Portal de Periódicos da CAPES

New Citizens for the Life Sciences

2009; Cell Press; Volume: 138; Issue: 6 Linguagem: Inglês

10.1016/j.cell.2009.09.007

1097-4172

Laura Bonetta,

Interdisciplinary Research and Collaboration

For years, the general public have been helping scientists to track weather, count birds, and observe the universe. Now such citizen scientists are starting to tackle research projects in the life sciences. Laura Bonetta reports. For years, the general public have been helping scientists to track weather, count birds, and observe the universe. Now such citizen scientists are starting to tackle research projects in the life sciences. Laura Bonetta reports. Every year from mid-December to early January tens of thousands of people spread out across North America to count and catalog birds for the Audubon Society's annual Christmas Bird Count (http://www.audubon.org/Bird/cbc/). The data collected are used by researchers to track the impact of, for example, West Nile virus and changes in bird migration patterns in response to global warming. Another army of volunteers submits to the National Weather Service precipitation data that they measure every morning from their backyards. The numbers are logged on a website that meteorologists consult daily (http://www.cocorahs.org/). And the “Eyes of the Reef Network” engages individuals in monitoring and reporting on coral reef bleaching, disease, and changing conditions in the waters surrounding Hawaii (http://www.reefcheckhawaii.org/eyesofthereef.htm). Welcome to the world of “citizen science.” Traditionally citizen science, or the enlisting of large numbers of individuals in collecting scientific data beyond the confines of the laboratory, has belonged to projects such as bird counting and weather monitoring and environmental and astronomy studies. But increasingly the internet is expanding the scope of citizen science to the life sciences, engaging nonscientists in a variety of research projects including protein engineering and genomics studies. There are nearly 100 science projects that use volunteer computing—meaning that users participate by volunteering their computers' time to automatically process data downloaded from a server. One of the first and most well-known examples of this so-called grid computing is [email protected], the screensaver that taps spare home computer power to sort through radio signals from space in the Search for Extraterrestrial Intelligence (SETI). Run by the space sciences laboratory at the University of California, Berkeley, this program was launched in 1999 and now has more than five million participants worldwide. In the life sciences, the project [email protected] run by the Scripps Research Institute farms out computations to volunteer PCs to conduct virtual screens for new inhibitors against the protease that is critical for the survival of the human immunodeficiency virus. Another project, MalariaControl.net, runs an application on volunteer computers for stochastic modeling of the clinical epidemiology of Plasmodium falciparum—the parasite that causes the most severe form of malaria in humans. And [email protected], a program designed by David Baker, an HHMI investigator at the University of Washington in Seattle, uses volunteer computing to search through possible shapes for newly designed proteins to identify the lowest-energy structures. Launched in 2005, about two million people around the world run [email protected] on their computers. As they do so, the computer displays the structures it is processing as a screen saver. After watching different shapes dance around on their screens, some users told Baker that they could do a better job than the computer in dreaming up potential structures. “People started asking whether we could make it more interactive so that they could go in and guide what the computer is doing,” says Baker. The result was the birth of FoldIt, an online game in which players shake, wiggle, and pull apart different parts of a protein molecule (http://fold.it/portal/). By moving the backbone or side chains, which look like pieces of colorful tubing, into more energy favorable positions a player gains points (Figure 1). “People try to get a better score,” says Baker. “The better the score, the better the prediction.” The best protein folders are not necessarily biochemists. “Many have zero scientific background,” adds Baker. The game, which was launched in 2008, takes players through the steps of designing a few test proteins. Along the way, players learn that hydrophobic groups (colored orange) like to be tucked inside the protein, that hydrophilic ones (blue) stick out on the outside, that hydrogen bonds between side chains help to make a protein more stable, and that charges in some regions of side chains repel each other if they get too close—causing the appearance of menacing red spikes that disappear once side chains are pulled apart. “You can get pretty far along in terms of learning about protein biochemistry. Then how far you get in the game has to do with spatial reasoning and three-dimensional visualizations, things that I am actually not very good at,” says Baker. “It's a bit like solving a three-dimensional jigsaw puzzle. You don't necessarily have to be a scientist to be good at doing it.” The best players are invited to Baker's lab where the researchers try to understand their strategy. “We are eagerly watching to see what determines who the best players are and apply their knowledge to the computer,” says Baker. In other biology fields, internet games that take advantage of volunteer thinking—not just computer power—have led to scientific discoveries. The Galaxy Zoo project, for example, engages 230,000 volunteers from all over the world to help classify one million images of galaxies taken by the Sloan Digital Sky Survey. Using volunteers' help, in July 2009, a team of astronomers at Yale University discovered a group of rare galaxies called the “Green Peas” (http://arxiv.org/abs/0907.4155). The researchers plan to pay tribute to the volunteers who helped by listing their names in the Acknowledgments section of their upcoming publication in the Monthly Notices of the Royal Astronomical Society. Although it is still early days, Baker thinks that FoldIt players will also help his lab make important discoveries about new proteins. “We are enlisting their help to design molecules that will block swine flu virus or enzymes that catalyze certain chemical reactions, to fix carbon dioxide, for example,” he says. And, just as many citizen science projects enlist people to monitor rainfall or the prevalence of particular bird species, new websites are encouraging people to keep track of health issues and to share their results with other users. One way in which such patient websites can interact with researchers is to provide cohorts of patients with a particular disease or set of symptoms. PatientLikeMe, a popular website launched in 2005 to build patient communities around certain medical conditions, for example, has started a collaboration with the California-based genomics company 23andMe to study the risk factors for Parkinson's disease. 23andMe is one of a handful of companies that give people access to their genomic information as a paid service. Other companies offering similar services include deCodeme (Reykjavik, Iceland), Navigenics (Foster City, CA, USA), and—the latest addition as of July 2009—Pathway Genomics (San Diego, CA, USA). These companies receive saliva samples from individuals interested in the service. After isolating DNA, they determine the pattern of hundreds of thousands of single-nucleotide polymorphisms (SNPs) across a person's genome. Because many SNPs are associated with disease-causing forms of genes, a person's particular SNP pattern, or genotype, can signal a genetic susceptibility to developing certain conditions. For $399, 23andMe provides information about genotypes and their association with particular traits, as well as information about ancestry. 23andMe makes both the raw data and their analysis available to customers though a private website. Clients can share their genome information with others to find connections. “The sharing component of our website is very popular,” says Linda Avey, who founded the company in 2006 with Anne Wojcicki (spouse of Google cofounder Sergey Brin). “As soon as you know something about yourself you want to know how you stack up against everyone else.” A discounted service is provided by 23andMe to individuals who agree to participate in research projects, such as the Parkinson's disease initiative, which is funded in part through a large donation from Brin, whose mother has Parkinson's disease. Patients with this disease who participate in the research project receive genotyping services for $25. By partnering with the Michael J. Fox Foundation (New York, NY, USA) and the Parkinson's Institute and Clinical Center (Sunnyvale, CA, USA), 23andMe has developed an online survey for Parkinson's patients to fill out. Information from the survey along with genomic data are analyzed by 23andMe researchers to find new associations and risk factors for the disease. “In less than 7 weeks we have recruited 2000 people,” says Avey, adding that they are aiming to have 10,000 people participate in the study. Avey says the company plans to make all of their findings available through scientific publications and other less conventional means. “We are particularly excited about giving attributions to all participants. We will have a way to acknowledge their contributions. That way participants can post that information on their webpages.” 23andMe plans to use their Parkinson's disease model to explore other conditions, including migraines and preeclampsia. “We have selected 10 diseases using input from our online community,” says Avey. Ordinary citizens also are providing their genomic information for a very different kind of study. The National Geographic Society's Genographic Project is a 5 year study to analyze the DNA genotypes of participants around the world to better understand our human ancestors and their migration patterns (https://genographic.nationalgeographic.com/genographic/index.html). For $99, participants receive a DNA collection kit. Their DNA is analyzed by testing either mitochondrial DNA—passed exclusively from the mother to her offspring—or Y chromosomes—which are passed down the male line. Participants will receive a report of their maternal or paternal ancestors—where they lived and how they migrated around the world many thousands of years ago. The data are also added to a growing database of ancestral genetic information. In July 2008, the Genographic Project released an updated version of its public participation mitochondrial DNA database, comprising 52,000 mitochondrial DNA genotypes from individuals from 180 countries. The sequence data allowed scientists to discover a rare mitochondrial DNA variant with a 154-nucleotide deletion. Other discoveries include the finding that as many as 1 in 17 men in the Mediterranean region may have a Phoenician as a direct male-line ancestor, and that before human populations moved out of Africa, they were small and isolated from each other for many tens of thousands of years. With personal genomic information making its way onto people's laptops, the Coriell Institute for Medical Research in Camden, New Jersey, is trying to find out whether giving citizens clinical research information, and making them more active participants in the research process, will benefit public health. The Coriell Personalized Medicine Collaborative will ultimately enroll 100,000 participants, who will complete extensive online health questionnaires and provide a saliva sample for genetic testing. Medical and genetic data are then combined to determine personalized risk factors. “Your risk for a certain condition based on body mass index or status as a smoker may be higher than the genetic risk,” says Michael Christman, Coriell's President and CEO. “Our goal as researchers is not to overhype genetic information, but try to determine how to use genome information to result in better health.” Unlike traditional genomic studies participants receive research results through a website. They are provided with risk factors for conditions deemed potentially “actionable,” meaning there is the potential to mitigate risk via medication or lifestyle changes. Follow-up surveys will determine what individuals did with the information. “If you found out you have increased risk for type 2 diabetes, we will ask you what you did with that information,” says Courtney Sill, Coriell's Director of Communications. “Did you change your diet? Your lifestyle? Did you decide not to change anything? Did the information make you anxious?” The Coriell Institute project may reflect the way forward in biomedical research. “Being told of results is new. The traditional model of large cohort studies is not to give research results before a study is completed and analyzed because they are tentative,” says Joan Scott of the Genetics and Public Policy Center based in Washington DC. As part of a 2 year $2 million pilot project funded by the National Institutes of Health, the Genetics and Public Policy Center gathered input on issues related to large population-based studies though a series of focus groups and surveys. “When we look at focus groups and surveys of people's attitudes, many people are interested in getting back research results,” says Scott. “Most people are still willing to participate in research studies regardless of whether they will get results back but they are more willing to do so if they are getting back results.” We can expect that more games like FoldIt will engage ordinary people in real-life research projects outside of the confines of a particular institution. In addition, online communities are making it easier for people to take part in scientific studies and to play active roles in research projects. It is too early to say whether such engagement will speed discoveries or result in better health care—but one thing is certain, citizen science projects are a great way to broaden people's interest in science. “It's certainly true that people are more excited about science. Many people tell us they want to go back to school,” says Baker. And Avey concurs. “When we first started the company, the first clients were people who already had some knowledge of genetics but now the demographics are changing,” she says. “That was always our mission, to take genetics into the public arena and make it less white coat and more street clothes.”