• Dr. Timothy Smith

How Gamers Beat Artificial Intelligence for Medical Research

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With the news frequently touting the latest triumph of computers beating people in some game such as chess or exceeding human capabilities in facial recognition, it is interesting to learn of a game in which people still outstrip computers by a long shot. The game called EteRNA has people solve complex, molecular 3D puzzles, which also helps advance medical science.

When trying to explain some personal attribute such as a passion for a sport, joy of gardening, or a love of the theater, people often say, "It's in my DNA." DNA, meaning the blueprint in our cells that contains all the instructions needed to build our bodies, help us grow, and even help us age. DNA stands for deoxyribonucleic acid, a very long chain of chemicals arranged in a particular order. Just as letters in a sentence need a specific order to convey an idea, DNA has specific sequences that convey how all the parts of cells and, by extension, our bodies get made. DNA sits in a protective envelope called the nucleus in every cell in our bodies, and when our cells need some instructions on how to make a protein or respond to stresses such as low sugar or a toxic chemical, that information gets transcribed from the DNA into a copy of the information. That copy can leave the nucleus while keeping the original blueprint intact. The concept is similar to the fact that you cannot take reference books out of the library, but you can make photocopies of reference materials to take out of the library and use elsewhere.

The copies of information from DNA made in the cell's nucleus go by the name RNA, and RNA can leave the nucleus to convey instructions. However, unlike DNA or reference books for that matter, RNA can get broken down and recycled when no longer needed. Moreover, scientists have found that RNA does more than convey messages from the DNA. RNA can make chemical reactions happen, regulate how DNA gets used, and more. Part of RNAs versatility comes from the different 3D shapes it can make depending on the sequence of chemicals in the RNA chain. To put it in perspective, just like how magnets can attract or repel each other depending on their orientation, different chemicals in the RNA chain can also attract or repel each other. The sequence of the various magnetic beads will form unique shapes based on attraction and repulsion. Getting RNA to fold into specific shapes has great medical applications in the diagnosis and curing of disease. In fact, the intersection between medical research and RNA study is known as RNA therapeutics.

However, figuring out how different chains of RNA will fold to get the desired shape turns out to be a complicated problem for scientists to solve even with the aid of supercomputers. Ten years ago, researchers at Stanford University and Carnegie Mellon University took a unique approach to solving complex RNA folding questions by turning the problem into a game. They called the game EteRNA, and since its launch, tens of thousands of people from around the world have spent millions of hours solving some of the most challenging RNA folding problems. (eternagame.org) The game proposes a shape that the gamers try to solve using different chemicals or links that attract or repel each other in the chain. Remarkably, EteRNA has demonstrated that gamers have solved many new RNA structures using logic that scientists in the field had not even considered. Some of the findings from the EteRNA gamers have been so significant as to achieve peer-review publication in scientific journals. For example, the paper titled "RNA secondary structure packages ranked and improved by high-throughput experiments" was authored by EteRNA gamers and published in the scientific journal, BioRxiv. (biorxiv.org). The RNA shapes that the EteRNA players solved were discovered to have applications in vaccine research.

DNA serves as the blueprint for all living things, but the blueprint must stay safely protected in the nucleus of every cell in animals and plants. When the cell responds to different stimuli such as a toxic substance or oxygen stress, it needs information from DNA. The required information gets copied into messages called RNA that can exit the nucleus for processing in the cell. However, RNA turns out to have many other functions beyond a recyclable message. RNA can make specific chemical reactions occur, regulate cells, and act as a medicine. These additional functions rely on RNA folding into particular shapes, and designing RNA to make these shapes occupies an essential part of medical research called RNA therapeutics. It turns out the folding requires a highly complex design that scientists armed with supercomputers still struggle with. However, researchers took a very different approach and turned the RNA folding puzzle into a game with great success. The game called EteRNA has harnessed the creativity of gamers around the world to solve thousands of RNA puzzles. A recent paper titled "Solving the RNA design problem with reinforcement learning" by researchers at Stanford showed that their artificial intelligence (AI) approach to solving the RNA puzzles solved 60 out of a set of 100 RNA puzzles solved by gamers. (journals.plos.org) It was a triumph in one sense since their AI got 60 right while the best supercomputer got 54 puzzles solved, but neither could solve at the level of humans. While AI does have its edge in games like chess and go, humans seem to have an the edge when it comes to folding RNA.

Dr. Smith’s career in scientific and information research spans the areas of bioinformatics, artificial intelligence, toxicology, and chemistry. He has published a number of peer-reviewed scientific papers. He has worked over the past seventeen years developing advanced analytics, machine learning, and knowledge management tools to enable research and support high level decision making. Tim completed his Ph.D. in Toxicology at Cornell University and a Bachelor of Science in chemistry from the University of Washington.

You can buy his book on Amazon in paperback here and in kindle format here.