In conversation with Diego Bohórquez
As Nature Neuroscience celebrates its 25th anniversary, we are having conversations with both established leaders in the field and those earlier in their careers to discuss how neuroscience has evolved, and where it is heading. This month, we are talking to Diego Bohórquez, an Associate Professor at Duke University School of Medicine. He is a self-described ‘gut–brain neuroscientist’ and spoke with me about his early life in the Ecuadorian Amazon and how his curiosity has led him to his current research topics.
Can you tell me a little bit about your background and how you became a scientist?
Imagine, it’s 1983 in the middle of the Amazon. The first road was going through the jungle in Ecuador. Today, the town where I grew up is only about two hours away from the main airport in Quito, but at that time it was half a day by bus. When I was five years old, I took the bus with my parents to the city, and it was six or seven hours through winding roads. That’s where I grew up.
First turn of events: I was 11 years old and my father informed me that I was going to military school, not in a negative way, actually in a very positive way. He obviously grew up in a different era. He was born in 1932, went through World War II, lost his father when he was six. So he had to drop out of school when he was in third grade because his mother couldn’t support him, but he learned that education is key. My mother was much younger than him, with a very similar story. And so when I was 11, I ended up in a military boarding school. At that time, it was the premier school in the country. The school had a zoo. I could see the lions from the classroom. Not even the country had a zoo. Eventually the school’s zoo became the main zoo of Quito. I mention that as a context because often we don’t realize the environment in which we are developing and how it is nurturing us and influencing how we think. One of the key things in military school was leadership, from day one. The way that they approached leadership in the military was making you believe that if you put in the work and you’re consistent every day, you will go places.
What was your next step after military school?
Every time I give a presentation, I say that there are two things that are influencing us daily: the food that we eat, and the people that we meet. So a couple of years before finishing at military school, I was at dinner with a friend of mine. And he asks, “What are you going to do after school?” I said, “Well, I’ll go to the Military Academy to become an officer.” And then he said, “Why are you going to do that? You should do something that will help your parents. Agriculture.” I thought, “Agriculture, do you really study for that?” Both of my parents were in the business of cattle trading and then they had farms. So I thought it would be good to learn something to help them produce more efficiently or manage the business. He told me about an agricultural private boarding school in Honduras that had been founded by the Cuyamel Fruit Company (predecessor of Chiquita Banana) tycoon, Sam Zemurray, and he said his friends who had gone there come back and they are leading companies and have a successful professional life. So that’s how I ended up at the Zamorano Pan-American Agricultural School (now University).
At Zamorano, half the time you do real work, farm work. They welcome you in with 12 different tools for you to work in the fields and if you didn’t finish, you didn’t go home. At least at that time it was like that. I spent four years there, and a few things happened. It was the first time that I heard the term PhD. I asked what that is, and they told me it’s someone with a high degree in science, and I quickly realized that the people that manage the university have a PhD. So I thought, “Maybe I should get one of those. I should ask where it is that they give those?”
And the second part was nutrition, my excitement for nutrients. I had an internship towards the end of my time at the school in California on a dairy farm. They had 2,000 cows milking every day. Two people milk those cows in 10 hour shifts. That was a crazy change from the 40 or so cows I was used to on my parents’ farm. I quickly noticed that the cows had a high rate of mortality. So I informed the owner that the cows were dying and asked if we should bring in a veterinarian. He explained to me that a visit from the veterinarian would cost more than a cow is worth and said that we need to call the nutritionist. I was curious why. He said because the issue was that the cows were weak because they don’t have the nutrients they need in their diet. So I realized the importance of nutrition.
As it happens, the same professor that I had seen in my first year at my school who had a PhD returned in my last year. He was at North Carolina State University, and he offered us to continue our studies there. I began with a small internship in the Department of Poultry Science, not to be confused with poetry. It did happen to me one time at a bus stop and I didn’t know why I was being told about all of these poets.
An impactful night for me in graduate school was when I went to my first Thanksgiving dinner, and I was sitting next to a woman who told me she’d had gastric bypass surgery a year earlier. She said, “Within six months, I lost 40% of my body weight. Within a week, my diabetes was gone. But the thing that I’m curious about, and I hope that you have an answer for this, is that before the surgery I could not even look at sunny side-up eggs, but now every time I go to breakfast with my husband, not only do I eat the yolk, I actually crave the yolk. I take the toast and I clean the plate.” I thought, “How does changing the gut change food preferences?”
Later, when I was presenting in a seminar, someone suggested that I consider doing a postdoc at Duke University in Gastroenterology. My mentor was Rodger Liddle, who had been the Chief of Gastroenterology and was the President of the American Gastroenterological Society. I am very grateful to Rodger because he really took a chance on me and he got a diversity supplement for one of his R01 grants to support me.
It’s so interesting to me to hear you tell the story of your life, and that there are so many of these very consequential turning points for you that come out in a simple conversation with someone. I wonder if that’s something that you think has been important to you, in terms of being open to new opportunities and listening to people. Do you think there’s a lesson there that’s worth sharing?
Absolutely. I think that we rarely know what we really want. We have an impulse, we have a feeling. But really articulating what it is that we want is more difficult. When we talk to people, and especially when they infuse the conversation with their excitement or meaningful moments from their life, it’s just like getting a very nice energy bar, right? It jolts your brain.
You’ve talked a lot about the path that you’ve taken and the kindness that other people have shown you in terms of presenting you with opportunities and guidance. Do you want to talk about any difficulties that you had? Did you feel like you were facing prejudice at any time? Was it difficult to transition into different cultures?
This is a fascinating point that you bring up, which is that I think it really comes down strongly to point of view. Someone I met at a conference once gave me feedback on my presentation, and I said, “Is there something that I should pay attention to so I can continue improving? And they said, “Out of every 10 people that you encounter, at least eight are trying to help you. People want to help. It makes them feel good.” So, I try to listen to how someone is trying to help me. If someone offers a piece of advice, that’s not necessarily because they want to suppress you. It’s just because they know other ways of doing things, perhaps better.
So it seems like you seek out the positive and you put less emphasis on things that were negative or things that were challenging.
Overall, I think that having that word “opportunity” at hand has definitely taken me places.
What did you work on during your postdoc, and now in your own lab at Duke?
When I landed in Rodger’s lab for my postdoc, it was like that scene in The Matrix when Neo is presented with the red pill and the blue pill. He asked, “Do you want to study a cholecystokinin (CCK)–GFP mouse or peptide tyrosine tyrosine (PYY)–GFP mouse?” And Rodger said, “Just remember, I have been working on CCK for the last 30 years.” And I said, “So I’ll go for PYY.” He asked, “Are you sure, you will be on your own.” I thought, “Well, he’s giving me the opportunity to take half of the pie. And we will learn together, right?”
The first thing that I observed was that these enteroendocrine cells had an arm-like process. For years we were calling it the ‘basal process’, then we added ‘axon-like basal process’, then it was ‘axon-like pseudopod basal process’. Eventually, it got so complex that it was hard to put it in an abstract. So, when we were about to publish our paper1, I said to Rodger, “I think that this is our last chance to change this name. How about we call it a neuropod?” And after thinking about it for a weekend, he said it has a really good ring to it. I wondered why they have an arm if they are just endocrine and spewing out signals? I already had anatomical evidence that they were contacting neurons, but contact does not mean connection. The key experiment came in 2012, 27 June, at 5 am. I couldn’t wait to get to the microscope. The idea had come to me while I was running, “How about if I put a single one of these cells in front of a neuron in a dish?” It was so beautiful how not only do they attract each other but they reconnect2. The next part, once I started my own lab, was tracing the circuitry from gut to brain, and showing that the circuitry is essential for the sensory transduction of nutrients3 and later that it is involved with guiding food choices4.
It was a journey showing that. I guess perhaps, that’s why we say, ‘trust your gut’. Because literally after we have identified the food that we want to eat, we swallow it. And then the gut has the wisdom and the ability to discern these molecules and then quickly inform the brain so the brain can adjust. And now in the laboratory we are seeing that, for instance, gut microbes seem to be tapping into this circuitry to guide our food preferences, and that the circuitry can also detect the absence of nutrients in the diet.
What is your ambition for where your lab will be in 10 years or 20 years? What are the discoveries that you want to contribute to?
I am fascinated by our relationship with plants. Seventy per cent of our diet comes from plants. For example, I grew up in the Amazon region. Native people there have a very close relationship with medicinal plants and with plants in general. In fact, they tend to have a garden with both plants for food and plants for medicine. It’s called chacra. I’m really interested in how the gut may sense compounds from plants, and how this is communicated to the brain.