Stopping the science that could stop the world

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1:23Do you ever feel like, I don't know, you take a step back one night after a long day at the lab and just be like, whoa. In a way, it's like playing God a little bit, inventing life. It's definitely fascinating to be able to do that. I don't think it's really playing God because if you think about it, everything that the creator made is part of the physics. It's part of the world, the universe that we exist in. And I'm not doing anything that goes outside of the existing universe. I'm still within the laws of physics. So in a way, I'm expanding on the creation, if you want to think, using that framework.

2:04I'm expanding on the ways in which biology can do life. I asked Kate Ademala about inventing life, because it's her job. Her lab takes biological bits and pieces, like membranes, proteins, and DNA, all dead, isolated parts, and they put them together into synthetic cells that can feed, grow, and divide. Kate says these cells are not alive. Not yet. but that they prove that making different versions of life is possible. You know, with all due respect to Mother Nature, there is a lot out there that nature never explored. And I think that's limiting the things that we can do. But I'm not limited by that.

2:56I'm limited by my imagination and laws of physics. And let's see what happens when you create lifelike forms that never existed before, that nature never had a reason, motivation, or tools to make. And when I talked to Kate last summer, I was struck by how many times this idea of physics and limits came up in this way. Sometimes people ask the questions of whether it's pushing the boundaries too far. And my answer is, as long as we are within the realm of physics, we're not doing something that's absolutely crazy. We're not doing something that's unnatural. I was struck by it because earlier in her career, Kate had abandoned a research project that she was really excited about.

3:40That is, until she realized that it had some pretty crazy and unnatural consequences. But that's kind of what the brain is for. We look at what could happen and say, this is too dangerous. We will not be doing it. Despite still thinking it's cool because it's too risky. This is the final episode of our series, Life from Scratch, all about this field of synthetic cell biology, where scientists like Kate are tinkering with life at its most fundamental levels in order to revolutionize medicine and save the planet. And to hear more about this utopian vision for the future, you should definitely listen to the start of the series.

4:31But today, I want to focus on the darker side. When scientists write their own rules for life, how do we know what could go wrong before it's too late? I'm Meredith Hodnott, and this is Unexplainable.

5:03In 2019, Kate was just a year and a half into running her own lab at the University of Minnesota. I was still very early in my career. I was still trying to find what exactly I'm going to focus on. So that was my first real adventure. That's when I first actually started considering making Mirror Life. Mirror Life. This can be tough to imagine, but stick with me. In chemistry, some molecules have special shapes that can come in two different versions, right-handed and left-handed. So think about how your hands are the same shape. They have all the same fingers in the same order, but they are mirror versions of each other.

5:51So when I give you two thumbs up, the fingers on my right hand curl to the left, while the fingers on my left hand curl to the right. It's the same thumbs up shape, just mirror versions of each other. These special molecules are called chiral, which comes from the Greek word for hand. A lot of the molecules needed for life inside of a cell are chiral. DNA, RNA, proteins, they all have this special handedness shape that means that they can come in two versions, a right-handed version and a left-handed version. But in the natural world, even though these molecules can have two versions, they only ever show up exclusively as one version or the other.

6:40DNA always twists to the right, no matter what living thing you got it from. All life on Earth follows this pattern, and we don't understand why. Except that to have something like this be such a bedrock, fundamental truth of life, the reason must go all the way back to the origins of life itself. Homochirality, or the same-handedness of biology, is still one of the biggest mysteries in science today.

7:16So, for one of her first big projects, Kate wanted to try and make a cell with the mirror versions of all of its molecules for life. So, for example, the DNA would have the same twisting shape that we'd recognize, but it would turn to the left in this proposed mirror cell, rather than turning to the right like it does naturally for all other life on Earth. We don't know how to make a mirror cell. We don't have a mirror cell. But that was a super attractive goal. I thought that we're going to learn a lot doing it. And we're going to develop a lot of technologies that we need. Kate's wildest dream is to make all the medicines, fuel, and materials we need through biology.

8:03And mirror life might have helped her get there because of its unique chemistry. Let's say chemical reactions are kind of like a molecular handshake. If I hold out my right hand, and you hold out yours, then our hands clasp. Thumbs up, palms touching, they are complementary shapes. But if I try to shake your left hand, things get a little awkward. Our hands just wouldn't fit. That's kind of like what would happen if mirror cells and natural cells would try to interact. And that had some advantages. Kate hoped to use mirror cells to make medicine that could target a cancerous tumor, for example, without the patient's immune system being able to chemically recognize it.

8:53We were hoping that it would be invisible to the immune system so it can become a therapeutic, that we can make eventually a mirror cell that we can inject into a patient's body and it can treat whatever disease we want it to treat. And for Kate's biomanufacturing dream, she hoped natural bacteria or viruses would have a harder time infecting a mirror cell. You could set up a factory with a living cell and that cell would not be susceptible to all the contamination that normal bioreactors are susceptible to. Now, to be very clear, a fully living mirror cell was an audacious goal. Something that would take decades and a lot of scientific collaboration to achieve.

9:42But Kate was excited to start down this path. I was really invested in that project. I was really excited about the possibilities of it. And because none of us on the original team were ecologists or immunologists, We were really excited about all those things that later became the biggest concerns of mirror life. That's after the break.

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12:30Magic mirror on the wall. Who is the fairest one of all? David Relman is a microbiologist, an infectious disease specialist, and he's the guy you go to if you want to gut check your concerns that some biological research could go very awry. I've thought for many years about pretty important threats from the microbial world. He led an assessment of diplomats and other government staff mysteriously falling ill with Havana syndrome. A cluster of unexplained concussion-like symptoms. He reviewed the FBI's scientific evidence for the cases of anthrax sent through the mail in 2001. In just a week's time, we have had four confirmed cases of anthrax, all with media connections.

13:21Once he even consulted for some Hollywood producers. I promised I wouldn't act on any of the ideas that I was suggesting to them as the plot line for a sinister movie. So in 2022, David's friend, Kevin Esvelt, an associate professor at MIT, called him up and invited him to dinner to talk about mirror life. And Kevin said, we thought it might simply be a laboratory curiosity. Now, Kevin said, I'm not so sure. I'm not so sure that it would be benign. Mirror life didn't exist yet. But for the first time, this research was starting to look feasible, even if it was decades away. So how do you parse the benign from the dangerous?

14:12To figure that out, David focused on how a mirror cell might interact with the natural biology of our world. What would be the fate of this cell outside a laboratory? Because if it couldn't grow, then we don't really have a problem. Right. It's like the wimpiness of it is important. Exactly. Exactly. To grow, a mirror cell would need to eat. It would need to interact with the Earth's natural biology for food. And to David's rising concern, he found out that it would probably be able to find some of the nutrients it needed. Things like glycerol, for example. Glycerol is a sugar. It's found widely on this planet.

14:57Bacteria can grow just fine on glycerol alone. But then our ecologist friends said, all right, but the real determinant of the fate of any living thing is not just can it grow, but will it die? Basically, outside of the lab, would a mirror cell have a predator? Something in our natural world of biology that could kill it. The more they looked, the more anxious David got. They found that natural organisms wouldn't be able to eat it and digest it. Viruses wouldn't be able to infect it. It would just be too chemically different. But one of the scariest moments for David was looking into the science of immune systems, how bacteria interact with our bodies.

15:53As I am sitting here now and you are sitting there, bacteria are getting into our bloodstream every single minute that we sit here. Tiny numbers, but they're getting through. Who are they? They're not disease-causing organisms. They are the healthy bacteria of your human body. They're leaking into your tissues and bloodstream. We know this because we can grow them from your blood. If you brush your teeth, there's a shower of organisms that go into your bloodstream, and they're gone in literally in minutes. Gone. Killed. How did that happen? Your immune system ate them, killed them, saw them as bacteria that don't belong there, and took care of them.

16:38And if that were to happen with a mirror bacterium, none of that control happens. The outcome is completely different now. Just a few could slip past an immune system completely unnoticed, totally invisible to our body's defenses. And so a nightmarish vision of the future was coming into focus for David. If even a simple mirror life cell could get into the bloodstream, it would just hang out, untouched, and reproduce, building up in our bodies and bloodstreams like plaque. So the long and short of it is, mirror bacteria would be able to grow, maybe in a wimpy way, but they would not be killed at all.

17:31And so the net balance is these things keep growing. It's like the ultimate invasive species. The ultimate invasive species, that's right. And that ultimate invasive species would act as an invasive species in the human body. The ultimate outcome, we think, is death for us. Our organs and our gut and our bloodstream would be choked with bacteria that would just keep on growing and could not be killed. and so that started to become a very sobering conclusion not just because humans would be at risk but the same thing would hold true for every animal on the planet worms the birds that eat the worms the predators that eat the birds the fish that become infected the predators that eat the fish.

18:36You can see where this goes. We won't know that it's in those species until we start to see dead bodies. And the ecologist told us that these ever-growing mirror bacteria, impervious to death, would slowly displace the normal bacteria in the soil and in the oceans. And now the geochemical cycles that maintain the balance of environmental conditions on the planet would be in jeopardy. So suddenly we're talking about something which, if we're right, could be a catastrophic threat to life on this planet as we know it. Yeah. What really scares me is that although I can't tell you how long it is before we start to see dying hosts around the planet, we will see them at some point.

19:37And once we do, we have no way of stopping it.

19:45Wow. Do you have a moment when that settled onto your shoulders? Yeah, I mean, I woke up in the middle of the night thinking about it. And my first reaction is, there's something wrong. This can't be right. This cannot be right. It really scared me because I really would rather think that humans are not capable of making something that doesn't exist, which could threaten life as we know it on the planet. I really, really would like that not to be the case.

20:24This was a lot to process. Mirror life wasn't like one of the worst-case scenarios that David usually studied in microbiology. Pandemics caused by deadly viruses or infectious bacteria. You know, the kind where a whole lot of humanity dies, but ultimately, after the devastation, life goes on. Mirror life would be different. The question now was, how far away was the technology that could potentially destroy the world? David knew that mirror life didn't exist yet, but he needed to talk to someone who was actually doing this research. Someone who was really on the path to building mirror life. It doesn't make for a good movie.

21:15Someone like Kate. It's not a story that is like one day you walk up and you realize I have to stop the end of the world. It's never that much fun. Over the course of a few months, Kate talked with David and the immunologists and ecologists that were a part of this slow-growing mirror life coalition. And we started asking what happens if there really is a cell in the environment that is invisible to the immune system, that's invisible to the predators. And as we started digging deeper into it, we realized that probably nothing good would happen. And that was pretty much the moment where I realized that, okay, if they're invisible Damien's system, then they should never exist.

22:01And that's what really caused Kate to go, you know, I may have been wrong. I may be wrong. I realized that I don't actually want to have anything to do with it because if I cannot justify to myself how to do it safely, then I can't really expect to justify it to anyone else. And now, to me, as someone who has heard enough stories about people who, for whatever reason, think about doing things that are really irresponsible or downright dangerous, I'm thinking, Kate, it's not you that I'm worried about. It's this crazy person over here who would do it. To David, the potential stakes of mirror life were so catastrophic that no one should even come close to opening that door.

22:49So he and a colleague went to someone you might recognize from the beginning of this series, one of the founders of synthetic cell biology. He's been really driving the science, but he's also been helping to build this international community. Kate's mentor, John Glass. and John was immediately receptive. They laid the whole thing out and said, can you think of a reason not to be worried? They were talking about the fact that mirror proteins are invisible to the immune system. And I kept coming up with things that I thought that would make it not be a thing. And everything I thought of, they shot it down with actual data.

23:32and it was mortified. It made me question a lot of what I was doing. Such a cell would potentially lead to the end of life on Earth as we know it. An environmental catastrophe equivalent to all-out nuclear war. John went, Jesus. You know, I'm convinced. In fact, I remember I hadn't even finished the whole story and John said, wow, I see your argument. I want to think about this more. I can tell you right now that building a mirror cell is feasible. They said, you know, their guess was 10 to 30 years. I think a committed team could do it faster if you had a half a billion dollars. I'm not sure, but why would anyone want to?

24:28This is something we don't need to do. Up until this point, David and the other scientists concerned about mirror life had been very cautious about bringing people into the conversation. In part because we thought if we were wrong, we could do some harm. It's like a crying wolf kind of fear? Yes, yes. But now they were feeling confident in the science. They had checked and rechecked their work, and they were ready to share their concerns with the world. By the end of 2024, David, Kate, John, and about three dozen other scientists from around the world came together to write an explosive paper in the journal Science.

25:15Beat by beat, they methodically laid out their argument that there should be a worldwide moratorium on mirror life research. David says that mirror life is unique both in its apocalyptic consequences, but also in that its development is so far out in the future. There's still time. There's still time to think through the guardrails and red lines that could stop mirror life from being possible, while still letting other synthetic cell research continue. It's going to be challenging, but I think possible. And so that's what makes this really unique. if we were to wait longer. Then it becomes harder and harder to draw a sharp line.

25:57And now it becomes much more like the cases that we've already had to address, like human germline genome editing. That was thrust upon us almost at the point where it was doable at that time. And we saw what the consequence of that was. People went ahead and did it anyway, just to show that they could, thinking it wasn't so bad. And that's something we cannot afford to have happen here. We cannot. The Mirror Life paper got a huge response. There's a new warning from a group of over two dozen biologists. They are calling for a ban on mirror cell research. Warning, it's too dangerous. So introducing it to Earth would be a bit like introducing an alien invasive species that nothing on Earth has evolved to deal with.

26:52The threat they pose is right up there with anything Hollywood could throw at us. Lawmakers and policymakers from across the globe have been taking these concerns very seriously, debating the best ways to safeguard this technology while letting scientists continue to pursue other less potentially catastrophic synthetic cell designs. But the real power to stop mirror life before laws and policies can be established, will be the scientific community making this research taboo. Fortunately, we started talking about it early enough that this is not a process that a single person or even a single very well-equipped lab or even a state actor can complete.

27:36We're far enough away from making a mirror cell that it requires the effort of a whole community. As scientists, everybody we've talked to has said, okay, we're not going to do this. And getting rules in place that could function worldwide, that is an admirable goal. But in reality, as long as this whole scientific community is aware that this is something we should never do, I think we can always keep this possibility 10 to 30 years away. You know, right now, no one stopped, no lawmaker, policymakers stopped mirror life research. This is all community driven. And that makes me feel a little safer because we're the people on the ground that would spot those risks first.

28:27Yeah. If you went back in a time machine to visit your 2019 self, what, is there something you would want to like communicate about mirror life? I would tell her to read more about immunology, but she would probably laugh at me because who am I to lecture her on immunology? But on the other hand, I'm actually glad it happened the way it did, because thanks to the fact that we had this mirror life research project going, people started truly believing that it's possible to make a mirror cell one day. Earlier, it was just almost a science fiction, like an abstract idea. And because we were actually working on it, making progress, research progress towards it, people started believing taking it seriously.

29:15People started believing that mirror life is not just a science fiction idea. It's like if you try to talk seriously right now to people about possible risks of time travel, no one would take you seriously. Everyone would just laugh. But if you had actual evidence that a time machine could be built within the next decade, oh, then people would take you seriously. So I think all in all, I wouldn't really change anything because this original little progress we made towards it only helped us now when we're talking about the risks. Are you scared that something you're working on now might be viewed very differently six years from now?

29:57there's always a possibility but this mirror life project taught me a lot about risk assessment um i'm doing it early and often now i'm looking at the technologies that we're developing and i'm trying myself to poke holes in every safeguarding scenario that we come up with so that kind of if anything made me feel a little better about that because the fact that we didn't miss the risk of mirror life, makes me a little more confident that we can spot those risks early. This was why I was really curious to hear last year that Kate only felt limited by her imagination and the laws of physics. Because part of that imagination is imagining potential consequences.