Editors' Choice: Clinical Trials Unite Mice and Humans

RESEARCH NEWS & VIEWS
EDITORS CHOICE
Adapted extracts from selected News & Views articles published this year.
CANCER
CLINICAL TRIALS UNITE MICE AND HUMANS

Leisa Johnson (Nature 483, 546548; 2012) In anticancer co-clinical trials, mice carrying known mutations are treated in parallel with patients enrolled in a simultaneous clinical study. Chen and colleagues present a compelling case for conducting co-clinical trials. If done properly, co-clinical trials may help to identify predictive genetic markers that can be validated in real time using samples from patients enrolled in a concurrent clinical trial. These integrated data sets may ultimately be better at predicting the results of the concurrent clinical studies, as well as providing, on the basis of the cancers genetic profile, a rationale for the observed differences in therapeutic response. More over, such coordinated processes could serve to inform the analysis and design of both current and future clinical trials, with a goal of increasing clinical success rates and decreasing health-care costs.
Nature 483, 613617 (2012).
ASTRONOMY
COLLISION COURSE
R. Brent Tully (Nature 488, 600601; 2012) In a series of three papers published in The Astrophysical Journal, van der Marel and collaborators discuss the timing and dynamics of the imminent or at least inevitable collision between the Milky Way and the neighbouring Andromeda galaxy. The question since 1959 has been whether the two galaxies would collide on first return or fly past each other. The first passage of Andromeda about the Milky Way is going to be close enough to make a big mess. Four billion years from now, our progeny will see, if they still have dark skies and keen eyes, quite a spectacle as Andromeda fills the horizon just imagine being a resident in one of the members of the pair of colliding spiral galaxies NGC 2207 and IC 2163 (pictured).
Astrophys. J. 753, 7, 8, 9 (2012).
THERMODYNAMICS
THE FRIDGE GATE

Renato Renner (Nature 482, 164165; 2012) Minimalism is a popular trend in design, striving to expose the essence of an object through the elimination of all non-essential parts. Writing in the Journal of Physics A, Skrzypczyk et al. have now applied this approach to the study of thermal machines such as heat engines and refrigerators. Reducing the complexity of a refrigerator to its extreme, they arrived at a device as simple as a single logic gate. At first sight, refrigerators have little in common with such information-processing gates. But as early as the 1960s, information processing was studied from a thermodynamic perspective. It turns out that knowledge can always be traded for coldness. It is therefore no surprise that information-processing devices, such as logic gates, can have useful thermodynamic properties. The new minimalist fridge is a beautiful manifestation of this. Although it operates like a simple three-bit logic gate, it has the functionality of a fully fledged refrigerator.
J. Phys. A 44, 492002 (2011).
evidence for the binding mode of opioids to their receptors. The papers present the long-awaited, high-resolution crystal structures of all four opioid receptors in ligand-bound conformations. To develop drugs that retain the therapeutic action of opioids but not the unwanted side effects, it is crucial to understand the specific receptor conformations that opioids stabilize to selectively activate signalling pathways. This important aspect of ligand binding to opioid receptors is not captured by the crystal structures, and should be the subject of future research. Nevertheless, these crystal structures of inactive opioid receptors will contribute crucial information to a broad range of therapeutic areas, including those focused on pain, addiction and mental disorders.
Nature 485, 321326, 327332, 395399, 400404 (2012).
CLIMATE SCIENCE
AEROSOLS AND ATLANTIC ABERRATIONS

Amato Evan (Nature 484, 170171; 2012) Over the past century, the surface of the North Atlantic Ocean has gone through warm and cool periods that are not observed in other ocean basins. This Atlantic Multidecadal Oscillation (AMO) is thought to affect climate processes ranging from the current high levels of Atlantic hur ricane activity to the devastating sub-Saharan droughts of the early 1980s. Booth et al. report their use of a state-of-the-art model of Earths climate to demon strate that, at least over the past cen tury, the AMO is largely the response of the upper ocean to changes in the concentration of pollution aerosols in the atmosphere. The authors evidence is compelling,
STRUCTURAL BIOLOGY
HOW OPIOID DRUGS BIND TO RECEPTORS

Marta Filizola & Lakshmi A. Devi (Nature 485, 314317; 2012) Opioid drugs such as morphine and codeine are powerful painkillers, but an assortment of adverse side effects limits their effective medical use. Four papers report crystal structures that provide the first direct
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2012 Macmillan Publishers Limited. All rights reserved
NASA, ESA & THE HUBBLE HERITAGE TEAM (STSCI)
2012
NEWS & VIEWS RESEARCH
366 DAYS:
the year in science
but their results are sensitive to model parameterizations of microphysical processes, particularly the interaction between cloud water droplets and aerosols, that are not well constrained by observations. If the results can be corroborated, then they suggest that multidecadal temperature fluctuations of the North Atlantic are dominated by human activity.
Nature 484, 228232 (2012).
BIODIVERSITY
REMOTE RESPONSIBILITY
Edgar Hertwich (Nature 486, 36-37; 2012) If you buy a set of chess figures carved from ivory, you can suspect that you have contributed to killing an elephant. But if you buy a sausage, you cannot know whether the pig that was turned into the sausage was fed soy meal sourced from a farm that had just expanded into elephant habitat. The effects on species diversity, however, are similar. Understanding the complete causality chains leading to animal species extinctions has proven an intractable problem. Lenzen and colleagues present an analysis of species threats associated with international traded commodities, based on a detailed model of the global supply chains that connect final consumption to economic activities. Their results indicate that 30% of instances of red-listed species worldwide are caused by internationally traded commodities, and that the United States, Japan and European countries are the main net importers of species threats, whereas southeast Asian countries are the main net exporters.
Nature 486, 109112 (2012).
tract, the gut microbiota. Devkota and colleagues work emphasizes the importance of viewing nutrition from a perspective that encompasses both our human and microbial genomes. As the authors elegantly show, diets that provide the same number of calories can have remarkably different effects depending on the type of fat. It will be interesting to identify the specific components of our diet that influence microbial community structure, and to find out whether diets rich in saturated fat can drive the expansion of Bilophila wadsworthia or other potentially harmful microbes in humans. In this study, diet-driven changes in the production of bile acids affected gut microbes that, in turn, triggered disease. This line of research could ultimately lead to dietary recommendations tailored to match the idiosyncrasies of each persons gut microbiota.
Nature 487, 104108 (2012).
FORUM Agriculture
COMPARING APPLES WITH ORANGES
(Nature 485, 176177; 2012)
NANOTECHNOLOGY
THE IMPORTANCE OF BEING MODULAR

Paul W . K. Rothemund & Ebbe Sloth Andersen
(Nature 485, 584585; 2012)
A meta-analysis of agricultural systems shows that organic yields are mostly lower than those from conventional farming, but that organic crops perform well in some contexts.
Carpenters have been turning trees into furniture and dwellings for thousands of years, and so the discipline of woodworking features wellestablished techniques. Nanotechnologists similarly try to use DNA as a material for crafting nanometre-scale shapes, but DNA-working techniques are still evolving. Wei et al. present a method whose intrinsic modularity enables arbitrary DNA shapes to be constructed with striking speed. In their system, each tile is a single DNA strand with four different binding domains that specify which four other tiles can bind to it as neighbours. The authors general scheme specifies a set of N tiles that self-assemble to form a rectangle, within which each tile adopts a particular position. By mixing together appropriate subsets of tiles and allowing them to self-assemble, arbitrary DNA shapes (pictured) can be prepared. Careful studies of yields, kinetics and mechanism will be required to circumscribe the conditions under which the method works best.
Nature 485, 623626 (2012).
THE FRUITS OF ORGANIC FARMING

John P . Reganold Seufert and colleagues study is an example of meta-analysis being a great tool for identifying broad patterns not immediately visible in primary field research. If we want to feed a growing world population, producing adequate crop yields is vital, and this study bolsters the argument that adoption of organic agriculture under conditions in which it performs best might close the yield gap between organic and conventional systems. Organic farming provides multiple sustainability benefits, and these findings indicate that it can play a part in feeding the world.
FOODCOLLECTION RF/GETTY IMAGES
GETTING BACK TO THE FIELD

Achim Dobermann It is time to accept that various types of agriculture can have a place in feeding the world, but we also need to leave vague, outdated concepts of sustainability behind. Organic or low-external-input agriculture is not always sustainable. There are also many conventional agricultural systems that are highly productive, resource-efficient and sustainable. Instead of doing further meta-analyses to attempt to determine the optimal combination of agricultural systems, scientists should return to their fields and laboratories, and concentrate their efforts on increasing the performance of both conventional and organic agriculture.
Nature 485, 229232 (2012).
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MICROBIOLOGY
FAT, BILE AND GUT MICROBES

Peter J. Turnbaugh (Nature 487, 4748; 2012) Humans never truly dine alone our diet is intimately linked to the functioning of the trillions of microbes that inhabit our gastrointestinal
2012 Macmillan Publishers Limited. All rights reserved

Editors' Choice: Clinical Trials Unite Mice and Humans

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RESEARCH NEWS & VIEWS

CLINICAL TRIALS UNITE MICE AND HUMANS

THE FRIDGE GATE

AEROSOLS AND ATLANTIC ABERRATIONS

HOW OPIOID DRUGS BIND TO RECEPTORS

2012 Macmillan Publishers Limited. All rights reserved

NASA, ESA & THE HUBBLE HERITAGE TEAM (STSCI)

NEWS & VIEWS RESEARCH

THE IMPORTANCE OF BEING MODULAR

THE FRUITS OF ORGANIC FARMING

GETTING BACK TO THE FIELD

FAT, BILE AND GUT MICROBES

2012 Macmillan Publishers Limited. All rights reserved

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