
Cambridge scientists create living organism with redesigned DNA - okket
https://www.theguardian.com/science/2019/may/15/cambridge-scientists-create-worlds-first-living-organism-with-fully-redesigned-dna
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gen220
The latest WIRED magazine had some truly mind-boggling articles in this vein.

[https://www.wired.com/story/synthetic-biology-vaccines-
virus...](https://www.wired.com/story/synthetic-biology-vaccines-viruses-
horsepox/)

This guy (a renowned smallpox researcher) was able to synthesize a cousin of
smallpox (horsepox) using commercially/publicly-accessible tools and
resources. He did this to try and create a new/better smallpox vaccine,
because he believes that motivated actors will be able to synthesize smallpox
in the next 20 years, and that the world needs to be ready with better
vaccines for the same. His team's resulting publication ("we made smallpox,
this is the gist of how") was met with strongly negative responses.

The gist of these articles is that while synthesizing functioning
viruses/microorganisms was possible in the past (TFA says the first
"synthetic" organism was made in 2010), it's _much_ easier/faster/cheaper to
do so today, when crispr techniques/tools are more generally wielded and
better-understood.

Cool/scary stuff!

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inciampati
How is CRISPR used for genome synthesis? I thought it was all driven by
synthesis, and overlapping homology of sticky ended fragments, and ligase, but
maybe that's the old days.

~~~
folli
It's not used for synthesis. It's very helpful for modifications of existing
genomes, but it has no relevance in commercial DNA synthesis (which is a
purely chemical process).

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hsikka
What are the design tools that synthetic biology researchers use to create
genomes? Is it some sort of EDA environment like Cello or Asimov, or is it
done manually?

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daijobu
Mostly its just manipulating text files w/ bash, R, python.

The tools used by this particular study:

[https://github.com/TiongSun/GenomeRecoding](https://github.com/TiongSun/GenomeRecoding)
[https://github.com/TiongSun/iSeq](https://github.com/TiongSun/iSeq)

~~~
hsikka
Thank you!

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gpvos
_> Known as Syn61, the bug is a little longer than normal, and grows more
slowly, but survives nonetheless._

Why is this? If AGC is identical in function to TCG, and the same holds for
the other replacements, shouldn't the new organism function _exactly_ the
same?

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ChrisSD
The Ars article has some more details:
[https://arstechnica.com/science/2019/05/researchers-make-
the...](https://arstechnica.com/science/2019/05/researchers-make-their-own-e-
coli-genome-compress-its-genetic-code/)

> Unfortunately, there's a big gap between what a DNA synthesis machine can
> output and the multi-million-base-long genome. The group had to do an entire
> assembly process, stitching together small pieces into a large segment in
> one cell and then bringing that into a different cell that had an
> overlapping large segment. "Personally, my biggest surprise was really how
> well the assembly process worked," Schmied said. "The success rate at each
> stage was very high, meaning that we could do the majority of the work with
> standard bench techniques."

> During the process, there were a couple of spots where the synthetic genome
> ended up with problems—in at least one case, this was where two essential
> genes overlapped. But the researchers were able to tweak their version to
> get around the problems that they identified. The final genome also had a
> handful of errors that popped up during the assembly process, but none of
> these altered the three base codes that were targeted.

So it sounds to me like the process wasn't quite perfect. They also note that
DNA "redundancy can also allow fine-tuning of gene activity, as some codes are
translated into proteins more efficiently than others".

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gwern
I wonder how many simple ordinary mutations (not necessarily codon-affecting
errors) are in the final E. coli genome? Any process like this... Probably
quite a few, all of which would be sand in the gears.

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ElijahLynn
That is some scary stuff, actually. Got the same feeling as watching some of
Boston Robotics' videos.

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atemerev
What about Mycoplasma laboratorium?

~~~
korm
It's partially synthetic according to Google

