Out of Order: Mutants Among Us

It might be time to start looking at the reasons why some people don't get certain diseases despite so many factors saying they should. Such an approach might help lead us to new ways of preventing or curing what ails us.

Randall C Willis
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We all know those people. The ones who never seem to get sick. The ones who chain-smoked in their youth or partied every night, living on the edge of social excess only to soldier on well into their 80s or 90s.
We also know other individuals who live incredibly healthy lifestyles—eating right, exercising regularly, going for regular medical check-ups—and yet suddenly drop with a heart attack or show up with a diagnosis of breast or colon cancer.
Why such a great divide in how people live their lives? Why do some seem so much more resistant to the ravages of lifestyle and time?
This was a question that arose recently in two separate conversations and signalled to me a significant philosophical change in how we try to understand human health and disease.
For the most part, health and healthcare of the last century have focused on illness rather than wellness. A patient complains of various symptoms, so we run a battery of tests and provide a diagnosis that becomes the foundation of treatment.
Over time, we perform physiological and epidemiological studies on several patients with the same diagnosis and try to determine patterns of disease—lifestyle, environment, genetics—that lead to new treatments.
But what if those hyper-healthy outliers could provide some deeper clue as to what was going on?
What if those individuals weren’t free of disease so much as free of disease pathology?
A few weeks ago, I was asked to judge a series of immunology graduate students at the University of Toronto on their ability to communicate their research to a lay audience—an amazingly worthy endeavor for any graduate department. One of the talks, however, pointed exactly to the hyper-healthy scenario.
The student in question was studying multiple sclerosis (MS), a condition that occurs in women three times as often as men, and in particular, she noted that healthy men had much higher, natural levels of a protein called PPAR-alpha than healthy women.
Several studies have shown that PPAR-alpha is a protective factor against auto-inflammatory responses typical of several conditions including MS. And perhaps helping to explain its natural gender imbalance, expression of PPAR-alpha is sensitive to androgen levels.
Thus, it would appear that men may just be naturally better protected against the onset of MS because of some natural biological advantage.
For the purposes of the Toronto immunologists, this opens the possibility of developing a better MS trap by finding ways to stimulate PPAR-alpha activity or levels.
But rather than rely on such clues to occur in the course of other research, The Resilience Project wants to actively identify such protective pathways. I first heard about this project when reading a blog by Hailey Reissman for TED2014.
“The vast majority of [healthy] people are not carrying genetic risks, but are there a few sets of individuals who are walking around with the risk that would cause a disease and yet something hidden within them is keeping them from exhibiting those symptoms,” opined Stephen Friend, project investigator, to the TED audience.
Friend is also president of Sage Bionetworks and affiliate member of Seattle’s Fred Hutchinson Cancer Center.
Thus, rather than simply screen the genetics of healthy individuals to provide a baseline contrast to the genes of disease patients, the project seeks those unique individuals who carry genetic markers for disease but who never manifest the disease.
In other words, those people who remain healthy despite their genetic legacy.
“Let us look at adults who are over 40 years of age,” Friend suggested, “with a family history of disease, maybe, and let’s go and screen them to find those who carry genes for childhood diseases—in hopes of finding those special strong heroes who somehow have avoided inherited childhood diseases.” 
Once those individuals have been identified, it may then be possible to determine what makes them so special and then how to leverage that knowledge to help the less advantaged, much as is being targeted with the work on PPAR-alpha in MS.
The approach completely flips the health paradigm, making wellness the focus and increasing the hope that the answers to disease may come from within rather than without.
And if you had to join the mutant class, you have to admit the self-healing properties of Wolverine—maybe without the pain of an adamantium skeleton—is a nice place to start.
You can read more about The Resilience Project at http://resilienceproject.me/.

Randall C Willis

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