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I think this could have far greater dangers in the creation of super diseases.

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?

Uh, what makes you think government bioweapon labs haven’t been doing that for decades, since the invention of genomics?
Most major governments have already admitted to it because it's the only way to study how to counter such attacks without actually engaging in said warfare.
Citation needed. Most governments that admitted to having a program, only admitted it after it had already been shut down.

Very few countries if any, admit to having a bioweapon program, let alone one based on gene-edited bioweapons.

Bioweapons are 1) Cheaper 2) Harder to control 3) Less reliable than traditional arms.

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.

Wait cheaper, how? Maybe in terms of development of say a fighter jet but it is certainly more expensive than a bunch of surplus Russian equipment.

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).

Something that would rapidly spread back into their own highly dense population centres and wipe them out? For the most part world leaders aren’t this stupid.

Mostly.

Eh. With gene drives we already have the technology to selectively target or not target particular ethnic groups.

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.

https://youtube.com/watch?v=J3FcbFqSoQY

When you release something it becomes subject to natural selection. It would evolve to target everyone. It’s still dumb.
It's also a sort of safeguard. Pathogens that are too deadly to the organisms they infect are selected out.
Not if they are eventually deadly, like HIV. If HIV spread in a targeted way, with the level of contagion in a common cold cold it would be bad. Of course, it’s not great if you want to prevent retaliation.
World leaders are getting more stupid before our eyes though, it's not like this tech is only available until Christmas or something. Couldn't targetting specific ethnicities seem feasible enough at some point that someone just might try it?
Look, I’m no big fan of China, but why do we suddenly think they’re out to commit genocide? Let’s calm down here.
Why are you putting words into my mouth, and then ask me to calm down? I asked a question, it was a serious one, so calm down and let someone have a honest shot at answering it.

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.

Someone had their coffee today.
I'm not allowed to have coffee, on account of I fell into the cauldron as a child. kicks rocks
They are committing genocide right now.
And what happens once discarded gene-editing technology is available to 14-year olds? There are few technologies in history, including nuclear, that haven't eventually been available to curious teenagers.
> There are few technologies in history, including nuclear, that haven't eventually been available to curious teenagers.

...because the world has been ended by kids making their own nuclear weapons? What?

I think he's talking about this incident https://en.wikipedia.org/wiki/David_Hahn

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.

We should never avoid discovering something out of the fear that it could be misused. We have an imperative to learn all that is learnable and then use the findings to ensure safety and develop countermeasures. Otherwise, someone else will discover it and we will be unprepared.

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.

Would you stand by your initial statement provided the discovery was something which was certain to eliminate all life?
Well the thing is you never know for certain if it really will eliminate all life until it does. During the Manhattan project there were concerns that the unprecedented temperatures might be enough to start runaway fusion reactions and ignite the atmosphere.
Sans of nuking civilization back to preindustrial age, this is going to happen. It's a question of when, not if. We should be preparing to mitigate the danger.
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China's better angle is to capitalize on their collectivist social attitudes, allowing them to discard as many babies as necessary to win the race to superhuman-ness.
Viruses aren't loyal, so nation states would not be likely to unleash such a thing. Its more likely that something like this would be created by a lone nut or a fanatical apocalyptic cult or terror group.
I imagine that viruses could very much be ‘loyal’- if we’re gene editing you could not so theoretically target ethnic-specific genes to attack.
If viruses can jump between animals and humans, they can jump between ethnicities.
Right but YOU’d be developing the payload...
The payload could also mutate, virus DNA isn't very stable.
The virus could very easily evolve to target a broader profile.
Do viruses normally evolve their payload on their own?
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Viruses have fast mutation rates and high generation sizes so they evolve very quickly.
Is China the new empire of evil? Why would they do such a stupidly suicidal thing?
The catch here is that pathogen has been evolving for billions of years, already.

If something like that fit in the constraints of life on earth it'd most likely be here already.

Taking this thread straight into nationalistic flamewar is wildly off topic and outright vandalism on this site. I'm sure you didn't mean it intentionally but please don't do this again.

https://news.ycombinator.com/newsguidelines.html

I think it’s been about 90 days. Can you at least re-enable the ability for people to vouch my comments?
Wasn't the intention, insert <any country> in place of China

Please delete the comment as I do not seem to be able to.

This just in: fucking with stuff we don't fully understand has negative consequences we don't fully understand.

I'm grateful this is happening, otherwise our hubris might get too out if hand.

Indeed.

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.

All of those are nothing but challenges. We'll figure all of them out, eventually.
You have too much faith in science.

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.

It's like if you had a version of C that replaced all compilation errors with undefined behavior.
There's a small part of me that wants this to exist. That sounds both horrifying and pretty hilarious at the same time.
Exactly.

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?

We were told the evolution do the thing this way exactly, but one error at a time.
Not really. It's more like a compiler, an optimizer/simulator, and compiler-compiler all pipelined in a circle. Seemingly random changes get incorporated into a starting binary that are selectively pruned/modified during the simulation/optimization phase, which generates a new compiler-compiler, which constructs a new compiler, which generates a new binary to run through the optimzer again.

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.

The equivocation to programming language is misleading, it implies the “language” is context free or context sensitive when dna is probably on the order of natural language complexity (posits I).
Far more complex, I would argue. The “compiler” (or perhaps the “linker”?) consists of laws of physics and chemistry that govern intra- and intermolecular bonding and protein folding with such complexity that it has been the subject of one of the largest distributed computing networks ever: https://en.m.wikipedia.org/wiki/Folding@home
Well I would say if you're going to use the programming metaphor that perhaps it's both compiled AND interpreted.

Compilation of DNA builds a phenotype and it gets interpreted during the phenotype's runtime resulting in epigenetics.

DNA is almost exactly machine code. It's directly executed by ribosomes and other cellular machines. Of course there are no guard rails.
Except that it doesn’t represent logic, it represents strings of amino acids that form proteins that fold up in unpredictable ways and interact with lots of other things to do stuff that half the time is weird and inefficient and doesn’t make sense.
That is logic, even if we cannot fully comprehend the system yet.
Call it that if you want to, but I’d be rather unhappy if that was how machine code worked.
I wouldn’t compare it to machine code alone and for it to be considered following under rules that can be broken down fundamentally to appeasing what we define as logic. I think of recursive functions calling other recursive functions with returning variables that effect the whole mess of a system when I read the perverse alterations to the animals in the article.
There's quite a bit of logic encoded. DNA has equivalents of conditional jumps, and stored state. That's in the stuff that for a long time was called "junk DNA" between the encoding sequences.
DNA is less formally complex than natural language. Natural language is somewhere between context-sensitive and context-free. Valid DNA sequences are fully characterized by {Start codon + {Amino Acid}* + Stop codon}*, a regular language.
That’s the lexer, consider the parser or the semantics?
Yes, however the "machine" that executes the code< namely the physical world is not deterministic and not a Turing machine, generally, at least because it is governed by unpredictable quantum effects.
So, should we put laws in place to prevent that kind of fuck up or is the "whataboutinnovation" screaming horde already owning the debate ? /s

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.

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We call that debugging, for short
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And delete all the builds which don't work?
Or make them into burgers.
Given that the human microbiome [0] takes up genetic material from the food we consume, I'd be concerned about eating this stuff.

[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711824/

I’d happily eat the frankenburgers. I don’t buy into the anti-GMO hype!
This paper is talking about horizontal gene transfer between bacteria of the gut and bacteria we consume.
So, a moot point if the food is cooked enough? (all the DNA will uncoil and denature)
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GMO
Sheesh,just meant same thing is possible with GMO. Unintended consequences are a real thing. I'll never understand why people are emotional over GMOs like it's a political subjecr.
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This is very conflicting. Clearly, we have to learn somehow... But this is just about the last kind of thing where you want to do trial and error.
What if the consequences are some kind of natural DRM?

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.

It is more like a low-level, holographic language. We have to figure a higher level one, which defines all the properties and create a compiler into DNA sequences. Most likely it will change quite a bit in the resulting sequence.
There's always the argument about "Playing God" but we do vaccinate ourselves right? I mean I think the real issue is inflicting a change to a being that will become "Sentient" or "Conscious". When we genetically alter that which has potential for "life", do we know, beyond a doubt, that the change we inflict will be positive for the individual AND positive for our species as a whole? If we cannot say for certain, then genetically altering sentient life (who have no choice), is not a good idea.
> There's always the argument about "Playing God"

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?"

I’m writing from a hard determinist mindset. I would argue that whatever is done in life is the will of God. Since choices are an illusion around oneself believing in free will. So basically life is predetermanism for every cause & effect. The phrase playing God just makes me think of something similar to how a bunch of game programmers have already created a simplified replication. The Sims. Who is to say the sims are any different than us. Anyway the create anything out of nothing is symbolic. I really do like your last sentence “last paragraph” and made me want to reply with mentioning this.
It’s interesting... I like to think that we have freedom to make decisions within the “hard bounds” of the system. I don’t think the existence of “hard bounds” indicate a system’s lack of potential for free will to exist. I do think “bounds” can limit an agents Choice, but not their ability to make a decision. Our current existence/system appears bounded in some aspects and unbounded in others. As we learn more, ideas and perception will be adjusted.
Yah free will believers like to think they have choices/decisions in the system. The reality is no, when you become the person you are now from every preceding event making you the person you are now. I would only see the possibility of persons having responsibility or free will if they decided to live this life before birth and with beforehand knowledge of how everything would play out. The illustration of how a deterministic system is similar to clockwork with every part being moved by the whole clock is helpful. If something outside the system does something to the clock and makes the parts believe the reaction has no deterministic essence from the clock, such as quantum theory may show.. well it still doesn’t change everything being outside the control of the clock but is just hidden variables to the clock system, inobservable until it happens and would be like god deciding to alter the determanistic system slightly.
From my laymans POV, DNA is just a shit ton of variables in a very complex code that interact with each other. No single point just does a single thing. They all interact with each other. No different than changing a variable in one piece of code and having it create a bug in another that was previously working.

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.

"No single point just does a single thing."

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.

GM foods are arguably no more dangerous than any massively engineered foods we've been eating for decades/centuries. Direct gene modification is more like using a scalpel rather than a 2x4. Still potentially dangerous, but far more precise.
Can you elaborate?
Selective breeding is the poor man’s genetic engineering.
Think about wolves. Over many generations of selective breeding, we have poodles.

No engineering required, but obviously a huge change.

Another example would be King Charles Spaniels, which are overbred to have tiny heads and big cute eyes - and are at high risk of seizures from compression of the brain by the skull :-(

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.

I wonder what possess people to want to own dog breeds that are physically deformed by design.

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.

It's easy to breed and sell dogs and hard to regulate/litigate against bad breeders. The US Kennel club prioritizes promoting 'breed standards' over the wellbeing of the animal. My informal observations suggest an overlap between such priorities and the general belief in animals as property/divinely ordained for human use/lacking in consciousness of any kind.
GM foods are actually more dangerous, due to how GM works.

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.

Why do you think cross breeding is safer then GM? Nature doesn't "know better", crossbreeding is just easier, and we only keep the results that work. Known-viable mammal hybrids tend to have poor health, with some obvious exceptions like mules.

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.

Personally, I think the monetization of GMO is the problem more than the GM.

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.

> Cross-breeding allows nature to combine things that fit together in all of the right place

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 have a pear tree with three different types of pears on different branch. Grafting has been going on for centuries.

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.

Intentionally confusing genetic modification with cross breeding is one of monsanto’s favorite talking points.

Genetic engineering is more like changing the byte code in your OS hoping to change its functionality. Without having the source code.

This analogy is getting tortured beyond the point of usefulness, because the the other side of this analogy is that cross breeding is mixing files from two different repos together and hoping they still work.
It's more like editing the raw binary of an executable. It's only more precise if you understand the binary representation and the impact of changes. Otherwise it's incredibly imprecise, as you are just randomly flipping switches.

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.

I was trying to reason about CRISPR (and other editing methods) and try to get an analogy. It sounds a lot like an efficient hex editor. Sure you can edit parts of the "code" but we don't have any debuggers readily available. We can edit randomly and "run" the code, but as far as I know that's about it.
And it turns out nature really likes operator overloading.
It's not a perfect analogy, but I think CRISPR is a bit like a regexp-replace edit function being used to hot-patch your live system memory. It has an extremely narrow pattern-recognition buffer, and you are gambling that you found a sufficiently unique signature at your edit point(s) so that it doesn't also corrupt unrelated parts of your system image that happen to match the same pattern.
I don't think it's really accurate to describe selective breeding as restricting how you can modify the underlying data. I'd rather say that the executable itself contains layer upon layer of consistency checks so if you modify it too much it will just refuse to "boot up." In fact selective breeding relies heavily on this mechanism since it can create hundreds or even millions of nonviable organisms for every viable organism.

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.)

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The problem with GM foods is that the overwhelming majority of them are modified for resistance to poison chemicals, which are dangerous and haremful
"GM foods are arguably no more dangerous than any massively engineered foods "

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

Any change analyzed in a vacuum is risky. The trick is to compare it to the alternative, and see if it is more risky. The alternative to GMO is applying random mutations, and then selecting a strain that has the behavior we want. This has much higher risk than changing only what we need, since many other components could be changed at the same time too, and each of them also have these many interactions.

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.

You’re probably right, but could you provide an example of an unexpected consequence of an inserted gene?
Arguably? Yes. Provable? No.

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?

Even if this hypothesis is correct, I would replace "dangerous" with "unpredictable", because the resulting effects of those interactions would be as likely to cause good as to cause harm.
Unpredictable, therefore being dangerous and extremely risky?

They're often partners in crime, when it comes to subjects not well understood. Especially with something as fragile as DNA.

Why do you think changes would be as likely to cause good as to cause harm? In complex, yet structured, systems - I think changes without fully understanding what you're doing are vastly more likely to cause harm than good. Software is the obvious example. Change a line of bytecode/assembly to something else. I think the chances of that change being good are extremely close to 0.
This guy is 100% right, and this is important, so please stop downvoting him.
But in nature most mutations are neutral, period. It is likely to be more don't cares although actual improvements are unlikely. Good outcomes from random chances are rare but that doesn't mean that bad outcomes must be the dominant component.

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'.

No, please, please. Do not do this. You eat your food. The purpose is different. It has been engineered to shit already.
Except food doesn’t tend to harm you if it’s DNA is a little different, you digest it, it doesn’t modify your cells directly.
The DNA doesn’t, no. But what does DNA do? For one thing, it contains instructions for constructing proteins. Proteins which you ingest with the DNA as part of the food. GMO foods have been shown to produce malformed proteins, and some of them appear to have harmful effects when eaten. And that just scratches the surface. https://responsibletechnology.org/gmo-education/health-risks...
That genetic modification can, and does, happen naturally, all the time. It’s how evolution works
That talking point has already been attempted by others. Using one term, genetic modification, for several completely different processes doesn’t hide the truth, it just confuses people.

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!

> Using one term, genetic modification, for several completely different processes doesn’t hide the truth, it just confuses people.

That’s exactly what the article you linked to does too. The takeaway is that any alteration to the genome of food is bad.

The article could have definitely been more specific. Good thing there are citations with all the specifics you could ask for...
The site you linked to is from this guy:

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.

No citations from you either. How about some peer-reviewed studies proving their long-term safety rather than ad hominem attacks on an author pointing out scientific studies proving actual harms? I’ll say it to you, too: Read the damn citations and get back to me with your own.

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.

The overall generalization lately appears to be that complex traits are encoded in all genes, such that each gene makes a linear contribution to the trait (the "omnigenic" model).

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.

Is this similar to the concept of pleiotropy?
Or the really scary part...if it not noticed for generations. For example, a reduction of IQ each generation or such.
You know I originally thought this was an outlandish idea, but I have to remind myself that the processes that govern reproduction are themselves encoded within the DNA... If those processes are affected adversely, it may well take many generations to realize the effects, at which point for those individuals it is far too late to undo the damage.
Not just for those individuals but it would have spread throughout the gene pool and been impossible to contain.
Very droll. Nice elude to dysgenics [0].

0. https://en.m.wikipedia.org/wiki/Dysgenics

why would evolution stop at the neck?

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

Sounds like a plot for the prequel to Idiocracy.
IMHO, getting good at genetic engineering mostly negates the potential dangers of newly introduced bugs that stay dormant for a long time. After all we then have the tools to fix them.
As long as the mistakes, or bugs, are survivable, or not transmitted like the flu is transmitted.
> From my laymans POV

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

[8]: https://en.wikipedia.org/wiki/RNA_world

C may let you shoot yourself in the foot, C++ may let you blow your whole leg off, but only CRISPR will let you turn it back into a tentacle.
So maybe The Thing was an alien CRISPR experiment gone wrong.
You just described the plot of Prometheus too.
How wide is the set of potential tentacles?
I don't think this really takes away from gp's argument, which is that editing genes is complicated and could wind-up with unforeseen consequences.

"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.

The "cut-and-paste" analogy is perfect here. Imagine you discover super-complex code for which you have only a rudimentary understanding. Now imagine replacing sections of code from one program with sections from another program and calling it an improvement before even testing the code!

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.

Exactly. It seems like we may want to develop more accurate models of how changing DNA and its environment affects its expression through (t)RNA, proteins, and reflexively itself, before making massive "production" changes in one go. In other words, perhaps we should be more methodical and patient in our approach? Curious what the experts have to say about this.
All true, but it's progress compared to some current GMOs (I'm not anti-GMO). Quite literally developed by exposing fields of fruit to massive amounts of radiation until you ended up with a generation that was better than the last.
It's funny that you can sell the irradiated fruit offspring as organic.
Sounds like it's time to refactor that system into something less crazy. Or better yet, rewrite it in Rust.
Someone should definitely disrupt that inefficient proteins assembly line.
That system is incredibly efficient and dynamically stable.
Too expensive, outsource it to rewrite in JavaScript
That actually makes cronix' point.
In keeping with the analogy, what you're saying is that the build system and deployment system are extremely complex and have a lot of parameters.
That's not only a layperson's POV. There was an article in The Atlantic (approx a year+ ago) - which I've looked for an cannot find (sorry) - on a scientist who long to short "I don't think things (i.e., DNA) are what most science thinks it is." Much like you he said, "it's not this simple. the mesh is more complex and has multiple currently unforeseen dependencies." Obviously, I'm paraphrasing.

And every month since I've read something that supports this and undermine the current conventional wisdom / proof.

It's not so much conventional wisdom as predominant wishful thinking. Everyone hypes up the possibilities for their piece of the grants, investors, and the media attention but every geneticist I've had a private conversation with has been little more than cautiously excited. CRISPR is the genetic equivalent to their first binary editor but the complexities of epigenetics and expression machinery have long been taught (and why everyone is so excited about it), as well as the giant missing pieces in embryology where we don't even have a cursory understanding of how to bootstrap an organism from a genome without artificially inseminating a very closely related species.
There's been a lot of discussion on how machine learning neural nets are at all like our brains or not - but wouldn't DNA likely be more similar? Lots of random factors that in a roundabout way increase/decrease trait propagation (a new generation before death). And splicing genes would be a bit like assuming you could transplant the bit of a neural net that you think recognizes zero, to be used to write better letter/glyphs for "o"s and/or "ø"s?

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?

This is why I am strongly against anything but the most urgent genetic engineering. We completely screwed up the industrial revolution. We have never recovered from it, and maybe never will.

So now we are going to start in on biology?

> We completely screwed up the industrial revolution.

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.

What price do you put on a species?

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.

Let's talk in 50 years. Odds aren't great, but there are still odds to talk about for a little while at least.
You can make that argument without all the histrionics and performativity. Please give it a try.
I don't believe I can.

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.

anigbrowl is right. Please don't post in the outrage style to HN. Your comments would be more persuasive for being less flamey. This is a case of medium-is-the-message.

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.

Apologies. I'd be in favor of removing the first line, and decapitalizing THAT. I feel everything else stands as content.

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.

I think you misinterpreted sgc's comment to mean that everything about the industrial revolution was bad. More likely it meant that some things, not all, were bad. Of course sgc didn't specify what things—which made that comment pretty unsubstantive. Still, that's no reason to go on a flamewar tangent.

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://news.ycombinator.com/newsguidelines.html

But if the benefit of it is enjoyed only by a few generations out of tens-thousands, then no. It'd be a failure.

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.

Our failure to do something about carbon (in the last 30 years we've comprehended it) doesn't diminish the progress made.

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.

> Something like "everybody will get Alzheimers by age 50" where it takes 50 years to even discover it.

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

So, look, don't do this.

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.

This is absolutely on topic because it’s exactly how the problem proliferates. In isolation it can be corrected but as soon as we build and industry on it and it becomes part of the economy...well... It may be cartoonish with sugar and diabetes but not so much when our entire species is at stake.
Hijacking the top comment to say that this thread is a mess. Nobody seems to know what they’re talking about and at several points it degenerates into arguments about GMO food. It would be really nice if some domain experts, if there are any here, would give us their opinion on the article and the issues it raises.
> From my laymans POV, DNA is just a shit ton of variables in a very complex code that interact with each other. No single point just does a single thing. They all interact with each other. No different than changing a variable in one piece of code and having it create a bug in another that was previously working.

Drew Endy did a lecture this a while ago. It's from one of the chaos computer club seminars.

https://vimeo.com/18201463

(comment deleted)
> No single point just does a single thing. They all interact with each other.

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.

Does the code for insulin do anything else?
As far as I know, no.

(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 )

> As far as I know, no.

So... not "well known and understood" then - if it were, a definitive "yes" or "no" would be the appropriate answer.

Exactly, as far as you know.

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.

This all sounds reasonable. On the other hand, you can randomly take half of someone's genetic code, complete it with half of someone else's and you get another fully functional one. That's not something you can say about programs written by humans.
The irony is too strong:

“”” 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.)

We'll, the reality is that most people will continue eating meat regardless of what people like me and you think of it, so it's probably a good idea to put some effort into minimizing the negative consequences.

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).

Good points, thanks!

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.

Meat could get very expensive soon if climate change reduces the amount of easily farmable land, and that might quickly change peoples opinions. Part of the reason I’m eating more vegetarian food is because the quality of meat that I want to be eating is very expensive.
This isn't zero sum. Some land is not suitable for farming (too dry or too hilly), but is useful for grazing. Land that's suitable for both often does better when rotated between crops and livestock. And grassland may be better than farmland at carbon sequestration.

It's probably a good idea to move away from feeding corn to livestock, though.

What's the agenda behind the spate of gene editing alarmism lately?

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.

I definitely don't want barriers on research. Rather, the issue is that this technology is being used by overzealous profiteers who likely care very little about potential consequences. Alarmism is warranted IMO when corporations that have proven to be sociopathic are using this technology and potentially affecting near every in the country (and maybe the planet). Haven't we learned anything from global warming?
The media has incentive to report controversy.

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.

I agree, it's awesome that we can now do targeted forward genetics on mammals. Weird phenotypes in mutants are a classic path to biological insight.
The most cynical answer assuming an actual agenda is 'vested interests' who fear that they won't be able to compete. however not all apparent agendas come from interests - at times they are essentially memes run amok. There isn't a rational interest behind anti-vaccination efforts yet they are sadly growing.
I don't understand. Some rabbits were born with longer than usual tongues as a result of an experiment. So kill them and iterate... What's the problem?
Quote: and they fear that mutated genes may spread unchecked as animals breed.

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...

> 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.

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.

The cautionary note is this wasn't discovered until the recessive gene effected about 10% of the cattle population.

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.

I share your general concern, but would like to point out that this particular example couldn’t happen in human genetics for a variety of reasons (we are less consanguineous, practice assortative mating, get extensive medical care including fertility treatments).

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.

Yes, you're interfering with an extremely complex system. Are we really so naive to believe there is some exact 1:1 mapping of genes to traits, or even close to that? The fact I've heard things like "75% of DNA is useless" [1] seems like such a laughably naive statement I fear for the future of humanity.

[1] https://www.newscientist.com/article/2140926-at-least-75-per...

...What future of humanity? Call me cynical, but we seem absolutely bound on wiping ourselves out one way or another. Our focus on money above all else is killing us all. We’re playing useless games, winning useless tokens, and spending them on useless prizes, all inside an arcade that’s on fire. Climate change, GMO foods, overpopulation, water pollution, nuclear war, ecosystem destruction, we’ll find a way eventually. Just a matter of time.
Listing all hard problems is a common trope/trend we see often these days with doomsayers. Is it an excuse to be a nihilist and not act on those problems ?
Not at all, and I did not intend to give that impression. But that “list of hard problems” contains things which are MORE LIKELY THAN NOT to kill us all. Climate change, in particular.

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...

I'm no biologist but I don't feel like we have a good enough theoretical understanding of DNA, in the same way that doing search and replace on object code in a hex editor doesn't mean you have a good understanding of programming. The little I know about systems biology from using Cytoscape and reading a few papers reminds me of learning to use a disassembler instead of a debugger.
Article says they are using an "older method" of gene editing. Well no wonder then, we know that older gene editing methods have a lot of off target effects, crispr cas9 using base modification (instead of deleting whole DNA stretches by splicing) is very safe. This is a FUD article.
Pretty likely the same thing was said about that older method.
> Article says they are using an "older method" of gene editing. Well no wonder then, we know that older gene editing methods have a lot of off target effects, crispr cas9 using base modification (instead of deleting whole DNA stretches by splicing) is very safe. This is a FUD article.

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.

They’re still actively discovering the modes of regulation via folding structures. They have noooo business messing with this shit
I share the worries of "messing with things we don't understand" but that comes after not accepting this practice of using conscious beings who can experience pain as objects. It's inventing more suffering on purpose, intentionally breeding animals that were born to potentially suffer. Breeding animals in general always has a chance to result in painful deformities but this is treating them like they don't matter.