My animal heart

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Over 100,000 people in America are currently waiting on a life-saving organ transplant.

And people often end up waiting for years.

They get weaker, they get sicker.

17 people die every day on the waiting list because there just aren't enough extra organs to go around.

But there are some possible solutions.

My colleague Dylan Matthews donated his kidney to a stranger.

He wants more people to donate theirs.

Scientists also have some ideas.

Building robot hearts, growing lungs.

Still, none of these has fundamentally changed the organ shortage, which is a persistent problem in almost every country.

But

there could be another way forward.

An experimental procedure that is giving hope to people who need organs.

I'm the first person in the world to get a heart transfer.

It sounds like some kind of bad plot from a sci-fi movie villain, but some scientists think this could actually be a realistic solution to the problem.

We might have a future where people are walking around with like whole pig hearts and pig kidneys that are keeping them alive.

This week on Unexplainable, reporter Manding Wynn on the potential of xenotransplantation.

Can animal organs really save our lives?

Okay, Mandy, I have so many questions here.

I feel like I don't even have a basic sense of how transplantation works.

I assume animal transplanting or xenotransplantation is harder than human transplantation.

Yeah.

So when a human body gets anything foreign, I mean, especially like a whole brand new organ, it basically like freaks out and launches an immune response and wants to just fight and destroy whatever new thing is in it.

Right.

And like even with organs, human organs that are considered a match to be transplanted, our bodies still do not like that.

So usually people who get regular human transplants, a lot of them need to be on immunosuppressants for basically all their lives, as long as they have it to manage that response to make sure the organ doesn't reject.

And being on immunosuppressants makes a person weaker and more susceptible to disease.

It's not ideal.

But when it comes to something like transplanting a pig organ, that immune response is a lot more intense, a lot stronger.

And so doctors can't really treat it like they would a human transplant.

They need like a lot more immunosuppressant drugs, maybe different types, maybe different doses.

This is one of the things that they're figuring out because it's just different.

And are they like the same?

I mean, besides for the fact that pig hearts are just weirder or more foreign than human hearts,

like the heart is the same.

It can do the same thing.

Yes, the heart is basically the same.

And that's actually why they have decided to use pigs as kind of the like main animal to transplant.

Because hearts, livers, they're approximately the same size as ours.

Okay.

And they pretty much look the same and they function the same.

Interesting.

And in the last few years, there's been a lot of progress on xenotransplantation, which is, you know, the transplanting of animal organs into people.

So there have been five total operations where living people have gotten these pig organ transplants.

Okay.

There's been two hearts and two kidneys all in the U.S.

and then one liver transplanted in China.

And I wanted to learn a bit more about these cases, like what we've learned from them.

And so I spoke to one of the surgeons who did the very first pig heart transplant to learn more about what happened.

Wow, the first pig heart transplant.

Yeah, and it was only a few years ago.

So his name is Dr.

Mohammed Mohoudin, and he's a surgeon at the University of Maryland and the director director of the cardiac xenotransplantation program there.

Such a cool title.

Yeah.

And he hopes that one day pig transplants can work just as well and maybe even better than human ones.

If we get to that stage, you know, the patient may choose a pig heart over a human heart.

I mean, this is this, you can call me crazy, but this is what I believe.

But I was also curious what made him and his team so confident to do this first pig heart operation, considering, you know, it's never been done before, it's never been done successfully.

What did he say?

Basically, it has to do with animal experiments.

Like

before these cases of transplanting pig organs into people, there's actually been a lot of research on doing xenotransplants between different other animal species.

And that's the kind of work that Muhammad's been doing for the past few decades.

So like putting a pig heart into a different animal or a different heart into a pig?

Yes, exactly.

Interesting.

And at first, when he was doing this, he never quite got past the issue of rejection.

You can see rejection happening right in front of your eyes when you put a unmodified pig heart without any immunosuppression into a baboon, and the heart gets black right away.

That is absolutely not what I would have expected.

That's crazy.

Yeah.

So again, he started doing this work 30 years ago without, you know, without much progress until the early 2010s or a bit over a decade ago, when there's this big breakthrough in xenotransplantation science.

It's basically when CRISPR comes along.

Can you just remind everyone what CRISPR is?

Do you want to try?

Okay.

My understanding of CRISPR is basically just that it is a tool that allows you to go in and actually kind of cut up and reassemble genetic code of

various types of things.

So you can start with a pig heart.

You can just cut up the genetic code a little bit and make it look much more genetically like a human heart.

Yeah.

In this case, they're genetically engineering and messing with the DNA of pig embryos to make sure their hearts don't grow too big, make sure they're less likely to get attacked by the immune system and things like that.

Just make it look less like a pig heart to the human body.

Yeah.

Wow.

So the attack is there, but it's not as severe.

What we want to do is to reduce that attack to almost negligible level or to the level where we can keep it suppressed with the help of drugs.

He eventually got to a point where he and his team were able to put these genetically engineered hearts in baboons and keep them going for longer than anyone else has been able to.

We were able to get the heart to survive for up to three years.

So from rejecting within minutes to getting it to three years, right, was a huge leap.

So all these different successful long-term experiments in monkeys and animals, it made Muhammad feel like there is a proof of concept.

You know, there was good enough gene edits, the right drugs and dosages to keep a pig organ going in a different species.

And that brings us to a few years ago when he and his team sought out approval to do it in a human.

How do you get approval for something like that?

Yeah, so they specifically wanted to get approval from the FDA for something called the compassionate use, which is when a terminally ill patient has no options and they're they're willing to try something experimental that hasn't been like approved yet.

So they looked for patients in the hospital that Muhammad worked at and they found a man named David Bennett.

57-year-old David Bennett had no other option.

He had end-stage heart failure and was basically living in the hospital hooked up to a machine that was acting as his heart.

Like he was just way too sick to get a human heart transplant.

With less than six months to live, doctors in Baltimore offered him a medical leap of faith.

They offer him this experimental pig heart bennett who had been hospitalized and bedridden for months saying in a statement it was either die or do this transplant i want to live i know it's a shot in the dark and in doing so they had to be really clear about the risks so muhammad was telling me that they were straight up in telling david you know

you might not make it on the other side we cannot guarantee that we can even

make you live for even a day

so so what happened?

When they put this pig heart in David, there was definitely this moment of anticipation to see if it would start.

We didn't see any rejection right away.

We see the heart started beating like it's supposed to.

So, they sew him up with his new working pig heart and they wait for him to wake up.

Nobody in the world knew how a human would react to a pig heart, right?

But next day, when that patient stood up and started talking, you know, it looks like science fiction, right?

And And then when we asked him, you know, how are you feeling?

He said, oink, oink.

So

he's got a sense of humor post-heart transplant.

No, I guess you have to.

That's like, wow.

This morning, a man in Maryland is living his fourth day with a pig heart beating in his chest after a groundbreaking surgery.

And for the first 50 days, the heart was beating like it was supposed to.

I almost kind of lived in the hospital for the next couple of months, you know,

and we we lived and died with that patient.

Unfortunately, after that, David deteriorated quickly and he died soon after.

Do we know what caused the change after 50 days?

They can't actually pinpoint one reason why.

There was like a few different things potentially going on.

So, again, David was also just already super sick and having him on a bunch of immunosuppressants.

Everything is weak, you know, everything's a little fragile.

But also, they had found a pig virus in the heart.

Oh.

And that might have caused some sort of inflammatory immune reaction.

But there was this other potential little culprit.

They actually also gave him some drugs to help stabilize his immune system.

And that actually ended up attacking some of the pig cells.

Oh.

So just a lot of these different things at once.

And this is kind of how it works in general for senotransplantation right now.

Scientists have figured out how to prevent kind of immediate rejection when they transplant a pig organ into a person, which means it doesn't immediately fail, you know?

But when it comes to long-term health and survival and being able to keep a person living for a decent amount of time, like that's still kind of a big question mark.

Like all four people in the U.S.

who have gotten transplants that I've mentioned before, none of them are still alive.

No one survived more than two months.

But Muhammad doesn't see any of these cases as failures.

They've actually learned a lot from each.

Like, for example, the pig virus that was found in the first transplant, now there's more sensitive tests to screen for viruses like that.

They've also more finely tuned the gene edits and the immunosuppression to keep the organ from being rejected longer.

There are certain things that still we won't know until we do a next transplant.

If we can prove progressive improvement in survival, you know, that is the key to the success.

I mean, that just feels like so

because one of the main things holding this back is probably the fact that they're not operating on healthy people.

But what relatively healthy person would be like, oh, if the doctor said, oh, you can have a human heart or a pig heart, who's going to be like, oh, give me the pig heart, right?

Exactly.

Like, it's the obvious question.

And it kind of brings up this question for me of like, should we be doing this?

Like, are we moving too fast here?

And so, you know, we'll get into that.

but after the break

what break this break

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Okay, Mandy, we're back.

Hi.

And

before the break, you were telling us how scientists are putting pig organs in people to try to save their lives, which sounds great.

Mohammed certainly seems to think it's great, but you're not totally sure it's great.

Yeah, so the trains basically left the station on Xeno Research.

Like it's full steam ahead, but I still feel a little uneasy about it.

Like, are we doing the right thing here?

How dangerous this is?

And

it's something where you immediately feel an ick.

You know what I mean?

So I reached out to a bioethicist and philosopher to help orient me to some of these questions.

My initial impressions of it were, boy, this doesn't really sound like something that's going to work.

That's El Sid Johnson.

She's a clinical ethics consultant and professor at SUNY Upstate Medical University.

It's very possible that xenotransplantation will never work, that no animal's organs could be made to support life in a human being.

Sid says there's three big problems here.

There's the risk to the human patients.

There's the risk of diseases jumping between species.

And then there's the question of whether what we're doing to these animals is ethical.

Okay.

Let's go through all three of them.

First one is the risk to patients.

Yeah.

And the question here is, is it worth the potential risk to the people who take on these pig organs?

The first 10, 20, 30, however many, right?

Until scientists figure out how to make this work consistently.

And, you know, maybe it's because all these cases have been with really sick people with no options, but there's also something ethically tricky there, too.

People who accept a pig heart so far, they do it because they want to live longer, like they want a chance to keep on going.

But in this case, they're not just patients, they're also research subjects.

This isn't a proven procedure that we know how to do well at all.

This is called the therapeutic misconception, where patients believe that being part of an experiment, that experiment is actually intended to benefit them.

And we can't say that at this point about xenotransplants.

To their credit, the surgeons and scientists working on this are working with ethicists and are thinking kind of really deeply about how to communicate this to their patients.

But I think her big concern is that this is something that it's possible it might not ever work and how many people

might be subject to hoping an experimental treatment will work when they have like no other options.

Yeah, I guess the scientists are learning a lot here

and

they're probably gaining a lot more from this interaction than the patients are, which feels kind of tricky.

Right.

And, you know, the people working on this really do believe it's on the verge of working and that this could save so many lives.

And it, and it might, you know, but that's still a question mark.

Another big concern is that putting pig organs in people might mean animal diseases spreading to people more easily.

Oh, yeah.

You know, pandemic era.

Yeah.

Yeah.

It's not great.

And, you know, even in that first pig heart transplant, again, they found that pig virus, which immediately raised a red flag.

You know, there is the concern that

putting an organ from an animal that has a virus into a human and that human is immunosuppressed will result in the mutation of a virus that might plausibly be transmitted to other humans.

And who who knows what the results of that could be.

I mean, the idea of a pig virus mutating in a human body to become infectious to other people, that was actually something that made me really concerned at first.

But the more I talked to scientists, the more I felt that it's a little bit more complicated.

How so?

Well, first, there's a lot of preventative measures, like the pigs that are raised for this are in really sterile facilities.

There's a lot more testing for viruses.

They've even figured out ways to make genetic edits to the embryo to basically remove some of the pig viruses.

But, you know, even with all these preventative measures, nothing's 100% foolproof.

You know, it is possible in theory for a pig organ, say if I had a pig organ, to be infected by a pig virus and for that to mutate and spread to other people.

But that risk seems a lot lower than the ways that we already interact with pigs.

So I feel a little bit less worried about it.

Yeah, what about the actual pigs?

That was another one of the issues here, right?

Right.

That's the third big problem: that these pigs just live super bleak lives.

They don't touch grass.

They never see the sky.

These are animals who would not exist at all except for our human intervention.

And I think we're really treating them like machines, just for the purpose of taking them apart to provide spare parts for humans.

And I think we really do need to reflect on what we're doing there and on the harms that we're causing to living conscious intelligent creatures

in part so that a handful of biotech companies can profit from their existence i mean i think that's a pretty powerful argument but i also think saving a life is just really important

and if we really can someday save a lot of people's lives with animal organs yeah

I don't know.

I'm not sure, but maybe

it's worth it.

That's actually something I talked to Muhammad about too he's had to go on his own kind of journey here grappling with the ethics I'm a religious person right I mean I'm a practicing Muslim so my parents when when they found out that I'm working with pigs and all they said oh you couldn't find any other species to work with oh man that that's got to be like the only way a Muslim parent would be upset with a with a surgeon for a kid like working with pigs.

Yeah, it's funny.

He actually told me that originally he was a bit skeptical of xenotransplantation, which makes sense, you know.

But once he started doing this research and once he starts, you know, seeing results more and more, it's just made him firmer in his opinion that this is something worth doing.

You know, my goal is to save a life.

And if it's a pig that can help

that human live, you know, that will be my goal.

So where do we go from here?

Well, scientists like Mohammed want to move this into real clinical trials, which means putting pig organs into more people, healthier people, so that they can actually see how to manage it long term and how to make this work.

But obviously that gets really tricky because what that process looks like and what those trials look like is debatable.

Sure.

Mohamed told me that he wants to start doing clinical trials with people who are a little healthier than the people we've seen in the past cases so that they can withstand more immunosuppressants.

But then there's another surgeon I spoke to who said that we need to be putting pig organs in people who are a lot healthier, specifically healthy enough for human organs.

But that feels obviously risky, right?

Yeah, which is why scientists and ethicists I've spoken to have said that actually more non-human experiments need to be done.

So there's even been recent studies where scientists are putting pig organs into brain-dead bodies to see how a functioning human body responds to a pig organ without putting a living person at risk.

Okay, that seems promising.

You know, it's limited in scope right now.

This is not happening everywhere.

But from the handful of experiments that have been done, we're learning a lot.

What do you think we should do here?

It just feels like there are

really strong competing values on both sides.

Do you think there's a good way forward?

Whew.

I mean, it doesn't seem like there's a great answer here for what's next.

And I definitely don't have that answer.

But I just go back to the fact that there's more than 100,000 people just waiting for organs, and a lot of them die because they can't get one.

Like, it makes sense to me why these surgeons and scientists are pushing to get this procedure to work, even if it means doing things like putting pig hearts into brain-dead bodies, which sounds like crazy.

Right.

But at the same time, the ethics here, they feel just really tricky.

Like, how far are we willing to push in the name of progress here?

Like, is this going to be the future of transplantation, or are we crossing a line that maybe we shouldn't?

So, even after all this, I don't really know.

Right now, I'm not sure we have those answers, but I think if we want to help people, we need to take these questions seriously.

This episode was reported and produced by me, Manning Wan.

We had editing from Matt Collette and Jorge Just, sound design and mixing from Christian Ayala, music from Noam Hasenfeld, fact-checking from Anouk Dusso,

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Special thanks to Jamie Locke, Dominique Martin, Brendan Parent, Suzanne London, and Olivia Cates.

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