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Xenotransplantation · Daniel and Kelly’s Extraordinary Universe

0:00
Speaker 1: Hey, friends, just a heads up that we're talking about
0:02
Speaker 1: organ shortages today and will touch on topics like death
0:06
Speaker 1: and animal research. So decide if this is an appropriate
0:09
Speaker 1: episode for you or your kiddos. According to Donate Life America,
0:28
Speaker 1: over one hundred thousand people are on the organ transplant waitlist.
0:32
Speaker 1: Approximately every eight minutes, another person is added to this list,
0:36
Speaker 1: So while you are listening to our show, approximately five
0:39
Speaker 1: people will have been told that their life depends on
0:42
Speaker 1: receiving a new organ. That weight might be quite long.
0:46
Speaker 1: Some folks will wait years before that organ becomes available,
0:49
Speaker 1: and during that weight the quality of their life could
0:52
Speaker 1: be quite poor. And unfortunately, not everyone on this waitlist
0:55
Speaker 1: is going to get an organ in time. Every day,
0:58
Speaker 1: about thirteen people on the waitlist will pass away because
1:01
Speaker 1: an organ was not made available soon enough. So what
1:04
Speaker 1: are our options. Well, today we're going to talk about
1:07
Speaker 1: one of those options that's looking more and more promising
1:10
Speaker 1: every day, and that option is zeno transplantation. That is
1:15
Speaker 1: taking organs from a non human animal pigs in this case,
1:19
Speaker 1: and implanting them into humans. This requires a fair bit
1:22
Speaker 1: of genetic engineering, and today we'll chat about how that's done.
1:26
Speaker 1: Welcome to Daniel and Kelly's Extraordinary Universe.
1:43
Speaker 2: Hi, I'm Daniel. I'm a particle physicist, and me and
1:46
Speaker 2: my microbes consider myself one hundred percent human.
1:49
Speaker 1: Hi, I'm a Kelly Wiener Smith. I study parasites and space,
1:53
Speaker 1: and yes, the community that makes up me is all me,
1:57
Speaker 1: and I feel great about it.
2:00
Speaker 2: Some one wonder and ask Katrina this question whether my
2:02
Speaker 2: microbes would be offended to be considered human because you know,
2:06
Speaker 2: they don't have the human DNA, but they are part
2:08
Speaker 2: of me.
2:09
Speaker 1: Yeah, you know, I feel like you could actually have
2:10
Speaker 1: a pretty interesting philosophical argument about what you really means,
2:16
Speaker 1: because you know, when we had Katrina on the show,
2:19
Speaker 1: she was talking about how bacteria sort of communicate with
2:21
Speaker 1: our brain via the vagus nerve vegas nerve. We both
2:24
Speaker 1: know I don't pronounce things correctly, ever, and so you know,
2:28
Speaker 1: I had to what extent your well being and behavior
2:32
Speaker 1: is influenced by what kinds of bacteria you have at
2:35
Speaker 1: the moment. I think it is a fascinating question. And
2:37
Speaker 1: so I contain multitudes.
2:39
Speaker 2: And maybe if you had different multitudes, you could pronounce
2:42
Speaker 2: things differently or better. Even right, I don't.
2:44
Speaker 1: Think anything could help me with that. Ever, I've always
2:47
Speaker 1: been this way no matter what my microbiome was up to.
2:51
Speaker 2: I'm going to ask Katrina to engineer some superbug to
2:54
Speaker 2: help you with your pronunciation.
2:57
Speaker 1: I would happily pay for that. That would be a
3:00
Speaker 1: So when I have to do the audiobook readings for
3:03
Speaker 1: my books, I'm always like, ah, this is going to
3:05
Speaker 1: be a disaster.
3:07
Speaker 2: But in general, I love when questions in science bump
3:10
Speaker 2: up against philosophical issues, you know, that make us ask
3:13
Speaker 2: questions like what do we really mean by your body?
3:16
Speaker 2: And it's not that hard to get there, you know,
3:18
Speaker 2: you can just even ask like, well, where does your
3:20
Speaker 2: body end? You know, is it at your skin, at
3:23
Speaker 2: your hair, a millimeter past it? It's your fuzzy personal
3:27
Speaker 2: space boundary. You know, it's not that hard to get
3:30
Speaker 2: stuck in weird philosophical questions.
3:33
Speaker 1: Yeah, and organ transplants, whether it's from one human to
3:35
Speaker 1: another or zeno transplantation, which we're talking about today, which
3:39
Speaker 1: is when you take organs from a non human animal
3:41
Speaker 1: and put them into a human. You know, causes a
3:44
Speaker 1: lot of philosophical questions or at least a lot of
3:47
Speaker 1: sort of emotional turmoil. There are stories about people who
3:50
Speaker 1: have gotten face transplants, for example, just feeling very uncomfortable
3:54
Speaker 1: looking at their face in the mirror. There's a story
3:56
Speaker 1: of one person who had a hand transplant and he
3:58
Speaker 1: ended up wanting the hand remove moved because he just
4:01
Speaker 1: was like, this is not my hand and it's just
4:03
Speaker 1: too weird. I'm not emotionally, I can't handle this.
4:06
Speaker 2: You can't handle it nice.
4:08
Speaker 1: Oh I didn't even get how clever even when I'm
4:11
Speaker 1: not trying.
4:12
Speaker 2: Man, Well, I was just going to raise that issue,
4:15
Speaker 2: like it's really a ship of theseus question. You know,
4:18
Speaker 2: if you get somebody else's liver, you feel like you're
4:21
Speaker 2: still you. What if you've got somebody else's liver and
4:23
Speaker 2: pancreas and heart and legs and arms and everything else
4:27
Speaker 2: except the brain, would you still be you? I think
4:29
Speaker 2: we mostly consider ourselves to be our brain, which is
4:34
Speaker 2: I don't know if that's philosophically naive or sophisticated or not.
4:37
Speaker 2: But the face is weird. Right to be in somebody
4:39
Speaker 2: else's face. That must feel strange.
4:42
Speaker 1: Yeah, that must feel strange. I still feel like, you know,
4:44
Speaker 1: for a lot of people, it must be a huge relief,
4:47
Speaker 1: depending on what happened to them to put them in
4:48
Speaker 1: the position where they needed a face transplant.
4:50
Speaker 2: Oh right, Yeah, I thought you were just saying, like,
4:53
Speaker 2: I'm not that happy with my face either, so would
4:56
Speaker 2: be a relief to have somebody else's face over here.
5:00
Speaker 1: I spent too much time in the sun. I could
5:02
Speaker 1: use a face with less evidence of that. But this
5:05
Speaker 1: is the face I got, and I'm going to stick
5:06
Speaker 1: with it. But yeah, you know, I as somebody who
5:09
Speaker 1: is working their way through paramenopause, and there are days
5:12
Speaker 1: where I'm feeling grumpy. I'm so interested in this question
5:16
Speaker 1: about like what makes you who you are, and like
5:19
Speaker 1: how your hormones influence the way that you behave or
5:22
Speaker 1: maybe how the bacteria that are releasing stuff, how that
5:25
Speaker 1: influences the way you behave. I think it's a really
5:27
Speaker 1: fascinating question that ties in with this question of like,
5:31
Speaker 1: you know, to what extent does it matter if the
5:33
Speaker 1: you parts have your genome in their nucleus or not.
5:38
Speaker 1: It's complicated. What do you think if you had lungs, hearts, kidneys,
5:42
Speaker 1: liver from somebody else, how would you feel about that?
5:46
Speaker 2: I would feel a little bit like I had some
5:48
Speaker 2: of them inside of me. Yeah, and I wonder how
5:53
Speaker 2: parents feel when their children's organs are reused after a
5:59
Speaker 2: tried to accident. Do they feel like, you know, little
6:02
Speaker 2: Timmy's heart is still beating and so we have still
6:05
Speaker 2: some part of him, I wonder, or if they just
6:08
Speaker 2: feel like that was a gift to help somebody else live.
6:11
Speaker 2: I don't know.
6:11
Speaker 1: It's fascinating, yeah, yeah, no, fascinating, And it must be
6:15
Speaker 1: very emotionally complicated. I imagine lots of people have different feelings.
6:18
Speaker 1: I think if I was in that situation, I would
6:20
Speaker 1: be glad that other families were spared the pain that
6:24
Speaker 1: I was going through and that, you know, our family
6:26
Speaker 1: was able to give that to them. But it would be, yeah,
6:29
Speaker 1: really complicated. So today our topic is a bit of
6:32
Speaker 1: a downer, But a lot of.
6:33
Speaker 2: Those philosophical issues can be partially sidestepped if you're not
6:37
Speaker 2: talking about a human to human gift, right, If you're
6:40
Speaker 2: talking about getting an organ from another animal, and this
6:43
Speaker 2: different set of philosophical issues, right, if you're getting it
6:46
Speaker 2: from a pig or from a baboon, and are they
6:48
Speaker 2: sentient and can they consent? And do they have rights
6:51
Speaker 2: and all this sort of stuff, But you do avoid
6:53
Speaker 2: the question of like taking organs from another person and
6:56
Speaker 2: then being part of you. So tell us, Kelly, how
6:58
Speaker 2: do we get started on this question?
7:00
Speaker 1: Well, the reason we got started on this question is
7:02
Speaker 1: because a listener, Jane, who's a pastor, wrote and wanted
7:05
Speaker 1: to know what kind of philosophical issues come up when
7:08
Speaker 1: you're using you know, pig organs, transgenic pig organs to
7:12
Speaker 1: keep people alive. So let's go ahead and listen to
7:14
Speaker 1: Jane's question and then we'll jump into talking about what
7:17
Speaker 1: xeno transplantation is and how it works.
7:20
Speaker 3: Hi, Daniel and Kelly, this is Jane from Redcar, England.
7:24
Speaker 3: I've got a question which is more philosophical and scientific.
7:28
Speaker 3: There's been a lot of news about transgenic pigs created
7:31
Speaker 3: for transplantation. The idea is that their genome becomes more
7:35
Speaker 3: and more human so that they trigger less rejection. My
7:39
Speaker 3: question is, at what point do we need to start
7:43
Speaker 3: treating them as human and therefore with more respect. Not
7:47
Speaker 3: that we always treat other humans with the respect, but
7:50
Speaker 3: that's a different question. I'm excited by the opportunities this offers,
7:55
Speaker 3: but I'm also conflicted by the ethics. I look forward
7:58
Speaker 3: to hearing your take on this. Thank you, for a
8:01
Speaker 3: great show.
8:02
Speaker 1: All right, So Jane and I had a pretty interesting
8:04
Speaker 1: conversation over email about the you know, the ethics of
8:08
Speaker 1: this question. And I guess I'm a little bit of
8:11
Speaker 1: a negative Nelly. I'm not sure anything is going to
8:14
Speaker 1: put a dent in the way we treat animals that
8:17
Speaker 1: we also eat. But it made me want to do
8:20
Speaker 1: a whole episode on zeno transplantation because there has in
8:24
Speaker 1: the news recently been some pretty exciting updates in this field,
8:28
Speaker 1: and so I thought this would be a great chance
8:30
Speaker 1: to sort of catch up on that research.
8:32
Speaker 2: All right, so let's get started. Why do we even
8:34
Speaker 2: consider taking organs from pigs? I mean, obviously I would
8:38
Speaker 2: prefer human organ if I'm going to receive a transplant.
8:41
Speaker 2: Why do we consider other species?
8:43
Speaker 1: Well, there's just not enough of the human organs. So
8:47
Speaker 1: last year there were forty eight thousand transplants that happened
8:51
Speaker 1: in the United States, and so that's a lot, and
8:53
Speaker 1: that's fantastic, but it's less than fifty percent of the
8:57
Speaker 1: number of people who are on the list and need organs.
9:00
Speaker 1: So there's this massive difference between the number of people
9:03
Speaker 1: who get organs and the number of people who need them,
9:06
Speaker 1: and there's probably even more people who need them, but
9:09
Speaker 1: they're not on the weight list for a variety of reasons.
9:12
Speaker 1: It could be that it just seems unlikely that an
9:15
Speaker 1: organ that's the right match will come through for them
9:17
Speaker 1: on time, and so some people who would like new organs,
9:21
Speaker 1: you know, don't even put themselves on the weight list.
9:23
Speaker 1: So if we had a lot of organs, then there's
9:26
Speaker 1: a lot more people who would be in a good position.
9:28
Speaker 1: So where do we get the organs we have now?
9:31
Speaker 1: So this is something we've already sort of hinted at
9:33
Speaker 1: in this episode. When somebody passes away, for example, in
9:37
Speaker 1: a car accident, they're organs. The organs that you know
9:41
Speaker 1: are still in good shape can be given to other
9:43
Speaker 1: people who need them if you can find people who
9:45
Speaker 1: are a good match. So being a good match. We
9:48
Speaker 1: have different blood types, you know, if you go in
9:50
Speaker 1: to donate blood, they'll tell you what your blood type is. Essentially,
9:53
Speaker 1: we've got stuff that stick out on our cells, and
9:56
Speaker 1: if your stuff that sticks out on your cells looks
9:59
Speaker 1: different the stuff that sticks out on someone else's cells,
10:02
Speaker 1: then your body's going to recognize that as foreign and
10:04
Speaker 1: the immune system is going to go after it and
10:06
Speaker 1: kill it. So the organ that you get needs to
10:09
Speaker 1: look like an organ that would have been in your
10:12
Speaker 1: body to begin with. Otherwise the immune system is going
10:14
Speaker 1: to go nuts.
10:15
Speaker 2: Fascinating, And then does having a good match guarantee that
10:18
Speaker 2: the immune system is going to be cool or do
10:20
Speaker 2: you still need to take immune suppressants your whole life.
10:24
Speaker 1: You still need to take immunosupressants your whole life, which
10:26
Speaker 1: means you might be at greater risk of things like infections. Also,
10:31
Speaker 1: I think immunosuppressants make it slightly more likely that you
10:34
Speaker 1: could get cancer later in your life. But you know,
10:37
Speaker 1: if the surgery goes well, then your life will be extended,
10:39
Speaker 1: even though you'll have these problems to deal with.
10:42
Speaker 2: I remember, in our conversation about type one diabetes, Katrina
10:45
Speaker 2: was saying that you could cure type one diabetes by
10:47
Speaker 2: getting a pancreaus donation. But then you have immunosuppression, and
10:51
Speaker 2: that's pretty hard for somebody who's very young.
10:54
Speaker 1: Yeah, and even today sometimes we don't get that immunosuppression
10:57
Speaker 1: level completely correct. And so if you give people too
11:00
Speaker 1: many immunosuppressive drugs, then you know, people can get horrible
11:04
Speaker 1: diseases and then they can pass away from those diseases.
11:07
Speaker 1: It's a very delicate balance, and so a fair bit
11:10
Speaker 1: of your life from then on out goes towards trying
11:12
Speaker 1: to like modulate your immune systems so that you don't
11:14
Speaker 1: get sick, but you don't reject this organ.
11:17
Speaker 2: And what organs are mostly the ones being donated? Is
11:20
Speaker 2: it mostly like kidneys and livers?
11:21
Speaker 1: Yeah, mostly kidneys, and then after that livers, and sometimes
11:25
Speaker 1: you'll get lungs or hearts. I think kidneys are so
11:29
Speaker 1: common because if you have a problem with your kidney,
11:32
Speaker 1: you can stay on dialysis. So dialysis is essentially a
11:35
Speaker 1: machine that cleans your blood, does the job that kidneys
11:38
Speaker 1: would have done, and so you can stay alive for
11:40
Speaker 1: years on this machine. It's not a great quality of life,
11:43
Speaker 1: but you can wait for years for an organ to
11:46
Speaker 1: come along, whereas it's harder to get machines that replace
11:49
Speaker 1: our heart or our lungs or our liver. You can
11:52
Speaker 1: do that, but it's not the kind of thing that
11:53
Speaker 1: you can do for like years at a time. And
11:55
Speaker 1: so kidneys are an easy ish organ to deal with
11:59
Speaker 1: or to wait for replacement. And another way that we
12:02
Speaker 1: get organs are through living donors, and so if you
12:05
Speaker 1: happen to have an identical twin who you get along with,
12:09
Speaker 1: and they're willing to give you one of their kidneys.
12:12
Speaker 1: If you two are a blood match, which you would
12:13
Speaker 1: be if you were identical twins, then they can donate
12:15
Speaker 1: one of their kidneys to you and they can still
12:18
Speaker 1: live with just one kidney, and then you get one
12:20
Speaker 1: of their kidneys. But say you don't have an identical
12:24
Speaker 1: twin and it turns out that your siblings and no
12:26
Speaker 1: one in your family is a good match, then for
12:28
Speaker 1: a while there you were kind of out of luck.
12:30
Speaker 1: But recently this system has been created called matching markets.
12:35
Speaker 1: So essentially, if I needed a kidney and Zach was like,
12:39
Speaker 1: I'll give you one of mine, and he's not that nice,
12:41
Speaker 1: I'm not sure he would, but no, I'm kidding, No,
12:43
Speaker 1: I'm kidding, he'd give me his kidney. But so if
12:45
Speaker 1: Zach was like, well, I'll give you my kidney, but
12:47
Speaker 1: it turned out we weren't a match, we could enter
12:49
Speaker 1: our names into a matching market and if somebody else
12:53
Speaker 1: had a you know, a sibling, a boyfriend, whatever, who
12:57
Speaker 1: was a match to me, And it turned out that
13:00
Speaker 1: Zach was a match to them, then we could create
13:03
Speaker 1: that loop and we could switch the kidney, so I
13:06
Speaker 1: would get you know, that boyfriend's kidney, Zach would give
13:08
Speaker 1: his kidney to you know, the other boyfriend, and then
13:12
Speaker 1: we would manage to make the loop that way. And
13:15
Speaker 1: you can get really complicated loops where people are swapping
13:19
Speaker 1: organs and you know, I think more than twenty of
13:22
Speaker 1: these pairs have gone through these loops. And so by
13:26
Speaker 1: having a bunch of people who are willing to donate,
13:28
Speaker 1: you can make a lot of matches in this system,
13:30
Speaker 1: and so some of the matches come from that, but
13:32
Speaker 1: those can be a little bit complicated because if everybody
13:35
Speaker 1: owes a kidney to somebody else, then you want to
13:38
Speaker 1: try to do those surgeries as much as possible at
13:41
Speaker 1: the exact same time, so that nobody wakes up in
13:43
Speaker 1: the morning and is like, never mind, I'm too nervous,
13:46
Speaker 1: I'm not going to do it, and then one person's
13:47
Speaker 1: gotten a kidney, and now somebody else is sort of
13:50
Speaker 1: left in the lurch.
13:51
Speaker 2: You want to like them all in beds in a row.
13:53
Speaker 2: You're just like, ask the kidney.
13:54
Speaker 1: Over to the left, right, Yeah, something like that, And
13:58
Speaker 1: so I think two percent of the time, you do
13:59
Speaker 1: have an instance where somebody will come in and you know,
14:02
Speaker 1: it's not necessarily that they like they've changed their mind
14:05
Speaker 1: or they got too scared to go through with it.
14:07
Speaker 1: Sometimes it's just like, hey, actually, it turns out that
14:10
Speaker 1: we discovered they have I don't know, some disease, and
14:12
Speaker 1: so they can no longer donate that organ. And so
14:15
Speaker 1: there's good reason for not being able to do it.
14:17
Speaker 1: But every once in a while you get a good
14:18
Speaker 1: Samaritan who doesn't necessarily know somebody who needs a kidney,
14:22
Speaker 1: but they're just willing to donate one, and then you
14:24
Speaker 1: can get this whole match set off and you can
14:28
Speaker 1: start doing a bunch of kidney transfers between people. So
14:31
Speaker 1: anyway there is a bunch of people who are alive
14:33
Speaker 1: and donate their kidneys, and because we only need one,
14:36
Speaker 1: you can do this. It happens less often with livers,
14:39
Speaker 1: so you can live with just part of a liver,
14:41
Speaker 1: so you could donate part of it. But this surgery
14:44
Speaker 1: is a little bit more high risk, and so it's
14:47
Speaker 1: asking a lot more than just asking someone to give
14:49
Speaker 1: you one of their kidneys.
14:50
Speaker 2: And what are the ethics around this because people have
14:53
Speaker 2: these very valuable resources which can save somebody else's life.
14:56
Speaker 2: But obviously you need their consent, but it feels like
14:59
Speaker 2: they could all be pressured into it. It reminds me
15:02
Speaker 2: of the questions people raise around end of life stuff.
15:04
Speaker 2: Or it's like, yeah, it's great if people get to
15:06
Speaker 2: decide when they exit, but do you want grandma to
15:09
Speaker 2: be pressured into the grave by her nephew who needs
15:12
Speaker 2: the inheritance? Right? Right? And so there's tricky issues.
15:16
Speaker 1: There, aren't there, Yeah, really tricky issues. And there was
15:19
Speaker 1: for a while, all right. So I'm pulling way back
15:22
Speaker 1: in my memory from when I was writing soonish, I
15:24
Speaker 1: think I'm going to get all of this right. But
15:26
Speaker 1: I ran used to allow legal selling of organs, and
15:31
Speaker 1: it did seem to be the case that the poor
15:33
Speaker 1: were getting exploited, and they were often not getting paid
15:36
Speaker 1: very much for their organs, and then when they had
15:39
Speaker 1: trouble of their own, for example, maybe they had a
15:41
Speaker 1: problem with their remaining kidney, they couldn't afford the care
15:45
Speaker 1: that they needed, oh gosh, And so that system was
15:48
Speaker 1: not working very well. There are folks who recommend, you know,
15:52
Speaker 1: in the US, for example, you had a system where
15:54
Speaker 1: if somebody is willing to donate their kidney, it doesn't
15:57
Speaker 1: go to a person in particular, Like some super rich
16:01
Speaker 1: person couldn't say I want Daniel's kidney in particular, but
16:05
Speaker 1: Daniel could say, you know, for a million dollars, which
16:09
Speaker 1: is about the cost of dialysis for a year. So
16:13
Speaker 1: like you can imagine a insurance company maybe saying, all right,
16:16
Speaker 1: we'll give Daniel a million dollars so that this other
16:20
Speaker 1: patient of ours doesn't have to be on dialysis for
16:22
Speaker 1: three years, and we promise that if Daniel ever has
16:26
Speaker 1: a problem with his remaining kidney, he goes to the
16:28
Speaker 1: top of the list and he always gets free medical
16:32
Speaker 1: care for anything related to kidney problems. But there's this
16:36
Speaker 1: concept of repugnance in economics, and there's some trades that
16:39
Speaker 1: people feel comfortable with and some trades that people don't
16:41
Speaker 1: feel comfortable with, and trading organs sort of falls into
16:45
Speaker 1: the category of repugnant. People just kind of feel uncomfortable
16:49
Speaker 1: about it. For the reason that you identified. There's so
16:51
Speaker 1: many ways to do it that feel ethically complicated, and
16:54
Speaker 1: you can absolutely imagine that people who are the most
16:57
Speaker 1: likely to donate their organs, or people who are in
16:59
Speaker 1: financial straits and wouldn't be doing it otherwise, but absolutely
17:03
Speaker 1: feel like they need to do it to like, you know,
17:05
Speaker 1: pay their bills or something. So it gets complicated. But
17:08
Speaker 1: in the US you are not allowed to pay for organs.
17:11
Speaker 2: And do you think it happens anyway?
17:13
Speaker 1: Probably?
17:14
Speaker 2: I mean, it definitely happens in the dystopian science fiction
17:17
Speaker 2: that I read. I don't know if that means it
17:19
Speaker 2: happens in reality.
17:20
Speaker 1: Yeah. Well, you know, when I was reading the Space
17:21
Speaker 1: Settlement literature, they cited the expanse a lot as though
17:23
Speaker 1: that was actually happening. So if it's happening in dystopian
17:26
Speaker 1: science fiction, it's probably happening in real life.
17:29
Speaker 2: Well, since we're talking about science fiction, why can't we
17:32
Speaker 2: avoid this problem by figuring out how to grow organs ourselves?
17:35
Speaker 2: Like why do you need a whole human being just
17:37
Speaker 2: to create a human kidney. Why can't you just grow
17:40
Speaker 2: a kidney in a vat somewhere or like three D
17:42
Speaker 2: print a kidney or something like that.
17:44
Speaker 1: Yeah, so people are working on that. So the idea
17:46
Speaker 1: here is that you extract some cells from a person,
17:49
Speaker 1: you grow up their own cells, and then you like
17:52
Speaker 1: extrude them through a three D printer or do some
17:54
Speaker 1: other sort of complicated technique to create an organ out
17:57
Speaker 1: of their own cells. If this worked, you wouldn't need
18:00
Speaker 1: to be on immunosuppressive drugs. It would be amazing. But
18:03
Speaker 1: the problem is that our organs are exquisitely complicated, and
18:08
Speaker 1: even just things like delivering nutrients and removing waste, which
18:12
Speaker 1: you know we usually do with our vasculature our blood vessels,
18:16
Speaker 1: is really hard to recreate with a three D printer,
18:19
Speaker 1: like on the microscale, And so right now we're good
18:22
Speaker 1: at printing what are called organoids. They're like slabs of
18:25
Speaker 1: organ and so that's good for like testing out drugs
18:28
Speaker 1: and stuff. So you know, if your liver drug kills
18:30
Speaker 1: your little liver slab, you probably don't move on to
18:33
Speaker 1: the stage where you're trying it out on humans. But
18:36
Speaker 1: at the moment, it's not good enough to replace any organs.
18:39
Speaker 1: People are working on that. There's some really amazing work
18:43
Speaker 1: to create like vasculature out of like sinered sugar, So
18:47
Speaker 1: you fuse the sugar so it looks like vasculature, and
18:50
Speaker 1: then you seed it with blood vessel cells and those
18:53
Speaker 1: blood vessel cells grow around the sugar and then you
18:56
Speaker 1: put hot water through there and you dissolve the sugar away,
18:59
Speaker 1: and your left with vasculature whoa, and then you can
19:02
Speaker 1: put like liver cells around that.
19:04
Speaker 2: But all this talk of sugar, I'm just imagining like
19:06
Speaker 2: a cotton candy kidney or something.
19:09
Speaker 1: Yum. Oh, we got to we kind of got to cannibalism.
19:12
Speaker 1: I think you know.
19:15
Speaker 2: I tricked you into it.
19:16
Speaker 1: That's all right, that's right, Okay, So let's take a break,
19:19
Speaker 1: and then when we come back from the break, we'll
19:20
Speaker 1: talk about xeno transplantation, where you're forgetting about human organs
19:25
Speaker 1: altogether and instead we're just seeing if we can use
19:28
Speaker 1: organs from other animals. Okay, So, xeno transplantation, which is
19:52
Speaker 1: when you use organs from other animals in human bodies,
19:56
Speaker 1: has a pretty long history. We're going to stick with
19:59
Speaker 1: the history in the twentieth century. And you know, I
20:02
Speaker 1: should say that the history of this field is august
20:05
Speaker 1: and amazing, and the scientific work that's been done is fantastic.
20:08
Speaker 1: But I am going to start with the guy who
20:11
Speaker 1: was implanting testicles for anti aging, because I'm me and
20:16
Speaker 1: that's obviously where I had to start.
20:18
Speaker 2: But you're saying these experiments are maybe not representative of
20:21
Speaker 2: the scientific calimber of the whole field.
20:23
Speaker 1: I mean, it was pretty representative of science in the
20:26
Speaker 1: nineteen twenties. But you know, I don't want you to
20:28
Speaker 1: judge the whole field based on this story I'm about
20:30
Speaker 1: to tell, all right, tell us the story, all right.
20:32
Speaker 1: So Sergey Varnoff in the nineteen twenties and nineteen thirties,
20:35
Speaker 1: he was doing these experiments. He was a Russian emigray
20:38
Speaker 1: living in Paris, and he was implanting slices of chimp
20:43
Speaker 1: and baboon testicles into human males as an anti aging thing.
20:49
Speaker 2: Where into human males, like.
20:51
Speaker 1: Near the testicles, it would be like you'd get a
20:53
Speaker 1: little slice of chimp nard behind yours and sorry everybody.
21:00
Speaker 1: And there were some people who reported afterwards that they
21:03
Speaker 1: felt more virile and alive, and I suspect that that
21:07
Speaker 1: was entirely placebo effect. And they're lucky they didn't get
21:12
Speaker 1: massive infections in their testicles from these foreign cells being
21:16
Speaker 1: placed in that so delicate of an area.
21:19
Speaker 2: But were they like wired up with blood vessels and
21:21
Speaker 2: stuff so they could live or it was just like
21:23
Speaker 2: a chunk of dead.
21:24
Speaker 1: Flesh yeah, it was a chunk of dead flesh that
21:26
Speaker 1: was definitely going to die, super gross. It was not
21:29
Speaker 1: going to be like producing more testosterone or anything like
21:31
Speaker 1: that the way they had done it. And if you
21:33
Speaker 1: went to the US, there was like a charlatan who
21:36
Speaker 1: I believe he was pretending to be a medical doctor,
21:38
Speaker 1: and he was giving folks testicles from like super viral goats.
21:42
Speaker 2: This is like zombie goat testicles. This is not good.
21:45
Speaker 2: I don't understand why anybody would say yes to this.
21:48
Speaker 1: So, I mean, I don't feel like this is a
21:49
Speaker 1: metaphor we need to double down on. But I would say,
21:53
Speaker 1: these goat testicles aren't like coming back to life inside
21:56
Speaker 1: of this human, you know. I think they're just like
21:59
Speaker 1: they're they're in there and they decay away and if
22:03
Speaker 1: you're lucky, it won't cause a massive infection, right, and
22:05
Speaker 1: that's the best case scenario. All right. So then this
22:08
Speaker 1: got dropped for a while because this wasn't really working out.
22:11
Speaker 1: In the nineteen sixties, we try transplanting chimpanzees and bonobo
22:15
Speaker 1: kidneys into humans directly. One woman lived with the chimpanzee
22:19
Speaker 1: kidney for about nine months wow, which was a pretty
22:22
Speaker 1: long time to have your life extended. But in general
22:24
Speaker 1: these surgeries don't work because human immune systems reject these
22:29
Speaker 1: foreign organs, and so some people the rejection takes a
22:31
Speaker 1: little longer, others it happens more quickly. But it becomes
22:35
Speaker 1: clear that just straight up implantation of kidney and banobo
22:40
Speaker 1: organs into a human is not going to solve our problems.
22:43
Speaker 2: Well, we heard earlier that not even all human kidneys work. Right,
22:46
Speaker 2: if I need a transplant, I can't just get a
22:47
Speaker 2: random human. I need a specific human that's probably not
22:50
Speaker 2: going to trigger my immune system. So that makes it
22:54
Speaker 2: sound very unlikely that any chimp would work. But when
22:56
Speaker 2: they do this, do they like choose a chimp that's
22:59
Speaker 2: less likely to trigger an immune system, and do you
23:01
Speaker 2: have like a chimp match. You know, some chimps were
23:04
Speaker 2: better for donating kidneys.
23:05
Speaker 1: So at this point we didn't really understand blood types,
23:08
Speaker 1: and so we were just kind of hoping that chimpanzees
23:11
Speaker 1: were closely related enough to humans that this would work.
23:13
Speaker 1: It was a little bit after this where we started
23:16
Speaker 1: to figure out that oh, hey, even within species, like
23:19
Speaker 1: with dogs, if you transfer organs from one dog to another,
23:22
Speaker 1: sometimes it works. Sometimes it doesn't, and it took a
23:25
Speaker 1: while for us to figure out that that all depended
23:28
Speaker 1: on blood types. And so once we figured that out,
23:31
Speaker 1: I think it was in dogs. I read this great
23:33
Speaker 1: book called Spare about the history of organ transplantation. They
23:36
Speaker 1: talk about blood type and how we figured that stuff
23:39
Speaker 1: out in more detail if anybody's interested. But once we
23:42
Speaker 1: figured it out in humans, we realized, Okay, so this
23:44
Speaker 1: isn't going to work with chimpanzees. They're two distantly related,
23:47
Speaker 1: same with bonobos. Even with humans, you need to figure
23:50
Speaker 1: out blood types. But I told you at the start
23:52
Speaker 1: of the episode that we've made some progress in zeno transplantation,
23:56
Speaker 1: and the way that we've done that is by genetically
23:59
Speaker 1: engineering pigs so that they look more human.
24:03
Speaker 2: That's really interesting, Kelly. I wouldn't choose pigs necessarily. Tell me,
24:06
Speaker 2: why would we choose pigs to be our organ farmers.
24:09
Speaker 1: That's such a great question, Daniel. So chimpanzees and bonobos
24:15
Speaker 1: are more closely related to us, so they seem like
24:17
Speaker 1: a more obvious choice. But they've got a couple problems.
24:20
Speaker 1: So first of all, they're smaller than us, so their
24:22
Speaker 1: organs are smaller. And that was a problem in some
24:25
Speaker 1: of the surgeries that were tried earlier. The chimp kidneys
24:28
Speaker 1: were too small, chimp hearts too small. But additionally, people
24:33
Speaker 1: feel much more uncomfortable about euthanizing chimpanzees and bonobos because
24:38
Speaker 1: they're more closely related to us, So there was this
24:40
Speaker 1: idea that they would be more of an ethical backlash.
24:43
Speaker 1: But perhaps even more than that, chimpanzees and bonobos take
24:46
Speaker 1: a long time to reach sexual maturity, and then they
24:49
Speaker 1: only have a few babies at a time, so you'd
24:52
Speaker 1: have to scale up in a way that would be
24:54
Speaker 1: very difficult, and we've never really done before to have
24:57
Speaker 1: enough chimpanzees and bonobos to meet the knee.
25:00
Speaker 2: You're talking about chimped farming, right. You're saying that it's
25:03
Speaker 2: hard to get a big population. Yeah, wow, So you
25:05
Speaker 2: want something that grows quickly and has babies young so
25:08
Speaker 2: that you can get that exponential factor go it early.
25:12
Speaker 1: Yikes, right, and your face is telling me that you
25:15
Speaker 1: feel uncomfortable about this suggestion, which almost everybody else did.
25:19
Speaker 1: The final nail in the coffin is that those more
25:21
Speaker 1: closely related organisms are more likely to have diseases that
25:24
Speaker 1: could jump from them to us, making this a little
25:27
Speaker 1: bit scarier. So pigs are an organism that we already
25:31
Speaker 1: know how to grow in like sort of production level. Yeah,
25:36
Speaker 1: so they reach sexual maturity when they're young, they have
25:40
Speaker 1: lots of babies. We know how to keep them alive.
25:43
Speaker 1: We understand these organisms fairly well. We've got like their
25:47
Speaker 1: genome and their organs are like fairly similar in size
25:51
Speaker 1: to humans in a lot of ways, and so we've
25:54
Speaker 1: sort of settled on pigs as our best bet as
25:57
Speaker 1: starting material to tinker with to make organs to keep
26:00
Speaker 1: us alive.
26:01
Speaker 2: I don't know if that logic really holds. It's like,
26:04
Speaker 2: this is ethically dubious, so let's do it on a
26:07
Speaker 2: creature we're already mistreating ethically, right, Like we already treat
26:11
Speaker 2: pigs as if they're objects, and so therefore it's okay
26:14
Speaker 2: to treat them as objects, where it's not okay to
26:16
Speaker 2: treat chimps as objects because we don't do that already, yes,
26:20
Speaker 2: Or is it just about being closer to us? Is
26:22
Speaker 2: this another like speciesism thing? Like how much of humanity's
26:25
Speaker 2: rights do you get? Chimps get a little bit and
26:27
Speaker 2: pigs get almost none?
26:29
Speaker 1: Yes, I mean I think everything that you just said
26:31
Speaker 1: is uncomfortable but true. But you've told me in a
26:34
Speaker 1: previous episode that you have accepted that humans are just
26:37
Speaker 1: sort of like a level above the other animals and
26:39
Speaker 1: you are okay with eating them. And I feel like
26:43
Speaker 1: you're not consistently applying that philosophy right now.
26:46
Speaker 2: No, you're right, because consistently applying that philosophy means arbitrarily
26:51
Speaker 2: labeling humans as better. And the point you just made
26:55
Speaker 2: with chimps and bonobos is that there's a spectrum, right
26:58
Speaker 2: and like where do you draw the line? And now
27:00
Speaker 2: you have to have a fuzzy delineation of how much
27:03
Speaker 2: of this like special glowy rights that you put on
27:05
Speaker 2: people and how much do you not? And what if
27:08
Speaker 2: somebody had a half pig half human hybrid, what would
27:10
Speaker 2: they get? You know? And so yes, I am not
27:13
Speaker 2: prepared to answer these questions. My philosophical framework here is
27:16
Speaker 2: quite naive.
27:18
Speaker 1: Yeah, I do think a lot of this stuff is complicated.
27:21
Speaker 1: Like you know, if you go to some countries they
27:24
Speaker 1: eat guinea pigs and it's like nothing. But if you
27:27
Speaker 1: told a child in the US that you were gonna
27:29
Speaker 1: have guinea pig for dinner, they'd probably be very upset
27:32
Speaker 1: because we think of those animals as pets and not food.
27:35
Speaker 1: And so I think a lot of it depends on
27:37
Speaker 1: what you grew up feeling comfortable with. Like I know
27:40
Speaker 1: some people who won't eat bunnies because they're too cute,
27:43
Speaker 1: but they will eat pigs because they think they're not cute.
27:46
Speaker 1: But I think pigs are cute, and I think anyway,
27:48
Speaker 1: humans have very complicated feelings. But pigs are an organism
27:51
Speaker 1: that I think a lot of people have decided is
27:54
Speaker 1: okay to eat, although I know that there are you know,
27:57
Speaker 1: cultures and religions for which that's not the case.
27:59
Speaker 2: And at least we're not committing any more crimes. We're
28:01
Speaker 2: committing more crimes on each individual, but we're not committing
28:04
Speaker 2: crimes on more individuals. We're already raising these folks for meat,
28:08
Speaker 2: and so might as well harvest their organs.
28:10
Speaker 1: Yeah, it's not that easy actually, So in the US
28:15
Speaker 1: we're very uncomfortable with eating genetically modified foods, and in
28:18
Speaker 1: the European Union, I think it may even be completely prohibited.
28:23
Speaker 1: And so I don't actually know if these pigs, after
28:26
Speaker 1: having their organs harvested, would be sent out to become bacon.
28:30
Speaker 1: For example, I will say that if the companies that
28:34
Speaker 1: made these pigs said, you know, we're going to sell
28:37
Speaker 1: pork from these animals that we used their organs for transplants,
28:41
Speaker 1: and it's safe we eat it ourselves, then that would
28:44
Speaker 1: be the pork that I would buy. But I don't
28:46
Speaker 1: actually know that that's how it would play out, all right, So.
28:48
Speaker 2: Then the key concept is that these aren't just normal
28:51
Speaker 2: farm pigs. These are pigs have been genetically engineered to
28:54
Speaker 2: make fair organs better for transplanting into humans. How do
28:58
Speaker 2: you do that? Do you just like randomly breed pigs
29:00
Speaker 2: or can we actually go in and tinker with the DNA?
29:03
Speaker 1: Yeah, so you're gonna have to tinker with the DNA
29:05
Speaker 1: because if you don't tinker with the DNA, you're always
29:07
Speaker 1: going to have this immune system problem. And so recently
29:10
Speaker 1: we got this major advance in tinkering with DNA. I'm
29:13
Speaker 1: sure just about everybody has heard of this. This is
29:15
Speaker 1: the CRISPER CAST nine system. So CRISPER stands for clustered
29:19
Speaker 1: regularly interspaced short palindromic repeats. I'm sure everybody's going to
29:23
Speaker 1: remember that the women who found this Jennifer Dudna and
29:27
Speaker 1: Emmanuel Chapatier. What you do French stuff? Right? How do
29:32
Speaker 1: you say that name?
29:33
Speaker 2: That sounded pretty good.
29:34
Speaker 1: Yeah, okay, fantastic. You know I've I've been working on
29:36
Speaker 1: French and du a lingo.
29:37
Speaker 2: To your microbiome.
29:38
Speaker 1: Okay. So they got the Noball Prize for this work.
29:41
Speaker 1: And so essentially this system is snagged from bacteria's immune system.
29:47
Speaker 1: So the way this works is that bacteria remember, not
29:51
Speaker 1: the same way that we remember things, but they remember
29:53
Speaker 1: a virus that has infected them by essentially, when they
29:57
Speaker 1: find that virus, they grab a piece of the virus's
30:00
Speaker 1: genetic material and they stick it into their own genome.
30:04
Speaker 1: And now whenever that viral sequence is found in their
30:07
Speaker 1: body again, Crisper goes and cuts it to break it up.
30:10
Speaker 2: So it's like a little bacterial immune system that like
30:12
Speaker 2: a library of viral codes that they've seen before that
30:15
Speaker 2: they're like.
30:15
Speaker 1: This is bad, kill it, right, So you essentially have
30:19
Speaker 1: a system that can recognize certain sequences of genetic code
30:23
Speaker 1: and then it goes in there and it cuts it.
30:25
Speaker 1: And so it's like targeted molecular scissors. And so we
30:28
Speaker 1: can use this. We can say Okay, here's a pig,
30:32
Speaker 1: and here is the code for a gene that we
30:34
Speaker 1: want to tinker with. And so you can tell Crisper like,
30:37
Speaker 1: go in there and cut it at the spots where
30:39
Speaker 1: we want you to cut it, and now you can
30:40
Speaker 1: deactivate a gene or when it cuts a gene. The
30:44
Speaker 1: way the DNA responds is it repairs itself by sort
30:48
Speaker 1: of joining the two ends back together after you've made
30:50
Speaker 1: the cut. But you can before it joins itself back
30:53
Speaker 1: together sort of slip in a new gene or some
30:55
Speaker 1: new genetic code. And so in that way you can
30:58
Speaker 1: both remove things or add things in specific locations that
31:02
Speaker 1: you want.
31:03
Speaker 2: Man, biological engineering is incredible. I can't believe this ever
31:06
Speaker 2: works because it's not like I imagine you'd need like
31:09
Speaker 2: tiny little tweezers and you're like moving it into place
31:12
Speaker 2: just right. But you can't do that right. You just
31:14
Speaker 2: have like a test tube with solution and you jiggle
31:16
Speaker 2: it and you hope everything lines up. It's crazy.
31:19
Speaker 1: It's so crazy. I cannot believe that it works, but
31:21
Speaker 1: it does. It's absolutely amazing. But so the next step
31:25
Speaker 1: from there I found sort of confusing, and I was
31:28
Speaker 1: reading the scientific papers I wasn't following, So I wrote
31:31
Speaker 1: e Genesis, which is a company that makes genetically modified
31:36
Speaker 1: pig organs in addition to making a bunch of other stuff.
31:38
Speaker 2: This is non science fiction. They exist in our world.
31:40
Speaker 1: E Genesis exists in our world. That's right.
31:42
Speaker 3: Wow.
31:43
Speaker 1: And I wrote them. I wrote for you know, their
31:45
Speaker 1: media contacts or whatever. And I was like, I don't
31:48
Speaker 1: speak molecular biology. I can't figure out exactly what was
31:51
Speaker 1: done here. Can you connect me with someone who can
31:53
Speaker 1: explain it? And so they connected me to Wenning Chin,
31:57
Speaker 1: who was the senior author on the Nature paper described
32:00
Speaker 1: how they made these genetically modified pigs amazing. She was
32:03
Speaker 1: so fantastic to talk to and so excited about this research.
32:07
Speaker 1: So she told me that there's three different classes of
32:11
Speaker 1: genetic changes that they made.
32:13
Speaker 2: So first, wait, hold on, did you talk to her
32:15
Speaker 2: and see a video or just over the phone over zoom?
32:18
Speaker 2: And did you see her only like you know, chest
32:21
Speaker 2: up or full body chest up? Okay, So she could
32:24
Speaker 2: have had like you know, pig legs under the table
32:26
Speaker 2: and you wouldn't even know.
32:27
Speaker 1: I had no idea where you were going with this.
32:31
Speaker 2: I mean, you're talking to somebody at a company who's
32:33
Speaker 2: like doing cutting edge like human animal weirdness. So like,
32:37
Speaker 2: I mean, you're not curious.
32:39
Speaker 1: I had no reason to believe that she was anything
32:42
Speaker 1: other than a you know, woman with no animal parts,
32:48
Speaker 1: and she was wonderful. So all right, okay, they had
32:52
Speaker 1: made three different classes of edits. The first thing they
32:54
Speaker 1: did was they removed all the pervs.
32:56
Speaker 2: The what's pervs.
32:58
Speaker 1: The pervs. Pervs are poor sign anddogenous retroviruses. So the
33:04
Speaker 1: pig genome has some viruses in it, and most of
33:08
Speaker 1: the time those viruses are either helpful. For example, they
33:11
Speaker 1: help with things like placenta formation, and we're going to
33:14
Speaker 1: have cap Ohannan on the show in the future to
33:16
Speaker 1: talk about how that works. But they also have some
33:19
Speaker 1: other viruses that are able to start replicating themselves at
33:24
Speaker 1: like sort of random times that we don't really understand
33:26
Speaker 1: how they choose when they want to start replicating themselves.
33:28
Speaker 1: And we've put these viral particles in plates with human
33:33
Speaker 1: cells and it looks like they can infect those human cells.
33:36
Speaker 2: Yeah, so you.
33:37
Speaker 1: Really don't want to get a pig organ and then
33:40
Speaker 1: discover that you are filled with pervs and that you
33:43
Speaker 1: are going to die from those viruses.
33:44
Speaker 2: Nobody wants a purview organ for sure.
33:46
Speaker 1: No, no, absolutely not. No. There's so much material we
33:50
Speaker 1: could work with here, but anyway, we won't get to
33:53
Speaker 1: too gross. And so they cut out the poor sign
33:57
Speaker 1: anddogenous retroviruses to make it so that wouldn't be a problem.
34:01
Speaker 1: They had to be pretty clever about how they did
34:03
Speaker 1: the cutting, but they made it so that they feel
34:05
Speaker 1: like this is no longer a risk to people who
34:07
Speaker 1: get these organs. Then the next thing they had to
34:11
Speaker 1: do was remove stuff on the pig cells that our
34:16
Speaker 1: immune system could use to say, hey, that doesn't belong
34:19
Speaker 1: to me. So pig cells have some sugars on them,
34:22
Speaker 1: and that's because pigs and humans, you know, diverge something
34:26
Speaker 1: like eighty million years ago. We've gone on very separate paths,
34:28
Speaker 1: and so our cells look different. And so what they
34:31
Speaker 1: did was they went in and they removed these sugars
34:34
Speaker 1: from the cells. They essentially depigged these cells so that
34:38
Speaker 1: our immune system would be less likely to see it
34:40
Speaker 1: and be like, you don't belong here. And then the
34:43
Speaker 1: next set of changes that they made were essentially humanizing
34:46
Speaker 1: the pig cells. So now on the cells they added
34:50
Speaker 1: stuff to make them look more human again so that
34:53
Speaker 1: the immune system wouldn't respond. And so my question when
34:55
Speaker 1: she told me about that was, well, if we have
34:58
Speaker 1: to worry about our immune s system attacking cells with
35:02
Speaker 1: pig sugars, why don't you have to worry about the
35:05
Speaker 1: pig bodies attacking the human sugars when the pigs are
35:08
Speaker 1: growing these organs.
35:09
Speaker 2: That was my question too. Yeah, well, but it's such a.
35:11
Speaker 1: Cool answer, and I should have known the answer as
35:15
Speaker 1: someone who works sort of adjacent to immunology. But anyway,
35:18
Speaker 1: the answer is that if you are a fetus, the
35:21
Speaker 1: things that you're exposed to when you're a fetus are
35:25
Speaker 1: what your body expects. And so if you grow a
35:29
Speaker 1: pig from the starting point, like as an embryo, with
35:32
Speaker 1: these human sugars, it's immune system is like, oh sweet,
35:36
Speaker 1: these sugars belong here, and it doesn't attack them.
35:38
Speaker 2: There's no ingrained knowledge in the immune system is just
35:42
Speaker 2: trained on examples from when your fetus. It's like a
35:44
Speaker 2: blank neural network.
35:45
Speaker 1: That's right, that's amazing. Yeah, And so like if fraternal twins,
35:49
Speaker 1: so twins that aren't exactly identical, like if they share
35:52
Speaker 1: a blood supply, you're more likely to be able to
35:55
Speaker 1: do transplants between them because they had that stuff in
35:59
Speaker 1: the vironments, so their immune systems less likely to attack it. Incredible. Okay,
36:03
Speaker 1: so those are the three changes that were made. Let's
36:06
Speaker 1: take a break, and when we come back, I'll tell
36:08
Speaker 1: you about what they did once they had crispired all
36:11
Speaker 1: of that stuff into existence. All right. So what Egenesis
36:34
Speaker 1: did is they collected cells from the ears of one
36:37
Speaker 1: hundred different pigs. They ran their crisper magic to make
36:41
Speaker 1: all of those three different classes of changes we talked about.
36:43
Speaker 1: They ended up making sixty nine changes total. They took
36:47
Speaker 1: an egg from pigs, they pulled out the nucleus in
36:52
Speaker 1: the egg, and they put in the genetic material that
36:55
Speaker 1: they had just created so with all of the changes,
36:59
Speaker 1: and then they grew that up into a pig.
37:02
Speaker 2: All right. So because before we're talking about genetic information
37:05
Speaker 2: sort of in the abstract. It's just like you have
37:07
Speaker 2: DNA in a vial, but it's not part of a cell.
37:09
Speaker 2: You're just like writing the code. Now you got to
37:11
Speaker 2: load that code into the hardware, so like the whole
37:14
Speaker 2: pig cell runs it.
37:15
Speaker 1: Yes, cool, And so they did that, and so now
37:18
Speaker 1: they have pigs that are adults and are growing these organs,
37:24
Speaker 1: and they have all the genetic changes that they put
37:27
Speaker 1: in there. And now when these pigs have babies, they
37:29
Speaker 1: will also have these genetic changes. So now you have
37:32
Speaker 1: lines of pigs that are making organs that should be
37:36
Speaker 1: able to go into humans.
37:38
Speaker 2: All right, So the first pig is an adult as
37:40
Speaker 2: the normal like piggy pervy organs, but you've put cells
37:44
Speaker 2: into it that have the edited DNA, and its children
37:49
Speaker 2: will have that edited DNA and they will grow up
37:51
Speaker 2: and generate the organs without the pervy bits. Is that right?
37:54
Speaker 3: Yeah?
37:54
Speaker 1: Yeah, So you could take a cell from that pig's ear,
37:57
Speaker 1: use Crisper cast nine to make a bunch of edit
38:00
Speaker 1: it's inside of that cell. Then take the nucleus out
38:03
Speaker 1: of that cell and put it in an egg from
38:05
Speaker 1: any pig really could be the same one that you
38:07
Speaker 1: took the ear stuff from. Oh, and then you use
38:10
Speaker 1: that egg to grow up new pigs.
38:12
Speaker 2: All right, wow, and so does it work? Do we
38:15
Speaker 2: have baby pigs growing human kidneys or or human is kidneys.
38:19
Speaker 1: Well, so the way that you test this stuff, so
38:22
Speaker 1: first you tend to try these organs out in like
38:25
Speaker 1: macaques or baboons, so you try them out in closely
38:29
Speaker 1: related primates and if it works okay in them, then
38:32
Speaker 1: you can say, all right, maybe we're ready to jump
38:34
Speaker 1: to humans. Sometimes you have an additional step in between,
38:38
Speaker 1: where you have a human who has had an accident
38:41
Speaker 1: and they've experienced brain death, but their organs are still working,
38:45
Speaker 1: and so then you put them on life support and
38:46
Speaker 1: you can put a genetically modified organ in them and
38:49
Speaker 1: see how their body responds. And so that's a way
38:52
Speaker 1: to see.
38:52
Speaker 2: You treat them as like a science experiment. Wow.
38:55
Speaker 1: Yeah, that's a not so nice way of putting it.
38:57
Speaker 1: I would say, you know, if I were in that
38:59
Speaker 1: sea situation and someone has to decide, does Kelly's body
39:04
Speaker 1: get used to try to like figure out this life
39:07
Speaker 1: saving technique and that's her last contribution to the world, Like,
39:10
Speaker 1: I would hope that somebody would say yes, because that
39:12
Speaker 1: I mean, that feels like it sucks that I died,
39:15
Speaker 1: but it would be amazing if I could help build
39:18
Speaker 1: the argument that was needed so that we could start
39:21
Speaker 1: using this amazing life saving technique in other people.
39:24
Speaker 2: And so so yes basically.
39:26
Speaker 1: So yes, yes, but you know, families get asked ahead
39:29
Speaker 1: of time. You know, it's all of this stuff fascinating.
39:31
Speaker 1: It has complicated ethical approvals that are needed ahead of time.
39:34
Speaker 1: But so E Genesis did get permission from the Food
39:38
Speaker 1: and Drug Administration to try these organs out. I believe
39:41
Speaker 1: that they're still getting tried out under what's called compassionate use.
39:44
Speaker 1: So it's getting tried out on patients who I believe
39:47
Speaker 1: are not able to get on the wait list for
39:49
Speaker 1: one reason or another. Like you know, for example, to
39:51
Speaker 1: have a blood type that is pretty rare, it's hard
39:54
Speaker 1: to find someone who's compatible. The probability that they will
39:57
Speaker 1: be on the wait list for longer than and they're
40:00
Speaker 1: likely to survive is high. And so we're trying it
40:04
Speaker 1: out on these folks, yeah, because it's a good option
40:06
Speaker 1: for them given the options they have. And so these
40:09
Speaker 1: folks tend to be fifty five to seventy years old
40:12
Speaker 1: and they're unlikely to get an organ in the next
40:15
Speaker 1: five years. So two of these surgeries have been done,
40:17
Speaker 1: and so far both of the people have survived. I
40:21
Speaker 1: think these surgeries were done in like February or March,
40:24
Speaker 1: and it's June now, and as far as I could
40:27
Speaker 1: tell searching through Google, the folks who received these organs
40:31
Speaker 1: are still alive and still doing well, which is so amazing.
40:35
Speaker 1: And then there's another company called United Therapeutics, and they
40:39
Speaker 1: also have used Crisper to modify pig organs. They only
40:42
Speaker 1: did ten edits. It sounds like maybe they're keeping their
40:45
Speaker 1: fingers crossed that those retroviruses aren't a problem. I don't
40:48
Speaker 1: think they did as many edits to those, but this
40:51
Speaker 1: is all sort of information that isn't made public. Exactly
40:54
Speaker 1: what edits you make probably, so anyway, they've also done
40:57
Speaker 1: some transplant experiments using their organs. One of the patients
41:01
Speaker 1: who had one of these genetically modified organs had it
41:05
Speaker 1: for four months and then her body started to reject
41:07
Speaker 1: it for unknown reasons and it had to be removed.
41:10
Speaker 1: So it's possible some more tinkering is going to need
41:12
Speaker 1: to get done with the pig organs, or we need
41:15
Speaker 1: to do a little bit more work figuring out the
41:17
Speaker 1: right amount of suppressive drugs. But you know, these organs
41:20
Speaker 1: are being trialed out, and if these initial trials go well,
41:23
Speaker 1: then the pool of people who could join trials to
41:27
Speaker 1: test these organs out will expand. And so that's where
41:31
Speaker 1: we are right now. We're kind of trying it out
41:33
Speaker 1: to see if we figured out all the changes we
41:34
Speaker 1: need to make.
41:35
Speaker 2: This feels like we're on the cusp of something really big.
41:37
Speaker 2: I mean, if this works, it could really change what
41:40
Speaker 2: it means to wait for an organ. How many people
41:43
Speaker 2: die waiting for organs. Yeah, it could really change the
41:46
Speaker 2: experience of being human and the experience of being pig unfortunately.
41:49
Speaker 1: Yeah, yeah, yeah, So these pigs need to be grown
41:52
Speaker 1: in facilities where they are absolutely not going to encounter
41:57
Speaker 1: additional viruses. So, for example, sometimes the flu can jump
42:01
Speaker 1: from birds to people. Sometimes it can jump from pigs
42:03
Speaker 1: to people. So you want to make sure that your
42:05
Speaker 1: pigs are not encountering any new flu strains. So they
42:07
Speaker 1: need to be in these like incredibly biosecure facilities. But yes,
42:12
Speaker 1: once you grow up enough of them and you expand
42:14
Speaker 1: the facilities, hopefully, you know, with a lot of procedures
42:19
Speaker 1: that are ethically you know, compassionate for the lives of
42:22
Speaker 1: the pigs, you could have organs that are ready at
42:25
Speaker 1: just about any time. So you know, somebody who has
42:28
Speaker 1: kidney issues wouldn't have to face down a few years
42:31
Speaker 1: of dialysis with the quality of their life is much lower.
42:34
Speaker 1: You know, they could discover they need a new kidney
42:36
Speaker 1: and they could, you know, have it a month later
42:38
Speaker 1: or something like that.
42:39
Speaker 2: Yeah, these kidneys are not tailored to an individual human, right,
42:42
Speaker 2: they're generically modified so that they're more acceptable to humans broadly.
42:47
Speaker 2: But we know the humans are different, right, and some
42:49
Speaker 2: humans reject or accept different kidneys. Is it possible that
42:53
Speaker 2: some kinds of people will be able to accept pigkinnys
42:55
Speaker 2: and others won't.
42:56
Speaker 1: I think yes. I think that is a live option.
42:59
Speaker 1: So the the woman who had the United Therapeutics kidney
43:03
Speaker 1: who eventually rejected it, I think we don't understand why
43:05
Speaker 1: she rejected it. It could be that there's some incompatibility
43:09
Speaker 1: issue that you know, might be specific to her. Maybe
43:12
Speaker 1: we will need to personalize these organs a bit more.
43:14
Speaker 1: And I'm sure the three D printing people are saying,
43:17
Speaker 1: if you print with your own cells, this will never
43:19
Speaker 1: be a problem, when you know that technology isn't here
43:22
Speaker 1: yet either. So yes, it could be that more tinkering
43:24
Speaker 1: needs to get done. It would have been beautiful if
43:27
Speaker 1: everyone who got these genetically modified pig organs accepted them
43:31
Speaker 1: with no problems right from the start, But that's that's
43:35
Speaker 1: not where we are right now, and.
43:36
Speaker 2: Our pig's the only place this is happening. Is there
43:38
Speaker 2: any other species that's in contention?
43:41
Speaker 1: Nope, just pigs. Wow, as far as I can tell.
43:43
Speaker 2: Yeah, So maybe society will get divided in the future
43:46
Speaker 2: into people who can accept pig organs and people who can't,
43:49
Speaker 2: the piggy people and the non piggy people.
43:50
Speaker 1: That's right, that's right, a little bit of levity and
43:52
Speaker 1: our otherwise sort of bummer of an episode. But so
43:55
Speaker 1: I've got a question you might not know the answer to.
43:58
Speaker 1: So there are some cultures that can't eat pork. So
44:01
Speaker 1: my husband is Jewish and he's a vegetarian too, so
44:04
Speaker 1: it's sort of a non starter. But do you think
44:06
Speaker 1: there'd be any rules about accepting organs?
44:09
Speaker 2: That is a great question and what I don't know
44:12
Speaker 2: the answer to. And one reason that it's a great
44:14
Speaker 2: question is that I'm sure the Rabbis will have a
44:16
Speaker 2: lot of fun arguing about it, because Rabbis have a
44:20
Speaker 2: lot of fun arguing about stuff like this, you know, like,
44:22
Speaker 2: can you turn on the light switch on Saturday? No?
44:25
Speaker 2: Can you hire someone to turn on the light switch?
44:27
Speaker 3: No?
44:28
Speaker 2: But can you pay them to do something else and
44:30
Speaker 2: then they turn on the light switch. Yes, so there's
44:32
Speaker 2: all these like creative ways to like find loopholes to
44:35
Speaker 2: satisfy all the requirements, and I think they get a
44:38
Speaker 2: lot of joy in arguing about it. So this seems
44:41
Speaker 2: like a really juicy question for them.
44:45
Speaker 1: That's right, that's right, And I have to admit, like
44:47
Speaker 1: I feel a bit uncomfortable. Okay, So since I moved
44:50
Speaker 1: on a farm, I have had a much harder time
44:53
Speaker 1: eating meat because I encounter the animals that I'm eating
44:57
Speaker 1: a lot more, and I have been very surprised by
45:00
Speaker 1: how dynamic their personalities are, and how good they are
45:05
Speaker 1: with their babies, and how.
45:07
Speaker 2: They obviously feel joy and pain.
45:09
Speaker 1: That's right, Yes, yes, Seeing like goats get zoomies and
45:12
Speaker 1: frolic around a field, You're like, ah, I really enjoy
45:16
Speaker 1: you in my euro And now I feel complicated about that.
45:21
Speaker 1: But you know, if my daughter needed an organ and
45:24
Speaker 1: it was between a pig and my daughter, I wouldn't
45:28
Speaker 1: have a hard time with that choice. And I guess
45:30
Speaker 1: same with me. So Jane at the start of this
45:33
Speaker 1: episode asked if we were to start treating pigs with
45:36
Speaker 1: more respect if they became a major source for our organs. Don't. Actually,
45:42
Speaker 1: I don't see that happening, to be honest, I think the.
45:44
Speaker 2: Opposite is true. No, I think the more useful they are,
45:47
Speaker 2: the more we convince ourselves that they're just things and
45:50
Speaker 2: not like people.
45:51
Speaker 1: Yeah. So for me, the more I encounter farm animals,
45:55
Speaker 1: the more I want to either not eat them or
45:58
Speaker 1: only eat animals that had really good lives, Like I
46:01
Speaker 1: feel more and more uncomfortable about factory farms. But I
46:04
Speaker 1: think that most of us are not seeing or engaging
46:08
Speaker 1: with these animals that we end up eating or you know,
46:11
Speaker 1: that are part of the various processes for products that
46:14
Speaker 1: we use in our lives, like leather or whatever. And
46:17
Speaker 1: so I don't see us treating animals nicer as long
46:21
Speaker 1: as we are not encountering them more and like needing
46:25
Speaker 1: to see what it looks like to get this done.
46:27
Speaker 1: I hope that we'll treat them ethically. It does seem
46:29
Speaker 1: like over time there have been more rules for treating
46:31
Speaker 1: animals ethically and trying to give them a nice life
46:35
Speaker 1: for as long as they've got it. But I, yeah,
46:38
Speaker 1: I don't think this is going to change things.
46:40
Speaker 2: Well, let's take a positive view if we have pigs
46:43
Speaker 2: that can grow organs for humans. It means more humans survive,
46:46
Speaker 2: and it means more jobs for philosophers to figure out
46:50
Speaker 2: whether or not we are bad people, and jobs for
46:52
Speaker 2: rabbis to answer these questions. So everybody wins except the pigs.
46:56
Speaker 2: I guess.
46:57
Speaker 1: Yeah. Okay, Well, so I'd like to end on a
46:59
Speaker 1: slightly high notes. So first of all, I don't know
47:04
Speaker 1: if this is a high note, but we already eat
47:05
Speaker 1: a lot of pigs, so this is apparently something where
47:08
Speaker 1: for the most part, already comfortable with. But let's focus
47:11
Speaker 1: for a second on how much amazing stuff we had
47:14
Speaker 1: to learn to get where we are today. You know,
47:16
Speaker 1: like we are harnessing bacteria's immune response to create organs
47:22
Speaker 1: that could save the lives of like over one hundred
47:25
Speaker 1: thousand people who are on the wait list right now.
47:28
Speaker 1: It is amazing to me that we have figured out
47:30
Speaker 1: how to get this far, like just the many giants
47:33
Speaker 1: whose shoulders we had to stand on to get to
47:35
Speaker 1: where we are today. And if this works, the suffering
47:38
Speaker 1: of many, many, many people could be alleviated, a lot
47:42
Speaker 1: more people could survive, and the people who are waiting
47:44
Speaker 1: for organs would have a much higher quality of life.
47:48
Speaker 1: I can't help but be inspired. Even though you know
47:50
Speaker 1: everything that has to do with humans seems like it's
47:53
Speaker 1: ethically complicated.
47:54
Speaker 2: It does. Yeah. On the other hand, I want to
47:57
Speaker 2: live and I want my kids to live.
48:00
Speaker 1: Yes, amen, And this might be a path towards making
48:02
Speaker 1: that happen for a lot of people. So I'm wishing
48:05
Speaker 1: them luck. And thank you to Wenningchin for chatting with
48:08
Speaker 1: me and for making me even more excited about this.
48:11
Speaker 1: Your enthusiasm was contagious.
48:13
Speaker 2: And thank you very much to Jane for sending us
48:15
Speaker 2: your question. And if you have a question about any
48:18
Speaker 2: kind of science you'd like to hear us breakdown, please
48:20
Speaker 2: write to us questions at Daniel and Kelly dot org.
48:23
Speaker 1: And let's close out by seeing what Jane thought about
48:26
Speaker 1: our episode.
48:28
Speaker 3: Hi, Daniel and Kelly, I'm so glad that my question
48:31
Speaker 3: spot such a super interesting discussion. Did you answer my
48:35
Speaker 3: question well, yes, but by giving me even more ethical
48:40
Speaker 3: and philosophical conundrums to worry about. I can't comment on
48:44
Speaker 3: the rabbi's response, but as a Christian pastor, I hold
48:48
Speaker 3: a high view of humanity. I've been on the ukogn
48:51
Speaker 3: done a register for decades, and it really suddens me
48:55
Speaker 3: that there are not enough people willing to donate organs
48:59
Speaker 3: that they've finished with. I just worry that this will
49:02
Speaker 3: be one more exciting scientific breakthrough which is pushed through
49:07
Speaker 3: without serious ethical consideration. Thank you so much, Kelly for
49:13
Speaker 3: looking into this and sharing your wonder and enthusiasm with us.
49:17
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49:28
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49:30
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49:33
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49:36
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49:42
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