What happens when everything you thought you knew suddenly no longer fits the world?
Exposome Perspectives Blog by Robert O. Wright, MD, MPH
“Very simple. It’s obvious, isn’t it? And yet, you’d be surprised how many people violate this simple principle every day of their lives and try to fit square pegs into round holes, ignoring the clear reality that Things Are As They Are.”
Benjamin Hoff, The Tao of Pooh
The “Te” of Danny
What I remember most are his eyes, they were all at once pleading, sad, hopeful, and gentle, as if he thought I had the ability to help him, which I knew even in that moment that I did not. The only thing I knew for certain was that I would let him down. Even so, his eyes had the ability to slow down time, even in the kinetic, hectic environment of a Saturday night in the Pediatric Emergency Room.
His name was Danny. It was 2005, and he was 10 years old. I remember the year because I later told the intern that in my ‘16 years’ of Pediatric practice, I had never seen this in a child. It was a busy night; it was July; outside, it was hot and muggy, so we had a disproportionate number of patients with fractures, lacerations, falls, dehydration, and summer viruses. The intern who presented Danny to me had just graduated from medical school, and this was his first shift. I was impatient, the ER was getting backed up, and we needed to pick up the pace. I didn’t let him finish the history and physical he was trying to present to me—the story of Danny. I heard only a few snippets. Danny was sent in by a pediatric endocrinologist to get his serum chemistries, blood sugar, and serum ketones checked but was otherwise stable. The intern went through his symptoms, which seemed relatively mild for an ER visit and eventually got to his medication list. He read it as I glanced over his shoulder at the growing line of charts piling up in the “to be seen” rack. At one point, the intern blurted out “Glee-blur-id”. I stopped him there. “Do you mean glyburide?” Correcting his pronunciation. “Why is he on glyburide?”
“It’s for his diabetes.”
“That’s for type 2 diabetes, he has type 1 diabetes—it’s different,” I told him.
“Actually, I think he does have type 2 diabetes.” He fumbled through his notes. “Yes, it’s type 2 according to his chart.”
“Kids don’t get type 2 diabetes—that’s adult onset. Kids only get type 1.” I told him over my shoulder as I marched down the hall to Danny’s room, with the intern dutifully following. I paused outside the door to try to create a teaching moment.
“How does glyburide work?” I asked.
“I think it works by stimulating insulin secretion in the pancreas.”
“That’s right,” I continued. “In type 1 diabetes, the beta cells that make insulin are destroyed by autoantibodies, so glyburide is ineffective because those cells are gone. That’s why it’s used for type 2 diabetes. Type 2 comes from chronic obesity and the slow onset of resistance to insulin. It takes decades to develop, so the islet cells still exist and can make insulin, but the body is resistant to its effects. Glyburide can only work in this setting. Danny must have a rare congenital illness if he’s on it. Let’s find out what that is.”
I swung open the door and whisked in to meet Danny and his mother.
He was about 4 and a half feet tall, but that’s just a guess based on memory. In our initial encounter, he was sitting on the gurney, so it’s hard to know. But in that moment, I reassessed everything I thought I knew about pediatrics while trying not to look shocked or surprised. I asked the intern for the chart. I had neglected to look at his weight during the presentation—108 kilograms, or over 230 pounds, at age 10. In my mind, I became a parent.
“He’s still a kid,” I thought to myself. “He’s self-conscious, trying to fit in everywhere he goes and likely not succeeding. Go easy on him.”
I proceeded to introduce myself and tried not to show any emotion or judgment when I looked at him and his mother. It took conscious effort, and the situation itself seemed to make time slow down. In that moment, I also realized I was wrong—Danny did have type 2 diabetes. His body was that of a middle-aged man who needed to change his lifestyle, but he was only 10. Everything I thought I knew was now open to reevaluation. The world had changed.
Later on, I apologized to the intern for my skepticism about his presentation. I needed to work on having an open mind. I was forcing a square peg into a round hole because I was unprepared to see the radically changing world. I tried to counsel him and his mother on eating habits and exercise, something I knew he had heard a thousand times in his young life and something that I, as an ER physician, was ill-prepared to do. Medical schools barely touch on nutrition counseling. His mother nodded along as I spoke. Hoping, I imagined, that this time would be different—that I had something helpful to tell them. As he waited for his lab results, I scanned through his chart to find his growth curve, history, and diagnosis. He had no known metabolic cause for his weight, he just liked to eat—particularly junk food, and he rarely exercised. He blushed when his mother told me that, trying to hide the shame I imagined, looking down at the floor. His mother didn’t deny that she bought endless junk food and seemed helpless as well when I asked why she gave him so much access. I wished I could offer a solution, but I didn’t think of food as an addiction in 2005. I think about it very differently today. This was where we ended up that night. As time passed, I saw more and more type 2 diabetes in children. “Adult-onset” diabetes had transformed into a pediatric disease.
By my count, by 2005 I had seen about 80,000 patients. I was certain by this stage of my career that I knew what was common and normal and what was not. In 2005, I learned the world was changing, but I had no clue why. Danny taught me something that day. Some may think that his life is suffering, but his story is not over. I see him as “Te”- which means virtue. Danny is a teacher who shows the power of the small. We should listen.
The Tao of Exposomics
Taoist philosophy teaches that what others see as negative can often be something positive. Meeting Danny taught me that the world had changed, and so I adapted my understanding of the world. Type 2 diabetes now happens in children. I learned that, but that doesn’t mean that I accept this state of things as natural. Too often a scientist’s view of biology is driven by the silos in which we train. We learn a set of tools to conduct studies through the lens of a discipline (genetics, psychology, chemistry, etc). We study the same diseases, but we often know little about the findings of a different field on the same illness. In Taoism, understanding weaknesses is the key to growth. This is the concept of the “beginner’s mind” vs the “expert’s mind”. Beginners have openness. They are eager and think without preconceptions. After we become “experts,” we develop fixed ideas and preconceived notions. We filter information based on what is “already known.” For example, this twin study shows that obesity is genetic so we must continue the search for the genes. Yet, this scientific “fact” denies the obvious. We have to eat food to gain weight. All food is not equal, and we all can easily recount how different our childhood environments are from today’s world. What most likely changed to cause the obesity epidemic- genes or environment? Yet, so many studies have been done on the genetics of obesity that the media has begun to tell us obesity is genetic.
On 60 Minutes, as recently as 2023, a physician stated, “If you were born to parents that have obesity, you have a 50-85% likelihood of having the disease yourself.” This has to be a twin study, and it flies in the face of increasing obesity rates, because so few of us are twins. Our parents’ generation was thinner than ours, and our grandparents were even thinner than our parents. Data that come from twin studies are discussed in the press as if the findings apply to everyone, but they don’t. There is an assumption that disease differences among identical and nonidentical twins are solely due to genetics, but twins always share the same pregnancy environment within their mothers, and they also share a lot of childhood environment as well. “Nature” may be shared but so is a ton of early life “nurture.” Twin studies can’t distinguish between “gene-environment interaction” vs “genetic” effects. To understand gene-environment interaction, you have to measure the environment. Both are equally important but that doesn’t happen in twin studies.
In the Tao of Pooh, Benjamin Hoff describes how science likes to put vague labels on what it cannot explain. “Curious: ‘Why do birds fly south?’; Science: Instinct’”, which sounds a bit like “Curious: Why are obesity rates increasing?; Science: Genes”. I will say it again. Our genes haven’t changed in the last 40 years, but our environment has radically changed. The chemicals and nutrients in our food, our water, and our air are different. The way we socialize, the economic stresses of buying a home, paying for college, covering our healthcare costs, our political polarization, etc. All of these environmental factors are different; our genes are not. So, what is the more likely cause of our changing rates of illness and obesity? If we think genetics is important, then we must also measure the environmental factors that control gene expression. Otherwise, we’ll never understand how genes work, and this cycle of incremental progress will continue.
Nature and Nurture: Please, no more studying “Nature” by itself.
We need to figure out what has happened to our society that made us so ill, so quickly. We need to stop ignoring the role of “nurture” just because a twin study claimed something is “mostly” genetic. It’s not Nature vs Nurture—it is “Nature and Nurture”. Biology doesn’t let our genes work without our environment. Our genes operate as a duality with our ever-changing environment. Our inability to find the specific “genetic” causes of diseases is now our reality. We point to twin studies to justify an ever-expanding genetic approach, even though these studies can’t get any more specific than claiming a percentage of the disease is genetic. This is our current reality, instead of looking for “gene-environment interactions.” Gene-environment interaction will never be found if the environment is never measured. We are stuck, but it doesn’t have to be that way. “Things are the way they are” while having a Human Genome Project and while not having a Human Exposome Project. The former didn’t solve our problems. That is not a coincidence, and nothing will change if we continue down this path. It has now been 20 years since Christopher Wild (i.e. the Christopher Robin of Exposomics) proposed the Exposome concept. We need a beginner’s perspective.
Nature and Nurture are the Yin and Yang of health and disease. Just as Yin and Yang are not in conflict in Taoism, neither are genes and environment in a battle. They are complementary forces, interdependent and constantly interacting to create a dynamic balance. We need to understand both to crack the complex disease code. Once again, our genes haven’t changed, but our environment has. So why aren’t we investing in figuring out our exposome with the same energy and resources that we put into the Human Genome Project? This would benefit geneticists as it’s not a radical shift in our understanding of biology. It is fully consistent with biology and would show us what was happening to Danny. He is 30 by now. He may soon have kidney disease, heart disease, joint problems, etc. All the problems that used to plague us in old age aren’t likely to wait much longer to attack him. He doesn’t have time to wait. These diseases will come earlier in his life than they did in ours. What is his future? What is the collective future of our children and grandchildren if we don’t turn these trends around? Do we think we will solve these problems with mass gene therapy? Along with treating obesity with GLP-1 drugs for those like Danny who need help immediately, perhaps we can also try to prevent it, so not everyone needs a drug for life? We must embrace curiosity and ask the question: “Why are these changes happening?” In our recent past, obesity was not the norm. In other countries today, like Japan, it is not the norm. So, reverting back to a healthier population is possible. It is not a pipe dream. Things are as they are. I don’t deny that, but when we look for genetic causes to “everything,” we are denying the obvious changes in our exposome that got us here. Genetics is a square peg and obesity is a round hole. So I ask again, politely, just as Pooh Bear would. “Could we please consider another approach to research other than Nature vs Nurture? It’s not working.” I don’t think this should be done alone. We should partner with genetics on this project. We can’t keep working in silos. Some of us can resist the changes in our environment. We know genetics plays a role, but it is part of a yin and yang with the environment and not the sole driving force. We need to look at both, which means finally investing in studying the exposome so we can get some answers. For our children’s sake.
“How can you do what you ought
If you don’t know What You’ve Got?
And if you don’t know Which To Do
Of all the things in front of you,
Then what you’ll have when you are through
Is just a mess without a clue
Of all the best that can come true
If you know What and Which and Who”
Benjamin Hoff, The Tao of Pooh