Speaker 1: I don't know if I told you about this show.
Speaker 1: It's called Raised by Wolves, but the second season of
Speaker 1: it just came out. It's Raised by Wolves too. Is
Speaker 1: it a movie, No, it's a series, okay, But it's
Speaker 1: basically living in three thy ninety nine. Okay, it's very different.
Speaker 1: And it really made me think, like, all the stuff
Speaker 1: that they're doing in that show, I'm like.
Speaker 2: Could this really be possible? What are they doing?
Speaker 1: They're using like droid robot things, but they look like
Speaker 1: people and they're able to do all these biological functions.
Speaker 1: And it reminded me of where we saw that pig
Speaker 1: heart transplant story a couple weeks ago.
Speaker 2: Do you remember? Yes, I do remember.
Speaker 3: And that kind of blew me away because I remember
Speaker 3: back in the day when they put the ear on
Speaker 3: the back of the rat and that.
Speaker 2: Was really big. Yes, that was in all the textbooks.
Speaker 3: Yes, But putting a pig heart into Homo sapien rte
Speaker 3: I was like, Man, we are really making leaps and
Speaker 3: bounds in our lifetime.
Speaker 1: I thought Raised by Wolves was three thousand ninety nine,
Speaker 1: but maybe it's twenty ninety nine.
Speaker 2: Maybe it's close with it, And I.
Speaker 3: Thought, welcome to dop Labs, a weekly podcast that mixes
Speaker 3: hardcore science, pop culture, and a healthy does of friendship.
Speaker 2: T T.
Speaker 1: I know I mentioned that I saw a pig heart
Speaker 1: transplant and that it feels like we are living in
Speaker 1: the year three thousand, that sci fi is upon us.
Speaker 2: But I feel like.
Speaker 1: I'm really blown away, Like how do we get here
Speaker 1: with all these new transplants and all of this technology.
Speaker 1: That wasn't the only one I saw. That's only one
Speaker 1: I can remember right now. I think we got to
Speaker 1: get to the bottom of it.
Speaker 2: Absolutely.
Speaker 1: This week we're talking about organ transplants specifically. We really
Speaker 1: want to know more about the process of getting approved
Speaker 1: for a transplant and how transplants actually work. Let's get
Speaker 1: into the recitation, So let's start with what we know.
Speaker 3: I feel like everything that I know about transplants is
Speaker 3: based off of what I've seen in movies in television.
Speaker 2: I think that's fine, is it.
Speaker 3: I think that's an okay starting point because then we
Speaker 3: can figure it out. Well now I feel empowered. I
Speaker 3: think one of the things that I think I know
Speaker 3: is that getting a transplant is not as easy as
Speaker 3: saying that I need this new organ. There is a
Speaker 3: process you have to see a number of doctors and
Speaker 3: then be put on a list.
Speaker 2: I think considering that list.
Speaker 1: Sometimes getting a transplant is easy, though some people get
Speaker 1: it from family members. But some people can't match with
Speaker 1: their family members. So I don't know a lot about
Speaker 1: the matching process. I know sometimes it's easy, or you know,
Speaker 1: if you have family members who match with you. But
Speaker 1: I got to save this for the next section because
Speaker 1: I don't know how you match.
Speaker 3: One of the things that I know is that not
Speaker 3: all transplants are created equal, and so getting a heart
Speaker 3: transplant and getting a kidney transplant are two very different beasts.
Speaker 1: The other thing I know is that there are a
Speaker 1: lot of rumors about transplants and the medical system. I
Speaker 1: think one of the most damaging things that has happened
Speaker 1: when it comes to organ transplants is the myth and
Speaker 1: rumor that went around that if you put that you
Speaker 1: were an organ donor on your driver's license, that the
Speaker 1: paramedics wouldn't try to save you.
Speaker 2: Do you remember this?
Speaker 3: Yes, I remember this, and I hate to say it frihim,
Speaker 3: but I was actually one of those people who believed
Speaker 3: it for a little while.
Speaker 1: That's all right, you were not alone but it is
Speaker 1: just that it's a myth, you know. I'm looking at
Speaker 1: this page from penn Medicine, so the University of Pennsylvania,
Speaker 1: the Perlman School of Medicine, and they're saying that you
Speaker 1: would have to be in the hospital on a ventilator
Speaker 1: and then pronounce dead in order to donate your organs.
Speaker 1: So it's not even that your organs are harvested if
Speaker 1: you're in a car accident, you know what I mean.
Speaker 1: That myth plays on people's fears of not having adequate care,
Speaker 1: but there are so many additional steps before you get
Speaker 1: to the donation of your organs. Another myth is that
Speaker 1: your family will be charged if you donate organs.
Speaker 3: I've never heard that one, but I can understand why
Speaker 3: people would think.
Speaker 2: That because it's an additional process right.
Speaker 3: Absolutely, And the medical care system it feels like a
Speaker 3: black box. Sometimes you go to the doctor or you
Speaker 3: have to rush to the hospital, and next thing you know,
Speaker 3: you have this huge bill and you don't know where
Speaker 3: these charges came from. You don't know how you're going
Speaker 3: to pay for it. So I can definitely understand where
Speaker 3: that confusion comes from.
Speaker 2: So what do we want to know though?
Speaker 3: What I want to know is how do they determine
Speaker 3: whether or not somebody is able to receive a transplant?
Speaker 3: Because I know, I mean, I don't know a lot
Speaker 3: about this stuff, but I see on TV that there
Speaker 3: are some folks who, you know, they get a transplant
Speaker 3: and their body rejects it or something like that. I know,
Speaker 3: what are the criteria that doctors are looking for to
Speaker 3: determine whether or not someone is able to get a transplant?
Speaker 2: Yes?
Speaker 1: And along those same lines, are those criteria the reason
Speaker 1: the waiting lists are so long? Why are there ninety
Speaker 1: thousand people waiting for a kidney but then a little
Speaker 1: over ten thousand four other organs? Is it related to
Speaker 1: the difficulty of replacing the organ, the surgery, the tools
Speaker 1: that are required, the costs. I'm just curious about, like
Speaker 1: why the lists are so long and were they always
Speaker 1: this long? Or is this like a backup from you know,
Speaker 1: delays in our medical system.
Speaker 2: Right, that's a good question.
Speaker 3: I think Another thing that we're both curious about is
Speaker 3: because we always are interested in it, and that is
Speaker 3: new technology. So what is the new technology and innovations
Speaker 3: in transplant sciences?
Speaker 2: Yeah, I'm sure they're not doing it the way they
Speaker 2: always used to. Now they can't be.
Speaker 1: Everything I know about how transplants work is pretty much
Speaker 1: based on John Q.
Speaker 2: You remember that movie.
Speaker 3: Yes, that's all I know, and I know I don't
Speaker 3: know if it was accurate, but that's what I feel like.
Speaker 2: I know Denzel was young in that movie. So young, Denzil.
Speaker 2: I'm expecting some changes.
Speaker 3: That age is a let's jump into the dissection.
Speaker 2: Yep, but its absolute. Our guest for today's lab is
Speaker 2: doctor Dave low Hi.
Speaker 4: My name is Dave low and I work for Thermo
Speaker 4: Fisher Scientific and I am head of research and development
Speaker 4: in our transplant diagnostics business.
Speaker 3: Thermo Fisher is a supplier of laboratory equipment and supplies.
Speaker 3: Me and Zekiah know them very well from all of
Speaker 3: our years in the lab. Their transplant diagnostics business focuses
Speaker 3: on developing and producing products with applications in both the
Speaker 3: clinical and the research side of organ transplants.
Speaker 1: Doctor Lowe's specialty is in histo compatibility, which is a
Speaker 1: word that isn't typically used, so we asked to to
Speaker 1: explain what it means.
Speaker 5: It's a hell of a mouthful, isn't it.
Speaker 4: If you've ever watched a medical drama on TV and
Speaker 4: somebody needs a transplant and they run around and they say, Okay,
Speaker 4: we've got a match. Then that's kind of the histo
Speaker 4: compatibility bit right there.
Speaker 3: Histo Compatibility means tissue matching, that the tissues of different
Speaker 3: individuals will be compatible. And by compatible, we mean that
Speaker 3: fusing tissues from two different people, so your donor and
Speaker 3: your recipient won't trigger a reaction from the immune system.
Speaker 1: I think it's important for people to remember when we
Speaker 1: talk about tissues. Tissues are just superstructures of cells. We
Speaker 1: can think about individual cells, but tissues are just a
Speaker 1: conglomerate of individual cells, and so at a cell to
Speaker 1: cell level, if those cells are not going to be compatible,
Speaker 1: then definitely those tissues aren't going to be compatible. And
Speaker 1: the thing that brings those tissues the nutrients that they
Speaker 1: need in the oxygen that they need to stay alive,
Speaker 1: that's the blood system, right. So you need your blood
Speaker 1: to match between your donor and your recipient. All of
Speaker 1: these things are physically interacting. You also need your tissues
Speaker 1: or the cells that make up the tissues to match
Speaker 1: between the donor and recipient too. And once you have
Speaker 1: all those things in your body, your immune system may
Speaker 1: recognize that donor tissue and in the case of a
Speaker 1: transfusion donor blood and say okay, I'm not going to
Speaker 1: attack it. Essentially, that's what histo compatibility is. They get
Speaker 1: together and they get along.
Speaker 3: Doctor Lowe's laboratory essentially develops and provides the tools that
Speaker 3: labs use to figure out how risky a transplant would
Speaker 3: be for each patient and how easy it would be
Speaker 3: to get them a transplant.
Speaker 1: So histel compatibility has multiple components, and one way that
Speaker 1: we already think about compatibility is in blood type, so
Speaker 1: ABO and then AB and O can be positive or negative.
Speaker 1: Blood type compatibility is certainly important for transplants, but there's
Speaker 1: a lot more to it with transplants. Compatibility or being
Speaker 1: a match is really framed in the context of the
Speaker 1: HLA system or human leukocyte antigens, and that's all about
Speaker 1: tissue matching.
Speaker 4: When we have people told about getting a match or
Speaker 4: not being a match, we're really talking about these specific
Speaker 4: antigens and what they are are proteins that are present
Speaker 4: on pretty much all of our cells and tissues, but
Speaker 4: they're highly diverse. Some of them are very common, and
Speaker 4: some of them are incredibly rare. So if a patient
Speaker 4: is unfortunate enough to have an incredibly rare tissue type,
Speaker 4: it's going to be much more difficult to get that
Speaker 4: patient donor.
Speaker 1: Another main factor in histo compatibility is antibodies, and we've
Speaker 1: talked a lot about antibodies before in various different contexts.
Speaker 1: Most recently we talked about it in Lab forty seven
Speaker 1: when we explore the immune system, and in that context
Speaker 1: we talked about antibodies really being these protectors to shield
Speaker 1: our bodies from invaders and foreign particles. That's generally a
Speaker 1: good thing, but in the context of transplantation and histo compatibility,
Speaker 1: antibodies can be a huge problem.
Speaker 3: Oh no, everything I thought I knew out the window.
Speaker 1: They're part of your immune system and they can trigger symptoms.
Speaker 1: We would generally categorize a sickness that's just your immune
Speaker 1: system responding, right, So if you have a lot of antibodies,
Speaker 1: they can recognize a lot of different things. That means
Speaker 1: they might recognize your donor tissue and give you a
Speaker 1: pretty bad reaction.
Speaker 3: So they're like, I, I this was not here before. Yes,
Speaker 3: that is not us attack.
Speaker 1: Yeah, you know what this reminds me of what in
Speaker 1: the matrix were like the mister Smith agents, like they're
Speaker 1: checking constantly for your signature.
Speaker 2: Yes, yes, this is so good.
Speaker 1: And so if you come back in like the same doors,
Speaker 1: like they're constantly looking for you, Like they were constantly
Speaker 1: looking for NEO in the matrix, that specific part of
Speaker 1: the matrix scared meat. That was terrifying, mister Smith, always
Speaker 1: in the same spots, just constantly looking for you.
Speaker 2: It was like a horror film.
Speaker 3: But that sounds exactly like what's happening in our immune system.
Speaker 2: Like those antibodies are.
Speaker 1: Just like right, But really it's great for your body
Speaker 1: if you have a FORID invader, a low level of virus,
Speaker 1: or a low level of bacteria, mister Smith, and mune
Speaker 1: system is constantly looking, constantly finding them, reading those green
Speaker 1: little characters scrolling down through your blood system. Okay, it's
Speaker 1: great to have antibodies looking for things on the surface
Speaker 1: of a bacterial cell or things on the surface of
Speaker 1: a virus. Not so great if those things appear on
Speaker 1: the surface of a donor tissue right right, they don't
Speaker 1: know those antigens, so they're like, yo, we got to
Speaker 1: get them out of here.
Speaker 3: And your antigens are defenseless essentially.
Speaker 1: Yeah, they're just things that they don't recognize. They say, hey,
Speaker 1: this is not part of the code.
Speaker 3: So the antigens, they can't even do the matrix thing
Speaker 3: that neo.
Speaker 2: Yeah, they can't do the Sierra.
Speaker 1: You know, Sierra was able to go back like that
Speaker 1: to do the neo and yeah, she's the only one.
Speaker 2: Those antigens are not doing that. Bruh. I remember trying
Speaker 2: to do that in high school. I was close. Really,
Speaker 2: I was.
Speaker 3: A different human being back then, not so different, just
Speaker 3: a different mobility.
Speaker 4: That's one thing that we find is on our transplant
Speaker 4: waiting lists, the more antibodies you have, the harder it
Speaker 4: is for you to get a transplant, and usually that
Speaker 4: means you will wait longer.
Speaker 3: So why would somebody have more antibodies than someone else.
Speaker 3: How do we even get the antibodies? We ask doctor
Speaker 3: Low how people who are on the waiting list for
Speaker 3: a transplant got so many antibodies that made them have
Speaker 3: to be on the waiting list for so long. Doctor
Speaker 3: Low says that there are three main ways.
Speaker 4: And the first is if you have a previous transplant,
Speaker 4: and quite often our patients when they have these previous transplants,
Speaker 4: they will form antibodies against some of those la and
Speaker 4: then the antibodies persist basically almost for the rest of
Speaker 4: that patient's life. So if you're then faced with a
Speaker 4: patient who has antibodies to HALA, all it does is
Speaker 4: it further reduces the number of potential donors for that patient.
Speaker 1: So if you have a previous transplant, remember that's cells
Speaker 1: that make up multiple different structures and that forms a tissue.
Speaker 1: That previous transplant will have antigens from the donor, and
Speaker 1: so your body, naturally, your immune system will make antibodies
Speaker 1: to that transplant. So now you have the antibodies that
Speaker 1: you already had that were part of your immune system,
Speaker 1: plus a new subset that have developed in response to
Speaker 1: your first transplant. So when it's time to get another transplant,
Speaker 1: you have an expanded set of antibodies, which could increase
Speaker 1: the likelihood that you would have a reaction.
Speaker 3: So is there a critical mass of antibodies where once
Speaker 3: it gets to that amount that your body automatically starts
Speaker 3: to react.
Speaker 1: I think that's a very good question. TT It is,
Speaker 1: I think two things. So it is volume of antibody
Speaker 1: and type of antibody. So you could have a variety
Speaker 1: of different types of antibodies, but if some of them
Speaker 1: are lower in number, it's less likely that you will
Speaker 1: have a strong immune reaction. Okay, does that make sense.
Speaker 3: Yeah, that makes sense. The next problem that some patients
Speaker 3: may run into that will cause them to have more antibodies,
Speaker 3: which makes it difficult for them to receive a transplant,
Speaker 3: is if they've had a blood transfusion.
Speaker 4: A lot of transplant patients get transfused quite a lot,
Speaker 4: and if there are cells in the transfused units that
Speaker 4: express HLA that is different, then there's a possibility in
Speaker 4: that way they can form antibodies as well.
Speaker 1: So a transfusion is having blood from a donor and
Speaker 1: putting it into a recipient. You know, and when we
Speaker 1: think about blood, you may just think, oh, red liquid,
Speaker 1: but it's not. It has cells in it, and those
Speaker 1: cells have antigens on their surface. So if I am
Speaker 1: a recipient and I initially didn't have antibodies that would
Speaker 1: react to those antigens that are on the surface of
Speaker 1: those cells. In my transfusion, there are components of my
Speaker 1: immune system that will recognize those antigens and begin to
Speaker 1: make antibodies. So now my antibody profile is expanded because
Speaker 1: my immune system has detected these other antigens, and now
Speaker 1: I have antibodies against those antigens plus whatever antibodies I
Speaker 1: initially had.
Speaker 3: Another way that folks can acquire antibodies that might keep
Speaker 3: them from being able to receive an organ transplant is
Speaker 3: a really tricky reason, and that is because your antibody
Speaker 3: profile can expand through giving birth.
Speaker 1: That sounds really wild, right, yes, but basically you have
Speaker 1: to think of when a baby is.
Speaker 2: Born magical times.
Speaker 1: Yeah, if a baby is born, the baby is not
Speaker 1: your clone, so it's gonna have half the genetic information
Speaker 1: from the other parent. And if that genetic signature causes
Speaker 1: the baby to express antigens that the birthing parent doesn't
Speaker 1: already have. As soon as that parents given birth, their skin,
Speaker 1: their womb, all of that is in contact with new antigens.
Speaker 1: We talk about that, right, And so then that immune
Speaker 1: system is like, hey, here's some foreign particles I've never seen.
Speaker 2: This wasn't with me.
Speaker 1: Before, and so at that moment, the birthing parents immune
Speaker 1: system makes antibodies to those antigens that are on the
Speaker 1: baby that came from the father that don't match with
Speaker 1: the birth and parents antigens that they already had. Now
Speaker 1: let's go back to early genetics. We know that when
Speaker 1: a parent birth's a child, it is not a clone.
Speaker 1: The other thing we know is that siblings are not clones.
Speaker 1: So every time there's a new birth, there's a new
Speaker 1: possibility of the birthing parent generating antibodies in response.
Speaker 2: To the baby.
Speaker 1: So let's say you are a parent of three, you've
Speaker 1: birthed three children. You are going up for a kidney
Speaker 1: transplant and they may say, have you ever had a
Speaker 1: blood transfusion? No, have you ever had a previous transplant? No,
Speaker 1: have you ever had kids? And it's like, whoa, And
Speaker 1: you know your antibody profile could be off the charts
Speaker 1: because I've been exposed.
Speaker 2: That's so tough. Wow, it was really tricky, you know.
Speaker 1: So if you think about that, that feels like that
Speaker 1: can really increase your antibody profile. Now here's the good news.
Speaker 1: This only happens about thirty percent of the time. So
Speaker 1: only thirty percent of the time do we see this
Speaker 1: type of antibody response after birth.
Speaker 2: But it's good to know. Yeah, it's good to know
Speaker 2: about that. Is this something that.
Speaker 3: We should be testing ourselves for or getting tested.
Speaker 2: For or is that like not until it's time to
Speaker 2: have a transplant.
Speaker 3: Okay, So we've talked about three main ways someone can
Speaker 3: get antibodies that makes it harder for them to match
Speaker 3: with a donor, like previous transplants, blood transfusion, and giving birth.
Speaker 3: But doctor Low told us about an even more unusual case.
Speaker 4: A patient many years ago who came for transplant and
Speaker 4: it was a male. He was a really big guy actually,
Speaker 4: and he'd never had a previous transplant, and he'd never
Speaker 4: had a transfusion either, so we were really confused because
Speaker 4: he had a ton of anti so we were trying
Speaker 4: to work out where he could have got these from.
Speaker 4: And it was only just one day that he told
Speaker 4: us that he used to be a bare knuckle cage fighter,
Speaker 4: so he'd been fighting for years and exchanging blood, which
Speaker 4: sounds horrible that he'd been exchanging bloods and other fluids
Speaker 4: I guess with his opponents, and he'd had a lot
Speaker 4: of antibodies. So don't do cage fighting if you ever
Speaker 4: want to get a kidney.
Speaker 2: I think these are things they don't tell you on
Speaker 2: Fight Club.
Speaker 3: Tyler Durton didn't say this so after the tissue type
Speaker 3: has been identified correctly in the antibodies confirm, the last
Speaker 3: step in checking a patient for histo compatibility is a
Speaker 3: cross match.
Speaker 4: You would get material from the donor, so you would
Speaker 4: get cells and tissue, and you would test for reactivity
Speaker 4: from your patient and if it's positive, then that usually
Speaker 4: means you don't go ahead. So I would often be
Speaker 4: performing these cross matches, and it usually turned out to
Speaker 4: be at three am, because often transplantation happens when you
Speaker 4: can when you have the donor. The cross match is
Speaker 4: absolutely crucial.
Speaker 1: Okay, So it seems like initially we're just looking at
Speaker 1: small things like the antibodies. Now we're pulling clumps of
Speaker 1: sales so tissues and saying, all right, are y'all gonna
Speaker 1: play well together? On paper, you look good together, but
Speaker 1: are y'all gonna play well together? And that cross match
Speaker 1: is where things can really start to look up.
Speaker 2: Right.
Speaker 1: The question is, you know, are you two gonna play
Speaker 1: well together? And so I think a cross match physically
Speaker 1: putting those tissues together is so important because if somebody
Speaker 1: made a mistake at the early stages of the antibody panel,
Speaker 1: or if there's something that wasn't detected. If you were
Speaker 1: to move forward with that transplant and they are not
Speaker 1: a good match, instantly the body will reject it, like
Speaker 1: within minutes seconds, even the organ begins to turn black. Wow,
Speaker 1: that's just how strong the immune response is in the body.
Speaker 3: Okay, let's take a quick break and when we get back,
Speaker 3: we'll get into another important part of organ transplants with
Speaker 3: doctor Low, and that's immunosuppression. We're back and we've been
Speaker 3: talking with doctor Dave Low all about organ transplants and
Speaker 3: how important the PROSS match is to make sure tissues
Speaker 3: will be compatible in an organ transplant.
Speaker 1: And I think that really gets us to the importance
Speaker 1: of another component of transplants, and that's immunosuppression. When a
Speaker 1: transplanted organ is rejected by the body, it's because of.
Speaker 3: A really strong immune response. And this is the worst
Speaker 3: case scenario.
Speaker 4: So when you have that antibody response that sort of
Speaker 4: floats onto that organ, the downstream effects of that antibody
Speaker 4: there are many different ways that that could lead to
Speaker 4: tissue damage.
Speaker 5: One of them is complement activation.
Speaker 4: So those antibodies bind to that target if you like
Speaker 4: that that foreign kidney or heart, whatever it may.
Speaker 5: Be, and they kind of group together and.
Speaker 4: They start this insane immunological cascade. They recruit lots of
Speaker 4: other proteins, and it ultimately forms a complex called the
Speaker 4: membrane attack complex, which basically just pumps holes in the tissues.
Speaker 1: And even though there's all of this testing that we
Speaker 1: talked about earlier for histocompatibility, most patients who end up
Speaker 1: receiving a transplant are not fully matched. They're compatible, but
Speaker 1: there is some degree of mismatching, which is usually okay.
Speaker 4: So we need to dampen down any potential immune response
Speaker 4: to help to make sure that that kidney or heart
Speaker 4: doesn't reject. But the immune system usually finds a way,
Speaker 4: so quite often the iminosuppression that is administered is really
Speaker 4: there to prevent the patient's T cells. The T cells
Speaker 4: are the kind of conductor of the immune response, so
Speaker 4: a lot of the iminosuppression is tailored to targeting those cells,
Speaker 4: and that enables you to transplant safely. It is effective
Speaker 4: in preventing the organ being rejected.
Speaker 1: And something I didn't realize is that once you receive
Speaker 1: a transplant, immunal suppression can be a lifelong commitment. Most
Speaker 1: patients continue on immunosuppressants for their whole lives.
Speaker 4: The holy grail is to achieve what we would term tolerance.
Speaker 4: So if you can get to a point where you
Speaker 4: can remove yourself from all help, so all your imminosuppression
Speaker 4: is taken away and your immune system is tolerant of
Speaker 4: that graph, that's extremely difficult to achieve.
Speaker 1: Once you receive a transplant. Immuno suppression is a lifelong
Speaker 1: commitment and there's a lot that comes along with that.
Speaker 1: You're taking a ton of medicine, and when you're taking
Speaker 1: that medicine, that means it can make you more susceptible
Speaker 1: because you're suppressing your immune system. It means it can
Speaker 1: make you more susceptible to colds, It can make you
Speaker 1: more susceptible to getting really sick from exposures that wouldn't
Speaker 1: disturb most people. So it changes your quality of life.
Speaker 1: It changes your quality of life. And if you're not
Speaker 1: having issues with your transplant, it may be easy to
Speaker 1: think like, Okay, maybe it's all right if I skip
Speaker 1: this for a day, or even just because it's difficult
Speaker 1: to keep up this type of regiment, you may unintentionally
Speaker 1: miss a day, right, you know, meantimes, I miss my
Speaker 1: allergy medicine, even though I know how awful I'm gonna feel.
Speaker 2: Yeah, it's not intentional, it's o.
Speaker 1: Can you imagine missing one pill in your routine and
Speaker 1: then having these things that you also can't see. We know,
Speaker 1: just human behavior, we delay things we can't see. We
Speaker 1: don't put as much importance on things that we can't see,
Speaker 1: and so it may not feel like there's going to
Speaker 1: be a media action, but that immune system is quick.
Speaker 4: And we see there's a lot of studies that have
Speaker 4: shown that actually sort of stopping taking the immuno suppression
Speaker 4: really a leading cause of transplant failure, especially in younger people.
Speaker 4: I think that's something to sort of consider, is that
Speaker 4: a lot of the imminosuppressive drugs out there, they're quite powerful,
Speaker 4: and they have a number of side effects that could
Speaker 4: be seen as quite undesirable, you know, like excess weight
Speaker 4: being gained and hair growth and things like that.
Speaker 3: This whole process might seem like a lot and it is.
Speaker 3: It used to take weeks to determine histo compatibility, but
Speaker 3: doctor Lowe was telling us that their technology has improved
Speaker 3: and what used to take weeks can now be done
Speaker 3: in a matter of hours, and.
Speaker 4: In those cases where it's a deceased donor, you've usually
Speaker 4: got much less time because as soon as the organ
Speaker 4: is retrieved from the donor and placed on ice, then
Speaker 4: the clock is ticking. We have this thing called cold
Speaker 4: ischemic time, which is used to describe the number of
Speaker 4: hours that the organ is placed on ice before we
Speaker 4: can implant into the recipient. So part of what we
Speaker 4: do is to make these tests as rapid as we possibly.
Speaker 1: Both of those points, doctor Lomay, are really important. That
Speaker 1: timeframe for determining compatibility and the ability to leverage more
Speaker 1: deceased donors, those are both really important because the demand
Speaker 1: for organ transplants is still very high.
Speaker 3: Right According to orgondonor dot gov, over one hundred thousand
Speaker 3: people are currently on the National Transplant Waiting List, and.
Speaker 1: The bulk of these folks are waiting for kidney transplants. Currently,
Speaker 1: there are ninety thousand candidates on the kidney transplant list.
Speaker 3: And the statistic that really got me is that every
Speaker 3: day in the US, seventeen people die waiting for an
Speaker 3: organ transplant.
Speaker 1: And so when you consider all of this, you know,
Speaker 1: we talked earlier in the dissection about compatibility and how
Speaker 1: that can be one of the biggest obstacles to getting
Speaker 1: a transplant. But we both wanted to know if that
Speaker 1: was the major cause of the long waiting list that
Speaker 1: we're seeing, or if there's like some other issue that
Speaker 1: we've seen in other places, like you know, specific types
Speaker 1: of demand for different organs.
Speaker 4: I think supplying demand is a good way to put it.
Speaker 4: You know, the number of people waiting on list, generally speaking,
Speaker 4: they outnumber the number of available organs. And then there
Speaker 4: are the reasons that we've talked about why some patients
Speaker 4: may wait longer than others. So the patients with a
Speaker 4: lot of antibodies, they're going to struggle to get a
Speaker 4: donor from the waiting list, so they're waiting for deceased donors.
Speaker 4: So I think that's important to talk about as well,
Speaker 4: that in some organs, like kidney, a large proportion of
Speaker 4: the transplantation is taken from live donors.
Speaker 5: So quite often it could be family members, a brother, a.
Speaker 4: Sister, mother, father, child, the people on the transplant weight list,
Speaker 4: you know, maybe they don't have a potential live donor.
Speaker 3: These challenges of supply not meeting the demand mean that
Speaker 3: scientists and doctors have to think a little more creatively
Speaker 3: about different ways to get patients transplanted successfully.
Speaker 4: So when I talked before about a lot of patients
Speaker 4: on the list have a lot of antibodies and disproportionately
Speaker 4: high numbers of female patients that you have to get
Speaker 4: a little bit creative and how are you going to
Speaker 4: get patients like this to have a transplant? And there
Speaker 4: are things you can do that I think they're really
Speaker 4: quite clever.
Speaker 5: One is pared donation.
Speaker 4: So you know, you might have a patient and they
Speaker 4: might have a lot of antibodies and their wife or
Speaker 4: sister or brother is willing to donate, but because of
Speaker 4: the antibodies, they're not compatible. So what often happens is
Speaker 4: they will enter into a paired donation scheme. So what
Speaker 4: they'll say is that, Okay, my brother can't give an
Speaker 4: organ to me, but we're going to go into this
Speaker 4: pool of people of patients and donors, and we're going
Speaker 4: to find out maybe there's a patient in there that
Speaker 4: he is compatible with, and maybe there's a donor in
Speaker 4: there that the patient is compatible with.
Speaker 5: In its simplest form, they.
Speaker 4: Literally just swap donors and then everybody gets what they
Speaker 4: need and if the patient is willing to accept a risk,
Speaker 4: you can do some more high risk transplants where you
Speaker 4: have a donor and they've got antibodies against them, but
Speaker 4: you use that donor anyway, and what you can do
Speaker 4: is you can do what's called desensitization therapy. So we
Speaker 4: will treat the patients and remove their antibodies. So usually
Speaker 4: we'll do it by plasmaphoresis, so we'll essentially hook them
Speaker 4: up to a machine and remove components of the blood
Speaker 4: and get the antibodies down to a level where we think, okay,
Speaker 4: we're not going to have a hyperacute rejection. The immunosuppression
Speaker 4: is going to be enough to stop that happening.
Speaker 1: But once again it's really important to note that for
Speaker 1: procedure like plasma poresis, they are removing all the antibodies, which,
Speaker 1: as we know from Lab forty seven, means a much
Speaker 1: much weaker immune system.
Speaker 4: That's one of the downsides is you're going to remove
Speaker 4: antibodies that kind of the patient needs.
Speaker 5: There's antibodies that protect you.
Speaker 4: Against bacteria, virus, whatever it might be, so you kind
Speaker 4: of run the risk of leaving your patient a little
Speaker 4: bit extra vulnerable and then you're going to give them
Speaker 4: amino suppression as well, so you can be double vulnerable.
Speaker 3: This is such a great point, and this is part
Speaker 3: of why it's so important that those patients who've received
Speaker 3: transplants have regular monitoring. For example, doctors may want to
Speaker 3: periodically screen patients to make sure that they aren't developing
Speaker 3: anybodies that might reject the transplanted organ, whether it's regular
Speaker 3: clinic visits or new technology that allows patients to take
Speaker 3: these samples at home. Being a transplant recipient is really
Speaker 3: a lifelong commitment, and in order to make this lifelong.
Speaker 2: Commitment more bearable.
Speaker 3: There's a lot of technological advances that scientists are trying
Speaker 3: to pour into so that it makes that commitment of
Speaker 3: a burden. So we ask doctor Low about some of
Speaker 3: the advances in transplant technology.
Speaker 4: There's been great advances over the last few years as
Speaker 4: we've gone from sort of the cells right through to
Speaker 4: various PCR techniques and now we're onto next generation sequencing
Speaker 4: and that gives you that deep level of understanding of
Speaker 4: the tissues so that we can have more information we
Speaker 4: can match to a higher and higher level. And this
Speaker 4: is amazing, and now we're trying to say, Okay, we
Speaker 4: can do it. But a lot of the time, some
Speaker 4: of these workflows take two or three days, so it's
Speaker 4: how can we speed it up? What can we do
Speaker 4: to speed it up? And I think that's some of
Speaker 4: the really exciting stuff that's going on right now.
Speaker 5: Is that you know, there's lots of.
Speaker 4: Us working on getting that deep level of resolution as
Speaker 4: quickly as possible.
Speaker 5: So it's kind of a race, you know, where everyone's
Speaker 5: working on it.
Speaker 1: So tt we consider it like that that we saw
Speaker 1: about the pig heart transplant. The recipient recently passed away. Yeah,
Speaker 1: I saw that, But they're also.
Speaker 2: Saying they don't know what the cause is.
Speaker 1: And one thing that we do know is when you
Speaker 1: have those types of transplants that you're taking a lot
Speaker 1: of them, you know, suppressant, so it could be anything. Right,
Speaker 1: This was really groundbreaking technology, but it was kind of
Speaker 1: a one off.
Speaker 3: Right, Yeah, I think it's a really great start when
Speaker 3: we're thinking about the future of organ transplant And so
Speaker 3: we asked doctor Low what does he feel as possible
Speaker 3: in the coming years. Is this the future of transplant technology?
Speaker 5: Yeah?
Speaker 4: I mean I don't know if I'll be anything like accurate.
Speaker 4: I guess we could meet in ten years or something
Speaker 4: and see. But xeno transplantation, so using an organ from
Speaker 4: another species is it's been around for quite a long time.
Speaker 4: There's been a number of high profile cases that have
Speaker 4: come up recently, and that's got us really interested. And
Speaker 4: what I've seen from some of these organs that have
Speaker 4: been used is that they've knocked out genes that express
Speaker 4: proteins that are thought to be important in the immune response,
Speaker 4: and they've engineered those genes out to presumably and hopefully
Speaker 4: make things safer. And they've engineered in certain human genes.
Speaker 4: So let's try and make that pig kidney or heart
Speaker 4: more closely resemble the recipient. So it's science fiction, but
Speaker 4: it's coming, it's here, and it's you know, it's really crazy.
Speaker 5: So I'll be really interested to see how these transplants
Speaker 5: go longer term.
Speaker 4: I think there's a lot we need to learn about
Speaker 4: how that immune response to that pig organ differs from
Speaker 4: a human and what challenges we might have. I know
Speaker 4: that in these cases, these recipients are extremely heavily immunosuppressed,
Speaker 4: so it's not easy. I think there's a long way
Speaker 4: to go and there's going to need to be a
Speaker 4: lot of large human trials.
Speaker 2: Immunology is everywhere.
Speaker 3: Yeah, I don't know much about immunology, but I feel
Speaker 3: a lot smarter after all of this, and I feel
Speaker 3: like the future looks bright for organ transplant science.
Speaker 1: I think it's really exciting, Like you said, it's bright,
Speaker 1: But I also am cautious. I think a lot of
Speaker 1: times we have the technology moving and it's divorced of
Speaker 1: this social context, And so I'm like, what does it
Speaker 1: mean for transplant technology? You know, as we start thinking
Speaker 1: about this new tech and until it's readily available for everybody,
Speaker 1: how are people going to decide who gets what? It
Speaker 1: feels like this technology and the implementation of it is
Speaker 1: ripe for abuse, you know, or more of the same
Speaker 1: where we see people with the most money get these things.
Speaker 1: And so I'm like, how can we do this better
Speaker 1: than we've done some of the other systems of healthcare?
Speaker 2: Yeah, but I feel excited about it.
Speaker 1: Like you said, what was it the ear on the
Speaker 1: back of the mouse, it's time to update the textbook photos.
Speaker 1: That's right, it's the genetically altered pig heart. Now, what's
Speaker 1: your one thing?
Speaker 2: Tt my one thing this week?
Speaker 3: Is a Dope Labs live show that is happening on
Speaker 3: April fourteenth at the Boston Museum of Science. We did
Speaker 3: a live show in Minnesota and so many people were like, oh, man.
Speaker 2: I wish I'd known, I would have come out to
Speaker 2: see you. So now you know. Tickets are free ninety nine.
Speaker 3: You can come April fourteenth at the Boston Museum of
Speaker 3: Science at seven pm. There'll be a link in the
Speaker 3: show notes so that you can reserve your ticket.
Speaker 1: My one thing this week is this citizen science project.
Speaker 1: I don't know if you remember the earthquake back in
Speaker 1: Haiti and what we consider seismology and how do we
Speaker 1: track all of these events. There's a system called Raspberry Shake,
Speaker 1: which are these small computers that allow you to track
Speaker 1: seismic activity at a smaller level. So there's a network
Speaker 1: of all these little computers giving us a worldview, and
Speaker 1: just regular citizens, you know, not institutions are tracking this
Speaker 1: information and sending it to this hub is raspberry shake
Speaker 1: dot org, and you can see all the different stations
Speaker 1: and track the most recent events, even really small events,
Speaker 1: at station view dot raspberry shake dot org.
Speaker 2: It's kind of cool. That's it for Lab fifty six.
Speaker 1: Call us at two zero two five six seven seven
Speaker 1: zero two eight and tell us what you thought, or
Speaker 1: you can give us an idea for a lab you
Speaker 1: think we should do. Either way, we love hearing from you.
Speaker 1: That's two zero two five six seven seven zero two eight.
Speaker 3: And don't forget there's so much more for you to
Speaker 3: dig into on our website. There will be a cheat
Speaker 3: cheet there for today's lab and additional links and resources
Speaker 3: in the show notes. Plus, you can sign up for
Speaker 3: our newsletter, so check it out at Dope Last podcast
Speaker 3: dot com special thanks to today's guest expert, doctor Dave Low.
Speaker 1: You can find more information about Davelow's work with organ
Speaker 1: transplantation on LinkedIn at one Lambda Incorporated.
Speaker 3: You can find us on Twitter and Instagram at Dope
Speaker 3: Labs Podcast.
Speaker 2: And TT's on Twitter and Instagram at d R Underscore
Speaker 2: t Sho, and you can find Zakia at z said So.
Speaker 3: Dope Labs is a Spotify original production from Mega owned
Speaker 3: Media Group.
Speaker 1: Our producers are Jenny Radlett Mast and Lydia Smith of
Speaker 1: WaveRunner Studios.
Speaker 3: Editing in sound design by Rob Smerciak.
Speaker 2: Mixing by Hannes Brown.
Speaker 3: Original music composed and produced by Taka Yasuzawa and Alex
Speaker 3: Sugier from Spotify, Executive producer Corinne Gilliard and creative producer
Speaker 3: Miguel Contreras. Special thanks to Shirley Ramos, Jess Borrison, Jasmine Afifikamu, Elolia,
Speaker 3: tillkrat Key, and Brian Marquis. Executive producers from Mega Own
Speaker 3: Media Group are US T T Show, Dia and Zakiah Wattley.