a human vaccine for Ebola virus? The shortanswer is no, not yet. For example, Sullivan et al. infected the monkeys with relativelysmall amounts of virus, equivalent in humanterms to only a few nanolitres of blood froman infected person7,8. True, this amount ofvirus did lead to the deaths of the unvacci-nated monkeys, but previous studies haveshown that antibody preparations that protect against low doses of virus may beineffective against higher doses9,10. It will be crucial to know whether the vaccine strategy can protect against more substan-tial challenge. Also, Sullivan et al. did notidentify the immune mechanism of protec-tion (antibody, cellular or both), and thismay be important in guiding further vac-cine development. Nevertheless, coupledwith earlier findings that monkeys can beprotected against high doses of Marburgvirus by a vaccine based on a modifiedalphavirus construct11, it seems hopeful thathuman vaccination against filoviruses willbe achieved.

Who will benefit from a vaccine for Ebolaor Marburg viruses? The obvious answer isthe local population in an outbreak area, andthe medical and support personnel travel-ling there. In reality, however, funds are likelyin the first instance to be directed towardssurveillance, hygiene and barrier-nursingmethods, which can be highly effective incontaining an outbreak6. An immediate ben-efit of a vaccine will be to increase the marginof safety for those studying the viruses, per-mitting more research into the control ofinfection. One such aspect of research is the

search for the natural reservoirs of thefiloviruses.

Finally, some have rightly raised concernsabout the amount of effort spent studyingEbola and Marburg viruses, given that theyaffect relatively few people compared withthe major pathogens in Africa, such as HIVand malaria. But our ability to predict devel-opments in our struggle with microbes islimited. We may yet encounter more danger-ous versions of the existing filoviruses, oreven new ones. To be prepared, by learninghow to control those viruses that are herenow, is only prudent. ■

Dennis R. Burton and Paul W. H. I. Parren are inthe Departments of Immunology and MolecularBiology, The Scripps Research Institute, La Jolla,California 92037, USA.e-mails: burton@scripps.eduparren@scripps.edu1. Sullivan, N. J., Sanchez, A., Rollin, P. E., Yang, Z.-y. & Nabel,

G. J. Nature 408, 605–609 (2000).

2. Peters, C. J., Sanchez, A., Rollin, P. E., Ksiazek, T. G. & Murphy,

F. A. in Fields Virology (eds Fields, B. N. et al.) 1161–1176

(Lippincott Williams & Wilkins, Philadelphia, 1996).

3. Feldmann, H. & Klenk, H.-D. Adv. Virus Res. 47, 1–52 (1996).

4. Peters, C. J & LeDuc, J. W. (eds) J. Infect. Dis. 179 (suppl. 1),(1999).

5. http://www.promedmail.org

6. http://www.cdc.gov/ncidod/dvrd/spb/mnpages/vhfmanual.htm

7. Bowen, E. T. W. et al. in Ebola Virus Haemorrhagic Fever (ed.

Pattyn, R. R.) 89–85 (Elsevier, Amsterdam, 1978) (available at

http://www.itg.be/ebola/).

8. Report of an International Committee. Bull. World Health

Organ. 56, 271–293 (1978).

9. Kudoyarova-Zubavichene, N. M., Sergeyev, N. N., Chepurnov,

A. A. & Netesov, S. V. J. Infect. Dis. 179 (suppl. 1), S218–S223

(1999).

10. Jahrling, P. B. et al. J. Infect. Dis. 179 (suppl. 1), S224–S234

(1999).

11.Hevey, M., Negley, D., Pushko, P., Smith, J. & Schmaljohn, A.

Virology 251, 28–37 (1998).

trons with tiny vibrations of the crystal lattice(phonons) leads to an attraction between thenormally repulsive electrons so that they canpair up and flow without resistance.

Over the same period, experimentalistswere searching for superconducting materi-als with higher transition temperatures, Tc,below which a material is superconducting.But progress was slow, and after a Tc of 23 Kwas reached in 1973, no further increase wasachieved for 13 years (Fig. 1). This led to alively discussion2,3 about whether 23 K wasclose to some theoretical upper limit to Tc.

This all changed in 1986, when super-conducting copper-oxide materials werediscovered4. The maximum Tc was quicklypushed up to well over 100 K. Unlike mostearlier superconductors, the copper oxidesare normally insulators rather than conduc-tors, and charge carriers have to be intro-duced into the material by chemical dopingbefore they can become superconducting. Itwas soon accepted that superconductivity in the copper oxides is not primarily due to a phonon mechanism, as in conventionalsuperconductors, but to an electronic mech-anism, the nature of which is still underdebate. So the high transition temperaturesfound for the copper oxides do not rule outthe possibility of a maximum Tc for phonon-driven superconductors.

Coincidentally, in 1985, chemists discov-ered a new form of carbon5 — known todayas buckyballs or fullerenes. Like the copperoxides, crystalline C60 is normally an insu-lator, but can be made metallic by chemicaldoping. In normal C60 there are no chargecarriers because the energy bands in its elec-tronic structure are either completely filledor completely empty. To create a metal, theconduction band has to be partly filled withelectrons (electron doping) or the valenceband has to be partly emptied (hole doping).In 1991 it was found that adding alkali atoms to C60 crystals leads to charge transferfrom the alkali atoms to C60 — that is, elec-tron doping. Such alkali-doped compounds(A3C60) can become ‘metallic’6 and, at lowtemperatures, superconducting7,8.

The superconductivity in A3C60 isthought to be due to an interaction betweenelectrons and phonons. The strength of thisinteraction is one of the factors that deter-mine the value of Tc. Modifying the crystal

news and views

528 NATURE | VOL 408 | 30 NOVEMBER 2000 | www.nature.com

The sudden drop in electrical resistivityat low temperatures that characterizessuperconductivity was first seen in

fullerenes such as C60 nearly a decade ago. Byintroducing electrons into the carbon lattice,fullerenes can become superconducting attemperatures up to 40 K. As reported bySchön et al. on page 549 of this issue1, it turnsout that superconductivity can be achievedat even higher temperatures if positivelycharged ‘holes’ are introduced instead ofelectrons.

Almost a century has passed since Kamerlingh Onnes unexpectedly discoveredsuperconductivity when he noticed that mer-cury’s resistivity abruptly dropped to zero at 4 K. Ever since then, this field has been anactive area of research, resulting in two Nobel

prizes in 1972 and 1987. Early ideas aboutconventional superconductivity culminatedin a theory put forward by Bardeen, Cooperand Schrieffer (BCS) in 1957. In the BCS theory, the interaction of conduction elec-

Superconductivity

C60 — the hole storyOlle Gunnarsson

Superconductivity has been demonstrated at a surprisingly hightemperature in a C60 solid, raising questions about its electronic propertiesand hopes of even higher temperatures to come.

Figure 1 The maximum transition temperature,Tc, for which superconductivity has been foundin conventional superconductors over the pastcentury. It is assumed that C60 superconductivityconforms to this standard phonon-drivenmechanism, in which tiny lattice vibrations(phonons) provide the glue that binds electronsinto superconducting pairs. Electron doping ofC60 crystals, and now hole doping of C60 by Schön et al.1, have allowed phonon-drivensuperconductors to reach much highertransition temperatures.

1900 1920 1940 1960 1980 2000Year

Hole–doped C

60

Electron–doped C60

0

20

40

60

80

100

?

Niobium

nitrideLead

Mercury

Sup

erco

nduc

ting

tran

sitio

n te

mpe

ratu

re, T

c

© 2000 Macmillan Magazines Ltd

lattice by introducing larger alkali atomsincreases the electron–phonon coupling asthe lattice expands. In an expanded lattice,such as Cs3C60 under pressure9, Tc can reach40 K. Surprisingly, Cs3C60 at normal pressureis not superconducting, perhaps because ofstructural distortions or the closeness to ametal–insulator transition. Either way, itindicates that Tc cannot be increased furtherby expanding the lattice. In view of their success with electron-doped C60, researchersare interested in hole-doping C60, in par-ticular because Tc is then predicted to be even higher10. But adding holes to C60 is very difficult, because C60 is strongly electro-negative, so it has not yet been achieved bychemical doping.

Schön et al.1 take a completely differentapproach to hole-doping C60. They grow anoxide layer on the surface of a C60 crystal andplace a gate electrode on top. By addingsource and drain electrodes to the under-lying crystal they create a field-effect transis-tor11 (Fig. 2). Applying a voltage to the gateelectrode induces charge in the surface layerof the crystal, doping the C60. If the appliedvoltage is positive, electrons are induced; if the voltage is negative, holes are induced.An essential aspect of this approach is theauthors’ ability to make devices that can takeelectric fields large enough to induce severalelectrons or holes per C60 molecule. They canalso vary the amount of doping by simplychanging the gate voltage, thereby findingthe optimal level of doping for a high Tc. Inearlier work they induced superconductivityat a Tc of 10 K in an electron-doped C60

crystal11. In the present paper1, they report aTc of 52 K for hole-doped C60.

A Tc of 52 K is very high for phonon-driven superconductivity — well above whathad usually been thought possible. And withthis technique, Tc may be increased evenmore. For electron-doped C60, expansion ofthe crystal lattice increases Tc. With holedoping, however, Tc is already very large forthe unaltered lattice structure, and its expan-sion, perhaps by incorporating inert mol-ecules, could increase Tc substantially. Just as with electron-doped C60, this approachwould probably also fail for hole-doped sys-tems if the lattice is expanded too much —for instance, the system could then become

an insulator. But the ability to continuouslychange the doping, even to fractional num-bers of charges per molecule, may allow Tc to be increased substantially before thishappens.

This work opens up several interestingavenues. The possibility of comparing elec-tron- and hole-doped C60, and of varying thedoping continuously, should improve ourunderstanding of the electronic structure inC60 in general, and of superconductivity inC60 in particular. With Schön et al.’s field-effect transistor, only the outermost layer ofC60 molecules is thought to be doped — thesystem is said to be quasi two-dimensional(2D). It will be interesting to compare thissituation with chemically doped 3D systems,both in terms of the electronic behaviour andin terms of 2D versus 3D superconductivity.There may also be potential for making practical devices, because with this system

it is possible to switch C60 between insu-lating and superconducting behaviour. Forinstance, one can imagine it being used as anideal switch11. ■

Olle Gunnarsson is at the Max-Planck-Institut fürFestkörperforschung, D-70506 Stuttgart, Germany.e-mail:gunnar@and.mpi-stuttgart.mpg.de 1. Schön, J. H., Kloc, Ch. & Batlogg, B. Nature 408, 549–552

(2000).

2. Cohen, M. L. & Anderson, P. W. in Superconductivity in d- and

f-band Metals (ed. Douglass, D. H.) 17–27 (AIP, New York,

1972).

3. Dolgov, O. V., Kirzhnits, D. A. & Maksimov, E. G. Rev. Mod.

Phys. 53, 81–93 (1981).

4. Bednorz, J. G. & Müller, K. A. Z. Phys. B 64, 189–193 (1986).

5. Kroto, H. W., Heath, J. R., O’Brien, S. C., Curl, R. F. & Smalley,

R. E. Nature 318, 162–163 (1985).

6. Haddon, R. C. et al. Nature 350, 320–322 (1991).

7. Hebard, A. F. et al. Nature 350, 600–601 (1991).

8. Tanigaki, K. et al. Nature 352, 222–223 (1991).

9. Palstra, T. T. M. et al. Solid State Commun. 93, 327–330

(1995).

10.Mazin, I. I. et al. Phys. Rev. B 45, 5114–5117 (1992).

11.Schön, J. H., Kloc, Ch., Haddon, R. C. & Batlogg, B. Science

288, 656–658 (2000).

news and views

NATURE | VOL 408 | 30 NOVEMBER 2000 | www.nature.com 529

Figure 2 The field-effect transistor configurationused by Schön et al.1,11 to induce charge carriersinto C60 crystals, changing them from insulatorsinto superconductors.

Gateelectrode

Drainelectrode

Sourceelectrode

Oxide layer C60 crystal

Put simply, evolution is the result of natural selection promoting or elimi-nating particular heritable ‘pheno-

typic’ differences in a population, such as abehaviour or a physical characteristic. Overthe past 150 years, many aspects of thisprocess have been explored. But one factor inthe equation has remained enigmatic — thesource of the heritable phenotypic variationitself.

On page 553 of this issue1, Kopp and col-leagues illustrate how developmental genet-ics can help to solve this problem. Their firstfinding is interesting enough: they have ident-ified a key genetic regulator of sex-specificdifferences in abdominal pigmentation inthe fruitfly Drosophila melanogaster. Evenmore impressive, they show that changes inthe regulation of this gene may have con-tributed to the variety of pigmentation pat-terns seen among different fruitfly species.Finally, they investigate how these findingsrelate to mating behaviour.

Nowadays it is thought that mutations inDNA sequences cause changes in phenotype.But it has proved difficult to identify evolu-tionarily relevant mutations — those thatalter phenotypes and persist in natural pop-ulations. There are three core difficulties.First, the DNA regions that encode genescontain vast quantities of so-called neutralvariations, which have no effect on either thephenotype or the fitness — the ability to sur-vive and reproduce — of an organism.

Second, many evolutionarily relevantmutations may occur outside the protein-coding regions of genes. Genes can be div-ided roughly into the DNA sequence thatcodes for RNA, which may in turn be trans-lated into protein, and regulatory regions,which encode instructions for regulatinggene expression. These instructions are deciphered by DNA-binding proteins calledtranscription factors, which recognize spe-cific DNA motifs and enhance or represstranscription. In doing so, they switch geneson or off in specific spatial and temporal pat-terns throughout development2. Althoughregulatory regions have a critical role indevelopment, we still have a poor under-standing of how their structure relates totheir function. The third difficulty is thateven dramatic evolutionary alterations inthe DNA of regulatory regions can result in no change in function3,4.

The upshot of all this is that many evolu-tionarily relevant changes in DNA sequencesare probably buried within vast quantities of neutral variation, within both protein-coding sequences and poorly understoodregulatory regions. Another obstacle toidentifying evolutionarily relevant muta-tions is the paucity of experimental systemsthat allow physical variations to be related to DNA variations.

The new discipline of evolutionary devel-opmental biology is ideally poised to tacklethese problems, by applying the experimen-

Evolutionary biology

The problem of variationDavid L. Stern

One genetic source of the sex-specific variation in pigmentation patternsof different fruitfly species has been identified. This study illustrates thepower of bringing together developmental and evolutionary biology.

© 2000 Macmillan Magazines Ltd