In a paper published in Developmental Biology in 2001, Scott Gilbert laid out a vision for the reintegration of developmental biology and ecology. While in its early days, developmental biology paid great attention to the environmental context, in the twentieth century the focus of the discipline shifted, first towards physiology and later to molecular genetics, taking the discipline indoors and away from the whole organism. In this paper, Gilbert argued that it was time to bring ecology and developmental biology back together again, both to enrich and diversify the questions being asked in these disciplines as well as to build knowledge to address the rising environmental concerns at the time. I spoke with Scott Gilbert about the origins of his interest in Ecological Developmental Biology (“eco-devo”), his memories of the making of this paper and its reception, and his reflections on the progress that has been made during this 23 years since the paper’s publication.
Date and place of interview: Interview conducted on 6 November 2024 at the Konrad Lorenz Institute for Evolution and Cognition Research (KLI).
Hari Sridhar: Scott, I’d like to begin by thanking you again for agreeing to do this interview.
Scott Gilbert: My pleasure.
HS: As we discussed over email, maybe we can start by talking a little bit about your motivation to write this paper and how it all began.
SG: Sure. The motivation really was to let developmental biologists know that there’s a whole world to be explored outside the laboratory, that our laboratory investigations are only the beginning of developmental biology, and that developmental biology is part of a much larger context – a much larger view – of science, where we actually look at relationships within the embryo, and between the embryo and the environment. Before then, the environment really was not considered as part of developmental biology. Genetic reductionism was pretty much the way people looked at things. I wanted to point out that this was a cultural artifact, that the way that developmental biology had progressed was only one of several possible ways. And so, I wrote this in kind of a joy of, you know, here’s this whole other thing developmental biology could be exploring, and it’s absolutely fascinating.
My theory of teaching is that when you hear something for the first time you don’t get it. What hearing it for the first time does is give you the receptors so that, when you hear it the second time, you can do something with it. I kind of feel like I have to go back a few inductions with regard to my interest in the environmental aspects of developmental biology too. It goes back really, to my training, in that, although I was trained in developmental genetics – in a very genetically oriented framework – I had a view that there was something else besides the genes that were important in creating phenotypes. One of the reasons for that was that I was involved in feminist theory with Donna Haraway. At the time, there was a whole group of scientific feminists – Lily Kay, Donna Haraway, Evelyn Fox Keller, Bonnie Spanier, Ruth Hubbard, and others – who were criticizing the notion of biology as destiny, who were getting away from the ideological notion that the genes tell you what you are. That was one of the influences. I was one of Donna’s first grad students, and I took her course in the history of embryology. Well, there I learned about the organicism of Waddington and other such people. Donna was writing her thesis book – Crystals, Fabrics and Fields – when I was with her at Johns Hopkins. This was part of what we talked about, and it was absolutely fascinating. So, I knew about organicism and the feminist critique of reductionism. And then I did a postdoc in immunology, where the major paradigm, clonal selection theory, was that the environment – the predators, the viruses, the microbes – would induce the formation of certain clones of pre-existing cells so that the amplification of that clone would be caused by the environment. You were changing the cells of the organism developmentally by an environmental factor. So, that was another thing pushing me to look at the environment in development. And then, when I came to Swarthmore College in 1980, I got to know Jack Berill. Berill was one of those British organicists. He wrote a textbook on patterns of growth, which, in 1961 or so, was the high water-mark of organicism in embryology. He didn’t have a gene in the book! It was before the Jacob-Monod model. Berill hated genetics. He said – and I’m quoting him – ‘genetics murdered our field!’. And he, once, in a paper, described genes – I’m trying to get the exact quote, but something like: a gene is a statistically significant little devil, collectively equivalent to one entelechy. He did not like genes as explanations for development. When I was at Swarthmore, I got to have tea with Jack and Jacqueline Berrill, which was just such a privilege. Jack would talk to me about his experiences in embryology and organicism. So, I came pre-adapted to this kind of thinking. And then, in 1984, I gave a lecture at the SDB meeting titled, “The state of developmental biology – 1984” looking at Oscar Hertwig’s book on pre-formation versus epigenesis and his critique of Weismann. That was probably my first talk about the environment.
Things came together in a big way in 1995 for me. I was at the Ishkabibble (ISHPSSB) meeting in Leuven, Belgium, where I was talking about Roux and his promise of evo-devo. Roux had, in the last part of his prolegomena to developmental mechanics, mentioned evolution, saying that once we had a mechanical theory of development, we could then look at how this relates to evolutionary biology. But in another session, Cor van der Weele was giving a talk on the environment and development. I went to that talk, where she criticized my book. She said my book did not include things like the developmental plasticity in insects, environmental control of metamorphosis, or environmental sex determination.
HS: This is the developmental biology textbook?
SG: Yes, this was my developmental bio textbook, which would have been the 1994 edition. And after her talk, I raised my hand and said something like, Hi, I’m Scott Gilbert, and I have to disagree with you. My book has all the things you said that it doesn’t have. And then she said, Yes, but you don’t have them in the main text. You have them in areas called Sidelights and Speculations. You literally have marginalized these things. So, we got together (probably for lunch) and I told her, Yes, I know about these things, but there’s no context. I can’t put them into a coherent chapter. And she said something like, try to find one! It was difficult. But that year, 1995 – I didn’t read these things immediately – three articles came out. One was the Mead and Epel article called Beakers and Breakers, which said that if you look at fertilization in beakers, you get just about 100% fertilization. But it has little to do with fertilization in tide pools and fertilization in the waves. You have to look at the environment. And when you do, you find all sorts of adaptations that the egg has to survive and be fertilized in the environment. Brilliant paper. Jessica Bolker wrote a paper in 1995 saying that the model systems that we use for developmental biology are all based on, having a quick separation of germline and soma, small size, rapid reproduction rate, and very little environmental impact on the phenotype. And that’s so that, when you could knock out a gene, you could say that your results in Vienna are the same as the results in Tokyo and New York City, because the environment does not play a role. Xenopus, the amphibian that kind of took over as our amphibian model system, instead of salamanders, has no breeding season. You could use it any time of the year. What amphibian doesn’t have a breeding season? We are using exceptions to the rule, and these exceptions get rid of environmental notions of inheritance and development. And then you have Lynn Nyhart’s 1995 book, Biology Takes Form, which was a revelation to me. She showed that the notion of the environmental determination of phenotype was a major part of embryology before Roux and Driesch and others formulated developmental mechanics and brought developmental biology indoors to be physiological. The original experimental developmental biology was stuff like: How does temperature affect development? How does salinity affect development? It was environmental. And she quotes letters from people like Haeckel lamenting that his students are going indoors, and that they were separating the study of development from its conditions of existence. So, that gave me a real context for integrating these episodes I had about environmental influence on development. Now I had a story I could tell about how the model systems became narrowed, how developmental biology had included the environment, and what happens if you go back and study something like fertilization in its natural context. You get a whole bigger picture. In 1996, Our Stolen Future came out, breaking the endocrine disruptor story. So, okay, I had the basis for a chapter. And in the 1997 (5th) edition of the textbook, we had our first chapter on the roles of the environment in constructing phenotypes.
The other big year was 1999. I’m writing this chapter, but the thing that allowed me to write this article was a whole group of papers that came out in1999. Fred Nijhout writes this incredible paper on plasticity, which basically says plasticity is everywhere; that life exists because of plasticity. Fred also gave the notion that, in insects, plasticity is not anything magical. It’s as simple as: the environment has a cue, the nervous system picks up the cue, transfers it to the endocrine system inside the body, causes an endocrine change, which changes gene expression inside the cell. It’s a nice, easy pathway, and you see it all the time in insects. Brilliant! Then, Margaret McFall-Ngai writes a summary of the squid-vibrio work, talking about detente in development. And Anurag Agrawal and colleagues write the paper on predator-induced polyphenism in plants and animals, an overarching view, with data saying this is not just the immune system. It is throughout nature that you see polyphenisms produced by the environment, and that the environment changes development in an adaptive way.
And then I got an email from Gary Schoenwolf, the editor of Developmental Dynamics, saying, for the new millennium, would you be able to write an article on holism? I said, Sure. And then I realized, as I went more and more into it: Oh, I don’t know anything about holism! I know one aspect of it, and there’s so much more. And so, I asked Sahotra Sarkar, who had written this wonderful article on the Richard Woltereck’s concept of Reaction Norm, if he would join me on this, and he said yes. And at the same time, I thought, okay, I’m going to write an article on why developmental biology needs to consider the environment. I kind of view these two articles– the paper with Sarkar and the 2001 paper on eco-devo— as companions. That’s kind of the story in terms of inducers of this paper.
HS: I’m really grateful that you took the trouble to make the notes and trace back the history in so much detail.
SG: I have to add a warning. This was 24 years ago! Also, anyone listening to these archives should know: don’t trust first-person recollections! I was at a lecture that Will Provine gave about Sewall Wright, and Sewall Wright was in the audience! At the Q&A period, Sewall Wright raises his hand. Everyone else kind of puts their hands down. And Sewall Wright challenged Provine, saying, that he didn’t say what Provine said he did. Provine just replied: Dobzhansky said you said that, Fisher said you said that, I believe you said that. And Sewall Wright sat down! So, be wary of first person interviews!
HS: I have so much to follow up on. First, did you already know Sahotra Sarkar at the time?
SG: Yes, I did. From meetings in Boston. We met in 1991 at a symposium on individuality and again in 1996 in a symposium on the history of molecular biology.
HS: How did you become interested in feminist theory and end up working with Donna Haraway?
SG: When I was an undergraduate, I majored in biology and in religion. I was interested in the role biology had in the larger society and how the larger society impacted biology. When I met Donna for the first time, I was finishing up a paper on social metaphors of biology and biological metaphors in society. Donna was working on her metaphor book – the Crystals, Fabrics and Fields book. We met at a developmental biology journal club at Johns Hopkins. And again, remember, this is only my account of it. A postdoc gave a talk on a recent paper in developmental biology on Hydra regeneration. When you cut off the head of a Hydra, you get a reorganization, and another head grows back and so forth. And everyone asks their questions, you know, calcium concentrations and other technical questions that grad students are trained to ask. Then, this hand goes up in the back of the classroom, and this woman cheerfully deconstructs the entire research program, relating it to Solly Zuckerman getting rid of the alpha male in a baboon troop – whatever – and just giving a new analysis of the regeneration story. That blew my mind. Who is this person? So, after the session ended, I went over and introduced myself to her. I said that I was a grad student in biology and asked if she were a new student. She said that she was the new hire in history of science. And the fact that she was doing history of embryology was just wonderful. We got together, and we found we had so many interests in common. I was doing a PhD in biology, and my advisor, Barbara Migeon, allowed me to go and take courses in the history of science department. She said, I don’t care what you do, as long as you finish your work. And so, I took many courses in the history of science department at Hopkins. One day, Bill Coleman came over and asked how many courses I took? I told him. He said, if you write a thesis, you can get a master’s here. I told him that I was writing something for Donna which she had wanted me to shorten. You are saying, I can expand it? So, I got a master’s in history of science under Donna’s aegis. I wrote a thesis on how the X-chromosome was the bridge between embryology and genetics.
Being Donna’s graduate student was one of the best experiences that I’ve ever had. And we’re still very close friends. I would come in with an idea, which I would be pretty certain about, and she would find a way of tweaking it. We would go back and forth, mixing it with other ideas, and at the end, it was a totally different idea. But wow, the path that we took to get there was always fascinating. And, you know, she had a background in community ecology. She started being a grad student in embryology with John Trinkaus, who was doing Fundulus fish embryology. And then, she transferred and worked with Evelyn Hutchinson. So, she knows ecology and embryology. She was a major influence in how I was able to write that paper.
HS: I wanted to ask you about the terms “eco-devo”, and “eco-evo-devo” which you used later on? Was this the first use of “eco-devo”?
SG: It was. I used it because “evo-devo” already existed. Evo-devo wasn’t a term anyone particularly liked. It was just a useful term. In 1994, Rudy Raff had a meeting in Indiana where we batted around other possibilities and stuff. But evo-devo came to stay, although devo-evo is probably better. But anyway, evo-devo became the term, and so I just said that what we’re looking at now is “eco-devo.” As a matter of fact, at the time, I made a whole list of satirical things. For example, if you believe Stephen Jay Gould, you study Stevo-devo! I don’t know if I had eco-evo-devo in that text or not.
HS: No, it’s not in this paper
SG: Okay, because I wasn’t thinking in evolutionary terms at that point. We hadn’t gotten there yet. Nor was I talking in terms of holobionts
HS: Yeah, that was another question I had.
SG: It was a singular paper that opened up my mind to the possibility of holobionts. Now, I knew the squid stuff and some stuff in parthenogenetic insects. But it wasn’t in mammals, you know, which was “what counted”! The 2001 paper by Hooper et al in Gordon’s lab showed that gut bacteria, especially Bacteroides thetaiotaomicron, could induce angiogenin gene expression in the Paneth cells of the mouse intestine. To me, that was the most amazing environmental agent. The bacteria were acting like embryonic cells. It was inducing gene expression in its neighbors. I’m reading this in the library, and I remember saying, “Oh, shit!” Here was a new concept that I hadn’t considered in my eco-devo article or chapter. I first thought I shouldn’t be saying “Oh, shit!” in the library. And then realized, well, that’s actually quite appropriate, given the subject matter.
I just couldn’t believe that we had not known about this. This was, like, the dark matter of developmental biology. Something like bacteria, which is all-pervasive, is inducing normal gene expression. This wasn’t the teratogenic effect of bacteria. This was normal, expected, gene expression. If you don’t have the bacteria, you don’t get the normal capillary network of the gut. That was amazing. And I wondered, how many other things are there that we don’t know about, where the bacteria are helping induce or mature cells in the body? And that opened up that door. Now, here’s one of the reasons why being in a liberal arts college is wonderful. Every year, I have to give a seminar, on any topic I wanted, and usually I spoke about developmental genetics. In the 2009 seminar, I decided to do environmental effects. And for the final exam for the students, which I asked them to do in a group, I told them: you could write a review paper, or you could make a play, or you could write songs. I want you to integrate something together. They decided to write a review paper, and asked me what would be a good thing to write on. I said, Well, you know, we discussed thermotolerance as something that symbionts give to plants. Maybe this is something that you could write about. I don’t see any review on this. And they worked together to write a paper for their final exam. I revised and submitted it and it got accepted in Phil. Trans. Royal Soc. That was my first foray into the topic, and holobionts are mentioned in that. And probably because of that paper, I was invited by Margaret McFall-Ngai and Michael Hadfield to a conference at NESCent in North Carolina, where they brought together many of the people who studied bacterial symbiosis with animals. That was an amazing meeting. We broke into groups – the physiology people, the medical people, the development people, the ecology people – and then we came back to a committee of the whole, and made our reports, and then again went back into groups and so on. And that’s when the big picture came out, which we communicated in an article in the Proceedings of National Academy of Sciences titled Animals in a bacterial world. The second part of the title, after the colon was: a new imperative for the life sciences. An imperative! That word came from a series of discussions between Margaret McFall-Ngai, Michael Hadfield, and Donna Haraway about what was the appropriate word. Imperative. You have to do this! If you’re going to talk about animals, you have to talk about them in terms of their symbionts. That was a paper that really got me into the holobiont discussion. And then, just as an aside: at the last committee of the whole that we had – all the 26 or so authors – we were talking about how a paper could be done and where to submit it and so forth. And I raised the point: do you realize that what we’ve done is we’ve just destroyed every biological notion of individuality that we have. I think we should put that in. There are like seven notions of the biological individual, and we have just come up with a new one, and have gotten rid of the others. That was too much for some people. They did not want that in a consensus article. We agreed that we’d have a website on this paper and I would write a pro, and someone else would write a con. I wrote the pro, but no one wrote a con. So, I asked if I could write this as a separate article? And they said, Sure. Again, I realized I was in over my head, and so I asked Fred Tauber and Jan Sapp if they would help me. We came out with an article about individuality. My guess is that I learned about holobionts from Jan Sapp’s book.
HS: Yes, I was struck by the fact that holobionts don’t figure in the table in which you list all the zoological areas covered by ecological developmental biology.
SG: It doesn’t have holobionts! And if you look at the Lynn Margulis paper, you’ll see she mentions holobionts in a table but she doesn’t discuss it. It was really, I think, the Rosenbergs who brought back the holobiont concept, in their coral work.
HS: I was curious about a note you add to the same table: “This is one only person’s view, and it is chiseled in 1% agarose”. Tell us more about that.
SG: What I want to say is, “it’s not chiselled in stone”. Because “chiselled in stone” means that it’s permanent: this is the way it is, folks. I figured it out! I wanted to convey that this is fluid. This is, you know, only my view. This is not a consensus view of the field. And when we run electrophoresis gels, they’re made of 1% agarose. They’re flimsy. They are the opposite of a stone. That’s why I said, this is chiselled in agarose. It’s up for grabs.
HS: You earlier mentioned that the first time that you wrote something along these lines is probably the chapter in your developmental biology textbook. How different was the paper from what you wrote in the chapter?
SG: I think it was very different. But I think it’s different because I wrote the chapter for 1997 edition of the book. And it was only in 1999, that those papers came out which really crystallized the field in a way it hadn’t been done before. So, I think that in the article I could have been a lot more certain of what I was writing.
HS: How did you choose the examples to include in Figure 1 of the paper?
SG: The butterfly I’m sure came from Fred Nyhout. The Daphnia is from the Agrawal paper. The two tadpole pictures: there was a whole bunch of studies that Rick Relyea was doing on tadpole morphogenesis, and so I got into the amphibians. And amphibians are kind of mentioned here a lot. If I wanted to use a vertebrate that’s well-studied, amphibians are, in a sense, or used to be, an emblem of developmental biology. Amphibians and sea urchins. Spemann did his work on amphibians, and the amphibian ecology people knew about developmental changes due to the environment. They knew about seasonal metamorphosis. They knew about predator-induced polyphenisms. They knew about the differences that symbionts had in oxygenating egg masses. They knew about stress-dependent cannibalism. They knew so much! They knew all sorts of changes in development brought about by the environment. That’s why the amphibian got chosen. And a photo from Gerd Müller’s paper is here too, because – I can’t remember when I read it – but that study linked this plasticity notion with evolution. That was probably the only thing I could do to link it with evolution at the time. The fact that the bird got a bone due to its movement in the egg – due to physical stress – was absolutely phenomenal. So, I put that in there too. I also liked bright pictures rather than graphs. One of the joys of developmental biology is its visual aspect.
HS: How did this interest in the environment intersect with your own empirical research at the time?
SG: I had been working on a topic that was a bit peripheral, that not many people in developmental biology were working on, which was branched organ morphogenesis. The kidney has branches. The lung has branches. The pancreas, the salivary glands, they all have branches. But they all look different. Well, how do you encode in the genome, for example, instructions for epithelial ducts to go 0.5 mm and branch at a 30 degree angle? How is that done? If you look at mouse kidneys, every 13-day mouse kidney looks like every other 13-day mouse kidney. How is that possible? And especially, at the very early stages of branching, they look alike, and the branching pattern of each organ is different, And so, I was looking at how paracrine factors from mesenchyme might induce gene expression in the epithelium and how the extracellular matrix might be remodeled. So, in a sense, I was looking at environmental changes, but the environment was still within the organism. And I was looking at things that could not be encoded in the genome. Then I found out at an SDB meeting that two excellent researchers were going into this area of research, and I realised that they could do, in a month, things that would take me two years to do with my undergrads. If Brigid Hogan and Saverio Bellusci were going into this field, I wasn’t going to survive. I decided I needed to change. Around 2000, right when I was writing this, I decided that I was going to change my research topic, and go into evo-devo. I literally made a list of possible things to do. I wanted to work on a developing organism that differed its development from the norm. For example, how does the firefly get its lantern was one of them. Others were: how does the turtle get its shell? How does the snake lose its limbs? Well, I didn’t want to do loss, because you can get losses in so many ways. I wanted to understand, do you get a gain of function? I also decided not to do fireflies because I’d never worked on insect development. But I’d worked in vertebrate development, and there were four labs in the Philadelphia area doing work on bone development. So, turtles sounded good, and I started the research with a John Simon Guggenheim grant for my sabbatical leave. And there was no molecular biology on turtles ever. Well, I shouldn’t say ever. The only turtle studies in molecular development were those that looked at Sox9 during temperature-dependent sex determination. But no one was looking at the molecular biology of turtle shell development – the development of an evolutionary novelty. An innovation. How do you get the turtle shell from an organism which wasn’t a turtle? I decided that’s what I would work on. I did a sabbatical leave in Rocky Tuan‘s lab, where we were using degenerate primers. We were using some things that now sound so antiquated, but we got results, and we found the gene expression that seemed to indicate how the turtle was forming its carapace. Indeed, it was using Fgf paracrine factors in a mechanism that looked homologous to limb formation. And what’s nice is that, since there were no molecular data on turtle shell development, I was able to publish these studies with my undergrads. This was new and different and interesting. And we published in Evolution and Development, and we got a cover. And again, as I was doing this work, I realised, there’s a lot more to this that I don’t know. Ann Burke had written her thesis at Harvard with Pere Alberch on turtle shell development, and I wrote to her, asking if she could send me her thesis. She had also come to the conclusion (on morphological grounds) that the turtle carapace formed in a manner that resembled limb development. After reading her thesis, I said to her that she’d done an amazing amount of work that had never been published and which confirmed our ideas, but in a different species. Would she want to be a co-author? And so, she became a co-author on this initial turtle paper, where we showed that what makes a turtle a turtle are its ribs. The ribs go horizontally. They don’t go to down to form a rib cage. They go out into the dermis, and the cartilage from the ribs forms the shell. It looks like they are being drawn to the edge of the dermis as it expanded outwards. And then, the bones form from the cartilage, and it seems like the ribs are acting as a signaling center to ossify the dermis. So, we were able, in that first paper anyway, to get an outline of how the turtle forms its shell, which, as Kevin Lala has shown in our new book, was at odds with the paleontologists. The paleontologists had a very different view of how the turtle forms its shell. And we’re saying: No, you might be looking in the wrong place. It’s the ribs. It isn’t ossifications of the dermis. It’s the ribs that go out.
I have to say that I did not write the turtle section of the new book. I would not be brave enough to say that the paleontologists were looking for the wrong fossils because they didn’t know turtle development. But whoever wrote that part of the chapter was brave enough, and I let it stay!
HS: So, you really just made a list of potential topics and decided turtles is the one you want to study.
SG: That’s right
HS: Did the interest in evo-devo, more generally, go back further?
SG: My interest in evo-devo goes way back. I was so lucky. One of the reasons I went to Hopkins is because my wife was going to try getting into medical school. And at that time, it was very hard for women to go into medical school. We decided, well, if she applies to a place out west, which is where she would want to go, there might be one school in Seattle, one school in Oregon; but in the Philadelphia-Baltimore-Washington area, there were, like, five medical schools, and the chances would be good that she could get into one of those five. Hopkins was in Baltimore, right in the centre, and Hopkins had some wonderful people who I wanted to work with. Hopkins also had a phenomenal history of science department. I had done my undergrad in religion as well as bio, and I was familiar with the history of religion’s interactions with science . So, I took a course in history of biology taught by Camille Limoges. Fantastic course, introducing the whole spectrum of biology. I asked him for a directed reading, because, through his course, I found out about a biologist whom I had never heard of before: Sir Richard Owen, the person who described vertebrate homologies. Richard Owen, I thought, was out-of-the-box brilliant. And I wrote a paper about Richard Owen’s work, seeing homologies between Owen’s account of the origins of homologous vertebrae and the Britten-Davidson model for the origin of homologous genes. Camille Lamoges left to become, I think, Minister of Education in Montreal. And Bill Coleman replaced him. Bill Coleman had written the paper on the nucleus, and he had written the paper on Chadwick and public health in Britain. He was brilliant, and I asked him if I could have a directed reading in the work of Thomas Huxley, Owen’s adversary. So, I was reading Owen and Huxley. In 1977, DNA sequencing come into being, and Gould writes his book on ontogeny and phylogeny. Again, I’m exapted. I know the arguments about homology, I know the arguments about macro-evolution. I know the arguments about growth versus epigenesis. And now we can test this. We have DNA sequencing, which means that we could look between species at what changed. Whoa! That year, 1977, what a great time to be a postdoc! And I eventually ended up working in Masayasu Nomura‘s laboratory, and I became involved in the some of the first-ever RNA sequencing. We started doing the sequencing before Maxam and Gilbert published their paper, because Nomura-sensei was at a Gordon conference where they were announcing this, and he sent a grad student, Leonard Post, to their lab to learn the technique. The grad student came back, and we learned DNA sequencing. Howard Temin was there; so, we had lots of reverse transcriptase. We could make DNA from RNA. And so, we did RNA sequencing, and it was so new that I had to have paper chromatography in addition to the sequencing gels to show that the paper chromatography results were consistent with our sequencing data. So, I got interested in evo-devo primarily from my history of science background. I didn’t learn anything about that in developmental biology courses.
HS: You choose to focus on animal development in this paper, because there was already lot known about environmental regulation of plant development. Why do you think this was the case?
SG: It’s really interesting. Plants continually develop, and it’s obvious. Each season they put forth new flowers, they put forth new leaves and so forth. If you’re studying plant development, you’re often studying adult plants. Plant physiology and plant development didn’t separate into separate fields. In animals, developmental biology has little to do with what the physiologists study, and what physiologists study has very little to do with what the embryologists study. But in plant biology, the developmental biologists are often plant physiologists, as well. And so, for example, the plant people were very cognizant of the role of mycorrhizal fungi in extending the roots. They knew about symbiosis as a normative aspect of development. It’s the animal people who didn’t. The plant people almost always situate their plants in an environment (at least until Arabidopsis). Their plants were in fields or in greenhouses where the environment can be experimentally altered. The plant people knew that the environment was critical for plant development. There is the whole notion of terroir – the land matters. In animal developmental biology, our model systems were designed to avoid that. So, I was mainly talking to the animal people in this paper. And of course, that’s where I’m from. I’ve only published one paper in plant development.
HS: In the paper, you focus on two case studies: amphibians and humans. You have already spoken about why you chose to focus on amphibians. Why humans for the second example?
SG: One of the things that astounded me was how so many things we think about in terms of physiology are actually developmental biology. When we go to the gym and exercise, that changes our phenotype, and it has to do with muscle stem cells, it has to do with paracrine factors that are being made. It has to do with testosterone. It has to do with all sorts of things involving development. Learning is also a developmental process. The fact that we are completely dependent on the environment in getting a nutritional co-factor. Most animals can make vitamin C. Humans can’t. We have a mutation on chromosome eight. We can’t do it. The fact that we’re dependent on the environment for our bone growth. We get rickets, otherwise. There are a number of things in humans that occur after birth but is still developmental biology. And so, I wanted to say, we’re not special. It’s not that humans have evolved so that we don’t need the environment anymore. That’s modernism. That’s the whole notion that we transcended the environment. I said, no, we are just like the other animals, in this respect. We need the environment to complete our development. I wanted to put humans in, just so that people would know that what I was talking about wasn’t only for amphibians and insects.
HS: In the Conclusion to the paper, you say: “We can give a definite answer to the question posed by Wolpert in 1994: Will the egg be computable? That is, given a total description of the fertilized egg—the total DNA sequence and the location of all proteins and RNA—could one predict how the embryo will develop? The answer has to be “No. And thank goodness.” The phenotype depends to a significant degree on the environment, and this is a necessary condition for integrating the developing organism into its particular habitat.” I was curious about the “And thank goodness” part.
SG: Why “thank goodness”? Because we’re not ruled by the tyranny of our genes. That’s a phrase from Barton Childs, who was talking about cognition. We can modify our phenotype. It’s not only what genes we have but how we use them that’s important. Our genome has evolved so that it can take signals from the environment and use those signals to change our phenotype. That’s an amazing trick of the genome. That’s the thing that makes the genome exciting. That it makes proteins is amazing in itself, but that it can change its pattern of expression based on what the environment calls out – this call and response from the environment– seemed to be critically important for learning and for adapting to the environment. That’s why I said, thank goodness we’re not controlled solely by the genes.
HS: What memories do you have of writing this paper – how long it took, when and where did you write it etc.?
SG: I am trying to think back. That was a very productive time in my career. I was writing about holism and organicism. It was a very heady experience to just realize that there is so much we don’t know. I remember talking with Susan Lindee, who co-authored that wonderful book called The DNA Mystique. She was asking biologists, how much do you think we know about nature? Do we know 25%, 50%, 100%, whatever? And I said, well, probably less than 0.5%. All that we know about in developmental biology are based on five species that grow in the laboratory. That’s it. It was just a very heady time. I had students who were working with me and whom I was bouncing ideas off of in seminars. It really was a wonderful period of time. It was the new millennium, after all, and, as an aside, I wrote probably the weirdest development paper I ever wrote, on the creation of Eve. Eve was supposedly created from Adam’s rib bone. No. It wasn’t the rib. It was the penis bone! Humans lack a penis bone. Most male mammals have one. Why don’t male humans have a penis bone? Well, this is an etiological story of why we don’t. I wrote this paper with a professor of Semitic literature from the University of Judaism in Los Angeles. He had the same idea as I did. Again, the advantages of working at a liberal arts college. I’m friends with the woman who teaches Hebrew and Christian scripture. So, I asked A.J. Levine, if there was anyone in Biblical Studies who’ve talked about this as a possibility of the “rib” being the penis bone. And she says, Yes, Ziony Zevit, a well-known, very well-respected professor, has talked about it, but he’s never written about it. So, I write a two page letter to the American Journal of Medical Genetics and sent it to Ziony. I asked if he still believed this, and, if he didn’t, could he tell me why. Moreover, if he did think I was correct, would he want to be a co-author on this paper, since he also had this same idea. And he said that he thought I was correct, and he provided even more evidence from biblical studies. And so, we published this paper on the bone of Eve. It got mentioned in La Monde, Biblical Archaeology Review, and several religion publications. I figure, after all my biology stuff is long forgotten, this will remain as my contribution to western civilization!
It was just such an amazing time in terms of seeing the possibilities for developmental biology and biology in general.
HS: Do you remember how you chose to submit this article to Developmental Biology?
SG: I wanted this idea to be seen by developmental biologists. And also, Developmental Biology had published a paper co-authored by John Opitz, Rudy Raff, and me in 1996, which was really an introduction to evo-devo. I was coming at it from vertebrate embryology, Rudy was coming at it from paleontology, modularity, and sea urchins, and John Opitz was coming at it from clinical dysmorphology. If you look at that paper you’ll see it’s an exercise in history of biology. It really says, here are the questions that were jettisoned when genetics became the way to look at developmental biology. We can now reopen these questions of macro-evolution, speciation mechanisms, and homology, And so, this eco-devo paper was kind of a continuation, if not an apology, for not mentioning it earlier. And so, Developmental Biology seemed to be the appropriate place for it.
HS: You acknowledge the help of J. Bolker and A. Agrawal at the end of the paper. How did they contribute?
SG: I can’t remember. Agrawal might have sent me a preprint of something, in addition to the photos for Figure 1. Jessica Bolker and I had many discussions because we were writing a paper together, on homologies of process. This was another part of the evo-evo story, which was just being discovered. For instance, what’s now called the FGF-RTK pathway, was found to be involved in forming the eye of Drosophila, it was involved in forming the vulva of C. elegans, and it was involved in promoting the mitotic rates of cancer. It was the same pathway, but being used in different parts of development. And we said, whoa, these pathways are homologous, just as bones between organisms are homologous. They’re not the same pathway, but they’re the basis of them; the underlying principle is the same in all these three cases. We argued about this, because she didn’t fully agree with me and I didn’t fully agree with her. And so, we formulated something together that we could agree on, because we both agreed that not only were structures homologous but you had processes that were homologous. Those papers came out about the same time. Jessica and I met at a meeting that Evelyn Fox Keller organized at the marine biology lab at Friday Harbor. And I remember walking with her on the beach, arguing, and Dick Burian was with us, as kind of the referee, restating what we had said in terms that could be accepted by both. It was a very intense and enjoyable time.
HS: Do you remember anything about the peer review of this paper?
SG: I remember nothing about it. And that’s good, because it means it probably was not a harsh review. There were other papers that I definitely remember the peer review on!
HS: Do you remember any reactions you got from people when the paper came out?
SG: Yeah, at meetings, people asked me about getting a session together. And we did. I got funding for a session – I think it was 2002 – at the SICB meeting. People said, we needed to bring all these things together and have the people talking about this, because at that time, it was a collection of isolated research programs. So, Jessica Bolker and I organised this at SICB, and we had a wonderful session bringing together people looking at different aspects of this topic. And the meeting was reviewed in Nature, which for a person at a liberal arts college was just wonderful.
And that was a meeting which ran over its time limit, because everyone wanted to meet each other. They had all been working separately in these areas, and now they realized that there were other people who may not be working in the same area but who had the same ideas about environment and development. It included talks on insect polyphenisms, sex determination in fish and reptiles, adaptive plasticity in plants, amphibians, and sea urchins, environmental regulation of life cycles, and mechanisms of endocrine disruption. Gerd Müller brought in an evolutionary aspect, discussing environmental production of evolutionary innovations. After the meeting officially ended, we went to an adjacent room where we exchanged ideas and email addresses. The proceedings of that symposium got published in Evolution and Development.
HS: How did the ecological developmental biology textbook happen? Was it connected to this paper in anyway?
SG: The textbook came much later. It used to be that publishers would go to scientific meetings, and the acquisitions editor would go hear talks, and would buttonhole people saying, “Do you want to write a book about this?” That doesn’t happen much anymore. I got to know the publishing people relatively well. And I remember the publishing people from Wiley asking me what books were needed for undergraduate developmental biology. I said that I could tell them right away what books are needed: we needed a good book on stem cells for undergraduates, and we need a book on ecological developmental biology. I knew what they were going to say next: could you write one? No, I can’t. I cannot write one because I have no time to write this. I’m writing another book. I can’t do it. But I said that the person who they should ask would be David Epel, because he’s written this paper about beakers and breakers, and he’s thinking in these terms.
Some years later, I get an email from David Epel: Hi, Scott. I’ve been asked by the people at Wiley to write a book on ecological developmental biology, and I decided I need a co-author! At that time, I was going on sabbatical leave. And I thought, this could be a thing I do on sabbatical leave. That was the genesis of that book. Eventually, Wiley dropped the project and we published with Sinauer Associates, who also published my developmental biology book.
HS: When did the meeting with Wiley happened? Was it after the paper?
SG: Oh, I’m sure it was after the paper. I think it was at the 2002 SICB meeting, where we had that symposium.
HS: What has been your involvement with the EES?
SG: Actually, I don’t consider myself all that involved with the EES. While EES has its roots in evolutionary biology, eco-devo is rooted in developmental biology. But in 2006, Kevin Lala, John Odling-Smee and I were at a meeting in Paris, and we were talking about evo-devo – maybe Kevin has more accurate memories of this than me – and we said we need to write a paper together about the fact that we’re really in disciplines that merge. There’s so much overlap in this. When I’m talking about symbionts in the gut, I’m, in a sense, talking about niche construction. The gut bacteria of cows are building the rumen. So, we’re really talking about similar things. We wrote a paper in 2008, which was called Building Bridges, about the need for eco-devo and EES to come together. And I would like to think this new book of 2024 may be the outcome of that. We finally got all the different strands of development together that we can talk about this. And the fact is that niche construction is not a big part of the new book. I think says a lot for Kevin’s ability to see niche construction as a part of a bigger picture. I think that’s wonderful.
HS: Do you remember what was the meeting in Paris?
SG: It was an incredible meeting at the Ecole Normale Supérieure in June, 2006. I believe Charles Galperin was the convener, It was on mechanisms and genes in development and how best to study them. And that was, I believe, the meeting where Michael Ruse – who I’m told just died; I did not know that until yesterday – said that our 1996 paper was “hogwash”. So, I had to explain to the people at the Paris meeting, that hogwash is an American rural philosophical term meaning: I don’t have the data, but I know it’s wrong. And then Michael Ruse and I went back and forth in Biological Theory about the creative aspects of development versus natural selection. And I came up – unfortunately, it wasn’t published then, but was later – with my notion that development has the creativity of the artist, while natural selection has the creativity of the curator.
HS: That definitely sounds like something you should write about more.
SG: Oh, now I’ve put that into articles.
HS: Today, 23 years after the paper was published, I would like you to reflect on the concluding lines of the paper, and tell us to what extent what you hoped for has happened: Unfortunately, the environment can also be the source of chemicals that disrupt normal developmental processes. If only a fraction of what books such as Our Stolen Future (Colburn et al., 1996) are saying is true, then developmental biologists are going to have to go to the forefront of conservation science. Ecological developmental biology must become a critical part of normative developmental biology if we are to base agricultural and industrial policies on scientifically accurate data. As we become aware of the complexity of development, we are realizing that development is critically keyed to the environment. Ecologists have known about “life history strategies” of organisms for over a century. However, the proximate causes of these histories (such as how a fish becomes male in one environment and female in another) are just beginning to be understood. Progress in kairomone isolation is just starting, and the genes responsive to kairomones and larval settlement cues remain to be isolated (see Okazaki and Shizuri, 2000). There is important research to be done, and whole new worlds for developmental biology to explore. “Eco-devo” can also play a balancing role in “evo-devo.” Most discussions of evolutionary developmental biology have focused on the phylogenetic, nonadaptive, and macroevolutionary parts of evo-devo (e.g., the Hox, Pax, and Distal-less gene families and the origin of phyla, classes, and orders). Eco-devo would complement this, focusing upon the ecological, adaptive, and microevolutionary aspects of evolutionary developmental biology. Van Valen (1973) claimed that evolution can be defined as “the control of development by ecology.” We are at the point where we can give some specific instances and mechanisms of where and how this happens.
SG: Ah, yes. I won’t say it’s prescient, because even 23 years ago, we knew what was happening. It’s become more and more important. The endocrine disruptors, the teratogens in the environment, are causing incredible harm. There was a paper that came out two or three weeks ago in Science, which said that we’re just scratching the surface of what these chemicals are doing. It’s a paper by Justin Crocker’s laboratory at EMBL. What he’s shown with, primarily, Drosophila larvae, but also with butterfly larvae, is that sub-lethal doses of over half the chemicals they tested – they tested like a thousand agro-chemicals, pesticides, insecticides, and all sorts of fertilizers used on the environment – cause behavioral anomalies in the larvae and lessened reproductive robustness in the adult. And we’re losing the insects. And when we lose the insects, we lose the birds. And the ecosystems crumble. Endocrine disruptor research, such as the recent papers from the Damdimopoulou laboratory, has shown that we’re not looking at the effects of single chemicals, but we’re looking at the effects of mixtures of chemicals, and those mixtures of chemicals affect the developing mouse brain. Does it affect ours? We can’t do the experiments, but I assume that it does. I think that sub-lethal doses of agrochemicals and plasticizers are doing damage.
The other thing that’s in here is the complexity of ecosystems, that development is what ties ecosystems together. Most organisms are larvae. Most organisms don’t survive to be adults. It’s the larvae that are keeping things together. And if we destroy the larvae, we destroy the ecosystems. This is what Deborah Bird Rose talked about: when dependence becomes a peril, not a blessing, when this wonderfully evolved interconnectedness is being cut. And when you cut it, the whole ecosystem disravels. Studies were beginning to say that global warming was altering the hatching of larval caterpillars relative to the hatching of young birds. So, yeah, realizing that development is critically key to environmental agencies is more important than ever.
HS: What do you feel about what you said in the Conclusions about the role that eco-devo needs to play in evo-devo? To what extent has that happened?
SG: I wish the funding was such that we’d have eco-devo labs flourishing. They’re not. I’m thrilled with the experiments that Justin Crocker has done, for instance, and the work integrating ecology, development, and evolution coming from Ehab Abouheif‘s work on ants and Armin Moczek‘s work on dung beetles. But they’re not the norm you see in developmental biology. Developmental biology is still very much looking at gene expression and gene regulatory networks in organ formation and morphogenesis. That’s been the core of developmental biology, and that’s not going away. And the thing is, we need that core, but we need to do things like the Abouheif and Moczek laboratories are doing, taking those core things and finding how they’ve been modified by the environment to help the organism survive in a particular environment. Ehab Abouheif looks at the wing morphogenesis pattern, where classical work has been done in Drosophila; but he’s now doing the same in the ant, and he finds that the environment is controlling some of these patterning genes, and it’s causing caste formation! That’s interesting and important, and it just opens up a whole area of biology for new research. Armin Moczek is showing that dung beetles thrive through a mixture of symbiotic and plastic strategies, and that plasticity can be an important factor in the rates of evolution.
HS: What I hear you saying is that it [eco-devo playing a role in evo-devo] hasn’t happened to the extent that you hoped for in the 2001 paper.
SG: Not nearly as much as I had hoped. I also really had hoped that developmental biology and community ecology would come together. I wrote a paper about this three years ago with Michael Hadfield, an advocacy paper in the journal Development, saying that we need to have an ecological approach to developmental biology. We’re seeing the extinction of species, and a lot of its extinction is because of the larval environments are not being sustained. Monarch butterflies are a good example, where the caterpillar’s food plant, milkweed, has been destroyed by agricultural practices. You need to look at larvae and embryos if you’re looking at sustainability. And you want to go beyond sustainability. You want to go to thriving and not merely be sustained. And so, we wrote an article saying, look, developmental biology needs to form its bridges with environmentalism.
HS: As you were talking. I was curious about something in the title: the use of the phrase “real world”. You don’t say “ecology”, you say “real world”, which is subtly different.
SG: Oh, yeah, definitely. “Real world” is not only the natural ecosystems. It is also our technological-industrial ecosystem, our anthrome that now covers over 75% of our planet’s ice-free surface. I don’t know if he used it, but the real world context might have come about in discussions with Tyrone Hayes. Hayes was working on the role of Atrazine in demasculinizing frogs. He was asked by the Syngenta company to look to see whether atrazine caused cancer. His results said, No, it doesn’t cause cancer, but it causes ovaries to form in male frogs. And he had a horrible time publishing this. The Syngenta people tried to defame him and everything. Tyrone has a figure in a paper about how Atrazine causes the feminization of frogs. In that, you see testosterone being converted to estrogen, estrogen causing female behaviours and whatnot. But above that chemical process is governmental and commercial processes that include the needs of farmers to grow crops in a competitive way. He put the real world into his picture of a chemical reaction. I thought, wow, that was an impressive thing to do. He’s putting politics and economics as causal factors in producing the chemical reactions. The importance of being in the “real world” is emphasized.
HS: I’d like to end this interview by talking just a little bit about the place of this paper in the body of research work that you have done. Did this paper, and the thinking around it, represent a shift in any sense? Did it change the way you did research after that?
SG: The model that comes to mind is metamorphosis. In metamorphosis, some things are jettisoned, some things are retained and repurposed, and some things grow anew. I think this paper is a stage of metamorphosis. In my thinking, the 1996 paper on evo-devo was the first, this paper on eco-devo was the second, and the paper that I wrote with Fred Tauber and Jan Sapp on the holobiont marked the third stage of my metamorphosis.
HS: Do you think of these three papers as your most important ones?
SG: Yes, I think these papers are probably my most important papers. I’m writing another one now! My newest paper is always the most important paper!
HS: That was my final question. I was wondering if there’s anything else you want to add that you think is relevant to this conversation.
SG: No, I’m thrilled that you asked me to talk about this, and it made me think about these things in a way I hadn’t thought before. So, thank you.
HS: Thank you so much, Scott.
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