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[THREAD: HYDROXYCHLOROQUININE]
1/24
@realDonaldTrump calls it the new magic bullet and extorts it from India. India calls it the magic bullet and pretends to be the savior of humanity. Scientists stand conflicted, laymen polarized. So what IS the matter?
1/24
@realDonaldTrump calls it the new magic bullet and extorts it from India. India calls it the magic bullet and pretends to be the savior of humanity. Scientists stand conflicted, laymen polarized. So what IS the matter?
2/24
First up, some abbreviations are in order:
- Q (quinine)
- CQ (chloroquine)
- HCQ (hydroxychloroquine)
This is important as not only it's a lot of work to type such long names repetitively but also a waste of Twitter real estate. Moving on...
First up, some abbreviations are in order:
- Q (quinine)
- CQ (chloroquine)
- HCQ (hydroxychloroquine)
This is important as not only it's a lot of work to type such long names repetitively but also a waste of Twitter real estate. Moving on...
3/24
HISTORY
It all started with quinine. The thing had been extracted off the bark of cinchona trees and used as a muscle relaxant by the Quechua tribals of the Andes for centuries until the Jesuits brought it to Europe at a time when Akbar still ruled India.
HISTORY
It all started with quinine. The thing had been extracted off the bark of cinchona trees and used as a muscle relaxant by the Quechua tribals of the Andes for centuries until the Jesuits brought it to Europe at a time when Akbar still ruled India.
4/24
By the end of the 16th century, quinine was already the standard apothecary-prescription for malaria. The world almost ran out of quinine during the second world war because malaria was rampant in the trenches. A more abundant alternative was needed pronto.
By the end of the 16th century, quinine was already the standard apothecary-prescription for malaria. The world almost ran out of quinine during the second world war because malaria was rampant in the trenches. A more abundant alternative was needed pronto.
5/24
That's when chemists from Hitler's Germany and FDR's America came up with a lab-cooked CQ. This remained mainstream for almost 2 decades before being supplanted by the less toxic HCQ. Now HCQ isn't entirely harmless either, but we'll get to that later.
That's when chemists from Hitler's Germany and FDR's America came up with a lab-cooked CQ. This remained mainstream for almost 2 decades before being supplanted by the less toxic HCQ. Now HCQ isn't entirely harmless either, but we'll get to that later.
6/24
CHEMISTRY
HCQ is a weak base (hint: the hydroxy- in HCQ is an alkaline feature). A superpower this lends the molecule is that it can easily dissolve in lipids and make its way through layers of'em. Lipids are what call membranes are made of.
CHEMISTRY
HCQ is a weak base (hint: the hydroxy- in HCQ is an alkaline feature). A superpower this lends the molecule is that it can easily dissolve in lipids and make its way through layers of'em. Lipids are what call membranes are made of.
7/24
What that means is that HCQ can seamlessly enter cells including the RBCs. And if you have malaria, this is where malarial parasites live too. Being basic, HCQ interacts with the acids inside the cell, this losing its alkalinity.
What that means is that HCQ can seamlessly enter cells including the RBCs. And if you have malaria, this is where malarial parasites live too. Being basic, HCQ interacts with the acids inside the cell, this losing its alkalinity.
8/24
When that happens, HCQ is no longer fat-soluble and can no longer pass through the lipid cell membrane thus ending up "trapped" inside the cell. This, experts believe, is how it kills malaria parasites, by inhibiting its ability to synthesize toxic molecules.
When that happens, HCQ is no longer fat-soluble and can no longer pass through the lipid cell membrane thus ending up "trapped" inside the cell. This, experts believe, is how it kills malaria parasites, by inhibiting its ability to synthesize toxic molecules.
9/24
Our cells also have something called lysosomes. Lysosome's job is to break down rogue proteins synthesized by a parasite, etc., that may hurt the cell. What comes out of this process is antigens that tell other immune cells to prepare for an invasion. This works fine.
Our cells also have something called lysosomes. Lysosome's job is to break down rogue proteins synthesized by a parasite, etc., that may hurt the cell. What comes out of this process is antigens that tell other immune cells to prepare for an invasion. This works fine.
10/24
When you have lupus, an autoimmune disease, the lysosomes produce the wrong kind of antigens that turn immune cells against your body's own cells. Basically, the body's immune system turns to itself hence the name "autoimmune." This is dead serious.
When you have lupus, an autoimmune disease, the lysosomes produce the wrong kind of antigens that turn immune cells against your body's own cells. Basically, the body's immune system turns to itself hence the name "autoimmune." This is dead serious.
11/24
But lysosomes are acidic which means HCQ can easily enter them and get stuck inside. Once the lysosome's pH goes high enough, it can't function the same as before. This means fewer antigens which means fewer immune soldiers going rogue. That's how HCQ fixes lupus.
But lysosomes are acidic which means HCQ can easily enter them and get stuck inside. Once the lysosome's pH goes high enough, it can't function the same as before. This means fewer antigens which means fewer immune soldiers going rogue. That's how HCQ fixes lupus.
12/24
COVID-19
Contrary to what you may believe, coronaviruses mostly don't kill you directly. What does is the immune response they generate. When a corona-infected cell dies, your body realized there's been an invasion. This triggers a counterattack using cytokines.
COVID-19
Contrary to what you may believe, coronaviruses mostly don't kill you directly. What does is the immune response they generate. When a corona-infected cell dies, your body realized there's been an invasion. This triggers a counterattack using cytokines.
13/24
Cytokines rally support from the body's immune system against the foreign invasion. When this happens, it's called an inflammation. Problem is, this immune response isn't very discrete and kills some healthy cells too. With limited infection, the damage isn't great.
Cytokines rally support from the body's immune system against the foreign invasion. When this happens, it's called an inflammation. Problem is, this immune response isn't very discrete and kills some healthy cells too. With limited infection, the damage isn't great.
14/24
But when the virus multiplies out of control as is the case with SARS-CoV-2, more infections lead to more cytokines being released in what's called a cytokine storm. This means more dead cells including healthy ones and, in turn, more cytokines. A positive feedback loop!
But when the virus multiplies out of control as is the case with SARS-CoV-2, more infections lead to more cytokines being released in what's called a cytokine storm. This means more dead cells including healthy ones and, in turn, more cytokines. A positive feedback loop!
15/24
It's this that ends up killing you. A collateral damage of your own immune campaign against the virus, if you will. This is where HCQ "might" come in handy. As with lupus, HCQ can help ramp down the body's immune response by taming lysosomes and prevent a cytokine storm.
It's this that ends up killing you. A collateral damage of your own immune campaign against the virus, if you will. This is where HCQ "might" come in handy. As with lupus, HCQ can help ramp down the body's immune response by taming lysosomes and prevent a cytokine storm.
16/24
This is one hypothesis. Another is that the HCQ molecules lock into the ACE2 receptors on cells that line up the lungs, windpipe, and intestines, effectively closing them for business to invading coronaviruses. These receptors are like the cell's CAPTCHA field.
This is one hypothesis. Another is that the HCQ molecules lock into the ACE2 receptors on cells that line up the lungs, windpipe, and intestines, effectively closing them for business to invading coronaviruses. These receptors are like the cell's CAPTCHA field.
17/24
There's also a third hypothesis that suggests HCQ and its anhydrous predecessor CQ could help impede coronavirus replication. This, in turn, could space things out for the the immune response and prevent a deadly cytokine storm. Each of these 3 hypotheses is promising.
There's also a third hypothesis that suggests HCQ and its anhydrous predecessor CQ could help impede coronavirus replication. This, in turn, could space things out for the the immune response and prevent a deadly cytokine storm. Each of these 3 hypotheses is promising.
18/24
Of course, all this is a ridiculously simplistic representation of all that actually goes down during a viral or bacterial invasion and every unpronounceable name I've mentioned has entire books dedicated to just explaining it. But for this conversation, it should suffice.
Of course, all this is a ridiculously simplistic representation of all that actually goes down during a viral or bacterial invasion and every unpronounceable name I've mentioned has entire books dedicated to just explaining it. But for this conversation, it should suffice.
19/24
So what's the problem? Pretty much the magic bullet Trump called it, right? Not really, at least not yet, and here's why: All these hypotheses come from "in vitro" tests. In vitro means in a petri dish. Or a test tube. Basically, not a live human body.
So what's the problem? Pretty much the magic bullet Trump called it, right? Not really, at least not yet, and here's why: All these hypotheses come from "in vitro" tests. In vitro means in a petri dish. Or a test tube. Basically, not a live human body.
20/24
Our bodies are a complex set of unpredictable variables that could greatly influence the outcome of any trial. Lab samples, in the other hand, are highly controlled environments with no unknown variables contaminating the outcome. The two are VERY different.
Our bodies are a complex set of unpredictable variables that could greatly influence the outcome of any trial. Lab samples, in the other hand, are highly controlled environments with no unknown variables contaminating the outcome. The two are VERY different.
21/24
So we need human trials, also called clinical trials. So far, one such trial has concluded in France and another in China. Both have failed to corroborate any of the anti-corona magic attributed to HCQ. https://www.sciencedirect.com/science/article/pii/S0399077X20300858?via%3Dihub
So we need human trials, also called clinical trials. So far, one such trial has concluded in France and another in China. Both have failed to corroborate any of the anti-corona magic attributed to HCQ. https://www.sciencedirect.com/science/article/pii/S0399077X20300858?via%3Dihub
22/24
That however isn't enough to dismiss the drug right away. Just that many more trials are needed before concluding anything either way. Meanwhile, remember what I said about HCQ ramping down immune system by neutralizing lysosomes? Well, that's a side-effect too.
That however isn't enough to dismiss the drug right away. Just that many more trials are needed before concluding anything either way. Meanwhile, remember what I said about HCQ ramping down immune system by neutralizing lysosomes? Well, that's a side-effect too.
23/24
There's more. In those with G6PD deficiency (a condition that causes RBCs to break down prematurely) HCQ can have life-threatening reactions. Also, it can slow the breakdown of heart medication digoxin which can lead to fatal heart rhythms if you're on that medication.
There's more. In those with G6PD deficiency (a condition that causes RBCs to break down prematurely) HCQ can have life-threatening reactions. Also, it can slow the breakdown of heart medication digoxin which can lead to fatal heart rhythms if you're on that medication.
24/24
So there you are, thing's promising but unpredictable. To change that, lives ought to be risked. What lives would you risk? Of course the cheapest ones, and where do you find those if you are @realDonaldTrump? Well, where else? https://www.telegraph.co.uk/news/2020/04/20/indian-slum-dwellers-guinea-pigs-controversial-hydroxychloroquine/
So there you are, thing's promising but unpredictable. To change that, lives ought to be risked. What lives would you risk? Of course the cheapest ones, and where do you find those if you are @realDonaldTrump? Well, where else? https://www.telegraph.co.uk/news/2020/04/20/indian-slum-dwellers-guinea-pigs-controversial-hydroxychloroquine/
