 To be able to study this, the first thing we need is sequence, not just one sequence, but tons of sequences. You all know where this comes from, right? It's the DNA, but it's not entirely trivial to argue how will this DNA sequence, how can we read it, for instance? With COVID and everything, now you've probably seen the swaps and everything, but the question is how do you get from a minute amount of DNA on a swab sample to actually being able to read out the sequences, spaces A, G, C and T? Well, that's not entirely trivial. The first problem, as we saw here, is that the amount of DNA on this swab is so small that there is no way you can do any experiment on it. Even if you used fluorescence probes or anything, we're talking about maybe a few hundred molecules or so. That's never going to work. So how does nature do it? Well, nature has a number of built-in fancy ways to replicate DNA, right? So if I start with the DNA sequence, I'm going to need some colors here, in general, if I have a sequence here, I could take the sequence and maybe get this to split if I have some way of getting this to split. And if this works, I could then have lots of small fragments join in here, right? So that I end up with two DNA spirals instead. Then I've copied it once. If I then repeat that, in the next step, I would have four, and then I would have eight, and then I would have 16, etc. So if I could just copy the DNA the way cells do it, I could amplify this signal and get something to work with. In principle, this is not that hard. You know what enzymes to use for this. The second the DNA is split, we just have to add the DNA polymerase enzyme and add a bunch of these mixed loose bases. If we do that, the DNA polymerase is going to start stitching the bases up so that we get two sequences. The problem though is that we're going to need to start by getting the DNA to split. How do we do that? It's actually very easy. We just heat it up. So if we heat this to 90 degrees centigrade or so, the DNA will loosen up and become two chains. There is only one problem here. What happens to this protein when we heat it up to 90 degrees? It unfolds. So then I have to add this protein again when I'm letting this cool down. In the second step here, I want to heat it up again, then I'm destroying my protein again, and then I need to add new protein, and I need to heat it up, and that new protein, you can probably see that this is going to be very labor-intensive and difficult. So what if it wouldn't be amazing if I could have a type of this protein that was heat-resistant so that it survived 90 degrees centigrade? So if all this worked, I could have a series of experiments where I just add the DNA and then I increase the temperature to get it to split. I reduce the temperature. This heat-resistant polymerase would make two copies. I heat it again, and then I have both copies split. I reduce the temperature, I increase the temperature, reduce the temperature, increase the temperature, reduce the temperature. You can see where I'm going, right? The number of DNA copies would grow as two to the power of n, where n is the number of steps. And as you know now, exponentials grow exceptionally fast. So after a handful of cycles like this, I'm going to have enough DNA to do anything. The only problem is that I need that heat-resistant form of the enzyme. It turns out that people found bacteria in the late 1970s, in particular in Yellowstone, one called Thermos Aquaticus, that thrives in hot geysers around like 60 to 70 degrees centigrade, literally thrives there. It can reproduce at those temperatures, in particular in geysers in Yellowstone. I think that's what gives these geysers a particular green color. This bacterium, it turns out, to be able to survive at these conditions, it has a version of this polymerase that is heat-resistant. Thermos Aquaticus polymerase, or TAC polymerase. So all you really need to do is take the polymerase from this particular bacterium. In principle, I think people might, I forgot whether you try to mutate a few residues to get it even more stable. But the point is that we now have an enzyme that survives up to 90, 95 degrees. It's not going to be efficient there, but that's fine. We don't need it to be efficient. I just need it not to unfold. And then when I drop the temperature back to 50 degrees centigrade or so, it's going to start re-repairing my DNA. So then I don't need to make any copies at all. The person who came up with this seemingly, it's a dirt simple idea, right? It was Kerry Mouldis, and he got the Nobel Prize in 1993 for this. And this process is called PCR, that's that's there. I can write it down. PCR polymerase chain reaction. Every single COVID test, well not every single common ones, there's so-called PCR tests. So can you imagine what they do? So then you take this one, and then you go into the hospital or test center, then you run through a number of these PCR cycles. And now I'm going to have a sample with a ton of viral DNA in it, or RNA in the case of the virus. The only question now, can I find a way to detect that? Because it could be any RNA. It could be my RNA for instance, right? So how do I detect that it's a viral RNA?