findings. Li et al.6 further showed that pre-senilin 1 is first synthesized as a zymogen (aninactive precursor protease), which does notbind the inhibitor, and becomes active onlywhen it is cleaved into amino- and carboxy-terminal fragments14. Both fragments appearto contribute to the active site of presenilinbecause, depending on the orientation ofthe crosslinking moiety, the inhibitor bindsto either of them6. This finding is consistentwith the model proposed by Wolfe et al.13,because each fragment contributes oneaspartate to the putative active site of g-secretase (Fig. 1). So we now have com-pelling evidence that presenilins are exam-ples of a new class of aspartyl proteases.

Is research into presenilin and g-secretasenow at an end? Certainly not, and muchmore work will be needed before we reallyunderstand how hydrolysis of peptide bonds in the hydrophobic cell membranecan occur. The possibility that the trans-membrane domains of presenilin provide ahydrophilic pocket, allowing water to enter

the catalytic site, needs further scrutiny. Theidentity and role of other proteins, thoughtby many investigators to be associated withthe presenilins in a multiprotein complex,also needs clarification. The putative catalyticsite of presenilin is especially intriguingbecause it is completely divergent from theconsensus site of classical aspartyl proteases.

The development of clinically useful g-secretase inhibitors is likely to be long and tedious. One hurdle will be the deliveryof such drugs to neurons in the brain. Forinstance, the inhibitors used by Li et al.6 andEsler et al.7 do not cross cell membranes effi-ciently, and will probably be of little use invivo. The good news is that pharmaceuticalcompanies now have another defined targetfor their drug-discovery machineries.

The insights of the current studies gobeyond research into Alzheimer’s diseaseand are highly relevant to cell biology. Thepresenilins are only the second class ofeukaryotic proteases found to be involved inregulated intramembrane proteolysis — aprocess that causes the proteolytic release of the cytoplasmic domain of integral membrane proteins. These proteins thenmigrate to the nucleus to activate the tran-scription of genes that are pivotal in cellular

differentiation, the unfolded-protein stressresponse and cholesterol biosynthesis15. Pre-senilin is apparently involved not only inAPP processing, but also in regulated intra-membrane proteolysis of the Notch receptor,which is a central player in development, andprobably of the Ire1 protein, which controlsthe unfolded-protein stress response9,15. Allin all, there remains much to do — in partic-ular, the hunt is now on for other substratesof presenilin, alias g-secretase, and for proteins that regulate its activity. ■

Bart De Strooper is at the Center for HumanGenetics, Flanders Interuniversitary Institute forBiotechnology, K. U. Leuven, B-3000, Belgium.e-mail: bart.destrooper@med.kuleuven.ac.be1. Haass, C. & Selkoe, D. J. Cell 75, 1039–1042 (1993).

2. Hussain, I. et al. Mol. Cell. Neurosci. 14, 419–427 (1999).

3. Sinha, S. et al. Nature 402, 537–540 (1999).

4. Vassar, R. et al. Science 286, 735–741 (1999).

5. Yan, R. et al. Nature 402, 533–537 (1999).

6. Li, Y.-M. et al. Nature 405, 689–694 (2000).

7. Esler, W. P. et al. Nature Cell Biol. (in the press).

8. Scheuner, D. et al. Nature Med. 2, 864–870 (1996).

9. Haass, C. & De Strooper, B. Science 286, 916–919 (1999).

10.De Strooper, B. et al. Nature 391, 387–390 (1998).

11.Zhang, Z. et al. Nature Cell Biol. (in the press).

12.Herreman, A. et al. Nature Cell Biol. (in the press).

13.Wolfe, M. S. et al. Nature 398, 513–517 (1999).

14.Thinakaran, G. et al. Neuron 17, 181–190 (1996).

15.Brown, M. S., Ye, J., Rawson, R. B. & Goldstein, J. L. Cell 100,

391–398 (2000).

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Figure 1 Generation of the amyloid peptide Ab.a, Amyloid precursor protein (APP) is firstcleaved by b-secretase, which releases itsextracellular domain. Presenilin is processedshortly after its biosynthesis by an unknownprotease, called presenilinase, to yield amino-terminal and carboxy-terminal fragments. b, These fragments remain non-covalentlyassociated and form the active g-secretase. Each fragment contributes one aspartyl residue(Asp 257 or Asp 385) to the active site. The b-secretase-cleaved APP fragment associateswith and becomes cleaved by presenilin in anunidentified subcellular compartment. c, Thisresults in the release of Ab (orange) in theextracellular ‘milieu’. Ab then aggregates intothe amyloid plaques observed in the brain ofpatients suffering from Alzheimer’s disease.

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Asmall semiconductor chip generatingcoherent light waves is commonplacein modern life, from global telecom-

munication networks to personal compactdisk players. This semiconductor light-emitting device is based on the principle of‘light amplification by stimulated emissionof radiation’ (laser). Quantum mechanically,matter can also be regarded as waves. Thereare two fundamental types of particle thatcan make matter waves: bosons and fermi-ons. As a consequence of the Pauli exclusionprinciple, two fermions cannot occupy thesame state, whereas bosons tend to occupythe same state. A laser is based on the fact thatparticles of light — photons — are alsobosons. According to quantum mechanics, a composite particle consisting of an evennumber of fermions behaves as a bosonicmatter wave. So we can imagine building alaser or amplifier for such a matter wave.Writing in Physical Review Letters, Savvidis et al.1 describe how they amplify matterwaves in semiconductors.

The composite particle amplified by Sav-vidis et al. is known as an exciton–polariton.An exciton is a bound state of a negativelycharged electron and a positively chargedhole, which is analogous to a hydrogen atom.

Semiconductors can create them by absorb-ing photons. Eventually the electron andhole in the exciton will recombine to pro-duce a photon. But if the photons emitted bythe excitons in the semiconductor are con-fined in a reflective microcavity, the excitonsand photons are mixed together to create aquasiparticle called a polariton (Fig. 1, over-leaf). This new particle is part light and partmatter, and consequently the polariton massis reduced by four orders of magnitude compared with the exciton mass.

Unlike a photon, a massive particle can-not be created from a vacuum. The totalnumber of massive particles must be con-served. In order to amplify a matter wave, areservoir of identical particles is needed.Moreover, a scattering mechanism to trans-fer a reservoir particle into the ground state isessential. If the particle is a pure boson with-out charge, for example a photon in vacuum,there is no such scattering mechanism. Butcomposite bosons, such as excitons, scatterwith each other owing to the fermionicnature of their constituents — electrons andholes. This non-bosonic feature of a com-posite particle is the gain mechanism for amatter-wave amplifier.

In the experiment of Savvidis et al.1,

Semiconductor physics

Half-matter, half-light amplifierYoshihisa Yamamoto

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two polaritons with the same quantumwavenumber are simultaneously created by acoherent laser pulse (the ‘pump’ pulse).These two polaritons are scattered to differ-ent energy states — the ground state and ahigher-energy state — in a way that con-serves energy and momentum between theinitial and final states. When the ground-state polariton is stimulated by anothercoherent laser pulse, an enormous gain of upto 100 is observed.

This might seem like a matter-wave ana-logue of a laser amplifier. However, it does notcorrespond to a laser amplifier in an exactsense, but rather to a ‘parametric’ amplifier.In the radiowave, microwave and optical-wave spectrum, there are always two types of amplifier: a negative-conductance ampli-fier and a nonlinear-susceptance amplifier. A negative-conductance amplifier is an incoherent system, in which only the energyof the pump pulse determines the systemdynamics. A laser amplifier is a classic exam-ple of a negative-conductance amplifier. Anonlinear-susceptance amplifier is a coher-ent system in which both the amplitude andthe phase of the pump pulse determine thesystem dynamics. A parametric amplifier is a classic example of a nonlinear-susceptanceamplifier. In the experiment of Savvidis etal.1, the ground-state polariton is amplifiedby a phase-coherent parametric process.

In a different study, Huang et al.2 create a direct matter-wave analogue of a laseramplifier using essentially the same struc-ture as Savvidis et al. In this experiment, tworeservoir polaritons with opposite quantumwavenumbers are scattered to the ground andexcited states with zero wavenumber. Ampli-fication is observed even after the reservoirpolaritons lose the phase information of thepump laser and reach thermal equilibrium.This means that matter-wave amplificationin this system could be achieved using elec-trically injected incoherent excitons.

Matter-wave amplifiers using atoms3,4

rather than excitons operate on the sameprinciple, but their working conditions arequite different. The effective temperature ofan exciton reservoir is about 10 K, whereasthat of an atomic reservoir (Bose–Einsteincondensate) is about 10 nK. The gain andloss rates of an exciton matter-wave amplifi-er are approximately 1012 s11, whereas thoseof an atomic matter-wave amplifier areapproximately 105 s11. The ratio of the aver-age spacing between two excitons comparedto their radius is about 30, whereas that of theaverage spacing between two atoms to theatomic radius is about 103. Exciton matter-wave amplifiers operate at a much highertemperature, gain and particle density thantheir atomic counterparts.

The exciton laser and amplifier can oper-ate with a much smaller pump power than a normal photon laser. A photon laser andamplifier requires more populations in an

excited state than in the ground state (so-called population inversion). But the excitonlaser and amplifier operate without inver-sion5. A wide bandgap semiconductor, suchas gallium nitride or zinc oxide, is more suit-able for constructing such an exciton laserand amplifier because the excitons in suchmaterials are stable at higher temperaturesand densities. Such semiconductor lasers are attractive because they are an efficientsource of blue light.

If the gain of a matter-wave amplifierexceeds the loss rate, the system is expectedto form a matter-wave laser (boser)5. But thespontaneous build-up of a coherent matterwave without continuous pumping by aninput matter wave has yet to be seen. Photo-luminescence studies of microcavities insemiconductor quantum wells6,7 suggestthat this goal is within the reach of currenttechnology. ■

Yoshihisa Yamamoto is at the QuantumEntanglement Project, Edward L. GinztonLaboratory, Stanford University, Stanford,California 94305-4085, USA, and NTT BasicResearch Laboratories, Atsugishi, Kanagawa, Japan.e-mail: yamamoto@loki.stanford.edu

1. Savvidis, P. et al. Phys. Rev. Lett. 84, 1547–1550 (2000).

2. Huang, R. et al. Phys. Rev. B 61, R7854–R7857 (2000).

3. Inouye, S. et al. Nature 402, 641–644 (1999).

4. Helmerson, K. Nature 402, 587–588 (1999).

5. Imamoglu, A. et al. Phys. Rev. A 53, 4250–4253 (1996).

6. Dang, L. S. et al. Phys. Rev. Lett. 81, 3920–3923 (1998).

7. Senellart, P. & Bloch, J. Phys. Rev. Lett. 82, 1233–1236 (1999).

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100 YEARS AGOThe widespread invasion and persistentdevastations of locusts in so many parts ofAfrica give interest to all trials andexperiments, as well as the ordinaryremedies, employed for the alleviation of thisruinous plague of the farmer. The followingnotes from Mr. W. C. Robbins, StockInspector of the Lower Tugela and MapumuloDistricts, are published in the Cape officialAgricultural Journal:- “For the past threedays I have been over the ground where mymen have been infecting locusts withGovernment fungus, and the result was that Ifound dead locusts everywhere. I send you asample; you will notice they are full ofworms, and we know from experience thatwhen locusts are found in this state wholeswarms die off. Some you will see, are halfeaten; these were eaten by their fellows. Ihave seen many clusters of locusts eatingdead ones.” The feeding upon bodies of deadlocusts suggests that diseased locusts maybe utilised as a substitute for locust fungus.From Nature 7 June 1900.

50 YEARS AGOThe gestural or ‘ta-ta’ theory of the origin oflanguage has a long pedigree, beginning withPlato and achieving its most notable modernexponent in Sir Richard Paget. That Prof.Jóhannesson had been attracted to thistheory was evident from his earlier work, “UmFrumtungu Indógermana og Frumheimkynni”;and the dedication of this new volume to SirRichard sets the author decisively amongthose who believe themselves capable ofdemonstrating that language originated inthe imitation by the vocal organs of physicalshapes and movement. This theory representsone branch of the more general doctrinewhich sees a natural connexion betweenthings and their names: and it is not to bedenied that certain sound-complexes seem,in fact, to be particularly appropriate to therepresentation of certain shapes — a field ofstudy in which Koehler and the Gestaltpsychologists have collected some interestingdata. But even supposing that these sound-complexes could be shown to involve vocalmovements related to the shapes concerned,this would teach us nothing about the originof language, which must be far remote fromthe attested or ‘reconstructed’ forms onwhich the theory is based — though Prof.Jóhannesson gives one the impression that hebelieves his hypothetical Indo-European formsat least to approximate to a primitive tongue.From Nature 10 June 1950.

Figure 1 A semiconductor matter-wave amplifier.Here, a semiconductor quantum well issandwiched between two reflectivemicrocavities, which are separated by one-halfor one wavelength. An exciton, which is a boundstate of an electron–hole (e–h) pair and thesolid-state analogue of a hydrogen atom, isconfined in the quantum well by the potentialbarrier between the quantum well and thesurrounding materials. A light field is trappedby multiple reflection from the reflectiveinterfaces. When a quantum-well exciton and acavity photon couple strongly with each other,they form a new quasiparticle called a polariton.Savvidis et al.1 show that the polaritons can beexcited resonantly by a laser producingamplification of the signal.

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