
Crispr gene editing in human embryos wreaks chromosomal mayhem - YeGoblynQueenne
https://www.nature.com/articles/d41586-020-01906-4
======
vikramkr
This highlights why it was so irresponsible to create CRISPR babies, and why
you take things slow in science. Don't let the analogies about bio being
programmable just like a computer fool you - it's not that easy or that
simple. Bio is messy and complex.

Note: looks like these findings are from preprint, and so still need to
undergo peer review. This is a phenomenon that was anticipated however based
on the science, even though as the article states there some controversy
around the specific mechanisms at play.

~~~
shpongled
As a biologist and programmer, nothing makes me roll my eyes harder than SV
types talking about biology like a computer.

The analogy might hold if we treated CPUs like a magical artifact that we
don't have the technology to understand.

~~~
vikramkr
I don't know if that would be enough to make the analogy hold, since what we
do know about biology includes a lot of things that are distinctly non-
computer like. At the end of the day, one is a system designed by humans for
humans, while the other is a system that's an emergent phenomena of billions
of years of chemistry, physics, and statistics. In computers you create the
rules and then build systems that follow the rules, and then push the rules to
their limits to see what you can do. In bio the only rule is that an
arrangement of atoms that's more likely to replicate a version if itself into
a future time period will be more likely to be found in that future time
period compared to an arrangement of atoms that isn't. And that principle has
had 4+ billion years to play with the rules of physics to see what it can do,
and we're just trying to decipher that now.

~~~
shpongled
I mean, I think that there is _some_ merit to biology-computer analogies, I
just don't think anyone can expect those analogies to hold in reality. But you
are exactly on point. There are presumably "rules" in biology, but they are
occluded by spooky action a distance and oodles of hidden and ever-changing
state.

~~~
jfarlow
I think it's important not to say that biology is somehow 'spooky', or not
governed by physical rules. We actually know the outlines of those rules
pretty well - they're just complicated.

The really big difference is that biology computes at _overlapping_ time and
distance scales, simultaneously. There are biological computational processes
that occur at microseconds, to millennia, from fractions of a nanometer to
kilometers all happing in concert and referencing each other. In the building
of our own computational tools we generally try to avoid mixing physical
scales like that. The analogies to computers aren't inherently wrong, they
just need to mix in a lot more complexity.

~~~
shpongled
"Spooky action at a distance" doesn't imply that it's not governed by physical
rules - and I think it's certainly a valid descriptor for biological systems
as a whole.

Yes, we can break down aspects of biology into nice subsystems that we can
define rules for - e.g. we have a pretty good idea of how DNA polymerase, or
the ribosome carry out their duties (in isolation). It's when we start looking
at the emergent properties of having all of these things in one larger system
that our understanding starts to break down.

~~~
ethbro
Valid / invalid for metaphors, to me, depends on the audience.

For laypeople, ill equiped to deal with high orders of complexity: spooky.

For people in the field: details.

For some audiences being accurate is less descriptive than being reductionist.
Because if you lose your audience's attention, you've communicated no
accuracy.

------
RocketSyntax
"the researchers used CRISPR–Cas9 to create mutations in the POU5F1 gene,
which is important for embryonic development."

Title should say "researcher succeeds in disrupting embryo development"

------
mrfusion
I’m confused. Don’t we use crispr all the time on other organisms? Mice,
drosophila, etc. wouldn’t we already have seen this?

~~~
_nothing
What makes you think we haven't?

"Previous work using CRISPR in mouse embryos and other kinds of human cell had
already demonstrated that editing chromosomes can cause large, unwanted
effects. But it was important to demonstrate the work in human embryos as
well, says Urnov, because different cell types might respond to genome editing
differently."

It says of one study "Of 18 genome-edited embryos, about 22% contained
unwanted changes". Such a failure rate probably isn't such a big deal in some
applications. In embryos, especially human embryos, it's definitely a big
deal.

~~~
klipt
In a way, large changes that make the embryo completely unviable would be less
bad: the embryo would be wasted, but at least you wouldn't have caused someone
a lifetime of genetic disease.

The worst case scenario would be a viable but badly diseased embryo.

I wonder if they can tell which of these outcomes they got from the
experiment.

------
reedwolf
Looks like biological systems are kind of complicated.

------
aurizon
Let's face it. Crispr was evolved by bacterial cells in the grip of a phage
virus invader. It had to act with enormous speed to try to get ahead of the
virus's high speed reproduction machinery and spread the word to successor
generations - if any. Fidelity was sacrificed to make an RNA threshing machine
and even then it lost more often than it won against the phage. The winners
trapped those palindromically patterned bits and lived to breed another day -
maybe.

------
xvilka
My intuition suggests that the precise editing will not work out no matter the
technology used. What I see is something that can read and combine traits from
multiple places scattered all over DNA, calculate some kind of acceptable
range, be able to change that range that "recalculates" DNA then edit it in
multiple places simultaneously. This will work on just tuning the genome
though.

------
xvilka
I wonder why I haven't heard about the efforts to design gene editing tools
from scratch using protein design. So they will not "steal" some poor bacteria
IP, but will build a customized tool based on the requirements. Hard problem?
Absolutely. But it will pay out in the long-term, also will allow to improve
these proteins over time.

~~~
aurizon
This exact scenario is now evolving in dozens of labs the world over to use
the essence of the initial CRISPR mechanism in a new and superior(patentable)
way to perform gene edits in the precise location with the precise new
information required. It will end up better, but probably slower and surer.

------
dafoex
Biological noob here, but isn't Cas9 not well suited for humans? I recall that
I read or heard somewhere that Cas12 was preferred for this usecase.

------
vaidhy
The double negative in the title of the original article is bad editing - it
either wrecks the chromosomes or creates a mayhem. If it wrecks the mayhem, it
is a good thing(TM).

~~~
shpongled
The title says "wreaks", not "wrecks".

~~~
dafoex
Yes, I believe that is correct. The expression is, after all, "wreaks havoc".

