News this Week

Science  25 Sep 2015:
Vol. 349, Issue 6255, pp. 1426
  1. This week's section

    Sage grouse not ‘endangered’

    DOI says a land conservation effort has reduced threats to sage grouse.

    PHOTO: © ALL CANADA PHOTOS/ALAMY STOCK PHOTO

    In a controversial move, the U.S. government has decided against declaring the greater sage grouse (Centrocercus urophasianus) an endangered species. The 22 September decision capped a lengthy debate over how best to protect North America's largest grouse, which has seen its numbers plummet by 90% over the past century (Science, 19 June, p. 1304). Some conservation advocates wanted the grouse to get the greatest legal protection available under the federal Endangered Species Act (ESA). But others feared a listing would cause massive economic harm in the 11 western states where the bird lives, and would fuel political efforts to gut the law. To avoid that outcome, federal officials are trying what some call “a 21st-century approach to conservation.” It essentially offers state governments and private landowners incentives to preserve and restore sage grouse habitat in exchange for avoiding restrictive regulation. The “historic effort … demonstrates that the [ESA] is an effective and flexible tool,” Secretary of Interior Sally Jewell said in a statement. Both industry and conservation groups, however, may sue to undo the deal. http://scim.ag/endangeredgrouse

    If you build a tree, will they come?

    Each branch in this new tree of life has a least 500 species at its tip.

    IMAGE: OPENTREEOFLIFE.ORG/DUKE UNIVERSITY

    Biologists have spent centuries trying to determine how life forms are related to one another. Now, with a few clicks, anyone can see what they have learned so far—well, almost. The Open Tree of Life (https://tree.opentreeofife.org) knits together about 500 family trees published by previous authors to create a “supertree” of 2.3 million species. It's the first such comprehensive charting of all organisms—but still includes only a fraction of 6800 published trees, most of which could not be used because they lack digitized data. For example, bacteria (above, red), are well represented in public databases, but not larger organisms. Therefore, this draft tree, reported online on 18 September in the Proceedings of the National Academy of Sciences, “does not summarize what we know,” says co-leader Karen Cranston, an evolutionary biologist at Duke University in Durham, North Carolina. But, Cranston says, the site was designed to make it easy for the community to fine-tune the supertree with feedback and additional data. “We hope the tree looks much different a year from now,” Cranston adds.

    Famed museum plans overhaul

    The Gallery of Paleontology and Comparative Anatomy is more than a century old.

    PHOTO: © DANIEL SANTOS MEGINA/ALAMY STOCK PHOTO

    One of Paris's most celebrated science museums needs to undergo a massive renovation that will last several years and may cost as much as €100 million. The Gallery of Paleontology and Comparative Anatomy, home to an impressive collection of skeletons and fossils, is at risk of flooding and in need of repairs. Housed in a brick, steel, and glass building built for the 1900 Universal Exhibition, the gallery is best known for its main hall, which displays hundreds of animal skeletons all facing the same way as if in a gigantic parade. The renovation is “the next big operation” for France's National Museum of Natural History (MNHN), of which the gallery is part, says MNHN director Bruno David. Another iconic MNHN institution, the Museum of Man, will finally reopen on 17 October after a 6-year renovation.

    $43,000,000,000,000—Projected economic damages due just to greenhouse gas emissions from thawing permafrost through the year 2100. That's on top of estimated global damages of $326 trillion because of other greenhouse gas emissions (Nature Climate Change).

    Around the world

    Krakow, Poland

    Fluorescence mission gets nod

    The €290 million FLuorescence EXplorer, or FLEX, was endorsed as the European Space Agency's (ESA's) next Earth Explorer mission by the agency's Earth Science Advisory Committee on 18 September. The satellite would measure the faint fluorescent glow of plants; when light strikes their chlorophyll molecules, about 1% of the light is re-emitted as a faint red glow. FLEX, which could launch in 2022, would measure that fluorescence at 300-meter resolution as a way to understand how plants soak up carbon dioxide under different environmental conditions. Formal selection of either FLEX or a rival mission proposal, CarbonSat, will be made in November, but ESA has always followed the recommendations of the advisory committee. http://scim.ag/ESAFLEX

    Cambridge, Massachusetts

    Stings and pee: the Ig Nobels

    A brave scientist's work on bee stings won an Ig Nobel.

    PHOTO: SCOTT CAMAZINE/SCIENCE SOURCE

    The most painful places to be stung by a honey bee include the nostril, the lips, and the shaft of the penis, according to Michael Smith, a Ph.D. student in entomology at Cornell University. Smith learned this the hard way: by stinging himself three times in each of 25 locations. His findings, published last year in PeerJ, have now earned him a 2015 Ig Nobel Prize, awarded 17 September at Harvard University's Sanders Theater. The Ig Nobels each year pay recognition to scientific research “that makes people laugh, and then think.” Other awards this year went to scientists who discovered that experiencing a sharp pain while driving over speed bumps is a sensitive predictor of appendicitis, and to a team that described the Golden Rule: that various mammals, from dogs to elephants, take about 21 seconds to pee, regardless of the volume of urine in their bladders. http://scim.ag/2015IgNobel

    London

    U.K. application to edit embryos

    A researcher has applied to the United Kingdom's Human Fertilisation and Embryology Authority (HFEA) for a license to edit the genes of human embryos. Some worry that such experiments could someday lead to genetically modified human babies. The application filed with HFEA would involve only embryos in the lab, however, not any intended to lead to a birth. The applicant, Kathy Niakan, a developmental biologist at the Francis Crick Institute in London, investigates the genes that are active at the earliest stages of human development, before an embryo implants in the womb. Niakan hopes to use genome editing to tweak some of the key genes thought to be involved and study the effects they have on development. http://scim.ag/UKembryoedit

    Washington, D.C.

    New research board proposed

    A U.S. National Academies' panel wants Congress to create a new entity to oversee federal policies that affect academic research. Its report, out this week, calls for a Research Policy Board that would be funded by universities and located within the White House Office of Science and Technology Policy. The quasi-governmental board would help federal officials develop new rules affecting the conduct of academic research and would also have the authority to police any institutions that violate those practices. Congress asked for the report in response to persistent complaints from U.S. universities that current rules are overly restrictive, redundant, burdensome, and dilute the nation's investment in academic research. http://scim.ag/researchboard

    Newsmakers

    Obama nominates next FDA chief

    President Barack Obama nominated veteran heart researcher Robert Califf to be the next head of the U.S. Food and Drug Administration (FDA). Califf, 63, was an administrator and clinical trial researcher at Duke University in Durham, North Carolina, for more than 30 years before coming to FDA earlier this year as deputy commissioner for medical products and tobacco. “Great news!” Francis Collins, director of the National Institutes of Health, tweeted in response to the 15 September White House announcement. The Wall Street Journal reported this week that Califf had received about $205,000 in consulting fees from pharmaceutical companies between 2009 and 2015. A spokesperson for Califf told the newspaper that the fees had been donated to nonprofit groups, and that Califf had ceased work with drugmakers when he was hired by FDA. If confirmed by the Senate, Califf would succeed Margaret Hamburg, who stepped down this past March.

    New head of Vatican Observatory

    Pope Francis has selected Jesuit brother Guy Consolmagno, the first clergyman to win the American Astronomical Society's Carl Sagan Medal, to head the Vatican Observatory, where he will supervise a staff of 11 other Vatican astronomers. Consolmagno, 63, previously oversaw the Vatican's meteorite collection. He graduated from the Massachusetts University of Technology (MIT) in Cambridge in 1975 with bachelor's and master's degrees in planetary science, received his Ph.D. in planetary science from the University of Arizona in 1978, and was a postdoctoral fellow, first at the Harvard College Observatory and later at MIT, until 1983, when he joined the Peace Corps and taught physics and astronomy in Kenya. He has co-authored five astronomy books, including Would You Baptize an Extraterrestrial? Consolmagno is the second American to lead the Vatican Observatory, located in the town of Castel Gondolfo outside of Rome.

    Australia's new science minister

    As part of a reshuffle by new Prime Minister Malcolm Turnbull, lawyer and veteran politician Christopher Pyne was sworn in as Australia's science minister this week. Pyne had been serving as the conservative government's education minister. Many Australian researchers say they hope Pyne's appointment will mark a turn in policy under Turnbull, who ousted Tony Abbott on 15 September after an internal party uprising. “After the weirdness of Abbott and the obtuse ideology of the hard right, we all hope for a better day,” says Peter Doherty, an immunologist at the University of Melbourne and Nobel laureate who criticized the last government. As the newly minted minister for industry, innovation, and science, Pyne takes over from former industry and science minister Ian Macfarlane, who has been bumped entirely from Turnbull's ministerial team. http://scim.ag/AustSMPyne

    Three Q's

    PHOTO: ALEX CRICK

    Twenty artists have contributed sculptures to an auction organized by Cancer Research UK in an effort to raise money to complete the construction of the Francis Crick Institute, a biomedical research center in London. Cancer Research UK gave each artist a “blank slate”—a sculpture in the shape of a double helix—and asked them to use it to craft an answer to the question, “What's in your DNA?” Among the sculptures to be auctioned on 30 September at Christie's is one by artist Kindra Crick, the granddaughter of Francis Crick, entitled What Mad Pursuit. http://scim.ag/crickart

    Q:How did you build your sculpture?

    A:I was influenced by my grandparents, Francis and Odile Crick. My grandfather worked on elucidating the structure of DNA, and my grandmother drew the first image of DNA, used in the 1953 paper written with James Watson. In my art I try to express the wonder and the process of scientific inquiry, drawing on my backgrounds in molecular biology and in art.

    Q:What themes do you explore?

    A:In my sculpture, the DNA strand that is rising is this black, dusty, chalkboard with quickly scribbled notations. On the complementary strand, I have this vibrant blue, with a golden helix. I have these growing, abstracted forms that spread and mutate up and down the sculpture. It's an abstraction of cellular life … or infectious ideas, which metaphorically grow and mutate.

    Q:What else would you like to add?

    A:There's going to be another item at the auction. My father, Michael Crick, worked with Dr. J. Craig Venter at Human Longevity Inc. to create The Crick Genome Portrait, an atlas of my grandfather's genome. It's a linear map of the 23 chromosomes and also includes his mitochondrial DNA. It's a single edition piece of artwork, signed by Venter.

    Findings

    New virus may be widespread

    A dangerous tick-borne virus that first surfaced in humans in Missouri in 2009 appears to be common in wildlife across the central and eastern United States, according to a new study. Scientists believe the so-called Heartland virus is transmitted by the lone star tick, Amblyomma americanum. Last week, reporting in the journal Emerging Infectious Diseases, researchers at the Centers for Disease Control and Prevention in Fort Collins, Colorado, reported finding evidence of antibodies to the Heartland virus in blood samples from deer, raccoons, coyotes, and moose in 13 states from Maine to Texas. This, they suggest, means doctors should be on the lookout for human patients who might go undetected. But other researchers are not convinced, noting that the lone star tick doesn't occur in northern New England, and that the antibodies found there may be directed against some other agent. http://scim.ag/heartlandvir

  2. Mutation and Human Disease

    Can 23andMe have it all?

    1. Kelly Servick*

    23andMe analyzes its customers' DNA with a customized “SNP chip,” which uses fluorescent tags to identify 650,000 potential genetic variants.

    PHOTO: SPENCER LOWELL

    How much do your eyes water when cutting onions? Does fresh cilantro taste like soap to you? Do you have stretch marks on your hips, thighs, or the backs of your arms? Have you ever been diagnosed with brain cancer?

    Mail off your spit for a $99 genetic analysis from 23andMe, and you will get information about your ancestry, served up on a web account. You will also encounter a list of optional survey questions. A lot of survey questions. Some are quirky queries about your tastes and habits. Others are intimate probes into your experiences with disease and medicine.

    For the team of more than 30 geneticists and statisticians behind one of the world's largest genetic biobanks, the surveys are bread and butter, allowing them to pin down links between DNA markers and people's health, appearance, and bodily idiosyncrasies. New medical and physiological connections have been incorporated into the $99 analysis, adding value for customers. The formula has enabled the Silicon Valley firm to outlast most of its competitors and become a poster child for the fledgling field of direct-to-consumer genetic testing.

    23andMe suffered a major setback in 2013 when the U.S. Food and Drug Administration (FDA) warned the firm it was illegally returning health information using tests that the agency hadn't vetted. But even though the growth of its customer base slowed after the company pulled the health data from its personal genome service for new customers, 23andMe's research team pushed ahead. Today, the company has collected DNA from more than a million people. (That amounts to more than 2000 liters of saliva.) And its self-curious customers seem almost addicted to participating in research; they collectively answer about 2 million new survey questions every week as the company searches for new health-related DNA sequences.

    Gradually, a research group that started out analyzing the genetics of freckles and the sneeze reflex has moved into deeper scientific waters: the hunt for disease-related genes that could make good drug targets. “It's really been an evolution from, ‘Tell us whether you're a morning person or not,’ to ‘Let's solve disease,’” says Joyce Tung, 23andMe's director of research.

    The company says it has made roughly 30 deals with pharmaceutical and biotech companies seeking access to its database—14 of them last year, most of them undisclosed. “There's no other group that has as many samples,” Tim Behrens, Genentech's senior director of human genetics in San Francisco, says of 23andMe's database of Parkinson's disease patients, which Genentech paid an initial $10 million to explore, with the promise of up to $50 million more.

    23andMe went even further in March, when it announced that it would hire a therapeutics team and begin drug discovery efforts of its own. That's a move even some of its champions see as audacious. “Their main contribution, to me, has been democratization of genomics,” says Eric Topol, a physician and geneticist at the Scripps Research Institute in San Diego, California, who studies digital health technologies. “This is a very different look, and a pivot. Maybe they'll accomplish it, but there are a lot of entities out there that are trying to develop drugs.”

    23ANDME SITS ALONG THE CALTRAIN tracks in downtown Mountain View, in a four-story glass cube that doesn't quite feel lived in yet. The company logo, a whimsical doodle of pink and green crisscrossed chromosomes, is still taped above the entrance, printed across four sheets of letter-sized white paper. On this summer morning, Anne Wojcicki is breezing around the deserted staff cafeteria in flip flops, preparing a hard-boiled egg. A row of treadmills outfitted with standing desks sits idle on the other side of the room.

    This is a building that Wojcicki, 23andMe's co-founder and CEO, intends to grow into. In May, the company abandoned its previous nest on the campus of Google, Mountain View's most famous corporate resident. Google was both an early investor in 23andMe and an influence on Wojcicki's vision. A biologist and health care investment analyst, she launched the company in 2006 with biologist Linda Avey and financial executive Paul Cusenza based on what she calls a social mission to “integrate genetic information into the world,” and on the theory that collecting DNA and health information from every person could turn disease research into “a data problem.”

    Tung, lured away from academia after a postdoc at Stanford University in Palo Alto, in which she studied the genetics of pigmentation in mice and people, was among the company's first recruits. At the time, skepticism abounded about the firm's vision of gleaning valuable data from a relatively cheap genetic test and an online survey. “My postdoc adviser was like ‘Well, it's nice that you guys want to do research, but you're never going to find anything real—like medical, or anything like that,’” she recalls.

    In a glass-walled meeting room upstairs from the cafeteria, Tung's thunderous laugh rings out at unpredictable moments. When asked what makes the database valuable for researchers now, she stretches her arms dramatically and exclaims: “It's big!”

    23andMe has extracted genetic information from its growing stockpile of samples by testing them for single nucleotide polymorphisms (SNPs, pronounced “snips”), relatively common variations in a single DNA base pair. DNA from each customer's saliva is broken into fragments and washed over a “SNP chip”—a credit card–sized plate of microscopic silica beads covered in DNA probes. Each single-stranded probe grabs the DNA fragment with a complementary sequence, leaving exposed the DNA letter at a location of interest. Then, free-floating nucleotides with fluorescent tags bind to and reveal the identity of that SNP.

    23andMe's scientific leadership (left to right): research director Joyce Tung, principal scientist David Hinds, senior research director Joanna Mountain, Chief Executive Officer Anne Wojcicki, platform architect Arnab Chowdry, and head of therapeutics Richard Scheller.

    PHOTO: DEANNE FITZMAURICE

    Biophysicist Arnab Chowdry, responsible for 23andMe's technology platforms, is always trying to squeeze more information from the limited chip real estate. The current model detects 650,000 SNPs, but using publicly available reference genomes, the team can also predict more than 14 million other variants that are likely to be inherited alongside those tested directly.

    For its customers, 23andMe uses the SNPs to predict ancestry and other traits. The analysis can say what percentage of a customer's DNA originates from a population in Northern Europe, for example. And until 2013, it could warn about potentially elevated risk of conditions including Parkinson's disease, breast cancer, and cardiomy-opathy. (One of the company's initial analyses famously informed Sergey Brin, Google's co-founder and Wojcicki's ex-husband, that he has a gene that substantially increases his risk of Parkinson's; Brin, who publicly disclosed that finding, has since become a major funder of research into the disease.)

    Using survey responses from more than 800,000 customers who have agreed to take part in the research, 23andMe's scientists look for new links between SNPs and physical traits, or phenotypes. Their stock-intrade is the genomewide association study (GWAS): They group customers who share a phenotype—haters of cilantro, or those with type 2 diabetes—and identify SNPs that occur more frequently in that group than a control.

    Since 2009, 23andMe has also provided its personal genome service for free to certain patient populations in exchange for their participation in more focused, disease-specific surveys. Its Parkinson's disease “community” now includes 12,000 people; smaller projects have targeted sarcoma, myeloproliferative neoplasms—a group of rare bone marrow diseases—inflammatory bowel disease, and lupus.

    All of the survey responses and genotypes are stripped of identifying information to protect privacy. And the participants readily volunteer more data. When the team sends out a new survey question, Tung says, it's not unusual to get millions of fresh data points within 24 hours. That responsiveness sets the 23andMe cohort apart from the average subjects recruited into a research study, who are often “ready to quit at the drop of a hat,” says George Church, a geneticist at Harvard University and a member of 23andMe's scientific advisory board. “The 23andMe cohort—for whatever reason, they're highly engaged.”

    23andMe has cultivated this community carefully. Its researchers devote part of their time to studies that will pique customer interest, but that are unlikely to win grants from the National Institutes of Health. They've found four SNPs associated with a tendency to develop stretch marks, for example, and observed that a variant nestled among olfactory receptor genes turns cilantro soapy for certain tasters.

    Yet the online surveys that have helped 23andMe's database flourish have also made it a questionable source of information in the eyes of some disease researchers. “It was met with incredible skepticism,” says Mark Cookson, a cell biologist studying Parkinson's disease at the National Institute on Aging's laboratory of neurogenetics in Bethesda, Maryland. Casual questionnaires seemed to many to be a poor substitute for a medical exam or a patient's health records. “The clinical guys were saying, ‘Well hang on, if you don't know that someone has Parkinson's, how will you get clean data sets?’”

    A cohort of customersCREDITS: (DIAGRAM) G. GRULLÓN/SCIENCE; (DATA) 23ANDME

    Cookson says that skepticism has faded somewhat. For one thing, the search for statistically significant associations between a trait and a DNA sequence “is a numbers game,” he says, and with enough responses, concerns about reliability “melt a little bit.” And 23andMe has shown in several studies that the associations its researchers turn up match results from other groups.

    By 2012, 23andMe had more than 180,000 customers, and had contributed to studies identifying new genetic associations for freckles, curly hair, alopecia, Parkinson's disease, and hypothyroidism. At that year's annual gathering of the American Society of Human Genetics (ASHG), 23andMe's principal scientist, statistical geneticist David Hinds, noticed that his status had changed. “Between one ASHG meeting and the next, it went from largely disinterest in what we were doing—thinking it was not very relevant—to being approached by lots of people who were interested in collaborating with us, getting access to our data.” As of this summer, the 23andMe team had put out more than 30 papers, many of them in collaboration with academic labs.

    The 23andMe team has also demonstrated—retrospectively—that its database can help guide drug discovery. At the 2014 ASHG meeting, they presented an analysis of 2751 candidate drugs showing that 23andMe data could predict which ones succeeded in clinical trials. They observed a nearly twofold increase in the odds that a drug would ultimately be approved by FDA if the 23andMe database revealed an association between the disease trait and a SNP somewhere on or around the gene whose product the drug targeted, compared with a drug without a genetic association.

    But association studies alone are feeble drug discovery tools. The SNPs linked to a disease are often just markers for a nearby region of the genome where the real disease-influencing mutation lies. Association studies also fail to lay out how illness might arise from a mutation, or how targeting a gene product might affect the body. Until recently, a completed GWAS was “sort of the end of the road” for the 23andMe team, Hinds says. “We were pretty limited, because we could find associations, but we're not set up to do biology.”

    INDEED, THE COMPANY'S WIDE-OPEN office space is more suggestive of a generic Silicon Valley internet startup than a biotech lab. Headset-clad customer service representatives field calls at their standing desks. “Welcome to our gene pool” balloons flag the workstations of new hires.

    But Richard Scheller, the most conspicuous new hire, is here to do biology. Last December, on the same day the 61-year-old drug discovery veteran announced his retirement from a 15-year career at Genentech, he got an email from Wojcicki. “I knew he had not retired,” she says. “I grew up on Stanford's campus. I know his phenotype. That man is never going to stop.” Wojcicki says she had long been debating whether the company should do its own drug discovery, and Scheller's enthusiasm for the idea pushed her over the edge.

    “It's really been an evolution from, ‘Tell us whether you're a morning person or not,’ to ‘Let's solve disease.’”

    Joyce Tung, 23andMe's director of research

    PHOTO: DEANNE FITZMAURICE

    At 23andMe, Scheller is on foreign ground. The informatics experts on Tung's team are not his scientific ilk. “They use algorithms with famous statisticians' names behind them, and I have absolutely no idea what they're talking about,” he says.

    Drug discovery is new territory for 23andMe's core research team, too. The group has long aspired to influence how drugs are developed, says Chowdry, but “I don't think most of us really imagined that we would ever bring it in-house.” Still, he quickly got on board. “If we actually believe that there's value in the database—which all of us do—having it in-house means that we get a bigger chunk of the value.”

    As head of the new therapeutics group, Scheller plans to hire about 25 scientists by sometime next year, and to double the team again in another year. He is checking out potential lab space in South San Francisco and talking to contract labs. Slowly, 23andMe may start to look more like a typical biotech firm, doing the dicey work of drug development: finding candidate genes, screening compounds that might interact with them or their proteins, testing the compounds in animals and then in people.

    The company has revealed almost nothing about what its new group will pursue. The only area definitively ruled out is neuropsychiatric disease—because of its “particular complexities,” says Scheller, who headed a Stanford neuroscience lab before joining Genentech. He also says that 23andMe's first drug candidates will likely be antibodies that target disease-related molecules, because they are easier to make than small molecule drugs.

    Running a drug discovery program will mean going beyond 23andMe's old standby, the SNP chip, to partial- or full-genome sequencing. SNP chips are generally geared toward flagging common mutations—occurring in roughly 3% to 5% of the population—and these have so far failed to explain a large percentage of a person's genetic risk for common diseases. 23andMe's chip has been tweaked to include many rarer SNPs, but it can't physically accommodate hundreds of uncommon variants for every given gene. And it can only probe for known mutations—not reveal new ones.

    Newer efforts to scan huge collections of DNA for disease-causing mutations—including geneticist J. Craig Venter's San Diego–based Human Longevity, Inc. and the 1-million-person cohort launched in January as part of President Obama's precision medicine initiative—are betting on large-scale genome sequencing instead (see sidebar, p. 1475). As DNA sequencing gets cheaper, “a whole realm of genetic variation that we've just not had access to is possible,” says Genentech's Behrens, who is heading an effort to sequence the genomes of 3000 Parkinson's patients in the 23andMe database. He says the company decided to ramp up its sequencing projects when the cost dipped to about $1600 last year.

    23andMe has preserved many other saliva samples, with the customers' permission, and they are ripe for fuller sequencing. But $1600 is still astronomical in the context of 23andMe's model of $99 genotyping for the masses. “Some people ask me, ‘Wouldn't it be much better if you just did sequences?’” Scheller says. “That would be $2 billion, and most of that sequence would be completely uninteresting to us.” Instead, he intends to use SNPs to identify interesting regions of the genome, and then use sequencing to zoom in on those regions in certain patients. (Wojcicki says the company will eventually integrate sequencing into the personal analysis it provides to consumers.)

    The bigger hurdle facing 23andMe is the one confronting any group with ambitions of genome-based drug development, Cookson says: the challenge of moving from a DNA region suspected of having a disease connection to a druggable target. “Can they get smart enough to really make contributions to the next stage? … I don't know,” he says, “But not that many people have really done that, so it would be churlish of me to say, ‘Oh, those guys will never do it.’ I haven't done it either.”

    FOR ALL THE BUZZ around 23andMe's new foray into therapeutics, much of Wojcicki's energy is focused on a more immediate business goal: relaunching its consumer health service. That service was shut down after FDA warned that the company hadn't demonstrated that its health-related tests were properly validated, or responsibly communicated to customers, who might be confused or alarmed by the estimates of disease risk.

    Wojcicki says the run-in with the agency arose from a poor understanding of government regulation and what was expected. 23andMe is now working with FDA to bring its health reports for customers back by the end of the year. In February, the agency approved 23andMe's test for whether a person carries a recessive mutation that could give offspring Bloom syndrome, a rare disease that affects the stability of DNA structure and elevates the risk of cancer. FDA also exempted other such carrier tests from its premarket review process, meaning the company won't have to seek approval before providing those results to customers. But it's not clear whether or when 23andMe will resume providing other kinds of health information, such as drug responses and disease risks. “There's going to be a path forward,” Wojcicki says, but “we might have to make certain kinds of compromises.”

    Meanwhile, the company is quick to dismiss the idea that it's shifting focus away from spit kits—and the customers whose willingness to expound on their experiences with cilantro and cancer built the drug discovery platform in the first place. “We make a consumer product,” Tung says. Part of her responsibility, she says, is to figure out “what is the next coolest thing that we can provide back to our customers?”

    In that light, there's a certain “inevitable logic” in a consumer genetics company turning to drug discovery, says Michael Eisen, a biologist at the University of California, Berkeley, and a member of 23andMe's scientific advisory board. “If there's really a long-term future in this, if it's anything more than just a curiosity for people, we've got to be able to use people's genetic information to provide them with actual treatment.”

    • * in Mountain View, California

  3. Mutation and Human Disease

    Who has your DNA—or wants it

    1. Jocelyn Kaiser

    Science compiled a list of the growing number of research databases that contain DNA from up to a million volunteers.

    The UK Biobank depends on robotic equipment to help store and access its many DNA samples.

    PHOTO: © PHIL NOBLE/REUTERS

    More and more groups are amassing computer server–busting amounts of human DNA. Science's informal survey found at least 17 biobanks that hold—or plan to hold—genomic data on 75,000 or more people. The data range from scans of common mutations known as single nucleotide polymorphisms (SNPs) to the protein-coding portions of the genome (exomes) to whole genomes.

    23andME

    SIZE: >1 million GENETIC DATA: SNPs

    This popular personal genomics company now hopes to apply its data to drug discovery (see main story, p. 1472).

    ANCESTRY.COM

    SIZE: >1 million GENETIC DATA: SNPs

    This genealogy firm now has a collaboration with the Google-funded biotech Calico to look for longevity genes.

    HUMAN LONGEVITY, INC.

    SIZE: 1 million planned GENETIC DATA: whole genomes

    Founded by genome pioneer Craig Venter, this company plans to sequence 100,000 people a year to look for aging-related genes.

    100K WELLNESS PROJECT

    SIZE: 107 (100,OOO planned) GENETIC DATA: whole genomes

    Led by another sequencing leader, Leroy Hood, this project is taking a systems approach to genetics and health.

    MILLION VETERAN PROGRAM

    SIZE: 390,000 (1 million planned) GENETIC DATA: SNPs, exomes, whole genomes

    This U.S. Department of Defense–funded effort is probing the genetics of kidney and heart disease and substance abuse.

    U.S. NATIONAL RESEARCH COHORT

    SIZE: 1 million planned GENETIC DATA: to be determined

    Part of President Obama's Precision Medicine Initiative, this project will use genetics to tailor health care to individuals.

    UK BIOBANK

    SIZE: 500,000 GENETIC DATA: SNPs

    Study of middle-aged British is probing links between lifestyle, genes, and common diseases.

    100,000 GENOMES PROJECT

    SIZE: 5500 (75,000 normal + 25,000 tumor genes planned) GENETIC DATA: whole genomes

    This U.K.-funded project focusing on cancer and rare diseases aims to integrate whole genomes into clinical care.

    deCODE GENETICS

    SIZE: 140,000 GENETIC DATA: SNPs, whole genomes

    Now owned by Amgen, this pioneering Icelandic company hunted for disease-related genes in the island country.

    KAISER-PERMANENTE BIOBANK

    SIZE: 200,000 (500,000 planned) GENETIC DATA: SNPs

    This health maintenance organization has published on telomeres and disease risks.

    GEISINGER MYCODE

    SIZE: 60,000 (250,000 planned) GENETIC DATA: exomes

    Geisinger, a Pennsylvania health care provider, works with Regeneron Pharmaceuticals to study DNA links to disease.

    VANDERBILT'S BIOVU

    SIZE: 192,000 GENETIC DATA: SNPs

    Focused on genes that affect common diseases and drug response, BioVU data have been permanently deidentified.

    BIOBANK JAPAN

    SIZE: 200,000 GENETIC DATA: SNPs

    This study collected DNA from volunteers between 2003 and 2007 and is now looking at genetics of common diseases.

    CHINA KADOORIE BIOBANK

    SIZE: 510,000 GENETIC DATA: SNPs

    This study is probing links between genetics, lifestyle and common diseases.

    EAST LONDON GENES & HEALTH

    SIZE: 100,000 planned GENETIC DATA: exomes

    One aim is to find healthy “human knockouts”—people who lack a specific gene—in a population in which marrying relatives is common.

    SAUDI HUMAN GENOME PROGRAM

    SIZE: 100,000 planned GENETIC DATA: exomes

    One aim of this national project is to find genes underlying rare inherited conditions.

    CHILDREN'S HOSPITAL OF PHILADELPHIA

    SIZE: 100,000 GENETIC DATA: SNPs, exomes

    The world's largest pediatric biorepository connects DNA to the hospital's health records for studies of childhood diseases.

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