Science Friday - Biologists Call For A Halt To ‘Mirror Life’ Research

Episode Date: January 8, 2025

You’re probably familiar with the concept of handedness—a glove made for your left hand looks basically like the one for your right hand, but won’t fit—it’s a mirror image. Many of life’s important molecules, including proteins and DNA, are chiral, meaning they can exist in either a left-handed or a right-handed form. But on Earth, nature only uses one version or the other in living organisms. Your proteins, for example, are all the left-handed version, while your DNA is all right-handed.With advances in synthetic biology, it could be possible to build an artificial organism that flips that shape, having right-handed proteins and left-handed DNA. Writing in the journal Science, an international group of researchers recently cautioned against anyone trying to create that sort of so-called mirror life, saying that it poses the threat of “unprecedented and irreversible harm” to human health and global ecosystems.Dr. Drew Endy, a synthetic biology researcher at Stanford University and one of the authors of that warning, joins Ira to discuss the concept of mirror life and why a group of researchers felt compelled to call for a halt to mirror life experiments.Transcripts for each segment will be available after the show airs on sciencefriday.com. Subscribe to this podcast. Plus, to stay updated on all things science, sign up for Science Friday's newsletters.

In a mirror organism, many important molecules would be in opposite-handedness of those in regular life. So why is that troubling to researchers? Why would you ever make a microorganism that's resistant to most of our antibiotics? That's a really bad idea. It's Wednesday, January 8th, and this is Science Friday. I'm SciFri producer Charles Bergquist. In so-called mirror life, proteins would be right-handed instead of left, while DNA would be left-handed instead of right. Recently, an international group of researchers argued that work toward creating that kind of organism should stop.

Just don't do it. Synthetic biology researcher Drew Endy spoke with Ira about the concept of mirror life and some of the concerns in the research community. Here's Ira. Dr. Drew Endy is one of the authors of that warning. He's also an associate professor of bioengineering at Stanford University. Welcome to Science Friday. Glad to be here, Ira. Thanks for having me.

Nice to have you. First of all, why might a researcher want to create some kind of mirror bacterium or other kind of life? It's like research in general. The motivations range from it's cool. Doing something new is unbelievable. There's that element of it. And then it's also practical. Like, what's it good for?

There's a lot of things that can be beneficial. If you can make mere molecules, they have different properties that might make a medicine last longer or have different better impacts, fewer side effects. So it's everything from just pure basic science and the love of science to some fairly, you know, useful possibilities. Right. Well, you certainly have my interest now. So I want to delve a little bit deeper into this. For example, would a mirror E. coli be just like a regular E. coli, but have right-handed proteins and left-handed DNA, for example? We think so is one thing to admit, right? We have every reason to believe it would be a bacteria, but just be the, mirror version of the bacteria. So imagine if you're looking at yourself in the bathroom mirror and the mirror version of yourself came out of the mirror into the world, you'd still expect it to be

you and just be the mirror version of you. So I think that's what it would be like at the bacterial level too for what that's worth. Do we have the technology for this today or are there still hurdles to actually overcome this? I would say significant hurdles. This is one of those things that is we believe possible but not eminent. One of the reasons why this article came together now is there's been tremendous progress in making mere enzymes. So the enzymes that make nucleic acids, RNA and DNA. There's been incredible work by colleagues in China, researchers in China, to make

mere RNA polymerase and mere DNA polymerase, and suddenly you can make mere nucleic acids, It's the things that are at the core of life, the so-called central dogma. So you look at that and you go, wow, this is really significant progress. On the other hand, other things that biology absolutely needs, like the ribosome, the so-called molecular machine that makes proteins, nobody's made a mere ribosome. And that's going to be a lot harder to pull off. So there's debate within the research community in terms of how far away are we from somebody being able to do this? and some of my colleagues will say it's 10 years away or 30 years away or it's never going to happen.

I don't look at this so much like a scientific project. I look at this like a construction project. One of the things I've learned is when you're trying to explain how long it might take to do something, if it's a science project, I think it really has a lot of ambiguity. But if it's a construction project, the better way of thinking about how long it's going to take is not how much time it's going to take, but how much money it's going to take. And so I might imagine that it would take somebody, you know, $500 million to make a serious attempt at building, say, a mere e-coli. Now, $500 million is a lot of money, to say the least. But when you look at the types of projects that get organized in research these days, you think about the artificial intelligence work.

There's a lot of people who can organize that amount of money. And so from my perspective, you know, that really helped me feel that it was important to talk. talk about this now before anybody could get organized enough to make a serious overall attempt at it. Okay, let's talk about this. You and your colleagues who wrote shared these opinions with you, you're very concerned about this. What are your concerns? Yeah, it's interesting. For me, before this conversation started within the research community, I wasn't waking up in the morning and going to go, oh, my gosh, mere life, what are we going to do about it? However, when some very good colleagues approached me to talk about it. My background in engineering is about building cells,

building regular cells, not mere cells. I bring that type of expertise to the puzzle. The initial concerns expressed are that if you made a mere E. coli, that such a bacteria would be able to get into our bloodstream, get into our bodies, and our immune system would have a very difficult time recognizing it, developing immune response to it. And so suddenly the type of infection you might be at risk of would be greater than normal. Eventually it might figure it out, but at which point your immune system might be on its heels. So that's more than a little bit concerning,

and you can start there. Of course, we should be able to develop antibiotics, but they'd have to be new antibiotics. And so if you look at this, why would you ever make a microorganism that's resistant to most of our antibiotics? That's a really bad idea. So a lot of people start with that,

and that in the itself is sufficient. actually, I should back up and say something pretty carefully. When people hear about the idea of, say, a mere E. coli, it'd be like, well, it would have to grow on mere food. You know, the inputs that power this E. coli, where are they going to come from? Because a mere bacteria would eat mere food, right? And that'd be a reasonable assumption to make. But not every molecule is a mere molecule. There are some things that don't have chirality, don't have handedness, things like glycerol.

And so e-coli can grow on things that are not chiral. And so within your bloodstream, there's enough food, we believe, for a mere version of a microorganism to reproduce. The other thing that people often wonder about is where are the amino acids, the building blocks of the protein is going to come from and have the mere handedness. And these bacteria that we already have in nature are pretty well equipped. They've got a good biochemical kit, and they actually can make all their amino acids if they need to.

And so E. coli can already make all 20 amino acids. And so a mere E. coli could make all the mere ingredients it needs to reproduce. But in any case, the thing that really did it for me was when we started talking about nature and ecology. And so imagine if a mere bacteria was made and it got out into the environment. It would come into competition with all the natural organisms. And, you know, I don't think it would take over in and of itself, but it would probably establish a niche, be hanging out there.

And so then the question is, so what? And then the problem becomes, and this might sound a little funny or strange, think about all the other creatures that are now going to encounter this thing. My favorite example is chipmarks. I love chipmunks. And so if a mere bacterium

could infect a person, it could probably infect a chipmunk too. And unlike a person, I'm not going to be able to go to clinic and get antibiotics, you know, the new mere antibiotics, the chipmunks just going to get be toast. And so having a mere microorganism that was promulgating through the environment and establishing itself as a basically in different new niches in the environment

would seem to offer the possibility of a fairly grave hazard to many, if not most other creatures out there in our various ecologies. And that, to me, feels closer to existential, something I don't want to touch with a 10-foot pole. Right. Do people working in this field see the threat that you do? You said that their existential threat is not quite your existential threat. But is there any form of ethics here about stopping this work like there was back in the 70s when genetic engineering started to stop it and say, hey, let's think about what we're doing here?

I think that's exactly what this article is about. You know, you've got a significant coalition of scientists from many countries. some of whom had been doing work towards building mere life, and we're all coming together and we're saying, don't do it. And let's talk about it. How would you get together and talk about it? There's a couple different things, right? So one thing we've done is created a resource

where people can ask for money to get together and have a conversation about it. So you track down a website called Mirror Biology Dialogues, and you want to have a meeting to talk about this, you know, seriously, you can get some support. So there's going to be a whole bunch of conversations throughout this year, including Institute Pesture to talk about it. Since you mentioned in passing the conversations in the 1970s, it's worth acknowledging that, you know, the big conversation happened in February of 1975 at Isilamar, California. So the 50th anniversary of that event is coming

up next month. That was a Paul Berg, I think, if I recall. Yeah, my late, my late college like Paul Berg and others, Maxine Singer, David Baltimore. They organized that meeting in February 1975. We are having an event at Asilamar at the end of February to talk about things arising in biotechnology today and how to best mind them. One of the five topics we'll discuss is building cells

and near cells, the possibility of near cells specifically. So that's another example of a conversation coming up soon. Right. That's interesting. to know because I remember that conference. Let me just backtrack a bit and understand exactly what you're saying. Are you saying do not ever do it at all or can you see a place in which it can be done safely? Right now we're saying don't do it. And let's stop working towards this goal and not proceed further. If people want to put forward a good case for why we're wrong,

we'd love to hear though. But right now our position is let's not do. this. I want to give a lot of credit to the colleagues working together to do this. Again, some of the signatories on this and authors of the piece are folks who had, until before we have this conversation, this is what they're doing. And they've decided that very courageously, it's like, actually, I've thought about this and this is a bad idea, and we shouldn't do it. Again, somebody's not going to do this tomorrow. It would take at least a thousand days of a thousand people working on it. That's as fast as you could do it. I think.

Right. And so it's a type of decision-making process. It's more like deciding where you want to sail when you're leaving the harbor, but before you leave the harbor or as you're leaving the harbor as opposed to, hey, I'd better steer the ship when we're about to crash on the reef. Right. What was it? It was in 2023 when he had a whole bunch of folks in artificial intelligence,

you know, frantically signing letters about the dangers of AI. But like, meanwhile, you've got huge organizations fired up running as fast as they can to make artificial general intelligence. That's what it looks like when you're trying to steer the ship and you're very close to crashing on the shores. Whereas I hear, I think, we're actually, some people would say you're too early. You know, this isn't eminent. But actually, that's when you want to make good decisions, what it is too early.

After the break, I'll look at some more hopeful applications of synthetic biology. Stay with us. You know, this all sounds somewhat threatening for just a few days into the new year. But let's talk about some positive things. What are you excited about in your field of synthetic biology? What should we be looking forward to? Well, I put my engineer hat on. The way I think about it is the physics of flourishing are really terrific.

Biology as a domain, living systems, they and we operate at this intersection of energy and materials. You think about photosynthesis, all the plants on Earth. They're harvesting about 100 terawatts of energy. civilization is running on about 20, terawatts of energy. So just 100 is five times more than 20. So when I say the physics of flourishing are outstanding or really good,

what that suggests, just the back of the envelope math, is if we could partner with biology correctly, we could get to a near future where within a generation, humanity would be able to equip ourselves with the capacities to make the stuff that we need without being in conflict with the rest of life on Earth, right? So it's barely easy for me to imagine things working out pretty well on this planet.

And for that to be true within our children's generation, if we just went all out and made it real. So then to come back to your question, I write, you know, like what's going on with synthetic biology? If you've never heard about synthetic biology before, it starts with the word synthesis. And I'm in love with the word synthesis. You go back into the history of that word, it means composition or putting together. a musical synthesizer, you know, composing a piece of music or performing a dance. And so when you put the word synthesis in front of biology, we're learning how to compose biology. This field in its modern form is about 20 years old now. And just looking at the arc of basic progress in the field, we're starting to get better and better and better at composing biology. People are building

very complicated pathways inside cells to make medicines in new ways. This last year, In 2024, I don't know about you, but I had two bioengineered creatures in my house. One was a bioluminescent petunia that emits light. I gave it to our boys that they were nightlights. And then these so-called blueberry tomatoes with some snap dragon genes in them that make antioxidants like in blueberries. I don't grow a lot of tomatoes, but these are the first tomatoes I grew and they're pretty good. But it's interesting, right? This is first time in my life, I'm a consumer of a, we have consumer electronics.

Now we have consumer biologics. And so that was shocking in a good way to me last year. I got a colleague Mike Fishbach at Stanford, who's done incredible work with his team on reprogramming the bacteria that live on our skin. There's a microbe called staff epidermitis, and they can have that organism present an antigen and tickle your immune system. so it develops an immune response. This has been done in mice, not people.

One of the early demonstrations was to develop an immune response against melanoma. So imagine having a skin cream that vaccinate you against skin cancer. There are a lot of reasons in my world to be excited about what biology could offer. And when you zoom all the way out to the planetary scale, you know, it feels like we can develop biotechnology in safe and responsible ways and basically give it to folks so that they can solve local problems. If I link it back to the topic of building cells, the thing that's still true about bioengineering today,

it's like before we had the light bulb, and Edison and folks were working on, how do you get a light bulb to work? And how many light bulbs did they have to, prototypes that they have to test? And it was like tinker and test, tinker and test. Bioengineering is like that still, because biology is still very mysterious at its core.

There's no cell on Earth that we totally understand yet. And so what that means is we take our best and brightest ideas. And once we implement them in a DNA molecule, we have to test that molecule to see if it's actually going to work. We don't know ahead of time. It's not like building a building or even building a bridge or airplane where our models are good enough. We can test it on the computer before we build it. You really have to test biology and reality to show that your designs work. The most exciting thing to me, I think we're on the precipice of understanding how to build

cells, natural cells, not mere cells, and that will become a foundational platform, a big breakthrough that makes routine the building of biological systems at the cellular scale. I think of it, like there were computers before operating systems, and then computers after operating systems, and I see that bioengineering is about to get its first operating system at the cellular scale. So that's what I'm most excited about, if you want me to nerd out. You know, that's where I am. Well, we'll have you come back and talk about this because this is fascinating. Dr. Indy, happy new year and thank you for enlightening us about this fascinating world.

Happy 2025, Ira, looking forward to making the world pretty good. And that's it for today. Tomorrow, we'll whisk you away through the magic of radio to the Pacific Northwest for a look at the world of Lykins. Lots of folks helping the show happen, including Jason Rosenberg. George Harper. Kathleen Davis. Shoshana Bucksbaum. And many more.

I'm sci-fire producer Charles Burkwest. Thanks for listening. We'll see you soon.