 Okay, we're back for live. This is Think Tech. I'm Jay Fiedel. It's a given Thursday morning. We have the honor of dealing this morning with Brett, wait, I'm blocking on it. Edgy Barn. He's a researcher, an MD researcher at MSU. That's Michigan State University has his own lab. And he's been working on fast, fast COVID tests, which is really important, and could be a game changer. May I say that, Brett? Yep, that's the goal. So we really need that in a hurry, actually, I would say. It's the sticking point where science and politics doesn't meet and you really have to have this fast test. So your test is much faster than any other test available right now, right? Yes, I would say so, or definitely up there as fast as they do seem to get. I have seen the Abbott test employed with fast results as well. So I know that that exists and has been available for some time. Some places are using it and others aren't. So in areas, another hospital where I work, they don't use that test. They use, I think they were critical of the sensitivity issue there and decided to use a different, more traditional process. So therefore the sample processing takes a little bit longer. Well, we're talking about new technology and the confluence of possible technological influences here. Can you talk about, you know, what the steps are in this test and how you derive them and how they work to the extent you can share them with us? Sure, sure. So the basis of our test is I was, we were chatting a little bit earlier, it's based on what's called loop mediated isothermal amplification or LAM. And this is a, I considered an advanced PCR technology. It's, I would say somewhat mature in the research field, but its utility in the actual clinical workspace has been somewhat limited so far over the 20 years or so that it has existed. So I have been intrigued by LAM for a long time and kind of utilize my own bioinformatics tools to figure out where you would implement LAM. And where I use it is to identify pathogens that cause septic type infections and conditions in humans. So my research background kind of started with this bioinformatics functional genomics they call it. You've used it on various antigens in the past. So this is something that works for various other antigens, including viral antigens. Exactly. So you could target bacteria, fungi, viruses, human elements, genetic elements, targeted sequence elements, really generally most things that have genetic code, you can employ this tool to get the answer quickly. So we've focused on all of the bad pathogens that you would face in a normal emergency situation from my standpoint. You can theoretically die from almost anything presumably, but there's really a list, a top 10 list of offenders that really take the humans down with far more prevalence than the rest. So I validated previously the top 50 sort of bacterial, fungal viral infections that we see commonly here. And even some more exotic ones from down in Peru, Lycemoniasis, we adapted our tests to be useful out on the Amazon River, I figured, you know, if I can make it work there, then I shouldn't really have a problem selling this is something that's a useful portable tool. So that's what we've been working with for a number of years. You know, one of the things that's interesting is that these things mutate. Before you even get to a question of virus last year, there was a lot of coverage in the media about new funguses, funguses that were ultimately fatal, funguses that were like MRSA, you know, that you couldn't stop them, they were resistant to any drugs. Is this a kind of system that will identify a mutated fungus, for example? You can adapt this system to look for the mutations. I generally, in my own explorations, try to avoid areas of high mutation, because you know, if we're looking for the offender again, if I need to get down to the level of mutation, to me, at least as a treating physician, if I know that it's MRSA, if I know that it's pseudomonas, if I know that it's COVID, if I know that it's influenza, I basically know what to do. It's when you're dealing with this nebulous, could it be this, could it, yeah, it could be all of this. And so doctors end up treating things very broadly. We order just a whole myriad of tests that are suggestive of the things that we're looking for. But the actual answer, whether it's COVID takes one hour, four hours, two days, three days, same as blood cultures, same as wound cultures, sputum cultures, you go on and on, it takes days to get these results. And the way we practice now is really just, well, I guess it's this, we'll treat it this way. So you don't need to do a nasal swab for this test. You can get along on what a chin swab, a rather a cheek swab inside your mouth. Can you get along on sputum along? So you'll read a lot of publications out there that they're claiming, you know, sputum's so sensitive and whatnot. But then if you read the details, they're having you spit like a cup worth of saliva. Then you concentrate, then you get the and finally have enough cells to give yourself, sorry, the dog is crazy, to give yourself a signal that you can see that you get a reliable readout. So we've tested the oral, it's probably works, the saliva, it theoretically could work. But I don't, I don't ever want to unnecessarily subject, oh, sorry about that. It's okay. I don't want to subject patients or lab workers. So I don't want to suggest patients or lab workers to any unnecessary exposure risks. Okay, so what does that mean in terms of the optimal way to use your test? What it goes to is, unfortunately, for the probably most people don't want to hear it, but the the nasal pharyngeal swab is the best. And the reason it's the best is because you gain the most material, genetic material when you do sex a swab. Well, the reason I ask is, you know, I'm sort of wondering whether we can develop a test where the, it can be DIY, you can do it yourself in the privacy of your own home. Yes. And I think it's hard to do that with a nasal, a nasal test. So when I, I have enrolled my own personal patients for the study. So and to do that, I want to know from beginning to end where any fail point might be. So I've supervised the nasal pharyngeal swabbing, the oral pharyngeal dysceliava, so that I know what is what. And I have tried to make it as easy and tolerable as I could make it for myself with the nasal pharyngeal swab. And really, when it comes down to it, every medical procedure that you're going to encounter is not a pleasant experience. So we did it first with just a simple acute type swab for our initial studies. Those worked just fine. And the general swab that you get, I just had patients either inserted themselves or I would just into the maybe about two inches, one and a half, two inches into the nasal, nasal cavity, let it sit for 10 seconds, twist it around a little bit, switch to the other side, let it sit for 10 seconds, swish it around a little bit, finish. It goes right into the inactivating solution and goes on from there. That's not painful. That's not hard to do if it's only that. It's really not, it's not so bad. As far as medical procedures go, it's the bottom end of, you know, tolerance level, I would say. So you say you put it into a certain solution. Does the patient do that? When I'm the idea myself, yeah. But to your point of home do-it-yourself testing, that is something that we've been working on development in my lab for a number of years. This actual instance is more useful than anything we could have come up with before. So the home testing kit has been on the menu for quite some time and we're really pretty close to having it where you, and we've tested it ourselves, you know, in the lab. If you're at home, what would you do with this? We tested it out. Well, it works like a charm. So that's the hope. Okay, so you take this material that comes out of the swab or off the cheek or the sputum, whatever the source of it is, and how do you process this to get a reasonably reliable your response, you know, an answer on whether the individual is infected? Mm-hmm. So after we drop the swab, it'll be in this little solution with about a milliliter, just a little bit of fluid in it. Take it to the laboratory workspace. We use the whole biosafety cabinet with ventilation filters and full PPE gear for technicians. But theoretically, it should be inactivated already in this solution. From there, you're going to take a small... So you've killed the virus. You've made the virus inert by this time. Exactly. Yep. But the magenta material should be preserved. So now we take just a small fraction of that and we run it through a purification column that's a quick easy spin on the desktop. It takes about a minute to do. Now you're doing this. This is not the pay, this is not DYI. I think it's done. They're finished. So this is real world right now. So then the laboratory technician takes that, cleans it up with this spin column, takes the pollutants out at the bottom, adds that to a master mix, and the reaction runs. Right now we run it for 30 minutes, just because we're trying to titrate all of our times and values. Okay, so this is the polymerase reading then. How does that work? So biochemically. Yeah. So biochemically, you have primers that we have developed, which are kind of like keys that open certain locks. And we're trying to open the COVID lock. So we have our keys that can pick that lock. And once the keys are already in the reaction well, once we add the master mix, if the COVID material is there, the keys get to work. The amplification begins with the heating aspect, which is your catalyst for everything to go on. You set the timer, wait 30 minutes, and you're either looking at a PCR machine output, or what I prefer is this color change out method where you just look at and see if it changed from a magenta, basically to a yellow. So it's a color spectrum difference that is clear to even a colorblind individual. Okay, so in the first technique, the polymerase technique rather than the heating, well, how does it present? It's not a color change. How do you read that result? So that one's run on a real-time PCR machine. And with that one, the master. These are easy to get, right? A real-time PCR machine easy to get. My recollection is that you can do 22 tests at a time with that machine, right? Yes, yes. With the 96 well plate format, you can fit 22 tests on one. Similarly, with our color change, we're running that on a 96 well hot plate digital bath. So that one, similarly, you can do one at a time, you can do 22 at a time. It kind of depends what your throughput and your needs are. The machine itself will read the presence of the virus, and the machine will come out with some digital readout telling you you have the virus in this sample. In the case of the color change, you'll have to apply heat. Where is the heat applied in the machine or before or after the machine? The heating element is just a digital drive. It's called a digital drive bath. It's got a digital heating thermometer on there. You set the temperature and go from there. We run those for 30 minutes at 65 degrees centigrade and check the result at the end, basically. So if it turns yellow, did you say? That means that the sample reflects an infection. Yeah, it shows. Yeah, reaction was positive. Okay, which one of those two methods? I guess the first method you describe can be taken down to five or six or seven or eight minutes, less than 10 minutes in any event. But the heat system that you described, that takes longer. Tell me how that works. Since it's a qualitative test, we want to be able to run it long enough to not miss anything at this juncture. So we haven't particularly performed the experiment where you would take a picture of the well at each moment and then develop your own amplification curve or your time to color change in the end. Instead, we just do a qualitative test at the end of 30 minutes, figuring that at that point, we shouldn't have missed anything and the reaction should be terminated. But it's interesting what your answer suggests that you could do a kind of AI comparison throughout the 30 minutes. Sure. And when you see the changes, you could get a lead, an early indication, so to speak, on what's going to happen. Exactly. Yeah, we'd planned a kind of a home unit where you could use your cell phone sitting on top of a little box that we created. And the cell phone could just do time-lapse shots, and you'd be able to then integrate all the fluorescence. We were using a fluorescence system for that, so it was a little bit trickier, but we found the phone could do it. But then some updated things came out from the vendors for the lamp polymerase. So that enabled us to do things even more simply, really. But yes, this is certainly something that does make sense, and you could turn this into values in the end. Well, that's really a fabulous possibility to have it on your cell phone. So can you tell me you had influences and collaborations in Japan in the original design of one of the elements, one of the critical elements here? How did you make that connection, and what did you derive from it? Okay, so the Japanese company Aiken Chemical first introduced lamp in 2000, and basically introduced the molecular technique that supported it. And afterward, they enabled scientists, researchers to use basically their web-based software to design isothermal amplification primers or whatever. They don't tell you what to do with it. They just say, here it is. So when I was first beginning my work in this area, I recognized that things need to be done in the sort of ER emergency timeframe, especially when it comes to something so broad and undifferentiated as infectious diseases is. So I looked at LAMP as an obvious tool that I could hopefully adapt and get these kind of real-time decisions made with real, accurate, prescriptive data instead of empiric guidance. So I did start, I filed a patent for use of isothermal amplification methods for microbial pathogen detection while I was in residency, and then have subsequently extension patent on that and another one pending. But basically, mine is just the adaptation of LAMP to septic organisms. So it's pretty wide. Coronavirus didn't exist before, but clearly you just adapt the same sort of method. Yeah, that's great. So are you collaborating with them now, or it's just a matter of using the technology that they developed? It'd be a matter of me when I'm all finished with this, if I can get it all said and done and have it all looking really good and get an FDA certified product and I'd have a licensing agreement with Hagan in place. Okay. Now you have a couple of, I saw in the coverage in the, I guess it was the Michigan State newspaper, and you had two researchers in your photo. One was Lee, Chinese, and one was Japanese. Absolutely. And are they American born, or are they they're from Asia? Yep, secret of my success. Yeah, so Jiangang and I have been working Dr. Lee for a number of years now. He was trained originally in China in kind of medical technologies and then had an extended period of research work at Emory University. And it was fortunate I was starting up my lab just, I guess time goes by quickly. So 2014 and he was looking to move to Michigan. So I got really lucky because he's he's got great great skills and he's he's very good at science. So that's fun. And then I'm in the biomedical engineering building. And once they I was getting moved over there, the director, Chris Contag said, oh, you should meet Yuki who comes from Japan and used to work on isothermal amplification stuff. So or two, Yuki for a number of years as well. And when this whole all started, Jiangang was told me there's bad stuff happening in China. We're like, oh, you want to work on this? He's like, yeah, I do. So I'm like, sounds good to me. So we started and then you had worked on the swine flu h1n1 and work on a team that made a rapid test for that specific influenza strain back in 2009. So he had expertise in viral stuff with with lamp also. And he's a really great scientist. So he makes sure all my stuff makes sense. And so in order to develop this this kind of test, you have to have at some point, the live virus. And you have to have to have the system in place. And you have to be able to test whether the system will identify the virus. My right, how do you how do you do that? You have to bring in live virus. Where do you get it from? And how do you do the testing to be sure that it is reliable? Yeah. So, um, originally, I used test samples acquired from emergency patients. And I inactivated the virus and tested that. Originally, originally, we synthesized the pieces of RNA that we intended that are correlate with the COVID to adapt our tests to those. So this dog killing me. So all the original testing is on, you know, synthetic stuff. And that's all we use when we're in our laboratory. And then after we got the synthetic material to all amplify and everything made sense, we had all our copy numbers and everything. Then we made arrangements and I got collaboration with Dr. John Gerlach, who runs the Cleo Lava at Michigan State University. And Dr. Gerlach was able to get us state samples that were archived positives from various sources that had been extracted and tested with the gold standard method and found to be positive. So we have 30 positive and 30 negative of those, which are live viruses virus, you know, samples in a viral transport media. So then we have to adapt our methods to account for this viral transport media. And kind of this weird you know, this weird solution of stuff that we had, you know, basically figure out how to kind of work get our samples answers to match up with theirs. So I'm sorry. That's okay. This is, you know, what we do here at Think Tech, where it's cinema, real, you know. So Brett, how effective, how reliable is the test both in the first mode, the polymerase, and in the heating system you've developed? So with, I think the most updated results, I haven't heard all the today, we're almost finished with that all those 60 samples that I spoke of. So the first week or so was needed to kind of tinker around with those and see sometimes they worked and others didn't. And then our internal control had problems. So we then it makes it difficult to see how reliable the test is. So we had to make some tweaks and improvements on the processing. These are for the sample sample that come from the hospital or the state lab. So once those tweaks were all done, then we were able to proceed. And I'd say our accuracy right now using a Roche thermocycler machine are about 75% or so. And then for the color change method, unexpectedly they were higher, probably more like 85% right now. So that's about where we're at for those... But you're shooting, you're shooting for 100%. How do you get from where you are? You have a plan to get from where you are 100%? Oh, certainly. We've done some concentration sort of steps that help quite a bit. And then I can't really go back and recheck some of them because we exhausted the archive. So we're going to end up importing new ones. And now, of course, the tidal wave has kind of passed us, it seems. So the number of... I did have two positive patients when I worked in the emergency department two nights ago in Lansing. So it's not all gone. And certainly I think there's great potential for a rebound effect. So we'll see. In the meantime, yeah, that's kind of what I've got. I think we can get up into the 90s pretty easily, but that's where I want to be more or less. Sure. Where are the other tests that are out there? Are they in the 90s? I don't think so. No. I mean, if you do the gold standard with... And I believe we would get up to 100 if we did the full extraction. But I'm really trying to squeeze what's like a three or four hour process down into like one or two minutes. So the sacrifice you pay is you're going to lose some, I think. Is there any risk? Is there any risk to this test? I don't know. Maybe there's no risk to any of them. You're not inserting virus either alive or dead into the individual. So where would the risk be, if any? No one likes to get the wrong answer, right? No one... You don't want to tell someone they have something terrible and they don't. That's ethically undefensible. And so that's the risk. Like there's not really a treatment for this. It's all supportive care. We've treated to saying all these viruses are supportive care, but it's still better to know for everyone if you've got it, right? Yeah. This may be outside your thinking, but one of the things that's occurred to me is we have all these cumulative totals of tests that have been taken in the U.S. And then when you make a cumulative total over say a two month period, you're going to get a total that is cumulative. But it's not now necessarily. And if you were going to make an effective testing protocol, I don't know if you thought about this, but how often would you test a given population? Seems to me with this test, you could test them a lot. You could test them anytime you feel like it. Going back to Trump's comment, anybody who wants to test can get a test. You can test them over and over again, which I think is what you've got to do. You've got to have multiple tests, not just cumulative numbers. Pretty much, I would say so. I know that people do clear the virus. I see that it goes away over time. People who bounce back to the ER a bunch of times, keep getting tested, and then suddenly it's gone. I do also hear cases where people should not reasonably have not recovered, right? So it's like they were sick. They're testing positive. A month has gone by. They're still sick and they're still positive. So that's tricky. Did they get sick twice? Did they ever recover? So these kinds of questions are difficult to answer. One of the things that's been in discussion in the newspaper is how many virion viral particles do you have to have in order to develop the disease? I don't know if there's been any real conclusion on that. But it seems to me if you've got one particle, that's probably not going to make you sick. But if you have a lot of particles that you've gotten from multiple sources over a long period of time, those particles are more likely to make you sick. So is that consistent with your understanding? And can we ever make a test that would determine the vigor, the vitality of these particles so we know how much infection is going on in a quantitative way in the individual? Yeah. It's hard for me to say because when you're doing, I have, again, now these undifferentiated samples from the state lab. They could be your sputum, saliva, nasopharyngeal, wash, swab, any sort of thing. And they're an aliquot of this viral transport media. The state lab samples, I don't, I keep myself off what the real ones look like. But we do have a quantitative real-time PCR output for each of them. So it will be curious for me when we do our final analysis to see where the cutoff for our misses might be. And if we're missing ones that are way out there, then that would kind of explain some things like we're basically without an extensive extraction not going to have the sensitivity necessary. But it's curious because the patients that I've sampled from who were positive were, I would say, mild, mild to moderate maybe level of illness. And their positivity is like 10,000, greater than 10,000 copies per reaction, well, well over. And again, their reactions when they're positive, it's like five minutes, six minutes, seven minutes, eight minutes. Would the tests that you're developing read positive for only a handful of particles? So you have to do the limit of detection determination for all of them. Basically, in vitro is the only way you can do it. And our copy numbers down at like 650 or 325, something like that at the lowest end of the detection limit. And that's just as low as our primers can go. And below that, it just, it won't really work. It won't really work. Yeah. So you'll see. The last thing I want to ask you is about the approval process. And it's troubling because it's troubling that you can't get approval right away. The first time I saw your report in the newspaper was on April 10th. That's over a month ago. Yeah. And at the time, you said it'll take a month to get approval from, I think there was a government laboratory you had to get through, and then you had to go to the FDA. So my question is, where are you on that approval continuum? And how long is it going to take? And why does it take so long? If there's no risk on this, and you can establish a certain amount of reliability, it should be five minutes. As long as the test itself, five minutes, why does it take so long? So to answer the question, to be fair, I didn't, I wasn't able to get the laboratory space to actually begin the operation until, I think, three weeks ago today. So that's when I was able to get the lab. Then we were able to get the samples from the state. That became like a Friday. So now, Friday, not Saturday, Sunday, Monday, started running samples. Didn't really know what we were dealing with there, because there were just tubes that had stuff in it. We had to figure out how to deal with that and the fact that it was a live virus and inactivating it and lysing the cells and then cleaning up whatever is in there and amplifying the product. All of these things had to be figured out. And then we're kind of like a little, you saw the operation size, three individuals. I kind of help coordinate and keep all the experiments going and try to debug when the problems hit. And overall, everybody else is either getting the work done or trying to make things better and overall validate it. So it's taken a while just with only a few of us. And as far as the FDA submission process goes, I am not really a person who likes to keep redoing the same kind of work over and over again. So we've already done all the preliminary limits of detection and all that's done on the paperwork. But what I really want is the numbers from the validated samples. So literally maybe today, maybe tomorrow we're finally finished with that original 60. I've already got a few of my own that I can bring in. But as with anything in science, it's like what kind of swabs did you use? What kind of media was it in? What kind of timing did we do? All of these things need to be very precise. And I don't malign the FDA approval process myself because I get it. There's just a ton of quackery out there. People trying to make a quick buck and sell you some garbage. I've been doing this too long and I take it too seriously to be doing that. So if it all works out perfect and great, it's so easy. But the real world throws you some... Yeah. Well, in the real world, let's assume that your numbers impressed them. Let's assume that they say, this is really good because it's fast and we need fast and we need easy. And we want to do this so, Brett, go ahead. Get it started. What happens then? You're effectively in a spot where you have to commercialize, where you either have to have a contract or a capital to manufacture and distribute. This is not easy because the demand is just huge. And although the White House says we've prevailed on this, we have it. And the key to reopening the economy is the ability to do intelligent testing. Everybody agrees on that. So the demand will be just extraordinary. How can this system meet that demand? Oh, I believe it can. I mean, all the vendors and all the materials that go into making my tests are all from legitimate quality controlled sources. So it isn't really much of a cowboy operation at all, I would say. Everything has been put together scientifically. And again, they're all big vendors. So when it comes down to it, they're more like, how big is the order? That's about all. And the way my method works, it doesn't encroach on the other systems that are out there. It's just a bypass freeway. So it's not really, shouldn't hinder the rest of the system in any major way. Well, we're in a time when we really need your system. And I mean, for what it's worth, I have a really good feeling about what you're doing in all ways. And for what it's worth, I hope that after you succeed in this and the FDA approves it, and you have all these manufacturers manufacturing it all over the world for 8 billion people, I hope you'll still talk to me. Oh, yeah. Michigan's lovely, and I grew up in California, but I'm every year, right about Christmas, I can't help it. I started living in the middle of Hawaii for at least beyond right now, almost in Michigan is barely one million. Brett Atchibon in the MSU, working on some really fabulous technology. Thank you so much. Thank you very much, Jay. I appreciate it. Aloha. For having me. Appreciate it. Aloha.