Embracing the mind-body connection

Stress is a constant factor in the daily lives of many. BIO5 researchers are working to assess the risks affecting us when feeling overwhelmed and understand the connection between health and emotions. BIO5 member Dr. Esther Sternberg is a Professor of Medicine, Professor of Psychology, and the current Director of Research at the University of Arizona's center for integrative medicine. She is recognized by the national library of medicine as one of 339 influential women “who changed the face of medicine.  Dr. Sternberg's research investigates the interconnected aspects of health such as the mind, body, and environment.

As you bring your mission of education, research, and learning to this next generation at the University of Arizona, what is one word to describe what science is to you? 

Curiosity. My father was a scientist and he used to say that curiosity is a disease and you just can't get over it, and it drives you. It's a need like trying to figure out how things work and why things are. Of course, the fact that, in the process of figuring it out you're helping maybe millions of people in many different ways. 

What were your original inspirations for the work you are doing today in integrative health and the built environment? 

Going back to childhood, my father was a professor at the University of Montreal in the same department as Hans Selye, who coined the word stress. As a child, my sister and I would play in my fathers lab and we would see Han Selye with his sort of gaggle of student geese walking  behind him, and he was quite intimidating. In that time in the 1950s, Han Selye was viewed with a lot of skepticism and concern because he went around the world proselytizing this concept of stress. He got the word stress into every language in the world, so that actually did not inspire me. Knowing that he was viewed with skepticism by his colleagues actually made me distance myself from this field of stress, because it’s sort of a fringed idea. 

As a high school student, I loved biology and for the students; if you don't know what you want to do with your careers, and you're sort of grappling with what you do want to do and you don't want to do; I did not want to go into medicine, even though my father was a physician and a professor of medicine. My high school guidance counselor encouraged me to apply to McGill University for a seven year medical program. I said “but I don't want to go into medicine”, and he said, “well that's okay, because you just do the same first three years in your bachelor's and your undergraduate degree, and you have three more years to make up your mind. If at the end of three years you don't want to go into medicine, then you finish your bachelor's and you're done, and if you do want to go into medicine, then you're all set.” 

At the end of three years as an undergraduate, I discovered that I love medicine: I love the scholarly part of medicine, I love the idea of working with people, I love the idea of helping people. When I volunteered in the hospital I got to know how it was to work with patients, and I also worked in my father's lab over the summer, and I just had a ball. I just loved working in the lab. It was amazing to me when an idea got tested and turned into an experiment. To see that it actually worked and to see the results was just mind boggling. That was when I fell in love with the idea of research and taking care of patients. I also have my aunt who is a professor of 

Physiology at McGill University, and so I had that role model of a woman who could be a professional in the biomedical sciences. All of that helped to shape my youth and my evolution.

It is interesting how your path is not necessarily linear. Your decision making in one moment doesn't necessarily reflect where you will end up, because I think we hear so many students struggling with that, and I think we all did at a certain point. We think every decision we make is the last one we are going to make, and it never is.

As you said, your path is not necessarily linear, it's never linear. Don't even think about it being linear. In everything I've done in my entire career, I don't end up doing what I thought I would at the beginning. You can think about it as rolling across a river that has a very strong current and you want to get from point A to point B. The current keeps pushing you in different directions, and you have to keep correcting courses in order to get to Point B. Maybe you decide you don't want to go to Point B, maybe you want to go to point C, and that's a big discovery and that's wonderful. Students should keep that in mind, and also it's really important. 

One thing I learned in my early career as a postdoctoral fellow where I was working on a project that was really a brilliant idea my supervisor had, and it took me two years to figure out it wasn't going to work. The chemistry didn't work with the biology, and I was devastated. I was crying, and I was in St. Louis at the time at Washington University, and a former mentor had come through. He was speaking at the university, and I just sat down in the cafeteria and cried because I was failing. He told me the most important piece of wisdom in my life–in my career, which is that we need the luxury to fail because it's from our failures that we learn better. He said, “if you were just churning out dozens of papers using some kit, you're not learning how to do research. These two years taught you how to really do research.” It's painful because it feels like a failure, it is a failure, but it teaches you how to go forward. I think it was Eleanor Roosevelt who said, “you only fail, when you give up.” So you just keep on trying new approaches, and success is not how many times you succeed, but how many times you turn a failure into a success. That is what success is. 

Even with those failures and those nonlinear things that happened during the course of your journey, it's really interesting when you look back a little bit further down the path, when you have the luxury of some perspective, that everything ended up how it was supposed to. Fast forward to today, you are a pioneer in this incredibly evolved thinking of the science of this mind-body interaction with illness and healing; how the role of our built environment and our place  contributes to our well-being. Talk to us a little bit about how you became passionate about this area specifically.  

Well, it all started with a single patient. I was finishing up my rheumatology fellowship training at McGill University, and I was called to see a patient at the Montreal Neurological Institute on Christmas Eve. Talk about not wanting to stay, and I was planning to go on a ski vacation, but I went to see the patient and the question–the reason was an emergency consult.

The neurosurgeons wanted to send the patient home for Christmas, the next day, but he had developed an autoimmune scarring disease while receiving an experimental treatment for his fatal form of epilepsy. Every time he tried to do something he would start to have an epileptic fit. They were giving him a drug which changed brain serotonin. It was before the time of SSRIs, and the idea was to increase brain serotonin because this form of epilepsy was thought to be related to too little serotonin. 

They wanted to know if it was safe to send him home and what we should do and whether this autoimmune inflammatory disease was related to the drug they were giving him. That image of that man in bed; the door of the room, the light was fading, it was four o'clock in the afternoon, and Montreal gets dark early in winter. The sheets were tended up over his legs, it was so painful he couldn't bear for the sheets to touch his legs. His arms were flexed, and he could not fully extend his arms because they were so scared. He looked like he'd had third degree burns all over his body. I was convinced that, from that case onwards, that the brain has something to do with the immune system. 

That was in 1978 or 1979 and at that time, the fields of neuroscience and immunology did not believe that the brain and the immune system talk to each other, or communicated. There was this thing called the blood brain barrier where immunologists said “well, immune molecules are so big they can't get across the blood brain barrier,” and neuroscientists said “well,  the neurotransmitters don't do anything to the immune system.” We know now that that was all wrong, but back then It just wasn't believed. The idea of the mind-body connection was considered so fringe that it was dismissed. People who were doing research on this were dismissed, but I was convinced by that single patient, which changed my career. 

Instead of going back into clinical practice, which I loved; I had been in family practice for two years before I went back and trained as a rheumatologist. We talked about curiosity being a disease, and I was so wrapped up in the search to try and understand how it could be that giving a drug that changes brain serotonin could trigger this disease. I realized in looking at the literature that nobody had done these kinds of studies, and I needed to do it myself. That led me to start looking at the effects neurotransmitters have on immune cells. I went to Washington University in St. Louis and there, I was sprinkling serotonin and other neurotransmitters on macrophages and culture; and I loved to watch these little macrophages gobble up plastic beads, I felt like a farmer. I could see with my own eyes that when you put serotonin on top of these macrophages, they started just gobbling more beads that activated those immune cells. 

I moved to the National Institutes of Health to the Intramural Research Program where I realized that there was no end of in vitro studies to prove how the brain and the immune system communicate. You've got to have the brain attached to the immune system in order to understand that, so I started doing animal studies in two different strains of rats that had been

inbred strains of rats, one that was highly susceptible to a whole host of autoimmune inflammatory diseases. The pattern of which depended on the antigen to which they were exposed. We gave them bits and pieces of streptococcal cell walls, other bacterias, or rheumatoid arthritis. If you gave them a ground up thyroid, they got Thyroiditis, and ground up spinal cord, they got something looking  like multiple sclerosis. They were highly susceptible to all these autoimmune inflammatory diseases, yet their cousins, the fisher rats, were highly resistant to exactly the same antigens and they didn't get sick, so I used those two strains of rats. 

That was another example of what I thought was a failure, but turned out to be the real insight. When experiments go exactly in the opposite direction than you think they should go, that's the most important insight and tells you really what's going on. If the experiment does what you think it should do, then you haven't really learned anything, you've predicted it and it's correct. Then we started giving them a drug that blocked brain serotonin, and I thought this would be the next great anti-inflammatory drug. We decided we had to give the drug every 12 hours for eight weeks, so this was not something I particularly felt like doing and neither did my collaborator, so we hired a bunch of summer students to do it because that's a great summer job, right? You come in in the morning and inject the rats, and come back at night. 

The first student who did it, who in full disclosure happened to be my cousin, who's now a world famous scientist in his own right, but it's important to know that he was my cousin because he called me at midnight and I don't think another student would have had the courage to do that.  He said, “I don't know what I've done wrong. I'm really terribly sorry my basketball game went late and I arrived two hours late and all the rats are dying.” I thought I better do a house call and it wasn't all of them, it was only the rats that were usually completely resistant to any inflammatory disease. He asked me “how can you explain that,” and we're walking down the halls at NIH at midnight with fluorescent lights in these long hauls, while I'm trying to figure out how am I gonna explain this. 

I realized that the drug we were giving was an experimental drug that had been developed for high blood pressure, and a lot was known about how it affected the brain and it was known that it blocked the brain stress center, the hypothalamus. I should tell you this drug was not put on the market, our studies showed that it shouldn’t be a drug.

Maybe what that drug was doing was preventing the brain stress center from giving the rats their own shot of cortisone when they needed it to protect them from that septic shock. That observation made me hypothesize that the brain’s stress center is important and susceptible to autoimmune inflammatory disease. I began to think maybe the reason the other rats get autoimmune inflammatory disease so easily is that they have a blunted hypothalamic pituitary adrenal axis stress response, and they're not putting out enough cortisol. So why did they survive when we gave them a drug that blocks the brain stress center? They'd already found a way around it and they had backup systems, so there wasn't anything for us to block with them. 

This is what we discovered when we went back and did the endocrine workup on these rats, that in fact, the Lewis rats, who were highly susceptible to inflammatory disease, had a blunted, almost non-existent hypothalamic pituitary adrenal axis response to anything. They’d behave like laid back California rats, as we used to call them, and you would put them in a new open cage where they went to sleep. They couldn't care less. The fisher rats with the highest stress had a hyper responsive hypothalamic pituitary adrenal axis response, and they had hyper responsive stress behaviors. 

When you put them in a new cage they started–just sort of grooming, running around chasing their tail. They were very anxious rats, and that was really a crucial observation that connected in a whole animal system: a blunted brain stress response to a tendency to higher autoimmune inflammatory disease. And then we did a whole bunch of studies to prove it, and did hypothalamic transplants in the two rats, and we corrected things, and we blocked the hypothalamus in the fisher rats and made them more susceptible, and so on.

 It was that single observation combined with three pieces of information that I had in my brain. That young woman who'd gone into septic shock and knowing that you need corticoids to treat it; the knowing that that drug affected the brain stress center; and the third thing is, I had been working with Candace Pert, who was at NIH, and she was one of the discoverers of the opioid receptor in the brain. 

At the time she was doing studies looking at interleukin one receptors in the brain, and I had seen the brain sections of rats and mice where she was able to show that there were indeed interleukin one receptors in the region of the hypothalamus. That connected all the dots for me. I said, “well, maybe what’s happening is when you're in septic shock, you're releasing these immune molecules. They trigger these centers in the brain stress center to then release cortisol eventually from the adrenal glands, which then shuts off inflammation and prevents you from going into septic shock.” So it all became clear by putting these three pieces of information together.

Wow, that’s an incredible story. My brain’s going to have to wrap my head around all that because that is pretty amazing. I think just the series of experiences you had that lead to that formulation of that in that moment, it’s really interesting.

Let me add something to that, I want to interrupt you, because for students, this is really, really important. I thought, “well, this is so obvious to me, it should be obvious to everybody, but no, no, no. You are the only one who has had your particular set of experiences that allows you to have certain insights that nobody else is going to have. It may be obvious to you, but it may not be obvious to anybody else, so go with your gut and go with your instinct. 

So that's one thing, and the other thing is when we write papers, we write papers backwards. We start off with a hypothesis, we say “I hypothesize that the brain and the immune system are connected with each other.” I did not, I mean I sort of did, I was looking for that connection, but I didn't hypothesize that the hypothalamus had anything to do with the immune system or with arthritis. I didn't know what had to do with it, but that observation allowed me to create the hypothesis that the problem was in the hypothalamus, and then I could do the studies that proved it.
 

You just mentioned this concept of how one's own personal experiences are what shapes them. We might be in the same room and come up with two totally different perspectives on what's happening because of our own personal experience. One of my own personal experiences, and one of the reasons I was really interested to talk to you,  is that I suffer from a little stress in my life. Some of the focus of your work today is on how stress makes us sick, how stress keeps us from being well and living in our best way, and how the biological mechanisms of that intersect with the space that we're in. I would love to hear a little bit about how a place can make me, a stressful person, well? How can it make me feel better, how can it make me have a better experience in my life?

Well, that came from another set of experiences. It was a combination of personal experiences with stress and with arthritis, and I'll get to that in a moment. A single question that was asked to me by the then Director of Research of the U.S. General Services Administration. It's the agency of the Federal Government that builds and operates all non-military federal buildings for over a million office workers across the United States and around the world: your libraries, your courthouses, your embassies, any federal building that's not military is operated and built and designed by the GSA. I was a scientist at the intramural research program at NIH, and Kevin Kampschroer, who was the Research Director at GSA, asked me to help him gather the data to prove that the built environment can actually affect people: the occupants, the workers’ happiness, stress relaxation response, mood, health, and ultimately productivity in order to design the spaces to optimize their health, well-being, and productivity.

He wanted the hard data, he needed the hard data to convince the powers that be that they should spend more money to build a beautiful building, like the one in your background there. That was the early 2000s. Certainly in the late 1990s, 1980s, the spaces that people worked in tended to be high wall cubicles, poor ventilation, loud mechanical noise, no sunlight, no windows, and he wanted to know how to design the spaces so people would be happy, healthy, and productive.

And so we started working on using wearable devices to measure the impacts of the built environment on these health outcomes. But before that, in my own personal experience, in the mid 1990’s, I had gone through a period of extreme stress. My mother was dying of breast cancer, I was a long-distance caregiver, I was under a lot of stress at work, and I developed inflammatory arthritis. 

Here I was, 9 years earlier I had discovered the importance of the brain’s stress center and arthritis in rats, and then I had become a poster-child for what I had discovered. I moved into a new house in Washington DC, and my neighbors were Greek and they knocked on the door and they saw me writing what was to become my first book. They asked me, “are you a writer,” and I said, “well, I don't know I don't think of myself as a writer, why do you ask?” Well, they said “we've always wanted a writer to stay at our cottage in Crete,” so I said okay I'm a writer. I went with them to Crete, just for a couple of weeks, and at that time my arthritis was pretty mad. I had gone into NIH, I'd plugged myself into an NIH early arthritis protocol, I'd had knee biopsies, I'd had a whole workup, and I was supposed to go back into hospital to get a liver biopsy and experimental drug treatment for this arthritis.

I was so exhausted from the hospital, and my mother had just died, and I said “no, I'm not going to do that. I'll delay and I'm going to go to Greece instead,” and I went with them to Crete.

It wasn't a miracle cure, but in the period when I was there, I began to walk. Every day, I was swimming in the ocean. I was eating a healthy Greek diet, Mediterranean diet we call it, with some fresh vegetables, fresh fish that the fishermen were hauling out of the ocean that morning, and lots of fruits. I would climb to the top of the hill above the village, which had the ruins of a temple to Asclepius, the Greek god of healing. I'd sit there for hours and just look at the Mediterranean; the blue, blue, blue Mediterranean and the white stucco buildings and the fuchsia bougainvillea. I inhaled deeply, and I listened to the sounds of the sheep and the goats.

I have learned since that I was meditating, I thought I was contemplating, but I was in the moment. All of these things: the support of my neighbors, of the other villagers, we know now those are all aspects of integrative health. I was practicing all those that the Andrew Weil Center for Integrative Medicine calls the seven core areas of integrative health. I was sleeping well, sometimes under the stars on the roof of their tiny little cottage. I was able to understand at an intellectual level when I made the discovery about the brain and the immune system and the rats, that the stress response has something to do with the immune system, I never really fully understood it at a visceral level until I went through it myself. When I went back to Washington and I saw my rheumatologist, I went back and looked at the notes in his chart, he said “she's so much better she doesn't need to go into the hospital.”

It's not that I had a miracle cure, but I realized that if I continued on the path I was before I went to Greece; eating cheeseburgers and French Fries every day for lunch, having a sedentary life, being stressed in many ways, I would continue to be sick. If I purposely, consciously changed my life to do the things I was doing in Greece, then I would get better, and that's what happened.

We did find in our first study that we published in 2010 that office workers in a retrofitted Denver office building were significantly less stressed on two measures of the stress response: salivary cortisol and heart rate variability, so the hormonal stress response and the neuronal stress response. They were significantly less stressed in the new, light, airy, beautiful, open office space with views to the mountains, with low mechanical noise, and with good airflow compared to when they were in, or when others were, in the old space that had six-foot high wall cubicles, was dark, it was musty, had high mechanical noise. 

I don't know why I was surprised. I think the reason I was surprised was that I was so used to working in these terrible spaces, I didn't pay attention to it anymore. Again, it's only when you see the difference that you realize, wow, that was awful. 

We continued after I came to the University of Arizona, so Dr. Andrew Weil and Victoria Maizes recruited me to come to the University of Arizona. It was a hard decision to leave NIH. I grew up in Montreal, I'm an east coast girl, and I never envisioned that I would live in the desert. But when I saw Tucson and the beauty of Tucson and the mountains, it's a city in a bowl of mountains, and the beauty of the Sonoran desert, the fragrances of the desert after the rain, I mean all of it is just so beautiful; and most important was the amazing Center for Integrative Medicine. 

The team there and how committed they are to training all generations of physicians in integrative health, and to think about health as much more than the absence of disease. That was really important to me, and that allowed me to bring together this research on the environment, which is a very complex experience I was doing at the molecular and immune system level to really think about the person, not only as a brain floating in the ether connected to a bunch of immune cells. Which is how my PowerPoint talks always showed a brain and then a bunch of immune cells, and it left out the rest of the person. It left out the people that people are interacting with, it left out the physical environment that you're in, and all of that is essential to physical health and emotional well being.

Being at the University of Arizona with people, and this is where BIO5 comes in as well, being able to collaborate across disciplines is just remarkable. It's not easy to do. The University of Arizona has a lot of infrastructure that fosters interdisciplinary cross college collaboration, so I have very close, and now long I've been here 10 years, collaborations with the College of Engineering, certainly the College of Architecture, Planning and Landscape Architecture, College of Science, Department of Psychology, College of Agriculture and Life Sciences, and on and on. It is just so exciting to be able to work with all these people who have knowledge and disciplines that I don't know anything about. I don't know anything about systems and industrial engineering, or mechanical and aeronautical engineering, or architecture and planning and landscape architecture.

I'm learning about it all, but I'm working with people who are really experts in these domains. It allows one to create these research projects that can tease apart these very complex interactions that lead to either illness or health.
 

As a non-scientist that is fortunate enough to hear and help share the work of so many incredible scientists, researchers, physicians, engineers, that's the common theme, and I feel so fortunate to be in a place like BIO5 where that's just embedded. I have learned that it's not really that common, even today, at UofA and in spaces like BIO5, and it is just something we value here. It's really incredible to see everybody come together and just work around these really complex things that will make a big difference in people's lives. Do you have anything really exciting coming around the corner, are you just continuing on with other really important things you’re working on? Is there anything exciting?

 In terms of exciting things that are coming down the pike, the Andrew Weil Center for Integrative Medicine is building a new building. Right down the street from where you are, just sort of catty corner from the Health Science Innovation Building, and literally across the street from BIO5. You can see the ground being dug up, I think the footings are already in, and what's so exciting about that is with an advisory committee, with faculty and the dean of the College of Architecture, Planning and Landscape Architecture, experts in sustainability, experts in landscape architecture, experts in architecture, and with my colleagues from the U.S. General Services Administration advising also on sustainability and post-COVID re-entry, which is a huge issue in office space. 

In terms of the new building, we have these wonderful advisors working with this amazing architecture firm, Line and Space, and the architects created not just one building, but three buildings that really embody the mind, the body, and the spirit, and it will be an oasis. It will be a destination for people across the campus, across the community, around the world to visit and see how you actually embody integrative health in a physical structure. You can go to the Andrew Weil Center for Integrative Medicine’s website and check out the new building on the webcam and the progress on the building. It’s supposed to be ready by the end of 2023. 

One more thing I do want to say about COVID. For two years, we got used to working at home. There's upsides and downsides to that, there's quarantining that's great, there's flexibility, there's loneliness, there's lack of ability to work with people and connectedness. Now going back to the office space, so many people around the world are doing this hybrid thing of working from home and going back to the office space. 

You need to remember that your susceptibility to getting sick from a virus depends on three things: one, your exposure to the virus, the dose of the exposure, the duration of the exposure, and the third thing is your resilience. Good ventilation systems, masking, distancing, filtration of the air, being outside, dilution of the virus, all that helps reduce your dose and duration of exposure, but your resilience is something you can do something about. 

Integrative medicine, integrative health, and those seven core areas of integrative health that the Andrew Weil Center for Integrative Medicine has defined can help you optimize your own resilience. It doesn't mean you won't get sick, it doesn't mean you're going to be protected totally from getting sick, but it will allow you to optimally prevent yourself from getting sicker than you might, so resilience is really important, and I would recommend that you provide in the materials associated with this, the My Wellness Coach app. The Center developed an app that came out, it was launched in February 2020, and we released it for free in March of 2020 when resilience was so important. It can help walk you through those seven core areas of health; sleep, resilience, movement, social interaction, spirituality, nutrition, and the environment and see which one you need to tweak to optimize your own resilience and protect you from getting too sick.

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