Hacker News new | past | comments | ask | show | jobs | submit login
Tramadol Is Not a Natural Product After All (corante.com)
217 points by crygin on Sept 15, 2014 | hide | past | favorite | 117 comments

Wait, let me make sure I am understanding this. So Tramadol was given to cattle in such large amounts that it made it into the soil and enough got soaked up by trees that it was thought that Tramadol came from those trees.

That is just incredible.

Once enough is coming up through grassblades then farmers can cease giving it to the cattle directly. The holy grail of Unlimited Tramadol!

Drugs company hates him!

now seriously, where do one find such abundance of opiates to feed cows of?!

I'm not sure if you're joking, but opiates are grown from opium poppy plants, so that would be a good place to start if you actually wanted an abundance to feed to animals. Tramadol, however, is an opioid, which is a term that encompasses both opiates and synthetic opiate-like drugs -- of which Tramadol falls in the latter.

that's the point. synthetic opiates are not cheap. and those farmers are feeding herd with it.

Tramadol seems to be relatively cheap to produce, and has all sorts of uses beyond just pain medication.

Exacerbated by the animals seeking shade near the trees and then relieving themselves in the shade.

This may also be a tribute to the sensitivity of modern chemistry's tests.

Can't help but be reminded of the Wikipedia circular citation phenomenon - http://xkcd.com/978/

I didn't even know that Frankie Boyle had taken up farming.

It's the circle of life!

I only wish we could get a wikipedia-news-citation cycle in on this story.

>The farmers apparently take the drug themselves, at pretty high dosages, saying that it allows them to work without getting tiree.

That's insane. Tramadol is among the worst painkillers to use recreationally, which is why it's often the next line of analgesic therapy after NSAIDs and before hydrocodone.

It is a comparatively weak mu-opioid agonist, so the dose a person would have to take to get a prototypical opioid high, likely quadruple a normal prescribed dose at minimum, is pushing the margin of safety.

I am not advocating drug use here, but if you're dead set on getting high, please use something else- namely something with a higher mu-affinity that would require a lower dose, and ideally something that's not combined with acetaminophen or other NSAIDs.

It doesn't sound like they're trying to get high, per se, just work harder without feeling it. A "recreational" dose would probably interfere with getting work done.

Not necessarily. Opioids, like other euphoriants, are somewhat "stimulating" (mentally) in small doses.

I know they aren't just "trying to get high". The problem is that in order to get any psychotropic effects from Tramadol, the dose is so high that a lot of other really nasty effects will come with it. A 5mg dose of hydrocodone would accomplish the effect they are after with very little negative physical effects.

If they were just using it as an analgesic, which the article clearly indicated is not the case, it would be a different story.

Wouldn't Tramadol be classified as a psychotropic just by virtue of it inhibiting your central nervous system?

As someone who takes Tramadol for pain, it does have an odd effect when I'm tired: I find I become less tired, as if the Tramadol is making me ignore my fatigue. Oxycodone, on the other hand, causes me to be more drowsy. This might be what the farmers are talking about.

First of all, I didn't say that Tramadol was not a psychotropic. I said it was not a potent one.

Second, the definition you are describing is a depressant, not a psychotropic.

This is not entirely true. Tramadol are often given in doses of 3x50 mg a day for pain relief. To a user with no tolerance, the most common lowest dose, i.e. 1x50 mg is certainly more than enough to give a euphoric feeling, ability to concentrate, stress relief and a whole range of other effects. Effects obviously can't be compared to "real" opiates, where the effect is much stronger and have more of a sedative effect. It should also be noted the effects vary quite a bit depending on the individual, i.e. some people don't have much of a reaction to Tramadol.

The article, and Zunger's G+ discussion as mentioned below, clearly established that they were taking very high doses.

That might be, but that's not relevant to the point of what dosage is necessary for a psychological effect.

You can't be serious. Are you advocating hydrocodone here which has one of the highest potential for debilitating addiction, so much so actually that it is banned in many countries and no longer available for medical use?

I explicitly stated that I was not advocating drug use. What I am advocating, if you would actually bother read my comments, was that the farmers' dose and dose frequency are pushing the therapeutic window (i.e. it nears toxicity). Regularly taking a therapeutic-level dose of hydrocodone would not push that window.

If you think repeatedly taking extremely high doses of Tramadol is somehow safer than small doses of hydrocodone, then you're unbelievably ignorant.

As a side note, hydrocodone is one of the least potent mu-opioid antagonists, but it is more potent than Tramadol. That is the only reason I mentioned it by name.

And I take no stock in governmental drug laws with regard to pharmacology, so your mention of it being removed from medical use in a handful of countries means nothing to me.

Half right. They're using for the benefits you cite, but taking a much higher than indicated dose (based on Yonatan Zunger's fascinating G+ thread on this topic).

Presumably they are getting the drug from supplies meant for the cattle. It's not like they have a choice of drugs to use.

The article actually seemed to imply that the farmers started taking it first and thought (for some reason) that the cows might also benefit.

I just want to note that acetaminophen (paracetamol) is not an NSAID. As a haemophilia patient who can't take NSAIDs but can take acetaminophen, this is an important distinction for me.

Tramadol recently became more regulated as a controlled substance and now requires patients to jump through more hoops (pain management visits, drug tests, etc.) to obtain. Source: Family member on Tramadol and http://www.businessinsurance.com/article/20140818/NEWS08/140...

I think its stupid they did that, but then I do remember widespread use of "Tromol" in Moscow. People would take it in high doses and veg out for days at a time.

Is this is the same Tramadol that is incredibly addictive and kills people if they taper off too quickly? Why wouldn't you want some hoops for this?

I was prescribed it after I broke a leg in judo. I was shocked when I looked it up and found forums rife with addicts in great distress.

It's not as addictive as other opiates. It is physically addictive though, yes.

Opiate withdrawals don't kill you, although you'll want to die; Tramadol has a weird secondary set of effects that act like an SSRI/anti-depressant, so you get both the opiate withdrawal symptoms as well as SSRI discontinuation syndrome symptoms which is a very unpleasant combination.

It's a decent painkiller, but like any opiate based pain medication has potential for abuse.

I think I read about seizures from cold turkey which required a 35 week long tapering schedule to avoid. Checking for a source I don't find this mentioned in official side-effects, only less formal guidance for addicts. Strange.

Seizures can also be caused in "overdose", which is unfortunately very very close to "recreational" doses. It's a very very weird drug in terms of secondary side-effects, the "SSRI" side can cause dangerous issues as well (serotonin toxicity when coupled with other serotonin affecting drugs).

Tramadol, like several other opioid drugs, e.g., hydrocodone and oxycodone, has been increasingly associated with dependence in recent years, so have been rescheduled to a more highly controlled classification by the DEA/FDA.

This is not a new phenomenon. Many opioids, including heroin, when introduced where thought to be "less addicting" than older opium-derived drugs. Of course, this turned out to be mistaken and now it's being played out with several "less addictive" opioids in common use.

I certainly wouldn't regard tramadol as innocuous, besides abuse and dependence, it can also have serious interactions with other medications, particularly serotonin overload which can be deadly.

Hoops are good, yes, and I don't disagree with the decision to reclassify it. The extra time and expense of new doctor appointments, urine tests, pill counting, questioning, etc. for someone who has been on the drug responsibly for a long time can just be aggravating.

That does sound a bit much. In the UK we'd expect free healthcare and doctor's appointment for re-ups.

> Natural products chemistry is getting trickier all the time

So now there's "natural" chemistry and "plain" chemistry? I thought molecules are molecules, and don't care how they came to be. What if humans were to artificially select some bacteria over a few generations to synthesize a certain molecule. Would that molecule now be "natural" or synthetic? In fact, it can be argued that many "natural" molecules are a result of that exact process, because their synthesizing organism has evolved to survive human effects.

EDIT: as pointed out by localhost, natural products chemistry is actually a well defined -- and widely accepted -- term.

Natural products chemistry is a very old branch of synthetic organic chemistry. See wikipedia article: http://en.wikipedia.org/wiki/Natural_product

If you do a quick search for Natural Products in Google Scholar, and you'll see that this is a widely accepted term in organic chemistry.

Now, what you're saying is something that generally irritates me to no end - differentiating between "synthetic" and "natural". An alkene is an alkene, regardless of whether it was synthesized by a natural process or in a reactor.

In fact I’d half-expect that synthetic products be generally safer, since you know exactly what you’re making and the extent to which it may be adulterated. If I want to eat everything that comes from the vanilla bean, I can buy extract. But if I want just vanillin, I can buy exactly that.

Natural products can be produced via a wholly synthetic method, they're just compounds which are also produced by non-human bits of nature.

Oh. I stand corrected.

Well, there is natural products chemistry, which is anything that is produced directly from biology. It is a useful thing to keep track of as if something complex is being produced by a biological process you can hook into it for precursors to make other complex molecules more easily. You can also completely synthesize a natural product and it doesn't stop the status of the chemical. All the name means is that it is known to be existent as the output of a biological process.

Yes. "Natural" flavoring often means something manufactured by a genetically engineered bacteria.

So, no organisation took samples of these trees/seeds to cultivate and study elsewhere and wondered why they weren't getting the same results!?

Cultivating the plants in a lab to study would have been a lot more difficult than what was actually done in this attempt to replicate the results, which was to just take samples from more than one region.

Guys, that was a genuine question so why the downvote?

I'm not a scientist and really can't understand why no-one wouldn't have done a controlled test or comparison in laboratory conditions.

Laboratory tests are expensive and time consuming and in this case completely unnecessary. Why would anyone do such an experiment?

Although the original paper only described the biochemical analysis they performed, it seems that cultivating the plants in the lab was planned for their future work, with the intent of figuring out the biosynthetic pathway by radiolabelling possible precursors.

Good point - as I said, I am not a scientist, so that's what I wanted to know and your answer helps me understand.

In my mind, it seems like declaring that a plant is growing gold, without testing the ground (or doing a lab test), and later finding out that its roots are picking up the gold from a seam near the surface.

At some point you have to stop. For examples: what was the geological reason for the gold seam? What is the transport mechanism from the roots to the rest of the plant? What is the evolutionary advantage to grow gold? What are the genetic differences between that plant and similar plants?

It's impossible to cover everything, so you have to get an idea of what's interesting enough to publish.

Then when you do submit it for publication, the reviewers will say "have you tried X?", where X is something which takes a lot more time and funding than you have, and you really just want to be done with the paper.

As an aside, carrots are a plant that takes up gold if given the oportunity.

Is there anywhere that one could read more about this?

I got it from Bob Cannard's lecture at Berkeley's Edible Education series 2013

Bob's - http://vimeo.com/album/2192316/video/51178467

The whole series - http://vimeo.com/album/2192316/page:2/sort:preset/format:thu...

I've just watched it again to double check, it wasn't a chore.

This year's - http://edibleschoolyard.org/library/edible-education-101-ris...

This drug is absolutely awful.

I had an abscessed wisdom tooth and was prescribed Tramadol for pain management while I waited for an appointment to get teeth extracted.

Not only did I feel like shit all the time, when I tried to stop taking it, I couldn't sleep at all. It was entire nights of frustration, tossing and turning. I was only taking 100mg a day to just get through work and whatnot too.

I decided to do some research and I read about people taking upwards of 700mg to 1000mg a day because of addiction. I can't imagine being addicted to this drug. It makes you feel foggy, your throat burns, you have headaches...

I've been sober for most of my life. I've never drank or taken prescriptions recreationally. So this experience was pretty terrible.

I give my aging lab Tramadol. It is easier on his liver than other painkillers. Vets routinely proscribe Tremadol as a painkiller to animals after surgery, as it's not hard on their organs.

But that doesn't mean you should take it. Stick to beer.

How are the farmers obtaining such large quantities of Tramadol?

they buy it. ag drugs are not very heavily regulated.

Tramadol is a low-grade narcotic, not an AG drug. Unless I'm missing something.

Could you expand or provide a link?

wtf are anti-depressants being given to cattle?

Tramadol is a painkiller, not an anti-depressant... but the question remains.

It's both a painkiller (mu-opioid agonist) and an anti-depressant (SSRI, or possibly SNRI style effects). The fact that many people - including many doctors - ignore the latter effects is, in my opinion, criminal negligence. The SSRI effects are NOT trivial, and last days compared to the "hours" of opiate effect you get.

Even worse, the "M1" metabolite of tramadol is itself an active drug in similar ways, and metabolized by the same P450 liver enzyme. So the rate the drug leaves your system is a nasty differential equation as it competes with itself for the the same enzymes. That equation gets even more insane if you have anything else in your system that interacts with it, even slightly.

Note: I'm not saying it's necessarily a bad drug - the SSRI effects by themselves can be useful for certain types of pain (neurological pain in particular), so it may be a better choice than morphine/{hydro}codine in some cases. People just need to be aware it's not a "trivial" drug, that it can interact with many things, and has more effects than the usual painkillers that may be contraindicated for some people.

Probably the same reason chickens are fed anti-biotics... to increase yields.

In the case of chickens... antibiotics keeps them disease free and promotes growth. Cows milk production is negatively affected by stress and unhappiness. Painkillers help keep them happy.

Tramadol is being investigated as a potential anti-depressant as withdraw symptoms mimic withdraw symptoms of SSRIs

[off topic] Wow, his last post created some bizarre drama on Reddit:


His criticism of a biotech CEO provoked a Reddit thread with two thousand comments, and the CEO showing up to write responses. And controversially the whole thing was removed by moderators, and Dr. Lowe briefly banned from the site.

Would you mind linking to the thread? I know it's been removed, but I'm curious which subreddit that happened in.

Also, did anyone ever explain why he was shadowbanned? Only Reddit admins can shadowban someone, and I thought they only issued bans for vote manipulation, not for causing controversy.

> Only Reddit admins can shadowban someone

I'm a mod of a default subreddit. We can't shadowban people from the entire site, but we can use AutoModerator to moderate comments and shadowban users in a specific subreddit based on certain criteria (e.g. one day old account with negative comment karma or if account mentions certain keywords) or by manually adding a user to a shadowban list. This is separate from reddit's built-in subreddit ban, which is much more obvious.

It's possible (and sounds a lot like) he got banned/shadowbanned in /r/news and the mods there thought his self-promotion went too far and got reported for spam to maybe be banned outright from reddit. That seems excessive though. I usually just tell people to do a better job contributing to reddit if they're being spammy, and I only report people when they're creating new accounts to harass others.

I don't mod a default, but in my experience it's historically been really easy to get someone shadowbanned for self-promotion by submitting to r/spam. I don't know if it's run by a script or just overworked interns, but anyone technically breaking the 20% rule over any period of time has tended to get the axe without consideration of mitigating factors (celebrity, posting to subs that encourage self-promotion, etc).

I don't know if that's changing with the drama over r/gamedeals company reps being repeatedly shadowbanned for trolls submitting them to r/spam, but not optimistic.

Someone might want to message the mods of whatever subreddit he was banned from. I don't know enough about the situation to feel justified in doing so. But I checked /r/spam, and found this:


Couple of very high karma users who sound like domain experts vouched for him.

That said, it doesn't look like he was shadowbanned sitewide. Most likely an automoderator action. I can still click on his user profile.

Edit: unrelated, but how do you generate a submission history for a user? I'm a mod of a smaller sub, that looks like a useful tool.

He used multiple accounts to vote-ring.

I highly doubt that a doctor who was receiving massive traction on reddit would stoop so low as to fake-upvote his own article.

> massive traction

For an example of one accused of such see [0] [0] http://en.wikipedia.org/wiki/Unidan

I know HN likes making endnotes and 0-based indexing... but this seems excessive

...and something of which I'm apparently very guilty[0] [0] https://news.ycombinator.com/threads?id=mendelk

Unidan has his own Wikipedia article? Wow, I didn't know the whole thing got well known enough for that outside of Reddit.

Vote rings can also downvote other articles.

What's your source?

My first thought would not have been, "Wow this tree's producing tramadol." It would be, "Wow this tree's contaminated, I wonder how?"

You could easily argue that everything that ever was or will be is natural, not really sure why the word is still used to describe products.

Hydrogen, oxygen, and nitrogen are natural. But this arrangement of the atoms does not occur unless humans want it to. https://en.wikipedia.org/wiki/Tramadol

Eh. If you leave hydrogen alone for long enough, it will turn into tramadol.

Yes, but you'll need a lot of it. Even a full universe sample takes almost 20 billion years to synthesize a relatively small amount.

And that was with a helium booster, along with a smidge of lithium. My guess is that with only hydrogen it would have taken even longer.

Yes that's what I'm saying, "unless humans want it to" still qualifies as natural. Humans are natural and a part of nature and so anything they create is as well.

If a beehive or beaver dam is considered natural then so is the empire state building, all three were created by animals native to this planet.

Sure, you can redefine the word in a way that makes it meaningless. Or you can use it the way the rest of the world does - where "natural" means "not the result of human intervention". By that definition, it's obvious why a beehive and beaver dam are "natural" and the Empire State Building is not. There is a degree to which this focus is arbitrary, but given that we are humans, it's sometimes a worthwhile focus to have. That in turn, of course, does not mean it's correct to care about it everywhere we seem to.

Zhuangzi had something to say about this:

'What do you mean,' pursued the earl, 'by the Heavenly, and by the Human?' Ruo replied, 'Oxen and horses have four feet - that is what I call their Heavenly (constitution). When horses' heads are haltered, and the noses of oxen are pierced, that is what I call (the doing of) Man. Hence it is said, "Do not by the Human (doing) extinguish the Heavenly (constitution); do not for your (Human) purpose extinguish the appointment (of Heaven); do not bury your (proper) fame in (such) a pursuit of it; carefully guard (the Way) and do not lose it: this is what I call reverting to your True (Nature)."'

— Zhuangzi, chapter 17 (“The Floods of Autumn”)


That's the point, it is a meaningless term.

No. The way most people use the term it has a meaning. It's the redefinition that is meaningless, and should thus be rejected as useless. That doesn't mean that people always reason correctly about it, but that should be confronted directly not by playing semantic games.

You have redefined a word to be entirely useless and then get upset when other people don't subscribe to your new definition of the word.

Doesn't that devalue the term if everything ever is 'natural' making it impossible for anything to be unnatural?

more importantly, the use of "natural" to describe a product with the implication that it being synthetic would be a bad thing is a fallacy.

Still, there is something nice about a chemical appearing in nature. Gives evidence that it doesn't do batshit crazy things to life.

Have you heard of the very natural Oxygen Catastrophe[1] that wiped out much of the life on Earth? Some organisms began dumping a toxic chemical (oxygen) into the atmosphere in such large quantities that it practically killed off everyone except for those weird mutants that evolved to actually breathe that dangerous toxin synthesized by the killers!

[1]: http://en.wikipedia.org/wiki/Great_Oxygenation_Event

Right. Oxygen was very bad for life when it appeared. Oxygen is good for life now, that evolved in its wake. I don't want massive quantities of stuff appearing that is bad for life now.

But that "bad stuff" is just as likely to be a natural product (as was oxygen during the catastrophe) as it's likely to be synthetic.

Yeah yeah it's not 100% but it's still reasonably strong evidence. If you find something in a plant that's eaten by many things then it's probably not very toxic.

Maybe that's some evidence, but it's certainly not reasonably strong (in fact, it's very weak evidence). First, some of those "many things" would need to have a metabolism that's close to ours. Secondly, even if those unaffected organisms are similar to us, we would need to consume that molecule at similar concentrations. Most toxins have adverse effect only beyond a certain dosage. Something can be harmless (like cyanide) in it's "naturally occurring" concentrations, and positively lethal in higher doses. Besides, synthetic molecules are tested before they're approved for human consumption, and they are usually tested on animals with similar metabolism to us, and at the appropriate dose. So actually, FDA approval is a much, much, much stronger evidence for a drug's safety than it being extracted from "nature".

'toxic' is a much weaker assertion than 'does batshit crazy things to life'

That idea might make you feel better, but it's not grounded in reality at all. Chemicals appearing in nature do batshit crazy things to life all the time.

If by "batshit crazy" you meant toxicity, then yes that's clearly incorrect, as others have repeatedly pointed out. Perhaps you meant chemical affinity in some general way --eg homochirality, or presence of commonly targeted functional groups?

If so, note this is the exact opposite of 'biocompatible' in the usual sense (as in 'inert'): biosynthesized molecules evolved precisely to be exceedingly good at reacting/interfering with biological processes, not the other way around. So if anything, it would be evidence they could well do batshit crazy, unintended things to life --as they often do.

Because no naturally occurring substances do batshit crazy things to life? It's all about the dosage.

Exactly, cyanobacteria are also natural as is tobacco. One can synthesize many natural products in purer and safer forms.

Cigarettes are very far from just dried tobacco leaves, as they've been engineered to maximize addiction with additives.



Agreed. "Organic" is pretty widely abused, too - want to drink some crude oil? It's organic...

Crude oil is [primarily] organic if your context is [petro]chemistry. It's not an organic foodstuff however.

Shock, horror, words have contexts which cause them to mean different things.

Why is it that you don't wish people to know where their food has come from and how it has been produced. What is the problem with that for you? If you don't care that your children's food is saturated with growth hormones, fungicides, hormones and pesticides or that the farmers you buy from use so much Tramadol that the environment tests positively for it [as in the current case], fine, but why does it matter so much if other people want to know the conditions their food has been grown in? Say, by looking for organic food certifications. [There see I included "food" in case it confused you, words can be so hard, huh.]

There's no great logic to the insistence that words can't be used for multiple well defined meanings - yes even in associated fields like chemistry and food science/agriculture - and AFAICT there's no detriment to you in others choosing to care more about the rearing or growing conditions of their food (which you don't have to eat).

So what is your problem?

"Shock, horror, words have contexts which cause them to mean different things."

Dunno what his problem is, but my problem is the context in which "organic" gets used with respect to foods: a massively expensive, misleading, anti-science marketing campaign by huge corporations intent on profiting from people's mistaken belief that "organic" products are--by virtue of being "organic"--healthier or better for the environment.

Since the people behind this huge corporate marketing campaign are also promulgating lies about GMOs in an attempt to force labeling on them and prevent their development, your claim "there's no detriment" to others from those who support them is false.

>an attempt to force labeling on them and prevent their development //

Labelling only provides people with the ability to chose. Against choice? Consumers can make uninformed choices, sure, but that choice is central to a democratic system.

Who are the corporations that you're referring to? The majority of organic stuff we get in the UK is from small corporations or local farms, it is the bigger corps that stand to lose most from a desire from the public to have organic (and similar ethos) production of food. For example factory farming chicken relies on being able to pump them full of antibiotics.

You say it's a mistaken belief that organic food is better - the meta-studies I've seen seem to flip between the two positions pretty rapidly. Can you cite maybe one or two studies that you would say show incontrovertibly that organic production is no better for people, animal welfare and/or the environment? Thanks.

I'm not the parent (I'm GP), but my position is that organic certification is good, but the universal association of "natural = good, synthetic = bad" is only harmful.

Yes, farmers pump animals full of chemicals and this should be documented and, if you are concerned about this, it's a good thing that there are organic food certs out there. However, whole industries fuelled by bullshit have sprung up off the back of this very common fallacy. There are people out there who don't take scientifically-proven medicine because it's "not natural" and lean towards quackery like homeopathy, and this is what I'm opposed to.

To reiterate, IMO organic or free-range farm produce is a good thing and I'm sure most people would agree with that. That's not what I was talking about so don't get rude with people based on a misinterpretation of the subject, it's unnecessarily disruptive.

I think you're casting me as a proxy in a larger argument.

You're also being pretty insulting about it.

Life's too short. I've no time for people like that.

Can't speak for the GP, but in my case, I object to laws requiring labels on GMO, etc. foodstuffs simply because I don't want to live in California, where literally everything has one or more dire warning labels attached to it. When everything is dangerous, nothing is. The labels end up not being taken seriously, and the consumer ends up less-informed than they otherwise would have been.

"Literally" applies, by the way, when the whole building you're in has a sign in the lobby that reads "This building contains substances known to the State of California to cause cancer, birth defects, and itchy rashes."

I'm worried that this is where the slippery slope of GMO labeling will lead.

So the solution is to label nothing, and actively mislabel everything? That doesn't sound right.


No, you label things when there is scientific evidence, of the peer-reviewed and -reproduced kind, that there is a non-obvious risk associated with a given foodstuff or other item. GMO labeling falls well short of that standard.

The idea, I think, is that humans have been sharing the planet with everything else for so long that anything especially dangerous that occurs "naturally" is likely to have been already tested- ie "artificial" drugs should be more unpredictable, and therefore potentially more dangerous, than whatever stuff some exotic culture has been fucking with for hundreds of generations (which is pretty much any interesting compound you can find "naturally").

Of course, unscrupulous-types will lean on whatever marketing stunt they feel will sell some short-term product, with little respect for the long-term dangers/benefits, so naturally words like "natural" and "organic" get abused.

Alcohol is natural, and dangerous. But at least we know the long term effects.

Applications are open for YC Winter 2022

Guidelines | FAQ | Lists | API | Security | Legal | Apply to YC | Contact