Precision Medicine: Challenging the One-Size-Fits-All Approach to Health - Paul Franks (Transcript)

Here is the full transcript of Dr. Paul Franks’ talk titled “Precision Medicine: Challenging the One-Size-Fits-All Approach to Health” at TEDxKI 2024 conference.

Listen to the audio version here:

TRANSCRIPT:

The One-Size-Fits-All Problem in Medicine

Imagine a world where there is only one size of shoe. It would be perfect for some of us. Others would get by, but some would experience great discomfort. Now, what if we lived in a world where medicine was designed as if one size fits all?

Where the average effects of treatments and risk factors at a population level were meant to reflect the effects in each and every one of you. That’s exactly the world within which we live. From a young age, I’ve had a passion for running.

Personal Journey into Health and Performance

I found ultramarathons and triathlons in my teens, and by the age of 21, I’d finished my first Ironman triathlon. I still love to run. In the middle of the pandemic, I took a few days off and I ran from Chamonix to Nice, a distance of 350 kilometers and 15,000 meters elevation.

This interest in human performance nurtures a deep curiosity in energy metabolism. I once wore a continuous glucose monitor during an Ironman. Over the course of 10 hours, I consumed energy gels and drinks with the same amount of sugar as 30 liters of cola.

And yet my blood sugar levels remained stable throughout because a healthy body has the machinery necessary to transfer sugar into the energy that the cells and the organs in our bodies can use. It’s a remarkably proficient machine when it works. My journey into understanding energy metabolism led me to study exercise physiology at university.

From Exercise Physiology to Diabetes Research

Here I took what I learned to optimize my own performance through tailored diet and training regimes. But my interest gradually shifted to a broader understanding of health and disease, particularly to elucidating the mechanisms that underlie type 2 diabetes. It turns out that the biological systems that help sustain long bouts of endurance exercise are the same systems that fail in diabetes.

Type 2 diabetes is sadly a very common disease, usually beginning in middle age. Its cardinal feature is chronically elevated blood sugar levels, which if left unchecked, will be toxic to the cells and tissues in the body. There are roughly 500 million men, women and children with diabetes on the planet today. And by the middle of this century, that number will have far exceeded a billion people.

Genetic Discoveries and Precision Medicine

Most of these people will die prematurely from cardiovascular disease. It’s devastating. My studies took me to Cambridge in 1999.

I entered the university at an exciting time because the first draft of the human genome was in the process of being completed and genetics was starting to transform medicine. The very week I arrived, one of the groups I was to work with published a landmark paper in the New England Journal of Medicine. The paper showed that some children with extreme obesity harbor mutations in a gene that encodes leptin, a hormone responsible for controlling appetite, energy expenditure and metabolism.

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This genetic discovery opened the door for genome-guided leptin therapy that had a profound and positive impact on the growth trajectories and on the cognitive development of these kids. But perhaps most importantly, genetics had helped these kids, who would otherwise have shouldered a tremendous lifelong health burden, live their lives to the full. Tools like this are the foundations to an approach in medicine that has improved the precision and accuracy of diagnoses and treatments, a concept that we now call precision medicine.

The Thrifty Genotype Hypothesis

At Cambridge, my research focused on the interplay between behavior, genetics and disease. I’d read a paper published in the 1960s by a clinician scientist called James Neal. The paper put forward a hypothesis that sought to explain why some people, particularly those from indigenous communities, are especially susceptible to obesity and type 2 diabetes.

Neal suggested that there may be a genetic predisposition born out of millennia of evolution where energy demands were high and food was often scarce that favored the transmission of genes that improved energy metabolism. Neal called his idea the thrifty genotype hypothesis. He went on to suggest that these gene variants have been advantageous throughout the majority of human evolution because they favored the storage of any excess energy as body fat and the prudent use of these reserves.

The Impact of Type 2 Diabetes on Native American Communities

But now, when we have abundant access to high energy foods and there’s a much diminished need to be physically active, these same gene variants are driving obesity and type 2 diabetes in these populations. This sparked my interest in the Native American communities of the US Southwest. So on completion of my doctoral training, I moved to Phoenix, Arizona to work at a small research center run by the US National Institutes of Health.

Here I bore witness to the diverse manifestations of type 2 diabetes and the profound impact this has on individuals and families alike. Soon after arriving, I drove out to the hospital at the Gila River Indian Reservation. There I met many young Native American adults with type 2 diabetes.

Some receiving dialysis because their kidneys were failing. Others had had lower limb amputations because the blood vessels that supply oxygen to the cells in the feet had died and others were blind also because of small vessel disease caused by diabetes. It became abundantly clear that a one-size-fits-all approach to healthcare and medicine was woefully inadequate and that we needed an approach that was more sophisticated and nuanced than one-size-fits-all can offer.

The Need for Precision Medicine

This really impacted the way that I viewed my work and it set me on the path towards precision medicine. Precision medicine is not only about making things more precise. It also needs to improve accuracy because we can be very precise by repeatedly getting things wrong.

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For precision medicine to work where contemporary medicines failed, it has to be on target each time.

In other words, the right medical recommendations for the right person at the right time and this needs to be reproducible. Now genetics is undoubtedly a powerful tool in the arsenal against disease by improving both precision and accuracy of diagnoses and treatments.

This is particularly true for rare monogenic disorders caused by DNA mutations that have a profound impact on diseases like childhood obesity through leptin mutations. But disorders like type 2 diabetes and cardiovascular disease are far more complex. They involve variations in hundreds or thousands of genes interacting with behaviors and environmental factors.

The Complexity of Precision Medicine Solutions

And so precision medicine solutions for these diseases need to be more complex too. And they need to use data, not just genetics. Social determinants of health and an individual’s needs, circumstances and capabilities are equally important in determining the success of healthcare and medicine.

In all likelihood, precision medicine of the future won’t be needed for all of us because contemporary medicine works reasonably well for many people, just not everyone. And it’s in that large subgroup of the population where new innovative solutions are needed. Over the past 25 years, much of my research has focused on understanding how lifestyle, diet and exercise impacts the risk of developing type 2 diabetes and cardiovascular disease.

The Misconception of One-Size-Fits-All Lifestyle Recommendations

There exists a common misconception that if we were all to follow standard lifestyle recommendations, this would universally guarantee wellbeing. But let me give you an example from the Lookahead trial, which studied about 5,000 adults with type 2 diabetes. The trial, rather disappointingly, initially found that intensive lifestyle interventions, with one-size-fits-all approaches, do not reduce cardiovascular risk in people with diabetes.

But subsequent analyses revealed nuanced results, showing that there are indeed some subgroups of the population of people with diabetes that respond well to standard lifestyle recommendations and their cardiovascular risk fell. But there are other groups of people with type 2 diabetes where the standard lifestyle interventions increased their cardiovascular risk. And that subgroup were people who had poor glucose control at the start of the study, probably because their medicines weren’t working well.

Precision Prevention: A Stratified Approach to Healthcare

This underscores the importance of stratified approaches to healthcare and medicine that really think about the individual characteristics, their behaviors, their biology. And this is something that we call precision prevention. Just last year, we published a series of papers in one of the Lancet journals.

These papers outlined a structured approach to developing and implementing precision medicine solutions for diabetes and cardiometabolic diseases. Our aim was to augment current medical evidence by integrating new ways of considering data and the translation of that into practice. Traditional medical approaches typically rely on population averages.

But as I’ve already said, one-size-fits-all approaches rarely work well in healthcare and medicine. Precision medicine pivots the focus towards subgroups of the population that share similar characteristics, thereby improving precision and accuracy of diagnosis and treatments. In a groundbreaking study published in 2015, researchers from Israel demonstrated the predictable and controllable effects of diet on blood sugar levels using AI to optimize an individual’s diets to those behavioral and biological characteristics.

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Advancements in Precision Medicine Research

A few years later, we published follow-up studies in the journals Nature and Nature Medicine that demonstrated the variable impact of diet and exercise on the metabolome and microbiome, two intricate molecular networks that influence biological processes integral in many diseases, not just type 2 diabetes. These findings really underscored the remarkable variability that exists in blood sugars and blood fat levels from diet and exercise, and both of those are key risk markers for diabetes and cardiovascular disease.

There are many other promising examples of precision medicine, particularly for the rare monogenic disorders caused by these single DNA mutations. But there are also many promising examples for these more polygenic forms and common forms of diabetes and cardiovascular disease. In a recent international consensus report that maps the evidence base for precision diabetes medicine published in the journal Nature Medicine, we showed again that there are both real possibilities to improve diagnostic classifications and the prediction of treatment effects at a more individual level.

Building on the Foundations of Contemporary Medicine

To see further than others, stand on the shoulders of giants, so Newton said. And through this lens, let’s just consider that any innovation in healthcare, particularly precision medicine, is likely to build on the foundations of contemporary medicine and not completely replace it. We should also keep in mind that most people on this planet who need access to precision medicine will not have available to them the cutting-edge medical facilities that we enjoy here in Scandinavia.

And so most precision medicine solutions will need to be tailored to the environmental, cultural, economic and social circumstances where they’ll be deployed and not just the individual characteristics. Moreover, raising expectations too high will inevitably lead to disillusionment, delaying the implementation of the much needed innovations in healthcare that precision medicine has to offer.

Conclusion: The Future of Precision Medicine

So let me conclude by saying that precision medicine stands at the forefront of a transformative era in healthcare. By integrating diverse data types, considering individual characteristics and strengthening our understanding of disease mechanisms, we can realize a future where healthcare is truly personalized, precise, effective and affordable. Together, let’s embark on this journey towards a healthier and more equitable world.

Precision Medicine: Challenging the One-Size-Fits-All Approach to Health – Paul Franks (Transcript)