Using a bacteria-derived antiviral mechanism against our own viruses sounds obvious to anyone who hears about CRISPR's origins for the first time, I'd hasard.
A less-explored idea is the one I first got from the title: would oversuse of CRISPR lead to "superbugs" issues like we had with antibiotics? This sounds like something interesting to work on, even before starting their large-scale use.
I guess a lot could go wrong if viruses started to become resistant to bacteria's immune system mechanisms.
I've been thinking about the nature of security in biology. How do you keep enemies out when you are guarding something valuable like an oasis or your heart/brain?
Well, we can install layers of access control like cell membranes which apply access control. We can cordon off the nuclear power plants (like mitochondria) with a "dumb" API that produces energy in return for nutrients and avoids "smart contracts".
In the medieval sense, we can dig a moat and install a drawbridge. Bridges adds latency, but at least you can retract them during wartime. But the enemy is pretty clever, so they carry long ladders across the desert that can span the moat.
So you add a winding cave before the moat so the ladders don't fit. But then they wisen up and pay spies behind your lines to lower the bridge, which is analogous to hijacking your immune system, or they invent a folding ladder, and so on.
But none of this helps you if your enemy can consume you at a macro scale by swallowing you whole. So complex species tend to grow larger or add multiple layers of specialised topology (organs) with disposable individuals - not to mention growing their societies.
I suspect there exists a "Shannon Information Theory of Survival" that can guarantee a defensible strategy as long as you can inject sufficient variance into the environment (high pressure, low pressure, vacuum, hot, cold, acidic, etc.) so that it would be more costly for an attacker to usurp you than to forge an alliance.
One potential risk I see would be that Crispr becomes too easy for anyone to do, and someone starts selling dodgy kits that allow for simple mistakes to turn into complex problems.
An extreme outcome might be like the fictional movie "I Am Legend", which was a horrible title for the movie. Someone gets desperate to cure a late stage cancer in a loved one and ends up creating a pathogen that can manage to spread to other people and wipe out a portion or all of the population.
Or perhaps someone starts selling kits that "make your muscles bigger", but in 0.7% of the population, that kit also makes the persons heart become oversized.
Is it safe to assume that these scenarios are too difficult to accomplish? I am asking because people will do what people can do and we will see online crispr kits before long.
The smart thing to do (and this has already been done in vitro) is to use phages to deliver spacers guided to antibiotic resistance genes. That way, the cells delete their own antibiotic resistance genes, and the phages propagate the changes throughout the bacterial population. Bonus points if you use a budding phage.
The "superbug" would probably need to take the form of essentially "encrypting" the genes to make them impossible to recognize, but somehow still having a way to decode them.
Could happen, but might also be evolutionarily difficult.
The delivery method is generally the missing piece.
For the first of the reports mentioned here the authors used bacterial conjugation [1] as the delivery method. They note that:
"In culture conditions that enhance cell-to-cell contact, conjugation rates approach 100% with the cis-acting plasmid."
So, I guess what is less clear is if this would me the case in a real bacterial infection. And would this generalize to a broad spectrum of pathogenic bacteria?
The delivery mechanism in the second, anti-viral, paper is less clear to me. Perhaps someone else can comment.
In general, I still like the idea of using bacteriophages. But finding broad spectrum bacteriophages seems problematic. Using DNA sequencing as a diagnostic to target therapies seems like in interesting idea (once DNA sequencing becomes cheap enough and easily available).
I'm not so convinced about using phages anymore, at least not on the same large scale that antibiotics are used (which is an economical necessity).
Bacteria co-evolve with phages, especially using CRISPR (https://www.nature.com/articles/s41586-019-1662-9) and can adapt much faster to a given phage strain than to antibiotics.
The really wild thing will be if autologous CAR-T or CAR-M can become a thing. Then you can just dump in already targeted and angry T-cells or macrophages to fight the infection. Additionally cool, fighting things like mold, yeast, and protist infections could then become "routine".
If the patient isn't too sick, you could even get to in situ programming of endogenous lymphocytes and myeloid cells a la Matthias Stephan's nanoparticle loaded with DNA or mRNA. https://stephanlab-fhcrc.squarespace.com/research-projects
I wonder if using Crispr would create a new class of pathogen that are tailored to a small set of population (or even to one individual). That would make research on that impossible and so cure also impossible. We can use Crispr only if we have studied and understood how the pathogen impacts our DNA. But over time, if the pathogen and individual DNAs divert far apart then no single research can be used as a generic cure. That would really suck and make cure a feature for the rich. Hope someone tells me I dead wrong.
There's only so much variation between people. Everyone uses the same proteins, more or less, to do the same things. Therefore, there's only so many ways to attack cells and you can bet that nature has already tried them all. There's a limited angle of attack, plus we already have broad immune systems to protect against most ways.
There's other problems with bioterrorism as well. If you make something lethal, it tends not to spread well because it kills the host too quickly. That's why way more people get the cold than Ebola. Pathogens tend to reach equilibrium within a generation inside a population. The narrower and more specific the group it infects, the harder it is for it to transmit.
Sure. You could even do a STUXNET type attack where the pathogen is highly transmissible and perfectly benign to everyone but your target. Release it in a train station in Budapest and wait.
[+] [-] MayeulC|6 years ago|reply
A less-explored idea is the one I first got from the title: would oversuse of CRISPR lead to "superbugs" issues like we had with antibiotics? This sounds like something interesting to work on, even before starting their large-scale use.
I guess a lot could go wrong if viruses started to become resistant to bacteria's immune system mechanisms.
[+] [-] pgt|6 years ago|reply
Well, we can install layers of access control like cell membranes which apply access control. We can cordon off the nuclear power plants (like mitochondria) with a "dumb" API that produces energy in return for nutrients and avoids "smart contracts".
In the medieval sense, we can dig a moat and install a drawbridge. Bridges adds latency, but at least you can retract them during wartime. But the enemy is pretty clever, so they carry long ladders across the desert that can span the moat.
So you add a winding cave before the moat so the ladders don't fit. But then they wisen up and pay spies behind your lines to lower the bridge, which is analogous to hijacking your immune system, or they invent a folding ladder, and so on.
But none of this helps you if your enemy can consume you at a macro scale by swallowing you whole. So complex species tend to grow larger or add multiple layers of specialised topology (organs) with disposable individuals - not to mention growing their societies.
I suspect there exists a "Shannon Information Theory of Survival" that can guarantee a defensible strategy as long as you can inject sufficient variance into the environment (high pressure, low pressure, vacuum, hot, cold, acidic, etc.) so that it would be more costly for an attacker to usurp you than to forge an alliance.
[+] [-] LinuxBender|6 years ago|reply
An extreme outcome might be like the fictional movie "I Am Legend", which was a horrible title for the movie. Someone gets desperate to cure a late stage cancer in a loved one and ends up creating a pathogen that can manage to spread to other people and wipe out a portion or all of the population.
Or perhaps someone starts selling kits that "make your muscles bigger", but in 0.7% of the population, that kit also makes the persons heart become oversized.
Is it safe to assume that these scenarios are too difficult to accomplish? I am asking because people will do what people can do and we will see online crispr kits before long.
[+] [-] COGlory|6 years ago|reply
[+] [-] ggggtez|6 years ago|reply
Could happen, but might also be evolutionarily difficult.
[+] [-] emiliobumachar|6 years ago|reply
[+] [-] new299|6 years ago|reply
For the first of the reports mentioned here the authors used bacterial conjugation [1] as the delivery method. They note that:
"In culture conditions that enhance cell-to-cell contact, conjugation rates approach 100% with the cis-acting plasmid."
So, I guess what is less clear is if this would me the case in a real bacterial infection. And would this generalize to a broad spectrum of pathogenic bacteria?
The delivery mechanism in the second, anti-viral, paper is less clear to me. Perhaps someone else can comment.
In general, I still like the idea of using bacteriophages. But finding broad spectrum bacteriophages seems problematic. Using DNA sequencing as a diagnostic to target therapies seems like in interesting idea (once DNA sequencing becomes cheap enough and easily available).
[1] https://en.wikipedia.org/wiki/Bacterial_conjugation
[+] [-] folli|6 years ago|reply
[+] [-] DrAwdeOccarim|6 years ago|reply
If the patient isn't too sick, you could even get to in situ programming of endogenous lymphocytes and myeloid cells a la Matthias Stephan's nanoparticle loaded with DNA or mRNA. https://stephanlab-fhcrc.squarespace.com/research-projects
[+] [-] yalogin|6 years ago|reply
[+] [-] COGlory|6 years ago|reply
There's other problems with bioterrorism as well. If you make something lethal, it tends not to spread well because it kills the host too quickly. That's why way more people get the cold than Ebola. Pathogens tend to reach equilibrium within a generation inside a population. The narrower and more specific the group it infects, the harder it is for it to transmit.
[+] [-] jcims|6 years ago|reply
[+] [-] RedBeetDeadpool|6 years ago|reply
[+] [-] valiant55|6 years ago|reply
[+] [-] aSplash0fDerp|6 years ago|reply
https://phys.org/news/2019-09-dna-held-hydrophobic.html
I'm using golf theory here, but if you're off a half a degree, the further it goes, the more errant the shot.
With so much missing/incomplete/invalid information about DNA, writing junk code sounds about right.
[+] [-] hateful|6 years ago|reply
[+] [-] DoreenMichele|6 years ago|reply
If it were easy to rewrite the code, we would create winged babies for shits and grins.
[+] [-] unknown|6 years ago|reply
[deleted]
[+] [-] AllegedAlec|6 years ago|reply