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Podcast: How to break America’s covid-19 testing bottleneck

MIT Technology Review’s Antonio Regalado explains the reasons why the US is still behind on testing, and outlines promising schemes to fix the problem at scale.

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Deep Tech is a new subscriber-only podcast that brings alive the people and ideas our editors and reporters are thinking about. Episodes are released every two weeks. We’re making this episode—like much of the rest of our coronavirus coverage—free to everyone.

When it comes to the latest technologies for testing, treating, and preventing the spread of covid-19, there’s no one on MIT Technology Review’s staff who’s better connected and better informed than Antonio Regalado, the magazine’s senior biomedicine editor. Since February, he’s been self-isolating with his family at their farm house in Maine, while continuing to report on the pandemic. We talked with Antonio about why it’s taking so long to scale up coronavirus testing, what new vaccine technologies look most promising, and why he started prepping for the worst way back in January.

Show Notes and Links

How to prepare for the coronavirus like a pro, February 28, 2020

A coronavirus vaccine will take at least 18 months—if it works at all, March 10, 2020

The race to find a covid-19 drug in the blood of survivors, April 10, 2020

What is serological testing?, April 15, 2020

How to test everyone for the coronavirus, April 16, 2020

Antigen testing could be a faster, cheaper way to diagnose covid-19, April 24, 2020

The US already has the technology to test millions of people a day, April 28, 2020

Episode Transcript

Antonio Regalado: This is not the time to count on a breakthrough. The breakthrough might happen, but it might not.

Wade Roush: To get the coronavirus pandemic under control, government officials say we’ll need brand-new technologies for testing that allow us to diagnose more people, faster. But Antonio Regalado, Technology Review’s biomedicine editor, thinks that’s a lot of eggs to put in one basket.

Antonio Regalado: I mean, a breakthrough is something that happens or it doesn't. I mean, it's hard to predict ahead of time. What we want is a technology where there's a clear path and it's a matter of doing it and a matter of overcoming obstacles.

Wade Roush: We’ll talk about why the effort to scale up coronavirus testing is going so slowly here in the US, and which technologies do have the best chance of working—both for diagnostic testing and, eventually, for making a vaccine against the virus. I’m Wade Roush, and this is Deep Tech.

[Deep Tech theme]

Wade Roush: Recently the head of the White House Coronavirus Task Force, Deborah Birx, went on Meet the Press and told NBC’s Chuck Todd that one key to ending the coronavirus lockdown and letting states restart their economies will be developing a new way to test whether people are infected.   

Deborah Birx: We have to have a breakthrough innovation in testing. We have to be able to detect antigen, rather than constantly trying to detect the actual live virus or viral particles itself, and to really move into antigen testing. And I know corporations in diagnostics are working on that now. We have to have a breakthrough. This RNA testing will carry us certainly through the spring and summer, but we need to have a huge technology breakthrough and we’re working on that at the same time.   

Wade Roush: Here at Technology Review, we’re all about covering breakthroughs. Which is why we know you can’t just snap your fingers and make one happen. Antonio Regalado covers the latest advances in biomedical research, and he’s been reporting for months on all aspects of the coronavirus response, from testing to antiviral drugs to novel types of vaccines. So I knew he’d have some thoughts about Dr. Birx’s pronouncement—and that he’d be able to tell us how close we really are to having a simple at-home antigen test that could substitute for the slow and complicated genetic testing that’s currently our main way to check for the virus.

I reached Antonio at his farm house in Maine. But before we even talked about the science, I wanted to know why he started getting ready for a crisis way back in January, before the rest of us were even paying attention to this new coronavirus.

Wade Roush: It didn't really take you long to start preparing for the coronavirus pandemic in a way that might have seemed extreme to the rest of us at that time. So how and when did you realize that this was going to be probably the most dramatic, most impactful pandemic of our lifetimes?

Antonio Regalado: When I first heard about the Wuhan virus—I guess as Trump calls it, we’re not supposed to call it that, at the time, though, in January, it was definitely the virus in Wuhan, far away—it looked basically exactly like  SARS. And so just personally, I said, well, you know, I spent a year working on SARS and then SARS went away. And so my decision early on was that. I was going to ignore this virus. And I would leave it to public health reporters to cover it.

Antonio Regalado: So that was early or middle of January. By the end of January, I had spoken to a venture capitalist named Robert Nelson. He's a partner at Arch Venture Partners, a kind of influential biotech investor. And his Twitter feed had turned quite alarming. Like, he was clearly very alarmed by this virus. So I called him up and I asked him to tell me, you know, what was going through his head. And he was very, very concerned that this was what he called sort of a global train wreck in slow motion. Within a couple of days of speaking to Robert Nelson, I sent my wife the following e-mail. and I'll read it to you. On January 28, 2020. Antonio Regalado wrote to his wife under the subject line, Pandemic Shopping List, "Please obtain: three bottles of bleach, several milks in box, the European kind you can keep at room temperature. Large bags of:  carrots, onions, potatoes, beans and rice."

Antonio Regalado: So on January 28, my paranoia was high and by then, I was trying to prepare by acquiring the supplies that I would need to weather the pandemic. But it wasn't until a month later that I actually wrote a story that we published in Technology Review about prepping, just for the reason that you mentioned. It seems like a crazy, paranoid thing to do when the virus is far away. In fact, my wife, I have her reply. She replied to me, “Really? Why? Is one coming?,” she said of the pandemic. And I said, back to her, “Well, there is one in China.”

Wade Roush: Yeah. Well, in retrospect, the idea of laying in weeks' worth of supplies, just in case you weren't able to go back to the store to get groceries, that seems really smart. And I'm just curious about whether in your mind, there's still a line between rational prepping and survivalist Montana mountain man prepping. Do you know what I'm getting at?

Antonio Regalado: I do. I do. Let's face it, prepping is anti-social. It is anti-social to acquire a bunch of supplies for your personal use, then lock the doors of your cabin. I don't really have much insight into the hardcore preppers, you know, people who have weapons and stuff and a bunker underground. I mean, clearly in a certain community of people close to technology, when they were worried about the virus, when they started prepping, has now become sort of a badge of honor. And they make noise of it. I would say in my case as a journalist, it was more an attempt to be close to the story and be part of the story. If other people are prepping and I'm going to write about it, then I wanted to prep, too.

Wade Roush: But you're glad to have the extra bottles of bleach and the extra cans of beans.

Antonio Regalado: I have a hundred pounds of flour. Other people can't get flour. And I'm trying to think about how I can participate, other than through the journalism. Should I stop doing journalism and become a contact tracer? Should I give away half my flour to somebody else who needs it? These are the questions of the day.

Wade Roush: Let's talk next about testing. So we know that one key to eventually scaling back self-isolation and quarantining and social distancing will be massively expanding the number of people who can get tested for the coronavirus up to the point where ideally you can test millions of people per day. But the dominant technology that's being used for that right now is something called PCR or RT-PCR. And it's apparently really difficult to scale up, because we're not doing very well at it. So could you explain for us what RT-PCR is, and why the expansion of that kind of testing is still taking so long?

Antonio Regalado: Yeah. Well, when these testing problems first started to arise and be reported, it was mind-boggling to me, because PCR, polymerase chain reaction, is not a new technology. It was developed in the ’80s. And it's something that every single graduate student in a biology lab knows how to do. So I was kind of astonished that there was a discussion going on about PCR. You know, how is it that people have forgotten how to do this bread and butter activity? And why is it that the ability to do this test is somehow contingent on some kind of government approval or government supplies? So all that was very strange to me, because PCR is so fundamental to genetic research. 

Antonio Regalado: What it does is basically just amplify DNA. You have a little bit of DNA and PCR is what you use to multiply it into lots of DNA that you can then easily measure. So it turns out, though, that the whole sort of infrastructure for doing PCR testing is more fragile than we knew, and harder scale up than we would have thought. And that is because initially some of the chemicals that were used to kind of guide the PCR reaction were flawed. They didn't work correctly. Then suddenly there was a shortage of those pieces. They're called primers. That was resolved. But then there was a shortage of something that else that you needed, another chemical to basically turn the virus's RNA into DNA. It's called reverse transcriptase. There was a suddenly a shortage of that.

Antonio Regalado: So you can think about it as cooking. You know, for cooking, you need flour and you need sugar and you need a bowl and you need a mixing spoon and you need all these things. And so what happened with the testing is, there was a crisis in the supply of every one of those things that happened at different times. So everybody wanted to cook brownies at exactly the same time. And that was the problem with scaling up. There just wasn't enough of all these different materials. But the process itself, apparently, is a little bit hard to scale up to millions or tens of millions just using PCR. So people are looking at different technologies that might be more amenable to sort of massive-scale testing.

Wade Roush: So Deborah Birx, who's the head of the White House Coronavirus Task Force, has started talking about antigen testing, which is an approach that wouldn't rely on PCR, as I understand it. That's one of the new forms of testing that could perhaps come to the rescue, but I imagine it has its own scaling issues.

Antonio Regalado: Getting to this question of how to scale up testing in a massive way, there's sort of two general categories of where new technology can help. One is massive centralized testing. And the second is massive decentralized testing. So let me just talk about the centralized testing first. Right now, the PCR testing is centralized. The samples are sent to clinical laboratories, public health laboratories, commercial companies like LabCorp or Quest Diagnostics that have centers, facilities that do the testing. And that accounts for the delay. Like people are having long delays in getting their test results, four or five days.

Antonio Regalado: So there are ideas that are coming out of the genome centers like the  Broad Institute of MIT and Harvard, out of UCLA, out of Berkeley. And these are schemes for doing massive testing by using the genome sequencing machines that are normally used to sequence human genomes. And so what people have come up with are schemes by which thousands, tens of thousands, even millions of samples, say, from all over the country could be pooled together and then read out on these speedy sequencing machines.

Antonio Regalado: So that's one idea people have. But it's still, even though they believe that it could get to the scale of millions, there are a couple of problems with it. One problem is just the logistics, like how do you get all those swabs into one place? And the other thing is that it's still not in real time. This massive centralized testing, there's still delay. You’ve got to collect the swabs. You got to send them somewhere, and then you have to get the results and you have to report the results back. So it's still a delay.

Antonio Regalado: The other category of test, which relates to Deborah Birx's comment, is massive decentralized testing. What happens if there was a test that everybody could use from home before you go to work? After you go to work? Once a week, twice a week, you could test yourself, and have an idea whether you were infected and if you were, then you could, you would know what to do. You'd have to stay home, get in touch with public health authorities, call your contacts and let them know that you have this virus. So there's different ways in theory to do this at home testing.

Deborah Birx is talking about an antigen test. An antigen test is when you have an antibody that sticks to the virus. It's in a little tiny test kit. You're looking for this spike protein on the surface of the virus or maybe some other thing that is actually on the virus poking out of it. The way I understand it is you have a test strip with antibodies and that that is going to stick to that antigen if it is in your nasal swab. But there's some questions about whether an antigen test is actually going to work. The problem with antigen tests is that they have not worked well for respiratory viruses.

Wade  Roush: Antonio says that there’s a potential middle ground here. It’s the idea of a simplified genetic test that would combine the accuracy of PCR-based testing with the convenience of decentralized at-home testing.

Antonio Regalado: Who's working on at-home genetic tests? Well, some of the molecular biologists who were working on the sort of large-scale schemes are also working on the chemistry for an at home test. One of them is Feng Zhang at the Broad Institute of MIT and Harvard. And he works with this technology CRISPR, which is known for gene editing. But it turns out you can adapt it also to make a simplified genetic test format. So they're trying to figure out, can they make it even simpler and can they package it up in a way that would make it the basis for an at home genetic test?

Another person working on it is a well-known entrepreneur named Jonathan Rothberg. He’s quite a character. He's in quarantine on his super-yacht, the Gene Machine. But he's also someone with a ton of resources which he has been marshalling to try and create an at-home genetic test. And they actually have prototypes that they're testing at Yale on real patient samples. And they are working on developing a little device, which would sort of automatically mix the samples, it’s about the size of a credit card. And the idea is that this would be a genetic test that you could do at home. And it turns out that the chemistry is not necessarily the hardest part. There’s all these other practical elements. 

Wade Roush: If we're gonna have a huge breakthrough, do you think it's going to come from the bottom up, or are there any signs of any sort of top-down leadership on this?

Antonio Regalado: I don’t know what Deborah Birx meant by a breakthrough, but from what I know of emerging technology, we shouldn't be counting on breakthroughs, right? I mean, breakthrough is something that happens or it doesn't. You know, it's hard to predict ahead of time. What we want is a technology where there's a clear path and it's a matter of doing it, and a matter of overcoming obstacles.

Antonio Regalado: Sri Kosuri is a researcher at UCLA who I spoke with. And he's working on a procedure by which tens of thousands of patient samples could be pooled together and then run on a sequencing machine. So he came up with this concept and I just asked him, well, who's gonna do this? Are you going to do this? Who's gonna do this? And he said that the problem was that kind of everybody is waiting for somebody else to take the action. The people who can solve the logistics, they don't necessarily believe that the technologists can do this massive testing, whereas the academics, they're not in a position to do the logistics of collecting the samples. So there's this kind of game of a chicken and egg is as he described it.

Antonio Regalado: I think that certain locations like Boston or San Francisco, where they have this concentration of academic medical centers and researchers, they're going to take the lead. And I think pretty soon we'll see a new testing scheme arise in those areas. And once they do that, other people will follow suit.

Wade Roush: Great. OK. So, Antonio, let's finish up by talking about the perhaps the biggest tool of all for ending this pandemic, and that's vaccines. To your mind, what are some of the most interesting and provocative approaches that people are exploring right now to developing a vaccine against the coronavirus?

Antonio Regalado: Yeah, well, actually, the vaccine efforts got underway very quickly, unlike the testing. As soon as that sequence of the coronavirus became available, the people working on vaccines immediately grabbed it and started work. The sequence of the virus is the essential starting point for the vaccine, and in fact, the first vaccine to reach clinical trials, I think they began in late February or early March, is one from a Boston-area biotech called Moderna Pharmaceuticals. And they have a new approach to making vaccines, in which they basically take the genetic code, a snippet of the genetic code from the virus, stick it inside a nanoparticle like a little ball of fat, and they inject that into people. So the goal is that your own cells will take that information and start making this little bit of the virus. Your body will react to it and you'll become immunized.

Antonio Regalado: And what's interesting about Moderna’s  approach is just the speed with which they were able to go from the sequence of the virus to their candidate drug or their candidate vaccine. It only took them a couple of months. So early on in the pandemic, we already had, you know, a new benchmark that was set for how fast a vaccine candidate could be prepared. Of course, it doesn't mean theirs will work. In fact, there's no vaccine of that type that's widely used or licensed. So we may end up looking instead to more conventional types of vaccines, of which there's a number of strategies to make them. And I looked at the World Health Organization, and I think that they count something like 50 or so different vaccine efforts. So there's a huge number of vaccines in development, each using a sort of slightly different technology.

Wade Roush: Ok, so one virtue of these new innovative approaches, like Moderna's, is they might be faster to implement. But do they also have the downside that they're just so new that we're not sure exactly how they're going to work in the body yet, and they have to go through like an equally lengthy testing period to make sure they are safe?

Antonio Regalado: Correct. And this gets back to the point of, you know, waiting for a breakthrough. This is not the time to count on a breakthrough. The breakthrough might happen, but it might not. So, you know, at different extremes is the Moderna vaccine, which is used as a very clever idea. It's very fast to get started. But there's no existing vaccine that's widely used that’s based on this technology. So it's simply unproven whether it makes an effective vaccine that could be manufactured at large scale. We just don't know that. At the other extreme or companies like Johnson & Johnson, Sanofi, and others who are using what they call vaccine platforms that have a history of success. There's actually vaccines that are out there that are made using these approaches. They take a little bit longer, or quite a lot longer, but they may in the end be the better bet. We just don't know. So I think a lot of people are saying, well, we need to bet and bet big on all the approaches.

Wade Roush: Ok, Antonio, thank you so much for sharing all this today. And stay safe up there in Maine.

Antonio Regalado: Great. Thank you, Wade.

Wade Roush: That’s it for this edition of Deep Tech.This is a podcast we’re making exclusively for MIT Technology Review subscribers, to help bring alive the ideas our reporters are thinking and writing about. But we’re making this episode free for everyone, along with much of the rest of the magazine’s coronavirus coverage.

Before we go, I want to let you know about a new virtual conference coming up June 8 through 10. It’s called EmTech Next 2020 and it’s a co-production of MIT Technology Review and Harvard Business Review. We’ll cover topics like business agility in this time of unprecedented change. How to make businesses’ digital operations more resilient. Advances driven by new technology, like machine learning and 5G. And how to leverage these emerging technologies to work better, and smarter. We’ll be joined by guest speakers such as Zoom CEO Eric Yuan, Slack co-founder Stewart Butterfield, and Amy Webb, the founder and CEO of the Future Today Institute. Find out more and register for your spot at emtechnext.com, that’s E-M-Technext, all one word, dot com. We hope to see you in June.

Deep Tech is written and produced by me and edited by Michael Reilly and Jennifer Strong. I’m Wade Roush. Thanks for listening, and we hope to see you back here for our next episode in two weeks.