Ep 150: Hormones gone wild (with John Wingfield)
How do hormones help animals cope with stress, seasons, and climate change? What is allostasis?
In this episode, our guest is John Wingfield, Emeritus Professor of Physiology and Behavior, at the University of California, Davis. John helped develop many fundamental hypotheses in the field of endocrinology through his work on wild bird populations, in particular the white-crowned sparrow. Fran Bonier, a former PhD student of John’s and now Professor of Biology at Queen’s University in Kingston, Ontario, also joined us for the chat.
We talk with John about how he got interested in understanding wildlife endocrinology, and discuss how he helped formulate the “challenge hypothesis”, “emergency life history hypothesis”, and the concept of “allostasis”. And at the end, John gives some advice to early career researchers, based on his experience as the head of the Biology Directorate at the National Science Foundation.
Cover art by Brianna Longo
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Marty Martin 0:04
Last week in Las Vegas, the inaugural Enhance Games went down, a competition where athletes were not just allowed to use performance-enhancing drugs, they were encouraged to dope.
Cameron Ghalambor 0:15
Testosterone, growth hormone, anabolic steroids, all of it under medical supervision, of course, but no testing, no apologies. The tagline was basically: "let's see what humans can really do when you take the shackles off".
Marty Martin 0:32
The whole thing was based on the idea that the Olympics are broken and that performance-enhancing medicines are the road to the fountain of youth. The prize money was real, $250,000 per event, and a million dollar bonus for anyone who broke a world record.
Cameron Ghalambor 0:49
The tournament wasn't as big as the Olympics, but there were a lot of events, including swimming, track and field, and weightlifting. The roster was a mix of Olympians, world champions, and retired athletes.
Marty Martin 1:02
The poster child among the competitors was James Magnussen, a former world champion swimmer who publicly pledged to demolish the 50 meter freestyle world record.
Cameron Ghalambor 1:12
He'd been on a steroid regime for months and showed up to Las Vegas looking, by most accounts, almost unrecognizable. He gained so much muscle mass that he started sinking in the pool and couldn't find a swimsuit that fit,
Marty Martin 1:27
And then he raced against guys who were mostly three weeks into their own drug programs. But, Magnussen, he finished last.
Cameron Ghalambor 1:35
Ha. The whole event was supposed to be a showcase of pharmaceutical superpowers.
Marty Martin 1:42
But across the whole competition, only one athlete managed to beat a world record.
Cameron Ghalambor 1:47
And that record won't even be officially recognized, because athletes in that event wore the polyurethane super suits that have been banned from competitive swimming since 2009.
Marty Martin 1:58
And the men's 100 meter dash, a feature event in every Olympics? It was won by Fred Kerley, who competed clean, even submitting to official drug testing beforehand to prove it. The enhanced athletes in the marquee event lost to a guy who took nothing.
Cameron Ghalambor 2:14
What's the story all about? First off, we're not here to litigate the Enhanced Games, nor are we here to advocate for them.
Marty Martin 2:22
We just can't think of a better recent illustration of something that today's guest has been arguing for decades before these games.
Cameron Ghalambor 2:28
The reason is that the games push the pop culture story by suggesting that steroids are a kind of simple performance dial, crank it up and get bigger, faster, stronger, a kind of biological cheat code.
Marty Martin 2:43
But what the Enhanced Games actually demonstrated—
Cameron Ghalambor 2:46
unintentionally and at considerable expense—
Marty Martin 2:48
is that hormones don't work like that. Flooding your system with testosterone doesn't just make you a better athlete, it makes you bigger and better in certain ways, but can also make you worse in other ways.
Cameron Ghalambor 2:58
In other words, steroids drive trade-offs. Biological systems, including humans, are not machines with a single throttle; they're networks of signals calibrated to context and beholden to the evolutionary past.
Marty Martin 3:14
And that insight is the core of what our guest today, John Wingfield, Distinguished Professor Emeritus in Neurobiology, Physiology, and Behavior at the University of California, Davis, formalized in his Challenge Hypothesis way back in 1990
Cameron Ghalambor 3:27
John's idea wasn't just that testosterone varies among individuals, including humans, but specifically in his case, birds. His idea was that it varies for particular reasons, ecological and evolutionary ones.
Marty Martin 3:42
For instance, testosterone in breeding male white-crowned sparrows, a favorite species of his, doesn't track dominance or aggression in a simple way. It rises in response to a social challenge, a rival, a territorial intrusion, some competition, and then, crucially, it comes back down. It's a context-sensitive pulse, not a simple fixed personality setting.
Cameron Ghalambor 4:04
This happens because the costs of keeping testosterone elevated are real. Testosterone can suppress immune function, elevate injury risk, interfere with parental care, all sorts of bad things.
Marty Martin 4:17
These costs of steroid activity mean that natural selection didn't build animals that run testosterone at a maximum. It built animals that deploy testosterone and other hormones appropriately when the environment demands it, and then pull it back.
Cameron Ghalambor 4:29
In nature, the winners aren't the most testosterone-saturated individuals. They're the ones that regulate testosterone the best.
Marty Martin 4:38
But testosterone was just the beginning, Wingfield's original hormone interest involved cortisol and other glucocorticoids, those steroids that largely drive stress responses. In collaboration with Bruce McEwen and many others, John developed the emergency life history hypothesis and elastasis ideas that emphasize how animals don't just react to perturbations, they anticipate them.
Cameron Ghalambor 5:00
To John, stress is not just something that happens to us or other wild animals. Stress involves active regulation of our internal state to match predicted demands before those demands arrive, using hormones to adjust our behaviors and our physiology to cope with or to get away from things that reduce fitness,
Marty Martin 5:20
Which brings us back to Las Vegas. James Magnussen perceived an opportunity, a million dollar prize, a chance in immortality, and responded to months of exogenous testosterone to build muscle he didn't need in proportions he couldn't use for a sport that requires hydrodynamics, not bulk.
Cameron Ghalambor 5:36
Magnussen's response to testosterone wasn't broken, it was exactly what you would expect. Testosterone would cause muscles to grow and other traits to change, but by no means would testosterone doping guarantee he'd transform into a human fish.
Marty Martin 5:51
Today on Big Biology, we talk with John, one of the founders of Field Endocrinology, about his seminal contributions, as well as his work as director of biology for the National Science Foundation,
Cameron Ghalambor 6:01
John helped us realize that animals are not passive responders to their environments. They are predictive, strategically organized systems that evolution has equipped with a hierarchy of programs for managing the tension between long-term reproductive investment and short-term survival.
Marty Martin 6:19
Stay tuned to hear more about these ideas from one of the people most influential to my way of thinking about biology. But before we get to that chat, a few things. First, we were very lucky that Dr. Fran Bonier from Queens University Biology joined us as guest host. Fran was a PhD student with John, but is also a friend and collaborator of Cam and me.
Cameron Ghalambor 6:38
Second, Big Biology continues to be a top rising science publication on Substack. Thank you so much for subscribing and following us. Growing our listenership helps us spread these biological stories, but also it helps practically.
Marty Martin 6:53
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Cameron Ghalambor 7:12
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Marty Martin 7:18
Importantly, though, if you're a student or just can't afford a subscription, send us an email, and we'll give you access for free. We don't want anyone to miss out on our conversations with the world's best biologists, because they can't afford it.
Cameron Ghalambor 7:29
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Marty Martin 8:01
Now onto the show.
Cameron Ghalambor 8:02
I'm Cameron Ghalambor.
Marty Martin 8:03
And I'm Marty Martin.
Cameron Ghalambor 8:04
And this is Big Biology.
Marty Martin 8:17
John Wingfield, thank you so much for joining us on Big Biology today.
John Wingfield 8:21
Yes, good to be here. Thank you for asking.
Marty Martin 8:23
So we're really excited to have you on today. And I think it won't be a surprise to hear that your work has been an inspiration for so many people, including me, my PhD advisor, Mark Wikelski, and another very important mentor and PhD committee member, Ayla Howe, who sadly just passed away last year, were postdocs with you, so I've had the chance to talk to you for quite some time and learn so much, but I'm going to sort of pass the torch to get us started to our guest host today, Fran Bonier. Hi, Fran.
Fran Bonier 8:51
Hello.
Marty Martin 8:52
because Fran earned her PhD in your group, and we invited Fran here today to talk about your research career, John, and origins. So, Fran, first question, take it away.
Fran Bonier 9:02
Yeah, so I was super excited when Cam and Marty asked me to be involved with this, because, of course, I'm happy for any excuse to have a chat with you, John, and I've got lots of questions, and we get to share your answers with all the listeners, so maybe we could start with your sort of origin story going back to before you were a biologist, do you want to tell us a bit about, you know, what you did before?
John Wingfield 9:28
Yeah, yeah, I can. I spent my childhood growing up, I was born in the same place in this small market town in Derbyshire, Southern Derbyshire is next to several national parks, and just lots of nature around. So, I've been exposed to this from my earliest memories. And one thing I did, and I remember very clearly, is that I noticed with the seasons that the birds changed what was there. So those that were here breeding, quite a few of those left, and then in the winter there were other ones that arrived. So this sort of got me interested in seasonality. Of course, I had no idea that what would possibly regulate that, because I was only what 10, 11 years old? But one other thing that really struck me was that in 1962/63 winter was really cold one with a lot of snow there for about three or four months, very unusual for England, down to -20 celsius. Those broke all sorts of records, and a lot of these birds just disappeared. I said, what they've gone away too. And I would find the occasional dead bird that was totally emaciated. So, that was what's going on here? So, in a way, my childhood growing up was preparing me for the answers I should.. I should probably be asking.
Fran Bonier 11:01
Did you have mentors or anyone in your family who were naturalists, who inspired that, or that just came from you?
John Wingfield 11:08
No. I was, I was the only academic in the family. Well, my grandmother was, was pretty good at identifying a lot of the birds. But it wasn't until I was much, well, older, 15 that I was, I was introduced to several other birding people, bird ringers or banders, and I actually got to ring some birds. My first bird was a black bird, a European black bird. Yeah, I was about 12 years old, and I was just smitten and thought this is what I want to do. And then I went to Sheffield University, which mostly a degree in zoology, but it could be zoology and endocrinology, because there were, I think, about two thirds of the faculty were endocrinologists. And so slowly, as I went through those first courses, I thought hmm this is what might, may be going on in these, in these birds. So the first ideas came then in my undergraduate degree.
Marty Martin 12:10
Wow, so am I understanding that correctly? The passion for birds and the accident of going to school at Sheffield had either sort of these two things coming together has a really big influence on the work that you did.
John Wingfield 12:23
Yeah
Marty Martin 12:24
Wow
John Wingfield 12:24
Yeah. I was primed.
Marty Martin 12:27
Yeah primed.
Cameron Ghalambor 12:28
So, so, John, I, you know, I haven't had the pleasure of working with you, but I've, you know, worked and know many of your, your offspring, and so I'm curious. So, after Sheffield, then who was your PhD advisor, and kind of put you onto your research track?
John Wingfield 12:46
Well at Sheffield, I was wanting to go to graduate school, or the equivalent in the UK, and do a PhD in ecology, which made a lot of sense to me at the time. But it turned out that that didn't, that didn't work out too well. The chair of our department had a long talk with me, and he said, "Would you like to go take a look at some of these labs that have scholarships to do endocrine work? And I said, "Yeah, okay". So I went to what was then called University College of North Wales in Bangor. It is now Bangor University. And they had a big marine station there, and boats. They wanted to go out onto the North Sea and beyond. There's some amazing adventures in these trawlers. I could tell you. We were expected to collect samples, collect fish, and bring them back to the aquarium and get blood samples, so we could start looking at it, because they didn't even know what hormones these things had at the time.
John Wingfield 13:51
So that set the stage, and really part way through, and I started to look at the changes in hormone levels, you know, and other effects. It seemed to me that you know we've been trawling the bottom of the North Sea or Southeast Iceland for the last four hours with no idea when the fish got in the net, and this is about as stressful an experience as you could ever have. So I said, "what does it mean?" So I started to look at stress effects of capture and handling, and sure enough, cortisol levels started to increase over a period of 24 hours, and then they turned off. And the whole hypothalamo-pituitary, adrenal, or interrenal axis just kind of was stalled. I thought, well, what the heck am I looking at here? So I said, well, first of all, I need to work with an animal in the same medium as me. Having said that, there are some of the fish endocrinologists who've sampled fish while scuba diving, but that was a bit beyond my capabilities, so instead, so I ended up going to work in the US at a lab, at the University of Washington in Don Farner's lab, and I chose him because he had a lot of field experience, you know, on this white-crowned sparrow. So got there, and of course, the first white crowns I saw, I said, these are the ones, so we could catch them and get samples very quickly, and the first ideas of stress series came then,
Fran Bonier 15:39
So that did the stress series sort of originate then with the idea about the trawlers in the North Sea, like what you saw in the fish, sort of inspired what now so many people do to measure the stress response?
John Wingfield 15:54
Yes.
Fran Bonier 15:54
That's so cool. I didn't know that,
John Wingfield 15:56
and Southeast Iceland and Irish Sea, which was very close to Bangor, that was quite an experience. I swear I got, I cured myself of seasickness, and one of those big storms in the 30 foot wave will get your attention.
Fran Bonier 16:13
I bet.
Marty Martin 16:14
Wow. So, in the, I mean, to bring the general listener into the stress series, because the four of us know this quite well. I mean, it's sort of just what happens to an animal when it's captured, and the sort of mobilization of these hormones into the blood. I mean, that's a sort of technique, in a sense, right? It developed into all of these amazing conceptual kind of things that we're going to get to in just a minute, but I remember when I was sort of getting going, I was working in this field, ecological immunology, and you were really encouraging about, you know, don't worry about these technical hurdles, we'll get over those, just keep pushing the envelope and keep, you know, there is a way forward. But the technical sort of constraints on doing endocrinology on wildlife were real, and I'm not sure we've even totally gotten around them now, but how did you navigate those early days when I would imagine a lot of endocrinologists were saying, what do you, what are you doing, why are you going outside and trying to measure hormones in a wild animal?
John Wingfield 17:12
I got a lot of that. Well, working locally around Seattle on breeding populations of white-crowned sparrows and a few other species. One of the things we thought a lot about was how to store the blood, keep it cool until we got back to the lab, and we could process it and harvest plasma, but also red blood cells, because the DNA is there. And the first few attempts were not that great a success, but it was just a case of using the materials available, and we got some nice thermos little boxes with that are insulated, and then we could put the blood in there, seal it in these capillary tubes, and put it in a specific tube, storage tube, in the ice. And then we go back to the lab about every, about every two or three hours, and then spin the blood, and it was fine. Later on, we said, "Well, what if we want to go more remote, and so we figured out ways to take us a centrifuge with us that we could spin the blood in the field, sometimes using the battery of the truck as a source. Another source was a crank. We dropped, we dropped that one quickly. By the time we got it spun down, everybody was sort of totally exhausted.
Fran Bonier 18:46
I bet I had one of those little mini centrifuges that you could plug into your cigarette lighter in the car.
Marty Martin 18:52
Yeah, me too.
Fran Bonier 18:53
Back when cars had cigarette lighters.
John Wingfield 18:57
When we first started, that those sorts of tools were not available, but so you know it's as Marty said, you keep on evolving and moving with what equipment is available.
Fran Bonier 19:11
But what did the standard, like lab endocrinologists, think of what you and Don Farner were doing, like you know, they want to study animals in these controlled environments, and you know, was there push back against, you know, you shouldn't even bother with the field work, let alone like whether it's feasible, but why bother?
John Wingfield 19:32
Exactly. Well, one of the things we found with the first year, first breeding season of working with the birds in the field, I got the assays done, compiled the data, and we looked at the pattern, and it was completely different from anything we saw in the lab, and that was variable according to species and individuals within a population, and so forth. Said, "wow, this is, we're just looking at the tip of the iceberg here." And I said, "you know, this, these data kind of direct the sorts of experiments one should be doing in the lab under control conditions, recapitulate the conditions in the field, social and otherwise." And Don Farner saw it immediately. I can remember him now, looking at that first graph. He was puffing on his pipe and looking, and he said, "Handsome data, John. Handsome data."
Fran Bonier 20:33
That's awesome.
John Wingfield 20:36
I said: "Does that mean I can go out next year?" He said: "Oh yeah".
Cameron Ghalambor 20:42
Well, I don't think it's an overstatement to say that you started an entire subfield of endocrinology, to take this work into the field. I know you know, as somebody who's attended the Integrative and Comparative Biology meetings, that you know the field endocrinology sessions are always, you know, very prominent at those meetings, and it's an amazing thing.
John Wingfield 21:07
Thank you for that.
Cameron Ghalambor 21:08
And to say that it's not just also that you sort of moved endocrinology into the field, but you also did so by training a huge number of people who've kind of really populated, I think, many, if not most, of the universities across the world, and I'm just curious, like, how you were able to inspire and build this amazing sort of network of people that were carrying out this work.
John Wingfield 21:42
I'm not sure. I just think students, and Fran could probably speak to this too, they were looking for a lab to work in, and we said, "Well, come out in the field with us, just get some experience. And a lot of these students just said, "Wow, this is what I want to do too."
Fran Bonier 22:01
That's what I did. Yeah.
John Wingfield 22:03
That's what Fran did. And Fran eventually was deeply involved in the development of evolutionary endocrinology, as well as the ecology, and that has become quite a field now. When you look at programs, at SICB, and so forth, a lot of evolutionary endocrinology, as well as ecological. And that, but also the standard molecular approaches to how hormones work. So I, at first, it was, you know, there were students coming into Farnah's lab, and I was a postdoc there, and I was essentially their de facto advisor, but after I came back in 1986, students started to knock on the door. So it was, it was, it was them, really, and they were students who talked to other students. And I think at the height, I think there's 12 graduate students in the lab.
Marty Martin 23:06
Wow.
John Wingfield 23:06
About six postdocs.
Fran Bonier 23:09
I think. You might have exceeded 12 for a little while. You really had an open door policy. You gave a lot of us a home, and also a lot of people opportunities to go on these great field expeditions, you know. We, I had to sadly turn down an offer to go to Tooly, but I did get to go to Barro and to Toolik Lake because of you, and the Barro trip was before I really studied birds. But maybe you want to tell us a bit about, like, you've traveled all over the world to study mostly birds, mostly hormones in birds, but some other things too. Do you have, like, your own favorite locations or adventures or science that you've gotten to do?
John Wingfield 23:53
I think Toolik Lake ranks up there. The view from the field station to the south to the Brooks Range is just beyond spectacular. And you're right there on the tundra, and in the earlier days of going up there, it was not unusual to have a grizzly bear walk right through camp, and people are sort of jumping into buildings and so forth to try and hide themselves. And the bears were totally unphased by this; they weren't interested in us at all. But then with over the years hunting up there, after they paved part of at least part of the Denali Highway, you start to see a lot of hunters coming up there, and so the really big grizzlies were gone, probably shot. So what we're seeing was a lot of newly independent two year olds, and so forth, so they're still around. But anyway, you know, the Denali Highway can take you from the Brooks Range, and the passes over the Brooks Range, down into this big valley, Atigun Valley, all the way out to through the foothills to the tundra, the really wet, Polygon Tundra. So everything changes, almost, you know, as you go from one habitat to another. You'll have Smith's longspurs in this one and red poles on the other at the next one, and then the predators change, depending on the ground squirrels are around, they call them siksiks, as they were called. That's their alarm call siksik.
Fran Bonier 25:47
Yeah. We caught a lot of siksiks in our potter traps.
John Wingfield 25:51
Oh yeah.
Fran Bonier 25:51
My field season at Toolik, they figured out we were putting seed baited traps out, and they're fattening up for their nine month hibernation.
John Wingfield 25:59
When we'd arrive in spring, the siksik would be there, saying, "Oh, hi, we're ready". They follow you around. Well, yeah, then they also killed some birds that were in the trap, so they're above ground squirrel carnivores as well.
Cameron Ghalambor 26:15
Yeah, I was telling Fran, reminding her that it was about 20 years ago that I got to go up to Toolik and, and help Paul Martin catch white ground sparrows, and you know, do some of this field endocrinology, and I was curious, so you know, not to embarrass any, any of your colleagues, or you know, students, but is there, is there any of these trips that kind of stand out, either you know, in terms of something funny that happened or particular discovery that you know you didn't expect from the outcome of the of the research.
John Wingfield 26:53
Yeah, I think the observation that some of these birds are really long distance migrants, like we have Northern wheatears there that are actually spending the winter in Africa, East Africa, 11,000 miles or kilometers, sorry, one way. And there were there were lots of experiences like that, but I think the one that stands out the most is that in some years, early in May, it's still winter, minus 20, and sometimes lower. And we were out there at a place called the Sag River DOT, that's the Sagavanirktok River Department of transportation. And we go there because there were several willows that the birds like to come into, but they were covered in snow.
Fran Bonier 27:48
I remember mist netting there. Yep.
John Wingfield 27:50
So we're standing by this gully, and it was just beautiful, you know, sort of snow, ice, blue, white, and this slow mist everywhere, and the sun trying to penetrate through, just absolutely spectacular. Then all of a sudden, I could hear this, and these ptarmigan, about 50 ptarmigan, appeared flying up the gully, probably still migrating, I thought. But then as they went by, right behind them came two other big birds that each one grabbed a ptarmigan. It was gyrfalcons.
Cameron Ghalambor 28:27
Wow
Marty Martin 28:27
Wow
John Wingfield 28:28
And they landed on the tundra, and they were just looking at me, glaring. Then they just took off, and I just realized that they've probably never seen a human before.
Cameron Ghalambor 28:38
Wow
Fran Bonier 28:41
Wow
John Wingfield 28:41
So it was anyway. I got a picture of one of the gyrfalcons, at least And lots, of course, pictures of Ptarmigan, but that event was really, I thought, summed up life on the North Slope.
Cameron Ghalambor 28:55
Yeah, and I guess for listeners who aren't familiar with gyrfalcons, these are, you know, the largest falcons, I think, in the world. They're, they're mostly white, and just, you know, one of the most spectacular birds, birds of prey that you could ever see.
John Wingfield 29:13
Yeah, they terrorize the tundra.
Marty Martin 29:24
Well, so maybe let's turn to the science. There's so many things that we can hit, and I'm hoping we get some more stories as the data were collected for the various different things that you worked on. John, I think we could do an entire series of episodes with the many different major contributions that you've made, we're going to try to boil it all down into bite sized pieces. And the first one that I wanted to start with was The Challenge Hypothesis. So, maybe tell us what that is, and especially its origin story. Was there some particular event that inspired that thinking? What data have been brought to bear on it, and where does the idea now stand?
John Wingfield 30:00
Yeah, The Challenge Hypothesis started to come together kind of in the second or third year of working in the field, and seeing how the patterns of testosterone in these birds differed greatly by species. And females sometimes had higher testosterone than we expected. And in some individuals you'd see virtually no increase in testosterone in spring at all, and in others you would get this, you know, several orders of magnitude higher surge, and what's going on here? I mean, they're all the same photo period, same food that's around, so why do you have these individuals that have high and others that have really low. And they're all territorial, mated, feeding young, so they're certainly viable birds. So that sort of sat with me for a while.
John Wingfield 31:09
And then when I left the University of Washington and moved to the Rockefeller University and their field station near Poughkeepsie in the Hudson Valley, started working with song sparrow,and found the same thing. They are fairly closely related to white crowns. But then I was getting really interested in the effects of hormones on behavior, and so I learned that that was the right place to learn behavior with Peter Marler's group and Fernando Nottebohm, Bruce McEwen, too, down in the city, so I had lots of people to let me think about that in the right way, and then to after about two or three years there I had four post docs who were just fantastic. These guys really helped formulate these ideas that maybe it's the interactions among males that is behind this sensitivity to environmental cues and the patterns of hormones that we were seeing. So that's what I thought, well, how do we test that? And there were people at the field station who were doing a lot of playbacks for behavioral ecology reasons, especially in red wings and cow birds, and what have you. They said, "Well, why don't we try that with the song sparrows and see if we get an effect? And nobody was more flabbergasted than me, and the fact we did. And this we started to look at the literature, and by this time we had there were enough studies that suggested that decreased testosterone in the males is correlated with feeding young, so if they are challenged, then you know they have to readjust their endocrine state to support, you know, a high level of aggression for a day. Sometimes these contests went on for a week, all sorts of issues about, you know, they had young in the nest, the male wasn't feeding them, the female had to compensate. There were all sorts of side stories there.
John Wingfield 33:24
So I said: "Well, what we can do is then implant these males, change the experimentally change their temporal pattern, then do these challenges, and also look at their parental behavior. So flying to the nest with food is really fairly easy to document. And what we found was that yes, testosterone did tend to decrease parental care in these males, and they were being very aggressive trying to drive away this persistent challenge, so working with people there at the field center, Peter Marler had a lot of people working with him, who we would have these fantastic discussions, and started to put together. Said, okay, early in the seasons, establishing a territory, testosterone is high. Once they have young, they're incubating, and so forth, testosterone levels must come down, so the males can contribute a lot more effectively. But if they're challenged, then males must respond and maintain their territory, or they would lose it. And so testosterone would increase, and as a result of the social challenge, and that would, there would be these rapid effects of testosterone on behavior, and that was that, that was a sore point, because a lot of people, the endocrinologists would say: "So well, you're telling us that you're seeing almost immediate increases in testosterone." I said: "Well within 30 minutes, certainly." And they said: "But it takes hours to days for testosterone to work binding to gene transcription factors that bind that are receptors for testosterone." And I thought: "Hmm. What's going on here?" And then, in the end, it became quite clear that testosterone was affecting the intensity of aggression. So, in other words, they would not just chase a bird away, they'd follow it for hundreds of meters. Every time they caught there would be in a big brawl, fight. So I said: "Well, there's no question that's what's happening." But then there's quite a lot of papers came out, well, not quite a lot, a few showing other rapid effects of steroid hormones, you know, in estrogens as well as androgens and corticosteroids
Fran Bonier 36:01
And glucocorticoids, yeah.
John Wingfield 36:02
Yeah. I said: "Well, there we have it." So slowly that manuscript and the challenge hypothesis in Amnat came together. A bit long-winded there, sorry.
Fran Bonier 36:16
No, that's great. That hypothesis has obviously sort of taken on a life of its own since you proposed it. Now it's been taken into all sorts of different fields, it's been applied to humans and all sorts of other, you know, things beyond birds. Are there any..
John Wingfield 36:34
Yeah, insects too.
Fran Bonier 36:35
Oh, really? Wow, are there any ways that it's been applied or interpreted that sort of surprise you, or you know that you disagree with?
John Wingfield 36:45
Not so much disagree with, but I think it's clear that there are still these species that don't respond, and that was another sort of headache of the hypothesis.
Fran Bonier 36:58
How to figure them out?
John Wingfield 37:00
And I said: "Well, at least, at least the simulated territorial intrusions are one way of testing this." And Wolfgang Goymann, working with these black redstarts in Europe, they do everything contra to what we would expect, they show no response, you can implant them with testosterone, and there is some response, but not terrific. And so that was quite clear that there are some birds that don't do this. And then about the same time we started working with Kiran Soma, and figured out that actually something very quickly was going on in the brain, and that led to the discovery that parts of the brain, certain nuclei that are involved in aggression, can actually synthesize their own testosterone without changing peripheral levels at all. I said, well, without changing peripheral levels, that would take care of the problem of not affecting or affecting parental behavior. It's all done centrally, so only the nuclei that are relevant are the ones that are expressing genes for these enzymes that make it their de novo in a neuron. And I said: "Well, so now we know that it's not just blood levels. We have to look at receptors with metabolizing enzymes in the neurons." And that worked out too in some of the song sparrow work back in Washington. These birds were contra the challenge hypothesis; they didn't show any response, but that's the one where we found they make steroids in the brain. And one key enzyme that converts the hydroxyl group, that carbon three, to a ketone, then biological activity, then that follow. She showed that with the song sparrow exposed to a simulated territorial intrusion, activity of this enzyme increases,
Fran Bonier 39:19
So it's not that they're an exception to the challenge hypothesis. They're just doing it differently,
John Wingfield 39:24
Right, they're doing it differently, and of course, then the next question is, well, what regulates changes in these enzymes? Right now, not a clue.
Marty Martin 39:31
Turtles, turtles all the way down.
Fran Bonier 39:37
So, so I had never really appreciated how the challenge hypothesis is really sort of related, overlaps almost, with emergency life history hypothesis, because when you talk about, you know, there's these prolonged challenges with territorial, you know, disputes and things like that. So, can you talk about the emergency life history hypothesis? And did it, did it come that sort of naturally from the challenge hypothesis, or am I making connections that weren't really there?
John Wingfield 40:08
I think it evolved separately, and then sort of interfaced with the challenge hypothesis,
Fran Bonier 40:14
And so this is the idea that you know you're an animal and you're doing one thing, you're breathing, you're migrating, whatever, and some perturbation comes along, some challenge that you have to cope with, like injury or food shortage, and you have to change what you're doing. So, yeah, maybe you could talk about how that came about.
John Wingfield 40:35
Well, that takes me back all the way to when I was a young boy in Derbyshire, and that severe winter, and a lot of blood has disappeared, you know. I said, "What the heck? And that's always been in the back of my mind. And being in New York, mid-Hudson Valley, we were far enough up the Hudson Valley that we're having, we were had a continental winter rather than a more sort of marine coastal New England kind of winter. And I talk about minus 31 degrees at times. And the song sparrows, we need more tracking data now, but the song sparrows would withdraw as it got very snowy and very cold, but I think only down to Long Island, Jersey Shore, somewhere like that. And some banding data supported that. And then they come back. I said, Well, okay, that makes a lot of sense. Is that regulated by corticosterone? And that that question is still somewhat open, because I think you need to look in the brain again to see, okay, those birds that don't conform to what we would expect with this severe weather, are they doing it all in the brain? So that they avoid these peripheral high levels of cort that explains why some of them do, some of them don't respond to well, not so much respond to the storm, but leave and then come back quickly as soon as they can. So that's it's sort of interface with the challenge hypothesis, in so far as some males that are responding increase testosterone, but then increase corticosterone. And then other species don't do that, so maybe that some are using genomic receptors in the brain for longer term responses to corticosterone and emergency life history stage, you know, the coping mechanisms. Oh, one other thing I'd say here is that it's always been taught, I'd always been taught that the stress response was bad,
Fran Bonier 42:55
Right.
John Wingfield 42:56
And I thought, doesn't make sense, why would you have a hormone response that is bad? You know, the hormone responses should be trying to establish a behavioral response, a physiological response that allows the animal to cope. These are all coping mechanisms, and so, for a while there, I was saying that these are anti-stress hormones. People didn't like that.
Fran Bonier 43:23
Yep.
John Wingfield 43:25
But that's essentially what was happening.
Fran Bonier 43:27
Exactly, and that idea hasn't really fully taken hold yet. You still hear a lot about how stress hormones are bad. And even in the human, you know, biomedical, which, of course, they can have negative effects, but you know, you really started with this idea of, you know, these aren't bad, this is highly conserved, we see it across species, and so it's doing something really important.
Marty Martin 43:50
Yeah.
John Wingfield 43:51
T hat also gave rise to the state levels idea that the changes in hormones daily, or even minute to minute, versus seasonally, you have that one level below which hormones are really pretty low, then that's the level A. Then, as they increase, they're getting this new level of sensitivity, level two, which is taking care of all the day-to-day homeostasis responses, and also the initial responses to challenges as a storm, or what have you, comes through. Level three, upper there, that level C rather is starting to see birds get into trouble, but at that time you see these drastic things that they leave the area completely.
Marty Martin 44:39
Well, that sounds like allostasis, John, and I think that's what we want to, we want to talk about in just a second, but I mean, I don't want to leave quite yet, probably because it's my own personal obsession with these hormones, this idea that the glucocorticoids are bad, because if you talk to an immunologist or somebody like me that almost went anaphylactic because I was doing too many of the wrong things around wasps and fire ants, I was very happy to be exposed to glucocorticoids and sort of recover from those kinds of things. But I think what about the emergency life history hypothesis that was so profound and exciting to me and continues to be something I think about is that it really reorients the focus of the hormone from the kind of molecular level of interaction to the organismal way of thinking about things. So it's not hard to find like deficiencies because of this hormone, if you're looking at a single system. But what the emergency life history helped me to think about was the sort of trade-off kind of way that if you're maybe not doing one thing or one thing becomes harmed, it's maybe to potentiate the other valuable kind of things, so you leave the stressor. It's kind of the sentiment of the sort of anti-stress hormone, right? It's sort of coping, when coping can take a variety of flavors, so it sort of enforces that organismal level of emphasis in thinking about what these molecules are doing
John Wingfield 45:57
Exactly. Yeah, and that inspiration for the emergency life history stage had been developing for a while, and then in the early 2000s we had this meeting, we had one of these center type meeting grants from NSF, and we had a European, Canadian Tony Williams and myself and managed to persuade NSF to give us some money to have these meetings and talk about exactly these kinds of things. And at one we had in Seattle in the early 2000s, Bruce McEwen came, because I've been corresponding with him from time to time, and he came and he gave the talk on allostasis and wear and tear. And I'm sitting there, everything all these bright lights going off, and my god, that's it, that's what that's how we can actually build a framework that we can start to look at this and see what experiments we really need to do. And after that I talked with him, after his talk, and he saw it immediately, too, in sort of a clinical way as well. So he was very excited that's when we collaborated and wrote that paper.
Cameron Ghalambor 47:15
Yeah, so, so let's talk more about allostasis, because I think people will automatically pick up on the idea that allostasis is sort of a variant of homeostasis, but maybe less familiar to people outside of endocrinology. And I'm really excited to talk to you about this, because I've, I've often struggled with the distinction between describing physiological responses as, as being either homeostasis or allostasis, and, and I've thought about this a lot in the context of fish osmoregulation, so cortisol plays a really important role in the control of gene expression and ion transport and maintaining plasma osmolality within a sort of a particular range. And I've always thought about that and as a homeostatic response but then others have also referred to it as an allostatic response. And I'd like to hear from you, like how you define and distinguish allostasis from homeostasis.
John Wingfield 48:26
Well, I feel that homeostasis is occurring constantly in the animal's daily routines, foraging, and any perturbations, mild perturbations within its territory will trigger homeostatic responses, no question about that. But the problem is that when you start to get more and more rigorous challenges to the animal that gets outside of its normal day to day foraging and interacting with others is at that time stage, corticosteroid levels start to increase and trigger other kinds of behaviors and physiology that, you could argue, are also homeostasis, but they're not predictive. And I think homeostasis is more the predictable daily routines, seasonal routines that are clearly homeostasis, but then when you get these big unpredictable events, that's where allostasis takes over, sort of an emergency life history stage. So it can modify homeostasis dramatically, but the two are kind of intertwined. But I think the allostasis is more focused on the unpredictable, which can catch you at the bad time, you know, you have a brood of young to feed, or you're in the middle of a bolt, and suddenly predator numbers go up. That's a big problem for birds, and some mammals too is, you know, the glucocorticoid axis tends to be turned off in molt, so they become resistant to a perturbation, but the problem with that is they don't have a lot of reserve to molt and take care of that, so you get fault bars and all sorts of problems with the plumage, so that's more or less how I distinguish between the two, is corticosteroids high levels will eventually stop the molt, so the bird can leave. And some birds do that, like shorebirds in the Arctic, the ones that are the last to migrate, usually males, they can withstand a lot of the autumn storms and so forth, and get the reserves, so they can then get out of there, but sometimes they're caught by these bad storms, and they have to wait. Whereas, others of the females, they tend to leave first, because they're in the poorest shape after producing four eggs that are more than her body weight. They blast out of there first, and the young birds of the last, hopefully this is making sense, but even within a population, there's a lot of variation with how they should respond to perturbations. But it's still wide open. It's really not a thing that's well known. There's a lot of work could be done there.
Cameron Ghalambor 51:31
So, there's the concept of allostatic load, so if you have these kind of unpredictable events, you know, a storm or such is the idea, then that if you have kind of a recurring stressor, environmental stressor like that, that these these sort of mechanisms are eventually going to kind of create sort of a wear and tear on the on the organism, and you start to move outside of the range of what would be kind of a tolerable range, where you start to then accumulate stress damage, the sort of really negative effects. So I think one of the things that is key here is, you know, how we define stress, because oftentimes people use that term in, in very loose ways, and there's a distinction between, like, what is a stressor and what is the accumulation of stress. So, yeah, what are your thoughts on that?
John Wingfield 52:38
Allostasis. Well, that's something that's bugged the heck out of me for a long time, and with Bruce McEwen, too, he said, you know, that this is a response to a perturbation, its allostatic load, and if allostatic load exceeds the resources, trophic resources immediately available, the animal is in trouble, and some of these predictable events, such as winter, and so migration, the stress of migration. Oh, that really bugs me, you know. It's a period of incredible energetic demand, and a lot of allostatic load, it goes into the foraging, and so forth, to be able to achieve that. But then that brings in one thing I was puzzled by for a long time was allostatic overload type two. And when you're talking about the wear and tear increasing and damage that can happen, that increases allostatic overload type two, which is permanent. It can't be, can't be reversed, whereas allostatic overload type one is very plastic. So it's been a deep one, but I think that's that's allostatic overload type two can be through in humans, it's been studied mostly with various diseases, alcoholism, drugs, and so forth, that have done damage, and they are much more susceptible to other perturbation factors, and that means that allostatic overload type one exceeds that threshold more quickly. It's a threshold that triggers the emergency life history stage. The more allostatic overload type two they have, the less flexibility they have with allostatic overload type one, and that builds up over life over the life of the individual, and can be very different among individuals, but how we get a good measure of that is still something people don't agree quite how to do it.
Marty Martin 54:50
Yeah, so I mean, allostasis is to me both inspiring and confusing to the point of frustration. And I think I think that it's because it feels like it could be mathematical, it feels like it's specific enough that with, you know, innovations in dynamic energy budgets and ecology and systems thinking from, you know, people that work on networks, it feels like we should be able to come up with mathematical models, and then maybe implicate the kind of substrates where we would go and collect the data to measure it, and say, "Oh, look, there's actually type one or type two load." Do you feel that we're on a path to be able to make it sort of conventional mathematical models, or where do you think that stands?
John Wingfield 55:43
No, I agree with you entirely. And one of the things I just failed miserably is that I felt that the allostasis models, and even the models before allostasis, lend themselves to mathematical approaches that would then generate new hypotheses, and so forth, but I could never get anybody interested in it.
Marty Martin 57:37
Wow,
Marty Martin 57:45
Yeah, well, I could ask you a thousand more questions about that, but I think I won't. It might be too indulgent.
Marty Martin 58:00
So, we talked about, you know, three of your really influential ideas, and again, there's so much more to say. We'll do the mini series on those later, but is there some idea that you had that was a favorite of yours that didn't really resonate in the way that you kind of expected it would? And I remember when I was a graduate student, I saw you talk about something you called Finite-State Machine Theory, that I think a grad student was it, Jerry Jacobs, that worked with you on that had a huge impact on the way I think about things. So, I'm a fan of that idea, but I didn't feel like that one ever really took off. Is that one or another one something that really excited you and kind of surprised you that the field didn't, didn't go for it?
John Wingfield 58:43
Yes, sometimes these things take a while to sort of percolate through the research community, but that one Finite-State Machine Theory has not drawn a whole lot of attention, but hopefully it will in the future. I think that that has a lot of interfaces with allostasis, like with climate change. One of the huge issues is that a lot of, you know, people say, well, reproduction is getting a life history stage, it's getting earlier and earlier, and what happens to that period between breeding and molt, you suddenly don't have overlap anymore, and you've got this void. I mean, what would you call that? What is that? But if molt then comes earlier, which seems to be happening, then autumn migration has to come earlier or get later, or you produce a new life history stage. And I think that it would be very interesting to look at that. But the problem is that I think that people studying these effects of climate change only tend to focus on one thing and don't put it in the context. At least the physiologists, ecologists have probably done a lot more than that. But ok, we see climate change is having an effect on breeding, having an effect on migration, and so forth, but all the other life history stages have to shift, and that results in what I call chaos in the life history stage that then increases the metabolic demand of an animal that's trying to do too much at once. And we have examples of that, I think, and I think there's a lot more can be done. But I don't think the work that we've done so far using Finite-State Machine Theory has really got through to more people who have additional insight that would help all of us. But I'm excited about it, calling it phenological chaos, because you've got the seasons changing, climate changing, so have all of that sort of the driving force behind seasonality is being disrupted, and the life history stages within an individual are being stretched, or just getting selection for those that can respond early. But then the question to me is, what about the other life history stages? Okay, you can cope with changing your breeding life history stage, but molt may be more resistant, so all of these life history stages don't change or respond to climate change in the same way, right?
Cameron Ghalambor 1:01:36
Yeah, I think a lot of people are interested in this in the context of like phenological mismatch.
John Wingfield 1:01:41
That too, and eventually that leads to phenological chaos. That's my feeling. I think there's some evidence that I've seen in the literature that that can result in sort of mass deaths, mass mortality in some species that their food source is sort of not where it should be at a certain time,
Fran Bonier 1:02:05
Right, especially sea birds, probably.
Fran Bonier 1:02:08
So, we've had a chance to talk a lot about the big ideas that you've had that have influenced the whole field. Maybe we could look forward a little bit now and talk about, so what your ideas are about exciting current and future directions that you see, you know, are there any questions that people are answering that you are excited about, or directions you think the field should be going?
John Wingfield 1:02:31
I think lots of things I've been particularly excited by working with the neurobiologists, neuroscientists on you know, the brain is doing a lot more than just regulating the hypothalamopituitary adrenal axis or the hypothalamopituitary gonad axis. They're not separate, they're talking to one another, as you said, and the brain is coordinating that, and that's quite a challenge, if you excuse the pun. You know, I think some technologies are required, being able to look at the transcriptome in a single neuron is phenomenal. But that brings in another problem, then that you mentioned, Marty, is big data. And when it was at NSF, that whole big data issue, and how within the genomics era, how to just even store that information, so it's available to the community at large, you know, with the birds, they're saying, well, okay, we're going to sequence the genomes of every single species on the planet. Well, how in the heck are you going to store that and have access to it? And if you had some question of, okay, I'm studying, let's take ten individuals of this population in North America, and a similar species of those in Asia, and then look, ask questions about how they cope with similar issues of climate change. Right now, there is no system, well I may be totally wrong, because I've been out of it for a while, but certainly when we were at NSF, there was really no way to do that kind of analysis, because one would think all the other things you could do. You know, I talked with the new curators of museums, and so forth, that developing collections of an individual bird who'd been followed in the field, and a lot of data, behavioral data, collected and they collect the bird and sequence the genome and many other things too. And that is so powerful, the potential for that, that you have all this behavioral information of a bird in its natural environment, and then all of the genomic data and the responses to climate change comparisons you could do with other species in similar environments, it's endless, but the I think right now the technology to actually deal with-
Fran Bonier 1:05:24
The computing power yeah.
John Wingfield 1:05:25
-data sets like that, yeah. I'm not sure where all of that stands now, but I know that that is an issue that really is the anchor around people's necks. How the technology is developing with big data, there are data repositories like Marty's hormone base, that exactly, that's another thing. You, how you put all that information in, do a big fancy analysis at many different levels, which the systems biology people would say, yes,
Cameron Ghalambor 1:05:38
yes, yes,
Marty Martin 1:05:38
Yes. Of course, more, please.
Cameron Ghalambor 1:05:38
I think, that's a good, that's actually a good segue into the this question that I really wanted to talk to you about, which is about the role of hormones as integrators and this potential for pleiotropy within organisms as these complex systems. And I ask this question because it's something that my postdoc Alex Mauro and I are really interested in right now, and again, this is in the context of osmoregulation. And so we observed that in the field guppies that we study, and we can keep at sea water in the lab avoid brackish water in the field. And in the brackish water is a competitor that, and when, if we experimentally move them, they get beat up in the salt water, but in fresh water they're competitively dominant. And we saw that there appeared to be this trade off between osmoregulation and being a good competitor. And we started looking into it, and I wasn't trained as an endocrinologist, but as we dug into the literature, you know, the work by people like Steve McCormick, you know, showed that cortisol, AVT, IGF1, a lot of these hormones play key roles in osmoregulation. And then there's a whole separate literature that never, that doesn't talk to each other on behavioral dominance and dominance hierarchies, and they study the same hormone. And so that started us thinking about, like, well, you know, maybe there's, there's some sort of hormonal basis to this, this trade-off that we're observing. And sure enough, we've, we've looked at, you know, gene expression in the brain, and we see that there does seem to be this sort of crosstalk, and I'm, I'm just curious, what you think about this idea of hormonal pleiotropy in, in this kind of maybe more evolutionary context, and as we move towards a more omics systems future, do you see that as an exciting sort of line of research? I'm excited by it, but I don't know if you are.
Marty Martin 1:05:38
We could tell. We could tell.
John Wingfield 1:05:38
No, I think you touched on a very important point there. You know, throughout the endocrine system, you know, the, you have these hormones that have actions on specific tissues that maybe vary a little bit from species to species, but that's their major action. And then they have actions on behavior in the brain that can be quite different, and now we know are probably regulated totally differently too. So one of the things that when I taught my last endocrinology course, I would say, well, you look at hormones, they have, some of them have genomic effects influencing physiology and morphology, important for later behavioral effects, so they provide the substrate, so to speak, to act on and regulate behavior. And that this can also be regulated by the same hormone in say a tissue like kidney or a salt gland in the nasal system, and also behavior. How does that happen? As you said, when you look at, you know, there's a lot of recent work being done on IGF1, and that's that, that's a big one for the future, I think, too. It's been totally neglected. But we know that can be produced in neurons in the brain, and it has the effects on growth hormone and other growth factors, and also can act directly on tissues and cells, so students get totally confused by that.
Cameron Ghalambor 1:05:38
It's complicated.
Marty Martin 1:05:38
I don't think it's just students I'm confused as well.
John Wingfield 1:05:38
Well that's good I'm confused to say I can't really teach it very well.
Fran Bonier 1:05:38
That seems to be a recurring theme.
Cameron Ghalambor 1:05:38
Yeah, well, you know, when I read these, like, reviews on, you know, a particular hormone, you know, it'll, you'll, in the introduction, they'll say, you know, corticosterone or cortisol has been shown to influence, you know, this, this, this, this, this, and there's this long laundry list, and then they'll say, here we're going to focus on just this to keep it simple.
John Wingfield 1:05:38
Well, that you know, this goes back to the origins of endocrinology. That one of the first things they did in the early 1900s was raise animals that you selected out variation. So you get a clone of white mice or white rats that are genetically almost identical, and the responses you cut out a lot of the individual variation in experiments, or this noise, as they used to call it, rather than thinking that that was interesting, but I think one thing that had to happen was to actually define the endocrine system in humans, for example, because of clinical approaches. And in agriculture, for agricultural work, they needed to get rid of as much individual variation as they could to actually get at good solid information on what that hormone is doing. And that just went on to even the present day, and people are beginning to realize more and more that these clones of, I'll call them clones, but they're doing that now too. These animals are so similar to one another that really it has no bearing on what is going on in the real world, where everything, all the interactions of that hormone system with other things, is really overwhelming, and so a lot of people say, well, I'm just going to focus on this, and they'll do it in a mouse, they'll do it in a mouse, they'll do it in a rat, and they can really get a hold of the question. But what that leaves us is frustrated with, well, but what are all these interactions mean? What did all this individual variation in hormone levels, even day-night changes are highly variable, depending upon the individual.
John Wingfield 1:06:00
So yeah, you're right it is very frustrating trying to bring all of these people together, so they at least talk to one another. You know, the grants we had for that research center talks, and so forth, was to bring ecologists and evolutionary biologists together with the endocrinologists to actually define where we're going to go in the future, and for I remember that first meeting was in the Netherlands, where we were trying to talk, and it was just no people just standing back, not wanting to say anything, because I think, because I don't want to sound stupid.
Fran Bonier 1:06:00
Yeah
John Wingfield 1:06:00
Being an ecologist talking about the actions of testosterone, I mean, I don't know enough about those systems. And the same for the endocrinologist, they were leery about talking about the ecology of the animal. Again, because I don't want to feel stupid. So nobody would talk, but that night, that evening at dinner, they had several bottles of wine out on the table, and after they'd had a couple of glasses of wine, everybody was talking, and the meeting was a resounding success, because people got over their inhibitions.
Fran Bonier 1:06:35
It seems like, and just generally biology is getting more and more integrative, and so those sorts of, you know, ecologists who also think about physiology or gene expression or whatever are becoming more common.
John Wingfield 1:16:08
Yeah.
Fran Bonier 1:16:17
We wanted to shift gears a bit, because in addition to all your contributions to science, you've also held a bunch of leadership roles in scientific societies and at the NSF, and given the current state of science, particularly in the US, but probably in the world, we wanted to hear your perspective on sort of where you see science going, and you know, maybe lessons you've learned from those leadership roles.
John Wingfield 1:16:46
Yeah. I'm really very concerned about where science in America is going, especially in the aftermath of them firing all of the National Research Council
Fran Bonier 1:16:59
Just this week, right? Didn't they just
John Wingfield 1:17:01
Yes
Fran Bonier 1:17:02
Yeah
John Wingfield 1:17:02
And when I was at NSF, head of Bio Directorate, we would interact, we would have meetings with the National Science Board every year, twice, and often the meetings were quite combative, but at the end of the day everybody came together, could agree on certain ways forward. Big data, for example, was one, because it involved all of the directorates, and you know, to get the National Science Board, which is people are appointed by the President, and to really strengthen the science going forward. That's gone overnight, that interaction. And NSF itself is staying very quiet over this, which is I remember that when we got criticized at other times for the Brain Initiative, for example, members of Congress and the Senate were saying, why is NSF funding neuroscience, that's NIH. They held a big testimony there. We testified. I testified for NSF. Francis Collins testified for NIH, and can't remember the other guy's name. He ran the DARPA, the Defense Advanced Research Projects. And they went after me, saying the same thing, you know, this is duplication, you should take all that money from NSF that has been assigned to the Brain Initiative, which was about $75 million at the time. You know, I sort of said no, no, and one of the reasons I suddenly stumbled on was neuroscience was the trigger was the trigger word, so we called it comparative neurobiology.
Fran Bonier 1:18:48
They were fine,
John Wingfield 1:18:52
So, you know, but, but I think things like that, you know, the Trump administration has said that they fired the National Science Board, because they felt they were not sufficiently in line with the administration's priorities. They intend to put people in on the Science Board who are going to work with Trump and this central administration, so we're going to see RFK Jr type science all over NSF too.
Fran Bonier 1:19:29
Probably.
John Wingfield 1:19:31
Yeah, so anyway, I'm very pessimistic until we see sort of a change in administration, and I don't think we're going to see any advancement of science, at least not how we think science should be done. It will be done. I hate to end on that kind of a sour note.
Fran Bonier 1:19:52
We can't leave it there. Yeah.
Cameron Ghalambor 1:19:55
I guess, in terms of, you know, thinking about the. The hypotheses that we talked about, like allostasis and coping mechanisms, emergency life histories. Do you have any sort of thoughts for especially early career scientists, like grad students, postdocs, young professors, about, you know, given your time at NSF and the current situation, what advice you would give on how to navigate this sort of new reality that everyone's dealing with?
John Wingfield 1:20:29
Yeah, I think by and large you can put in a proposal where you avoid addressing issues like diversity, find some other way of doing it, and not neuroscience, but comparative neurobiology is one way you can sort of get into a fundable spot at NSF, but you know, one thing that struck me while I was at NSF was just the volume of proposals coming in sometimes were literally overwhelming. So they introduce the pre-proposal as a way of pre-selecting a manageable number of proposals, and that worked for a while. But then they've changed again to a different approach, where they have a panel meeting when they reach a certain number of proposals. So try and be aware of that, and talk with the program directors, and if you have a wild idea that nobody's excited by, is just being what, but you just need to get more preliminary data, however you can.
John Wingfield 1:21:40
And I always said in the early days at Rockefeller, and when we went back to Washington, because I'm in the same boat here to try and get funding. And I said, if you need, there's certain criticisms, you need more data, I said one thing you can always do is take a notepad and a pencil, get on your bike and go out into the field, and just observe different days. If it's, if it's stormy and rainy, put rain gear on. When I first did that, I was astonished. It was kind of like there was a truce, and all the birds would be down low, not always feeding, because there was not enough food, but even you know, over here there'd be a sharp shin sitting there thinking, you know, normally the birds would be down. So I said, you know, there's an awful lot you can see and do that will direct what you want to do in the future, or direct other people to do, but otherwise it is a tough road ahead, I think. So, having projects that you can do fairly easily, and keep expanding the particular topic is one way you can eventually get funding. Sometimes you is well, I won't say lucky, you just, you just hit the spot with the reviewers, maybe one in ten times? But as you get older and you resubmit one in five times. Once you get funded, then I think you there, you go, you can just keep on going and developing the system.
Fran Bonier 1:23:21
It's a good message for young people, I think, to hear, though, that you can do it on a budget, like some amazing breakthroughs can come with just a field notebook and some binoculars, and get it, getting out there. A
John Wingfield 1:23:33
A lot of the old leading lights in biology have been saying that too that at the end of the day, there's nothing like a notepad and pencil binoculars, and just watching what happens. That's what I did, a lot of that, starting way back when a boy.
Marty Martin 1:23:52
Well, John, I mean, this has been really fantastic, but we want to be mindful of your time, and the last question that we always ask of our guest is sort of, what else would you like to say? Is there anything we didn't prompt you want to leave listeners any scientific ideas to speculate about, or more advice about how to navigate the current world?
John Wingfield 1:24:14
Oh, yes, all of the above. I think finding a system that you can go to locally, as we were just talking, and with a note and pencil, and getting to know the animal that you work with. I remember, there's one psychologist I interacted with many years ago, and he said: "You know, you have to get to know your animal before you can really start doing anything meaningful". He says, "And that takes at least seven years." I said: "Well, what do you do in the interim, you know?" But I can appreciate that comment. Because then, when you write a proposal, or write anything, a paper, really, if you know what your animal is, what it does and you know what this individual does versus that individual versus another individual over there, you can start to put together these these questions of systems physiology and systems interfacing with other systems. That that gets pretty complicated pretty fast, but if there's some way you combine that with your field observations, then I think you're going to see new ideas,
John Wingfield 1:25:27
And one other thing, actually two things now I think about it—education. One thing I tried to get into at NSF, and I've tried it a couple of times since, is that I think we should change the curriculum for first year biologists, first year people, whether they're doing medical or ecological stuff. It's just to be taught the basic mathematics, to be able to know who you should go talk to, at least. And also be able to deal with handle genomes, just do a lot of work that certainly I was not able to do throughout my career. But I think if I was starting again, that I would want the ability to understand and work with transcriptomics, genomics, and other mathematical techniques that take you down to the field level ways looking at populations, individuals, and so forth. That got a profound silence from people at the NSF that I was talking to, that they said, okay, everybody agrees that yes, we need those techniques, but how, as a student, beginning her or his academic career, going to be able to understand or never mind actually work with these kinds of big datasets? And then there are other things too that they should be aware of, and I think now that a lot of that, more of that is being done, but the problem is, how do you find somebody who will teach it? You go to a mathematics department, and they're really not interested, because they're interested in other things. That are equally fantastic. So I think it's going to have to come from the faculty, those faculty that are using these techniques daily, or somebody is in the lab.
John Wingfield 1:27:28
And then finally, I think what we're going to see more of, and I think Cam referred to this earlier, is more teams. No one person can do it all anymore. It's you need teams of people to go from the field to the endocrinology to the analysis to genomes, phenomes, and so on. I guess one person working with bacteria, E. coli, what have you, could do that, but not with these big systems. So hopefully that can develop while science is protected.
Marty Martin 1:28:04
Let's hope. Well, thank you so much, John. This has really been fantastic. We appreciate your time. It's been great chatting.
John Wingfield 1:28:11
Well, thank you for asking me. I've enjoyed to think about these things again, and it takes me back to my NSF days, and what is possible. So, thank you.
Cameron Ghalambor 1:28:23
Thanks so much for, yeah, taking time. We really appreciate it. It's been a pleasure.
Fran Bonier 1:28:27
Yeah, it was great.
John Wingfield 1:28:29
Good. Well, it's been great for me too to talk to you all. Thanks so much.
Marty Martin 1:28:45
Thanks for listening to this episode. If you like what you hear, let us know on BlueSky, Twitter, Facebook, Instagram, LinkedIn, or leave a review wherever you get your podcasts. And if you don't like something, we'd love to know that too. All feedback is good feedback.
Cameron Ghalambor 1:28:57
Thanks to Steve Lane, who manages the website, and Molly Magid for producing the episode.
Marty Martin 1:29:02
Thanks to Caroline Merriman and Cass Biles for help with social media, Brianna Longo, who produces our awesome cover art, and Clayton Glasgow, who blogs about topics covered in the main show. Check out his work on our Substack page.
Cameron Ghalambor 1:29:13
Thanks to the College of Public Health at the University of South Florida, our Substack and Patreon subscribers, and the National Science Foundation for support
Marty Martin 1:29:22
Music on the episode is from Poddington Bear and Tieren Costello.
Transcribed by https://otter.ai