Picking up Evolution's Beat

NEWSFOCUS PROFILE: PARDIS SABETI Florida, with a large extended family. She traces her academic success to her Picking Up Evolution’s Beat on April 24, 2008 early life in this close-knit clan. “My mother Pardis Sabeti mixes geek cool with hot science as she studies how human created a summer camp in our house, where populations have evolved to resist malaria and Lassa fever she would teach the children and make us do book reports. And my sister, who is 2 years CAMBRIDGE, MASSACHUSETTS—Over the Stevie Wonder, and Meryl Streep), and CNN older than me, would teach me and my past 72 hours, Pardis Sabeti has managed named her one of eight “geniuses who will cousin what she had learned in school.” only 2 hours of sleep each night, most of change your life.” Sabeti says mathematics was her first love. them inside a crumpled blue sleeping bag Sabeti also seems to have a genius for Her high-energy personality, she adds, she keeps under a desk at the Broad Institute raising money. While still a postdoc, her appeared in those early years. “I’m a hyper www.sciencemag.org Center for Genome Research in Cambridge, own grants totaled more than $600,000, and person,” she says. “My parents always told Massachusetts. Sabeti, who burst on the sci- she is currently a co-investigator on a me to relax.” entific scene in 2002 with a novel test for $2 million Bill and Melinda Gates Founda- Reich, who met Sabeti when they were natural selection in the human genome, has tion grant. She was recently hired as a Har- both grad students at Oxford, says she has been racing to meet the submission deadline vard assistant professor, turning down offers always been “very driven.” Her habit of for a National Institutes of Health (NIH) from several other leading universities. pulling all-nighters was well-established by grant to support her research on the evolu- And then there’s the band: She’s the lead then, recalls Hans Ackerman, a fellow Downloaded from tion of resistance to malaria and Lassa fever. singer in the Boston-based alternative Rhodes scholar who is now a medical fellow Also in her schedule this year: serving as a group Thousand Days, which plays gigs up at NIH in Bethesda, Maryland. “I would panelist at the World Economic Forum in and down the East Coast and has released come into the lab and find her asleep under Davos, Switzerland; a research trip to three albums. Sabeti’s singing voice is her desk after a full night of doing PCRs.” Africa; speaking to young women about “sweet and sexy,” wrote one music Why does she work so hard? “I guess careers in science; and writing songs and reviewer, adding wryly that “it’s nice to I just want to make my parents proud of recording for her pop/rock band. know she has a successful back-up career me,” she says. To manage all this, Sabeti, 32, has been in case her attempts at winning the Nobel Although Sabeti’s workaholic ways have sleeping under desks for much of her rela- Prize don’t pan out.” brought her scientific success, Broad Insti- tively short career. The petite Iranian-American The band may boost Sabeti’s visibility, tute Director Eric Lander and others also with a toothy smile has cut a wide swath but it’s her scientific drive that elicits note her charisma and her efforts to reach through the research world, racking up enthusiasm from her colleagues. Broad out to the community. For example, as an awards and honors at a dizzying pace: a Institute geneticist David Reich, who has undergrad at the Massachusetts Institute of Rhodes scholarship at Oxford University, a worked closely with Sabeti, sums her up Technology, Sabeti founded a still-thriving L’Oreal Women in Science award, and this way: “She is a very cool person but also program to help incoming freshmen summa cum laude honors at Harvard Med- sort of a nerd.” develop leadership skills. She also worked ical School, to name a few. She’s also made a Sabeti was born in Tehran, Iran, where with RNA pioneer David Bartel, who name in the wider world: The London Daily her father was a high-ranking official in the recalls only one glitch in their association: Telegraph recently called her one of the “top Shah’s government. He sought asylum in the “She gave out the lab phone number as the 100 living geniuses” (she tied for 49th place United States shortly before the 1979 revo- contact” for the leadership program. So with Henry Kissinger, Richard Branson, lution, and Sabeti grew up in Orlando, many students called, “we had to change the CREDITS (LEFT TO RIGHT): NISHA BROODIE; CHIUN-KAI SHIH; BRIAN BERNIER 442 25 APRIL 2008 VOL 320 SCIENCE www.sciencemag.org Published by AAAS NEWSFOCUS Hyperactive. Pardis Sabeti—malaria was made. “This test is one of the most researcher, role model for young scientists, exciting developments in the field in the and rock performer—keeps on the move. past few years,” says Chris Tyler-Smith, a genome researcher at the Wellcome Trust had developed dozens of tests for Sanger Institute in Hinxton, U.K. Evolu- detecting “signatures” of natural selec- tionary biologist Martin Kreitman of the tion in the genome (Science, 16 June University of Chicago, who had developed 2006, p. 1614), but they had very low a similar test but was beaten into print by a power to detect more recent evolution- few months, says he has “nothing but ary changes, particularly during the last praise for her contributions.” He adds that 10,000 years, when many of the diseases Sabeti’s most recent contribution, a that afflict humankind, including genome-wide search for selected genes in malaria, arose. collaboration with Lander, the Interna- Working with Reich and with her doc- tional HapMap Project, and others, “is a toral adviser, Dominic Kwiatkowski of beautiful piece of work.” Oxford University in the U.K., Sabeti hit Lander says Sabeti’s test anticipated the on a novel way of combining two types of detailed information that the HapMap would genetic information to create a more pow- later make available. “Pardis has a very erful test: the frequency of a particular energetic imagination,” he says. “Not many variation and the structure of the genome people think about what they would do if surrounding it. Normally, variants are they had data they don’t yet have.” shuffled in a random fashion across the The genome-wide study, published in number,” says Bartel. genome. But if a particular variant is the Nature last October, identified two genes Sabeti also took the lead at Harvard Med- target of recent natural selection, its rapid called LARGE and DMD that are involved in on April 24, 2008 ical School, producing a lighthearted orien- increase in frequency can create so-called Lassa fever infection and show strong sig- tation video for first-year students, featuring haplotype blocks, groups of genes that have nals of natural selection in West Africans. prancing, juggling, balloon-wielding stu- “hitchhiked” along for the Darwinian ride Despite striking about 300,000 people each dents and faculty. She now presents this (see graphic, below). Some earlier selection year and killing 20,000 of them, Lassa fever video in person to each entering class. In tests looked at both variant frequencies and has been neglected by public health experts. fact, she’s still making videos. One will be haplotypes in humans, but they weren’t very Sabeti hopes to use her test to identify vari- shown during a N OVA profile of her to be sensitive. Sabeti used her math skills to ants protective against the disease, which aired in July, featuring appearances by devise a genetic “clock,” based on haplotype could eventually help in the search for new researchers including Lander, as well as structure, that could reveal whether recent, therapies and a vaccine. Looking at Lassa’s www.sciencemag.org Sabeti’s music. evolutionary history is “a very Sabeti’s band, Thousand Before selection After selection innovative approach” that Days—which describes itself on “might breathe some new life MySpace as a “love child” into field research” into the dis- between the rock group U2 and ease, says Lassa fever expert the pop band Mazzy Star—has Joseph McCormick of the been a regular presence on the University of Texas School of Downloaded from New England music scene for Public Health in Brownsville, several years. Sabeti writes her who is a consultant to Sabeti own songs, including one called on the project. “Coming Up” that seems a At the moment, Sabeti seems metaphor for her career. She says to be flying high. But some col- she “loves the creative spirit” in leagues are concerned that her both music and science but is fame could set her up for a big “more at home” in science. fall if her hyper pace slackens. “I Given her scientific schedule, Hitchhikers. When a genetic variant favored by selection (pink bar) spreads worry that too many expecta- she hasn’t found time to perform rapidly in a population, other variants linked to it come along for the ride. tions are being put on Pardis,” in recent months. says one researcher. But Nancy She continues to focus on the research high-frequency variants were due to selec- Oriol, Harvard Medical School’s dean of she began at Oxford: teasing out signs of tion or just chance—greatly strengthening students, isn’t worried. “If you are motivated selection in the human genome.

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