Pushkin from Pushkin Industries. This is Deep Background the show where we explore the stories behind the stories in the news. I'm Noah Feldman. A few weeks ago on the show, I spoke to Nobel Prize me economist Paul Romer, and Paul had what he considered a simple plan to reopen the economy without risking people's health. All we need to do is switch to a strategy where we're testing everybody with regularity. As soon as we find somebody who's positive, we need to isolate them without isolating lots of people who could otherwise just go back to daily life and work. Paul is not alone. Public health experts have been almost unanimous in saying that we need a lot of tests very soon in order to protect health and eventually reopen the economy. And yet we are behind Germany, Canada, and even Italy when it comes to per capita testing. And as of now, less than one percent of the US population has been tested for coronavirus. So what is the hold up? What are the bottlenecks that stand between us an effective testing? To learn more about coronavirus testing both for diagnosis and then for antibody testing to see if people have already had the disease. I'm joined by doctor Ohmi Garner. He's the director of Clinical Microbiology Testing for UCLA Health. His lab does more than one point five million tests a year of all kinds, and so he finds himself right in the thick of the question of how we test for COVID. Oh my, I'm so grateful to you for agreeing to talk to me. I want to ask you to help guide us through the process of just why testing takes so long to generate and to cause to function. So start wherever you want. Maybe start with the diagnostic tests first. What are the challenges to having millions of diagnostic tests up and running on a daily basis? You know, that's the million dollar question. I think that there are lots of challenges for many ends, and so just I think it's used to a little bit walk through the process of getting a diagnostic test for COVID nineteen by PRECR because it starts to then outlay where the challenges are in the system. And so the first part of the diagnostic test is the collection of the sample. This is the part I think people are most familiar with. You either go to your doctor's office, or a hospital or a drive through location, and a swab is inserted deep into nasal cavity and then that sample is sent to a centralized testing lab. I think there's a bit a little bit of confusion around this because they call those locations testing locations, but no actual testing happens there, and so I think people think, why would it takes so long if the test happens right where you collected it. So the sample needs to be sent to a centralized laboratory like my laboratory where we perform the PCR test, and the PCR test, depending on which platform is used, can take anywhere from two to six hours. And I think this is also something that's not well known because if the test only takes two to six hours, why are people waiting seven to fourteen days to be able to get a test result right? And I think one of the infrastructure challenges around this particular outbreak and testing itself, is that there are just not enough centralized laboratories that are able to do this testing right now. And this starts to key in on why we don't have testing across the country and a lot of and we have labs, so it's not to say that there aren't centralized clinical laboratories. There are centralized clinical laboratories in almost every single city across this country. The challenges that each one of those laboratories does not have the equipment to be able to test for COVID nineteen, and the labs that do have the equipment there is such a shortage on they test themselves that many labs that have the equipment still can't run the capacity of tests they could run within a day. One of the fascinating questions to me is is there some alternative technology potentially in the pipeline they would make it easier to collect samples by means other than the long swab that goes deep into the nasal cavity. You know, Donald Trump himself said it was a miserable experience for him to have that done, And though I'm not super worried about his own experience, it does mark the fact that we need not only the swabs, that we need medical professionals to do the swabbing, Whereas it might be a lot faster and more efficient if people could do it at home or there was just alive a test right now, why is it the case that we can't do that? I think that a lot of this is about clinical sensitivity of what you're collecting. And when I say that, I mean how likely is it for a false negative to be given to a patient. So in the vironment of COVID nineteen, we want to try our best to avoid a false negative, and in order to do that, you want to take the best possible specimen to increase your likelihood of actually collecting virus. Now this is really then the question is where is the virus? Right, Is the virus out at the end of the nasal cavity, Is the virus very very deep in the nasal cavity. Is the virus in the throat? Is the virus in different various oral fluid compartments. And the reason why nasal pharyngeal collection was the first thing that was used is because that's where we know other respiratory viruses live. And so whether you're doing a PCR test for influenza or a PCR test for something like respiratory sinciitio virus, the best possible specimen, meaning the specimen that gives you the highest likelihood for recovery of virus, is actually that really deep nasal pharyngeal specimen. So then I think ultimately the question is do you need to take the best possible specimen or in this particular case, with this particular virus, can you find an equal amount of virus in some of these other specimens? And those studies are ongoing. I agree with you if we could just use oral fluid, I would change all of my test to oral fluid tomorrow. But I won't do it if it's going to mean we produce more false negatives. Now let's turn to the lab. So you were saying the sample comes to you, it reaches you in the lab, and you're going to perform a PCR test. What is a PCR test. The test is actually in two components, with PCR being the second component. So the first component is really it's called RNA extraction. And what happens is that when the sample comes in, this first step actually takes out all the nucleic acid from that sample. And so now what you have is instead of the full sample from the patient, you just have a pool of RNA and then you run the PCR test. And so the PCR test is called an rtPCR test. It's a reversed trend description polymerase chain reaction that's that rt PCR, and what it does is because we're looking for RNA, PCR is a technology that examines DNA. So the first step is you have to turn the RNA into DNA, and that's that reverse transcription. The second test then is the polymerase chain reaction, and the polymerase chain reaction is really a way to amplify a specific target on DNA to see whether or not that target is there. And of course the target we're looking for is COVID nineteen, and so if some of that viral RNA is there, it's been converted to DNA, and then PCR can target to tell you whether or not that viral RNA was originally in that specimen. And it's exquisitely sensitive. The test that we're using in my laboratory get down to about five hundred copies of virus per mill of fluid, and so what I'd like to tell people is that if the virus is in the sample, the test will find it. That's super clarify and helpful. Now, you said that there are enough laboratories in the United States to handle even a substantial volume of testing, and that the problem is that they don't have the necessary equipment in a concrete sense, what is missing in these labs, because if we could figure out what that is, maybe we could talk about how we provide it. Sure So, there are now I don't know somewhere around twelve FDA Emergency Used Authorization approved PCR tests for COVID nineteen. The challenge is that the manufactures of those tests need to get those tests to those laboratories to be able to provide testing. So, giving an example from my own laboratory, I actually run four different FDA approved tests for COVID nineteen. And the reason why I do that is because I can't get one manufacturer to give me enough volume of test kits to meet the need, so I actually have to bring in four different tests to be able to do that. You get a couple one hundred a day from one place, you get a couple one hundred a day from another place, and you combine all of that volume together and I can get up around the thousand tests a day or so that I can offer in my laboratory. This is a significant challenge and the shortage by the manufacturers of the diagnostic tests really is contributing to our inability to have widespread testing. And I don't want to put the blame on the manufacturers for this. What they've been asked is very very difficult, which is to basically pivot their entire operation. And these are diagnostic manufacturers that make all kinds of diagnostic tests, HIV viral load tests, goneria, clamydia PCR tests, and they're saying to them, Okay, we need you to make a COVID nineteen test and ramp it up a hundred times more the volume you would normally make for testing. What do you think is slowing them down in doing that? I mean, just at the most basic level, picturing the factory where they make the tests, and I'm picturing them shifting over the functionality they usually have to produce other kinds of tests onto producing COVID nineteen tests. What's the hold up for them that stops them from doubling or tripling, to say nothing of going up to one hundred times. So I think one of the hold ups is just manufacturing capacity, because you can't just stop making the other tests because people still have those other diseases, and so it's almost like you need to on top of what you were making before. Now go ahead and produce one hundredfold times COVID nineteen testing, and so you know, I really think it's a manufacturing bottleneck. You can only do so many runs at a time because you only have so much manufacturing capacity in that setting. In speaking with the manufacturers, this is what I've been told. The other part of the problem that we've discovered kind of over time is that a lot of these manufacturers rely on some of the same chemicals to make their own proprietary test kits. And if one chemical, let's say that multiple manufacturers use, is in shortage, that then stops all of them from making more tests. So there's a whole supply chain here of the chemicals that are necessary to make this work. And so one has to go back a further step and go to the chemical companies and make sure the chemical companies are manufacturing more of this in terms of stopping though the production of their other tests can't. An argument be made that given the tremendous, almost unimaginable cost of keeping our economy shut down, and given the testing is so crucial to reopening, that they actually should stop manufacturing the other tests rely on whatever backlog they have and just prioritize COVID nineteen tests ahead of everything else. I can agree with you there. You know, I don't work for the companies. I can only speak as an end user that's in an academic medical and running these tests. That yes, I think that the pivot needs to be fast. I think part of the challenge as well, though, is that these companies aren't made to pivot like that, and so you know, getting the either federal support or whatever would be necessary to encourage them to be able to do this is one of the challenges. But yes, I will agree with you. Overall, to meet this immediate need, there needs to be a shifting, and I know a lot of companies are shifting. It's just the scale of the shifting. You know, when we think of clinical lab testing. You know, there has never been a test in my laboratory where I need to do two thousand tests a day. So the scale of this is just it's mind boggling from an overall diagnostics perspective, because I don't want to represent it as something like, well, the manufacturers just should have shifted and this would have been relatively easy for them to do, and they're negligent to not do that. That's not what's going on. This is really an unpress sedented shift that's being asked for, Yet at the same time we have to be able to do it in your lab. The PCR test, if you have the equipment, can be run in two to six hours. So what is driving the backlog that causes people to have to wait seven to ten days for a result. A lot of that is that every single state doesn't even have large scale testing that's available. One of our reference laboratories in California, Quest Diagnostics was receiving samples from New York and New Jersey. Well, if you're shipping samples across the country to be able to have them tested at a facility, and then once they get to that facility, if the queue or line is two hundred thousand tests long, you can see that it just increases exponentially the turnaround time, which is the expression that we use in lab diagnostics for the amount of time it takes from the sample to be collected all the way to the person getting the result back. Is there any in centralized national planning for where tests should go. I mean, it seems very crazy that someone could be tested in New York and then have their samples sent to LA so that a lab there can do the work. But I get that you have to send the test where there's access. It sounds like the kind of thing which would benefit from a centralized model. I agree with you. I think a centralized model would be helpful. But you know, I think that this is tied into our healthcare system, and our healthcare system is not built around a centralized model. And so I think this is why you see some of the great disparity across the country is because there is no centralized model, and thus individual areas some can be very very fast, and some may not have access to testing at all. What realistically is going to happen in your view, if in the next few weeks, you know, sort of like end of April, first few weeks of May, we see an effort to get people back to work, coupled with big companies trying to get tests done for their employee eventually over the course of the summer, campuses like university campuses trying to get people tested in a systematic way is not at all realistically doable from your perspective, Given where we stand, I mean, you're perfectly placed to give a credible answer to this question because most people are just speaking theoretically. Yeah, I'm optimistic. So within that optimism, and again I talk to multiple manufacturers of these tests on a daily basis. Everybody is ramping up. And as everybody ramps up, I see more and more hospitals, even just in the Los Angeles area, being able to provide testing. And so I think we're moving in the right direction. The question is are we moving in a direction fast enough to match what we're going to do with changes in social distancing policies? And that's a really difficult thing to be able to predict because I think the two need to be tethered together. As we increase our testing capacity, I think that's one way for us to start in a responsible way, opening back up, getting people back to work. But you know, I think if you just flip the switch on May fifteenth or whatever arbitrary day that said, it's going to so outpace our pace of testing that we're going to end up right back where we were. So, you know, I think that states that are going to be able to do this in a scientific and educated way to meet the testing needs while you open up, I think that we can be successful at it. We'll be back in just a moment. So far, we've been talking about PCR testing, which is to see if a person from whom example has been taken has the virus now, but part of opening up will also be extensive antibody testing. Do you guys do that in your lab? So not yet. I'm going through the validation process now, and so my expectation is that we should go live at UCLA with antibody testing, hopefully sometime early to mid next week. I do want to make kind of a general comment about the antibody testing compared to the PCR though, so I said they were like nine to twelve manufacturer of the PCR test. Ultimately they're using the exact same technology, even though there are small differences between the tests, and so you can really see those tests as the same tests. So whether I offer a PCR test or hospital down the street offers a PCR test, they're all going to be kind of the equivalent sensitivity and high quality. Unfortunately, that is not true for antibody testing at all, and so the challenge of antibody testing is that it was unregulated by the FDA to begin with, So there were a lot of tests that flooded the market that were very very low quality, and every single antibody test manufacturer, because I'm now talked to five or six of them, are using a different target on the virus to be able to look for antibodies, and that distinctly affects whether or not these tests are cross reactive, and they produce false positives. And so unfortunately, what you're going to see with antibody testing is that depending on the platform each testing area uses, they could have vastly different results. And this makes antibody testing then, in determining kind of what it means, very very challenging. So how did you go about the process of choosing the approach that you're going to use in your lab? So I was looking for the best test possible, right, I think the challenge with antibody testing is that it needs to be of the highest quality if we're going to have any chance of trying to establish some level of immunity or even affect behavior by having something like a positive test result. And so in speaking with the companies, what I really wanted to look at was the size of their validation data, whether or not they proved non cross reactivity with something like seasonal coronavirus, influenza, some other viruses that we all have IgG four that you would not want to be cross reactive in a COVID nineteen antibody test, And so we did a long process of evaluation and then now once we've chosen our company, we want to move forward with I'm going to do an extensive in lab validation with serum that I already have from COVID nineteen positive patients and from patients with other viruses to prove that it works before I go forward with a test for my patients. So you're actually doubling up. First, you're choosing what you think is the best test, and then you're going to test it yourself in the lab to make sure that you have confidence in it before you start using it. Absolutely, I think it's the only way in the current environment with the amount of anibody tests that are out there. It's just I have to be sure because clinical decisions are going to be made based on these results. Personal decisions are going to be made based on these results, and so you know, that's really the role of a clinical lab director in choosing the best possible. One of the things that has fascinated me is to hear about scientists around the country trying to come up with outside the box solutions to massively increase testing capacity. And one of the most intriguing ones that I read about was produced by a group at the Broad Institute here in Cambridge, Massachusetts, which is where I'm based, not at the Broad but in Cambridge, that was proposing, at least theoretically, a massive throughput approach where they would bar code, using a crisper like DNA technique, bar code samples so that they could then run through sequencers hundreds of thousands of tests at a single run. That's obviously a very different technology, and it's using very different kinds of methods than are used in most clinical labs. As someone who does it the old fashioned way, as it were, what do you think are the odds of success here? I mean, it might be worth trying it even if the probability of success is very low, because it will be great to test so many people so quickly. What are the big challenges that that approach faces in your view? Yeah, So the scientists that run these approaches are very talented scientists, you know, their research based scientists, and I think that they will be able to successfully put together a system that could theoretically do one hundred thousand samples. Part of what differentiates a research test from a clinical test, something that's allowed to be used on patients is that you have to prove that it works before you can actually use it clinically. And part of the challenge of a system like this I lives literally having this exact same conversation with some researchers at UCLA, is that in order to prove that it works on scale, you need to test fifty thousand samples one hundred thousand samples. And the challenge of doing that is how do you get those samples within a research setting under IRB approval and not have it take nine months, a year, a year and a half, which is typically what these sorts of things would take before or you even began to have enough data to submit to the FDA to get approval of your new technique. And so, while I do think that this could work, I don't know if it's going to move in a time frame that's going to make it feasible. There are other concerns that I have kind of wrapped up in this. A lot of the challenges of let's say, the paper that you had talked about, it doesn't use rtPCR uses LAMP, which is a different nucleic acid amplification technology that can have sensitivity issues. This is also part of some other challenges when you pool large things together, is that on an individual sample basis, sometimes you're just not as good as the gold standard. And these would be the things that these places would have to prove to the FGA before they got approval to do massive testing. In addition, you know, while I respect the fact that you can run one hundred thousand samples at one time, just collecting a hundred thousand samples, getting them sent to one area and getting them processed to be able to run is a phenomenal challenge that's wrapped up on the pre analytical side, or kind of even before the testing begins. So I am excited about this because I actually don't think this is going to be our last pandemic. There isn't anything to suggest it would be. And so if we can get things online like this and really start thinking about how the country when we need to, could pivot to mass scale testing for a virus, that's a really good thing to have in our back pocket. Is this something that's going to work for COVID nineteen. I don't know if the time scale is actually going to meet up with the technology. If I could close our conversation on a modestly lighter note, but it nevertheless an important one. I read that you had said that watching Cuba Gooding Junior in the nineteen ninety five film Outbreak was one of the things that inspired your career path, and of course a lot of us now feel like we're living Outbreak the sequel. Yes, what does that feel like for you personally to be, you know, on the front lines here? It's interesting. So twenty fourteen, we had our Ebola crisis in the United States and at UCLA, I was part of the ebola treatment team, and so in that setting, you know, as an ebola treatment a person participating in the treatment of the patient, you have to get fully suited up. So if you can imagine Cuba getting Junior an outbreak in that yellow suit, that's similar to what you wear when you're attempting to discern whether or not somebody has ebola. So it was that moment I really kind of had my outbreak moment. This one I have felt it's a little bit strange because until we kind of all moved forward with masking, it was a pandemic but everything looked fine, So it was kind of different from the outbreak scenario. It was like a shift in what I thought a pandemic would look like. And that's what I found to be the most surprising of this whole thing. Hundreds of thousands to potentially millions of people worldwide are going to die of this disease, but it's not like running around in the biosafety level four suits. All of the movies, TV shows, and so forth, none of them has a scene where people say, well, we should all suit up. Oh but wait a minute, we don't have enough suits. You know, that's not a plot detail that they've ever taken advantage of in the past, though I suppose we'll see it going forward. Yes, thank you, Ohmi. This was extraordinarily clarifying and helpful. I really hugely appreciate your step by step patients in explaining what you do every day to us. Thank you for doing the work that you're doing, and we all appreciate it. Excellent. Thanks for having me out. No, I appreciate it. Listening to doctor Ohmi Garner. I had moments of optimism because he himself said that he thinks we are scaling up our capacities in a way that will facilitate a lot more testing than we're doing at present. That was the good news. On the other hand, Olmi also made it very clear that there are significant limits to how many tests we can do under current circumstances. We have the shortage of chemicals in the existing tests, we have limited capacity, and when it comes to antibody testing, we still don't really know how well the various tests work. Last, but not least, Although Omai thinks that some of the most fascinating experimental techniques being proposed to test hundreds of thousands of people at the same time have a good shot of working, he's concerned that it may not be possible for that kind of testing at that kind of scale to be ramped up in time to help us address the COVID nineteen epidemic as opposed to future epidemics. Above all, a doctor Omai Garner is a kind of model of the clear speaking, clear thinking scientist who can explain things to all of us, and I feel very lucky that he's at the helm of an important lab like the one at UCLA. Until the next time I speak to you. Be careful, be safe, and be well. Deep Background is brought to you by Pushkin Industries. Our producer is Lydia Gencott, with research help from Zooe Wynn. Mastering is by Jason Gambrel and Martin Gonzalez. Our showrunner is Sophie mckibbon. Our theme music is composed by Luis GERA special thanks to the Pushkin Brass, Malcolm Gladwell, Jacob Weisberg, and Mia Lobel. I'm Noah feld I also write a regular column for Bloomberg Opinion, which you can find at Bloomberg dot com slash feld To discover Bloomberg's original slate of podcasts, go to Bloomberg dot com slash Podcasts. You can follow me on Twitter at Noah R. Feldman. This is Deep Background.

Pushkin from Pushkin Industries. This is Deep Background the show where we explore the stories behind the stories in the news. I'm Noah Feldman. A few weeks ago on the show, I spoke to Nobel Prize me economist Paul Romer, and Paul had what he considered a simple plan to reopen the economy without risking people's health. All we need to do is switch to a strategy where we're testing everybody with regularity. As soon as we find somebody who's positive, we need to isolate them without isolating lots of people who could otherwise just go back to daily life and work. Paul is not alone. Public health experts have been almost unanimous in saying that we need a lot of tests very soon in order to protect health and eventually reopen the economy. And yet we are behind Germany, Canada, and even Italy when it comes to per capita testing. And as of now, less than one percent of the US population has been tested for coronavirus. So what is the hold up? What are the bottlenecks that stand between us an effective testing? To learn more about coronavirus testing both for diagnosis and then for antibody testing to see if people have already had the disease. I'm joined by doctor Ohmi Garner. He's the director of Clinical Microbiology Testing for UCLA Health. His lab does more than one point five million tests a year of all kinds, and so he finds himself right in the thick of the question of how we test for COVID. Oh my, I'm so grateful to you for agreeing to talk to me. I want to ask you to help guide us through the process of just why testing takes so long to generate and to cause to function. So start wherever you want. Maybe start with the diagnostic tests first. What are the challenges to having millions of diagnostic tests up and running on a daily basis? You know, that's the million dollar question. I think that there are lots of challenges for many ends, and so just I think it's used to a little bit walk through the process of getting a diagnostic test for COVID nineteen by PRECR because it starts to then outlay where the challenges are in the system. And so the first part of the diagnostic test is the collection of the sample. This is the part I think people are most familiar with. You either go to your doctor's office, or a hospital or a drive through location, and a swab is inserted deep into nasal cavity and then that sample is sent to a centralized testing lab. I think there's a bit a little bit of confusion around this because they call those locations testing locations, but no actual testing happens there, and so I think people think, why would it takes so long if the test happens right where you collected it. So the sample needs to be sent to a centralized laboratory like my laboratory where we perform the PCR test, and the PCR test, depending on which platform is used, can take anywhere from two to six hours. And I think this is also something that's not well known because if the test only takes two to six hours, why are people waiting seven to fourteen days to be able to get a test result right? And I think one of the infrastructure challenges around this particular outbreak and testing itself, is that there are just not enough centralized laboratories that are able to do this testing right now. And this starts to key in on why we don't have testing across the country and a lot of and we have labs, so it's not to say that there aren't centralized clinical laboratories. There are centralized clinical laboratories in almost every single city across this country. The challenges that each one of those laboratories does not have the equipment to be able to test for COVID nineteen, and the labs that do have the equipment there is such a shortage on they test themselves that many labs that have the equipment still can't run the capacity of tests they could run within a day. One of the fascinating questions to me is is there some alternative technology potentially in the pipeline they would make it easier to collect samples by means other than the long swab that goes deep into the nasal cavity. You know, Donald Trump himself said it was a miserable experience for him to have that done, And though I'm not super worried about his own experience, it does mark the fact that we need not only the swabs, that we need medical professionals to do the swabbing, Whereas it might be a lot faster and more efficient if people could do it at home or there was just alive a test right now, why is it the case that we can't do that? I think that a lot of this is about clinical sensitivity of what you're collecting. And when I say that, I mean how likely is it for a false negative to be given to a patient. So in the vironment of COVID nineteen, we want to try our best to avoid a false negative, and in order to do that, you want to take the best possible specimen to increase your likelihood of actually collecting virus. Now this is really then the question is where is the virus? Right, Is the virus out at the end of the nasal cavity, Is the virus very very deep in the nasal cavity. Is the virus in the throat? Is the virus in different various oral fluid compartments. And the reason why nasal pharyngeal collection was the first thing that was used is because that's where we know other respiratory viruses live. And so whether you're doing a PCR test for influenza or a PCR test for something like respiratory sinciitio virus, the best possible specimen, meaning the specimen that gives you the highest likelihood for recovery of virus, is actually that really deep nasal pharyngeal specimen. So then I think ultimately the question is do you need to take the best possible specimen or in this particular case, with this particular virus, can you find an equal amount of virus in some of these other specimens? And those studies are ongoing. I agree with you if we could just use oral fluid, I would change all of my test to oral fluid tomorrow. But I won't do it if it's going to mean we produce more false negatives. Now let's turn to the lab. So you were saying the sample comes to you, it reaches you in the lab, and you're going to perform a PCR test. What is a PCR test. The test is actually in two components, with PCR being the second component. So the first component is really it's called RNA extraction. And what happens is that when the sample comes in, this first step actually takes out all the nucleic acid from that sample. And so now what you have is instead of the full sample from the patient, you just have a pool of RNA and then you run the PCR test. And so the PCR test is called an rtPCR test. It's a reversed trend description polymerase chain reaction that's that rt PCR, and what it does is because we're looking for RNA, PCR is a technology that examines DNA. So the first step is you have to turn the RNA into DNA, and that's that reverse transcription. The second test then is the polymerase chain reaction, and the polymerase chain reaction is really a way to amplify a specific target on DNA to see whether or not that target is there. And of course the target we're looking for is COVID nineteen, and so if some of that viral RNA is there, it's been converted to DNA, and then PCR can target to tell you whether or not that viral RNA was originally in that specimen. And it's exquisitely sensitive. The test that we're using in my laboratory get down to about five hundred copies of virus per mill of fluid, and so what I'd like to tell people is that if the virus is in the sample, the test will find it. That's super clarify and helpful. Now, you said that there are enough laboratories in the United States to handle even a substantial volume of testing, and that the problem is that they don't have the necessary equipment in a concrete sense, what is missing in these labs, because if we could figure out what that is, maybe we could talk about how we provide it. Sure So, there are now I don't know somewhere around twelve FDA Emergency Used Authorization approved PCR tests for COVID nineteen. The challenge is that the manufactures of those tests need to get those tests to those laboratories to be able to provide testing. So, giving an example from my own laboratory, I actually run four different FDA approved tests for COVID nineteen. And the reason why I do that is because I can't get one manufacturer to give me enough volume of test kits to meet the need, so I actually have to bring in four different tests to be able to do that. You get a couple one hundred a day from one place, you get a couple one hundred a day from another place, and you combine all of that volume together and I can get up around the thousand tests a day or so that I can offer in my laboratory. This is a significant challenge and the shortage by the manufacturers of the diagnostic tests really is contributing to our inability to have widespread testing. And I don't want to put the blame on the manufacturers for this. What they've been asked is very very difficult, which is to basically pivot their entire operation. And these are diagnostic manufacturers that make all kinds of diagnostic tests, HIV viral load tests, goneria, clamydia PCR tests, and they're saying to them, Okay, we need you to make a COVID nineteen test and ramp it up a hundred times more the volume you would normally make for testing. What do you think is slowing them down in doing that? I mean, just at the most basic level, picturing the factory where they make the tests, and I'm picturing them shifting over the functionality they usually have to produce other kinds of tests onto producing COVID nineteen tests. What's the hold up for them that stops them from doubling or tripling, to say nothing of going up to one hundred times. So I think one of the hold ups is just manufacturing capacity, because you can't just stop making the other tests because people still have those other diseases, and so it's almost like you need to on top of what you were making before. Now go ahead and produce one hundredfold times COVID nineteen testing, and so you know, I really think it's a manufacturing bottleneck. You can only do so many runs at a time because you only have so much manufacturing capacity in that setting. In speaking with the manufacturers, this is what I've been told. The other part of the problem that we've discovered kind of over time is that a lot of these manufacturers rely on some of the same chemicals to make their own proprietary test kits. And if one chemical, let's say that multiple manufacturers use, is in shortage, that then stops all of them from making more tests. So there's a whole supply chain here of the chemicals that are necessary to make this work. And so one has to go back a further step and go to the chemical companies and make sure the chemical companies are manufacturing more of this in terms of stopping though the production of their other tests can't. An argument be made that given the tremendous, almost unimaginable cost of keeping our economy shut down, and given the testing is so crucial to reopening, that they actually should stop manufacturing the other tests rely on whatever backlog they have and just prioritize COVID nineteen tests ahead of everything else. I can agree with you there. You know, I don't work for the companies. I can only speak as an end user that's in an academic medical and running these tests. That yes, I think that the pivot needs to be fast. I think part of the challenge as well, though, is that these companies aren't made to pivot like that, and so you know, getting the either federal support or whatever would be necessary to encourage them to be able to do this is one of the challenges. But yes, I will agree with you. Overall, to meet this immediate need, there needs to be a shifting, and I know a lot of companies are shifting. It's just the scale of the shifting. You know, when we think of clinical lab testing. You know, there has never been a test in my laboratory where I need to do two thousand tests a day. So the scale of this is just it's mind boggling from an overall diagnostics perspective, because I don't want to represent it as something like, well, the manufacturers just should have shifted and this would have been relatively easy for them to do, and they're negligent to not do that. That's not what's going on. This is really an unpress sedented shift that's being asked for, Yet at the same time we have to be able to do it in your lab. The PCR test, if you have the equipment, can be run in two to six hours. So what is driving the backlog that causes people to have to wait seven to ten days for a result. A lot of that is that every single state doesn't even have large scale testing that's available. One of our reference laboratories in California, Quest Diagnostics was receiving samples from New York and New Jersey. Well, if you're shipping samples across the country to be able to have them tested at a facility, and then once they get to that facility, if the queue or line is two hundred thousand tests long, you can see that it just increases exponentially the turnaround time, which is the expression that we use in lab diagnostics for the amount of time it takes from the sample to be collected all the way to the person getting the result back. Is there any in centralized national planning for where tests should go. I mean, it seems very crazy that someone could be tested in New York and then have their samples sent to LA so that a lab there can do the work. But I get that you have to send the test where there's access. It sounds like the kind of thing which would benefit from a centralized model. I agree with you. I think a centralized model would be helpful. But you know, I think that this is tied into our healthcare system, and our healthcare system is not built around a centralized model. And so I think this is why you see some of the great disparity across the country is because there is no centralized model, and thus individual areas some can be very very fast, and some may not have access to testing at all. What realistically is going to happen in your view, if in the next few weeks, you know, sort of like end of April, first few weeks of May, we see an effort to get people back to work, coupled with big companies trying to get tests done for their employee eventually over the course of the summer, campuses like university campuses trying to get people tested in a systematic way is not at all realistically doable from your perspective, Given where we stand, I mean, you're perfectly placed to give a credible answer to this question because most people are just speaking theoretically. Yeah, I'm optimistic. So within that optimism, and again I talk to multiple manufacturers of these tests on a daily basis. Everybody is ramping up. And as everybody ramps up, I see more and more hospitals, even just in the Los Angeles area, being able to provide testing. And so I think we're moving in the right direction. The question is are we moving in a direction fast enough to match what we're going to do with changes in social distancing policies? And that's a really difficult thing to be able to predict because I think the two need to be tethered together. As we increase our testing capacity, I think that's one way for us to start in a responsible way, opening back up, getting people back to work. But you know, I think if you just flip the switch on May fifteenth or whatever arbitrary day that said, it's going to so outpace our pace of testing that we're going to end up right back where we were. So, you know, I think that states that are going to be able to do this in a scientific and educated way to meet the testing needs while you open up, I think that we can be successful at it. We'll be back in just a moment. So far, we've been talking about PCR testing, which is to see if a person from whom example has been taken has the virus now, but part of opening up will also be extensive antibody testing. Do you guys do that in your lab? So not yet. I'm going through the validation process now, and so my expectation is that we should go live at UCLA with antibody testing, hopefully sometime early to mid next week. I do want to make kind of a general comment about the antibody testing compared to the PCR though, so I said they were like nine to twelve manufacturer of the PCR test. Ultimately they're using the exact same technology, even though there are small differences between the tests, and so you can really see those tests as the same tests. So whether I offer a PCR test or hospital down the street offers a PCR test, they're all going to be kind of the equivalent sensitivity and high quality. Unfortunately, that is not true for antibody testing at all, and so the challenge of antibody testing is that it was unregulated by the FDA to begin with, So there were a lot of tests that flooded the market that were very very low quality, and every single antibody test manufacturer, because I'm now talked to five or six of them, are using a different target on the virus to be able to look for antibodies, and that distinctly affects whether or not these tests are cross reactive, and they produce false positives. And so unfortunately, what you're going to see with antibody testing is that depending on the platform each testing area uses, they could have vastly different results. And this makes antibody testing then, in determining kind of what it means, very very challenging. So how did you go about the process of choosing the approach that you're going to use in your lab? So I was looking for the best test possible, right, I think the challenge with antibody testing is that it needs to be of the highest quality if we're going to have any chance of trying to establish some level of immunity or even affect behavior by having something like a positive test result. And so in speaking with the companies, what I really wanted to look at was the size of their validation data, whether or not they proved non cross reactivity with something like seasonal coronavirus, influenza, some other viruses that we all have IgG four that you would not want to be cross reactive in a COVID nineteen antibody test, And so we did a long process of evaluation and then now once we've chosen our company, we want to move forward with I'm going to do an extensive in lab validation with serum that I already have from COVID nineteen positive patients and from patients with other viruses to prove that it works before I go forward with a test for my patients. So you're actually doubling up. First, you're choosing what you think is the best test, and then you're going to test it yourself in the lab to make sure that you have confidence in it before you start using it. Absolutely, I think it's the only way in the current environment with the amount of anibody tests that are out there. It's just I have to be sure because clinical decisions are going to be made based on these results. Personal decisions are going to be made based on these results, and so you know, that's really the role of a clinical lab director in choosing the best possible. One of the things that has fascinated me is to hear about scientists around the country trying to come up with outside the box solutions to massively increase testing capacity. And one of the most intriguing ones that I read about was produced by a group at the Broad Institute here in Cambridge, Massachusetts, which is where I'm based, not at the Broad but in Cambridge, that was proposing, at least theoretically, a massive throughput approach where they would bar code, using a crisper like DNA technique, bar code samples so that they could then run through sequencers hundreds of thousands of tests at a single run. That's obviously a very different technology, and it's using very different kinds of methods than are used in most clinical labs. As someone who does it the old fashioned way, as it were, what do you think are the odds of success here? I mean, it might be worth trying it even if the probability of success is very low, because it will be great to test so many people so quickly. What are the big challenges that that approach faces in your view? Yeah, So the scientists that run these approaches are very talented scientists, you know, their research based scientists, and I think that they will be able to successfully put together a system that could theoretically do one hundred thousand samples. Part of what differentiates a research test from a clinical test, something that's allowed to be used on patients is that you have to prove that it works before you can actually use it clinically. And part of the challenge of a system like this I lives literally having this exact same conversation with some researchers at UCLA, is that in order to prove that it works on scale, you need to test fifty thousand samples one hundred thousand samples. And the challenge of doing that is how do you get those samples within a research setting under IRB approval and not have it take nine months, a year, a year and a half, which is typically what these sorts of things would take before or you even began to have enough data to submit to the FDA to get approval of your new technique. And so, while I do think that this could work, I don't know if it's going to move in a time frame that's going to make it feasible. There are other concerns that I have kind of wrapped up in this. A lot of the challenges of let's say, the paper that you had talked about, it doesn't use rtPCR uses LAMP, which is a different nucleic acid amplification technology that can have sensitivity issues. This is also part of some other challenges when you pool large things together, is that on an individual sample basis, sometimes you're just not as good as the gold standard. And these would be the things that these places would have to prove to the FGA before they got approval to do massive testing. In addition, you know, while I respect the fact that you can run one hundred thousand samples at one time, just collecting a hundred thousand samples, getting them sent to one area and getting them processed to be able to run is a phenomenal challenge that's wrapped up on the pre analytical side, or kind of even before the testing begins. So I am excited about this because I actually don't think this is going to be our last pandemic. There isn't anything to suggest it would be. And so if we can get things online like this and really start thinking about how the country when we need to, could pivot to mass scale testing for a virus, that's a really good thing to have in our back pocket. Is this something that's going to work for COVID nineteen. I don't know if the time scale is actually going to meet up with the technology. If I could close our conversation on a modestly lighter note, but it nevertheless an important one. I read that you had said that watching Cuba Gooding Junior in the nineteen ninety five film Outbreak was one of the things that inspired your career path, and of course a lot of us now feel like we're living Outbreak the sequel. Yes, what does that feel like for you personally to be, you know, on the front lines here? It's interesting. So twenty fourteen, we had our Ebola crisis in the United States and at UCLA, I was part of the ebola treatment team, and so in that setting, you know, as an ebola treatment a person participating in the treatment of the patient, you have to get fully suited up. So if you can imagine Cuba getting Junior an outbreak in that yellow suit, that's similar to what you wear when you're attempting to discern whether or not somebody has ebola. So it was that moment I really kind of had my outbreak moment. This one I have felt it's a little bit strange because until we kind of all moved forward with masking, it was a pandemic but everything looked fine, So it was kind of different from the outbreak scenario. It was like a shift in what I thought a pandemic would look like. And that's what I found to be the most surprising of this whole thing. Hundreds of thousands to potentially millions of people worldwide are going to die of this disease, but it's not like running around in the biosafety level four suits. All of the movies, TV shows, and so forth, none of them has a scene where people say, well, we should all suit up. Oh but wait a minute, we don't have enough suits. You know, that's not a plot detail that they've ever taken advantage of in the past, though I suppose we'll see it going forward. Yes, thank you, Ohmi. This was extraordinarily clarifying and helpful. I really hugely appreciate your step by step patients in explaining what you do every day to us. Thank you for doing the work that you're doing, and we all appreciate it. Excellent. Thanks for having me out. No, I appreciate it. Listening to doctor Ohmi Garner. I had moments of optimism because he himself said that he thinks we are scaling up our capacities in a way that will facilitate a lot more testing than we're doing at present. That was the good news. On the other hand, Olmi also made it very clear that there are significant limits to how many tests we can do under current circumstances. We have the shortage of chemicals in the existing tests, we have limited capacity, and when it comes to antibody testing, we still don't really know how well the various tests work. Last, but not least, Although Omai thinks that some of the most fascinating experimental techniques being proposed to test hundreds of thousands of people at the same time have a good shot of working, he's concerned that it may not be possible for that kind of testing at that kind of scale to be ramped up in time to help us address the COVID nineteen epidemic as opposed to future epidemics. Above all, a doctor Omai Garner is a kind of model of the clear speaking, clear thinking scientist who can explain things to all of us, and I feel very lucky that he's at the helm of an important lab like the one at UCLA. Until the next time I speak to you. Be careful, be safe, and be well. Deep Background is brought to you by Pushkin Industries. Our producer is Lydia Gencott, with research help from Zooe Wynn. Mastering is by Jason Gambrel and Martin Gonzalez. Our showrunner is Sophie mckibbon. Our theme music is composed by Luis GERA special thanks to the Pushkin Brass, Malcolm Gladwell, Jacob Weisberg, and Mia Lobel. I'm Noah feld I also write a regular column for Bloomberg Opinion, which you can find at Bloomberg dot com slash feld To discover Bloomberg's original slate of podcasts, go to Bloomberg dot com slash Podcasts. You can follow me on Twitter at Noah R. Feldman. This is Deep Background.