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Science Demonstrating Uncertainty Gerard J.Milburn Science339,770(2013): AAAAS DOl:10.1126/science.1234109 This copy is for your personal,non-commercial use only. If you wish to distribute this article to others,you can order high-quality copies for your colleagues,clients,or customers by clicking here. Permission to republish or repurpose articles or portions of articles can be obtained by following the guidelines here. The following resources related to this article are available online at www.sciencemag.org(this information is current as of February 15,2013 ) Updated information and services,including high-resolution figures,can be found in the online version of this article at: http://www.sciencemag.org/content/339/6121/770.full.html A list of selected additional articles on the Science Web sites related to this article can be found at: http://www.sciencemag.org/content/339/6121/770.full.html#related This article cites 3 articles,1 of which can be accessed free: http://www.sciencemag.org/content/339/6121/770.full.html#ref-list-1 This article appears in the following subject collections: Physics http://www.sciencemag.org/cgi/collection/physics Science(print ISSN 0036-8075;online ISSN 1095-9203)is published weekly,except the last week in December,by the American Association for the Advancement of Science,1200 New York Avenue NW,Washington,DC 20005.Copyright 2013 by the American Association for the Advancement of Science;all rights reserved.The title Science is a registered trademark of AAAS

DOI: 10.1126/science.1234109 Science 339, 770 (2013); Gerard J. Milburn Demonstrating Uncertainty This copy is for your personal, non-commercial use only. colleagues, clients, or customers by clicking here. If you wish to distribute this article to others, you can order high-quality copies for your following the guidelines here. Permission to republish or repurpose articles or portions of articles can be obtained by www.sciencemag.org (this information is current as of February 15, 2013 ): The following resources related to this article are available online at http://www.sciencemag.org/content/339/6121/770.full.html version of this article at: Updated information and services, including high-resolution figures, can be found in the online http://www.sciencemag.org/content/339/6121/770.full.html#related found at: A list of selected additional articles on the Science Web sites related to this article can be http://www.sciencemag.org/content/339/6121/770.full.html#ref-list-1 This article cites 3 articles, 1 of which can be accessed free: http://www.sciencemag.org/cgi/collection/physics Physics This article appears in the following subject collections: registered trademark of AAAS. 2013 by the American Association for the Advancement of Science; all rights reserved. The title Science is a American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the on February 15, 2013 www.sciencemag.org Downloaded from

PERSPECTIVES a means for further optimizing the editing more,the recombination should be fast,effi- References performance of Cas9. cient,and scalable.Compared to the most 1.L.Cong et al.,Science 339.819 (2013): Efficient strategies for directed editing 10.1126/science..1231143 promising currently available genome edit- 2.P.Mali et al.,Science 339,823 (2013): of mammalian genomes will enable sophis- ing systems(zinc finger domains and TAL- 10.1126/science.1232033. ticated genetic engineering for both funda- ENs),the RNA-guided Cas9 nuclease prob- 3.B.L Stoddard,Structure 19,7 (2011). 4.F.D.Urnov,E.]Rebar,M.C.Holmes,H.S.Zhang. mental and applied purposes.Especially in ably is closest to meeting these requirements P.D.Gregory,Nat.Rev.Genet.11,636 (2010). medical applications,high-fidelity target rec- However,efficiency and specificity still can 5.A J.Bogdanove,D.F.Voytas,Science 333,1843 (2011) ognition is critical,as off-site nuclease activ- be improved-for instance,by laboratory 6.K.Eisenschmidt et ol.,Nucleic Acids Res.33,7039 (2005). ity will jeopardize the safety of the engineer- evolution.Applying these genome surgery 7.B.Wiedenheft,S.H.Sternberg,]A.Doudna,Nature ing operation;thus,long stretches of nucle- techniques to correct human disease-asso- 482,331(2012) otides should be specifically recognized.In ciated genetic mutations,resulting in func- 8.E.R.Westra et al..Annu.Rev.Genet.46.311(2012). 9.E.Deltcheva et al,Nature 471,602(2011). addition,adjusting the system's specificity tional gene therapy and in curing genetic dis- 10.M.Jinek et al.,Science 337,816 (2012). toward new target sequences should be easy orders,will therefore take time.The spectac- 11.G.Gasiunas,R.Barrangou,P.Horvath,V.Siksnys,Proc. and affordable;this is a major advantage of ular recent development of dedicated nucle- Natl.Acad.Sci.U.S.A 109,E2579 (2012). 12.M.Jinek et ol.,ele2013;2:300471(2013). the Cas9 system,as it merely requires chang- ases suggests,however,that we are entering ing the sequence of the guide RNA.Further- the final stage of this quest. 10.1126 science.1234726 PHYSICS Demonstrating Uncertainty Heisenberg's uncertainty principle is demonstrated with a vibrating macroscopic mirror. Gerard J.Milburn s nyone using a modern camera is cles.This observation eventually led to laser changed by the tidal forces exerted by gravi- implementing an optical position cooling and the field of atom optics. tational waves.This length difference leads measurement.In an active autofo- The history of using optical transduc- to changes in the interference of light at the cus camera,a pulse of infrared light is emit- ers to monitor the quantized position of an output mirror.Monitoring the output inten- ted from the camera,and the time taken for object at the Heisenberg limit goes back to sity can thus be used to measure the relative it to be reflected back to the camera is used the early proposals for the optical detec- position of the end mirrors. to compute the distance between the object tion of gravitational radiation (3).The rel- The effect is small,however,and very and the image plane.Imagine how difficult ative length of the two orthogonal arms small changes in the intensity need to be it would be to operate such a system if the in a Michelson-Morley interferometer is detected.This eventually runs into a problem object recoiled every time the caused by the essential granular infrared pulse was reflected from nature of light (light pulses are it.Heisenberg suggested that this made up of individual photons). is precisely what would happen if Even the most carefully stabi- light were used to determine the lized laser produces light with eo] position of a quantum object as intensity fluctuations due to the accurately as his famous uncer- random arrival of individual pho- tainty principle would allow.On Inaident tons,called shot noise.We rarely page 801 of this issue,Purdy et need to account for this as the rel- Transmitted al.(/demonstrate this quantum Reflected ative size of the intensity fluctua- back-action effect in an optical tion falls off as the inverse square measurement of the position of a root of the intensity,so we can macroscopic mirror. always increase the intensity to The mechanical action of improve the signal-to-noise ratio. light has long been known(2). But there is another problem. Kepler suggested that the rea- If we take into account the son comet tails point away from mechanical action of light,we the Sun is due to the mechani- see that a price must be paid for cal action of light.In the early 1970s,Arthur Ashkin of Bell An optical cavity with a vibrat- Laboratories showed that optical ing mirror.As this mirror moves,the intensity of the transmitted light can intensity gradients could exert a Probe be used to monitor its position.(Inset) force on micrometer-size parti- When the quantum nature of light is included,the random reflection of Centre for Engineered Quantum Systems,The University of Queensland,StLucia,Brisbane, individual photons shakes the mirror, QLD 4072,Australia.E-mail:milburn@ adding radiation pressure noise to the physics.uq.edu.au position measurement. 770 15 FEBRUARY 2013 VOL 339 SCIENCE www.sciencemag.org Published by AAAS

770 15 FEBRUARY 2013 VOL 339 SCIENCE www.sciencemag.org PERSPECTIVES Demonstrating Uncertainty PHYSICS Gerard J. Milburn Heisenberg’s uncertainty principle is demonstrated with a vibrating macroscopic mirror. a means for further optimizing the editing performance of Cas9. Efficient strategies for directed editing of mammalian genomes will enable sophis￾ticated genetic engineering for both funda￾mental and applied purposes. Especially in medical applications, high-fidelity target rec￾ognition is critical, as off-site nuclease activ￾ity will jeopardize the safety of the engineer￾ing operation; thus, long stretches of nucle￾otides should be specifically recognized. In addition, adjusting the system’s specificity toward new target sequences should be easy and affordable; this is a major advantage of the Cas9 system, as it merely requires chang￾ing the sequence of the guide RNA. Further￾more, the recombination should be fast, effi- cient, and scalable. Compared to the most promising currently available genome edit￾ing systems (zinc finger domains and TAL￾ENs), the RNA-guided Cas9 nuclease prob￾ably is closest to meeting these requirements. However, efficiency and specificity still can be improved—for instance, by laboratory evolution. Applying these genome surgery techniques to correct human disease-asso￾ciated genetic mutations, resulting in func￾tional gene therapy and in curing genetic dis￾orders, will therefore take time. The spectac￾ular recent development of dedicated nucle￾ases suggests, however, that we are entering the final stage of this quest. References 1. L. Cong et al., Science 339, 819 (2013); 10.1126/science.1231143. 2. P. Mali et al., Science 339, 823 (2013); 10.1126/science.1232033. 3. B. L. Stoddard, Structure 19, 7 (2011). 4. F. D. Urnov, E. J. Rebar, M. C. Holmes, H. S. Zhang, P. D. Gregory, Nat. Rev. Genet. 11, 636 (2010). 5. A. J. Bogdanove, D. F. Voytas, Science 333, 1843 (2011). 6. K. Eisenschmidt et al., Nucleic Acids Res. 33, 7039 (2005). 7. B. Wiedenheft, S. H. Sternberg, J. A. Doudna, Nature 482, 331 (2012). 8. E. R. Westra et al., Annu. Rev. Genet. 46, 311 (2012). 9. E. Deltcheva et al., Nature 471, 602 (2011). 10. M. Jinek et al., Science 337, 816 (2012). 11. G. Gasiunas, R. Barrangou, P. Horvath, V. Siksnys, Proc. Natl. Acad. Sci. U.S.A. 109, E2579 (2012). 12. M. Jinek et al., elife 2013; 2:300471 (2013). 10.1126/science.1234726 Anyone using a modern camera is implementing an optical position measurement. In an active autofo￾cus camera, a pulse of infrared light is emit￾ted from the camera, and the time taken for it to be reflected back to the camera is used to compute the distance between the object and the image plane. Imagine how difficult it would be to operate such a system if the object recoiled every time the infrared pulse was reflected from it. Heisenberg suggested that this is precisely what would happen if light were used to determine the position of a quantum object as accurately as his famous uncer￾tainty principle would allow. On page 801 of this issue, Purdy et al. ( 1) demonstrate this quantum back-action effect in an optical measurement of the position of a macroscopic mirror. The mechanical action of light has long been known (2). Kepler suggested that the rea￾son comet tails point away from the Sun is due to the mechani￾cal action of light. In the early 1970s, Arthur Ashkin of Bell Laboratories showed that optical intensity gradients could exert a force on micrometer-size parti￾cles. This observation eventually led to laser cooling and the field of atom optics. The history of using optical transduc￾ers to monitor the quantized position of an object at the Heisenberg limit goes back to the early proposals for the optical detec￾tion of gravitational radiation (3). The rel￾ative length of the two orthogonal arms in a Michelson-Morley interferometer is changed by the tidal forces exerted by gravi￾tational waves. This length difference leads to changes in the interference of light at the output mirror. Monitoring the output inten￾sity can thus be used to measure the relative position of the end mirrors. The effect is small, however, and very small changes in the intensity need to be detected.This eventually runs into a problem caused by the essential granular nature of light (light pulses are made up of individual photons). Even the most carefully stabi￾lized laser produces light with intensity fluctuations due to the random arrival of individual pho￾tons, called shot noise. We rarely need to account for this asthe rel￾ative size of the intensity fluctua￾tion falls off as the inverse square root of the intensity, so we can always increase the intensity to improve the signal-to-noise ratio. But there is another problem. If we take into account the mechanical action of light, we see that a price must be paid for Centre for Engineered QuantumSystems,The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia. E-mail: milburn@ physics.uq.edu.au Incident Reflected Transmitted Signal Probe Signal Probe An optical cavity with a vibrat￾ing mirror. As this mirror moves, the intensity of the transmitted light can be used to monitor its position. (Inset) When the quantum nature of light is included, the random reflection of individual photons shakes the mirror, adding radiation pressure noise to the position measurement. Published byAAAS on February 15, 2013 www.sciencemag.org Downloaded from

PERSPECTIVES increasing the accuracy of the measurement quantum motion of a collective vibrational The experiment of Purdy et al.repre- by increasing the intensity.As individual degree of freedom of a mechanical element. sents one of the few approaches that dem- photons are reflected from a movable mir- In their experiment,the mechanical element onstrate the physical mechanism respon- ror,it will recoil,and the shot noise of indi- is a 7-ng square dielectric membrane placed sible for enforcing the Heisenberg uncer- vidual photon arrivals will lead to a fluctu- inside a Fabry-Perot optical interferometer. tainty limit.Can we beat this limit by creat- ating force on the mirror:it will begin to The bulk mechanical resonance frequency is ing light sources with no intensity fluctua- shake ever more violently as the intensity above I MHz with a linewidth less than 1 Hz tions at all?Such squeezed light sources are is increased,limiting the gain in accuracy (see the figure). indeed under development,yet they will be due to increasing intensity.This is the radi- As the membrane moves,it modulates the of no use in trying to beat the Heisenberg ation pressure shot noise,and it is the phys- frequency of the optical resonance and con- limit in optomechanical systems.The rea- ical mechanism enforcing the Heisenberg sequently modulates the amplitude and phase son is that if the intensity of a light source is uncertainty principle in an optomechanical of the transmitted light.This motion can be well defined,its phase becomes increasingly position transducer. detected with high efficiency by means of randomized-a quantum optical Heisen- Balancing the effects of shot noise and optical detection.Fluctuations of the mem- berg principle-and an interferometer can- radiation pressure noise leads to the stan- brane due to radiation pressure noise appear not be operated with a rapidly fluctuating dard quantum limit for an optomechanical in the noise power spectrum of the optical phase.A natural extension of the Purdy et position transducer.Large interferometers signal.In the experiment,two optical modes al.experiment would demonstrate precisely designed to detect gravitation waves are not were used:one with high power,the signal. this trade-off. yet at this limit,which would require more is the source of the radiation pressure shot 9 laser power than the optical components noise,while the other,weaker probe beam References could stand,yet it will need to be taken into monitors the displacement of the membrane 1.T.P.Purdy,R.W.Peterson,C.A.Regal,Science 339,801 (2013). account in the next generation of detectors. to detect the radiation pressure noise.The 2.P.Meystre,Atom Optics (Springer Verlag,New York,2001). Purdy et al.report the first direct demon- experiment can also be thought of as a quan- 3.C.M.Caves,K.S.Thorne,R.W.P.Drever,V.D.Sand- stration of the radiation pressure shot noise. tum nondemolition measurement of the pho- berg.M.Zimmermann,Rev.Mod.Phys.52.341(1980). Their study is a landmark in the emerging 4.M.Aspelmeyer,P.Meystre,K.Schwab,Phys.Today 65,29 ton number in the strong signal beam using a 5 (2012). field of quantum optomechanics(4),where coupling to the signal beam mediated by the the objective is to coherently control the mechanical element. 10.1126/science.1234109 PLANETARY SCIENCE A meteorite with a chemical makeup A Unique Piece of Mars resembling that of rocks from Mars'Gusev Crater has been identified. W Munir Humayun ollowing the pioneering Mars Explo- known martian meteorites with respect to Ga,older than SNC meteorites but younger ration Rovers,NASA's Curiosity age,oxygen isotopes,and petrology. than ALH 84001 (6).What makes NWA rover is actively exploring the crustal One might wonder whether such a rock 7034 so exciting is that its major element rocks of Mars.Despite the exciting results should even be construed to be of mar- composition is a close fit with the chemi- returned by the rovers,there is no substitute tian origin.Oxygen isotopes are the mete- cal data returned by the Mars rovers,as well for a hand sample of crustal rock.Because oritic equivalent of DNA fingerprinting, as with the global chemical composition of such samples will not be returned to Earth each unique signature implying a different Mars'crust returned by the orbiting gamma- anytime soon,geochemists who want a piece planetary reservoir (5).One of the big sur- ray spectrometer onboard Mars Odyssey(4). of Mars in their labs must satisfy themselves prises in NWA 7034 is that its oxygen iso- NWA 7034 appears to be a chemical analog with martian meteorites (/)These comprise topes are shifted to greater 60 depletion, of rocks from Gusev Crater (3). a group of igneous rocks with telltale signs and to heavier isotopic compositions,than Given that the other known martian mete- of martian alteration products (2)and have those of the SNC(shergottite,nakhlite,and orites are a poor match for crust exposed at provided ground truth for the information chassignite)martian meteorites.Had it not the martian surface,what can we learn from returned by the rovers.Oddly,however,the been for the alertness of Agee et al.,NWA a meteorite that resembles just about any hundred or so known martian meteorites are 7034 would likely have been classified as rock from Mars?The first important dis- chemically unrepresentative of the martian a unique achondrite (an asteroidal sample) covery is that the new meteorite has a dis- crust determined by missions(3).On page on the basis of its distinct oxygen isotope tinctly greater deficiency of the 0 isotope 780 of this issue,Agee et al.(4)put an end composition.However,they showed that the among its oxygen isotopes than the other to this conundrum with the finding of a new mineral chemistry of pyroxenes from NWA martian meteorites,which are bunched so martian meteorite,Northwest Africa(NWA) 7034 plot on the distinct FeO versus MnO close together on an oxygen isotope plot that 7034.a basaltic breccia unique among trend defined by other martian meteorites. they can be classified as a group on the basis Another distinguishing characteristic of of a single measurement of their A70(5). Department of Earth,Ocean and Atmospheric Science and martian meteorites over achondrites is their That this should be the case was anticipated National High Magnetic Field Laboratory,Florida State Uni- versity,Tallahassee,FL 32310,USA.E-mail:humayun@ young radiometric ages[<4 billion years ago by pioneering studies that found the mar- magnet.fsu.edu (Ga)];NWA 7034 has been dated about 2 tian hydrosphere and atmosphere to have www.sciencemag.org SCIENCE VOL 339 15 FEBRUARY 2013 771 Published by AAAS

www.sciencemag.org SCIENCE VOL 339 15 FEBRUARY 2013 771 PERSPECTIVES A Unique Piece of Mars PLANETARY SCIENCE Munir Humayun A meteorite with a chemical makeup resembling that of rocks from Mars’ Gusev Crater has been identifi ed. increasing the accuracy of the measurement by increasing the intensity. As individual photons are reflected from a movable mir￾ror, it will recoil, and the shot noise of indi￾vidual photon arrivals will lead to a fluctu￾ating force on the mirror; it will begin to shake ever more violently as the intensity is increased, limiting the gain in accuracy due to increasing intensity. This is the radi￾ation pressure shot noise, and it is the phys￾ical mechanism enforcing the Heisenberg uncertainty principle in an optomechanical position transducer. Balancing the effects of shot noise and radiation pressure noise leads to the stan￾dard quantum limit for an optomechanical position transducer. Large interferometers designed to detect gravitation waves are not yet at this limit, which would require more laser power than the optical components could stand, yet it will need to be taken into account in the next generation of detectors. Purdy et al. report the first direct demon￾stration of the radiation pressure shot noise. Their study is a landmark in the emerging field of quantum optomechanics (4), where the objective is to coherently control the quantum motion of a collective vibrational degree of freedom of a mechanical element. In their experiment, the mechanical element is a 7-ng square dielectric membrane placed inside a Fabry-Perot optical interferometer. The bulk mechanical resonance frequency is above 1 MHz with a linewidth less than 1 Hz (see the figure). As the membrane moves, it modulates the frequency of the optical resonance and con￾sequently modulates the amplitude and phase of the transmitted light. This motion can be detected with high efficiency by means of optical detection. Fluctuations of the mem￾brane due to radiation pressure noise appear in the noise power spectrum of the optical signal. In the experiment, two optical modes were used; one with high power, the signal, is the source of the radiation pressure shot noise, while the other, weaker probe beam monitors the displacement of the membrane to detect the radiation pressure noise. The experiment can also be thought of as a quan￾tum nondemolition measurement of the pho￾ton number in the strong signal beam using a coupling to the signal beam mediated by the mechanical element. The experiment of Purdy et al. repre￾sents one of the few approaches that dem￾onstrate the physical mechanism respon￾sible for enforcing the Heisenberg uncer￾tainty limit. Can we beat this limit by creat￾ing light sources with no intensity fluctua￾tions at all? Such squeezed light sources are indeed under development, yet they will be of no use in trying to beat the Heisenberg limit in optomechanical systems. The rea￾son is that if the intensity of a light source is well defined, its phase becomes increasingly randomized—a quantum optical Heisen￾berg principle—and an interferometer can￾not be operated with a rapidly fluctuating phase. A natural extension of the Purdy et al. experiment would demonstrate precisely this trade-off. References 1. T. P. Purdy, R. W. Peterson, C. A. Regal, Science 339, 801 (2013). 2. P. Meystre, Atom Optics (Springer Verlag, New York, 2001). 3. C. M. Caves, K. S. Thorne, R. W. P. Drever, V. D. Sand￾berg, M. Zimmermann, Rev. Mod. Phys. 52, 341 (1980). 4. M. Aspelmeyer, P. Meystre, K. Schwab, Phys. Today 65, 29 (2012). 10.1126/science.1234109 Following the pioneering Mars Explo￾ration Rovers, NASA’s Curiosity rover is actively exploring the crustal rocks of Mars. Despite the exciting results returned by the rovers, there is no substitute for a hand sample of crustal rock. Because such samples will not be returned to Earth anytime soon, geochemists who want a piece of Mars in their labs must satisfy themselves with martian meteorites (1). These comprise a group of igneous rocks with telltale signs of martian alteration products (2) and have provided ground truth for the information returned by the rovers. Oddly, however, the hundred or so known martian meteorites are chemically unrepresentative of the martian crust determined by missions (3). On page 780 of this issue, Agee et al. ( 4) put an end to this conundrum with the finding of a new martian meteorite, Northwest Africa (NWA) 7034, a basaltic breccia unique among known martian meteorites with respect to age, oxygen isotopes, and petrology. One might wonder whether such a rock should even be construed to be of mar￾tian origin. Oxygen isotopes are the mete￾oritic equivalent of DNA fingerprinting, each unique signature implying a different planetary reservoir (5). One of the big sur￾prises in NWA 7034 is that its oxygen iso￾topes are shifted to greater 16O depletion, and to heavier isotopic compositions, than those of the SNC (shergottite, nakhlite, and chassignite) martian meteorites. Had it not been for the alertness of Agee et al., NWA 7034 would likely have been classified as a unique achondrite (an asteroidal sample) on the basis of its distinct oxygen isotope composition. However, they showed that the mineral chemistry of pyroxenes from NWA 7034 plot on the distinct FeO versus MnO trend defined by other martian meteorites. Another distinguishing characteristic of martian meteorites over achondrites is their young radiometric ages [<4 billion years ago (Ga)]; NWA 7034 has been dated about 2 Ga, older than SNC meteorites but younger than ALH 84001 (6). What makes NWA 7034 so exciting is that its major element composition is a close fit with the chemi￾cal data returned by the Mars rovers, as well as with the global chemical composition of Mars’ crust returned by the orbiting gamma￾ray spectrometer onboard Mars Odyssey (4). NWA 7034 appears to be a chemical analog of rocks from Gusev Crater (3). Given that the other known martian mete￾orites are a poor match for crust exposed at the martian surface, what can we learn from a meteorite that resembles just about any rock from Mars? The first important dis￾covery is that the new meteorite has a dis￾tinctly greater deficiency of the 16O isotope among its oxygen isotopes than the other martian meteorites, which are bunched so close together on an oxygen isotope plot that they can be classified as a group on the basis of a single measurement of their ∆ 17O ( 5). That this should be the case was anticipated by pioneering studies that found the mar￾tian hydrosphere and atmosphere to have Department of Earth, Ocean and Atmospheric Science and National High Magnetic Field Laboratory, Florida State Uni￾versity, Tallahassee, FL 32310, USA. E-mail: humayun@ magnet.fsu.edu Published byAAAS on February 15, 2013 www.sciencemag.org Downloaded from

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