The proposal being that of the AC to whom I was originally replying; who brought up prions in the first place. Its only real utility would be to weaken a general population (again, with foolishly low success rates.) I find it amusing how some posters are ignoring the ineffectiveness of these methods of killing and then saying "yeah, but I think it's scary," as though we should legislate against bogeymen.
The "rerouting around plaques" explanation makes sense. I expect there's a maximum plaque formation rate which is mostly a function of the protein's normal kinetics, localization and availability.
Anthrax was a one-trick pony, now spent; people are too paranoid for that to work again. Someone said that as much could have been accomplished by mailing an envelope full of white sugar. The anthrax was not engineered or modified beyond the addition of powdered glass, which when mixed with the air would make the lungs of the victim more vulnerable. The mutations seen in the anthrax was simply a product of natural drift in the sample's genome—good for forensic fingerprinting, but not actually meaningful.
Prions take years and years to become relevant; you may want to read the replies to that post where we summarily beat the idea to death. The difficulty of containment, low fatality rate, and ridiculous amount of research required to make them useful makes it solely the purview of Bond villains, much like stupidly large lasers and melting the ice caps.
And yet the diseases that do manage to spread so quickly are aggressively contained due to improvements in sanitation and quarantining. SARS killed 775 people, mostly in China and Hong Kong, and there were only 8273 cases in total. The spreading characteristic of viruses and bacterial pathogens is all but defeated by modern practices.
It happens, but only as long as the environment is a little contaminated. If there are no antibiotics around, then it's just dead weight. Environmental bacteria with antibiotic resistance are proof that we're massively overusing antibiotics.
I've put up the explanation in another comment, but the gist of it is this: the DNA in bacteria and viruses evolves to do whatever is necessary to survive. If you do not set it up so that your construct is vital to the cell's survival, it will drop that functionality within a few days to a week of propagating in the wild. Viruses have been very frustrating to use for controlled engineering tasks like gene replacement because they tend to kill more target cells (without replication) than they transfect, and because viral genomes are so unstable, anything not immediately vital to its function will be gone by the time it's left the host. You'd be better off poisoning the target(s) with Polonium.
Bacteria take a little longer to screw everything up, but they have their own problems, in that they're pernicious gene-exchangers. The majority of genes in any given bacterium can be found in most of the other species from the same environment; this strategy has allowed them to defend against unexpected stressors like antibiotics and plant chemical defences (allelochemicals). As a result, either the payload will be dead in a week or two (a problem that has often marred many good iGEM projects), or on the off-chance it's actually useful, you can expect it to have spread around the world in a few years. That's great for rogue madmen, but an impediment to goal-oriented terrorist organisations and nation states.
No, a static virus would be recognized by the body too quickly. The immune system constantly circulates a huge pool of antibody-producing cells, each of which detects a different target (antigen). If something gets detected, then the antibody-producing cell responsible is told to reproduce aggressively. The memory functionality is simply accomplished by keeping more of that cell line around. It's like a very basic single-layer neural network. Short of killing the entire organism simultaneously, no static virus can be effective. Even HIV, a very rapidly-mutating virus, has problems overcoming the immune system immediately following an infection.
And there's a very good reason for that! A nuclear scientist who defects may justify his or her actions as giving a small country leverage against a bigger one's economic clout. No nukes need to be fired; it's just that (for example) India can't threaten Pakistan with nukes. It's a completely peaceful transfer of power, making it a guilt-free action on the part of the defector.
With biological weapons, the most dangerous ones are already out there—Malaria, Ebola, et cetera. These are already found in third-world countries, and engineering pathogens can't improve on them much... and for various reasons, they're impractical as a weapon against a developed country like the US; you would do better to send a hitman or nerve gas in most cases.
Really, there's no such thing as a biological WMD.
Unfortunately, anything in a virus that's static makes it vulnerable to culling by the immune system. A virus has to be able to change constantly in order to survive, and if you try to have it both ways, the frozen part will just stop working and be replaced by the dynamic part.
I think the proposed usage was more of a "I want to destroy all of civilization by poisoning schoolchildren's lunchmeat" scenario than a targeted weapon. This is a totally different scenario from normal warfare, for which an unmodified form of the disease vector would do just fine. Speaking generally, I would guess that the period before symptoms manifest on a given prion is unmodifiable, and is directly linked to that protein's role in the organism.
If you're referring to the Spanish flu as your "one little bug", it lasted for three years and only killed 3-5% of the population. Furthermore, it was only able to spread as effectively as it did because of a communications blackout. Today, it would be no more dangerous to public health than SARS.
And if you're thinking of Malaria as your "another", that's somewhat treatable with Mefloquine, and like all existing diseases, could easily be imported by a smuggler.
You don't need a citation for that, just a clever method of concealment at airport security, an experienced drug mule, or any other common household method of smuggling.
Weaponisation of prions is an interesting angle I hadn't considered, although it looks like research into BSE and CJD is far enough along that, if Kuru were weaponised today and spread amongst a million people, we would notice it and cure it before it started causing symptoms. (That might be a little on the optimistic side, but presumably funding and other resources would be reallocated in such a situation.) Engineering new prions also seems like a woefully wasteful plan, and ultimately all such superdiseases run into a classic shortcoming of zombie stories: it's not currently practical to defend yourself or your people from getting infected, too.
The Marburg virus, like other BSL-4 diseases, falls under the other clause of this debate, which is that it doesn't require a biologist to disseminate, and so monitoring researchers wouldn't do a lick of good. I've already noted similar of other diseases like Ebola. As a general rule such diseases kill so aggressively that they can be only used with a handful of targets, in which case it would be more reliable and cost-effective to send a hitman, or use a nerve gas attack.
The mechanism is actually understood, now; like SARS and H5N1 it causes a cytokine storm. A 2003 publication produced results suggesting that cytokine storms can be treated. Moreover, both SARS and H5N1 were largely defeated by public awareness and proper sanitation; in contrast, the 1918 flu spread throughout Europe in a time when military censors prohibited publication about it, making things worse. In fact we call it the Spanish flu because Spain wasn't subject to that censorship.
In that case, most of the precautions taken are in the fume hoods. If a BSL-3 lab has a containment breach, typically the entire building will go under quarantine until everyone has been properly screened; a friend of mine had the misfortune of going through one once.
Engineered bioweapons cannot propagate. Incubation period is inversely proportionate to severity of symptoms, except for complex organisms like protozoans. Bacteria and viruses both mutate too quickly for a delayed lethal phenotype to be in their interest, otherwise we would see this more frequently in the wild.
The only highly-spread bioweapon (that comes to mind) not defeated by a combination of sanitation and the environment is malaria. Rather crucially, malaria is very common in third-world countries, which means that restricting the activities of researchers provides a uselessly small amount of security.
And there's a key theme—communicability is inversely proportionate to impact, particularly with viruses. They don't really have incubation periods; cells get infected and effects worsen until the immune system can't keep it under control. If the symptoms are extreme, people die right away. And if you really want to kill a handful of people immediately, why bother with a disease at all? Envelopes of anthrax spores is a gimmick that works once before everyone gets suspicious. There is no advantage over a normal assassination or a poison gas attack.
Your suggestion is a perfect example of why engineering wouldn't work.
Rhinoviruses are successful because they mutate rapidly. The only thing that prevents them from corrupting their genes completely and disappearing is the tiny chance that they won't misfold and will, instead, produce new viable virions after host infection.
A payload protein specifically meant to interfere with a normal cellular function would (a) be selected against due to a high rate of failure and (b) not serve the virus in any capacity, thereby causing it to fail through mutation. (And I don't know enough about virology to say for certain, but I don't think enteroviruses integrate with the genome normally, so there goes that approach.)
You would probably have more luck trying to engineer a really aggressive strain of HPV, but that's easily eliminated with sanitation.
Honestly, Malaria would give far better results, in which case harassing disease researchers won't accomplish anything. My point was that engineered diseases are futile.
Slashdot Mirror
The proposal being that of the AC to whom I was originally replying; who brought up prions in the first place. Its only real utility would be to weaken a general population (again, with foolishly low success rates.) I find it amusing how some posters are ignoring the ineffectiveness of these methods of killing and then saying "yeah, but I think it's scary," as though we should legislate against bogeymen.
The "rerouting around plaques" explanation makes sense. I expect there's a maximum plaque formation rate which is mostly a function of the protein's normal kinetics, localization and availability.
An interesting strategy, but I've concluded it's probably nowhere nearly effective as just ignoring it.
Anthrax was a one-trick pony, now spent; people are too paranoid for that to work again. Someone said that as much could have been accomplished by mailing an envelope full of white sugar. The anthrax was not engineered or modified beyond the addition of powdered glass, which when mixed with the air would make the lungs of the victim more vulnerable. The mutations seen in the anthrax was simply a product of natural drift in the sample's genome—good for forensic fingerprinting, but not actually meaningful.
Prions take years and years to become relevant; you may want to read the replies to that post where we summarily beat the idea to death. The difficulty of containment, low fatality rate, and ridiculous amount of research required to make them useful makes it solely the purview of Bond villains, much like stupidly large lasers and melting the ice caps.
And yet the diseases that do manage to spread so quickly are aggressively contained due to improvements in sanitation and quarantining. SARS killed 775 people, mostly in China and Hong Kong, and there were only 8273 cases in total. The spreading characteristic of viruses and bacterial pathogens is all but defeated by modern practices.
Actually, they screen for that. You can be held for quarantine when leaving some countries if you're not able to prove good health.
Right. As a general rule, eukaryotic parasites don't need our engineering to destroy civilization, just a little bit of transport.
Sure, but not scarier than a bucket of hydrofluoric acid! Chemical weapons are much better at producing dramatic horrors.
It happens, but only as long as the environment is a little contaminated. If there are no antibiotics around, then it's just dead weight. Environmental bacteria with antibiotic resistance are proof that we're massively overusing antibiotics.
I've put up the explanation in another comment, but the gist of it is this: the DNA in bacteria and viruses evolves to do whatever is necessary to survive. If you do not set it up so that your construct is vital to the cell's survival, it will drop that functionality within a few days to a week of propagating in the wild. Viruses have been very frustrating to use for controlled engineering tasks like gene replacement because they tend to kill more target cells (without replication) than they transfect, and because viral genomes are so unstable, anything not immediately vital to its function will be gone by the time it's left the host. You'd be better off poisoning the target(s) with Polonium.
Bacteria take a little longer to screw everything up, but they have their own problems, in that they're pernicious gene-exchangers. The majority of genes in any given bacterium can be found in most of the other species from the same environment; this strategy has allowed them to defend against unexpected stressors like antibiotics and plant chemical defences (allelochemicals). As a result, either the payload will be dead in a week or two (a problem that has often marred many good iGEM projects), or on the off-chance it's actually useful, you can expect it to have spread around the world in a few years. That's great for rogue madmen, but an impediment to goal-oriented terrorist organisations and nation states.
No, a static virus would be recognized by the body too quickly. The immune system constantly circulates a huge pool of antibody-producing cells, each of which detects a different target (antigen). If something gets detected, then the antibody-producing cell responsible is told to reproduce aggressively. The memory functionality is simply accomplished by keeping more of that cell line around. It's like a very basic single-layer neural network. Short of killing the entire organism simultaneously, no static virus can be effective. Even HIV, a very rapidly-mutating virus, has problems overcoming the immune system immediately following an infection.
My mistake.
And there's a very good reason for that! A nuclear scientist who defects may justify his or her actions as giving a small country leverage against a bigger one's economic clout. No nukes need to be fired; it's just that (for example) India can't threaten Pakistan with nukes. It's a completely peaceful transfer of power, making it a guilt-free action on the part of the defector.
With biological weapons, the most dangerous ones are already out there—Malaria, Ebola, et cetera. These are already found in third-world countries, and engineering pathogens can't improve on them much... and for various reasons, they're impractical as a weapon against a developed country like the US; you would do better to send a hitman or nerve gas in most cases.
Really, there's no such thing as a biological WMD.
Unfortunately, anything in a virus that's static makes it vulnerable to culling by the immune system. A virus has to be able to change constantly in order to survive, and if you try to have it both ways, the frozen part will just stop working and be replaced by the dynamic part.
I think the proposed usage was more of a "I want to destroy all of civilization by poisoning schoolchildren's lunchmeat" scenario than a targeted weapon. This is a totally different scenario from normal warfare, for which an unmodified form of the disease vector would do just fine. Speaking generally, I would guess that the period before symptoms manifest on a given prion is unmodifiable, and is directly linked to that protein's role in the organism.
You'll have to get in line behind the rest of 4chan. Is this a parlour trick, or do you talk like this during job interviews too?
If you're referring to the Spanish flu as your "one little bug", it lasted for three years and only killed 3-5% of the population. Furthermore, it was only able to spread as effectively as it did because of a communications blackout. Today, it would be no more dangerous to public health than SARS.
And if you're thinking of Malaria as your "another", that's somewhat treatable with Mefloquine, and like all existing diseases, could easily be imported by a smuggler.
You don't need a citation for that, just a clever method of concealment at airport security, an experienced drug mule, or any other common household method of smuggling.
Weaponisation of prions is an interesting angle I hadn't considered, although it looks like research into BSE and CJD is far enough along that, if Kuru were weaponised today and spread amongst a million people, we would notice it and cure it before it started causing symptoms. (That might be a little on the optimistic side, but presumably funding and other resources would be reallocated in such a situation.) Engineering new prions also seems like a woefully wasteful plan, and ultimately all such superdiseases run into a classic shortcoming of zombie stories: it's not currently practical to defend yourself or your people from getting infected, too.
The Marburg virus, like other BSL-4 diseases, falls under the other clause of this debate, which is that it doesn't require a biologist to disseminate, and so monitoring researchers wouldn't do a lick of good. I've already noted similar of other diseases like Ebola. As a general rule such diseases kill so aggressively that they can be only used with a handful of targets, in which case it would be more reliable and cost-effective to send a hitman, or use a nerve gas attack.
You sound like you have a very childish grasp of sexuality.
The mechanism is actually understood, now; like SARS and H5N1 it causes a cytokine storm. A 2003 publication produced results suggesting that cytokine storms can be treated. Moreover, both SARS and H5N1 were largely defeated by public awareness and proper sanitation; in contrast, the 1918 flu spread throughout Europe in a time when military censors prohibited publication about it, making things worse. In fact we call it the Spanish flu because Spain wasn't subject to that censorship.
In that case, most of the precautions taken are in the fume hoods. If a BSL-3 lab has a containment breach, typically the entire building will go under quarantine until everyone has been properly screened; a friend of mine had the misfortune of going through one once.
Engineered bioweapons cannot propagate. Incubation period is inversely proportionate to severity of symptoms, except for complex organisms like protozoans. Bacteria and viruses both mutate too quickly for a delayed lethal phenotype to be in their interest, otherwise we would see this more frequently in the wild.
The only highly-spread bioweapon (that comes to mind) not defeated by a combination of sanitation and the environment is malaria. Rather crucially, malaria is very common in third-world countries, which means that restricting the activities of researchers provides a uselessly small amount of security.
And there's a key theme—communicability is inversely proportionate to impact, particularly with viruses. They don't really have incubation periods; cells get infected and effects worsen until the immune system can't keep it under control. If the symptoms are extreme, people die right away. And if you really want to kill a handful of people immediately, why bother with a disease at all? Envelopes of anthrax spores is a gimmick that works once before everyone gets suspicious. There is no advantage over a normal assassination or a poison gas attack.
Your suggestion is a perfect example of why engineering wouldn't work.
Rhinoviruses are successful because they mutate rapidly. The only thing that prevents them from corrupting their genes completely and disappearing is the tiny chance that they won't misfold and will, instead, produce new viable virions after host infection.
A payload protein specifically meant to interfere with a normal cellular function would (a) be selected against due to a high rate of failure and (b) not serve the virus in any capacity, thereby causing it to fail through mutation. (And I don't know enough about virology to say for certain, but I don't think enteroviruses integrate with the genome normally, so there goes that approach.)
You would probably have more luck trying to engineer a really aggressive strain of HPV, but that's easily eliminated with sanitation.
Honestly, Malaria would give far better results, in which case harassing disease researchers won't accomplish anything. My point was that engineered diseases are futile.