Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy
82 comments
·May 24, 2025NortySpock
shanemhansen
Science News is a big part of my childhood. My stepdad's dad was a subscriber and every issue was handed down to us gently used. I have thousands of back issues.
pugworthy
Same. My highschool library in the 70’s had a subscription and I would read through them with relish.
porphyra
It's always weird to me that acetaminophen has such a low therapeutic index, like in order to get enough for it to do anything, you're also on the verge of liver failure (especially if you also drink alcohol). Also it just doesn't work super well in my personal experience --- I hardly feel anything when I take it. And yet it's one of the most commonly taken medicines worldwide.
oliwarner
"Therapeutic index" is a strange number to worry about. Those index scores are the balance between efficacy and toxicity.
Acetaminophen is an effective analgesic, just toxic in large doses. It's perfect for lower intensity pain. It's non-addictive, doesn't have long term issues like NSAIDs. It's popular for a reason.
pipes
Calpol in the UK, paracetamol for children in liquid form (which is British name for acetaminophen) works wonders for kids with a fever. I'm not exaggerating when I say that every doctor I've seen with my kids has said not to withhold it as it really helps with fever.
dreamcompiler
Two tablets work great for me for headaches but results do vary. The danger zone for liver damage is roughly 14 tablets taken all at once. (Less if you've been drinking.) From what I'm told, acetaminophen overdose is quite an unpleasant way to die.
dogtorwoof
You die from liver failure. Which is a horrible way to die. You’re bleeding and clotting at the same time. Your abdomen swells with fluid. Then your legs and your whole body. Your skin turns yellow and you’re itching constantly. You become increasingly confused and violent. Infections start brewing in that pool of fluid in your abdomen.
johnisgood
You are exaggerating, because acetaminophen-induced liver damage is both preventable and treatable. They give you NAC at the hospital, and you do not need to go to the hospital for NAC, it is a commonly available as a supplement. But then again, you should not take such a large dose, nor should you take it on a daily basis. Take ibuprofen or diclonefac if acetaminophen does not work for you.
andai
I am going to cancel my internet subscription...
chistev
The maximum single dose of paracetamol is 1000 mg, and four doses (4000 mg) in 24 hours.
Any more and it's liver damage.
johnisgood
Not if you take NAC (that is how they treat acetaminophen-induced liver damage) and silymarin. In any case, I see no reason to take that much, just take diclofenac or ibuprofen instead, then.
Ey7NFZ3P0nzAe
It's terrible that you are counting in tablets instead of actual amount of acetaminophen
hgomersall
It's for this reason in the UK paracetamol (as we call acetaminophen) is only ever manufactured to 500mg tablets. I don't know if that is global.
Jolter
But how many cases of poisoning occur each year?
mulderc
“56,000 emergency department visits and 2600 hospitalizations, acetaminophen poisoning causes 500 deaths annually in the United States” -Acetaminophen Toxicity Suneil Agrawal; Brian P. Murray; Babak Khazaeni. https://www.ncbi.nlm.nih.gov/books/NBK441917/
reedf1
I take it mostly as an anti-pyretic (fever reducer). For which it is extremely effective. It's my drug of choice for colds, flu, etc.
MichaelRo
Well, it doesn't work for high fever (> 39-40 Celsius). For that, I alternate Ibuprofen and sodium metamizole every 4 hours.
For pain release, paracetamol it's very modest. Some effect for light head pain, zero for strong pain. Zero effect for strong back pain. Ibuprofen works better in all these cases but comes with stomach damage if taken for long.
Ey7NFZ3P0nzAe
Paracetamol is nicely synergic with all known painkillers. For example prescribing it with morphine leads to less morphine consumption.
Also: it's a terrible rule of thumb to take an NSAID routinely for general infectious symptoms like fever.
whymauri
acetaminophen should not be an OTC drug
Mizza
She didn't even break the top 10 in this content: https://www.societyforscience.org/regeneron-sts/2025-student...
I'm impressed beyond words by these kids, though I think I'd give her the top prize. Watching my grandfather's final days taken away from him by the effects of morphine has always made me wish so much that we had much more effective non-narcotic painkillers
irjustin
https://www.societyforscience.org/press-release/regeneron-is...
She's in top 4, awarded $600? I dunno this is a confusing layout/structure for how the program is conducted seeing as how the headline is $9m awarded.
ricardobeat
Reversible computing, materials science, genetic research… it’s insane that these kids are doing this level of work in high school.
timr
They aren't doing it on their own. Most of these kids are working with established researchers who give them the shape of the project, as well as the tools and the expertise to accomplish it.
More recently the US scientific funding bodies have had summer programs for kids who wouldn't otherwise get that kind of access, but it's still the exception. It takes more than a summer to do this kind of work.
Edit: quick search for the father's name brings up this professor of biochemistry at UT Tyler:
https://www.uttyler.edu/directory/chemistry/lee-jiyong.php
and mom's name brings up this professor of pharmaceutical science:
https://www.unthsc.edu/college-of-pharmacy/eul-hyun-suh
I don't mean to take anything away from the kid or suggest that they don't work hard, are smart, etc., but these kinds of science fairs are fundamentally about access.
carlmr
>these kinds of science fairs are fundamentally about access.
Completely agree there, which kind of brings me to a related thought:
One thing I do wonder is, if you look at a few hundred years ago a lot of the inventors in math, physics, engineering, were a tiny group of people with access to resources and education. You're always reading the same names.
It seems if we as a society could decide that science is more important to us, with 8 billion people on earth, if we gave more access, time and incentives to people we should be able to increase the amount of scientific results exponentially.
AStonesThrow
Science projects are a family affair, more often than not. Ask me how I know.
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fracus
I thought morphine didn't cause health damage to the human body apart from addiction and withdrawal symptoms.
shanemhansen
Well it absolutely muddles your mind when you're on it and it causes constipation. It can also depress your respiratory system.
dreamcompiler
And it can make some people very nauseous.
Nobody discusses these mundane drawbacks when they talk about the evils of heroin addiction. When you're high, you puke and you cannot give a shit. Both figuratively and literally.
cjbgkagh
Morphine, like all neurotransmitter drugs, affects the autonomic nervous system which can yield a cornucopia of unwanted and seemingly unrelated side effects. It’s a complex system that’s best treated with care.
lenerdenator
at least according to these people [0], you can overdose on morphine, same as any opiate or opioid. not sure their credentials but it makes sense; it's an opioid/opiate and those can cause respiratory depression.
[0]https://www.addictiongroup.org/drugs/opioids/morphine/overdo...
DontchaKnowit
Yeah its like any other opiod- it depresses respiratory function which can cause death but it isnt directly toxic to any organs like APAP is
dreamcompiler
Oh yeah morphine overdose will kill you dead because you will stop breathing and you won't even know it happened.
The instant antidote is Narcan which is available over the counter at pharmacies in some states.
AStonesThrow
Nurses in palliative care and hospice are well-known to generously administer morphine in increasing doses, because it eventually takes away all the pain and suffering (of the families and nurses).
Kevcmk
That’s a controversial take
apwell23
> Watching my grandfather's final days taken away from him by the effects of morphine
Those were not prbly his final days. he was artifically kept alive by modern medicine. Those final days are not natural part of dying.
petesergeant
Journavx!
djtango
The key synthetic step using Ir was published after I graduated (and left Chemistry...) way to make me feel old :)
I'm very impressed by the level of chemistry demonstrated by a 17 year old. During my time as a chemistry student this level of project and synthesis probably could have been included as a chunk of a master's thesis. Did she perform all the synthesis herself? That takes a decent amount of experimental skill and more importantly what lab did she do all of this in?
Any uni ought to be delighted to get a precocious talent like this!
ItsHarper
This would be incredibly cool if it works in reality and not just simulation. Remarkable that the author is just 17.
fracus
She's also a very talented violinist.
epcoa
I’m not going to shit on it, nothing wrong with going into the family business - but it isn’t a complete coincidence that her dad is a PhD biochemist at UT Tyler.
hooo
And look at her mother -- https://profiles.unthsc.edu/profile/381 -- hmmm
jmcgough
Yeah, it's great to have kids excited about science, but at 17 it's extremely unlikely that she taught herself enough chemistry, organic chemistry and biochemistry to come up with this. She needs years more of college-level coursework. Essentially impossible without a biochemist in the family to guide her.
buckle8017
It never is, the winner of this competition is in astral radio telescopes.
Something tells me he didn't launch the satellite.
felineflock
With mentorship from Caltech and access to data from NASA’s NEOWISE mission, Matteo created a machine learning algorithm and compiled a groundbreaking database called VarWISE.
https://www.societyforscience.org/regeneron-sts/2025-student...
14
Seeing articles like this is almost hard to read. My kids are very smart but this girl is 1000 times what they are doing. This girl is 1000 times what I am doing. Maybe it is just imposter syndrome but sometimes I read articles like this and think I fell short in life. But I am also top of my peers at work and I am a health care provider and my clients all request me so I know I am doing good. Sometimes I just wonder what mark I will leave on this world.
Glyptodon
My experience is that stuff like this isn't because someone is wildly smarter than everyone but because there are connections, support, and resources of some form.
14
I understand that and I do know that I am actually very intelligent and smart. Same for my children I mean damn I have already taught my 8 year old how to solder as good as a professional and am working on programming with him. And as a health care worker I can look after even the most difficult complex care clients where other health care workers struggle. That is what I am known for at work. But sometimes seeing literal teens doing things that seem so far ahead of me it
throwawaymaths
it's just a four step synthesis. with the help of a phd chemist you could probably learn the steps in three months, and if you put your mind to it you could learn the ochem in a year. this project is the culmination of at least a year-maybe even up to three-of work.
whats surprising is that parents let their kids do ochem at 17!! thats some toxic shit :). safety is why chemistry is not a super popular field at high school level science fairs.
mofunnyman
C'mon, who doesn't like their kids dusted with methylmercury?
nenaoki
it's sad to compare.
apart from that: the word "mark" comes from a root for "boundary" or "border", and really it doesn't need to be about that; we're all in this together.
nandomrumber
Can acetaminophen be packaged with n-acetyl cysteine to render it not rate limited by same?
meew0
The problem is that N-acetylcysteine tastes and smells awful (like farts/rotten eggs) and often causes nausea and vomiting as a side effect.
The vast majority of people use acetaminophen in a safe way, and acetaminophen doesn't really have many side effects by itself, so you'd make life more unpleasant for a large number of people in order to prevent a tiny number of acute poisonings.
Probably if this were implemented, most acetaminophen users would switch to e.g. ibuprofen which is less acutely toxic in overdose but has much more chronic toxicity (to the stomach and the kidneys) when used over a long period of time, even at a normal dose. I'd wager this change might even be a net negative on the whole.
Ey7NFZ3P0nzAe
Always wondered that.
Maybe too many people would take even more?
throwawaymaths
impressive for a high schooler but this just adds a protecting group onto tylenol. am i missing something?
edit: oh i see. its really blurry but the silyl modified tylenol is predicted to have good trpv1 binding computationally. afaict no in vitro or in vivo studies were done. could be cool. not sure if diethylethynylphenylsilyl group has good Lipinski properties though (i suspect not)
edit: s/aspirin/Tylenol
abrookewood
It isn't aspirin - Acetaminophen, also known as N-acetyl-para-aminophenol (APAP) or paracetamol
throwawaymaths
lol yeah sorry brain too deep into synthetic chemistry bits. thanks.
snibsnib
I'm not an expert in pharmaceutical chemistry, but this looks like a series of relatively complex and low yield reactions. Would it be likely that this would push the price of this product beyond what is reasonable for a general use drug?
maxerickson
The starting point is ~free (like 2 or 4 cents retail per dose for generic in the US). Given my relatively light usage of pain drugs, I would certainly pay 10x that for reduced toxicity.
And then it isn't necessarily the case that the identified reactions are the most cost effective available.
toast0
If you have light usage, do you need reduced toxicity?
Acetaminophen's effective dose is pretty close to the dangerous dose, but I would take light use to mean you take something maybe once a month max and only a single dose (or maybe even just one pill when the dose is two pills). At that level of use, I don't think you're at risk of anything.
Otoh, if the title is accurate and it can be more effective at pain release and less damaging to the liver, that would be great for people who experience pain frequently.
w10-1
If it makes it to market at a high price, it wouldn't compete directly but be targeted to those at risk of toxicity.
aethrum
Reminds me of this drug company I was pitched a while ago:
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mewse-hn
so is this already patented by Regeneron?
throwawaymaths
regeneron is the sponsor of STS. used to be well known as the Westinghouse STS, then intel took it over in the aughts
colingauvin
They would need to show efficacy to patent it. It seems like this is all computational.
throwawaymaths
no she did the synthesis and the yields are averaged? over >5 replicates <== just doing that is pretty (spiritually?) impressive, most phd chemists wouldn't do that kind of reproduction of results.
refurb
Only for a utility patent, not for a composition of matter patent.
aaron695
[dead]
The same website is also for the excellent Science News print magazine, which will ship you top notch science reporting right to your door. My father was a subscriber since, well, whenever blue LEDs were invented, because I recall reading about them in Science News.
Strong recommendation for any science-lover.