NEWS & VIEWS RESEARCH Yet possible restoration solutions exist. Yelenik and D’Antonio posit that the native Acacia trees should be able to establish themselves in the declining exotic grassland, but their heavy seeds just cannot get there. By contrast, the seeds of the exotic Morella are bird-dispersed, so this species easily wins the colonization race. But the race could be fixed by seeding Acacia into the exotic grassland, where it is likely to grow well. The question then arises of whether addition of nitrogen to the soil by the trees’ fixation will reset the system and allow a replay of the grass invasion cycle. If so, the period of negative feedback could represent an opportunity to further reduce exotic-grass abundance to such a point that there is insufficient grass in the newly wooded regions to carry
fire, thereby minimizing the return of the initial positive feedback. Positive feedbacks provide sources of growth, explosion, erosion and collapse8, and consequently will continue to challenge how we approach conservation and restoration. Yelenik and D’Antonio’s study highlights the importance of understanding how mechanisms of feedback shift, and how these shifts affect species persistence. Although we will never eliminate surprises, this new perspective will inform where and when we might best intervene in systems to capitalize on their changing dynamics. ■ Katharine N. Suding is in the Department of Environmental Science, Policy, and
Management, University of California Berkeley, Berkeley, California 94720, USA. e-mail: [email protected] 1. Scheffer, M. Critical Transitions in Nature and Society (Princeton Univ. Press, 2009). 2. Yelenik, S. G. & D’Antonio, C. M. Nature 503, 517–520 (2013). 3. Ehrenfeld, J. G. Annu. Rev. Ecol. Evol. Syst. 41, 59–80 (2010). 4. D’Antonio, C. M. & Vitousek, P. M. Annu. Rev. Ecol. Syst. 23, 63–87 (1992). 5. Mack, M. C. & D’Antonio, C. M. Ecol. Appl. 13, 154–166 (2003). 6. D’Antonio, C. M., Hughes, R. F. & Tunison, J. T. Ecol. Appl. 21, 1617–1628 (2011). 7. Suding, K. N. & Hobbs, R. J. Trends Ecol. Evol. 24, 271–279 (2009). 8. Meadows, D. H. Thinking in Systems: A Primer (Chelsea Green, 2008). This article was published online on 20 November 2013.
regolith breccia. Lunar soils are also rich in these elements, because they have been bombarded by chondritic meteors and, over time, become contaminated with their debris. The composition of chondritic meteors is thought to reflect the primordial composition of the terrestrial (rocky) planets before these elements were sequestered Analysis of a meteorite found in northwest Africa, prosaically named NWA 7533, indicates that it is the first sample of the regolith, or ‘soil’, of Mars, and is derived into the planets’ cores. Contamination by chondritic material also accounts for the high levels from the earliest Martian igneous crust yet identified. See Letter p.513 of iridium found in strata on Earth from the Cretaceous–Tertiary geological boundary, H A R R Y Y. M C S W E E N drives soil scientists mad). Regolith breccias famously cited as evidence that a meteor are soils compacted and cemented into rocks impact was responsible for the extinction of the ASA’s decadal survey for planetary by impact-derived melts. Many lunar samples dinosaurs. science 1 concludes that return returned by the astronauts of the Apollo The real surprise is the ancient age reported ing samples of the ancient crust of missions are regolith breccias. for NWA 7533: 4.4 billion years, demonstratMars to Earth ranks among its highest priNWA 7533 contains clasts (fragments) that ing that this breccia is a sample of the earliest orities for exploring the Solar System. In this texturally resemble impact-derived melts in Martian crust. The age was determined by anaissue, Humayun et al.2 (page 513) describe a lunar regolith breccias, but with chemical com- lysing the radioactive-decay products of uraMartian meteorite sample already on Earth, positions unique to Mars. The compositions of nium in zircon crystals, which concentrate this albeit without the geological context that the clasts are nearly identical to those of basal- element. Zircon crystals typically form during samples collected on Mars would have. None- tic rocks and soils analysed by the Spirit rover magma crystallization, and these impervious theless, it is a revealing discovery. during its trek through the Gusev Crater on crystals probably survived pulverization and The meteorite, which is called NWA 7533 Mars. The high abundance of normally rare ele- melting of their host rocks by impacts. The (Fig. 1; NWA is an acronym for northwest ments in the clasts, such as nickel, osmium and age differs from that previously reported3 for Africa, where it was found), was part of a iridium, supports the idea that NWA 7533 is a NWA 7034 (2.1 billion years), an age that was celestial rock that broke up obtained using the decay of during its passage through radioactive rubidium. The the atmosphere, producing younger age determination, at least five recovered stones. based on analysis of the bulk Another member of this rock, may represent a mixture group of stones, NWA 7034, of the ages of formation of difwas described previously 3 ferent components that make as a volcanic breccia, which up the breccia, or may record means that it is composed of some isotopic disturbance fragmentary material prothat occurred long after the duced from basaltic lava. igneous crystallization of the Humayun et al. have interoriginal basaltic rocks. The preted NWA 7533 — and, new, older age implies that a by extension, NWA 7034 thick Martian crust formed — as being a regolith brecwithin the first 100 milcia. Regolith is the planetary lion years or so of the planet’s surface layer that is pulverhistory, coeval with the forized by meteor impacts mation of the Moon’s crust. (planetary scientists often These new Martian meteor use the terms ‘regolith’ and Figure 1 | A piece of the NWA 7533 meterorite found in northwest Africa. ite breccias are fiendishly com‘soil’ interchangeably, which The width of the stone is 40 mm. plex rocks, and forthcoming P L AN ETARY SCIENCE
A chunk of ancient Mars
LUC LABENNE/WWW.METEORITES.TV
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2 8 NOV E M B E R 2 0 1 3 | VO L 5 0 3 | NAT U R E | 4 7 3
© 2013 Macmillan Publishers Limited. All rights reserved
NEWS & VIEWS RESEARCH investigations will surely reveal more surprises and conundrums. Detailed studies of the various types of breccia clast, including age dating and analysis of their geochemistry and petrology, could help to unravel the geological record of early Mars. It has become apparent that Martian meteorites have different chemical compositions from rocks analysed on the planet’s surface4. Various explanations have been proffered to explain this difference5,6. But with the discovery of these latest meteorite breccias, we have a handful of paired meteorites that have the composition of Mars surface rocks, as well as one rock from the Martian surface with a composition like that of the meteorites7.
Increasingly, the world’s meteorite collections are being augmented by finds in hot (northwest Africa) and cold (Antarctica) deserts. Both sources have revealed previously unknown meteorite types, but it is unfortunate that these unique Martian meteorites fell in Morocco rather than on Antarctic ice. The acquisition of meteorites from hot desert countries for research typically depends on the ability to buy them, as opposed to the case with Antarctic meteorites, which are collected, curated and subsampled under nearly pristine conditions and allocated widely and free of charge on the basis of the scientific quality of proposals to study them. But we will gladly accept more samples of Mars from wherever we can get them. ■
Harry Y. McSween is in the Department of Earth and Planetary Sciences, University of Tennessee, Knoxville, Tennessee 37996–1410, USA. e-mail: [email protected] 1. National Research Council. Visions and Voyages for Planetary Science in the Decade 2013–2022 (National Academies Press, 2011). 2. Humayun, M. et al. Nature 503, 513–516 (2013). 3. Agee, C. B. et al. Science 339, 780–785 (2013). 4. McSween, H. Y. Jr, Taylor, G. J. & Wyatt, M. B. Science 324, 736–739 (2009). 5. Tuff, J., Wade, J. & Wood, B. J. Nature 498, 342–345 (2013). 6. Balta, J. B. & McSween, H. Y. Jr Geology 41, 1115–1118 (2013). 7. Zipfel, J. et al. Meteorit. Planet. Sci. 46, 1–20 (2011). This article was published online on 20 November 2013.
the villainous masterminds of malignancies. No drugs that combat Ras-driven human cancers have so far been developed, and the stakes for doing so are high: we cannot win the war on cancer without taming Ras. Accordingly, the US National Cancer Institute this After three decades of unsuccessful efforts to develop small molecules that year allocated US$10 million specifically neutralize the cancer-causing Ras proteins, an approach has been found to develop such drugs, and key researchers that opens up fresh avenues for anticancer research. See Letter p.548 in the field have committed to making this effort a reality3. In fact, medicinal chemists have long GIDEON BOLLAG & CHAO ZHANG attempted to halt unregulated Ras, but Previously reported were unable to identify small molecules binding pocket ne-third of all tumours harbour that could access the nucleotide-binding mutations in RAS genes1, but the pocket in Ras in order to do so. Drug Ras proteins encoded by these development at large pharmaceutical Switch-II mutant genes have steadfastly eluded companies had therefore been focused targeting by therapeutic agents. On on inactivating Ras indirectly by croppage 548 of this issue, Ostrem et al.2 preping its lipid tail — a feature that it uses to sent perhaps the most promising strategy attach itself to cell membranes. This led ever pursued towards developing an anti to the discovery of compounds known cancer drug that targets mutant Ras proas farnesyltransferase inhibitors, which teins. The authors’ clever approach was stall an enzyme that is involved in attachto make compounds that affect a subset ing the lipid tail to Ras. But although of Ras mutations in which a particular these compounds were active in animal amino acid — glycine-12 — in the promodels, they were ineffective in human tein is replaced by another amino acid, patients with cancer, because cancer cells cysteine. This kind of mutation, dubbed replaced the cropped tail with an alternaG12C, is found in a substantial proportive one4. Earlier this year, biochemists tion of lung cancers. Because the G12C discovered another target5 to prevent the mutation exists only in tumour cells, membrane localization of Ras: a protein drugs that target it could be exquisitely called PDEδ. The first PDEδ blockSwitch-I GTP selective, and therefore potentially much ers to be developed inhibit the cancerNew binding less toxic than many current anticancer causing activity of mutant Ras, but an pocket Cys 12 drugs. anxious wait is in store before we know Normal cellular Ras is a small protein whether this approach will yield effective that serves as a switch for cell signalling1. anticancer drugs. It binds the nucleotide GTP, hydrolysing Figure 1 | Binding pockets for Ras inhibitors. In the G12C With recent improvements in drug it to form another nucleotide, GDP, and cancer-causing mutant of the protein Ras, depicted here as design guided by protein structures, so cycles between GTP-bound ‘on’ and a ribbon diagram, a cysteine amino acid (Cys 12) replaces a there is renewed interest in targetGDP-bound ‘off ’ states. Mutations such glycine. Cylindrical sections indicate α-helices; ribbons indicate ing Ras directly. The latest generation as G12C impair GTP hydrolysis and β-sheets. The protein’s substrate, the nucleotide GTP, is bound of drug developers has thus replaced 5–7 trap Ras in the GTP-bound ‘on’ state, at the bottom right. Previously discovered Ras inhibitors the previous sledgehammer approach bind to a region between switch-I and switch-II, which are the causing unregulated signalling that can main regions of Ras that interact with regulators and effector with one that has scalpel-like precilead to cancer. In the human body, Ras molecules. Ostrem et al.2 have discovered inhibitors that bind sion. Within a year, three groups have is therefore both friend and foe: the non- irreversibly to Cys 12. This led to the identification of a new reported small molecules that directly mutated protein is the beating heart of binding pocket, which in turn allowed the authors to prepare Ras modulate Ras activity6–8. However, the cell signalling, but mutated versions are inhibitors of increased potency. compounds bind weakly to the protein, DRUG D ISCOVERY
Pocket of opportunity
O
2 8 NOV E M B E R 2 0 1 3 | VO L 5 0 3 | NAT U R E | 4 7 5
© 2013 Macmillan Publishers Limited. All rights reserved
fire, thereby minimizing the return of the initial positive feedback. Positive feedbacks provide sources of growth, explosion, erosion and collapse8, and consequently will continue to challenge how we approach conservation and restoration. Yelenik and D’Antonio’s study highlights the importance of understanding how mechanisms of feedback shift, and how these shifts affect species persistence. Although we will never eliminate surprises, this new perspective will inform where and when we might best intervene in systems to capitalize on their changing dynamics. ■ Katharine N. Suding is in the Department of Environmental Science, Policy, and
Management, University of California Berkeley, Berkeley, California 94720, USA. e-mail: [email protected] 1. Scheffer, M. Critical Transitions in Nature and Society (Princeton Univ. Press, 2009). 2. Yelenik, S. G. & D’Antonio, C. M. Nature 503, 517–520 (2013). 3. Ehrenfeld, J. G. Annu. Rev. Ecol. Evol. Syst. 41, 59–80 (2010). 4. D’Antonio, C. M. & Vitousek, P. M. Annu. Rev. Ecol. Syst. 23, 63–87 (1992). 5. Mack, M. C. & D’Antonio, C. M. Ecol. Appl. 13, 154–166 (2003). 6. D’Antonio, C. M., Hughes, R. F. & Tunison, J. T. Ecol. Appl. 21, 1617–1628 (2011). 7. Suding, K. N. & Hobbs, R. J. Trends Ecol. Evol. 24, 271–279 (2009). 8. Meadows, D. H. Thinking in Systems: A Primer (Chelsea Green, 2008). This article was published online on 20 November 2013.
regolith breccia. Lunar soils are also rich in these elements, because they have been bombarded by chondritic meteors and, over time, become contaminated with their debris. The composition of chondritic meteors is thought to reflect the primordial composition of the terrestrial (rocky) planets before these elements were sequestered Analysis of a meteorite found in northwest Africa, prosaically named NWA 7533, indicates that it is the first sample of the regolith, or ‘soil’, of Mars, and is derived into the planets’ cores. Contamination by chondritic material also accounts for the high levels from the earliest Martian igneous crust yet identified. See Letter p.513 of iridium found in strata on Earth from the Cretaceous–Tertiary geological boundary, H A R R Y Y. M C S W E E N drives soil scientists mad). Regolith breccias famously cited as evidence that a meteor are soils compacted and cemented into rocks impact was responsible for the extinction of the ASA’s decadal survey for planetary by impact-derived melts. Many lunar samples dinosaurs. science 1 concludes that return returned by the astronauts of the Apollo The real surprise is the ancient age reported ing samples of the ancient crust of missions are regolith breccias. for NWA 7533: 4.4 billion years, demonstratMars to Earth ranks among its highest priNWA 7533 contains clasts (fragments) that ing that this breccia is a sample of the earliest orities for exploring the Solar System. In this texturally resemble impact-derived melts in Martian crust. The age was determined by anaissue, Humayun et al.2 (page 513) describe a lunar regolith breccias, but with chemical com- lysing the radioactive-decay products of uraMartian meteorite sample already on Earth, positions unique to Mars. The compositions of nium in zircon crystals, which concentrate this albeit without the geological context that the clasts are nearly identical to those of basal- element. Zircon crystals typically form during samples collected on Mars would have. None- tic rocks and soils analysed by the Spirit rover magma crystallization, and these impervious theless, it is a revealing discovery. during its trek through the Gusev Crater on crystals probably survived pulverization and The meteorite, which is called NWA 7533 Mars. The high abundance of normally rare ele- melting of their host rocks by impacts. The (Fig. 1; NWA is an acronym for northwest ments in the clasts, such as nickel, osmium and age differs from that previously reported3 for Africa, where it was found), was part of a iridium, supports the idea that NWA 7533 is a NWA 7034 (2.1 billion years), an age that was celestial rock that broke up obtained using the decay of during its passage through radioactive rubidium. The the atmosphere, producing younger age determination, at least five recovered stones. based on analysis of the bulk Another member of this rock, may represent a mixture group of stones, NWA 7034, of the ages of formation of difwas described previously 3 ferent components that make as a volcanic breccia, which up the breccia, or may record means that it is composed of some isotopic disturbance fragmentary material prothat occurred long after the duced from basaltic lava. igneous crystallization of the Humayun et al. have interoriginal basaltic rocks. The preted NWA 7533 — and, new, older age implies that a by extension, NWA 7034 thick Martian crust formed — as being a regolith brecwithin the first 100 milcia. Regolith is the planetary lion years or so of the planet’s surface layer that is pulverhistory, coeval with the forized by meteor impacts mation of the Moon’s crust. (planetary scientists often These new Martian meteor use the terms ‘regolith’ and Figure 1 | A piece of the NWA 7533 meterorite found in northwest Africa. ite breccias are fiendishly com‘soil’ interchangeably, which The width of the stone is 40 mm. plex rocks, and forthcoming P L AN ETARY SCIENCE
A chunk of ancient Mars
LUC LABENNE/WWW.METEORITES.TV
N
2 8 NOV E M B E R 2 0 1 3 | VO L 5 0 3 | NAT U R E | 4 7 3
© 2013 Macmillan Publishers Limited. All rights reserved
NEWS & VIEWS RESEARCH investigations will surely reveal more surprises and conundrums. Detailed studies of the various types of breccia clast, including age dating and analysis of their geochemistry and petrology, could help to unravel the geological record of early Mars. It has become apparent that Martian meteorites have different chemical compositions from rocks analysed on the planet’s surface4. Various explanations have been proffered to explain this difference5,6. But with the discovery of these latest meteorite breccias, we have a handful of paired meteorites that have the composition of Mars surface rocks, as well as one rock from the Martian surface with a composition like that of the meteorites7.
Increasingly, the world’s meteorite collections are being augmented by finds in hot (northwest Africa) and cold (Antarctica) deserts. Both sources have revealed previously unknown meteorite types, but it is unfortunate that these unique Martian meteorites fell in Morocco rather than on Antarctic ice. The acquisition of meteorites from hot desert countries for research typically depends on the ability to buy them, as opposed to the case with Antarctic meteorites, which are collected, curated and subsampled under nearly pristine conditions and allocated widely and free of charge on the basis of the scientific quality of proposals to study them. But we will gladly accept more samples of Mars from wherever we can get them. ■
Harry Y. McSween is in the Department of Earth and Planetary Sciences, University of Tennessee, Knoxville, Tennessee 37996–1410, USA. e-mail: [email protected] 1. National Research Council. Visions and Voyages for Planetary Science in the Decade 2013–2022 (National Academies Press, 2011). 2. Humayun, M. et al. Nature 503, 513–516 (2013). 3. Agee, C. B. et al. Science 339, 780–785 (2013). 4. McSween, H. Y. Jr, Taylor, G. J. & Wyatt, M. B. Science 324, 736–739 (2009). 5. Tuff, J., Wade, J. & Wood, B. J. Nature 498, 342–345 (2013). 6. Balta, J. B. & McSween, H. Y. Jr Geology 41, 1115–1118 (2013). 7. Zipfel, J. et al. Meteorit. Planet. Sci. 46, 1–20 (2011). This article was published online on 20 November 2013.
the villainous masterminds of malignancies. No drugs that combat Ras-driven human cancers have so far been developed, and the stakes for doing so are high: we cannot win the war on cancer without taming Ras. Accordingly, the US National Cancer Institute this After three decades of unsuccessful efforts to develop small molecules that year allocated US$10 million specifically neutralize the cancer-causing Ras proteins, an approach has been found to develop such drugs, and key researchers that opens up fresh avenues for anticancer research. See Letter p.548 in the field have committed to making this effort a reality3. In fact, medicinal chemists have long GIDEON BOLLAG & CHAO ZHANG attempted to halt unregulated Ras, but Previously reported were unable to identify small molecules binding pocket ne-third of all tumours harbour that could access the nucleotide-binding mutations in RAS genes1, but the pocket in Ras in order to do so. Drug Ras proteins encoded by these development at large pharmaceutical Switch-II mutant genes have steadfastly eluded companies had therefore been focused targeting by therapeutic agents. On on inactivating Ras indirectly by croppage 548 of this issue, Ostrem et al.2 preping its lipid tail — a feature that it uses to sent perhaps the most promising strategy attach itself to cell membranes. This led ever pursued towards developing an anti to the discovery of compounds known cancer drug that targets mutant Ras proas farnesyltransferase inhibitors, which teins. The authors’ clever approach was stall an enzyme that is involved in attachto make compounds that affect a subset ing the lipid tail to Ras. But although of Ras mutations in which a particular these compounds were active in animal amino acid — glycine-12 — in the promodels, they were ineffective in human tein is replaced by another amino acid, patients with cancer, because cancer cells cysteine. This kind of mutation, dubbed replaced the cropped tail with an alternaG12C, is found in a substantial proportive one4. Earlier this year, biochemists tion of lung cancers. Because the G12C discovered another target5 to prevent the mutation exists only in tumour cells, membrane localization of Ras: a protein drugs that target it could be exquisitely called PDEδ. The first PDEδ blockSwitch-I GTP selective, and therefore potentially much ers to be developed inhibit the cancerNew binding less toxic than many current anticancer causing activity of mutant Ras, but an pocket Cys 12 drugs. anxious wait is in store before we know Normal cellular Ras is a small protein whether this approach will yield effective that serves as a switch for cell signalling1. anticancer drugs. It binds the nucleotide GTP, hydrolysing Figure 1 | Binding pockets for Ras inhibitors. In the G12C With recent improvements in drug it to form another nucleotide, GDP, and cancer-causing mutant of the protein Ras, depicted here as design guided by protein structures, so cycles between GTP-bound ‘on’ and a ribbon diagram, a cysteine amino acid (Cys 12) replaces a there is renewed interest in targetGDP-bound ‘off ’ states. Mutations such glycine. Cylindrical sections indicate α-helices; ribbons indicate ing Ras directly. The latest generation as G12C impair GTP hydrolysis and β-sheets. The protein’s substrate, the nucleotide GTP, is bound of drug developers has thus replaced 5–7 trap Ras in the GTP-bound ‘on’ state, at the bottom right. Previously discovered Ras inhibitors the previous sledgehammer approach bind to a region between switch-I and switch-II, which are the causing unregulated signalling that can main regions of Ras that interact with regulators and effector with one that has scalpel-like precilead to cancer. In the human body, Ras molecules. Ostrem et al.2 have discovered inhibitors that bind sion. Within a year, three groups have is therefore both friend and foe: the non- irreversibly to Cys 12. This led to the identification of a new reported small molecules that directly mutated protein is the beating heart of binding pocket, which in turn allowed the authors to prepare Ras modulate Ras activity6–8. However, the cell signalling, but mutated versions are inhibitors of increased potency. compounds bind weakly to the protein, DRUG D ISCOVERY
Pocket of opportunity
O
2 8 NOV E M B E R 2 0 1 3 | VO L 5 0 3 | NAT U R E | 4 7 5
© 2013 Macmillan Publishers Limited. All rights reserved
