Proteomics in human Parkinson's disease research

During the last decades, considerable advances in the understanding of specific mechanisms underlying neurodegeneration in Parkinson's disease have been achieved, yet neither definite etiology nor unifying sequence of molecular events has been formally established. Current unmet needs in Parkinson's disease research include exploring new hypotheses regarding disease susceptibility, occurrence and progression, identifying reliable diagnostic, prognostic and therapeutic biomarkers, and translating basic research into appropriate disease-modifying strategies. The most popular view proposes that Parkinson's disease results from the complex interplay between genetic and environmental factors and mechanisms believed to be at work include oxidative stress, mitochondrial dysfunction, excitotoxicity, iron deposition and inflammation. More recently, a plethora of data has accumulated pinpointing an abnormal processing of the neuronal protein α-synuclein as a pivotal mechanism leading to aggregation, inclusions formation and degeneration. This protein-oriented scenario logically opens the door to the application of proteomic strategies to this field of research. We here review the current literature on proteomics applied to Parkinson's disease research, with particular emphasis on pathogenesis of sporadic Parkinson's disease in humans. We propose the view that Parkinson's disease may be an acquired or genetically-determined brain proteinopathy involving an abnormal processing of several, rather than individual neuronal proteins, and discuss some pre-analytical and analytical developments in proteomics that may help in verifying this concept.     

Motivated research

While Europe is locked in the debate about basic versus applied research, Louis Pasteur solved the problem more than 100 years ago. Antoine Danchin comments on Pasteur''s notion of ‘motivated research'' and how it leads both to new discoveries and to new applications.Three years ago, a senior politician attended his country''s Annual Congress for the Advancement of Science to give the introductory lecture. He asked the attending scientists to make science and research more attractive to young students and the general public, and asked his countrymen to support scientists to address the urgent challenges of global climate change, energy needs and dwindling water resources. It was neither a European nor a US politician, but the Indian Prime Minister Manmohan Singh who made this speech about the relationship between research and its practical applications. This is such an important topic that one might think it deserves appropriate attention in Europe, yet we fail to address it properly. Instead, we just discuss how science should serve society or contribute to the ‘knowledge-based economy'', or how ‘basic'' or ‘fundamental'' research is opposed to ‘applied'' or ‘industrial'' research and how funding for ‘big science'' comes at the expense of ‘little academic'' research.This dichotomy between the research to generate knowledge and the application of that knowledge to benefit humankind seems to be a recent development. In fact, more than 100 years ago Louis Pasteur avoided this debate altogether: one of his major, yet forgotten, contributions to science was the insight that research and its applications are not opposed, but orthogonal to each other (Stokes, 1997). If Niels Bohr ‘invented'' basic academic research—which was nevertheless the basis for many technological inventions and industrial applications—Pasteur developed what we might call ‘motivated'' research.How is research motivated and by what? By definition, scientists are citizens and members of the general public and, like the public, they are motivated by two forces: on the one hand, in Rudyard Kipling''s words, “man''s insatiable curiosity”; on the other hand, a desire for maintaining and improving their well-being. These are not contradictory to one another; curiosity nourishes dreams of a brighter future and leads to discoveries that contribute to well-being.Pasteur understood that it is essential to take account of society''s demands and desires; that science must be motivated by what people want. Still, there are severe misgivings about the nature of research. These stem from the mistaken but popular assumption that the scientists'' main task is to find solutions to current problems or to fulfil our desires. Problems and desires, however, are not enough, because finding solutions also requires creativity and discovery, which, by their very nature, are unpredictable. Often we do not even know what we need or desire and it is only through curiosity and more knowledge that we find new ways to improve our well-being. Motivation by itself is, therefore, not enough to lead to discovery. Motivation simply helps us choose between many different goals and an infinite number of paths to gain novel knowledge. Subsequently, each path, once chosen, must be explored using the scientific method, which is the only way to new discoveries.Motivation helps us to ask relevant questions. For example, why do wine and beer go sour without any apparent reason? Pasteur set out to design experiments that showed that fermentation is caused by microorganisms. A few years later, silkworms were suddenly dying of a terrible disease in the silk factories of southern France. The French government called on Pasteur for help, who eventually found that a parasite had infected silkworm eggs and proposed solutions to eradicate the disease. The original question therefore led to germ theory and bacteriology, helped to develop solutions to infectious diseases, and eventually created the whole field of microbiology.Motivation leads to conceptual and experimental research, which generates discoveries and new technologies. Discoveries, in turn, are the basic resource for the creation of general knowledge and the development of new products, services and other goods that fulfil public demands and generate jobs. The study of the ‘diseases'' of beer and wine also led to the development of fermentation processes that are still in use today. The same motivation that drove Pasteur in the nineteenth century now enables us to tackle current problems, such as pollution, by studying microbial communities that make compost or thrive in garbage dumps. Motivated research therefore reconciles our curiosity with the creation of knowledge and enables us to address pressing needs for humanity.Because it is strongly inspired by—even rooted in—society''s demands and desires, motivated research also raises accompanying ethical, legal, social and safety issues that should be compelling for all research. As mentioned above, scientists are members of the public who share the same concerns and demands as their fellow citizens and therefore participate with a general, public intelligence that, too often, is absent from academic research. This absence of ‘common sense'' or societal expectations generates the misunderstandings concerning research in biology and the development of biotechnology. These misconceptions—whether about the purported risks of genetically modified organisms or the exaggerated expectations for cancer therapies—can create real suffering in society and inefficient allocation of limited resources. It is therefore advisable for researchers to listen more to the public at large in order to find the motivation for their work.     

Social interaction in nonhuman primates: an underlying theme for primate research.

Social living is assumed to be a critical feature of nonhuman primate existence inasmuch as most primate species live in social groups in nature. Recent USDA legislation emphasizes the importance of social contact in promoting psychological well-being and recommends that laboratory primates be housed with companions when consistent with research protocols. Our goals were to examine the link between social housing and psychological well-being and to explore the idea that research may be compromised when primates are studied in environments that vary too greatly from their natural ecological setting (individual cage housing versus group housing). Three general points emerge from these examinations. First, providing companionship may be a very potent way in which to promote psychological well-being in nonhuman primates; however, social living is not synonymous with well-being. The extent to which social housing promotes psychological well-being can vary across species and among individual members of the same species (for example, high- and low-ranking monkeys). Secondly, housing conditions can affect research outcomes in that group-housed animals may differ from individually housed animals in response to some manipulation. Social interaction may be a significant variable in regulating the biobehavioral responses of nonhuman primates to experimental manipulations. Finally, a larger number of socially housed subjects than individually housed subjects may be necessary for some biomedical research projects to yield adequate data analysis. Thus, social living has significant benefits and some potential costs not only for the animals themselves, but for the research enterprise.     

Implications of new research and technologies for malolactic fermentation in wine

The initial conversion of grape must to wine is an alcoholic fermentation (AF) largely carried out by one or more strains of yeast, typically Saccharomyces cerevisiae. After the AF, a secondary or malolactic fermentation (MLF) which is carried out by lactic acid bacteria (LAB) is often undertaken. The MLF involves the bioconversion of malic acid to lactic acid and carbon dioxide. The ability to metabolise l-malic acid is strain specific, and both individual Oenococcus oeni strains and other LAB strains vary in their ability to efficiently carry out MLF. Aside from impacts on acidity, LAB can also metabolise other precursors present in wine during fermentation and, therefore, alter the chemical composition of the wine resulting in an increased complexity of wine aroma and flavour. Recent research has focused on three main areas: enzymatic changes during MLF, safety of the final product and mechanisms of stress resistance. This review summarises the latest research and technological advances in the rapidly evolving study of MLF and investigates the directions that future research may take.     

Marine scientific research and marine pollution in China

Abstract

In recent years coastal states everywhere in the world have paid attention to the preservation of the marine environment and the conduct of marine scientific research. The scope and nature of China's marine scientific research have been expanded and diversified since the late 1970s because of the growing importance of the ocean for the “Four Modernization “ programs. More and more programs have been designed and executed to find fishing resources, search for offshore oil and gas, promote maritime defense, help alleviate the marine pollution problems, reinforce China's territorial claim in the South China Sea, participate in Antarctic scientific research, and to better understand the whole marine environment. This article first examines China's attitude toward the legal regimes of marine pollution and marine scientific research. It depicts China's marine scientific research activities from the early 1950s. Finally it suggests that more scientific research programs will be designed in support of China's ocean development plans in the future.     

Funding source and research report quality in nutrition practice-related research

Background

The source of funding is one of many possible causes of bias in scientific research. One method of detecting potential for bias is to evaluate the quality of research reports. Research exploring the relationship between funding source and nutrition-related research report quality is limited and in other disciplines the findings are mixed.

Objective

The purpose of this study is to determine whether types of funding sources of nutrition research are associated with differences in research report quality.

Design

A retrospective study of research reporting quality, research design and funding source was conducted on 2539 peer reviewed research articles from the American Dietetic Association''s Evidence Analysis Library® database.

Results

Quality rating frequency distributions indicate 43.3% of research reports were rated as positive, 50.1% neutral, and 6.6% as negative. Multinomial logistic regression results showed that while both funding source and type of research design are significant predictors of quality ratings (χ2 = 118.99, p<0.001), the model''s usefulness in predicting overall research report quality is little better than chance. Compared to research reports with government funding, those not acknowledging any funding sources, followed by studies with University/hospital funding were more likely to receive neutral vs positive quality ratings, OR = 1.85, P <0.001 and OR = 1.54, P<0.001, respectively and those that did not report funding were more likely to receive negative quality ratings (OR = 4.97, P<0.001). After controlling for research design, industry funded research reports were no more likely to receive a neutral or negative quality rating than those funded by government sources.

Conclusion

Research report quality cannot be accurately predicted from the funding source after controlling for research design. Continued vigilance to evaluate the quality of all research regardless of the funding source and to further understand other factors that affect quality ratings are warranted.     

Academic labour shortages. A lack of trained scientists could slow down research in Europe

A shortage of skilled science labour in Europe could hold back research progress. The EU will increase science funding to address the problem, but real long-term measures need to start in schools, not universities.Scientists have always warned about the doom of research that could result from a shortage of students and skilled labour in the biomedical sciences. In the past, this apocalyptic vision of empty laboratories and unclaimed research grants has seemed improbable, but some national research councils and the European Union (EU) itself now seem to think that we may be on the brink of a genuine science labour crisis in Europe. This possibility, and its potential effects on economic growth, has proven sufficiently convincing for the European Commission (EC) to propose a 45% increase to its seven-year research and development budget of 45%—from €55 billion, provided under the Framework Programme (FP7), to €80 billion—for a new strategic programme for research and innovation called Horizon 2020 that will start in 2014.This bold proposal to drastically increase research funding, which comes at a time when many other budgets are being frozen or cut, was rigorously defended in May 2012 by the EU ministers responsible for science and innovation, against critics who argued that such a massive increase could not be justified given the deepening economic crisis across the EU. So far, the EU seems to be holding to the line that it has to invest more into research if Europe is to compete globally through technological innovation underpinned by scientific research.Europe is caught in a pincer movement between its principle competitors—the USA and Japan, which are both increasing their research budgets way ahead of inflation—and the emerging economies of China, India, Brazil and Russia, which are quickly closing from behind. The main argument for the Horizon 2020 funding boost came from a study commissioned by the EU [1], which led the EC to claim that Europe faces an “innovation emergency” because its businesses are falling behind US and Japanese rivals in terms of investment and new patents. As Martin Lange, Policy Officer for Marie Curie Actions—an EU fellowship programme for scientists—pointed out, “China, India and Brazil have started to rapidly catch up with the EU by improving their performance seven per cent, three per cent and one per cent faster than the EU year on year over the last five years.”According to Lange, Europe''s innovation gap equates to a shortage of around 1 million researchers across the EU, including a large number in chemistry and the life sciences. This raises fundamental issues of science recruitment and retention that a budget increase alone cannot address. The situation has also been confused by the economic crisis, which has led to the position where many graduates are unemployed, and yet there is still an acute shortage of specialist skills in areas vital to research.This is a particularly serious issue in the UK, where around 2,000 researcher jobs were lost following the closure of pharmaceutical company Pfizer''s R&D facility in Kent, announced in February 2011. “The travails of Pfizer have affected the UK recruitment market,” explained Charlie Ball, graduate labour market specialist at the UK''s Higher Education Careers Services Unit. The closure has contributed to high unemployment among graduates, particularly chemists, who tend to be employed in pharmaceutical research in the UK. “Even among people with chemistry doctorates, the unemployment rate is higher than the average,” he said.The issue for chemists, at least in the UK, is not a skills shortage, but a skills mismatch. Ball identified analytical chemistry as one area without enough skilled people, despite the availability of chemists with other specialties. He attributes part of the problem to the pharmaceutical industry''s inability to communicate its requirements to universities and graduates, although he concedes that doing so can be challenging. “One issue is that industry is changing so quickly that it is genuinely difficult to say that in three or four years time we will need people with specific skills,” Ball explained.So far, the EU seems to be holding to the line that it has to invest more into research […] to compete globally through technological innovation underpinned by scientific researchAlongside this shortage of analytical skills, the UK Medical Research Council (MRC) has identified a lack of people with practical research knowledge, and in particular of experience working with animals, as a major factor holding back fundamental and pre-clinical biomedical research in the country. It has responded by encouraging applications from non-UK and even non-EU candidates for doctoral studentships that it funds, in cases where there is a scarcity of suitable UK applicants.But, the underlying problem common to the whole of Europe is more fundamental, at least according to Bengt Norden, Professor of Physical Chemistry at the University of Gothenburg in Sweden. The issue is not a shortage of intellectual capital, Norden argues, but a growing lack of investment into training chemists, which in turn undermines life sciences research. Similarly to many other physical chemists, Norden has worked mainly in biology, where he has applied his expertise in molecular recognition and function to DNA recombination and membrane translocation mechanisms. He therefore views a particularly acute recruitment and retention crisis in chemistry as being a drag on both fundamental and applied research across the life sciences. “The recruitment crisis is severe,” Norden said. “While a small rill of genuinely devoted‘young amateur scientists‘ still may sustain the recruitment chain, there is a general drain of interest in science in general and chemistry in particular.” He attributes this in part to sort of a ‘chemophobia'', resulting from the association of chemistry with environmental pollution or foul odours, but he also blames ignorant politicians and other public figures for their negative attitude towards chemistry. “A former Swedish Prime Minister, Goran Persson, claimed that ‘his political goal was to make Sweden completely free from chemicals'',” Norden explained by way of example.Scientists themselves also need to do a better job of countering the negative perceptions of chemistry and science, perhaps by highlighting the contribution that chemistry is already making to clearing up pollution. Chemistry has been crucial to the development of microorganisms that can be used to break down organic pollutants in industrial waste, or clear up accidental spillage during transport. In fact, chemistry has specifically addressed the two major challenges involved: the risk that genetically engineered microorganisms could threaten the wider environment if they escape, and the problem that the microorganisms themselves can be poisoned if the concentration of pollutants is too high.A team at the University of Buenos Aires in Argentina has solved both problems by developing a material comprising an alginate bead surrounded by a silica gel [2]. This container houses a fungus that produces enzymes that break up a variety of organic pollutants. The pores of the hydrogel can limit the intake of toxic compounds from the polluted surroundings, thus controlling the level of toxicity experienced by the fungus, whilst the fungus itself is encapsulated inside the unit and cannot escape. Norden and others believe that if such examples were given more publicity, they would both improve the reputation of chemistry and science in general, and help to enthuse school students at a formative age.…Europe''s innovation gap equates to a shortage of around 1 million researchers across the EU, including a large number in chemistry and the life sciencesUnfortunately, this is not happening in schools, according to Norden, where the curriculum is failing both to enthuse pupils through practical work, and to inform them of the value of chemistry across society: “school chemistry neither stimulates curiosity nor does it promote understanding of what is most important to everybody,” he said. “It should be realized that well-taught chemistry is a necessary tool for dealing with everyday problems, at home or at work, and in the environment, relating to function of medicines, as well as what is poisonous and what is less noxious. As it is, all chemicals are presented simply as poisons.”Norden believes that a broader cultural element also tends to explain the particular shortage of analytical skills in chemistry. He believes that young people are more inclined than ever before to weigh up the probable rewards of a chosen profession in relation to the effort involved. “There seems to be a ‘cost–benefit'' aspect that young people apply when choosing an academic career: science, including maths, is too hard in relation to the jobs that eventually are available in research,” he explained. This ‘cost–benefit'' factor might not deter people from studying subjects up to university level, but can divert them into careers that pay a lot more. Ball believes that there is also an issue of esteem, in that people tend to gravitate towards careers where they feel valued. “Our most able graduates don''t see parity in esteem between research and other professions being represented by the salary they are paid,” he explained. “That is an issue that needs to be resolved, and it is not just about money, but working hard to convince these graduates that there is a worthwhile career in research.”Our most able graduates don''t see parity in esteem between research and other professions being represented by the salary they are paid,Lange suggests that it would be much easier to persuade the best graduates to stay in science if they were able to pursue their ideas free from bureaucracy or other constraints. This was a main reason to start the Marie Curie Actions programme of which Lange is a part, and which will be continued under Horizon 2020 with a new name, Marie Skłodowska-Curie Actions, and an increased budget. “The Marie Curie Actions have been applying a bottom-up principle, allowing researchers to freely choose their topic of research,” Lange explained. “The principle of ‘individual-driven mobility'' that is used in the Individual Fellowships empowers researchers to make their own choices about the scientific topic of their work, as well as their host institutions. […] It is a clear win–win situation for both sides: researchers are more satisfied because they are given the opportunity to take their careers in their own hands, while universities and research organizations value top-class scientists coming from abroad to work at their institutes.”Lange also noted that although Marie Curie Fellows choose their own research subjects, they tend to pursue topics that are relevant to societal needs because they want to find work afterwards. “More than 50% of the FP7 Marie Curie budget has been dedicated to research that can be directly related to the current societal challenges, such as an ageing population, climate change, energy shortage, food and water supply and health,” he said. “This demonstrates that researchers are acting in a responsible way. Even though they have the freedom to choose their own research topics, they still address problems that concern society in general.” In addition, Marie Curie Actions also encourages engagement with the public, feeding back into the wider campaign to draw more people into science careers. “Communicating science to the general public will be of importance as well, if we want to attract more young people to science,” Lange said. “Recently, the Marie Curie Actions started encouraging their Fellows to engage in outreach activities. In addition, we have just launched a call for the Marie Curie Prize, where one of the three Prize categories will be ‘Communicating Science''.”Another important element of the EU''s strategy to stimulate innovative cutting edge research is the European Research Council (ERC). It was the first pan-European funding body for front-line research across the sciences, with a budget of €7.5 billion for the FP7 period of 2007–2013, and has been widely heralded as a success. As a result, the ERC is set to receive an even bigger percentage increase than other departments within Horizon 2020 for the period 2014–2020, with a provisional budget of €13.2 billion.Leading scientists, such as Nobel laureate Jean-Marie Lehn, from Strasbourg University in France, believe that the ERC has made a substantial contribution to innovative research and, as a result, has boosted the reputation of European science. “The ERC has done a fantastic job which is quite independent of pressures from the outside,” he said. “It is good to hear that taking risks is regarded as important.” Lehn also highlighted the importance of making it clear that there are plenty of opportunities in research beyond those funded, and therefore dictated, by the big pharmaceutical companies. “There is chemistry outside big pharma, and life beyond return on investment,” he said. Lehn agreed that there must be a blend between blue sky and goal-oriented research, even if there is an argument over what the blend and goals should be.…the ERC has made a substantial contribution to innovative research and, as a result, has boosted the reputation of European scienceThere is growing optimism that Europe''s main funding bodies, including the national research councils of individual countries, have not only recognized the recruitment problem, but are taking significant steps to address it. Even so, there is still work to be done to improve the image of science and to engage students through more stimulating teaching. Chemistry in particular would benefit from broader measures to attract young people to science. Ultimately, the success of such initiatives will have much broader effects in the life sciences and drug development.     

Small gods,rituals, and cooperation: The Mentawai water spirit Sikameinan

Cognitive and evolutionary research has focused on the powerful deities of large-scale societies, yet little work has examined the smaller gods of animist traditions. In a study of the water spirit Sikameinan of the Mentawai people (Siberut Island, Indonesia), we address three questions: (1) Are smaller gods believed to enforce cooperation, especially compared to bigger gods in larger-scale societies? (2) Do beliefs in these deities encourage people to engage in behavior otherwise perceived as costly? and (3) Does ritual reinforce beliefs in these deities? Drawing on interview responses, data from healing ceremonies, and ethnographic observation, we show that Sikameinan is believed to punish people who violate meat-sharing norms and that people ‘attacked’ by Sikameinan pay shamans to conduct healing rituals. The public nature of rituals, involving prestigious individuals apologizing to Sikameinan for the patient's stinginess, reinforce onlookers' beliefs about Sikameinan. The most widely shared beliefs about Sikameinan are represented in rituals while beliefs not represented vary considerably, indicating that ritual may be potent for cultural transmission. These results suggest that moralizing supernatural punishers may be more common than suspected and that the trend in the cultural evolution of religion has been an expansion of deities' scope, powers, and monitoring abilities.     

Task Design Influences Prosociality in Captive Chimpanzees (Pan troglodytes)

Chimpanzees confer benefits on group members, both in the wild and in captive populations. Experimental studies of how animals allocate resources can provide useful insights about the motivations underlying prosocial behavior, and understanding the relationship between task design and prosocial behavior provides an important foundation for future research exploring these animals'' social preferences. A number of studies have been designed to assess chimpanzees'' preferences for outcomes that benefit others (prosocial preferences), but these studies vary greatly in both the results obtained and the methods used, and in most cases employ procedures that reduce critical features of naturalistic social interactions, such as partner choice. The focus of the current study is on understanding the link between experimental methodology and prosocial behavior in captive chimpanzees, rather than on describing these animals'' social motivations themselves. We introduce a task design that avoids isolating subjects and allows them to freely decide whether to participate in the experiment. We explore key elements of the methods utilized in previous experiments in an effort to evaluate two possibilities that have been offered to explain why different experimental designs produce different results: (a) chimpanzees are less likely to deliver food to others when they obtain food for themselves, and (b) evidence of prosociality may be obscured by more “complex” experimental apparatuses (e.g., those including more components or alternative choices). Our results suggest that the complexity of laboratory tasks may generate observed variation in prosocial behavior in laboratory experiments, and highlights the need for more naturalistic research designs while also providing one example of such a paradigm.     

Stem-cell battles. Stem-cell research in the USA is facing new legal and political challenges

The US still leads the world in stem-cell research, yet US scientists are facing yet another political and legal battle for federal funding to support research using human embryonic stem cells.Disputes over stem-cell research have been standard operating procedure since James Thompson and John Gearhart created the first human embryonic cell (hESC) lines. Their work triggered an intense and ongoing debate about the morality, legality and politics of using hESCs for biomedical research. “Stem-cell policy has caused craziness all over the world. It is a never-ending, irresolvable battle about the moral status [of embryos],” commented Timothy Caulfield, research director of the Health Law Institute at the University of Alberta in Edmonton, Canada. “We''re getting to an interesting time in history where science is playing a bigger and bigger part in our lives, and it''s becoming more controversial because it''s becoming more powerful. We need to make some interesting choices about how we decide what kind of scientific inquiry can go forward and what can''t go forward.”“Stem-cell policy has caused craziness all over the world…[i]t is a never-ending, irresolvable battle about the moral status [of embryos]”The most contested battleground for stem-cell research has been the USA, since President George W. Bush banned federal funding for research that uses hESCs. His successor, Barack Obama, eventually reversed the ban, but a pending lawsuit and the November congressional elections have once again thrown the field into jeopardy.Three days after the election, the deans of US medical schools, chiefs of US hospitals and heads of leading scientific organizations sent letters to both the House of Representatives and the Senate urging them to pass the Stem Cell Research Advancement Act when they come back into session. The implication was to pass legislation now, while the Democrats were still the majority. Republicans, boosted in the election by the emerging fiscally conservative Tea Party movement, will be the majority in the House from January, changing the political climate. The Republicans also cut into the Democratic majority in the Senate.Policies and laws to regulate stem-cell research vary between countries. Italy, for example, does not allow the destruction of an embryo to generate stem-cell lines, but it does allow research on such cells if they are imported. Nevertheless, the Italian government deliberately excluded funding for projects using hESCs from its 2009 call for proposals for stem-cell research. In the face of legislative vacuums, this October, Science Foundation Ireland and the Health Research Board in Ireland decided to not consider grant applications for projects involving hESC lines. The UK is at the other end of the scale; it has legalized both research with and the generation of stem-cell lines, albeit under the strict regulation by the independent Human Fertility and Embryology Authority. As Caulfield commented, the UK is “ironically viewed as one of the most permissive [on stem-cell policy], but is perceived as one of the most bureaucratic.”Somewhere in the middle is Germany, where scientists are allowed to use several approved cell lines, but any research that leads to the destruction of an embryo is illegal. Josephine Johnston, director of research operations at the Hastings Center in Garrison, NY, USA—a bioethics centre—said: “In Germany you can do research on embryonic stem-cells, but you can''t take the cells out of the embryo. So, they import their cells from outside of Germany and to me, that''s basically outsourcing the bit that you find difficult as a nation. It doesn''t make a lot of sense ethically.”Despite the public debates and lack of federal support, Johnson noted that the USA continues to lead the world in the field. “[Opposition] hasn''t killed stem-cell research in the United States, but it definitely is a headache,” she said. In October, physicians at the Shepherd Center, a spinal cord and brain injury rehabilitation hospital and clinical research centre in Atlanta, GA, USA, began to treat the first patient with hESCs. This is part of a clinical trial to test a stem-cell-based therapy for spinal cord injury, which was developed by the US biotechnology company Geron from surplus embryos from in vitro fertilization.Nevertheless, the debate in the USA, where various branches of government—executive, legislative and legal—weigh in on the legal system, is becoming confusing. “We''re never going to have consensus [on the moral status of fetuses] and any time that stem-cell research becomes tied to that debate, there''s going to be policy uncertainty,” Caulfield said. “That''s what''s happened again in the United States.”Johnson commented that what makes the USA different is the rules about federally funded and non-federally funded research. “It isn''t much discussed within the United States, but it''s a really dramatic difference to an outsider,” she said. She pointed out that, by contrast, in other countries the rules for stem-cell research apply across the board.The election of Barack Obama as US President triggered the latest bout of uncertainty. The science community welcomed him with open arms; after all, he supports doubling the budget of the National Institutes of Health (NIH) over the next ten years and dismantled the policies of his predecessor that barred it from funding projects beyond the 60 extant hESC lines—only 21 of which were viable. Obama also called on Congress to provide legal backing and funding for the research.The executive order had unforeseen consequences for researchers working with embryonic or adult stem cells. Sean Morrison, Director of the University of Michigan''s Centre for Stem Cell Biology (Ann Arbor, MI, USA), said he thought that Obama''s executive order had swung open the door on federal support forever. “Everybody had that impression,” he said.Leonard I. Zon, Director of the Stem Cell Program at Children''s Hospital Boston (MA, USA), was so confident in Obama''s political will that his laboratory stopped its practice of labelling liquid nitrogen containers as P (Presidential) and NP (non-Presidential) to avoid legal hassles. His lab also stopped purchasing and storing separate pipettes and culture dishes funded by the NIH and private sources such as the Howard Hughes Medical Institute (HHMI; Chevy Chase, MD, USA).But some researchers who focused on adult cells felt that the NIH was now biased in favour of embryonic cells. Backed by pro-life and religious groups, two scientists—James Sherley of the Boston Biomedical Research Institute and Theresa Deisher of AVM Biotechnology (Seattle, WA)—questioned the legality of the new NIH rules and filed a lawsuit against the Department of Health and Human Services (HHS) Secretary, Kathleen Sebelius. Deisher had founded her company to “[w]ork to provide safe, effective and affordable alternative vaccines and stem-cell therapies that are not tainted by embryonic or electively aborted fetal materials” (www.avmbiotech.com).…the debate in the USA, where various branches of government—executive, legislative and legal—weigh in on the legal system, is becoming confusingSherley argued in an Australian newspaper in October 2006 that the science behind embryonic stem-cell research is flawed and rejected arguments that the research will make available new cures for terrible diseases (Sherley, 2006). In court, the researchers also argued that they were irreparably disadvantaged in competing for government grants by their work on adult stem cells.Judge Royce C. Lamberth of the District Court of the District of Columbia initially ruled that the plaintiffs had no grounds on which to sue. However, the US District Court of Appeals for the District of Columbia overturned his decision and found that “[b]ecause the Guidelines have intensified the competition for a share in a fixed amount” of NIH funding. With the case back in his court, Lamberth reversed his decision on August 23 this year, granting a preliminary injunction to block the new NIH guidelines on embryonic stem-cell work. This injunction is detailed in the 1995 Dickey-Wicker Amendment, an appropriation bill rider, which prohibits the HHS from funding “research in which a human embryo or embryos are destroyed, discarded or knowingly subjected to risk of injury or death.” By allowing the destruction of embryos, Lamberth argued, the NIH rules violate the law.This triggered another wave of uncertainty as dozens of labs faced a freeze of federal funding. Morrison commented that an abrupt end to funding does not normally occur in biomedical research in the USA. “We normally have years of warning when grants are going to end so we can make a plan about how we can have smooth transitions from one funding source to another,” he said. Morrison—whose team has been researching Hirschsprung disease, a congenital enlargement of the colon—said his lab potentially faced a loss of US$ 250,000 overnight. “I e-mailed the people in my lab and said, ‘We may have just lost this funding and if so, then the project is over''”.Morrison explained that the positions of two people in his lab were affected by the cut, along with a third person whose job was partly funded by the grant. “Even though it''s only somewhere between 10–15% of the funding in my lab, it''s still a lot of money,” he said. “It''s not like we have hundreds of thousands of dollars of discretionary funds lying around in case a problem like that comes up.” Zon noted that his lab, which experienced an increase in the pace of discovery since Obama had signed his order, reverted to its Bush-era practices.On September 27 this year, a federal appeals court for the District of Columbia extended Lamberth''s stay to enable the government to pursue its appeal. The NIH was allowed to distribute US$78 million earmarked for 44 scientists during the appeal. The court said the matter should be expedited, but it could, over the years ahead, make its way to the US Supreme Court.The White House welcomed the decision of the appeals court in favour of the NIH. “President Obama made expansion of stem-cell research and the pursuit of groundbreaking treatments and cures a top priority when he took office. We''re heartened that the court will allow [the] NIH and their grantees to continue moving forward while the appeal is resolved,” said White House press secretary Robert Gibbs. The White House might have been glad of some good news, while it wrestles with the worst economic downturn since the Great Depression and the rise of the Tea Party movement.Even without a formal position on the matter, the Tea Party has had an impact on stem-cell research through its electoral victoriesTimothy Kamp, whose lab at the University of Wisconsin (Madison, WI, USA) researches embryonic stem-cell-derived cardiomyocytes, said that he finds the Tea Party movement confusing. “It''s hard for me to know what a uniform platform is for the Tea Party. I''ve heard a few comments from folks in the Tea Party who have opposed stem-cell research,” he said.However, the position of the Tea Party on the topic of stem-cell research could prove to be of vital importance. The Tea Party took its name from the Boston Tea Party—a famous protest in 1773 in which American colonists protested against the passing of the British Tea Act, for its attempt to extract yet more taxes from the new colony. Protesters dressed up as Native Americans and threw tea into the Boston harbour. Contemporary Tea Party members tend to have a longer list of complaints, but generally want to reduce the size of government and cut taxes. Their increasing popularity in the USA and the success of many Tea Party-backed Republican candidates for the upcoming congressional election could jeopardize Obama''s plans to pass new laws to regulate federal funding for stem-cell research.Even without a formal position on the matter, the Tea Party has had an impact on stem-cell research through its electoral victories. Perhaps their most high-profile candidate was the telegenic Christine O''Donnell, a Republican Senatorial candidate from Delaware. The Susan B. Anthony List, a pro-life women''s group, has described O''Donnell as one of “the brightest new stars” opposing abortion (www.lifenews.com/state5255.html). Although O''Donnell was eventually defeated in the 2 November congressional election, by winning the Republican primary in August, she knocked out nine-term Congressman and former Delaware governor Mike Castle, a moderate Republican known for his willingness to work with Democrats to pass legislation to protect stem-cell research.In the past, Castle and Diane DeGette, a Democratic representative from Colorado, co-sponsored the Stem Cell Research Advancement Act to expand federal funding of embryonic stem-cell research. They aimed to support Obama''s executive order and “ensure a lasting ethical framework overseeing stem cell research at the National Institutes of Health”.Morrison described Castle as “one of the great public servants in this country—no matter what political affiliation you have. For him to lose to somebody with such a chequered background and such shaky positions on things like evolution and other issues is a tragedy for the country.” Another stem-cell research advocate, Pennsylvania Senator Arlen Specter, a Republican-turned-Democrat, was also defeated in the primary. He had introduced legislation in September to codify Obama''s order. Specter, a cancer survivor, said his legislation is aimed at removing the “great uncertainty in the research community”.According to Sarah Binder, a political scientist at George Washington University in Washington, DC, the chances of passing legislation to codify the Obama executive order are decreasing: “As the Republican Party becomes more conservative and as moderates can''t get nominated in that party, it does lead you to wonder whether it''s possible to make anything happen [with the new Congress] in January.”There are a variety of opinions about how the outcome of the November elections will influence stem-cell policies. Binder said that a number of prominent Republicans have strongly promoted stem-cell research, including the Reagan family. “This hasn''t been a purely Democratic initiative,” she said. “The question is whether the Republican party has moved sufficiently to the right to preclude action on stem cells.” Historically there was “massive” Republican support for funding bills in 2006 and 2007 that were ultimately vetoed by Bush, she noted.…the debate about public funding for stem-cell research is only part of the picture, given the role of private business and states“Rightward shifts in the House and Senate do not bode well for legislative efforts to entrench federal support for stem-cell research,” Binder said. “First, if a large number of Republicans continue to oppose such funding, a conservative House majority is unlikely to pursue the issue. Second, Republican campaign commitments to reduce federal spending could hit the NIH and its support for stem-cell research hard.”Binder added that “a lingering unknown” is how the topic will be framed: “If it gets framed as a pro-choice versus pro-life initiative, that''s quite difficult for Congress to overcome in a bipartisan way. If it is framed as a question of medical research and medical breakthroughs and scientific advancement, it won''t fall purely on partisan lines. If members of Congress talk about their personal experiences, such as having a parent affected by Parkinson''s, then you could see even pro-life members voting in favour of a more expansive interpretation of stem-cell funding.”Johnson said that Congress could alter the wording of the Dickey-Wicker Amendment when passing the NIH budget for 2011 to remove the conflict. “You don''t have to get rid of the amendment completely, but you could rephrase it,” she said. She also commented that the public essentially supports embryonic stem-cell research. “The polls and surveys show the American public is morally behind there being some limited form of embryonic stem-cell research funded by federal money. They don''t favour cloning. There is not a huge amount of support for creating embryos from scratch for research. But there seems to be pretty wide support among the general public for the kind of embryonic stem-cell research that the NIH is currently funding.”In the end, however, the debate about public funding for stem-cell research is only part of the picture, given the role of private business and states. Glenn McGee, a professor at the Center for Practical Bioethics in Kansas City, MO, USA, and editor of the American Journal of Bioethics, commented that perhaps too much emphasis is being put on federal funding. He said that funding from states such as California and from industry—which are not restricted—has become a more important force than NIH funding. “We''re a little bit delusional if we think that this is a moment where the country is making a big decision about what''s going to happen with stem cells,” he said. “I think that ship has sailed.”     

A critique of 'countryside biogeography' as a guide to research in human‐dominated landscapes

Proliferation of redundant terms in ecology and conservation slows progress and creates confusion. ‘Countryside biogeography’ has been promoted as a new framework for conservation in production landscapes, so may offer a replacement for other concepts used by landscape ecologists. We conducted a systematic review to assess whether the 'countryside biogeography' concept provides a distinctive framing for conservation in human‐dominated landscapes relative to existing concepts. We reviewed 147 papers referring to countryside biogeography and 81 papers that did not. These papers were divided into categories representing three levels of use of countryside biogeography concepts (strong, weak, cited only) and two categories that did not use countryside biogeography at all but used similar concepts including fragmentation and matrix. We revealed few distinctions among groups of papers. Countryside biogeography papers made more frequent use of the terms 'ecosystem services', 'intensification' and 'land sparing' compared with non‐countryside biogeography papers. Papers that did not refer to countryside biogeography sampled production areas (e.g. farms) less often, and this related to their focus on habitat specialist species for which patch‐matrix assumptions were reasonable. Countryside biogeography offers a conceptual wrapper rather than a distinctive framework for advancing research in human‐modified landscapes. This and similar wrappers such as ‘conservation biogeography’ and ‘agricultural biogeography’ risk creating confusion among new researchers, and can prevent clear communication about research. To improve communication, we recommend using the suite of well‐established terms already applied to conservation in human‐modified landscapes rather than through an interceding conceptual wrapper.     

Recreation ecology research in East Asia's protected areas: Redefining impacts?

Recreation ecology, the scientific study of visitor impacts and their effective management, has been developed largely in North America, Europe, and more recently in Australia, in response to growing impacts of visitor use to protected area resources. A body of literature has been accumulated that contributes to sustainable visitor management in protected areas. This paper traces the development of recreation ecology research in East Asia and examines the field's relevance to East Asia's protected natural areas which endure both a long history of human utilisation and contemporary recreation and tourism pressure, much of which originates from surrounding densely populated urban areas. The formative, expanding and strengthening stages of recreation ecology research in this region were identified through an extensive review of literature published in English and East Asian languages. Each of these three developmental stages was illustrated with examples and compared with the general state of research during the same period. Key challenges and opportunities for future recreation ecology research in the region are discussed in light of this review.     

Perspectives on human stem cell research

Human stem cell research draws not only scientists' but the public's attention. Human stem cell research is considered to be able to identify the mechanism of human development and change the paradigm of medical practices. However, there are heated ethical and legal debates about human stem cell research. The core issue is that of human dignity and human life. Some prefer human adult stem cell research or iPS cell research, others hES cell research. We do not need to exclude any type of stem cell research because each has its own merits and issues, and they can facilitate the scientific revolution when working together. J. Cell. Physiol. 220: 535–537, 2009. © 2009 Wiley‐Liss, Inc.     

Physical enrichment research for captive fish: Time to focus on the DETAILS

Growing research effort has shown that physical enrichment (PE) can improve fish welfare and research validity. However, the inclusion of PE does not always result in positive effects and conflicting findings have highlighted the many nuances involved. Effects are known to depend on species and life stage tested, but effects may also vary with differences in the specific items used as enrichment between and within studies. Reporting fine-scale characteristics of items used as enrichment in studies may help to reveal these factors. We conducted a survey of PE-focused studies published in the last 5 years to examine the current state of methodological reporting. The survey results suggest that some aspects of enrichment are not adequately detailed. For example, the amount and dimensions of objects used as enrichment were frequently omitted. Similarly, the ecological relevance, or other justification, for enrichment items was frequently not made explicit. Focusing on ecologically relevant aspects of PE and increasing the level of detail reported in studies may benefit future work and we propose a framework with the acronym DETAILS ( D imensions, E cological rationale, T iming of enrichment, A mount, I nputs, L ighting and S ocial environment). We outline the potential importance of each of the elements of this framework with the hope it may aid in the level of reporting and standardization across studies, ultimately aiding the search for more beneficial types of PE and the development of our understanding and ability to improve the welfare of captive fish and promote more biologically relevant behaviour.     

Reforming the Department of Health's research and development policy: from the devil to the deep blue sea?

Research into health and social services in Britain is largely funded by the Department of Health. Regional NHS research and development has recently been reformed and a new report now proposes replacement of the 13 research units funded by the department with three or four large multidisciplinary centres. Evidence to support such a step is lacking, and many criticisms of the existing units arise from poor departmental planning rather than deficiencies of the units themselves. Large units may make research less responsive to the department''s needs, and it is essential that the proposed new structure is thoroughly evaluated before it is introduced.     

Centring individual animals to improve research and citation practices

Modern behavioural scientists have come to acknowledge that individual animals may respond differently to the same stimuli and that the quality of welfare and lived experience can affect behavioural responses. However, much of the foundational research in behavioural science lacked awareness of the effect of both welfare and individuality on data, bringing their results into question. This oversight is rarely addressed when citing seminal works as their findings are considered crucial to our understanding of animal behaviour. Furthermore, more recent research may reflect this lack of awareness by replication of earlier methods – exacerbating the problem. The purpose of this review is threefold. First, we critique seminal papers in animal behaviour as a model for re-examining past experiments, attending to gaps in knowledge or concern about how welfare may have affected results. Second, we propose a means to cite past and future research in a way that is transparent and conscious of the abovementioned problems. Third, we propose a method of transparent reporting for future behaviour research that (i) improves replicability, (ii) accounts for individuality of non-human participants, and (iii) considers the impact of the animals' welfare on the validity of the science. With this combined approach, we aim both to advance the conversation surrounding behaviour scholarship while also serving to drive open engagement in future science.     

Intraspecific variation in body size and sexual size dimorphism,and a test of Rensch's rule in bats

The magnitude and direction of sexual size dimorphism (SSD) may vary considerably within and among taxa, and the primary causes of such variation have not been thoroughly elucidated. For example, the effect of abiotic factors is frequently attributed to explain intra‐ and interspecific variation in SSD. Rensch's rule, which states that males vary more in size than females when body size increases, has rarely been tested in bats. Therefore, whether bats follow Rensch's rule remains unclear, particularly when females are larger than males. We investigated whether four bat species presented SSD, as well as whether their body sizes varied within each sex across localities, testing the hypothesis that intraspecific SSD varies substantially depending of sampling localities. We finally examined whether bats followed Rensch's rule by simultaneously using intraspecific and interspecific approaches. Although SSD was not observed for most bat species within each locality, the females of three of the four captured species exhibited differences in body size between particular localities. Usually the females varied more in size than did males across localities, mostly exhibiting a female‐biased SSD. Significant differences in SSD were observed (i.e. mean values of the sexual dimorphism index), even though Rensch's rule was not followed.     

The academic birth rate. Production and reproduction of the research work force, and its effect on innovation and research misconduct

Universities have been churning out PhD students to reap financial and other rewards for training biomedical scientists. This deluge of cheap labour has created unhealthy competition, which encourages scientific misconduct.Most developed nations invest a considerable amount of public money in scientific research for a variety of reasons: most importantly because research is regarded as a motor for economic progress and development, and to train a research workforce for both academia and industry. Not surprisingly, governments are occasionally confronted with questions about whether the money invested in research is appropriate and whether taxpayers are getting the maximum value for their investments.…questions about the size and composition of the research workforce have historically been driven by concerns that the system produces an insufficient number of scientistsThe training and maintenance of the research workforce is a large component of these investments. Yet discussions in the USA about the appropriate size of this workforce have typically been contentious, owing to an apparent lack of reliable data to tell us whether the system yields academic ‘reproduction rates'' that are above, below or at replacement levels. In the USA, questions about the size and composition of the research workforce have historically been driven by concerns that the system produces an insufficient number of scientists. As Donald Kennedy, then Editor-in-Chief of Science, noted several years ago, leaders in prestigious academic institutions have repeatedly rung alarm bells about shortages in the science workforce. Less often does one see questions raised about whether too many scientists are being produced or concerns about unintended consequences that may result from such overproduction. Yet recognizing that resources are finite, it seems reasonable to ask what level of competition for resources is productive, and at what level does competition become counter-productive.Finding a proper balance between the size of the research workforce and the resources available to sustain it has other important implications. Unhealthy competition—too many people clamouring for too little money and too few desirable positions—creates its own problems, most notably research misconduct and lower-quality, less innovative research. If an increasing number of scientists are scrambling for jobs and resources, some might begin to cut corners in order to gain a competitive edge. Moreover, many in the science community worry that every publicized case of research misconduct could jeopardize those resources, if politicians and taxpayers become unwilling to invest in a research system that seems to be riddled with fraud and misconduct.The biomedical research enterprise in the USA provides a useful context in which to examine the level of competition for resources among academic scientists. My thesis is that the system of publicly funded research in the USA as it is currently configured supports a feedback system of institutional incentives that generate excessive competition for resources in biomedical research. These institutional incentives encourage universities to overproduce graduate students and postdoctoral scientists, who are both trainees and a cheap source of skilled labour for research while in training. However, once they have completed their training, they become competitors for money and positions, thereby exacerbating competitive pressures.Questions raised about whether too many scientists are being produced or concerns about the unintended consequences of such overproduction are less commonThe resulting scarcity of resources, partly through its effect on peer review, leads to a shunting of resources away from both younger researchers and the most innovative ideas, which undermines the effectiveness of the research enterprise as a whole. Faced with an increasing number of grant applications and the consequent decrease in the percentage of projects that can be funded, reviewers tend to ‘play it safe'' and favour projects that have a higher likelihood of yielding results, even if the research is conservative in the sense that it does not explore new questions. Resource scarcity can also introduce unwanted randomness to the process of determining which research gets funded. A large group of scientists, led by a cancer biologist, has recently mounted a campaign against a change in a policy of the National Institutes of Health (NIH) to allow only one resubmission of an unfunded grant proposal (Wadman, 2011). The core of their argument is that peer reviewers are likely able to distinguish the top 20% of research applications from the rest, but that within that top 20%, distinguishing the top 5% or 10% means asking peer reviewers for a level of precision that is simply not possible. With funding levels in many NIH institutes now within that 5–10% range, the argument is that reviewers are being forced to choose at random which excellent applications do and do not get funding. In addition to the inefficiency of overproduction and excessive competition in terms of their costs to society and opportunity costs to individuals, these institutional incentives might undermine the integrity and quality of science, and reduce the likelihood of breakthroughs.My colleagues and I have expressed such concerns about workforce dynamics and related issues in several publications (Martinson, 2007; Martinson et al, 2005, 2006, 2009, 2010). Early on, we observed that, “missing from current analyses of scientific integrity is a consideration of the wider research environment, including institutional and systemic structures” (Martinson et al, 2005). Our more recent publications have been more specific about the institutional and systemic structures concerned. It seems that at least a few important leaders in science share these concerns.In April 2009, the NIH, through the National Institute of General Medical Sciences (NIGMS), issued a request for applications (RFA) calling for proposals to develop computational models of the research workforce (http://grants.nih.gov/grants/guide/rfa-files/RFA-GM-10-003.html). Although such an initiative might be premature given the current level of knowledge, the rationale behind the RFA seems irrefutable: “there is a need to […] pursue a systems-based approach to the study of scientific workforce dynamics.” Roughly four decades after the NIH appeared on the scene, this is, to my knowledge, the first official, public recognition that the biomedical workforce tends not to conform nicely to market forces of supply and demand, despite the fact that others have previously made such arguments.Early last year, Francis Collins, Director of the NIH, published a PolicyForum article in Science, voicing many of the concerns I have expressed about specific influences that have led to growth rates in the science workforce that are undermining the effectiveness of research in general, and biomedical research in particular. He notes the increasing stress in the biomedical research community after the end of the NIH “budget doubling” between 1998 and 2003, and the likelihood of further disruptions when the American Recovery and Reinvestment Act of 2009 (ARRA) funding ends in 2011. Arguing that innovation is crucial to the future success of biomedical research, he notes the tendency towards conservatism of the NIH peer-review process, and how this worsens in fiscally tight times. Collins further highlights the ageing of the NIH workforce—as grants increasingly go to older scientists—and the increasing time that researchers are spending in itinerant and low-paid postdoctoral positions as they stack up in a holding pattern, waiting for faculty positions that may or may not materialize. Having noted these challenging trends, and echoing the central concerns of a 2007 Nature commentary (Martinson, 2007), he concludes that “…it is time for NIH to develop better models to guide decisions about the optimum size and nature of the US workforce for biomedical research. A related issue that needs attention, though it will be controversial, is whether institutional incentives in the current system that encourage faculty to obtain up to 100% of their salary from grants are the best way to encourage productivity.”Similarly, Bruce Alberts, Editor-in-Chief of Science, writing about incentives for innovation, notes that the US biomedical research enterprise includes more than 100,000 graduate students and postdoctoral fellows. He observes that “only a select few will go on to become independent research scientists in academia”, and argues that “assuming that the system supporting this career path works well, these will be the individuals with the most talent and interest in such an endeavor” (Alberts, 2009).His editorial is not concerned with what happens to the remaining majority, but argues that even among the select few who manage to succeed, the funding process for biomedical research “forces them to avoid risk-taking and innovation”. The primary culprit, in his estimation, is the conservatism of the traditional peer-review system for federal grants, which values “research projects that are almost certain to ‘work''”. He continues, “the innovation that is essential for keeping science exciting and productive is replaced by […] research that has little chance of producing the breakthroughs needed to improve human health.”If an increasing number of scientists are scrambling for jobs and resources, some might begin to cut corners in order to gain a competitive edgeAlthough I believe his assessment of the symptoms is correct, I think he has misdiagnosed the cause, in part because he has failed to identify which influence he is concerned with from the network of influences in biomedical research. To contextualize the influences of concern to Alberts, we must consider the remaining majority of doctorally trained individuals so easily dismissed in his editorial, and further examine what drives the dynamics of the biomedical research workforce.Labour economists might argue that market forces will always balance the number of individuals with doctorates with the number of appropriate jobs for them in the long term. Such arguments would ignore, however, the typical information asymmetry between incoming graduate students, whose knowledge about their eventual job opportunities and career options is by definition far more limited than that of those who run the training programmes. They would also ignore the fact that universities are generally not confronted with the externalities resulting from overproduction of PhDs, and have positive financial incentives that encourage overproduction. During the past 40 years, NIH ‘extramural'' funding has become crucial for graduate student training, faculty salaries and university overheads. For their part, universities have embraced NIH extramural funding as a primary revenue source that, for a time, allowed them to implement a business model based on the interconnected assumptions that, as one of the primary ‘outputs'' or ‘products'' of the university, more doctorally trained individuals are always better than fewer, and because these individuals are an excellent source of cheap, skilled labour during their training, they help to contain the real costs of faculty research.“…the current system has succeeded in maximizing the amount of research […] it has also degraded the quality of graduate training and led to an overproduction of PhDs…”However, it has also made universities increasingly dependent on NIH funding. As recently documented by the economist Paula Stephan, most faculty growth in graduate school programmes during the past decade has occurred in medical colleges, with the majority—more than 70%—in non-tenure-track positions. Arguably, this represents a shift of risk away from universities and onto their faculty. Despite perennial cries of concern about shortages in the research workforce (Butz et al, 2003; Kennedy et al, 2004; National Academy of Sciences et al, 2005) a number of commentators have recently expressed concerns that the current system of academic research might be overbuilt (Cech, 2005; Heinig et al, 2007; Martinson, 2007; Stephan, 2007). Some explicitly connect this to structural arrangements between the universities and NIH funding (Cech, 2005; Collins, 2007; Martinson, 2007; Stephan, 2007).In 1995, David Korn pointed out what he saw as some problematic aspects of the business model employed by Academic Medical Centers (AMCs) in the USA during the past few decades (Korn, 1995). He noted the reliance of AMCs on the relatively low-cost, but highly skilled labour represented by postdoctoral fellows, graduate students and others—who quickly start to compete with their own professors and mentors for resources. Having identified the economic dependence of the AMCs on these inexpensive labour pools, he noted additional problems with the graduate training programmes themselves. “These programs are […] imbued with a value system that clearly indicates to all participants that true success is only marked by the attainment of a faculty position in a high-profile research institution and the coveted status of principal investigator on NIH grants.” Pointing to “more than 10 years of severe supply/demand imbalance in NIH funds”, Korn concluded that, “considering the generative nature of each faculty mentor, this enterprise could only sustain itself in an inflationary environment, in which the society''s investment in biomedical research and clinical care was continuously and sharply expanding.” From 1994 to 2003, total funding for biomedical research in the USA increased at an annual rate of 7.8%, after adjustment for inflation. The comparable rate of growth between 2003 and 2007 was 3.4% (Dorsey et al, 2010). These observations resonate with the now classic observation by Derek J. de Solla Price, from more than 30 years before, that growth in science frequently follows an exponential pattern that cannot continue indefinitely; the enterprise must eventually come to a plateau (de Solla Price, 1963).In May 2009, echoing some of Korn''s observations, Nobel laureate Roald Hoffmann caused a stir in the US science community when he argued for a “de-coupling” of the dual roles of graduate students as trainees and cheap labour (Hoffmann, 2009). His suggestion was to cease supporting graduate students with faculty research grants, and to use the money instead to create competitive awards for which graduate students could apply, making them more similar to free agents. During the ensuing discussion, Shirley Tilghman, president of Princeton University, argued that “although the current system has succeeded in maximizing the amount of research performed […] it has also degraded the quality of graduate training and led to an overproduction of PhDs in some areas. Unhitching training from research grants would be a much-needed form of professional ‘birth control''” (Mervis, 2009).The greying of the NIH research workforce is another important driver of workforce dynamics, and it is integrally linked to the fate of young scientistsAlthough the issue of what I will call the ‘academic birth rate'' is the central concern of this analysis, the ‘academic end-of-life'' also warrants some attention. The greying of the NIH research workforce is another important driver of workforce dynamics, and it is integrally linked to the fate of young scientists. A 2008 news item in Science quoted then 70-year-old Robert Wells, a molecular geneticist at Texas A&M University, “‘if I and other old birds continue to land the grants, the [young scientists] are not going to get them.” He worries that the budget will not be able to support “the 100 people ‘I''ve trained […] to replace me''” (Kaiser, 2008). While his claim of 100 trainees might be astonishing, it might be more astonishing that his was the outlying perspective. The majority of senior scientists interviewed for that article voiced intentions to keep doing science—and going after NIH grants—until someone forced them to stop or they died.Some have looked at the current situation with concern, primarily because of the threats it poses to the financial and academic viability of universities (Korn, 1995; Heinig et al, 2007; Korn & Heinig, 2007), although most of those who express such concerns have been distinctly reticent to acknowledge the role of universities in creating and maintaining the situation. Others have expressed concerns about the differential impact of extreme competition and meagre job prospects on the recruitment, development and career survival of young and aspiring scientists (Freeman et al, 2001; Kennedy et al, 2004; Martinson et al, 2006; Anderson et al, 2007a; Martinson, 2007; Stephan, 2007). There seems to be little disagreement, however, that the system has generated excessively high competition for federal research funding, and that this threatens to undermine the very innovation and production of knowledge that is its raison d''etre.The production of knowledge in science, particularly of the ‘revolutionary'' variety, is generally not a linear input–output process with predictable returns on investment, clear timelines and high levels of certainty (Lane, 2009). On the contrary, it is arguable that “revolutionary science is a high risk and long-term endeavour which usually fails” (Charlton & Andras, 2008). Predicting where, when and by whom breakthroughs in understanding will be produced has proven to be an extremely difficult task. In the face of such uncertainty, and denying the realities of finite resources, some have argued that the best bet is to maximize the number of scientists, using that logic to justify a steady-state production of new PhDs, regardless of whether the labour market is sending signals of increasing or decreasing demand for that supply. Only recently have we begun to explore the effects of the current arrangement on the process of knowledge production, and on innovation in particular (Charlton & Andras, 2008; Kolata, 2009).…most of those who express such concerns have been reticent to acknowledge the role of universities themselves in creating and maintaining the situationBruce Alberts, in the above-mentioned editorial, points to several initiatives launched by the NIH that aim to get a larger share of NIH funding into the hands of young scientists with particularly innovative ideas. These include the “New Innovator Award,” the “Pioneer Award” and the “Transformational R01 Awards”. The proportion of NIH funding dedicated to these awards, however, amounts to “only 0.27% of the NIH budget” (Alberts, 2009). Such a small proportion of the NIH budget does not seem likely to generate a large amount of more innovative science. Moreover, to the extent that such initiatives actually succeed in enticing more young investigators to become dependent on NIH funds, any benefit these efforts have in terms of innovation may be offset by further increases in competition for resources that will come when these new ‘innovators'' reach the end of this specialty funding and add to the rank and file of those scrapping for funds through the standard mechanisms.Our studies on research integrity have been mostly oriented towards understanding how the influences within which academic scientists work might affect their behaviour, and thus the quality of the science they produce (Anderson et al, 2007a, 2007b; Martinson et al, 2009, 2010). My colleagues and I have focused on whether biomedical researchers perceive fairness in the various exchange relationships within their work systems. I am persuaded by the argument that expectations of fairness in exchange relationships have been hard-wired into us through evolution (Crockett et al, 2008; Hsu et al, 2008; Izuma et al, 2008; Pennisi, 2009), with the advent of modern markets being a primary manifestation of this. Thus, violations of these expectations strike me as potentially corrupting influences. Such violations might be prime motivators for ill will, possibly engendering bad-faith behaviour among those who perceive themselves to have been slighted, and therefore increasing the risk of research misconduct. They might also corrupt the enterprise by signalling to talented young people that biomedical research is an inhospitable environment in which to develop a career, possibly chasing away some of the most talented individuals, and encouraging a selection of characteristics that might not lead to optimal effectiveness, in terms of scientific innovation and productivity (Charlton, 2009).To the extent that we have an ecology with steep competition that is fraught with high risks of career failure for young scientists after they incur large costs of time, effort and sometimes financial resources to obtain a doctoral degree, why would we expect them to take on the additional, substantial risks involved in doing truly innovative science and asking risky research questions? And why, in such a cut-throat setting, would we not anticipate an increase in corner-cutting, and a corrosion of good scientific practice, collegiality, mentoring and sociability? Would we not also expect a reduction in high-risk, innovative science, and a reversion to a more career-safe type of ‘normal'' science? Would this not reduce the effectiveness of the institution of biomedical research? I do not claim to know the conditions needed to maximize the production of research that is novel, innovative and conducted with integrity. I am fairly certain, however, that putting scientists in tenuous positions in which their careers and livelihoods would be put at risk by pursuing truly revolutionary research is one way to insure against it.