Mail-Order CRISPR Kits Allow Anyone to Hack DNA
scientificamerican.comHere's a transcript of a recent talk given by Josiah Zayner: http://diyhpl.us/wiki/transcripts/diy-human-gene-therapy-wit...
[20:40] “If you look at Step 3 - which is, uh, you know, I like steps and lists, they are awesome - uhm, there are actually websites out there that have this infrastructure completely built. You can go in, type in the name of a gene. Not even the name, you could type in the name you think a gene should be named, and what it will do is predict the best guide RNAs, the best 20 bases, to use, so that Cas9 enzyme can cut in your genome in this exact place."
"Literally, you don’t have to do anything, right? You have to go in, type in the name of a gene, and press enter, and you could modify yourself with CRISPR. Right? That’s what this DNA basically is. This DNA, if you think about, took me about 5 minutes to make. Actually, it happened so fast, I had to go back and verify it a couple of times. I didn’t think I could create DNA that could modify my own genetics with CRISPR in 5 minutes. Now, if that doesn’t blow your mind, I, I really don’t know what does. And, the next question comes down to, 'What’s holding us back; what’s stopping us?' And I dunno, to me, I, I don’t really know what’s stopping us, you know? I, I think about it a lot, because, I have this really, you know, bad snaggle-tooth, and I think like what happens if I could change that?"
"No but if you think about, people are born with things that they have no decision over. And then everybody else says, 'Oh, no, fuck you, I'm athletic and 6 feet tall and, you know, good looking, and you just, you just, the genetic lottery - you lost. That's the truth. You lost the genetic lottery and you have to suffer through it.' How does it make sense?"
http://www.the-odin.com/diyhumancrispr
personally i'm down to fund projects like this, so if any of you are interested, get in touch & let's deploy.
Back in the days of Mac OS classic, there was a tool called ResEdit. You could use it to explore and modify apps. Or the core OS. While it was running.
It warned you this was a bad idea, but I did it anyway. It took ten years before I saw a computer lock up that hard again.
That’s how I see humans DIY hacking their own genome. If you’re lucky you’ll get what you were after. If not, you now have sexuality transmissible lycanthropy which (as a side effect) lobotomies you as your new skull shape was designed by an artist and not a biologist.
It doesn't really work like that though. The genes that cause much of your form dictate growth processes between embryo and adulthood. If you could change them everywhere you wouldn't change at all.
But it's also not how CRISPR/CAS9 works either. Gene therapies usually involve a process of extracting stem cells, modifying a small number of them in vitro, growing them, and then either using them to grow tissues out of the body for later implantation, or injecting them into targeted tissues.
It's not an injection you take that goes out and edits every cell and you magically change shape. It makes for good scifi, not so much good science.
> It's not an injection you take that goes out and edits every cell and you magically change shape
I don't think that's what they were referring to. It seems that the concern is you make an edit, it is unsuccessful in implementing whatever you wanted but also breaks something critical (e.g. proper skull formation), and that gene is passed to your children who then suffer the consequences. That seems feasible to me, but I'm not a bio expert, don't play one on TV, and haven't stayed in a Holiday Inn in years.
Gene therapies are targeted to specific tissues/organs. The only way you pass on the genes is by using CRISPR/CAS9 to modify an embryo or gamete in IVF.
Your suggestion is much more plausible than mine, especially as it won’t be noticed for at least 9 months after the modification. I was mainly inventing a nicely dramatic failure mode that seemed plausible on the assumption humans are just a bunch of self-replicating chemicals, so you could inject genes that say “send self-destruction signals to nearby cells that have not been modified like me, then grow into the gap they leave in [shape of new structure]”, much like the sexually transmitted genital cancer dogs can get that was in the news a while ago.
I guess you can backup your genes by putting seed/eggs on ice :)
> If you’re lucky you’ll get what you were after.
No, if you're lucky, nothing happens. The majority of the other alternatives are just death.
Just imagine a complex codebase and then you start changing parts of it randomly. What are you going to get? Either nothing or more likely, some sort of a crash which in biology means death.
What's the probability that you'll get a feature or fix a bug doing that? Almost 0.
What about a complex codebase with nearly 8 billion subtly different running copies? Your copy has a bug, so you find a copy that doesn't and monkey-patch the assembly. Have you fixed the bug? Unless it was in some initialization code that won't get run again, your odds are pretty good.
A lot of genetic disorders are simply "whoops, your gene for X protein/enzyme/whatever is corrupted". I'd sure be tempted to patch that in myself.
“Lucky“ in the sense that the tutorial you followed didn’t miss a step, that you followed it perfectly, and that you correctly understood what it did. How often do people copy the wrong thing from stackoverflow, for example? Or miss an important step, or the last character of text?
I rather doubt many people will try to hack their own DNA by keyboard mashing a new sequence.
Finally, what about the nightmare scenario: Is CRISPR so easy to use that we need to worry about biohackers—either accidentally or intentionally—creating dangerous pathogens? Carroll and others think that the danger of putting CRISPR in the hands of the average person is relatively low. “People have imagined scenarios where scientists could use CRISPR to generate a virulent pathogen, ” he says. “How big is the risk? It’s not zero, but it’s fairly small.” Gersbach agrees. “Right now, it’s difficult to imagine how it’d be dangerous in a real way,” he explains
It's hard for "normal" people to imagine how sociopaths or those with destructive aims will behave when given flexible tools like this. It's kind of like how no one anticipated how social media networks whose ostensible purpose is to connect friends could be used to undermine elections, abet fraud, commit character assassination, and drive people to suicide. And while the real-life example of using CRISPR to switch the limbs of tiny crustaceans sounds harmless, wait til someone mutates something bigger and more familiar for "better" attributes or capabilities that can cause direct harm or inadvertent effects. It's probably already happened ... but we may not understand the impact for years.
As other people have said, it has been possible to make bioweapons for a long time, but engineered bioterrorism hasn't happened.
There are a few reasons I think. Firstly, there is a cultural disconnect between fundamentalism and science heavy weapons development. In the same way that ISIS is not building gigawatt lasers or rail guns, the groups capable of terrorism don't prioritise research. They are often very atavistic, wanting a return to a less technical, less advanced society.
The second thing is that engineering even the simplest organsim is still hard. If you are trying to build a pandemic virus, you need a fairly elaborate set up to do it and avoid killing yourself first. This is far less accessible than making explosives, or obtaining guns.
The biggest risk is state funded labs in eg North Korea, or the emergence of contract labs willing to do anything for a fee, eg a 'biohacking' equivalent of Hacking Team.
Aum Shinrikyo actually had a bio-weapons program that failed, seemingly due to a lack of technical expertise: http://www.nti.org/analysis/articles/revisiting-aum-shinriky...
That was a fascinating and disconcerting read. The part where a cult member falls into the fermentation tank supposedly filled with botulinum toxin and comes out unscathed I guess illustrates the point I was trying to make.
I have a feeling that suicide is easier when the costs are low. Once a terror organization develops respectable level of technical capability, like north Korea, they would tend to evolve into a criminal organization. I don't know if that is much better since a rational criminal organization may pose a much bigger threat than a fanatical group of terrorists.
When I was a bio undergrad student I learned once (in discussion with a professor) about a disturbingly simple and effective GMO path to weaponized microbes discovered back in the 70s by some bio-weapons researchers. This was long before CRISPR. Totally ingenious, simple, and absolute nightmare fuel. I will not repeat it here. The ideas are out there but I'm not going to help anyone find it.
Suffice to say that I think it's pure luck that we have not yet had a biological 9/11 attack or worse. Normal people do have trouble imagining what psychopaths will do with things. Our brains do not naturally go there.
A good example is what is now being done with social media, mobile, and the Internet in general: radical "dopamine" gamification to make it actually addictive, extreme political manipulation, and all powered by ubiquitous surveillance. There's presently a race to develop the first true AI con artist capable of autonomously conning humans into believing arbitrary things. I did not imagine most of this in 2000 because I'm not a psychopath. I was aware of the surveillance dangers of the Internet but I never pictured the degree to which it would be weaponized against the population by amoral or actively malicious actors.
https://thinkprogress.org/hermann-park-protest-houston-28895...
Now whoever triggered that "flash mob" for teh lulz can mail order CRISPR.
Sleep well.
I'm not surprised to learn such a pathway exists, but I was surprised it was around in the 70s. And then I realised what you were probably talking about.
For what it's worth, I think I know how to make a directed energy weapon that could cause 50% probabilty of lethal effects that are only noticable hours afterwards (you could probably get a lethal shot even if you power it with a potato battery, too); and I realised a few years ago that when I was 9 years old I already knew enough basic chemistry to make a chemical weapon that could kill everyone on a London underground station. I'm neither a chemist nor a physicist, these are both things other people invented and I just saw a way they could be abused.
Despite that, I don't fear terrorists. They're demonstrably idiots, because it took them how long to realise that guns are highly effective tools for killing lots of people quickly? And then they decided to switch from guns to mimicing Carmageddon?
Edit:
Just to add, yes, I agree, ban it. All it takes is one, so the risk outweighs any benefit from encouraging more biologists.
Guns don't self-replicate. It only takes one.
I've been worrying about this since the late 90s.
It's so easy to create and release a zero-resistance >99% kill rate pandemic nightmare that I absolutely agree. And the power of the Internet makes it trivially easy to research and design that nightmare.
CRISPR is the equivalent of selling megaton nukes on Amazon.
99% is tough for various evolutionary theoretic reasons, but another bubonic plague is a hell of a lot easier.
These things are more dangerous than nukes. Any technology for creating GMOs should be regulated and licensed for the same reason that we regulate and license fissile material. This should remain true until and unless we can stop killing and hating each other and until a decade goes by without some nut opening fire on a bunch of kids in a church.
That guy can now order a CRISPR kit.
The people who hang out on 4chan /pol and "pray" for ebola to go airborne so it will de-populate Africa can mail order a CRISPR kit. It wouldn't be the dumbass meme-slinging shitlords. It would be that one lurker with a bio Ph.D and a shrine to Adolf Hitler and a collection of books by Julius Evola and the Protocols of the Elders of Zion all full of highlighting and underlining.
"He was just kind of quiet. Seemed nice. Said hi to the neighbors. He spent a lot of time on the Internet and got a lot of FedEx packages. Saw him come and go at night a lot."
"Police say the suspect tested the pathogen on human victims to perfect it. He took his victims mostly from homeless camps or hired prostitutes. A mass grave has been discovered on a remote property owned by the suspect and meticulously catalogued tissue samples have been found in a storage locker..."
"The disease's lethality was increased by the suspect's attempts to make it fatal only to certain ethnic groups as the inclusion of human antigens causes a reaction similar to that experienced by organ transplant recipients..."
"Officials say they can't provide a time-table for how long the quarantine will last. The army is being mobilized to deliver supplies..."
... then a few weeks later just the tone and a scrolling message ...
https://www.youtube.com/watch?v=3HlP2GHn_Ck
I have children. Ban this stuff right now.
Edit:
I just picked a contemporary motive. There's an endless supply of wills-of-God and causes "that will not be understood now... but history will judge me..."
relevant book: https://en.wikipedia.org/wiki/The_White_Plague
> It's hard for "normal" people to imagine how sociopaths or those with destructive aims will behave when given flexible tools like this.
Given enough time, you just need one misanthropic individual.
Edit: and it doesn't just need to be CRISPR. It could be AI, fusion, you name it. The power of the individual to impose their will on larger and larger numbers of people and parts of the planet keeps increasing with technology.
Remember the guy in Snow Crash who drove around with his brains wired to a fusion bomb.
I wonder what it says about me that it's extremely easy for me to think of most of these implications..
People are just territorial, violent animals that are barely domesticated via a few thousand years of society.
I am not afraid of what "biohackers" can do with CRISPR. It's very hard to come up with "pandemic viruses", even for nature, let alone for scientists, or even hobbyists.
At worst, the capabilities CRISPR and other techniques from synthetic biology give to genuine researchers will offset any mischief a hobbyist can do.
The democratisation/commoditization of a technology increases the probability that any given one capability of that technology will be discovered [1]. If what you think of as "very hard" is rooted in historical and present capabilities, those with angst on the issue are uncertain how long it will remain "very hard". Given that there is radical change, I do not think that sense of dread is misplaced.
[1] This is no a frivolous statistical argument. It helps establish a lower threshold and when other factors are considered the effect is strictly increased. The are some counter reasons, they help to think about he problem, but they are less convincing.
"Hard" in evolutionary terms means that there are dozens or hundreds of steps, which are individually very unlikely, compounding to the improbability of them happening.
Evolution solves these things by brute force, but only if there is an evolutionary pressure. "Pandemicity" is at best an accident, from an evolutionary standpoint, and so is lethality. Both happening at once, thus, is very hard.
An engineer could arrive at a solution faster, given that he knows the steps. But knowing which steps to take is actually the hardest part of synthetic biology.
Nature doesn’t ”want” lethal pandemic diseases. It’s evolutionary suicide to wipe out your own host.
I saw John Sotos, Chief Medical Officer of Intel talk at DEF CON 25 about bio-hacking. This guy is at the top of his field and whip-smart. He's without a doubt an expert in this field and it was one of the most terrifying talks I've ever attended at DEF CON. Bio-hacking has the potential of being one of the gravest threats to humanity in far more ways than just killing people. This is a MUST WATCH:
This will really take homebrew beer to the next level.
I can't imagine these kits allow modification of anything more than a bacteria,virus, or fungus.
I'm no biologist though.
Is someone making a black death 2.0 in their garage even possible ?
There's a reason bioterrorism isn't a thing, even though terrorism-minded people could get access to dangerous pathogens like Y. pestis or EBV if they wanted to.
At least in my opinion, it's just too damn hard for them to merit the effort, even compared to a sophisticated bomb. Trying to engineer (and test) a strain, "weaponize" it, takes a lot of space, time and resources.
And then the delivery is also very difficult.. So hard, that even militaries haven't totally figured it out.
The hard part is protecting your side against the effects.
If you're not worried about protecting a population, pathogen production and delivery becomes rather simpler.
Protecting anyone hasn't historically been a concern for terrorists at all. Islamic terrorists, in particular, hit entirely Muslim targets all the time.
And no, even then, production and delivery isn't easy. There are no pathogens which are both highly infectious and highly pathogenic, both because those traits are mutually inhibiting, and such a pathogen would already have run its course in the world. Any attempt to increase infectiousness and pathogenic potential, however, would require a very large foot print, virtually guaranteeing discovery by law enforcement.
“Islamic” is probably the wrong level to group them. I would be surprised if many people in Daesh are cool with their own terrorists killing lots of Daesh supporters no matter how many Shia Muslims they kill without losing sleep.
I did mean the group of terrorists who refer to some version of Islam (as by their interpretation), and regardless which subtype in this group, they all seem to be killing a lot of muslims, again without particular regard of which kind of muslim.
I admit this is an overgeneralisation, and there is a lot of subtle details with significance, but my point was simply that terrorists often don't care about their "partisan" civilians.
That's true but we'll let this one pass since the earlier discussion was anemic.
Why a moral panic instead of celebrating the achievement?
xx years ago, mail-order computer kits allowed absolutely anyone to hack code (and, gasp! illegally copy software or create computer viruses!)
yy years ago, mail-order color printers and scanners allowed absolutely anyone to hack paper (and, gasp! forge documents)
Is this part of a war against freedom? Then we are inconsistent. We should also lament on how Intel ME backdoors have become less efficient due to free software activist disabling them, or the demise of the Clipper chip promoted during the Clinton years.
CRISPR allows germ-line propagating modifications. Think about creating a combo modification that expresses itself only after a 2nd or 3rd generation but also increases reproduction success for intervening generations- you could wipe out whole species, in a fairly straightforward manner.
A modified flu could deliver a 'Children of Men' style germline infertility. This is like making everyone a little Kim Jong-un.
> Why a moral panic instead of celebrating the achievement?
Maybe they did some A-B testing and found that the story with the moral panic resulted in more ad views than the uplifting version?
These DIY Crispr kits aren't even remotely close to mail order computer kits.
At the moment, they are about as sophisticated as sea monkey kits, and less reliable at that.
People are worried about the humans lives that will be wiped out as free software activists disable the broken ones.
What if someone targets genotypes that are prevalent in, say, a specific race, and puts this in the drinking water?
Fortunately there is difference between creating deadly virus or bacteria and weaponizing it. Effective weaponization requires stabilization. Biwoweapon must survive in the environment and there must good delivery mechanism. Creating epidemic requires optimizing the delivery, contagiousness and symptoms.
It seems that North Korea has remote islands dedicated to bioweapon development and testing. Biosafety level 4 laboratories are must if your researches go to home each night. But if you can do the most dangerous parts in islands where people are in quarantine and have prisoners to experiment with, it's easier. It's impossible to know how well they have weaponized their bioweapons.
Description of North Korea’s BW Program from ROK Parliamentary Audit 2015:
>North Korea has 13 types of biological weapons in the form of agents, and it can cultivate and weap- onize them within ten days. In an emergency, it is likely that the North would prioritize using anthrax which is highly fatal and smallpox which is highly contagious. Special forces, airplanes, and contam- inated carcasses are the potential delivery means. It appears that the North has not developed missile warheads with BW payload.