EteRNA

EteRNA, later written Eterna, is an online puzzle game in which players design molecules of RNA that fold into target shapes, and in which the designs voted best by the players are made and tested in a real laboratory. It was conceived in 2009 by Adrien Treuille of Carnegie Mellon University and Rhiju Das of Stanford University, both of whom had worked on the protein-folding game Foldit, and its software was written by Treuille's doctoral student Jeehyung Lee. It opened to the public in early 2011.^[1] By 2020 it had more than 250,000 registered players.^[2]

An RNA molecule is a chain of four kinds of base, A, U, G and C, and a single strand folds back on itself wherever stretches of it can pair: G with C, A with U, and less strongly G with U. The game shows a target shape, a pattern of loops and paired stems, and the player chooses the base at each position. An energy model on screen predicts how the chain will fold, and in the training puzzles the model is the judge.

The game's distinctive part was the laboratory. In the "lab" puzzles the model is not the judge. Each week the community voted on candidate designs for a target, and the eight leading sequences were sent to the Das laboratory at Stanford, which synthesized them and measured their folding by chemical mapping.^[1] The results came back to the players, who learned which of the model's predictions failed in a test tube.

In 2014 the project's scientists reported in the Proceedings of the National Academy of Sciences that a community of about 37,000 players, using this remote feedback, had found new design rules that markedly improved the accuracy of RNA designs. The rules, distilled by machine learning into an algorithm called EteRNABot, outperformed earlier design programs in independent tests. The paper called the arrangement "a massive open laboratory". Its list of authors ends with a collective name, "EteRNA Participants", after eleven scientists, and the players were credited the same way, as "Eterna Participants", on the vaccine paper of 2022.^[3]

In 2020 the game turned to the COVID-19 pandemic. Its OpenVaccine project asked players to design messenger RNA that would resist breaking down, because instability made mRNA vaccines hard to store and ship, and designs were tested in the laboratories of Das and Maria Barna.^[2] A public machine-learning competition built on the players' data produced models that predicted where RNA strands degrade, published in 2022.^[4]

In 2024 Molecular Reality Corporation wrote a set of answers for its mascot, Keltar, to give at what it called the Question Desk of its website. One question asked "How does this compare to the Borderlands game/Folditathome/EteRNA and other gamified citizen science projects?", running Foldit and Folding@home together into one word. The answer described Maxine's Quest as a way to make the drudgery of collecting data with purpose-built devices more pleasant.^[5]

The two projects divide the work in opposite ways. In EteRNA the players design and a laboratory at Stanford measures, and none of the players handles RNA. The company's plan for experigaming, first set out in 2022, gives the measuring to the players, each with a nanopore instrument at home, and calls them "a decentralized Army of Player Scientists™".^[6]

• Borderlands Science
• Player Scientist