There's a hidden clock that underlies every process of every living thing – from when our cells start dividing to how quickly we age. Researchers at Darpa, the Pentagon's extreme science agency, believe they can find it, using a mash-up of biology, code-cracking, mathematics and computer science.

If the effort succeeds – and, boy, is that a big if – the recently announced Biochronicity program could help us understand why cancer is so hard to beat, how stem cells self renew and why cells are programmed to die. In other words, it'll be one of the biggest breakthroughs Darpa has ever had.

Scientists these days have a half-decent sense of how our internal processes work. For example, we know that the carbs we eat are broken down into glucose and then broken down further into ATP, the energy that powers every cell. ‪But when exactly that breakdown happens, what precisely triggers it and how long each step takes is less known.‬ Considering how important timing is in other areas of science — from chemistry experiments to quantum mechanics — it's surprising how little emphasis it's given in biology.

Because it's clear that all life processes depend on some internal time keeping. This can occur once in a lifetime – say, the hormones released during puberty – or as daily occurrence, as in the regular metabolizing of food into energy. While scientists have uncovered many different components of our inner clocks, "none have been identified as the single lynchpin or master regulator of the greater system that controls temporal expression."

Darpa wants to find the master regulator, and then use that knowledge to develop "predictive models of molecular-timed events, cell-cycle progression, lifespan, aging, and cell death, response to stress, and useful treatment strategies and drug delivery." The key word is predictive. Darpa is no longer content with biology as a descriptive enterprise, watching cells and enzymes do their thing. Now, it wants mathematical models and algorithms and theories to tell what they'll do next.

In that way, the agency is looking to piggyback on the work of Alan Turing, the computer science pioneer who predicted that much of biology would be revealed to be the result of a series of patterns; more than five decades later, he's largely been proven right.

For the biological processes where timing plays an obvious role, such as aging or cancer, we still don't have a clear sense of when – or why – they take place. Scientists know that certain bits of DNA on the end of chromosomes called "telomeres" shorten each time the cell divides, playing a role in cell aging and eventual cell death. They also are pretty sure that normal cells turn into cancer through a series of mutations that interfere with error-correcting and normal tissue growth. Yet precisely when a cell will reach its pre-programmed death or when a cancer cell will begin to replicate is still unknown.

"While time evolution is paramount in physics, chemistry and engineering, the full implications and working mechanisms of biological time have not yet been discovered," the report states. Darpa hopes a slightly different way of doing biology will put these processes back on the clock, so to speak.

The when of biology hasn’t been completely ignored. New research has uncovered how stress levels and diet can affect the biological age of an organism as opposed to chronological age, or calendar years. Since the first "clock genes" were discovered in the 1970's, scientists have uncovered all sorts of genes that play a role in the daily rhythms and processes in everything from cyanobacteria to humans.

But there is much that remains a mystery, not least of which is how all these genes, cellular processes and environmental factors interact. For years scientists thought that sequencing DNA would uncover the "gene-for" almost everything, unraveling the mysteries of disease and resulting in new drugs and gene-specific treatments. It didn't exactly pan out that way. Scientists now know that many other factors — from conditions in the womb to signals within the cell — affect how, and when, genes are expressed.

So to uncover the calculus within the genome, it might take some looking beyond the genome. Genes may contribute a few elements to the inner clock, but they interact within a larger scaffolding of cell processes and environmental factors. Furthermore, all those interactions may not be subject to any top-down control of a particular actor. Darpa's "master regulator" may turn out to be more of an interlocking network of systems.

Darpa was once known for taking on the most absurdly complicated challenges – from building artificial brains to developing energy weapons to grokking the depths of quantum mechanics. But, in recent years, the agency has devoted more and more of its resources towards the relatively mundane, like social media analyses, online medical portals.

Biochronicity is a return to the fundamentals, the building blocks of science. Of course, this mission to uncover how time is encoded in our biology will begin with tiny steps. But now could be the perfect time to start.

Photo: pickerel/Flickr

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