4 ms·

One issue with chimeras (the article doesn’t mention) is that they open the door to a new philosophical question about the zoonotic transmission risk. Human-an

by bertil 3y ago

One issue with chimeras (the article doesn’t mention) is that they open the door to a new philosophical question about the zoonotic transmission risk. Human-animal barriers are hard to pass for infections (bacteria or virus) because there’s very little material shared between organisms: occasional spittle of saliva, maybe blood drops during butchering, but not much. Therefore, there’s hardly ever an opportunity to mutate in an environment that would select for human compatibility. In a chimera, there’s a life-long tissue-sized opportunity. Even for one individual, hat’s enormous. If pigs routinely carry a pathogen to which they are immune or that has no apparent symptoms, we wouldn’t know. We know it happens, but we have no more way of knowing than Christopher Columbus did. If any pathogen proves easily transmittable but deadly to humans, it’s over. Every bridging case tells us such infections are likely, numerous even. Chimeras are the perfect ground to mutate those until it’s too late — not for the individual recipient, but potentially for the entire human population. This is a very easy-to-imagine and, overall, quite likely extinction event. We don’t know what pigs have that could be it. We could and do raise chimeras in total isolation, hoping they would not catch anything like that. Still, every step of the process, from the circumstances of the pigs’ birth to where the food comes from, is an opportunity for such contamination. Philosophically, we know, but we don‘t know: we know what it would look like, so if nasty things happen, we would understand; however, we have no sure way to prevent it until it happens. The closest equivalent in fiction would be the opening chapter of _The Last Of Us_ (spoilers): tell every epidemiologist this is it, set yourself on fire, and beg a foreign country to immediately nuke your country out of existence, hoping that will be enough. I find that new conception of risk interesting, but have been pondering that scenario for decades (one of my professors was the first to suggest that path). I realize that it sounds a lot grimmer than vegans and Muslim people finding the practice “revolting” without nearly as dark a shadow over the practice.

Natsu 3y ago
I mean, depending on what you believe about certain humanized mice studies, this may have already lead to a highly human-adapted pathogen appearing out of seemingly nowhere.
michaelbarton 3y ago
Great comment and I would add that this has already happened: https://www.technologyreview.com/2022/05/04/1051725/xenotransplant-patient-died-received-heart-infected-with-pig-virus/ https://www.technologyreview.com/2022/05/04/1051725/xenotran...
- pazimzadeh 3y ago
  Yeah, but that operation was rushed seemingly so that the team involved would get more glory. No one from the International Xenotransplantion Association, nor any other collaborators in academia, were consulted prior to the procedure. Source: I know people "close to the matter" since my mom started the collaboration with Revivicor while she was at the University of Maryland, Baltimore.
  - iancmceachern 3y ago
    Very interesting, thank you. I've worked in the LVAD/Artificial Heart and Dialysis industries designing products for 20 years. I've been following the Revivacor stuff (all xenotransplantation stuff really) for years. I remember seeing some of the folks involved speak and prefict this progress in recent ISHLT and ASAIO conferences. I'm happy to have learned yet something new on this topic, thanks!
- bertil 3y ago
  > this has already happened is by far the worst possible response to a thread detailing an extinction event, with the closest equivalent being the mycologist self-immolation in _The Last Of Us_. But… thank you for the reference. I missed that. I'm happy we are not dead.
generic92034 3y ago
> This is a very easy-to-imagine and, overall, quite likely extinction event. I do not get how you are arriving at that conclusion. Would the huge genetic variance in humanity not make an extinction event quiet unlikely, for any kind of transmissible disease?
- tonymillion 3y ago
  Depending on who you ask that variance is 0.1-0.4% which is extremely tiny, so I'm not sure what you mean by "huge genetic variance in humanity".
  - wedernoch 3y ago
    Human to Chimpanzee: 1.3%-4% difference (depends on where you look) Human to Friutfly: 40% difference I thik just the % number is pretty meaningless
  - generic92034 3y ago
    You can see how differently human bodies are reacting to any known transmissible virus or bacterial disease. Some will die, some do not even notice they were infected. Are there any exceptions? Obviously there so far never was an easily transmissible disease killing everyone, or we would not be here. That is no guarantee for the future, but it makes claims of likely extinction events sound a bit too strong, IMHO.
    - tonymillion 3y ago
      Actually there are (Ebola, haemorrhagmific fever etc) are mostly deadly and easily transmissible - however they tend to be self limiting in part because they are so deadly and (luckily) because they aren’t airborne and thus distance … literally the distance between groups of people helps limit them. (Also the fairly short incubation period). However all of that is irrelevant since the GP was musing on the “huge genetic diversity of humans” being a barrier to xenomutation of animal viruses to humans. Thats not the case, because humans are pretty much genetically identical to near a 1000th of a percent - so a particularly virulent virus that mutated from an animal to a human because of an organ transplant has a pretty good chance of causing a major pandemic. You don’t even have to take my word for it, Covid, swine flu, h1n1 are all examples of animal infections jumping - and that’s without the added long term exposure / selection pressure a transplanted organ would provide. Caveat: I’m all for this kind of research and development given the lack of transplantable organs in many health departments, but I’m also in favor of r&d for artificial replacements too.
frisco 3y ago
Fun story I heard recently: apparently a bunch of pigs were placed on various small islands in the pacific in the 19th century so in case sailors were running out of food, they would have a known self-sustaining backup option. Many of those pigs were completely isolated for over a hundred years and entirely missed out on the globalization of tons of infectious diseases. A while ago a group of them were picked up and brought to a special protected refuge in New Zealand, where they are being used for artificial organ research (https://nzeno.nz/ https://nzeno.nz/) basically for the reasons you highlight.
- bmer 3y ago
  Wow, this is extremely depressing. Am I just crazy? Do others not wonder that if pigs and humans have remarkably similar biology, then this increases the chance that pigs and humans might also have similar mental features? (I'm not claiming we're equally intelligent, just that it's well known that pigs are [quite intelligent](https://en.wikipedia.org/wiki/Pig#Behavior https://en.wikipedia.org/wiki/Pig#Behavior): > Pigs are highly intelligent animals,[64] on par with dogs,[65] and according to David DiSalvo's writing in Forbes, they are "widely considered the smartest domesticated animal in the world. Pigs have demonstrated the ability to move a cursor on a video screen with their snouts and understand what is happening onscreen, and have learned to distinguish between the scribbles they had seen before and those they were seeing for the first time."[66][a][70] But forget about the capacity to process information. How do we expect to improve as a society, in terms of treating other humans in a non-disposable fashion, if we regularly treat animals in a disposable fashion, given that a standard tactic in feeling okay about mistreating humans involves reducing ("de-anthropomorphizing") humans (via comparisons, propaganda, statistics, etc.) to be like "other animals"? Suppose aliens were to visit us one day, and sci-fi-magically were to give certain animals a voice and a say, and those animals advocated for giving humans what they got from them: putting humans on little islands, where they multiply, and then a few years later, animals/aliens/etc. come by to use them as transplant sources. Clearly, the chances of that happening are next to zero. However, equally clearly, if this were to happen, the fact that humanity is reduced to such a state would be horrific. Yet the animals are giving us tit-for-tat: does it only become horrific for party A, when party B is able to do the same in return? Damn. My heart goes out to those pigs. Sleep peacefully, this world isn't a nice place anyway.
simmerup 3y ago
Why would it be an extinction event? Surely our immune systems would figure it out eventually
- mortureb 3y ago
  It depends. If something like HIV was airborne, it might very well spread to everyone on the planet. You might get 5% of people that don’t get it but will that be enough to sustain a future.
  - simmerup 3y ago
    Someone needs to make an animated youtube video of this eventuality so I can watch it unfold
    - ekaryotic 3y ago
      It would be quite boring. There are many movies about the subject, 28 days later and sequels, more that i have forgotten because they were funded to be a government propaganda vehicle and lost their artistic integrity. There's a video game called Plague Inc that is said to be a quite accurate simulation.
  - generic92034 3y ago
    I would not call that an "extinction event", though. Maybe it would disrupt civilization, but that is not the same.
- bertil 3y ago
  Most of the infections would not be, but having an unending stream of infections would allow for the deadliest to mutate with the most contagious. It doesn’t have to lead to an extinction-level threat, but we are putting an awful lot of dice in that bowl, hoping not a single one of them will hit a Nat 1.
- Turskarama 3y ago
  "Eventually" is the key word, our immune systems need to figure it out before it's too late. That is by no means a guarantee. That said, total extinction of the human race is unlikely since there are small isolated populations in various places around the world. The end of civilization though is a real possibility.

by bertil 3y ago

Natsu 3y ago

I mean, depending on what you believe about certain humanized mice studies, this may have already lead to a highly human-adapted pathogen appearing out of seemingly nowhere.

michaelbarton 3y ago

Great comment and I would add that this has already happened: https://www.technologyreview.com/2022/05/04/1051725/xenotransplant-patient-died-received-heart-infected-with-pig-virus/ https://www.technologyreview.com/2022/05/04/1051725/xenotran...

pazimzadeh 3y ago
Yeah, but that operation was rushed seemingly so that the team involved would get more glory. No one from the International Xenotransplantion Association, nor any other collaborators in academia, were consulted prior to the procedure. Source: I know people "close to the matter" since my mom started the collaboration with Revivicor while she was at the University of Maryland, Baltimore.
- iancmceachern 3y ago
  Very interesting, thank you. I've worked in the LVAD/Artificial Heart and Dialysis industries designing products for 20 years. I've been following the Revivacor stuff (all xenotransplantation stuff really) for years. I remember seeing some of the folks involved speak and prefict this progress in recent ISHLT and ASAIO conferences. I'm happy to have learned yet something new on this topic, thanks!
bertil 3y ago
> this has already happened is by far the worst possible response to a thread detailing an extinction event, with the closest equivalent being the mycologist self-immolation in _The Last Of Us_. But… thank you for the reference. I missed that. I'm happy we are not dead.

generic92034 3y ago

> This is a very easy-to-imagine and, overall, quite likely extinction event. I do not get how you are arriving at that conclusion. Would the huge genetic variance in humanity not make an extinction event quiet unlikely, for any kind of transmissible disease?

tonymillion 3y ago
Depending on who you ask that variance is 0.1-0.4% which is extremely tiny, so I'm not sure what you mean by "huge genetic variance in humanity".
- wedernoch 3y ago
  Human to Chimpanzee: 1.3%-4% difference (depends on where you look) Human to Friutfly: 40% difference I thik just the % number is pretty meaningless
- generic92034 3y ago
  You can see how differently human bodies are reacting to any known transmissible virus or bacterial disease. Some will die, some do not even notice they were infected. Are there any exceptions? Obviously there so far never was an easily transmissible disease killing everyone, or we would not be here. That is no guarantee for the future, but it makes claims of likely extinction events sound a bit too strong, IMHO.
  - tonymillion 3y ago
    Actually there are (Ebola, haemorrhagmific fever etc) are mostly deadly and easily transmissible - however they tend to be self limiting in part because they are so deadly and (luckily) because they aren’t airborne and thus distance … literally the distance between groups of people helps limit them. (Also the fairly short incubation period). However all of that is irrelevant since the GP was musing on the “huge genetic diversity of humans” being a barrier to xenomutation of animal viruses to humans. Thats not the case, because humans are pretty much genetically identical to near a 1000th of a percent - so a particularly virulent virus that mutated from an animal to a human because of an organ transplant has a pretty good chance of causing a major pandemic. You don’t even have to take my word for it, Covid, swine flu, h1n1 are all examples of animal infections jumping - and that’s without the added long term exposure / selection pressure a transplanted organ would provide. Caveat: I’m all for this kind of research and development given the lack of transplantable organs in many health departments, but I’m also in favor of r&d for artificial replacements too.

frisco 3y ago

Fun story I heard recently: apparently a bunch of pigs were placed on various small islands in the pacific in the 19th century so in case sailors were running out of food, they would have a known self-sustaining backup option. Many of those pigs were completely isolated for over a hundred years and entirely missed out on the globalization of tons of infectious diseases. A while ago a group of them were picked up and brought to a special protected refuge in New Zealand, where they are being used for artificial organ research (https://nzeno.nz/ https://nzeno.nz/) basically for the reasons you highlight.

bmer 3y ago
Wow, this is extremely depressing. Am I just crazy? Do others not wonder that if pigs and humans have remarkably similar biology, then this increases the chance that pigs and humans might also have similar mental features? (I'm not claiming we're equally intelligent, just that it's well known that pigs are [quite intelligent](https://en.wikipedia.org/wiki/Pig#Behavior https://en.wikipedia.org/wiki/Pig#Behavior): > Pigs are highly intelligent animals,[64] on par with dogs,[65] and according to David DiSalvo's writing in Forbes, they are "widely considered the smartest domesticated animal in the world. Pigs have demonstrated the ability to move a cursor on a video screen with their snouts and understand what is happening onscreen, and have learned to distinguish between the scribbles they had seen before and those they were seeing for the first time."[66][a][70] But forget about the capacity to process information. How do we expect to improve as a society, in terms of treating other humans in a non-disposable fashion, if we regularly treat animals in a disposable fashion, given that a standard tactic in feeling okay about mistreating humans involves reducing ("de-anthropomorphizing") humans (via comparisons, propaganda, statistics, etc.) to be like "other animals"? Suppose aliens were to visit us one day, and sci-fi-magically were to give certain animals a voice and a say, and those animals advocated for giving humans what they got from them: putting humans on little islands, where they multiply, and then a few years later, animals/aliens/etc. come by to use them as transplant sources. Clearly, the chances of that happening are next to zero. However, equally clearly, if this were to happen, the fact that humanity is reduced to such a state would be horrific. Yet the animals are giving us tit-for-tat: does it only become horrific for party A, when party B is able to do the same in return? Damn. My heart goes out to those pigs. Sleep peacefully, this world isn't a nice place anyway.

simmerup 3y ago

Why would it be an extinction event? Surely our immune systems would figure it out eventually

mortureb 3y ago
It depends. If something like HIV was airborne, it might very well spread to everyone on the planet. You might get 5% of people that don’t get it but will that be enough to sustain a future.
- simmerup 3y ago
  Someone needs to make an animated youtube video of this eventuality so I can watch it unfold
  - ekaryotic 3y ago
    It would be quite boring. There are many movies about the subject, 28 days later and sequels, more that i have forgotten because they were funded to be a government propaganda vehicle and lost their artistic integrity. There's a video game called Plague Inc that is said to be a quite accurate simulation.
- generic92034 3y ago
  I would not call that an "extinction event", though. Maybe it would disrupt civilization, but that is not the same.
bertil 3y ago
Most of the infections would not be, but having an unending stream of infections would allow for the deadliest to mutate with the most contagious. It doesn’t have to lead to an extinction-level threat, but we are putting an awful lot of dice in that bowl, hoping not a single one of them will hit a Nat 1.
Turskarama 3y ago
"Eventually" is the key word, our immune systems need to figure it out before it's too late. That is by no means a guarantee. That said, total extinction of the human race is unlikely since there are small isolated populations in various places around the world. The end of civilization though is a real possibility.