Me, too. Well, thank you, Sophia, and it’s been my pleasure. And again, I really appreciate you reaching out, and let’s stay in touch in the future. If you ever need anything, or if you want to talk more just please feel free to reach out, okay?
Sophia: Yep, thank you again, and I hope you have a great rest of your day.
Isaac Hilton: You too. Bye bye.
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