How to break new ground in the era of “big science”

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Leslie Sage, a senior editor at Nature, and Joanne Baker, Nature‘s Books & Arts editor and a former observational cosmologist, write from the astronomy perspective about the risks of ’big science’ in Nature Physics (6, 233; 2010). From their article:

Astronomy is in an era of unprecedented change. Once the preserve of a dedicated few who travelled to remote observatories to investigate the heavens, the discipline is now ‘big science’, carried out on an industrial scale by a workforce of postdocs. Just as bankers have been seduced by the sophistication of computer analyses, more and more astronomy papers are showing evidence that familiarity with the essential ‘dirtiness’ of data and models is being lost.

Overly confident with their polished results, researchers are tempted to cut corners. In competitive fields, such as searches for high-redshift galaxies, it is now common for papers to be presented for publication without showing the actual data on which the conclusions are based; error bars are often omitted. As journal editors who follow manuscript submissions, we are concerned that this indicates that astronomers are less inclined to consider the limitations of their data in an era of huge databases and automated reduction procedures. This remoteness is only set to increase — more and more students have never been to an observatory, let alone fought cranky equipment and poor weather. Theorists who use other people’s code run the same risk — they are not aware of the limitations and assumptions under which it was written.

In an era of big science, where will the maverick views come from that will break new scientific ground? Astronomers have long researched independently. By harnessing the competitive drive and curiosity of individuals and small teams, astronomical discoveries have multiplied in the last fifty years, from the cosmic microwave background to black holes and pulsars. Now we routinely see papers authored by over 200 people, happy to sign off that “All authors contributed significantly to the work reported here”. Such large collaborations distance researchers from the coal face of science and are dishonest in accrediting work. Postdocs and students fare worst, because it is hard to shine in such a crowd, and permanent jobs may escape the best, being awarded to those who have someone senior to lobby for them.

There are positive aspects to the growth in collaboration. Costly new telescopes become feasible and more people have access to more data. There is a gratifying trend towards multiwavelength studies, which require team members with expertise in the different fields. But collaborations involving hundreds of people are notoriously difficult to run. Formal memoranda of understanding between institutions that specify in excruciating detail how every communication is handled — down to the idiocy of gamma-ray-burst alerts having to go to a publications committee before being issued — are inimical to the free-wheeling world of astronomy. In private, many astronomers say that they regret being part of large collaborations because the rules don’t work for them.

There are solutions. The training of young astronomers should be seen as a greater priority; it is too common that they are used as data slaves and then cast adrift. Students need to understand how an instrument works, how data are collected and reduced, and they need to see that the effort they expend will be rewarded by recognition. They could be taught professional skills, such as how collaborations work in real life and how to manage projects, by looking at past examples. Astronomy’s long history includes many stories of success and failure in team-working. And being pragmatic, graduate schools should accept that more than half of their students will forge careers beyond academia and broaden the base of experience to better prepare students for alternative careers.

As journal editors, we can encourage people to write better papers and not aim only for the preprint timestamp to beat a competitor. We can exhort that more care be given to considering the quality of a person’s work, not just its quantity or whether it made a big splash, for right or wrong reasons. But it falls to the community itself to create its own culture.

In moving to big science, astronomy is adopting practices that go against decades of experience in how to keep our science innovative. The alarm has been sounded, but few are listening because the crisis is not yet upon us. It will come a generation from now, but it is coming.

Special focus on genome instability

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The March issue of Nature Reviews Molecular Cell Biology presents a web focus on genome instability. The integrity of the genome is crucial for tumour suppression and for the propagation of genomic information to subsequent generations. DNA damage can result from cellular metabolism, exogenous genotoxic agents or routine errors in DNA replication and recombination. To combat these attacks and maintain genome integrity, cells have evolved a response system that induces cell cycle arrest, allowing sufficient time for DNA repair by specialized proteins. The DNA damage response system activates the appropriate DNA repair pathway or, in the case of irreparable damage, induces apoptosis. The special focus contains research highlights, review articles, a journal club and a NPG library of related articles. There is also a brief editors’ summary of the contents.

Accompanying the same issue of Nature Reviews Molecular Cell Biology is a Poster, by Eric J. Bennett, Mathew E. Sowa and J. Wade Harper, which illustrates the different deubiquitinating enzyme (DUB) families and highlights the cellular pathways in which some DUB-associated complexes act. Download a copy here.

Nature Reviews Molecular Cell Biology journal home page.

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All Nature Reviews journals in the life and clinical sciences.

Nature Genetics on conclusion by exclusion

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“Science is a way to distinguish things we know not to be true from other things. Large challenges lie ahead as we apply the scientific method to understanding biochemical systems, cellular organization and the functions of complex organs such as the brain.” So begins the February Editorial in Nature Genetics (42, 95; 2010). If the success of the early years of molecular biology can be attributed to the simplicity of the problems to solve, combined with rigorous experimental design including disprovable hypotheses and decisive experiments, what of todays immensely more complex scientific landscape and greatly increased number of scientists, not to mention orders of magnitude more computer power? Are we better equipped to generate, experimentally test, and choose or discard competing hypotheses?

The Editorial argues that “the complexity of a research project does not change the basic requirement for inference so long as the results are intended to be understood by human brains. A model or predictor aids secure inference when it is treated as a falsifiable hypothesis with falsifiable sub-hypotheses. Therefore, we would expect to publish a list of conditions in which the model or predictor is not valid, and tests demonstrating conditions in which it is not valid, as well as hypotheses drawn from the model or predictor and tests that disprove these hypotheses.

There are a number of benefits to separating the logical gems that authors are prepared to have tested by others from their setting of consistent observations and rhetoric that is not directly part of the scientific work of the paper. These pluses are: to allow peer referees to do their job and readers to understand the work; to make clear the caveats and limits to application of results to other fields; to limit proliferation of useless observational studies and reduce duplication and waste of effort.

It may also be possible to distinguish the direct influence of the research independently of the publications that describe it. In order to do this, each of these two components—hypotheses and experiments—will need to be coded with unique identifiers and separately cited. Such an extreme cultural change may not be needed if publications are carefully structured. Surely it is obvious that a study providing strong inferences will be both well used and highly cited.”

Synthetic systems biology, ten years on

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Synthetic biology goes beyond classic genetic engineering as it attempts to engineer living systems to perform new functions not found in nature. Ten years ago, Nature published a pair of seminal papers that stimulated ‘systems biology’ thinking in the field. The journal has now collected these papers, together with other, more recently published articles and an accompanying free podcast and video, as a web focus on ‘Synthetic systems biology’.

The collection includes a News Feature ‘Bioengineering: Five hard truths for synthetic biology’ (Nature 463, 288–290; 21 January 2010), which is free to access online. In this News Feature, Nature asks whether engineering approaches can tame the complexity of living systems by exploring five challenges for the field and how they might be resolved.

Also in the focus is a free online Editorial from Nature, ‘Ten years of synergy’ (Nature 463, 269-270; 21 January 2010), which suggests that contributions to and from basic science are the part of synthetic biology that most deserves celebration. In an accompanying podcast, one of Nature’s biology editors, Tanguy Chouard, discusses toggle switches, flashing colonies of bacteria and the challenges ahead for synthetic biology. And you can see a Nature video of synchronizing bacteria.

For these and other Nature articles on synthetic biology (commissioned editorials and original research papers), please visit the web focus.

RNA silencing: first in NSMB series of web features

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During 2010, Nature Structural & Molecular Biology is publishing a series of quarterly web features devoted to diverse areas within the journal’s scope. The first of these is on RNA silencing. Since initial observations indicating that small RNAs can mediate this process, silencing has come to be recognized as a key means of gene regulation, participating in a variety of processes across species. Still, research into small RNA-mediated regulation and the scope of this regulation, as well as its role in disease, continues to yield new insights and surprises. The NSMB Web Focus on RNA silencing comprises a core collection encompassing a specially commissioned Perspective; recently published Research Articles covering a range of current topics in the field; and a library that brings together additional recent advances in the field published at NSMB and other Nature journals.

Nature Structural & Molecular Biology journal website.

NSMB focuses and supplements.

Nature Publishing Group’s RNAi gateway.

Nature’s microRNA collection.

Nature Biotechnology focus on synthetic biology

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The December 2009 issue of Nature Biotechnology focuses on synthetic biology, in a special feature (subscription) containing news, opinion, comment and research articles on the topic. The focus discusses some of the progress in synthetic biology towards practical applications, as this latest iteration of genetic engineering, although still in its infancy, offers the prospect of the design and construction of new life forms from biological parts, devices and systems. If, however, you aren’t sure exactly what synthetic biology is, Nature Biotechnology asked 20 specialists for their definitions, so you can take your pick.

The Editorial that begins the focus asserts that “it is not too hard to imagine a future where, with relatively little effort, we can create alternative life forms—minimal-genome chassis organisms with interchangeable standardized gene circuits—that will enable genetic engineers to rapidly move from one industrial project to another. The technology is disruptive, with the potential to transform biological engineering, which until now has been limited to tinkering with natural organisms, and relies on a good deal of serendipity for success.

At the turn of the last century, the Wright brothers achieved manned flight not by mimicking natural systems, but by applying the principles of engineering and aerodynamics. Similarly, synthetic biology allows us to dispense with biological mimicry and design life forms uniquely tailored to our needs. In doing so, it will offer not only fundamental insights into questions of life and vitality but also the type of exquisite precision and efficiency in creating complex traits that genetic engineers could previously only dream of.”

One of the articles in the focus that I particularly enjoyed is Parts, property and sharing by Joachim Henkel of the Munich Universtiy of Technology and Stephen M. Maurer of the University of California, Berkeley, who suggest that synthetic biology should look to other industries’ models for ownership and open sharing. The authors write:

“Synthetic biology is bound to change the rules of the game in genetic engineering. Its reliance on large numbers of parts turns the field into a complex technology, and the importance of shared learning implies network effects and makes winner-take-all outcomes likely. Both aspects are compounded by weaknesses of the IP system—in particular, its lack of transparency. Although these problems may seem modest today, they are likely to become much more serious once the synthetic biology industry starts to generate significant profits.

For these reasons—and even though the general usefulness of patents in the life sciences is beyond doubt—reasonable steps to grow the commons and support open sharing seem highly advisable. We have already argued that an embedded Linux-style open parts collaboration makes good legal and economic sense. Furthermore, the open parts idea enjoys widespread support, not just in the academic community but also, to a large extent, in industry. For every front-runner, there are several firms for whom sharing is the only way to catch up. Similarly, companies that sell synthetic genes and other support services know that cheap, abundant, high-quality parts are good for business. Open parts are the best way to deliver this result. Finally, government has repeatedly intervened to promote open source-style sharing in software and, more recently, stem cell research. We think it will be similarly predisposed to support an open parts project. Yet no matter how synthetic biology is made more open, it needs to happen soon.”

Nature Biotechnology focus on synthetic biology.

Nature Insight on biomaterials

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Biomaterials research has come of age, write Nature journal editors Rosamund Daw and Stefano Tonzani in their introductory Editorial (Nature 462, 425; 2009, free to access online) to the latest Insight collection, Biomaterials. Since antiquity, the editors write, humans have been taking whatever substances are at hand — natural materials, glass, metals or polymers — and using them to replace body parts that have been damaged by disease or injury. But it is only recently, with the advent of molecular biology, that the field has become interdisciplinary, enabling materials scientists to design materials that impart a specific biological function. The field of biomaterials is also broadening as we improve our understanding of how the physical sciences can help to explain biology and indeed of how biological principles, mechanisms and molecules can be applied in the design of materials for non-biological applications. The articles in this Insight (listed below) explore areas of research in which recent advances in basic biology are driving materials scientists to think differently when developing new materials.

Overview

Inspiration and application in the evolution of biomaterials

Nathaniel Huebsch & David J. Mooney

Reviews

Designing materials to direct stem-cell fate

Matthias P. Lutolf, Penney M. Gilbert & Helen M. Blau

Biomaterial systems for mechanosensing and actuation

Peter Fratzl & Friedrich G. Barth

Materials engineering for immunomodulation

Jeffrey A. Hubbell, Susan N. Thomas & Melody A. Swartz

Perspective

Drivers of biodiagnostic development

David A. Giljohann & Chad A. Mirkin

More Nature Insights.

Nature Medicine classics collection

In 2010, Nature Medicine will celebrate 15 years as the leading translational-research journal. To mark this anniversary, the journal has launched the Nature Medicine Classics Collection. This collection brings together some landmark articles published in Nature Medicine over the past 15 years, making them freely available to all readers together with a series of recent articles on different fields of biomedicine to illustrate the breadth of the journal.

The Nature Medicine editors write: Since 1995, our journal has been at the forefront of publishing translational medicine, way before the term was even coined. Our focus on publishing basic and preclinical work that has direct relevance to human disease has been a key characteristic of Nature Medicine that has helped establish the reputation of the journal in the translational research landscape.

To put together this sampler, we have chosen a series of recent articles from our pages, organized them by therapeutic area, and made them freely available in order to give you a glimpse of the breadth of Nature Medicine’s coverage, as well as the quality of the science we publish.

In addition, we have chosen a few landmark articles that we had the privilege to publish over the past 15 years in an effort to illustrate why Nature Medicine is the home of translational research.

Nature Medicine Classics Collection by subject:

Classic articles

Cancer

Cardiovascular disease

Immunology

Infectious diseases

Metabolism

Neuroscience

See also:

Nature Medicine‘s free podcast.

Journal press releases.

Spoonful of Medicine, the journal’s blog.

Two views of the Lindau Nobel chemistry laureates’ meeting

Each year since 1951, young researchers and Nobel laureates have gathered on the shores of Lake Constance for a unique scientific conference. In 2009 the meeting was dedicated to chemistry, and laureates and students all came away enriched by their experiences. Martin Chalfie, one of the three recipients of the 2008 Nobel prize in Chemistry, reports what they learned from each other in the November issue of Nature Chemistry (1, 586-587; 2009) He writes:

“From their reading or from simply listening to my talk, the students generated a large number of fascinating questions. They wanted to know details of the experiments and they wanted to discuss potential future experiments. Conclusions about my research that had taken me years to realize (and which I have not written about or described in my talk) were instantly suggested by several of the students at the session. Seeing their excitement and quickness was humbling, but also invigorating.

The meeting allowed the students (as well as the laureates) to broaden their horizons, to have a chance to meet, exchange ideas, and learn about new areas of research from investigators from all over the world (the conference participants came from 67 different countries). The word ‘exchange’ is important here, because I don’t believe that the real benefits were associated with hearing advice from a bunch of older scientists who had been fortunate enough to get some recognition for their work.” The meeting’s significance is “the acknowledgement it gives to young scientists, especially at a time when they do not get much recognition, that they are on their way to succeeding in science, and that we think that they are important. Although they really do not need any seal of approval, everyone likes to get the occasional pat on the back.”

In a companion article in the same issue of Nature Chemistry (1, 587-590; 2009), Jeffrey R. Lancaster, a fourth-year graduate student in the Department of Chemistry, Columbia University, looks back at what he got out of the Lindau meeting: “two subtle points have ultimately distinguished the Lindau meeting for me as a unique event of which I was honoured to have been a part.

First, conversation and the sharing of ideas were fostered not solely between scientists with comparable levels of experience, but also across scientific generations and geographies. I had worthwhile discussions with my peers from Australia, China, India, the Netherlands, Poland and Spain (to name but a few), and was able to speak to scientists at various stages of their careers, from undergraduate to graduate students, postdocs, professors, governmental scientists and, of course, Nobel laureates. Second, the activities pursued by scientists outside of publishable, academic research also featured prominently at the meeting. That scientists might have a life apart from, and in addition to, their research is most often a topic best reserved for conference happy hours, not keynote addresses.”

Goodbye from Nature Reports Stem Cells

We are sad to announce that this month brings the last update of Nature Reports Stem Cells.

When we launched in June 2007, we wanted to support the stem cell field and the interested public by providing freely available content. Stem cell research was then – and is still – exciting and expanding. It requires highly varied experts to think and work together, and it requires the support and understanding of non-scientists. We believe we have been successful in creating a venue that highlights and explores the many facets and implications of stem cell science. It is now time for us to move on to fresh publishing challenges.

We have been helped by many contributors and experts who have generously given their time and insight. We give a heartfelt thanks to everyone who wrote articles or gave interviews, advice, and words of encouragement.

NRSC and its blog, the Niche, will continue to remain online as an archive. Nature and its sister titles remain committed, as ever, to publishing new research and news about stem cells.

Monya Baker, Editor

Natalie DeWitt, Editor at Large