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Deformities Alarm Scientists Racing to Rewrite Animal DNA

137 points| hodgesrm | 7 years ago |wsj.com

207 comments

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[+] cronix|7 years ago|reply
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.

[+] akira2501|7 years ago|reply
> 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

[+] gus_massa|7 years ago|reply
> 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.

[+] feistypharit|7 years ago|reply
Or the really scary part...if it not noticed for generations. For example, a reduction of IQ each generation or such.
[+] chiefalchemist|7 years ago|reply
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.

[+] jf-|7 years ago|reply
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.
[+] hanniabu|7 years ago|reply
> 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

[+] laretluval|7 years ago|reply
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.

[+] sgc|7 years ago|reply
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?

[+] projectileboy|7 years ago|reply
Exactly, exactly, exactly. The hubris of people thinking that they understand “this gene has this discrete effect” is astounding to me.
[+] macoovacany|7 years ago|reply
> 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

[+] e12e|7 years ago|reply
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?

[+] credit_guy|7 years ago|reply
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.
[+] bumby|7 years ago|reply
Is this similar to the concept of pleiotropy?
[+] jayalpha|7 years ago|reply
"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.

[+] nerdponx|7 years ago|reply
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.

[+] johnchristopher|7 years ago|reply
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.

[+] Valmar|7 years ago|reply
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.

[+] buboard|7 years ago|reply
We call that debugging, for short
[+] laretluval|7 years ago|reply
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.

[+] trevyn|7 years ago|reply
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.

[+] AlexCoventry|7 years ago|reply
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.
[+] trophycase|7 years ago|reply
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?
[+] Nasrudith|7 years ago|reply
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.
[+] dpflan|7 years ago|reply
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.)

[+] tardigraded|7 years ago|reply
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).

[+] Gibbon1|7 years ago|reply
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...

[+] ejstronge|7 years ago|reply
> 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.

[+] trophycase|7 years ago|reply
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...

[+] anigbrowl|7 years ago|reply
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.
[+] rubatuga|7 years ago|reply
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.
[+] vxxzy|7 years ago|reply
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.
[+] all2|7 years ago|reply
> 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?"

[+] _bfhp|7 years ago|reply
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.
[+] jchw|7 years ago|reply
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.
[+] kingkawn|7 years ago|reply
They’re still actively discovering the modes of regulation via folding structures. They have noooo business messing with this shit
[+] mentos|7 years ago|reply
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?