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The next wave of COVID tests take advantage of some really cool molecular biology. They can be run by hospitals and doctors on-site, and many turn around results in an hour or less!

COVID-19 News & Updates: https://www.youtube.com/playlist?list=PLsNB4peY6C6IQediwz2GzMTNvm_dMzr47

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Sources:
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Images:
https://commons.wikimedia.org/wiki/File:CDC_2019-nCoV_Laboratory_Test_Kit.jpg
https://commons.wikimedia.org/wiki/File:Cycling_amplification_and_elongation_steps_of_RT-LAMP_method.png
https://en.wikipedia.org/wiki/File:15_Hegasy_Cas9_DNA_Tool_Wiki_E_CCBYSA.png
[♪ INTRO].

This episode was filmed on April 21st, 2020. If we have any updates on testing, we will link to them in the description.

It's always been helpful to be able to test for specific ailments. But during a pandemic, testing becomes essential, because it's much harder to fight a disease when you don't know who has it. And detecting pathogens isn't as easy as checking off a list of symptoms.

For example, as we noted a few weeks ago, the new coronavirus behind COVID-19 may have distinctive symptoms, or, it may look a lot like seasonal allergies or the flu or it may look like nothing at all. So to be sure of infections, you have to run some kind of test. Until recently, that could take days; in part because the test itself takes several hours to run, but also because it has required getting samples to specialized labs with expensive equipment.

But the new wave of COVID tests can be run by hospitals and doctors on-site, and many turn around results in an hour or less. And that's because they take advantage of some really cool molecular biology. The tried-and-true, and somewhat slow, method for detecting coronavirus is something called RT-PCR.

If you got a COVID test any time before, like, right now, so late April, it was almost definitely tested this way. The short version is that RT-PCR uses molecular tools to spot the viruses' genetic material lurking in your bodily fluids. The RT stands for Reverse Transcriptase, an enzyme that lets us turn the virus' RNA genes into DNA.

And then PCR stands for Polymerase Chain Reaction, a technique that makes /billions/ of copies of that DNA so it's easier to see. Because, you know, DNA molecules are pretty small. This whole process takes a few hours because the PCR bit requires lots of temperature cycles that take several minutes each.

So you could detect the virus a whole lot faster if you could somehow speed up this DNA copying. And it turns out you can, if you use isothermal amplification instead. You see, the reason PCR involves a lot of heating and cooling is that it uses heat to separate DNA into individual strands.

Isothermal means “same temperature,” so isothermal amplification uses DNA-copying enzymes that can unwind and separate DNA strands all by themselves, no heat cycling required. So the most common variety of this method, called LAMP, also adds several special primers, which stick to each other. These warp the DNA into weird dumbbell shapes, and that creates open starting points for the enzymes that actually do the copying to latch onto.

Tests relying on this kind of amplification weren't rolled out as quickly as the RT-PCR tests, possibly because it can be challenging to design those special primers. These are the basics. It's actually a little bit more complicated than this, but the benefit is that the machines only need to hold at one temperature, so they can be much smaller, much cheaper, and much more portable.

The copies of the DNA are made much faster, too. So much faster that one company's US FDA-approved test can deliver results within 15 minutes! Though, that's with their not-so-cheap, all-in-one machine and one-time-use cartridges, which not all doctors or hospitals have on hand.

And each of these machines can only run one test at a time. So you need lots of them if you want to run a lot of tests in one day. Other groups developing COVID-19 tests say their isothermal amplification can take 20 to 30 minutes.

They then spruce up the detection side of things, too, by using a super-precise CRISPR system. Usually, when we're talking about CRISPR, we're talking about editing DNA using CRISPR/Cas-9. The Cas9 is an enzyme designed to recognize specific genetic sequences, and when it does, it snips them out, like laser-guided scissors.

The enzymes in CRISPR-based virus tests, on the other hand, are Cas-12 or Cas-13, which are more like paper shredders. When they find genetic material they recognize, they cut that sequence as well as any other DNA or RNA around it. The tests also include reporter molecules that do things like glow or change color when this shredding happens.

So basically, if you see something change, then the enzyme has found the viral genes, and the test is positive. These can take less than an hour to run, from swab to result, and they don't need a lot of fancy equipment, so they can be performed on-site at a doctor's office or in a hospital. Initial results from one suggest that they're about as accurate as standard PCR tests.

They might also be super-precise, able to detect even a single letter change in a virus' genome. But you won't see these CRISPR tests in your doctor's office quite yet. They're taking a little while to develop and test - as with any newish technology, researchers want to be extra sure they are reliable and accurate before rolling them out.

Meanwhile, some companies are working on even faster tests that are also easier to use. These tests don't search for viral genes. They're called immunoassays because they detect pathogens using antibodies,.

Y-shaped molecules created by our immune system in response to infections. So immunoassays don't detect antibodies, they use antibodies that are found somewhere else to detect the presence of the virus. The immune system is complicated, but basically, antibodies work by sticking to specific things.

And immunoassays use this stickiness to their advantage. Essentially, they take a patient's sample and incubate it with lab-grown antibodies specifically tailored to target the pathogen. Additional ingredients, like enzymes that'll change color if the antibodies hit their mark, then let the doctor see if the sample is positive.

Antibodies can be grown in lab animals that have been exposed to the virus or parts of it, or even from the blood cells of people who have recovered. Or, the gene for a desired antibody may be inserted into the genome of a bacterium or yeast to coax it to mass-produce them. The trick is finding the right antibody, one that reliably sticks to what you want, and not to anything else.

That's why immunoassays take longer to develop than RNA- or DNA-finding tests. They can also be a bit less accurate. But once they're ready, they're generally much easier to use and lightning quick.

They can even be put into dipsticks, like a home pregnancy test, that require no fancy equipment at all. So, one could imagine something similar coming onto the market that uses a drop of blood from a finger prick to spot the SARS-CoV-2 virus. And at least one antibody has been created for the new coronavirus, so this kind of test is probably on the horizon.

Now, all of these tests are useful, even essential, but they have a blindspot. They can only detect if a person has the virus inside them right now, not if they've been exposed and fought it off. Luckily, the antibodies a person generates to fend off a pathogen tend to stick around in their body for at least a little while afterwards, forming a kind of immune memory and helping ward off future infections.

And researchers have also been designing tests to look for those antibodies in our bodies. So, essentially, this is the reverse of the test we just talked about. Instead of using antibodies to detect the virus, these tests generally use bits of the virus to detect antibodies.

For one technique, called an ELISA, you add a patient's serum to a special plate coated in viral proteins. You also add a protein or a compound that produces some kind of signal if antibodies in the serum bind to the bits of virus. So, if you see a signal, you know that person has had COVID.

Because it takes a little bit for your body to make these kinds of antibodies, this kind of test isn't really useful for figuring out if someone has been infected. It might tell you they have the antibodies, in which case they probably have been infected but might not be currently, or they might be infected and not have the antibodies yet. But these tests can be really important for helping health authorities track chains of infection and understand how the virus is spreading.

So soon, hopefully, doctors will not only be able to quickly determine whether a patient has COVID, they'll be able to see if they had it in the past. These data will help health professionals track the pandemic and determine the most effective actions to take. So all these new tests aren't just improving on tried-and-true methods, they're helping us fight diseases faster and more efficiently.

Thanks for watching this episode of SciShow News! To find more of our coverage of the COVID-19 pandemic, you can check out the playlist in the description. Before I go, I'd like to give a special thank you to everyone who watches and supports SciShow, especially our patrons on Patreon.

We are not exaggerating when we say we couldn't make episodes like this without our patrons. So thank you to all of you who are members of that wonderful community. And if you want to learn more about joining that awesome group of people, you can head over to Patreon.com/SciShow. [♪ OUTRO].