Imagine yous are a young Bar-tailed Godwit, a big, gangling shorebird with a long, probing bill hatched on the tundra of Alaska. As the days become shorter and the icy winter looms, you feel the urge to commence on one of the most impressive migrations on Earth: a nonstop transequatorial flight lasting at least seven days and nights across the Pacific Ocean to New Zealand 12,000 kilometers away. Information technology's practice or die. Every year tens of thousands of Bar-tailed Godwits consummate this journey successfully. Billions of other young birds, including warblers and flycatchers, terns and sandpipers, set out on similarly spectacular and dangerous migrations every jump, skillfully navigating the nighttime skies without any help from more than experienced birds.

People have long puzzled over the seasonal appearances and disappearances of birds. Aristotle thought that some birds such as swallows hibernated in the colder months and that others transformed into different species—redstarts turned into robins for the wintertime, he proposed. Only in the past century or so, with the advent of bird banding, satellite tracking and more than widespread field studies, have researchers been able to connect bird populations that wintertime in 1 area and nest in another and show that some travel vast distances betwixt the two locales every year. Remarkably, even juvenile long-haul travelers know where to go, and birds frequently accept the aforementioned routes year later year. How do they find their way?

Migrating birds use angelic cues to navigate, much every bit sailors of yore used the sun and stars to guide them. But unlike humans, birds also notice the magnetic field generated by Earth's molten cadre and use it to decide their position and direction. Despite more than than 50 years of research into magnetoreception in birds, scientists accept been unable to work out exactly how they use this information to stay on form. Recently we and others accept made inroads into this indelible mystery. Our experimental evidence suggests something extraordinary: a bird's compass relies on subtle, fundamentally quantum effects in short-lived molecular fragments, known as radical pairs, formed photochemically in its eyes. That is, the creatures announced to be able to "see" Earth'due south magnetic field lines and use that information to chart a course between their convenance and wintering grounds.

A Mysterious Sense

Migratory birds have an internal clock with an annual rhythm that tells them, among other things, when to migrate. They likewise inherit from their parents the directions in which they demand to wing in the autumn and jump, and if the parents each have different genetically encoded directions, their offspring will stop upward with an intermediate direction. For example, if a southwest-migrating bird is crossed with a southeast-migrating bird, their offspring will head s when the fourth dimension comes. But how do the young birds know which direction is southwest or south or southeast? They have at least iii unlike compasses at their disposal: one allows them to extract information from the position of the dominicus in the sky, some other uses the patterns of the stars at nighttime, and the tertiary is based on World's always present magnetic field.

In their starting time autumn, young birds follow inherited instructions such every bit "fly southwest for iii weeks and then south-southeast for ii weeks." If they brand a mistake or are blown off course, they are generally unable to recover because they do not yet take a performance map that would tell them where they are. This is one of the reasons why only xxx percent of pocket-sized songbirds survive their outset migrations to their wintering grounds and back again. During its kickoff migration a bird builds upward a map in its brain that, on subsequent journeys, will enable information technology to navigate with an ultimate precision of centimeters over thousands of kilometers. Some birds brood in the same nest box and sleep on the same perch in their wintering range year after year. Equipped with this map, about l percent of adult songbirds make it back to their nesting site to breed every year.

Migratory birds' navigational input comes from several senses—mainly sight, smell and magnetoreception. By observing the apparent night rotation of the stars around the North Star, the birds larn to locate due north before they embark on their showtime migration, and an internal 24-hour clock allows them to calibrate their sun compass. Feature smells tin can help birds recognize places they have visited earlier. Scientists know a great deal almost the detailed biophysical mechanisms of the birds' senses of sight and olfactory property. Simply the inner workings of their magnetic compass have proved harder to empathise.

The magnetic direction sense in minor songbirds that migrate at dark is remarkable in several of import respects. First, observations of caged birds exposed to carefully controlled magnetic fields bear witness that their compass does not behave like the magnetized needle in a ship's compass. A bird detects the axis of the magnetic field and the bending information technology makes with Earth's surface, the so-chosen inclination compass. In laboratory experiments, inverting the magnetic field'due south direction so that it points in exactly the opposite management has no issue on the bird'south ability to orient correctly. Second, a bird's perception of World's magnetic field tin exist disrupted by extraordinarily weak magnetic fields that reverse their direction several 1000000 times per second. Last, fifty-fifty though songbirds fly at night under the dim calorie-free of the stars, their magnetic compass is light-dependent, hinting at a link between vision and magnetic sensing.

In 1978, in an attempt to make sense of these features of avian magnetoreception, Klaus Schulten, and so at the Max Planck Establish for Biophysical Chemical science in Göttingen, Germany, put along a remarkable thought: that the compass relies on magnetically sensitive chemical transformations. At get-go glance, this proposal seems preposterous considering the energy bachelor from Globe's magnetic field is millions of times too small to break, or even significantly weaken, the bonds between atoms in molecules. Simply Schulten was inspired by the discovery 10 years previously that curt-lived chemic intermediates known as radical pairs have unique backdrop that make their chemistry sensitive to feeble magnetic interactions. Over the past 40 years researchers have conducted hundreds of lab studies of radical-pair reactions that are afflicted by the application of magnetic fields.

To appreciate why radical pairs are and then special, we need to talk about a quantum-mechanical property of the electron known as spin angular momentum, or "spin" for short. Spin is a vector with a direction as well as a magnitude, and it is often represented past an arrow, ↑ or ↓, for example. Particles with spin have magnetic moments, which is to say they comport like microscopic magnets. Most molecules have an fifty-fifty number of electrons arranged in pairs with opposed spins (⇅), which therefore abolish each other out. Radicals are molecules that accept lost or gained an electron, meaning that they contain an odd, unpaired, electron and hence have a spin and a magnetic moment. When ii radicals are created simultaneously past a chemic reaction (this is what we mean by radical pair), the two unpaired electrons, 1 in each radical, can have either antiparallel spins (⇅) or parallel spins (↑↑), arrangements known as singlet and triplet states, respectively.

Immediately after a radical pair is created in a singlet country, internal magnetic fields cause the two electronic spins to undergo a complex quantum "waltz" in which singlet turns into triplet and triplet turns dorsum into singlet millions of times per 2d for periods of upwardly to a few microseconds. Crucially, under the right weather, this dance tin can be influenced past external magnetic fields. Schulten suggested that this subtle quantum event could class the footing of a magnetic compass sense that might answer to environmental stimuli a million times weaker than would usually exist thought possible. Inquiry that we and others take carried out in recent years has generated fresh back up for this hypothesis.

Graphic shows how cryptochromes send molecular signals about Earth's magnetic field from a bird's retina to its brain.
Credit: Jillian Ditner (birds and eyes) and Jen Christiansen

A Possible Mechanism

To be useful, hypotheses demand to explain known facts and make testable predictions. Two aspects of Schulten'due south proposed compass mechanism are consequent with what is known nearly the birds' compass: radical pairs are indifferent to exact external magnetic field reversals, and radical pairs are often formed when molecules absorb calorie-free. Given that the birds' magnetic compass is low-cal-dependent, a prediction of Schulten'due south hypothesis is that their eyes play a part in the magnetic sensory arrangement. Nearly ten years agone the inquiry group of one of us (Mouritsen) at the Academy of Oldenburg in Germany establish that a brain region called Cluster Due north, which receives and processes visual information, is by far the most active part of the brain when sure night-migrating birds are using their magnetic compass. If Cluster N is dysfunctional, research in migratory European Robins showed, the birds tin can yet apply their sun and star compasses, but they are incapable of orienting using Earth's magnetic field. From experiments such as these, it is clear that the magnetic compass sensors are located in the birds' retinas.

Ane early objection to the radical-pair hypothesis was that no one had always shown that magnetic fields as tiny equally Earth's, which are 10 to 100 times weaker than a fridge magnet, could affect a chemic reaction. To address this point, Christiane Timmel of the University of Oxford and her colleagues chose a molecule chemically different annihilation 1 would find inside a bird: one that contained an electron donor molecule linked to an electron acceptor molecule via a molecular bridge. Exposing the molecules to dark-green calorie-free caused an electron to jump from the donor to the acceptor over a distance of about four nanometers. The radical pair that formed from this reaction was extremely sensitive to weak magnetic interactions, proving that information technology is indeed possible for a radical-pair reaction to exist influenced by the presence of—and, more than of import, the direction of—an Earth-strength magnetic field.

Schulten's hypothesis also predicts that there must exist sensory molecules (magnetoreceptors) in the retina in which magnetically sensitive radical pairs can be created using the wavelengths birds need for their compass to operate, which another line of enquiry had identified as lite centered in the bluish region of the spectrum. In 2000 he suggested that the necessary photochemistry could take place in a then recently discovered protein chosen cryptochrome.

Cryptochromes are constitute in plants, insects, fish, birds and humans. They have a variety of functions, including light-dependent control of plant growth and regulation of circadian clocks. What makes them attractive as potential compass sensors is that they are the just known naturally occurring photoreceptors in any vertebrate that form radical pairs when they absorb blue light. Six types of cryptochromes have been plant in the eyes of migratory birds, and no other blazon of candidate magnetoreceptor molecule has emerged in the past 20 years.

Like all other proteins, cryptochromes are composed of bondage of amino acids folded upwardly into complex three-dimensional structures. Buried deep in the centre of many cryptochromes is a xanthous molecule called flavin adenine dinucleotide (FAD) that, different the rest of the protein, absorbs blueish light. Embedded among the 500 or so amino acids that make upward a typical cryptochrome is a roughly linear chain of three or four tryptophan amino acids stretching from the FAD out to the surface of the protein. Immediately after the FAD absorbs a blueish photon, an electron from the nearest tryptophan hops onto the flavin portion of the FAD. The first tryptophan then attracts an electron from the second tryptophan and so on. In this way, the tryptophan chain behaves like a molecular wire. The net result is a radical pair fabricated of a negatively charged FAD radical in the center of the protein and, two nanometers abroad, a positively charged tryptophan radical at the surface of the protein.

In 2012 ane of us (Hore), working with colleagues at Oxford, carried out experiments to examination the suitability of cryptochrome equally a magnetic sensor. The study used cryptochrome-1, a poly peptide establish in Arabidopsis thaliana, the establish in which cryptochromes had been discovered 20 years before. Using short light amplification by stimulated emission of radiation pulses to produce radical pairs inside the purified proteins, nosotros found that we could fine-tune their subsequent reactions by applying magnetic fields. This was all very encouraging, but, of course, plants don't migrate.

We had to expect well-nigh a decade before we could make similar measurements on a cryptochrome from a migratory bird. The beginning challenge was to determine which of the six bird cryptochromes to look at. We chose cryptochrome-4a (Cry4a), partly because it binds FAD much more than strongly than do some of its siblings, and if at that place is no FAD in the protein, there will be no radical pairs and no magnetic sensitivity. Experiments in Oldenburg also showed that the levels of Cry4a in migratory birds are college during the spring and autumn migratory seasons than they are during wintertime and summer when the birds exercise not drift. Calculator simulations performed by Ilia Solov'yov in Oldenburg showed that European Robin Cry4a has a chain of four tryptophans—1 more than the Cry1 from Arabidopsis. Naturally, nosotros wondered whether the extended chain had evolved to optimize magnetic sensing in migratory birds.

Our next claiming was to get large amounts of highly pure robin Cry4a. Jingjing Xu, a Ph.D. student in Mouritsen'southward lab, solved it. Afterward optimizing the experimental conditions, she was able to apply bacterial cell cultures to produce samples of the protein with the FAD correctly jump. She also prepared versions of the protein in which each of the four tryptophans was replaced, one at a time, past a unlike amino acrid so as to block electron hopping at each of the four positions along the concatenation. Working with these culling versions of the protein would allow us to test whether the electrons are really jumping all the way along the tryptophan chain.

We shipped these samples—the start purified cryptochromes from whatever migratory animal—to Oxford, where Timmel and her husband, Stuart Mackenzie, studied them using the sensitive laser-based techniques they had developed specifically for that purpose. Their inquiry groups constitute that both the 3rd and fourth tryptophan radicals at the end of the chain are magnetically sensitive when paired with the FAD radical. Nosotros suspect that the tryptophans work cooperatively for efficient magnetic sensing, biochemical signaling and direction finding. We besides speculate that the presence of the fourth tryptophan might enhance the initial steps of signal transduction, the process past which nerve impulses encoding the magnetic field direction are generated and ultimately sent along the optic nerve to the encephalon. We are currently conducting experiments to identify the proteins that collaborate with Cry4a.

1 more than cryptochrome finding deserves mention here. We compared robin Cry4a with the extremely similar Cry4a proteins from two nonmigratory birds, pigeons and chickens. The robin protein had the largest magnetic sensitivity, hinting that evolution might have optimized robin Cry4a for navigation.

Open Questions

Although these experiments confirm that Cry4a has some of the properties required of a magnetoreceptor, we are still a long way from proving how migratory birds perceive World'due south magnetic field lines. One crucial side by side stride is to determine whether radical pairs actually course in the eyes of migratory birds.

The most promising way to exam for radical pairs inside the birds' eyes was inspired by the work of chemists and physicists who, in the 1980s, showed that fluctuating magnetic fields alter the way radical-pair reactions reply to static magnetic fields. Their work predicted that a weak radio-frequency electromagnetic field, fluctuating with the aforementioned frequencies every bit the "singlet-triplet waltz," might interfere with the birds' power to use their magnetic compass. Thorsten Ritz of the University of California, Irvine, and his colleagues were the beginning to ostend this prediction in 2004.

In 2007 Mouritsen began similar behavioral experiments in his lab in Oldenburg—with intriguingly dissimilar results. During the spring and fall, birds that travel between nesting and wintering grounds exhibit a behavior called Zugunruhe, or migratory restlessness, equally if they are anxious to get on their way. When caged, these birds usually employ their magnetic compass to instinctively orient themselves in the direction in which they would fly in the wild. Mouritsen found that European Robins tested in wooden huts on his university's campus were unable to orient using their magnetic compass. He suspected that weak radio-frequency noise (sometimes chosen electrosmog) generated past electrical equipment in the nearby labs was interfering with the birds' magnetic compass.

European Robin.
Bar-tailed Godwit.
European Robin (top) and Bar-tailed Godwit (bottom) are among the many birds that migrate long distances. Credit: Adrian Coleman/Getty Images; Imogen Warren/Getty Images (top and bottom)

To confirm that electrosmog was the source of the problem, Mouritsen and his squad lined the huts with aluminum sheets to cake the stray radio frequencies. On nights when the shields were grounded and functioned properly, the birds oriented well in Globe's magnetic field. On nights when the grounding was asunder, the birds jumped in random directions. When tested in an unshielded wooden shelter typically used for horses some kilometers outside the city and well abroad from electrical equipment, the aforementioned birds had no trouble detecting the direction of the magnetic field.

These results are significant on several fronts. If the radio-frequency fields affect the magnetic sensor and not, say, some component of the signaling pathway that carries nerve impulses to the brain, then they provide compelling evidence that a radical-pair mechanism underpins the bird'south magnetic compass. The main competing hypothesis, for which in that location is currently much less support, proposes that magnetic iron–containing minerals are the sensors. Whatsoever such particles that were big enough to align like a compass needle in Earth's magnetic field would be far too big to rotate in a much weaker field that reversed its direction millions of times per second. Furthermore, the radio-frequency fields that upset the birds' magnetic orientation are astonishingly weak, and nosotros don't yet empathize exactly how they could corrupt the directional information available from the much stronger magnetic field of Earth.

It is also remarkable that the birds in the Oldenburg lab were disoriented much more effectively past broadband radio-frequency noise (randomly fluctuating magnetic fields with a range of frequencies) than by the single-frequency fields more often than not used by Ritz and his collaborators. We hope that by subjecting migratory songbirds to bands of radio-frequency noise with different frequencies we will be able to determine whether the sensors really are FAD-tryptophan radical pairs or whether, equally some other investigators have suggested, another radical pair might be involved.

Many questions well-nigh the birds' magnetic compass remain, including whether the magnetic field furnishings on robin Cry4a observed in vitro also be in vivo. Nosotros besides want to see whether migratory birds with genetically suppressed Cry4a production are prevented from orienting using their magnetic compass. If nosotros can show that a radical-pair mechanism is backside the magnetic sense in vivo, then we volition take shown that a biological sensory organization tin can respond to stimuli several million times weaker than previously thought possible. This insight would raise our understanding of biological sensing and provide new ideas for artificial sensors.

Working to gain a total understanding of the inner navigation systems of migratory birds is non only an intellectual pursuit. One effect of the enormous distances migratory birds travel is that they face more astute threats to their survival than most species that breed and overwinter in the same place. It is more hard to protect them from the harmful effects of human activity, habitat destruction and climate modify. Relocating migratory individuals abroad from damaged habitats is rarely successful because the birds tend to instinctively render to those unlivable locales. Nosotros hope that by providing new and more mechanistic insights into the ways in which these extraordinary navigators find their way, conservationists will have a ameliorate hazard of "tricking" migrants into believing that a safer location actually is their new home.

When you next see a small songbird, pause for a moment to consider that it might recently have flown thousands of kilometers, navigating with great skill using a brain weighing no more than than a gram. The fact that breakthrough spin dynamics may take played a crucial part in its journey only compounds the awe and wonder with which we should regard these extraordinary creatures.