Jennifer Doudna on FDA Approval of First CRISPR Treatments

CHRISTIANE AMANPOUR, CHIEF INTERNATIONAL ANCHOR: Bye. And next, to a discovery that is changing the world. More than a decade ago, pioneering biochemist, Jennifer Doudna co-invented CRISPR, the gene editing technology, which earned her a Nobel Prize. Now, the very first treatment based on CRISPR has been approved in the U.K. and the United States, a landmark decision for treating sickle cell disease and for the possibilities of the rapidly advancing field. Dr. Doudna joins her biographer, our own Walter Isaacson to discuss what her technology could mean for the future of how we live, and the potential dangers also of its use or its misuse.

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WALTER ISAACSON, CORRESPONDENT: Jennifer Doudna, welcome back to the show.

JENNIFER DOUDNA, NOBEL LAUREATE, CHEMISTRY AND CHANCELLOR’S CHAIR, BIOMEDICAL AND HEALTH SCIENCES, U.C. BERKELEY: Great to see you, Walter.

ISAACSON: You and your colleagues won the Nobel Prize in Chemistry for the discovery and the perfection of a tool known as CRISPR that allows a molecule that has RNA and sort of a scissors — an enzyme that acts like a scissors that can edit, that can cut our DNA. The FDA has approved this for treatment of sickle cell anemia. First of all, explain to us how that would work on sickle cell anemia.

DOUDNA: Well, Walter, it’s an amazing time. We’re seeing a real transformation, I think, in medicine, where now we can edit the actual cause of the genetic disease, like sickle cell disease, to provide patients with a durable cure. And in the case of sickle cell, what happens is that it’s possible now to permanently turn on the production of a second protein, a protein that is called fetal hemoglobin, that can protect people that have the sickle cell gene from experiencing disease phenotypes. And so, they basically have an opportunity to experience a long-term treatment that may ultimately be effectively a cure for this disease. It’s really exciting.

ISAACSON: In the book I wrote about you, “The Code Breaker,” I have a picture of Victoria Gray, who was the first person on which it would testing this technology down in Mississippi. You went and you met with her not too long ago. Tell me what that was like and what you learned about her. This is a real person getting cured of a bad disease because of a technology you created.

DOUDNA: When I met Victoria Gray, it was a truly exciting moment for me as a scientist to see the impact of research and technology on a person’s life and how it can be transformative. She explained to me how, in her case, sickle cell disease had really controlled her life and made it very difficult for her to work, to be a mom to her four kids. And now, with this durable treatment with CRISPR, she’s able to take back her life. She can go back to school. She’s able to work. And for her, I think it’s really been a life-changing experience.

ISAACSON: Totally life-changing, but I think it now costs close to $2 million, because you have to extract the stem cells from the human body and then reinsert them. It’s not something simple. Have you been working on ways to bring down that cost?

DOUDNA: Well, that’s right. I mean, I think, you know, for scientists like me, it’s a — you know, it’s a moment where we’re both very hopeful about the future, but we also recognize how much work there is still to be done. And as you point out, the treatment right now is over $2 million a patient. It also requires a long-term treatment that involves hospitalization. And so, we’d love to find ways to bring down that cost by making it easier to deliver the therapy into patients, maybe some one day not requiring hospitalization at all, but allowing a onetime injection and also making it possible to distribute this therapy more widely around the world.

ISAACSON: Do you think insurance companies are going to pay $2 million each for everybody with sickle cell?

DOUDNA: Well, Walter, it’s an important question. I think we have to do the math and ask how much it costs to treat a patient over their lifetime with a chronic disease like sickle cell disease or many other genetic disorders versus having a one and done cure for that type of disease. And I think this is, you know, a very important question that now has to be addressed.

ISAACSON: Well, wait. Do you think it really can be done by math? I mean, what happens if the math says no, let them continue to have the disease?

DOUDNA: Well, it can’t be just math, of course. It has to also involve our technical and societal efforts. And we’re doing this through the Innovative Genomics Institute, where I work in the Bay Area to figure out how we can address this challenge technically, for one thing, and also how we can work with patient groups to help them understand the therapy, how it works, whether it’s right for them, and also to advocate for lower costs and better distribution efforts.

ISAACSON: Now, the way to lower the cost, it would seem, would be just to have a pill or an injection in which this editing tool can go right into human cells where you want it to. What’s the problem with getting it into human cells?

DOUDNA: Well, that’s right. And the challenge there is that CRISPR is a big molecule. And we also have to figure out how to get it right to the cells that need editing and not anywhere else. As you mentioned, the sickle cell therapy involves editing what are called blood stem cells. These are cells that produce the mature red blood cells in our bodies and live in our bone marrow. So, right now, the sickle cell treatment involves what is effectively a bone marrow transplant, but we envision a day when it will be possible to provide a onetime injection that targets the CRISPR molecules directly to those blood stem cells and doesn’t touch any other cells.

ISAACSON: Now, if you do it, you’re doing it in a patient right now, but you could, in theory, and in fact in practice, do it in what’s called a germline way, which is in reproductive cells so that you could make edits that would be inherited, and you’d get sickle cell wiped out from whole families and maybe from the human race. You’ve been a little — very cautious, I should say, about inheritable or germline editing. Do you think we’ll eventually get to the place where we say, let’s make inheritable edits so nobody will have sickle cell, not even your children or grandchildren?

DOUDNA: Well, you’re right that that could be an approach to be taken in the future. I think today, the technology isn’t there yet to use it safely in that fashion. And as you point out, there’s a very profound ethical question to be addressed when we think about using CRISPR in a heritable fashion, because it truly does change DNA in, you know, future generations. So, we have to be cautious, I think, about that type of use.

ISAACSON: And when would you say we should be willing to cross that line?

DOUDNA: Well, I think it would require several things. First of all, we have to be sure that technically and scientifically the technology would be safe in that fashion. And we’re certainly not there today. Secondly, I think we have to really be quite transparent about the applications of heritable germline editing. How would we actually decide who is going to use it that way and for what types of indications? So, this is something that I’ve been advocating for several years in terms of thinking together about how we use the technology responsibly.

ISAACSON: Well, as you know far too well, a Chinese scientist, He Jiankui, who I think took a — it’s in my book, took a selfie with you at Cold Spring Harbor Labs once, he made inheritable edits in twin girls that were born in China, and the Chinese cracked down on him for a while, but I notice he’s now out of house arrest and back working in the lab again. Is it going to be possible to keep this genie in the bottle?

DOUDNA: Well, I think what’s very important to note about that situation is that there was a true international backlash against his announcement in 2018, which was that he had used CRISPR in two human embryos that were transplanted into a woman to create a pregnancy. And I think internationally, it was clearly the case that scientists rejected that type of use of CRISPR and decided that this should not be something to be encouraged. So, I’m heartened by that effort, and I think that, you know, there may be a time in the future when we decide that germline editing is appropriate, but we’re not there today.

ISAACSON: And you’ve helped convene international groups on this issue. You and David Baltimore and a lot of people. Have the Chinese been cooperative on this?

DOUDNA: Yes. We’ve found that Chinese scientists have been quite engaged. They’ve been interested in working together on this. I think there’s an appreciation that with a powerful tool like CRISPR, we have to work together to ensure that it’s used safely in the future.

ISAACSON: Let me talk about a hypothetical, which is if you can do something like fix one letter mutation eventually that causes sickle cell or do what you did with fetal cells. You could also enhance it. So, I could decide that my blood cells will carry much more oxygen than ordinary people’s and eventually maybe my kid. I could design a kid that would have blood cells that carried more oxygen, be great sprinters, be wonderful athletes. How do we — or should we try to draw a line between what’s treatment for a problem, a disease, and what’s enhancement so people can design better kids?

DOUDNA: Well, I’d first like to point out that for the most part, it’s not very easy to do the things that you mentioned today, or maybe not possible because we don’t know the genetics well enough to control those kinds of traits. But as you’re indicating, someday we will. And so, we do have to be grappling with the challenge of how we use CRISPR in a safe and ethical fashion going forward. I don’t have any easy answers to that, but I certainly think it requires open discussion and really international coordination.

ISAACSON: There’s a lot of genetic diseases that we can deal with, and I guess the ones that CRISPR, this gene editing tool we’ve been talking about, could be most useful on where they’re just simple mutations. One of the simplest being sickle cell, which is just a one letter mutation. But what other syndromes and maladies are susceptible to gene editing now?

DOUDNA: Well, quite a few. There’s a number of diseases that have a single gene that’s known to be causative. And ones that come to mind are cystic fibrosis, Duchenne muscular dystrophy, Huntington’s disease, which is a neurodegenerative disease, and there are many others. So, I think that there are great opportunities going forward with CRISPR if we can figure out this delivery challenge, which is how we get the CRISPR editing molecules into the right cells of the body.

ISAACSON: You just mentioned Huntington’s. Just a god-awful disease. Partly because you don’t know you have it usually until after childbearing age. And so, it just goes down in the families and it’s just a death sentence. Would that be one of the first cases where we might say inheritable edits make moral sense?

DOUDNA: Well, I certainly think that would be the kind of situation where we might come to that conclusion if and when we get to a point where CRISPR is truly known to be safe to use in germ cells.

ISAACSON: So, tell me about the other diseases. You say muscular dystrophy. Are those ones — how would they be treated?

DOUDNA: Well, they would be treated using an editing approach that might either correct the disease-causing mutation or make a different change to the DNA that could mitigate disease. And what’s exciting is that CRISPR is not only a tool that can be used as the therapeutic itself, but it can also be used as a research tool. And so, what we’re seeing right now in the field of scientific research is that more and more CRISPR is integrated into medical research projects where we can really understand the genetics of disease at a level that will make it possible one day to probably treat them using editing.

ISAACSON: What about Alzheimer’s?

DOUDNA: Well, yes, Alzheimer’s is, you know, again, a devastating disease. It affects many families. I think one thing to consider there is that as we understand better the genes that make any of us susceptible to a disease like Alzheimer’s, it may in the future be possible to provide preventive treatment. In other words, editing that would provide protective genes against a disease like Alzheimer’s.

ISAACSON: And I noticed that some experiments may be done at Penn, correct me if I’m wrong, involving the eye. Why is that an organ that we can edit more easily and what could be done there?

DOUDNA: Well, the eye and actually the liver as well are two organs where delivery of CRISPR molecules or other kinds of molecules is relatively easier than other parts of the body. And for that reason, it’s attractive to try to treat genetic eye diseases or liver diseases using the CRISPR technology because we have strategies today that allow delivery into those organs.

ISAACSON: I notice that you’ve been working quite a bit on the microbiome. Those of us who maybe eat Greek yogurt are trying to figure out what is the microbiome. Tell me what it is and why CRISPR could be useful.

DOUDNA: Well, we’re all trying to figure out the microbiome, Walter, and also how it connects to human health and disease. But there’s increasing evidence that the bacteria that live in our bodies and actually in our environment as well have an enormous influence on our health and also our susceptibility to disease. So, what we’re doing today with the CRISPR technology here at the Innovative Genomics Institute is we’re using it to make changes, targeted changes to the microbes that populate the human gut to reduce disease susceptibility and we hope one day to actually provide disease protection.

ISAACSON: You’ve said that before we encounter a whole lot of CRISPR technologies in our doctor’s office, we’re going to encounter it a lot more on our food plate. Tell me what’s happening in the field of agriculture with gene editing.

DOUDNA: Well, gene editing will have a huge impact in agriculture. No question. And the reason is that it essentially gives plant breeders a tool for making precise changes in plants without introducing a lot of other alterations to genes that don’t need changing. And as a result, we have now the way to change plants to provide drought resistance, to increase nutritional value, even to increase yield of crops. And all of these things are already happening using CRISPR. I think, you know, this will raise questions about, you know, how we regulate or don’t regulate that kind of use of CRISPR. And that’s again, a very active area of discussion currently.

ISAACSON: And people talk about genetically modified organisms and GMOs and how they’re against them. Are they dangerous if you edit the genes of plants and animals we eat?

DOUDNA: Well, let’s think about it. Everything we eat is genetically modified, going back thousands of years because humans have been breeding plants for, you know, as long as we’ve had agriculture. And as a result, everything that we consume has modified genes. What CRISPR does is simply gives us the tools to make those changes precisely rather than randomly as is currently done.

ISAACSON: So, they could be safer actually?

DOUDNA: I feel they could. Yes.

ISAACSON: One of the disheartening things that happened with COVID was — well, one of the great things was we found all sorts of ways to treat it with — you know, with science and vaccines. But then, there was a backlash, people afraid of the science or people skeptical about it. One of the reasons I think you cooperated with me on the book I wrote was we wanted to explain exactly how the science works so people wouldn’t be as mystified or afraid of it. Do you think we have to do better communications now that there’s been, I think, an undercurrent of anti-science backlash in this country?

DOUDNA: Well, I think it’s incredibly important to explain what science is going on, how taxpayer money is used to support research and what benefit it provides to society. I think we — maybe we scientists haven’t done as good of a job as we should have over the past few decades of explaining that. And I think it’s maybe even more important now with the social media and the rapidity with which misinformation can flood the internet, for example. We really need to be sure that we’re putting out there real information, real data that’s trustworthy so that people know where to get information they can count on.

ISAACSON: Dr. Jennifer Doudna, thank you once again for being with us.

DOUDNA: Thank you, Walter.