
It is now easy to edit the genomes of plants, animals and humans - thomasrossi
http://www.economist.com/news/briefing/21661799-it-now-easy-edit-genomes-plants-animals-and-humans-age-red-pen
======
astazangasta
Having worked with this technology, there is a ton of hype.

This is NOT easy. First of all you cannot target any sequence; it must match a
certain consensus pattern. Second, while cutting is easy (to delete or knock
out a gene), introducing a substitution is hard and requires a lot of chance.
Third, the process is extremely noisy. You cannot guarantee your edit will
occur. Usually you must verify by resequencing, which is actually worse than
shRNA.

Finally we are far away from full body gene therapy this way, which would
involve delivering a CRISPR kit to every cell.

In short this is a powerful experimental tool but it is extremely far from
freely editing the genome.

~~~
dave_sullivan
Question for anyone working with CRISPR...

What's the current state of the art for using computers to model or simulate
how a gene change will impact the rest of an organism?

Separate but related, if you were to collect data on that sort of thing during
an experiment, how would you? I assume there's quite a bit of variation
depending on experiment goal... Is imaging technology to the point where you
can record what happens as video?

~~~
pak
This is actually something one of my thesis committee members worked on.
[http://www.cell.com/abstract/S0092-8674(12)00776-3](http://www.cell.com/abstract/S0092-8674\(12\)00776-3)
In silico whole cell models are an extremely new concept, and his study
demonstrated its capabilities for one small bacterium. Needless to say, we
have a long way to go before we can make top-down simulations of multicellular
organisms, much less one as complex as a human. There are many people trying
to generate "good enough" simulations for certain human diseases though, by
modeling interactions between genes and biomolecules among a few tissues
within the relevant organ system.

With regard to your second question, there are many "omics" assays that can
now capture e.g. every mRNA, every protein, etc. at a given timepoint but you
have to kill the cells. Fluorescence microscopy can work for "movie-like" time
resolution on a live cell but you have to label the cellular elements with
stains or antibodies and you can only utilize so many of those simultaneously
on a single sample (1-5 is typical).

~~~
ccvannorman
>There are many people trying to generate "good enough" simulations

Who? As a 3D software engineer moving into this space, this is extremely
relevant to me. :-]

~~~
pak
Pretty much anything in the "network biology" field will likely interest you,
but here are a few sample articles (heavily biased toward people that I
currently work with):

[http://www.ncbi.nlm.nih.gov/pubmed/18344982](http://www.ncbi.nlm.nih.gov/pubmed/18344982)

[http://www.ncbi.nlm.nih.gov/pubmed/19337271](http://www.ncbi.nlm.nih.gov/pubmed/19337271)

[http://www.ncbi.nlm.nih.gov/pubmed/18462017](http://www.ncbi.nlm.nih.gov/pubmed/18462017)

------
datashovel
My only hope, with regard to genetic engineering, is that the people who are
actually discovering this stuff are strong enough to prevent large corps from
patenting all of the most important intellectual property that will empower
future generations.

My active imagination hypothesizes that the people who go to work every day to
invent / discover this stuff go to work only with the meager hope of
collecting on their 6-figure salaries to provide for their families and pay
their children through higher education. Perhaps even a stint at an Ivy League
school. Meanwhile empowering large multinational corporations / conglomerates
with the enormous wealth of intellectual property that their grandparents
would be ashamed of.

~~~
ci5er
I don't know. In the US you get 20 years of protection from a patent from time
of filing. If somebody beats you to it, you don't. This means that a lot of
tech filings are going to be pre-commercial. This means that once on the
market, it will need to be tested by the market. Once the market decides that
it is a better/faster/cheaper tool than the competitive
product/process/genome, you've got, what, 7~10 years? Maybe?

So, during this window, if you over price it, it isn't better/faster/cheaper.
If it is priced competively, people benefit. The only "losers" are those that
have to wait 10 years to rip off your research and clone your product and
undersell you.

What's the problem here?

~~~
datashovel
I agree that it seems, by today's standards, a non-issue. And in reality
perhaps it is just my active imagination that is the enemy here. Although I
would posit that though 7-10 years seems like a reasonable timeframe to most
people today, it will probably appear to be a lifetime to future generations.

If you really think about it, how long do Cell Phones last on the market
before they're no longer a threat commercially? If I had to put a number to it
I'd say no more than 1 year. After that you better have something new, and
hopefully patented to prevent competition.

Now amplify that by 2x, maybe 3x, or 10x. Now perhaps only the patent holder
has legal rights to experiment on a given range of problems (given the nature
of the patent). I imagine if someone plays their cards right, and hits the
"patent lottery", you end up with a "waterfall-effect", or in other words,
centuries worth of patents by a single entity with no end in sight.

Perhaps those in the field recognize that biology is just as diverse if not
more diverse than most other fields. And my concern could be a red herring. I,
personally, have no doubt that the field of biology is enormously diverse, and
in most academic settings I'd consider this pretty much a non-issue. I think
the over-arching fear is the US has nominated 9 people, none of whom are
likely to know a significant amount about genetic engineering, to decide (in
essence) the fate of genetic engineering and the "patentability" of specific
inventions / discoveries.

What I think the field of genetic engineering may need in its future, is the
equivalent of a Linus Torvalds in their field. Someone who will cut through
the BS, and donate the overwhelming majority of their work / research to the
public domain to prevent or reduce the possibility of some calamitous scenario
from unfolding.

~~~
hackuser
> What I think the field of genetic engineering may need in its future, is the
> equivalent of a Linus Torvalds in their field. Someone who will cut through
> the BS, and donate the overwhelming majority of their work / research to the
> public domain to prevent or reduce the possibility of some calamitous
> scenario from unfolding.

Didn't most research used to be published openly in scientific journals? Has
that changed, or was that a golden age that never existed?

Based on my meager understanding, openly sharing research was one of Bacon's
foundations of the Enlightenment and the scientific enterprise.

~~~
ejlperello
The CRISPR IP battle is being fought between universities, not corporations.

CRISPR aside, the IP situation in biotech and specifically in synthetic
biology (parts-based biology) is not a good one. Currently there exists IP
around many small DNA components (you can think of them as genes though this
wouldnt be correct in all cases - more like DNA programs).

Currently in biology, if I want to build a composite part, that incorporates
many separate parts, each with IP around them, I need to get a license for all
of those parts.

The tech industry had a similar problem back in the "golden age" of computer
parts development. It is often so expensive and difficult for any innovation
to happen to happen under these circumstances, as so many patents and licenses
and what not must be obtained, which typically frightens investors from
putting cash in small startups. The tech industry has solved this with EDA
tools - we need something similar in biotech.

What I'd call a DNA Part or cassette, techs call an "IP" or silicone block IP.
They have worked out a system where it appears the big design software houses
act as brokers and clearing houses for their users. They aggregate not only
the necessary licenses, but also the documentation and design rules for how to
use a specific part. Then the design tool compiles all these parts down into
something that is sent for synthesis by the foundry. They're really light
years ahead of the biotech industry on this.

I recommend this fascinating overview of how intellectual property rights in
integrated circuit design have evolved. It would be great to see similar
things happen in my industry.

[http://timreview.ca/article/442](http://timreview.ca/article/442)

------
arvinjoar
Here's a Radiolab segment about it (CRISPR) if anyone is interested:
[http://www.radiolab.org/story/antibodies-
part-1-crispr/](http://www.radiolab.org/story/antibodies-part-1-crispr/) I
highly recommend listening to it

~~~
belltyler
I came here to post the same thing - an awesome listen.

------
mirimir
The article links to another on "gene drives" that use CRISPR to spread genes
far more quickly through populations.[0] _Cities of the Red Night_?

>ANIMALS typically have two versions of any given gene stored on two different
chomosomes—basically large DNA molecules—and the two versions can have
important differences. Offspring normally inherit only one of each pair of
chromosomes from each parent, and thus each version of the gene typically gets
into only half of them. Technologies like CRISPR make it possible to break
this rule with something called a gene drive—a gene that uses gene-editing
techniques to copy itself from one chromosome to the other, so that whichever
chromosome the offspring inherit they get the same version. The same will then
apply to their offspring, too (see diagram).

[0] [http://www.economist.com/news/briefing/21661801-giving-
bits-...](http://www.economist.com/news/briefing/21661801-giving-bits-dna-
power-edit-themselves-intriguing-and-worrying-possibility)

~~~
thomasrossi
nice, thanks. I think the most important step we are still missing are: 1) the
reverse drive, so say that some edit is spreading, you must have a way to stop
it eventually; 2) telomere-elongating or other DNA repairing goodies (maybe
copying from water bears).

~~~
eggie
The most important step we are missing is the first one, where we "easily"
edit the genomes of humans. It is not yet easy, despite the enormous hype
surrounding CRISPR-based approaches.

Edit: and I understand that gene drive _could_ make it easier to introduce
biallelic changes, but this isn't really easy because the drive systems
themselves are not even 10% efficient at introducing the exact modification
which is desired.

------
nsns
I would say these so-called "ethical questions" are always a red herring (not
because they're unimportant, but rather because we don't have a reliable
authority to handle them); the real problems that should really be explored
beforehand are matters of jurisprudence (e.g. commercial control vs. state
control and its implications) and potential weaponization.

~~~
realusername
And also to define guidelines on what to do if shit hits the fan. As an
example (nothing related to DNA modification but anyway), I have a few
neighbours who planted balsamine plants (I guess it's this one:
[https://en.wikipedia.org/wiki/Impatiens_glandulifera](https://en.wikipedia.org/wiki/Impatiens_glandulifera))
because it's a bee friendly plant. The problem is it's an invasive plant, it's
now absolutely everywhere and spread kilometres away from the original point.
I don't mind because it's harmless and the pink flowers are quite beautiful
but it's an example of the kind of unforeseen consequences that can happen.

~~~
hga
When you're making just a few changes to an organism it's a lot easier to
predict and test the outcome, vs. inserting a complete batch of genes in the
form of a new to the ecosystem plant like the balsamine you mention. That
Wikipedia article details a bunch of ways in which balsamine can out compete
local plants and do other undesirable things like encourage erosion by dying
each season.

In either case a degree of caution is warranted. Which scientists did for
genetic engineering, during a period when I was preparing to join them
(actually did some E. Coli genetic work in the summer of 1977 in a NSF Summer
Science Training Program between my high school sophomore and junior years):
[https://en.wikipedia.org/wiki/Asilomar_Conference_on_Recombi...](https://en.wikipedia.org/wiki/Asilomar_Conference_on_Recombinant_DNA)

The restrictions resulting from the conference were relaxed over time as
appropriate as we gained the relevant knowledge, especially the way in which
genes naturally jump around all the time between species. I.e. nature has
already tried out a lot of stuff we might want to try, given zillions of
organisms and years.

------
obel1x
There was a great talk on the topic of CRISPR-Cas9 at the Hacker News London
meet up this month by Edward Perello. Video is here:
[https://vimeo.com/137001197](https://vimeo.com/137001197). It's a good
introduction to the topic from a hacker's perspective.

------
dekhn
It's more accurate to say, CRISPR represents a technology which makes it
easier to change genes in living organisms, possibly in a heritable way.

It makes no changes to the delivery mechanism, that is, you still have to make
the genomic changes in the cells that matter.

I'm greatly appreciative of CRISPR because it elegantly solves the "specific
template problem": by providing a generalized sequence non-specific mechanism,
any target sequence can be addressed using DNA synthesis. previously, you
would have to engineer a unique protein to locate a specific sequence, and
because peoples genomes differ, you'd have to reengineer the protein for
individuals.

------
marktangotango
The difficulty in realizing the promise of genetic engineering to treat
disease, or even do the more esoteric things like enhance abilities or create
new species has not been altering genomes. The difficulty has been and
continues to be the tremendous difficulty in understanding how proteins fold,
given a DNA sequence, and on top of that understanding the biochemical
reaction pathways and feedback loops. In the 90's early work showed that sime
changes could profound and often detrimental effects.

~~~
ejstronge
Perhaps this is what you mean but I'd add an additional difficulty - we can't
predict the organismal impact of many of the genetic manipulations we make.

As a result of this, we must perform time-intensive experiments using model
organisms like bacteria, flies, mice, etc.

~~~
marktangotango
Yes that's what I was attempting to illustrate, thank you!

------
ccvannorman
Where would I go to get a job as a software engineer working on CRISPR
simulations?

~~~
ejlperello
Hi there, this is Edward (I spoke at the HN London event a few weeks ago on
CRISPR - [https://vimeo.com/137001197](https://vimeo.com/137001197)).

I'd encourage you to get in touch with us at Desktop Genetics. We are always
on the lookout for talented developers with an interest in biology!

------
hadeharian
Nice paywall you have there.

------
TylerH
"easy"

