We’re talking at CRISPRcon, where I’m pretty sure everyone recognizes him.
Sarah Zhang: How did you first get interested in studying biology?
Feng Zhang: I actually didn’t like biology in the first place. It was like, identifying different leaves, classifying things. I was more interested in math, chemistry, and computers—taking things apart and putting things back together.
Sarah Zhang: That actually sounds a lot like what you’re doing with CRISPR. CRISPR originally comes from bacteria, which use it to cut it up DNA, and it was first discovered by scientists working on kind of obscure bacteria. You put it into human cells, and it can also cut DNA. Do you spend a lot of time reading obscure microbiology literature?
Feng Zhang: Google is pretty good, and PubMed is pretty good, so you can search for different things. The way I look for things is that I have some hypothesis or an idea. And then you search things related to that hypothesis. And then just read broadly around that area to see if anything touches on the subject.
Sarah Zhang: You worked in a gene-therapy lab in high school, and gene therapy has had this interesting arc. [Gene therapy inserts normal versions of a gene into someone who has missing or defective ones; gene-editing with CRISPR can be theoretically used to insert, delete, or modify existing genes.] Gene therapy was so hyped in the early ’90s. Then it went through a dark period, and now finally we’re seeing gene therapies getting approved by the FDA. Have you followed that arc? Has it given you perspective on CRISPR’s future?
Feng Zhang: Absolutely. I first heard about gene therapy in that Saturday class on molecular biology. This was back in 1994, 1995 maybe, and the potential of gene therapy was really apparent. If we can fix disease at the genetic level, then we can treat many things.
So then when I was in high school, it happened to be that in Des Moines there was a gene-therapy lab, and they were taking volunteers, so I began working there as a sophomore. I was exposed to all types of approaches in gene therapy.
A major challenge with gene therapy is delivery. How do we get the therapeutic gene into different tissues? In the lab at the time, there were people working on all sorts of viral vectors: Moloney murine leukemia virus or herpes simplex virus or adeno-associated virus or adenovirus. These are all different ways people were exploring to get medicines into patients. And it was very exciting that researchers were making progress in making it possible.
And then in 1999, that’s when the news from the University of Pennsylvania came out.
Sarah Zhang: You mean the death of Jesse Gelsinger in a clinical trial. He died after the virus used to insert his gene therapy caused a massive immune response.
Feng Zhang: That was a very sobering moment for everybody in the field. So some of the things, back in the day, we didn’t fully understand the delivery systems enough. We didn’t know the biology of these viruses sufficiently. A lot of that applies to gene editing, too.