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  • Epidemics, and even pandemics are occurring at an accelerating pace. And we anticipate

  • to see outbreaks every year or two. So our laboratory has been orienting toward a rapid

  • discovery program, where we can respond immediately and seek antibody treatments or preventions

  • in real time, as they happen. We've been prototyping this in previous epidemics. We've been preparing

  • for this moment, and now we're activated around responding to a coronavirus.

  • Hi, I'm James Crowe. I'm Director of the Vanderbilt Vaccine Center.

  • Dr. Crowe is part of a special team of experts, universities,and advanced genetic sequencing

  • groups that are trained to deliver rapid treatments in the midst of an outbreak.

  • It was a concept launched back in 2017 by the Defense Advanced Research Projects Agency.

  • DARPA usually puts out calls for research about things that can't be done right now.

  • They pitch a vision for something that is desirable, it's an aspirational goal, sort

  • of crazy ideas. So the pandemic prevention program, or P3,

  • the idea was an epidemic occurs, and in 60 days, groups would take blood samples, and

  • be ready to treat people 60 days later. Normally, drug programs take a decade, or certainly

  • years. So it was a crazy idea. Last year, we did a simulation in which we pulled the

  • timeframe down to about 78 days. So we were pretty excited about that success,

  • and it's the fastest anyone has gone from a blood sample to an antibody cure. That we

  • know of. And we were just simulating last year.

  • But this year, we're doing it for real. The goal is to safely develop an antibody

  • therapy that can provide immediate immunity, potentially before a vaccine is ready.

  • The clock started to tick once this coronavirus outbreak switched from epidemic to global

  • pandemic. The pandemic started in China, and certainly

  • we knew in December that something unusual was going on there. But it wasn't clear in

  • December 2019 that this would spread anywhere else.

  • By January, the first case occurred in the United States. And by then, our team got concerned

  • that we really needed to activate around this. Fortunately, as soon as the outbreak occurred,

  • the sequences of the virus were published. It's an RNA virus. And we know that there's

  • only one major protein on the surface of the cell, and it sort or looks like spikes, so

  • people have called it the spike protein. And we know that's what attaches to your cells,

  • and attacks you and inserts the virus in. Your body has an immune system, and it responds

  • to threats in various ways. The principal way after you're infected that you prevent

  • the infection from occurring again, is through a network of proteins in your body called

  • antibodies. Once you've seen a virus, like coronavirus or flu, you remember that virus

  • when it comes back. You already have antibodies, and they're sort of a shield.

  • So the idea is, if we have antibodies that can attach to the spike protein and cover

  • the virus, it'll block the virus from being able to get in.

  • So we know what we're looking for. We want antibodies to that spike protein.

  • To find antibodies, they need to secure blood samples from patients first.

  • We actually contacted the providers, the medical teams who were taking care of the first cases.

  • And in fact, the sample from the first case in the United States came to us through that

  • network. There's a cloud of chaos around these cases.

  • There are family members, and press, and lots of people in PPE. It's actually hard to get

  • the communication to the subject themselves, or their families. When we do that, almost

  • invariably the people say, "I would love to contribute. I would not want anyone else to

  • go through what I went through." These are important samples.

  • We've been working with FedEx Critical operations, and they've been essential to our success.

  • So not only just barcoding like they normally do. We could watch. The package goes into

  • the truck, and it's coming toward us, so we go "It'll be here in 30 seconds."

  • We do whatever it takes to move this stuff around. But we do it safely, but we're tracking

  • everything very carefully. We start with whole blood. It's got a lot

  • of red blood cells, which carry the oxygen and the white blood cells. And so we pull

  • the white blood cells out, and those are the immune system cells. And there are the B cells

  • for antibodies. And so we pulled those out...It's like a needle in a haystack, we know a few

  • of those in there are for the recent infection, like coronavirus.

  • And so that's where the high technology comes in, is drilling down and finding the individual

  • cells that make an antibody. Now we have a little cell, and it's very fragile,

  • very small, and we have to manipulate that, and get it to make the antibody and confirm

  • yes, I'm a coronavirus cell. At which point, we bust the cell open, and

  • inside that are the genes for the antibody. So we recover the genes from a single cell

  • and we just sequence it, and we can print the gene out in a DNA printer. The machine

  • gives us the DNA back. It's pretty amazing. That's come out of a revolution in science

  • called synthetic genomics. So you can synthesize DNA, at very high scale.

  • Then we can put that back into a cell in the laboratory, and that cell becomes a factory

  • to make that antibody. Then we have lots of the antibody, which is

  • a protein we can give to people and protect them.

  • So there's a lot of steps involved, and some of its conventional, but some of it's magical

  • We run into obstacles. We have to overcome those obstacles immediately, like within minutes

  • sometimes. We have about four or five thousand antibodies

  • in our pipeline now, that we've gotten from single cells from survivors and then we'll

  • down-select. We'll look at about 20 of them in mice. And

  • then we'll end up with two of them in monkeys, and we'll be done. That's the sprint. The

  • first human trials of any antibody are likely to be in the June to August window. And that's

  • when we just put antibody into 20 people, and make sure nothing bad happens. And then

  • there's a next step where we need to figure out, what's the dose? So usually we give 100

  • people a dose, another 100 people a lower dose.

  • And then finally you do what's called a phase III trial, and you figure out if it works.

  • And that's thousands of people. If the antibody works, and we already know it's safe, then

  • it would be released to the public. That's going to take an uncertain amount of time.

  • Probably year, year and a half before it would fully be released to the public, because we

  • have to do this methodically. And you could say, "Well you have it, just give it to me.

  • Why don't you just give it to me?" But, some treatments make people worse. Hopefully by

  • public health measures, social distancing and that sort of thing, we slow things down.

  • It'll remain to be seen whether this becomes a winter thing, and we have a whole nother

  • season. That's why everybody's pushing. It's interesting to watch our team operating, because

  • they're kind of in a flow state. These guys are working about 20 hours a day since January.

  • But at the same time, they're actually doing the work at an unprecedented pace for something

  • that's killing thousands of people. So there's a passion and a mission in it. Scientists

  • typically are very methodical. They like to repeat things, they like to be sure. They

  • don't like to tell people the result until they've done it more than once. And in this

  • type of science or discovery, we can't do that. And we're constantly trying to retrain

  • ourselves to think more like. You know, what's good enough? What's the 80% solution? We got

  • to move forward. And it's not natural to think that way.

  • Coordinated response teams that can deliver rapid therapies will be a critical component

  • in future pandemic preparedness. But how can we get ahead of this next time?

  • You cannot pick the next one. You can't predict, "I know it's going to be a filovirus, or a

  • flavivirus, or an alphavirus. But you know one of them is coming.

  • And what we've been advocating is, why don't we get antibody cures for all these teed-up

  • ahead of time? And when it happens, we don't have this scramble.

  • So we've been methodically making antibodies. And we're about 40 into it. We have antibodies

  • to other coronaviruses. But they don't cross-react with this one. But I think preparing ahead

  • of time makes more sense than always waiting.

Epidemics, and even pandemics are occurring at an accelerating pace. And we anticipate

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