Water, Life’s Eclectic Timepiece

Dr. James Morré, the Dow Distinguished Professor of Medicinal Chemistry at Purdue University, and his wife Dr. Dorothy Morré, also of Purdue University, have recently published a number of interesting papers on the human body clock.  The subject has been a lifelong curiosity for the Mr., who has managed to satisfy his curiosity despite working on some six hundred and fifty odd other published papers on numerous topics over his prolific scientific research career.  One aspect of their biological clock discovery that fascinates me is this: it appears to be based upon a type of natural oscillatory cycle inherent, perhaps, to liquid water…

Drs. Morré and Morré were searching for the genesis of an equally interesting observation- that cells grow in regular spurts in between periods of rest, and that these periods are precisely timed- when they found a class of proteins whose dynamic functions continuously generate the characteristic rhythm they were seeking.  This quote is taken from a 2008 paper published in the Journal of Inorganic Chemistry (full reference below):

“The ECTO–NOX proteins carry out hydroquinone (NADH) oxidation for 12 min and then that activity rests.  While the hydroquinone (NADH) oxidative activity rests, the proteins engage in disulfidethiol interchange activity for 12 min.  That activity then rests as the cycle repeats.”

Exactly 60 repetitions of this cycle fill a 24-hr day…  Some see coincidence, but they are not research scientists…

Ignoring the not insignificant details which make a concise summation possible, Dr. James Morré and his team followed a thread that led from the protein itself to water.  They noted that the protein contains copper, and performed experiments with an aqueous copper solution (no protein) and NADH, and found a remarkably similar pattern of redox potential oscillation.  It turns out, however, that copper only serves to modulate an underlying oscillatory cycle in liquid water: when a solution of NADH in pure water was studied, it displayed the same characteristic pattern as the copper and protein solutions, but with a reduced overall period of just 18 minutes (instead of the original 24).  The inclusion of the copper ion adjusts the period of oscillation so that it is a subharmonic of the circadian period (e.g. one 24-hour day).

But what in water makes this possible?  The likeliest candidate at present seems to be instabilities in the water molecule itself, whose two hydrogen nuclei can shift between ortho and para states.  These are configurations in which the spin states of the two hydrogen nuclei of a water molecule are either parallel (the ortho state) or anti-parallel (the para state).

This is an interesting hypothesis because measurements have shown a good correlation between oscillations in the ratio of ortho to para water states in the solution and the overall time-keeping oscillation studied, and also because the time required for the ratio of ortho to para water states to reach equilibrium at a given temperature is perhaps the only candidate dynamic in water that is sluggish enough to produce the 18-minute period found.  Most things in water happen far, far faster by comparison.  The final explanation remains at large, however, since the equilibrium ratio of ortho to para water in a solution depends upon temperature, and the effects that Dr. Morré and his team have observed are temperature independent.  There is also no clear mechanism to explain how the ratio of ortho to para water states is maintained in steady oscillation.

Why doesn’t it simply reach the equilibrium ratio and stay there?  Instead, it seems to oscillate around equilibrium, never quite arriving.  This sounds somewhat like a “dissipative structure”, meaning a stable dynamic produced by the flow of energy through a system.  The energy is “dissipated” in the production of an increasingly complex and ordered dynamic structure.  Perhaps it is simply quantum instability Life has somehow found the way to harness and organize.  Perhaps I should stop hypothesizing before I really do get myself into trouble.

The search for the dog that is wagging this ephemeral subatomic tail continues, and has led to some interesting additional observations.  The protein-water-clock system has been shown to be responsive to various environmental cues.  Influences such as low frequency EMF, blue light, red light, and the addition of melatonin or valerian have all been shown to influence the phasing of the system.  Further, in a lecture given last October at the Conference on the Physics, Biology and Chemistry of Water held in Vermont, Dr. Morré noted that changes in the phasing of the systems studied has even been correlated to solar flares and changes in solar activity.

Living processes, and perhaps even water itself, responding to cosmic influences?  Could it be?

The beauty and intricacy of the interconnected processes at work in the support of our living condition is incredible.  I am left to wonder…  At what point in our evolutionary history did biology “discover” that copper combined with water could produce a reliable timepiece?  What advantage did this confer on its finder?

What is time, anyway?

A Few References

Morré, DJ, et al. “Regular Oscillatory Behavior of Aqueous Solutions of CuII Salts Related to Effects on Equlibrium Dynamics of Ortho/Para Hydrogen Spin Isomers of Water”. Journal of Inorganic Biochemistry 102 (2008), 260-267.

Morré, DJ, et al. “Response of the Regulatory Oscillatory Behavior of CopperII-Containing ECTO-NOX Proteins and of CuIICl2 in Solution to Electromagnetic Fields”. Journal of Inorganic Biochemistry 102 (2008), 1812-1818.

© Michael Mark, 2010