Teenage Mutant Ninja Fruit Flies

October 18, 1943 - allied forces were advancing through Nazi-held Italy.   In a desperate attempt to weaken German forces occupying the village of Calvi Veccia, British infantry called in for aerial bombardment.  In the last moments, British ground forces were able to capture the town, but were unable to establish radio contact to cancel the bombing.  In a panic, a message was tied to the leg of a carrier pigeon named G.I. Joe.  As soon as he was let loose from his cage, Joe shot into the air and bee-lined directly for HQ.  He flew 20 miles in 20 minutes, successfully delivering the note just as the bombers were taxiing on the runway, saving more than a thousand British and Italian lives.

G.I. Joe receiving his medal for gallantry.

Similar stories of avian navigational prowess are common, including the tale of the intrepid Cher Ami, a WWI carrier pigeon who saved a battalion of trapped soldiers.  Cher Ami flew 25 miles in 25 minutes, despite being shot by enemy soldiers (blinded in one eye, wounded in the left breast, with a left leg that was blown to pieces), delivering a critical request for reinforcements that saved almost 200 men.  These inadvertently brave birds were prized for their ability to rapidly return to their roost, even when they were taken many miles away from home in a small, dark cage. 

If all this sounds familiar, then you may have heard it first on Radiolab in their Bird’s-Eye View episode.  These accounts invoke a mysterious power held by our fine-feathered friends, who are able to voyage vast distances without the aid of maps or GPS.  This brings us to a recent suite of scientific discoveries involving avian extrasensory perception (hereafter referred to as magnetoreception).  

 

Magneto - master of magnetism.

The word magnetoreception conjures super-human mutant powers from X-Men comics, but it refers to the subtle ability of birds (and other animals, including sea turtles, salmon, and fruit flies) to perceive magnetic fields (Wiltschko and Wiltschko, 1996).  There are two competing theoretical mechanisms for how this sense functions: magnetite particles (tiny magnets) in the bird’s beak and light-induced chemical reactions in the eye (Edmonds, 1996; Ritz et al., 2000).  Ritz et al. (2000) proposed a viable mechanistic pathway for the latter hypothesis, by which the product yields of quantum chemical reactions are altered by weak magnetic fields (i.e. the Earth’s magnetic field).  This mechanism has been empirically supported by several recent studies (Solov'yov et al., 2007; Gegear et al., 2010; Gauger et al., 2011).

Cryptochrome, showing the flavin residue in red and the tryptophan residues in yellow.

 

In a nutshell, a light-sensitive protein called cryptochrome is thought to mediate bird magneto-vision via a magnetically-sensitive chemical reaction.  Cryptochrome contains a flavin (FAD) molecule that is excited by blue/green light.  Excited FAD passes an electron off to a chain of tryptophan residues, which carry the electron away, giving rise to a spatially separated quantum-entangled radical electron pair (turning the protein to its ‘on’, or signaling state).  As one electron experiences a slightly different magnetic field than its partner, the pair oscillates between singlet and triplet spin states via hyperfine coupling.  The back-transfer of the electron to the FADH radical (see below) returns it to its ‘off’ (non-signaling) state, but this process is spin-dependent (requiring a singlet state). 

 

Because the magnetic field influences the proportion of radical pairs that are in the singlet vs. triplet state, the field determines how long the molecule will be turned on or off.  As these proteins are embedded in the retina, they create a mosaic of long-lived ‘on’ cryptochromes and cryptochromes in their ‘off’ position (depending on how the field changes) across the surface of the eye.  Due to their presence in the retina, some have speculated (Ritz et al., 2000) that cryptochrome signaling influences photoreceptor cells.  If this is the case, then the bird might distinguish the geomagnetic field as patterns of light and dark, which would change depending on the angle of the bird’s view relative to the field lines (see below).

Quantum Bird Vision - A panorama of Frankfurt, Germany.  This figure shows the cryptochrome signal alone (grey-scale), and if it were layered over the visual signal (color).

Until recently, it was assumed that living organisms were too ‘warm and wet’ to allow for delicate and transitory quantum entanglements to persist for any length of time.  A paper published this year in Physical Review Letters (Gauger et al., 2011) demonstrated that the entangled electron pairs produced in avian magnetoreception are able to persist in an entangled state for up to 100 microseconds.  This is incredible, as experimental physicists find it difficult to maintain an entangled quantum state for more than 80 microseconds under cryogenic (very low-temperature) laboratory conditions.  Evolution uses all tools that the physical universe lays at its doorstep, so we shouldn’t be surprised to observe biological adaptations that make use of quantum-level phenomena.  If we could learn how to mimic the physiochemical conditions that shield these fragile quantum states over microsecond timescales at ambient temperatures, then we could make huge technological advances in the development of quantum technologies (e.g. quantum computation).     

D-Wave - the first commercial quantum computer?

 

It is fascinating to ponder sensations that we are unable to feel.  For example, how does it feel when a rattlesnake sees a rodent with its infrared heat-sensors?  What is the sensation that a shark gets when it feels the electromagnetic signature of a fish swimming past?  Perhaps we can better identify with magnetoreception, because it seems to be closely linked to vision, although we’ll never quite know the exact impression that a robin gets from seeing the Earth’s rippling electromagnetic field, like light playing across an underwater landscape…or will we?  A recent article, published in Nature Communications (Foley et al., 2011), shows that human cryptochrome proteins (also located in the eye) are able to restore magnetoreception in Drosophila (fruit flies).  These little insects, like birds, are able to orient themselves relative to magnetic fields.  Foley et al. (2011) genetically altered their flies by removing the Drosophila cryptochrome gene, rendering them blind to magnetism.  Incredibly, when they inserted the human cryptochrome gene into these mutant flies, their magnetic sight was restored.  Humans, therefore, possess functional cryptochromes in their retinas, but we may have lost the capability to translate this sensory input into a downstream biological response.  These findings could lead us towards a sixth human sense!  Imagine how art, culture, and science would evolve in some future magnetoperceptive world.

Teenage Mutant Magnetoreceptive Turtles!

References

Edmonds, D. (1996). A Sensitive Optically Detected Magnetic Compass for Animals Proceedings of the Royal Society B: Biological Sciences, 263 (1368), 295-298 DOI: 10.1098/rspb.1996.0045

Foley, L., Gegear, R., & Reppert, S. (2011). Human cryptochrome exhibits light-dependent magnetosensitivity Nature Communications, 2 DOI: 10.1038/ncomms1364

Gauger, E., Rieper, E., Morton, J., Benjamin, S., & Vedral, V. (2011). Sustained Quantum Coherence and Entanglement in the Avian Compass Physical Review Letters, 106 (4) DOI: 10.1103/PhysRevLett.106.040503

Gegear, R., Foley, L., Casselman, A., & Reppert, S. (2010). Animal cryptochromes mediate magnetoreception by an unconventional photochemical mechanism Nature, 463 (7282), 804-807 DOI: 10.1038/nature08719

RITZ, T. (2000). A Model for Photoreceptor-Based Magnetoreception in Birds Biophysical Journal, 78 (2), 707-718 DOI: 10.1016/S0006-3495(00)76629-X

Solov’yov, I., Chandler, D., & Schulten, K. (2007). Magnetic Field Effects in Arabidopsis thaliana Cryptochrome-1 Biophysical Journal, 92 (8), 2711-2726 DOI: 10.1529/biophysj.106.097139

Wiltschko, W., Wiltschko, R. (1996) Magnetic orientation in birds.  Journal of Experimental Biology. 199:29-38.

Exquisite Machines

The synthesis of non-equilibrium thermodynamics and biology, pursued in fits and starts over the years by an eccentric cast of thinkers, has produced a few scientific red herrings, but the overall idea has expanded our biophysical horizons.  I'll summarize what I've come to understand about the development of biological thermodynamics and its implications, while trying to skirt the rabbit holes.

First, I suppose a brief explanation of thermodynamics is needed.  To put it concisely, thermodynamics is the branch of physics that deals with the conversion of energy into different forms.  We derive our physical conceptions of temperature (average kinetic energy of matter, i.e. how fast atoms and molecules bounce off of one another within a substance), heat (energy transferred between two bodies or systems in thermal contact), work (force multiplied by distance, i.e. joules), Gibbs free energy ('useful' energy, or energy available to do work) and entropy (disorder) from thermodynamics.  The first and second laws state that 1) energy can be neither created nor destroyed within an isolated system, only modified in form, and 2) entropy will never decrease within an isolated system.  Early work in classical thermodynamics involved designing engines that were able to perform mechanical work by transferring energy from a warm region to a cool region (like the sterling engine; see below).  Modern thermodynamics has evolved beyond heat engines to encompass chemical reactions and molecular/atomic theories of matter (chemical thermodynamics and statistical mechanics).  

The image above depicts a heat engine.  T refers to temperature, Q to heat, and W to work.  The subscripts H and C denote 'hot' or 'cool', respectively.  As heat flows from a high temperature reservoir to a low temperature reservoir via an engine (circle), a certain amount of that heat energy is converted to work.

 Parallels can be drawn between our planet and a heat engine.  The hot sun radiates high-energy light (hv) that is absorbed by our planet and re-emitted back to cold space as lower-energy infrared radiation.  A certain proportion of this flow is used to drive the circulation of our oceans, our atmosphere, and to sustain life (via photosynthesis).

Erwin Schrödinger (a founding father of quantum physics), in his work entitled What is Life? (Schrödinger, 1944), attempted to reconcile biology with the observed laws of chemistry and physics.  He proposed two biological research programs: 'order from order' and 'order from disorder'.  The former was based on the fact that life involved self-replicating ordered structures that depended upon a strange 'crystalline molecule' called DNA that Watson, Crick, and Franklin would later demystify.  This 'order from order' hypothesis became the central dogma of molecular biology and led to an explosion of research and understanding.  The 'order from disorder' hypothesis (a misnomer; see below) lay dormant for many years due to its assumed contradiction of the fundamental laws of thermodynamics.  In his work, Schrödinger observed that, at first glance, living systems seem to defy the second law of thermodynamics, which states that within isolated systems entropy should be maximized - disorder should reign.  Schrödinger, therefore, strayed from the traditional equilibrium-based thermodynamics that had been developed up to that point and began to investigate the thermodynamics of non-equilibrium systems.  

A non-equilibrium system is defined in terms of external gradients maintaining a state at a certain distance away from equilibrium (Schneider & Kay, 1994).  These gradients (fluxes of energy and matter in and out of the system) somehow allowed non-equilibrium processes (convection cells, tornadoes, planetary rings, etc.) to maintain organized internal structures, vaguely reminiscent of living systems.  Schrödinger proposed that life itself is a non-equilibrium process by which localized order is maintained at the expense of larger global entropy production, suggesting that the study of living systems from a non-equilibrium perspective would reconcile biological self-organization and the inorganic world (Schrödinger, 1944).  When ordered processes (physical or biological) emerge from a non-equilibrium state, they develop and grow at the expense of increasing the disorder at higher levels in the system’s hierarchy.  Living organisms swim against an entropic stream, which tends to carry everything to an inert state of equilibrium, by catalyzing an accelerated increase in higher-level disorder proportional to the magnitude of biological organization.  Thus, metabolism allows the organism to export the internal entropy that it cannot help but produce by being alive (von Stockar & Liu, 1999). 

Perhaps the simplest illustration of biological thermodynamics is microbial metabolism (pictured below).  E. coli can consume organic compounds (glucose, for example) and “breath” oxygen to stay alive (aerobic respiration).  Energy-rich electrons are stripped away from glucose and made to flow through an electron transport chain, ending up in H₂O.  This downhill flow of electrons is harnessed to pump ions across a membrane, much like a windmill pumps water from underground, creating an electrochemical gradient that can be used to do the work of building and maintaining the cell.  The Gibbs energy difference (∆G) between food and the metabolic waste product determines the driving force of metabolism (von Stockar et al., 2008), just as elevation gradients determine how quickly water rushes down a stream.  The exact metabolic rate is controlled by the balance of energy released through catabolism (breaking down molecules), consumed by anabolism (building up molecules) and the differences in chemical entropies between metabolic reactants (food) and products (waste).  The principal entropic byproduct of aerobic respiration is heat, which heightens disorder in the surrounding environment by increasing the temperature (atoms jostle against one another more vigorously) and 'pulls' metabolism in a forward direction (just as a gas is 'pulled' into a vacuum). The bacterium siphons away some proportion of useable electronic energy to perform uphill work (building proteins, sugars, nucleic acids, and lipids), while the rest is relinquished to pay the thermodynamic piper.  In other words, life buys its lunch with disorder.

The total entropy change (∆S) is a combination the chemical entropies of the products of metabolism and the heat lost during the breakdown of the substrate (glucose).

It is necessary to point out that Schrödinger's 'order from disorder' hypothesis, while conceptually useful for its time, is fundamentally flawed.  What he should have said was 'biological order from non-biological order'.  In reality, the organization that we observe in the universe cannot be derived from disorder.  Contemporary order is descended from the Big Bang (and the occasional statistical fluctuation), when all the space, matter and energy in the cosmos were compressed into a single, infinitesimally small point.  At that moment, the universe was in its maximum state of order.  Since then, the echoes of that ancient uniformity are found in coherent structures like plants, galaxies, and Tupperware.  It is from the energy differentials created by this diluted cosmological order that life arose and has persisted. 

Nope.

Today, the idea that life is derived from the inorganic world seems relatively straightforward.  We accept that living things obey the laws of physics.  Understanding the dynamics of energy and matter within living systems allows us to predict biological phenomena from physical laws.  Because life is so vastly complex, these predictive powers have remained elusive.  After a century of extraordinary research in molecular biology and evolution (order from order – driven by genetics), and advances in large scale data collection and computation, science is positioned to answer Schrödinger’s call to address 'biological order from non-biological order'.  Brilliant trailblazers, like Ilya Prigogine, have illuminated foundational relationships between non-living processes and living organisms through non-equilibrium thermodynamics.  Sub-disciplines, like astrobiology and biogeochemistry, have flowered from these insights.  James Lovelock established the gaia hypothesis (Lovelock and Margulis, 1974), which integrated living organisms into the dynamic chemistry of our oceans and atmosphere.  Lovelock's predictions have led to potential spectroscopic methods for detecting life-bearing planets outside of our solar system by looking, for example, for significant quantities of methane in oxidized atmospheres.  James Brown has proposed a metabolic theory of ecology (Brown et al., 2004), hypothesizing that patterns of species diversity vary predictably with temperature, suggesting a biophysical approach to ecology.  Brown’s theories could be employed to help predict ecological shifts due to changing climate conditions.  Perhaps most interestingly, these ideas may culminate in the discovery of how life arose (or could have arisen) on Earth, and how it might develop elsewhere in the universe.

In conclusion, we cannot separate ourselves from the rest of the physical universe.  The distinction between life and non-life is arbitrary.  We are exquisite machines, sustained by electrochemical currents.  Life on Earth has achieved amazing longevity due to its evolutionary memory, which is recorded and passed down from cell to cell via the genetic code.  This Darwinian ratchet has been characterized to such an extent that we can now read and even write our own biological prose.  3.8 billion odd years ago, the chance marriage of DNA/RNA software to physiological hardware became what we recognize as life.  Just as life began as a synthesis of memory and muscle, our nascent understanding of life should proceed through a coupling of evolutionary biology (the genetic history of life) and biophysics (the structural framework and physiochemical engines of life that have survived natural selection and earned a place in the genetic code).

Update:

Recent work by Jeremy England has addressed the thermodynamics of self-replication and adaptation, bringing us closer to the conceptual synthesis envisioned in this post. See Jeremy talk about his work here: https://t.co/qjG7tHN7az

Echoes of ancient uniformity, the inorganic precursors to life - A clip from the new film "Tree of Life".

References

Brown, J., Gillooly, J., Allen, A., Savage, V., & West, G. (2004). TOWARD A METABOLIC THEORY OF ECOLOGY Ecology, 85 (7), 1771-1789 DOI: 10.1890/03-9000


Hatsopoulos, G.N., Keenan, J.H. (1965) Principals of General Thermodynamics. New York: John Wiley & Sons Co.

LOVELOCK, J., & MARGULIS, L. (1974). Atmospheric homeostasis by and for the biosphere: the gaia hypothesis Tellus, 26 (1-2), 2-10 DOI: 10.1111/j.2153-3490.1974.tb01946.x


Schrödinger, E. (1944) What is Life? Cambridge: Cambridge University Press. 

Toussaint, O.; Schneider, E.D. (1998). The thermodynamics and evolution of complexity in biological systems Comparative Biochemistry and Physiology - Part A: Molecular & Integrative Physiology, 120 (1), 3-9 DOI: 10.1016/S1095-6433(98)10002-8

Schneider, E. (1994). Complexity and thermodynamics Towards a new ecology Futures, 26 (6), 626-647 DOI: 10.1016/0016-3287(94)90034-5

von Stockar, U., & Liu, J. (1999). Does microbial life always feed on negative entropy? Thermodynamic analysis of microbial growth Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1412 (3), 191-211 DOI: 10.1016/S0005-2728(99)00065-1

VONSTOCKAR, U., VOJINOVIC, V., MASKOW, T., & LIU, J. (2008). Can microbial growth yield be estimated using simple thermodynamic analogies to technical processes? Chemical Engineering and Processing: Process Intensification, 47 (6), 980-990 DOI: 10.1016/j.cep.2007.02.016