Around the beginnning of the 21st Century, a husband and wife team consisting of Dorothy and D. James Morre, confirmed that the biological clock – timekeeper for virtually every activity within living things, from sleep patterns to respiration – is a single protein.

This protein has been proven to be responsible for setting the length of periods of activity and inactivity within cells. If the protein is altered, an organism's body will experience "days" of different length – ranging from 22 to 42 hours in length in some cases. The discovery could have far-reaching implications for medicine. "We can now begin to understand the complex chain of events that connect the clock to events in the body," said Morre. "Since the clock affects nearly every bodily activity, this discovery holds myriad potential applications, from minimizing jet lag to determining when best to administer cancer drugs."

The research, which appeared in the journal Biochemistry, was the culmination of four decades of work and a lifelong fascination of James Morre. "I first set out to find the source of the biological clock in 1962, when I was still a student," he said. "Back then the question was the subject of perennial and lively scientific debate. Theories abounded as to why the body was able to keep its own rhythm – some thought it was bound up in cellular chemistry, but others thought it could be influenced by anything from the lunar cycle to sunspots. No one could prove anything conclusively, though, so the physicists had a field day arguing about it."

The argument was more than just an intellectual exercise. Early in the 1960s, scientists already knew that cancer patients and the elderly often experienced disorders thought to be related to the biological clock. Later in that same decade, it was found that astronauts suffered bone loss and muscle wastage due, in part, to space travel's effects on their internal clocks, and the first evidence of the clock-related ailment of jet lag, was being experienced by air travelers. "We knew little for certain," Morre said. "But I always thought a better understanding of life's processes would result if we knew what made them tick."

Previous research also provided another clue to the puzzle in the form of heavy water. This isotope of hydrogen -- or water made of two atoms of deuterium -- was found to alter the biological clock to run on an extended day. "Lots of heavy water was available back then, as it was needed for nuclear reactors," Morre said. "Investigators discovered that if you fed cells heavy water, they would operate on a 27-hour day. It was a clue that the clock had a biochemical basis, but heavy water's effect was almost forgotten as other explanations for the clock gained favor." As forty years passed, Morre used his research time to work on other projects. However, he never completely stopped his efforts to investigate the workings of the biological clock.

Another project involving an examination of cellular growth, yielded an important discovery. The Morrés discovered that cells increase in size at a periodic rate – they enlarge themselves for 12 minutes, then rest for 12 before growing again. The complex interaction of proteins is the basis for many activities within cells, and James Morre theorized that some undiscovered proteins were responsible for the 24-minute growth cycle. The new discovery came when the team found that a single cylinder-shaped protein molecule with a unique characteristic regulated the cell enlargement cycle. This particular protein had two activities: one served as a catalyst for growth activities for 12 minutes and then rested while its other activity took over for the next 12 minutes.

"Our model is that of a Janus-head protein with two opposing faces," he said. "One 'face' handles cell enlargement. Then the protein 'flips over,' allowing the second face to carry out other activities while cell enlargement rests. While two functions from a single protein had been seen before, what is totally unique here is that these activities alternate, and with very precise timing. The activities don't both run all the time, but instead alternate to generate the 24-minute period length." To confirm that the protein was responsible not just for regulating growth but for all activities set by the biological clock, Pin-Ju Chueh, (at that time, a microbiology graduate student in Dorothy Morre's lab), isolated the gene which produced the protein within cells.

The team then cloned the protein and altered it in ways that produced different period lengths. "We found that we could produce clocks with cycles of between 22 and 42 minutes," James Morre said. "The 'day' which the cell experienced was precisely 60 times the period length of the protein's cycle. We even found that feeding cells heavy water gave them a 27-minute cycle of growth and rest, so that old piece of information served to confirm our theory." Morré confirms that this discovery could be applied to a great number of biological issues.

"Now we have an opportunity to tell how organisms tell time," said Dorothy Morre, Professor of Foods and Nutrition in Purdue's School of Consumer and Family Sciences. "This could give us new insights into cellular activity, such as cholesterol synthesis, respiration, heart rhythms, response to drugs, sleep, alertness – there's so much." While it is presently difficult to make the biological clock speed up or slow down, it can be reset, a fact which could assist the sleep-deprived.

"This discovery also affords an opportunity to improve our methods of clock setting, from minimizing jet lag to correcting sleep disorders," Morre said. "We might even be able to develop simple artificial clock-setting environments to aid astronauts and those living near the Arctic Circle, where day-night cycles are absent for long periods." While the research could be applied to many disorders, the newly discovered protein first needs further attention.

"It is very difficult to look at the protein," James Morre said. "Usually with unknown proteins you can crystallize them and then examine them with a high-energy X-ray beam, but this one can't be crystallized because it's constantly moving. A better picture of the protein switching back and forth would greatly assist future practical applications of the discovery."

This research was sponsored in part by NASA, the National Institutes of Health and the Purdue Botanicals Center. James Morré is a member of the Purdue Cancer Center, one of eight National Cancer Institute-designated basic-research cancer centers in the United States. Established in 1976, the center is committed to helping cancer patients by identifying new molecular targets and designing future agents and drugs for effectively detecting and treating cancer.

Both are members of the Purdue-UAB Botanicals Center, which in collaboration with the University of Alabama-Birmingham, promotes interdisciplinary botanicals research for the prevention of age-related diseases. The center has received support from the National Institutes of Health to study compounds in botanicals purported to reduce the risk of cancer, osteoporosis, cardiovascular disease, cognitive function and other age-related diseases. The Purdue-UAB Botanicals Center is one of four NIH-funded Botanicals Research Centers in the United States. Original version / written circa 2002

Time Is Not Absolute: Revisiting the Biochemical Clock

Dorothy M. Morré and D. James Morré continued  pursuing a question that had occupied James Morré since his student years: What actually makes a living cell keep time?

In 2002, the Morrés and colleagues Pin-Ju Chueh, Jake Pletcher, Xiaoyu Tang and Lian-Ying Wu published an intriguing answer in the journal Biochemistry. Their paper, “Biochemical Basis for the Biological Clock,” described unusual proteins on the external surfaces of cells then called ECTO-NOX proteins.

These proteins appeared to possess an extraordinary characteristic: their biochemical activities oscillated.

Rather than performing a single function continuously, the proteins alternated between two activities in a remarkably regular cycle of approximately 24 minutes. The researchers proposed that this much shorter, or ultradian, oscillation might somehow function as a fundamental timing mechanism underlying the approximately 24-hour circadian rhythms of cells.

They put that possibility to an experimental test.

The researchers introduced proteins with altered oscillation periods into cultured cells. A protein exhibiting a 22-minute period was associated with an approximately 22-hour cellular rhythm, while altered proteins producing periods of 36 or 42 minutes were associated with correspondingly longer circadian biochemical cycles.

The relationship was striking: the cellular circadian period was approximately 60 times the period of the protein's oscillation.

For the Morré team, this constituted evidence that ECTO-NOX proteins might operate as biochemical oscillators contributing to cellular timekeeping.

It also offered a possible explanation for an older scientific curiosity involving heavy water, or D₂O. Biological experiments had shown that replacing ordinary hydrogen with its heavier isotope, deuterium, could lengthen biological rhythms. The Morrés found that heavy water also lengthened the oscillation associated with their ENOX system, strengthening their hypothesis that these short biochemical cycles were connected to longer biological rhythms.

The implications appeared potentially enormous.

Circadian timing influences sleep and wakefulness, metabolism, hormone secretion, cardiovascular activity, drug responses and many other physiological processes. Understanding the machinery by which cells measure time therefore promised applications ranging from chronotherapy and sleep disorders to aging and cancer research.

But science did not stop in 2002.

Over the following decades, the molecular understanding of circadian timekeeping expanded dramatically. Research involving the PERIOD, CRYPTOCHROME, CLOCK and BMAL1 proteins established an interconnected system of transcriptional and translational feedback loops as a central mechanism of mammalian circadian clocks. In 2017, Jeffrey C. Hall, Michael Rosbash and Michael W. Young received the Nobel Prize in Physiology or Medicine for discoveries explaining molecular mechanisms controlling circadian rhythm.

Consequently, the strong interpretation sometimes attached to the Morrés' early work—that a single protein had been identified as the biological clock—should now be treated cautiously. Contemporary biology describes biological timekeeping as a distributed molecular system involving interacting genes, proteins, cellular oscillators, environmental signals and coordination between central and peripheral clocks.

That does not make the Morrés' work disappear.

Their ECTO-NOX research continued. The proteins became known as ENOX proteins, and in 2008 the Morré group and collaborators reported cloning and characterizing human ENOX1, a protein encoded on chromosome 13. Their research also expanded toward ENOX proteins associated with aging and cancer, including ENOX2, which became the subject of research into tumor biology, cancer detection and potential therapeutic targeting.

Pin-Ju Chueh, the Purdue graduate researcher involved in the original biological-clock work, went on to become a professor at National Chung Hsing University in Taiwan, pursuing research in tumor biochemistry and related biomedical fields.

More than two decades later, therefore, the original story becomes more interesting—not less.

The question is no longer simply whether one protein is “the biological clock.” It is how multiple oscillating biochemical systems interact to create what we experience as biological time.

A cell contains processes operating over seconds, minutes and hours. Individual tissues possess their own clocks. The brain coordinates rhythms across the organism. Light can reset those rhythms. Chemistry can alter them. Disease and aging can disrupt them.

And beneath the familiar 24-hour day may exist shorter oscillations whose biological significance researchers are still working to understand.

When I originally encountered this research near the beginning of the twenty-first century, its implications fascinated me enough to connect it with a larger idea I was already exploring:

Time Is Not Absolute.

Nearly a quarter-century later, the science has changed considerably.

The question has only become more interesting.

Years ago, I wrote a short post about an idea that had lodged itself in my head after reading Brian Greene's The Elegant Universe and Richard Feynman's QED: The Strange Theory of Light and Matter.

The original thought went something like this:

Everything is moving through spacetime at c, the speed of light. Move faster through space and you move more slowly through time. Somehow, it all adds up to c.

More than twenty years later, that turns out to be a surprisingly good memory of Greene's explanation—with an important qualification.

In special relativity, an object's trajectory through four-dimensional spacetime can be described using something called four-velocity. The magnitude of that four-velocity for any massive object is invariant and equal to c.

That gives us a useful way of thinking about time dilation.

When I am sitting still relative to you, essentially none of my motion relative to you is through space. My clock therefore advances normally relative to yours. Accelerate me to an enormous fraction of the speed of light relative to you and our clocks no longer agree about how much time passes between the same events.

From your reference frame, my clock runs more slowly.

It isn't quite correct to say that ordinary speed through space and speed through time simply “add up” to c. Space and time are related through the geometry of Minkowski spacetime rather than ordinary Euclidean geometry.

But the intuition that fascinated me remains useful:

Increasing motion through space corresponds to decreasing elapsed proper time relative to another observer.

And that leads to the wonderfully strange limiting case of light.

A photon travels through vacuum at c. For light, the proper time between emission and absorption is zero. It isn't really valid to construct a photon's ordinary inertial “point of view,” but mathematically the spacetime interval along a lightlike trajectory contains no elapsed proper time.

That alone would have been enough weirdness for one short blog post.

Then I read Feynman.

Does light always travel at c?

In QED: The Strange Theory of Light and Matter, Richard Feynman presents an even stranger picture.

Quantum electrodynamics does not calculate the behavior of light by assigning a photon one neat classical trajectory and calling the problem finished. Instead, quantum amplitudes associated with possible histories contribute to the final probability of what we observe.

Feynman explicitly discusses amplitudes corresponding to propagation faster or slower than the conventional speed of light.

When I originally encountered that passage, I interpreted it as meaning that c was effectively an average—that individual photons could actually be caught breaking the cosmic speed limit.

That's the part I would write differently today.

The existence of a quantum amplitude associated with such a history is not equivalent to observing a photon carrying energy or information from one place to another faster than c.

Over macroscopic distances, the contributions associated with nonclassical propagation interfere and largely cancel. What emerges is the familiar result:

Light in vacuum propagates at c.

Relativity survives.

And c is considerably more profound than merely the average speed of a bunch of unruly photons.

So what exactly is c?

Calling c “the speed of light” is historically understandable, but almost undersells it.

It is a fundamental constant built into the relationship between space and time.

Light travels at c because massless excitations propagate along the lightlike structure of spacetime. c also appears in the relationship between mass and energy, in relativistic causality, and throughout modern field theory.

In that sense, perhaps my younger self had the emphasis slightly backwards.

It isn't that light happens to travel at a peculiar universal speed.

Rather, the universe possesses a fundamental invariant speed—and light obeys it.

Which brings me back to the idea behind these old writings in the first place.

Time Is Not Absolute.

That statement has aged considerably better than my explanation of photons.

There is no single universal clock whose definition of “now” governs the entire universe. Observers moving relative to one another can disagree about elapsed time and, for sufficiently separated events, even about whether those events occurred simultaneously.

Yet they can transform their measurements into one another's descriptions according to precise physical laws.

Space and time aren't independent stages upon which the universe performs.

They are parts of the same structure.

And c sits right in the middle of the relationship.

So, twenty-something years after writing:

// c's the day //

…I think I'd keep the title.

I'd just change what I thought the joke meant.

When I originally wrote about this question, I was trying to connect several ideas I had encountered in popular accounts of relativity and quantum mechanics.

My understanding at the time went something like this:

General relativity describes gravity as a distortion of space and time. Mass represented some kind of resistance to that distortion. Under ordinary circumstances that resistance remained constant, as suggested by Newton's familiar relationship between force, mass and acceleration. But as an object approached the speed of light, its resistance to further acceleration increased. Eventually spacetime could be distorted no further, and the object's apparent mass approached infinity.

That was my attempt to reconcile Newton, Einstein and what I was reading about quantum physics.

More than twenty years later, I would explain it differently.

First: yes, the speed of light is finite

The speed of light in vacuum, represented by c, is exactly:

299,792,458 meters per second.

That's approximately 300,000 kilometers per second—or about 186,000 miles per second.

Finite, but extraordinarily fast.

In fact, c has become so fundamental to our understanding of measurement that we no longer define a meter independently and then ask how many of them light travels in one second.

We do essentially the reverse.

Since 1983, the meter has been defined using the speed of light: one meter is the distance light travels through vacuum during 1/299,792,458 of a second.

So c isn't merely something we measure.

It is now part of how we define what we mean by distance.

But why can't something exceed it?

This is where my original explanation needs correction.

Mass isn't the resistance of spacetime to being distorted, and spacetime doesn't reach some maximum distortion as an object approaches c.

The modern explanation begins with special relativity.

A massive object possesses what physicists call its invariant mass or rest mass. If I accelerate a spacecraft faster and faster relative to Earth, the spacecraft's rest mass does not continually increase.

Its energy and momentum do.

The closer its velocity gets to c, the more energy is required to produce an additional increase in speed.

At everyday velocities this difference is imperceptible, which is why Newton's familiar physics works extraordinarily well:

F = ma

But at relativistic velocities, Newton's approximation is no longer sufficient.

The relationship between energy and velocity becomes increasingly nonlinear. As the velocity of an object possessing mass approaches c, the energy required to accelerate it further grows without bound.

Reaching c would require infinite energy.

So a massive spacecraft can approach the speed of light arbitrarily closely in principle, but it cannot simply accelerate through c.

There is no moment when spacetime says, “That's enough distortion.”

The geometry of relativity itself prevents the crossing.

And what does gravity have to do with it?

This is where Einstein's other great theory enters the story.

Special relativity describes physics in the absence of gravity—or, more precisely, in locally inertial frames.

General relativity extends the picture.

Gravity isn't treated simply as a force pulling objects across an otherwise fixed background. Matter and energy affect the geometry of spacetime, and objects follow trajectories through that curved geometry.

That is a much subtler relationship than my original description of mass as “resistance.”

Mass and energy help determine spacetime curvature.

Spacetime curvature helps determine how matter and energy move.

And c remains woven into the mathematics connecting space, time, matter and energy.

Something else has changed since I first wrote this

There is an almost philosophical twist hidden in the modern definition of c.

For centuries, humans constructed standards of length and then attempted increasingly precise measurements of how rapidly light crossed that length.

Eventually our measurements became so good that we reversed the relationship.

We fixed c.

And we defined our unit of length from it.

That means asking:

“Exactly how fast is light in meters per second?”

has become slightly circular.

The answer is exactly 299,792,458 m/s because that is now part of the definition of the meter itself.

The deeper scientific questions concern why the universe possesses this invariant speed, why massless particles propagate according to it, and why the same constant appears throughout the fundamental relationship between space and time.

Which brings this back to the question I was really asking when I originally created Time Is Not Absolute.

Light doesn't merely move extremely quickly through an otherwise ordinary universe.

The constant c helps define the causal structure of spacetime itself.

Distances depend upon frames of reference.

Durations depend upon frames of reference.

Observers can disagree about both and still be correct.

Yet c remains invariant.

So perhaps the more interesting question isn't:

Is the speed of light finite?

It is.

The question that has survived the intervening decades is:

Why does the universe have a speed limit at all?

And why is that limit so deeply entangled with what we mean by space, time, and ultimately reality?

That is a question worthy of revisiting under a name I chose a very long time ago:

T.I.N.A. — Time Is Not Absolute.