To Crowdfund Research,Scientists Must Build an Audience for Their Work

As rates of traditional sources of scientific funding decline, scientists have become increasingly interested in crowdfunding as a means of bringing in new money for research. In fields where crowdfunding has become a major venue for fundraising such as the arts and technology, building an audience for one''s work is key for successful crowdfunding. For science, to what extent does audience building, via engagement and outreach, increase a scientist''s abilities to bring in money via crowdfunding? Here we report on an analysis of the #SciFund Challenge, a crowdfunding experiment in which 159 scientists attempted to crowdfund their research. Using data gathered from a survey of participants, internet metrics, and logs of project donations, we find that public engagement is the key to crowdfunding success. Building an audience or “fanbase” and actively engaging with that audience as well as seeking to broaden the reach of one''s audience indirectly increases levels of funding. Audience size and effort interact to bring in more people to view a scientist''s project proposal, leading to funding. We discuss how projects capable of raising levels of funds commensurate with traditional funding agencies will need to incorporate direct involvement of the public with science. We suggest that if scientists and research institutions wish to tap this new source of funds, they will need to encourage and reward activities that allow scientists to engage with the public.     

Funding resources for rare disease research

Research is an expensive venture requiring multiple sources of funding for small projects that test new theories, large projects to make major advancements, training the next generation of researchers and facilitating meetings to share findings and support collaboration. For rare conditions, such as Batten disease, research funds can be difficult to find.To see how investigators supported their work in the past, we did a key word search of the Acknowledgement Section of peer-reviewed literature published in Batten disease in the last 6.5 years. Interestingly, we discovered 193 separate funding sources. The authors hope that, by showing where funds are available, we will enable Batten disease researchers to continue their pursuits and expand their studies; moving key findings from discovery to application phases. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease.     

Focus: Rare Disease: Patients as Partners in Rare Disease Diagnosis and Research

There is great value in understanding the patient perspective in rare disease diagnosis and research, and in partnering actively with patients and their families throughout the process. Meaningful and respectful interaction between patients and researchers leads to learning on both sides, and ultimately, to better research outcomes. Researchers can help patients understand how research is conducted and what the latest advances and perceived gaps in research are, and patients, who have direct experience living with their health conditions, can impart to researchers what is most important to them. We describe our engagement with patients in the Undiagnosed Diseases Network (UDN) program, as well as the lessons we have learned to date. In the UDN, patients have been instrumental in bringing meaning to the work of clinicians and researchers, building patient communities, making the network aware of unmet patient needs, advocating for additional research funding, and disseminating UDN research findings. Although patient engagement in the UDN has already had a significant positive impact on our work, we continue to strive to involve patients earlier in the process, in the research design itself, and in addressing power dynamics that may arise between clinicians, researchers, and patients.     

Tapping the crowds for research funding

Scientists are exploring crowdfunding as a potential new source of cash for their research.One day early in 2011, Jarrett Byrnes and Jai Ranganathan, both ecologists at the National Center for Ecological Analysis and Synthesis, Santa Barbara, CA, USA, had a great idea about an alternative way to fund research projects. Byrnes was sitting in his office when Ranganathan came in to tell him about a proposal he had seen on the crowdfunding website Kickstarter (www.kickstarter.com) to erect in Detroit a statue of RoboCop, the robot-human hero of a US science fiction action film. “The RoboCop project seemed a little esoteric, but the proposers had done a fabulous job at communicating why it was both interesting and important,” Byrnes said. It took the internet by storm and raised more than US$65,000 from almost 3,000 backers.If this could be done for RoboCop, Byrnes and Ranganathan wondered whether it could be done for science as well. They asked friends and fellow scientists whether they would be interested in crowdfunding a research project and, after receiving substantial positive feedback, launched #SciFund Challenge in November 2011 with 59 research proposals. #SciFund Challenge helps researchers put together a crowdfunding proposal, supports their outreach activities and launches coordinated campaigns on the crowdfunding website of their partner RocketHub (www.rockethub.com). “We thought we would do it all at the same time so we could help each other out,” explained Byrnes, who is now chief networking officer for #SciFund Challenge.Crowdfunding is the practice of funding a project by raising many small contributions from a large number of individuals, typically via the internet. An artist, film-maker or musician would put together an online profile of their project and choose a platform such as Kickstarter, RocketHub or Indiegogo for its presentation. If people like the project, they can pledge money to it. Backers are usually charged only if the project succeeds in reaching its funding goal before the deadline. Kickstarter is one of the largest crowdfunding portals and focuses on creative projects; in 2012, more than 2 million backers pledged more than US$320 million to Kickstarter projects (http://www.kickstarter.com/year/2012?ref=what_is_kickstarter#overall_stats).Creative projects always work towards a concrete product—an exhibition, a DVD or a computer game—which is not necessarily the case for science, particularly basic researchThe challenge for Byrnes and others is whether crowdfunding works for science. Creative projects always work towards a concrete product—an exhibition, a DVD or a computer game—which is not necessarily the case for science, particularly basic research. Would people donate money for the pursuit of knowledge? In a time of economic crisis and budget cuts, many scientists are eager to give it a try. Crowdfunding of science has exploded in recent years, with funding goals becoming increasingly ambitious; some projects have attracted US$10,000–20,000 or even more. New platforms, such as Petridish, FundaGeek or Microryza, specifically cater to research projects [1]. The academic system is starting to adapt too: the University of California, San Francisco, CA, USA, has made a deal with the crowdfunding site Indiegogo that allows backers to make money donated via the site tax deductible [2].Kristina Killgrove, now assistant professor in the department of anthropology, University of West Florida, USA, became interested in crowdfunding when traditional ways of funding research were not available to her. “At the time, I did not have a permanent faculty job. I was an adjunct instructor, with a contract for only one semester, so there was no good way for me to apply for a grant through regular channels, like our National Science Foundation,” she explained. Her proposal to study the DNA of ancient Roman skeletons to learn more about the geographical origins and heritage of the lower classes and slaves in the Roman Empire was part of the first round of #SciFund Challenge projects and attracted donors interested in ancient Rome and in DNA analysis. She exceeded her financial target of $6,000 in less than 2 weeks and eventually raised more than $10,000 from 170 funders.Ethan Perlstein had also reached an academic deadlock when he first turned to crowdfunding. His independent postdoctoral fellowship at Princeton University, USA, came to an end in late 2012 and his future was unclear. Grants for basic research came in his experience from the government or foundations, and he had never questioned that premise. “But as I felt my own existential crisis emerging—I might not get an academic job—I started to think about crowdfunding more seriously. I searched for other scientists who had tried it,” Perlstein said.“It is time to experiment with the way we experiment,” Perlstein''s crowdfunding video proclaims. Indeed, he approached crowdfunding in a scientific way. He analysed various successful projects in search for some general principles. “I wanted a protocol,” he said. “I wanted to do as much as I could beforehand to increase the likelihood of success.” Together with his colleagues, David Sulzer, professor in the departments of neurology and psychiatry at Columbia Medical School, New York, NY, USA, and lead experimentalist Daniel Korostyshevsky, he asked for $25,000 to study the distribution of amphetamines within mouse brain cells to elucidate the mechanism by which these drugs increase dopamine levels at synapses. The crowdfunding experiment worked and their project was fully funded.Creation of a good website with a convincing video is a crucial step towards success. “When crafting your project, it is important to try to put yourselves in the shoes of the audience,” recommended Cindy Wu, who founded San-Francisco-based science crowdfunding company, Microryza, with Denny Luan when they were in graduate school. “You as a scientist find your work absolutely fascinating. Communicating this passion to a broader audience is absolutely key,” said Byrnes. However, recruitment of people to the website is at least as important as the site itself. Many successful crowdfunders build their campaign on existing social networks to channel potential funders to their own website [3]. “Building an audience for your work, having people aware of you and what you are doing, is of paramount importance,” Byrnes explained, and added that crowdfunding can be as time consuming as grant applications. “But it''s a different kind of time. I find it actually quite satisfying,” he said.“Be scientific about it,” Perlstein advised. How many donors are needed to reach a funding goal? How many page views would be required accordingly, assuming a certain conversion rate? “If you approach a crowdfunding campaign methodically, it doesn''t guarantee success, but at least you implement best practices.” Perlstein is now an independent scientist renting laboratory space from the Molecular Sciences Institute, a non-profit research facility in Berkeley, CA, USA. “Academia and I were in a long-term relationship for over a decade but we broke up,” he explained. With federal and state funding flat or on a downwards trend, he sees his future in fundraising from patrons, venture philanthropists or disease foundations in addition to crowdfunding. Yet Perlstein remains an exception. Most scientists do not use crowdfunding as an alternative to normal funding opportunities, but rather as a supplement. A typical crowdfunding project nowadays would raise a few thousand dollars, which is enough to fund a student''s work for a summer or to buy some equipment [3].A typical crowdfunding project nowadays would raise a few thousand dollars, which is enough to fund a student''s work for a summer or to buy some equipmentCrowdfunding is also ideal to get new ideas off the ground, which was a key incentive to found Microryza. Cindy Wu''s experience with the academic funding system in graduate school taught her how difficult it was to get small grants for seed ideas. Together with her colleague Denny Luan she interviewed 100 scientists on the topic. “Every single person said there is always a seed idea they want to work on but it is difficult to get funding for early stage research,” she said. The two students concluded that crowdfunding would be able to fill that gap and a few months later set up Microryza. “Crowdfunding is a fantastic way to begin a project and collect preliminary data on something that might be a little risky but very exciting,” Byrnes said. “When you then write up a proposal for a larger governmentally funded grant you have evidence that you are doing outreach work and that you are bringing the results of your work to a broader audience.”Crowdfunded projects cover a wide range of research from ecology, medicine, physics and chemistry to engineering and economics. Some projects are pure basic science, such as investigating polo kinase in yeast (http://www.rockethub.com/projects/3753-cancer-yeast-has-answers), whereas others are applied, for instance developing a new method to clean up ocean oil spills (http://www.kickstarter.com/projects/cesarminoru/protei-open-hardware-oil-spill-cleaning-sailing-ro). Project creators may be students, professors or independent scientists, and research is carried out in universities, companies or hired laboratory space or outsourced to core facilities. Some projects aim to touch people''s heartstrings, such as saving butterflies (http://www.rockethub.com/projects/11903did-you-know-butterflies-have-std) and others address politically relevant topics, such as gun policy and safety (https://www.microryza.com/projects/gun-control-research-project).Some proposals have immediate relevance, such as the excavation of a triceratops skeleton to display it in the Seattle museum (https://www.microryza.com/projects/bring-a-triceratops-to-seattle). Backers can follow the project and see that the promise has been kept. For many projects in basic research, however, progress is much more abstract even if there are long-term goals, such as a cure for cancer, conservation strategies to save butterflies or so on. But will a non-scientist be able to evaluate the relevance of a particular project for such long-term goals? Will interested donors be able to judge whether these goals are within reach? Indeed, science crowdfunding has drawn criticism for its lack of peer review and has been accused of pushing scientists into overselling their research [1,4,5]. “There is a risk that it provides opportunities for scientists who are less than scrupulous to deceive the general public,” commented Stephen Curry, professor of structural biology at Imperial College, London, UK.…science crowdfunding has drawn criticism for its lack of peer review and has been accused of pushing scientists into overselling their researchMany scientific crowdfunding sites have systems in place to check the credibility of research proposals. “At #SciFund Challenge we have what we like to call a gentle peer review. If an undergraduate is promising to overthrow they theory of gravity we will have some questions about that,” explained Byrnes. Microryza would also not let any project pass. The team checks the proposal creator''s identity and evaluates whether the proposal addresses a scientific question and the project goals are within the capabilities of the researcher. “We plan to have some sort of crowd-sourced peer review sometime in the future,” said Wu. Other platforms, such as FundaGeek, have discussion forums where potential donors are encouraged to debate the merits of a proposal. As crowdfunding does not involve spending large amounts of public money, it might be an ideal way to try out new forms of peer review. According to Curry, however, there are important aspects of academic peer review that cannot be provided by these systems. “The advantage of grant committees considering many applications in competition with one another is that it allows the best ones to be selected. Details of prior work and expected feasibility are necessary to judge a project,” he said.Crowdfunding is selling science to the crowd, and, just like in any outreach activity, there might be cases of conveying projects too optimistically or overstating their impact. Yet, a main advantage of crowdfunding is that it allows donors to stay involved in projects and that it encourages direct interaction between scientists and non-scientists [3]. If a crowdfunding project does not live up to its promises, the donors will find out. “Microryza is really about sharing the discovery process directly with the donors,” Wu explained. “Every time something happens in the lab scientists post an update and an email goes out to all donors.” Perlstein also maintains close contact with his backers, having met many of them in person. “If we accept their money we are going to give them front row seats to the science,” he said. Research is a labour-intensive, slow process that includes technical difficulties and reconsideration of hypotheses, a fact that might come as a surprise to non-scientists. “We are actually doing a service here to enlighten the non-scientists that this is the rhythm of basic science,” said Perlstein.Crowdfunding of science has exploded in recent years, with funding goals becoming increasingly ambitious; some projects have attracted US$10,000–20,000 or even moreCrowdfunding is by no means a gold mine, with most research projects raising only a few thousand dollars. Byrnes, however, is optimistic that it will grow and inspire a larger crowd to get involved. “Now you see $10 million projects in gaming technology and the arts. That took some years to happen. We will get there, but we still have a lot to learn. I think science crowdfunding is still in the early growth phase,” he said. As crowdfunding increases, scientists will find themselves confronted with some questions. The open sharing of the scientific process with a broader public is a key aspect of crowdfunded projects. In many cases, scientists make the primary record of a research project publicly available. What does this entail when it comes to publications or patents? “Most journals don''t have a policy on open notebooks,” acknowledged Wu. Filing of patents could also become difficult if scientists have already made all their work and results public.Crowdfunding also enables projects to be undertaken outside the academic system where rules and regulations are less well defined. uBiome, a citizen science start-up, draws on crowds not only for funding but also for providing data. The company collected more than US$300,000 through Indiegogo to sequence the microbiome of its donors (http://www.indiegogo.com/projects/ubiome-sequencing-your-microbiome). Whereas academic biomedical research involving humans has to be reviewed by an independent ethics committee, this requirement would not apply to the uBiome project. “[P]rojects that don''t want federal money, FDA approval, or to publish in traditional journals require no ethical review at all as far as we know,” Jessica Richman and Zachary Apte, cofounders of uBiome, wrote in an invited guest blog on Scientific American (http://blogs.scientificamerican.com/guest-blog/2013/07/22/crowdfunding-and-irbs-the-case-of-ubiome/). The researchers worked with an independent institutional review board to provide ethics oversight. Some crowdfunding websites, such as Microryza, make sure their researchers have approval from an institutional review board. Greater consistency is needed, however, to ensure that research is carried out according to ethics standards.Crowdfunding is not going to substitute public funding … rather, it would coexist as a more democratic form of philanthropyCrowdfunding is not a one-size-fits-all revenue stream for science. It might be easier to get support for ‘catchy'' topics than for investigation of molecular interactions or protein structures. Crowdfunding is not going to substitute public funding either; rather, it would coexist as a more democratic form of philanthropy. But for those who embrace it, crowdfunding can be a rewarding experience. “I had a lot of fun being part of #SciFund—I got to meet a lot of other interesting scientists, I raised some money, and I learned a bit about working with journalists and science writers to get my ideas and results disseminated to the public,” Killgrove said. Crowdfunding provides an opportunity for public engagement, raises public awareness, and gives scientists an incentive to communicate their research to a broader public. “In many cases, scientists do not receive any real incentive for doing outreach work” Byrnes said. “Crowdfunding can be seen as a means to reward them for their effort.”     

A Guide to Scientific Crowdfunding

Crowdfunding represents an attractive new option for funding research projects, especially for students and early-career scientists or in the absence of governmental aid in some countries. The number of successful science-related crowdfunding campaigns is growing, which demonstrates the public’s willingness to support and participate in scientific projects. Putting together a crowdfunding campaign is not trivial, however, so here is a guide to help you make yours a success.     

Focus: Personalized Medicine: Taking Control of Castleman Disease: Leveraging Precision Medicine Technologies to Accelerate Rare Disease Research

Castleman disease (CD) is a rare and heterogeneous disorder characterized by lymphadenopathy that may occur in a single lymph node (unicentric) or multiple lymph nodes (multicentric), the latter typically occurring secondary to excessive proinflammatory hypercytokinemia. While a cohort of multicentric Castleman disease (MCD) cases are caused by Human Herpes Virus-8 (HHV-8), the etiology of HHV-8 negative, idiopathic MCD (iMCD), remains unknown. Breakthroughs in “omics” technologies that have facilitated the development of precision medicine hold promise for elucidating disease pathogenesis and identifying novel therapies for iMCD. However, in order to leverage precision medicine approaches in rare diseases like CD, stakeholders need to overcome several challenges. To address these challenges, the Castleman Disease Collaborative Network (CDCN) was founded in 2012. In the past 3 years, the CDCN has worked to transform the understanding of the pathogenesis of CD, funded and initiated genomics and proteomics research, and united international experts in a collaborative effort to accelerate progress for CD patients. The CDCN’s collaborative structure leverages the tools of precision medicine and serves as a model for both scientific discovery and advancing patient care.     

Medical crowdfunding and the virtuous donor

Patients and families are increasingly turning to crowdfunding to help them cover the cost of medical care. The ethics of crowdfunding has garnered some attention in the bioethical literature. In this paper I examine an ethical aspect of medical crowdfunding (MCF) that has received limited attention: the role of donors. I defend a virtue ethical approach to analyzing the role of donors in MCF. Vicious donation, where donors do not exercise the relevant virtues, can compound some of the ethical risks associated with MCF, as seen in the several recent, high‐profile cases. My primary contention in this paper is that encouraging donors to think about how donating to a particular campaign would measure against the virtues I outline could help to discourage acts of ethically problematic donation to MCF campaigns.     

Towards efficiency in rare disease research: what is distinctive and important?

Characterized by their low prevalence, rare diseases are often chronically debilitating or life threatening. Despite their low prevalence, the aggregate number of individuals suffering from a rare disease is estimated to be nearly 400 million worldwide.Over the past decades, efforts from researchers, clinicians, and pharmaceutical industries have been focused on both the diagnosis and therapy of rare diseases. However, because of the lack of data and medical records for individual rare diseases and the high cost of orphan drug development, only limited progress has been achieved. In recent years, the rapid development of next-generation sequencing(NGS)-based technologies, as well as the popularity of precision medicine has facilitated a better understanding of rare diseases and their molecular etiology. As a result, molecular subclassification can be identified within each disease more clearly, significantly improving diagnostic accuracy. However, providing appropriate care for patients with rare diseases is still an enormous challenge. In this review, we provide a brief introduction to the challenges of rare disease research and make suggestions on where and how our efforts should be focused.     

Focus: Personalized Medicine: Value of Organoids from Comparative Epithelia Models

Organoids have tremendous therapeutic potential. They were recently defined as a collection of organ-specific cell types, which self-organize through cell-sorting, develop from stem cells, and perform an organ specific function. The ability to study organoid development and growth in culture and manipulate their genetic makeup makes them particularly suitable for studying development, disease, and drug efficacy. Organoids show great promise in personalized medicine. From a single patient biopsy, investigators can make hundreds of organoids with the genetic landscape of the patient of origin. This genetic similarity makes organoids an ideal system in which to test drug efficacy. While many investigators assume human organoids are the ultimate model system, we believe that the generation of epithelial organoids of comparative model organisms has great potential. Many key transport discoveries were made using marine organisms. In this paper, we describe how deriving organoids from the spiny dogfish shark, zebrafish, and killifish can contribute to the fields of comparative biology and disease modeling with future prospects for personalized medicine.     

Big Science vs. Little Science: How Scientific Impact Scales with Funding

Agencies that fund scientific research must choose: is it more effective to give large grants to a few elite researchers, or small grants to many researchers? Large grants would be more effective only if scientific impact increases as an accelerating function of grant size. Here, we examine the scientific impact of individual university-based researchers in three disciplines funded by the Natural Sciences and Engineering Research Council of Canada (NSERC). We considered four indices of scientific impact: numbers of articles published, numbers of citations to those articles, the most cited article, and the number of highly cited articles, each measured over a four-year period. We related these to the amount of NSERC funding received. Impact is positively, but only weakly, related to funding. Researchers who received additional funds from a second federal granting council, the Canadian Institutes for Health Research, were not more productive than those who received only NSERC funding. Impact was generally a decelerating function of funding. Impact per dollar was therefore lower for large grant-holders. This is inconsistent with the hypothesis that larger grants lead to larger discoveries. Further, the impact of researchers who received increases in funding did not predictably increase. We conclude that scientific impact (as reflected by publications) is only weakly limited by funding. We suggest that funding strategies that target diversity, rather than “excellence”, are likely to prove to be more productive.     

Linking organ donors and the medical/scientific research community: a US perspective

The International Institute for the Advancement of Medicine (IIAM) provides non-transplantable organs and tissues for medical and scientific research, education, and drug & device development. The benefits of using human organs and tissues for research are vast, and donating for research provides donor families with a valuable option if their loved one??s organs are unsuitable for transplantation. The use of these organs and tissues enables the faster development of more efficacious drugs with improved safety profiles, and enhanced understanding of basic disease processes that directly affect humans. Human organs and tissues offer unique advantages over the use of animal organs and tissues as it is human diseases and conditions which we seek to treat, and so logically the results can be more directly applied. The added advantage of accessing non-transplantable, human organs is that they are in superb condition, and so experiments can be conducted in a very physiologically-relevant system. Although the US is a sizeable country with a large population and individual regulations governing human tissue collection and usage for each of the 50 states comprising the US this article will discuss how IIAM succeeds in immediately linking organ donors and qualified researchers, ultimately to the great benefit of patients.     

How to study the impact of sex and gender in medical research: a review of resources

There is a growing appreciation by the biomedical community that studying the impact of sex and gender on health, aging, and disease will lead to improvements in human health. Sex- and gender-based comparisons can inform research on disease mechanisms and the development of new therapeutics as well as enhance scientific rigor and reproducibility. This review will assist basic researchers, clinical investigators, as well as epidemiologists, population, and social scientists by providing an annotated bibliography of currently available resource tools on how to consider sex and gender as independent variables in research design and methodology. These resources will assist investigators applying for funding from the National Institutes of Health since all grant applicants will be required (as of January 25, 2016) to address the role of sex as a biological variable in vertebrate animal and human studies.     

TRUSTED CONSENT AND RESEARCH BIOBANKS: TOWARDS A ‘NEW ALLIANCE’ BETWEEN RESEARCHERS AND DONORS

We argue that, in the case of research biobanks, there is a need to replace the currently used informed consent with trusted consent. Accordingly, we introduce a proposal for the structure of the latter. Further, we discuss some of the issues that can be addressed effectively through our proposal. In particular, we illustrate: i) which research should be authorized by donors; ii) how to regulate access to information; iii) the fundamental role played by a Third Party Authority in assuring compliance with the reciprocal expectations and obligations of donors and scientists. Finally, we briefly analyse two issues that might represent important elements of a ‘new alliance’ between researchers and donors to which the trusted consent could pave the way: i) the correlations between needs and rights of the two parties, and ii) possible economic transactions.     

A new testing strategy to identify rare variants with either risk or protective effect on disease

Rapid advances in sequencing technologies set the stage for the large-scale medical sequencing efforts to be performed in the near future, with the goal of assessing the importance of rare variants in complex diseases. The discovery of new disease susceptibility genes requires powerful statistical methods for rare variant analysis. The low frequency and the expected large number of such variants pose great difficulties for the analysis of these data. We propose here a robust and powerful testing strategy to study the role rare variants may play in affecting susceptibility to complex traits. The strategy is based on assessing whether rare variants in a genetic region collectively occur at significantly higher frequencies in cases compared with controls (or vice versa). A main feature of the proposed methodology is that, although it is an overall test assessing a possibly large number of rare variants simultaneously, the disease variants can be both protective and risk variants, with moderate decreases in statistical power when both types of variants are present. Using simulations, we show that this approach can be powerful under complex and general disease models, as well as in larger genetic regions where the proportion of disease susceptibility variants may be small. Comparisons with previously published tests on simulated data show that the proposed approach can have better power than the existing methods. An application to a recently published study on Type-1 Diabetes finds rare variants in gene IFIH1 to be protective against Type-1 Diabetes.     

A prospective multiple case study of the impact of emerging scientific evidence on established colorectal cancer screening programs: a study protocol

In this editorial, we reflect on the arguments for starting a scientific society focused on research on how to improve healthcare. This society would take an inclusive approach to what constitutes healthcare. For instance, it should include mental health healthcare, treatment for substance abuse, the work of allied health professions, and preventive healthcare. The society would be open to researchers from all traditions. Thus, we take an inclusive approach to what constitutes scientific research, as long as it uses rigorous methods, is focused on improving healthcare, and aims at knowledge that can be transferred across settings. The society would primarily target scientific researchers but would invite others with an interest in this area of research, regardless of their discipline, position, field of application, or group affiliation (e.g., improvement science, behavioral medicine, knowledge translation). A society would need fruitful collaboration with related societies and organizations, which may include having combined meetings. Special links may be developed with one or more journals. A website to provide information on relevant resources, events, and training opportunities is another key activity. It would also provide a voice for the field at funding agencies, political arenas, and similar institutions. An organizational structure and financial resources are required to develop and run these activities. Our aim is to start an international debate, to discover if we can establish a shared vision across academics and stakeholders engaged with creating scientific knowledge on how to improve healthcare. We invite readers to express their views in the online questionnaire accessed by following the URL link provided at the end of the editorial.     

Is bigger better?

To close the gap between research and development, a number of funding organizations focus their efforts on large, translations research projects rather than small research teams and individual scientists. Yet, as Paul van Helden argues, if the support for small, investigator-driven research decreases, there will soon be a dearth of novel discoveries for large research groups to explore.What is medical science all about? Surely it is about the value chain, which begins with basic research and ends—if there is an end—with a useful product. There is a widespread perception that scientists do a lot of basic research, but neglect the application of their findings. To remedy this, a number of organizations and philanthropists have become dedicated advocates of applied or translational research and preferentially fund large consortia rather than small teams or individual scientists. Yet, this is only the latest round in the never-ending debate about how to optimize research. The question remains whether large teams, small groups or individuals are better at making ‘discoveries''.To some extent, a scientific breakthrough depends on the nature of the research. Einstein worked largely alone, and the development of E = mc² is a case in point. He put together insights from many researchers to produce his breakthrough, which has subsequently required teams of scientists to apply. Similarly, drug development may require only an individual or a small team to make the initial discovery. However, it needs many individuals to develop a candidate compound and large teams to conduct clinical trials. On the other hand, Darwin could be seen to have worked the other way around: he had an initial ‘team'' of ‘field assistants''—including the crew of HMS Beagle—but he produced his seminal work essentially alone.Consortium funding is of course attractive for researchers because of the time-scale and the amount of money involved. Clinical trials or large research units may get financial support for 10 years or even longer and in the range of millions of dollars. However, organizations that provide funding on such a large scale require extensive and detailed planning from researchers. The work is subject to frequent reporting and review and often carries a large administrative burden. It has come to the point where this oversight threatens academic freedom. Principal investigators who try to conduct experiments outside the original plan, even if they make sense, lose their funding. Under such conditions, administrative officials are often not there to serve, but to govern.There is a widespread perception that small teams are more productive in terms of published papers. But large-scale science often generates outcomes and product value that a small team cannot. We therefore need both. The problem is the low level of funding for individual scientists and small teams and the resulting cut-throat competition for limited resources. This draws too many researchers to large consortia, which, if successful, can become comfort zones or, if they crash and burn, can cause serious damage.Other factors should also inform our deliberations about the size of research teams and consortia. Which is the better environment in which to train the next generation of scientists? By definition, research should question scientific dogmas and foster innovative thinking. Will a large consortium be able to achieve or even tolerate this?Perhaps these trends can be ascribed to generational differences. Neil Howe described people born between 1943 and 1980 as obsessed with values, individually strong and individualistic, whereas the younger folks born after 1981 place more trust in strong institutions that are seen to be moving society somewhere. If this is true, we can predict that the consortium approach is here to stay, at least for some time. Perhaps the emergence of large-scale science is driven by strong—maybe dictatorial—older individuals and arranged to accommodate the younger generation. If so, it is a win–win situation: we know the value of networking and interacting with others, which comes naturally in the ‘online age''.A down side of large groups is the loss of individual career development. The number of authors per paper has increased constantly. Who does the work and who gets the honour? There is often little recognition for the contribution of most people to publications that arise from large consortia, and it is difficult for peer-reviewers to assess individual contribution. We must take care that we measure what we value and not value what we measure.While it is clear that both large and small groups are essential, good management and balance is required. An alarming trend in my opinion is the inclination to fund new sites for clinical trials, to the detriment of existing facilities. This does not seem to be reasonable or the best use of scarce resources.In the long-term interest of science, we need to consider the correlation of major breakthroughs compared to incremental science with the size of the research group. This is hard to measure, but we must not forget that basic research produces the first leads that are then developed further into products. If the funding for basic science decreases, there will soon be a dearth of topics for ‘big science''.Is there a way out of this dilemma? I would like to suggest that organizations currently funding large consortia allow investigators to set aside a percentage of the money to support basic, curiosity-driven research within these consortia. If they do not rethink their funding strategy, these organizations may find with time that there are few novel discoveries for large groups to explore.     

Synthetic biology: mapping the scientific landscape

This article uses data from Thomson Reuters Web of Science to map and analyse the scientific landscape for synthetic biology. The article draws on recent advances in data visualisation and analytics with the aim of informing upcoming international policy debates on the governance of synthetic biology by the Subsidiary Body on Scientific, Technical and Technological Advice (SBSTTA) of the United Nations Convention on Biological Diversity. We use mapping techniques to identify how synthetic biology can best be understood and the range of institutions, researchers and funding agencies involved. Debates under the Convention are likely to focus on a possible moratorium on the field release of synthetic organisms, cells or genomes. Based on the empirical evidence we propose that guidance could be provided to funding agencies to respect the letter and spirit of the Convention on Biological Diversity in making research investments. Building on the recommendations of the United States Presidential Commission for the Study of Bioethical Issues we demonstrate that it is possible to promote independent and transparent monitoring of developments in synthetic biology using modern information tools. In particular, public and policy understanding and engagement with synthetic biology can be enhanced through the use of online interactive tools. As a step forward in this process we make existing data on the scientific literature on synthetic biology available in an online interactive workbook so that researchers, policy makers and civil society can explore the data and draw conclusions for themselves.     

Microarray,SAGE and their applications to cardiovascular diseases

The wealth of DNA data generated by the human genome project coupling with recently invented high-throughput gene expression profiling techniques has dramatically sped up the process for biomedical researchers on elucidating the role of genes in human diseases. One powerful method to reveal insight into gene functions is the systematic analysis of gene expression. Two popular high-throughput gene expression technologies, microarray and Serial Analysis of Gene Expression (SAGE) are capable of producing large amounts of gene expression data with the potential of providing novel insights into fundamental disease processes, especially complex syndromes such as cardiovascular disease, whose etiologies are due to multiple genetic factors and their interplay with the environment. Microarray and SAGE have already been used to examine gene expression patterns of cell-culture, animal and human tissues models of cardiovascular diseases. In this review, we will first give a brief introduction of microarray and SAGE     

Discriminant analysis of principal components: a new method for the analysis of genetically structured populations

Background

The etiology of complex diseases is due to the combination of genetic and environmental factors, usually many of them, and each with a small effect. The identification of these small-effect contributing factors is still a demanding task. Clearly, there is a need for more powerful tests of genetic association, and especially for the identification of rare effects

Results

We introduce a new genetic association test based on symbolic dynamics and symbolic entropy. Using a freely available software, we have applied this entropy test, and a conventional test, to simulated and real datasets, to illustrate the method and estimate type I error and power. We have also compared this new entropy test to the Fisher exact test for assessment of association with low-frequency SNPs. The entropy test is generally more powerful than the conventional test, and can be significantly more powerful when the genotypic test is applied to low allele-frequency markers. We have also shown that both the Fisher and Entropy methods are optimal to test for association with low-frequency SNPs (MAF around 1-5%), and both are conservative for very rare SNPs (MAF<1%)

Conclusions

We have developed a new, simple, consistent and powerful test to detect genetic association of biallelic/SNP markers in case-control data, by using symbolic dynamics and symbolic entropy as a measure of gene dependence. We also provide a standard asymptotic distribution of this test statistic. Given that the test is based on entropy measures, it avoids smoothed nonparametric estimation. The entropy test is generally as good or even more powerful than the conventional and Fisher tests. Furthermore, the entropy test is more computationally efficient than the Fisher's Exact test, especially for large number of markers. Therefore, this entropy-based test has the advantage of being optimal for most SNPs, regardless of their allele frequency (Minor Allele Frequency (MAF) between 1-50%). This property is quite beneficial, since many researchers tend to discard low allele-frequency SNPs from their analysis. Now they can apply the same statistical test of association to all SNPs in a single analysis., which can be especially helpful to detect rare effects.