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Jennifer Doudna: I think to get the economy back and get people out of their homes and back to work is going to require, I think, you know, pretty widespread testing and tracking of the spread of the virus. … We’re kind of in the middle of an interesting sociological experiment, I have to say, and I don’t know how it’ll turn out.

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Introduction

Paul Laudicina: I am Paul Laudicina, chairman emeritus of Kearney and founder of its Global Business Policy Council, and this is “Coronavirus: a world transformed.”

We’re recording this on Thursday, April 16. 

We reported last week on the growing incidence of COVID-19 globally and its devastating economic consequences. We also noted glimmers of hope from encouraging signs of control in various parts of the world driven largely by draconian national lockdowns. We know as well that until we have a vaccine to insulate us against this virus—something which most experts project will be 12 to 18 months away at best—we will have to continue to rely on disease containment measures. 

To be truly effective, we know these measures will require two advances: reliable and readily available therapeutic interventions to treat those afflicted by coronavirus on the one hand and testing at scale with widely available, easy to administer, inexpensive, quick resolution testing both to determine who is infected and who might be protected by COVID-19 antibodies on the other. 

We’re also learning that COVID-19 is one of some 30,000 catalogued coronaviruses which could challenge us in the future in a world where already about two-thirds of all human disease is animal transmitted. So the questions we are grappling with today: the adequacy of our healthcare systems and supplies to handle a surge of contagion, our inability or unwillingness to manage contact tracing while protecting basic civil liberties, the fragility of our supply chains, the lack of effective global cooperation—all of these things may well re-emerge if we don’t learn from this global affliction and prepare ourselves to better manage future disease transmissions. 

These are some of the many vexing issues which are coming into clearer focus this week as we continue to look for signs of ongoing hope in the midst of much so suffering, anxiety, and economic dislocation. 

Today’s guest, Dr. Jennifer Doudna, is one of those rays of hope. In this interview, which has been edited and condensed, world-renowned biochemist and co-discoverer of a revolutionary process of gene editing, Dr. Doudna will help us understand how her scientific innovations are being used in the development of a simple, inexpensive, quick diagnostic tool which can bring us testing at scale while at the same time seeking a longer-term way to give us immunity from COVID-19 and other viruses which might threaten us in the future.

Interview with guest

Paul Laudicina: Dr. Jennifer Doudna, welcome. I’m delighted to have this opportunity to talk with you about some of the amazing things that you and your colleagues at your Innovative Genomics Institute are doing, using your pioneering genome editing capability to mount an all-out effort to help slow the spread of COVID-19. And I can remember well, how spellbound you had our distinguished guests a couple of years ago at our CEO retreat in Taormina, Sicily, when you were sharing insights into the extraordinary potential of this revolutionary gene-editing tool that you co-discovered, CRISPR-Cas9 and its potential, among other things, to eradicate previously incurable diseases. 

Well, here we are in the midst of a global pandemic, the likes of which we haven’t seen in a century and none of us at that time around the table in Taormina could have envisioned. And now you’ve turned the might of this tool on COVID-19. If you would, Dr. Doudna, Jennifer, tell us a bit about what you hope to achieve and how it’s going.

Jennifer Doudna: Well, thanks very much for inviting me to talk with you about this. As you say, we are in an extraordinary moment around the world with this pandemic we’re facing with COVID-19. And I have been working very hard with colleagues and students and postdocs at the Innovative Genomics Institute in Berkeley, California to figure out how we can help address this urgent need. And one of the things that we identified early on was the desperate need for additional testing, just making sure that we can track virus infections and figure out who is affected directly by the virus and who might be impacted through spread by asymptomatic people. 

And so that’s something that we’ve now been working on for just over a month at the Innovative  Genomics Institute. We put in place a clinical testing laboratory, three weeks start to finish, sort of an extraordinary effort by many, many people to make that happen. And now that we have this lab up and running, it’s putting us in a great position to not only help with just the urgent on-the-ground need for patient sample testing, but also to do work that we hope will advance new types of diagnostics using the CRISPR technology. And we’re also working with teams of researchers who are interested in advancing CRISPR as an actual therapy against this virus.

Paul Laudicina: So if I understand that correctly, Jennifer, you’re beginning with the testing challenge, and hopefully, you’re also at the same time as I understand it, also getting insights into possible therapeutics or preventative interventions. But the testing challenge itself, it seems still to be a major obstacle to control the spread of COVID-19. What is it about your approach to testing that you think might help get us to where we need to be with quicker, less expensive, more readily accessible testing, then seems to presently be the case?

Jennifer Doudna: Well, the first thing I would say is that I think there's an opportunity for institutions like ours to put up pop-up labs that can advance the pace and turnaround times for testing right in this moment. 

So I think one of our goals is simply to help speed up the pace of testing not only at our own facility, but also help colleagues to do this elsewhere. That’s going to be critical not only to just understanding the spread of this disease, but frankly, also to getting America and eventually the rest of the world back to work. We have to be able to get a handle on the transmission of the disease in the short term. 

And then beyond that, we’re actually also excited to use our testing lab to advance new diagnostic techniques and to help teams of researchers that are testing the potential for existing drugs to be repurposed as therapeutics for this emerging virus. As you probably know, I think until there’s a vaccine, which is not likely to be available until early next year at the very earliest, we’re in a situation where we simply have to be able to track transmission, and we have to be able to do everything we can to come up with therapies that could at least mitigate the effects of the disease in the short term.

Paul Laudicina: And so, on the testing front, how far along are you, Jennifer, and what might we see coming out of the lab soon?

Jennifer Doudna: Well, right now, we’re running a test that’s quite standard. It’s a test that looks directly for the virus, nucleic acid, the virus RNA. So this is a test called PCR (polymerase chain reaction). Interestingly, it’s a standard technique that all of our students, graduate students, postdocs in our research labs use virtually every day. 

We’re at a point where we’ve now run close to 600 patient samples. We’re finding about a 1 percent rate of positives in the folks that we’ve tested. But I think, you know, in the longer term, we’re actually very interested in working with teams of scientists, both at Berkeley and elsewhere, who are looking into ways to track transmission. So there are, as you probably know, a number of groups that are investigating opt-in apps on cell phones that, for example, that could be used to help people track their exposure through messaging that would go out automatically when someone is identified as positive for infection with this virus. 

And then beyond that, in terms of research, we’re actually also excited about benchmarking this PCR-based test against newer technologies for detecting the virus that include a CRISPR-based approach but also various tests that look for antibodies against the virus because, of course, that’s also important to understand who’s already been exposed and maybe is now resistant to future infection.

Paul Laudicina: Well, that’s especially encouraging, I expect, in as much as the extent to which we want to restart the economy even before we have a vaccine and therefore can ensure broad immunity that you can test for the extent to which certain individuals are more likely to be immune just because of the degree to which they’ve been exposed to the virus previously.

Jennifer Doudna: Exactly. And as you probably know, that’s one of the big questions right now: how soon will people develop neutralizing antibodies to this virus? Will those antibodies be protective against future exposure to this virus? Are they going to be broadly neutralizing against other coronaviruses? You know, these are all questions that are still out there, and I think a testing lab like this can help address.

Paul Laudicina: I understand that you and your colleagues are working to help use CRISPR to also attack the virus in a kind of Pac-Man-like search and destroy mission, if you will. What can you tell us about how you have been using these tools to have a kind of effective therapeutic intervention or as a preventative, and does it hold out, from your perspective, much hope for treatment in the medium term?

Jennifer Doudna: One of the things that’s interesting about CRISPR is that it’s actually an ancient immune system that’s existed for a long time in bacteria to fight viruses. So I think many people who have studied CRISPR or are actively working in the field have said, “Gee, maybe we could take this immune system and turn it against the coronavirus.” Wouldn’t that be, that’d be awesome. 

And in the lab of Stanley Qi, who’s a colleague of ours at Stanford, it has been doing exactly that. So his idea was let’s take one of the CRISPR proteins that has been identified as a protein that can target RNA molecules and can be used to destroy RNA viruses in bacteria. And let’s turn it against this coronavirus. And so he’s already posted an article, a scientific article on a preprint server that shows how they’re doing this in his research laboratory. 

The challenge is how do we take that and which can, you know, sort of show a proof of principle demonstration that this CRISPR approach can work in a lab? How do we turn it into an actual therapy that could work in a patient? That’s a tall order at any time but certainly when we’re in the midst of an emergency where we need to do this not over many, many years, but over a matter of a few weeks or months. 

And so what we’re doing with Stanley is to help him get access to a what’s called a BSL-3 laboratory that allows direct testing with this coronavirus under safe conditions that don’t spread the virus or expose personnel to it. And then we’re also working with him at the Innovative Genomics Institute to take technology that we’ve been developing for delivery of CRISPR molecules into patient cells and tissues and use it to deliver into the lungs because this is really where you would want to have a CRISPR tool that could chew up the virus, especially for people that are affected very seriously and severely by coronavirus where they have difficulty breathing. And that’s the approach that we’re taking currently. Will it work? I don’t know. But it’s, I think, it’s a really clever approach that the Qi lab has developed, and we really hope we can help them with the delivery piece.

Paul Laudicina: Yeah, one of the things that I think all of us are kind of puzzled by is why this virus seems to affect different people in such extraordinarily different ways, where it’s hard to understand or, at least as I understand that, as a layman, it’s still difficult to understand why some people seem to be relatively mildly or unaffected, asymptomatic, and others very quickly moved to a state of their life being in peril. Are you getting any insights about any of that in the work that you’re doing thus far in your lab, Jennifer?

Jennifer Doudna: One of our goals going forward with our testing lab is to look into exactly that. So we have two wonderful epidemiologists at Berkeley, Lisa Barcellos and Eva Harris. Both are professors in public health who have studied viral transmission for a long time and in different settings and internationally. And they have an approved study right now to look at 5,000 asymptomatic individuals as well as people that have actually contracted this coronavirus to be able to identify what properties might make people particularly susceptible. And this would be looking at the level of their genes, right, trying to figure out what genetically might differentiate people that are suffering from severe infection versus those that are not at all. 

Paul Laudicina: Well, and part of the thing that makes me so excited about the work that you’re doing is when you think about how many coronaviruses are out there, as I understand it, there are over 30,000 coronaviruses that have been cataloged. So that right behind COVID-19 could be another coronavirus that crosses the animal-to-human transmission threshold. And here we are back again with another crisis on our hands, and conventional medicine, which is dealing with the effects, doesn’t quite get at it quickly enough, and it takes a long time to develop a virus-specific vaccine. So what you’re doing to try and understand the genetic structure of the disease and to address and conquer the virus by using CRISPR is an extraordinarily different and hopeful sign. What am I getting wrong?

Jennifer Doudna: Well, I think what you’re what you're getting at correctly, actually, is that, you know, we really need scientists, from all stripes to step up right now and take whatever expertise they have, whatever tools they have, whatever research approaches they’re using for things that are maybe completely unrelated to coronavirus and bring them to bear on this current pandemic. And you know, you I think you’ve very rightly pointed out that this is not the first time that human beings have been challenged by coronaviruses, they’re actually quite common and It certainly won't be the last. And so the more that we can do to both understand the biology of this virus and its transmission, but also to really think about how we prepare as a country and globally to get ready for the next coronavirus or anything else, you know, that comes along in the future I think will be critical. I think if there’s a silver lining here, it’s maybe the renewed commitment to public health and to the necessary infrastructure to ensure that we guard public health in the future.

Paul Laudicina: Well, you know, we know from experience in history going back to the earliest epidemics and plagues and so forth, that there is often a period of isolation, where people, they’re trying to protect themselves against threats to their health, look for scapegoats, and actually turn in on themselves rather than open up and try and understand how they can better collaborate. Tell me about internationally, Jennifer, Dr. Doudna. To what extent are you seeing cooperation also across borders? Even though there is a lot of chatter in the policy community about lack of cooperation internationally, how is the medical and scientific community dealing across borders these days?

Jennifer Doudna: Well, I can just tell you about my own experience. I’ll give you two examples. One is in the work that we documented in this manuscript posted on the preprint server Med Archive. So that work attracted the attention of a group in the United Kingdom that has been working to do a similar thing. And so that’s been very instructive because we ended up getting in touch with them. We’ve been going back and forth about potentially publishing our protocols back to back somewhere so that we can, you know, really try to flesh out what the issues were on both sides of the Atlantic for doing something like this. So I think that’s one outcome that could be very interesting. 

And then again, going forward, it may be possible to coordinate with them to look at some of the things that we discussed earlier, like, you know, what really are the rates of asymptomatic transmission? Are they the same in different countries? Are they different? 

And then the other thing, the other little story, is that I’ve had a number of colleagues in China reach out to me. These are scientific colleagues, folks that I know from, you know, just work that we’ve done over the years, either together or, you know, in the same field. And they’ve reached out just very, very thoughtfully and very kindly just to say, you know, “We know it’s difficult, a difficult time right now for you in the US. And, you know, let me share the experience here in China.” At this very human level, you know, we realize that we’re kind of all in this together.

Paul Laudicina: Absolutely. And I guess if, if you zoom out a little bit on all of these issues, how sanguine are you about the prospects? And give us a little bit of insight even though it’s not knowable, but I know our audience certainly would like to have your view on timeline of when you think we might be more confident about therapeutic interventions as well as about ultimately the development of a vaccine and certainly in the immediate, about accessible, easy to administer, inexpensive, quick, reliable testing.

Jennifer Doudna: Right. Well, you know, these are all tall orders, and I certainly don’t want to over-promise here. But I think that my perspective right now is that I think what we’ll see over the next, over the coming weeks, is that there will be a drastic increase in testing probably around the world but certainly in the US and Europe that will help track the spread of the disease. So at a minimum, we’ll have a handle on just how widespread the exposure has been. 

I suspect that fairly soon we’ll see a good serological test for antibodies against this coronavirus so that we can understand who has already been exposed, even if they’re not currently infected. And also whether those antibodies are in fact, protected because of course, that’s also very important to figure out. 

Regarding therapies, I think it’s highly dependent on a big element of luck, frankly, because honestly, to get a therapy implemented quickly for this disease would probably require using a drug that’s already been through safety trials and has been approved or as close to approval for something else, where it can be quickly repurposed for this pandemic. And it’s very hard to say, you know, whether that will happen or not, of course, I hope it does, and many people are trying. So I think, you know, if it’s possible, it will happen. It's just hard to say whether that’s going to come about in the timeframe that we need. 

And then, you know, with regard to a vaccine, you know, realistically, it won’t be available until early next year at the soonest. And so that really means that I think to get the economy back and get people out of their homes and back to work is going to require, I think, you know, pretty widespread testing and tracking of the spread of the virus, and if we can actually do that, which as you know, there’s extraordinary challenges there. Part of them are cultural. But if people are willing to do this, then I think it’s at least possible that we’ll be able to get a part of our economy back up and running in the near term. And a lot of it will depend on, you know, decisions made at local levels by governments as well as the willingness of the public to cooperate in these efforts. We’re kind of in the middle of an interesting sociological experiment, I have to say, and I don’t know how it’ll turn out.

Paul Laudicina: To be sure, it sounds like we are going to have to use a whole toolbox of testing at scale, innovating around therapeutic interventions, contact tracing, and probably some form of containment when testing indicates that we have increased exposure, increased infection rates and so forth, until such time that a vaccine is available. 

But if you turn the page, and we look ahead, in an era in what seems like an increasing progression of these kinds of pernicious and ominous contagions, whether it was AIDS to SARS to H1N1, to Ebola, and now COVID-19. This is all ricocheting around the world with COVID-19, with even greater velocity than the previous episodes of coronaviruses. What do you think we should be doing as a global community before the next virus emerges? We’re all playing catch-up on this one to be sure. But how do we prevent the next virus from exacting the kind of pain and suffering that the world is now experiencing from this one?

Jennifer Doudna: Well, I certainly think one thing that needs to be done is to build back up the Public Health Service across the US and globally. Supporting the World Health Organization is absolutely critical. This is not a moment to be divesting from them. It’s actually a moment to be investing in what they do because this is really the way that we’ll be able to understand outbreaks in the future and at a minimum, at least detect them early so that they can be, they can be monitored, and people can be warned. I think that having a robust testing capability spread throughout our Public Health Service will be key. 

Imagine that we had an ability to quickly pivot and test for new viruses as they emerge. I mean, this would have been something very valuable to have not only here in the US, but elsewhere, early in this pandemic, and so I think that’s something I’d like to see happen now to prepare for the next emerging virus.

And then finally, I would say that, you know, you mentioned earlier about the prevalence of coronaviruses. So I do think that investing in fundamental research about these types of viruses as well as other viruses like influenza, that are also, you know, can emerge as pandemics as we are well aware and just understanding as much about the biology of these viruses as possible so that we're prepared to meet challenges as they emerge. I think it’s, you know, it’s always hard to prepare for something that you can’t predict. But I do think that by having a very rich, robust knowledge of biology and these particular types of viruses as well as being prepared to quickly test for new emerging disease is critical.

Paul Laudicina: Jennifer, how can our listeners help support you? 

Jennifer Doudna: Well, we’d love you to come check out what we’re doing on our website, innovativegenomics.org, or you can just type in IGI Berkeley into Google, and it will pop up. 

We welcome financial contributions. We welcome intellectual contributions. We’ve had a number of people after we announced our testing lab who contacted us with personal protective equipment for our personnel, which has been incredibly helpful. 

I would love for people to feel empowered to participate in this effort. I think we need everybody, you know, whether you’re a scientist or something else. You know, I think everybody has something to contribute here, and we welcome input through our website.

Paul Laudicina: Dr. Doudna. Jennifer, we’re certainly grateful to you and your colleagues who are working day and night we know without personal gain. Transcending, as we talked about it, the normal competitive constraints that can often impede maximum speed and effectiveness on an issue as important as this, and you are truly in the frontlines of this battle. And so on behalf of a very grateful global community, I’d like to say thank you sincerely. And we all wish you the best of luck in the fight you’ve courageously taken on and certainly thank you for taking the time to share your insights with me today. Thanks very much, Jennifer.

Jennifer Doudna: Thank you for hosting me.

Wrap-Up (Paul Laudicina)

Thank you to Dr. Jennifer Doudna for joining us. You can learn more about her work, including the intellectual property that her lab makes readily available, at innovativegenomics.org.

Now, to recap what we discussed. The prescription for COVID-19 as we understand it today is that, as we await a proven vaccine, which is going to take some time, there are a few measures that we absolutely must focus on in the interim. First is testing at scale. Secondly is contact tracing and quarantining those who test positive. And then finally, developing therapies and treatments for more effective recovery from the virus. 

We appreciate scientists like Dr. Jennifer Doudna who are making headway on these very measures.

There’s only so much ground we can cover in a 30-minute interview, and we’re aware there are undoubtedly many more questions that you might wish we had been able to discuss during each podcast. So don’t hesitate to be in touch with me with any additional insight we might be able to provide by contacting me at [email protected] or on Twitter at @paullaudicina, and I would be happy to respond. 

We’ll be back with new episodes of “Coronavirus: a world transformed” soon. So stay tuned. More is coming.