Episode 10: Food For Thought (Transcript)

Peter  0:00 

What are you feeling right now?

Dr. Schwartz  0:02 

Well, I’m really bad at identifying the flavors. I mean, it tastes like some kind of sandwich, some onion flavor. And maybe something like avocado. Maybe have some chicken in it. Some kind of like chicken fajita-y kind of taste.

Peter  0:21 

Sure you can open up your eyes and take a look. So this is an arepa, it is from a Venezuelan restaurant called Guasaca. I realized you probably don’t have time to go grab food before your flight.

Hi, and welcome back to The Gastronauts Podcast. My name is Peter and I’ll be your host. Here at Gastronauts we are committed to exploring communication throughout the body, with a particular focus on the crosstalk between gut and brain. We invite experts in this field to share both their research and their incredible journeys. So come join me as we explore the steps that go into shaping a scientist on The Gastronauts Podcast.

Today, we have Dr. Gary Schwartz, a Professor in The Departments of Medicine, Neuroscience, and Psychiatry and Behavioral Sciences at Albert Einstein College of Medicine. Dr. Schwartz completed his Ph.D. in physiological psychology from the University of Pennsylvania, his post-doctoral fellowship in neurophysiology at the Monell Chemical Senses Center. He received his first faculty appointment at Johns Hopkins and since 2004 has been at Albert Einstein. His research focuses on communication between the gut and brain and how this circuitry and in particular the vagus nerve regulates food intake and energy balance. So I want to start with the fact that you now serve on the International Advisory Council at Monell Center, which must be a nice coming full circle for you allowing you to advise for the institution which you trained at. Could you tell me some more about this?

Dr. Schwartz  2:17 

Sure. Monell is a very unique institution in the United States that has had a history of both academic and commercial support, sponsorship and interaction. And it’s a basic research institute that is focused on identifying things that were very important to me in my career, and that is the neurobiological basis and the chemical basis for chemical senses smell and taste. So it has collaborations with investigators around the world, and in particular University of Pennsylvania. And as a postdoctoral trainee there I was interested in moving from the study of eating behavior and how taste and taste nerves affected eating behavior to actually try to identify how the brain encoded the sense of taste that was important to control eating. So, my PhD had been in really the very fine grain analysis of actual eating, behavior, licking, chewing, etc. and the roles of the nerves that supply the tongue. So I would interact by transacting those nerves and seeing the effects on actual eating and licking behavior. And while that was very intriguing, it got me to thinking about what types of signals were actually available in those nerves that I was interrupting or what types of signals actually arose from the tongue when we eat, and where and how were they transmitted to the brain and how did the brain respond to those. And so I really wanted to move on to what I thought was at the time, harder science, which was actual neurophysiology or how nerve cells respond. And at the time, Eva Kosar was studying the neurophysiological responses of taste stimulated cells in the brain in particularly in cortex. And she had really pioneered the identification of a region of the brain that received input directly from the tongue. And so when we think about how the body is represented in the brain, we think of a map of the body surface along the brain. And what Eva Kosar had done was to map how taste is identified in the brain, not just the tongue, but taste in particular. And so my postdoctoral experience there was perfect for me because I learned how to identify the regions in the brain that were sensitive to tastes on the tongue. And I already knew how those tastes would affect eating behavior. So I felt that I was getting insight into how we actually processed taste and how taste could reach the level of the brain where we could be conscious of it, we could learn from it and we could act on it so I thought I was getting at the wet biology of taste.

Peter  5:01 

Really interesting. So from taste and our understanding of taste in the brain were you looking at particularly the circuitry that links these taste buds to regions in our brain? Or were you looking at particular signaling molecules? How exactly is that information conveyed?

Dr. Schwartz  5:16 

The types of studies that we were doing were to try to, we’re based on again, the behavior- […] my perspective was formed from my behavioral studies that showed that the different basic qualities of tastes that we now consider to be not only solved sour, bitter and sweet but also umami, or the amino acid or protein taste. It […] was early in those times, but people were beginning to study the molecules that were in the taste cells on the tongue that were responsible for the generation of signals at the tongue, but we didn’t know how those types those five basic types could represented in the brain, whether they were in a mixture of cells that were all mixed together, or whether like the visual system, perhaps there were particular columns of cells that mapped particular taste qualities, or there was another mapping possible that had to do food, how I interpreted my behavioral studies. And that was, the oral cavity, in general, has multiple taste nerves, one for the front of the tongue, one for the back of the tongue and one for the palate. And so another possible organizing strategy, or organizing framework could be that each nerve projected to a particular region of the brain so that there’d be a map of the different taste nerves and thereby a map of the front of the tongue versus the back of the tongue versus the palate. And as we started to place so it was a circuit perspective, but it was also sort of a mapping perspective or a mapping outlook that is based on the map of the tongue and its sensitivity. How was that map repeated or represented in the brain that we see a remapping of the tongue in the brain, according to the nerves, or according to the tastes. So the experiments were really designed to try a variety of tastes in a very systematic order in the front of the tongue, in the back of the tongue, and on the palate, with or without the nerve […] so that we could distinguish between those two possibilities. And what we found is that, in fact, there’s both kinds of maps […] And so different tastes stimulate different populations of neurons in the taste cortex, and as well as the different nerves corresponded to slightly different regions of the map. So the segregation of the information arising from a particular place on the tongue, and a particular chemical on the tongue was preserved. So there was sort of a high fidelity mapping of the oral expression variance at the highest level of the taste brain in the cortex.

Peter  8:04

Cool. That’s really interesting. Yeah, I had not known specifically about that. I think I hear colloquially a lot about tastes and like, Oh, I really like this because of how it tastes, but not really understanding how that reaches certain circuits within our brain.

Dr. Schwartz  8:18 

And in in the brain as it reaches it. This region of the cortex is the earliest processing in the cortex. There are other regions of the brain that tastes reach that are important for choice and are important for effects that are important for our emotional responses to taste for animal models of understanding taste behavior, you know, We can’t use verbal communication, so we have to use tests of animals willingness to continue to eat or to reject. And those responses happen. Typically they happen very quickly. Sometimes they happen by reflexes that happen in the brainstem. So very early on in the brainstem. The first place […] where taste information comes in. And that information has access to motor neuron neurons or motor nerve cells that actually control our jaws, and our tongue and our swallowing muscles. It’s important for species especially like rodents who don’t have emesis, they’re not able to expel or vomit. So[…] the oral decision to continue to ingest or to spit out can be life determining, right, because they only have one chance- if they ingest a toxin then they have to face the consequences of that toxin. So it’s very important to have some very hard-wired early detection mechanisms for the sensation of something that’s potentially good versus potentially bad. So that[…] the organism has the ability to either ingest or reject, so that it doesn’t have to survive bad consequences. And so that mapping is also present at the level of brainstem, but then for higher species with more cortex and other, more developed central nervous systems that have more capability for learning, that have more capability for choice and that have different kinds of effect, it’s important to have that information represented at other higher levels of the central nervous system such as the cortex. So it has both a sort of a cognitive mapping, if you will, a sensory mapping as well as a hedonic affective map.

Peter  10:24 

Cool. So then from there, you moved further down the alimentary tract, and then you started studying the gut. What was going through your head when you were thinking, at least from your graduate work, studying tastes to moving kind of to post-ingestive sensing. Why did you make this switch?

Dr. Schwartz  10:39 

I think that’s a really interesting question. To answer it, I want to take a step back as an undergraduate at Hopkins, I had the opportunity to be in work study and I knew I wanted to work in a laboratory, and I was interested in behavior in general and the laboratory that I found was with Elliott Blass. And in fact, Tina Williams, and they were involved in understanding how we develop the control of eating. Eating in mammals [and] especially in humans, there’s a critical phase because human infants are altricial. You know, they rely on the mom. And so rodent models are appropriate to study the beginnings of feeding, the development of feeding and what controls it. And I was really fascinated by the idea that, you know, smell became very important for these young rodents who were born hairless and blind and couldn’t thermoregulate well. Smell was an important sensory control. And then, other studies were underway where the oral cavity was stimulated with nutrients and that could control eating as well. So those early undergraduate experiences really made me interested in how food can drive sensation per se. And so in my undergrad and my graduate school work I then studied specifically in the oral cavity. But it became clear that the oral cavity is really only the beginning of our interaction between the external environment and our inside-most intimate selves, the internal mileu. And what became clear was that, sure, the acceptance or rejection of food is important, but then what becomes very important are the consequences of that food for nutrition for our basic biology. So it made sense to start to look at conservation of mechanism, the oral cavity is important to accept or reject, and the post oral area of the elementary tract is important to absorb and digest, then there must also be some important chemosensation there. And we also know from a variety of studies that have been done well before that, you know, that there are certain sensations that we Have from the gastrointestinal tract that help determine our feeding. So it was a natural segue for me. And for me, it was sort of it was my move to something more novel at that time, because people really weren’t working on those types of signals in that way from the perspective of how chemosensation drives feeding and how, when, what the neural circuits that mediate that controller. Yeah, now it’s really hot area.

Peter  13:26 

Understanding gut sensing is very popular. Do we have a good understanding of if something is palatable or tastes good, but in our gut, we have some sense of the fact that this is a non-nutritive material or something that is non-rewarding with regards to gut sensation. How are those two lines of information conveyed? Or is there a way to compute both of those?

Dr. Schwartz  13:49 

[…] I think the short answer is we don’t know. There’s several lines of evidence. First of all, this is a very hot area of investigation. For a couple of obvious reasons. Our body’s able to discriminate between things that are nutritionally good for us and nutritionally not good for us. And yet we eat them anyway and and our food sources designed to […] bypass our normal biological controls and precipitate overeating for example. And so, you know, one can imagine from a health perspective with overeating and obesity or serious epidemic problems, especially in childhood. Now, it becomes really important to appreciate how our guts are or are not sensitive to either naturally occurring nutritional sources or unnatural non-nutritional sources. So, we know first of all that there are tastes like cells not only in the oral cavity, but also in the gastrointestinal tract. And in fact that when nutrients or even these non-nutrient artificial sweetener-like molecules are placed directly into the intestines, they can actually affect food in similar ways, suggesting that they we can fool our natural detectors by synthetic compounds. And some of the consequences of that could be to overeat […] It also turns out that some of the artificial sweeteners and some of the sensors that we have in our gut may be enough- the artificial sweeteners may be enough to drive the secretion of factors that can precipitate diabetes, for example, so that […] the artificial sweeteners might act on Beta cells to drive insulin release. And you don’t want that unless you really have nutrition available for the insulin to have its effects on glucose absorption, so that could drive insulin insensitivity. So it becomes from a practical day-to-day health perspective, very important to understand the degree to which our gut actually does sense nutrients and how well it discriminates among those nutrients and how it can or can’t be fooled by artificial sweeteners. And if so, what are the molecules that are responsible for transmitting that signal from the sweetener, the artificial or real to the brain?

Peter 16:09

So some of these signaling molecules or the way that our gut senses different macronutrients have some overlap, right? In the sense that some enteroendocrine cells or some of the cells in our gut that sense nutrients or any stimuli within the gut are able to convey this information to our brain through different signaling molecules. I was wondering, we think traditionally of this is a satiating food, or this is a food that decreases the amount of my appetite. But do you think there is finer resolution of information? How is that more detailed information encoded to the brain?

Dr. Schwartz  16:45 

The answer to that is I’m really not sure. What we do know from studies of the sensors of the gut is two classes of information: one, the actual sensors that are responsible for detecting lipids or detecting carbohydrates or detecting amino acids in generating a neural response in the gut sensory nerves are not well known. Some taste cell elements are present, and those are for sweeteners. Some sodium-like elements are present, but sodium chloride is not really an important constituent in terms of nutrient absorption. So, the actual sensors, the molecular characterization of those sensors is really still in its infancy and we can’t make a mapping or a one to one correspondence of which transducers are for which nutrients. Also, it’s important to remember that when we eat food, it’s not just the nutrient that’s in that food, that food has physical and chemical properties in addition to the nutrient itself. And because there are endocrine cells in the gut the nutrients also have the ability to drive secretions of hormonal or paracrine hemical factors that themselves can activate nerves. So we can think about it maximally as the simple something as simple as a nutrient in the gut really has a mechanical properties that occupies space, it can stretch etc. It can have pH properties that are relevant. It could as osmotic or viscosity properties that are relevant, even if it’s diluted, it has the nutrient and it has the ability to secrete factors that can act on the nerves so […] even when it gets passed from the stomach to the duodenum, it’s a very complex stimulus, and the nerves have the capability to respond to multiple dimensions of those. Having said that, I think that it is very unlikely and one can make the analogy of sort of two point discrimination. You know, we know from a skin sensitivity perspective that our fingertips are very sensitive to the distance between two sharp points, but if we put those two points on our back, we can’t tell There are two we feel it as one object. And I think that certain types of feedback from the gut about food are like that, that we just really need to know we certainly need to know something about caloric density and that we do know that because gastric emptying and the delivery of nutrients is directly proportional to how many calories per per unit volume of food we have. So calories are sensed somehow. But other than that, we really have a sense of food, and that food can either be more or less satiating, depending on a variety of things. How calorically dense it is, how many endocrine factors are releases over what timeframe and how fast or slow it tends to empty which correlates with the calories again. And people’s ability importantly for the real gist of your question, behaviorally people’s ability to discriminate how they feel in their guts is notoriously poor. We’re not really tuned into exactly how our guts feel. And in fact, one could make the argument that with the plethora of sensory stimulation that we get from the outside world, every day, we become even less sensitive, you know, we become more inured. And you know, there’s many reasons to eat and to continue eating. So we have 24-7 access to food, if not food, then pictures of food on television. We go to the refrigerator, we go to the convenience store, etc. So the head factors, our head senses, the sight, the sound, the smell, the touch of food, are always being driven, and our behaviors or habits about eating and the consistent availability of food, if anything, promote the acquisition of food, and really, I think can help make us less sensitive to the gut signals. And in fact, along those lines, there’s evidence to suggest that the ability of the gastrointestinal tract and neurons in the gastrointestinal tract to dictate certain features of foods actually gets dampened during obesity. So carrying around excess adipose tissue or having too much energy stored on board in the form of fat causes the release of factors that contribute to a dampening of the neural signals both in the central nervous system and even in the gut in terms of gut sensing. So it’s really sort of a triple whammy, we have an accentuation of the head factors, the sight, the smell, the constant availability of food and the ease of acquisition of food, our habits of eating that food, the fact that having eaten it, we become less sensitive to the filling effects of food. So those three things really conspire to make us even less sensitive to this kind of rich environment.

I want to mention briefly though, let’s look at the flip side. You know, now in this country, unfortunately, it’s more rare to have normally scheduled meals: morning, afternoon night. Even with the social aspect, everyone’s busy: kids are busy, families busy, so we don’t all sit together at time. And so we lose both the social context and the temporal context that determines nutrient availability. So our stomachs are full all the time, irrespective of the social interaction and irrespective of the time of day. Well, that just wreaks havoc with any kind of biological rhythm of waxing and waning of energy-use, exercise, how tired you are, how awake you are. The reason I bring that up is that when one can establish a social rhythm of eating that is in-sync with the circadian rhythm, those types of social constructs have very beneficial biological consequences, and those been beneficial. So those, we can modify our behavior to have those traditional experiences and that by itself, I think will go a long way to improving the ability of our gut senses to do what they’re supposed to do rather than to act in ignorance of them?

Peter  23:04 

Yeah, there’s so many complex factors, even the surrounding factors, not even the food itself, which is already a very complex particle or a stimulus that we have to ingest or comprehend. Right? And I think a lot of approaches to understanding this is really simplifying it down, right, taking a particular macronutrient or taking a particular composition of the food to study how it is signal to the brain. What is I guess the significance of breaking it down into individual macronutrients? If that is not typically what we ingest or consume?

Dr. Schwartz  23:36 

So that’s, that’s a really great question. And I think part of the answer that question, quite frankly, is that at least Western science tends to approach biological problems in a very reductionistic way, where we use the knowledge that we do have about how the physical and chemical world is organized and apply that directly to biology as if it would be appropriate. However, because even throughout evolution, there are […] animals with very specific appetites […] for different kinds of insects or different kinds of prey, etc. But in general, almost everything that everyone eats is typically has a mixture, or we make mixtures of a variety of macronutrients. And I think part of the rationale for studying individual macronutrients or individual stimuli is that we sort of have to start somewhere and I think that is guided by and it could be you know, insufficient, but is guided by our rudimentary understanding of how biochemistry works between receptors and ligands […] we know that this is how biology is organized to some degree, it is an important organizing principle. And so for the periphery, it makes sense to try to parse that. It does sidestep the question of well, in real life, you’ve got everything happening at once. So, what does it matter? And so now I want to bring in another aspect and that is related to the idea that foods are complex stimuli. And that is that in biology even though we apply the individual tools, we also know that there’s multiple sensitivities. And so we know that in biology for any system that it is very important, like eating, there needs to be redundant mechanisms to get a signal across. So I think that the analytical approach provides the opportunity to see the contribution of each individual and it also provides the opportunity to say, well, does the sum provide a greater signal than the individual parts? And if not, fine, and if so, how did does that work? So I think there is some sort of conceptual benefit to this analytical approach, remembering that it allows recombination and then assessing how the real world phenomenon works when you have the whole food available.

Peter  26:15 

So kind of breaking a complex problem into smaller parts and then seeing whether or not these two these parts together-

Dr. Schwartz  26:21 

Together account for the whole. And if not, that becomes very [nice] and even if so either way, it becomes very interesting.

Peter  26:27 

Certainly, and I think this is a nice segue to asking a bit about one of the grants that you’re funded for. I saw on the NIH reporter that you’re funded for a P30 Grant on animal physiology and animal phenotyping. Could you tell us a little bit more about what this entails?

Dr. Schwartz  26:42 

Sure. So the P30: that’s a code that the National Institutes of Health use for what’s called a center grant. And this in particular, there are two center grants that I’m involved in the New York Obesity Research Center, which is headquartered at Columbia University. And the Albert Einstein-Mount Sinai Diabetes Research Center, which was originally based at Einstein, for the last 30 some years and over the last five years, we’ve joined forces with investigators at Mount Sinai. And these center grants are funded through the National Institutes of Health and particularly the National Institute of Digestive and Kidney Diseases, to bring together investigators with expertise in a variety of approaches both human & animal, not only live animal but also tissue based approaches and molecular and computational approaches. So that one can attack a problem from multiple perspectives. And so that when there are a critical mass of investigators in one of these center granted institutions, then the different investigators bring their own separate research questions and their own research expertise to the forefront. The function of the animal physiology cores that I run is to help investigators understand the whole landscape of energy balance in the animal models or in the human conditions under investigation. So let’s say someone finds a new mouse genetic strain that exhibits overeating and obesity in development. And they want to understand how that happens. So the function of the grant, the part of the core that I serve as director of is to help them break that down. It’s like, well, what part of their phenotype is due to overeating? And do they overeat only certain nutrients? What is their local motor response like and what is their basal energy expenditure, their basal metabolic rate like and are they very susceptible to exercise? What is their hormonal profile like? So in order to really understand the multiple causes of obesity or diabetes, one needs to have a systematic way of examining contribution of behavior and metabolic physiology and organ physiology and molecular biology. That’s what this core does in sort of multi-level, multi-disciplinary, taking apart the energy balance equation, energy intake and energy expenditure, energy availability and energy expenditure and how it happens. And then we work with the investigator to understand what is it about the phenotype of that animal? What is it about the gene expression of that animal that can lead to these different behavioral and metabolic changes? So we try to take either natural experiments that result in obesity or diabetes, or targeted experiments where genetic susceptibility to obesity or diabetes has been identified in humans and to try to develop animal models, which will then allow us to probe how will this genetic change manifest itself in either the behavior of theology and that’s what we do.

Peter  29:58 

At what stage in your career did you think that this was, oh gee, I think I would love to be a director of an animal core?

Dr. Schwartz  30:04 

So this was something that I fell into. I mean, I was recruited because I have my own R01s: regular grants from a principal investigator that where I study gut-brain communication and nutrient detection, etc. And I was recruited to the Diabetes Center because they were interested in the way that the brain communicated with the peripheral organs to control metabolism, which 15 years ago was a newer idea in the field. We knew about gut-brain for feeding, but people hadn’t been looking at the role of the brain as much in terms of the control of metabolism. And so for me, it provided an opportunity to learn about metabolism. And as a result, it became clear that there were certain capabilities that I used in my own research that were amenable to the Diabetes Research Center group at large. And so it was at a realization on your end or other people or sort of both. So because I sometimes get bored easily or I’m very interested in learning other things, I became interested in moving outside of feeding behavior and into neural control of metabolism. And at the same time, the field was moving in a direction of neuro-control metabolism. So other investigators at Einstein & Sinai had been becoming very interested in this, and I was the one who had actually developed sort of the range of tests that could directly be applied to those so it became sort of a natural fit.

Peter  31:32 

This is something that I have not thought much about. As early in my career, how to become more involved in overseeing larger projects or larger opportunities. Is there some way that you would recommend a younger trainee or someone earlier in their graduate career going out and interacting with other professionals? Is there a way that you approach this?

Dr. Schwartz  31:52 

It’s interesting, because this core directorship business, you know, it’s not something that you want to necessarily pursue as you become a senior investigator. Because you have your own projects that you’re really running and your other grants and other interests, but it is a great career development tool for young investigators these days in the field. So in the feeding and metabolism, there are so many good meetings. And so many approaches that are being used that the younger investigator can really take advantage of expertise from people with very specialized interests and specialized approaches. And by going to meetings, they can start to really identify the outlines of their interests and what things fit into their interests. And as they do so, they will gain […] expertise in the techniques that are required to really address their problem. I guess the point I’m getting at is, as a junior investigator, you have a problem that you think you’re interested but you don’t really necessarily yet understand the full ramifications of that problem or how many ways into that problem. There are how many experimental ways into that problem. And as you mature and as you encounter other research programs, hopefully you maintain your interest in your core problem that you began with, then you’ll naturally start to find yourself interested in other ways that people have of tapping into that problem. And that may express itself in Oh, well, I really need to incorporate this kind of measurement into the way I’m doing experiments and into the way I’m thinking about the problem, because the problem is maybe a little bigger than I thought it was. Or there’s other ways and those ways require some technical and conceptual advance. And so your stick-to-itiveness about your initial problem as a junior investigator, and your curiosity will help feed your growing knowledge base of finding out who’s doing similar work, and are they approaching it the same way and if not, oh, well, that might open a new perspective for you that you can incorporate into your own. I think one of the guiding features of successful career development is how, as people mature intellectually, they gain a greater perspective by appreciating what other people’s work can bring to their own. Both technically and conceptually. And that’s how you grow intellectually. And that’s how you become authoritative. And that compels you to become more thoughtful. And the more thoughtful you are, the more you read and the more you meet and incorporate other people’s ideas. The core answer to your question about, you know, well, how would you advise a, you know, a junior investigator to consider, you know, directing a core or being involved in these multiple kinds of projects? Part of the core of the answer is that I think I was trained this way. I feel fortunate to have been trained this way that science is, in essence, a very human endeavor, a social human endeavor. We do hear of people working away in a basement lab by themselves coming up with some amazing discovery, but those days are mostly gone. And in fact, you know, a lot of high profile work, it’s no exaggeration to stand that, to say that, you know, people stand on the shoulders of giants that they really do represent collaborations in real time but also collaboration of historical growth from concepts and incorporating concepts and techniques that others have developed. And junior investigators, I think successful junior investigators learn how to effectively communicate and draw from other people bounce challenge their own ideas with other people or against other people and take from that, how they can really synthesize and incorporate and advance their problem. So I think that the key to the successful trajectory is identifying what you think you’re interested in, testing the strength of your interest by challenging it with other people. And as a result of that incorporating their sense of the problem. And finding out however you can, how to approach it by any means necessary and making it part of yourself. That’s really what I think.

Peter  36:28

Wow, that’s really powerful. Knowing that you’ve served on several study sections and you’ve reviewed many grants, do you think this is actually a weakness of a lot of young investigators coming in who are approaching it with more of, I guess, a siloed approach from writing a proposal? Does the fact that this kind of lack of desire to challenge their approaches with other faculty or leaning on more experienced members, and limit kind of their ability to see alternative approaches, potential pitfalls. Are these things that you see as common weakness in early grants?

Dr. Schwartz  37:02 

I think a couple of things. One, while the electronic data age and you know, PubMed are great, amazing tools. I think that many junior investigators, through no fault of their own have developed their mentality about science or their mentality about their specialty area of interest from reading abstracts on PubMed. I don’t think that’s really an over-exaggeration. You know, papers have become larger and larger, more complex, but there’s large bodies of literature, older literature where the papers are smaller and simpler, but junior investigators typically have not had as part of their graduate education, the discipline to really read through the actual corpus of how science progressed to the point where there and I don’t mean going back 100 years, although sometimes it might take that, but I do mean the actual discipline of going to the trouble to find out the sources and really read them so that you have the ability puzzle over them. And I think that comes across in grant writing in grantsmanship. Because your ability to conceptualize a problem and justify what you think is important about it typically is too shallow, because there are typically many other findings that one could reference that actually have the thread of the thought that provide a very strong rationale. And in the culture where the background and significance or rationale sections are just done by pegging citations from a few paragraphs, it’s short sells the significance of a grant, so that the significance sections and the rationales are either very self contained. Look, I did all these experiments, I have 48 preliminary figures, in complete ignorance of the fact that a field had developed of this several times with, you know, large findings, or at least a lot of the major concepts already laid out. So it’s not that the person’s rationale or experiments aren’t interesting or potentially important. It’s that they could be even more so had they taken into account a consideration of the idea of body hosting that had occurred before. I think that’s a major issue. The other side of that from a study section perspective, is that so you know, people get older, they get more senior they rotate off study section, and the NIH has guidelines dictate that people who do have R01 you know, the primary Principal Investigator Grants are the ones who are now reviewing others. And if they themselves have this rather formulaic, superficial approach to okay, well, here’s how I took in my grantsmanship course: I have to have a background significance. I have to have certain preliminary data and this should sell and they use those criteria to evaluate a proposal, then that perpetuates this cycle. In addition, those younger reviewers because they don’t have the background in this way, they’ve been themselves siloed. They don’t really appreciate that, or it’s more difficult to appreciate that study sections function through advocacy, both for and against. And advocacy requires the ability to compellingly convince people about how important the research perspective and how important the research rationale is. Okay? So not only is the pursuit of the scientific experiment a human endeavor, but the evaluation of a scientific research program for the purposes of funding is a very social endeavor and requires advocacy either for or against that where the reviewers actually are able to instill in the other panel members an understanding of the perspective of where that grant is coming from. And if those younger PI’s themselves have never really developed what it means to have that kind of perspective, then they’re not going to be as effective advocates. So both from the applicant and the reviewer perspective, I view the superficiality and the ease of you know, making bullet points and making citations and sort of more confined turf protection, if you will, you know, defending your own turf or your own specialized research area has really significant complications and impediments to the review process for science.

Peter 41:21

If you aren’t an expert in the field of the proposal that you are reviewing, how do you read deeply into that?

Dr . Schwartz 41:28

It depends on who you are, but you learn. You learn how to become a reviewer. It’s on-the-job training and you learn how to learn. Part of going to college and going to graduate school is not to do a project particularly, but it is actually how to learn how to learn, so that when you find out what you’re interested in, you have the intellectual tool kit to do it. The same is true for evaluation of science, you need to learn. Hopefully you’ve learned how to learn and that skill can be applied to disciplines outside of your own. Again, junior investigators have not typically been pushed that way, because it’s very labor intensive to start over. Where do I start? How do I read? Learning how to read. You get better at it with age. You get better at sorting wheat from chaff in terms of the findings and what the significance of the findings and your ability to peg facts if they are hypothetically deductive or if there are logical flaws. You get much better at your critical acumen of whether or not someone has put the pieces of the story together logically, scientifically according to the scientific method or not. You also get better because you do expand your knowledge base just with age if you’re reading at all. There’s an inundating amount of reading to be done, but you do get better with that and as a result, your knowledge base broadens and your knowledge base of other people and their expertise broadens too and so your ability to tap into and at least begin with an intuition of what the problem is helps target your reading. There are people who have come to study section who read every single grant and try to develop the expertise, but that’s not sustainable in any stretch. But more senior people and junior people too, as they read and interact, and as they make doing science their identity for intellectual function, it comes more naturally. But make no mistake, it’s real work and it requires that you immerse yourself in someone else’s intellectual effort. Put yourself in someone else’s head. And that’s a very unique, a little bit scary position to be in and one of great responsibility and so I think that the reviewers have a really great responsibility to the field.

Peter 43:55

Well, I want to thank you for your time Dr. Schwartz.

Peter 44:09

Dr. Schwartz showed us how little we actually understand about a process that we conduct multiple times a day: eating. How unique properties of food are relayed and interpreted in the context of behaviorally complex individuals is a question that has only begun to be answered. In order to get to the crux of some of these challenging, but essential research questions, Dr. Schwartz has taught us to truly put ourselves in the shoes of others. Dig deep into the existing literature, appreciate what other’s research can bring to your own, and continuously teach yourself to learn. In doing so, we can begin to ask more thoughtful and compelling questions that will advance our research. Thank you all so much for listening and we’ll see you on the next episode. For more of our content, you can follow us on twitter @gutbrains or visit our website @thinkgastronauts.com. The Gastronauts podcast would be impossible without our incredible team. Meredith Schmehl is our producer and theme music composer. And special thanks to the founders of Gastraonuts: Dr. Diego Bohórquez and the Bohorquez laboratory.