"Science" & Facts

On to part two of this series, but first, a reminder of what has come to pass in the past few days - America has moved to sever all ties with the WHO (projected back in February), and China's foreign minister has openly declared that "[they were on the brink of] Cold War [Two]" (as no-duh-ed last October); honestly, that brought back memories of how the WHO was warning about tottering on the brink of a pandemic for weeks, as the obvious unfolded around them. The geopolitics of our brave new era will be deferred to a later post, but here's hoping all readers have made their preparations. Or in Mandarin, 武汉肺炎, 尚可挽回; 反应迟钝, 无可救药 [N.B. Notably, the Chinese-language Wikipedia article on the coronavirus currently states its origin as unknown, while the English-language version states that the first outbreak was in China, with the index case in Wuhan; we'll return to this later.]

With the understanding that all of the following is said in my personal capacity, today's subject is on how science, facts and authority - at least what's being propagated by your favourite establishment media outlets and social influencers - may not be all it's cracked up to be. Take for a start face masks, discussed in the previous post and back in Feb: the non-necessity and uselessness of masks had been drilled into the public consciousness by various medical experts for a couple of months, while chaps who figured that, wait, one of the main lessons from SARS 1 in 2003 was that face masks made for some of the best protection against it, so why wouldn't it help with SARS-CoV-2, were deried as conspiracy theorists.

Be smart; get involved only with the *right kind of* model;
good-looking, firm, shapely, well-vetted, that kind

So, this sage advice turned out to be probably unwise (and likely motivated by logistical rather than scientific concerns), and as such, can the experts up there really blame the public (including mainstream media employees, so it seems) for not trusting them quite as much? One can imagine a regular Joe scratching his chin and reasonably figuring that, if these over-credentialed know-it-alls couldn't even get their policy recommendations on something as self-evident as face masks straight, should we really just go with them injecting dubious fluids into our bodies? Again, I support the concept of vaccination in general, and can understand why physicians are oft loathe to own up to mistakes (crippling liability), or simply admitting to not knowing (bedside manner expectations); it just doesn't change the reality, or hide the consequences.

Back on other models, another common suspicion that, eh, shouldn't closing borders and barring international travel (especially from the virus' source country) as early as possible save plenty of pain, would be dismissed out of hand by the WHO... only for researchers to come back this month saying, gee, it seems that preventing people flying from places where the virus is likely widespread to places where it's not yet prevalent does help to slow or even stop the spread, whaddya know? Now, I can kinda sympathize with the WHO here since dictating billions worth of international travel might be a little over their pay grade, but the record of their chief on covering up previous epidemics frankly doesn't inspire confidence.


The Bee hits it out of the park again
(Source: babylonbee.com)

Next, on to the wonders of hydroxychloroquine (HCQ), previously raised in April. Now, if you're dependant on the establishment FAKE NEWS for your news fix, or allow Reddit/Facebook etc. free rein to curate your views for you, the latest big update would probably be something like "Hydroxychloroquine: WHO suspends clinical trial of drug touted by TRUMP as 'coronavirus cure' over safety fears". The corresponding discussion threads were moreover all but bursting with unbridled joy at Orange Man being proven wrong. There was something unsettling about the whole spectacle - even in war, one treats life-threatening conditions of enemy combatants (though I would understand if, say, torturers were bumped to the back of the line); here, you had a bunch of Internet strangers celebrating there being no cure.

Further, it's one thing if the hope for HCQ had been scientifically unsubstantiated, or an outright gaffe (e.g. as with disinfectant, or UV light, which seems actually under heavy development); consider that GEOTUS clearly hadn't come up with the HCQ suggestion by himself, because none of his many doctorates are in medicine. This would appear to imply that HCQ had been put forward by medically-qualified personnel as a plausible treatment, and the motivation indeed seems supported by HCQ's mechanism of action on ACE2 receptors, the effect of which has been observed in vitro, including in chloroquine form for the original SARS in 2005. This was sufficient for the early French studies that sparked initial interest, which was followed by happy news on HCQ from Italy, Spain, Turkey, South Korea, Costa Rica, Brazil and India, amongst other nations. One could suppose that all of these doctors operating throughout the world are dumb, evil or irresponsible, but mayhaps it makes slightly more sense that they were legitimately convinced of HCQ's potential based on sound reasoning and empirical efficacy?

One would barely recognize this from the U.S. establishment media (including Reddit), however, as they blared studies from top journals - NEJM, JAMA and The BMJ (we're leaving The Lancet for later) - purporting that HCQ BAD, it causes additional deaths, and that TRUMP has a stake in a HCQ manufacturer (seemingly true, but less than US$3,000). Commentators who noted that, well, these all seem like retrospective studies where HCQ was probably prescribed to the sickest patients without appropriate supplementation, at which point it's a toss-up anyway and why have our top journals come to pushing non-controlled trials as gospel truth, were hardly acknowledged. Science Translational Medicine's resident pundit was no more charitable, and when the first known study on HCQ+AZ plus Zinc came in from NYU and actually suggested positive effects, the dismay was almost palpable. Thankfully for this fellow, a big Lancet paper on nearly 100,000 patients appears to have put the nail in HCQ's coffin last week - but we'll come to that.

For now, it might suffice to note that Wired's fairly-balanced summary of the HCQ situation up till the beginning of May suggested that it was too early to tell, if anything. The attraction of being able to employ HCQ is quite clear - it's been kicking around as an antimalarial since at least 1955 with millions of prescriptions annually and is thus well-understood, and is no longer under patent and thus affordable - hardly a negligible consideration for a coronavirus treatment, given the number of less-resourced countries that are under siege. Meanwhile, proprietary Big Pharma offerings are getting treated with kid gloves in the media despite demonstrating no better results, and having their own studies yanked.

Admittedly, HCQ has its drawbacks, the first being that speculation could reduce supply for existing patients, but this seems like a short-term issue. The far bigger problem is that if it actually works as a preventive prophylactic, people wouldn't die, they would be able to get back to normal life, the economy would recover, and TRUMP's re-election chances would rise (beyond him getting proven right, yet again). Can't be having that, can we? Fine, musing about slightly-odd study designs and potential conflicts of interest might be churlish, but it was still instructive to watch how Detroit Democrats censured a lawmaker simply for testifying that she had been cured with HCQ, Klobuchar having to admit that it helped save her husband (happy for both of them), and Gov. Whitmer asking the Feds for supplies, 'cause it surely don't work!

Honorable man of action that GEOTUS is, he has put himself on the line as usual, and completed a week-and-a-half course of HCQ as a protective measure (with zinc, goes without saying), in the best traditions of self-experimenting great men like Dr. Barry Marshall; by the way, his political opponents' calls for him to discontinue treatment were probably not even ethical and likely disrespectful, from how they're discounting the expertise of the White House's Physician to the President, who one suspects has the necessary data. In any case, medicos remain tiptoeing about on Reddit going "c'mon, surely some of you are using it, let's talk", while the NIH and the UK gear up to do proper clinical trials, with the latter already doing HCQ bulk purchases. Well, best of luck to them!

The Lancet Saga

And we come to the yuge Lancet publication on May 22, "Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis" by Mehra et al. - over ninety-six thousand coronavirus patients from 671 hospitals in six continents, HCQ fail. To say that this paper was influential is an understatement; within four days, the WHO halted their ongoing HCQ trials based on it, which was rapidly followed by France, Italy and Belgium, based on safety concerns raised within. Surely this must be the end of Drumpf?

And then, a funny thing happened. Just as the average r/politics Redditor was jerking himself off to what seemed to be a conclusive repudiation of HCQ, 146 scientists signed an open letter to the authors and journal, with a list of very pertinent concerns (which also makes for a nice case study following our recent post on peer-review). Points one to four relate to inadequate adjustment for confounders, lack of code/data/ethics review and even a mention of the participating countries & hospitals, which while not ideal, probably aren't that out of place. The real accusations then began, as the signatories observed that Australian data contradicted official reports (too many cases than reasonable for five hospitals and more in-hospital deaths than that for the entire country in that period), unlikely sophistication for African data, oddly small variances across continents and overly-high HCQ doses, implausible chloroquine/HCQ ratios, and seemingly-impossible confidence intervals (as advertised in the previous post on reviewing!)

Now, unless somebody took the trouble to do a heck a lot of fabrication, there are some pretty big names behind this letter - fellows from Oxford, ICL, UCL, Harvard, UPenn, UPittsburgh, Vanderbilt, Duke, UBC, UToronto, McGill, UMelbourne, USydney, Monash, Karolinska Insitutet and a host of other well-regarded institutions, nothing to sneeze at. A Melbourne-based doctor has raised the other question no doubt on many researchers' minds, which is how did just four authors manage to complete a study of such complexity so quickly, and what exactly the heck is this Surgisphere company that supplied the data, that he's never heard of. For now, the authors have acknowledged an error in including an Asian hospital in the Australian data, but one suspects that a whole can of worms has been opened.

I will be following the developments extremely keenly, it goes without saying, but a little pertinent background may be in order. The Lancet is indisputably one of medicine's Big Four journals, and is the only one of those not owned by a medical organization. This has allowed it to earn something of a crusading, swashbuckling reputation, maintained from original founder Thomas Wakley, to reigning editor Richard Horton (note: this description is largely lifted from former BMJ editor Richard Smith's The Trouble with Medical Journals, which I have to recommend - particularly to clinican-scientists - yet again; it's an engrossing read for anybody remotely interested in the oft-salacious history of these journals. Smith goes on to state that Horton's been described as "[the kind of man] who don't mind about being kicked blue if they can only get talked about".)

Smith goes on to note that he doesn't think medicine and politics can be separated, and that "any journal that wants to influence health and medicine will have to deal with the political". I agree with that. That said, Smith wasn't exactly agreeable with The Lancet carrying nine articles on the 9/11 attacks - a tendency that doesn't seem to have moderated. Don't get me wrong, I'm hardly against a good dollop of advocacy - for instance, on the health of Palestinians - but let's just say that riding wild and free raises the chances of falling off the edge. Quite a bit of the current anti-vax movement might for one be traced back to Wakefield's infamous Lancet paper linking the MMR vaccine to autism, which was only fully retracted twelve years after initial publication, when the damage had been done. The Lancet is a pillar of the profession with a venerable past, and it would really be sad to see them on the wrong side of history again.

...they ain't winning this one, are they?
(Source: dailykos.com)

Alas, they appear to have been digging themselves deeper from the beginning of this pandemic, at least from a mid-February letter condemning "conspiracy theories suggesting that COVID-19 does not have a natural origin". Of course, critical thinkers immediately seized on the straw-man, which was that the prevailing theory was that the virus had escaped from the lab, after being naturally transmitted (either in the wild, or in the lab). Sure as clockwork, studies have suggested that the virus didn't come from the wet market, a WHO advisor has admitted that a leak was likely, U.S. intelligence is looking deeply into the possibility, the virus seems strangely well-adapted to infect humans from the get-go, early evidence was destroyed (whoops), and China is now open to an independent investigation, which seems to at least imply the possibility. Most importantly, the fact was that there was no way The Lancet could plausibly have ruled out a lab leak, given all the circumstantial hints. It might have been fair attempt at politics; it definitely wasn't good science.

But like I said, they were digging themselves in more deeply, and followed up in mid-May by posting an unsigned editorial (no prizes guessing who it's from, though) in support of the US Centers for Disease Control and Prevention (CDC), and urging Americans not to re-elect TRUMP. Now, this looks like very brassy interference in foreign politics, but in their defence, they were fresh from taking their own United Kingdom and then Brazil on. To this, an informed Redditor noted that the CDC's budget had actually tripled after an emergency supplemental package in early March, and got -41 karma at last count for his pains. Guy who pointed out that the CDC's homegrown test kit screwed up, America's situation is actually kind of unremarkable compared to other developed countries, and The Lancet's editorial wasn't helping anyone, received -192 karma.

The Donald's incomparable troll senses must have activated at that, and two days later, the GOD-EMPEROR would tweet his own open letter to the WHO, that included prominently on the first page that "The World Health Organization consistently ignored credible reports of the virus spreading in Wuhan in early December 2019 or even earlier, including reports from the Lancet medical journal." Obviously, GEOTUS didn't have to mention The Lancet by name here, and there were any number of other journals he could have referenced, but one supposes he knows exactly what he's doing. Horton pounced instantly, loudly counter-tweeting "Dear President Trump - You cite The Lancet in your attack on WHO. Please let me correct the record. The Lancet did not publish any report in early December, 2019, about a virus spreading in Wuhan. The first reports we published were from Chinese scientists on Jan 24, 2020". A native speaker of English would duly remark that TRUMP is ackchyually entirely correct, because "of the virus spreading in Wuhan in early December 2019 or even earlier" is the relevant clause here, and the actual Lancet report could have come out after that, i.e. in late January, as self-admitted by Horton, and which does indeed state that the virus started in December.

Professional linguists might have their say on the above, but it sure looks like HIS TRUMPNESS has managed to make the editor of one of the world's most prestigious medical journals lose his basic command of English. Is there anything at all in this world, that THE MAN can't do? As the old canard goes, who the GOD-EMPEROR wishes to destroy, he first makes mad, and from how Horton is now frantically tweeting about for support as America withdraws from his beloved WHO, he can't be far off the precipice of mental health there. I did quite appreciate his 2015 report on how medical research is unreliable at best, and fradulent at worst, which seems to follow on from Ioannidis' celebrated essay; here's to hoping he cools off after a bit.