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“Some of us should venture to embark on a synthesis
of facts and theories, albeit with secondhand and
incomplete knowledge of some of them – and at the
risk of making fools of ourselves.”
So said Erwin Schrödinger in 1943 upon his foray
from quantum physics into genetics. He would soon
back up these words with his hugely influential 1944
book, What is Life?, in which he predicted that genetic
information is stored within an aperiodic crystal – an
idea that would be confirmed by Francis Crick and
James Watson less than a decade later when they
discovered the structure of the double helix. Today,
a small but increasing number of us would echo
Schrödinger’s sentiments, even though the case has
yet to be made conclusively for a causal link between
some of the weirder aspects of quantum mechanics
and biology.
It is certainly true that although many examples
can be found in the literature dating back half a
century, there is still no widespread acceptance
that quantum mechanics – that baffling yet powerful
theory of the subatomic world – might play a
crucial role in biological processes. Of course, biology
is, at its most basic, chemistry, and chemistry is
built on the rules of quantum mechanics in the way
atoms and molecules behave and fit together. But
biologists have (until recently) been dismissive of the
counterintuitive aspects of the theory – they feel it
to be unnecessary, preferring their traditional balland-stick
models of the molecular structures of life.
Likewise, physicists have been reluctant to venture
into the messy and complex world of the living cell.
Why should they when they can test their theories
far more cleanly in the controlled environment of
the physics lab, where they at least feel they have a
chance of understanding what is going on? But now,
experimental techniques in biology have become so
sophisticated that the time is ripe for testing a few
ideas familiar to quantum physicists.
Sticking together
Of all the quantum processes suggested as playing a
role in biology – which include quantum coherence,
superposition and entanglement – one of the least
contentious and best studied is quantum tunnelling.
This is the mechanism whereby a subatomic particle,
such as an electron, proton or even a larger atomic
nucleus, does not have enough energy to punch
through a potential barrier (essentially a force field),
but instead behaves as a spread-out fuzzy entity that
can leak through the barrier and so occasionally find
itself on the other side. This phenomenon is familiar
in physics and is the mechanism responsible for radioactive
decay and nuclear fusion. Quantum tunnelling
is also well known in chemistry, for example in
the form of hydrogen tunnelling in hydrogen-bonded
dimer molecules, such as benzoic acid.
It turns out that even in biology it is now well established
that electrons quantum tunnel in enzymes,
allowing certain chemical processes to speed up by
several orders of magnitude. But one particular question
that I, and others, have been exploring over the
past few years is whether quantum tunnelling of hydrogen
nuclei (protons) in the form of a hydrogen bond
Quantum frontiers: Quantum biology
has a role to play in one of the most important processes
in molecular biology: DNA mutation. Hydrogen
bonds are stronger than Van der Waals forces but
weaker than ionic and covalent bonds, being a happy
medium that hold certain organic molecules together.
Crucially, they are strong enough to help build stable
structures, but not so strong that they cannot be broken,
which is why the structures can be rearranged
into new configurations. The hydrogen bond is also
responsible for stabilizing proteins and for modulating
the speed and specificity of chemical reactions.
In physical terms, the hydrogen bond can be
described as a proton trapped in a double, often
asymmetric, finite potential well. The two potential
minima exist because the proton is happiest being
close to one or other of the two atoms at each end of
the bond, with an energy barrier in the middle, which
the proton can only get over classically if given sufficient
energy. To understand the proton’s behaviour
we need to map the shape of this well, or potential
energy surface, very accurately. This is no trivial matter
as its shape depends on many variables. Not only
is the bond typically part of a large complex structure
consisting of hundreds or even thousands of atoms,
it is also usually immersed in a warm bath of water
molecules and other chemicals. Moreover, molecular
vibrations, thermal fluctuations, chemical reactions
initiated by enzymes and even UV or ionizing radiation
can all affect the behaviour of the bond both
directly and indirectly. In addition to all this, and
what is of most interest here, is that the small mass
of the proton means it is able to behave quantummechanically
and very occasionally tunnel through
the potential barrier from one well to the other (see
for example the 2011 paper by Angelos Michaelides
and colleagues at University College London – Proc.
Natl Acad. Sci. 108 6369).
This discussion is certainly relevant to DNA, which
consists of two nucleotide chains wrapped around
each other in a double helix. They are held together
and stabilized by hydrogen bonds, which link the base
pairs: adenine to thymine (A–T) and cytosine to guanine
(C–G). If we consider the A–T base pair, which
is held together by two hydrogen bonds, then as a
result of the different possible positions of the hydrogen
atoms that form the bonds, two different structures
are possible. Normally, the protons form what is
called the canonical (keto) structure of the base pair
(figure 1), but occasionally they can be found shifted
across to the opposite sides of the hydrogen bonds to
form the rare tautomeric (enol) form.
After their landmark paper, which was published
60 years ago next month, Watson and Crick’s interests
quickly turned to the biological implications of
the double-helix structure and in a follow-up paper
of 1953 they suggested that spontaneous mutation – a
change in the genetic code, for example from ATCAT
to ATCAC – may be caused by a base taking on its
higher-energy, rarer, tautomeric form. A decade
later, the Swedish physicist Per-Olov Löwdin boldly
proposed that the tautomeric base pair that leads to
a mutation is formed through double proton transfer,
with each particle quantum tunnelling through the
barrier separating the two asymmetric potential wells
Jim Al-Khalili is a
theoretical nuclear
physicist and holds a
chair in public
engagement in
science at the
University of Surrey,
UK. He is also a
broadcaster and
author whose latest
book is Paradox:
the Nine Greatest
Enigmas in Physics
published by Bantam
Press, e-mail
j.al-khalili@
surrey.ac.uk
Physics World March 2013 43