EDIT: The PCR test quote was fact checked and deemed to be misleading, but it still sounds like they are not very accurate [0].
[0]: https://www.reuters.com/article/uk-factcheck-pcr-idUSKBN2442...
The relevant quotes from Kary are:
"With PCR, if you do it well, you can find almost anything, in anybody"
"If you can amplify one single molecule up to something that you can really measure - which PCR can do - then there's just.. very few molecules that you don't have at least one single one of them in your body"
"It doesn't tell you that you're sick"
My interpretation is that Kary Mullis did believe it was at least possible to "misinterpret" the results of a PCR test. It doesn't seem such a stretch to believe that you could be sick with the flu, while also having a single molecule of a coronavirus gene present in your nasal cavity (triggering a positive coronavirus test).
Note: I know this is an inflammatory topic. The views of Kary Mullis are not necessarily my own. I am posting this here because I think it is interesting.
https://www.mcgill.ca/oss/article/technology-history/man-who...
See my other comment here for the reasons why I believe almost all SARS-CoV-2 PCR positives are true positives (as to whether the patient is or was very recently infected; the kernel of truth is that they don't necessarily indicate that the patient could infect others right now).
I have no stake or attachment to Kary Mullis, whether he's wrong or right is irrelevant to me. I just find it interesting that the creator of PCR, which has a lot of attention these days, had opinions that don't get a lot of attention these days. I'll give your comment a look, but am also curious if anybody else has a counter to Mullis' claims.
And yours was an argument from authority. You gave no explanation of or support for Mullis's arguments, and you gave no reason to believe his conclusion except a positive aspect of his reputation (i.e., his discovery of PCR in the first place).
In that case, negative aspects of his reputation (i.e., the fluorescent raccoon; or, closer to the domain in question, his belief on HIV and AIDS) are surely also relevant. They don't mean what he's saying is false, but they'd cause a reasonable person to approach his unsupported statements with more care.
For convenience, I'm linking my other comment below. This is a detailed explanation of why I believe almost all patients who test positive by PCR are (or were very recently) infected with SARS-CoV-2, fully referenced. It has so far received zero interaction.
https://news.ycombinator.com/item?id=26984429
If you think I'm wrong, please explain why, and I'll reply. If you think I'm right, then I'd also appreciate a reply. The belief that coronavirus cases are grossly over-diagnosed is a common element of claims that no precautions against it are necessary, which cause real harm; so I hope you don't want to falsely spread that belief.
ETA: And for completeness, here's a paper discussing the ability to culture virus from PCR-positive samples. I believe that's the real point Mullis was alluding to in his comments, that people who test PCR positive aren't necessarily shedding replication-competent virus; but that's a separate question from whether they are (or very recently were) infected.
https://academic.oup.com/cid/advance-article/doi/10.1093/cid...
I wonder if the same mistakes are being repeated.
> These tests, called “home brews,” are not commercially available, and there are no good estimates of their error rates.
So this is about clinical use of an uncharacterized test. Why is that relevant to the test for SARS-CoV-2, which has probably now been run more times than any other PCR test in history, including on large populations with extremely low test positivity (e.g., most of Australia, <0.1%), which bounds the specificity (e.g., to >99.9%)?
Seriously, engage with the evidence. There are still zero replies to my detailed explanation linked above. Did you read it? What did you think?
Nice try but your tit for tat doesn't quite work. I explicitly said I have no attachment to Mullis or his claims. I didn't make an argument myself. I was asking "the creator of PCR made this claim, what are the counter-arguments?"
Then, and now again, you gave your irrelevant ad-hominem points. I don't care if he believed in voodoo or saw pink elephants in the sky, because they're irrelevant to my question. And as I already said, Newton believed some outlandish things, yet I still believe in physics. I'm interested in what the counterpoints to his argument, not his reputation, are.
I also read your comment, and it's also not relevant to my question. You seem upset that it's gotten zero interaction, and I'm not sure what I'm supposed to do about that. But I'm not looking for info on why PCR tests are true positives, I'm looking for arguments on Mullis' claims
The comment you replied to was speculating about "false positives where flu cases get labeled as Covid". Mullis's comments are not too coherent, but I read them as a claim that PCR tests will result in false positives, and I assumed that was why you thought they were relevant. At least one other user seems to have read them the same way, since user theclap responded with a link to a different article explicitly about PCR false positives. Do you read them as something else?
Here's a quote from another reply to my original comment:
> > Kary Mullis: I think misused PCR is not quite ... I don't think you can misuse PCR. No, the results, the interpretation of it. See if you can say, if they wanted, if they could find this virus in you at all, and with PCR if you do it well you can find almost anything in anybody. It starts making you believe in the, sort of buddhist notion, that everything is contained in everything else. Right, I mean because if you can amplify one single molecule up to to something that you can really measure which PCR can do, then there's just very few molecules that you don't have at least one single one of them in your body. Okay, so that could be thought of as a misuse of it just to claim that it's meaningful. It is, there's very little of what they call HIV and what's been brought out here by Phil ... the measurement for it is not exact at all, it's not it's not as good as our measurement for things like apples. An apple is an apple. You know, you can get something that's kind of like, if you've got enough things that look kind of like an apple you stick them all together you might think it as an apple. And HIV is like that. Those tests are all based on things that are invisible, and they are the results are inferred in a sense. PCR is separate from that, it's just a process that's used to make a whole lot of something out of something that's why it's not, it doesn't tell you that you're sick and it doesn't tell you that the thing you ended up with really was going to hurt you or anything like that.
An example of what I'm looking for info on is this in particular:
> PCR is separate from that, it's just a process that's used to make a whole lot of something out of something that's why it's not, it doesn't tell you that you're sick and it doesn't tell you that the thing you ended up with really was going to hurt you or anything like that.
I don't have an opinion myself and I'm just looking for someone informed to comment on how today's use of PCR for diagnosing covid aligns with the inventor of PCR's comments that it isn't useful for diagnosing illness. Not whether or not today's covid tests are false or true positives
> It can be observed that at Ct = 25, up to 70% of patients remain positive in culture and that at Ct = 30 this value drops to 20%. At Ct = 35, the value we used to report a positive result for PCR, <3% of cultures are positive.
https://academic.oup.com/cid/advance-article/doi/10.1093/cid...
So it's absolutely true that some of the people who test positive by PCR would never have infected anyone else, and there was no need for them to isolate. But it's hard to distinguish who--the viral culture takes too much time to run for each patient, and no one really knows how sensitive that is anyways. So to be conservative, they just advise everyone to isolate.
People have talked about advising isolation only if Ct is less than some lower cutoff, since there's a clear correlation between Ct and positivity in culture. But since a patient early in the infection might have high Ct now but lower Ct later, public health authorities haven't done so.
The second way that PCR tests are being used is to diagnose the cause of illness--a patient comes in sick, and the doctor is trying to find the cause. At this point, we already know that the patient is sick, because they're coughing, complaining that they feel terrible, etc. The PCR test isn't what tells us that they're sick, but rather what tells us that the cause of their sickness is SARS-CoV-2. The alternative hypothesis is that people are dying of some different disease, and by coincidence the excess mortality due to that different disease correlates strongly with SARS-CoV-2 test positivity (which e.g. is why that's high in the USA, and low in Australia; you can also see the correlation within a single region if you look at the time series). That would be a pretty strange coincidence, and no one has proposed any mechanism for that.
So do the above clinical uses seem reasonable to you? Or is there some other clinical use that seems unreasonable to you in light of Mullis's comments?
Perhaps this confusion comes from the definition of "illness" or "sick". In a certain sense, if I don't feel sick, then no test can tell me otherwise. For example, was Typhoid Mary "sick"? Is an HIV patient with no symptoms? Kary Mullis says no:
> A man with gray hair and a goatee raises his hand. He says he's been HIV-positive since 1984, that he took the anti-AIDS drug AZT for a couple years but stopped. Now, he says, his T-cell count -- the number of a kind of white blood cell that is killed by HIV -- has gone way down.
> Mullis interrupts him: "Change doctors!"
> The man continues. His T-cell count is down to 150, which is usually thought of as dangerously low. He asks Mullis for advice.
> "I would say there is no evidence that I can find in the scientific literature that you should worry about HIV or your T-cell count," Mullis tells him. "If you'd stop worrying, maybe you'll be all right. You look pretty healthy to me."
https://www.washingtonpost.com/archive/lifestyle/1998/11/03/...
Do you think he gave that patient good advice?
- On HIV and PCR: https://www.youtube.com/watch?v=V__Zx0qS7uI&t=101s - On Fauci and PCR: https://www.youtube.com/watch?v=5aISPlTLbJo
> Reporter: .... misuse PCR to estimate all these so supposedly free viral RNAs that may or may not be there?
> Kary Mullis: I think misused PCR is not quite ... I don't think you can misuse PCR. No, the results, the interpretation of it. See if you can say, if they wanted, if they could find this virus in you at all, and with PCR if you do it well you can find almost anything in anybody. It starts making you believe in the, sort of buddhist notion, that everything is contained in everything else. Right, I mean because if you can amplify one single molecule up to to something that you can really measure which PCR can do, then there's just very few molecules that you don't have at least one single one of them in your body. Okay, so that could be thought of as a misuse of it just to claim that it's meaningful. It is, there's very little of what they call HIV and what's been brought out here by Phil ... the measurement for it is not exact at all, it's not it's not as good as our measurement for things like apples. An apple is an apple. You know, you can get something that's kind of like, if you've got enough things that look kind of like an apple you stick them all together you might think it as an apple. And HIV is like that. Those tests are all based on things that are invisible, and they are the results are inferred in a sense. PCR is separate from that, it's just a process that's used to make a whole lot of something out of something that's why it's not, it doesn't tell you that you're sick and it doesn't tell you that the thing you ended up with really was going to hurt you or anything like that.
Some people may also be worried that they do have covid (or will get a false positive), and don't want to get a positive test due to quarantine requirements, embarrassment, etc.
The flu didn't happen here either according to the long standing sentinel testing program.
https://www.folkhalsomyndigheten.se/folkhalsorapportering-st... (Swedish, published today)
Summary: 145k people were tested (1.4% of the total population), 29 people tested positive for an influenza variant during the winter season 2020/2021. Typical numbers for previous years are in the thousands.
Graph comparing winter seasons: https://www.folkhalsomyndigheten.se/contentassets/a9433fcecd...
(X-axis: week number, Y-axis: number of cases.)
https://www.cbc.ca/news/canada/edmonton/alberta-nears-end-of...
On the other hand PCR test are not inaccurate at all, at least regarding false positives. There are detailed articles and even Youtube videos on the process and if you take a look, you will understand why it's quite accurate.
In essence, they create a reaction that will mass produce specific parts of the virus gene until it's detectable with a sensor. They run the reaction multiple times and then the sensor looks for luminance if I recall correctly.
Because you can't accidentally produce Covid-19 genes, the tests are very accurate. However, you might not get enough virus material when taking the sample from the patient(which can fail your reaction or you might need more cycles than usual to create a detectable amount) or it could be the case that there's a mutation in the gene that you are attempting to multiply, therefore you can get a negative test for an infected person.
https://www.thelancet.com/journals/lanres/article/PIIS2213-2...
between 0.8% and 4% false positive rate according to that, making them completely unsuitable for mass testing. On top of that BBC's panorama did a program pointing out the sloppy standards at centers where the tests are processed.
I'm not being snarky, I simply want to outline the alternatives I'm aware of.
I respect the accuracy of the PCR, it can literally tell us why people in India are dying off on the streets right now in thousands and we even cannot see the assailant through optical magnification. It can also tell us that it's the same thing that caused the exact same situation in NY and Italy.
It's amazing, much more intriguing than any other explanation that I came across.
* This rate could translate into a significant proportion of false-positive results daily due to the current low prevalence of the virus in the UK population, adversely affecting the positive predictive value of the test.2 Considering that the UK National Health Service employs 1·1 million health-care workers, many of whom have been exposed to COVID-19 at the peak of the first wave, the potential disruption to health and social services due to false positives could be considerable.*
On the other hand, it's a pretty good accuracy when you have a hospital full of sick people. Sure, you may end up recommending 14 days of staying at home every now and then when it's not necessary.
See, the PCR test is just one of the clues that is used to diagnose people. Negative test with clearly Covid-19 symptoms and medical image of the lungs showing spots gets you a bed and treatment in the hospital. Positive test and no symptoms gets you stay at home and wear a mask recommendation.
https://www.alberta.ca/stats/covid-19-alberta-statistics.htm...
PCR tests work by selectively amplifying DNA. Each PCR test cycle approximately doubles the amount of the selected DNA. (for SARS-CoV-2, an RNA virus, the RNA is first converted to DNA)
Since each cycle approximately doubles the amount of selected DNA present, PCR tests can be extraordinarily sensitive if enough cycles are used. In theory, just a single fragment of RNA could result in a positive test. As Health Canada says:
"There are numerous studies that demonstrate prolonged detection of SARS-CoV-2 RNA that extends beyond the resolution of COVID-19 symptoms and can persist for several weeks or months." https://www.canada.ca/en/public-health/services/diseases/201...
Hospitals are testing pretty much everyone who comes in the door for COVID-19. The fact that people can test positive long after they were actually infected should obviously raise questions about the accuracy of our statistics with regard to COVID-19 hospitalization and death rates.
Additionally, contamination is a potential problem. For example, the BBC's undercover reporting found significant cross-contamination between samples at one testing lab: https://www.bbc.com/news/uk-56556806
Contamination could be showing up as a multiplier on true positives: as positive % increases, opportunities for contamination also increase. Since PCR tests work by replicating DNA, they also have the unusual property that the testing process itself creates large quantities of potential contamination. Good lab practice will eliminate that problem. But that's hard to guarantee when testing volume is increased enormously in a short period of time.
Thankfully we don't have to stop with a PCR test.
The fraud is not in the test itself, but in the reporting of test results. When a PCR test comes back positive, more often than not it is assumed the patient is infected with COVID (which may not be the case) - and cases of infected people are reported widely using these PCR test results.
What other method would you suggest in replacement to verify if a person is possibly infectious?
https://covidlive.com.au/report/positive-test-rate
A Lancet article cited below references a paper that estimates much worse specificity of PCR tests for SARS-CoV-2 based on the specificity of tests for other RNA viruses (original SARS, MERS, influenza, etc.):
https://www.medrxiv.org/content/10.1101/2020.04.26.20080911v...
But why would anyone do that, when we have direct experience with the actual test for the actual virus?
Of course the false positive rate in heavily-affected areas may be higher, due to sample contamination--with more true positive patients, there's more opportunity for one true-positive patient to contaminate multiple samples. But such cross-contamination can occur frequently only if there are actually lots of true positive patients.
For another sanity check, the sensitivity of antibody tests is established on a sample of patients who tested positive by PCR, who are assumed to all be true-positive. So any PCR false-positive among those patients will show up as an antibody false-negative, so that bounds the apparent sensitivity of those antibody tests. But antibody tests show sensitivity around 85%:
https://journals.plos.org/plosone/article?id=10.1371/journal...
So even if the antibody tests were perfect, at most 15% of their positive sample was false-positive. (Note that this is a different quantity from the PCR specificity, and can't be translated into such without knowing the true prevalence in the population that the sample was drawn from.) Of course the antibody tests also aren't perfect, and I'd guess that 15% is almost entirely antibody false-negatives rather than PCR false-positives.
You can also compare reported COVID deaths (which are generally established by PCR) with year-over-year excess mortality. The agreement isn't perfect, but it's pretty close.
The vast majority of patients who test positive by PCR are or were infected by the virus. That's a different question from whether a positive test indicates the presence of replication-competent virus (i.e., whether the patient could infect others right now), since RNA from dead virus can trigger the positive too; but that dead virus had to come from somewhere.
I'm also struggling to understand how symptom overlap would lead differences in the number of confirmed cases with PCR tests. These aren't cases confirmed by doctors talking to you and running through a checklist, these are tests that with a great degree of accuracy confirm if you have flu or covid in your system
Maybe corona virus is an enabler of some other disease, like a particularly virulent flu or some other respiratory infection.
This questions are inconvenient, so they'll go unasked by the media, let alone answered.
Literally an infinite number of questions go unasked by the media. Often because they're a pointless waste of time.
I'd say if leading virologists around the world looked at it in a lab and agree it's not some mystery illness, most media will go with that. At least the reputable ones not fishing for cheap attention from paranoid conspiracy theorists.
> At least the reputable ones not fishing for cheap attention from paranoid conspiracy theorists.
We're not talking about paranoid conspiracy theories here, we're talking about the inexplicable disappearance of influenza globally, when it should have the same transmission characteristics as corona virus. Corona might spread more rapidly, but it should spread in the same manner.
It's entirely possible that the bulk of people with symptoms actually have a concurrent infection (eg, the flu). We already know the vast, vast majority of deaths have a 'comorbidity.'
That's just like not true. Different diseases spread differently. It seems like covid will spread better through smaller droplets for example. And even if it were you just said that covid spreads easier. Disease transmission isn't linear so if interventions were enough to dip Flu's reproduction rate below 1 we'd see more or less what we've seen. Very little spread. Even if we ignore all of that and pretend you're right and really this year of horror has just been Flu cases, the health care system almost collapse in Italy, NYC, LA, and now India is still a huge deal. Hugely more people are dying this year than do in an average year. People died, literally dies in all of these places because they weren't able to get into a hospital. I don't care if it was actually covid (it was) or not killing them
This I can agree with. But our way of dealing with the problem hasn't solved that going forward whatsoever. Are we going to ignore the fact that NYC has been shutting down hospitals for decades[1]?
> Hugely more people are dying this year than do in an average year.
Not according to the numbers I've seen.
> People died, literally dies in all of these places because they weren't able to get into a hospital.
What are the death rates for people in hospitals compared to people dying with covid outside of hospitals? What interventions are hospitals providing to most patients that are conclusively saving their lives? At first, it was ventilators, but that has quietly become not recommend for most patients.
I happen to be close friends with someone that worked on the covid floor in a major regional hospital. Most people in the hospital were being treated for pneumonia, some of them were on supplemental oxygen. The hospital was never overrun, only a small portion was dedicated as a covid wing.
My friend never contracted covid, nor did anyone else they worked with.
1: https://indypendent.org/2014/04/nycs-vanishing-hospitals/
The second just seems wrong. Like it could have been true a year ago, but it really would be known by now and there really isn't any reason it would be inconvenient for any sort of narrative. Diseases that weaken your immune system enough for some other disease to be killing loads of people are still worrying and big deals. We would still be calling for lock downs regardless of if covid is directly or indirectly causing extra deaths
Why are some people to be weakened and not others? Maybe that's what we should be investigating.
https://www.cdc.gov/flu/weekly/index.htm
It says right on the page that Covid makes the data difficult to interpret, the thing I'm pointing to is the 900,000 samples tested.
Between the flu and covid, case reporting numbers are wildly unreliable.
One might ask, what incentives are there to over report a given illness at any given time?
It allows the government to create fear and panic and pass broad sweeping bills with huge budgets. All in the name of "Covid Relief" etc.