"blue benzoquinone has the capacity to act against the bacteria that cause tuberculosis, while the red one is effective against Staphylococcus aureus."
How quaint! Blue colorless molecule is different from the red colorless molecule!
Maybe I shouldn't. But then I have to deep-dive into yet another flagrant cheap hallucination. You see, when a molecule oxidize, it becomes a different molecule.
It is impossible for a benzoquinone to oxidize, yet remain a benzoquinone. There are just two of them [1], and the two are isomers [2]. Transforming one into another would be isomerisation, not oxidation.
Not to mention that "oxidize on contact with air" is such a pile of nonsense. Just look at those molecules - benzene ring with a couple of oxygens sticking from it [1] - that stuff is pretty darn stable.
If you’ve ever wondered why the symbol of health is a snake spiraling a staff (the Greek god Asclepius’s staff to be specific), it’s because in Ancient Greece they used small amounts of snake venom to treat serious illnesses
I always assumed what I felt was obvious: Numbers 21:4-9, where God instructs Moses to make a bronze serpent and place it on a pole to heal Israelites dying from poisonous snake bites.
I was taught that the symbol came from Egypt, specifically a reference to standard guinea worm treatment whereby the worm was extracted from under the skin by winding it around a stick.
There’s also electroacupuncture, which is gaining popularity in physical therapy clinics in the US.
> Like traditional acupuncture, electroacupuncture uses needles placed in the same spots. Then, a small electrode is attached to the needles. A small amount of electricity runs through the electrode and gives a slight vibration or soft hum during treatment. (1)
Since they use the same spots as traditional acupuncture even now, I would think traditional acupuncture does work to some degree.
I read a paper that basically said that the spot itself didn't matter so much, that part was voodoo, but the needling produced a response from your body that helped.
I did a course of dry needling for tendon inflammation. It's basically just poking tendons with needles. It's an accepted treatment and it works, but the spots don't matter at all (as long as they are in the same area).
It's just relying on poking stuff with needles to improve the blood flow.
They also did an episode about rapamycin that I thought was really cool. I had no idea the history of it and found it fascinating and it really gets the imagination going thinking about what other things are hidden all around us.
That article doesn’t explain why acupuncture works, just gives a hint of a possible mechanism. It also doesn’t contain any evidence that acupuncture works at all (other than as a placebo).
"Researchers have developed", yeah. When I read such things, I always recall https://en.wikipedia.org/wiki/Epimerox - this thing promised wonders - very broad spectrum, very low toxicity - and, most importantly, it was targeting a conservative essential protein - so nearly zero resistance. And there were no updates for more than a decade.
Something developed in a lab is something we, most likely, will never see - and will never know why the thing didn't reach the 2nd stage (or the 1st).
Is this particular drug head and shoulders above other candidates? Is it possible that the reason it hasn't gotten attention is because researchers have been looking at other cheaper or more promising candidates? (I do not know, I am genuinely asking.)
I agree... Medication Resistant bacteria is a problem everywhere. There's probably no money in a new antibiotic, but... Having something new to fight TB would be nice, and there's still prestige, even if you "just" brought it to market and didn't discover it.
I would think there are pharma teams in China or India, maybe even Russia that could replicate and further develop something like this, given the initial paper and PR.
My immediate thought - there probably are these teams overseas doing these things - just, our media/markets shun them.
I mean, the covid vaccinations - people are/were doing their nut about the Euro/US versions, but the Russians had their own, the Chinese had two, and I am aware that the Chinese were handing it out to other countries as part of their aid programs (the effectiveness of those vaccines, however, has been questioned, especially in comparison to the Euro/US ones, but I'm not sure if that's reality or politics, it's so damned hard to tell these days)
The reality is that 95+% of drug candidates fail the trials. And a lot of them only fail during the Phase-3 where the efficacy is tested. It's likely that large companies tried it in-house and found that it's either too toxic or is ineffective in-vivo.
Looks like there are none, which is the typical result. If you worked in a drug-discovery-adjacent field, this is an utterly normal scenario:
1. University/startup company finds a promising drug candidate that works in-vitro. They make a press-release, researchers write their theses, and move on.
2. Drug companies pick that up and run small-scale tests. These tests are negative, usually because of unexpected toxicity.
Looking at the molecule in question, it's likely what happened here. It's a covalent inhibitor, meaning that it permanently binds with the protein. It's also allosteric, meaning that it binds to the target enzyme but not at the actual active site. This is a huge red flag for toxicity, because it's likely going to bind to other proteins that can have similar configurations.
3. But the underlying idea is sound, so companies keep working on alternative approaches. They are likely looking for non-covalent compounds now, or for things like "suicide inhibitors".
4. You'll see actual trials in 10-15 years after the initial press-release. Most likely for completely different compounds, targeting the same mechanism.
There was what I thought was a breakthrough in Schizophrenia diagnosis and treatment - the University of Washington held that groups of genes acting in concert were causing the disease, and, in fact, there were multiple variants of genes producing (what had always been suspected) different diseases that were bing lumped together.
For the longest time I had bee trying to figure out why nobody was taking the research seriously, why there weren't diagnostic kits available that determined which variant people were actually suffereing from, and using the appropriate drug regime to manage the specific condition the patient had.
Then, last year I saw a paper being discussed (some 5 - 10 years after the initial paper), and it was building on the Washington research - it appears to me now (keeping in mind that I am a layman and an outsider) that the research /had/ been taken seriously, but it's seen as a signpost on the pathway rather than the destination.
It was pretty common for message board users to come together to do group buys for novel research chemical synthesis 15-20 years ago. Not sure why things like this would be any different.
This is because a broad spectrum antibiotic with low resistance is an essential public good that will likely rapidly be made generic by either legal action or international disregard for copyright law. So no major pharma companies will want to invest resources into the development of something like this, and governments are not under the gun enough to produce new abx to invest the billions needed to get it through the approval process. The compromise is to leave it sitting at this phase until some disaster creates enough public incentive to socialize the completion of its development.
It depends - if someone uses the same compound but provably for a different indication (like maybe anti-periodontic diseases or something) or for a different intake mechanism, they could get another patent and proceed with trials.
Granted, it's not going to be easy because the original patent has expired so it's going to be very easy for an upstart Indian company to conduct basic clinical trials, use part of the data of the second patent's holder to prove equivalency (they did this test so we don't need to do this test), and then get approved through an accelerated pathway in the FDA. Which is why even well-capitalized players will shy away from what could be a cash cow.
Anti-periodontic diseases are highly irrelevant compared to cavities. Not even the original cavity application did manage to get enough funding at the time. So there will be no Indian upstart, there is and likely will be nobody who invests the money into ultra expensive trials. The ship has sailed.
I am addicted to hot peppers. What I do in the morning is get one Scotch Bonnet (or two smaller ones), two oranges, lime and a piece of ginger into a cold press and then drink it in one go.
Can't describe it exactly, but it's like being transported to another dimension for a few seconds, then there is pain, then there is relief and then a nice warm feeling in the belly.
The last time I bit into a nice juicy spicy pepper in the morning, I had to crouch in pain for 5 minutes as I felt stabbed right in the heart. The pepper wasn't even spicy like a bonnet, but I had an empty stomach.
I don't generally love super spicy food (the most I do like 95% of the time is the Taco Bell Fire Sauce), but every now and than I want something really spicy.
I'm not sure why this is the case, but I'll go to a place with some Habanero sauce and get that on a meal. It will hurt (and my time in the bathroom the next day might be a little unpleasant), but it satisfies the urge.
I know if my Mexican wife is angry depending on how hot is the food and the sauces that she makes. I have also learned that very hot sauces can damage your nails as you scratch the walls the next day.
I too am addicted to hot peppers. But doesn't this... IDK, it seems like it would mess up my stomach or esophagus lining or something. All that acid and capsaicin on an empty stomach?
I would be worried about long term damage. In 10 years you might be in a world of hurt from this. At the very least I would let your doctor know that you are doing this and see what they think of it.
I have struggled with various infections over the last 15 years. One of them, among the worst being h-pylori. Of all these infections, I've been forced, due to absence of healthcare and aversion to the medical industry in general, to treat myself across the board.
H Pylori is a very interesting subject, deeply misunderstood until a certain Australian hero brute forced through the arrogance of the day by infecting himself to prove ulcers weren't the product of psychosomatics.
Ending the rant there, I discovered through research that capsaicin (only one of the virtues of peppers) has a manifold effect upon various bacteria, notably pylori. Aside from encouraging the pylori to swim away from the capsaicin, it disrupts their biofilm behavior, and empirically, can drastically help with ulcers counter to expected problems with its spicy nature.
Adjacently, it can also encourage mucosal stimulation and protection.
I've found, co administered with mastic, oregano, NAC, and a few things presently inaccessible to the ol' cabbage.... Ahh, that's one... Cabbage juice! -- the infection can be reduced to sustainable levels without conventional antibiotics. Modern research is suggesting that h pylori, partly due to its ubiquity (50% of population +) and the ravages of antibiotics, it may be best to simply reduce it to manageable levels where the immune system and general well being keep it controlled.
There is also the wonder of fermented chilies which is good for many things, includes probiotics, improves most meals and really irritates assholes, which is righteous.
Hats off, not only were they able to isolate just two molecules, but also established that they were colorless.
I don't think this is a usual definition for benzoquinones:
"heterocyclic compounds that do not contain amino acids".
I can smell Sam Altman's socks reading this article.
...and then dozen of words further on:
"blue benzoquinone has the capacity to act against the bacteria that cause tuberculosis, while the red one is effective against Staphylococcus aureus."
How quaint! Blue colorless molecule is different from the red colorless molecule!
> These molecules have a particular property: When they come into contact with air, they oxidize and change color. One becomes blue and the other red.
Maybe I shouldn't. But then I have to deep-dive into yet another flagrant cheap hallucination. You see, when a molecule oxidize, it becomes a different molecule.
It is impossible for a benzoquinone to oxidize, yet remain a benzoquinone. There are just two of them [1], and the two are isomers [2]. Transforming one into another would be isomerisation, not oxidation.
Not to mention that "oxidize on contact with air" is such a pile of nonsense. Just look at those molecules - benzene ring with a couple of oxygens sticking from it [1] - that stuff is pretty darn stable.
[1] https://en.wikipedia.org/wiki/Benzoquinone
[2] https://en.wikipedia.org/wiki/Isomer
We’ve come full circle
https://en.wikipedia.org/wiki/Dracunculiasis
> Like traditional acupuncture, electroacupuncture uses needles placed in the same spots. Then, a small electrode is attached to the needles. A small amount of electricity runs through the electrode and gives a slight vibration or soft hum during treatment. (1)
Since they use the same spots as traditional acupuncture even now, I would think traditional acupuncture does work to some degree.
(1) https://www.webmd.com/pain-management/cbd-cbn-what-is-differ...
It's just relying on poking stuff with needles to improve the blood flow.
https://news.ycombinator.com/item?id=48095536
https://radiolab.org/podcast/interstitium
They also did an episode about rapamycin that I thought was really cool. I had no idea the history of it and found it fascinating and it really gets the imagination going thinking about what other things are hidden all around us.
https://radiolab.org/podcast/dirty-drug-and-ice-cream-tub
Something developed in a lab is something we, most likely, will never see - and will never know why the thing didn't reach the 2nd stage (or the 1st).
One thing bugs me though - why don't other countries with different research structures pick this up and run with it?
I would think there are pharma teams in China or India, maybe even Russia that could replicate and further develop something like this, given the initial paper and PR.
I mean, the covid vaccinations - people are/were doing their nut about the Euro/US versions, but the Russians had their own, the Chinese had two, and I am aware that the Chinese were handing it out to other countries as part of their aid programs (the effectiveness of those vaccines, however, has been questioned, especially in comparison to the Euro/US ones, but I'm not sure if that's reality or politics, it's so damned hard to tell these days)
Oh yeah, "corporations", "end-stage capitalism", blah blah.
The reality is that 95+% of drug candidates fail the trials. And a lot of them only fail during the Phase-3 where the efficacy is tested. It's likely that large companies tried it in-house and found that it's either too toxic or is ineffective in-vivo.
1. University/startup company finds a promising drug candidate that works in-vitro. They make a press-release, researchers write their theses, and move on.
2. Drug companies pick that up and run small-scale tests. These tests are negative, usually because of unexpected toxicity.
Looking at the molecule in question, it's likely what happened here. It's a covalent inhibitor, meaning that it permanently binds with the protein. It's also allosteric, meaning that it binds to the target enzyme but not at the actual active site. This is a huge red flag for toxicity, because it's likely going to bind to other proteins that can have similar configurations.
3. But the underlying idea is sound, so companies keep working on alternative approaches. They are likely looking for non-covalent compounds now, or for things like "suicide inhibitors".
4. You'll see actual trials in 10-15 years after the initial press-release. Most likely for completely different compounds, targeting the same mechanism.
For the longest time I had bee trying to figure out why nobody was taking the research seriously, why there weren't diagnostic kits available that determined which variant people were actually suffereing from, and using the appropriate drug regime to manage the specific condition the patient had.
Then, last year I saw a paper being discussed (some 5 - 10 years after the initial paper), and it was building on the Washington research - it appears to me now (keeping in mind that I am a layman and an outsider) that the research /had/ been taken seriously, but it's seen as a signpost on the pathway rather than the destination.
This one is quite tinfoil-hat inspiring, as the research was moved to defense-focused Draper Labs and then immediately disappeared.
https://www.cremieux.xyz/p/the-rise-and-impending-fall-of-th...
The patents expired, so nobody can raise the hundreds of millions to do the phase II/III safety trials.
Granted, it's not going to be easy because the original patent has expired so it's going to be very easy for an upstart Indian company to conduct basic clinical trials, use part of the data of the second patent's holder to prove equivalency (they did this test so we don't need to do this test), and then get approved through an accelerated pathway in the FDA. Which is why even well-capitalized players will shy away from what could be a cash cow.
[0] https://xkcd.com/1217/
Can't describe it exactly, but it's like being transported to another dimension for a few seconds, then there is pain, then there is relief and then a nice warm feeling in the belly.
So yeah no more peppers without rice for me.
I'm not sure why this is the case, but I'll go to a place with some Habanero sauce and get that on a meal. It will hurt (and my time in the bathroom the next day might be a little unpleasant), but it satisfies the urge.
H Pylori is a very interesting subject, deeply misunderstood until a certain Australian hero brute forced through the arrogance of the day by infecting himself to prove ulcers weren't the product of psychosomatics.
Ending the rant there, I discovered through research that capsaicin (only one of the virtues of peppers) has a manifold effect upon various bacteria, notably pylori. Aside from encouraging the pylori to swim away from the capsaicin, it disrupts their biofilm behavior, and empirically, can drastically help with ulcers counter to expected problems with its spicy nature.
Adjacently, it can also encourage mucosal stimulation and protection.
I've found, co administered with mastic, oregano, NAC, and a few things presently inaccessible to the ol' cabbage.... Ahh, that's one... Cabbage juice! -- the infection can be reduced to sustainable levels without conventional antibiotics. Modern research is suggesting that h pylori, partly due to its ubiquity (50% of population +) and the ravages of antibiotics, it may be best to simply reduce it to manageable levels where the immune system and general well being keep it controlled.
There is also the wonder of fermented chilies which is good for many things, includes probiotics, improves most meals and really irritates assholes, which is righteous.