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
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.
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.
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.
Time and experience has shown that "scientific innovation" cannot be made to happen faster by throwing more money at it, and a promising young person would be much better off by putting their talents to use doing something less random [2]. You can produce more good research in aggregate (maybe), but only in the same way that you can find more gold by crushing more rocks. Either way, you have to crush the rocks.
For example, the US government dramatically increased grad school funding through the 80s-2000s, and the primary outcome was an employment crisis amongst PhDs in the sciences. In the 40s-70s it was fairly straightforward to establish a career in research, but these days it's Hunger Games. I sort of fundamentally believe that the reason most science came out of the European aristocracy was not due to inequity, but because only someone well-off could devote their lives to something so erratic. Science is an avocation, not a vocation.
Science fairs and the like are a weird little subculture of college-application polishers, in part because nobody in their right mind actually wants to become a scientist. I think it's a safe bet that the young woman in this article ends up doing something more lucrative with her life (and good for her, if she does).
[1] Or even more cynically: the organizers do know, and are doing it because it builds their own careers.
[2] Or at least, with a higher alpha.
Also probably about that US Gov funding. I've heard it's more about knowing how to write a grant than it is about being worthy of getting one. Better direction, better active identification of candidates (instead of the passive system that's biased towards large players), better stability. All of those would help.
However, there's a _lot_ of stuff that would be within reach, were only enough mass manufacture involved to drive down the adoption cost and break through the catch 22. Many things only need for gathering the correct sort of people, giving them enough room to work on a clear goal, and seeing where things really are.
The big business problems with that are figuring out if the return is plausibly worth the investment, and feeding the baby long enough that it can become a working adult.
Aren't those effectively the same thing? At least in the given context where society doesn't have the resources available for everyone to live like that.
People who can afford a garage full of antique race cars only exist due to inequity.
What's the difference between those statements? As far as I can tell the latter includes the former while adding an implicit assumption about total available resources versus total population.
Apologies if it seems like I derailed things. Your comment was interesting but I didn't understand (still don't) the significance of the distinction you went out of your way to draw there. That said, I think the trailing remark that "only someone well-off could devote their lives to something so erratic" really hits the nail on the head. Even today you can see elements of that, for example on certain parts of youtube. People with excessive expendable income occasionally do some really impressive stuff.
The comment above yours is a really poor strawmanning attempt.
Thanks. I mean, it's not like I have direct experience with this stuff or anything, as one of those 9,999,999 who spent years of my life doing science, only to end up in industry.
Also, it's not like we would do better by skipping the years of science and going directly to the productive part, or that those (now grown up) "kids" are encouraged to continue circling the airstrip of life by the funding programs that are happy to pay postdoc salaries -- postdocs being the best kind of cheap, indentured labor -- to keep the dream alive just a little bit longer. After all, walking away from a PhD/postdoc(s) is only just a bit harder than chewing off your own leg to escape a bear trap.
It's clearly much better to waste the time of our smartest people by injecting false economic incentives into the system in an effort to socially engineer some kind of scientific command economy. Let's grind those rocks, and turn the cheap gravel into concrete to build glorious future!
The issue with your argument is that you’re conflating two different points on the academic pipeline by shitting on high school science fairs because of the post-doc hellscape further down the line.
The latter is a special case of low wage, dead-end jobs that are inherent to capitalism, which can more generally leave anyone paralyzed in a vicious grind loop. Improving this may require capitalistic reform such as UBI and increased housing supply, but is the human condition of the quest for satisfaction in one’s niche.
The former is exposure to future possibilities that could satisfy the constraints of economic and intellectual well-being, likely through incremental progress but with the potential for breakthrough in either realm.
That's how ML research is - all you need is sufficient compute and some torrented training data. It gives rise to a new problem of drowning in the literature. I think we simply don't have the tooling and institutions to integrate simultaneous scientific advancements from any significant portion of the population.
Yep, but we collectively decided that it is more profitable to put the best minds that manage to survive the education trials to either shaving off 0.0000001 cents of each financial transaction and to still make billions of dollars off of that or to sell ads so people get convinced they need to buy something. And those that get dropped along the education pipeline, we either let them stay on the road side and let them rot in poverty or we just use them as yet another source of labor ready to be exploited.
As someone getting a PhD at a top school and the first in my family to ever make it past high school I can assure you all these kids are raised from birth in a test tube by their parents.
[0]https://www.addictiongroup.org/drugs/opioids/morphine/overdo...
The instant antidote is Narcan which is available over the counter at pharmacies in some states.
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.
As for "depress your respiratory system", yeah, in high enough doses, or if you are especially sensitive to it.
Pharmaceutical opioids are pretty much safer than NSAIDs. The side-effects of NSAIDs are actually worse than the side-effect of opioids. You will not get ulcers, blood clots, stroke, heart issues, GI issues, and all sorts of other issues with opioids.
Those were not prbly his final days. he was artifically kept alive by modern medicine. Those final days are not natural part of dying.
Fentanyl, my brother claims to be the best. It, too, can work wonders under a controlled environment.
Unfortunately, it's tainted by illicit use. Damned to only be used in dire circumstances. It's a shame, really.
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
How expensive are the steps? They look like advanced steps that can be done in a lab to prepare a few micrograms, but I'm not sure if they can be scaled to industrial production.
Why silicon instead of just a carbon? Is it better blocking the docking? Is it better moving the orbital energy levels? Is it as safe as the poster claim?
https://www.science.org/content/blog-post/silicon-drug-molec...
that molecule almost certainly fails the ClogP not greater than five lipinski rule (it's too greasy)
IIUC from the "In the pipeline" article, drugs with silicon are too similar to their equivalent with carbon, and more difficult to make: "so why bother?"
Are they using the silicon to avoid the usual rules of substitutions in benzene cycles? Is it possible to do the same trick with carbon?
> that molecule almost certainly fails the ClogP not greater than five lipinski rule (it's too greasy)
Is it possible to fix it adding some -NH2 (or -COOH ?) group in the second aromatic cycle?
[I understand it's a nice science fair project but the article oversell it.]
Strong recommendation for any science-lover.
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!
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.
Also: it's a terrible rule of thumb to take an NSAID routinely for general infectious symptoms like fever.
It’s the exact opposite of what you claim. Cannabis is orders of magnitude less destructive to the body than paracetamol.
If you honestly believe what you wrote, you need to check your sources. There is a lot of drug war propaganda still out there.
Acetaminophen indeed has a shitty therapeutic index and cannabis in any (natural) form has basically no acute toxicity.
But i'd take 1g of acetaminophen daily for the rest of my life starting at age 1 instead of taking 1 cannabis joint equivalent every day. And that's even if we're talking edible form or vaping (i.e. not considering tars).
What about you?
Any more and it's liver damage.
https://emedicine.medscape.com/article/820200-treatment - Treatment for liver damage is NAC (N-acetylcysteine) which is available as a supplement.
> N-acetylcysteine (NAC) is the mainstay of therapy for acetaminophen toxicity
https://www.ncbi.nlm.nih.gov/books/NBK537183/
Again, NAC is readily available without prescription.
Additionally, see https://www.medscape.com/viewarticle/422884 for Silymarin (which is found in Milk Thistle).
That said, do not exceed the maximum dose. Try ibuprofen, diclofenac, or whatever else, but they are not without risks either. For the record, acetaminophen is the only painkiller you can take on an empty stomach without it causing any GI issues.
It needs to be administered within 12h and 5% will have a severe anaphylactic-type reaction with risk of respiratory arrest. And the liver can still have been irreparably damaged due to other factors.
In the context of this being a miserable way to kill yourself, it's absolutely awful because there is very much a cut off point where you will still be suffering immeasurable pain and no amount of NAC will save you.
Ultimately, what one needs to do is just... not consume high amounts, or too frequently.
Trigger warning for self harm.
The real tragedies with acetaminophen are "cry-for-help" situations where someone thinks it is the same as aspirin, and swallows a handful, perhaps washing it down with alcohol. What might have been a suicide hesitation mark becomes an entry on a liver transplant list - if they are lucky. If you have children, make sure they know which one can be deadly, especially before going off to college.
One memory I have of visiting our U.S. head office with a bunch of UK people was the “we have to get to Target because they sell Tylenol in ungodly quantities.” And I thought bottles of 200 pills felt ridiculous up here in Canada.
I'd be interested to know if I'm wrong though.
Two years ago, I was prescribed the maximum dosage: 2 × 500 mg every six hours for a couple of months. Because it wears off more quickly than that, I tried to reduce it to one and a half pill more often but that wasn't enough to have any effect. Caffeine is supposed to reinforce the effect, but of course I had to avoid that to sleep.
I also got it as intravenous liquid at a time when I couldn't swallow.
That ain't much, I don't think I've seen boxes with that little around here. Normal packaging is 30~40, and you can get larger boxes, all without a script.
Are the boxes that small because sweden tends to use an other analgesic as primary culturally e.g. aspirin or ibuprofen and paracetamol is for more exceptional situations?
> Caffeine is supposed to reinforce the effect, but of course I had to avoid that to sleep.
If the goal was pain relief, you can combine ibuprofen and paracetamol. They can be staggered or taken together (in which case there's less duration coverage but some evidence that the combination works better than either separately).
I prefer acetaminophen due to the main metabolite being a reuptake inhibitor of CB-active transmitters and I don't drink. I take maybe two-four grams per year, so your 40-pill box would last for a decade.
No, I'd say paracetamol is the most common. I think there was an increase in teenagers that tried to overdose on it to commit suicide some years ago. You could easily get 1000mg pills before that.
There absolutely ARE situations where ibuprofen should not be used (kidney, infections, others), even at the usual dosage.
Hence I believe that it's a terrible idea to write on the internet "they can be staggered or taken together" as if they had a simimar safety profile
Can't put a source but I had lessons explaining that the US had insane rates of tylenol suicide, and that are apparently correlated with the size of boxes sold otc. Years ago many countries including france put a limit on the quantities sold at once and the suicides plummeted. The US didn't because of lobbies or something.
So sad and obvious.
In my case I was talking about 500 mg tablets which are commonly branded in the US as "Extra Strength Tylenol."
The point I was trying to make is that the deadly dose divided by the therapeutic dose for acetaminophen can be as small as 7. This is a much smaller ratio than for most other common over-the-counter drugs. There's not much room for error with acetaminophen.
Well yes it is possible to define an absolute toxic dose. 100 grams is an absolute toxic dose of acetaminophen in humans, 8294 tablets is not a dose.
(You might need a Time Machine first)
Some of those are probably intentional suicide attempts. What’s the maximum number of tablets for one purchase? Sweden has it regulated down to 14, because that’s just enough to not cause permanent damage in a depressed teenager.
https://www.fda.gov/consumers/consumer-updates/dont-overuse-...
“While a majority of adult overdoses are linked to suicide attempts, many cases are accidental, often due to the use of more than one paracetamol-containing product over an extended period.[106] […] Overdoses are frequently related to high-dose recreational use of prescription opioids, as these opioids are most often combined with paracetamol.[110] The overdose risk may be heightened by frequent consumption of alcohol.[111]“
So, combination drugs being used recreationally, yeah I guess I can believe that would lead to not keeping track of how much paracetamol you took today. And especially over time.
I figured it would be pretty hard to accidentally exceed 4000 mg in a day, but if you’re high on some stronger painkillers, which you’re developing some tolerance for, then it’s easy to just keeping taking more than you did last time.
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.
I have never taken acetaminophen since then. If it's a low intensity pain, then I can handle it myself. If I need actual pain relief I'll use an NSAID.
Finding out later that paracetamol dosage is super close to overdose, and how it actually kills you... That put the tin hat on it.
I agree, paracetamol isn't perfect for every type of pain. NSAIDs help relieve pressure and can help, and opioids can waffle-stomp most pain but only for a little while and with dire risks of dependency, but for-purpose drugs like gabapentin are usually a lot more effective at blocking even high intensity neuropathic pain. Unlike NSAIDs, you can take them long term without needing a cocktail of PPIs to keep your stomach from imploding, and they're non-addictive.
If it was discovered tomorrow rather than last century, it would never get OTC approval, because while for some people (like me) it's useful, the dangers are too high, so they'd definitely make it prescription-only. I'd probably still come back from any surgery with a bag of paracetamol because it's cheap and the surgeons can prescribe it to somebody it works on without worrying (it's not like an opioid, nobody is going to get unnecessary surgery so as to secure more paracetamol) but it would not be in cold & flu meds if they hadn't found it last century when they were more lax about safety.
[Edited to insert crucial omitted "not"]
To be fair though I really haven’t been involved with more than a handful of medications. I’m sure there’s many that work very crisply.
As an adult using it as a pain killer it has been ineffective.
Would that not make it a very effective pain killer? /s
But seriously - you are not supposed to "feel" a drug. Opiates work on a much different mechanism, and you do "feel" them, but that is also the same mechanism that make them so addictive. What you want is a drug that helps you manage pain and not be addictive.
My concern is about the relatively recent findings about potential Alzheimer risk [1]:
> During a median follow-up of 12.3 years, 6407 (3.0%) participants developed new-onset all-cause dementia. Participants who regularly used paracetamol had a significantly higher risk of new-onset all-cause dementia (adjusted HR, 1.18; 95%CI: 1.10-1.26), compared with non-users. However, there was no significant association between regular use of ibuprofen and new-onset all-cause dementia (users vs. non-users; adjusted HR, 1.06; 95%CI: 0.97-1.16).
I don't follow the research closely enough to know if this is reliable evidence, but there are other studies showing the same thing.
Paracetamol also well known as mood-altering, apparently inhibiting empathy [2], which may be part of why it has an analgesic effect. That isn't as scary on a personal level, but imagine a society full of millions of people on paracetamol whose ability to feel empathy has been blunted.
COX-1 is involved in the gastric mucosa, among other roles, which is why blocking it can cause stomach bleeding.
COX-2 is involved in maintaining the endothelium of blood vessels, and can increase stroke and infarction risk by stiffening and degrading the lining of the blood vessels over time.
Studies are a bit conflicting regarding whether blocking COX-1 or COX-2 is safer, as there seems to be downsides to both, and the difference in risk isn't that clear.
And then it isn't necessarily the case that the identified reactions are the most cost effective available.
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.
Maybe too many people would take even more?
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.
The smell is reminescent of a high-potency cannabis strain. (Sulfur-containing molecules.)
The taste is very acidic and a bit astringent.
Generally the smell and taste of something isn’t a concern with medication. I don’t think acetaminophen tastes great.
I’ve never encountered or seen the digestive issues that are often mentioned. I’ve seen other side effects which were noticeable – mast cell and histamine related I believe, kind of weird ones, like psoriasis kind of drying out a bit and the skin on the lips “refreshing” itself. (Really!) Subtle side effects and hard to put into words without making them seem bigger and weirder than they are, but NAC can nonetheless be a sort of histamine and mast cell “flusher”, so to speak and as it seems. Beneficial in the long run imo ime, but tricky to package universally.
Still, NAC is also tragically unknown and unused! There’s tons of fascinating literature on it. They fried rats’ brains with methamphetamine and fixed them with NAC; Brutal study, intriguing results on very significant mechanisms.
Nausea or vomitting is rare, I imagine if it were common those hangover cure sellers would go out of business
Did you check if drinking alcohol was safe? ;)
And yeah I was 100% skeptical too!
Now I’m more sceptical of the kinda “nothing is known, nothing is knowable” angle, you know? There is so much knowledge, actionable, often unread, often unused.
(Have to mention it, if useful: Na—R-ALA (alpha lipoic acid) and ambroxol are kind of in the same vein. Ambroxol is strangely a sort of bromine counterpart to NAC and its sulfur atom. Sold as a mucolytic but is… alllll over the place. Funny how mucus, mucous membranes, the nervous system, and oxidation/redox stuff is all so adjacent it seems.
I have no idea why but after a severe period of stress, I happened to take Na-R-ALA as sometimes do and 60mg of ambroxol as mucolytic cough syrup. For a cough. And… the feeling was like in the movies where they stab someone with a giant syringe to revive them. Trainspotting or Pulp Fiction or whatever. I felt like I gasp-crawled out of a pit inside myself. It makes no sense. It was… a very distinct experience. And it didn’t seem like an airway clearance thing, more like my nervous system was refreshed.
So I hit the books. And it turns out ambroxol crosses the blood-brain barrier and is an antioxidant, and affects ion balance in neurons, and there are studies indicating it helps with… Parkinson’s and fibromyalgia (!!!). And those papers are pretty interesting and appear to be constructed on solid molecular biological premises.
idk)
As a detail, I clearly experience the better bioavailability of Na-R-ALA. Often marketed as “stabilized”. As well as what I believe is the increased bioavailability of Na-R-ALA dissolved in water.
The main point I wanted to make is that it occurred to me when reading your comment that I know myself to be somewhat “oxidatively burdened”, if that’s a term? I have mild psoriasis, which is known to use oxidative and redox capacity in the immune system’s activation in the rash. (afaik immune cells “fire bullets” of oxidization at perceived intruders.) There are other stressors in my life which are also inherently oxidising in the molecular biology of it. I’d bet a nice bottle of Oban that that is a factor in the sense of relief.
In my 20's I discovered Excedrin (acetaminophen + caffeine) and, surprisingly, it not only worked, but worked very well. One tablet would kill most of headaches I was having at that time of my life in about 15 minutes.
Unfortunately, it stopped working for me by the time I was 30. It no longer has any noticeable effect.
Aspirin, Naproxen, Ibuprofin, and Tylenol 3 have no effect, either.
I would be very suspect of a Medication Overuse Headache (MOH) due what appears to be acute/abortive use of painkiller medication as compared to a prophylactic usage of other drugs. I'll do this exercise mostly ignoring the #1 concern because presumably your doctors would be hyperaware of that.
# Pathways
0. Excedrin is combination of aspirin, acetaminophen, & caffeine.
1. Aspirin --> COX-1 (/2) inhibition --> Reduces Prostacyclin/Prostaglandin/Thromboxane Synthesis --> Decreased inflammation, nociceptor sensitization, pain signaling
2. Acetaminophen --> Central COX Inhibition, possible COX-3 inhibition (splice variant of COX-1) --> Reduces Prostacyclin/Prostaglandin/Thromboxane Synthesis --> Decreased inflammation, nociceptor sensitization, pain signaling
3.a. Acetaminophen --> Metabolized to N-Arachidonoylphenolamine (AM404) --> Inhibition of reuptake of Anadamide (endogenous cannabinoid) --> Increased activation of CB1 receptors
3.b. Acetaminophen --> Metabolized to N-Arachidonoylphenolamine (AM404) --> Transient Receptor Potential Vanilloid (TRPV1) agonist --> active? at periaqueductal (central) gray --> opioid receptors that send descending axons to modulate pain at the level of the dorsal horn of the spinal cord
4. Acetaminophen --> Enhancement of serotonergic descending inhibition (5-HT pathways)
5. Caffeine --> Adenosine anatagonist (nonselective A1, A2A, A2B) --> Inhibition of vasodilation --> Cerebral vasoconstriction
6. Caffeine --> Analgesic Adjuvant --> Enhances availability of aspirin and acetaminophen.
# Thoughts
1. Selective: -COX, +CB1, +TRPV1, +Opioid, -Serotenergic, -Adenosine, -Inflammation, +Vasoconstriction/-Vasodilation
2. Aspirin doesn't work in isolation.
3. Tylenol-3 (acetaminophen) doesn't work in isolation (surprising!!!).
4. Headaches probably not -COX mechanisms
5. Caffeine is likely needed for -adenosine, vasculature effect implicating cerebral vasodilation
6. Densensitization strongly implicates +CB1/+TRPV1 as well as -adenosine, +Sero, +Opioid.
# Concluding Thoughts
0. Need to address MOH, this should be a conversatio with your real doctor.
1. Then for the headache, normal first-line would probably be a TCA prophylaxis such as amitriptyline with bonus target +sero/+opioid. Assuming you've tried this.
2. The failure of your other drugs means you should probably try CGRP Inhibitors to target vascular and pain-signaling effects. Maybe even gepants (acute)
3. Botox could be a consideration in a complex CDH case.
4. Zebras: Ditan/Lasmiditan. I assumed +vasoconstriction, but could be -vasoconstriction which is why non-combination drugs failed. Target 5-HT1F and avoid vasoconstriction for symptomatic relief, but doesn't treat underlying. Probably avoid due to MOH.
# Clarifying questions for your doctor, not me
1. Is your headache pulsatile/throbbing (migrane) or dull, tight, & persistent (tension-type)?
2. Onset characterized by stress (tension-type)?
3. Is it unilateral (migrane) or bilateral (tension-type)?
# What I would do next
1. Make an appointment with a neurologist
2. Before the appointment, make a detailed headache diary (when your headaches start/end, intensity of the pain, location and quality of the pain, associated symptoms (nausea, light senstivity), any potential triggers, what you did to try to relieve the headache and if it worked)
I didn't understand why this post had so many votes
ItsHarper•6mo ago
epcoa•6mo ago
buckle8017•6mo ago
Something tells me he didn't launch the satellite.
felineflock•6mo ago
https://www.societyforscience.org/regeneron-sts/2025-student...
qzw•6mo ago
jmcgough•6mo ago
hooo•6mo ago
fracus•6mo ago
14•6mo ago
Glyptodon•6mo ago
14•6mo ago
throwawaymaths•6mo ago
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•6mo ago
nenaoki•6mo ago
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.
kranner•6mo ago
First, what would such a mark be like for you? Is it something you could plausibly achieve with all the resources within your reach? Is it well-defined or is it nebulous? Is it likely to remain stable over the time you would require to achieve it, or is it more defined by the whims and fancies of the world which seemingly change every other week now?
Then, even if you did achieve it, how long would it continue to matter to you? Would you remain satisfied with it or could you become habituated to the achievement in a week, month or year and replace it another mark that would then become the one task you must complete before you die? Even if you did remain satisfied with your great achievement, would it really matter to you at the end of your life, or would you completely forget about it in the physical and mental anguish that many people seem to experience at the end of their lives?
And after you are dead, how long would that achievement be remembered before being supplanted in the public eye by something bigger?
And would it really make a difference to you at that point? Whether it remains a grand success for a thousand years or is forgotten in a day, you won't be there to know the difference anyway. It really only matters to you for the brief periods of time in which you're thinking about it right now. During times that you're distracted, tired, enjoying and appreciating something else or are simply asleep, it's hard to believe it matters at all.
If you're happy, healthy, not harming others, making a decent and honourable living, raising kids, I think you're already winning.
If the idea of having to leave a mark is making you unhappy, maybe it's better to just drop the idea.