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U.S. surgeons transplant pig heart into human patient

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Re: U.S. surgeons transplant pig heart into human patient

#261

Post by light_hue_1 »

tricky wrote: post #26

You might be asking, why a pig? I don't know, but forever ago I wrote software for a cardiovascular imaging lab and pigs were their primary test subjects. I was like, "why pigs?" and the PI was like, "Imaging-wise, pig hearts aren't too different from humans. Plus, we can give them a heart attack in the scanner and not go to jail. Some labs use dogs. I just can't do that."

There are important advantages to pigs over non-human primates.

Originally, research was centered around non-human primates (NHPs). But it didn't work out all. Sure, they're a bit closer to us genetically, but we still reject their tissues, so we would need to genetically engineer them. Humans are also much bigger than the non-human primates we can grow in the lab with ease and that have a fast enough reproductive cycle to make genetic engineering work out. So the organs would all be undersized. Ease of breeding is a big issue too, litter sizes for NPHs are very small compared to pigs.

It gets even worse though. Because NHPs are so close to us, they easily catch infections from us. So they're much more likely to catch diseases from us and to give us their diseases.

There are also ethical concerns with primates being so close to us, which don't exist with pigs given that they're primarily food animals.

It took around a dozen or so genetic changes to knock out markers that allow our immune system to recognize that pig organs are foreign. In particular, primates (including us) are sort of strange in that Alpha-gal, a sugar that's all over all other animal bodies, doesn't exist in us and our immune system violently rejects anything that contains it. Understanding this took a long time, but then we eventually figured out how to prevent pigs from expressing Alpha-gal.

That's basically the story here. Figure out why rejection is happening, knock it out, repeat. There are also many forms of rejection and it happens differently in different tissues. But, we're getting there.

If you want to read more, here's an awesome recent review of the history and state of the field: https://www.frontiersin.org/articles/10.3389/fimmu.2019.0306...

Re: U.S. surgeons transplant pig heart into human patient

#262

Post by Hnrobert42 »

Sporktacular wrote: post #230
dexwiz wrote: post #61

Earlier quoted context omitted.

Pigs are really common in biomedical testing. They are physically a similar size and weight to humans. They also reach maturity in about 6 months. Much cheaper to raise than primates, and more likely to get approval for testing. My friends in biomed grad school named one of theirs cyber pig because it has about 30 different experiments ran on it before it was killed, and afterwards it was portioned out for further te…

Weird how this is said without a shred of sympathy or concern for an intelligent, helpless creature. Weirder how it can be said without a sympathetic or concerned response. I hope we can someday move beyond seeing animals as a mere resource.

I think for things like this, being dispassionate is a coping mechanism. If you engage the sympathy part of your brain, you won’t be able to do it. If you don’t do it, then humans die instead.

Re: U.S. surgeons transplant pig heart into human patient

#263

Post by frozenport »

Sporktacular wrote: post #230
dexwiz wrote: post #61

Earlier quoted context omitted.

Pigs are really common in biomedical testing. They are physically a similar size and weight to humans. They also reach maturity in about 6 months. Much cheaper to raise than primates, and more likely to get approval for testing. My friends in biomed grad school named one of theirs cyber pig because it has about 30 different experiments ran on it before it was killed, and afterwards it was portioned out for further te…

Weird how this is said without a shred of sympathy or concern for an intelligent, helpless creature. Weirder how it can be said without a sympathetic or concerned response. I hope we can someday move beyond seeing animals as a mere resource.

I don't see them as intelligent

Re: U.S. surgeons transplant pig heart into human patient

#264

Post by redanddead »

woke_neoliberal wrote: post #35

The pig was modified to remove presentation of immunogenic sugars on the cell surface. Unfortunately, the recipient needs to be on immunosuppressants the rest of their life. This rekindles discussions back in school about chimeras... in order for the organs to be immunocompatible, the donor needs to be partially human. What % is too human to harvest for organs? I suppose it's still too soon to answer such questions,…

I think people will only accept 3d printed organs, pig and animal things are too controversial for some people.

I was listening to a podcast on the CBC about AI and consciousness, and the idea that humans are distinct from an animal (beastmachine, great name for a butcher shop btw) comes from Descartes, who we revere in philosophy (for fair reasons)..

I think we can't blame people for wanting to separate themselves from animals.

Re: U.S. surgeons transplant pig heart into human patient

#265

Post by tptacek »

cwkoss wrote: post #122
dexwiz wrote: post #61

Earlier quoted context omitted.

Pigs are really common in biomedical testing. They are physically a similar size and weight to humans. They also reach maturity in about 6 months. Much cheaper to raise than primates, and more likely to get approval for testing. My friends in biomed grad school named one of theirs cyber pig because it has about 30 different experiments ran on it before it was killed, and afterwards it was portioned out for further te…

Are pigs used in biomedical testing ever butchered for their meat? Seems like we kill a lot of pigs every year anyways. Would be neat if we could get multiple birds from one stone - for experiments where there isn't a risk of making the meat dangerous at least.

It depends! One of my kids is a biochemist wrapping up his degree this semester in a vet-med lab (send job opportunities!). He's done one study with pigs, where they were developing new enteric vaccines. At the conclusion of the study there's nothing wrong with the pigs --- they're just hyper-vaccinated --- but without a place to send them, all they can do is euthanize. He spent a week or two trying to re-home the pigs, but he's at UIUC and there is no pig shortage in the area. You could have taken those pigs for free and ultimately butchered them.

Euthanizing research pigs seems especially difficult. I'm really into butchery --- invested in a butcher in the area --- and would happily attend a slaughter. But the circumstances attending euthanizing research pigs are tricky; the pigs are all in a common area, and they're social animals and know something's up when you put one of them down. It messed with the boy.

Re: U.S. surgeons transplant pig heart into human patient

#266

Post by redanddead »

dexwiz wrote: post #61
tricky wrote: post #26

You might be asking, why a pig? I don't know, but forever ago I wrote software for a cardiovascular imaging lab and pigs were their primary test subjects. I was like, "why pigs?" and the PI was like, "Imaging-wise, pig hearts aren't too different from humans. Plus, we can give them a heart attack in the scanner and not go to jail. Some labs use dogs. I just can't do that."

Pigs are really common in biomedical testing. They are physically a similar size and weight to humans. They also reach maturity in about 6 months. Much cheaper to raise than primates, and more likely to get approval for testing. My friends in biomed grad school named one of theirs cyber pig because it has about 30 different experiments ran on it before it was killed, and afterwards it was portioned out for further te…

What is it about primates that make them expensive?

Re: U.S. surgeons transplant pig heart into human patient

#267

Post by mlyle »

JetAlone wrote: post #228
TravHatesMe wrote: post #163

Earlier quoted context omitted.

Bit of a tangent: I read the article to my wife and she mentioned that there is an episode of Grey's Anatomy where they wanted to perform a transplant of a pig's bowels but the Jewish (or Muslim?) lady refused. Interesting how one might choose to their faith over their life.

I'd want to question why I'm doing it. For example do I have kids I need to stick around to support? Or am I just going to be discharged to mostly play video games, alone? Because I don't see a need to extend that life. Then I'd want to think about what it symbolizes. Is it really so irrational to just let my body die when my God-given guts fail instead of depending on the hands of man to possibly convert my body int…

Conversely, there's this well-worn pseudo-parable:

A fellow was stuck on his rooftop in a flood. He was praying to God for help.

Soon a man in a rowboat came by and the fellow shouted to the man on the roof, “Jump in, I can save you.”

The stranded fellow shouted back, “No, it’s OK, I’m praying to God and he is going to save me.” So the rowboat went on.

Then a motorboat came by. “The fellow in the motorboat shouted, “Jump in, I can save you.”

To this the stranded man said, “No thanks, I’m praying to God and he is going to save me. I have faith.” So the motorboat went on.

Then a helicopter came by and the pilot shouted down, “Grab this rope and I will lift you to safety.”

To this the stranded man again replied, “No thanks, I’m praying to God and he is going to save me. I have faith.” So the helicopter reluctantly flew away.

Soon the water rose above the rooftop and the man drowned. He went to Heaven. He finally got his chance to discuss this whole situation with God, at which point he exclaimed, “I had faith in you but you didn’t save me, you let me drown. I don’t understand why!”

To this God replied, “I sent you a rowboat and a motorboat and a helicopter, what more did you expect?”

Re: U.S. surgeons transplant pig heart into human patient

#268

Post by mlyle »

aaaaaaaaaaab wrote: post #187
SomeHacker44 wrote: post #178

Earlier quoted context omitted.

Actually, I heard an NPR story over the holidays about a tick borne disease that causes a meat allergy, and how pigs raised for another purpose then became suitable for butchering to eat their meat for people with that disease... So it happens in at least one case.

“ In 2020 the U.S. Food and Drug Administration approved genetic modification of pigs so they do not produce alpha-gal sugars. Pigs developed with the trademarked name GalSafe may be able to be eaten safely by people with alpha-gal allergy.[44] They may also produce alpha-gal-safe drugs,[45] and their organs can also be used for xenotransplantation.” https://en.m.wikipedia.org/wiki/Alpha-gal_allergy

Which, is the exact genetic modification discussed in the article (along with 2 other carbohydrates getting knocked out).

Re: U.S. surgeons transplant pig heart into human patient

#269

Post by tired_medicine »

kashunstva wrote: post #227
Blikkentrekker wrote: post #201

Earlier quoted context omitted.

Would artificial valves then not work as well or even better?

The tissue component of bioprosthetic valves is treated ex vivo in such a way as to greatly reduce the immune reactivity. It's practically not a consideration. Mechanical prosthetic heart values are generally favoured only in older patients where re-operation is not likely to be required. The reason being that bioprosthetic valves have a more limited long-term durability. So why not always use mechanical valves? Thei…

Mech valves are actually favored in younger patients, since they don't become calcified, like bioprosthetic valves. However, they do require life long anticoagulation with warfarin, which is dangerous to live with.

Re: U.S. surgeons transplant pig heart into human patient

#270

Post by mhalle »

323 wrote: post #95
robbiep wrote: post #51

Earlier quoted context omitted.

They’re not making the pig more human, they’re removing the markers of ‘foreign’ that would make it an immune target. So it’s a nice vanilla organ that minimally attracts the attention of the immune system.

Just removing some sugars can't possibly work, since the pig heart will lack correct MHC class I molecules, which will make it a target. So the patient will need permanent immune-suppression.

Plenty of transplant recipients from deceased or living human donors are on permanent immunosuppression. Depending on the organ and the person, day-to-day life can be almost completely normal. Source: I am a liver transplant recipient.
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