Deformities Alarm Scientists Racing to Rewrite Animal DNA
wsj.com
wsj.com
For me, the real scary part is altering something, which inadvertently changes something else that isn't quite as obvious and visible or noticeable. Something that might not present itself until whatever organism it is reaches maturity, or beyond. Something like "everybody will get Alzheimers by age 50" where it takes 50 years to even discover it. And in the meantime, they thought whatever they originally tweaked was a success and made other tweaks during those 50 years thinking everything was just fine.
It's just so much more complicated than that.
There is an additional huge array of variables like introns[1] and exons[2].
There's also the fact that not all base pairs encode even for genes, there's things like tRNA[3] and ribosomes[4] and the super amazing ribozymes[5].
Even after all that you have specific DNA binding factors[6] that along with the insane machinery[7] of our DNA regulate which base pairs are even exposed or copied into proteins or other cellular products.
Our genetic code is far more complex than just being "genetic codes." And we're still uncovering more layers of complexity and self-reference[8] the closer we are capable of looking.
[1]: https://en.wikipedia.org/wiki/Intron
[2]: https://en.wikipedia.org/wiki/Exon
[3]: https://en.wikipedia.org/wiki/Transfer_RNA
[4]: https://en.wikipedia.org/wiki/Ribosome
[5]: https://en.wikipedia.org/wiki/Ribozyme
[6]: https://en.wikipedia.org/wiki/DNA-binding_protein
[7]: https://en.wikipedia.org/wiki/Regulation_of_gene_expression
"Genetic engineering" is more like "cut-and-past-programming" on a stream of data that is not-really-code. Fully understanding the implications of even "simple" changes may wind-up impossible.
Older versions of genetic engineering are like pasting code into a random section of a program. CRISPER-CAS9 is more like replacing one section of code with another. Better? Sure. But we still dont really understand the system.
Some parts have a very straightforward meaning. For example the DNA code for insulin is well known and understood, you can copy it to bacteria to make them produce a 100% accurate version of human insulin. https://en.wikipedia.org/wiki/Insulin
> The human insulin protein is composed of 51 amino acids, and has a molecular mass of 5808 Da. It is a dimer of an A-chain and a B-chain, which are linked together by disulfide bonds. Insulin's structure varies slightly between species of animals. Insulin from animal sources differs somewhat in effectiveness (in carbohydrate metabolism effects) from human insulin because of these variations. Porcine insulin is especially close to the human version, and was widely used to treat type 1 diabetics before human insulin could be produced in large quantities by recombinant DNA technologies.
Many enzymes have also a similar straightforward DNA->protein->function story.
(The regulation method to decide what enzymes to produce and how much of them is more complicated, but some are well known.)
If you want to identify the genes for more general traits like height or intelligence, then you will get something like what you said, that is a very complicated interaction on many genes that we don't understand.
(There are some examples of molecules families. You have many variants of it encoded in the DNA, and each is optimized for a different task. IIRC the idea is that some molecule is used for two similar thing, then after a lot of generations by a random chance you get two copies of the code in the DNA, then after a lot of generations each copy is used for one task, then after a lot of generations each copy evolves to be optimized for it's task. See the variants in https://en.wikipedia.org/wiki/Hemoglobin#Types_in_humans and also the distant variant https://en.wikipedia.org/wiki/Myoglobin )
Why produce insuulin if you can’t use it. The mere presence of that sequence may have consequences for other development. Some sequences may be if, then, else statements, there is so much we don’t understand.
We are playing russian roulette, except the number of bullets changes every round.
But we’ve done this before, “humans can’t possibly alter the global environment”. Even climate scientists were saying that until about 20 years ago.
So... not "well known and understood" then - if it were, a definitive "yes" or "no" would be the appropriate answer.
If intelligence isn't heritable and has nothing to do with genetics, please teach a paramecium how to do quantum physics and I'll give you a million dollars
https://www.sciencealert.com/an-amoeba-has-solved-an-exponen...
It's not quantum physics, so I'll settle for $100k
And every month since I've read something that supports this and undermine the current conventional wisdom / proof.
Yup, and my then the market is established and the companies creating the market will say it's impossible to know that the side effect was actually caused by altering your DNA, and go on knowingly selling services that are destroying lives all in the name of money
This isn't about whether and to what degree "companies" are cartoonishly evil. And when you divert the conversation into that very well worn path, you distract from other problems.
There are lots of threads on HN where complaints about corporate ethics are on topic.
https://www.cell.com/cell/fulltext/S0092-8674(17)30629-3 https://www.quantamagazine.org/omnigenic-model-suggests-that...
For such a system to work, there must be great robustness in the way that traits are encoded. The omnigenic model implies graceful degradation, as also observed in neural networks. Only vanishingly rarely is a single neuron/gene critical.
So now we are going to start in on biology?
Wait, WHAT?!
The thing that allowed millions of people to ascend from what would now be seen as abject poverty and subsistence farming?
The thing that enabled mass tool manufacture that eventually led to the Green Revolution and boosted agricultural yields enough to increase the planet's carrying capacity a few orders of magnitude?
THAT screw up?!
Say what you want about the environmental consequences and our failure to manage carbon and toxic byproducts.
But there's objectively no way you can say the Industrial Revolution didn't vault the entire world's population technologically, medically, and materially forward.
We are losing 150-200 species of plant, insect, bird and mammal every 24 hours.
That’s an estimated 1,000 times the natural rate.
We fucked up real bad, and the fact that there’s 7 billion of us now and we’ve got iPhones doesn’t change that a shred.
we Will pay for this destruction, in unforeseen, invisible, and difficult to imagine ways.
We could have done better, and ignoring that blocks our path to a better way.
If the oil lobby hadn't suppressed research and political will from doing something about climate change back in the 70s, we could be saying something different.
We wouldn't be having this conversation but for the Industrial Revolution, because none of us would be wealthy enough (in real terms) to afford the technology to do so.
Indeed, the technology itself likely wouldn't exist because the world as a whole wouldn't be wealthy enough to afford the research.
Avoiding progress out of fear for its effects is Luddite in the truest sense. And I don't say that pejoratively -- simply to note that it's tantamount to advising "Stop making progress!"
Innovate. Overcome challenges. Build and discover a better future.
I'm honestly flabbergasted that I read "Burn the mechanized mills!" on Hacker News.
I'm not advocating groupthink, and there are certainly ways we could have built a better present, but the blind ungratefulness to say "Mass manufacture and electricity were mistakes" deserves some outrage.
Also, please don't use quotes to make it look like you're quoting someone when you're not. That's also a flamewar trope and a vector in the unwanted direction.
I'll try to limit double quotes to avoid confusion, though I was under the impression quote consensus was > demarked.
I'd certainly characterize my reaction as incredulous and shocked. I re-read the parent 3 times to make sure I wasn't misunderstanding their point.
I realize we're not making progress in some areas we should be as a species, but I had no idea people had gotten this cynical.
The site guidelines try to address this like so: "Please respond to the strongest plausible interpretation of what someone says, not a weaker one that's easier to criticize. Assume good faith."
https://www.damninteresting.com/on-the-origin-of-circuits/
...and now extrapolate to biological systems evolving over a much longer period.
Drew Endy did a lecture this a while ago. It's from one of the chaos computer club seminars.
It might work with good, continuous testing (ie, with bacteria were you can test x generations in n specimen) - but it's hard to see how it would ever work reliably in higher animals?
Evolution is like Motie Engineers (https://wikipedia.org/wiki/The_Mote_in_God's_Eye). I would summarise the essential difficulty as non-heirarchical.
Exactly this! And this is why GM foods are more dangerous than you might expect. Even if gene x does only x in organism A, there is no guarantee that gene x does only one thing or the same thing in organism B.
In the case of genetics, we have a some understanding, but it is fairly limited. There is real potential for unexpected harm, given how much we don't know and the complexity of the code. Of course, we can do some amazing things with the parts we do understand.
Selecting breeding is like using a high level GUI that is decently functional. Like most GUIs, it significantly restricts how you can modify the underlying data. The plus side is that it is harder to put the data in a bad or dangerous state using only the controls offered by the GUI.
If the consistency checks in the natural genome don't stop you, pretty much by definition whatever you're doing could happen through an unlikely coincidence of selective breeding (especially if you involve a wild virus to take the place of the lab virus.)
This may be your opinion. While GM foods are not per see dangerous, the long tail risk is tremendous, exactly because you can not tell what a gene is going to do in another organism. Take my word for it, I have a PhD in that shit.
Taleb also advocates the precautionary principle: https://arxiv.org/pdf/1410.5787.pdf
Honestly, Taleb should stick with what he knows: finance. In other fields I trust his opinion about as much as I would any other Wall Street banker.
Genetic engineering is more like changing the byte code in your OS hoping to change its functionality. Without having the source code.
Until we know how the system works your ideas are only ideas.
In and adult your precise change might have minimal impact, but what if that sequence is checked during embryo development, and if it’s not present “exactly” as expected the embryo aborts?
How long do you think it will take to figure out that your “precise” change now prevents humans from reproducing?
No engineering required, but obviously a huge change.
I have shepherds and there's a big philosophical split between shepherd owners who want 'working line' dogs and those who want 'show dogs' that are significantly more likely to have health problems. Dog breeding is a very poorly regulated market and the outcomes are just as depressing as you would imagine.
What kind of brain injury do you have to have to go out of your way to want to breed these dogs?
And why the hell don’t / haven’t animal rights activists, and society in general, vigorously pursue regulation to ban these absurd breeds.
Cross-breeding allows nature to combine things that fit together in all of the right places. And we just don't know how that even happens, or why. We don't understand nature's algorithm for DNA. No even the tip of the iceberg.
Sure, nature isn't always correct, but does thing properly 99.999% of the time. And that's good enough.
It is utterly incomparable to GM done by humans ~ genes are inserted, but the results are not equivalent to what is done by nature, because we don't understand DNA enough to know where we should be placing the inserted DNA, so that things don't massively fuck up inexplicably somewhere down the line.
What you're seeing as "nature knowing what's best" is really just life being able to function with all kinds of random genes all over the place, because the core biochemical pathways are close enough.
We have turned seeds into the equivalent of Gillette razors. A farmer buys patented seeds and the complimentary chemical to kill everything else.
The problem is that as farming has turned into a big dumb business, centuries of best practices with respect to land management are getting tossed. Farmers near where I grow up (who are left) don’t rotate and are being ground into bankruptcy as larger and larger entities dominate.
I feel like this is putting too much faith in "natural" methodologies.
Eg, who's to say a cross breeding solution is less dangerous than a GM solution?
If the concern is that it may take 50 years to know the GM is bad, why are we assuming the non-GM is good now? You could say that people have been cross breading for many many generations, but i'm unsure why we'd know that one cross breed being safe means all crossbreeds are safe. I'm not inherently defending GM. I'm attacking the notion that man made tricks like cross breeding are inherently safe.
I think the fear around gmo is that food will be less healthy. The same way prepared food takes a few elements of food mixes with chemicals to get strong favours without the depth of flavour. They do this to save costs. GMO companies are making seeds that create plants that do not get eaten by pests. It sounds great until we realize those plants have a toxic substance inside that harms us.
And no, grafting entire sections of bacterial DNA into plant genomes absolutely does not happen in nature.
Please read the link, then get back to me with any actual scientifically founded refutations you may have. Citations are throughout the link, but I don’t see any from you!
https://en.m.wikipedia.org/wiki/Jeffrey_M._Smith
Who has written 2 anti GMO books and made a movie about it. It’s a direct conflict of interest, there’s no point in reading what he writes because it’s obviously biased.
He’s not a scientist either and the Institute for Responsible Technology is just his personal blog.
And now having written a book about a subject which you are knowledgeable about and writing about that subject online together form a “conflict of interest”? Sure, but trusting studies funded by the food industry stating food industry products are safe for consumption by the entire population with absolutely zero long-term safety studies is completely sensible.
That’s exactly what the article you linked to does too. The takeaway is that any alteration to the genome of food is bad.
Just look at Atomic gardening [https://en.wikipedia.org/wiki/Atomic_gardening] - a practice which should be /way/ worse if mutations really did produce bad effects most of the time. Instead the effects were either dud seeds or a few useful byproducts as opposed to 'this grapefruit is now rich in cyanide'.
They're often partners in crime, when it comes to subjects not well understood. Especially with something as fragile as DNA.
I'm grateful this is happening, otherwise our hubris might get too out if hand.
Back to the trees !
edit: it's a loaded question. It happened with the agro-industry and it's happening with the AI industry and the biotech industry right now.
DNA is the most fucking complex and complicated programming language. We have barely any understanding of how the whole thing hangs together, let alone how it's parsed and written, and how it all translates from stem cells to whole organs, an immune system, the complex interrelation between organs, the nervous system, the whole gamut.
And that's not even touching on the nature of mind and consciousness in relation to the body, a perhaps even more enigmatic mystery than the whole story of DNA itself.
It's more in-depth, because I'm abstracting away the elegance of protein/enzyme selection and translation through biochemical/mechanical fitness... But it's all there.
I'm just afraid of the predilection humanity as a collective has for not taking into account/being able to reason through higher order network effects.
Our economic/environmental woes prove that anything approaching the periodicity of a human lifespan becomes extremely hard to analyze/predict in any meaningful way. It seems to work though... So some days I feel like I can't really frame an argument against it.
It's kind of hard to argue that it isn't working when you have air conditioning.
And that's why the OP is a bit horrifying.
DNA's compiler seems to love undefined behaviour ~ probably because the DNA writers knew precisely what to do, without errors.
Undefined behaviour? Whatever ~ creativity ftw!
So, life is greatest and laziest hacker, confirmed, lol?
Compilation of DNA builds a phenotype and it gets interpreted during the phenotype's runtime resulting in epigenetics.
Scientists are highly fallible, and prone to making errors, as well as being corruptible by politics and corporate greed.
DNA is ridiculously hard to understand, and it continues to defy current theories.
So, messing with DNA at this time is extremely dangerous, due to just how incomplete our knowledge of DNA is shown to be, and just how fragile DNA is in terms of resilience to random changes.
The OP is case in point, as to where we currently are.
The article cites the July Nature Biotechnology article about unintended consequences of CRISPR-Cas9 but subsequent work has eliminated many such consequences using slightly different techniques. No word of that fact in this article.
If consequences of genetic engineering are poorly understood, then this isn't reason to worry about reckless research. It's reason to rapidly accelerate the research, and remove as many barriers as possible, so that we can reach understanding and controllability quickly, while obviously taking precautions before products of such engineering are widely available.
The fact is that the majority of this work is happening in China, where no one cares what the moral mavens of the WSJ and the NYT think. I don't understand why such sources continually call for barriers to be put in the way of genetic engineering research.
Certain other nations have incentive and experience with sowing controversy and conflict.
There’s probably more incentive structures involved, but those two + a small native group of alarmists seem sufficient to support current levels of perceived alarmism.
“”” The goals are to improve agricultural productivity, produce hardier beasts and reduce practices that are costly or considered inhumane. “””
I can’t help but think about Oryx and Crake.
I’m more interested in applying these principles and efforts and resources to plants and non-animal sources. I feel that further modifying animal agriculture is orthogonal to direction we can move civilization and is not necessary if we can essentially apply the same techniques for increasing commodity yields to non-animal ag.
(I would love counter arguments and opinions to this. Perhaps I am not seeing the whole picture or far enough.)
Also, we can research lots of things at once, and research funding is not a zero-sum game. I don't think anybody's defunding non-animal agriculture research for this.
Finally, there's a good chance that this sort of research will produce results that will be useful in other fields (e.g. for genetically engineering of plants, or curing genetic disorders in humans).
1. This is true, I do feel that such consumption is guided by and influenced by culture more so than just taste buds.
2. I feel there could be a bias towards whichever research leads to the best economic results, and with the current economic system we live in, I feel the most wealth generating outcome will overshadow.
3. I agree, science is non-linear and we can do much more of it these days, the benefits of many parallel efforts will compound.
It's probably a good idea to move away from feeding corn to livestock, though.
Reminds me, similar thing happened with cattle. Some breeding bulls are used to impregnate tens of thousands of cows. I fail to remember the details but one of them 30-40 years ago had a genetic defect which contaminated a lot of the US stock.
Found a link
https://www.theatlantic.com/health/archive/2016/10/the-dairy...
The other side to that story is that, while the breeding male's genes led to more spontaneous abortions (i.e., pregnancies that ended unexpectedly with calf loss), his daughters produced a lot more milk. From the same article:
> That’s a crazy number, but here’s an even crazier one: Despite the lethal mutation, using Chief’s sperm instead of an average bull’s still led to $30 billion dollars in increased milk production over the past 35 years. That’s how much a single bull could affect the industry.
Given the unknowns there is the potential that malign genetics wouldn't be discovered until several generation have passed. Human generations are 20-40 years. Possible that propagating rare mutations that appear to have beneficial effect may come at a high cost that is only apparent 50-100 years from now.
A bigger issue would be one particular implementation of genetic testing taking off in a group of humans who might otherwise be expected to produce offspring together. Perhaps - community of wealthy families all ordering the same IQ boosting agent may find that their grandchildren all share some unusual, genetically recessive ailment.
[1] https://www.newscientist.com/article/2140926-at-least-75-per...
I don’t advise inaction. But I’d be a hypocrite if I said I’m personally doing anything to change it. I’m just trying to live my life and get by. Problem is, that’s EVERYONE.
So if we’re headed off a cliff, and nobody is grabbing the wheel... Where’s the hope? Why would humanity have a sudden change of heart, come together, solve our shared problems, and move forward with a plan that could actually prevent climate change? How would we get everyone to do that simultaneously?
Because if anyone can answer that question, they’ve just saved the world. And if nobody can...
Base editors are a very new (first published in the last two years) and have a whole new class of off-target effects compared to the ‘standard’ Crispr-Cas9 approach, namely editing multiple bases in the targeted regions.
I’m not sure why you would say that’s base editing is inherently superior to homologous recombination at the point in time.
I come from a religious background and this is an argument that has ceased to have meaning to me. We can't possibly play God. We can't create something from nothing. All we can do is fiddle around with this existence we're in. Part of that happens to be genetics.
What drove me to change my mind was the question "if you have the ability to treat a genetic disease, and you don't exercise that ability, are you complicit in the person's condition?"
Like if you can't cut out that gene to remove X without also altering Y and you can't live with the possibility of altering Y in a negative way then you cannot remove X.
How long until China turns this into a weapon by creating a virus with the spread of a common cold and the devastation of Ebola?
Please delete the comment as I do not seem to be able to.
Mostly.
Bio weapons are amongst the top threats we pose to ourselves as a species.
There’s a youtube series by a guy who made a virus to cure himself of lactose intolerance via gene therapy, that was pretty eye opening. To go from what he did to making a targeted bioweapon is not that much of a leap.
--
I was responding to someone talking about world leaders, after all. And maybe targetting on not being an ethnicity would be possible to, but who knows? So it seems China might actually be more vulnerable to something like this, having so many Han Chinese. I have no clue with what that corresponds with genetically, if anything -- but how you get from what I said to "us" "suddenly thinking" that "China is out to commit genocide" you'd have to explain, the opposite seems much more "obvious" -- the most obvious thing to engage with would be with what I actually wrote though.
The overarching point here, to me, is maybe opening a pandora's box for a few benefits, most of which we could mostly have with good diet and being nice to each other, and possibly giant or species-ending drawbacks, might be a bad idea, and how "nobody would be so stupid because it would be indiscriminate" doesn't strike me as very convincing. Not even if it was necessarily indiscriminate I would be convinced by that, but let's just take that bit for granted. Why would it be indiscriminate though? Serious question, serious answers please.
...because the world has been ended by kids making their own nuclear weapons? What?
Backyard nuclear devices don't end the world, but can still cause a lot of harm. Superdiseases made in a garage might one day have civilization-crippling consequences.
Top scientists would struggle to create a super disease today. Worrying that a kid will do it when the technology is commoditized is putting the cart well before the horse.
They irradiated their own planet ?
If something like that fit in the constraints of life on earth it'd most likely be here already.
Very few countries if any, admit to having a bioweapon program, let alone one based on gene-edited bioweapons.
This makes them great weapons for poor countries who don't care about indiscriminate killing, but bad weapons for large countries that want precision strikes against specific enemies.
Not to mention most combatants don't do their own arms development - that only really makes sense if you are nearing state of the art or effectively lack a market (say nuclear weapons).