Biologists Call For A Halt To ‘Mirror Life’ Research

IRA FLATOW: This is Science Friday. I’m Ira Flatow. You’re familiar with the concept of handedness, right? A glove made for your left hand looks basically like the one for your right hand, except it’s a mirror image.

Well, many of life’s important molecules, proteins, DNA, and more, can also exist in either a left-handed or a right-handed form. But it turns out nature only uses one hand or the other in living organisms. Your proteins, for example, are all the left-handed version.

But now, with advances in biology, it could be possible to build an artificial organism that reverses that order, mirror life, so to speak. Writing in the journal Science, an international group of researchers recently cautioned against anyone trying that experiment, saying that it poses the threat of unprecedented and irreversible harm to human health and global ecosystems.

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.

DREW ENDY: Glad to be here, Ira. Thanks for having me.

IRA FLATOW: Nice to have you. First of all, why might a researcher want to create some kind of mirror bacterium or other kind of life?

DREW ENDY: That’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 there’s also practical, what’s it good for. There’s a lot of things that can be beneficial if you can make mirror 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 useful possibilities.

IRA FLATOW: 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?

DREW ENDY: We think so. It’s one thing to admit. We have every reason to believe it would be a bacteria but just be the mere 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. It’d just be the mirror version of you. So we think that’s what it would be like at the bacterial level, too, for what that’s worth.

IRA FLATOW: Do we have the technology for this today? Or are there still hurdles to actually overcome this?

DREW ENDY: I would say significant hurdles. This is one of those things that is we believe possible but not imminent. One of the reasons why this article came together now is there’s been tremendous progress in making mirror 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 mirror RNA polymerase and mirror DNA polymerase. And suddenly you can make mirror nucleic acids, 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 mirror 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 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 $500 million to make a serious attempt at building, say, a mirror 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, a lot of people who can organize that amount of money. And so, from my perspective, that really helped me feel that it was important to talk about this now before anybody could get organized enough to make a serious overall attempt at it.

IRA FLATOW: OK. Let’s talk about this. You and your colleagues who shared these opinions with you, you’re very concerned about this. What are your concerns?

DREW ENDY: Yeah, it’s interesting. For me, before this conversation started within the research community, I wasn’t waking up in the morning and going, oh my gosh, mirror 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 mirror cells. And I bring that type of expertise to the puzzle.

The initial concerns expressed are that if we’ve 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 an 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 then 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 and of itself is sufficient.

Actually, I should back up and say something pretty carefully. When people hear about the idea of, say, a mirror E. coli, it’d be like, well, it would have to grow on mirror food. The inputs that power this E. coli, where are they going to come from because a mirror bacteria would eat mirror food? And that that’d be a reasonable assumption to make.

But not every molecule is a mirror 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 mirror 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 proteins, going to come from and have there the mirror 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 mirror 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 mirror bacteria was made and it got out into the environment, it would come into competition with all the natural organisms. And I don’t think it would take over in and of itself, but it would probably establish a niche. It’d 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 chipmunks. I love chipmunks.

And so if a mirror 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 a clinic and get antibiotics, the new mirror antibiotics. The chipmunk’s just going to be toast.

And so having a mirror microorganism that was promulgating through the environment and establishing itself 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.

IRA FLATOW: 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 and say, hey, let’s think about what we’re doing here?

DREW ENDY: I think that’s exactly what this article is about. You’ve got a significant coalition of scientists from many countries, some of whom had been doing work towards building mirror life. And we’re all coming together, and we’re saying, don’t do it, and let’s talk about it.

IRA FLATOW: How would you get together and talk about it?

DREW ENDY: There’s a couple different things. 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 seriously, you can get some support. So there’s going to be a whole bunch of conversations throughout this year, including Institut Pasteur, to talk about it.

Since you mentioned in passing the conversations in the 1970s, it’s worth acknowledging that the big conversation happened in February of 1975 at Asilomar, California. So the 50th anniversary of that event is coming up next month.

IRA FLATOW: That was a Paul Berg, I think, if I recall.

DREW ENDY: Yeah. My late colleague Paul Berg and others, Maxine singer, David Baltimore, they organized that meeting in February 1975. We are having an event at Asilomar at the end of February to talk about things arising in biotechnology today and how to best mine them. One of the five topics we’ll discuss is building cells and mirror cells, the possibility of mirror cells specifically. So that’s another example of a conversation coming up soon.

IRA FLATOW: 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?

DREW ENDY: 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 that. 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 had 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 1,000 days of 1,000 people working on it. That’s as fast as you could do it, I think. And so it’s a type of decision-making process that’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 better steer the ship when we’re about to crash on the reef.

What was it? It was in 2023 when you had a whole bunch of folks in artificial intelligence frantically signing letters about the dangers of AI. But 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 here, I think, we’re actually– some people would say you’re too early. This isn’t imminent. But actually, that’s when you want to make good decisions, when it is too early.

IRA FLATOW: 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?

DREW ENDY: 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’s 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.

So it’s fairly 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, Ira, 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.

If you go back into the history of that word, it means composition or putting together. Think of a musical synthesizer 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. They’re night lights.

And then these so-called blueberry tomatoes with some snapdragon 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. This the 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 Fischbach, at Stanford, who’s done incredible work with his team on reprogramming the bacteria that live on our skin. There’s a microbe called Staph epidermidis, 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 a melanoma. So imagine having a skin cream that vaccinates 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, 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 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 in 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, that’s where I am.

IRA FLATOW: Well, we’ll have you come back and talk about this because this is fascinating. Dr. Endy, Happy New Year, and thank you for enlightening us about this fascinating world.

DREW ENDY: Happy 2025, Ira. Looking forward to making the world pretty good.

IRA FLATOW: We, too. Dr. Drew Endy, associate professor of bioengineering, Stanford University.

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