NEWS & VIEWS
dissecting this drugs mechanism of action and
its side effects.
Roland Martin is at the Institute for
Neuroimmunology and Clinical Multiple Sclerosis
Research, University Medical Center-Eppendorf,
D-20251 Hamburg, Germany.
e-mail: roland.martin@zmnh.uni-hamburg.de
1. Kappos, L. et al. N. Engl. J. Med. 362, 387401 (2010).
2. Cohen, J. A. et al. N. Engl. J. Med. 362, 402415
(2010).
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(2005).
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5. Johnson, K. P. et al. Neurology 45, 12681276 (1995).
SOLID-STATE PHYSICS
Golden ratio seen in a magnet
Ian Affleck
The golden ratio an exact magic number often claimed to be observed
when taking ratios of distances in ancient and modern architecture,
sculpture and painting has been spotted in a magnetic compound.
According to Albert Einsteins formula E = mc2,
when several particles form a collective bound
state, the mass (m) of the system is reduced
from the sum of the constituent masses by the
binding energy (E) of the ensemble divided
by the square of the speed of light (c). For the
strong forces, which hold together protons
and neutrons in nuclei, and quarks in protons
and neutrons, the ratio of the systems mass
to the sum of the constituent masses can be
significantly reduced from 1. For such rela-
tivistic bound states of matter, in which the
constituents rotate around each other at close
to the speed of light, calculation of these mass
ratios is a challenging problem and requires
methods of quantum-field theory (those in
which functions defined at all points in space
are treated as quantum variables). Writing in
Science, Coldea and colleagues1 describe how
they measured such a mass ratio in a magnetic
material, and show that it agrees well with an
old exact theoretical prediction2.
Calculations of mass ratios for bound states
of quarks are generally tackled by large-scale
computer simulations, which yield large uncer-
tainties3. But there are integrable models of
quantum-field theory in which particles
are restricted to a universe of only one spatial
dimension for which such mass ratios can
be calculated exactly4. In some of these integra-
ble theories, particle binding is so strong that
which particles are fundamental and which are
bound states may be a matter of interpretation.
Geoffrey Chew argued5, in an idea he dubbed
nuclear democracy, that it is possible that all
particles are bound states of matter, and so are
in some sense equal.
Although our Universe has at least three
spatial dimensions (even more according to
362
6. Miller, D. H. et al. N. Engl. J. Med. 348, 1523 (2003).
7. Pascual, A. M. et al. Mult. Scler. 15, 13031310 (2009).
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10. Chiba, K. et al. J. Immunol. 160, 50375044 (1998).
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(2002).
13. Cinamon, G. et al. Nature Immunol. 5, 713720 (2004).
14. Miron, V. E. et al. Ann. Neurol. 63, 6171 (2008).
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(2000).
16. Premenko-Lanier, M. et al. Nature 454, 894898
(2008).
17. Leypoldt, F. et al. Neurology 72, 10221024 (2009)
The author declares competing financial interests. See online
article for details.
been predicted much earlier4,810. This work6
string theory), experimental realizations of
lower-dimensional universes can be found
in condensed-matter systems. One example
is the electrical insulator copper benzoate
(Cu(C6H5CO2)23D2O), which contains chains
of magnetic copper atoms that interact with
their neighbours through antiferromagnetic
Heisenberg interactions. Classically, below a
critical temperature, these interactions cause
the magnetic moments (spins) of neighbouring
atoms to point oppositely but along an arbi-
trary axis in three-dimensional space. Because
the chains in copper benzoate are weakly cou-
pled to one another, each chain can be regarded
approximately as a separate one-dimensional
universe, one in which the spins act together to
form quasiparticles collective bound states
Figure 1 | The golden ratio in ancient architecture. The semi-base, height and apothem of the
Great Pyramid of Giza, constructed around 2,550 bc in Egypt, are in the proportions 1::, where
= 1.618034 is the golden ratio. Coldea and colleagues1 find that, under a particular magnetic field,
the masses of two quasiparticles in cobalt niobate approach the golden ratio.
2010 Macmillan Publishers Limited. All rights reserved
NATURE|Vol 464|18 March 2010
of matter that propagate through the system
much like a particle does.
Neutron-scattering experiments6 performed
on copper benzoate measured the energies and
momenta of low-energy quasiparticles in this
system; the properties of a beam of neutrons
scattered off the material vary by an amount
that depends on the energies and momenta of
the quasiparticles. Three quasiparticles were
found whose energies have the same momen-
tum dependence as the energies of three types
of massive relativistic particle, if the speed of
light is replaced by the much lower quasiparti-
cle velocity of approximately 1,100 m s1. The
masses of these quasiparticles were measured
from the relativistic energymomentum rela-
tionship. By taking into account some rather
unusual magnetic interactions in copper ben-
zoate, it was later shown7 that the low-energy
behaviour of this material is governed by an
integrable quantum-field theory in one spatial
dimension, known as the sine-Gordon model,
for which exact bound-state mass ratios had
thus provided what may have been the first
experimental test of exact mass-ratio predic-
tions for integrable quantum-field theories
in one spatial dimension, and the agreement
was good.
Coldea et al.1 report results of a neutron-
scattering experiment on another quasi-one-
dimensional magnetic compound, cobalt
niobate (CoNb2O6). In this case, the spins of
the Co atoms in a chain order magnetically at
low temperatures according to the one-dimen-
sional Ising model of ferromagnetism: all spins
point in the same direction, either up or down,
along a fixed easy axis. The authors show that,
at a critical magnetic field of 5.5 tesla applied
transverse to the easy axis, the system under-
goes a quantum-phase transition beyond which
the Ising magnetic order is destroyed, and each
spin may be thought of as going into a quantum
superposition of the up and down orientations.
At field strengths slightly below the critical
P. SVARC/PHOTOLIBRARY.COM
NATURE|Vol 464|18 March 2010
value, they1 treat the weak inter-chain Ising
couplings, in a standard approximation, as
giving an effective longitudinal magnetic field
which acts on the nearly isolated chains
NEWS & VIEWS
approach the golden ratio, indicating that E8
might underlie the low-temperature physics
of this system. Whether such a ratio applies
to other solid-state systems remains to be */(-'( (3(.-
(-'( (3(.-

in addition to the transverse field.
It has previously been shown theoreti-
cally 2 that the one-dimensional Ising model
of ferromagnetism at the critical transverse
field, combined with a very weak longitudinal
+(%--3
field, is a realization of a particular integrable
quantum-field theory. The lightest two parti-
cles of such a theory, labelled A and B, obey a
type of nuclear democracy: particle B can be
regarded as a bound state of two particles of
type A and, at the same time, particle A can
be regarded as a bound state of two particles
of type B. This situation was shown2 to require
particle masses in the golden ratio: the unique
solution of mB/mA = (mA + mB)/mB for positive
masses, which is about 1.618034. Physicists
have found this type of quantum-field theory
especially intriguing because of its hidden E8
structure. E8 is the largest of the exceptional
symmetry Lie groups and occurs in various
models of elementary particle physics, includ-
ing both grand unified field theories (in three
spatial dimensions) and string theories.
In their experiment, Coldea and colleagues1
show that, in the vicinity of the critical
transverse field, the masses of two different
low-energy quasiparticles in cobalt niobate
CANCER
A lower bar for senescence
Manuel Serrano
Cellular senescence is a physiological mechanism for thwarting the
proliferation of tumour cells. Encouraging cancer-prone cells to senesce
might therefore be a way to nip this disease in the bud.
Genetic mutations are routine cellular events:
it is estimated that each gene is mutated once
in every 20,000 cells1. Considering both the
fact that an organism has trillions of cells and
the variety of oncogenic mutations, at any
given time there are probably millions of cells
primed to become cancerous (oncogenically
primed). Fortunately, most of these danger-
ous cells are disposed of through programmed
cell death (apoptosis) and cellular senescence.
Two papers2,3, including one by Lin et al.2 in
this issue, shed light on the molecular mecha-
nisms underlying cancer-associated senes-
cence, reporting results that could have clinical
relevance.
Cellular senescence is a stress response that
is characterized by robust inhibition of cell
proliferation; this often becomes irreversible
and independent of the initial stress trigger4.
Signalling by oncogenic proteins, oxida-
tive damage and persistent DNA damage are
among the best-studied triggers of senescence4.
seen. More generally, the golden ratio of two
quantities has intrigued mathematicians for
at least 2,400 years, and has been shown to
occur in modern and ancient architecture
(Fig. 1), sculpture and painting. It has even
been claimed to exist in nature, for example in
the arrangement of branches along the stems
of plants and of veins in leaves.
Ian Affleck is in the Department of Physics and
Astronomy, University of British Columbia,
Vancouver, V6T 1Z1 British Columbia, Canada.
e-mail: iaffleck@phas.ubc.ca
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(2000).
4. Zamolodchikov, A. B. & Zamolodchikov, Al. B. Ann. Phys.
120, 253291 (1979).
5. Chew, G. F. The Analytic S-Matrix: A Basis for Nuclear
Democracy (Benjamin, 1966).
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Aeppli, G. Phys. Rev. Lett. 79, 17501753 (1997).
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(1997).
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34243450 (1975).
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138139 (1975).
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10391049 (1975).
In experimental mouse models, senescent cells
can be engulfed by phagocytic cells in a pro-
cess that is essentially similar to the removal of
apoptotic cells5. The clearance of oncogenically
primed cells by induced senescence is gaining
increasing attention as accumulating evidence6
points to its role in tumour suppression.
Tumorigenesis can usually be divided into
three stages: the initial proliferation of cells
carrying oncogenes (pre-tumoral stage); the
formation of a non-invasive tumour (pre-
malignant stage); and the formation of a locally
invasive and metastasizing tumour (malignant
stage or, simply, cancer) (Fig. 1). The transi-
tion from one stage to the next is generally
accompanied by an increase in the levels of
the senescence-inducing stressors mentioned
above. Most human and mouse tumour cells
stop proliferating and undergo senescence at
the pre-malignant stage6, suggesting that it is
at this stage that senescence-inducing signals
reach sufficient intensity to be effective (Fig. 1).
2010 Macmillan Publishers Limited. All rights reserved
#5#+.$231#22
4,.41 .1,+ Pre-tumoral Pre-malignant
23%# 3(224# tissue tumour 34,.41
#-2(3(9#" .1,+
!1(3(!+/.(-3 !1(3(!+/.(-3
$.12#-#2!#-!# $.12#-#2!#-!#
,/1.5#"!-!#1
/1.3#!3(.-
.2("###!32
Figure 1 | Manipulating the threshold for
senescence.With increasing levels of
senescence-inducing stress (oncogenes,
DNA damage, oxidative damage), tumour
development goes through three stages. The
stressors normally reach sufficient intensity to
trigger senescence only at the pre-malignant
tumour stage. Two groups2,3 show that the critical
point for triggering senescence can be lowered by
inhibiting either Skp2 or CDK2. Decreasing this
critical point results in cellular senescence at the
pre-tumoral stage, which translates into better
protection against cancer.
Moreover, mutations that disable the senescence
response are instrumental in the transition of
oncogene-harbouring cells to a malignant
stage, again highlighting the importance of
senescence in countering malignancy 6.
Although the tumour-suppression machinery
is highly efficient, it is obviously not infallible.
In thinking of ways to improve it, one wonders
why tissues wait until the pre-malignant stage
to unleash senescence. Would it not be better
to trigger this defensive response earlier, at the
pre-tumoral stage? Lin et al.2 (page 374) and
Campaner and colleagues3 have independently
attempted to lower the bar of senescence and
look at the effects on cancer.
Both teams find that the key to lowering
the bar for senescence lies in the activity of a
group of enzymes known as cyclin-dependent
kinases, or CDKs. Earlier work4 has shown that
inhibition of CDK2, CDK4 and CDK6, all of
which mediate the initial (G1) phase of the cell-
division cycle, is crucial for establishing senes-
cence. Senescence-inducing stressors inhibit
these G1 CDKs by increasing the expression of
CDK inhibitory proteins (CKIs), which include
p16, p21 and p27 (refs 4, 7). Because of a large
degree of functional redundancy among the
three G1 CDKs, elimination of each of these
enzymes individually or even in pairs has only
minor effects on the normal physiology of a
mammalian organism7. The present studies2,3
build on these previous findings and explore
whether decreasing the activity of G1 CDKs
might lower the critical point for triggering
363