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.
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.
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.
"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.
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.
> 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.
Peer-review has its problems but I don't think the solution is 'we need more people carelessly injecting themselves and others with things with unknown effects'. I think the covid crisis aptly showed that the 'plucky outsider that defies a reactionary authority' archetype doesn't actually exist in real life. And biohacking itself is largely a grift.
> I think the covid crisis aptly showed that the 'plucky outsider that defies a reactionary authority' archetype doesn't actually exist in real life.
How so? I think if anything it shows the many flaws of the Nation-State model, and its inability to curtail the hygienic issues (wet markets) from rapid Industrialization in China in the best case scenario, and at worst that this is in fact a weaponized form of the COVID strain created by the CCP.
The CCP has been guilty of many crimes against Humanity, you need only look at Tibet, Xianjing, and Hong Kong to affirm that; moreover the CCP actively tried to spread this into Hong Kong when they were lying to the World about its ability to be transmitted between Humans and then forcing HK to keep its borders open to mainlanders to use a vectors despite HK medical professionals stance (who had to deal with SARS before this) and were dissapearing journalists and punishing physicians who spoke out in the Mainland.
I fail to see what you are seeing, its not like random injections led to this outcome, this is solely a result of malfeasance and corruption of the CCP, which in my view should see them be tried for Crimes Against Humanity.
> And biohacking itself is largely a grift.
I would take this statement more seriously if you didn't do it behind a throwaway so I can see what background you have to substantiate this, so I will just use this opportunity to elucidate some notable Biohackers: Gregor Mendel (the father of Modern Genetics) was a Biohacker with no formal education in Biology; Charles Darwin was the son of generational physicians in England, but detested school and completed a degree in what could best be described as 'general studies.' He dropped out of medical training but remained interested in Botany and Insects, this then turned into him developing his theory of Natural Selection when he took the trips to Galapagos, again Biohacking his way into a theory that quite honestly couldn't hold up without the work of the aforementioned biohacker: Gregor Mendel.
So, you see, Biohackers have come to define Biology and make some of the most notable breakthroughs in the Life Sciences and are hardly a 'grift' if you actually know what you're talking about. Robert Hooke, the man who would invent microscopy and Cell Theory, was a polymath and architect with a deep fascination of Natural Philosophy that too led him to Biohack his way into Scientific prominence.
In a more modern view of Biohackers: Josiah Zayner, a PhD and former NASA researcher at AIMS involved in the terraforming of Martian soil was one of the first to introduce the idea of fecal transplants from patient to patient to alter his gut biome, an notion that had previously been thought to be absurd and has now become mainstream. Not only did he do so successfully, but he was lauded for his efforts by the very same Media that subjected him to a great deal of scrutiny and ridicule, and is what he is best known for, not his PhD in Bio-physics nor his time at NASA. Also worth noting, he came from a rural part of Illinois where he was deeply fascinated with Nature and got see and interact with it from a very young age, and like most of us fell in love with it. He is honestly one of my favorite Humans ever.
He now runs the Odin, and runs a convention called Biohack the Planet.
I can tell you this, many Life Scientists I've known often go into a deep depression sometime around our junior year when we realize that what was sold to us in University was a total farce. I personally had a deep interest, bordeline obsession, with Vitamin D (particularly in inducing apoptosis via P53 in certain Cancer cell lines) and was constantly told by my professors that while it had merit it wouldn't warrant further research because it couldn't be monetized and that it would be in my interest to forget it entirely and move on to a career in Lab benchwork if I didn't want to continue my studies to the MS/PhD level.
Flash forward to today where we see a DIRECT CORRELATION of Vitamin D deficiencies and severe COVID symptoms that require hospitalization and often lead to death.
I was never after fame or recognition, and I knew money was not going to be the deciding factor in pursuing this as I just wanted to contribute and be a part of the study of Biology that I was so enamored of. But the fact that studies like these were never explored is why I detested my time in University the most after all the negative things that took place: that's what hurt the most as I know I will never be as driven as I was back then.
I've done some crazy things before and after, like walking into one of my lab practicals and midterm exams with pieces of glass in my arms as I replaced my tire on the side of the freeway on my way to school after work. I was literally picking some of it out when I was waiting in line to drop off my exam. I've done crazy things before and after, but I wish I still had that kind of drive in my 30s, especially because by then I had already accepted University had let me down and could still some how justify doing that anyway.
Brilliant, young minds get their wings clipped at a time when they are most able and inclined to want to radically change the World, only to be told that what awaits you is the dreary, pathetic World of 'publish or die' mantra of academia that ends up pushing papers that no one reads, much less ever re-creates [1] before you ever get close to being able to receive grants and a lab to do it.
I'd say the World needs Biohackers now more than ever, and I hope we can make that happen as I would absolutely love to be able to teach anyone who wants to listen about Plant, Food and Agriculture Science as I have had a presence in all of those fields despite my background as an Educated and Trained Cellular and Molecular Biologist.
As I said, in terms of the Sciences: Biologists are as punk as it gets and many of us are proud of our motley crew and adventurous history.
You have put a lot of thought in your post and I actually agree with most of it but I just want to interject about a few things:
-Darwin, Mendel etc. are seen as foundational because we as humans need plucky heroes in our narrative of history. But they are anything but. Natural selection did not spontaneously arise as an idea when Darwin put it into written words. Early farmers, herders and semi-nomadic gatherers knew all about artificial selection (which is just natural selection speeded up and driven by humans) and have been doing it for thousands of years, so the knowledge was definitely out there. There are also quite a few ancient texts conjecturing that "man came from apes and the more primitive lifeforms" etc. Of course this is not proper wording for a modern educated scientist, but again, the ideas were there. Only, Darwin was the first person with a name (and what's more, a Western and English name) to notice it, and so he became a legend. Anonymous accounts don't.
-Likewise, there's absolutely no way the Odin guy was the first to come up with the idea of fecal transplants. He's just the first public figure that you've heard of who did, because he's flashy and fancy and trendy and lives in a fancy and trendy place where all the fancy and trendy people congregate. Even excluding the studies suggesting it prior to his stunts, people knew for a while that farm kids eating soil (dirt) from time to time turned out to be suspiciously healthy for their gut.
So I maintain my previous assumption, that biohacking is largely a grift that attempts to repackage previously obtained knowledge from more obscure and less widely acknowledged (read: non-American, non-Western, etc.) sources and fashion it into a cool-looking product to swindle rich people out of their money.
The scientific world doesn't need biohackers, stunt-pullers and other grifters, it needs to acknowledge the humble and the lesser-known and the anonymous common knowledge.
in biology nothing is private or even in a class because in biology there is no designer, so there is no need for encapsulation.
One of the more and more prominent insights in biology is that almost every gene apparently appears to influence everything else.[1] Which is why I think methods like CRISPR are fundamentally misguided for anything but the most simple problems.
Trying to impose deliberate change on biological systems by editing a single gene is like trying to turn a story from drama into comedy by switching out individual letters.
One can never be sure, but from all the evidence it looks like that if there was a designer, they weren't operating at this level, so the parents point is unaffected by this concern.
are we talking god or like ancient aliens prometheus engineers here
I don't believe in god because I don't believe in anything magical or spiritual, for reasons too trivial to list here and I don't see the slightest hint of any design in any biological systems
I don't know if reality is a simulation or not, however there's no clear way to prove it or not so in the absence of any evidence I'm not inclined to believe it, this is my approach to everything. Extraordinary claims require extraordinary evidence and I don't tend to assume that improbable things are true if the world works just fine without them.
I'm not sure why someone 200 years ago would accuse me of being superstitious.
"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.
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).
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.