Building Life from Scratch with Kerstin Göpfrich

Summary

StarTalk Radio
Episode: "Building Life from Scratch with Kerstin Göpfrich"
Host: Neil deGrasse Tyson
Co-host: Matt Kirshen
Guest: Prof. Dr. Kerstin Göpfrich, Center for Molecular Biology, Heidelberg University
Release Date: September 2, 2025

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Episode Overview

This StarTalk episode takes listeners into the cutting-edge world of bottom-up synthetic biology: the science of building novel forms of life from the most basic components. Astrophysicist Neil deGrasse Tyson and comedian Matt Kirshen sit down with Professor Kerstin Göpfrich, biophysicist and leader of the Max Planck Research Group at Heidelberg University, to explore what it means to create life in the lab, what definitions of "life" scientists work with, and how this emerging field could revolutionize both our understanding of biology and future technologies.

Their lively conversation covers not just the nuts and bolts of building synthetic cells, but also the philosophical, ethical, and practical implications of “playing God” in the laboratory, what counts as alien life, and where this research could lead scientific advancement and humanity itself.

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Key Discussion Points and Insights

1. What Does It Mean to Build Life from Scratch?

• Defining Life (06:01):

  • Scientists haven't reached consensus, but synthetic biologists work with the NASA definition:
    "A self-sustaining chemical system capable of Darwinian evolution."
    -- Prof. Göpfrich (06:15)
  • They aim for "open-ended evolution," meaning systems that can increase in complexity and evolve new functions, not just survive.

• Darwinian vs. Open-ended Evolution (07:01):

  • Darwinian evolution involves survival-based changes; open-ended evolution offers a broader exploration of possible forms and new properties.
  • Prof. Göpfrich emphasizes the importance of mortality for evolution:
    "Introducing death into living systems is absolutely crucial... otherwise, you just have exponential growth and the resources will be exploited."
    -- (08:10)

2. Bridging Chemistry and Biology: Historical Context (09:44)

• The Miller-Urey Experiment:
  • Simulated the early Earth environment to show that simple life building blocks, like amino acids, can arise from non-living chemistry (10:12).
  • Göpfrich draws a parallel between early chemists disproving that only life can synthesize organics, and today’s goal to transition from matter to life in the lab (11:58).

3. The Bottom-up Approach: How to Construct Life

• Starting with Biomolecules (13:07):

  • Göpfrich’s group assembles cell envelopes (lipid vesicles) and builds molecular machinery from RNA, inspired by theories of the “RNA World” (13:57).
  • Instead of mechanical tools, they use computationally designed DNA to code RNAs that fold into functional nanostructures (15:49).
  • "We are trying to assemble a synthetic gene from scratch... DNA which encodes an RNA that folds up into a desired structure while transcribed."
    -- Prof. Göpfrich (15:04)

• RNA Origami:

  • Designing RNA to fold into structures that mimic cytoskeletal components or pores, enabling basic cell-like functions.

• Design Iteration (22:15):

  • Start with computational design, then build and test structures via cryo-EM, tweaking DNA as needed.

4. Creating "Alien" Life—How Different Could Synthesized Life Be?

• Synthetic Life vs. Re-creating Known Life (22:41):

  • Göpfrich describes approaches ranging from encapsulating cellular proteins to creating wholly novel systems.
  • She explains the massive complexity of natural cells—just translating RNA into protein needs 150 genes—and their aim is to simplify: "If we can circumvent the use of proteins... and just build a functional machinery from RNA... then we can reduce the complexity of the system quite a lot."
    -- Prof. Göpfrich (24:02)

• Implications for Astrobiology (26:27):

  • Tyson probes if life elsewhere would use the same DNA-RNA-protein machinery.
  • Göpfrich doubts inevitability:
    "The evolutionary landscape is vast. With life as we know it, we are just exploring a tiny, tiny, tiny, tiny, tiny bit of that."
    -- (27:20)
  • By creating minimal synthetic cells, scientists may discover alternative metabolisms, offering insight into how life could differ across the universe.

• Carbon vs. Silicon Life:

  • Carbon's chemical versatility and abundance make it the clear winner, but exploring alternatives is a frontier for both synthetic biologists and astrobiologists (28:22).

• Convergent Evolution:

  • Tyson and Kirshen highlight how evolution often "finds the same solutions" via unrelated routes—suggesting certain forms are optimal for survival (30:12).

5. Deep Dives: Molecular Handedness and the Limits of Biology

• Molecular Chirality (32:26):

  • All known life uses left-handed amino acids (homochirality).
  • Tyson wonders if right-handed life could exist undiscovered; Göpfrich says no traces have been found.
    "Make me believe very strongly... that the left-handed version is the one that made it."
    -- Prof. Göpfrich (36:32)

• Ethics of Creating Life (40:09):

  • Are we risking dangerous life forms, or "overlords"? Göpfrich reassures: "What we are creating is very, very fragile and requires a lot of care... Ethics is, of course, extremely important."
    -- (40:49)
  • She calls for extending biosafety and containment rules, even for synthetic life forms (41:41).

6. Motivations and Practical Applications (43:02)

• Why Do It? Human Curiosity and Practical Uses
  • Göpfrich: "I'm just super, super curious about what life is and what it could be." (43:02)
  • Building synthetic cells could provide revolutionary manufacturing tools, including advanced therapeutics, vaccine delivery, evolvable materials, and deeper insight into both evolution and medicine (44:05).
  • RNA origami techniques allow more stable and compact therapeutics, with impacts for real-world health (46:05).

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Notable Quotes and Memorable Moments

• On evolution and death:
  "You're the first biologist I've heard be honest about the fact that Darwinian evolution requires that everybody dies."
  — Neil deGrasse Tyson (08:38)

• On ambitions of synthetic biology:
  "In the end it would be amazing to have not just biology 2.0, but also 3.0, 4.0, 5.0 and so on."
  — Prof. Göpfrich (25:22)

• On molecular design:
  "We are trying to assemble a synthetic gene from scratch, a piece of DNA which encodes for an RNA that folds up during transcription... into a desired structure."
  — Prof. Göpfrich (15:04)

• On the vastness of possible biochemistries:
  "The evolutionary landscape is vast. With life as we know it, we are just exploring a tiny, tiny, tiny, tiny, tiny bit of that."
  — Prof. Göpfrich (27:20)

• Philosophy and playfulness:
  "Tell your parents that, too, in case they were wondering."
  — Neil deGrasse Tyson to Matt Kirshen, on being “a part of civilization” (02:32)

• On motivations:
  "It's somehow intrinsic to human curiosity to ask what life is and why it's there and so on. And recreating it, building it is one way to really bring our understanding of life to a new level."
  — Prof. Göpfrich (43:02)

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Timestamps for Important Segments

• [06:01] — Working Definition of Life and Open-Ended Evolution
• [09:44] — Miller-Urey Experiment and Historical Context
• [13:07] — Lab Methods: Lipid Vesicles, RNA Nanotechnology
• [15:04] — RNA Origami: Designing and Building Synthetic Genes
• [22:41] — Natural vs. Synthetic Life; Simplifying Complexity
• [26:27] — Life in the Universe: Would Aliens Use the Same Machinery?
• [32:26] — Chirality: Why All Life is Left-Handed
• [40:09] — Ethics and Containment: Should We Worry?
• [43:02] — Motivation: Curiosity, Technology, and the Promise of Evolvable Tools
• [46:05] — Practical Applications: Stable RNA Therapeutics

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Tone and Language

The conversation is both playful and intellectually rich, brimming with curiosity and humor. Tyson and Kirshen keep the mood light with jokes about playing God and “illegal aliens”—while Göpfrich stays grounded, pragmatic, and infectiously enthusiastic about the possibilities of her research.

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Conclusion

This episode offers a lively, accessible, and deeply informative journey through the frontiers of synthetic biology. The insights into how scientists define life, the nuts and bolts of building it from scratch, the ethical and philosophical quandaries, and the tantalizing implications for medicine, astrobiology, and the future of life itself, make this a must-listen for anyone intrigued by humanity’s quest to understand (and perhaps reinvent) life as we know it.

Transcript

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[Neil deGrasse Tyson]

So, Matt, she's making aliens in the laboratory.

[Matt Kirshen]

She is the puppet master. She's the new creator of the universe. And it's quite terrifying.

[Neil deGrasse Tyson]

But fun.

[Matt Kirshen]

It's informative, but terrifying.

[Neil deGrasse Tyson]

Scientifically enlightened, I would say very. Coming up on StarTalk. Welcome to StarTalk, your place in the universe where science and pop culture collide. StarTalk begins right now. This is Start Talk. Neil Degrasse Tyson, your personal astrophysicist. I got with me today, Matt Kirschen. Matt, welcome back.

[Matt Kirshen]

Thank you so much, Neil. It's good to be back.

[Neil deGrasse Tyson]

Yeah, it's been too long.

[Matt Kirshen]

It's been a while. It's nice to be back in New York, in the office.

[Neil deGrasse Tyson]

It's great, but where are you based?

[Matt Kirshen]

I'm in la. I'm still in la.

[Neil deGrasse Tyson]

Oh, you're a LA guy. I knew that. I knew that.

[Matt Kirshen]

Yeah. So it's nice to be back over on this coast.

[Neil deGrasse Tyson]

So we nab you every time you slip by.

[Matt Kirshen]

Anytime I'm anywhere near, I will hit your people up. And.

[Neil deGrasse Tyson]

And now you're on tour, apparently. Oh, my God.

[Matt Kirshen]

Yeah. Well, I'm on two, sort of. So I'm touring at the moment with. Opening for Sarah Milliken, who's a great UK comic. So I'm doing lovely businesses coming through the stage. She's doing the US and then I'm also doing my own headlining spots kind of off the back of those shows. So I'M like, hey, loads and loads of people. If you enjoyed me for 15 minutes in this massive room and want to see me do a headline show in a significantly smaller room, then so, yeah, I'm doing those. So, yeah.

[Neil deGrasse Tyson]

Okay, cool. So we can find you matkirshen.com mattkirchen.com.

[Matt Kirshen]

All the tour dates and the links are up there.

[Neil deGrasse Tyson]

Very cool. Such a big fan of comedians. Thanks for being a part of civilization.

[Matt Kirshen]

Oh, well, I've never heard it put like that. That is a much deeper way than I've ever had my job described before. And I love that.

[Neil deGrasse Tyson]

Tell your parents that, too, in case they were wondering.

[Matt Kirshen]

Mom, dad, you know that degree that I did nothing with and then ran off to join the circus? Well, I am a deep part of civilization.

[Neil deGrasse Tyson]

Exactly. There you go. Well, today's topic. Oh, my gosh. Oh, my gosh. We're talking about making life.

[Matt Kirshen]

Yeah.

[Neil deGrasse Tyson]

Speaking from scratch.

[Matt Kirshen]

Speaking of parts of civilization or making.

[Neil deGrasse Tyson]

Life from scratch, which technically would be alien life, if you think about it that way. Right. I mean, if it's life that has never existed on Earth before.

[Walmart Wellness Participant]

Yeah.

[Matt Kirshen]

What are the rules? Cause if it's made from scratch on Earth, is that alien or what?

[Neil deGrasse Tyson]

I don't know.

[Matt Kirshen]

I guess we're getting to immigration questions now.

[Neil deGrasse Tyson]

Are they illegal aliens or. Illegal aliens?

[Walmart Wellness Participant]

Yeah.

[Matt Kirshen]

Is their birthright laws for if you.

[Neil deGrasse Tyson]

Make them in the United States, they're native to America. Right, Right. All right.

[Matt Kirshen]

Or if you make them on an army base in another country, then, I don't know, like, what are we doing here?

[Neil deGrasse Tyson]

So I don't have sufficient expertise on this. And as what we do on StarTalk is find the expertise wherever it is. And that took us to Heidelberg.

[Matt Kirshen]

Nice. Oh, my gosh, Beautiful city.

[Neil deGrasse Tyson]

Join me in welcoming. Cor. Kirsten Goprich. Did I pronounce that correctly?

[Walmart Wellness Participant]

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[Neil deGrasse Tyson]

Neil, that was two thumbs up.

[Matt Kirshen]

Two thumbs up. Two thumbs up.

[Neil deGrasse Tyson]

Kirsten, thanks for agreeing to this conversation. You are professor at the center for Molecular Biology at Heidelberg University. Love it. And you led the Max Planck Research Group in biophysical engineering of life.

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[Neil deGrasse Tyson]

Now just remind me, because there's a Max Planck Institute for Astrophysics. So there are Max Planck Institutes for many different branches of science, correct?

[Walmart Wellness Participant]

Indeed there is. There's more than 80 Max Planck Institutes across Germany and abroad, actually. Yeah.

[Neil deGrasse Tyson]

I didn't know there were even that many. Max Planck is basically birth quantum physics.

[Matt Kirshen]

Right.

[Neil deGrasse Tyson]

With a paper he published in 1900 saying, hey, wait a minute, maybe energy is not a Continuum, maybe it comes in quantized amounts, I don't know.

[Matt Kirshen]

So he, we consider the father of.

[Neil deGrasse Tyson]

Well he.

[Matt Kirshen]

One of the fathers of quantum physics.

[Neil deGrasse Tyson]

He planted this seed that completely blossomed a century ago, like Max Planck. And he's duly honored in all of these institutes throughout Germany. You got your PhD at the University of Cambridge and where you were a Marie Curie Fellow in Synthetic biology.

[Matt Kirshen]

Wow.

[Neil deGrasse Tyson]

That means you are Dr. Frankenstein, creating life in a laboratory. Have I mischaracterized you in any way by calling you that?

[Walmart Wellness Participant]

I'm not Dr. Frankenstein. No. And that's not our aim. Our aim is really to create a synthetic cell from the bottom up. So to achieve a transition from method to life in the laboratory. That's. That's right, yes.

[Matt Kirshen]

So just to be clear, you don't have to wait for lightning to strike the lab before.

[Walmart Wellness Participant]

No, not, not really. Not really. And we are also doing it for, with the best intentions, I have to say.

[Neil deGrasse Tyson]

The lightning is metaphor for an energy source.

[Matt Kirshen]

Right.

[Neil deGrasse Tyson]

That would then infuse the life form. So why don't we just start from the beginning? Do we have a sufficiently good definition of life for us to then know the moment you may have created it?

[Walmart Wellness Participant]

Yeah. So there's many definitions of life out there. Right. And there's not really consensus on one. But I would say in my field, bottom up, synthetic biology, what we really use as a working definition, and you'll be happy to hear this Neil, is a self sustaining chemical system capable of Darwinian evolution. And that definition was put forward by the NASA and we extended. We don't just want a system capable of Darwinian evol, we actually want a system capable of open ended evolution. So it can essentially increase itself in complexity. It can evolve to perform any desired task in the end. So that's what we are after.

[Matt Kirshen]

So what's the, Sorry, what's the difference between Darwinian evolution and open evolution?

[Walmart Wellness Participant]

So Darwinian evolution can be. There can be open endedness in Darwinian evolution. So what we are really after is a system where the evolutionary landscape is large enough so that at any given time, time and the number of genotypes only exploit a sufficient, sufficiently small, small space on that evolutionary landscape. So to say. So there's really, there is really a lot of space to introduce serendipity, to introduce changes, to introduce, well also some, some kind of emergent properties that, that are inherent to living systems.

[Neil deGrasse Tyson]

So Darwinian would presume that the change is favored only for the survival of the organism. And you're suggesting there might be forces Operating that just simply change the organism without reference to its survival. Is that a fair way to think about open ended evolution?

[Walmart Wellness Participant]

Yeah, well, yeah, to essentially go for systems that increase in complexity and do interesting things. So that's what we are after.

[Neil deGrasse Tyson]

So if an organism never dies or lives sufficiently long, then it can't undergo Darwinian evolution.

[Walmart Wellness Participant]

So on the population level, I think introducing death into, into living systems is absolutely crucial because otherwise, you know, you just have exponential growth and the resources will be exploited.

[Neil deGrasse Tyson]

I never heard anybody say that before. We have to make sure you die in order to, for us to evolve you.

[Matt Kirshen]

That kind of, that makes perfect sense. Yeah, again that, that sort of a little mind blowing. Yeah, of course.

[Neil deGrasse Tyson]

I'm not saying it doesn't make sense. I'm just saying I never heard anybody admit that. Yeah, so you're the first biologist I've heard be honest about the fact that Darwinian evolution requires that everybody dies.

[Walmart Wellness Participant]

Yeah. So I mean on the population level at least, when we think about synthetic cells, we really think about very, very minimal living entities that are much simpler than the cell that we currently know on Earth. So much simpler. We are really talking something where essentially we, we want to get to the point where chemical evolution becomes biological evolution. Right, that's where we want to get. And in that context I'm saying that if we manage to construct a system which is capable of self replication, then eventually resources will be exploited. Especially if you have, if you have of course limited resources. Right. And then this stage, this is where, you know, we have a situation where survival of the fittest is what's driving evolution.

[Neil deGrasse Tyson]

Essentially we have a situation on our hands. So, so this, this conversion from complex chemistry to simple biology that harkens back to the Miller Urey experiment, very famous experiment. When was that? In the 1960s, was it perhaps early 70s? Could you remind us about the Miller and Urey experiment and what that did in your field back then?

[Walmart Wellness Participant]

Yeah, so I think it was earlier even than that. It was around 1950, 1952 or so. Where. Yeah, so, so it was the first time that essentially Miller was, was, was performing chemical reactions in a way that is kind of similar, similar to early Earth to the environment on early Earth. So he was trying to recreate the atmosphere that was present on early Earth. And then he could see that very simple building blocks of life, such as some amino acids which build proteins, so to say were present in that solution after he provided the system with energy. So that kind of shows that organic synthesis is possible under prebiotic conditions essentially. And you Know, that's far away from a biological system. So we're talking really individual amino acids. But it shows that prebiotic conditions can give rise to organic molecules like amino acids that build proteins today.

[Neil deGrasse Tyson]

So in the Miller Urey experiment, they knew to start with organic molecules, right? They knew to start with that and they went to then see what the organic molecules might do for themselves when left unmonitored and left alone. But they had to give it an energy source. Right. And if memory serves, that energy source was a little spark. Very Frankenstein, like simulating lightning, so to.

[Walmart Wellness Participant]

Say on early Earth. Yeah.

[Neil deGrasse Tyson]

You want a big light switch or something?

[Matt Kirshen]

Yeah, I want a massive, I want a massive lever that someone that. A henchman. Do you have a henchman? I'm hoping you have a henchman.

[Walmart Wellness Participant]

I'm afraid no. But what I, what I find interesting about, about this experiment is that, you know, even before that, about 100 years earlier, there was the common belief among chemists at the time was that organic molecules are molecules which can only be synthesized by living things. Right? Like that organic synthesis in the laboratory is essentially impossible. And then chemists at that time, like 1800 something, managed to actually make the first organic molecule synthetic in the lab. And that was actually urea. And that proved that we as human beings can synthesize organic molecules which are otherwise made by living things from scratch. Right. And I see synthetic biology or the bottom up creation of synthetic life a little bit at a similar, at a similar point right now where, you know, kind of a proof of principle is needed to show that we cannot only make organic molecules like the ones that were, that were made in the Miller Urey experiment, but that we can also actually achieve a transition matter to life in a laboratory setting.

[Neil deGrasse Tyson]

How does your work follow this and what is, what's different about your approach?

[Walmart Wellness Participant]

So essentially we start at a much, much later point. So we start when we start with biomolecules and we ask ourselves the question whether it's possible to actually assemble molecules in such a way that we can create a system that's capable of undergoing, create a self sustaining chemical system that's capable of, of evolution. So that's our starting point and end goal. And what we do in order to get there is we are making lipid vesicles, so kind of the envelope of a cell and we are building, constructing our own molecular machinery. And we do so with rna, RNA nanotechnology, and that may be a little bit reminiscent of the RNA world hypothesis and the origins of life field.

[Neil deGrasse Tyson]

As I understand your work or Any work that anyone does, you are only as effective as the tools you use. And if you are trying to assemble molecules, you need something that can. Are they tweezers? You need some tools that are small enough to, to take this molecule over here and attach it to that molecule over there. And it seems like this is the RNA nanotechnology that you're referring to. Your toolkit are not mechanical tools, they're biological and chemical tools. Is that a fair way to characterize what you're doing?

[Walmart Wellness Participant]

Indeed, indeed. So we don't use tweezers on a nanoscale, although they exist. Right. That's actually amazing part of physics. They do exist. But what we do is we actually do something very similar to what a protein designer would do. Right. Protein design won the Nobel Prize last year and we do something similar, or we're trying to do something similar with rna. And that's a much less explored field. Indeed. So RNA origami is quite new. But what, what we are essentially trying to do is we are trying to assemble a synthetic gene from scratch, a piece of DNA which encod for an RNA that folds up during transcription. So while the DNA is read off, it folds up into a desired structure. That could be something that resembles a cytoskeletal element, or it could be something that resembles a nanopore that assembles into the lipid membrane of a cell. So we can feed it, for instance, the functionality, the forms are really driven by the function that we would like to create. Design happens with computational tools essentially.

[Neil deGrasse Tyson]

All right, so the folding. I'm fascinated by the folding.

[Walmart Wellness Participant]

Absolutely.

[Matt Kirshen]

Me too.

[Neil deGrasse Tyson]

As a kid I was into origami and I still am a little bit. I have big pudgy fingers. But I was very delicate with the, with my little birds and I can still do it. Okay, I got like three left in my repertoire that I could.

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[Walmart Wellness Announcer]

Honey, do not make plans. Saturday, September 13th. Okay?

[Walmart Wellness Participant]

Why? What's happening?

[Walmart Wellness Announcer]

The Walmart wellness event. Flu shots, health screenings, free samples from those brands you like.

[Walmart Wellness Participant]

All that at Walmart.

[Walmart Wellness Announcer]

We can just walk right in, no appointment needed. Who knew we could cover our health and wellness needs at Walmart?

[Walmart Wellness Participant]

Check the calendar.

[Walmart Wellness Announcer]

Saturday, September 13th Walmart wellness event. You knew.

[Walmart Wellness Participant]

I knew.

[Walmart Wellness Event Narrator]

Check in on your health at the same place you already shop. Visit Walmart. Saturday, September 13th for our semiannual wellness event flu shot. Subject to availability and applicable state law, age restrictions apply. Free samples while supplies last.

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[Matt Kirshen]

I'm Nicholas Costella and I'm a proud.

[Walmart Wellness Announcer]

Supporter of Startalk on patreon. This is StarTalk with Neil DeGrasse Tyson.

[Neil deGrasse Tyson]

Do you know in advance how you need to fold your proteins? Because the protein itself is obviously not yet life. So do you know what you're doing if you don't know? I mean, it's rumored that this is what Einstein said, research is what I'm doing when I don't know what I'm doing. Right. So if you're not targeting a life form you already know about, then how do you direct the decisions you make towards a life form that has never existed before?

[Walmart Wellness Participant]

Well, essentially we know what functions we need to realize, right? So we want, in the end, a self replicating system which is capable to evolve. And in order to have that, first of all, this system needs to be able to build up its own molecular machinery. And that machinery we build from rna. And one piece that we think is crucial for such a machinery is actually a machinery which can divide a lipid vesicle, essentially impose a certain amount of membrane curvature on the membrane of a vesicle. In natural cells, this happens via an architecture that's called the cytoskeleton, the skeleton of a cell. One of the first things that we build with rna, that we built from RNA was actually cytoskeletal mimics, so to say but all from rna, not from protein. So we look at them, we look at how they look in nature, we look at how they function in nature, and we are trying to design something which looks very similar, that could be, first of all, small building blocks that then assemble into micrometer score long filaments that then can, for instance, attach to the membrane so that the membrane can be deformed. Because they are genetically encoded, we now have actually a quite powerful helper, and that's evolution. So essentially we can then start to go to the DNA level, to the DNA level again and introduce mutations so that we can evolve the RNA structures towards even better function.

[Neil deGrasse Tyson]

Well, so you. So you are introducing your own mutations?

[Walmart Wellness Participant]

Well, we have biological machinery introduce them, essentially, yes.

[Neil deGrasse Tyson]

You're not going to wait around a billion years or a million years. You're doing it yourself.

[Walmart Wellness Participant]

We're doing two things here. We start with a rationally engineering starting point, right? So we already know what we want to get, so we have a very simple version that already works a bit, and then we let evolution brush it up.

[Neil deGrasse Tyson]

So to say, where does information theory fold into this? Because when we're taught DNA in school, we think of it less of a molecule, of course, that's what it is, but as something that encodes the information, biological information. And so how do you make sure that the information that's in there is the information you need?

[Walmart Wellness Participant]

So that's where computational design really comes in. Right. So we really start with, we think of what kind of 3D architecture do we want to create from RNA. And then we essentially design a synthetic gene, a synthetic piece of DNA which upon transcription, so when it's read by the biological polymerase, will make an RNA that folds up on itself in desired way, essentially.

[Matt Kirshen]

How much of the sort of design in the folder you said it's done compute computationally. So how much of it is sort of designed computationally and how much is it? You physically do it and then you see what you end up with and adjust.

[Walmart Wellness Participant]

First we design computationally and then we physically do it. We check it in the lab with experimental techniques like cryo electron microscopy to really visualize single molecules and their architecture. And then we can essentially see if the structure is entirely correct, if or if we need to make improvements on the DNA sequence level in order to, in order to fix certain things that we would like to look ever so slightly different.

[Neil deGrasse Tyson]

Is there a difference between you creating a life that we already know about? So synthetically creating a simple life, because it seems to me that would be easier because you already have, you already know exactly what you're aiming for versus putting all this together and creating something no one has ever seen before. You'd still get a lot of credit in this world if you created a life form that already exists on earth just out of raw ingredients. That would still be amazing. But that's not good enough for you. You want something else to crawl out of the test tube.

[Walmart Wellness Participant]

So essentially there are different branches in the field of bottom up synthetic biology which use different types of, of molecules, different types of molecular building blocks, so either the very natural ones, so really taking pieces from cells, essentially proteins that you just encapsulate and boot, so to say inside of a lipid vesicle. And then there is others who take entirely synthetic pieces and then there is us who are somewhere in the middle. And you know, there is pros and cons to using the biological machinery. But in the end, you know, I could imagine that bottom up synthetic biology brings about multiple examples of synthetic life, the ones that are very similar to life as we know it, and ones that are quite far away. The problem with biology as we know it is that it's already extremely complex, right? So to give you an example here, right, all life on earth that we know adheres to the central dogma of molecular biology, which states that DNA makes rna, RNA makes proteins, and now this machinery alone, this step from RNA TO protein requires 150 components, 150 genes just for this step. So if we can circumvent the use of proteins and we just build a functional machinery from rna, so we have our genotypes, our genotypes stored in DNA, but we have the function in the rna, the phenotype is introduced by rna, then we can reduce the complexity of the system quite a lot. And you know, life has not always been that complex. At the origins of life, simpler solution must have been capable of sustaining self replication and evolution. And therefore I believe that building our own molecular building blocks, so to say, can actually be a shortcut. But we'll see. You know, all of these approaches are super cool and in the end it would be amazing to have not just biology 2.0, but also 3.0, 4.0, 5.0 and so on. So all of this is valid.

[Neil deGrasse Tyson]

I like the fact that you took a look at life and said, I can do a better job and simplify it.

[Matt Kirshen]

It's very complex.

[Neil deGrasse Tyson]

Yeah, I can, I can make, I can be, I can simplify that. That's delightfully audacious.

[Walmart Wellness Participant]

Essentially it's a little Bit similar to, you know, we came from the Miller Ury experiment, right, where also you start with very, very simple building blocks. And I'm sure at the origins of life, self replication and evolution have been sustained by a simpler set of building blocks. And you know, one can ask if it's, if it's possible to use such, to use, well, to use such building blocks to start not from where life is right now, because that took 4 billion years to get there, right. But to start actually at a simpler stage essentially, but still have a system capable of evolution. That's really, that's really the holy grail I would say here, because, you know, it's a part of the fundamental definition of life and B will help us to, to get somewhere interesting.

[Matt Kirshen]

So do you think life on another planet is likely to have something very similar to our DNA RNA protein system or do you think it could be a completely different self replicating thing? Like is it likely?

[Neil deGrasse Tyson]

That's a million dollar question. Because if we're looking for carbon based, DNA based life on other planets, we might miss it. So another way to word this, I think is how inevitable in the biochemistry of an early planet is what happened here on this planet with DNA to RNA to folded proteins. Is that so inevitable that you're saying, yeah, any place we find life, it would have been through this, it would.

[Matt Kirshen]

Have run the same solution, would have.

[Neil deGrasse Tyson]

Found the same solution. Are you prepared to say that, in.

[Walmart Wellness Participant]

Other words, even like if we replay, if we replay history on this planet, right, Would we end up with essentially the same thing or could we end up with something quite different? I said the evolutionary landscape is vast, right? We are just, with life as we know it, exploring a tiny, tiny, tiny, tiny, tiny bit of that. And I believe that the idea of creating very minimal living systems from scratch will ultimately be able to help us to, to address these kind of kinds of questions, right? So you could for instance, introduce metabolic pathways that are completely different from the ones that we know from life as we know it into such artificial systems and study them. So at the moment we don't have EV for silicon based life, right? But I think there's, personally, I think there's also reasons for that, right? Like both of them can do, can, can make four bonds, right? But, but, but seems that carbon is just much more versatile.

[Neil deGrasse Tyson]

But you know, your carbon in the universe is also like five times more abundant. So silicon sits right under carbon on the periodic table. So just as she said, they can each bond four ways. Everything in that column can. So carbon has four Four electrons in its outer shell and it can take four more. Right. Which is a highly versatile situation to be in. But silicon can do that too. But we don't need be fun to find silicon based life. We just don't need it because carbon is everywhere in the universe, does the.

[Matt Kirshen]

Same job, but kind of better.

[Neil deGrasse Tyson]

Yeah. So do astrobiologists call you and get your insights into what they might be looking for?

[Walmart Wellness Participant]

I would say the field is very, very interdisciplinary, bottom up. Synthetic biology is very interdisciplinary. And we are for sure, we are for sure keeping the discussion entirely open with astrobiologists and really also think about implementing, well, solutions that evolution may not have explored. Right. So that's for sure a super interesting conversation to be had.

[Neil deGrasse Tyson]

You know something, evolution did not come up with a four legged vertebrate creature that also has wings. But we have Pegasus. Pegasus popped some wings out his back.

[Matt Kirshen]

Right.

[Neil deGrasse Tyson]

That is not in the plan. Okay, so when you look at life on Earth, do you say here's something that evolution coulda, shoulda, maybe, but didn't?

[Matt Kirshen]

Well, it does say again, from my limited knowledge, it does seem that evolution does seem to keep landing on the same solutions for.

[Neil deGrasse Tyson]

Oh, interesting.

[Matt Kirshen]

There are a bunch of different animals that have evolved through different pathways, the same things.

[Neil deGrasse Tyson]

Yeah, yeah. Carsten, is that, that. I like what he said there.

[Matt Kirshen]

Is that the same at the lower level?

[Neil deGrasse Tyson]

Yeah. Evolution has found similar pathways to solve its survival problems that in some are even unrelated, but they land in the same place. So that might give you insight. Does it to for what biochemistry likes?

[Walmart Wellness Participant]

Yeah. And I think one place where we could see this, for instance, is that when we build our life, our very, very minimal synthetic cell as the minimal unit of life, and I don't mean really a cell as we know it, but a very, very simple version of that, essentially that that cell is by far not as efficient as life as we know it because it's based, its catalytic activity is based on RNA and RNA catalysis is much slower than what proteins can do. And the moment you introduce proteins to the system, so a way of having translation of, of making producing proteins inside of a synthetic cell, you may find that this is actually a much more efficient solution. So this may be why we don't see an RNA world around us anymore. Simply because, you know, once you have proteins, they win in a direct competition. But again, if we start with a simple system, evolution may bring about these more complex systems. Right. So in fact, in fact, if you look at the ribosome though, so the ribosome is the component in the cell, which is responsible for turning RNA into protein. So it's doing this translation inside of the cell, then that ribosome, the catalytic activity, the core of the catalytic activity actually comes from RNA and not protein. So indeed we have some of the most intricate molecular machines that cells use today are actually RNA based.

[Neil deGrasse Tyson]

We want, when the aliens come, we want you in the room when that happens so that you might be able to understand what kind of life they are. Right. You'd be perfectly suited for this. Is that correct?

[Walmart Wellness Participant]

Well, let's see what they look like. Right. I may or may not, as I.

[Neil deGrasse Tyson]

Understand it, correct me if I'm wrong. All life on Earth has a certain handedness in its molecules. Like it's all left handed or it's all right, whatever it is, because some molecules are, they're not symmetric, like they're mirror versions of them.

[Matt Kirshen]

Right.

[Neil deGrasse Tyson]

And so we're all one kind of molecule. Which one is it? Left or right handed? I forgot which.

[Walmart Wellness Participant]

It is left handed. Yeah. So that origins of homochirality, actually, so the handedness of life, so to say, is another very, very interesting question. So in fact we talked about the Miller Urey experiment, right, where amino acids were produced. And actually in that experiment a racemic mixture of these, of these molecules was produced. So the left handed version as well as right handed version. Right. So that experiment does not solve the origins of homochiality at all. And that's an another very, very interesting field of study, I have to say. Of course, the molecules that we use are all the standard handedness you know, that life uses today.

[Matt Kirshen]

This might be a dumb question, but of the left handed and right handedness of the molecules, which one's good and which one's evil?

[Walmart Wellness Participant]

Well, I'd say which one has nature chosen? And that's the left handed one.

[Neil deGrasse Tyson]

Yeah, that's a separate lab, they're working on that.

[Matt Kirshen]

Okay. Okay.

[Neil deGrasse Tyson]

Since biochemically there's no difference between making life forms with left or right handed molecules, in principle, both handedness could have started on Earth. Is there a search for right handed colonies of life on Earth that are thriving in their own little world and no one knows about them? And somehow the left handers took over the world, suppressing any uprising of the right handed molecules.

[Matt Kirshen]

I don't like their kind. I don't like those righties.

[Neil deGrasse Tyson]

We do it for less as humans, don't we.

[Walmart Wellness Announcer]

Honey? Do not make plans. Saturday, September 13th. Okay.

[Walmart Wellness Participant]

Why, what's happening?

[Walmart Wellness Announcer]

The Walmart wellness event, Flu shots, health screenings, free samples from those brands.

[Walmart Wellness Participant]

You like all that at Walmart, we.

[Walmart Wellness Announcer]

Can just walk right in. No appointment needed. Who knew we could cover our health and wellness needs at Walmart?

[Walmart Wellness Participant]

Check the calendar.

[Walmart Wellness Announcer]

Saturday, September 13th Walmart wellness event. You knew.

[Walmart Wellness Participant]

I knew.

[Walmart Wellness Event Narrator]

Check in on your health at the same place you already shop. Visit Walmart, Saturday, September 13th for our semi annual wellness event, Flu Shot. Subject to availability and applicable state law, age restrictions apply. Free samples while supplies last at Capella University.

[Capella University Advertiser]

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[Neil deGrasse Tyson]

Is any thought as to whether if we look harder, we might find a right handed colony of life?

[Walmart Wellness Participant]

I believe we should should see traces of such forms of life if they were existent. So the fact that we don't see those traces, the fact that we don't find any, you know, wherever we take probes on earth, we don't find any of these molecules. Make me believe very strongly and I don't know, it's not my field, but make me believe very strongly that, you know, the left handed version is the one that made it.

[Neil deGrasse Tyson]

It's the good that has triumphed over the evil. I think this is. She didn't say that, but that's what she meant.

[Matt Kirshen]

Well, we don't know. We don't know. Or the evil that triumph over the good. There's no way to.

[Neil deGrasse Tyson]

Oh yeah, if you only have one, you don't know whether you're the evil one or the good one.

[Matt Kirshen]

Which one has the mustache? The mustache.

[Walmart Wellness Participant]

You can of course make mirror versions of molecules in the lab, so that is possible and that Sometimes can even be desirable, for instance, for therapeutic applications. Because their degradation and recognition properties and so on are different. Right. Because our machinery in the cells, well, does not really. Does only recognize its own kind, so to say. So in that sense, yeah, it's interesting to think about it.

[Neil deGrasse Tyson]

So, Kirsten, just like in the Miller Urey experiment, they tried to create what they thought were the conditions in the early Earth. You, in your biochemical experiments, presumably the environment has some temperature, some air, mixture of molecules. Presumably you're doing the same thing, but in a more advanced way. We now have a catalog of nearly 6000 exoplanets and we know some things about them. Are these conditions that can inform your experiments as we look for life on other planets? And are the conditions you do your experiments in? How realistic are they? Because we have life on Earth that is living in the ice and living on the sides of volcanoes and all the extremophiles. So are you testing for conditions that would. An extremophile would be happy in, rather than just us?

[Walmart Wellness Participant]

So typically we test conditions that are compatible with our research budgets. And this typically means that we take conditions which are asked simple as possible. Right. So we often.

[Matt Kirshen]

So you're not in a volcano right now?

[Walmart Wellness Participant]

Yeah, exactly. Like if you want to work into, in an atmosphere that's not, you know, what is around us, experiments all of a sudden become much more complex and costly and difficult. Right. So. So in our case, when we, when we, you know, what we want to do is to create a version of synthetic life and we don't really care. We want to make our lives as easy as possible because the question itself is. Is hard enough. Right. So we typically try and work it at either room temperature or 37 degrees, which all laboratory equipment is designed to be compatible with. And we work with DNA and rna. We produce synthetic genes in standard manners that biology has come about and so we take the conditions as they are. Of course, these days you find sophisticated experiments and sophisticated pieces of equipment which were, which are at least partially trying to replicate these more extreme conditions where we could talk, you know, astrophysics and alien life, or conditions that resemble more the origins of life on early Earth. In our case, we're just taking what.

[Neil deGrasse Tyson]

Works, the simplest system, 37 degrees Celsius.

[Walmart Wellness Participant]

Oh, I'm sorry, yes.

[Neil deGrasse Tyson]

You're speaking to us from Europe. We are here in America. Let's talk about something that I know is on everyone's mind. What are the ethics of this exercise? Might you create something that will crawl out of the beaker or out of the test tube and then become our overlord or infect us all and we all die.

[Matt Kirshen]

And would it see you as its.

[Neil deGrasse Tyson]

Natural parent or as its creator? Creator, yeah, she is their God.

[Matt Kirshen]

Right, their God. But then also they hit the rebellious teenage phase and they're like, I don't even know how to be alive.

[Walmart Wellness Participant]

So no, I don't think anything we create will crawl out of the test tube anytime soon. Right. So we are after a very, very minimal version of a synthetic cell which is much less complex than life as we know it. Right. So essentially, you know, life as it evolved came with robustness. What we are creating is very, very fragile and requires a lot of care, so to say. And, but you're completely right. Like ethics, to consider ethics is, is of course extremely important. So, you know, one may think about things like, okay, once you have a self replicating system, should the same rules apply as for life as we know it in terms of biocontainment, for instance? Instance. So we have very good containment rules for organisms, especially for engineered organisms. We have to work at certain biosafety levels, depending on their risk for the environment and the human being. And so to use these kinds of rules also, or to extend these kinds of rules also for synthetic life and to understand the risks as well as the opportunities is, is super important. Of course.

[Neil deGrasse Tyson]

Let me ask the most basic question of them all. Why are you doing this?

[Matt Kirshen]

It's a question I ask myself every day.

[Neil deGrasse Tyson]

Did you wake up one morning, now you're going to be responding for everyone in your field with this question. Did you wake up one morning and say, you know, I'm not happy with the biodiversity of life on earth, I want it even more diverse. And then you say, I want to invent life, because that's a different goal from just trying to understand how life formed on earth, how we went from organic molecules to self replicating life that has a certain accessible. Yeah, I understand that's the frontier of biology. But now you want to create something. So where's the ethical line between trying to understand how life started and trying to create life?

[Walmart Wellness Participant]

Yeah, look, we have extremely limited knowledge about the exact conditions on early earth. Right? And there's only so much we can know about this. So experiments in the end need to be reproducible. We have only one example of life as we know it. And I'm just super, super curious, you know, about what life is and what it could be. Right. So all those questions that your parents can't answer when you were a kid. Right. So I Think it's, I think it's somehow intrinsic to human curiosity to, to ask what life is and why it's there and so on. And recreating it, building it is one way to really bring our understanding of life to a new level, I believe. But from a practical point of view, right, where you could, you could think about evolving something with such very minimal entities, research very minimal entities towards user defined goals. So this could be an immunology, this could be a new way of making evolvable materials. So this could really be a new way of manufacturing, manufacturing in the end. So while, you know, we come in with curiosity, we are synthetic cells and synthetic life have really the potential to revolutionary, to revolution, revolutionize the way we manufacture on earth, right? I mean, just, just look around you, right? I mean if you. It's amazing to see the generative power of evolution, right? Like nature has built ginormous architectures that capture CO2. I mean, look at trees. Nature has built cells which, which capture pathogens inside our body, right? So in all of this just comes from the same common ancestor. So imagine we could create synthetic life and evolve it really towards user defined goals. And I think, yeah, I think, I think this is, in the end, what motivates us is a very fundamental question and the creation of tools and evolvable systems that can be evolved in the end. And I think RNA design is a really nice example where we talked about it earlier, where, where both of it comes together, right? I mean we all know about RNA therapeutics, that's a, is a 30 billion dollar market right now. And so advancing RNA design has immediate implications also on the, on the therapeutic level. And at the same time it allows us to answer some of the, or to address to, to deal with some of the very fundamental questions. So I feel like it's a super nice sweet spot to study RNA and lipids and their interactions and so on.

[Neil deGrasse Tyson]

Yeah, I'm embarrassed I didn't think of any of that when I asked you that question, so I should have. Of course, now that you mention it, it's so clear and present that there are things that your work can do that can improve the state of human health in the world and our relationship to other animals or the biome that, that we're immersed in, in our gut, on our skin. Just, you could, you could be the, the savior of us all.

[Walmart Wellness Participant]

What's clear, for instance, right, we talked about RNA RNA folds and RNA design. So RNA like MRNA as it is in our vaccines, is inherently unstable, right? That's what makes the deployment so difficult, you have to cool it down to preserve it. And now when you fold RNA in distinct ways, you know, the RNA origami, the RNA nanostructures we make, they are stable at room temperature for just on the bench. So by folding rna, we can also package more on a smaller footprint. Right, Right. So by making nanostructures from rna, I really think we can advance the way we build therapeutics and at the same time actually also address these very fundamental questions on origins of life and creating of very minimal synthetic cells and synthetic life.

[Neil deGrasse Tyson]

So I think we got to end it there. But this has been a brilliant conversation. Delighted to learn that such a field exists that is vibrant and that you're in the middle of it. That gives me confidence that only good will come of this. Again, thank you for your time and like I said, delighted to know that this is a field that's vibrant and probably still growing. And I look forward to see what it will deliver to civilization for sure. Yes. All right. Thank you for being on StarTalk.

[Walmart Wellness Participant]

Thank you, Matt.

[Neil deGrasse Tyson]

Thanks for coming through.

[Matt Kirshen]

This is fascinating. Thank you for having me.

[Neil deGrasse Tyson]

And I keep forgetting you're in la. I'm in la, and I got a book coming out in a few months.

[Matt Kirshen]

Yeah, we're going to steal you for probably Science, if we can.

[Neil deGrasse Tyson]

I'd be happy to go on. Might be Science. Sorry, what's it called?

[Matt Kirshen]

We think it's Science. Probably. Science is my podcast.

[Neil deGrasse Tyson]

What comes out of my mouth will be science. Change the name of the show for that's the one.

[Matt Kirshen]

Yeah, when you're on. We change the name. Otherwise, probably when it's us and other comedians who know very little.

[Neil deGrasse Tyson]

All right, so that's all we've got here on StarTalk. Neil DeGrasse Tyson, as always, bidding you to keep looking up.

[Walmart Wellness Announcer]

Honey, do not make plans. Saturday, September 13th, okay?

[Walmart Wellness Participant]

Why? What's happening?

[Walmart Wellness Announcer]

The Walmart wellness event. Flu shots, health screenings, free samples from those brands you like.

[Walmart Wellness Participant]

All that at Walmart?

[Walmart Wellness Announcer]

We can just walk right in, no appointment needed. Who knew we could cover our health and wellness needs at Walmart.

[Walmart Wellness Participant]

Check the calendar.

[Walmart Wellness Announcer]

Saturday, September 13th, Walmart wellness event. You knew?

[Walmart Wellness Participant]

I knew.

[Walmart Wellness Event Narrator]

Check in on your health at the same place you already shop. Visit Walmart, Saturday, September 13th, for our semi annual wellness event, Flu Shot. Subject to availability and applicable state law. Age restrictions apply. Free samples while supplies last at Capella University.

[Capella University Advertiser]

Learning online doesn't mean learning alone. You'll get support from people who care about your success, like your enrollment specialist who gets to know you and the goals you'd like to achieve. You'll also get a designated academic coach who's with you throughout your entire program. Plus, career coaches are available to help you navigate your professional goals. A different future is closer than you think with Capella University. Learn more at Capella Eduardo.