Chapter 9 – Emerging Biophysics Techniques  425

Two competing models for magnetoreception in birds use either classical physics in

alluding to a magnetic particle (the presence of small magnetic particles of magnetite is found

in the heads of many migratory birds) or a quantum mechanical model based on the gener­

ation of radical pairs. The latter theory implicates a molecule called cryptochrome—​a light-​

sensitive protein that absorbs a blue light photon to generate two radical pairs (molecules

with a single unpaired electron).

This effect has been studied most extensively in the migratory patterns of a bird Erithacus

rubecula (known more commonly as the European robin, the one you have probably seen

yourself, if not in the flesh, then from its ubiquitous images on Christmas cards). Evidence

has grown since the original study published in 2004 (Ritz et al., 2004) that each robin poten­

tially utilizes a chemical compass in the form of cryptochrome that is expressed in certain

cells in the retinas of the birds’ eyes (cryptochromes have also been found in photoreceptor

nerve cells in the eyes of other birds and insects and in some plant cells and bacteria).

Cryptochrome contains a flavin cofactor called “FADH” (the hydrogenated form of flavin

adenine dinucleotide, the same cofactor as occurs at various stages in Krebs tricarboxylic

acid cycle; see Chapter 2). One hypothesis is that molecular oxygen can enter a molecular

binding pocket of the cryptochrome molecule, and a radical pair can then be formed upon

the absorption of a single photon of blue light consisting of FADH· and the molecular oxygen

superoxide O2

, where “·” indicates an unpaired electron. In this case, an expectation is, from

the possible combinations of spins of the products, a proportion of 25% of pairs will be in the

singlet spin state and 75% in the triplet spin state, though magnetic coupling with the radical

states due to both internal and external magnetic fields, nuclear hyperfine, and Zeeman

coupling, respectively, to the Earth’s magnetic field (see Chapter 5), may also enable singlet/​

triplet interconversion.

If the radical pair is in its singlet state, the unpaired electron from the superoxide radical

may transfer to the FADH radical, forming a singlet (FADH−A +​ O2) state, which has lower

free energy and is magnetically insensitive (note that this electron transfer is not possible

from the triplet state of the radical pair since this would not conserve total spin). That is, the

radicals are self-​quenched. However, if the superoxide radical escapes from the molecular

pocket before this quenching electron transfer occurs, then this can result in an extended life­

time of the magnetically sensitive radical states for as long as the spins between the electrons

of the FADH· and the O2

exhibit quantum entanglement. This presents an opportunity for

an external magnetic field to affect the reaction by modulating the relative orientation of the

electron spins.

If the singlet/​triplet radical products have sufficiently long quantum coherence times, they

may therefore be biologically detectable by as a chemical compass—​in essence, the entangle­

ment would imply that the extent of any coupling observed depends on the local magnetic

field. One hypothesis is that the superoxide formed in the radical pair is particularly important

in magnetoreception. This is because the oxygen radical does not exhibit hyperfine coupling,

and so any observed coupling is a metric of the external magnetic field.

Quantum entanglement–​based magnetoreception is speculative at several levels. First, it

implies that modulation of the reaction products by a magnetic field would lead to a behav­

ioral modulation of the bird’s flight through, presumably, the bird’s sense of vision combined

with moving its head to scan the B-​field landscape, for example, generating brighter or darker

regions on the bird’s retina. But there is no clear experimental evidence for this effect. Also, it

is unclear specifically where in the bird’s eye this putative radical pair reaction would actually

takes place. It may well be that high-​resolution biophysical structural imaging tools, such as

AFM, may provide some future insight here, at least into mechanisms of free radical forma­

tion upon light absorption.

Most challenging to this theory, however, are estimates that the entangled state would

need to last >100 μs to have sufficient sensitivity for use a chemical compass given the low

strength of the Earth’s B-​field of ~5 mT. However, the longest entangled states observed to

date experimentally in the laboratory have lifetimes of ~80 μs, seen in a special inorganic

molecule from a class called endohedral fullerenes (or endofullerenes or simply fullerenes for

short) known as “N@C60” that consists of a shell of 60 carbon atoms with a single nitrogen

atom at the center and is highly optimized for extended quantum entanglement since the