New organisms have been formed using the first ever 6-letter genetic code

http://www.sciencealert.com/new-organisms-have-been-formed-using-the-first-ever-6-letter-genetic-code

by walterbell • 9 years ago

275 145 9 years ago

Very interesting. I like how about half the article was about reassurance that this won't lead to out of control monsters.

Along with the recent article about pig embryos, I wonder if the not-too-distant future will lead to bizarre custom pets, like something out of the Spore video game.

andai3• 9 years ago

When I was very young I spoke with a man who informed me in no uncertain terms that the digital age was old news and the next big thing would be bio-entertainment.

DiabloD3• 9 years ago

I'm not sure if that refers to highly customized psychoactive drugs... or prostitution.

singularity2001• 9 years ago

"create organisms with wholly unnatural attributes and traits not found elsewhere in nature" I'd argue that this shouldn't add anything categorically new, just like switching from 32 to 64 bit programs doesn't change the world.

Neliquat• 9 years ago

Maybe not "new" in a systems perspective, but new outcomes thanks to being able to control the system.

rmah• 9 years ago

This is less like 32bit to 64bit and more like moving from binary to trinary logic.

jcoffland5• 9 years ago

Even more like a move from 4bit to 6bit logic.

mikeash• 9 years ago

Which also wouldn't do anything remarkable.

lorenzhs• 9 years ago

Well binary and ternary number systems can express the same numbers, they just do it in a different way. I don't think there's a good computer analogy here.

m000z0rz• 9 years ago

If future work can add new artificial amino acids mapped that can be specified using the new base pairs, then it would be adding something categorically new - but still seems pretty far off.

madebysquares2• 9 years ago

"The other reason we don't need to be freaking out, says Romesberg, is that these molecules have not been designed to work at all in complex organisms, and seeing as they're like nothing found in nature, there's little chance that this could get wildly out of hand."

This is how the plot of every horror/disaster movie starts.

mitchty• 9 years ago

This is how the plot of every horror/disaster movie starts.

Because its a trope. Can you explain how it gets wildly out of hand beyond speculation?

madebysquares2• 9 years ago

Just making a joke

klibertp2• 9 years ago

Just noting: not getting/ignoring the joke should not be the reason for downvotes.

zhengyi132• 9 years ago

At the risk of oversimplifying, because "even the very wise cannot see all ends."

Unknown unknowns. You can know your specific problem domain inside and out, and still have other things show up that rapidly invalidate your assumptions about the set of possible outcomes.

fauigerzigerk• 9 years ago

That's true. I also noticed that whenever I see a helicopter on a screen, the chances of it not crashing or getting shot down are slim.

So in order to protect us from getting whiped out by rogue bacteria from a research lab we MUST ban disaster movies NOW!

tyingq• 9 years ago

I'm no expert, but aren't there non-complex organisms and structures that are pretty dangerous? "Brain Eating Amoeba", Prions, and so forth...

hellbanner2• 9 years ago

Recently on HN: a "Cursed City of the Monkey God" features flesh-eating bacteri! https://news.ycombinator.com/item?id=13396968

SpicyPython• 9 years ago

Welcome, to Jurassic Park!

amelius• 9 years ago

It seems we're one step closer to explaining the Fermi Paradox, [1].

[1] https://en.wikipedia.org/wiki/Fermi_paradox

lamontcg• 9 years ago

That is what leapt to my mind as well.

Its entirely possible that there were other self-replicating molecules on Earth that evolved first, but DNA simply out-competed them to extinction.

If we ever produce a competitor to DNA that was more 'virulent' than DNA, it would similarly out-compete DNA.

It would be the most pandemic of plagues that would affect every form of life. Even if we could protect our own DNA against attack somehow, it would attack all the bacteria that is symbiotic with us and which we need to survive.

88e282102ae2e5b5• 9 years ago

Definitely interesting work, and some very clever solutions to difficult problems, but to be clear, they only had a single unnatural base pair, and it was only in a plasmid.

Addressing the other comments about this leading to some crazy scifi scenario, imagine telling someone you used machine learning to identify spam emails and they started freaking out about how you're going to start Skynet. If you understand how things really work you can see it's not just implausible, it's that things fundamentally don't work that way.

Joeri• 9 years ago

Then again, nobody knows how skynet will get started. If it does happen, you can be sure it'll be done by someone who is sure that things just don't work that way, right up to the moment they are crushed by a giant metal boot.

jcoffland5• 9 years ago

Let's hope that Skynet is not able to feed off of spam. There's so much of it's food already. We'd never be able to stop it.

88e282102ae2e5b5• 9 years ago

That's true, but my argument is that we can basically guarantee that a simple neural net won't become self-aware, in the same way that we know that a linear regression library won't become self-aware. The complexity is bounded, just like it is in the experiments described in this paper.

JoeAltmaier• 9 years ago

...won't get started

zepto3• 9 years ago

Software systems are relatively predictable, and built on mathematical models and rules that we designed. Even so, there are still many negative unforeseen consequences of their operation.

Biological systems are relatively unpredictable, and based on rules that we didn't design and cannot begin to claim we fully understand.

Your analogy therefore strongly predicts negative unforeseen consequences.

tstactplsignore3• 9 years ago

Difficult to see how this comment, as common as it is, is anything but unscientific. Biological systems are often highly predictable in many circumstances - in fact "biological predictability" is what accounts for the general success of all modern medicine and agriculture.

If the field "cannot begin to claim we don't fully understand" things now, when do we reach the point where we suddenly "know enough to begin to do things", and why should we be listening to you about that point instead of experts in the field?

The reality is that this system is highly predictable in the way it was intended, and the changes made are understood extremely well at a molecule and cellular level. You can't come up with a specific concern with this system because you don't have a clue about it. Anyone who does cannot come up with a specific concern of this system because it is extremely predictable.

This anti-scientific Taleb-esque argument is just used by people who have no idea what they're talking about to try and speak over those who do, and is anti-intellectual and anti-scientific to its core. The OP's comment holds very well- this is no different from a layperson worrying about someone implementing an SVM on some dataset "becoming skynet, because computers aren't always predictable!" - it's nonsensical the minute you have any idea what you're talking about.

pbhjpbhj• 9 years ago

Well one way to reduce spam is to kill all humans! /Bender

beaconstudios2• 9 years ago

if nothing else, at the fundamental level there aren't any ribosomes that would parse the new base pairs. Engineering a new ribosome to produce something useful given an "alien" base pair would be the trigger that could make the new base pair potentially harmful. Until that point, it's completely inert.

_throwaway18433• 9 years ago

Star Trek depicted one of the scarier applications of such a technology: There, The Jem'Hadaar are a genetically engineered race of warriors controlled by the Dominion, who exert power over them by being the sole provider of a substance (Ketracel-White) that they need in order to survive:

https://en.wikipedia.org/wiki/Dominion_(Star_Trek) http://memory-alpha.wikia.com/wiki/Ketracel-white

If my reading of the paper is correct, the unnatural XY base pair doesn't have any function per se, but without it the organism fails to replicate its DNA and quickly dies. Hence you can argue that after introducing it, the XY base pair has a vital function, as without it the organism can't survive anymore. And since the organism has no way to synthesize X & Y itself, it needs to be supplied from the outside for its whole lifetime. This, in turn, provides a neat way to build "self-terminating" organisms that depend on a steady supplement of the given substance. One could of course argue that vitamins are exactly the same, but contrary to those the artificial base pairs would not be found in the wild, so supply could be controlled more easily.

protomyth3• 9 years ago

That was also part of the plot of the original Jurassic Park novel. The dinosaurs were [edit][edit]bred[/edit][/edit] with a need for lysine.

throwaway34987• 9 years ago

The dinosaurs were bread?? The film never showed the bakery!

andai3• 9 years ago

bred* :)

dghughes• 9 years ago

I just watched an old X Files episode (season 1) apparently aliens have six base pairs.

dnautics6• 9 years ago

I remember that gel! It turns out though that you would never be able to make that gel, because the distance those bands are from the top depends on being able to incorporate the six base pairs using your PCR, so the idea of banding with gaps doesn't make sense, instead you would have a traffic jam at the spot where there was an alien base pair.

astrodust3• 9 years ago

It's a common trope. See also: Evolution, Fifth Element.

_yosefk• 9 years ago

It's good as long self-termination is a nice-to-have feature. If you REALLY want them to self-terminate but you found out that they mutated and can now synthesize X & Y, you're in trouble.

Genetically modified organisms are a bit scary, but genetically modified organisms that replicate autonomously are more than a bit scary. As programmers - a profession that managed to spread Shellshock, the dumbest imaginable backdoor, so widely as to make much of human population vulnerable, we should understand this better than others. We have no idea what happens in our own code, code that we copy from place to place ourselves, written in languages we designed and running on machines we designed, and there's nothing like mutation and self-replication with this stuff, for the most part. I kinda doubt that biologists modifying "code" which is actually pretty large molecules existing and interacting in a 3D space with a lot of forces pulling and pushing things, and without the benefit of comments or design documents, can make something that can be trusted to autonomously replicate and gradually mutate.

jcoffland5• 9 years ago

We have no idea what happens in our own code

That's an overstatement. Sure code can be very complex but we actually can see exactly what's going on whenever we really want to. It's just that we cannot see what's going on with all the code all the time.

colordrops3• 9 years ago

No, GMOs are inherently safe and you are anti-science /s

SilasX• 9 years ago

It's good as long self-termination is a nice-to-have feature. If you REALLY want them to self-terminate but you found out that they mutated and can now synthesize X & Y, you're in trouble.

Also, if they get powerful enough that they can take over your synthesis facility...

stcredzero2• 9 years ago

We have no idea what happens in our own code, code that we copy from place to place ourselves, written in languages we designed and running on machines we designed, and there's nothing like mutation and self-replication with this stuff, for the most part.

Documented: Computer viruses mutating in the wild by two different viruses accidentally copying themselves into overlapping regions of memory.

eivarv4• 9 years ago

    Genetically modified organisms are a bit scary...

Why?

taneq2• 9 years ago

If you REALLY want them to self-terminate but you found out that they mutated and can now synthesize X & Y, you're in trouble.

There's a good hook for a sci-fi story. Some low-level manager in a biochem company starts siphoning off XY juice to sell on the black market, and doesn't realise that by slowly ramping up their thievery they're evolving the killswitch out of their engineered organisms...

clouddrover• 9 years ago

If you REALLY want them to self-terminate but you found out that they mutated and can now synthesize X & Y, you're in trouble.

And speaking of the Jem'Hadar, there was an episode of Deep Space Nine based on this idea:

http://memory-alpha.wikia.com/wiki/Hippocratic_Oath_(episode...

fatboy93• 9 years ago

It's good as long self-termination is a nice-to-have feature. If you REALLY want them to self-terminate but you found out that they mutated and can now synthesize X & Y, you're in trouble.

That's the premise of Jurassic Park 1, except with an amino acid.

dnautics6• 9 years ago

I think the goal is to give it a function. But in order to have it replicate in a cell, you need to have a way of selecting for it. Biosafety through selection is an easy "add-on" because you already had it by virtue of the fact that you needed it to get the real result.

robbiep• 9 years ago

If my reading of the paper is correct, the unnatural XY base pair doesn't have any function per se, but without it the organism fails to replicate its DNA and quickly dies.

That's actually differently to how I've read it - it appears to me that the XY pairing is stable and not harmful to the host and so is not degraded or removed (recognised as foreign by mis-sense DNA proof readers) but is therwise not performing any function, although some of the technical details are missing.

As to your second point, we already have highly perfected 'terminator' technology, currently in 3 forms:

1) the infamous Monsanto terminator technology, where second generation seeds would not be viable (which, incidentally, would be a significant benefit to some farmers growing genetically engineered cotton and potentially their crops, as spilt seed from harvest would not germinate)

2) in bacteria and other organisms etc in the form that you describe above - ie lack of a substance is fatal - usually this substance is some generic low dose antibiotic that triggers a genetic switch when present

3) as you suggest, removing an organisms ability to synthesise a particular amino acid and having it dependent on food

_throwaway18433• 9 years ago

Yes very good point, I didn't want to mention Monsanto but I also think they're probably the company that is most likely to use such a technology on animals in the future, if they might get the chance to do so.

stcredzero2• 9 years ago

One of the proposals for prolonging human life by eliminating cancer is to engineer humans who have no stem cells and no mechanisms for repairing telomeres. Instead, such engineered humans would have to undergo massive stem cell and telomere repair therapy once every few years or so.

Such a mechanism would also do for an explanation for a Blade Runner style replicant that had an extendable lifespan.

zhengyi132• 9 years ago

Am I ridiculously cynical to think that similar problems around social/economic control of the new humans would immediately spring up?

gort• 9 years ago

There are a number of questions that are probably answered behind the paywalled article...

* In order to reproduce (and maintain the new bases in its DNA), does the organism need a source of these nucleotides in its growth medium? (i.e. in its food?) The alternative would be to produce them itself, but that would require scarily advanced genetic engineering, I think.

* If one of these bases is in a gene, what happens during mRNA transcription? Total failure?

Point 1 at least should more-or-less ensure this can't escape the lab.

philipov2• 9 years ago

I don't see a paywall.

elcct• 9 years ago

So 5 letter codes are all taken now?

george_ciobanu• 9 years ago

Damn!

philipov2• 9 years ago

How do you propose to make pairs out of an odd number? Each nucleotide binds to only one other nucleotide.

dnautics6• 9 years ago

romesburg made 5 letter pairs, by allowing let's say a third one called "P" for no good reason, to do the following matches:

A:T T:A C:G G:C P:P

sharpneli• 9 years ago

Nucleotide that binds only to itself.

Ericson2314• 9 years ago

It would be really cool, once the new base pairs code for something, to see whether this increases evolutionary fitness.

I'm not at all sure whether or not denser information and thus bigger-step mutations are evolutionary advantageous.

hellbanner2• 9 years ago

Confusing to me that "X and Y" are the name of these new letters when X and Y are commonly referred to as sex chromosomes

jcoffland5• 9 years ago

How do you do algebra?

88e282102ae2e5b5• 9 years ago

Well, the actual names of the base pairs they used are dNaM, d5SICS and dTPT3. It doesn't seem to me there are any good choices.

ambrop7• 9 years ago

Can the organism replicate the XY pairs during DNA replication (and pass it on to divided cells)? I haven't seen that mentioned, only that it "holds onto it for its entire lifespan" which is not clear to me.

There's also nothing about the interaction of these pairs with existing mechanisms, like transcription (DNA-->RNA) and translation (RNA-->protein). Could the new new pair increase the space of aminoacids from which proteins can be formed?

oever• 9 years ago

The XY pairs are not replicated. To replicate them would require the presence of a slew of specialized proteins that can deal with XY pairs.

The achievement is that the E. Coli lifetime is not affected. The XY's are probably inserted in a part of the DNA that is not transcribed.

dnautics6• 9 years ago

I 150% guarantee you they are in a place that is transcribed. Otherwise there would be no selection pressure to maintain it and the bacteria would kick it out in favor of one of the plain old bases.

88e282102ae2e5b5• 9 years ago

The paper specifically states that these unnatural base pairs were chosen because they can be handled by natural polymerases. Also, the only way to maintain a plasmid over time is to replicate it. In fact, the whole logic of the strategy is to have Cas9 target mutations to the plasmid so that loss of the XY base pair during replication would lead to loss of the plasmid, and thus loss of the antibiotic resistance gene that it also carried.

mvm• 9 years ago

Artificial base pairs are replicated, it is seen from fig.5 in original article, with nearly 100% retention

88e282102ae2e5b5• 9 years ago

It can replicate them, but the XY pairs are just in a plasmid and not in the genome of the bacteria. They were chosen because natural polymerases could use them.

However, there are no corresponding RNA unnatural bases, and there's no tRNA that would recognize that even if there were. So it's going to take a lot more work before you can use these for coding for noncanonical amino acids.

This really is just a proof of concept.

te_chris• 9 years ago

Getting closer and closer the world of MaddAddam.

steffenfrost• 9 years ago

What could possibly go wrong?

msl09• 9 years ago

We are only 2 pairs away from encoding 8 bits DNAs

grandalf• 9 years ago

The four letter genetic code is simply one mechanism that works, and leverages many properties of chemistry and physical chemistry.

https://www.ncbi.nlm.nih.gov/pubmed/19046126

http://pubs.acs.org/doi/abs/10.1021/acs.jpcb.5b01983

vivekd2• 9 years ago

So will this actually mean anything? Can adding extra letters to an organisms genetic code actually have the capacity to change it's attributes in any meaningful way. Every biological characteristic on the planet seems to have been achieved through using the same 4 molecules, will the addition of more molecules create new characteristics or be useful in any way?

maxander• 9 years ago

Not really; essentially all DNA "really does" is code for RNA, which in turn codes for amino acid sequences that fold into proteins. As long as the RNA and amino acid libraries are the same, it's just representing the same stuff with a different set of symbols.

In practice, it's probably going to be used as tools for manipulating organisms for experimental purposes, since scientists can do things to the synthetic bases that can't be done to real ones (or that effect natural and synthetic bases differently.)

dnautics6• 9 years ago

The biggest application will be introducing unnatural amino.acids into proteins.

NeutronBoy2• 9 years ago

But Romesberg says there's no need for concern just yet, because for one, the synthetic base pair is useless. It can't be read and processed into something of value by the bacteria - it's just a proof-of-concept that we can get a life form to take on 'alien' bases and keep them.

While it might not be useful to the organism, could the synthetic base pairs lead to a way to store data? Imagine a bacteria that can be used as a living, self-healing datastore.

jakeogh• 9 years ago

http://www.extremetech.com/extreme/134672-harvard-cracks-dna...

NeutronBoy2• 9 years ago

Yeah that's the sort of thing I'm thinking of! From my total layperson perspective, the OP article seems to be a step in the right direction for this.

sebleon• 9 years ago

This seems like technology for technology's sake, with zero consideration for ethics.

sperglord• 9 years ago

On what are you basing that? I'm sure they've also read Jurassic Park.

sidlls• 9 years ago

What's wrong with that?

jayajay• 9 years ago

Initially, the engineered bacteria were weak and sickly, and would die soon after they received their new base pair, because they couldn’t hold onto it as they divided.
Finally, the team used the revolutionary gene-editing tool, CRISPR-Cas9 to engineer E. coli that don’t register the X and Y molecules as a foreign invader.
"This will blow open what we can do with proteins."
[The base pairs] can't be read and processed into something of value by the bacteria - it's just a proof-of-concept that we can get a life form to take on 'alien' bases and keep them.
...have not been designed to work at all in complex organisms, and seeing as they're like nothing found in nature, there's little chance that this could get wildly out of hand.

To quote Jeff Goldblum, "life, uh... finds a way".

tunnuz• 9 years ago

This question that I asked on StackExchange a while ago seems relevant here http://biology.stackexchange.com/questions/2874/why-are-ther...

peter303• 9 years ago

There may be a simpler two codon system embedded inside the three codon system currently by Earth life. That is when multiple codons specify the same amino acid, they almost always share the first two nuclides. So it could be that Earth life experimented with 2 and 3 and maybe even higher codon systems before settling on the one nearly all life uses. There may have been tradeoffs in protein complexity, reliability, energy requirements, etc with system that survived. Maybe just some accidental luck too.

hodwik• 9 years ago

This opens a lot of possibilities for genetic manipulation, especially in connection with CRISPR. I imagine the X and Y bases are being kept secret for proprietary reason

New organisms have been formed using the first ever 6-letter genetic code

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