Deep phenotyping expands how we measure health and disease
Making sense of complex relationships
Consider cholesterol: It's agreed that high cholesterol can block blood flow and cause serious health problems, yet some with "high cholesterol” live long, healthy lives.
When nutritionists can’t even decide which foods are healthy, it’s hard to avoid feeling like this whole “health” thing is anything more than a random gamble. One can’t help but wonder, What are these “healthy” people doing right? Is it just “good genes”? What control do I even have? As individuals striving to be healthy, we share this frustration on a very personal level.
As biomedical researchers, we sympathize with the contradictory nutritionist. We are at an awkward stage in medical discovery. We know the right questions to ask about family history. We know lifestyle matters. We know the details of how cholesterol is made by the cells of the liver or harvested from the foods we eat. What we don’t know is exactly how all these factors interact. If someone has risk genes for heart disease but eats a lean diet and exercises regularly, will they develop heart disease? Did their lifestyle change their fate or did other genes play a role? For the first time in history, we have the opportunity to collect and compute the huge amounts of information needed to identify such complex interactions.
Evolving standards in medicine
Until the 19th century, our knowledge of medical ailments was largely philosophical. Since the time of the ancient Egyptians, bloodletting was administered as a treatment for anything from flu-like symptoms to seizures. While we may consider such a practice barbaric by today’s standards, physicians at the time thought they were helping patients by restoring balance to the body. With time, scientific discoveries introduced the ways bacteria, viruses, toxins, and even our own genes are often the culprits behind disease.
Today’s physicians and medical researchers are highly trained to assess commonalities between symptoms and patients to identify the root cause of an ailment and tailor treatment accordingly. Your doctor can deduce whether your sore throat is caused by a virus or bacteria, and then prescribe a targeted treatment to quickly attack the perpetrator of your symptoms and minimize symptom progression or other unnecessary interventions.
In some areas, like cancer, genetic information has proven useful not only for diagnosis, but also for predicting response to treatments. Often referred to as “personalized” or “precision” medicine, assessing disease in the context of an individual’s unique genetics and lifestyle factors provides the information required to optimize care.
Seemingly in spite of all this knowledge, we still struggle to predict an individual’s health journey. For reasons unknown many will not respond to the most personalized and effective therapies. Some are not diagnosed at all, as physician after physician is puzzled by a constellation of symptoms and limited tools to measure them. We stand on the precipice of countless discoveries; the key is to improve the ways in which we measure health and disease.
Deep phenotyping is a growing approach in biomedical research that focuses on understanding the full spectrum of possibilities for any aspect of health. This may not seem too revolutionary, and that’s because it isn’t. We have always known that individuals are unique, and that individuality is reflected in the ways we experience health and disease. Deep phenotyping emphasizes the detailed analysis of these variations.
Traditionally, “outliers” were considered a blight to research - the 3 people out of 10,000 who did not respond to treatment; how some people may have symptoms drastically different from those with similar genetic markers or predispositions. These data points questioned the central premise of the study. Maybe the drug wasn’t working exactly as expected...Maybe the gene was less important than previously thought...
...Or, maybe there is something unique about those individuals which changed their response. This isn’t always a negative quality. Think of the healthy individual with high cholesterol. What makes them handle this risk factor differently? Deep phenotyping can help answer these questions by understanding the health on an individual level. If we can better map how our genes, habits, and environment all interact then we will identify new ways to treat disease and promote health.
A path to improving clinical care
Our mission is to spark discovery for rare diseases. Through community support, we can collect the information needed to fuel the next decade of discovery. Precision medicine requires an understanding of individual health stories to capture the true spectrum of health and disease. Additionally, we must document and comprehend how these traits change over time in each of us to uncover the impact of other genetic and environmental factors.