Seeking Answers in the Gut-Brain Connection: Dr. Nicholas Talley, Professor of Medicine at the University of Newcastle

Caleb Furnas: Hi, I'm Caleb Furnas, welcoming you to Raise the Line with Osmosis from Elsevier, an ongoing exploration about how to improve health and healthcare. Today we continue our look at medical education around the globe by welcoming distinguished laureate Professor Nicholas Talley, an international authority in the field of neurogastroenterology with more than 1,000 peer reviewed publications. Much of his work centers on functional gastrointestinal disorders, also known as disorders of gut brain interaction, including functional dyspepsia, irritable bowel syndrome, and GI complications in diabetes. 

Dr. Talley is currently professor of medicine at the University of Newcastle and an adjunct professor at the University of North Carolina. Earlier in his career, he was chair of the Department of Internal Medicine at Mayo Clinic, Florida. He was past emeritus editor-in-chief of the Medical Journal of Australia, and a past editor of the American Journal of Gastroenterology and Elementary Pharmacology and Therapeutics. Thank you so much for joining us today.

Dr. Nicholas Talley: Pleasure to be here. Thanks for having me.

Caleb: Awesome. So we'd like to start with learning a bit about the background of our guests. What got you interested in a career in medicine and particularly gastroenterology?

Dr. Talley: Well, I guess my interest in medicine began when I was about the age of sixteen when I decided I wanted to go to medical school. Literally just came out of the blue. Now, I do have a background with a medical family. My grandfather was a physician, my father was a physician. So you might say, well, it was all in the family and this is kind of what you might expect. But to be perfectly honest, until I was sixteen, it was the last thing I thought I would want to do. So it was really interesting. And then I buckled down and worked very hard to get into university and to get into medical school to go through this. 

I was always interested in humanities and the arts as well as in science and I guess I wanted a career that married those aspects -- the humanities and the sciences -- and medicine somehow was the only professional approach that really would do this in the way I wanted. So in a sense, that's how I got there. Otherwise, I might've been a marine biologist or perhaps a historian or something else. But anyway, here I am in medicine. I'm very pleased I went that way and I have no complaints about the career at all. It's been terrific.

Caleb: And then what made you decide to pursue the sort of academic route, become a teacher and a researcher?

Dr. Talley: Yeah, look, it's interesting. When I was going through med school, I wanted to do research, or at least I was interested in the idea of creating new knowledge, but I had no idea how to really approach it. When I was going through med school, there was very little research training as part of your curriculum, very, very little, but it was really minor. 

So I decided after that I'd missed out somehow on doing research and I would make that up somewhere along the line as I was training and moving towards subspecialty medicine in the future. I hadn't decided what subspecialty, but I did decide that whatever it was, I would do some research as part of this, and I've always liked teaching, even when I was a student, even when I was a junior resident, I would do as much teaching as humanly possible just because I really loved it. 

So for me, teaching was an easy part of this actually, and a real pleasure. And then I was just lucky, really, to get into research the way I did. I was lucky enough to find a really good mentor at the end of my internal medicine training, and that's how I ended up in gastroenterology. Otherwise, I ended up a neurologist or something else. I really thought about neurology as one of the areas I'd be interested in.

Caleb: Interesting. So it was really truly just the mentor who you found in GI?

Dr. Talley: Yes, it really was. My father was a gastroenterologist and I thought I'd never be a gastroenterologist. He's also got the same first name as me, so I thought if I became a gastroenterologist and he was a gastroenterologist, everyone would be confused who's who, and guess what? That's exactly what happened! Everyone was confused about who's who. They still are. People still think I'm my father. It's really quite incredible because we both were gastroenterologists. 

But it was the mentor, it was a particular individual, who really inspired me and really led me into the field of research. And the area of research I do was really built from the foundations of that work with him and his team many years ago.

Caleb: Well, it sounds like you guys can almost share white jackets, if not the same monogramming...you and your father. So that's a pretty cool story.

Dr. Talley: Well, perhaps we look a little bit different, but he was an amazing clinician and mentor as well. A really interesting guy, my father. But yeah, I've tried hard to focus on the research side in a big way, which was a little bit different to him. He was a clinician in practice more than a researcher. I was a researcher and clinician and educator, but I always wanted to marry those three areas together.

Caleb: So in reading through your bio, you have one thousand publications. What's currently the most interesting or the most curious aspects of gastroenterology to you and what keeps you going?

Dr. Talley: So what keeps me going is this idea that gut brain connections are going to be very important, not just in gastrointestinal diseases, but in fact in many diseases that affect people across the spectrum of internal medicine. And what's really been exciting is this opening up of the gut brain connections and how the bacteria and other organisms in the gut communicate with the rest of the body. I guess that's been a huge area that we're now deeply engaged in with in my research team. 

So what's been really exciting is finding pathology in some of these unexplained gut disorders like irritable bowel syndrome and functional dyspepsia, for example. And the idea that we may be able to unlock what's going on with these disorders in the future and perhaps cure them is driving at least our research at the moment. But even more importantly, there are links between these disorders and neurodegenerative diseases, and we're trying to work out what those links are and what they mean, but they seem to be particularly exciting and we're working hard on that.

Caleb: Yeah, I mean reading through some of your research, albeit superficially, I was reminded about these almost age-old debates between a western medicine and an eastern medicine approach to the mind/body that doesn't distinguish between the mind and the body. I wonder, do you come across those distinctions? Do they still hold water for you and the work that you do?

Dr. Talley: So traditionally in the past, people have split up the body and the mind. They've looked at them separately, but they're clearly greatly integrated. The body talks to the mind, the mind talks to the body, and that's relevant to disease and to health and we're exploring how this happens -- the mechanisms -- and what we can do to interfere if you like, to make a difference and perhaps restore health by doing so. That's kind of a lot of the work that we are doing and others are doing around the world in this field. 

But it's very exciting because it is possible to affect those. For example, there are bacteria that communicate with the brain through the nervous system, and there are ways to modulate that and they're not even difficult ways and they're fairly safe. So these are approaches that I think are going to be very exciting going forward. As this field progresses, I can see most areas of medicine being relevant to gut disease. So it's going to be a very interesting journey for the next fifty years, I suspect.

Caleb: For sure. And I feel like just as a lay person, the microbiome is very much in the ether, right? There was a lot of discussion around it, and obviously social media is filled with various scientists and medical types and self-improvement types who are always pushing another model and so there was a lot of attention paid to eating better bacteria, resistant starch, et cetera. I imagine you get any number of questions from friends from laypeople about this. What do you try to communicate to people who are curious about these things? 

Dr. Talley: I certainly work hard to explain that first of all, it is complex. It's not very simple, but there are certain principles that are very clear, and we're starting to understand some of those principles, which means we're starting to really understand what is going on. But randomly taking probiotics or randomly changing your diet won't necessarily improve your health. It doesn't work like that. 

It is a system that requires more specificity, if you like, for real effectiveness, and that's why probiotics -- which are widely available and many people take them -- really have very limited health benefits based on all the evidence we have. We just aren't using the right bacteria in the right way to have the right effects. But if you can target -- which is what we're working on, of course -- if you can target these, then there really is potential and we're very excited about some of that targeting approach. We're working on that. 

We're working on ways to improve cognitive function in healthy people, for example. So there's work we're doing in that field through gut microbiome manipulation as well as ways to modulate the contents, if you like, of the bacteria that are there to change and improve various aspects of health. Many others are working on this, of course. There are new discoveries every single day. There's a lot of data out there, some of it good, some of it not so good. So it's not easy, don't get me wrong, but it is great fun and really very exciting I think.

Caleb: Totally. In the future, do you imagine that there will be particular pharmacological interventions or diet interventions or a mix of all the above, or what do you see as the most promising pathway for this kind of thing?

Dr. Talley: I am absolutely sure diet manipulation is going to be very promising. The problem with diet manipulation is it's hard to do. It's hard for people to follow the kinds of diets that will be needed to make the right manipulations. But we have good evidence that dietary change alters gut bacteria in a positive or a negative way depending on what you do, and we are certainly working on that area, and that's exciting. 

But I think we're going to have pharmacological manipulations. We're going to have very specifically targeted molecules that will change what's going on at the microbiome or at the mucosal or surface lining level and that is going alter and lead to reductions in disease or improving health going forward. Based on what we know so far, that seems highly likely and already some of that work is ongoing.

Caleb: Just to double back, can you pick out one particular change in the scientific understanding around this that in your view was the most transformative? Was there one particular discovery or investigation that kind of put all this on new footing in particular for you?

Dr. Talley: The trouble is there are many, but I think one was fecal microbial transfer. We know now that it works for certain things, certain diseases. For example, a particular bacterial infection of the large bowel, clostridium difficile infection -- which is very nasty, often in hospitalized sick people -- can be cured by fecal microbial transfer, by literally giving a healthy person's stool to a sick person. In 95 - 99% of people who get that treatment, they get better, which is just remarkable. It’s better than antibiotics, better than any other treatment. 

I think that information has really stimulated many of us to think, well, we don't quite know what that treatment's doing exactly, but it's clearly making a huge difference and therefore there's great opportunities for this kind of approach or related approaches to make huge differences as well, if we can get them right. So that's I think one of the important advances in the field of gastroenterology. There are many others that have played into this that have given us information, but that's been particularly important. 

Caleb: How do you think about communicating those kinds of discoveries in the context of educating future doctors and researchers? Because it seems like on the one hand, medical education has to hue very closely to the bona fide established medical, not dogma, but just science. And part of the challenge is that there's just more science than you can possibly cover. But as an educator yourself, how do you balance this new world that almost seems uncanny or unbelievable with the foundational stuff that everybody has to learn? Is there a best way to approach that kind of dichotomy?

Dr. Talley: I think the best way to do this, in my view, is to excite medical students and others about what's going on. You can't provide all of the information that is out there. In fact, it's impossible to teach in medical school everything they need to know nowadays. The exponential growth of medical knowledge is stunning. It's absolutely amazing. It's doubling every few years now – doubling -- which means all of us are having trouble keeping up, even in our own subspecialty fields and even in our super subspecialty fields. It's remarkable. 

But if you can excite people and encourage people to self-directed learning as well as provide that foundational knowledge people must have, which we hopefully do well, then I think that will be the best way to get people excited and interested. I also think we now train our medical students in many parts of the world to do research. They get a bit of a hands-on research experience. They get a chance to realize, “Oh, there's so much knowledge in one little, tiny area.” And of course, every area has so much knowledge and they really get that depth approach by doing a bit of research and some methodology assessments so they can understand the literature. Because being able to read what's being published critically remains an important skill which medical students really need to have in their brains so they can understand what's really useful and what perhaps is less useful, and that's terribly important.

Caleb: Just returning to this idea that you mentioned of trying to have your students be self-directed in their learning, what's your experience been trying to implement that sort of approach within a medical school, which is by definition, something of the opposite, right?

Dr. Talley: It is a little bit of the opposite. And of course in some parts of the world, there's a big focus on passing barrier exams rather than actually really getting into what you need to know and depth of knowledge, which I think is so critical. So I think it's just very important for those who are in charge of and are teaching in medical schools to ensure they provide that approach as part of the curriculum. At least in my view, that's incredibly important. 

We do it in my institution here. We did it at Mayo Clinic when I was there for many years. It's incredibly important to do so as well as provide that foundational knowledge so they can pass their national boards or equivalents, et cetera. That's obviously critical, too. You don't want that to fall over as part of what you do. 

Because I think it is clear medicine is going to fundamentally change in the next twenty, thirty years. I think so much that it will really stress medical school education in new ways that we haven't currently got solutions for. And with AI and other new tools suddenly available, transforming the field as we look at it now, it is going to be a very different world going forward. 

I think probably most important will be to have physicians who can really think and truly be custodians of not just knowledge - because knowledge will be all available to everybody -- but actually integrating that knowledge, synthesizing that knowledge, understanding where that should be applied and how it should be applied for best patient outcomes, best patient care. That's going to be a little bit different to what we do now with our current exam approaches, which really are still very much knowledge focused rather than something else. So, interesting times ahead.

Caleb: For sure. What do you think is a good intermediate step as far as what the medical classroom should look like now, taking into account these two things? And obviously there's touchstones and there's movements around flipped classroom, team-based learning, and you can do your didactics offline. What in your view is the best blend of the available methods and what have you found most effective?

Dr. Talley: So in my view, obviously there's knowledge and certain skills you've got to train people in. It's really terribly important, at least for training the doctors that are going to come out of the system, training them in the approach to clinical diagnosis and management that is the deep thinking approach rather than, “Oh, I just follow the guideline blindly and don't worry about anything else and don't think about it very deeply at all.” Because anyone can follow a guideline. You don't need to be a physician to follow a guideline. You can have other health personnel can do that extremely well, probably do it better actually than physicians sometimes. 

But it's getting to the place where patients enter the guideline in the appropriate way, for example, the right diagnosis. So, as I'm teaching medical students in the current curriculum, I always try to make sure that we inculcate the sense that their approach is the critical approach for diagnosis, the critical approach for thinking about should this patient be managed in one way or another way depending on the situation. So it's just getting that right and that means clinical exposure in ways that ensures that they learn these skills and it isn't just rote learning when they do ward rounds, for example, which is much less useful these days than it used to be.

Caleb: Right, because it's just learning by rote or it's too kind of didactic.

Dr. Talley: I think learning by rote and being very didactic and just learning by pattern recognition isn't really going to serve people very well. As everything starts to change, as we have better tools that can obtain the information, for example, and provide it to us, people who can't adapt to the changes coming are going to really struggle I think, going forward because they'll be replaced. I mean, that's what's going to happen if you haven't got ways of changing yourself as a physician. I think you could find yourself even potentially unemployed as AI gets better and better and better. 

At the moment, it's not good enough, but oh, come on, it's exponentially improving. So that means very soon it will be way better than almost anything else in terms of obtaining information. For example, even giving differential diagnoses and recommending treatments... that's coming right now, which is a big change in what's going on in medicine.

Caleb: For sure. In your own institution, is there a wide variety of responses to AI and its implementation?

Dr. Talley: People are using it in different ways, interestingly. You've got some people who are, and I'm aware of this, who are using AI to record interviews. They're recording their interviews using AI to generate reports and AI to generate notes. And it is fascinating. I'm not sure the AI is quite up to this yet, to be honest. It has to be pretty carefully vetted if you do that right now. But you can see that really changing going forward and this obsession with what we do now -- which is a lot of note writing and documentation -- perhaps that's going to really change in the future somewhat for the better because some of that documentation is inaccurate that we currently do and just not very useful. 

So that may really get improved with AI, but we run the risk of AI then driving what we all do, which is perhaps not always in the patient's interest because patients don't follow textbooks. They just don't. They don't always even follow the literature and we've just got to be aware of that as physicians seeing complex medicine, which is what I do every day.

Caleb: Well, this is all fascinating stuff, and we could talk for days -- I know that I could -- but do you have one piece of advice that you'd like to share with our audience of students about a generalized approach to medical school in light of these opportunities, in light of doing something itself, but also availing themselves to all the opportunities that are out there?

Dr. Talley: Yeah, look, that's a very hard question because there are many aspects to it that I think are worth paying attention to for medical students starting out. First of all, I think to realize your career options are almost endless after you graduate, and it will get even broader going forward. There'll be more different types of careers for physicians in the future, which I think is really exciting and something to remember. So you don't necessarily have to box yourself into a particular approach and perhaps the really innovative students may want to think about different kinds of careers as they go forward. 

I do think it will be incredibly important to be able to synthesize clinical data really well. One of the great skill sets that I think is still very useful, and will probably remain useful for an awfully long time, is this ability to really take a very good history and do an exam where appropriate, and synthesize that information in a really critical, sensible manner. To be honest, not everyone can do that as well, and that's a core skillset that will serve you well if you can acquire it. So, learning that is really done by seeing lots of patients and getting lots of mentoring, actually, in many areas and that can come together as a very important core skill set. 

I must say one of the good things about the Australian and the British system is they've really focused on that to a significant extent in their core training. So I think that's a good system and it's certainly worthwhile learning how to do that. 

And then I think the other piece of this is to do some research. I really believe the best clinicians I know have done some research or still do some research as part of what they do. I think the skills you gain doing clinical research serve you well for the clinical skills you need to look after patients really well. And also the knowledge gain that you obtain by doing research teaches you how to research your patients when you need to for difficult diagnostic dilemmas, which otherwise can be not solved. 

I guess I've always believed that's our job as physicians...to solve those difficult dilemmas, not to just pass them to someone else and say, “Well, I dunno what it is, but I'm not going to do any work to try and find out. I'm just going to let someone else worry.” I think that's the exact opposite of the right attitude if you want to be a great clinician, which I think every medical student should aspire to.

Caleb: I agree, and that's a wonderful answer. And it's one of those deals where -- even in light of all the technological and scientific advances -- there are no shortcuts. I think that that's the reality and obviously the appropriate way to pursue medical education. Well, thank you so much. I really appreciate your time, Dr. Talley.

Dr. Talley: Oh, thanks for having me. It's been a great, great pleasure to be here. Thank you.

Caleb: Awesome. So with that, I'm Caleb Furnas. Thanks for checking out today's show. Remember to do your part to raise the line and strengthen the healthcare system. We're all in this together.