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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.
Do you want World War Z?! Because that's how you get World War Z!
Sometimes things go wrong. Therefore, never do things.
Not all things that go wrong are equal. You want to be careful doing things that go wrong in geometric progression.
The misfolded proteins you fear occur in nature and are ancient. Are you going to stay indoors?
If it was a 15ft woman eating mice, slashdot would totally freak though.
Unless she was green and covered in grits.
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.
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.
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.
Life, uh... finds a way.
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.