From Kinexum Founder - An Epiphany

Zan Fleming, MD

We are entering the season of lights, celebrations, and imagining peace on earth.  The Christian celebration of Christmas ends on January 6 with the observance of Epiphany, marking the visit of the Magi—wise men—to the stable.  I love the word and concept of epiphany, which is much broader and older than its liturgical use.  To the ancient Greeks, ἐπιφάνεια, epiphaneia, meant a striking manifestation, an experience of sudden and striking realization.  Its meaning evolved to include the unexpected grasp of reality precipitated by a simple event or other trigger.


I experienced an epiphany at the first Metabesity Congress in London though this event did not qualify as simple.  It was one of the most enlightening, engrossing, and consequential conferences of any that I have ever experienced.  As Thomas has described, it was a meeting of preeminent experts from multiple, diverse disciplines who deeply connected with one another around a very broad theme. 

My epiphany is that after a career centered on developing therapies to manage or palliate disease, I should devote my remaining days to things that prevent disease or restore health.  Though my career has focused largely on pharmaceuticals and biologics and was enriched by many exciting chapters therein, my epiphany includes the realization that drugs will be only part and perhaps a minor part of solutions that prevent disease. 

We still have opportunities to develop better drug treatments for diabetes and cardiovascular disease, but we are hitting the wall in developing cholesterol and glucose lowering therapies.  We have promising technologies such as the closed-loop insulin pump/artificial pancreas and encapsulated insulin-secreting cells, but these are likely to be eclipsed by approaches that restore physiologic insulin secretion.  Progress in cancer therapeutics is startling, but we continue to be stymied in developing treatments for glioblastoma and pancreatic cancer.

We do not yet have any good leads on preventing these devastating cancers, but we are starting to see opportunities to reduce their risks.  Part of the opportunity for reducing risks of not just cancer but other members of the Metabesity constellation—neurodegeneration, diabetes, cardiovascular disease, and the aging process itself—involves attacking the shared metabolic roots of these conditions.  This is not to imply that we will find silver bullets that will eliminate broad swarths of chronic diseases.  More likely, we will find interventions that primarily improve one major condition, but leverage improvements in others. 

Metformin is perhaps the best example of such a prospect.  This old, naturally-occurring drug has long been the first line therapy for type 2 diabetes, but increasing evidence suggest that metformin reduces cancer and dementia risks and the aging process.  The hypothesis that metformin could reduce risks of age-related complications is elegantly described by speakers at the London conference, Nir Barzilai and Stephen Kritchevsky and their co-authors.[i]  Their hypothesis is about to be tested in the TAME (Targeting Aging with Metformin) trial, which will use a composite primary efficacy endpoint that includes cardiovascular events, cancer, dementia, and mortality.  This is truly a Metabesity trial of epic importance.  TAME could lead to an indication for use of this simple, inexpensive drug in all humans.  

Another sensibility of the ancient Greeks that I love is that they viewed time as having multiple aspects. Their word, Chronos (χρόνος), corresponds to our modern use of the word, time, and its units of hours, days, and years. The Greeks used another word, Kairos (καιρός), to indicate the right, critical or opportune moment.  We are now in the era of Kairos for preventing non-communicable diseases.  This represents the next, and perhaps the ultimate, frontier of medical science.  We are just at the beginning of this quest to prevent these major diseases and modify the aging process.  The challenges are daunting, but the opportunity is formed by the shared understanding that preventing these major diseases is approachable as a multidisciplinary project.  Each of us can contribute to this venture.  Will you join me?