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Adding New DNA Letters Make Novel Proteins Possible (economist.com)
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.
Genetically-improved E. coli.
#DeleteChrome
Do you want World War Z?! Because that's how you get World War Z!
Sometimes things go wrong. Therefore, never do things.
Some DNA is just more equal than others.
Not all things that go wrong are equal. You want to be careful doing things that go wrong in geometric progression.
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 basement, whichever one comes first. No. People have complained and lamented every technological advance since the beginning of time, and each and every one was going to bring our doom. Guess what, we are still here. So stop whining. If you don't like what these guys are doing, get out there and give us an alternative.
The misfolded proteins you fear occur in nature and are ancient. Are you going to stay indoors?
True, the Chinese definitely fucked up their choice of government. Point taken. Oh, wait, you meant...
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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.
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Something about the way you said that is awesome.
But they taste like quinoa.
Sometimes things go wrong -- and you can't walk them back. Therefore, be more fucking careful!
If it was a 15ft woman eating mice, slashdot would totally freak though.
Unless she was green and covered in grits.
Ugga? Ugga wugga ugga?
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.
"There is more worth loving than we have strength to love." - Brian Jay Stanley
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.
I really hope this is happening in an off-world level 5 containment facility.
"The ability to delude yourself may be an important survival tool" - Jane Wagner -
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 highly sophisticated changes to E. coli, create two extra bases, ensure that they translate those two extra bases into the right unnatural amino acids, so that they can make specific PEG-attachments in order to prevent Interleukin-2 from binding the alpha-subunit.. whoa.. have they ever thought of a more convoluted way? Pro-tip: just mutate Interleukin-2 to no longer (or at least weaker) interact with the alpha subunit like here [1] (paper from 2013).
[1] http://www.jimmunol.org/content/jimmunol/early/2013/05/15/jimmunol.1201895.full.pdf
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.
We used to have a Bill of Rights. Now, with the rights gone, all we have left is the bill.
What? My mother was a saint!
We used to have a Bill of Rights. Now, with the rights gone, all we have left is the bill.
Damn Furries...
We used to have a Bill of Rights. Now, with the rights gone, all we have left is the bill.
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.
We used to have a Bill of Rights. Now, with the rights gone, all we have left is the bill.
Where will they find a supply of x and y in the wild?
What's wrong with synthesising them de novo in vivo?
Every end has half a stick.
Jesus, dat u?
Every end has half a stick.
And six is the smallest perfect number. Also, all numbers are interesting anyway. So not sure we lost any numerological perfection here.
The Economist article actually did it the best way: using smallcaps for DNA, RNA, A, T, C, G, X, Y. In contrast to full caps, smallcaps letters don't "pop out" of the text and attract undue attention, making the text smoother to read.
If you don't have smallcaps available, both full-caps and lower-case letters are legitimate style choices for such abbreviations, as long as you do it consistently. (For instance, in electronics it's quite common for "ac" and "dc" to be consistently spelled using lower-case letters. It's also very common for abbreviations in the software world.)
Full caps is however more common outside of tech, and personally I'd prefer it to lower-case letters just to make it easier to see how one should pronounce a word (i.e. if "dna" should be pronounced "dnah" or "dee-enn-ayh".)
However, in my opinion, the best choice is the most traditional one: using smallcaps for abbreviations.
Life, uh... finds a way.
Are they wholly synthetic or naturally occurring but unused?
The adaptive immune system works by randomly editing the binding site and then culling self-reacting cells. There's no reason that novel proteins would be unbindable just because they had different constituent amino acids; you can use metal as an adjuvant and we obviously don't code for aluminum in our DNA. Diseases that the adaptive immune system has trouble with are ones where the accessible surface proteins change too rapidly, not ones that are non-interactive with the immune system. To achieve the latter, they'd end up inert enough not to be able to bind to your cells, either, and could therefor not cause much trouble beyond something like mechanically clogging you up like silica dust or so on.
Nature is not an idiot. And the 4 billion years of evolution made the base pairs what they are. They should be asking why rather vigorously, not tinkering with the way it is presently. If this gets into human germ cells and is passed along from generation to generation along with other "improvements," may we (humans) not some time in the future be forced to say..."ooops, maybe we shouldn't have done that?"
E Proelio Veritas.
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.
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.
I would say that X and Y are nucleobases, rather than amino-acids.
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.
1. You're lying
2. You've identified yourself as an anti-vivisectionist, so now everyone knows you're a crackpot.
Contribute to civilization: ari.aynrand.org/donate
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.
We used to have a Bill of Rights. Now, with the rights gone, all we have left is the bill.
So ... Furries with even weirder fetishes, gotcha.
We used to have a Bill of Rights. Now, with the rights gone, all we have left is the bill.
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.