Adding New DNA Letters Make Novel Proteins Possible (economist.com) 102
An anonymous reader quotes a report from The Economist: The fuzzy specks growing on discs of jelly in Floyd Romesberg's lab at Scripps Research in La Jolla look much like any other culture of E. coli. But appearances deceive -- for the dna of these bacteria is written in an alphabet that has six chemical letters instead of the usual four. Every other organism on Earth relies on a quartet of genetic bases: a (adenine), c (cytosine), t (thymine) and g (guanine). These fit together in pairs inside a double-stranded dna molecule, a matching t and c, g. But in 2014 Dr Romesberg announced that he had synthesised a new, unnatural, base pair, dubbed x and y, and slipped them into the genome of E. coli as well. Kept supplied with sufficient quantities of X and Y, the new cells faithfully replicated the enhanced DNA -- and, crucially, their descendants continued to do so, too. Since then, Dr Romesberg and his colleagues have been encouraging their new, "semisynthetic" cells to use the expanded alphabet to make proteins that could not previously have existed, and which might have properties that are both novel and useful. Now they think they have found one. In collaboration with a spin-off firm called Synthorx, they hope to create a less toxic and more effective version of a cancer drug called interleukin-2.
Interleukin-2 works by binding to, and stimulating the activity of, immune-system cells called lymphocytes. The receptor it attaches itself to on a lymphocyte's surface is made of three units: alpha, beta and gamma. Immune cells with all three form a strong bond to interleukin-2, and it is this which triggers the toxic effect. If interleukin-2 can be induced to bind only to the beta and gamma units, however, the toxicity goes away. And that, experiments have shown, can be done by attaching polyethylene glycol (PEG) molecules to it. The trick is to make the PEGs stick. This is where the extended genetic alphabet comes in. Using it, Synthorx has created versions of interleukin-2 to which PEGs attach themselves spontaneously in just the right place to stop them linking to the alpha unit. Tested on mice, the modified molecule has exactly the desired anti-tumor effects. Synthorx plans to ask permission for human trials later this year.
Interleukin-2 works by binding to, and stimulating the activity of, immune-system cells called lymphocytes. The receptor it attaches itself to on a lymphocyte's surface is made of three units: alpha, beta and gamma. Immune cells with all three form a strong bond to interleukin-2, and it is this which triggers the toxic effect. If interleukin-2 can be induced to bind only to the beta and gamma units, however, the toxicity goes away. And that, experiments have shown, can be done by attaching polyethylene glycol (PEG) molecules to it. The trick is to make the PEGs stick. This is where the extended genetic alphabet comes in. Using it, Synthorx has created versions of interleukin-2 to which PEGs attach themselves spontaneously in just the right place to stop them linking to the alpha unit. Tested on mice, the modified molecule has exactly the desired anti-tumor effects. Synthorx plans to ask permission for human trials later this year.
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They really should release these e.coli into the wild, along with any other organisms they can infuse with XY nucleotides. I want to see what evolution does with it, just to see what happens!
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Where will they find a supply of x and y in the wild?
What's wrong with synthesising them de novo in vivo?
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If it was a 15ft woman eating mice, slashdot would totally freak though.
Unless she was green and covered in grits.
Re:opps! (Score:5, Interesting)
This isn't such a bizarre notion. I mean, not what what was suggested, but this actually frightens me more than any amount of normal genetic engineering. This has the potential to make virulent strains of organisms that cannot possibly be targeted by the immune system. In general, antigens react to protein coats on bacteria and viruses. If those proteins are made in ways that aren't just novel, but are which outside our immune system's ability to even see as a protein, that can pose a large problem. It wouldn't be recognized as self, it wouldn't be recognized as foreign, it just wouldn't be recognized at all.
The unintended consequences here are astoundingly worrisome.
Re:opps! (Score:4, Insightful)
Well, as long as the building blocks of those amino acids X and Y cannot be found in the wild, I'm not that worried. These things would then simply and literally starve to death.
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I would say that X and Y are nucleobases, rather than amino-acids.
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But they taste like quinoa.
Just what we need (Score:2)
Genetically-improved E. coli.
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Perhaps TacoBell will taste better.
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Re:What could possibly go wrong? (Score:5, Insightful)
Sometimes things go wrong. Therefore, never do things.
Re: What could possibly go wrong? (Score:1)
True, the Chinese definitely fucked up their choice of government. Point taken. Oh, wait, you meant...
Re:What could possibly go wrong? (Score:5, Interesting)
Not all things that go wrong are equal. You want to be careful doing things that go wrong in geometric progression.
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--
Not all things that go wrong are equal. You want to be careful doing things that go wrong in geometric progression.
--
Something about the way you said that is awesome.
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I'm an American, like Churchill said, I have to try all the wrong answers before I'm going to know what the right thing to do is.
You have to make the mistakes before you know what to be careful about, after all!
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The AC comment above makes a point: "all the wrong answers" is a heuristic that implies all "sensible" wrong answers. An answer that if goes wrong goes catastrophically wrong may or may not be sensible, depending on what you are trying to accomplish.
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You never did learn about the 1930s, did you?
What a shame. You're putting yourself in the position of arguing without context.
The wrong answers being discussed were already obviously wrong, and did have catastrophic consequences. The point was, we do the right thing once we see the catastrophe, even though it would have been much easier to prevent than it was to stop. Still, we'll pay that extra price to have the results clearly weighed.
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Don't know what you're talking about. What I'm talking about is if you set out to solve a problem, and chose a path that can have possibly catastrophic consequences -- meaning one that can lead to ruin -- you evaluate that against the benefits you gain by solving the problem.
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Right, but when somebody points to history as an example, and you admit you don't know what they're talking about... stop arguing. Duh.
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Re:What could possibly go wrong? (Score:5, Interesting)
The misfolded proteins you fear occur in nature and are ancient. Are you going to stay indoors?
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Ugga? Ugga wugga ugga?
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What? My mother was a saint!
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Nah, Jesus was an Italian
Proof:
1. He lived at home at 33.
2. He thought his mom was a virgin.
3. His mom thought he's a god.
Z! (Score:4, Insightful)
Do you want World War Z?! Because that's how you get World War Z!
Re:Z! (Score:5, Funny)
This is also how you get Leeloo. I'm OK with this.
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Multipass!
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So you're into oddly-unattractive androgynous orangeheads.
It's all good; some people still eat their boogers...
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lol, look, a neckbeard who is frightened and confused by a woman with an athletic figure!
There are a bunch of kids in the next tour group, if you'll do that thing you said with the boogers I'll make sure they double your soda at snack time.
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I don't know if I would say androgynous she was skinny and flat chested when she did that movie but she wasn't always.
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You know, a couple of years ago I got real excited because I heard they were making a sequel: Lost City of Z [wikipedia.org]. Even though Brad Pitt quit the film and they replaced him with some dude, I thought it could still be good. But there were no fucking zombies! Every time it started to get good, like when one of the guys is vomiting blood in a scary jungle, or when they run into a bunch of cannibals, the movie would suddenly switch back to England with women in lacy dresses running around and fainting because t
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In the 50s, "Radiation" made superheroes and supervillains. Genetic experiments are our new "radiation".
In reality, they will probably do as much good and bad as radiation have done. Our expanding knowledge of how genes and biological processes work will do a whole lot of good though.
4 proteins good, 6 proteins better! (Score:1)
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Re: Not feeling good about this (Score:1)
So we should just go back to our hunter-gatherer days of sitting around the fire, with even trying for forward progress? Oops, wait, hunting is cruel to animals, so that's out. Gathering leads to deforestation, so bad for the environment, so that's out, too. And a fire? Now were just polluting the environment with greenhouse gases AND deforesting the planet. Crap, were screwed. The world dealt us a horrible hand. I guess we should just lay around playing Xbox until we die, or mom kicks us out of the basemen
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Damn Furries...
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So ... Furries with even weirder fetishes, gotcha.
Og, the millennial stenographer (Score:1)
I guess it's not surprising that millennials never leave home. They can't even find their own shift key.
After dna, a, t, c, and g, Og somehow managed E. coli (more than once, even, though not in italic).
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Sounds awesome (Score:3)
A whole bunch of whiners here seem to be worried about this - not one post on super awesome positive human mutations that may occur.
Live it up a little and stop worrying so much!
This is just the kind of thing I would think especially the trans-human community would be super into.
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The problem is that we don't have good debugging tools.
You can test some edits out a bit, maybe try them in other animals, but ultimately you have to run that code in a real human. If it turns out to be buggy it's pretty difficult to patch in-place. Also sometimes it takes ages for the code to crash, like 40 years or more, so the debug/test cycle is pretty slow.
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isolation (Score:2)
I really hope this is happening in an off-world level 5 containment facility.
Old.. and old... (Score:1)
1) Making proteins with unnatural amino acids has been possible and done before.. like a lot of times.
2) Attaching PEG to proteins, a process called pegylation, has been done before and is a routine process.. although it is rather random. Most pharmaceutically used proteins are pegylated, as the attached PEG seems to make them more long-lived/potent. Making it more specific can be done in much much easier way than this (via Cysteines or surface engineered Lys etc., just to name two options).
So now they make
The sky ain't falling, relax (Score:5, Insightful)
OMG,genetically modified bacteria are gonna kill us!
No. They won't. That's the beauty about this stuff. To be blunt, I'm no big fan of GMO myself, but this is the kind of GMO I could get behind. Why? Because it has a built in kill switch. Those bases X and Y don't exist in the wild. In other words, for your bacteria to live and multiply, you have to keep feeding them these things after artificially creating them. You want your bacteria to die? Just literally starve them to death by not providing X and Y.
This is the kind of therapeutic GMO bacteria that are just perfect. Use them while you need them, then after they've done their job just cut off their supply of food and they're dying. Beautiful.
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I'm sure if you keep them long enough, some of them will eventually evolve the ability to synthesize the new X and Y bases.
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That it can be done safely does not mean it will always be done safely. Someone will mess it up given enough time and it only takes one. Now it's hard to quantify what advantages of using the new bases will be evolutionarily speaking, but if there's an advantage, we will eventually see it out in the wild.
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That was my thought as well. Or to simplify growing this E. coli, we'll genetically engineer a yeast to make X and Y bases. Then that escapes, and all hell breaks loose.
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I'm sure if you keep them long enough, some of them will eventually evolve the ability to synthesize the new X and Y bases.
Not necessarily. It might be physically impossible to express bio-machinery required to synthetize X and Y using normal DNA+XY. That would explain why those extra bases never happened in natural world - even if some mutation happened, there was no chance it would be self-sustaining.
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1. You're lying
2. You've identified yourself as an anti-vivisectionist, so now everyone knows you're a crackpot.
So, which amino acids? (Score:2)
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Protein synthesis works by translating DNA to RNA, then feeding the RNA through a cell structure called a ribosome. Three nucleotide bases code for one amino acid, so the RNA steps through the ribosome three bases at a time (each trio is called a codon), adding one amino acid to the protein chain each time.
There are more different codons than there are amino acids in nature, but here Life does something clever; the extra codons code for the same or similar amino acids.
Theoretically it should be possible to
This seems to be an extremely dangerous thing (Score:2)
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