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affect anything of any importance in thereal, macroscopic world? Amazingly, theydo, and the paper by Ghosh et al.1 on page48 of this issue demonstrates just that.
Ghosh et al. report experiments involvingthe magnetic salt compound LiHo0.045Y0.955F4
(see refs 4–6 in ref. 1). The atoms in this saltall behave like small magnets, interactingwith each other as well as adjusting them-selves to any external magnetic field (mod-elled by an Ising chain of interacting spins).The authors1 investigated the magnetic sus-ceptibility of the system for a range of lowtemperatures. Susceptibility tells us howmuch the magnets align with each otherwhen an external magnetic field is applied,sothe greater the susceptibility the more themagnets align when the external magneticfield is increased. Our intuition would tell usthat the more correlated the magnets, thehigher the degree of susceptibility we should
expect. Also, as the temperature increases,the magnets heat up and their behaviourbecomes more random, less correlated2,3.Wewould therefore expect the susceptibility todecrease with temperature. Experimentshows that it does (Fig. 1a), but how dotheoretical predictions compare?
One way of deriving the macroscopicproperties of a physical system — known asthe ‘royal route’ in the technical jargon — isby classical statistical mechanics. Here thefirst and most important task is to constructthe partition function of the system underinvestigation. This is a sum over the variousenergy states that the system can occupy andtells us how the system distributes itself overthe available states in terms of probabilities.Once we have the partition function, we canthen compute all the other relevant (andmacroscopically observable) properties,such as the internal energy of the system, itspressure, entropy and susceptibility and soon. This is quite remarkable: knowing thedifferent energy states that the system canoccupy is sufficient to construct all the othermacroscopic quantities needed to describethe physical system completely. But, ulti-mately, this conclusion is erroneous, as canclearly be seen in the disagreement shown byGhosh et al.1 between the classical predic-tions and experimental results (Fig.1a).
Quantum mechanically, if we wish to fullyspecify the state of a system, we need to knowboth the energy levels and the particular statescorresponding to these energy levels. Looselyspeaking, this means that for a salt such asLiHo0.045Y0.955F4 we need to know the orienta-tions of the magnetic atoms and not just theiroverall energy. More significantly, these statescould, through quantum mechanics, displayan excess of correlations between the individ-ual magnets over and above anything allowedin classical physics — they could be entan-gled2,3.And, amazing though it may seem, thepresence of this entanglement can make a dif-ference in observed macroscopic quantities.As the quantum correlations are stronger thanclassical ones,we can predict that the suscepti-bility will be higher according to quantummechanics. This is indeed demonstrated by Ghosh et al.1, and they also show that other quantities, such as the heat capacity,depend on the presence of entanglement (seeFig.2 on page 49).
This work is important for at least tworeasons: one is that it is no longer enough forphysicists to investigate only the energy spec-trum of a system, but some other features —such as entanglement in this case — are ofparamount importance in the overall behav-iour of the system. The other reason is thateven a very small amount of entanglementcan produce significant effects in the macro-scopic world (Fig.1b).
Finally, I should like to indulge in a littlespeculation. It is widely accepted that quantum mechanics is our most accurate
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28 NATURE | VOL 425 | 4 SEPTEMBER 2003 | www.nature.com/nature
Crowding also seems to affect the way inwhich bacteria adapt to large changes in theconcentration of osmotically active mole-cules in their environment: bacteria grownunder widely disparate osmotic environ-ments show significant differences in theirintracellular concentrations of macro-molecules, as well as of smaller molecules(S. Cayley, Univ. Wisconsin–Madison).Other processes influenced by crowdinginclude: the regulation of metabolic path-ways associated with signal transduction(H. Westerhoff, Free Univ. Amsterdam); theextraordinary stability of the crystallin pro-teins in the lens of the eye (J.Clauwaert,Univ.Antwerp); and the synthesis of compact pro-teins from peptide fragments by enzymesthat catalyse the opposite reaction, polypep-tide breakdown, in the absence of crowding(R. Roy, Natl Inst. Immunol., New Delhi).Moreover, when DNA is in the crowding-induced compact conformation — ratherthan the worm-like coiled shape seen indilute solution — several enzyme-catalysedDNA-processing reactions are accelerated bymany orders of magnitude (J. L. Sikorav,CEA-Saclay,Gif-sur-Yvette).
One of the more dramatic effects ofcrowding is the stimulation of the rate andextent of formation of rod-like proteinaggregates. Examples are the amyloid fibresof synuclein that are implicated in Parkin-son’s disease (A.Fink,Univ.California,SantaCruz), microtubules (D. Hall, Univ. Cam-
bridge ), and large arrays of the protein FtsZ,essential to bacterial division (J. Gonzalez,CIB-CSIC, Madrid). Also, the rate of forma-tion of fibres of deoxygenated haemoglobin S(the mutant form found in patients withsickle-cell anaemia) can vary over severalorders of magnitude depending on thedegree of crowding. This dependence can beaccounted for quantitatively over the entirerange of experimental observation by rela-tively simple hard-particle models of exclu-ded volume (F.Ferrone,Drexel Univ.).
It seems likely from the observationsreported at this meeting, and reviewedrecently1,2, that macromolecular crowding invivo is involved in many aspects of cellularfunction. Given that crowding was not dis-covered yesterday,one may wonder why littlemention of this phenomenon is found incurrent textbooks of biochemistry and mol-ecular and cell biology. ■
R. John Ellis is in the Department of BiologicalSciences, University of Warwick,Coventry CV4 7AL, UK.e-mail: [email protected] P. Minton is at the National Institute ofDiabetes and Digestive and Kidney Diseases,National Institutes of Health, US Department ofHealth and Human Services, Bethesda,Maryland 20892-0830, USA.e-mail: [email protected]. Ellis, R. J. Trends Biochem. Sci. 26, 597–604 (2001).2. Hall, D. & Minton, A. P. Biochim. Biophys. Acta 1649,
127–139 (2003).3. Medalia, O. et al. Science 298, 1209–1213 (2002).
Entanglement describes a correlationbetween quantum mechanical sys-tems, such as photons or atoms, that
does not occur in classical, newtonianphysics. Under scrutiny since the birth ofquantum theory, such correlations havebeen used to highlight a number of appar-ent paradoxes at the heart of quantumphysics, but their existence has neverthelessbeen confirmed in a number of differentexperiments since the beginning of the1980s. For instance, the entanglement oftwo photons means that once the state ofone photon is known, we immediatelyknow the state of the other; entanglement isalso the basis of the quantum computer.But who, apart from possibly a few phil-osophers of physics and some computerscientists, actually cares about statisticalcorrelations between two or more systems?In other words, do quantum correlations
Quantum physics
Entanglement hits the big timeVlatko Vedral
Entanglement is a quantum phenomenon usually associated with themicroscopic world. Now it is clear that its effects are also relevant onmacroscopic scales, such as in the magnetic properties of some solids.
© 2003 Nature Publishing Group
and behavioural traits (its phenotype). Onebroad type of genetic screen is the pheno-type-driven screen, in which mutations aregenerated at random across the genome, andoffspring are scrutinized for phenotypes ofinterest. Mutant phenotypes that are herita-ble can then be mapped to the mutatedregion of the genome; next, the region isnarrowed down, and the precise gene that isaffected can be pinpointed.
This kind of approach has driven bac-terial, yeast and invertebrate genetics foryears, and has recently been applied togenome-wide screens in zebrafish. In mice,
NATURE | VOL 425 | 4 SEPTEMBER 2003 | www.nature.com/nature 29
the chemical N-ethyl-N-nitrosourea (ENU)is the mutating agent (mutagen) of choicefor such screens; there are several large-scaleENU-based screens under way worldwide2,3.Unexpected phenotypes, particularly relat-ing to human disease, arise from ENUscreens, because all kinds of mutations aregenerated, not just those that inactivategenes. For this reason, ENU-mutagenizedeggs or sperm4 and embryonic stem cells5,6
can also be used in a sequence-based searchfor new variants (alleles) of known genes.
Phenotype-driven screens for dominantmutations (those in which just one of the twocopies of a given gene need be mutated toproduce a physical effect) can be performedon a large scale in mice, because phenotypescan be identified in the first-generation off-spring of a mutated animal. Nevertheless,only about 1% of offspring reveal any sort ofmutant phenotype, and good quantitativescreening tools are needed to detect what canbe fairly subtle effects.
By contrast, screens for recessive muta-tions, in which both copies of the gene needto be mutated to produce an effect, yieldmutant phenotypes at a high rate. Suchscreens are an effective way of finding newmutations that cause embryonic death —even small screens have yielded mutationsthat identify new molecular players in devel-opment7,8. But the drawback here is that it ishard to cover the whole genome, because ofthe numbers of mice involved and the diffi-culties in following pedigrees (family trees).
Tackling the genome one region at a timehas advantages, as shown a few years ago9, ina strategy in which one part of a chromo-some was deleted and mutations weredetected on the other copy of that chromo-some. Deletions of any size and position cannow be engineered in the mouse genome.But many deletions turn out to be lethalwhen introduced as one copy into mice. It isthus not possible to use deletions to cover thewhole genome for mutations. Instead, Kile et al.1 took a leaf from the book of the fruitflygeneticists: they used a ‘balancer’ chromo-some to enable them to isolate mutations inone particular chromosomal region easily,even though mutations were induced acrossthe genome by ENU (Fig.1,page 31).
By using chromosome-engineering strat-egies pioneered by Bradley and colleagues10,Kile et al. made an inversion within one ofthe two copies of their chromosome of inter-est, chromosome 11. The inversion spanned2% of the genome, and an estimated 700genes. It also disrupted the essential geneWnt3, found at one end of the invertedsequence — so the inversion-bearing chro-mosome has to be balanced at all times by anormal copy of chromosome 11 (explainingwhy the inversion-bearing chromosome iscalled a balancer). Finally, the inversion wasengineered to carry a foreign gene thatresults in yellow fur.
Figure 1 Far-reaching effects of entanglement. In the absence of a magnetic field, the magneticmoments of atoms in a solid point in random directions (inset); as a magnetic field is applied, themagnetic vectors tend to align with the field. But the alignment is greater than predicted by classicalcalculations, the excess correlation of the vectors being explained by the existence of quantumentanglement between them. Working with the salt LiHo0.045Y0.955F4, Ghosh et al.1 have demonstratedthe influence of quantum entanglement on the macroscopic properties of a solid. a, Theirmeasurements of the salt’s magnetic susceptibility as a function of temperature are consistent withthe prediction that includes quantum entanglement: models based on classical energy levels in thesystem, and on quantum energy levels but without entanglement, do not describe the data. b, Theinfluence of entanglement on magnetic susceptibility is also seen through the ratio of magnetic ‘g-factors’ (which define the relationship between magnetization and spin in directionsperpendicular and parallel to the applied magnetic field). The measured ratio and susceptibility (at fixed temperature) for LiHo0.045Y0.955F4 are again consistent with the presence of entanglement.(Graphs derived from Figs 1 and 4 on pages 48 and 50.)
Withoutentanglement
Withentanglement
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description of how atoms combine to form molecules, and it lies behind all chemistry.Chemistry in turn provides a basis for bio-logical processes, including the metaboliccycles and the replication machinery makingit possible for life to be sustained.So,might itbe not only that quantum effects are respon-sible for the behaviour of inanimate matter,but that the magic of entanglement is alsocrucial in the existence of life4? ■
Vlatko Vedral is in the Blackett Laboratory,Imperial College, Prince Consort Road,London SW7 2BZ, UK.e-mail: [email protected]
1. Ghosh, S., Rosenbaum, T. F., Aeppli, G. & Coppersmith, S. N.
Nature 425, 48–51 (2003).
2. Arnesen, M. C., Bose, S. & Vedral, V. Phys. Rev. Lett. 87,
017901 (2001).
3. Gunlycke, D., Kendon, V., Vedral, V. & Bose, S. Phys. Rev. A 64,
042302 (2001).
4. Landsberg, P. T. Nature 203, 928–930 (1964).
Genetics
A balancing actJanet Rossant
Mutations in model organisms are grist to the geneticists’ mill: theyhelp in assigning function to genes. Chromosome engineering in micemakes it easier to pinpoint the location of randomly induced mutations.
High throughput and high tech are thewatchwords in the rush to developnew tools for genomic analyses. But
traditional genetic screens of whole organ-isms still have a part to play. On page 81 ofthis issue, for instance, Kile and colleagues1
show how tricks borrowed from fruitflygeneticists allowed the efficient isolation ofmany new mutations in mice.
Geneticists are always eager to have newmutations in ‘model’ experimental organ-isms to study, because mutations allow themto investigate how an organism’s geneticmake-up (its genotype) relates to its physical
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