Dr. Jennifer Doudna

It's called Crisper, a bacterial defense system that can edit genetic material. It already shows promise in eradicating malaria mosquitoes, appearing to cure patients with sickle cell anemia, improving cancer therapy, and diagnosing COVID nineteen more quickly and at the height of the pandemic. Dowd n Up, along with Emmanuel Sharpetier, won the Nobel Prize in Chemistry for their Crisper innovations, But there are major ethical questions looming. How and when

is it right to edit a gene? Is Crisper playing god? One Chinese scientist claims he's already edited the genes of twin girls, giving them immunity to HIV and sparking an international uproar. Right or wrong, one thing is clear, Crisper will change the human race forever. Joining me on this edition of Bloomberg Studio at one point, Oh biochemist and Crisper co invector, Jennifer dowdne You grew up in Hawaii, and I am so curious. I grew up in Hawaii

as well. How did your upbringing shape your curiosity about the natural world and the origins of life? When I think back on that time in my life, it was kind of a wonderland. Um, you know, well what it's like in Hawaii. It's a very special place, and I found myself just wondering, you know, how is it that these plants and animals have evolved to be specialized for Hawaii And there are so many examples of that in

the natural environments in the islands there. So I did definitely think that was behind my thinking about, you know, why it would be interesting to become a scientist in the future. As a budding scientist, you developed an early fascination with RNA well before it took center stage in the pandemic, and also now a key player in vaccines.

What is it about RNA that gripped your attention? When I was an undergraduating college we were, or at least I felt like the the the message we received was that RNA was kind of the boring intermediary between DNA, which encodes all genetic information in cells, and proteins that do the work in the cell, and so those were kind of the important big molecules in biology, and then

there was this kind of boring, uh intermediary called RNA. However, when I got to graduate school, I met the the person who would become my future advisor, Jack Shostak, and he was fascinated by the possibility that r and A in fact was the original biological molecule on Earth, that it was really responsible for the evolution of life as we know it here on Earth. And that idea was so interesting and so compelling to me that I, you know, I I joined his lab and I started studying R

and A, and I sort of never left it. Now, you spent most of your career working at universities. You're joining us now from Berkeley, where there's a lab named after you, But you briefly ventured into the Corporate Biotech World in two thousand nine and worked at Shenentech for just two months. Why was that so brief and what

did you learn? It was a really important experience for me, I have to say, even though short, because at the time I was I had been running my academic research lab for close to fifteen years and I was starting to question, you know, what the impact of my work would really be was I was I actually going to at the end of my career feel that I had

contributed to solving real world problems? And so that was a big motivation for me to join the team at Genentech, a wonderful company where I knew a number of the scientists and some of the leadership team. However, once I got to the company, I quickly realized that I just

I really missed my colleagues at Berkeley. I missed the academic environment of you know, being able to just think crazy ideas and you know, run into people and the coffee line and chat about experiments in a way that would be very difficult to do in a company, of course, because you have to be very focused on UM, you know,

the plans and development UM pipeline of the of the company. Fortunately, my colleagues at Berkeley took me back and I refocused my efforts at the time on studying crisper, which in the end was you know, turned out to be a very productive line of work. It's been called molecular scissors, if you will. What is crisper and what can it do?

It turned out that that crisper is in fact a system in bacteria that detects and cuts virus genetic material, whether it's DNA or RNA, and it was by studying how that actually works, and we did this in collaboration with Emmanuel Sharpontier's lab um to study the function of a protein known as crisper CAST nine. That line of research led to an understanding of the function of this molecule that allowed us to harness it as a tool for genetic manipulation, namely for altering DNA sequences in any

cell in a precise fashion, in a programmable fashion. That gives scientists now a very powerful way to understand the function of genes, but importantly also to change the function of genes in a targeted way. When did you realize the power and usefulness of this discovery, Well, I would

say almost right away. I mean, it's a relatively simple technology that can be easily adapted and adopted to different applications, and so very quickly after we published our work in the summer of two thousand twelve, labs around the world began to adapt Crisper for various kinds of geno editing. And it's just increased since then. The pace of Crisper research the application has been startling. It's been incredible to watch. What are the current use cases that inspire you the

most well. I always think about Victoria Gray, who was the first patient with sickle cell disease to be treated with Crisper here in the US. Her story is so inspiring. I mean, you know, she is somebody who is benefiting right now from the Crisper technology to be able to live a normal life without being impacted by an otherwise quite devastating genetic disease. And other patients are in are

similarly being impacted by the Crisper technology. So I think that's one area where we will see increasing developments, more and more clinical trials that are starting. In fact, at the Innovative Generalmics Institute that I started a few years ago here in the Bay Area, we have just received approval from the Food and Drug Administration for our own invasion Investigational New Drug or i n d UH trial

for sickle cell disease. So you know, this is really an extraordinary moment I think in terms of thinking about cures for genetic disorders. Once Crisper was confirmed as a gene editing tool, leading researchers raced to start their own companies, and it turned into kind of a competitive free for all, and the battle for the intellectual property is still going on to determine who can commercialize this technology. How do

you reflect on all of that. One thing important to point out is that despite the ongoing disputes over patents, which by the way, isn't unique to Crisper, I would I would argue that any any really excited technology is going to have multiple claims to it. In the case of Crisper, because the technology is relatively straightforward to deploy, It's meant that the field has moved quickly. As you mentioned,

there are multiple companies. There are multiple companies that are now publicly traded and more coming down the pike UM as well as all sorts of new companies and UM and then established firms that are adopting the technology as well. So from a scientific perspective, I think that's exactly what should be happening, right. This is such an enabling technology you wanted to see it deployed as widely as possible. This is my conversation with Jennifer downa biochemist and Crisper

co inventor. Coming up, we dive deep into the morality and ethics of gene editing and Dowton his reaction to the world's first so called designer babies, her thoughts on using Crisper to edit the genes of human embryos. I'm on only Chat and this is Blue Brick Studio. At one point out at what point in your research and discovery of Crisper did you start becoming worried about the

ethical implications. Well, quite early on, because it was clear from you know, those very early days that Cristopher was a broadly enabling technology that you know, it was useful and you know, worked in essentially any cell type, and that meant that it worked not only in fully developed differentiated cells or tissues, but it could also be used in embryos, and in fact, that was one of the very early uses in the research world was to make you know, modified mice at the you know, at the

at the embryo level, so those mice then had genetic changes introduced by Crisper that could be passed on to future generations. And it didn't take too much of a stretch to think about the possibility that that could also be done in human embryos, which of course, I think comes along with with just very profound ethical questions. I think it was two thousand and fifteen we organized the first meeting out here in California on the topic of

human germline editing human embryo editing with Crisper. That developed into a much broader international effort to understand the technology and importantly to put in place criteria that scientists globally should respect in terms of applications of Crisper, especially in the human germ line. Let's talk a little bit more about the reasons, if, and when to edit Jeanes is a profound and complicated question. How do you even begin

to that? And to answer that question, I think first of all, one has to ask, are there situations where, at least in principle, manipulating the human germ lines in the embryo would be the best, uh possible way to deal with genetic condition UM. And by the way, I'm focused here on, you know, just really strictly things that relate directly to health, rather than changes that might be you know, desirable to somebody for some reason, but actually

have no benefit to health. And right now we know that although yes, it can be used in human embryos and there are you know, multiple scientific publications about that, we also know that it's difficult to control it and to make sure that editing is happening exactly as the

scientists or experiment or might might be desiring. And so that to me is already a red flag that you know, even if there were situations where we said, g that might be the best way to deal with the disease UM, you know, the technology still needs to be further developed before that would be I think even a possible strategy. Every new gene editing technology has its sort of cultural

shocker moment. You had the first test two baby Dolly the Sheep, and then of course in the so called Designer Babies, where twin girls their genes were allegedly edited by a Chinese scientist Gan Quay. What was your first thought when you heard that news, Um, well, uh, shocked for sure, definitely. Um, you know, I guess it wasn't entirely unexpected that someone would try to do this. I had no idea that it would happen as soon as

it did. But um, you know, it had been discussed at meetings, of course, and that was in fact the purpose of these prior uh you know, conferences on the topic. So it seemed you know, it certainly seemed possible that

someone would would do this. I didn't think someone would would actually proceed, however, to actually create a pregnancy with edited embryos um as as was announced in two thousand eighteen, and I think it really was a wake up call to the international community that we can't sit back and just say, well, you know that that's a problem for the future. No, no, this is this is something we need to deal with right now, and we need to take a strong stand. And I think fortunately that's exactly

what happened. Are other scientists trying these things elsewhere, we really haven't heard about that kind of manipulation going on in certainly in any organized way. So I just think that at least I hope that the international reaction, which was really negative to you know, to this announcement has has I think, at least for the time being, really put a damper on anyone that might be trying to do that kind of human manipul elition for you know, fame,

for example. I do feel an ongoing sense that we need to be really proactive about this and not not you know, not get complacent. And importantly I I include in in sort of ethical considerations also thinking about widespread availability and affordability of the technology, because I think, you know, this is something that we have to pay attention to. I mean just thinking back to the example of Victoria Gray, who I mentioned earlier, who has received a Christopher treatment

for her sickle cell disease. Wonderful you know news about that. However, her therapy currently costs two million dollars, so you know, that's just not going to be affordable to most people around the globe that might need this. So we're working hard to think about ways that we can mitigate those costs. Wanting to eliminate a genetic disease seems like an important cause. Do you think the case, the moral case to eliminate a genetic disease is stronger than the case not to.

I think we have to consider it, you know, on a case by case basis. I mean, one could argue, for example, like let's go back to sickle cell disease that you know right now, the therapy is designed to be used in individuals, and it doesn't make a germ line change, right It's not a change that they would pass on to children. It's just a change that affects their body. And so in that sense, it's like any any other type of therapy or or drug that we

might use to treat disease UM. Whereas you could imagine that in a family that has a genetic disease that is you know, is sort of you know, spread across their family, many people inheriting a gene that you know predisposes them to disease, and believe me, I hear from

families like that almost daily. You could imagine that, you know, at some point in the future, if the Crisper technology were safe and robust, that some families might make the decision to UM, you know, to to remove that disease causing mutation at the source so that you know, future generations don't have to worry about it and I think that's you know, that that would make a lot of sense. But again, there's a number of things that have to happen,

I think before that will be possible. Back in the seventies, Test two babies were controversial, and now IVF is widely acceptable, accepted available. Do you think it will be the same

with crisper edited babies over the coming decades. I think sure, I think absolutely, You know that because this is what happens, isn't it is that you know, people um get comfortable with an idea if it's useful, you know, if it has proven and and this is you know, this is still remains to be seen, like if Christopher proves to be useful um and and and you know, kind of controllable in human embryos, and that is still in the

realm of research. But if that were to happen, then you know, I think it becomes a possibility that in vitro fertilization clinics offer that to their clients, and and so then you know who should make that decision? Should governments be regulating that? Well, that doesn't actually doesn't really happen for IVF clinics right now. In fact, you know, there's as you probably know, there's you know, different different regulations across different states in the US, and of course

in different countries is different. And so I think, you know, the same thing could possibly happen with Christopher, where you know, it becomes a something that you know, some clinics offered and parents will have to decide do I want to

do that or not. If you're listening to my conversation with Crisper Cohen mentor and Nobel Prize winner Jennifer down Up up next amidst an ongoing pandemic, how the biochemists made a pivot in advance Crisper as a diagnostic technology for COVID nineteen and after winning the Nobel Prize, Dowdnup shares inspirational advice to girls and women studying stem fields everywhere. I'm emily changed. This has boom Brick Studio one point out,

stay with us. The ethical controversies around Crisper came screeching to a halt when the pandemic hit. What was going through your mind when the world met COVID nineteen, Well, I think, like like like like many people, you know,

it was quite quite a shock. This was something that we really had to face head on, and that was actually, for me as a scientist, really a motivation for pivoting the focus of our work at least over the last year to creating a clinical testing lab at the Innovative Genomics Institute and also to advancing crisper as a diagnostic technology. You've had this fascination with RNA for so long and did you ever think that your are in a specialty would have a moment like this the key to fighting

a global pandemic. Well, uh no, I never thought that for sure. And let me just point out, since you read up ourn A, I think it's fascinating that, first of all, the coronavirus, the stars covie two virus that causes COVID nineteen is an RNA virus. So it's a piece of RNA that's you know, been causing all this havoc. And furthermore, many of us have received vaccinations with r N A right, so I received a vaccination that is a messenger RNA that carries a message into human cells

telling them make antibodies against this virus protein. And so that's been that's been also very interesting, so RNA to fight RNA, and then with Christopher, we have a third type of RNA that potentially could be useful I think primarily in this case as a diagnostic tool, a way to detect the coronavirus RNA and report on his presence. Couldn't Crisper one day also be used to edit our genes to make us less susceptible to viruses? Well maybe,

I mean there's definitely speculation about that. You know, would it be possible to um you know, I think about it sort of like genetic vaccination in the sense that, you know, could we educate our selves ahead of time to be you know, sort of um ready in case of virus shows up? And it's you know, it's a tricky thing, right because you know, you have to kind of know what to be ready for and and so you know, there would have to be some interplay there.

But I think already we're seeing opportunities to use Crisper to edit immune cells. And then this is being done in conjunction with cancer immuno therapy for patients, for example. So you could imagine taking that a step further and saying, well, can we educate our immune cells to be ready for

a virus? What do you say to the skeptics who say that Crisper is playing God, Well, I guess my my answer there is that, um, you know, there are so I mean, I don't even know how one defines playing god because you know, there's so many things, you know, ways that we manipulate our environment. Now. For example, all the food we eat is essentially engineered because of you know, plant breeding that's been going on for you know, thousands of years really, and so when new technologies come along,

they enable new science. When new science is done, they enable new technologies, etcetera. And in the end, you know, that's really what drives human advancement, and it drives our economy in many ways. So I feel that overall this is all positive. But you know, but you know, scientists really need to be engaged in, you know, accepting that responsibility for what they're doing and making sure that they're involved in the discussions and the you know, decisions that

have to be made as technology advances. And that's certainly true for Cristoper. Let's go ahead another hundred years. If the next COVID nineteen happens in another century, how will things be different? How will we be more prepared? Will our genes have already been edited to prevent us from getting the next big deadly disease. I wonder, I guess. I I imagine that certainly, within a hundred years we

will know so much more about our own genomes. And you know, the more we learn, honestly, the more complicated it clearly is um but you know, but so there's there, There will be plenty to keep all of us busy. But but look, I think in a hundred years we will know so much more about our own genetics, including the genetics of our immune systems and our interactions with virus.

So my hope would certainly be that, you know, if the next hundred year pandemic comes along, that we will be certainly much better prepared to manage it than we were for this one. So, in the middle of this global pandemic, in October, news came in that you won the Nobel Prize for Crisper, which you shared with a man, All Scharpentier, two women winning the Nobel Prize. Looking back on those days when you were told girls don't do chemistry, what do you have to say to inspire the girls

out there who might want to follow in your footsteps? Well, it's you know, just such a kind of humbling experience for me in a way, because I mean, who you know, I certainly never, ever, in a million years would have imagined that, you know, I would have won the Nobel Prize. And um, I'm even sort of shocked hearing myself say

it right now. And uh, you know, and I but here's an interesting thing that's happened, and that is that I've heard from many, many girls and women since then, some of whom I knew from my past life, but some of many of whom I don't know, who have reached out from all over the world to um tell me their stories, to tell me that our work is

inspiring to them. And I really hope that that message gets through very clearly to students, especially to two women or other people who feel maybe they have been um excluded in some ways from or just been underrepresented in the STEM fields that you know, I certainly didn't come. I'm not a likely person to have won the Nobel in a way, you know, because I came from a you know, a small town. Nobody in my family was a scientist. I just kind of wanted to do science.

I thought it was cool, and and that's the message I try to tell those students you can do this well. Thank you for paving the way for women and for all of the girls who will come after UM and congratulations, Dr Jennifer Downutt, thank you so much for joining us on this edition of Studio one Point. Oh. It's been wonderful to have you. Bloombrook Studio at one Point I was produced and edited by Kevin Hines. Our executive producer is Alison Weiss. Our managing editor is Daniel Culbertson, with

production assistants from Lauren Allis and Mallory Abelhausen. I'm Emily Chang, your host and executive producer. This is Bloomberg