CRISPR and the future of gene editing: scientific advances, genetic therapies, disease treatment potential, and ethical considerations | Feng Zhang, Ph.D.

**Peter Attia** (0:11)
Hey, everyone, welcome to the Drive podcast. I'm your host, Peter Attia. This podcast, my website and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness, and we've established a great team of analysts to make this happen. It is extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members, and in return, we offer exclusive member-only content and benefits above and beyond what is available for free. If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of the subscription. If you want to learn more about the benefits of our premium membership, head over to peterattiamd.com/subscribe. My guest this week is Feng Zhang. Feng is a professor of neuroscience at MIT, as well as an investigator at the Howard Hughes Medical Institute and a core member of the Broad Institute of MIT and Harvard. He earned his bachelor's degree in chemistry and physics from Harvard University, after which he went on to earn his PhD in chemical and biological engineering at Stanford University, where he worked with one of our previous podcast guests, Carl Desiroth, in developing the technique of optogenetics. From there, he returned to Harvard as a research fellow before starting his own research lab and professorship at MIT in 2011, where he subsequently contributed mightily to the development of the CRISPR-Cas9 system for gene editing. Feng has earned numerous honors and accolades for his work, including being selected for membership in the National Academy of Sciences, the National Academy of Medicine, and the American Academy of Arts and Sciences. He is also a fellow of the National Academy of Inventors. In this episode, we explore the origins of CRISPR and discuss Feng's early work in optogenetics at Stanford. We discuss the foundations of gene editing, discussing the challenges and breakthroughs in the field and how CRISPR revolutionized the process. We talk about the practical implications of CRISPR, such as its potential to treat genetic diseases, the importance of delivery methods, and the current success and limitations in targeting cells, like those in the liver and eye. We discuss the ethical considerations of gene editing, touching on the debate surrounding germline modification. Finally, we reflect on Feng's personal journey, the significance of mentorship and education, and where he sees potential for the future of science and genetic medicine. So without further delay, please enjoy my conversation with Feng Zhang.
Hey, Feng. Thank you so much for detouring your trip and coming through Austin. I've been really looking forward to sitting down with you for frankly about a year. So this is a topic that I don't think there's anybody who's heard this podcast, who hasn't heard the term CRISPR. But I think very few people can actually explain it and explain what a powerful tool it is. But I do think that before we get there, it would be really helpful to kind of understand a little bit more about your journey, on one hand, and then the journey of gene editing as a parallel. Let's start with yours. You and I overlapped a little bit because, I mean, not temporally, but you were at Stanford. Were you a postdoc in Karl Desiroth's lab?

**Feng Zhang** (3:35)
Well, first of all, thank you for having me be on this podcast. I've listened to your podcast on and off, especially when I'm running around or exercising. And as always, I learn a lot from listening to the podcast.

**Peter Attia** (3:46)
Oh, awesome.

**Feng Zhang** (3:46)
Thank you for having me here. So back to Stanford, I was there as a graduate student. I was in the lab of a researcher named Karl Desiroth. I was there for five years.

**Peter Attia** (3:57)
That's right, you did your PhD there with Karl. Now, as you know, Karl and I were classmates. Karl's been on this podcast. And so maybe folks who either didn't listen to that podcast or who did but have forgotten, give us kind of a quick summary of the type of work that you and Karl did.

**Feng Zhang** (4:14)
When I was working with Karl Dyseroth, we developed a technology called optogenetics. And it's a way of studying brain cells in the brain, how they are connected together, and how they mediate memory, mediate different types of physiological function. The way it works is that we took a gene from a green algae. And this is a gene that senses light and converts it into electrical current in the cell. So we can put this gene from the green algae right into the brain cells in a mouse, and we can shine blue light or yellow light and control the brain activity in these mice. So for example, if you wanted to study sleep, you can put this gene into different groups of cells in the brain and stimulate them. And you can find out which ones of these are controlling wakefulness, or which one are causing the mouse to become more sleepy. So if you do this systematically, one by one, from one type of cell to another type of cell, you can gradually start to put together a picture of how the brain is wired together, and then also what are the different components that govern all sorts of behaviors, from sleep and wakefulness, to thirst and hunger, to memory, and even to motivation and happiness. So it was really fun to be at Stanford and working with Carl.