CRISPR / CAS9

[jakerman999]

When I was younger I had great interest and desire for technology and was excited by each and every development. Now, I think my greatest hopes for it involve not being subjected to excessive surveillance, and it not killing me before my natural lifespan is exhausted :)

I've had most of the same thoughts, and I'm not that far into my twenties. I have one more hope, and that's that we start colonizing other celestial bodies before we burn or blow up this one.


How long does everyone think it'll be before they try to weaponize gene modifications? Do our concerns stop at super soldiers, or could we potentially see some sort of CRISPR fueled super-virus? We can make malaria not a thing by changing mosquitoes, but we could also change them to carry even more potent diseases. Everything biological is a target with this one.

On the other hand, what does this mean for advances in other science? Gene modification might be used in parallel with or to bolster cloning, and we could see extinct species like the woolly mammoth breathe again.

I think it's a good thing that laws and regulations are as tight as they are regarding this stuff. Some really crazy things could happen otherwise. Makes me thing of that one Rick & Morty episode.

[LupusExMachina]

Actually, the old laws for GMO won't tackle CRISPR for several reasons.
First, older techniques were crude, left virus DNA in the modified cells and there has been no way to control where the inserted gene would end up. It was just incorporated at some random point of the DNA, potentially leading to unwanted effects depending on where it ended up.
So, as both things do not apply to CRISPR, it is good and bad.
Good because now we know what is going to happen (at least a very big freaking lot more than before). And bad because there is no way to distinguish a modified cell from a naturally mutated one. There is just no way to tell if someone tempered with a cell.

As for the mosquito thing. Yes, potentially it is possible to create super disease carrying mosquitos. But it should be considered, that the malaria extinction modification is a single gene which has been taken from wild mosquitos. So, that has already been created by nature. Creating something on our own is a lot harder. And in general, to break something in biology is a lot easier than to make something.

As for what it will be used in I see a lot more potential and less social headwind.
It's true, there will surely be a lot of people very skeptic and dismissive about this. But there is also the point that everyone is suspect to diseases and cancer is a threat that looms above every human individual. The rich and the poor alike. And the carrot of not dying a slow painful death and living healthy for longer is a big and juicy one. I'm sure a lot of people will rather take the dangers it might bring in the face of the potential good it can do. For them, personally.
And as this is something that effects the rich and powerful just as the poor I don't see where it will be banned. Certain uses for sure, but not in general.

As for apocalyptic stuff and super viruses.... CRISPR is able to target "subspecies". I don't know what it means exactly but somehow I'm thinking of ethnic groups. And as that info came from George Church I'm willing to believe it without having read up on it.
To me that is the true danger and the first thing that is going to be banned. Targeting of human subspecies.

The mosquito thing isn't that much of a problem after thinking about it for a while. We've done a lot worse and the world didn't end. Like bringing animals to places where they were not native before. There has been a lot of tempering like this in australia.
So, we already brought myriads of new genes into an ecosystem. And the effect a fully functional genome (speak: an animal with all its genes) is surely a lot bigger than a single gene in the mosquito population. And it's reversible. So I assume malaria will be gone a decade from now. Probably sooner. Zika will follow. Boreliosis is on the list. I'm fine with that.

[Sarudak]

I think it's a good thing that laws and regulations are as tight as they are regarding this stuff. Some really crazy things could happen otherwise.

Is it though? Because here's the thing. On the one side this technology has huge huge potential benefits for everything from food production to life extension to biocomputing. On the other side is the fact that the genie is already out of the bottle. Even if in some parts of the world we crack down on this technology in some other part of the world people will be working on it because the potential benefits are so huge. Bad actors will be especially motivated, what might have happened if Germany developed the bomb first because the US decided is was too dangerous?

In addition to this unlike nukes for which we currently have no practical defense, the best way to defend against destructive use of biotech is biotech itself. This is even ignoring the fact of how many people might die who's lives could have been saved by this technology if we allowed it to move forward.

[Sarudak]

BTW, you'll really love this article on post-cyberpunk: https://medium.com/the-last-night-devbl ... .s5u0m6jjf

I read this article and watched the video in it (https://www.youtube.com/watch?v=ziHCvpikLh8) I have to say it was an interesting experience. If you haven't watched the video you may want to watch it before I spoil it.

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I really liked the video up until the dark turn at the end which I feel like ruined it. Not because of the dark nature of potential mind control and the implied rape (which I'm not a fan of either), but up until that point there was a lot of ambiguity to me of if this is a utopian future or a dystopian one. Gamification is fun and by wrapping a skinner box around everything and guiding the player (???) through life you can increase their motivation and effectiveness. However is that really living? I think it's way too easy to turn to the dark potential for future technology that obscures the question of wether the good future we imagine is actually good.

In the movie basically every choice he makes is guided or prompted by the computer. The computer tells him what thing in his fridge he should eat and even how thick to slice the cucumber. It tells him he has a date and suggests what he should wear. Even on the date itself he is prompted by the computer for everything, he may have to work out some of the simple details but the game is the one driving his actions by the skinner box and the prompts. Is he really living his life anymore? Is he in control at all?

Now imagine we produce superintelligent AI (which seems like a near certainty to me) and computers and robots are so good at every task that they can completely out-compete humans at everything. Now assume that the AI remains benevolent and everyone gets to partake in the massive production surplus. Many people like to assume that humans then will be free to create and invent. Except the one problem that AI will be better at that too. Will we actually paint and compose music when the AI does it better than us? Will we bother trying to invent anything when AI is so much smarter and faster than us that it has already thought of the things we would try to think of? What will be left to humans other than the pleasures of leisure with no real meaningful accomplishment? Might as well stick a wire in my brain and turn on the happy.

[Gilberreke]

Don't get me wrong, I'm happy to observe or participate in a lively debate on the topic. Just given the wording, specific examples you provided, and history involved, it was hard not to take it as a jab / mild troll. No biggy, just a reminder that it's a topic near and dear to me.

Didn't cross my mind at the time. I'll try to explain a little, using parts of posts as an example:

Now imagine we produce superintelligent AI (which seems like a near certainty to me) and computers and robots are so good at every task that they can completely out-compete humans at everything. Now assume that the AI remains benevolent and everyone gets to partake in the massive production surplus. Many people like to assume that humans then will be free to create and invent. Except the one problem that AI will be better at that too. Will we actually paint and compose music when the AI does it better than us? Will we bother trying to invent anything when AI is so much smarter and faster than us that it has already thought of the things we would try to think of? What will be left to humans other than the pleasures of leisure with no real meaningful accomplishment? Might as well stick a wire in my brain and turn on the happy.

I don't worry about things like this. Of course we'll produce a superintelligent AI. We already have AI that beats humans at about every complex thinking problem, except for pattern recognition. What we're seeing with the latest batches is truly creative AI. AI that has "the creativity spark" we consider so singularly human (and maybe slightly available to some primates).

What these debates come down to to me usually:

1) We don't actually need the new tech to commit the suggested doom scenario:
The mosquito thing above is a good example. CRISPR/CAS9 is bad because it could create new deadly diseases? We've been able to weaponize diseases for centuries now (medieval catapults firing rotting corpses into cities for example) and we've been able to create deadly diseases for decades now. CRISPR/CAS9 lets us target ethnic groups maybe? So what? The truly bad people will kill people regardless. All Stalin needed to kill a dozen MILLION people was just plain old hard work. Columbus murdered an entire population basically by himself (and not accidentally through disease, this douche deliberately murdered an entire population of a whole region of the world). Pol Pot went so far as to destroy any trace of cultural identity in his genocide. Leopold II bought an entire region of Africa as private property and murdered more people than Hitler.

2) We're a lot further ahead scientifically than people think:
Your smart watch is able to beat Kasparov in chess now. Not just beat, humiliate. People said just a few years ago that in 20 years, computers might be able to beat top players at Go. All it took was someone to really focus on that. We probably could've done it earlier. In about 3 years, your smartwatch will probably be able to do it too. The Jeopardy AI called Watson basically read a few thousand books (actual reading with comprehension, as humans do) per second to beat humans at Jeopardy. When AI programmers got bored of beating world class chess players, they started playing AIs against each other. In the beginning, AI beat humans through sheer positional play, but what they'd never ever be able to do is play truly creatively like Bobby Fischer or Mikail Tal, right? Wrong. The new AIs that play other AIs need an edge, so they started doing deep, narrow searches (as opposed to the normal shallow, but broad searches chess AI used to beat Kasparov) to get creative moves that can outperform the other AIs. Turns out the moves they come up with are straight out of Tal's playbook, only they do it in a game that is already positionally perfect. Neural networks similar to the Go AIs were created by Google to try and solve the image recognition problem. They haven't solved the problem yet, but what they did "accidentally" do is create an AI that can paint creatively. There goes another thing that was supposed to require a human consciousness to do.

3) We can't actually predict the future, so speculative doomsday theories are usually way too specific and archaic:
Steam engines were going to be the end of humanity, because trains were scaring cows and that would cause the global milk market to collapse. Instead, what they did was create a billion applications that transformed the entire world into one that would be unrecognizable by those people. The problem is, the total amount of knowledge humans have doubles every X years (3 IIRC). It DOUBLES. At this point, there's so much more knowledge than a single person can even comprehend, that predicting 2 years into the future is futile. When I look back at the 90's, I see a completely different world in many ways. The only reason it stays conceivable is because humans don't adapt to technology as fast as we think. When Hitler decided to leverage technology, he accidentally caused us to go into space (V2 rocket program), because he was batshit crazy and took away that adaptation time. This ties back into point 1. A truly scary fuck of a person can do things we can't even conceive with or without the tech.


So that's why I don't worry. Not because I don't believe we can't destroy ourselves, but because I believe we always could, going back decades, even centuries. Inherently humans have always had that power, ever since our brains expanded, because we can actually look at any system we are stuck in and utterly break it. So, there's two options: either we destroy ourselves quickly, through a doomsday scenario and I can't do anything to change that. We're waaaaay ahead of the point where we could do that, so there's no way that stop that. The second option is that I assume we don't and act accordingly. I try to stop the slow doomsday scenarios (like climate change) and try to work locally, stopping plain old humans from being dicks to plain old humans. It also means I encourage potentially dangerous technologies such as these, because it could actually help me with that second option, while only very marginally making the first option more likely (if at all, again, Stalin could have destroyed us with WWII era tech that looks laughable now).

The last point I'd like to mention is that I'm really emphatic. When I see a person suffer, my heart breaks into a million pieces. I devote large chunks of my free time to charitable work. But we don't need new technology to make people suffer, we can do that just fine with a pointy stick. Chimpansees know the concept of genocide and war, so even going back to cave times, like some hippies suggest, wouldn't change that. CRISPR/CAS9, atomic bombs or steam engines won't destroy humanity, humans will. And they don't need any of those techs to make it happen.

[Sarudak]

To be clear my AI scenario was not a doomsday scenario. It was actually the classic superintelligent AI utopian scenario. My argument is that as a human it sounds like that utopia would totally suck.

[Gilberreke]

To be clear my AI scenario was not a doomsday scenario. It was actually the classic superintelligent AI utopian scenario. My argument is that as a human it sounds like that utopia would totally suck.

I'm just saying that you can't look ahead past such an event. It won't be better or worse, it'll be radically different and not comparable to anything you can conceive of. Is our current world better or worse than pre-industrial times? It's really really hard to answer that question in any meaningful way with hindsight. Now imagine asking that question to a farmer in 1700?

[kregoth]

I am beginning to see some real upsides that I didn't anticipate mind you, especially with regards to the accessibility of information. I'm noticing a real change in how people communicate over time as a result. IMO, younger people are becoming far more concerned with accuracy of information in general communication with requests for references and such becoming a day to day part of life. I'm realizing that in the past there was a boatload of false info that would fly around during your average conversation due to the laborious nature of fact checking, that simply wouldn't fly today.

That's a very positive sign to me, and when I realized it was happening it put a big old smile on my face. I think there's a potential for young people growing up today to be far more educated, and effectively intelligent, on average, as a result.

So, maybe the trade-offs will be worth it in the long run, and maybe I'm just an old coot that's too attached to outdated concepts of privacy and such.

I agree with this completely! it's nice seeing the overload of information on the internet being a source for everything one would need to understand the world they are born into. the huge benefit is the current generation growing up in a time where there are no borders for social and educational interactions. We live in a world now where you can play a video game and learn orbital mechanics and the basics of spaceflight! Which in it's own small way, gave a huge boost to the interest of space exploration in children and adults. Being able to instantly share new scientific discoveries is rather awesome!

And with the topic at hand here, the concept of the human body will no longer mean the same thing 10 or 20 years from now. The concept of Death in the future might become muddled in terms of human life expectancy. I am very excited to see what kind of new medical discoveries we discover over the coming years. I for one would love to see modular human body parts, and the dawn of bionics! Replace my smoke ridden lungs, with my own newly 3d printed lungs please!

There's a potentially interesting conversation there as well, as I am truly torn on whether technology has improved my life or not, and what, if anything I hope it will improve in my life in the future.

When I was younger I had great interest and desire for technology and was excited by each and every development. Now, I think my greatest hopes for it involve not being subjected to excessive surveillance, and it not killing me before my natural lifespan is exhausted :)

That's my first dream for the future, people stop using facebook! Oh that and Trump is never let into politics ever again, or Hillary!

[FlowerChild]

Oh that and Trump is never let into politics ever again, or Hillary!

Oi vey. You trying to turn the forums into WWIII? :)

[Sarudak]

Oh that and Trump is never let into politics ever again, or Hillary!

Oi vey. You trying to turn the forums into WWIII? :)

So.... Vote Gary Johnson 2016? :P

[FlowerChild]

So.... Vote Gary Johnson 2016? :P

I'm strictly supporting that modular biological organism in the video jorgebonafe linked at the beginning of the thread :)

[jorgebonafe]

I'm strictly supporting that modular biological organism in the video jorgebonafe linked at the beginning of the thread :)

Seconded. At least it will probably be leading the future of humanity to interesting new directions.

[Gilberreke]

I'm strictly supporting that modular biological organism in the video jorgebonafe linked at the beginning of the thread :)

It would make for a good politician, it's got the flip-flopping down and someone owns several parts of it :D

[FlowerChild]

It would make for a good politician, it's got the flip-flopping down and someone owns several parts of it :D

The modular hairpiece attachment really helps sell its image too...

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[Rianaru]

Actually, the old laws for GMO won't tackle CRISPR for several reasons.
First, older techniques were crude, left virus DNA in the modified cells and there has been no way to control where the inserted gene would end up. It was just incorporated at some random point of the DNA, potentially leading to unwanted effects depending on where it ended up.
So, as both things do not apply to CRISPR, it is good and bad.
Good because now we know what is going to happen (at least a very big freaking lot more than before). And bad because there is no way to distinguish a modified cell from a naturally mutated one. There is just no way to tell if someone tempered with a cell.

Genetic modification laws still apply to CRISPR/cas9 as far as I'm aware, can you cite the facts that led you to believe otherwise? Also, standard procedure for using the CRISPR/cas9 system uses a sort of DNA sequence that acts as a tag that allows researchers to differentiate modified sequences from the original more easily. It's actually very easy to differentiate modified and unmodified cells using these tags. And actually previous to CRISPR/cas9, it was possible to direct the site of integration using a 'sticky end' method, although this method has a much lower accuracy than the new methods.

As for apocalyptic stuff and super viruses.... CRISPR is able to target "subspecies". I don't know what it means exactly but somehow I'm thinking of ethnic groups. And as that info came from George Church I'm willing to believe it without having read up on it.
To me that is the true danger and the first thing that is going to be banned. Targeting of human subspecies.

Allow me to explain what it means. Subspecies and species are differentiated from each other by combinations of sequences that are similar between the in-group, but different from the out-group. If you can identify these sequences, you can identify what species or subspecies that they belong to. Basically the differences between two species or subspecies are the amalgamation of all the sequences that are different between the two groups, but common within themselves. So yes, if you target the CRISPR/cas9 system towards one or more of these sequences that are peculiar to a specific ethnic group, BUT you would only be able to target those sequences that are actually different between multiple groups. This makes it virtually impossible to do anything harmful with it, as the majority of these differences are superficial(repeating fragment length polymorphisms, in case anyone knows what those are) don't have anything to do with our health or our day to day lives. So there is very little to be lost by allowing its use. And besides, who's going to fund this ethnic targeting research? I certainly don't see any profit in it, and just so you all know, the equipment required costs millions of dollars, not to mention paying for the researchers themselves and the cost of developing entire new fields of knowledge. The kind of development that you're talking about costs so much money that I doubt a racist madman would ever have enough to do it.

Banning targeting of human subspecies would be severely crippling the utility of CRISPR/cas9. To be clear, when I say 'targeting' I'm referring to the ability to isolate and retrieve specific DNA sequences that give human subspecies resistance to environmental factors or diseases, NOT the ability to cause any pain or misery whatsoever. Every human subspecies has different genetic resistances to things like various cancers, carcinogens, poison, etc. For example, peoples of African descent statistically have fewer cases of skin cancer than every other ethnic group, but a higher incidence of testicular cancer. Peoples of European descent have resistance to cancers of the heart, but are more susceptible to skin cancers. People of Asiatic descent are reported to have incredibly high resistance to prostate cancer, but a slightly higher incidence of many other types of cancer. Imagine a human that had the best of every subspecies ability to resist cancer. This would be impossible if researchers aren't able to study what makes us different. Besides, tons of people agree that mixed race people are more attractive right? I see no problem with that ;)

PS-sorry if I came across as angry or something, I don't mean it that way. This is an important issue to me, and I tend to get excited when I talk about it xD

[LupusExMachina]

-snip-

No worries man, you did a great job at staying objective.

The thing about not being able to indentify crispr modified cells is still an issue. While older techniques left traces in any case, as it was just part of the technique, it was a no brainer to find out if a cell had been modified. Crispr on the other hand demands a tag that is set by hand. I know, it has upsides, but it won't be there by default.
Also, I assume you could vary the tag, making it even harder to tell from the outside, but easier for your team.
That is the reason I believe the old rulings can't be applied as they are.

And as for the banning. Yet again I see why the whole topic is so problematic. A lot of good and a lot of bad might happen.

The thing about my thinking is focused on the long term on that subject. There is an example from german history that kinda demonstrates what I mean. There had been a pink list in the german kingdom, listing all homosexual people that the police had been aware off. As homesxuality had been illegal at that point, these listed people could have been improsened. Pratical coniderations prevented that though as there was very little to gain from improsining a lot of random people who didn't harm anyone. On top there had to be a lot of new prison buildings just to house them.
So nothing was done about it.
When the NSDAP came to power, the list was used. And the solution proposed by the nazis did not need any prisons.

So, while this doesn't match completly, as the list didn't do anything good in the first place, I think it demonstrates what I mean and why the work done now should be looked at with it's possible long term consequences.

And while that list is a no brainer to forbid, crispr is a lot harder to categorize and deal correct with, considering all the good it could do.

Your information is valuable to me, I understand a little more about the topic.
And yet I am not convinced that it is not dangerous. Once more I don't know if it could work, but is there a gene that defines the colour of black people? I assume it isn't that easy, but if it would... well, there is a market out there for thoughts of that magnitude.

In any way, I hope everything goes well with this one. I finally have hope for my old age and am a little less scared of cancer. I think a lot of people will be. Maybe the sickness will just be like a distant bad dream. When our bodies turned on themselves and killed us slowly.
The first clinical trial has been approved two days ago and will start by the end of the year or early next. It's a modified version of the T-Cell treatment which has been used to send the little girl into remission last year. This time implemented with crispr instead of TALENs. 18 people, various cancers. The goal is not to cure their cancer, but to see if it safe to use in humans.
And maybe they will get well again in the process. Exiting times.

You might want to read it.
http://www.nature.com/news/first-crispr ... el-1.20137

[Rianaru]

No worries man, you did a great job at staying objective.

The thing about not being able to indentify crispr modified cells is still an issue. While older techniques left traces in any case, as it was just part of the technique, it was a no brainer to find out if a cell had been modified. Crispr on the other hand demands a tag that is set by hand. I know, it has upsides, but it won't be there by default.
Also, I assume you could vary the tag, making it even harder to tell from the outside, but easier for your team.
That is the reason I believe the old rulings can't be applied as they are.

You can test for the presence of CRISPR itself though, which would mean that you can detect whether or not sequences have been modified in the organism. From there it would be pretty easy to full a full genome sequencing and identify the elements that don't belong(barring replacing malfunctioning sequences for healthcare purposes of course, as you would see what you would expect to see in a healthy individual).

And as for the banning. Yet again I see why the whole topic is so problematic. A lot of good and a lot of bad might happen.

The thing about my thinking is focused on the long term on that subject. There is an example from german history that kinda demonstrates what I mean. There had been a pink list in the german kingdom, listing all homosexual people that the police had been aware off. As homesxuality had been illegal at that point, these listed people could have been improsened. Pratical coniderations prevented that though as there was very little to gain from improsining a lot of random people who didn't harm anyone. On top there had to be a lot of new prison buildings just to house them.
So nothing was done about it.
When the NSDAP came to power, the list was used. And the solution proposed by the nazis did not need any prisons.

So, while this doesn't match completly, as the list didn't do anything good in the first place, I think it demonstrates what I mean and why the work done now should be looked at with it's possible long term consequences.

And while that list is a no brainer to forbid, crispr is a lot harder to categorize and deal correct with, considering all the good it could do.

Medical information, especially genetic sequences, are considered the holy grail of data privacy, and most data of that sort is anonymized immediately upon collection, making it nearly impossible to keep track of individuals using their medical information. I'd recommend doing some research on data anonymity laws in your area, but most countries protect medical privacy like a mother bear would protect her cub. And besides, you wouldn't need to make lists of people to advance the science at all. In fact, in order to give the entire human race a beneficial mutation, a researcher would only need the sequence data itself. It's not necessary to track people in order to do this. In fact, you don't even need to collect a sample to do it, you just need the sequence data, which could come from any of the millions of anonymized sources out there, including the Human Genome Project, which is completely anonymized and open source to the best of my knowledge.

Your information is valuable to me, I understand a little more about the topic.
And yet I am not convinced that it is not dangerous. Once more I don't know if it could work, but is there a gene that defines the colour of black people? I assume it isn't that easy, but if it would... well, there is a market out there for thoughts of that magnitude.

Several genes working together in concert, in fact, although the system as a whole is not completely understood yet. And it depends what you want. Do you want the color itself, the resistance to sunburn, the oil properties, etc, etc? Also, there are at least 5 known variants of melanin in the human body, all of which combine in different proportions to create the exact skin, hair, and eye tones in each individual. I don't really feel like doing the math right now, but I'd venture a guess that there are many more possible variants of skin color for humans than there are humans by several orders of magnitude at least. Not to mention it is also determined to a large extend by environmental factors that have nothing to do with the sequences of any associated genes. So I guess what I'm saying is that the nature of the beast makes it difficult/impossible to categorize people the way I think you mean, and even if you could, you'd have a hell of a time actually accomplishing your intended 'genetic programming' considering all the random factors that also have an influence on the outcome. It's generally agreed that an organism develops according to how its genetic programming responds to environmental stimuli. Its about half of each, but when you combine the two, prediction is a near impossibility. We can predict natural phenomena, and we can predict the outcome of strictly controlled genetic environments, but try to predict things when the two come together and you might as well be trying to roll a 1 on a googolplex sided die. I'm still of the opinion that biology is a little less exact than this thread gives it credit for. It is a result of a process that is optimized in part by random variability and statistical trends after all.

In any way, I hope everything goes well with this one. I finally have hope for my old age and am a little less scared of cancer. I think a lot of people will be. Maybe the sickness will just be like a distant bad dream. When our bodies turned on themselves and killed us slowly.
The first clinical trial has been approved two days ago and will start by the end of the year or early next. It's a modified version of the T-Cell treatment which has been used to send the little girl into remission last year. This time implemented with crispr instead of TALENs. 18 people, various cancers. The goal is not to cure their cancer, but to see if it safe to use in humans.
And maybe they will get well again in the process. Exiting times.

You might want to read it.
http://www.nature.com/news/first-crispr ... el-1.20137

Yeah one of my old professors actually sent me one of the original proposal papers a week or two ago, it's really exciting stuff! Baby steps and all that, but I'm hoping the first few flagship treatments like this really get people to support the idea in general. Science can save lives and improve everything in our world if we let it, but only if we let it.