
GM microbes created that can’t escape the lab (2015) - JumpCrisscross
http://www.nature.com/news/gm-microbes-created-that-can-t-escape-the-lab-1.16758
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bagrow
Life... uh... finds a way.

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adrianN
They literally use the same method: Make the bacteria dependent on a supplied
nutrient.

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EGreg
So they use "selection" to engineer such bacteria and hope that random
mutations and gene-swapping won't find a way out of this?

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greggyb
Gene-swapping is at least mentioned in the fourth paragraph of the article. I
would like some more detail on this part, too. They also have more references
to virus resistance for what sound like the same reasons:

> Fourth paragraph:

> The microbes also do not swap their engineered DNA with natural counterparts
> because they no longer speak life’s shared biochemical language.
> “Establishing safety and security from the get-go will really enable broad
> and open use of engineered organisms,” says Farren Isaacs, a synthetic
> biologist at Yale University in New Haven, Connecticut, who led the other
> study.

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skosuri
This effort was made possible by the earlier work by Isaacs and Church groups
on reclaiming the UAG stop codon by removing all instances of it genome wide
[1]. Today the Church group published a followup on progress on removing six
more codons [2]. If they can finish this, they should be able to make an
organism dependent on not one but 4 different synthetic amino acids. Yes, life
might evolve away from needing one, but with proper design all four would make
an organism that would be exceedingly unlikely to escape.

[1].
[http://science.sciencemag.org/content/342/6156/357](http://science.sciencemag.org/content/342/6156/357)

[2].
[http://science.sciencemag.org/content/353/6301/819](http://science.sciencemag.org/content/353/6301/819)

EDIT COI: I am a former member of the Church lab.

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tiles
More exciting will be the first mutation that undermines this constraint.

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guard-of-terra
They could hide it in a deep potential well, where such mutation will be
virtually impossible to happen before the lifetime of the universe.

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pfarnsworth
We have proven time and time again that humans have a terrible ability to
predict the "virtually impossible."

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guard-of-terra
It's not hard to do a lousy job, doesn't mean it's the only possibility.

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tomkinstinch
Full PDF (not open access):
[http://www.nature.com/nature/journal/v518/n7537/pdf/nature14...](http://www.nature.com/nature/journal/v518/n7537/pdf/nature14121.pdf)

Auxotrophy[1] been exploited for years to select for engineered organisms.
Reverse mutation to prototrophic strain is often an issue. This work by
Mandell, et al., is novel because it relies on the organism being auxotrophic
for a non-standard amino acid, L-4,49-biphenylalanine. It's cool the system is
stable.

1\.
[https://en.wikipedia.org/wiki/Auxotrophy](https://en.wikipedia.org/wiki/Auxotrophy)

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prof_hobart
I feel the key sentence is “Our strains, _to the extent that we can test them_
, won’t escape,

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mnkmnk
Is GM a common abbreviation to be used in a headline?

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ricardobeat
Thanks! Only after reading your comment the headline started making sense
grammatically. I was wondering why would they write such a malformed sentence,
with "General Motors" in my head the whole time.

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Cpoll
I notice a lot of people are concerned that these GM microbes will evolve and
escape.

Could anyone comment on the probability of that compared to the probability of
an equally severe microbe surfacing in the wild?

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JumpCrisscross
Curious overlap between biocontainment and encryption. You're trying to
"encrypt" away from the life form some "key" it needs and that you control.
Your key needs to be sufficiently complex that evolution can't brute force it;
your "lock" thoughtfully integrated so something similar enough to it can't be
substituted.

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dTal
That's a great analogy. Although I think it's rather more like DRM - you want
a "program" to only "run" if some "key" is present, and your adversary wants
to make the smallest possible change to the program to run it without the key.

It was something of a lightbulb moment for me when it finally clicked why
"perfect" DRM is impossible: no matter how convoluted and obfuscated your
locking mechanism is, somewhere in there it all boils down to a final if-then
- "did the authentication pass?". And this can always be patched to return
"yes" instead of "no", trivially bypassing the whole thing. And you can't get
around it even with drastic measures like encrypting the source and providing
the key on demand - the key can always be saved. The code can _always_ be made
to run, and DRM can _always_ be short circuited.

Carrying the analogy back to biology: so they've made their organisms reliant
on a new amino acid. Who's to say it won't learn to _synthesize_ its needed
building block? After all, it's all the same atoms. The key can always be
saved...

Still, it seems they did attempt to provoke this, and failed. DRM doesn't have
to be theoretically perfect to be effective. It's impressive stuff,
engineering organisms with an incompatible genetic code - maybe not be a
panacea, but it definitely helps.

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api
A simple fix for many of the objections in this thread: can't means low
probability.

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Qantourisc
And they took out all the genes that would prevent an easy fall-back to
working without this amino acid ? As well as the code/DNA required to steal
genes from other bacteria ?

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scythe
Why can't the bacteria evolve enzymes to produce these amino acids? After all,
they evolved enzymes to produce every _other_ amino acid...

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pavel_lishin
Anyone instantly thinking of Neal Stephenson's Zodiac?

How are they generating the amino acid?

[edit] I also noticed that this article is over a year old.

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jrjr
I guess we can look forward to Jurassic Pork.

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clint
Sounds familiar somehow

