Curiosity Unbounded, Ep. 3: Decoding the tree of life
[MUSIC PLAYING] SALLY KORNBLUTH: Hello, I'm Sally Kornbluth, president of MIT, and I'm thrilled to welcome you to this MIT community podcast Curiosity Unbounded. In my first few months at MIT, I've been particularly inspired by talking with members of our faculty who recently earned tenure. Like their colleagues in every field here, they are pushing the boundaries of knowledge.
Their passion and brilliance, their boundless curiosity, offer a wonderful glimpse of the future of MIT. Today my guest is Greg Fournier, associate professor of geobiology. Greg's work centers on the microbial world.
He and his team study microbial evolution to further our understanding of the evolution of life on Earth. Greg, I've been looking forward to this. Thanks so much for being here. GREG FOURNIER: Well, thank you for inviting me. SALLY KORNBLUTH: I heard that, as a child growing up in rural Connecticut, you liked to wander in the woods with your friends and would come upon signs of life, human life from years earlier, barbed wire embedded deep within a tree, crumbling stone foundations.
And I understand that it was these early discoveries that helped fuel your interest in the evolution of life itself. So how did that interest lead you to become a geobiologist? GREG FOURNIER: Well, I think when you have the opportunity to really explore in the natural world, especially a place that doesn't have trails or a guide, that when you are 10 or 12 years old, as far as you know, you're the first person to ever discover it. And that leads you to genuine exploration experiences.
And in a way, you always want to get back to that feeling. It's a bit different than the adventures you can have when there's already a trail, or there's already a mountain peak, or there's already a list of things you're supposed to see. I think I've always been drawn to that kind of exploration. And the work we do looking at the evolution of microbes and genes and genomes over billions of years is not only new as a discipline, but it's also still a place where you can really explore, you can reconstruct the histories of these large data sets, and you can discover something that no one else has really put together before. And in a field that's as old as evolutionary biology, it's exciting to be able to bring a new perspective and still be part of that kind of tradition.
SALLY KORNBLUTH: Yeah I can imagine that, as a kid, you don't have a sense of the long, long history of time. And when you come upon things that are completely different from your day to day experience, and you see no evidence of immediate human touch, you sort of have that wonder of, wow, I'm seeing something that someone who maybe lived 100 years ago or 1,000 years ago has seen and no one's seen it since. And when you think about evolutionary time, it's even more abstract, right? Like, it's something that's happened eons ago and you're like picking up the fingerprints of it. GREG FOURNIER: Yeah, I think that's exactly right, and it's something that even when you study this for 20 years, it's hard to wrap your head around, just how much time we're talking about. SALLY KORNBLUTH: Exactly. I've heard kids talk about-- they'll look at some old book and say, wow, this book must be 10,000 years old, not really understanding what the actual history of human time is.
Never mind the history of microbial time. It's really interesting to think about that. So I'm told you just came back from a sort of a geological road trip to some incredible sites out west including one called Craters of the Moon. What were sort of the impressive and exciting things you saw out there? GREG FOURNIER: I had a chance to do some driving around out west a few weeks ago. I went to a few national parks and got to see some really amazing geology and geomorphology. I had been to Yellowstone before, so I skipped that one on this trip.
But that let me go to some of these much less frequently visited parks, like Craters of the Moon. It's one of the few places in the United States where you can just still see lava fields and cinder cones and this volcanic landscape. And then, right around the bend, there will be just grasslands and mountains and fields and deer, some very ordinary things. So the abrupt changes of the landscape you see out there were really amazing.
I was able to go to a few other parks, like Wind Cave, which is in the southwest corner of South Dakota. And that has one of the largest cave networks in the United States. But aside from that, it also has a really great landscape of hills and fields and hiking trails. And on one of the loop hikes I was planning to do, I went around a corner and there was a bison. SALLY KORNBLUTH: Wow.
GREG FOURNIER: And it wasn't going anywhere, so I just had a chance to have a nice staring contest with a bison for a while, and then I decided to turn around and go back the way I came, which is always the right thing to do. But those kind of unplanned experiences or encounters were just great, and the trip was full of them, so it was really a nice opportunity. SALLY KORNBLUTH: Do you use your geologists mind when you're doing this sort of hiking? You know, I might go out and say, that's kind of a pretty rock, you know? But I'm not thinking about the origins, and how things got there, and what sort of seismic forces might have led to the landscape. And so do you reflect on these things? And how do you think about some of the things that you saw in that respect? GREG FOURNIER: So in some ways I do.
For me, especially out west, it's always interesting to think about the fact that this used to be at the bottom of an ocean. Coming back to Wind Cave, if you go into the cave network and you look on the ceiling, you can see little shells and fossils of little sea creatures just everywhere. And that's all in the limestone of the cave, which has been dissolved away over time, leaving behind all of these structures.
And in some cases, you can see the fossils that were on the bottom of this ocean during the Mesozoic era. SALLY KORNBLUTH: Oh, that's really cool. That's really cool. I have to go visit there. I've never been there. GREG FOURNIER: Yeah, you really are just surrounded by direct evidence that there's a continual set of changes happening on Earth.
And this was not always the top of a mountain. This was not always a plain. There were not always bison here. Intellectually, it's one thing to understand that. But to be 300 feet underground in South Dakota and say, oh, yeah, that's a seashell, is really an amazing experience.
SALLY KORNBLUTH: Yeah, that's really interesting because I think we tend to think of the ground we're standing on as a solid, immutable thing. And obviously, over geological time, that's not true. It's really interesting to reflect on that and having really visual, clear markers of change we don't notice it in our everyday life. But the notion of seeing seashells on the ceiling of a cave is a great illustration. Some of your stories here recounting your trips and your interest in long scales of time and evolution bring me to ask how that relates to your own work. So when you look, for instance, at microbe evolution, how does that impact our understanding of Earth's history, of mass extinctions? You know, what do we learn from the science of microbes and the history of genomes that actually relates to the bigger picture that we see? GREG FOURNIER: Even in talking about how ancient all of these geological features are, they're all quite young compared to the age of the Earth itself.
So whether we're talking about the Rocky Mountains, which are relatively young in terms of mountains, or the Inland Sea that used to cover a lot of North America, these are all Mesozoic. And when we reconstruct the evolutionary history of microbes, we can go far beyond that. In fact, we probably are reaching earlier than there are any rocks at all on the Earth. So the very oldest rocks, deposited sedimentary rocks on Earth are maybe 3.8, 3.9 billion years old. The very oldest scraps of material we have are little crystal zircons that are a little older than 4 billion years old.
But we don't know when life originated on Earth. But it was very likely at least as old as 3.8 billion. And so when we reconstruct the relationships of genomes between all of the groups on the tree of life, we're actually creating these threads that are reaching back to even before the oldest rocks. So in a way-- SALLY KORNBLUTH: That's so interesting.
GREG FOURNIER: Yeah. Yeah. And so in a way it's the oldest record we have of processes or events on the early Earth. And trying to figure out what tiny scraps of information might still be in there and how we can use that to understand the history of life in the Earth is, really, one of the most important things that I think we work on. SALLY KORNBLUTH: Tell me a little bit about your sort of work studying the Permian-Triassic mass extinction. I think people also have a real trouble wrapping their minds around the notion of mass extinctions.
You know, aside from the sort of movie hype. How do you think about this and what have you learned? GREG FOURNIER: Moving forward in time from thinking about the earliest origins of microbes, all the way into the Phanerozoic era, so the quote "modern era." But still before the dinosaurs, before the Mesozoic, you had one of the largest of the five mass extinctions of complex life in Earth history. And that happened at the end of the Permian about 250 million years ago.
It was definitely by far the largest catastrophe that complex marine and terrestrial life has ever faced on Earth. We've understood this from the paleontological record for some time. And it's correlated with the emergence of large igneous provinces in Siberia, huge lava fields that cover thousands of square miles that are associated with the tectonic events that likely caused this mass extinction.
And also, we see evidence in the fossil record of the vast majority of species just vanishing. And the organisms that do survive and diversify in many cases are quite different afterward. And that's the beginning of the Mesozoic era. SALLY KORNBLUTH: I guess I never thought about tectonic changes as instruments of mass extinction. In other words, in the popular lore, it's always a meteor or something like that, rather than sort of intrinsic forces, volcanic activity, et cetera. So that's really interesting.
GREG FOURNIER: Yeah. I think it's especially interesting when you realize just how large these forces are. Over tens of thousands of years, when the Earth releases a tremendous amount of volcanic material in terms of magma and gases, and especially carbon dioxide, what you see is a radical change of the climate. Processes that we observe happening today, like ocean acidification for example, were the main drivers of this greatest mass extinction. What our work was trying to do is examine the causes in a different way by looking at the evolutionary history of microbes that may have evolved in response to these changes. SALLY KORNBLUTH: So if I extrapolate from that-- not to be doomsday, but if we think about on a much longer time scale the impact of climate change and changing CO2 in the atmosphere, et cetera, we could imagine some of the gradual extinctions we're seeing.
If you play that out over much longer time, it's like it was sped up with these massive events. Is that a correct way to think about it? And if the answer is no, say no, and I'll ask a different question. GREG FOURNIER: I think, interestingly, it seems to be the opposite. And the changes that we're seeing now are likely much faster. SALLY KORNBLUTH: Really? OK, so this is really interesting and scary. GREG FOURNIER: It is scary.
And at the same time, there's so much uncertainty because we understand these mass extinctions looking back over millions of years at the accumulated consequences. But, during the event itself, it's very hard to say what those future consequences are going to look like. We don't know how much disruption the climate or biogeochemical cycles or food webs can take before you have, perhaps, run away collapses that look like a mass extinction. SALLY KORNBLUTH: So your comment that it's faster is based on some snapshot of time, the time we've seen in terms of species extinction, versus what we can extrapolate from the fossil record? In other words, how do you compare those rates? GREG FOURNIER: It's especially tricky because the fossil record is very sparse. The sampling of organisms that we see in the fossil record is biased by what tends to die in an environment that is likely to be preserved. SALLY KORNBLUTH: Yes.
GREG FOURNIER: And organisms that are the most sensitive to extinction may already be ones that have smaller population sizes, so less likely, statistically, to be preserved in the record. SALLY KORNBLUTH: Oh, interesting. GREG FOURNIER: But what's concerning is more about the rate of the change in the carbon cycle. So the increased rate of CO2 production through anthropogenic processes is much faster than the modeled increased rate of CO2 production during these mass extinction events. But still, it accumulates over a very long period of time. And we've only been really doing this for 200 years.
That's where the uncertainty comes in. SALLY KORNBLUTH: I see. That's really, really interesting. I've heard that you like to use the local landscape to educate your students on environmental diversity. Where does that take you here in Massachusetts? I hear there's a place called purgatory chasm, which I want to assure our listeners is not at MIT.
Maybe you can tell me a little bit about that. GREG FOURNIER: Purgatory chasm is a rock formation in Sutton, Massachusetts, so about an hour southwest of here. And it is likely formed by glacial meltwater, which tore a hole through this part of the landscape and resulted in about this mile long miniature cnayon that you can hike and explore in. And you can still see the scrape marks of boulders that were likely moved by these glacial meltwaters, and some rock formations that just show you the force with which these very recent processes occurred that shaped our landscape here in New England.
So it's just a really nearby dramatic accessible example of those kinds of processes. SALLY KORNBLUTH: Oh very cool. I'm definitely going to have to go and take a look.
That sounds really interesting. Are you seeing artificial intelligence as a tool in your work at all? Does that impact any of the things that you're doing now? GREG FOURNIER: Interestingly, it did for the very first time only about a month ago. SALLY KORNBLUTH: Oh, really, interesting. Tell me about that. GREG FOURNIER: One of the projects we've been working on for some time is reconstructing the most ancient evolutionary events within protein families that are conserved across the entire tree of life.
And we're specifically interested in these proteins called aminoacyl tRNA synthetases. So these enzymes are responsible for enforcing the genetic code. These proteins are found in every cell across the whole tree of life and two main groups of them are related to each other. But if they're present in all life, it means that they must have diversified from one another before the single last common ancestral lineage of all life on Earth.
SALLY KORNBLUTH: Oh, that's interesting. GREG FOURNIER: So when we reconstruct their relationships we're actually reaching back to before the last common ancestor of all life on Earth to look at the evolutionary events that were likely directly involved with establishing the rules of evolution as we understand them. SALLY KORNBLUTH: When you say that this divergence occurred before sort of life as we know it, you're saying that they were evolving in cellular life forms that are no longer known to us.
GREG FOURNIER: In a way, yes. So the way to think about it is life evolves by this branching tree where species give rise to other species and then go extinct. So if we work backwards by looking at living things that exist today, we create this tree.
But we can only go as far back as the common ancestor of all of the groups that survived until the present day. SALLY KORNBLUTH: OK. GREG FOURNIER: But we know by comparing the similarities of all of this diversity of life that this last common ancestor was already a modern looking cell that had all of the machinery that modern cells have. But that machinery itself must have evolved from even simpler states. SALLY KORNBLUTH: Yes And presumably, if you compare tRNA synthases to other molecules, other families, you can see things that also might have diverged before common ancestors, or that things that had much later divergence will give you insight into the fact that those organisms must have existed. GREG FOURNIER: Yes.
There are similarities between very distantly related proteins in terms of how their secondary structures fold. And we can see those superclasses of protein families being very diverse. So that must have been established at some time. But the aminoacyl tRNA synthetases, if we trace back to their common ancestor, it was likely involved in the same thing that synthetases are today, which is making sure the correct amino acid goes on to tRNA so that the genetic code can be translated in a faithful manner. The difficulty with recovering this history is proteins, in a way, are like rocks, in that, over billions of years, so many processes and forces can change them that they get altered.
And more recent evolutionary events can overprint and replace older changes. And over time, the distance, the dissimilarity between these proteins becomes so great that it becomes very difficult to determine what parts share a common ancestry with what other parts. SALLY KORNBLUTH: I see, because it may have been overwritten many, many times. GREG FOURNIER: Exactly, almost certainly, in many cases. This is a problem that we call alignment.
And for more closely related proteins or proteins that evolve very slowly, it's more or less a solved trivial problem. But for highly divergent proteins, we have to use some special tricks. And one of those special tricks is to compare structure because the three dimensional structure of the proteins changes much more slowly than their particular amino acid sequence. And these structures are understood by X-ray crystallography. But the problem is not all proteins can be crystallized.
And even for proteins that can-- for example, there are hundreds of aminoacyl tRNA synthetase proteins in protein structure databases. But if you look at them, there are regions of those proteins that are not in the crystal structure because they're the floppy parts, usually on the end of the protein, that probably contain a lot of information but are so variable and they don't crystallize well. So usually, you just cut those parts off. And coming back to AI, we wanted to extract as much information as we could out of these protein sequences so that we could get a robust evolutionary signal to align and generate their deepest evolutionary relationships. SALLY KORNBLUTH: I see, interesting.
GREG FOURNIER: So If we can't do it on sequence alone, and we don't have the crystal structures because of those limitations, it turns out that there are AI-based tools now that will solve protein three dimensional structures. And so we applied some of those tools to these proteins that had uncrystallizable regions, and they gave us structures that were conserved across different versions we tried, and allowed us to detect and extract these very divergent aligned sequence regions. And in one case, one protein, it's involved in loading valine onto tRNA, we discovered that there's actually a duplication in this protein region. And that duplication was confusing all the alignment programs. So in a way, we use AI to fill a gap in our understanding so that we could apply more traditional established methods to extracting as much information as we can from this very, very ancient signal. And it works fantastically.
SALLY KORNBLUTH: That's cool. So basically you're using the similarities in 3D structures without having to go through the step of crystallizing the proteins. And AI can essentially extrapolate the 3D structure and then make the comparison. GREG FOURNIER: In this case, yes. SALLY KORNBLUTH: I know it's not that simple, and we're not putting all X-ray crystallographers out of business, but that's really interesting. Coming back to sort of an earlier thing that occurred to me then, when you look at, let's say a protein family, and you, as you said, believe the common ancestor is before sort of the cells that we know of now, I guess these proteins are too complex to make the claim that there would have been independent origin.
Correct? In other words, they had to have come from a common ancestor. GREG FOURNIER: Yes. Even for relatively small proteins. So there are 20 different amino acids. And so-- SALLY KORNBLUTH: So the combinatorial-- GREG FOURNIER: Oh, it explodes to the point where, if you take the average size protein, the probability of two of those arising by chance is like 1 over the number of subatomic particles in the universe squared by itself.
It's just-- it's hyper astronomical. There are no numbers. SALLY KORNBLUTH: Fair enough.
Fair enough. I asked that as a naive question or sounding naive question. I kind of knew that but I wanted to tease that out for the audience because that kind of question does come up, particularly when people are discussing evolution, which sometimes can be hard to think about on the long time scales. GREG FOURNIER: In a way it is a trick question because the reality is evolution doesn't need to find an exact sequence to do something.
SALLY KORNBLUTH: That's exactly right. You also, I think, when you think about microbial evolution and how things might move over time, thinking about things like horizontal gene transfer and how microbes sort of pass genetic information back and forth, maybe you can sort of tell our listeners a little bit about what that is and how that helps you understand evolution of the microbes around us. GREG FOURNIER: Sure. It's really important. For the most part complex life acquires this genetic information through parent cells and then it passes them on to progeny.
However, microbes don't necessarily need to rely on that. They don't need to only rely on mutations or changes that were acquired by their direct ancestors and passed on. They can acquire genetic material, DNA, directly from the environment.
Sometimes this happens through viruses. Sometimes this happens just through taking up pieces of DNA as food. And microbes are prokaryotes. They don't have a nucleus. So their DNA is just floating around in a tightly packed bag of proteins and everything else. So some of that DNA can recombine into their genome.
And if it's not particularly harmful, it won't be removed and it won't kill the cell. And if you're especially lucky, it may actually be expressed and have a function that increases fitness in the long run. And it doesn't matter if this is an incredibly rare event because there are a lot of microbes. SALLY KORNBLUTH: Right.
Right. So you've been at MIT for a while. I understand that in your academic career you somehow kept circling back to MIT. And it may not have been totally intentional, but can you talk a little bit about your experience at MIT, the intellectual community, how that's influenced your work. GREG FOURNIER: It is true that I seem to keep on ending up back here. I was a technician for a few years in a few different labs right after undergrad.
And then I went to graduate school at the University of Connecticut. And then afterwards got the NASA postdoctoral fellowship and ended up being hosted by a lab here in course one at MIT. And then was fortunate enough to get a position in the EAPS Department. I think one of the best things about MIT, and why it works so well for the kind of work I want to do, is people here, first and foremost, want to study interesting problems and come up with interesting solutions. And that matters a lot more than discipline or department or field or methodology or approach.
And if you have an idea and you reach out and talk to somebody, they will likely be excited about it. And if they don't want to work on it or can't work on it, they will certainly help you find someone that does. And that kind of collaboration and interdisciplinary or cross-disciplinary approach or vision is, I think, fantastic for the kind of work that I want to do. And I also think it's really good for students. Because in the real world, this is how things get done.
SALLY KORNBLUTH: Every time I think of some sort of interesting question or something that strikes me while I'm here, and I look to see if anybody at MIT is doing whatever it is, the answer is pretty much always yes. You can find somebody who's working on almost any area of science and engineering and that, with your example, you could-- if I were in a lab, I could reach out to for help with a project or to think about things, it's really kind of amazing. GREG FOURNIER: It really is. And I think people here really do care about helping each other do the best work they can and about exploring things that they really care about and are excited about. SALLY KORNBLUTH: If someone's like just starting a career in m I think the impression is that PIs who are here really had success at every step of the way.
And from my own experience, I know that's not true, right? You're always taking turns. Like, I'll give you an example from my sort of own career, which is when I was originally working on cell proliferation and cell cycle. That's what I started my lab on. And we set up this really incredibly complicated experiment. Every time we set up this experiment, the nuclei would essentially explode.
OK? And we were looking under the microscope, what is that? What is that? And then we suddenly realized from some pictures I'd seen elsewhere in a journal that we had, essentially, been looking at apoptosis or cell death in the microscope. And someone else had actually reported an in vitro reconstitution of that as well. But we had been looking at completely different stimuli. And I was like, oh, that's why the way we set up this experiment happened. And it actually led to more than half of my lab working on cell death.
But it started out as months of failed experiments, and then the light bulb went off. Oh, when you do x, y, and z, the cell dies. So when you do x, y, and z, the nuclei falls apart. It looked like an error.
It was just all really frustrating. And then you go, well, maybe there's actually an intelligent interpretation of this. So there are any moments you might share where you had any doubts, or when something went wrong in an unexpected way, or opened new doors? GREG FOURNIER: That's a good example. So there's a project that we're still currently working on that is about the evolutionary history of genes and microbes that get energy by oxidizing iron.
All living things use iron. It's one of the most abundant elements on Earth. But it is actually found in very, very low concentrations in the ocean. Most environments are hard to get reduced iron because we have oxygen everywhere. And so if there's iron and oxygen, you get rust, and that precipitates out. So hanging on to iron is something that life had to evolve and learn how to do.
And it's very, very good at doing it. So we were hoping that we could just find the genes involved in metabolisms for oxidizing iron, and they would reach back billions of years and tell us about how iron worked in the Archean ocean before there was oxygen and iron was freely available to all for energy metabolism. But every time we reconstructed the histories of these genes, they didn't reach back deep in time. They were only found within relatively narrow groups on the tree of life. SALLY KORNBLUTH: Yet you knew other organisms had to be handling iron somehow. GREG FOURNIER: Right.
And we probably looked at 30 or 40 genes. We tried so many different enzymes and functions that are even tangentially related to these iron metabolisms. And no matter what we looked at, it was the same answer. Like, there was no record.
And so this is not what we hoped to find. And it's a bit frustrating. And after discussing it with our students and postdocs in the lab and thinking about it, we're like, well, OK, maybe if we flip this on its head, it's actually telling us something very interesting, which is maybe there are some ancient metabolic processes and microbes that are invisible because what's happening is evolution is throwing them out and replacing them so frequently. Or different groups on the tree of life are replacing one another. Which is something that we know is the case for complex life, but really isn't how we think of microbes for the most part. But if that's the case, then we're only seeing the snapshot of relatively modern microbial life that's doing iron oxidation.
And this niche was probably way bigger 3 billion years ago, but the microbes doing it have either changed jobs or the genes have been replaced or changed. SALLY KORNBLUTH: Interesting. GREG FOURNIER: So maybe there's some kind of instability in this niche where it's being overwritten or overprinted with more recent diversity, the way we see after a mass extinction, or the way we see in complex life. So maybe this is a hint that, in some ways, microbial life actually works a little bit more like complex life than we really previously appreciated.
Where there are turnovers or faunal successions of different eco types that replace, even down to individual enzymes, older lineages, even though they were doing the same job. SALLY KORNBLUTH: It's funny. My PhD thesis advisor used to always say, you can learn as much from the experiments that didn't work if you really think about them-- now, of course, that assumes you didn't, like, mess up the experiment. But when you've done something legitimately correctly and you get a really unexpected result, or a failure in what you anticipate, it can sort of open up whole new doors in terms of how to think about things. And I think students, when they're doing their graduate work, that can just be seen as a long frustration because, obviously, it can take a long time.
But sometimes it really does open really interesting new doors. GREG FOURNIER: It really does, and it also helps teach us how to formulate hypotheses instead of we fail to prove the hypothesis or we did not. Instead think of it as, well, here are multiple scenarios, and then we'll see what the data and analysis says which one of these scenarios is more likely.
And ideally, all of them are interesting in their own way. So instead of accepting or rejecting a hypothesis, it's about, do our observations and data and analysis support one narrative over another one? And then tell that story. Because there's always an interesting story. SALLY KORNBLUTH: Exactly. I still remember this really well because there's, actually, a friend of mine who's at University of Connecticut-- Bruce Mayer, he was across the bench from me in graduate school.
And we had been working-- all the lab had been working on cancer causing genes that were part of a family called tyrosine kinase that attach phosphates to tyrosinase. And he had just been sequencing this cancer causing gene, and we assumed it was going to be another one of these enzymes. And it had the same structure at the n-terminus but then there was no kinase domain. And it turned out to be a whole new class of signaling proteins that he had not anticipated.
You know? And at first it was like, what's wrong with this sequence? And then it was like, ha ha, there's nothing wrong with the sequence. This is what it looks like. So that was kind of cool. GREG FOURNIER: Well, that's really interesting considering how conserved those domains are. SALLY KORNBLUTH: Right. So it was sh2 sh3 domains and no kinase domain.
These little modular sh2 and sh3 signaling molecules are known to be modular. I think if you think about long term evolution, a lot of these little pieces of protein find themselves in lots of different contexts. Just maybe the last thing, when you're training new young scientists, do you have any kind of important words of advice for them? GREG FOURNIER: I think the advice I find myself giving students repeatedly is to try a lot of different things and then follow up on the ones that seem to be going somewhere and that you're excited about. SALLY KORNBLUTH: You have just talked about evolution. In other words, try a whole bunch of different things and then the selective pressure of your experimental findings should force you along a pathway that leads to your successful outcome.
Anyway, thank you so much for being with us here today. GREG FOURNIER: Thank you very much. It was a pleasure. SALLY KORNBLUTH: To our audience, thanks again for listening to Curiosity Unbounded. I very much hope you'll join us again. I'm Sally Kornbluth.