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Tuesday 20 July 2021

Testing Times

 So Piers Corbyn has irrefutable evidence that PCR tests don't work.

It's known where this idiocy comes from, because he's been spouting this bullshit everywhere, so let's deal with it properly.

PCR or, to give it it's full name, polymerase chain reaction, is a process for rapid replication of DNA. It's the basis for the vast majority of DNA or RNA based work in biochemistry. 

The basic process is fairly straightforward, if a little complicated in execution. Here's the short version:

We start with a buffer. You can think of the buffer as your cauldron of water. This is witchcraft, after all. 

Into the buffer we throw some ingredients. Some polymerase, an enzyme that promotes the building of polymers - long molecular chains, a nice little soup of nucleobases - the basic constituents of DNA, the DNA sample we want to look at, and some primers. 

The primers are the key. They're essentially the map of the target. In Dambusters talk, they're hawhehawhawhehawwhahwwwhahw or, once the radio muzzle is removed*, which bit of DNA we're looking for.

It's like a photocopier, quite literally. It looks at what's there and, if it finds the target indicated by the primer, it amplifies it by making a shitload of copies via repeated heating and cooling, driving rapid replication. In principle, really simple.

For RNA, there's a conversion process known as reverse transcription, governed by an enzyme called, funnily enough, reverse transcriptase (biologists love their little jokes). This process converts RNA into a complementary DNA strand for analysis (the major difference between RNA and DNA is a single nucleobase. In DNA, the bases are adenine, cytosine, guanine, and thymine, hence A, C,G,T (for anybody who's seen the movie Gattaca). In RNA, uracil sits in thymine's purported 'spot' (down, Sheldon).

There's a video doing the rounds and being shared of a talk given by Kary Mullis, who won the Nobel Prize for the invention of the PCR. Just to make sure I don't get accused of misrepresenting, here's the video.

So, first things first; at no point does Mullis say that PCR can't be used to test for a virus. It's important to note context here. Mullis was speaking at a gathering of sceptics of the notion that HIV causes AIDS. I've done some digging into Mullis' history in this, and I can only say that his initial questions were well-motivated, from a scientific perspective. He'd been commissioned to do some work in designing tests for HIV, and was required to cite primary literature in his writings. He was unable to find a robust link in the literature at the time.

It's not clear to me whether he ever changed his position on this, but it isn't enormously important for our purpose here. What's important is the context of what he said.

The key phrases, then:

PCR can't tell you if you're sick.

No, it can't. It's a process. It looks for something specific and, if it's there, it replicates it so that it's detectable. 

You don't need to test for HIV... it's a pretty rare virus... if you have it, there's a good chance you have a lot of other ones... to test for that one and say that one has any special meaning is what I think is the problem.

I've condensed a bit here, but I think I've retained the essence. What he's saying here is that the PCR test does not, in and of itself, make the connection between HIV - the virus, and AIDS - the syndrome. It also does not, by the same logic, tell you that SARS-CoV-2 - the virus, causes COVID19 - the syndrome.

What it does do, unequivocally and quantitatively, by the man's own words, is tell you whether the HIV virus is there, or whether the SARS-CoV-2 virus is there. If the connection between one and the other is established (yes, in both cases, unambiguously), PCR can tell you whether you have it.

Mullis is absolutely correct in everything he says here. Unfortunately for Piers, and not for the first time, he isn't in agreement with the idiots.

So, the only conclusion that can be drawn by dragging Mullis into this discussion is that a PCR can't tell you whether SARS-CoV-2 causes COViD-19. Whoopie doo. We've already established that connection beyond doubt.

In fact, PCR tests are extremely reliable. What little unreliability they do have comes mostly from handling, as contaminants are a serious problem for a system that sends replication of DNA into overdrive, which renders them prone to false positives.

By comparison, lateral flow tests are considerably more prone to false negatives. I would hope I don't have to explain why a false positive is better than a false negative.

And for the record, it wouldn't matter in the slightest whether Kary Mullis thought that PCR couldn't be used to test for a virus. It's a simple principle of the process involved that this is possible.  

*Showing my age.

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