We have developed a new type ofendoscopy, which for the first timeallows painless endoscopic imaging

of the whole of the small bowel. This proce-dure involves a wireless capsule endoscopeand we describe here its successful testing inhumans.

The invention of fibre-optic endoscopy1

made visualization of the whole stomach,upper small bowel and colon possible.The procedures used to examine these(gastroscopy, small-bowel endoscopy andcolonoscopy, respectively) cause discomfortbecause they require flexible, relatively widecables to be pushed into the bowel — thesecables carry light by fibre-optic bundles,power and video signals. Small-bowelendoscopy in particular is constrained byproblems of discomfort and limitations ofhow far enteroscopes can be advanced intothe small bowel. There is a clinical need forimproved methods of examining the smallbowel and colon, especially in patients withrecurrent gastrointestinal bleeding.

The invention of the transistor made itpossible to design swallowable electronicradio-telemetry capsules for the study ofgastrointestinal physiological parameters.These capsules were first reported in the1950s and were used to measure tempera-ture2, pressure2,3 and pH3,4. We have devel-oped and tested a new type of video-telemetry capsule endoscope that is smallenough to be swallowed (11230 mm) andhas no external wires, fibre-optic bundles orcables. By using a lens of short focal length,images are obtained as the optical windowof the capsule sweeps past the gut wall,without requiring air inflation of the gutlumen. The capsule endoscope is propelledby peristalsis through the gastrointestinaltract and does not require a pushing forceto propel it through the bowel.

The video images are transmitted usingUHF-band radio-telemetry to aerials tapedto the body which allow image capture, andthe signal strength is used to calculate theposition of the capsule in the body (seeSupplementary Information); the imagesare stored on a portable recorder. This sys-tem allows more than 5 hours of continu-ous recording. The patient need not beconfined to a hospital environment duringthe examination and is free to continue hisor her daily routine.

The design of the video capsule wasmade possible by progress in the perfor-mance of three technologies: complemen-tary metal oxide silicon (CMOS) imagesensors, application-specific integratedcircuit (ASIC) devices, and white-light-

emitting diode (LED) illumination. Noveloptical design, better energy managementand overall system design were also impor-tant in creating the capsule.

The addition of a buffer amplifier oneach pixel reduced the output noise that

was initially associated with CMOS imagesensors and has allowed CMOS chips toachieve an image quality comparable tothose of charge-coupled device image sen-sors5, but using much less power.

Advances in ASIC design allowed theintegration of a very small video transmitterof sufficient power output, efficiency andbandwidth into the capsule. Synchronousswitching of the LEDs, the CMOS sensorand the ASIC transmitter minimize powerconsumption. By careful design of theoptics, we were able to eliminate internalreflections which are a common problemwhen the illumination and imager areincorporated under the same dome.

With ethical committee approval, thefirst studies were performed on ten normalhuman volunteers. The capsule was easilyswallowed and caused no discomfort. Pro-pelled by peristalsis (see SupplementaryInformation), it successfully transmittedvideo images (Fig. 1) from the stomach,small bowel and caecum (mean gastrictransit time was 80 min, range 17–280 min;mean small-bowel transit time was 90 min,range 45–140 min; mouth-to-evacuationtime was 24 h, range 10–48 h). High-qualityimages were received throughout the videotransmissions, lasting up to 6 hours. Gavriel Iddan*, Gavriel Meron*, Arkady Glukhovsky*, Paul Swain†*Given Imaging Ltd, Building 7, New IndustrialPark, Yoqneam 20692, Israel†Royal London Hospital, Whitechapel, London E1 1BB, UK1. Hopkins, H. H. & Kapany, N. S. Nature 173, 39–41 (1954).

2. Zworkin, V. K. Nature 179, 898 (1957).

3. Mackay, R. S. & Jacobson, B. Nature 179, 1239–1240 (1957).

4. Noller, H. G. Deutsche Med. Wsch. 85, 1707 (1960).

5. Fossum, E. R. Proc. SPIE 1900, 2–14 (1993).

Supplementary information is available on Nature’s World-Wide

Web site (http://www.nature.com) or as paper copy from the

London editorial office of Nature.

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NATURE | VOL 405 | 25 MAY 2000 | www.nature.com 417

Wireless capsule endoscopyThe discomfort of internal gastrointestinal examination may soon be a thing of the past.

Figure 1 Samples of images of the small bowel acquired by the

capsule endoscope during human in vivo studies. a,b, Gastric

folds in the body of the stomach; c,d, villous pattern of the small

bowel enhanced by the presence of a little water and an air bub-

ble in the lumen; e,f, airless images of normal jejunum, viewed

with the lumen closed in front of the optical dome of the capsule;

g,h, views of the terminal ileum.

Cell biology

Non-thermal heat-shockresponse to microwaves

Exposure limits set for microwave radia-tion assume that any biological effectsresult from tissue heating1: non-

thermal effects have been reported butremain controversial. We show here thatprolonged exposure to low-intensity micro-wave fields can induce heat-shock responsesin the soil nematode Caenorhabditis elegans.This effect appears to be non-thermal,suggesting that current exposure limits set

for microwave equipment may need to bereconsidered.

Heat-shock proteins (HSPs) are in-duced in most organisms by adverseconditions (such as heat or toxicants) thatcause damage to cellular proteins, acting asmolecular chaperones to rescue damagedproteins2. To detect HSP responses, we havepioneered the use of transgenic C. elegansstrains carrying reporter-gene constructs(encoding b-galactosidase in strain PC72or green fluorescent protein (GFP) instrain PC161) regulated by homologoushsp16 heat-shock promoters3. Whenexposed to diverse stressors at 20–25 °C,

© 2000 Macmillan Magazines Ltd

‡Medical Countermeasures, CBD Porton Down,Salisbury, Wiltshire SP4 0JQ, UK§Department of Biochemistry and MolecularBiology, University of British Columbia, 2146 Health Sciences Mall, Vancouver V6T 1Z3,Canada

1. ANSI/IEEE C95.1-1992 American National Standard-Safety

Levels with Respect to Exposure to Radio Frequency

Electromagnetic Fields, 3 kHz to 300 GHz (IEEE, New York,

1992).

2. Parsell, D. & Lindquist, S. Annu. Rev. Genet. 27, 437–496

(1993).

3. Dennis, J., Mutawakil, M., Lowe, K. & de Pomerai, D.

Aquatic Toxicol. 40, 37–50 (1997).

4. Candido, E. & Jones, D. Trends Biotechnol. 40, 125–129

(1996).

5. Daniells, C. et al. Mutat. Res. 399, 55–64 (1998).

6. Snutch, T. & Baillie, D. Can. J. Biochem. Cell Biol. 61, 480–487

(1983).

7. Gandhi, O., Lazzi, G. & Furse, C. IEEE Trans. Microwave Theor.

Tech. 44, 1884–1897 (1996).

8. Nishizawa, J. et al. Circulation 99, 934–941 (1999).

9. Williams, P. & Dusenbery, D. Environ. Toxicol. Chem. 9,

1285–1290 (1990).

10. Jewitt, N., Anthony, P., Lowe, K. & de Pomerai, D.

Enzyme Microb. Technol. 25, 349–356 (1999).

these worms express readily detectablereporter products, whereas controls showminimal expression4.

Worms were exposed overnight tocontinuous-wave microwave radiation at750 MHz and 0.5 W in the transverseelectromagnetic (TEM) cell described previ-ously5. Figure 1 shows temperature profilesfor reporter expression in both irradiatedand control (foil-shielded) worm cultures.In microwave-exposed cultures, expressionis comparable to that of controls at 24.0 °C(P¤0.05), but then rises steeply through24.5 and 25.0 to 25.5 °C (P*0.001). In non-exposed controls, heat-induced reporterexpression follows the pattern for HSP16(ref. 6), increasing sharply only above 27 °C(to a maximum at 30 °C). There is thus adisparity of 3 °C between exposed and con-trol induction profiles.

A thermal explanation for this disparitywould require that the exposed wormsbecome 3 °C warmer than controls — ormore if only a minority of worms/tissues isaffected. We reject this thermal explanationon several grounds, not least the diffusionof heat over 18 hours.

First, no temperature difference isdetectable between control and exposedcultures after irradiation5. This is also truefor concentrated (50% w/v) worm suspen-sions incubated for 18 h at 25 °C alongside asaline solution alone, under exposed versuscontrol conditions (24.6850.116 °C s.d.,P40.28, for all 16 measurements underfour conditions using a sensitive copper–constantan microthermocouple). Tempera-ture differences of 0.5 °C (that is, worms

1 °C warmer than the saline) would havebeen easily detectable in this experiment.

Second, in situ detection of reporterproducts shows that lacZ is expressedthroughout the gut in PC72 worms (Fig.2a,b), and also that GFP is expressed inmany embryos within adult PC161 worms(Fig. 2c,d). These expression sites togetherconstitute about half of worm tissues.

Third, the field at the centre of our TEMcell is 45 V m11, and the measured permit-tivity of concentrated worm suspensions (at615 MHz) gives a conductivity of about0.48 V11 m11. The calculated specificabsorption rate (SAR) is only 0.001 W kg11,which is much less than published values7

for mobile phones (0.02–1.0 W kg11).Mobile-phone manufacturers claim thatSARs in this range are insufficient to causemeasurable tissue heating within thehuman head, and we are not disputing this.

We suggest instead that the induction ofheat-shock proteins described here couldinvolve non-thermal mechanisms. Thesecould include microwave disruption of theweak bonds that maintain the active foldedforms of proteins; enhanced production ofreactive oxygen species (known to be induc-ers of HSPs8); or interference with cell-signalling pathways that affect HSP induc-tion (by heat-shock-factor activation). Allthese mechanisms are testable using thefunctional genomic tools that are availablein C. elegans. Because of the universality ofthe heat-shock response2, a similar non-thermal induction might also occur inhuman tissues exposed to microwaves, apossibility that needs investigation.David de Pomerai*, Clare Daniells*, Helen David*, Joanna Allan*, Ian Duce*,Mohammed Mutwakil*, David Thomas†,Phillip Sewell†, John Tattersall‡, Don Jones§, Peter Candido§*Molecular Toxicology Division, School of BiologicalSciences and †School of Electrical and ElectronicEngineering, University of Nottingham,Nottingham NG7 2RD, UK

418 NATURE | VOL 405 | 25 MAY 2000 | www.nature.com

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Figure 1 Saline9 suspensions of young adult PC72 worms grown

synchronously at 15 °C (ref. 10) were split between three condi-

tions for a total of 18 h: (1) exposed to microwaves (in TEM cell at

750 MHz and 0.5 W; ref. 5) within a Leec LT3 incubator; (2) tem-

perature controls shielded with aluminium foil in the same incuba-

tor; (3) baseline controls at 15 °C. Incubator temperatures of

24.0, 24.5, 25.0 and 25.5 °C were tested using 12 replicates for

each condition; controls only (6 replicates of condition 2) were

also run at 22, 26, 27 and 28 °C. All worm samples were

assayed fluorometrically4,5 for b-galactosidase activity. Enzyme

activities were normalized against 15 °C baseline controls (100%)

within each batch to allow comparison of reporter induction at dif-

ferent temperatures. Squares, blue solid line; reporter activities

(5s.e.m.) in microwave-exposed cultures. Circles, red dashed

line; control reporter activities (5s.e.m.) at each temperature.

Figure 2 PC72 and PC161 (similar to PC72, but carrying an additional GFP reporter under hsp16 control) worms were either exposed for

18 h at 25 °C to microwaves (750 MHz, 0.5 W) or kept as 25 °C controls, then reporter expression was localized in situ by staining with

X-gal (PC72) or viewing under ultraviolet light on a fluorescence microscope (PC161). a, Exposed PC72 worm, showing nuclear staining

for b-galactosidase throughout the gut; b, typical PC72 worm under control conditions: no observable staining; c, exposed PC161 worm,

showing GFP fluorescence throughout ovoid embryos; d, typical control PC161 worm, showing yellowish gut autofluorescence (also in c)

but no GFP fluorescence in embryos. Note that many worms in a and c show little reporter expression. Scale bars, 50 mm.

Structural biology

Proton-powered turbineof a plant motor

ATP synthases are enzymes that canwork in two directions to catalyseeither the synthesis or breakdown of

ATP, and they constitute the smallest rotarymotors in biology. The flow of protons pro-pels the rotation1 of a membrane-spanningcomplex of identical protein subunits, thenumber of which determines the efficiencyof energy conversion. This proton-poweredturbine is predicted to consist of 12 sub-units2–4, based on data for Escherichia coli5.The yeast mitochondrial enzyme, however,has only 10 subunits6. We have imaged theATP synthase from leaf chloroplasts byusing atomic force microscopy and, surpris-ingly, find that its turbine has 14 subunits,arranged in a cylindrical ring.

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© 2006 Nature Publishing Group

NATURE|Vol 440|23 March 2006 BRIEF COMMUNICATIONS

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(inside intact forests) and the combinedimpact of humans and climate change (outsideintact forests).

We combined an atlas of Russia’s intact forestlandscapes4 with a land-cover map9 drawn upfor 1999–2000 to delineate intact and non-intact forests (see supplementary information).The total area covered by the atlas4 is 1,118 mil-lion ha, including 205 million ha of intactforests. Active fires detected by the Terra satel-lite10 were used to derive our fire database forthe period 2002 to 2005 (Fig. 1). These activefires were separated into those that fell inside oroutside intact forests. Active fires that were spa-tially and temporally concurrent were thengrouped together to identify individual fireevents. Finally, fire events were attributed to thezone in which they started.

We found that 85% of the 23,818 active firesin intact forests in 2002 were located within a10-km-wide buffer zone inside the perimeterof the intact forests, indicating that the bordersof these areas could have been affected by firesstarting on the outside. We therefore selecteda new subset of ‘most-intact’ forests to repre-sent more strictly the concept of intact forest— these comprised the largest individualintact areas and the individual intact areaswith the smallest perimeter-to-area ratio. The

resulting subset of 17 intact areas totals 25% ofthe total intact area.

During seasons of climatic anomalies (2002and 2003), fire-event densities in the most-intact forests were twice the normal density(Table 1). But, more surprisingly, density ratiosof forest-fire events outside and inside most-intact forests are at least 7.9 and as high as 14.4during the four-year study period. Theseresults show that human impact had a con-stant ‘multiplication’ effect on the fire events,and that a maximum of 13% of fire ignition inthe non-intact forests is explained by naturaldisturbance, with the rest being directlyinduced by humans.

Forest regions of boreal Eurasia, and partic-ularly Siberia, have seen a reduction in popu-lation following the creation of the RussianFederation. But the human impact on theforests through fires is higher owing to lack of control, ineffectual fire-management poli-cies and new socioeconomic conditions in the region7,11,12. It is also a consequence of theoil boom in Siberia13. The fact that recentincreases in ‘wild’ fires in Eurasian borealforests are primarily a result of human behav-iour on the ground has implications for theglobal carbon budget3 and should be takeninto account in future mitigation policies.

Danilo Mollicone, Hugh D. Eva, Frédéric AchardInstitute for Environment and Sustainability, Joint Research Centre of the EuropeanCommission, TP 440, 21020 Ispra, Italye-mail: frederic.achard@jrc.it

1. Thompson, D. W. J. & Wallace, J. M. Science 293, 85–89(2001).

2. Dale, V. H. et al. BioScience 51, 723–734 (2001).3. Schiermeier, Q. Nature 435, 732–733 (2005).4. Aksenov, D. et al. Atlas of Russia’s Intact Forest Landscapes

(Global Forest Watch Russia, Moscow, 2002); available athttp://forest.ru/eng/publications/intact/

5. Sukhinin, A. et al. Remote Sens. Environ. 93, 546–564(2004).

6. Goldammer, J. G., Sukhinin, A. & Csiszar, I. Int. Forest FireNews [online] 29, <http://www.fire.uni-freiburg.de/iffn/iffn_online.htm> (2003).

7. International Research Institute for Climate Prediction IRIMap Room (2005); available athttp://iridl.ldeo.columbia.edu/maproom

8. Mouillot, F. & Field, C. B. Global Change Biol. 11, 398–420(2005).

9. Bartalev, S., Belward, A. S., Erchov, D. & Isaev, A. S. Int. J. Remote Sens. 24, 1977–1982 (2003).

10. Justice, C. O. et al. Remote Sens. Environ. 83, 244–262(2002).

11. Achard, F., Stibig, H.-J., Laestadius, L., Yaroshenko, A. &Aksenov, D. Identification of “Hot Spot Areas” of Forest CoverChanges in Boreal Eurasia (European Commission,Luxembourg, 2005); available athttp://ies.jrc.cec.eu.int/364.html

12. Karpachevskiy, M. Forest Fires in the Russian Taiga: NaturalDisaster or Poor Management? (Taiga Rescue NetworkFactsheet, Jokkmokk, Sweden, 2004).

13. Dienes, L. Eurasian Geogr. Econ. 45, 319–345 (2004).

Supplementary information accompanies thiscommunication on Nature’s website.Received 11 November 2005; accepted 2 March 2006.Competing financial interests: declared none.doi:10.1038/440436a

RETRACTIONCell biology: Non-thermal heat-shock response tomicrowavesD. de Pomerai, C. Daniells, H. David, J. Allan, I. Duce,M. Mutwakil, D. Thomas, P. Sewell, J. Tattersall,D. Jones, P. CandidoNature 405, 417–418 (2000)

Our claim that weak microwave fields induce a heat-shock response in Caenorhabditis elegans by a non-thermal mechanism is invalidated by new findingsshowing that there is a small heating effect underthese conditions (A. Dawe et al. Bioelectromagnetics27, 88–97; 2006). This temperature rise (about0.2 �C) causes heat-shock induction comparable tothat noted in our communication.C.D., J.A., M.M., D.J. and P.C. were not available tosign this retraction.doi:10.1038/440437a

Table 1 | Number and density of fire events in forests of the Russian Federation

2002 2003 2004 2005

Forest type* Number of fire events

All forests in study region 5,929 6,461 4,627 3,796

Non-intact forests 5,420 5,967 4,417 3,477

Intact forests 509 494 210 319

Most-intact forests 109 96 49 119†

Density of fire events (10�3 per km2)

All forests in study region 1.09 1.19 0.85 0.70

Non-intact forests 1.60 1.77 1.31 1.03

Intact forests 0.248 0.241 0.102 0.128

Most-intact forests 0.202 0.178 0.091 0.115

Density ratio of fire events

Ratio non-intact/intact 6.5 7.3 12.8 8.1

Ratio non-intact/most-intact 7.9 9.9 14.4 9.0*The area of all forests in the study zone is 543 million ha, of which 338 million ha is non-intact forest and 205 million ha is intactforest. The total area of ‘most-intact’ forest (a subset of intact forest; see text) is 54 million ha. The fire season is considered tolast until 21 September. †From these 119 fire events in most-intact forests, 57 are located in two large intact forest areas in the basin of the Taz River,where oil was being prospected (as revealed by fine spatial resolution imagery) in 2005. Intact areas were delineated usingsatellite imagery from the year 2000; some areas may no longer have been intact in 2005, in particular as a result of the oil boomin Siberia13. Fire-event densities are estimated without these 57 fires.

Smoking gun: an image at 1-km resolution from the Terra satellite in August 2002 shows forest fires (red polygons) with white smoke plumes.

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