Scientific Discovery Games for Biomedical Research

Abstract

Over the past decade, scientific discovery games (SDGs) have emerged as a viable approach for biomedical research, engaging hundreds of thousands of volunteer players and resulting in numerous scientific publications. After describing the origins of this novel research approach, we review the scientific output of SDGs across molecular modeling, sequence alignment, neuroscience, pathology, cellular biology, genomics, and human cognition. We find compelling results and technical innovations arising in problem-oriented games such as Foldit and Eterna and in data-oriented games such as EyeWire and Project Discovery. We discuss emergent properties of player communities shared across different projects, including the diversity of communities and the extraordinary contributions of some volunteers, such as paper writing. Finally, we highlight connections to artificial intelligence, biological cloud laboratories, new game genres, science education, and open science that may drive the next generation of SDGs.

Keywords: citizen science; cloud laboratory; crowdsourcing; interactive media; scientific discovery games; video games.

Figure 1

A history of SDGs in biomedical research. (Top) Selected key events concerning the emergence and maturation of SDGs in biomedical research. (Bottom) Selected key events that have influenced the development of SDGs or may impact SDGs in the future. Key developments not explicitly listed include Wikipedia, the Internet, online games, virtual and augmented reality, mobile computing, and social media. Screenshots and logos are taken from the SDGs themselves; other graphics are used with permission from the NASA Image Library (Galaxy Zoo), Reference (Foldit crystal), Reference (malaria image), the Seung Lab Flickr photostream (EyeWire), and Wikipedia (AlphaGo). Abbreviations: AI, artificial intelligence; NIH, National Institutes of Health; SDG, scientific discovery game.

Figure 2

Anatomy of a scientific discovery game, illustrated by the paradigm-setting Foldit. (a) First-time players of Foldit first navigate to the project home page, where a link can take the user to a FAQ page. The FAQ contains an explanation of protein folding, a description of the scientific problems Foldit is tackling, a description of how game playing contributes to curing diseases, and a list of scientific publications. On either page, the user can download Foldit applications for Windows, Mac, or Linux. (b) Players can participate in published science puzzles and contests created by other players and can see top players and top player groups. Player groups can complete protein folding challenges together. (c) Foldit gamifies certain biological concepts while introducing the relevant science. For example, in the first tutorial, the player is told that “the blue sidechain on the right is either glutamate or glutamine, which have the same shape.” The player goes through 38 folding challenges in the tutorial sequence. During game play, the score updates on the top of the screen based on how well the protein folded. The goal of each puzzle is to create a protein conformation with the lowest energy. After completing a puzzle, a congratulatory animation is played. The player can save a solution or share their solutions with other players. The player’s global rank and score are displayed at the top of the graphical user interface. The interface also contains a public chat display, which allows players to communicate with and receive help from other players. The puzzles can either be solved by individual players in the soloist competition or by teams that work collaboratively on a solution in the group competition.

Figure 3

Successes of scientific discovery games. (a) Foldit-refined models of a Mason–Pfizer monkey virus retroviral protease (purple and green) that led to successful crystallographic phasing and an experimental solution of the enzyme’s structure (blue). (b) RNA sequences designed by Eterna players achieve a secondary structure termed The Branches (top panels), while algorithmic solutions do not (bottom panels). (c) An EyeWire reconstruction of circuitry of OFF-type starburst amacrine cells and bipolar cells in the mouse retina. (d) Project Discovery players identify novel localizations to cytoophidia (red; also known as “rings and rods”) of the protein C21orf59 (green), which appear together as yellow in the panel due to colocalization; cell nuclei are stained in blue (25). Panels adapted with permission from (a) Reference , (b) Reference , (c) Reference , and (d) the Human Protein Atlas.

Figure 4

Emergent properties of scientific discovery game (SDG) player communities. (a) Spikes in new visits to the SDG Fraxinus correspond to press releases (red) and social media mentions (blue). (b) The global distribution of Fraxinus game players. (c) Drops in player counts for progressively more involved tasks in the SDG Eterna (5). (d) Drops in activity in days since Fraxinus game release. (e–g) Examples of player contributions highlighted (yellow) in author lists and affiliations of scientific manuscripts (16, 96, 97). Panels a, b, and d adapted with permission from Reference .

Figure 5

The life cycle of a scientific discovery game (SDG). Each symbol represents approximately 1,000 people (for players) or 1–2 people (for game developers, scientists, experimentalists, and player-developers) during development (phase 1), deployment (phase 2), and ongoing development (phase 3), with numbers representative of the Eterna SDG.