How Did Multicellular Life Evolve? | Podcast: The Joy of Why

00:44:26
https://www.youtube.com/watch?v=MsvDAGKRO4c

Zusammenfassung

TLDRIn this episode of 'The Joy of Why', hosts Steve Strogatz and Janna Levin engage in a fascinating discussion about the origins of multicellularity, featuring biologist Will Ratcliff. They delve into the historical context of unicellular organisms and the significant evolutionary leap to multicellularity, which has occurred independently around 50 times across various life forms. Ratcliff shares insights from his research on yeast, where he aims to induce multicellularity in the lab. The conversation highlights the advantages of multicellularity, such as increased size and resource efficiency, while also addressing the challenges these organisms face, including diffusion limitations. The episode emphasizes the importance of constructive criticism in scientific discourse and the collaborative spirit of scientific inquiry.

Mitbringsel

  • 🧬 Multicellularity evolved independently about 50 times.
  • 🔬 Yeast is being used to study the transition to multicellularity.
  • 🌍 Understanding multicellularity can inform us about life on other planets.
  • 💡 The evolution of multicellularity offers advantages like size and resource efficiency.
  • ⚗️ The Multicellularity Long-Term Evolution Experiment (MuLTEE) is ongoing.
  • 🧪 Snowflake yeast forms clumps due to a mutation preventing cell detachment.
  • 🌊 Oxygen can limit growth in larger multicellular organisms.
  • 📊 Challenges include diffusion limitations and structural integrity.
  • 🤝 Constructive criticism is vital in scientific research.
  • 🎙️ The podcast emphasizes collaboration and curiosity in science.

Zeitleiste

  • 00:00:00 - 00:05:00

    Steve Strogatz and Janna Levin introduce the podcast 'Joy of Why', discussing the exciting topics for Season Four, including the origin of multicellularity, a subject that has intrigued both hosts despite their different scientific backgrounds.

  • 00:05:00 - 00:10:00

    Levin shares her fascination with the long period of single-celled organisms on Earth before multicellularity emerged, prompting a discussion on why this transition took so long and whether it occurred multiple times independently.

  • 00:10:00 - 00:15:00

    Strogatz reveals that multicellularity has evolved independently around 50 times across different biological kingdoms, leading to questions about how unicellular organisms make this transition and the significance of Will Ratcliff's lab work on yeast.

  • 00:15:00 - 00:20:00

    Ratcliff explains the basic characteristics of unicellular versus multicellular life, emphasizing the evolutionary advantages of multicellularity, such as increased complexity and the ability to perform functions that single-celled organisms cannot.

  • 00:20:00 - 00:25:00

    The conversation shifts to the timeline of multicellularity's evolution, with Ratcliff detailing when various organisms, including cyanobacteria and fungi, began to evolve multicellularity, highlighting the ecological factors that influence these transitions.

  • 00:25:00 - 00:30:00

    Ratcliff discusses the benefits and challenges of multicellularity, including how larger size can provide advantages in resource competition, while also introducing new constraints related to growth and resource acquisition.

  • 00:30:00 - 00:35:00

    The hosts explore the concept of clusters versus organisms, with Ratcliff clarifying the distinctions between multicellular groups, Darwinian individuals, and true multicellular organisms, emphasizing the importance of cellular specialization.

  • 00:35:00 - 00:44:26

    Ratcliff concludes by discussing the implications of his lab experiments for understanding the historical evolution of multicellularity, suggesting that while the details may differ, fundamental processes are likely universal across different lineages.

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Video-Fragen und Antworten

  • What is the main topic of this episode?

    The episode discusses the origins of multicellularity and ongoing research to induce it in yeast.

  • Who is the guest on the podcast?

    The guest is Will Ratcliff, a biologist at Georgia Tech.

  • What organism is being studied to understand multicellularity?

    Yeast is being studied to understand the transition to multicellularity.

  • How many times has multicellularity evolved independently?

    Multicellularity has evolved independently around 50 times.

  • What is the significance of oxygen in the evolution of multicellularity?

    Oxygen can limit growth in larger organisms, affecting their evolutionary path.

  • What is the 'snowflake yeast'?

    Snowflake yeast is a type of yeast that forms clumps due to a mutation preventing daughter cells from detaching.

  • What is the Multicellularity Long-Term Evolution Experiment (MuLTEE)?

    MuLTEE is an experiment to observe how simple groups of cells evolve into complex multicellular organisms.

  • What are the benefits of multicellularity?

    Benefits include increased size, division of labor, and better resource acquisition.

  • What challenges do multicellular organisms face?

    Challenges include diffusion limitations and the need for structural integrity.

  • How does the podcast address criticism in scientific research?

    The podcast discusses the importance of constructive criticism and the impact of dismissive attitudes in science.

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Untertitel
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Automatisches Blättern:
  • 00:00:06
    STEVE STROGATZ: I'm Steve Strogatz. JANNA LEVIN: And I'm Janna Levin.
  • 00:00:08
    STROGATZ: And this the 'Joy of Why', a podcast from Quanta Magazine
  • 00:00:10
    exploring some of the biggest unanswered questions in math and science today.
  • 00:00:16
    STROGATZ: Hi Janna. Great to see you. LEVIN: Hey Steve,
  • 00:00:18
    how you doing out there? STROGATZ: Good. Welcome,
  • 00:00:22
    this is Season Four. We’re back! LEVIN: We’re back. Looking forward to this.
  • 00:00:25
    STROGATZ: Yeah, me too. This is gonna  be a really exciting season and I’m so
  • 00:00:29
    thrilled that we’re doing it together. LEVIN: Yeah. And you’re kicking it off
  • 00:00:32
    this season. You have the first episode. STROGATZ: Yeah, so I did. And the topic
  • 00:00:37
    was one I had never thought about before,  I wonder if you’ve run across it. It’s the
  • 00:00:41
    question of the origin of multicellularity. LEVIN: Weirdly, I have thought about this.
  • 00:00:47
    STROGATZ: You have? LEVIN: Well, I found it
  • 00:00:50
    fascinating that single-celled organisms waffled  for so long on the Earth. And that just nothing
  • 00:00:57
    was happening for a very, very long time, billions  of years. And then something finally happened. I
  • 00:01:02
    always thought that was just remarkable. STROGATZ: But, so, I think of you thinking
  • 00:01:06
    more about, like, black holes,  space time, astrophysical stuff,
  • 00:01:10
    but why are you thinking about this? LEVIN: Because science is fascinating. I like
  • 00:01:15
    the science that other people are doing too. And  sometimes I just wanna hear about it. You know,
  • 00:01:19
    I muse about things that I don’t  plan on working on necessarily.
  • 00:01:22
    STROGATZ: Okay, I see. So not from some  astrobiology, life-on-other-planet type.
  • 00:01:27
    LEVIN: Not yet. Not yet anyway. STROGATZ: Huh. But you make the point
  • 00:01:29
    about waffling. That single-celled critters,  like we had bacteria, maybe cyanobacteria in
  • 00:01:35
    the oceans, taking them a long time to get  their act together to go multicellular. And
  • 00:01:40
    you said you wondered why it took so long? LEVIN: Yeah. Right, I mean if you ask about
  • 00:01:44
    astrobiology, is that happening on other  planets? It’s just taken a really long time,
  • 00:01:48
    and they’re just single-celled  organisms floating around out there?
  • 00:01:51
    STROGATZ: Right, what took so long? LEVIN: Yeah.
  • 00:01:54
    STROGATZ: And did it only happen just once? And  apparently, and this came as a shocker to me,
  • 00:02:00
    it did not just happen once, it happened  something like 50 times independently.
  • 00:02:04
    LEVIN: That’s shocking. STROGATZ: Yeah, why wasn’t I informed?
  • 00:02:06
    LEVIN: Yeah, why am I the last to know? STROGATZ: Well, I think when we were in high
  • 00:02:12
    school and they were teaching us biology, they  didn’t know that. But it’s now understood that,
  • 00:02:17
    you know, in all these different kingdoms or  whatever they call them in biology — so whether
  • 00:02:22
    it’s animals, plants, fungi — they all figured  out their own way to do it, to go multicellular.
  • 00:02:29
    But in any case, one question then is how does  a unicellular organism manage to make this
  • 00:02:34
    transition, in any of these cases? I mean, there’s  the historical question of ‘How did it happen?’,
  • 00:02:39
    but what’s so amazing and really very courageous  about our guest — Will Ratcliff is his name,
  • 00:02:45
    he’s a biologist at Georgia Tech — is that he  wants to do this in the lab. He wants to induce
  • 00:02:50
    a multicellularity transition in a single-celled  organism that we’ve all heard of — yeast — like
  • 00:02:56
    the yeast in making beer or bread rising,  whatever, which normally lives as a eukaryotic,
  • 00:03:03
    single-celled organism. He has found a  way to get them to act multicellular,
  • 00:03:08
    to clump together into… Are they a colony? Are  they trying to be a multicellular organism in
  • 00:03:13
    their own right? LEVIN: Well,
  • 00:03:15
    I really hope that stays in the lab. STROGATZ: You don’t wanna see that thing
  • 00:03:20
    coming at you. LEVIN: Unleashed.
  • 00:03:22
    STROGATZ: Coming at you on the street. LEVIN: I don’t want it coming out of my
  • 00:03:24
    kitchen sink drain, you know, like  one of those crazy cyclops fungi.
  • 00:03:30
    STROGATZ: Well, we’re not there yet. I can tell  you. That’s not where the episode is going. But
  • 00:03:35
    as we’ll hear from Will, it is controversial.  There are colleagues of his who feel what he’s
  • 00:03:40
    doing is irrelevant to the history of life on  Earth, that he’s just doing something in the lab,
  • 00:03:45
    and it may be telling us very little  about what happened in real biology.
  • 00:03:50
    Whereas other people think, it’s fundamental  mechanisms that he’s getting at. It’s opening
  • 00:03:55
    up a realm of possibilities for us  to explore. Some may have occurred,
  • 00:03:59
    some may not have occurred, historically. But,  still, it shows us what biology is capable
  • 00:04:03
    of. So, um, you ready for Will Ratcliff? LEVIN: Fantastic. I’m ready. Let’s do it.
  • 00:04:07
    STROGATZ: Okay. Let’s do it. STROGATZ: Oh, hey there, Will.
  • 00:04:15
    WILL RATCLIFF: Hey Steve, how’s it going? STROGATZ: Good. I’m really excited to have
  • 00:04:18
    you on the show today. Can we begin by  talking about your hobby farm? You know,
  • 00:04:22
    I have to admit, I’m not sure I know what a  hobby farm really is, or what happens there.
  • 00:04:27
    RATCLIFF: I think it mainly means that we spend  much more money than we would ever gain from
  • 00:04:30
    any proceeds from the farm. We have goats.  We have chickens, which lay more eggs than
  • 00:04:35
    we can eat. We have peacocks, which haven’t  hit maturity yet, so my neighbors are still
  • 00:04:40
    okay with them. The males, I think, make a like  a call that is like a “ah-AH-ah”, but you know,
  • 00:04:45
    a hundred decibels or more. And, uh, we’ll  see. We may be getting rid of those.
  • 00:04:50
    STROGATZ: Some natural selection there. RATCLIFF: Indeed.
  • 00:04:53
    STROGATZ: So, in addition to raising animals  and plants though, you do, as we’re going
  • 00:04:57
    to be talking about today, raise yeast. But before we get to that, could we just talk
  • 00:05:02
    about, more broadly, the question of unicellular  life versus multicellular life? What are some of
  • 00:05:09
    the basic characteristics of each type? RATCLIFF: Yeah, so, you know, life on
  • 00:05:14
    Earth has a very long history. It evolved around  three-and-a-half billion years ago. And by then,
  • 00:05:19
    we had honest-to-goodness cells, with the  things that you’ve probably learned about in
  • 00:05:23
    your high school biology class, right. They have  a nucleus, which contains the DNA that encodes the
  • 00:05:28
    genetic information that the cells use to perform  their basic functions that, you know, then makes
  • 00:05:34
    proteins that are the action parts of a cell. And  so, cells are these fantastic biological machines,
  • 00:05:40
    right, in which you have this concentrated  soup of highly functional macromolecules.
  • 00:05:48
    Now, life wasn’t always cellular. Cells are like  one of these great innovations of life. And once
  • 00:05:53
    sort-of cells evolved, they really took off, and  it has been the sort-of basic building block of
  • 00:05:58
    life for the last three-and-a-half billion years. Multicellular organisms are a kind of organism
  • 00:06:04
    that is built upon the basis of cells, but  where many cells live within one group and
  • 00:06:12
    function essentially collectively. So, we  are a multicellular organism, we contain
  • 00:06:16
    approximately 40 trillion cells, which divide  labor and perform all these various functions
  • 00:06:22
    to allow us to do things in the multicellular,  you know, environment — run around, have eyes,
  • 00:06:28
    see things, talk on podcasts — that wouldn’t be  possible for single-celled organisms, right? So,
  • 00:06:34
    the evolution of multicellularity is a way of  increasing biological complexity by taking what
  • 00:06:39
    were formerly free-living individuals and turning  them into parts of a new kind of individual: a
  • 00:06:45
    multicellular organism. And it’s evolved, not once  or twice, but many times. We don’t really have a
  • 00:06:51
    great number, because we keep discovering more,  actually. But there’s at least 50 independent
  • 00:06:56
    transitions to multicellularity that we know of. STROGATZ: Whoa! That’s not something I remember
  • 00:07:01
    hearing in my high school biology class.  That’s something we only figured out,
  • 00:07:07
    what, in the past few decades? RATCLIFF: Uh, yeah, I think it’s
  • 00:07:11
    been a gradually increasing number. But I think  as people, we tend to be very animal-centric,
  • 00:07:16
    but then there’s a whole slew of things  that are a little bit more esoteric. There’s
  • 00:07:21
    cellular slime molds that live on land  that, you know, move around like a slug,
  • 00:07:26
    and then will grow as single cells  and come together, like a transformer,
  • 00:07:29
    to then do something as a group, you know. So, there’s different flavors of multicellularity
  • 00:07:34
    that have evolved in different lineages. And I  think partly we’ve known about this for a while,
  • 00:07:38
    but especially as we develop the tools to  understand bacteria and archaea — the big
  • 00:07:43
    domains of single-cell life that have been  around for a very long time — we’re finding
  • 00:07:48
    more and more types of multicellular bacteria and  archaea that we just didn’t know existed, because,
  • 00:07:53
    unless you’re looking at them with a high-powered  microscope or using other advanced techniques,
  • 00:07:57
    you can’t just see it, right? STROGATZ: So, one thing I
  • 00:08:00
    was wondering about here is dates. RATCLIFF: We have reasons to think that cellular
  • 00:08:04
    life exists around three-and-a-half billion  years ago, and Earth is only four-and-a-half
  • 00:08:08
    billion years old total. So, it’s fairly early  in Earth’s, you know, history as a planet.
  • 00:08:14
    But it probably happened earlier, and by that  time they’ve already done the things that are
  • 00:08:18
    required to evolve cells, and have all these  basic building blocks of life, like DNA, which
  • 00:08:22
    contains the, sort-of, code of the organism. STROGATZ: Good. Yeah, this is very helpful,
  • 00:08:27
    because there are so many interesting  transitions to talk about, each of them
  • 00:08:31
    being astonishing. You know, the origin of life  from non-life would be one. But the very famous
  • 00:08:38
    one that everybody hears about is the Cambrian  explosion. And, if I’m hearing you right,
  • 00:08:43
    that is not quite what we’re talking about. RATCLIFF: It’s one of the transitions. Well, let’s
  • 00:08:49
    put it this way. The evolution of multicellularity  is broader than just animals. It’s a process,
  • 00:08:54
    through which lineages that are single-celled  can form groups, which then become units of
  • 00:09:00
    adaptation. Evolutionary units that can get more  complex through, you know, natural selection. And
  • 00:09:05
    the Cambrian explosion is an incredible period  where animals, which had already been around for
  • 00:09:13
    probably 100 million years or more, just start  to figure out all of these innovations which are
  • 00:09:20
    hallmarks of extant animals. Before the Cambrian  explosion, things were soft and gelatinous and
  • 00:09:25
    didn’t have eyes or skeletons. It’s questionable  if they had brains. They don’t have any of these
  • 00:09:31
    things. And then in a relatively short period  of time, just a few tens of millions of years,
  • 00:09:36
    all of these things show up. And we think it’s  probably due to these, like, ecological arms
  • 00:09:41
    races, where you have predators attacking prey.  The prey start evolving defensive mechanisms. So,
  • 00:09:46
    you know, you have just this explosion of animal  complexity in what appears to be a very short
  • 00:09:52
    period of time in geological terms. STROGATZ: But that Cambrian explosion,
  • 00:09:55
    when the animals start to figure out all  these evolutionary innovations, that’s later,
  • 00:10:00
    right? Any estimate of how much later that is  than this first appearance of multicellularity?
  • 00:10:04
    RATCLIFF: Great question. So, the interesting  thing about multicellularity, it’s evolved in
  • 00:10:08
    very different time periods and different  lineages. So, cyanobacteria were evolving
  • 00:10:13
    multicellularity with honest-to-goodness  development and cell differentiation around
  • 00:10:19
    3 billion years ago. It doesn’t take that  long after you get cells that you start to
  • 00:10:23
    get multicellular organisms evolving. So, the red algae, which are a seaweed,
  • 00:10:29
    they begin evolving multicellularity around a  billion years ago. The green algae start doing it
  • 00:10:33
    around then too. Fungi, probably anywhere between  a billion and half a billion years ago. Plants,
  • 00:10:39
    we know that pretty well, that’s about 450  million years ago. Animals, they really start
  • 00:10:45
    to take off around 600 million years ago. Again,  it’s really hard to put an accurate date on that,
  • 00:10:49
    so we have to be, sort of you know, hedgy.  And then the brown algae — the most complex
  • 00:10:53
    kelp — they actually only began evolving in  multicellularity around 400 million years ago.
  • 00:10:58
    And you know, I think we should not think of  it as one process, but something where there
  • 00:11:02
    are ecological niches available for multicellular  forms, and there has to be a benefit to forming
  • 00:11:10
    groups and evolving large size. That benefit has  to be fairly prolonged. And most of the time,
  • 00:11:14
    there isn’t, but occasionally there will be an  opportunity for a lineage to begin exploring
  • 00:11:19
    that ecology and not be inhibited by something  else that’s already in that space. That might
  • 00:11:24
    be why something like animals has only evolved  once, because once you already have an animal,
  • 00:11:29
    then it suppresses any other innovation to  that space, like a first-mover advantage.
  • 00:11:32
    STROGATZ: So, what are the benefits  and what are the things that would
  • 00:11:35
    inhibit you from that transition? RATCLIFF: Yeah. So, John Tyler
  • 00:11:39
    Bonner is an evolutionary biologist, who  worked on multicellularity decades ago,
  • 00:11:43
    and he has this quote that I really like, that  there’s always room one step up on the size scale,
  • 00:11:48
    right? So, you know, the ecology of single-celled  organisms, that’s a niche that’s been battled
  • 00:11:54
    over for billions of years. And there’s lots  of ways to make a living in that space and
  • 00:11:59
    that’s why we are in a world of microbes. But,  once you start forming multicellular groups,
  • 00:12:04
    you can participate in a whole new ecology  of larger size. You might be immune to the
  • 00:12:09
    predators that were eating you previously, or  maybe you’re able to overgrow competitors for
  • 00:12:14
    a resource like light. If you imagine that you’re,  you know, an algae growing on a rock in a stream,
  • 00:12:19
    single-celled algae will get the light  but, hey, if something can form groups,
  • 00:12:22
    now they’re intercepting that resource  before it gets to you. They win, right? Or,
  • 00:12:27
    you know, groups also have advantages when  it comes to motility and even division of
  • 00:12:31
    labor and trading resources between cells. So, there’s many different reasons to become
  • 00:12:36
    multicellular. And there isn’t just one reason  why a lineage would evolve multicellularity.
  • 00:12:41
    But what you need for this transition to  occur is those reasons have to be there,
  • 00:12:45
    and that benefit has to persist long enough  that the lineage sort of stabilizes in a
  • 00:12:50
    multicellular state and doesn’t just go back to  being single-celled or die out. You can imagine
  • 00:12:55
    there’s lots of ephemeral reasons to become  multicellular, and then they go away, and then the
  • 00:13:00
    single-celled competitors just win again, right? STROGATZ: That is very fascinating. I actually
  • 00:13:04
    took biology with John Tyler Bonner. RATCLIFF: That’s really cool.
  • 00:13:07
    STROGATZ: He was a very sweet man too. And  you know what else, he had a lot of interest
  • 00:13:12
    in physics, and I was a math and physics  student, and this teacher, Professor Bonner,
  • 00:13:18
    started talking about scaling laws as creatures  get bigger, how does their metabolism scale with
  • 00:13:24
    their body mass and things like that. And it was  suddenly there was all this math in biology class,
  • 00:13:29
    so I felt at home. But I’m bringing it up, not  just to tell my own story, but because I get the
  • 00:13:33
    feeling you’re some kind of math, physics,  computer-ish kind of person. Is this true?
  • 00:13:38
    RATCLIFF: No, I came to biology early and I came  to computation and theory and physics late. But
  • 00:13:44
    you’re right that we use all of those different  approaches. My longest running collaborators are
  • 00:13:49
    with a physicist at Georgia Tech, Peter Junker,  and a mathematician in Sweden, named Eric Libby,
  • 00:13:54
    who is a theorist, and I’ve been working with both  of them for 10 to 15 years. All of my students,
  • 00:14:01
    you know, basically work at the interface  of theory computation experiments. I guess
  • 00:14:07
    that’s the space that we inhabit. We also throw  synthetic biology into that pot, which is one of
  • 00:14:11
    the beautiful things about working with yeast. STROGATZ: Wow. Let’s go into yeast now,
  • 00:14:15
    I think it’s time. You’ve probably said it  already but, what is the big idea underlying
  • 00:14:20
    research you’ve been doing now for some years? RATCLIFF: Big picture, we want to understand how
  • 00:14:26
    initially dumb clumps of cells, cells that are one  or two mutations away from being single-celled,
  • 00:14:32
    don’t really know that they’re organisms — they  don’t have any adaptations to being multicellular,
  • 00:14:38
    they’re just a dumb clump — how those dumb  clumps of cells can evolve into increasingly
  • 00:14:43
    complex multicellular organisms, with new  morphologies, with cell-level integration,
  • 00:14:50
    division of labor, and differentiation amongst the  cells. Just like, we want to watch that process
  • 00:14:55
    of how do these simple groups become complex. And this is, like, one of the biggest knowledge
  • 00:15:01
    gaps in evolutionary biology. I mean, in my  opinion. But it’s something where, you know,
  • 00:15:05
    we can use the comparative record. We know  multicellularities evolved dozens of times,
  • 00:15:10
    and the only truly long-term evolution experiments  we’ll have access to are these ones that happened
  • 00:15:15
    on Earth over the last hundreds of millions or  billions of years. But because they’re so old,
  • 00:15:21
    and because those early progenitors,  those early transitional steps,
  • 00:15:25
    aren’t really preserved, we don’t really know  the process through which simple groups evolve
  • 00:15:30
    into increasingly complex organisms. So, what we’re doing in the lab is,
  • 00:15:34
    we are evolving new multicellular life  using in-laboratory directed evolution over
  • 00:15:41
    multi-10,000 generation timescales, to watch how  our initially simple groups of cells — dumb clumps
  • 00:15:48
    of cells — figure out some of these fundamental  challenges. How do you build a tough body? How
  • 00:15:53
    do you overcome diffusion limitation when you,  after you’ve built a tough body and made a big
  • 00:15:57
    group? How do you start to divide labor amongst  yourselves when you only have one genome? How can
  • 00:16:03
    you make that one genome be used for different  purposes in different cells to underpin new
  • 00:16:08
    behaviors at the multicellular level? Does this  thing become entrenched in a multicellular state
  • 00:16:13
    which prevents it from ever going back, or at  least going back easily, to being single-celled?
  • 00:16:17
    And so, we’re watching this stuff occur  with a long-term evolution experiment,
  • 00:16:22
    which, we’re now on generation 9,000 of  what we call the Multicellularity Long-Term
  • 00:16:28
    Evolution Experiment… M.U.L.T.E.E… MuL-TEE…  absolutely a pun. It’s also named in homage
  • 00:16:36
    of the long-term evolution experiment, which  is a 70,000 and counting generation experiment
  • 00:16:41
    with single-celled E. coli, started by  Rich Lenski and now run by Jeff Barrick.
  • 00:16:47
    So, we’re basically trying to do something  similar, but in the context of understanding
  • 00:16:51
    how multicellular organisms evolve from scratch.  How they can, sort of, co-opt basic physics and
  • 00:16:57
    bootstrap their way to becoming organisms. STROGATZ: Beautiful. That’s great. That is
  • 00:17:00
    incredibly ambitious. I mean, I hope the listeners  get a feeling of the courage it takes. And I’m
  • 00:17:08
    sure your critics would say hubris or you’re  playing God or, you know, but still, this is
  • 00:17:13
    a wild idea to try to make multicellularity happen  in the lab. So maybe you should tell us — you said
  • 00:17:19
    directed evolution. That’s a little bit of an  unclear phrase unless you’re a professional. So,
  • 00:17:24
    what are you doing to encourage this transition? RATCLIFF: Yeah. So, you know, we start out
  • 00:17:30
    with a single-celled yeast. We did some  preliminary experiments where we evolved
  • 00:17:35
    them in an environment — it’s just a test tube  that’s being shaken in incubator — where it’s good
  • 00:17:40
    to grow fast, because they have access to sugar  water, and the faster you eat the sugar water,
  • 00:17:45
    the more babies you can make. And it’s, you know,  scramble competition, everyone has access to the
  • 00:17:49
    same food. And then at the end of the day,  we put them through a race to the bottom of
  • 00:17:55
    the test tube, where we just put them on the  bench for initially five minutes, but as they
  • 00:18:00
    get better and better at sinking quickly, we make  that time shorter and shorter to keep the pressure
  • 00:18:05
    on them. And here, there’s an advantage to being  big, because big groups sink faster through liquid
  • 00:18:11
    media than small groups. This is just due  to, you know, surface area-to-volume scaling
  • 00:18:16
    relationships. Bigger groups will have more,  you know, gravity pulling them down relative to
  • 00:18:20
    the friction from their surface. You take the  winners of that race to the bottom, the best
  • 00:18:25
    ones. They go to fresh media and you just, kind  of, keep repeating this very simple process.
  • 00:18:31
    So, yeast have a budding mechanism, where a mother  cell will pop off a baby, from one of their poles,
  • 00:18:37
    and then they can keep dividing and adding  new cells to the same cell, right? So, in our
  • 00:18:44
    early experiments that were just open-ended,  we got these simple groups forming that have
  • 00:18:48
    this beautiful fractal geometry. We had this easy  mutation — it turns out it’s just one mutation in
  • 00:18:54
    a regulatory element of the cell — that prevents  daughter cells from separating. Super simple.
  • 00:19:00
    Every time the cells divide, they pop off a baby  but remain attached. And so, you get this sort
  • 00:19:05
    of growing fractal branching pattern. Imagine  something like a coral, or maybe like a branching
  • 00:19:10
    plant. They kind of look like that, and they end  up becoming more spherical with these you know
  • 00:19:14
    nice branches. We call our yeast snowflake yeast.  And you have this life cycle where they grow until
  • 00:19:20
    they start to have packing-induced strain, they  run out of space. And now if they add more cells,
  • 00:19:25
    they just break a branch. And so, you have this  emergent life cycle where they’re growing, they’re
  • 00:19:29
    jamming, they’re breaking branches. Those little  baby snowflakes pop off. And they even have a
  • 00:19:34
    genetic bottleneck in this life cycle, in that the  base of the branch that came off is one cell. So,
  • 00:19:40
    as mutations arise, they get segregated between  groups, and every group is basically clonal.
  • 00:19:46
    Every cell in the group has the same genome. STROGATZ: Let me pause here. There’s a lot of
  • 00:19:50
    things going on. I want to keep track of  them, see if I got you. So, first of all,
  • 00:19:53
    the big mutation is the one that doesn’t let  the daughter detach from the mother, right?
  • 00:19:59
    RATCLIFF: That’s the key thing for forming simple  groups, correct, yep. So, we figured out what this
  • 00:20:04
    mutation was, and when we started our long-term  evolution experiment, we started them with
  • 00:20:10
    basically one genotype, so one clone, that already  had this mutation engineered into it, but with
  • 00:20:16
    replicate populations. Because what we want to  understand is, how do these simple groups of cells
  • 00:20:21
    evolve to become more complex? And I don’t want  that to be confounded by the mechanism through
  • 00:20:26
    which they form groups in the first place. So, we have actually 15 parallel evolving
  • 00:20:32
    populations, that started out the same in  the beginning, but we actually have different
  • 00:20:37
    metabolic treatments for them. So, one of them,  is taking all their sugar, and they are burning
  • 00:20:42
    it up with aerobic respiration, using air from the  environment to respire their sugar. One of them,
  • 00:20:48
    we broke their mitochondria in the very beginning,  so they don’t get to use respiration, they can
  • 00:20:53
    only ferment, and they get a much lower energetic  payoff from that. But they don’t have to worry
  • 00:20:58
    about oxygen diffusion anymore. So, sort of a  trade-off there. And then one of them can do both;
  • 00:21:03
    it first ferments and then it respires. STROGATZ: Okay. So, when you spoke of 15
  • 00:21:09
    different lines, they all have the property  that their daughters will stay attached. But
  • 00:21:15
    then you say some get to use oxygen, in this  advantageous way for their metabolism through
  • 00:21:21
    respiration, others have to use fermentation. RATCLIFF: Which is how you make beer, by the way.
  • 00:21:28
    STROGATZ: Yeah. Okay, so we have different  ways. And then you said some of them,
  • 00:21:31
    at least, don’t have to worry about  oxygen diffusion. What’s the worry?
  • 00:21:36
    What is the scary thing about oxygen diffusion? RATCLIFF: So, we thought initially, that the
  • 00:21:41
    ones that could use oxygen would be the ones that  evolved the most interesting multicellular traits.
  • 00:21:47
    But it turns out that they’ve actually stayed very  simple for almost 10,000 generations. They haven’t
  • 00:21:55
    done that much in the last 8,950 generations. STROGATZ: They peaked early.
  • 00:21:59
    RATCLIFF: They peaked early, and they’re only  about six times bigger than the ancestor,
  • 00:22:04
    and we don’t see any beginnings of cell  differentiation. They’re just simple kind
  • 00:22:09
    of bigger snowflakes. The anaerobic ones, they  have evolved to be more than 20,000 times bigger
  • 00:22:17
    than their ancestor. STROGATZ: What?
  • 00:22:19
    RATCLIFF: Yes. STROGATZ: Six in
  • 00:22:20
    one case, 20,000 in the other case? RATCLIFF: Yeah, yeah, yeah. And it
  • 00:22:24
    turns out that this is because there’s a trade-off  that’s introduced by oxygen. If you form a body,
  • 00:22:31
    and oxygen is this valuable resource that  if you get it you can grow a lot more,
  • 00:22:35
    but it can’t diffuse very far into the organism,  then all of a sudden, the bigger you are,
  • 00:22:41
    the smaller a proportion of your cells are  able to access this really valuable resource,
  • 00:22:45
    and your growth rate just falls off a cliff. STROGATZ: Oh, wow, your interior is
  • 00:22:50
    so small compared to your surface. RATCLIFF: Exactly. The bigger you are,
  • 00:22:53
    the larger your radius is, the smaller a  proportion of your biomass has access to
  • 00:22:58
    oxygen. And so, in our case, the anaerobic  line, they’ve done the interesting things
  • 00:23:03
    because they’re not being constrained by oxygen.  They’ve evolved large size. They’ve evolved all
  • 00:23:08
    these interesting behaviors. And they’re solving  all these fundamental multicellular problems.
  • 00:23:12
    STROGATZ: If I’m hearing you right, you’re  saying something like that the anaerobic ones,
  • 00:23:16
    because they don’t get this a sugar high  from the availability of oxygen early on,
  • 00:23:21
    they have to be resourceful. They have to come up  with all kinds of other innovations, and they do.
  • 00:23:26
    RATCLIFF: So yeah, I like the way you  phrased that, but to be just a little bit
  • 00:23:28
    more precise with our system. STROGATZ: Yeah, please.
  • 00:23:30
    RATCLIFF: The ones that have access to oxygen,  as they get bigger and bigger, their slower and
  • 00:23:35
    slower growth rates really push back against  them, and kind of act in the opposite direction
  • 00:23:39
    of any benefits that come from size. But if you  remove oxygen, now bigger is better. The smaller
  • 00:23:45
    ones go extinct and the bigger ones win. And then  they figure out a way to get bigger. And they can
  • 00:23:50
    really push the envelope on size and explore large  size in a way that the ones with oxygen can’t,
  • 00:23:55
    because they’re getting pushed back on by growth  rate. But then as they get bigger and tougher,
  • 00:24:00
    they actually start to have real trade-offs that  are created by forming big bodies. They’re so big
  • 00:24:06
    that now they’re struggling to bring sugar into  these groups, because they’re actually becoming
  • 00:24:10
    macroscopic. You know, they’re bigger  than fruit flies now. They’re large.
  • 00:24:15
    STROGATZ: That’s wild. RATCLIFF: Yeah. And, they also face
  • 00:24:18
    another constraint. I mentioned that they grow  and would normally break due to physical strain
  • 00:24:24
    arising from packing problems. But they solve  that, by figuring out how to make tough bodies, by
  • 00:24:31
    making their cells long enough that they actually  wrap around one another and entangle. This is now
  • 00:24:36
    a vining procedure where, if you break one branch  of a vine, you know, the ivy is still not coming
  • 00:24:41
    off your shed. I live in Atlanta, I’m tugging  ivy on trees and sheds all the time and it’s
  • 00:24:46
    very difficult, because entanglement percolates  those forces throughout the entire, you know,
  • 00:24:51
    entangled structure. And so now, you don’t just  break one bond to break apart the snowflake yeast,
  • 00:24:56
    you have to break apart hundreds of thousands.  And it becomes much, much tougher as a material.
  • 00:25:02
    And we even understand the genetic basis of this,  all the way up to the physics, it’s really cool to
  • 00:25:07
    be able to watch mutations arising that change  the properties of cells that underpin emergent
  • 00:25:13
    multicellular changes, which natural selection  can see and can act upon, and can, sort-of,
  • 00:25:19
    drive innovation in that multicellular space. LEVIN: It’s all very surprising, right? Because
  • 00:25:28
    he’s got this hypothesis going on, on the basis  of what we believe about the importance of oxygen,
  • 00:25:33
    and we even talk about it when we’re looking  for other planets and life on other planets.
  • 00:25:36
    Will there be oxygen, and is there water? And  all this stuff that we’re really so certain
  • 00:25:42
    is what’s needed to really accelerate life and  life radiating. But now, he’s amazingly saying,
  • 00:25:50
    well maybe, maybe that’s just not the case here.  You have these oxygen hogs that got stuck.
  • 00:25:56
    STROGATZ: Oh, I love your exobiology  perspective on this. I wouldn’t have
  • 00:25:59
    thought of that. That’s so interesting.  I don’t know what to make of it. To me,
  • 00:26:02
    it sort of sounded like if you’ve got a hand tied  behind your back and you’re forced to ferment,
  • 00:26:09
    you’re gonna be resourceful. You’re gonna be like  that old folk saying about whatever doesn’t kill
  • 00:26:13
    you makes you stronger, or something like that. LEVIN: Right. Evolution, as they always remind me,
  • 00:26:17
    is not just mutation. It’s mutation  and environmental pressure. So,
  • 00:26:24
    it’s the hostility of the environment in  some sense that drives the mutation.
  • 00:26:30
    STROGATZ: Interesting point. We will  hear more from Will after the break.
  • 00:26:39
    STROGATZ: Welcome back to The Joy of Why.  We’re here with Will Ratcliff and we’re
  • 00:26:49
    discussing the evolution of multicellularity. STROGATZ: I’d like to get into a question about
  • 00:26:58
    clusters versus organisms. What would make  an organism different than a colony? And
  • 00:27:03
    how do you know which kind of thing you’re  getting through these selection experiments?
  • 00:27:06
    RATCLIFF: It’s a great question. And it  really cuts to the core of what do we mean by
  • 00:27:11
    multicellularity. And I think a lot of confusion  in my field, for the last half a century, has come
  • 00:27:16
    down to poorly resolved questions of philosophy  about what do we mean by these words, and people
  • 00:27:24
    inadvertently speaking at cross purposes. Okay, so part of this is that the word
  • 00:27:29
    multicellular really means three different things,  and we’re not very clear with our language. It’s
  • 00:27:34
    treated as a noun in English to say, you know,  multicellularity, but it’s really an adjective
  • 00:27:38
    which modifies different nouns. So, you could  have a multicellular group. That’s just, you know,
  • 00:27:44
    a group that contains more than one cell. You  could have a multicellular Darwinian individual,
  • 00:27:49
    and that is a multicellular group which  participates in the process of evolution
  • 00:27:54
    as an entity at the group level. So, something  which reproduces, where mutations can arise
  • 00:27:59
    which generate novelty in a multicellular trait,  and which natural selection can act on and cause
  • 00:28:05
    evolutionary change in a population of groups.  That’s adaptation at the group level so that would
  • 00:28:10
    be a multicellular Darwinian individual. And then  you have multicellular organisms. And the sort of
  • 00:28:17
    philosophical distinctions of what’s an individual  and what’s an organism, there’s been a lot of work
  • 00:28:21
    done in the last 20 years, and I’m pretty happy  with the results of where that field is right now,
  • 00:28:25
    which is that organisms are functional units.  Organisms have integration of parts and work
  • 00:28:32
    well at the organismal level with, you  know, high-function minimal-conflict.
  • 00:28:38
    And so, we are all three. We’re a group. We’re a  Darwinian individual. And we’re organisms. And so,
  • 00:28:46
    the distinction is that are, sort of,  progressively higher bars for how you
  • 00:28:50
    get to these additional steps, and they tend  to occur sequentially. The first step would
  • 00:28:55
    be forming a group. The second step would  be making that group capable of Darwinian
  • 00:28:59
    evolution. And then, as a consequence of  group adaptations, you can get organisms,
  • 00:29:05
    which would be functional integration of cells,  which are now parts of the new group organism.
  • 00:29:12
    And so, a trait that would be diagnostic  of that would be cellular specialization
  • 00:29:17
    or differentiation, especially if it comes down  to reproductive specialization. People love that
  • 00:29:22
    in evolutionary biology because if cells give  up their direct reproduction, they’re no longer
  • 00:29:27
    making offspring, that’s something which is a  behavior that you really can’t ascribe to the
  • 00:29:31
    direct fitness interests of that cell, right? So, your skin cells will never make a new Steve,
  • 00:29:36
    right? Never. They are entrenched in the,  not on the line of descent. But it’s okay,
  • 00:29:43
    because they are helping you make you know your  reproductive cells reproduce. And so, the vast
  • 00:29:49
    majority of our cells are not directly on the  line of descent, but that is a derived state.
  • 00:29:55
    Originally, every cell made copies of itself.  They were on the line of descent. Originally,
  • 00:30:00
    simple groups don’t have this kind of reproductive  specialization. But over millions of generations
  • 00:30:06
    of multicellular adaptation, you get organisms  that have, now, cellular parts, where those
  • 00:30:11
    parts work together to allow the organism to  do things that it couldn’t have done before,
  • 00:30:16
    and an important part of that is specialization. STROGATZ: Just to make sure I get that point. What
  • 00:30:20
    does it mean to be in the line  of descent, in relation to skin
  • 00:30:23
    cells versus what, like gonadal cells? RATCLIFF: Yeah, sperm and eggs. And this
  • 00:30:29
    isn’t a strict requirement, right? You could  have something like plants that don’t have
  • 00:30:33
    this type of line of descent segregation. But  nonetheless, you know, if you look at a tree,
  • 00:30:39
    it makes flowers, it makes seeds, right?  You have this differentiation into cells
  • 00:30:44
    that will be the reproductive structures,  and those that don’t. If you’re a wood cell,
  • 00:30:49
    you just give up your life to make wood.  Wood is basically a series of tubes. You
  • 00:30:53
    differentiate into a tube, then you die. STROGATZ: They’re doing it for the good of
  • 00:30:57
    the multicellular group, or something. RATCLIFF: That’s right, and it’s also
  • 00:31:02
    for the good of their own genome. STROGATZ: And their genome, yeah.
  • 00:31:04
    RATCLIFF: Because usually those that are on the  line of descent are related to them. And that’s
  • 00:31:09
    how you, kind of, square it. So, there’s apparent  altruism at the level of the cell, but there isn’t
  • 00:31:14
    really altruism at the level of the genome. STROGATZ: I mean, when you start talking about
  • 00:31:18
    Darwinian adaptation at the level of the group, I  hear Richard Dawkins’s British accent in my ear,
  • 00:31:25
    drilling in that there’s no selection except at  the level of the gene. And then if it were Stephen
  • 00:31:30
    Jay Gould talking to me, he would say there’s no  selection except at the level of the individual.
  • 00:31:34
    RATCLIFF: Yes. STROGATZ: I think. I’m
  • 00:31:36
    oversimplifying, but group selection is where  people traditionally start yelling at you.
  • 00:31:40
    RATCLIFF: That’s correct. You’re totally right,  and I think there should be some sociological
  • 00:31:46
    studies on this in evolutionary biology, because  it has been much more, do you believe the
  • 00:31:52
    consensus rather than, like, actually rigorously  thinking through it. And in the last 15, 20 years,
  • 00:31:58
    I’d say the anti-group selection sentiment, that  was very powerful all the way up through the
  • 00:32:04
    2000s, has mostly melted away, as people have  embraced more pluralistic philosophies that,
  • 00:32:10
    like, there is sort of one evolutionary process,  you can view it through different perspectives,
  • 00:32:16
    sometimes it makes more sense to  use a group selection model. And,
  • 00:32:20
    I think if we’re thinking about individuals, in  this, in the Gould sense, selection acting on the
  • 00:32:26
    traits of individuals, for multicellular  organisms those individuals are groups.
  • 00:32:30
    STROGATZ: Of course, that’s why it’s always a  little bit of a confusing distinction, right? I
  • 00:32:34
    mean, the individual is made of other things. RATCLIFF: Yes, and people are happy to sort-of
  • 00:32:38
    round them up to just one, but there was a point  where it wasn’t just one. It was a simple group,
  • 00:32:43
    and it wasn’t so clear that that group  was an individual. Like a snowflake yeast,
  • 00:32:48
    you can break off any cell, put it into  its own flask of media, and it’ll turn
  • 00:32:52
    back into another snowflake yeast, right? That  wouldn’t happen with one of my arm cells.
  • 00:32:56
    Now, if you go for a really long time in my  experiment, that stops happening. But in the
  • 00:33:00
    beginning, cells are just in groups as vehicles.  And then over time, they gain enough adaptations,
  • 00:33:07
    as a consequence of selection acting on the traits  of groups, and really caring about the fitness of
  • 00:33:12
    groups, that cell-level fitness, outside of the  context of groups, starts to really take it on
  • 00:33:19
    the nose. They don’t do so well as being outside  of groups anymore. And you know, they’re evolving,
  • 00:33:24
    the beginnings of division of labor, different  cell states from one genome. This is unpublished
  • 00:33:30
    work, so I want to be appropriately hedged here.  But we’ve done like single-cell RNA sequencing,
  • 00:33:35
    and we can see new cell states evolving over the  five thousand-generation timescale. We go from
  • 00:33:40
    one, sort of, putative cell type to three. And we  think we know what they’re doing, like we think
  • 00:33:45
    it is actually adaptive differentiation,  as opposed to just sort of noisy chaos.
  • 00:33:49
    STROGATZ: If this pans out, it’s saying that  the cells have differentiated in their gene
  • 00:33:54
    expression. Is that what you’re saying? RATCLIFF: Exactly, into different sort
  • 00:33:57
    of behaviors. STROGATZ: Well,
  • 00:33:59
    all right. So, you’re seeing these  interesting transitions in your lab,
  • 00:34:03
    you’re inducing them through the  selection you’re putting on. But,
  • 00:34:06
    to what extent do we think these multicellular  transitions that you’re provoking shed any light
  • 00:34:13
    on what happened historically in the wild? RATCLIFF: That’s a great question. I mean,
  • 00:34:17
    actually I love that question, because it’s an  important scientific question. It’s something
  • 00:34:21
    I’ve thought a lot about, in the sense that  in order for our experiments to have meaning,
  • 00:34:25
    they need to be somewhat generalizable. Now,  I think the caveat here is that there is no
  • 00:34:31
    one answer to how multicellularity evolved.  It likely evolved in very different ways,
  • 00:34:36
    and for very different reasons, in plants  and animals and mushroom-forming fungi.
  • 00:34:41
    You know, it’s not a single thing. But nonetheless, the thing that does
  • 00:34:45
    unite it all is this evolutionary process. You  have to have group formation, those groups become
  • 00:34:50
    units of selection, and they turn into organisms  as a consequence of group adaptation. And that
  • 00:34:56
    evolutionary process, while it might play out  in different ways in different lineages, some of
  • 00:35:01
    these things are fundamental. So that transition  to individuals that become organisms, that’s
  • 00:35:07
    universal. And size is universal, and the physical  side-effects that come with size, scaling laws,
  • 00:35:13
    challenges with diffusion, and the opportunities  that come to break those trade-offs through
  • 00:35:19
    innovations, those things are all generalizable,  even if they take different paths in different
  • 00:35:25
    lineages, because they’re all proximate creatures  of their environment and their gene pool,
  • 00:35:30
    right? And we’ve never seen those processes play  out in nature. And I don’t know that we ever will,
  • 00:35:36
    because they’re historical things that we  don’t have the actual samples to see it.
  • 00:35:41
    And one of the things that we can do is, while  we’re not saying this is how multicellularity
  • 00:35:44
    evolved in any one lineage, what we’re saying  is this is how multicellularity can evolve,
  • 00:35:50
    and this is how some of these things that, maybe  looking in hindsight, you think you need really
  • 00:35:55
    complex developmental control… oh, actually it  turns out you don’t, because physics gives you
  • 00:36:00
    all these things for free, that are kind of  noisy, but they work, and you can bootstrap
  • 00:36:05
    those into your evolutionary life cycle  and build upon them, without necessarily
  • 00:36:09
    having to evolve those traits for a reason. So, a lot of things in our experiment have turned
  • 00:36:14
    out to be easier than we expected, and while the  details may differ, I suspect that some version of
  • 00:36:21
    these things that we’re seeing in our experiment  play out in the different transitions in nature.
  • 00:36:26
    STROGATZ: You seem to have some practice with  answering that question. You have thought about
  • 00:36:31
    that one a lot. I like that answer. RATCLIFF: Thanks.
  • 00:36:34
    STROGATZ: Well, all right. You mentioned earlier,  a scientist named Rich Lenski, who had done this
  • 00:36:40
    very long-term evolution experiment with bacteria,  and that that’s been passed on now. Do you have
  • 00:36:46
    a Jeff Barrick lined up? You’re not quite close  to retirement, yet I don’t suppose. But have you
  • 00:36:51
    thought about this? Is this experiment going  to outlive you, I guess is what I’m asking?
  • 00:36:55
    RATCLIFF: I would hope so. But, first of all,  I want to say I’d be remiss if I didn’t say
  • 00:36:59
    that our experiment is actually run in my lab by  Ozan Bozdag, who’s a research scientist with me,
  • 00:37:05
    who started the MuLTEE as a postdoc in 2016.  And it’s kept working and kept succeeding, and
  • 00:37:13
    he’s making his career essentially running this  experiment. So, like, without Ozan, I wouldn’t
  • 00:37:19
    be here and doing this. He’s the one that,  kind-of, figured out how to really make it work.
  • 00:37:23
    I’d actually be interested in doing this a little  bit differently perhaps than the way the LTE has
  • 00:37:29
    been run, which is, I want to run the standard  MuLTEE myself, but I wouldn’t mind doing like
  • 00:37:34
    a multiverse-type thing and have collaborators  or others that were interested in running their
  • 00:37:39
    own version of the experiment. There’s no reason  that it has to be one timeline. I mean, you know,
  • 00:37:43
    we could go all Loki. STROGATZ: I see,
  • 00:37:44
    separate universes doing the experiment. RATCLIFF: Sure, I mean, we already have kits
  • 00:37:48
    that we send to teachers, where they can evolve  their own snowflake yeast, or do experiments
  • 00:37:52
    with predators. We’re actually making a new  kit this summer for these hydrodynamic-flow
  • 00:37:57
    behaviors that we’ve been observing that snowflake  yeast actually act like volcanoes or sea sponges,
  • 00:38:03
    pulling nutrients through their bodies and  shooting them up at the center of the group,
  • 00:38:07
    which totally overcomes diffusion limitation. But  also, if scientists want to work on our system,
  • 00:38:13
    then, I think, if we democratize this  and make it a resource for the community,
  • 00:38:16
    science benefits, right? STROGATZ: So, you’ve been
  • 00:38:19
    very good about responding to what are  some aggressive questions here. Do you
  • 00:38:25
    ever find it discouraging? And do you ever think  about, you know, I don’t need this aggravation?
  • 00:38:30
    RATCLIFF: Not for a long time. I felt mostly like  good vibes from the broader community for many
  • 00:38:36
    years now. But when I was just starting out, I  did have some experiences that were discouraging.
  • 00:38:41
    Like Carl Zimmer had interviewed me for the New  York Times, and then got a bunch of critiques,
  • 00:38:45
    and then re-interviewed me and I, as a postdoc,  had to like defend myself to very senior faculty
  • 00:38:50
    that I really looked up to. And, um, that  didn’t feel very good. It felt sort of,
  • 00:38:56
    like, I wasn’t welcome in those communities  where it seemed like at the time, maybe, we
  • 00:39:01
    were just bullshitting and trying to spin a good  story, and there wasn’t much substance there.
  • 00:39:07
    That definitely affected my own approach to  science, and my own thoughts on inclusion and just
  • 00:39:14
    being really supportive of younger scientists.  Anytime you critique a paper in my field,
  • 00:39:20
    you might think you’re critiquing the senior  scientists on the paper, but they usually have
  • 00:39:25
    a graduate student or a postdoc who wrote the  thing. It’s their life for years, and they’re
  • 00:39:30
    the ones that really feel the critique, right? And so, criticism is critical for science. And I
  • 00:39:35
    love good, rigorous, critical debate. Like, I hang  out with physicists and mathematicians. In those
  • 00:39:41
    communities, it’s a sign of respect to be direct,  to ask hard questions, and to endeavor to get at
  • 00:39:48
    the truth. And I really like that. But at the  same time, I love writing why I like a paper. I
  • 00:39:54
    love writing why I think this paper is important,  and how it changes the way I think about a field.
  • 00:39:58
    And so, when I’m reviewing papers and grants,  the first thing I do is write a detailed review
  • 00:40:03
    of why the paper is important and cool. Even  if I have major concerns and questions, which
  • 00:40:08
    I will get to, I always make time to acknowledge  the importance of the work. And similarly, like,
  • 00:40:14
    in the context of multicellularity, I’m always  trying to bring new people into the field. Like,
  • 00:40:19
    we’re pluralists, we want new people to come in,  we want you to bring your systems and your ideas,
  • 00:40:24
    there isn’t just one way of thinking about  this. I think those early experiences that I
  • 00:40:28
    had were fairly rough and made me, sort of,  avoid interacting with those communities,
  • 00:40:33
    maybe for longer than I wish I had in hindsight. STROGATZ: Do you think the harsh criticism,
  • 00:40:38
    or at least penetrating criticism, did it  sharpen you up? Do you think it improved the
  • 00:40:43
    work? Did you write better discussion sections?  Did you write more persuasive introductions?
  • 00:40:47
    RATCLIFF: Perhaps. Well, you remember when you  asked me, you know, what’s the importance of
  • 00:40:51
    your work? And I had a polished answer, and  that’s because I’ve been challenged on this
  • 00:40:56
    enough times over the last 15 years that I had to  really think hard about that, right? And certainly
  • 00:41:01
    thinking hard about it changes the way you do  your science, right? You develop the areas that
  • 00:41:05
    you think are more general and more impactful,  as opposed to just doing the next experiment.
  • 00:41:11
    That being said, the criticisms, the sharp and  penetrating criticisms I’ve always appreciated,
  • 00:41:15
    because that makes your science better. The  criticisms that are simply dismissive are the ones
  • 00:41:20
    that I always have found the hardest, the most  frustrating. Because, you know, if someone says,
  • 00:41:25
    and I’ve gotten this a lot, “It’s cool what you  do, but snowflake yeast aren’t multicellular”. I
  • 00:41:32
    mean, then I have to question, okay, am I going  to spend the next 10 minutes explaining the
  • 00:41:35
    philosophy behind what multicellularity is? Like,  there isn’t just one thing here, right? And so,
  • 00:41:41
    it’s the sort of dismissive side of the criticism  that I’ve found the least productive. Whereas
  • 00:41:46
    like, sharp, penetrating, tough questions… I mean,  we’re scientists… we kind-of like that stuff.
  • 00:41:52
    STROGATZ: So good. Thank you, Will. I really  appreciate it because, you know, you have fielded,
  • 00:41:57
    I’ve tried my best to sort-of simulate those tough  questions and give you a chance to respond them.
  • 00:42:02
    So, maybe in the future you can just play this  for some of those people. Save your breath.
  • 00:42:07
    RATCLIFF: That’s right, that’s right. STROGATZ: Anyway, it’s been really a
  • 00:42:10
    great pleasure talking to you. RATCLIFF: Likewise, so much.
  • 00:42:13
    STROGATZ: Thank you very much. So, we had  Will Ratcliff with us, talking about the
  • 00:42:16
    evolution of multicellularity, and  it has really been fun. Thank you.
  • 00:42:20
    RATCLIFF: Thanks, Steve. STROGATZ:
  • 00:42:26
    What about that? Do you have any  personal experiences with that,
  • 00:42:29
    or maybe you’ve seen it with your own students? LEVIN: Oh man. I’m still a student of the subject,
  • 00:42:34
    and even now, it really resonated in that, it can  be very discouraging if someone’s dismissive. He’s
  • 00:42:41
    exactly right. It’s okay if somebody’s, like,  really critical and you’re exploring together,
  • 00:42:45
    and you’re gonna get to the answer. If  it’s right, it’s right. If it’s wrong,
  • 00:42:48
    it’s wrong. But to be dismissive, that is  something that, it’s not only hard to hear,
  • 00:42:54
    it sort of engenders a little bit of distrust, I  think. ‘Cause there’s something about that that
  • 00:43:00
    doesn’t feel like the program, you know. STROGATZ: The person who would dismiss you?
  • 00:43:05
    You feel like, I don’t trust  that person so much anymore?
  • 00:43:07
    LEVIN: When I hear people being  dismissive, it doesn’t have to
  • 00:43:10
    just be at me, I get a little suspicious. STROGATZ: Uh-huh, like they have another
  • 00:43:14
    agenda about self-promotion or something else? LEVIN: Maybe, yeah. You know, something. Because
  • 00:43:18
    aren’t we here because we’re driven by excitement  and curiosity? That so emanates from him. What a
  • 00:43:24
    great colleague to have. I wanna get a letter of  review from him. I want him to review one of my
  • 00:43:29
    papers. But what a great colleague, that’s what  you want people to bring to the table. And yeah,
  • 00:43:35
    you want people to tell you, you know, this  isn’t the right direction if it really isn’t,
  • 00:43:38
    and to explain why, and, you  know, be able to navigate
  • 00:43:40
    that. But that requires real engagement. STROGATZ: Something about his phrasing that,
  • 00:43:46
    to be dismissed is not productive. I  thought that was such an interesting
  • 00:43:50
    operational word to use. I mean, not that it’s  insulting or hurtful; it’s not productive.
  • 00:43:54
    LEVIN: Yeah. And it could take the wind out of  your sails, because then there isn’t anything
  • 00:43:58
    to discuss. If you have something to hang onto  and a point to respond to with a compelling,
  • 00:44:04
    rational, mathematical, formal, experimental  argument, whichever avenue is required,
  • 00:44:09
    that you can keep going. STROGATZ: It doesn’t help you
  • 00:44:11
    be a better scientist. It doesn’t help you  make new discoveries, to just be dismissed
  • 00:44:15
    like that. Well, this has been so much  fun talking to you about this episode.
  • 00:44:20
    LEVIN: Always STROGATZ: I can’t wait to do the next one.
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