Episode 22: Innovation happens one breath at a time

Science Talks Podcast with white microphone on a dark blue background, surrounded by white icons representing various science fields/tools
World-renowned physician-scientist Dr. Fernando Martinez says that true innovation goes against the established way of thinking and should surprise people.
Dr. Brittany Uhlorn, BIO5 Institute

One in every 13 Americans suffers from asthma. UArizona Regents’ Professor Dr. Fernando Martinez, also a former director of the BIO5 Institute, describes how witnessing his mother’s asthma attack ignited his passion to research and treat patients with this condition. The Director of the Asthma & Airway Disease Research Center shares what the buzzwords “transdisciplinary” and “innovation” mean to him, and how he keeps both of these factors in mind when studying genetic and environmental interactions when thinking about potential treatments and a cure for asthma. 

 

What originally sparked your interest in studying asthma?
I always love to tell this story because it really marked my life. 

I was four or five years of age when I was awakened in the middle of the night by my dad shouting, “breathe in, breathe out,” to my late mother, who was having a very severe asthma attack. I opened the door of my room, and I could see my mother struggling to breathe. My father was pumping a hand nebulizer so that she could breathe, but she was having very great difficulty. 

I promised myself that if I could, I would one day find a cure for asthma, and it was ingrained in me for all my life. Fortunately, I have been able to work in the field, and while I haven't been able to cure it yet, at least I have tried to find new ways in which to prevent and treat it.

You've made many important contributions to understanding the role of gene-environment interactions in asthma and other illnesses. How is this novel path driving further discovery in the prevention of these illnesses, and how is that woven into your projects?

BIO5, by definition, is an interdisciplinary enterprise. There are few other examples that I know of that are clearer about the importance of interdisciplinary research than the discovery of the importance of gene-environment interactions in asthma. 

Because of the way we're trained, scientists all over the world go in our silo, and so for many years and still today, scientists that are experts in the environment study asthma from the point of view of the environment, and scientists that are experts in genetics study asthma from the point of view of genetics.  

Important discoveries and prevention, therapies, and new understanding of what causes asthma have come from both environmental and genetic studies, but what we were among the first to discover is that these really work in conjunction with each other. They don't work separately. 

With this dual approach, we can get exactly the right group of people who are going to benefit most by a preventive strategy. If you put in the potential genetic factors that may enhance the preventive effect of a pharmaceutical product, you're going to target the right population.

This way of thinking, which appears so obvious to me, was just not there initially.
 
That's the extraordinary thing about innovation. Innovation is always strange and often opposed because it is not the way people think. But that’s why innovation is so important - because it goes against what has been thought. If people don't get very surprised by what you're proposing and oppose it, maybe it's not sufficiently innovative.

Initially it's not successful because there is an established way of thinking, which has been important for many years. I'm not denying that I'm part of an established way of thinking, but the reality is that's the way we advance. We advance with new ideas. I always say innovative ideas are always crazy. The problem is that not all crazy ideas are innovative. They're just crazy. 

You have to have a lot of ideas, and if they're crazy, you just go to the next one. Don't be afraid of something that looks very crazy. Just test it, and if it's not working, go to your next idea. That's how all these things, like studying gene-environment interactions, come about.

Some of your work focuses on the role of the microbiome in asthma. Tell us a bit more about how microbes affect our overall health.

Much like you need to be tested to learn how to walk, your immune system also needs to be tested to develop. We don't come with a program that is going to develop our immune system in the way it needs to develop when we’re young. We come with a very elementary system that is based on maternal influences, so the child needs to interact with the environment so their immune system can learn how to distinguish between danger and friend. 

The way to train it is to be exposed. When you decrease exposures, you decrease the capacity of the new system to be trained, and therefore the immune system is not capable to distinguishing friend from foe.

In the last hundred years or so, we have changed the way in which we were raised from the previous hundred thousand years, which was to basically be exposed to everything. We didn't even know what a bacterium or a virus was, so we were exposed, and this led to a lot of deaths. What's happening now is that we will have to teach our children artificially to learn what is foreign and what is friend because we don't want to go back to exposing our children to all the risks of the world out there. 

That's the quest our group is on now - what do we need to do to simulate the microbiome, and how are we going to replace the effect that they have in allowing our immune system to be trained and mature in the right way? 

You've had, and are still involved in, several long-term studies, and you’ve gone on to lead the Asthma and Airway Disease Research Center. I'd love to hear a little bit of an update on the longevity and the impact of these projects. 

We're a truly transdisciplinary group. We have a basic immunologist, epidemiologists, clinicians, statisticians, and molecular biologists that are all working together at the Center around these human-based studies to which we apply all this knowledge together. 

One of those studies is the Tucson Children's Respiratory Study that has been funded continuously for the last 41 years. It's a group of newborns that were initially enrolled in 1980-84, and we are still following between 700 and 800 of the original 1,200. We have still, in the freezers at BIO5, the cord blood that we collected 40 years ago. With that blood and new technologies, we will be able to know if proteins that were present at birth determined the risk for respiratory disease, which is quite extraordinary. 

For example, the factors that determined the maturation of the fetus are factors that determine the way in which we age. The placenta must age, because that's the way it's going to be able to detach from the uterus and be expelled. Sometimes it starts aging earlier, and the children in those cases grow less. Those same children who had this problem when they were in utero are the ones that age faster later in life. 

In other words, what you experienced when you were in utero has an influence on what is going to happen in your life.
 
It's just a very recent discovery we have made that teaches us new ways to understand processes like aging of the lung in our case, but I'm sure it applies to anything else that may be useful in the future for better aging.

That's what transdisciplinary truly means - to have an open mind and to pursue collaborators for discoveries may have an influence on health. The great power of these very long studies is that they connect things that otherwise cannot be connected. 

You are a practicing physician alongside of an incredible research career. For those who are aspiring physician-researchers, talk about some of the opportunities that you've had because you were able to take what you were learning and apply it in a controlled setting?

My role as a physician is to solve the problem of the patient. That's the big advantage of physician-scientists - the basic scientists have the advantage that they may discover relativity, just because they want to. The great advantage of physician-scientists is that they may discover the cause of cancer or certain type of cancer, or they may discover the cause of asthma, or they may discover the new ways to make a better life for the elderly. 

We have the patients in front of us. We know what their problems are, and therefore we can address and try to solve those problems. Both basic science and physician approaches are legitimate, and both are necessary. We just need to give young scientists and physicians the opportunities to take both. 

BIO5 is one of those great opportunities. We need to put this into the brains of kids that come for KEYS that there's opportunity everywhere in science and within the BIO5 enterprise. And one of the opportunities is people who think about the patient in the first place - they have the advantage that they can answer questions that those patients are eagerly needing an answer for.


About the University of Arizona BIO5 Institute
The BIO5 Institute at the University of Arizona connects and mobilizes top researchers in agriculture, engineering, medicine, pharmacy, data and computational science, and basic science to find creative solutions to humanity’s most pressing health and environmental challenges. Since 2001, this interdisciplinary approach has been an international model of how to conduct collaborative research, and has resulted in disease prevention strategies, innovative diagnostics and devices, promising new therapies, and improved food sustainability. 


LAND ACKNOWLEDGEMENT We respectfully acknowledge the University of Arizona is on the land and territories of Indigenous peoples. Today, Arizona is home to 22 federally recognized tribes, with Tucson being home to the O’odham and the Yaqui. Committed to diversity and inclusion, the University strives to build sustainable relationships with sovereign Native Nations and Indigenous communities through education offerings, partnerships, and community service.