This is an absurd technical accomplishment. Identifying and cloning 21 genes on its own is a ton of work, but doing so in a way that replicates a synthetic pathway is amazing. Hats off to the scientists who managed to get this to work.
Six or so years ago, a friend of mine and I were talking about how the US had destroyed poppy fields in Afghanistan on a large scale (I think to block Taliban funding or something) despite the WHO listing morphine as a critical drug in short supply.
Being enterprising sophomore Bio students who had a basic grasp on cellular machinery, we then somehow spun that story into the idea of mass-producing plant alkaloids from rapidly reproducing microbes (except we imagined bacteria rather than fungi). We always had "crazy" discussions like that and I never gave it a second thought afterward.
What's really funny to me is what a pipe dream (no pun intended) it seemed like at the time-- maybe the beginning of a bad sci-fi story at best. But here we are today and it's so incredible to me that this team was able to bring that idea to life.
Now I'm left wondering what other crazy discussions will turn into practical real-world applications in the next six years.
You're not the only person who has thought along those lines. I've seen multiple proposals to mass-produce plant alkaloids using microbes (bacteria or yeast). Very few people have the skills required to do this; you have to be an expert in chemistry, as well as molecular biology, and also be patient and good at running experiments and getting funded. And you've probably also have to be lucky in choosing what synthesis to work on.
See also the iGEM competition:
https://www.igem.org/Main_Page
the students who work on those projects often come up with really clever ideas and implementations, which has the potential to push the field along faster than if it was just academically funded professors and some startups.
I'm well aware that ideas are a dime a dozen and that there is no realistic way that I could have brought that idea to life.
I wasn't trying to make a "I had that idea first! I could have made millions!" type of comment. My point was just how wild it is that it seemed to unrealistic at the time but now it's reality. I also thought it was an interesting coincidence that we happened to think of the same alkaloid that this project created.
Once the proper genes to make this work are identified by one group, how hard is it for another group to replicate the results?
I'm just wondering when drugs are created with this method if bioengineers will be able to 'easily' create reproductions of the yeast by following a template of the process, or if people in their footsteps will be mostly using clones of their original work.
it's entirely non trivial. cloning genes is tedious, slow, manual labor. People are working on scaling it up (so more genes can be cloned at a time) and making it easier (so you can press a button and receive a yeast).
Rather than directly replicating the experiment, it would be easier for the team to disseminate their cells to others, who could then grow the cells up, sequence them, and compare the sequence to a wild type yeast to verify the genes were included, then do a few other transcription experiments and blocking assays to show that the genes that got cloned in were actually the ones carrying out the synthesis.
It is impressive. But I'm going to burst your bubble. The team did not necessarily discover an entirely new biosynthetic pathway. Endogenous pathways for thebaine/opiate synthesis have been known for some time; for example: http://www.genome.jp/dbget-bin/www_bget?cpd:C06173.
Fair criticism. I didn't say that they discovered an entirely new biosynthetic pathway. I said they identified and cloned genes (I think your confusion stems from a false interpretation of what I said; I didn't mean to imply that the team identified every single gene). Those are two different things; note for example the link you pointed me at is effectively an abstract pathway.
So, since you're making a technical nitpick with a short detail of my comment, I'll apply the full flame of my technical capabilities. We'll start with the paper itself:
The abstract says " We combined enzyme discovery, enzyme engineering, and pathway and strain optimization to realize full opiate biosynthesis in yeast. The resulting opioid biosynthesis strains required expression of 21
(thebaine) and 23 (hydrocodone) enzyme activities from plants, mammals, bacteria, and yeast itself"
So the authors say that they discovered enzymes. This is consistent with my statement. Your statement is irrelevant; discovering a biosynthetic pathway is a distinct thing from discovering the enzymes that carry it out (but, I will agree that in many cases, when you discover a biosynthetic pathway you can identify the enzymes and genes that code for them at the same time. It's not necessary, though). What the authors did here is engineer a biosynthetic pathway.
Next statment that supports my position from the paper:
"Also, key enzyme(s) that epimerize the (S)-benzylisoquinoline scaffold to the (R)-enantiomer, which is the biosynthetic precursor of the promorphinan and morphinan scaffolds, have remained unknown even after decades of study until recently identified by two groups (19, 20) and by our team as described below."
Note the above extract from the paper, if correct, completely abolishes your point. The authors cite their own recent work, as well as the work of others, which was required for engineering biosynthetic pathway.
At this point I rest my case. My original statement stands, as it does, and your criticism appears to be only a pointless and ultimately irrelevant nitpick of my statement.
Further, I would appreciate not using the term "burst your bubble". It's immature, and when said to a person who's been studying synthetic biology for more than 2 decades, who can read the primary literature, and compose a coherent reply, makes you look petty.
I have a friend who suffered from 'auto-brewery syndrome' last year. From wikipedia:
Auto-brewery syndrome, also known as gut fermentation syndrome, is a rare medical condition in which intoxicating quantities of ethanol are produced through endogenous fermentation within the digestive system. One gastrointestinal organism, Saccharomyces cerevisiae, a type of yeast, has been identified as a pathogen for this condition.
Now imagine an auto-brewery syndrome with this modified yeast...
...until it stops being enough, either due to gradual tolerance making them seek a stronger and stronger fixes, or due to something that disrupts production by the yeast-culture.
The yeast is not meant to be ingested, only harvested to refine the opiates.
Jay Keasling, a Synthetic Biology Professor at Cal [https://en.wikipedia.org/wiki/Jay_Keasling] uses E. Coli & Yeast to produce a precursor to a Malaria drug (artemisinic acid), as well as for environmental cleanup.
They too convert glucose to a complicated chemical structure of artemisin, which is purified through biological pathways further reducing cost.
Sigh, I'm a cynic, this is an amazing accomplishment and all I could do was think that yeast will now be considered a controlled substance that I have to give my drivers license to buy like Sudafed.
From the article this was only because they were being stolen, if anything I think that's less regulatory, even though we know addicts are using them stores are free to do what they want.
Fun fact - Although the tech might have improved, a lot of the seeds never used to get irradiated properly.
yeah, but presumably its just like other yeast - if "non-authorized users" get hold of just a little bit, they can make as much of it as they want. (There's a whole bunch of bakers here in Sydney who sell "Sonoma Sourdough bread", which - story goes - all comes from the same small batch of not-quite-legally-acquired-and-imported yeast.)
I'm wondering who's going to be the first politician or law enforcement chief to suggest we need to lock up sugar and require government issued ID to be presented before purchase...
There was an article about this in the New Scientist (UK) a few weeks back. They highlighted concerns that unlike mass illegal cannabis production the heat/energy footprint of producing opium in something like a bathtub would be almost undetectable.
If someone finds a way to produce addictive drugs from yeast then a whole new ball park could be opened up in the war on drugs.
>If someone finds a way to produce addictive drugs from yeast then a whole new ball park could be opened up in the war on drugs.
More like a whole new ballpark in the devastation of human rights. How exactly do you fight against this without a totalitarian police state? The gene labs could be anywhere in the world, bringing a new strain in would be as simple as tiny sealed pocket in just about anything you could imagine. Would the yeast itself be considered illegal? How much would be, a few micrograms?
And this is just the early days of gene manipulation. Way better and more potent combinations will be made at some point, because even though it may be 'somewhat' difficult, there is a lot of money to be made. Which turns back to the government now monitoring everybody that has knowledge and ability in the genetics world since they could be a drug manufacture.
The answer is of course repealing the war on drugs. Maybe legalization of cannabis paves the way to the realization that regulation, taxation and harm reduction are much better ways of combating not only the violence and corruption that stems from the black market but especially the health issues.
Oh I certainly agree with that, unfortunately a sizeable portion of the population doesn't. A significant lobby base in the U.S. fights actively against legalization and will throw tons of money at the current racket too.
> More like a whole new ballpark in the devastation of human rights.
Depends, if the technique is easy enough for individuals to accomplish, it becomes a health issue rather than a crime one, because nobody will need suppliers/dealers/smugglers.
The real problem is the middle-ground, where it's an easy production mechanism that criminal syndicates can control, but not so easy that individuals can do it without making payments. For example, perhaps the cultivation/extraction/concentration process is too difficult, or the strain is engineered to require a proprietary chemical to live--a reasonable safety precaution in any event--or the "root species" is kept secret while strains that self-destruct after a certain number of generations are used for production at scale or resale.
During the USA's prohibition of alcohol, condensed grape juice was sold in "bricks" which came with a warning to not to reconstitute with water then leave in the darkened cupboard for 20 days, lest it self-ferment into wine.
> Would the yeast itself be considered illegal? How much would be, a few micrograms?
According to the report on the radio I heard this morning, the yeast itself is considered a controlled substance and its distribution is restricted in the same way as the drugs themselves.
Realistically interdiction of yeasts producing controlled substances would be a losing game. People regularly smuggle much more obvious contraband whereas a decent amount of starter culture could be easily concealed in the average travelers personal effects and would not be detectable without dna testing that would take more than 24 hours to carry out.
If the DEA were concerned about it's ostensible mission this would be the point where they give up and start looking at Portuguese style decriminalization. As it is, expect them to start busting homebrewers and yoghurt makers and expanding their civil forfeiture efforts into creative new forms of thievery.
Why not to hook electrodes directly into brain? Electricity is legal, cheap as dirt, and cannot be detected. As bonus, it will do no harm to your body.
If you know how to do that with little to no risk, you can get extremely rich - but you wouldn't really care, as the electrodes in your brain will deliver more enjoyment than all that money could.
Question to biologists: Is cross contamination an issue? e.g. Monsanto corn has contaminated non-monsanto corn through wind/pollen/whatever natural mechanism.
Is there a non zero probability that sometime in the future I'll buy standard yeast for cooking at the store and get some of the kind described in the article?
No. First of all, this modification brings a significant handicap to the organism (it's wasting its resources), so it can't spread in nature. And even without any competition from wildtype yeast, it's likely to get rid of the opium pathway by itself once enough generations have passed.
Anyways, yeast culture is done in closed environments with specific varieties as stems.
The invasive potential of some Monsanto varieties that you mention arises from the fact that they were modified to be resistant to specific pesticides, giving them a significant advantage since these pesticides are everywhere.
