The Current - Could genetically modified pig organs save human lives?

Episode Date: March 19, 2025

An Alabama woman received a kidney transplant from a genetically modified pig in November, in an experimental surgery that doctors said was her only chance at survival. We discuss the science — and the ethics — of cross-species transplantation.

In Scarborough, there's this fire behind our eyes. A passion in our bellies. It's in the hearts of our neighbors. The eyes of our nurses. And the hands of our doctors. It's what makes Scarborough, Scarborough. In our hospitals, we do more than anyone thought possible. We've less than anyone could imagine.

But it's time to imagine what we can do with more. Join Scarborough Health Network and together, we can turn grit into greatness. Donate at lovescarborough.ca. This is a CBC podcast. Hello, I'm Matt Galloway, and this is The Current Podcast. And now I'm taking the clamp off the artery. And it should be nice and pink.

Yeah. Yeah, it is. Beautiful. Gorgeous. Yeah. It's beautiful. Gorgeous. It looks beautiful. In an operating room in New York City last November, Dr. Robert Montgomery and his surgical team had reason to celebrate that beautiful pink site was of a successful kidney transplant, specifically a pig kidney put into a human patient. Tawana Looney had been on dialysis for eight years before agreeing to try this experimental surgery. Doctors said it was her only chance at survival, so the FDA, the Food and Drug Administration,

made a special exception to its usual clinical study requirements. The kidney pinked up and looked just like a human kidney. It made urine within just a few minutes. And by the time we saw her that evening, we all noticed it. It's this miraculous change that these patients get after a transplant. Tuanah Looney is the longest living recipient of a pig organ transplant.

Last month, the FDA gave two biotech companies the green light to conduct clinical trials, transplanting genetically modified pig kidneys into patients with kidney failure. One of those companies given the green light is eGenesis based in Massachusetts. Mike Curtis is president and chief executive officer at eGenesis. Mike good morning. Good morning. Thanks for the opportunity.

Thank you for being here. What are you hoping to do with these trials? Yeah, so these are the first studies of transgenic porous organ into living patients. And really these initial trials are super important to understand how to manage the patients in the post-transplant period. So, you know, with Ms. Looney and Mr. Andrews, we're really focused on how to take care of these patients

to get long-term outcomes from these transplants. And so what are you going to be doing? So right now it's controlling the immunosuppression. So we've done the genetic engineering. So if we step back for a moment, what we've done to the pig genome is really three different types of editing. We've reduced the risk of zoonosis

by inactivating retroviruses. We've eliminated antigens that lead to hyperacute rejection. If I take a pig kidney and transplant it into a person, it will be rejected in minutes to hours. But with the engineering that we do, we get these longer-term outcomes. Then the third class of edits is we introduce human transgenes or human genes into the porcine genome

to promote long-term graft function. We studied this in monkeys for years, and we had achieved over two years of post-transplant graft function in monkeys. And now what we're trying to see is, does that translate into long-term outcomes for patients? There are a few things that you're trying to deal with, and we'll walk through them.

One is the zoonosis issue. This is the idea of an infectious disease that would spread between animals and humans. Obviously, people don't want that for a bunch of reasons. One is that it could lead to diseases spreading in a human population. I mean, it's a nightmare scenario in some ways. How concerned are you about that?

This is one of the large ethical concerns that people have when it comes to xenotransplantation. No, and we completely agree. And it's one of the things that we focus on. Half of our efforts are around controlling zoonosis or what we call pathogen risk. And if we rewind the clock back to the 90s, then one of the reasons the field

of cross-species transplant stalled was the discovery that porcine retroviruses could infect human cells. Fast forward to early 2000s and the discovery of CRISPR-Cas9, it gave us a tool that we could engineer the pig in a way that eliminated that retroviral risk. And then the other thing that we're leveraging is modern genomics.

And so we do run a technique called metagenomics where we screen all of our donors by sequencing and look for any changes in the metagenome. And what that allows us to do is look for pathogens that we're not currently looking for. So there are viruses we know we need to eliminate. But I think one of the fears is you're gonna have a virus that you're not looking for and that could blindside us. COVID-19 is a good example of a virus

that we weren't looking for and all of a sudden showed up. And so we screen all of our animals with this metagenomic approach to give us the best chance of catching any potential pathogen risk for patients. And then once we do the transplant, we continue to monitor these patients for any potential unknown pathogens. What are the other concerns is around rejection. People reject human organs.

You can take drugs that can help mitigate some of that rejection, but it can open you up to any number of other complications, including forms of cancer. How are you going to address the complications when it comes to rejection? Sure, and I think one of the advantages we have in cross-species transplantation is we're able to leverage several decades of experience in managing human-to-human transplant.

Where we start with immunosuppression is the current standard of care for a human kidney transplant. Then we add to that modulators of what we call T-cell rejection. It's been shown and there's actually studies in human-to-human transplant going on right now, that if you can inhibit what we call T-cell co-stimulation, we can start to block that immune response.

So managing the immune suppression is the key to long-term graft function currently. And that's what the physicians that are managing, Ms. Looney and Mr. Andrews are focused on now. Tell me about Tim, you mentioned Mr. Andrews, tell me about Tim Andrews. Yeah, so Tim is a great story, and I listened to the audio clip that started this piece

of a transplant that's completely changed his life. And so, and maybe even back up a step before that with Mr. Slayman, right? So we were fortunate to be able to do the first porous kidney transplant of living patient last March with Mr. Rick Slayman. Rick was imminently facing the loss of dialysis, had really run out of options and agreed to be the first patient to receive a transgenic porous kidney. He lived for 51 days, the kidney functioned beautifully. Unfortunately, Mr. Slamon also had significant cardiovascular risk and he passed away following a cardiovascular event. We met with the FDA over the

summer to discuss his case and they suggested and we agreed that we should do the next transplant in a patient with lower cardiovascular risk. That leads us to Mr. Andrews. So Mr. Andrews had been on dialysis for just a little less than two years, but his health had been declining. He had become relying on a wheelchair. He was just feeling terrible. And the prognosis was pretty poor.

So he agreed to be the second patient. And very similar to the Ms. Looney story, immediately following transplant, it just changed his life. He no longer needed the wheelchair, he no longer needed dialysis, and now he's 53 days post-transplant, and the nephrologists are focused on managing his immunosuppression. So we need to manage this in a way that gives the graft the best possibility of functioning for the long term. So he's doing great, but we're learning a lot of how to manage suppression in these patients.

What is success to you? Some of these patients are living for weeks or months. What does success look like? Well, if we use the primate model as the baseline where we can achieve over two years of post-supreme graft function, that's what we're shooting for. So we're shooting for multiple years of graft function, and the trick will be how do we manage that suppression over the long term? Because I think you're absolutely right. We have to balance the side effects of immunosuppression against preserving graft function.

And that is really the art and science of immunosuppression. And again, leveraging many years of experience in immunosuppression in patients with kidney, heart, and liver transplants puts us in a really strong position that 30 years ago we didn't know. And so we're able to leverage a lot of that knowledge plus evolution and improvements in immunosuppression drugs. Ethically, can these patients actually consent to this sort of experiment?

There are so many unknowns. There are all these things that, sure, this may extend their life for days or weeks or months, but there are all these things that we've talked about that are still black boxes. Can they actually consent to this? It's like with any experimental therapy, there are always unknowns,

and the patients have to balance the risk and potential benefit, right? And take those unknowns on their full knowledge. So I believe so. I mean, I believe we do a very good job of explaining what we know, what we don't know, what the potential risks are, and then also what mitigation are, right?

So if we run into trouble with the kidney, what's the resolution? Well, one resolution is to remove the kidney, and then the patient goes back on dialysis. We have multiple mitigation steps for potential infectious disease or pathogens, right? So we have an entire group that's focused on pathogen control.

And if we were to see a virus, so there are viruses that are discovered in human to human transplant. One of those is called BK virus. And the nephrologists and infectious disease docs have a good experience of how to manage that. So part of managing the unknown is really working with very experienced groups on how we did this in Aloe, right? Because at one point, if you rewind the clock 50 years, people were concerned about human to human

transplant with a lot of the same concerns. And so we can learn from that experience to make Xeno as safe as possible. I have to let you go, but very briefly, you have said that if this works, we are entering a transformative era in organ transplantation. What do you mean by that? Well, we look at patients like Ms Miss Looney and Mr. Andrews who have faced historically very bleak futures where they're going to basically spend the rest of their life on dialysis until they, you know, and now there's the potential to get those folks

off of dialysis into transplant and greatly improve their quality of life and potentially improve their overall survival. Mike Curtis, we'll leave it there. It's good to speak with you. Thank you very much. Thanks for the opportunity. Mike Curtis is President and Chief Executive at E-Genesis. It's a biotech company based in Cambridge, Massachusetts. Sid Johnson is a professor

and ethics consultant at the Center for Bioethics and Humanities at Upstate Medical University in Syracuse, New York, and she's been listening. And Sid, good morning to you. Good morning. This is an idea that arrives with enormous promise, in part because in this country, there are thousands of people who are awaiting organ transplantation. In the United States, it's more than 100,000 people. What do you make of the idea of transplanting organs

from pigs, genetically modified pigs, into human beings? Well, as you already have discussed, organ transplants, and what's the goal of organ transplantation? Is it to give a patient who has an organ that doesn't function and give them a new organ that will enable them to function? And what's the goal of organ transplantation? And what's the goal of organ transplantation? And what's the goal of organ transplantation? And what's the goal of organ transplantation? And what's the goal of organ transplantation? And what's the goal of organ transplantation is to give a patient who has an organ that doesn't function

and give them a new organ that will enable them to live. But right now, we haven't seen long-term survival in any of the patients who have received these pig organs. We have a couple of patients who are alive right now who have been going for a couple of months. But prior to that, the four previous recipients only lived for a couple of months. That's not what people want out of an organ transplant. And so I think we are, one of my concerns is we're not actually there yet.

We're not ready for humans here because we're only really offering people maybe a short-term solution. That short-term solution cannot solve the bigger problem of the organ shortage. We have a chronic shortage, lots of people who die waiting for organs, lots of people who are stuck on dialysis for years. But if we're only talking about using pig organs as a bridge to a human transplant, so we'll get you through the next few months or through the next few years,

that doesn't solve the organ shortage problem at all, it just kicks the can down the road. That shortage of organs is going to persist unless we can actually do something about the causes of organ failure or find better ways to treat organ failure so that people don't need organ transplants at all. How worried are you, and I want to come back to what we do about the shortage, how worried are you about, as I said, the nightmare scenario that we are taking something from something else and putting it in us. And that in doing that, you run the risk of a virus that we don't know anything about that might operate in a pig suddenly appearing in a human being.

I think that is a really significant concern and it is a nightmare scenario. We're now in year five of the COVID pandemic. This was a novel virus that we had never seen before, which emerged and ended up being transmitted to humans. We know that in the first heart recipient of a pig heart, that the heart was infected with porcine megalovirus. And that was despite the gene editing that was done on the pig to remove that virus.

This has also been found in the monkey experiments, where they have transplanted pig organs into monkeys. So to date, it doesn't appear that the genetic modifications that are intended to eliminate those viruses have worked flawlessly. And there's very little room for error there. The risks of failure could be catastrophic for the recipient, but we're also talking about potential collective harms from the introduction of a novel mutated virus.

These patients are immunosuppressed, which means that their immune systems are unable to fight off infections as well as someone who's not immunosuppressed. And under that scenario, a virus has the opportunity to stay in that person's body and mutate. And we don't know what might happen in the long run if something like that would occur with a transplant. Are you at all concerned, I can imagine there are people who are listening that think we're raising, you know, breeding animals for our benefit. And we do that all the time in any number of ways

and people can raise concerns around that. But is this different than how we would otherwise use animals, if I can put it that way? It's certainly a different use of animals. Now, some of it is the same. You know, Animals are genetically modified for human purposes, for experimentation and things like that. And of course, pigs are killed for food in the millions. And I think a lot of people might accept that pigs

are bred and killed for food and still have concerns about the way we treat those animals and the way that they're bred and they're raised. The pigs that are being created for xenotransplants are not created to survive and I think there are also questions here about what impact all of this genetic editing might actually have both on the health and well-being of the pigs themselves and for the long-term survival of those organs. The edits are not made to benefit the pigs. The conditions under which the pigs have to be raised, they're bred, they're cloned, they're living in unnatural environments

and in isolation, they face multiple invasive medical procedures and tests. They're born by caesarian section and then taken away from their mothers immediately. These are environments that don't allow the pigs themselves to flourish and to live the kind of life that would be good for a pig. So I think there are genuine welfare concerns here about what we are doing to these animals in the hope that someday this might

actually save a human life because so far we have not saved any human lives. The hope, and that's where I need to end, we are at a time, but the hope is real because as we started out saying, I mean, and you've admitted, this is a formidable problem, the organ shortage that exists. People are dying waiting for transplants

and the belief is if we can do something that will help ease that suffering. What do we, if this kind of xenotransplantation isn't the answer, what is? So we need to find better ways to treat people's chronic illnesses, things like diabetes, common illnesses that can lead to kidney failure. There are other experiments going on to try to grow human organs using human tissue, and those would be organs that you might get from your own tissues,

and so there would be no worry about rejection, for example. And of course, treatments that might help prevent organ failure or treat organs that are near to failure so that people don't need transplants at all. A transplant's a big deal. This is not an easy solution to the end stage of an illness. You're talking about a major surgery. You're talking about lifetime immunosuppression, and with the pig organs, all of those risks are magnified. We have experimental organs, experimental immunosuppression, and we're just not sure what's going to happen. We don't know if these organs could function in the long term because it's never happened so far.

Sid Johnson, good to speak with you. Thank you very much. You're welcome. Sid Johnson is a bioethicist at the Center for Bioethics and Humanities at Upstate Medical University in Syracuse, New York. In Scarborough, there's this fire behind our eyes. A passion in our bellies. It's in the hearts of our neighbors. The eyes of our nurses.

And the hands of our doctors. It's what makes Scarborough, Scarborough. In our hospitals, we do more than anyone thought possible. We've less than anyone could imagine. But it's time to imagine what we can do with more. Join Scarborough Health Network and together, we can turn grit into greatness. Donate at lovescarborough.ca.

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researchers are looking at manufactured organs. In Australia this week, a man was given a titanium heart to extend his life while he awaited a human heart. He is able to walk out of the hospital living for three additional months with this bivac or heart until he got a human heart transplant. Dr. Ali Rabi is a cardiac surgeon at Massachusetts

general hospital in Boston. Also the incoming surgical director for heart transplant at university health Network in Toronto. Dr. Robbie, good morning to you. Good morning. Thanks for having me. Can you describe, I'm looking at photos of this thing now, describe what this titanium heart looks like? Yes, so it basically looks like metallic, sort of an object, spherical with four big hoses coming in and out of it, representing

the input and output from the left side and the right side of the heart. Looks like something I might find under the hood of my car or like a part of something for plumbing or something like that. It is actually very much so like a plumbing. Interestingly, the inventor of this device actually learned his craft by helping out his father in a plumbing business. So I think you're not far off.

How does it work? I mean, we're talking about it being a titanium heart and the heart might be in quotation marks, but how does it work? So the best way of thinking about human heart is to think about two separate pumps functioning in unison. So you have the right side of the heart and the left side of the heart.

The job of the right side of the heart is to receive blood from the body and pumps it out to the lung to get oxygenated. The blood that comes to the heart is without oxygen because the rest of the body just consumed the oxygen. So it goes to the lung to get oxygen and then comes back to the left side of the heart. And now the left side of the heart

is really the motor that pumps the blood back into the rest of the body, the brain, the kidneys, the liver, everything else. So these two parts of the heart have to work in unison and very, very precisely synchronized. Otherwise you'll have issues with backflow of the blood into the lungs or into the rest of the body. And those are actually signs and symptoms of heart failure.

So the innovation here is to manufacture this pump, which is actually a single pump, but works as two separate pumps that can work in synchrony and it has a lot of engineering and a lot of electronics built into it to be able to control this flow of the blood in synchrony to the right side of the heart and receive blood from the right side of the heart into the left side, or I should say the pump, and then pump it back into the rest of the body. So I think that ingenuity and what is different here is the ability to have these two separate

pumps come together as one in one unit and yet the function is flawless. And this isn't a permanent solution. If we're talking about this individual in Australia, it's a temporary solution, right? This person got this such that he was able to survive until he was able to get a human heart transplant. Absolutely. So we have been utilizing pumps and motors to assist the heart for over a decade now,

but the pumps that we have been using permanently or sort of semi-permanently for the patient to be able to go home, only we're able to assist the left side of the heart. Now this pump is able to assist both sides of the heart and it has been implanted in human body before in several other centers. And in Australia, the unique thing about it is that

the patient was actually well enough to be able to go home. But the strategy there when you're putting a pump in someone is twofold. One is someone who we think can receive a heart transplant and that's called bridge to transplant. So we are bridging them to get a transplant. And then the other strategy is if you think that person can actually live permanently with those pumps, especially the left side of the pump is what we have been doing so far

and we have the most experience with. And that's called a bridge to recovery. So this pump currently, the total artificial heart is used as a bridge to transplant strategy. But I know that the designers and the doctors who are using it are also hoping to actually have it one day as a permanent solution for the patients. As somebody who is involved in transplantation

and transplantation surgery, what do you make of that? Again, we talk, and I was talking to your colleagues at UHN about this and elsewhere, about the need to think of how to address the shortage, that we have more patients than we have donated organs, and that people are thinking, whether it's xenotransplantation or through medical innovation to try to close that gap.

What do you make of the idea that at some point in time, perhaps you could use something like a titanium heart, not as a bridge, but as a permanent solution? Yeah, I think this is a problem that's only going to grow in magnitude and in severity. It's going to take more and more lives and cost more and more for the healthcare system. As our population ages and we're able to have people in the later decades of life, we're going to see more and more people with heart failure or in general organ failure. So we are going to have to come at this problem

from not just one angle, but multiple angles. Xeno transplantation you talked about, that's definitely one angle that has been explored. And I think innovative solutions to increase the pool of donors, including different types of donation for both heart and other organs, and finally using pumps that can actually be implanted and have the patient live with those pumps for the rest of their lives or other different solutions.

But going back to what your guest earlier said, I think starting with medical therapy and trying to optimize in the patient's own heart is the first solution. That's always the first line of therapy for any heart failure patient. I was saying earlier that it sounds something like the Wizard of Oz but it actually is more science fiction right in some ways that you could do this taking a look again at this this plumbing part that would end up being the key plumbing part in our body. Yes absolutely I think and this think this ability to do a heart transplant and have the patient go back home or put a permanent pump in a person who was really suffering and has been admitted

multiple times to the hospital really secluded from their society and their community and being able to have that patient go back to their communities is really something fascinating. It is fascinating indeed. Doctor, good to speak with you. Thank you very much. Thank you. Dr. Ali Rabi is the incoming surgical director for heart transplant at the University Health Network in Toronto. He joins that team later this year.