A man in Maryland has received a pig heart transplant. What an interesting idea! People have been talking about xenotransplants of this magnitude for decades, and now someone actually gets to try it. It’s also a terrifying idea.
- My first thought was of Baby Fae, the infant in 1984 who received a baboon heart. It was a disaster. The surgeon didn’t believe in evolution and dismissed concerns about the degree of relatedness, and the donor was blood type AB and Fae was type O. They also didn’t have any means of genetically modifying the baboon. Would you believe there are ethical concerns and responsibilities in this sort of thing?
- The Washington post article is all about the ethics of the surgery, which is good. It takes a really cock-eyed perspective, though: the recipient was a bad guy who stabbed and paralyzed someone, failed to pay court-ordered compensation to his victim, and also has a history of being sloppy and undisciplined about his medications. Should he have been given this gift?
YES.
Jesus, it’s not even in question. Doctors should deliver health care based on need, not passing judgment on the worth (in all senses of the word) of their patient. What next? Will doctors decide on my treatment based on my credit score? Yeah, you don’t have to tell me that here in the good ol’ USA that is the de facto situation. It’s not good. - For the retribution crowd, relax. He is being punished. He’s an experimental guinea pig for a treatment that’s going to buy him a little time. The pig was extensively manipulated with 10 genes modified to reduce, but not totally eliminate, the chance of rejection. He’s going to be trapped in a hospital bed for a good long while, with nurses waking him up every few hours through the night to do blood tests, and he’s going to be taking so many pills. I’ve been in that place for relatively trivial surgeries, it’s a necessary hell. Have a little pity.
- He’s probably going to die in a few months, anyway — I’ll be surprised if his new heart isn’t shredded by rejection in short order. I’ll be pleasantly surprised if he gets a significant survival time, though, since that means this could be a very promising treatment for everyone.
- Except the pigs. You do realize that this implies the existence of pig farms for animals whose fate is to be chopped up as needed for organs, right? It’s a tiny drop in the slaughterhouse bucket, since humans butcher 1.5 billion pigs per year to make pulled pork sandwiches and bacon, so it’s not the numbers that are daunting, it’s the fact that right now there are cloned pigs being modified and raised in artisanal farms in the hopes that genetic refinement will make them incredibly valuable to corporations. These are long term investments!
- No one is talking about how much these expendable pigs cost. We aren’t talking about the ethics from the pig’s perspective, and we’re suspiciously mum about what the bill is going to be. This lucky (?) fellow in Maryland is benefitting from a bit of scientific curiosity — hey, we’ve been raising all these special pigs for a decade or so, how about if we splice one heart into a test subject and see what happens — but if it works and becomes a relatively routine intervention, who’s going to be able to afford it?
- While I’m on the pig’s side, what do these gene modifications do to the health of the pig stock? Does this compromise their immune systems? Are these going to be bubble-pigs that need to be raised in a sterile environment?
- I got to wondering about the scientific methodology behind making pigs with all these genetic modifications. Here’s an article on practical approaches for knock-out gene editing in pigs. It’s a multi-step, multi-generational process to produce pigs with specific mutations. Scientists have been working for years to make these pigs.
Schematic workflow of the different steps needed to generate a gene edited pig. (A) Efficiency analysis of mutations induced by CRISPR-Cas9 system. (B) Different strategies to generate one-cell stage porcine edited embryos. (C) Gene editing analysis of the founder pigs (F0) and offspring produced by crossbreeding F0 pigs (F1).
- The above article describes the mechanics, but not the research that goes into discovering candidate genes to reduce the immune response. Everyone is fumbling forward in the dark, finding likely genes that are affecting rejection, but they have to put that pig donor tissue in a human host to see if they actually got ’em all. This man in Maryland is very much a wildly experimental test subject, a scientific experiment in progress. The most likely result is they’ll find that “oops, we missed an important gene” and they’ll go back to the pig farm with a new CRISPR/Cas target and raise another generation with 11 modified genes for the next attempt. Meanwhile, this host is dead. But he will have contributed to Science with his demise!
Anyway, my brain is currently split between a Frankensteinian fascination with this bold experiment, and a humane dismay at the cost in suffering for humans and pigs.
It is more complicated than this.
The number of people waiting for transplants is far greater than the number of organs available.
So docs and the system prioritize based on many factors. One important one is ability to take care of themselves and the donated organ. Because if they don’t, the transplant will fail and you’ve wasted an organ and likely killed another patient who dies on the waiting list.
People who shredded their liver with alcohol can’t get a new liver unless they stop drinking. Many alcoholics fail that test.
One of the main requirements for transplant patients is to get all available vaccines. Because, due to the anti-rejection drugs, they are sitting ducks for any infectious diseases that are always around.
This is relevant today because many antivaxxers are refusing to get the Covid-19 virus vaccines. There are a number of cases where transplant patients who are antivaxxers have gotten Covid-19 virus and promptly died of it.
In most places, antivaxxers aren’t eligible for organ transplants.
Antivaxxers are the new Plague Rats.
Objective requirements to maximize the probability of success are one thing, but making moral and economic judgments on the worth of the patient are not acceptable.
“Transplant recipients who become sick with the coronavirus have a 20 to 30% fatality rate – a shockingly higher figure than the rest of the population, at about 1.6%.”
Explains it here. No one wants to waste scarce donor organs on antivaxxers because they have a high probability of dying from the ubiquitous Covid-19 virus.
This is yet another way to learn some immunology. This article gets at some of the complexity:
https://www.frontiersin.org/articles/10.3389/fimmu.2019.03060/full
I was wondering how MHCs would be handled (HLA in humans/SLA in pigs). But there’s obstacles galore including pre-existing antibodies against α1,3-galactose (α-Gal):
“The major HAR xenoantigen is galactose-α1,3-galactose (α-Gal), which is expressed by α1,3-galactosyltransferase (α1,3GalT; also known as GGTA1) (20, 21). GGTA1 is functional in most mammals, including pigs, but not in humans or Old World monkeys (22). In human blood, ~1% of all circulating antibodies are directed against α-Gal epitopes (23, 24). These natural anti-α-Gal antibodies are universally induce during neonatal life by gut bacteria that expressed GGTA1 (25).”
There’s complement activation, antibody-dependent cellular cytotoxicity and those pesky NK cells.
And from a virology angle, this was covered in the previous article, but in another article we have PERVs:
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.048186
“The third recent breakthrough was reported in 2016 when CRISPR-based gene editing was successfully used to simultaneously edit and functionally disable all 62 copies of the pig genes encoding for porcine endogenous retrovirus (PERV), first in cell lines and then to generate viable, fertile pigs.42 In the late 1990s, demonstration that PERV could productively infect specific permissive human cell lines43 raised the specter that pig-to-human xenografts might cause infection in the xenograft recipient and risk pandemic viral infection.44”
My first thought was of Baby Fae, the infant in 1984 who received a baboon heart. It was a disaster. The surgeon didn’t believe in evolution and dismissed concerns about the degree of relatedness…
Wait, WHAT?! Did the surgeon’s religious beliefs affect his medical-care decisions? I don’t remember hearing that at the time. That sounds like, at the very least, a serious malpractice claim.
I don’t have a problem at all with using solid organs from genetically modified pigs as long as it works. We’ll see if this one rejects in a few months. I am more optimistic. I think this is being carried out with a scientific understanding that was entirely lacking in the case of Baby Fae. Though I am not vegetarian, I would like to see factory farms eliminated and meat consumption reduced drastically and eventually eliminated. If we are still raising pigs for organs at that point, that’s not ideal from an ethical perspective, but it is a drop in the bucket as PZ said.
Also, these pigs should be completely isolated from the rest of the pig population and treated as humanely as possible. Yes, that starts my morbid imagination running to the idea of what if you did that with human clones. Pigs are sentient, but they’re not human, and since I’ve already acclimated to the idea that we raise them for slaughter, I’d rather see a liver or kidney used to save a human life than on a dinner plate (or more likely ground up as pet food, since organ meats have declined in popularity).
The infrastructure needed to raise genetically modified pigs is indeed daunting, but so is the cobbled together system now used by UNOS to get solid organs from previously healthy victims of sudden trauma to where they are needed by recipients, or the complicated system used for voluntary kidney donations (including donor chains). Unlike genetically modified animals, there is no way to “scale up” these systems. Ideally, we are going to reduce the rate of trauma death not increase it, and the best we can do with voluntary donors is persuade. Also, at the end of the day, you still don’t have a compatible organ and you’re stuck taking antirejection drugs. They’re better than the once were, but they are not free of side effects, including immunosuppression (which is the actual purpose) and increased risk of cancer.
So, again, if it works xenotransplantation is a huge win for humanity. When the day comes that we can regenerate a compatible organ from our own stem cells either in a lab our own bodies (like Star Trek IV) then I’m all for sparing the pigs. Till then, let’s work on all these solutions (including artificial organ replacements) as aggressively as possible.
One thing that worries me (but only a little) is what if this works so well that those with existing organ transplants are actually worse off, being stuck on antirejection meds. Will we keep improving the quality of those drugs or just treat these patients as the human equivalent of “legacy” software?
My daughter is a kidney transplant recipient, so yeah, this is not theoretical to me.
It was at a religion owned and run medical school, Loma Linda in southern California.
The religion that runs that school are the Seventh Day Adventists. The SDAs are hard core anti-evolutionists. They periodically have purges of evolution accepting biologists at their school and universities. Their operating policies are modeled on those of Joseph Stalin.
Yeah, it was a fiasco from start to finish.
Raging Bee@6 A lot has been written about the Baby Fae case. Basically, it never should have happened. There is no way a baboon heart was going to work longterm in a human. It was just this one surgeon in Loma Linda with some very idiosyncratic beliefs. There is also a question of informed consent. The parents felt they were pressured to accept this treatment because there were no other options, but in fact, it might have been possible to find a human transplant heart. I believe they sued, though I don’t remember the details anymore. You might be able to find some in Wikipedia.
It’s hard for me to imagine anyone is even asking this question. Are we living in medieval times? Nobody should be denied medical treatment as a “punishment”. E.g., in prisons precisely because we’ve denied people autonomy to seek their own medical care, society has an even greater responsibility to care for them. (But yeah, this is the US, and we might as well be living in medieval times. We’ll be there soon.)
Medical treatment may need to be rationed, and organ transplants are particularly fraught since there is a fixed supply, so committees do make what appear to be judgments between “deserving” and “undeserving.” In the case of low compliance, the real issue is that you have an improved outcome if the patient will actually take their meds consistently. That, and not their “good behavior” is what makes them a better candidate. In practice, of course, it’s more complicated and I’m sure there is a great deal of bias.
And anyway, the gift is going from the patient to other organ recipients, because it is a risky procedure, and we will never know if it works in practice until we test it.
@raven, ran into a tidbit that suggests evidence that the black plague was spread more via human fleas, rather than murine or other fleas. Apparently, human flea infestation was a thing during that era.
@hemidactylus, color me dubious as to PERV infectivity, as ERV’s by nature are broken by the host’s immune system, leaving them more as genetic litter in most cases (and evolutionary tools in other cases), incapable of forming an infective retrovirus. Add in the use of porcine products in everything from liver dialysis to body components as grafts without evidence of infection in multiple studies, I’m thinking that’s a non-issue.
@Raging Bee, that was in the dark ages of 1984, when physicians as a group were still learning how to spell ethics… The quack claimed to have extensively informed both parents, despite the father never being present for such sessions and the consent form mother signed was changed after she signed it.
But, doctor’s defense would’ve been that Fae was born without a functional left ventricle and hence, would’ve swiftly died without such “care” (ostensibly, to await a donated human heart, which were essentially non-existent at that time and are still quite rare). Shady, but from memory of that era, it’d likely have worked as a defense against malpractice.
I’d have gone for his medical license over the falsified consent forms, as heaven only knows what else he falsified.
I suspect that the recipient will do slightly better than with a human heart transplant, in part due to increased observation and care, in part due to slightly lesser antigens in the graft. But, PZ is spot on, the immune system and mammalian genetics in general are still bleeding edge research, with many, many unknowns to confound things. Just as using this singular example as a benchmark would be similarly confounded seven ways to Sunday.
I can see peer review turning any likely paper on this into a stand-in for a machine gun target – full of holes and missing its center.
Hm, can they create pigs with dual hearts working in parallell?
-The news about the heart is not too surprising, I refer you to the 1990s book ‘The Engineer In The Garden’.
Also Freeman Dyson’s book ‘The Sun, The Genome And The Internet’.
Do you think Elon and Jeff should have to settle for a mere pig’s organs when the need arises? Not in this plutocracy! Non-consensual genetic modification of market captive workers doesn’t have to stop at mere organ suitability though, think what enhancements to raise worker productivity by 0.18% would do for their wealth. That kind of ROE would more than pay for the drone organ donor program. GenMod workers ceasing function before retirement would be a boon for the welfare state too.
(maybe I’m spending to much time scrolling r/antiwork)
I kinda got sidetracked from part of my original question regarding transplants, how human NK cells might view the porcine MHC Class I molecules. From the first article I linked:
“Xenograft rejection is mediated by NK cells through direct NK cytotoxicity or by antibody-dependent cellular cytotoxicity mechanisms (Figure 2A). In the direct NK cytotoxicity pathway, through interaction of activating receptors and ligand, NK cells release lytic granules, leading to the lysis of the donor endothelial cell (43, 44). The direct cytotoxicity of NK cell is tightly regulated by the balance between activating and inhibiting signal pathways mediated by a variety of NK cell receptors (45). The activating NK receptors NKG2D (46) and pULBP-1 (47) bind to its pig ligand NKp44 and an unidentified molecule, respectively, to trigger lytic granule release. However, the inhibitory receptors on human NK cell, KIR, ILT2, and CD94/NKG2A, poorly recognize the porcine major histocompatibility complex (MHC) class I molecule, swine leukocyte antigen I, consequently disabling inhibitory signals for NK cell activation (48, 49). The destruction of pig endothelial cells occurs by the recognition of receptors on NK cells. The natural and elicited antibodies deposits on the graft endothelium are recognized by Fc-fraction (FcRs) on NK cells (Figure 2A). Interaction between FcRs and antibodies causes cytotoxic granules to release from NK cells and, in turn, to trigger target cell apoptosis (50). In addition to xenoantibodies bound on the endothelium, the induced antiswine leukocyte antigen (anti-SLA) class I antibodies are recognized by NK cells, also leading to antibody-dependent cellular cytotoxicity (51).”
So not good. Getting sidetracked back to our precious antibodies that just happen to be ready to bind pig antigens. Well first there was as above: “natural anti-α-Gal antibodies are universally induced during neonatal life by gut bacteria that expressed GGTA1”. That’s interesting. But another group of antibodies against pig stuff perhaps arose differently: “Anti-Neu5Gc antibodies can be induced in humans after dietary intake of porcine tissues from diet”.
https://www.frontiersin.org/articles/10.3389/fimmu.2019.03060/full
That nifty immunological detail aside, given dietary restrictions and views towards pigs in Judaism and Islam, I wonder how rabbis and/or imams would rule on such transplants.
Dorght @ 13
They may do profitable business with the Chinese. Those Falun Gong prisoners have quite healthy organs (NOT a joke. It has been happening for years).
Apropos of nothing…
I recall a report of Jesse Helms receiving a heart valve transplant from “another pig”.
I just remembered that my aortic valve implant has a bit of pig or cow tissue in it. So far so good. We used to feed our dog with pig heart valves that were rejects for heart valve replacements. Altogether different degree of replacement of course but this kind of thing has been coming.
@11-wzrd1
OK maybe PERVs aren’t an issue, but they developed ways of eliminating them. The first article I linked said: “Recombinant virus PERV-A/C exhibits increased infectivity toward human cells” with a paywalled link. The other article said: “Studies of PERV have demonstrated that human infection was generally, but not exclusively, the result of viral recombination between 2 PERV strains (A and C) that produced a strain more capable of replication in specific human cell lines.” So cell lines in a dish but not in living hosts (us)?
This is kinda interesting: “Furthermore, cellular restriction factors, such as APOBEC3G, play a key role in preventing PERV infection. Primary cells expressing APOBEC3G are difficult to infect. By contrast, HEK 293 cells, which are the most susceptible to PERV infection, do not express APOBEC3G”
Major detour:
APOBEC3G is a cytidine deaminase that uses hypermutation as means to fight retroviruses.
https://en.m.wikipedia.org/wiki/APOBEC3G
“The deamination activity ultimately results in G→A hypermutations at “hot spots” of the proviral DNA. Such hypermutation ultimately destroys the coding and replicative capacity of the virus, resulting in many nonviable virions.”
It has a family relationship to a cytidine deaminase that does cool stuff to antibody genes.
https://academic.oup.com/mbe/article/22/2/367/963921
“The results presented here support a scenario in which AID and APOBEC2 are the ancestral members of the AID/APOBEC family with APOBEC1 and APOBEC3 being later arrivals, derived from AID, and restricted to mammals. We cannot formally exclude the possibility that APOBEC1 and/or APOBEC3 arose early but were then lost in fish and chickens. However, because bony-fish diverged from the tetrapod lineage around 450 MYA and birds diverged around 310 MYA (Benton 1990; Kumar and Hedges 1998), this hypothesis would seem unlikely, because it implies that APOBEC1 and APOBEC3 were independently lost in distant lineages.“
Back to your regularly scheduled show already in progress…
SC@16 (I usually avoid opening up a discussion with you, but if you’ll indulge my babbling…)
Right. And Ishiguro’s scenario did come to mind. In fact, pigs are pretty smart and certainly appear to be self-aware. If we were starting from an ethical blank slate and were going to ask if these autonomous creatures could be bred and groomed for scheduled lifespans after which their organs are harvested, it would be shocking. I mean, animal slaughter is shocking to most young children and should be shocking. It requires social conditioning to habituate to this act of violence.
Ishiguro simply posits the idea for human beings, and what if we started out with the moral error that clones were somehow subhuman and then got dependent on killing them. That’s creepy and disturbing and a great premise for a novel and movie seen from the clones’ perspective. However, the moral error of slaughtering animals for meat was made long ago, making it less shocking in practice that we might also raise pigs for organs on a much smaller scale.
I’m not a morally good person. There’s a point where pragmatism kicks in. I know people who would benefit greatly from widely available solid organs and I want them to have them. I’d kill the pig myself I had to, though I wouldn’t kill one for sausage. This is not a utilitarian argument in the sense that I’d try to justify it morally. I am just saying that this is how I would act in that situation.
Though a religious quotes holds little weight here, I’m going to defer to St. Augustine’s prayer: “Lord, make me chaste—but not yet.” Let’s stop slaughtering animals… but not yet if we can figure out how to use them to save lives.
Should go without saying, pigs are intelligent, sentient beings.
But? They don’t have “souls” which means they can neither go to heaven nor suffer (or their suffering doesn’t matter); and they, the earth, and everything on it is god’s gift to us to endlessly exploit so humans can multiply babies for the greater glory of god?
There have to be better alternatives. No?
stroppy@21
Currently, the alternatives are dying, getting an organ from another human being (usually deceased at an unpredictable time, but occasionally living and voluntary such as for kidney and a portion of the liver), or in the case of kidneys, you can go on dialysis, which is pretty lousy way to live, though quality of life varies a lot by individual.
Right now, killing a pig does not even exist as an alternative, because there is no convincing evidence that it works. Killing a pig to get bacon, ham, and ribs is widespread, though and I agree there are much better alternatives in that case if the goal is merely to obtain protein for human consumption.
In the case of someone who needed an organ to enjoy a reasonable quality of life (including getting off dialysis), if killing a pig existed as an alternative, I would gladly kill the pig myself, ending its sentience as my sentience will one day end. And no, I don’t believe either of us have souls that will keep on after that.
Again, not justifying. Just explaining what I would actually do. If I could confront the pig and explain why I planned to kill it, I would be more comfortable doing that than explaining to a potential organ recipient why I was hesitating for even an instant.
robro @18
I had an aunt that received a pig valve in the early 90s. She has since passed but she lived with it for than 20 years.
robro@18
Yow. What was your source for that?
Surprised no one has mentioned pigoons! Once again, Margaret Atwood’s out ahead….
Regarding worthiness considerations, we had a publicised case of a struggle for an ICU bed.
The woman in the bed had terminal cancer. The person needing the bed had severe covid symptoms. The argumant for swapping in the covid patient wasa logistical one. The woman with cancer had very slim chances of surviving for very long. The managing nurse handling the cancer case for the last year was considering the request. Then she asked a question. “Is he vaxxinated?” Turns out covid guy was anti vax. The nurse then said no, to which the manager seems to have been releived.
Is that a judgement of worth or just a sort of “fuck you and your costly choices”?
Neither.
It is a rational calculation of the probability of the antivaxxer surviving. An antivaxxer with Covid-19 virus is 15-20 times more likely to die than someone who is vaccinated.
Actually it is probably both. Everyone is totally burned out by the antivaxxers by now, especially the health care workers. These patients have crowded out huge numbers of other patients who need treatment for the usual run of human diseases such as cardiovascular, pulmonary, infectious disease, etc. conditions and they keep the pandemic fueled up and running.
They attack the health care workers often, praise god when the antivax patients live, and claim the hospital killed them when they quite often…die.
birgerjohansson @15
Damn, that blew my tongue in cheek post out of the water. Satire eclipsed by the ability of reality to worse than I had imagined.
PaulBC, I don’t have time for a back-and-forth right now (nothing specific to you – I don’t have the time in general; I hadn’t seen your mention of human clones when I posted #16). I will say two things and then let you carry on. First, your repeated proclamations that for this purpose you’d “kill the pig myself I had to” or “I would gladly kill the pig myself, ending its sentience as my sentience will one day end” sound odd and oddly performative to me, especially given that this is an implausible hypothetical scenario. Perhaps the performance is self-directed, because…
Second, you’ve implied a few times that you don’t think eating animals when alternatives exist is justified. You recognize that “animal slaughter is shocking to most young children and should be shocking. It requires social conditioning to habituate to this act of violence,” and that “there are much better alternatives in that case if the goal is merely to obtain protein for human consumption.” But then suggest that you’ve “acclimated to the idea that we raise them for slaughter.” I don’t believe you’re all that acclimated to it. You say you wouldn’t kill a pig for meat yourself, and “would like to see factory farms eliminated and meat consumption reduced drastically and eventually eliminated.” At the same time, you’re not a vegetarian/vegan yourself. Your assertion that “I’m not a morally good person” isn’t convincing and sounds like a cheat.
In short, I think that whatever your thoughts about some theoretical system of exploiting pigs for human organ transplants, you’re quite conflicted about the existing system of exploiting them for food! So my suggestion is that you go vegan – conflict resolved!
:D
SC@29
Yes. It’s performative. Why oddly? I had hoped to add some color to my writing for emphasis and to eliminate any ambiguity.
I’m not conflicted. I believe it’s wrong. I’m just lazy. I can believe something is wrong and still be a hypocrite about it. Meat is a convenient source of protein. I could stop eating it, but I really don’t want to prioritize my life around it.
I think that raising pigs for organs is actually a very reasonable stopgap if it works, until we have something better. So I’m not conflicted about that either. I would very much like to see a scalable supply of solid organs for transplant and I think it would be quite terrible for any human being to wait until there is a solution that does not require a sentient host (though obviously a human host is out of the question).
The boundary between nonhuman animals and humans considered subhuman has always been porous.
“The ‘Father of Modern Gynecology’ Performed Shocking Experiments on Enslaved Women”:
…btw, I thought this was a much more interesting implausible hypothetical scenario:
And yes… performative. All the world’s a stage, after all.
Rohin has a good breakdown of the issues. Including ethical.
https://youtu.be/0d8svvqX1c0
@hemidactylus.
“…AID/APOBEC family…”, cool! I was wondering if we’ve found more in the APOBEC line, I remember a few blurbs I ran into in random reading, I can’t even begin to imagine what we’ll know in 20 more years!
As I’ve frequently said, it’s amazing what one can create with only 4 “letters”, unsurprising that things break when one letter gets munged. :)