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.
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.
> 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.
> As a biologist and programmer, nothing makes me roll my eyes harder than SV types talking about biology like a computer.
Same.
But in truth, I'm glad this experiment took place, we need to adhere to the rigors that uphold the notion of incremental progress for a desirable end, and this begins by quantifying just how immense this problem really is. I'm glad that Dr. Jiankui He did it anyway.
It cost him his career and he will likely remain as a cautionary tale for all other future biologists in academia, but in Biohacking scene he is really no different then the pioneers in cell biology that often resorted to self experimentation, History in Biology is such a fickle thing: we'll laud them when the outcomes favour conventional wisdom and it accepts there methods, but infamy awaits anyone who defies to go out of its per-ordained confines. Even though we all accept that the walled garden of peer-reviewed publication is flawed and riddled with so many unnecessary things that encumber its ability to live up to its potential when it can use unorthodox or unconventional means and methods.
The Health Sciences, specifically that of genetics and cellular and molecular biology, has a history of being the punk-rock branch. Where even a monk playing with peas in his free time can help establish the notion of inheritable mutation (Mendelian genetics) based on adaption created by a British Medical school drop out who took to sea-fairing and island hopping to create the concept of what we'd eventually call Darwinian Evolution.
This is our History and as a Cell/Molecular Biologist myself, I take great pride in it and I have tried my best to live up to this reputation and apply this to my work in Agricultural and Food Sciences after abandoning my career as a lab scientist.
Dr. He got consent from the parents to undergo this procedure and move Biology in a territory it otherwise would never go for another couple of decades at the earliest. This is more than what some physicians did not too long ago, and the data we obtained from those experiments proved incredibly useful to this day.
"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.
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.
Brief background: CRISPR originated as a pseudo-adaptive immune system in bacteria to fight against phage viruses, including the Cas9 protein. We can use it outside of bacteria (ie, in eukaryotes) because we can customize the adapter/recognition RNA molecules used, usually around 25-30 baseppairs long IIRC.
Some quick reasons:
- A 25 base-pair RNA can probably kinda-sort-sometimes bind/recognize sequences as short as around 5 basepairs. It may not be the majority of incidences, but it can happen.
- There are different Cas9 proteins. They do many things, with some are more effective at certain activities and some eliciting a stronger host response. There's a balancing act.
- The human genome is somewhere around 1000 times larger than a bacteria like E. coli.
- We have seen them! Tons of them! Scientists will customize and tweak proteins and RNAs to match a given organism. It's obviously harder in humans...
FTA: Previous work using CRISPR in mouse embryos and other kinds of human cell had already demonstrated that editing chromosomes can cause large, unwanted effects.
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.
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.
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.
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.
Readit News
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.
The analogy might hold if we treated CPUs like a magical artifact that we don't have the technology to understand.
"Brain computation by assemblies of neurons"
https://www.pnas.org/content/117/25/14464
> As a biologist and programmer, nothing makes me roll my eyes harder than SV types talking about biology like a computer.
Same.
But in truth, I'm glad this experiment took place, we need to adhere to the rigors that uphold the notion of incremental progress for a desirable end, and this begins by quantifying just how immense this problem really is. I'm glad that Dr. Jiankui He did it anyway.
It cost him his career and he will likely remain as a cautionary tale for all other future biologists in academia, but in Biohacking scene he is really no different then the pioneers in cell biology that often resorted to self experimentation, History in Biology is such a fickle thing: we'll laud them when the outcomes favour conventional wisdom and it accepts there methods, but infamy awaits anyone who defies to go out of its per-ordained confines. Even though we all accept that the walled garden of peer-reviewed publication is flawed and riddled with so many unnecessary things that encumber its ability to live up to its potential when it can use unorthodox or unconventional means and methods.
The Health Sciences, specifically that of genetics and cellular and molecular biology, has a history of being the punk-rock branch. Where even a monk playing with peas in his free time can help establish the notion of inheritable mutation (Mendelian genetics) based on adaption created by a British Medical school drop out who took to sea-fairing and island hopping to create the concept of what we'd eventually call Darwinian Evolution.
This is our History and as a Cell/Molecular Biologist myself, I take great pride in it and I have tried my best to live up to this reputation and apply this to my work in Agricultural and Food Sciences after abandoning my career as a lab scientist.
Dr. He got consent from the parents to undergo this procedure and move Biology in a territory it otherwise would never go for another couple of decades at the earliest. This is more than what some physicians did not too long ago, and the data we obtained from those experiments proved incredibly useful to this day.
What's "SV"?
Title should say "researcher succeeds in disrupting embryo development"
"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.
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.
Some quick reasons:
- A 25 base-pair RNA can probably kinda-sort-sometimes bind/recognize sequences as short as around 5 basepairs. It may not be the majority of incidences, but it can happen.
- There are different Cas9 proteins. They do many things, with some are more effective at certain activities and some eliciting a stronger host response. There's a balancing act.
- The human genome is somewhere around 1000 times larger than a bacteria like E. coli.
- We have seen them! Tons of them! Scientists will customize and tweak proteins and RNAs to match a given organism. It's obviously harder in humans...
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