Octopus Technology (artwork by Ricard Solé)
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Sara Walker: I think that philosophy that assembly offers is deeply interesting, very provocative, and allows this entirely new creative space for thinking about the physics of life.


Abha Eli Phoboo: From the Santa Fe Institute, this is Complexity

Chris Kempes: I’m Chris Kempes.

Abha: And I’m Abha Eli Phoboo.


Abha: So Chris, last week we looked at how physics and life are deeply connected. And we talked to two people who started out as physicists who avoided the field of biology but ended up quite deeply entrenched in it

Chris: Yes, and I think what we're starting to see is how arbitrary the divides between physics, chemistry, and biology really are. We see that as we start to bring these different disciplines together, we can answer bigger questions.

Abha: I agree and today we're going to take a step further to look at how life originated here on Earth, bringing together ideas and tools from disciplines that don't necessarily always work together and also where else life might be in the universe.

Chris: That’s great, as an astrobiologist, this is right up my alley. It’s dinosaurs and space all over again. 

Abha: It is. And so you actually have a lot to say about this topic too, right?

Chris: Yeah, I definitely have some thoughts on the topic, it’s been the main focus of my work for 20 years. And I’m thrilled that we’re hosting two of my favorite scientists Sara Walker and Ricard Solé.

Abha: Ricard Solé is a researcher at the University Pompeu Fabra in Barcelona. He’s searching for the principles of organization responsible for the emergence of fundamental components of complexity, which include the origins of self-reproduction, development, life cycles, computational processes, and multicellularity. Or, to put it simply, he’s studying how it all started.

Ricard Solé: I was very lucky as a kid. At home, we didn't have much money, we have a big library. So I was interested in living systems very early. I wanted to be a biologist.  But I have this teacher in high school, a physicist that taught us physics and, I mean, I fell in love with physics. And at the same time I have this teacher in mathematics that was interested in something as strange then as how to make models of brains. \\

Chris: When Ricard was young, he saw something that changed his life: the film Frankenstein

Ricard: And with a close friend at that time, we kind of built a skeleton, which we dressed with some clothes, like building a monster, of course, when everything was done and not much happened. But it was like all the magic of the mystery, but the potential of that for happening. And actually for me, Frankenstein has been a kind of a big motivation over time to think about what's possible about life and the living and non-living and life and death also. And to me as a kid, there was not much distinction about this universe of amazing, fantastic stories and the fact that science might be part of this kind of... amazing ideas.

Abha: So what was that thing that made the creature in Frankenstein turn from a heap of cold, useless body parts into something that was alive? How is being alive even possible? Why is it that our world has trees and humans and birds and fungi and not just rocks and gas and chemical soup? And if we found life in other parts of the universe, would we even know that we were looking at it?


Chris: Part one: Life here on Earth. How did it begin?


Abha: So the universe begins with the Big Bang, which we’ve all heard of. Now, let’s fast forward to 13.8 billion years later. Everything from that explosion has cooled down to the types of matter we’re used to seeing today. And that matter has spun down into solar systems and stars, and over here we have our little solar system. And inside that solar system is our home that we call planet earth, floating around the sun. 

For Part One, we’re going to touch down on earth for a moment, and we are going to look at some of the key characteristics of how life evolved here. At this point in time, if you look at the planet, you might think there’s nothing living on it — right now, it’s just a bunch of hot liquid. But that hot liquid has simple organic compounds that have clung together to form polymers.

Chris: Now, how exactly this chemical soup gives rise to complex life is still up for debate. But, once you get cells, and as time continues to pass, something wild happens. There’s a little cell here, a little cell there, a colony of cells over there. And then suddenly, more complex forms are showing up all over the place. Organisms that can swim and wiggle and eat, that have antenna and digestive tracts and a front end and a back end. At first there were none, and now they’re everywhere. This period, the Cambrian Explosion, is when major animal phyla emerge: arthropods, worms, and chordates. It will take another 520 million years, give or take, to get to the present day. But in the history of our planet, the Cambrian Explosion is a period of incredibly fast evolution. So why do these organisms emerge so suddenly and quickly? Here’s Ricard again.

Ricard: They emerge in an arms race between new kinds of creatures and preys and predators started to be there. I mean, reacting to the environment required memory.

Chris: Memory. Information and memory are key.

Ricard: And there's a consensus that associative learning, this kind of idea that you have a neural network that is able to connect different kinds of inputs, external inputs, and make sense of your world was part of the big revolution that probably paved the way into brains. And then if you go up, I like the example of memory in humans. Humans, of course, they are kind of far away from the origins of life. But it's very interesting to see that, in fact, we probably were so successful because memory became the engine of the future. We were able to create mechanisms to use the same systems that are used to store memory, to actually imagine not only the next moment in the future, but imagine entire futures.

Abha: Memory allows an organism to adapt to its environment. It doesn’t just take in information from its surroundings, it stores information that can be used later.

Chris: One thing that often surprises people is just how much memory bacteria have. So we often think of bacteria as these tiny little, very simple organisms. But they have these really rich and impressive genomes that carry around memory of all these different functions that are useful for responding to different environments. And so you could almost look at that like a lookup book where I say, “This environmental condition is happening. I've seen this in the past.” And I just sort of scan through my lookup book and say, “Oh, right, this is the response I have for that.” You know, it's almost like a very simple chat bot that just knows how to respond to sentences that it's seen in the past, where the sentence is something from the environment and the response is the thing that works in that environment. 

Ricard: Definitely. The fact that you can store information provides you safe ways of actually adapting to future changes. So probably as soon as memory was in place, even a very short, simple memory, perhaps in a short single molecule that was storing basic information out of the environment, that was probably propelled quickly.

Abha: According to Ricard, another basic component of life is computation.

Ricard: You can define life as something that is able to manage understanding the environment. So in a way, capturing the environment and reacting in adaptive ways. And you could say that this is a computation. And for sure, as soon as memory came as being part of the story, probably a lot of revolutions happened.

Chris: But really, I think we can reduce computation to say input operation output. And then under that umbrella, lots of things count, including much of what's going on in the simplest life forms.

Abha: This advantage of having memory pushes evolution down the path from little blobs hanging out in chemical soup — all the way to human brains and elephants and whales. And what starts out as very simple inputs and outputs turn into very sophisticated behavior and abstraction: this incredibly diverse planet we live on today. 

Sara: On this planet, we've seen some very complex chemistry get selected in cells and persist over billions of years and then eventually scaffold and build all of these other more complex architectures on top of it, leading all the way up to like, cities and satellites. 

Abha: That’s Sara Walker.

Sara: Sure, I’m Sara Walker. I'm a professor at Arizona State University and also an external faculty at SFI, and I am a physicist primarily. I guess that's how I think about the world. 

Abha: Sara’s love of physics started when she was in college. 

Sara: I went to community college for my first two years of college because I didn't know what to do and also, like my family hadn't gone to university. And so I took my first semester, just all the science classes I could. I just remember going to physics and the professor there was like super casual. He was like lecturing with like tea in his hand and he was talking about magnetic monopoles and how scientists had predicted them. And nobody knew if they existed, but we could go out and look for them. And I was just so deeply fascinated by this idea that human minds could come up with these theories that we didn't know if they were right or not, and then actually go test them against reality was so interesting to me. I just dropped everything I thought I wanted to do before that and immediately decided I wanted to be a physicist. 

Abha: But, like our other guests, she eventually branched out beyond the confines of physics to study life.

Sara: But the problems I'm interested in addressing with my work are primarily about what life is and how we can understand how life emerges and what other kinds of life might exist in the universe. 

Abha: And like Ricard, Sara also thinks memory is important for evolution. But to be more precise, the accumulation of time and information. 


Chris: You and Lee Cronin recently published a paper in Nature on assembly theory.


Sara: I vaguely recall some other contributors… [Laughs]


Chris: [Laughs] Yeah, I should say you and Lee Cronin and Michael Lachmann, who’s at the Santa Fe Institute and myself and two really wonderful postdocs, just published this paper on assembly theory.


Abha: Those two wonderful postdocs are Abhishek Sharma and Dániel Czégel. Lee, Sara, Chris and Michael met every week over Zoom during the pandemic. They discussed and argued about assembly theory for hours at a time, only stopping every so often to eat a snack or stretch their legs. So according to assembly theory, for any living being —

Sara: It also takes time to build the object. 

Abha:  As in, time for evolution to happen. 

Sara: And so I have an interpretation of assembly as an actual physical property where evolved objects have a size in time that's associated with how much information is necessary for them to come into existence. And I think that philosophy that assembly offers for understanding the physics of life is deeply interesting, very provocative, and allows this entirely new creative space for thinking about the physics of life and the temporality of life and how life relates to information. And so information and time and matter are all kind of the same thing in assembly. And they're, they're manifest in objects that are deep products of evolution. 

Abha: We couldn’t have all the plants and animals that exist on earth today without all of the evolutionary steps that happened before we got here. And Sara argues that those steps didn’t just spontaneously happen — 

Sara: I was taught that it's possible for things to spontaneously fluctuate into existence because that's consistent with our current theories of physics, whether it's thermodynamics or quantum mechanics, and so that sort of permeates a lot of scientific culture where people think you can get complexity for free and you don't need an evolutionary process to generate it. But assembly theory makes a really concrete statement that in chemical space there is a boundary that exists at a certain number of steps for assembling a molecule above which you should never expect the object to exist without selection in evolution. And so there is no spontaneous fluctuation. The only way to get to these high complexity objects and observe them in any abundance is via the process of selection in evolution. 

Chris: To illustrate, let’s pretend that all the chemical building blocks for life are Lego bricks. And you have a Lego set for Hogwarts, the castle in Harry Potter.

Sara: Lego bricks have certain ways that they can fit together. And so there's certain structures you can build in the Lego universe. And some structures like the Lego Hogwarts Castle require very specific instructions for you to build them. If I just gave you all the pieces on the table right now, you know, you'd probably be very hard to build it, even with the idea of a castle in your mind and maybe having some memories of what the Hogwarts castle looks like from the movies, you probably wouldn't exactly be able to reproduce it. But if I said, “Forget about building it yourself. Just shake the table.” Do you think it's likely that Lego Hogwarts is going to spontaneously assemble out of those building blocks? It's very intuitive that that's probably not going to happen. You know, not in the lifetime of the universe of shaking that table would it happen And I actually think it would be impossible for that to happen. So how do you actually get a structure like Lego Hogwarts emerging? Well, you need to actually have a, you know, the information to specify that specific structure on the specific pathway to build it. And so this is sort of the one of the key concepts of assembly theory, like if you had a really simple Lego object, you might be able to build it. But if you had something complex like Lego Hogwarts, it really requires a lot of informational constraints to get to that specific object. And so the space of possible Lego castles is huge. The possible space of Lego objects you could build out of the same set of building blocks is even vaster. And so you have to think about how many constraints in the space to get to that specific structure, to really think about how it's a signature of this evolutionary process of selection for this specific structure to exist. And so this shows a few features of assembly theory. One is we build objects always based on some recursive process, so you can only build up to an object if you've built the parts already. And so this is sort of part of the historical contingency in memory that we feel like is embedded in every object, that every object contains the ways that that the universe could build it. And also the idea that how hard it is for an object to be selected is embedded in the object by this sort of minimal depth to generate the object. 

Chris: There are so many different ways those Legos could come together, and there’s a reason the final product is a Hogwarts castle and not a bunch of random appendages. Assembly theory says that although there are many, many possibilities for assembling different shapes with those Legos, they don’t all come into existence. Just that castle, over the course of a very, very long time. And when you think about it, that’s a pretty spectacular thing. It tells us that something is  being selected.


Chris: In Part One, we looked at some of the crucial factors of life evolving here on earth: the accumulation of information and memory, the ability to compute, and time. We’re now going to speed up to the late 1940s here in the United States.

Abha: That’s right — we’ve landed in the middle of the 20th century. And the mathematician and physicist John von Neumann is trying to design a machine. He wants something that will grow and evolve on its own, basically like a 20th-century version of artificial intelligence. And he wants to figure out what a machine needs to replicate itself, to reproduce like organisms do. So as he’s working this out, he comes up with a theory that this self-replicating machine must store instructions somewhere, and in order to reproduce, it reads the instructions.

Ricard: But during the process of replication, these instructions are also replicated. In trying to answer the question of what is needed for a machine to self-replicate, he ended up in a logic organization that had instructions, a replicator, all kinds of things.

Abha: A few years later, it’s the early 1950s in rainy London. Scientists at Kings College are able to use x-ray diffraction to look way down into the nucleus of the cell and at the structure of the material inside. And, what do they find?

Ricard: Instructions, a replicator, all kinds of things.

Abha: It’s DNA. Remember – von Neumann came up with this theory of replication when he was just trying to apply it to a machine, before anyone knew it was central to our own human existence. It turns out, maybe von Neumann’s theory is pretty fundamental to life replicating everywhere.

Chris: Yeah, I mean, that's something I think is worth stepping back and really appreciating, that the way that computer science took on early theories, you know, the Turing machine, which is heavily reliant on this linear tape as sort of the essential feature of a Turing machine, which is really the way that we model most computational systems. It's the foundation of most computer science theory. And then the way, as you mentioned, that von Neumann envisioned computation, all the different sorts of tapes that we built for early computers. It is sort of amazing that then when we finally figured out what was happening inside cells with the genetic system, it involved all these tapes. So you have this DNA tape that gets read off by these polymerases, and then that passes another set of tapes into the ribosome, which then creates all these functional proteins. And so it's actually a multi-tape system where you keep reading these linear tapes through devices. And sure, there's maybe more steps there than you would need for an abstract computer. There's more steps of passing one type of tape to another type of machine and using that eventually to produce function. And that part might be a little bit arbitrary. The multi-step part might not be preserved. But you're pretty committed to linear polymers, you know, these linear tapes as a fundamental aspect of life anywhere, at least for the information and memory system.

Ricard: Yeah, definitely. If these linear polymers are kind of the fundamental constraints to the complexity of information-carrying molecules, then this probably has a lot of implications in constraining the universe of what we can find out somewhere else.

Abha: The fact that there could be instructional tapes — linear polymers that map out the codes for life and reproduction — is a possible law of life itself, just like information, memory, computation, and time. And this brings us to the next phase of our journey: if we were to look for other life out in the universe, would that life be built on linear instructions, too? What else does our own world tell us about what might be possible elsewhere?


Chris: This is Part Two: Life in the universe. If we looked for life elsewhere, would we know how to find it?


Chris: In biology, we frequently refer to a concept called conservation. Conservation, to put it simply, is when we see shared characteristics across very different organisms. For example, you and I are very different from, say, a spider in your attic, or a great white shark. But we all have cells with DNA and eyes that see. 

And these shared traits point back to the underlying laws of life that we’ve been exploring in the past two episodes.

Ricard: In many cases, the specific solutions to particular problems, like the way the brains are wired or the way our eyes are structured, have been found again and again independently all over the history of evolution. And the solutions seem to be the same, as if there was kind of a fundamental logic that is inescapable. And that's kind of the dream we have, whether we could actually build some theoretical framework, \\ 24:39 but in terms of the logic, I do think there are very, very fundamental constraints on what is possible.

Chris: For me, I think of evolution across the universe like a bowling alley, but a kid's bowling alley where the bumpers have been put up. So these bumpers, if you remember, are sort of the things that people put up on the side of the bowling alley to keep the ball from going into the gutter. So for me, evolution is sort of a wandering path of a bowling ball thrown maybe by a kid who's not so good at bowling down one of these alleys. But the bumpers on that alley are the laws of physics or the laws of chemistry or certain sorts of informational computational laws that have recently been discovered. So evolution creates all this diversity and creates a lot of unique solutions, but always in sort of this well-defined alley and this constrained alley. And so I think the way we get to the universals of life are to think about what's shaping the two sides of the bowling alley, and less about the sort of detailed, messy path that the bowling ball follows down that alley. So when I'm thinking about any planet, the things I want to think about first are sort of the physical constraints. You know, what's the pressure like? What's the gravity of the planet like? What's the viscosity of the fluid?

Abha: These bowling alley bumpers that allow life to form result in conservation: the same characteristics and dynamics showing up again and again, no matter where life arises.

Ricard: And one of my favorite examples comes from artificial life. This field that emerged three decades ago, that essentially is trying to see, reproduce or mimic life and evolution of life within computers, which means that we don't play with DNA or biological matter, we play with algorithms, programs, we mimic things that we see in natural systems, but actually many different things could happen in principle because it's, you know, it's in silico, it's something that can evolve in totally different directions, but the truth is that when you try to make a simulation, artificial life simulation of an ecosystem that evolves in time, it's amazing to see that over time you see emergence of parasites, hyper parasites, predators and prey, sex, cooperation. You see these kind of forms of organization were inevitable. Suggesting that maybe if we were able to get back in time and rerun the tape of evolution, the biosphere will be different, but clearly familiar.

Chris: So because computer simulations evolve parasites, and we see parasites across the tree of life and for all sorts of different organisms ranging from bacteria up to very complicated things like mammals, are you willing to bet there are parasites everywhere in the universe? Anywhere there's life, there's parasites? 

Ricard: Yeah, yeah, yeah. That's one of the things that I would love to see a proof of that. Because it looks to be such a general thing. You mentioned in life, and from viruses to complex organisms, parasitic entities are always apparently ripe to appear. But even I will bet that we can see similar forms of parasitism in social and economic organizations. So to me, parasites are probably something that you cannot avoid when you have a complex system that can evolve.

Abha: Okay so parasites, predators, prey, cooperation — these are some of the common things that we might find if we were to go looking for life in the universe. And so far, we’ve talked about many characteristics of life, so we can predict all kinds of things about what alien life might look like and how it would behave. But, is there a simpler, more fundamental way to determine what life is? If we were searching for life on another planet, could we take one object, point at it, and definitively say, “This thing was once alive, and it’s a product of evolution?”

Chris: Let’s return to Sara and our work on assembly theory. We think it may be possible to use assembly theory to do just this: to measure how complex an object is, and therefore how evolved it is. And that could be the clue as to whether or not it’s a living organism or from a living organism.

Sara: Assembly theory has two observables, one is the assembly index — 

Chris: That’s the measure of complexity..

Sara: And the other is copy number. 

Chris: So if only one of this object exists, or if there are many. 

Sara: And so for any object you can think about building it up from elementary parts by sticking two parts together and then taking any things that you've built in the past and sticking them together recursively to build up to your object. And the shortest path in that is what we call the assembly index. And then we also want to look for how many copies of an object you have. And this is tied to experiments because it turns out from molecules you can measure this minimal path to assemble the molecule using an instrument called the mass spectrometer, which basically fragments the molecules. And if you count the number of peaks in the mass spec, you can correlate with the assembly index. And in fact, it's not dependent on a mass spec to measure this property of molecules. You can do it with NMR and infrared measurements. But in the initial experiments it was just done with mass spec, and then also, in order to detect evolution, you have to detect objects in high abundance, which allows you to talk about, like ruling out the hypothesis that they could have been formed randomly. Because a random event of, you know, like a certain number of steps in an exponential space might happen, you know, once in a you know, I don't know, once in a lifetime of the universe, but never again. And so actually this was part of the reason that we had some sense that there should be a threshold, because if you're doing these, building up of steps, say you're you're attaching atoms and making bonds and building up, if you go about 15 steps, the likelihood of producing a particular molecule is about one in a mole. A mole is, you know, 10 to the 23, so Avogadro’s number of molecules, you might have one of a particular configuration. And so that’s what Lee’s lab did — they went in the lab and took a whole bunch of samples and tried to measure the assembly of different non-living and living samples. And some of them were provided by NASA but blinded and to determine if there actually was a threshold above which molecules were only found in life with very high assembly index. And indeed that's what the experiments actually verified. If you look at all these diverse samples, living things are the only things that produce molecules with more than 15 steps. 

Abha: If assembly theory is true, it’s groundbreaking — it reshapes the way we think about physical beings, time, and information altogether. If we went looking for life in other parts of the universe, the theory tells us that we’d want to look for molecules with an assembly index of 15. That guarantees life. But if we did find life elsewhere, who knows if it would appear to be anything close to what life looks like here on earth. It’s hard to imagine what we don’t know.

Chris: It sort of reminds me of thinking about, you know, you go into the kitchen and you say, I want to build a revolutionary new type of cookie that’s unlike any cookie anyone’s ever eaten before. And you sit down, and the first thing that comes to mind is your grandmother's cookie recipe, and it’s so good, and you know everything about it, and it's really hard to not let that knowledge seep in to think of grandma’s chocolate chip cookie recipe, right.

Abha: It’s important to be open to the idea that what we think we know isn’t always guaranteed to be fact. For Ricard, this even extends to natural selection itself.

Ricard: There are so powerful principles of creating complexity that are tied to natural selection that it’s difficult to think outside of that particular box. And I always wondered in a different context, could it be possible to actually have laws ]distinct from natural selection that can trigger the emergence of complexity? I have a hard time to imagine that, but I do have an open mind.

Chris: The reality is, understanding when and how life originates, and what even constitutes life, is an ongoing conversation. We can find evidence for concepts like conservation across species or assembly theory, but it’s important to remember that science, like life, evolves too. We started off today’s conversation by asking two researchers, both trained in physics, about the origin of life on earth and the universal qualities of life. But when I asked Sara what physics can tell us about the search for life, she was hesitant to talk about physics as something that is complete.

Sara: People usually have this sort of connotation of known physics and not the act of doing physics. And I think those are different things. So there's physics as a discipline that's taught in universities that has sort of a, you know, a set of approaches it uses in a set of problems it addresses. And people do try to use those those bodies of knowledge to try to apply to understanding life in the universe. But the way I approach using physics to study life in the universe is to is to think much more about the nature of the abstractions that we use to describe how the world behaves and whether we need to come up with new theories or new abstract principles or ideas that could explain what life is. And that's sort of the act of doing physics. But, but in a much more sort of, existing at the frontier of the field or the boundary of the field, because it's physics that we don't know yet, because we haven't we haven't discovered what those abstractions are, what those law-like regularities are, those theories. It's using the sort of art of doing physics to come up with new tools.


Abha: After our conversations with Ricard and Sara, Chris and I sat down to talk about his perspective on assembly theory.

Abha: You are one of the coauthors, along with Sara and Lee Cronin on the recent paper published in Nature about assembly theory, and it stirred up a huge discussion in the scientific community. What's the reaction been like and what do you think about it? Where's the science in assembly theory now?

Chris: Yeah, So I think the reaction has been really interesting and I actually think most of the reaction comes down to rhetoric. So I think there's been sort of an interesting rhetorical debate that has emerged, and I think it centers around what do we mean by evolution? What do we mean by selection? So we say “selection” in this paper. And and we really meant generalized selection. But people are naturally because of the history thinking about natural selection by Darwinian evolution using genetics. And our point really is when you get to talking about genetics, you're already very far down the origin of life trajectory. We need new types of theories, new types of descriptions that allows one to talk about the very earliest moments in the evolutionary history of life. Assembly theory is one way to do that. Assembly theory is one way to capture early evolution.

Abha: There was a lot of criticism. And I think one of the criticisms that came to the fore was the fact that this was not a new idea.

Chris: So, I'm sort of an extreme pluralist in that I at some level don't think there's any such thing as a new idea. I think all ideas build on the past and there's a long history in evolution of thought for almost any idea. I think Einstein was — it's at least attributed to him that — you know, “genius is disguising your references.” And I think that's a clever way of him, if he said it, I think it’s apocryphal, you're always taking ideas from the past and reshaping them into the future. 

Abha: What about the quantitative critiques? 

Chris: So it’s interesting that there have been many assertions made about assembly theory. And we’re actually working on another paper to show that some of these assertions are simply not true as far as we can tell. 

Abha: How does it feel to be writing a paper in response to public debate?

Chris: I think it's great that assembly theory has generated so much debate. In fact, I think in some parts of the sciences, we don't have enough debate.  And that really limits science. I would argue that the nature of physics was always to say, let's take everything seriously and let's try to disprove everything. If someone has a brand new theory, that's great. Let's see if it holds up against all the things we know. And so all we can say for theory is so far it hasn't been disproven. That's what the process of physics is. And so I think a lot of what Sarah was talking about and a lot of my perspective is seeing physics as process rather than physics as knowledge. So I'm happy about the debate with assembly theory. I think it's good for us to rigorously question every new theory that is proposed. 


Abha: Coming up on Complexity, we’ll ask: why is our biosphere so diverse?

Brian: Under different climate change scenarios, under different human land use scenarios, under different extinction scenarios, what's going to happen to the biosphere?

Abha: That’s next time, on ComplexityComplexity is the official podcast of the Santa Fe Institute. This episode was produced by Katherine Moncure, and our theme song is by Mitch Mignano. Additional music from Blue Dot Sessions, and the rest of our sound credits are in the show notes for this episode. I’m Abha, we’ll see you next time.