correspondence build confidence, have an open and honest transgender and queer or questioning) Michelle McMurry-Heath ✉ dialogue about the past, and work with local representation on biotech company boards, Biotechnology Innovation Organization, community leaders who can be that in C-suites and in functional leadership Washington, DC, USA. trusted voice. positions. ✉e-mail: [email protected] While the BIOEquality Agenda will BIO is deeply committed to address inequities in healthcare delivery, both BIOEquality and the Right Published online: 11 September 2020 STEM (science, technology, engineering Mix Matters campaign. In these https://doi.org/10.1038/s41587-020-0688-8 and math) programs and minority difficult and uncertain times, we will entrepreneurship, BIOEquality complements continue to build support for a more Competing interests M.M.-H. works for industry trade organization the the Right Mix Matters initiative we launched equitable future for the biotech sector and Biotechnology Innovation Organization (BIO). She was last year to accelerate gender, racial, the millions of patients across the world who employed by Johnson & Johnson and holds stock in ethnic and LGBTQ (lesbian, gay, bisexual, depend on our success. ❐ Johnson & Johnson.

Leveling up

To the Editor — Over the past decade, online science discovery games (SDGs) have become an increasingly popular practice for engaging the public in research activities. This methodology has had the most impact in molecular and cell biology, where participants are recruited for not only data collection and classification tasks, but also solving complex computational problems that require human supervision or insight. As the sciences move toward increasingly large and ambitious projects, however, there is a need to complement existing models that try to attract users to yet another third-party website. Here we describe our experience with Borderlands, a massively multiplayer that embeds citizen-science problems into its virtual universe and engages a new user base, with implications for future citizen science initiatives seeking to meet the Fig. 1 | Arcade booth allowing the to access Borderlands Science in Borderlands 3. growing demands of biology.

Citizen science in biology Since 2008, the team has recruited like Foldit take advantage of large groups OpenVaccine or OpenCRISPR from the online participants to predict protein 3D of participants for identifying skilled users EteRNA project. structure via a 3D puzzle game distributed and promising solutions to a hard problem. Recruiting large groups of volunteers as a standalone program for personal In contrast, Phylo and related SDGs aim should also serve long-term objectives and computers1. This project helped refine to harness the wisdom of the crowd by not be confined to solving a specific problem a retroviral protease structure2 and later detecting collective behaviors of the gamers without a larger context. Projects like discovered novel protein folds3. Two years while solving small instances of the problem, ENCODE8 or the Earth Microbiome Project9 later, Phylo4 pushed the gamification and using this knowledge to build a involve hundreds of scientists worldwide and concept to reach a broader public by global solution. require assembly and coordination of many comparative genomics tasks Having sustainable and large crowds of diverse areas of expertise. At all stages of the via tile-matching puzzle games. Other participants is necessary for opening this research pipeline and at various degrees of successful projects include web-based games technology as a service to the whole scientific involvement, collection, curation and analysis for RNA structural modeling (for example, community7. Popular SDGs represent the of the data need the supervision of human EteRNA5) and neuron segmentation best option for solving on-demand problems experts. But as the size and complexity of the (for example, EyeWire6). for many groups of independent scientists. project teams expand, so too does the cost of The efficiency and effectiveness of SDGs Although few such platforms have yet to human intervention and logistics, which may is necessarily determined by the number of be deployed, this approach constitutes a not be sustainable. To expand the boundaries contributors and volume of data collected, natural and promising evolution of SDGs of the system, we need to refactor the regardless of citizen-science strategy. Games that is exemplified by recent initiatives like organization of large scientific projects.

1124 Nature Biotechnology | VOL 38 | October 2020 | 1123–1126 | www.nature.com/naturebiotechnology correspondence

The state of affairs Remarkably, engagement was also very toward any other part. Therein lies the true The most successful citizen science high, with an average of 100 tasks solved power and challenge of this approach. initiatives have reported several hundreds per participant. Overall, these statistics Enter Borderlands Science: an of thousands of volunteers, and eventually represent a considerable improvement over intersectoral collaboration between more than a million if we aggregate statistics those of previous projects. The rationale scientists, engineers and game developers from distinct projects using the same for the approach taken by MMOS is both that strives to demonstrate the formidable infrastructure over years of operation. simple and efficient; instead of trying to potential of an alliance of citizen science and Notably, following a pattern commonly attract users to yet another third-party the highest profile AAA games. Borderlands observed in user participation, the majority website, bring citizen science to the virtual Science is a casual tile-matching game of the contribution is completed by the universes that users already inhabit. This (inspired from the previous SDG Phylo) that participants during the first days or weeks strategy is even more powerful given that is distributed within Borderlands 3 — a fast following the launch of the project. To gamers are already expert at developing action role-playing first-person . prevent this drop-off, projects like Stall problem-solving skills. Each puzzle in Borderlands Science is made Catchers or EyeWire organize various events With the introduction of Project of fragments of microbial 16S ribosomal and competitions to renew participant Discovery, citizen science entered the AAA RNA gene sequences collected by the interest and maintain engagement. Foldit video game scene. (AAA is an informal American Gut Project13, and the results are and EteRNA also regularly unveil new classification used for video games aggregated to improve a reference alignment challenges and datasets designed to produced and distributed by a mid-sized of millions of sequences. support research in different areas, such as or major publisher, typically having a high At first glance, the match between user COVID, tuberculosis or synthetic biology. development and marketing budget.) But base and scientific problem seems unlikely. Nevertheless, in case, the volume another crucial step is needed to make The fast-paced, first person shooter–looter of work generated reaches a couple of this approach broadly accepted by both game filled with dark humor is primarily hundreds of hours of work per day10. researchers and game developers. Eve designed for gamers seeking adventure and Although such a number is useful, it Online is a very special game. The player action. But what could be a dead end turns hardly meets the demand of large-scale base is more mature and attuned to science out to be the strength of this initiative. science projects. than other player communities. The game A deployment in the Borderlands universe Therefore, despite undeniable successes is also slower paced and more complex, offers an opportunity to reach a public not not only in scientific impact but also in making it an almost too perfect match for particularly exposed to science, while at the science outreach to the general public, the citizen-science activities. same time it opens the door to a large and vision of online citizen science initiatives is The deployment of SDGs within strong online community of players who can still out of range of current methodologies. fast-paced games with a wide and diverse carry and amplify the impact of this initiative. A model based on distributing scientific audience is the next frontier. It has the To complete this picture, the partnership tasks through a web page or mobile potential to bring millions of contributors to with the Microsetta Initiative (the parent application managed by academic the most ambitious scientific endeavors, but organization of the American Gut Project) researchers appears to have reached its comes with new challenges. The integration provides another central piece of this project. limits. Even when a project benefits from of these new activities must preserve the Only a long-term scientific endeavor with extensive media coverage, the core of its immersion experience and seamlessly apparent benefits for the public can trigger audience remains confined to participants integrate into the ecosystem of the host the interest of a large audience and justify the already naturally interested in the scientific platform. Whereas a game like Foldit scale of such an enterprise. subjects, which is unfortunately only a small requires extensive training and substantial fraction of the population. investment of time from the participants, The challenges of design this may be incompatible with action games. A tight collaboration between the game Reach out to your public design and scientific team is essential to Fundamentally, the goal of citizen science Choosing the right game guarantee the success of the integration. is to organize science at population scale. The sophistication and gamification of Since its inception, Phylo aimed to The internet has been a key technology for SDGs vary considerably. However, there be a . Still, its adaptation gathering crowds of participants worldwide is a common motif in the gamification of to Borderlands required a complete in a short time, and the development of classic citizen science projects: the game redesign. The scoring system had to be SDGs has been equally important for is formed around the scientific problem. simplified, while preserving its relevance enabling citizen scientists to participate When integrating citizen science activities to science. Intuitive rules and swift-moving in the resolution of complex problems. with AAA games, the opposite approach mechanisms were also essential to accelerate But the next frontier is to bring SDGs must be taken. To be appealing to an the pace of the game. In particular, to the general public. In 2016, Massively established player base of millions, we must entry- puzzles had to be quick to Multiplayer Online Science11 (MMOS) first understand their world. This means complete to promote engagement. Finally, proposed an original solution to this that we cannot approach game developers the presentation of the activity had to problem. The first implementation was a with a fixed agenda, but rather work as match the host universe. These factors led collaboration with the video game company intermediaries to find the best-fitting us to embed Borderlands Science into a CCP to integrate citizen science activities scientific problem: one that resonates with retro-style arcade video game that suits in the science fiction massively multiplayer the player base, one that fits aesthetically well the postapocalyptic atmosphere of online role-playing game Eve Online. and thematically and, most importantly, one the main game (Fig. 1). But this work on In less than a year, Project Discovery that doesn’t risk breaking immersion. If such adaptation also provides access to powerful enrolled more than 300,000 online gamers a match can be found, we can expect the mechanisms. For instance, rewards in to classify fluorescence microscopy same level of enthusiasm and activity toward the form of boosters or skins can be used images for the Human Protein Atlas12. the citizen-science feature in the game as to engage the gamers. (In video games,

Nature Biotechnology | VOL 38 | October 2020 | 1123–1126 | www.nature.com/naturebiotechnology 1125 correspondence boosters are items that gamers collect to guarantees for longevity. Borderlands objectives and constraints of the other. temporarily improve attributes of their Science was released with one of the first Finally, the enthusiastic participation character, while skins are cosmetic elements downloadable contents of Borderlands 3, of the scientific team at all stages of the used to personalize it.) which offers not only high visibility but also promotional campaign is essential for The adaptation of Borderlands Science the opportunity for introduction early in reinforcing the credibility of the project and from Phylo enables us to directly quantify the the life cycle of the video game. Yet, if the satisfying the curiosity of the gamers. impact of the more recent implementation SDG is expected to run for several years, its If properly executed, the potential impact and calibrate our expectation for this purpose must also be maintained over the of the uncanny partnership of researcher methodology. In fewer than three months, same period. and public is huge. After all, as Turing Borderlands Science reached more than 1 We designed Borderlands Science to awardee Donald Knuth put it: “Biology million active participants who solved at help us align microbial 16S rRNA sequences easily has 500 years of exciting problems to least one open task, whereas Phylo had an from the human microbiome. The same work on; it’s at that level”15. ❐ estimated 350,000 participants over ten years. framework can be applied to work with data During those three months, we collected from different origins, such as soil samples Jérôme Waldispühl 1 ✉ , Attila Szantner2, 50 million puzzle solutions, resulting in an from the Earth Microbiome Project, or Rob Knight 3, Sébastien Caisse4 and average of slightly under 50 puzzles solved obtained with different techniques, such as Randy Pitchford5 per player. This is one order of magnitude shotgun metagenomic sequencing. Recently, 1McGill University, Montréal, Québec, Canada. higher than that of Phylo, which has a mean the Microsetta Initiative started to collect 2Massively Multiplayer Online Science, Monthey, number of 5 solved tasks per volunteer, and is data to study the spread of SARS-CoV-2 Switzerland. 3University of California San Diego, consistent with previous observations made and factors influencing susceptibility to La Jolla, California, USA. 4Gearbox Studio Québec, in Project Discovery9. Strikingly, the volume COVID-19, which are a natural match for Québec, Québec, Canada. 5Gearbox Entertainment of work generated by Borderlands Science is this project. Applications such as aligning Company, Frisco, Texas, USA. oscillating between 10,000 and 15,000 hours coronavirus genome sequences highlight ✉e-mail: [email protected] of work per day, which can be compared the impact that partnerships with the video to the couple of hundreds of hours per day game industry may have during emergency Published online: 24 September 2020 reported in other projects8. The fact that a situations when the scientific community https://doi.org/10.1038/s41587-020-0694-x mainstream shooter–looter action videogame could benefit from a platform that quickly References managed to translate a scientific problem to mobilizes large numbers of participants 1. Cooper, S. et al. Nature 466, 756–760 (2010). a wide audience of millions of players with to complete urgent tasks. Finally, minimal 2. Khatib, F. et al. Nat. Struct. Mol. Biol. 18, 1175–1177 (2011). such unprecedented success is a clear proof modifications of the game play could 3. Koepnick, B. et al. Nature 570, 390–394 (2019). 4. Kawrykow, A. et al. PLoS ONE 7, e31362 (2012). of the validity and viability of the original authorize new types of alignment, including 5. Lee, J. et al. Proc. Natl Acad. Sci. USA 111, 2122–2127 (2014). proposition. protein sequences. 6. Kim, J. S. et al. Nature 509, 331–336 (2014). Although it is too early to fully Adhering to the principle of sustainability 7. Kwak, D. et al. Genome Biol. 14, R116 (2013). 8. ENCODE Project Consortium. Nature 489, 57–74 (2012). comprehend all the implications of this requires applying this strategy to problems 9. Tompson, L. R. et al. Nature 551, 457–463 (2017). project, it already demonstrates the with high relevance to multiple areas 10. Sauermann, H. & Franzoni, C. Proc. Natl Acad. Sci. USA 112, formidable potential of partnerships of science and a broad community of 679–684 (2015). 11. Szantner, A. in Levelling Up: Te Cultural Impact of Contemporary with video game companies to engage researchers. At the same time, the ability Videogames 103–110 (Brill, 2016). large communities of citizen scientists in to easily adapt the presentation of the 12. Sullivan, D. P. et al. Nat. Biotechnol. 36, 820–828 (2018). addressing complex scientific tasks. The data is another strong asset that facilitates 13. McDonald, D. et al. mSystems 3, e00031-18 (2018). reach of video games grows by the day and SDG integration. A sequence-based 14. Harari, Y. N. Te meaning of life in a world without work. Te Guardian (8 May 2017); https://www.theguardian.com/ will very likely continue to do so. In 2019, problem like Borderlands Science fulfils technology/2017/may/08/virtual-reality-religion-robots- 65% of adults in the United States played these requirements, but graph-based sapiens-book games (https://www.theesa.com/esa-researc models, such as biochemical networks or 15. Anonymous. Donald Knuth–Computer Literacy Bookshops Interview (Computer Literacy Bookshops, Sunnyvale, Calif., h/2019-essential-facts-about-the-compu COVID-19 contact tracing data, also seem 7 December 1993); http://www.literateprogramming.com/ ter-and-video-game-industry/). As players perfectly suited. Mass spectrometry and clb93.html spend more and more time in these virtual flow cytometry data are also promising worlds14, it is imperative for us as a society candidates. Competing interests J.W. is supported by a Genome Canada grant (Genomic that we find all possible ways to extract value Overall, the evolution of our project Applications Partnership Program) that is co-funded by from this time. Tapping into this virtually from Phylo to Borderlands Science Gearbox Studio Québec Inc. and Massively Multiplayer limitless resource might well be one step suggests a pattern for others to follow for Online Science (MMOS Sàrl). A.S. is the CEO of Massively to advance toward the dream of building a successful integration. Once a scientific Multiplayer Online Science (MMOS), which operates science-oriented society. problem is identified, the scientific team the middleware of Borderlands Science. MMOS received operating fees from Gearbox Studio Québec Inc. S.C. is should develop a prototype to explore co-studio head and director of operations at Gearbox Future opportunities the potential for gamification and collect Studio Québec Inc., which develops the game Borderlands Inevitably, developing such a platform has feedback from citizen scientists. Equipped 3 and the citizen science game Borderlands Science. a substantial cost in time and resources, as with this information, they can begin the R.P. is president of Gearbox Entertainment Company the final product must also meet industry collaboration with the game designers. Our Inc., which develops the game Borderlands 3 and the citizen science game Borderlands Science. Borderlands standards and consumer expectations. To experience suggests that multiple rounds Science is a free mini-game available within the justify this investment, any citizen-science of discussion are necessary and that each Borderlands 3 game, but Borderlands 3 is sold as a game must be sustainable and provide party must have an open mind about the premium game.

1126 Nature Biotechnology | VOL 38 | October 2020 | 1123–1126 | www.nature.com/naturebiotechnology