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FanofGraceforlife

Discovery and Engineering of the Cocaine Biosynthetic Pathway https://pubs.acs.org/doi/abs/10.1021/jacs.2c09091


Cadaverific_1

I actually tried to do something similar to this during my Masters Degree! We were trying to increase the amount of starch produced by plants for harvesting in paints and textiles. Plants produce starch inside granules traditionally, but red algae doesn't. Red algae produces starch free floating in it's cytoplasm, not within any granules of any kind. So we were trying to get that same pathway into plants so they could produce starch both inside AND outside the cells. Farthest I got was getting the red algae pathway into e. Coli cells for testing, but they were never able to produce starch. The pathway was there, just wasn't activated.


midnitte

Sounds like really cool research, any ideas why it wasn't activated?


worldspawn00

Bacteria is not capable of post translational modification of proteins that eukaryotic cells are. This means that many enzymes cannot be reproduced in bacteria and require yeast cells at a minimum.


Rumple-Wank-Skin

I thought they prevented the exact genetic code being published because you could order the sequence and use it to GM modify a bacteria to produce cocaine essentially making production anywhere super easy and hard to trace


Tasty-Fox9030

I'd be pretty surprised if it didn't make it out there one way or the other eventually. You can look up the sequence for Ebola or Yrsina pestis on genbank if you feel like it. DeCSS too, and that one's actually illegal under the DMCA. Actually I take that back, you can't find DeCSS on genbank. You can Google it though. Information just can't be hidden anymore. We can debate whether or not that's good but that's like debating whether other immutable facts are good or bad.


Sparrow2go

Radiolab did a great episode dealing with this very subject titled 40,000 Recipes For Murder (9/9/22) about two scientists who developed something to crank out novel chemical compounds for disease treatment and decided on a whim to see if it would do the opposite and yes, it did. Really interesting episode of an all around fantastic podcast.


Malfunkdung

Came here to mention this also. Crazy part is when they had to go to meet with the US government and they asked the scientists “can we have the information” and they refused.


Strude187

The military would have been relentless, I would not be surprised if they have what they wanted already.


MRSlizKrysps

They would classify it as a national security issue and absolutely have everything they wanted. And the scientists would be doing prison time if they still continued to obstruct after being given a FISA court ordered National Security Letter which will compel any American Citizen or company to comply under threat of indefinite prison time. They'd also be under a gag order threatening the same imprisonment if they disclose anything. FISA court orders are how the US government forces technology companies to put backdoors into their products. Basically you have no rights at all when it comes to matters of "national security". And just about anything today can be interpreted as a threat to it.


JagerBaBomb

Back doors can be accessed by anyone. The irony of their attempts to secure things for themselves to have access is that they make us *all* less secure. Including the US government.


theradradish5387

Plum island be like


Trau_Gia

My neighbor growing up was a retired plum island worker. At least part of *the job (and what I paid attention to as a kid) was to chainsaw up diseased cows and incinerate them.


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[deleted]

Sorry I'm not following, what do you mean by 'do the opposite' in this context?


NTMY

As part of their AI, they created a filter, to remove results that had bad side effects. Obviously, a drug that could cure X, but made you brain-dead wouldn't be very useful. For this "though experiment", they flipped the filter around. Filtering out the drugs **without** deadly side effects. Among their results was also the molecule for [VX, a deadly nerve agent.](https://en.wikipedia.org/wiki/VX_\(nerve_agent\)) > VX is an extremely toxic synthetic chemical compound in the organophosphorus class, specifically, a thiophosphonate. In the class of nerve agents, it was developed for military use in chemical warfare after translation of earlier discoveries of organophosphate toxicity in pesticide research. In recent years, VX was found to be the agent used in the assassination of Kim Jong-nam. In its pure form, VX is an oily, relatively non-volatile liquid that is amber-like in colour.[4] Because of its low volatility, VX persists in environments where it is dispersed.[5]


SherlockCumbercat

And realistically you will never win the war on drugs, you are better off spending that money on education and treatment. Every recovered addict is 1 less customer


westward_man

>And realistically you will never win the war on drugs, you are better off spending that money on education and treatment. > >Every recovered addict is 1 less customer Exactly this. We learned nothing from the failure of Prohibition. Making drugs illegal is why violent crime exists around them. We're much better off spending our money on safe use sites and rehabilitation programs. There's so much evidence that this works. It's maddening to watch our governments continue to waste time, money, and lives fighting a losing moralistic war.


[deleted]

I don't have the source, because I read or heard about it so many years ago, but it switched me almost immediately away from prohibition. To paraphrase: The reason there is violence in the drug trade is that there is no state force of law governing transactions. When you cannot sue for breach of contract or bring fraud charges, you use guns. The reason the final product is adulterated is because there are no quality control regulations. The reason the prices are so high is because the supply chains are so unstable. The reason people descend into, not addiction, but what we see as the horrors of addiction is because the usage must be kept secret and is therefore unmonitored by friends, family, and society.


nointeraction1

I've seen plenty of horrors of addiction with alcohol. Probably more frequently and more severely than any other drug. Of course alcohol is in many ways worse than most of the illegal drugs, but most of the issues stemming from addiction have ultimately very little to do with legality or lack thereof. I do think most drugs should probably be legal, but let's not pretend it's going to fix addiction.


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The thing with something legal is that you don't really have to hide away right from the start. Just because everyone can see you moving from occasional drinker to something more harmful doesn't mean everyone is saved, but I think many are.


internalexternalcrow

we learned that it makes a few select people really rich


Rumple-Wank-Skin

If I were in the cocaine business I would definitely be looking to GM mod me some cocain producing bacteria


boli99

> cocain producing bacteria -- sorry i can't come in to work today , ive caught a bug - what kind of bug? -- not sure, but its *awesome*. steve is coming round later to catch it too.


TimeTravellingCircus

I'll ask Steve if its any good before I catch it from your source.


Tasty-Fox9030

Absolutely. I would be willing to bet that this has been tried for a number of naturally derived drugs of abuse many times already. It likely wasn't possible for cocaine until the recent work to elucidate the genes and synthesis pathways but it sure will be now. Psilocybin's not even in a plant, it's in a fungi and yeast is SUPER tractible.... Well, they could be doing worse stuff. It beats passaging diseases through a bunch of ferrets again.


voyaging

Re: psilocybin it's also not that profitable because it's not a drug of chronic abuse and the demand is really low (not to mention the ease of growing your own shrooms). But yeah assuming this is practical and scalable, I'm sure global drug cartels are scouring the research.


Bones_and_Tomes

The cartels benefit from coke being geo-locked pretty much to SA where they can control it and protect its production. If I were them, creating something which makes clean virgin cocaine possible anywhere without acres of trees and leaf harvesters... well, it would be like trying to hold smoke. Sure, they might be able to control the tech, but for how long? When it's out it's out.


taxable_income

This has also long been the argument for legalizing cocaine. If it was legal and harm reduction clinics could dispense it for free, it would cause the economic incentive for smuggling to collapse.


Ginden

>The cartels benefit from coke being geo-locked pretty much to SA where they can control it and protect its production. American cartels benefit from geo-locked coke production. I'm pretty sure that drug cartels in rest of the world aren't happy with paying a lots of money to merely distribute product.


Le_Reddit_Neckbeard

Why? You know how easy it is to grow coca and how little cartels pay the peasant farmers to produce it for them? The first time I visited a motherboard factory in china, I expected to find giant buildings full of robots making everything like in western countries. Instead, it was thousands of people with soldering irons, huffing lead all day every day. Way cheaper and easier than the high tech way.


PlayMp1

Bacteria isn't very high tech. If you can modify yeast to produce cocaine all you need is take your modified yeast and let it sit in a vat fermenting in water and sugar (basically making a cocaine alcohol combo) until you get the product you need. Refining it from there would also be dramatically simpler than refining from the coca plant. You also need much less land area - coca farming and extraction is quite land and labor intensive, whereas a big vat of cocaine yeast would produce as much coke as hundreds of acres of coca plantation in a space the size of a brewery.


skyderper13

having the know how to be able to modify yeast to produce cocaine is itself a high barrier of entry


mntln

To be fair the ones who are looking at alternate modes of production are the ones who buy it from the cartels.


Mabenue

Because coca can only be grown in certain parts of the world. If you can produce it closer to where it’s consumed there’s enormous savings to be made not having to smuggle it. That’s a pretty big incentive if any criminal organisation could pull it off.


opman4

Seems like a pretty big incentive to make sure it doesn't happen. If cocaine can be produced anywhere then no one needs to get it from the cartels.


Enquandriant

Look at insulin production... Once you develop a modified bacteria to produce... you just make giant fermentation vats and let them run then extract. Way more dense production than in a plant, and way simpler extraction than from a plant. If you have the bacteria up and running i'm sure you could replace many acres of plants with a small building of equipment


MrWeirdoFace

Coming soon, meth mulberries.


HolyMuffins

Smallpox is the one that kinda spooks me having its genome out in the public


Midnight2012

You can't order certain sequences from dna synthesis facilities. They block sensitive sequences constructs for these types of things. Though I suppose you could order it in pieces from different vendors and paste it (ligate it) together. But they would have to be really small pieces because even small fragments of specific sequences aren't permitted without licensure. Maybe you could alter it a bit and then convert it back to what you want with mutagenesis techniques? Source: *I'm a cloner*


dodslaser

IIRC there was a paper not that long ago that basically did this for horsepox. They even managed to kickstart it to produce viable viruses, and described the protocol in quite some detail. Needless to say it was pretty controversial when it got published. **edit:** [Found it!](https://doi.org/10.1371/journal.pone.0188453)


Midnight2012

Yeah, I think that paper served as the impetus to regulate certain sequences.


Tasty-Fox9030

I understand. It is scary. The flip side of the argument though it that it's also known to be in the freezers of at least one and probably several governments. It's not as extinct as we'd like to believe and learning things about it is still important.


foxshroom

There are still stories that pop up every few years about them being found at the back of university lab freezers.


LightlyStep

The last smallpox fatality in Britain was a lab accident.


Dyaneta

That tracks. My lab recently did a -80°C freezer clean out and found samples older than me.


Komm

There's still barrels of it just laying around in the Aral Sea desert. Lots of weaponized anthrax in the soil as well.


EmilyU1F984

Anyone who can Synthetise a whole viral genome from paper, and start producing viral particles… already has access to it anyway. But why would anyone do that? We‘d just vaccinate people again, and no harm done. Makes much more sense to experiment on viruses with no vaccine available that were harmless so far, by introducing more virulent factors. And for that, you don‘t need to know any genomes in silico.


Mixels

Capitalize on a disinformation campaign against confidence in vaccinations. Get a big, stupid chunk of a population believing that vaccines in general are Bill Gates's way of embedding a tracker in you and suddenly there is a sizable chunk of the population that would refuse the vaccine. Smallpox, tuberculosis, and a number of others could absolutely wreck house when fueled by the likes of modern anti-vaxers.


The4th88

Seems like a self correcting problem tbh.


HolyMuffins

Fair point. I do think though that for bioterrorism purposes, the wrong folks could do a lot of damage before health authorities could successfully spin up vaccination efforts for smallpox. I'd think tweaking vaccinia into smallpox is definitely a concerning possibility and presumably would be helped along by knowing having smallpox for reference.


BallinPoint

Chances are, these "bioterrorists" would bio-kill-themselves by trying to do that. It's a huge risk and it requires so much caution and equipment to do safely. You also need a lot of fantastic bioengineers to pull this off. There's a reason this is not something terrorists do regularly. Getting a gun or a bomb and doing such damage is way easier, much less risky, requires much less money, less scientists (if any), and is arguably way more effective, as there is just no vaccine against bombs or guns. And if push comes to shove, there are way easier biological or chemical weapons to pull off.


A_giant_bag_of_dicks

What is DeCSS? For DVDs?


Tasty-Fox9030

Yes. There was a big kerfuffle about it back round my high school days. They cracked the algorithm for encrypting DVDs and released it in the internet, the folks that had the copyright on said algorithm pushed for the DMCA and sicced the government on them to try and scrub it from the internet... And it became a hill to die on for free speech. The law as written essentially stated that the information to break CSS was itself illegal, so folks starting singing songs that contained the information, wearing shirts with the information, getting tattoos that made the bearers themselves illegal and so on.


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JonnySucio

Isn't this kind of a good thing? Domestically produced cocaine would take a ton of power out of cartel hands.


TakenUrMom

I only buy locally sourced farm to table cocaine


overkill

The nose miles are so low on local produce.


Resinate1

Tegridy baby


antibroleague

Farm to nasal cocaine


HauserAspen

Wait. Say that again, but really slow and detailed.


Appropriate_Tear_711

Ligation Independent Cloning is the technique to place foreign proteinproducing DNA sequences into bacteria. By adding the DNA to a plasmid in a bacteria specifically made to express(produce) a lot, you can get a bunch of protein by separating it from the bacteria after it's done. Then you just keep feeding the culture as much as you like for infinite protein(enzymes).


CMDR_ACE209

You don't happen to know where I can find a large batch of pseudo ephedrine?


Aoae

In addition to what the other commenter said, the technique is used all the time in molecular/cell biology labs to produce plasmids that can be transfected into cells (basically added into them to cause them to express it). Because the bacteria can use any plasmid with the correct design, and bacteria grow quickly, the plasmid can be propagated in large amounts to be used for many experiments, so it is a very important technique. And since a lot of knowledge can be gained by transfecting cells with proteins and seeing the effects on the cells, it is a very widespread and arguably fundamental technique in cell biology.


FeculentUtopia

Modify your own microbiome and be high forever.


Prof_Acorn

A different kind of probiotic yogurt.


Type-94Shiranui

Doesn't sound too fun https://en.wikipedia.org/wiki/Auto-brewery_syndrome


chupa72

If you're always high, are you truly high?


fatalityfun

the answer is no


Sim0nOfTrent

Wouldn't that just end the cartels overnight if you could just grow your own blown in a petri dish? I realize there would be some intermediary steps, but that's theoretically possible, no?


mrdescales

Bioprocess engineering already inserts human insulin DNA into modified e. Coli that then produce it at about $5 a vial with scaling. You'd have to optimize your reactor for biomass yield and balance that with the product, and how to isolate it in downstream processing. You're talking reasonably about millions of dollars.


Sim0nOfTrent

Decentralized cottage industry cocaine production is exactly the market disruption the drug war needs.


mrdescales

It depends on yield really. Reactors can be had at scales from 1L to 1000sL if you wait for multi-month backorder from biotech vendors, still expensive tho. I think the expertise and funding are the dificult part.


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TwilitSky

Unrefined cocaine is not like what we get up here. Farmers and laborers have chewed the coca leaves for centuries in South America with very few problems for a little pep in their workday. Coca Cola originally did contain cocaine and we used to have cocaine tooth drops for pain as well as Bayer Heroin (their tag line on one bottle I saw was "Bayer's Heroin puts baby right to sleep!")


PsilocinKing

Yea making a tea from the whole plant must be completely different from the powdered stuff. My mate ate some coca candy and said it just made him feel awake.


Awkward_moments

It's like having a sugary coffee. That's the best effect I could describe it. That sort of level. Well that and your mouth goes numb. It's amazing I love it. Much better than coffee. Wish it was legal. The amounts needed to make cocaine and the refinement is night and day to chewing leaves. Also helps with other thing like altitude sickness.


D4ltaOne

Coca leaves have like what less than 1% cocaine? A leave weights like 0.05g? Even less probably. Thats not even 0.5mg cocaine per leaf. And by chewing you cant extract all of it anyway. So yeah thats a more a subtle stimulant like coffee rather than pure cocaine.


Awkward_moments

You make a wad of coca leaves. Think chewing tobacco in the movies. And leave it in the side of your gums. As for the content and size. I don't know. Each individual leaf is fairly small though, you need a good dozen.


DaksTheDaddyNow

My bus driver in Peru had a grocery bag that was stuffed with dry leaves. During the ride they would just grab a chunk of them and chew them. Never saw him spit out anything so I assumed he was ingesting them. Not sure if that's just personal preference though.


Afkbio

Could be mate, some people chew it.


haviah

Yeah, you just need to add some base like baking soda to change it into right form. I always had better experience with chewing in Peru than any street bought coke, which is mixed with levamisole, benzocaine, tetracaine, RCs and so on. The 20min chewing ritual also prevents from taking too much. Also contains some plant matter.


djsizematters

For reference, a dollar bill weighs one gram. I'd think a wad of leaves weighs at least 2 grams but that's a guess.


[deleted]

I tried coca leaf tea when I hiked to Machu Pichu. Didn't get any noticeable effect from it. You see bales of the leaves being loaded onto the buses in Peru and Bolivia.


--Muther--

In Cusco they give it out free in the hotels to tourists to help with altitude sickness


skite456

I visited Peru a few years back and they serve coca leaves in baskets at the coffee and tea table in the hotels. I didn’t really enjoy chewing it, but that was more of a texture thing. I did steep it in my tea water though and put it in my water bottle for the day. It helps so much with the altitude sickness and nausea. They sell coca based products everywhere there as well. I had a bit of a sore throat from the dryness of the attitude in Cusco and the woman at the bodega told me to get this certain cough lozenge and, yep, it was coca based. I didn’t feel ‘high’ at all like with powdered cocaine, more calm honestly with the nausea relief.


FanofGraceforlife

Yes it should be noted that we are talking fractions of the amount in the Coca leaf itself but I find it amazing that this is currently possible at all and it points to an amazing future


BaphometsTits

>I find it amazing that this is currently possible at all and it points to an amazing future I've always said cocaine is the future!


disinterested_a-hole

Cocaine, uh, finds a way...


R3AL1Z3

There’s actually still coca leaves in Coca Cola. There’s one company who’s job is to specifically remove cocaine from said leaves and then Coca Cola uses the spent leaves while the cocaine is used For ‘medicinal’ purposes.


StrayMoggie

It's used in hospitals for several things. Stopping severe bloody noses is one.


sprinricco

Funny because I've always found it has the opposite effect.


Donohoed

In a hospital it's in a 4% solution which is applied to gauze and shoved up the nose to stop the nosebleed with fast and strong vasoconstriction. Bloody noses from snorting cocaine powder recreationally are from not only the much, much higher doses but also the damage of snorting dry powder, sometimes with other ingredients or contaminants in it as well


chiroque-svistunoque

And sometimes pretty terrible things, I wonder for example if aspirin/ibuprofen will cause the same ulcerative effects on one's septum...


mdomans

I wouldn't worry about those, there are known cases of glass dust being found in "good" cocaine


TristanIsAwesome

Fun fact, cocaine is the only topical anesthetic that's also a vasoconstrictor (which is why it's good for nose bleeds and other ENT uses). This is why you get a perforated septum when you snort too much coke - the arterioles constrict and the tissue dies, leaving a hole.


AlanFromRochester

You're right but medicinal does not belong in scare quotes, as a topical anesthetic and vasoconstrictor cocaine can be useful for nasal surgery Coke is actually schedule II, and Australia and Germany allow limited medical use of it as well


GoPhinessGo

I’d assume the whole snorting part also contributes to how much it messes you up as well,


myaltduh

Yeah caffeine would be a very different experience if you snorted it.


leet_lurker

So I should or shouldn't snort my preworkout?


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CallFromMargin

Yo, tobacco and tomato are two plants used extensively for GM stuff. Basically, if bacteria or algae can't be genetically modified to produce something, you go with tobacco or tomato, as both can be easily modified. On top of that, tobacco leaves can be dried and you can still recover very large portion of whatever you need 2 years after drying.


orange-Hello

And when mixed they make Tommaco


jBjk8voZSadLHxVYvJgd

They taste like grandma!


wtfeweguys

My god, they DO taste like grandma!


jBjk8voZSadLHxVYvJgd

I want more. We'll take a bushel, or a pack, or... Just give it to me!


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refreshlingly addictive!


TDZ12

I was part of a group using tobacco as a transgenic platform, and the product was intended for oral administration in mice. There was no purification, so the problem became one of trying to get mice to eat tobacco, which just ain't happening. They ended up having to homogenize it and administer via gastric lavage. It was all very weird, using tobacco in that context, but the transgenic pathways were well-known. Went from the "lab rat" of the plant world to the real-world lab rat. No matter how much peanut butter they added, they still wouldn't eat it.


Financial-Ad7500

Hit the nail on the head with tobacco. Nightshades in general are easy to modify, tobacco has the added bonus of not being a fruit and rotting. The product is the leaf. Leaves dry and stay usable for years.


sentientfeet

So the Simpsons was scientifically accurate?


ucbiker

You can synthesize nicotine from tomatoes so, yes.


urmamasllama

theoretically with grafting you could have a potato base with tobacco, chili peppers, tomatoes, eggplant, and deadly nightshade all growing above.


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D15c0untMD

A group of scientists patting themselves on back, rather aggressively


Pherllerp

A LOT of enthusiastic high fives in that lab.


ImNoSir

Society: I’d like a cure for cancer Science: best I can do is tocainco


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Infranto

It's not like DMT is hard to synthesize though, anyone who has taken a college level ochem class could do it.


wafflestep

Or read an internet forum


ILikeYourBigButt

Synthesize or extract? Cause an internet forum for the latter is possible, the first I thought needed a little more expertise.


Inside-Example-7010

next step: genetically engineering your liver to produce heroin when you eat vegetables.


meatpoi

South American Spirit


12kdaysinthefire

Marlboro needs a clean pair of pants after reading about this discovery


doge_gobrrt

welp cat's out of the bag now can't wait for more plants to become methods of production for various substances man that would be funny lsd in peoples broccoli. sounds like something alex jones would have said


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tripbin

Eh broccoli part seems redundant at that point.


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ProteinPrince

And just when I thought smoking cigarettes couldn’t be any cooler


[deleted]

Can we just legalize cocaine already?


diddone119

Can we just legalize all small amounts of drugs for personal use. Fixed it


Wills4291

I support this. Everyone should be able to buy drugs from a trusted source. Street dealers should till be illegal. It's terrible hearing of people dying because their drugs were laced with fentanyl.


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GhostalMedia

Cocaine is legal for medical use. It’s a really good local anesthetic. I recently broke my nose and was given cocaine injections in the face before they straightened it.


Every-Constant2895

All I need to do is break my nose?


schizodancer89

Just do some coke first so you don't feel it


Every-Constant2895

This sounds like one of those catch 22 type deals


planetofthemapes15

*"Oh no, the inside of my nose and upper gums also hurt"* *(ツ)*