Friday, August 12, 2011

A Case for BioHydrogen

Our energy dilemma

The hydrocarbon economy is faltering as oil reserves dwindle worldwide (Hirsch, 2008).  Commodity prices have begun to fluctuate drastically due to the uncertain cost of petroleum, which resulted in food riots around the world in 2008.  With a steadily decreasing energy supply and the demands on energy systems continually growing, the planet is in dire economic, geopolitical, and environmental straits.  In order to halt the advance of climate change, prevent ecological collapse, rescue the global economy, and ensure our energy security, humanity must find a way to harness currently available (non-fossilized) energy.  The largest source of energy on Earth, excluding the future potential for thermonuclear fusion reactors, is the sun.  Human civilization consumes 15 TW annually while approximately 80,000 TW of solar energy fall on the Earth’s surface each year (Makarieva et al., 2008).  For hundreds of millions of years, this solar flux has been the driving force for life on Earth.  It is estimated that photosynthesis absorbs and distributes seven times more energy to the biosphere (~100 TW) than is consumed anthropogenically each year (Makarieva et al., 2008).  There are many promising technologies in development that will cheaply harness solar output, like next generation photovoltaics, advanced wind turbines, tidal power systems, wave energy generators, solar thermal collectors, biofuels, solar fuels, electrofuels, etc.  In the end, some combination of these solutions, coupled with improved energy and transportation infrastructure, will be needed to resolve our energy dilemma.  In this article, I focus on cyanobacteria and their potential for hydrogen production, which, if properly developed, could provide sustainable fuel for transportation and industry in a post-petroleum world. 

BioHydrogen Airship of the Future?

Cyanobacteria and the rise of oxygenic photosynthesis

Approximately four billion years ago, after the formation of Earth, the first signs of life began to appear, scratching out a lithotrophic existence in an oxygen-starved atmosphere (Towe, 1996; Cleaves et al., 2008).  Anoxygenic photosynthesis probably developed very early in evolution (Pierson and Olson, 1989), harnessing the power of the sun, but the real metabolic revolution didn’t occur for another billion or so years, when photosynthetic eubacteria evolved the ability to split water into electrons, protons and gaseous oxygen (Nisbet et al., 2007).  This new metabolic mode, termed oxygenic photosynthesis, effectively gave living organisms access to an endless supply of electrons from water and became such a prolific process that it filled Earth’s atmosphere with oxygen, fundamentally transforming the biogeochemistry of the planet (Wille et al., 2007).  Moving electrons from chemically stable water molecules to high-energy carbon-carbon bonds spanned an immense reduction-oxidation (redox) gap, powered by a reliable stellar wind of solar electromagnetic radiation, which ultimately increased the size and scope of life and made the development of structurally complex eukaryotic (multicellular) organisms possible (Blankenship and Hartman, 1998).  Almost all ecosystems on Earth today are directly or indirectly dependent on oxygenic photosynthesis.

The subjects of this Earth-transforming story, and the only organisms known to have evolved oxygenic photosynthesis, are the cyanobacteria (Nisbet et al., 2007).  For a billion years, the electrons in water sat untouched by photosynthetic life because it was energetically unfeasible to oxidize water and reduce NADP+ (an electron carrier needed for the reduction of inorganic carbon) in a single step.  In an evolutionary leap, cyanobacteria pioneered the coupling of two photosynthetic reaction centers, P680 and P700 (named for the wavelengths of light they optimally absorb), referred to as photosystem II (PSII) and photosystem I (PSI), respectively (Allen and Martin, 2007; Mimuro et al., 2008).  Thus, the redox problem was resolved by first pumping low-energy electrons up the redox gradient to a temporary reservoir (the quinone pool/electron transfer chain), from which the second photosystem (PSI) could pull out excited electrons in order to transfer them to an even higher energy state, sufficient for the reduction of NADP+ to NADPH + H+.

The rising concentration of oxygen in the atmosphere presented new challenges to early life on Earth.  Most species at the time were obligate anaerobes or microaerophiles, and only those organisms that had the ability to deal with highly reactive oxygen radicals and persist in an oxygen-enriched atmosphere would inherit the majority of Earth’s habitats (Brioukhanov and Netrusov, 2007; Bendall et al., 2008).  Cyanobacteria, in addition to overcoming the general toxicity of oxygen (a byproduct of their new metabolism), had to find a way to acquire nitrogen under aerobic conditions (fixing atmospheric nitrogen gas into biologically-available ammonia).  The molybdenum-iron nitrogenase enzyme is highly conserved among diazotrophs (nitrogen-fixers) and is very sensitive to oxygen, which destroys the activity of the enzyme.  Cyanobacteria got around this issue by separating oxygenic photosynthesis and nitrogen fixation, either spatially or temporally (Tsygankov, 2007).  Some cyanobacteria only activate nitrogen fixation under dark anaerobic conditions, when PSII is unable to evolve oxygen.  Other cyanobacteria, like filamentous Nostoc punctiforme, form a specialized cell type for nitrogen fixation, called a heterocyst.  Heterocysts deactivate their PSII complexes, grow thickened cell walls, and exhibit higher intracellular respiration rates, which keep oxygen levels very low (Cardona, 2009).  Vegetative cells provide the heterocysts with carbohydrates, while the heterocysts provide the vegetative cells with fixed nitrogen (Cardona, 2009).  

Nostoc punctiforme

Hydrogen metabolism in cyanobacteria

Nitrogenase is responsible for the following reaction: N2 + 8 H+ + 8 e + 16 ATP → 2 NH3 + H2 + 16 ADP + 16 Pi (Tikhonovich and Provorov, 2007).  This process is very energy-intensive, requiring 8 moles of ATP for every mole of ammonia produced.  In addition to ammonia, the nitrogenase enzyme also produces a molecule of hydrogen gas for every molecule of gaseous nitrogen that it fixes.  Hydrogen production via nitrogenase is relatively inefficient, due to the large amounts of ATP required, but it can still be used to produce measurable amounts molecular hydrogen.  One impediment to producing hydrogen in this way is the presence of uptake-hydrogenases (Schütz et al., 2004), which oxidize nitrogenase-produced hydrogen in order to minimize the energy loss from N-fixation by reclaiming ATP via the oxyhydrogen reaction, removing oxygen from the interior of the cell and providing reducing equivalents for other cellular processes (Tamagnini et al., 2007).  Concordantly, uptake-hydrogenase enzyme activity has been shown to correlate with nitrogenase activity (Schütz et al., 2004).  Therefore, it is not surprising that a Nostoc uptake-hydrogenase knockout mutant exhibits a significantly higher hydrogen output than the wild-type (Lindberg et al., 2004).

Bidirectional hydrogenases, as their name implies, are capable of reversible catalysis of hydrogen formation or consumption (2H+ + 2e- <=> H2).  Unlike the uptake-hydrogenases, the activity of these enzymes is independent of nitrogenase activity (Schütz et al., 2004).  These enzymes seem to act as putative escape valves for the excess reducing power that could build up during metabolism, but their exact function is still under debate (Tamagnini et al., 2007).  Cyanobacterial bidirectional hydrogenases have a nickel-iron active site.  These nickel-iron hydrogenases are more aerotolerant, but less productive than the iron-iron hydrogenases found in other anaerobic eubacteria and in eukaryotic green algae (Ghirardi et al., 2007).  Both nickel-iron and iron-iron hydrogenases require maturation proteins in order to attain catalytic activity, but it has also been suggested that certain [Fe-Fe] hydrogenases do not require a maturation process (Asada et al., 2000; King et al., 2006).  These maturation proteins are involved with the insertion of metal clusters into the active site of the hydrogenases (Fontecilla-Camps et al., 2009).  Hydrogenases are much more efficient hydrogen producers than nitrogenases, and hold great promise for future biotechnological applications (Tamagnini et al., 2007).

The overall physiology of heterocystous cyanobacteria is highly complex.  Advances in genomics, transcriptomics, proteomics and metabolomics are helping scientists develop a holistic view of hydrogen metabolism (Cardona, 2009).  In terms of the obstacles facing photobiological hydrogen production, they can be broken down into a few basic issues (Tamagnini et al., 2007).  The first main hurdle is that the most prolific hydrogen-producing enzymes, the [Fe-Fe] hydrogenases, are highly oxygen sensitive.  For a photobioreactor to be cost-effective, it should produce hydrogen under atmospheric conditions.  Some investigations have looked into finding or engineering oxygen-tolerant hydrogenases (Ghirardi et al., 2007).  The difficulty with oxygen-tolerant hydrogenases is that their hydrogenase activity has so far been inversely proportional to their level of oxygen tolerance (as seen in [Ni-Fe] hydrogenases).  In heterocystous cyanobacteria, this obstacle has been overcome by creating an anoxic microenvironment inside the heterocyst.  Another complication arises due to the competition of different metabolic pathways for electrons from PSI.  Most of the reducing power generated via oxygenic photosynthesis is diverted towards carbon and nitrogen fixation in Nostoc punctiforme.  The goal is to better insulate energy-yielding pathways from competing metabolic processes (Agapakis et al., 2010).  Dr. Matthias Rögner, from Ruhr-Universität in Bochum, estimated at a recent conference in Sigtuna, Sweden, that under optimal growth conditions ~75% of all electrons coming from PSI could potentially be diverted to hydrogen production without negatively impacting the organism.  While metabolic engineering can be vastly complex, scientists can theoretically simplify this problem by catching the electrons at their source (PSI).  PSI hands its electrons off to a ferredoxin, which then shuttles the electrons away to various pathways (Tamagnini et al., 2007).  One idea is to physically link a ferredoxin ligand to a hydrogenase, in order to compete with the native ferredoxins and snatch electrons away from alternate pathways and transfer them directly to the hydrogenase (Agapakis et al., 2010).

The ideal hydrogen-producing organism

Nostoc punctiforme was isolated from a mutualistic association with a cycad (Costa and Lindblad, 2002).  Nostoc, when living symbiotically, has a higher heterocyst frequency than it does as a free-living organism, and will devote much of its metabolism to the production and secretion of specific nitrogen-rich metabolites that are beneficial to its plant host (Enderlin and Meeks, 1983).  Since Nostoc has evolved to mass-produce a specific metabolite when living symbiotically, it seems almost pre-programmed for fuel production.  Heterocystous N-fixing cyanobacteria have minimal nutritional requirements, high photosynthetic efficiencies and can create anoxic microenvironments inside specialized cells that allow anaerobic processes to occur under aerobic conditions.  All of these attributes are conducive to affordable bioreactor design for hydrogen production.  If Nostoc hydrogen metabolism can be effectively engineered, using novel synthetic biology tools, the door to developing successful photobiological hydrogen-yielding technologies is opened. 

Nostoc living symbiotically in plant tissue.

Synthetic biology: an emerging field

An astounding result of recent genomic sequencing projects is that the length of a genome does not predict the morphological or physiological complexity of an organism.  For example, length of the human genome is similar to that of the fruit fly (Mukherji and van Oudenaarden, 2009).  Instead, it has been found that biological modularity can help explain the diversity of form and function in the natural world (Mukherji and van Oudenaarden, 2009).  A limited subset of predictable biological “parts” can be assembled in various ways to produce molecular “devices”, which can be arranged into “systems” to carry out different functions.  In this light, one can view a living cell as a combination of co-regulated genetic circuits, working in tandem.  Another surprising discovery made recently shows the inherent resiliency of biological circuitry to rewiring.  Isalan et al. (2008), in order to test the limits of perturbing regulatory networks in biological systems, found that randomly rewiring Escherichia coli transcriptional networks by synthetically altering transcription factor/promoter pairings only resulted in faulty growth in 5% of cases.  This level of tolerance to random restructuring of biological networks is highly conducive to the adaptation and evolvability of living systems by allowing large-scale alterations to be made to an organisms genome without significantly impeding its growth (Isalan et al., 2008; Mukherji and van Oudenaarden, 2009).  Biological modularity and network resiliency provide powerful mechanisms for the rapid evolution of novel or optimized processes by reshuffling pre-existing genes/proteins (Isalan et al., 2008; Mukherji and van Oudenaarden, 2009; Picataggio, 2009). 

Transcriptase enzymes moving along the DNA strand, from a recent synthetic biology comic book published in Nature.
As our understanding of biology grows in breadth and in depth, we come closer to the goal of being able to rationally design biological systems.  Thanks to the enormous accumulation of whole-system biological data and the discovery of the modular nature of genetic and enzymatic elements during the past few decades, coupled with advances in in silico data analysis/modeling and rapid in vitro DNA synthesis technology, a new field, called synthetic biology, has emerged (Picataggio, 2009).  Synthetic biology allows for the rational manipulation of microbial phenotypes by combining systems biology, bioinformatics, protein design and engineering.  With a comprehensive understanding of the molecular regulation of gene expression and protein function, biologists can begin to assemble a toolbox of reliable promoters, repressors, activators, ribosomal binding sites, reporters, signaling devices and enzymes, that can be used to design metabolic circuits in a cellular chassis - an autonomous self-replicating framework, or superstructure, that acts as the platform for synthetic circuitry (Picataggio, 2009).  Standardization of genetic tools will streamline process engineering and expand the potential to quickly develop microbial systems for the production of renewable fuels and high-value molecules (Picataggio, 2009).

Synthetic biologists have already succeeded in characterizing thousands of biological parts with defined functions and performance parameters, which can be accessed openly at the wiki site maintained by the Massachusetts Institute of Technology, but they are not yet capable of engineering whole biological systems with the same precision and reliability that, say, electrical engineers are accustomed to.  One of the main challenges is to identify the subset of genes that are absolutely necessary for the survival of a minimal genome - the smallest number of genes that allows for the replication of an organism in a particular environment (Cho et al., 1999).  Until researchers can build a living cell from the ground up, they won’t totally understand the limits of metabolic engineering.  The immense potential for engineering crucial synthetic metabolic circuits has already been demonstrated by the work of Dr. Jay Keasling, who produced an important precursor to the anti-malarial drug artemisinin in E. coli (Hale et al., 2007).  Keasling’s work has cut the cost of artemisinin by ten fold and will provide many people in the third world with access to crucial malaria treatments, literally saving millions of lives. 

Dr. Jay Keasling

E. coli is an ideal cellular chassis for molecular reprocessing of low-value substrates into high-value products, but in order to use synthetic biology to tackle humanity’s energy needs, it is important that we move away from heterotrophic organisms and focus on developing a photosynthetic chassis that can harness the power of the sun.  Approaching solar fuel production via direct synthesis from sunlight avoids the drawbacks of traditional fermentation-based methods whose biomass feedstocks often compete directly with food crops (Tenenbaum, 2008).  Researchers at UC Davis have recently developed efficient synthetically-derived fuel (isobutyraldehyde, which can be converted to isobutanol) from cyanobacteria (Atsumi et al., 2009).  This result is encouraging, and suggests that the field of photosynthetic fuels will continue to grow.  In the absence of a minimal genome, heterocystous cyanobacteria seem to be ideal chassis for hydrogen production.  

The development of synthetic biology tools for cyanobacteria

The creation of standard biological parts (promoters, ribosomal binding sites, repressors, activators, etc.) for cyanobacteria is simplified by the work already completed in E. coli and by the current open-source nature of synthetic biology resources, fostered by organizations like the BioBricks Foundation ( and iGEM ( With our current understanding of transcriptional and translational regulation in cyanobacteria, we can re-design genetic regulatory elements and codon-optimised genes from distantly related organisms in silico and synthesize these constructs in vitro for expression in cyanobacteria.  A team in France has developed codon-optimized (for expression in E. coli, Synechocystis, Nostoc and Anabaena) synthetic [Fe-Fe] hydrogenase genes from Chlamydomonas reinhardtii and Clostridium acetobutylicum that have been linked to a synthetic ferredoxin ligands derived from a chlamydomonal ferredoxin (Jaramillo, A., 2009, École Polytechnique, Palaiseau, France, privileged information).  Recently, researchers in the Department of Photochemistry and Molecular Science at Uppsala University have characterized Ptrc promoters, derived from the lacUV5 promoter, ribosomal binding sites and an expression vectors (pPMQAK1 and pPMQAC1) that are broadly functional in E. coli and in cyanobacteria (Brosius et al., 1985; Huang et al., 2010; Gibbons, 2010).  With these tools, it is now possible to express prolific [Fe-Fe] hydrogenases and their respective maturation proteins in cyanobacteria.  It is only a matter of time before viable hydrogen-yielding systems are in place. 

Synthetica, a novel branch to the tree of life.


In this post, I wanted to provide a glimpse of recent developments in photobiological hydrogen production (a field that I'm familiar with), but this is just one small piece of the puzzle.  There are many teams of brilliant researchers around the globe chipping away at their own corners of sustainable energy.  The future green economy will have to take a multi-faceted approach to energy, incorporating dozens of the most successful technologies, alongside behavioral and policy reform (i.e. less consumption, governmental regulation of greenhouse gasses, more localized food production, ecosystem preservation/restoration etc.).  My point was to inspire hope, despite all the doom and gloom surrounding climate change, by illuminating a subset of the work and ideas of our best and brightest, who toil day and night to build a better tomorrow.  While we cannot ignore the perils that lie ahead, we must maintain a certain degree of hope in order to keep our heads above water and look towards a better horizon.  Fear not, fellow humans - for every Senator James Inhofe, there are a hundred thousand scientists, social activists, community horticulturists and conservationists.


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Sunday, August 7, 2011

The Interactome

Fernández & Lynch (2011) recently mapped out the likely origins of an intimidating tract biological complexity - the interactome - in the journal Nature.  Concisely put, the interactome is the complete set of molecular interactions within an organism, just as the genome is a complete account of an organism’s genetic make-up.  The authors posit that as the effective population size (N) of a species decreases, the level of genetic drift increases.  For example, prokaryotes (bacteria and archaea) have such large Ns that non-adaptive changes to protein structure are quickly and efficiently selected against and weeded out of the gene pool.  Organisms with a smaller N, like oak trees or gorillas, do not experience the same selection intensity (individuals have more per capita value, and cannot be thrown away as readily without imperiling the survival of the species), and therefore tend to accumulate more deleterious mutations.  These non-adaptive changes often lead to unstable protein folding, which can result in reduced biochemical function and impair an organism’s fitness.  As a result, the authors propose that this structural instability promotes the recruitment of novel protein-protein interactions, which help stabilize protein function.  Concordantly, multicellular eukaryotes have seen the complexity of their interactome exceed that of unicellular organisms (see figure below) to compensate for the added burden of slightly non-adaptive alleles.  The expanded interactome web not only resolves proteomic instability inherent to low N species, but also gives rise to the phenotypic diversity and plasticity that is a cornerstone of eukaryotic life.  

Figure 2a from Fernández & Lynch, 2011.

The authors establish an elegant mechanism for this rise in interactome complexity.  In chemistry it is commonly said that “like dissolves like”, so it follows that water (a polar solvent) dissolves charged or polar molecules (i.e. table salt) and minimizes contact with neutral molecules (i.e. olive oil).  Beholden to these same rules, cellular proteins require a stable hydration shell in order to persist in their native conformation.  These proteins tend to have a hydrophilic (water-loving) exterior and a hydrophobic (water-fearing) interior.  While the chemical side chains of proteins can by hydrophilic or hydrophobic, the protein backbone has an overall polar character.  Mild structural deficiencies in a protein can give rise to solvent-accessible backbone hydrogen bonds (SABHBs), which render the molecule more vulnerable to denaturation.  This vulnerability arises due to a protein-water interfacial tension (PWIT) introduced by deleterious mutations.  If the protein backbone is unshielded by a sufficiently hydrophilic side chain, it may be pulled out into solution in order to reduce the PWIT, which then deforms the molecule so that it no longer functions properly.  In order to prevent this, proteins bind to one another to cover their vulnerable SABHBs (see below) and collectively reduce their PWIT.  By this mechanism, novel protein-protein relationships are forged.

Figure 1a from Fernández & Lynch, 2011.  Tension is created when the protein backbone becomes unshielded, but that tension is relieved by the binding of another molecule (left to right).

The authors calculated PWIT values (v) for several characterized proteins from different species ranging in interactome complexity.  They found v was low in smaller or single-celled organisms (lower meaning less PWIT, i.e. higher stability), and higher for larger eukaryotes.  For example, the haemoglobin protein is a monomer (single molecule) in the common liver fluke (Fasticola hepatica) and a tetramer (four monomers bound together) in humans.  A monomer subunit of human haemoglobin has a higher v than the fluke haemoglobin, but the v calculated for the human tetramer drops to the same level as that of the F. hepatica monomer (see below).  Thus, in the lower N species, an interaction of several subunits has lead to stable, functional haemoglobin.

Figure 1c from Fernández & Lynch, 2011.  Grey lines show SABHBs.  In the middle pannel, the white dots indicate additional SABHBs that become exposed when a monomer of human haemoglobin is in its unbound state.
In order to verify that complex interactomes arise more by the enhanced genetic drift of low N species than by evolutionary distance alone, the authors calculated v for several proteins shared by free-living and endosymbiotic bacteria.  Endosymbionts have a lower theoretical N than their free-living brethren, so that if a difference in interactome complexity is observed then it is likely due to the increased pressure of genetic drift and not to deep evolutionary divergence.  Their results were consistent with the hypothesis (below), showing that, indeed, endosymbiont proteins suffered from higher PWIT, resulting in greater interactome complexity.

Figure 2c from Fernández & Lynch, 2011.

The remarkable by-product of this expanding interactome is to create a vast pool of functional and genetic diversity for evolution to pull from.  Like a random-walk algorithm, evolution explores the confines of environmental landscapes.  Per cell, eukaryotes harbor a larger variety of structural protein variants that perform their evolved functions while randomly exploring new structural and interactive capabilities within the cell.  Biology has turned the lemon of severe genetic drift into the lemonade of enhanced interactome complexity.  We might envision prokaryotic proteins as very large families settled into their own cozy energetic valleys, and eukaryotic proteins as smaller, less fecund homesteads nestled in their own dells and dales.  In either case, the children are beset by a restless wanderlust (random variation by mutation).  Because the prokaryotic families are so prodigious, they can spare an occasional runaway to seek out a new home over the next ridge, while the work of the homestead is faithfully carried out.  The eukaryotic family, however, cannot spare any hands.  The eukaryotic children must rely on intermarriage (protein-protein interaction) with inhabitants of other valleys in order to explore new ground.  Both familial genera are able to seek out new, uninhabited drainages by alternate means.   Thus, regardless of N, life retains its ability to lithely traverse the rough topology of biological potential.

A proteinaceous adventurer strikes out for new territory.  Blue denotes structurally stable protein conformations, while green and red are unstable protein conformations.

Fernández, A., & Lynch, M. (2011). Non-adaptive origins of interactome complexity Nature, 474 (7352), 502-505 DOI: 10.1038/nature09992

Thursday, July 28, 2011

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!


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.