In 2022, surgeons transplanted the first genetically engineered pig heart into a human. Fifty-seven-year-old  David Bennett, a patient with heart failure, survived almost two months with a pig heart beating in his chest, one of five people who have received pig organs as a part of an experimental procedure called xenotransplantation — the transplanting of living cells, tissues, or organs from one species to another.

Some scientists view these pig organs transplants as potentially lifesaving for many like Bennett.

In the US alone, more than 100,000 people are waiting for an organ transplant, and almost 20 people die every day because they can’t get one in time. But a major challenge remains in making xenotransplantation work: scientists haven’t figured out how to get a human body to accept a pig organ for very long. None of the five patients who received these pig organs have survived beyond two months, though researchers believe they’re making progress toward overcoming rejection and eventually moving to clinical trials.

This push to make pig organs viable for humans also comes with enormous ethical implications — from concerns surrounding the use of humans in an experimental procedure that they’re highly unlikely to survive, to the impacts on animals who are supplying the organs themselves. At first glance, the pursuit can feel like hubris. I wanted to better understand these questions, so I spoke with bioethicist L. Syd Johnson, author of a 2022 paper on the ethics of xenotransplantation, for Unexplainable, a Vox podcast that explores unanswered scientific questions. A portion of our conversation, edited for clarity, is included below. 

Mandy Nguyen: Before you started doing this research, what were your general impressions of xenotransplantation?

L. Syd Johnson: My initial impressions of it were, “Boy, this doesn’t really sound like something that’s going to work.” It’s something that in theory might be possible, but there have actually been experiments in xenotransplantation going back to the 1960s, and some of the first experiments involved hearts from chimpanzees.

One of the reasons why doctors were looking to get organs from other animals was because there wasn’t a supply of [human] organs at the time. Transplantation was sort of just starting out and they were just starting to have success with figuring out how to do it, but there was no legal mechanism at that time to obtain organs from humans who had died. So they were looking at animals, which they could kill and take their organs. 

I think the first time I ever heard of xenotransplantation involved a case in the 1980s, which was a pretty famous case involving an infant named Baby Fae, who received a baboon heart. She was born with hypoplastic left heart syndrome, which is a fatal condition, and then, as now, it was very difficult to obtain organs that were the right size for an infant. 

That was a really famous case where the doctor involved was actually sort of notorious and was criticized for what he had done. And of course, Baby Fae also died.

From those initial experiments that failed, how did we suddenly get to this being done in living people today? What was that jump?

The leap was that we have this relatively new genetic editing technology, CRISPR Cas9, and it has enabled scientists and investigators to perform lots of gene edits on an animal.

Several decades ago, the US Public Health Service essentially told investigators that it was too dangerous to try to transplant organs from monkeys, baboons, chimpanzees [into humans], because they were so similar to humans and had a lot of viruses that could be transmitted to a human patient through an organ. That took organs from nonhuman primates off the table. 

The effort to use pigs comes about because of the ability to genetically modify those pigs. We are not nearly as closely related to pigs as we are to the nonhuman primates, so the development of CRISPR, the ability to do lots of gene edits on an animal, is what has led to the current optimism on the part of scientists about the possibility that xenotransplantation using organs from pigs might be able to work.

Right. And now to temper that optimism — what do you see are the biggest ethical concerns or potential harms when it comes to the people who get the transplant?

The biggest concern is that we haven’t figured out how to make this work. It’s very possible that xenotransplantation will never work, that no animal’s organs could be made to support life in a human being, that the risk of xeno-zoonotic transmission of viruses from pigs to humans is still a live possibility. 

That for me is a major concern. We’re in the middle of a zoonotic pandemic right now, the Covid pandemic. We are still dealing with another zoonotic pandemic in AIDS, which is a worldwide problem. There is a concern that putting an organ from an animal that has a virus into a human, and that human is immunosuppressed [as organ transplant recipients are], will result in the mutation of a virus that might plausibly be transmitted to other humans, and who knows what the results of that could be.

Right. So in my mind, there are two big buckets of potential harm to people. One is the infectious disease aspect, and one is the danger to the patients themselves and the ethics around informed consent. I’d love to hear a little bit more about that. What are the concerns there?

The living patients that they have attempted these organ transplants in have been individuals who are quite sick, who are in organ failure, and who are not able to get an organ from a human. So those are all patients who have few good options. Some of them are facing almost certain death if they don’t get a transplant of some kind. So the worry is that we are making these patients an offer they just can’t refuse because their alternative is that they are going to die.

You have to be concerned about whether or not they’re truly providing voluntary informed consent under those circumstances, whether they really understand the risks of xenotransplantation — which so far has never worked and has never actually saved a human life in all the decades of experimentation — and whether or not those patients understand the difference between being part of an experiment and receiving therapeutic treatment. This is something called the therapeutic misconception, where patients believe that being part of an experiment, that experiment is actually intended to benefit them. And we can’t say that at this point about xenotransplants.

But unfortunately, the patients who have agreed to these transplants have all said in media interviews that it was their last chance at survival, that they really had to do this because they had no other options. And that suggests that they did truly believe that these transplants would save their lives, and that is, unfortunately, a misconception. And unfortunately, all of these patients so far have died.

I’ve spoken to scientists and ethicists who are working with scientists to try to make sure informed consent is really tight and transparent. Do you think that’s a possible solution? Is it possible to get informed consent from someone who’s put in this position?

Of course it’s possible, and someone might go into this thinking, well, it’s never worked before and it’s really a long shot and it’s probably not going to work for me, but a one in a million chance is better than a zero in a million chance, so I’m going to take it. We can provide patients with all of the information that they need in order to make an informed choice.

There’s been lots of research showing that despite our best efforts, lots of people who are enrolled in clinical trials or enrolled in experimental therapies do still misunderstand what might happen and that the purpose of the experiment is not to benefit them, but to benefit others, to acquire more scientific knowledge that will be a benefit to patients in the future.

But I think people are complex and they can understand both of those things at the same time, and still have this hope that this might work for them. 

You’ve done a lot here on animal research and the use of animals as models for humans. How are you thinking about xenotransplantation here?

So two things. One is, there are questions about what’s happening to the pigs, and the welfare of these pigs. And the other is that we are actually still doing research transplanting monkeys with these pig organs. 

So far the longest that monkeys have been kept alive with a pig organ is two years. There’s not a lot of information about what happened to that monkey, what that monkey had to undergo in order to get it to survive for that long. Any time we’re talking about experimenting on animals, there are welfare concerns about what happens to those animals and how we’re using them. But there’s also the fact that having a monkey living in a laboratory in a cage where we can do just about anything we want to that monkey is very different from the circumstances in which human patients exist.

A human patient doesn’t want to spend the rest of their life in a hospital bed. They want to be able to go home and go on with their lives. So we’re not replicating the conditions of a human life or a human existence in a laboratory animal. So I have concerns that what we’re doing with those monkeys actually isn’t really telling us anything very useful about whether or not this will work in humans and whether it will provide the kinds of benefits that we’re hoping it would provide to humans.

So one question is whether what we are doing with other animals is telling us anything useful about long-term survival for humans with pig organs. 

For the pigs themselves, there are a few concerns here. One is what the effects of the genetic modifications are on those pigs, on their health, on their survival, and on their well-being. Of course, those pigs are not actually created to survive. We are creating them to produce organs so that they can be killed and those organs can be used in humans. 

With gene editing, we’re trying to sand off the edges of pig organs to force it to fit into a human and to work in a human. So what are we doing to the pigs under those circumstances? What are the conditions under which they are bred or cloned and raised? Much of it requires them to stay in unnatural environments in isolation, with multiple invasive medical procedures and tests, and that’s before they’re killed for their organs. 

These are animals who would not exist at all, except for our human intervention. And I think we’re treating them just for the purpose of taking them apart to provide spare parts for humans. They don’t see the sky. They’re not going to touch grass. And we are attempting to undo 80 million years of evolutionary divergence in this way that involves the radical exploitation of an animal that we’ve created and built for a purpose. I think we really do need to reflect on what we’re doing there and on the harms that we’re causing to living, conscious, intelligent creatures, in part so that a handful of biotech companies can profit from their existence.

I was recently reading how GalSafe pigs, a kind of pig being used for xenotransplantation research, were recently FDA-approved for both consumption and therapeutic uses. I think there’s something really strange about the idea that someone could get a pig heart from this pig and also be eating the same pig. It’s very bizarre.

That does raise some weird issues. That I am now part pig, I have this heart that I got from a pig, and it saved my life, so that I could go eat parts of that pig’s relatives.

Say we get into a future where xenotransplantation works, it becomes common. Is there a concern that we’re just replicating some of the environmental harm of, say, factory farming?

This would absolutely be factory farming. These would be animals grown and bred and raised in a facility. And you presumably have a fairly resource-intensive facility, even perhaps beyond what we see currently with pig farms. 

These are pigs that are being grown and created and controlled by these private biotech companies with this hope that we might actually have on-demand organs for everyone who needs one at some point in the future. But we are talking about expanding the footprint of factory farming — expanding the use of resources to grow these animals. And we would be talking about growing perhaps millions of these animals rather than however many we are currently growing.

It has been really interesting to learn how much funding is coming from these biotech companies into all this research. Are there any other concerns around that that you have?

This is sort of what biotech companies do. They spend a lot of money and invest it in products that are speculative, that may or may not work, that may or may not improve human life for people in general. And part of my concern is that they are currently in control of what is being done experimentally.

They create the pigs, they create the organs, and they are paying investigators at academic research hospitals to do these experiments on their patients. You can’t just find patients on the street — you have to access them through doctors who have patients who are in dire straits and who don’t have good options. So what we have now is this kind of private enterprise with lots of hype around it, but not enough attention, I think, to the profit motive behind this and how much that is driving research in xenotransplantation.

Do you think we’re moving too fast here? What needs to be done to be able to get to a point when it feels safe to do clinical trials? Or do you think that’s not really possible?

I think we’re not close to that yet. But I also think it’s important for us to think about what else we might be doing as an alternative to xenotransplantation. In some sense, xenotransplantation seems like the least likely technology to be used out of the gate as the solution to this problem. 

We have other options that people are also working on, things like being able to grow a human organ from the cells of the actual recipient, which would be an organ that is made from that person’s own cells where they wouldn’t face problems of rejection. There is potential for therapeutics that would actually help address organ failure so that the patient doesn’t get to the point where they need an organ transplant. 

There are opportunity costs in terms of the time and the effort and the resources that are being put into xenotransplantation, which, if it doesn’t work, is a lot of money and a lot of time and effort down the drain. There are other possibilities that we could be pouring more resources into that don’t require us to overcome 80 million years of evolutionary divergence between humans and pigs. 

A really important option, one of the least glamorous ones, is what else could we be doing to prevent organ failure in the first place — because an organ transplant, whether that organ comes from an animal or comes from another human, is not a quick, easy fix. You’re looking at a patient who has a lifetime of immunosuppressive therapy ahead of them. There’s always going to be the potential for the rejection or the failure of that transplant for that individual where they may need another transplant somewhere down the line.

One of the major causes of kidney failure is diabetes, and another one is hypertension. And those are both illnesses that we have treatments for, if we provided them to the people who actually need them. And so instead of pouring however many billions of dollars are being poured into xenotransplantation research, what if we put that money somewhere else where we might actually be able to prevent organ failure in the first place? That would truly benefit lots and lots of patients.

While it can sometimes seem like humanity is hell-bent on environmental destruction, it’s unlikely our actions will end all life on Earth. Some creatures are sure to endure in this age of mass extinction and climate crisis. Over time, they will adapt to a harsher world we’ve helped create, evolving to meet the moment as best they can. 

Some of these transformations have gotten underway in our lifetimes. Climate change, some research suggests, is already “shape shifting” animals — shrinking certain migratory birds and speeding up the life cycles of amphibians, for example. No one knows exactly what changes to plants and animals will transpire in the years to come. Still, evolutionary biologists say it’s worth trying to imagine what creatures will evolve in the future. 

“I do think it’s a really useful and important exercise,” Liz Alter, professor of evolutionary biology at California State University Monterey Bay, says on the latest episode of Unexplainable, Vox’s podcast about unanswered questions in science. In thinking about the animals of the future, Alter says, we must consider how we’re changing the environment now. “It’s a very sobering thing to think about the long future,” she says.

I spoke to several evolutionary biologists and paleontologists who, along with Alter, helped me imagine what animals might exist one day — say, millions of years into the future — and how our actions could spur their arrival. At the very least, it’s reassuring to know that life almost certainly will find a way, with or without us. 

But it may never be the same. 

Animals that might make it

What animals are likely to exist tens of thousands, or even millions of years from now?

That’s the big question I posed to everyone I spoke with, and their responses fell along three main lines of thinking. 

Some started off by thinking about which animals alive today are most likely to endure human-caused climate change and mass extinction. (Scientists have identified five major extinction events in natural history, and many say we are living through or on the cusp of a sixth one now, caused largely by human activity.) Others began by imagining the potential environments of the future, and what adaptations might lead creatures to survive in them. A third group thought about the deep history of life on Earth, and what types of animals that used to roam the planet might return, in new forms, long after we are gone.  

First off, the survivors: “These are rats, rodents, and also things like cockroaches and pigeons,” said Jingmai O’Connor, a paleontologist at the Field Museum in Chicago. These animals “are doing just fine despite the worst that we’re doing to this planet.”

If these species survive the ecological changes that are occurring now, they might also evolve to fill ecological space left behind by extinct animals. For instance, if tigers go extinct in the next million years, perhaps flightless, carnivorous pigeons and rats will grow to the size of ostriches and snack on the animals that tigers once ate. It’s impossible to predict which specific adaptations might emerge in which animals, but it’s clear that as some species die off, they leave a gap in the food chain that can be filled by other species.

In the far, far future, rodents are especially well poised to thrive if mammal species continue to go extinct. By introducing rats everywhere we’ve settled, humans have increased the genetic diversity of rats, which makes them more adaptable to their surroundings. More genetic diversity means “potential solutions to different [environmental] challenges they might face,” says Alexis Mychajliw, a paleoecologist at Middlebury College. Already, scientists have noted rats evolving adaptations to thrive in specific cities, like New York. They might even be able to further adapt to living amid heavy metal pollution and radioactivity, or to be able to eat toxic waste, Mychajliw says. 

And if life on land grows too harsh, rats may be able to slowly adapt to water. Perhaps their evolutionary descendants will lose their fur or sprout flippers, developing streamlined bodies suited for a fully aquatic existence. Other marine mammals, like seals and whales, have followed this path in their transition from land-dwelling creatures to aquatic ones. 

Again, these specific evolutionary paths are pure speculation. But experts say they’re within the realm of possibility.

The environments of the future that will shape evolution

The second way to think about animals of the future is by imagining the environments of the future. Environments can drive evolution by exerting selection pressure, favoring some traits over others. For example, some birds have evolved long, pointy beaks to draw nectar out of flowers.

If anything, there will likely be plastic in the environment well into the future. Of all the elements that humans have introduced into the environment, plastic waste is already ubiquitous, and remnants of it might linger for millennia if humans go on producing it as we have. Plastic is “a big source of carbon, which all living things depend on,” said Sahas Barve, an evolutionary ecologist at the Smithsonian National Museum of Natural History. Plastic, he added, could become food, and “any animal that can exploit that will be successful.”

In a way, this development would kind of go full circle: Many plastics are made from petroleum, which is called a fossil fuel precisely because it derives from ancient, transmogrified plant and animal remains. So new life forms could learn to eat the leftovers of really, really old ones.

Termites could be one such critter. These insects already have a gut microbiome — a collection of microorganisms that help with digestion — that breaks down cellulose. Like plastic, cellulose is made of a complex carbon polymer, so it’s not a stretch to imagine termites adapting to break down another polymer like plastic.

“I could easily imagine them evolving a microbiome that helps them then digest plastic,” Barve says. Some fungi and bacteria, including some found in the stomachs of cows, are already able to break down plastic.

The distant future is also likely to be more watery, as sea-level rise decreases the portion of the planet covered by dry land. In envisioning a world of rising seas and altered coastlines, some scientists think about how certain animals might take to living in more marine environments. 

Sharlene Santana, a professor of biology at the University of Washington, considers how a bat species might evolve to live off of, and around, the oceans. She imagines a bat with a six-foot wingspan taking shape, capable of gliding like an albatross instead of flapping its wings, perhaps covering hundreds of miles in search of food or islands to roost. It might use finely-tuned echolocation to sense ripples in the water in order to detect fish. (In fact, some bats already do this.) 

“This bat is doing something that bats cannot do today, which is to sail and soar on ocean air currents for very long distances,” Santana says. “I call it the sailing bat.”

Looking to the past to predict the future 

Many of the scientists who spoke to Vox imagined a future environment where humans are no longer around. In doing so, they often drew from animals that existed on Earth before our time — perhaps these types of creatures could make a return down the line. 

If humans were to go extinct, our carbon emissions could still remain in the air for a long time, Alter, the Cal State professor of evolutionary biology, said. That could lead to boom times for plants, some of which can thrive in a CO2-dense atmosphere.

The increased density and diversity of plants, in turn, might eventually increase the concentration of oxygen in the atmosphere. Researchers have hypothesized that the growth of insects depends in part on the concentration of oxygen in the atmosphere, which could lead to insects developing larger bodies, Alter says. So a future, oxygen-rich world is one that might be able to foster rabbit-sized praying mantises, or “ants as large as hummingbirds and dragonflies as large as hawks,” Alter said.

It sounds extreme and these visions of the future are merely educated guesses. Then again, something like it has happened before: About 300 million years ago, in the Carboniferous era, the atmosphere was more than 30 percent oxygen, compared with 21 percent today. The fossil record reveals that insects around that time were far larger. 

Mairin Balisi, a paleoecologist at the La Brea Tar Pits in Los Angeles, thinks about what type of apex predators might rise to the top of the food chain if humanity does blink out. To that end, she considers what predators existed before humans.  

“When we think about large predators in North America alone, we think of the gray wolves, the mountain lion, or the grizzly bear,” Balisi says. But large predators on the continent were much more common up until around 12,000 years ago, during the Pleistocene epoch or most recent Ice Age, with many species of saber-toothed cats and bone-crushing canines roaming the land. 

In a future world devoid of human beings, Balisi speculates, such large predators might be able to evolve once again. She is most confident about the saber-toothed cats, whose long, sharp teeth and bulky limbs “evolved independently multiple times in the last 40 million years.” If some lineage of felines persists eons into the future, history could very well repeat itself.

What future do we want?

Modern humans have only been around a few hundred thousand years, but what we do today is likely to have ripple effects for how the natural world looks tomorrow. 

The evolution of life depends on the “genetic and development toolkit” as we know it today, says Santana, the biologist at the University of Washington. Because there’s natural variation between animals, some are better at competing for resources and surviving, with the least helpful traits tending to fizzle out, while others crop up with new adaptations. As species continue to go extinct, whether due to habitat loss, agriculture, poaching, or human-caused climate change, many potential sources of diverse life are extinguished from the future, too. 

Scientists can still imagine a world where animals that are endangered today carry on and start new branches on the evolutionary tree. The future doesn’t have to belong to just the rats, pigeons, and insects. As long as manatees, polar bears, and monarch butterflies are around, for example, there remains the possibility of their descendants entering the picture sometime in the future.

All of which is worth thinking about if we are to take full responsibility for our role in shaping what the planet will look and feel like long after we’re gone. When we imagine what creatures could come next, we can ask ourselves: What future do we want for the planet? How hard are we willing to work so that future generations of humans are still around to live alongside it? 

Giant bugs evolving in the future would be “really, really cool,” Alter said. Especially so, she added, “if humans are actually around to see them.”

In the meantime, while it’s heartening to imagine how different species might bounce back in millions of years, “you don’t want to stop investing in the life that’s around us today,” said Mychajliw, the Middlebury paleoecologist. “There’s a lot we can do right now to ensure that we protect species, protect their genetic diversity, and protect their ability to respond to change.”