The
New Science
Brain
of the
NGM.COM FEBRUARY 2014
GARRISON KEILLOR: MY HOMETOWN
When there is the potential
for violence, crowds can
have a calming influence.
page 134
58
Olivia Rowe keeps pigeons. Her ...
An Elephant Never Runs Out
The mammal’s six sets of chompers
are enough for a lifetime of chewing.
Rooftop Tsunami Refuge
...
2X POINTS ON TRAVEL AND
DINING AT RESTAURANTS.
Purchase and balance transfer APR is 15.24% variable. Cash advances and ove...

EDITOR’S NOTE
PHOTO: ERIKA LARSEN
Keillor likes driving rural
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evening,” says photogra-
pher Erika ...
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O Order prints of select National Geographic photos online at NationalGeographicArt.com.O Order prints of select National ...
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  • 1. The New Science Brain of the NGM.COM FEBRUARY 2014 GARRISON KEILLOR: MY HOMETOWN
  • 2. When there is the potential for violence, crowds can have a calming influence. page 134 58 Olivia Rowe keeps pigeons. Her sisters prefer horses and sheep. They are the great-granddaughters of Garrison Keillor’s Aunt Josephine. ERIKALARSEN February 2014 Secrets of the Brain “It’ll take me a moment to locate your brain,” the scientist says. With new technologies, he’s able to shed light on life’s great unsolved mystery: how the human mind really works. By Carl Zimmer Photographs by Robert Clark There’s No Place Like Home When a man lives in one place for most of his life, he doesn’t need GPS. He is guided by memories of boyhood bike rides, the ever present Mississippi, and the undeniable power of rhubarb. By Garrison Keillor Photographs by Erika Larsen Brunelleschi’s Dome How did a hot-tempered goldsmith create the miraculous edifice in Florence? By Tom Mueller Photographs by Dave Yoder Special Poster: The Cathedral of Florence and Redefining the Dome Gold Fever in theYukon Prospectors invade Canada’s great wilderness. By Tom Clynes Photographs by Paul Nicklen Karma of the Crowd Millions of pilgrims flock to a Hindu gathering in India—and find inner peace in numbers. By Laura Spinney Photographs by Alex Webb 28 58 84 96 120
  • 3. An Elephant Never Runs Out The mammal’s six sets of chompers are enough for a lifetime of chewing. Rooftop Tsunami Refuge It will be built atop a new school in Westport, Washington. The Benefit of Pruney Digits The ridges could have helped ancient hu- mans catch fish or clamber over slick rocks. Fly Like an Owl A barn owl barely flaps. Engineers aim to mimic its wings to make quieter aircraft. Quinoa Conquers the World The high-protein Andean seed could help fight hunger—if we can grow enough of it. The 50-Million-Year-Old Bird A newly discovered fossil is thought to be a cousin of the hummingbird and the swift. Why Women Remember Faces They’re better scanners than men. 18 136 138 4 6 8 10 16 Editor’s Note Letters Survival Guide VISIONS NG Connect The Moment Found On the Cover The colorized fibers connect different regions of the brain. Magnetic resonance image by Van Wedeen and L. L. Wald, Martinos Center for Biomedical Imaging, Human Connectome Project Your Shot ART: FERNANDO G. BAPTISTA, NGM STAFF DIGITAL EDITIONS February 4 NEXT Contributions to the National Geographic Society are tax deductible under Section 501(c)(3) of the U.S. tax code. Copyright © 2014 National Geographic Society All rights reserved. National Geographic and Yellow Border: Registered Trademarks ® Marcas Registradas. National Geographic assumes no responsibility for unsolicited materials. Printed in U.S.A. Subscriptions For subscriptions, gift memberships, or changes of address, contact Customer Service at ngmservice.com or call 1-800-NGS-LINE (647-5463). Outside the U.S. and Canada please call +1-813-979-6845. Please recycle. PRINTED ON 100% PEFC-CERTIFIED PAPER Human Brain Map Audio Slide Show Brain imaging guides a surgeon’s work. Florence’s Cathedral 360° View You won’t even need to crane your neck. National Geographic is available on the iPad, the Kindle Fire, and the iPhone.
  • 4. 2X POINTS ON TRAVEL AND DINING AT RESTAURANTS. Purchase and balance transfer APR is 15.24% variable. Cash advances and overdraft advances APR is 19.24% variable. Penalty APR of 29.99% variable. Variable APRs change with the market based on the Prime Rate, which was 3.25% on 08/15/13. Annual fee: $0 introductory fee the first year. After that, $95. Minimum Interest Charge: None. Balance Transfer Fee: 3% of the amount of each transaction, but not less than $5. Note: This account may not be eligible for balance transfers. Cash Advance Fee: 5% of the amount of each advance, but not less than $10. Foreign Transaction Fee: None. Credit cards are issued by Chase Bank USA, N.A. Subject to credit approval. You must have a valid permanent home address within the 50 United States or the District of Columbia. Restrictions and limitations apply. Offer subject to change. See chase.com/sapphire for pricing and rewards details. © 2014 JPMorgan Chase & Co. INTRO ANNUAL FEE OF $0 THE FIRST YEAR, THEN $95 SEE FRESH IN A NEW WAY. Chase Sapphire Preferred® chase.com/sapphire
  • 5.  EDITOR’S NOTE PHOTO: ERIKA LARSEN Keillor likes driving rural Minnesota roads. “One evening,” says photogra- pher Erika Larsen, “I went along.” She shot this near Buffalo Lake. A few years ago I was in the middle of a meeting when one of our senior editors ushered in a tall man with a large, expressive face, wearing owlish glasses and dressed in a khaki suit. In a voice once described as “a baritone that seems precision-engineered to narrate a documentary about glaciers,” he addressed the group and pitched a story idea. He wanted, he told us, to do a story about his own “personal geography.” That man was the author, radio personality, and story- teller Garrison Keillor, and there could be only one answer to the appeal. Keillor’s reminiscence, “There’s No Place Like Home,” is the result. You might say it’s a piece he’s been writing his whole life. Ostensibly, it’s about Minneapolis-St. Paul. He conjures word pictures of neighborhoods with stucco bungalows, lakes with names like Minnetonka and Nokomis, and the sweep of the rocket tail fins on a white Cadillac convertible. But it’s also something different and very special. Keillor’s piece is an interior geog- raphy; it’s the map of a man’s soul. In summoning up the Twin Cities of his youth and adulthood, he talks about what it means to be not just from a place, but of a place. Early on, he says, he realized that Minneapolis-St. Paul was a much better place than Manhat- tan in which to be an original. In his essay Keillor tells us why where you come from matters. “If you want to know the truth,” he says, “I feel understood there.” A Prairie Home It’s a piece he’s been writing his whole life.
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  • 7. national geographic february  NATIONAL GEOGRAPHIC MAGAZINE EDITOR IN CHIEF Chris Johns CREATIVE DIRECTOR Bill Marr EXECUTIVE EDITORS Dennis R. Dimick (Environment), Matt Mansfield (Digital Content), Jamie Shreeve (Science) DIRECTORS OF PHOTOGRAPHY Keith Jenkins, Sarah Leen MANAGING EDITOR David Brindley TEXT DEPUTY DIRECTOR: Marc Silver. STORY DEVELOPMENT EDITOR: Barbara Paulsen ARTICLES EDITOR: Oliver Payne SENIOR EDITORS: Robert Kunzig (Environment), Jane Vessels (Graphics). SENIOR EDITOR AT LARGE: Victoria Pope. EDITOR AT LARGE: Cathy Newman. FEATURES EDITORS: Peter Gwin (Expeditions), Glenn Oeland. EDITOR MISSION PROJECTS: Hannah Bloch. ASSOCIATE EDITORS: Jeremy Berlin, Amanda B. Fiegl. SENIOR WRITERS: Tom O’Neill, Rachel Hartigan Shea, A. R. Williams ADMINISTRATION: Nicholas Mott; Katia Andreassi, Ashleigh N. DeLuca CONTRIBUTING WRITERS: Caroline Alexander, Don Belt, Joel K. Bourne, Jr., Chip Brown, Bryan Christy, Robert Draper, Cynthia Gorney, Peter Hessler, Jennifer S. Holland, Mark Jenkins, Peter Miller, David Quammen DEPARTMENTS DIRECTOR: Margaret G. Zackowitz EDITORS: Johnna Rizzo, Daniel Stone. ADMINISTRATION: Catherine Zuckerman PHOTOGRAPHY DEPUTY DIRECTOR: Ken Geiger SENIOR EDITORS: Bill Douthitt (Special Editions), Kathy Moran (Natural History), Kurt Mutchler (Science), Susan Welchman. EDITOR AT LARGE: Michael Nichols SENIOR PHOTO EDITORS: Pamela Chen, Alice Gabriner, Kim Hubbard, Todd James, Elizabeth Krist, Sadie Quarrier. PHOTO EDITOR: Jeanne M. Modderman. RESEARCH EDITOR: Mary McPeak. STAFF PHOTOGRAPHER: Mark Thiessen. STUDIO: Rebecca Hale. DIGITAL IMAGING: Edward Samuel, Evan Wilder. PHOTO ENGINEERING: Walter Boggs, David Mathews, Kenji Yamaguchi. RIGHTS MANAGER: Elizabeth Grady. ADMINISTRATION: Jenny Trucano; Sherry L. 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NATIONAL ADVERTISING DIRECTOR: Robert Amberg. VICE PRESIDENT MARKETING: Jenifer Berman. VICE PRESIDENT BUSINESS AND OPERATIONS: Margaret Schmidt. NATIONAL MANAGER: Tammy Abraham INTERNATIONAL MANAGING DIRECTOR: Charlie Attenborough. DIRECTORS: Nadine Heggie (International), Rebecca Hill (Marketing), David Middis (British Isles) EXECUTIVE VICE PRESIDENT WORLDWIDE CONSUMER MARKETING AND MANUFACTURING: Terrence Day VICE PRESIDENTS: John MacKethan (Financial Planning and Retail Sales), John A. Seeley (International). DIRECTORS: Christina C. Alberghini (Member Services), Anne Barker (Renewals), Richard Brown (New Business)
  • 8. “I can think of no one better qualified to guide [readers] to health, healing, and wholeness.” —Andrew Weil, M.D. Take Charge of Your Health! W ant to take health care into your own hands? Steer clear of hospitals and doctors’ offices? Cut back on over-the-counter and prescription drugs and find milder, more natural ways to get well? Then this is the book for you. Tieraona Low Dog, M.D., integrative physician and expert in natural medicine, has collected her favorite remedies and recipes—tried and true, for children and adults, the ones she has used in her own home over the years—and shares them, along with wise, practical advice on when to call the doctor and when to stay put and use your own resources to get healthy at home. Also available from National Geographic LIFE MEDICINE IS YOUR BEST “A must-read for anyone who cares about optimal health.” JOE & TERRY GRAEDON OF THE PEOPLE’S PHARMACY FOREWORD BY ANDREW WEIL,M.D. A Woman’s GuidetoHealth, Healing,and Wholeness atEveryAge AVAILABLE WHEREVER BOOKS ARE SOLD nationalgeographic.com/books Like us on Facebook.com: Nat Geo Books Follow us on Twitter.com: @NatGeoBooks ©2014NationalGeographicSociety
  • 9. October 2013 “ThecoverphotographofSharbatGu la proves her to be THE WORLD’S MOSTBEAUTIFULFEMALEofanyageandtime.” another pair of eyesthatw ill CAPTURE MY ATTENTION like those.” “I do not think Iwilleverse e “It INVOKES FEELINGS never experienced from any other painting, sculpture, or photograph.” “I couldn’t stop looking, trying to understand what s he was feeling behind those C APTIVATING GREEN EYES.”  national geographic February  FEEDBACK Readers shared their thoughts on what makes the Afghan Girl so memorable. Corrections OCTOBER 2013, THE PRICE OF PRECIOUS The graphic on page 56 is incorrectly labeled. It should read “Number of personal electronics owned by adults in the U.S.” In addition, five million is the metropolitan area population of Atlanta, not the population of the city proper. Reading Sharbat Gula’s story and learning about her life helped me understand why I could never forget her face. I could see the determi- nation and fear in her eyes, a combination of vulnerability and strength that is so difficult to capture. This photograph by Steve McCurry is a reminder of human endurance regardless of gender, age, or culture. CRISTINA GOSSEREZ-SEELYE Weston, Florida Enough of the Afghan Girl already. We don’t want to see her anymore. MARC BERNSTEIN New York, New York With banks of yellow-spine mag- azines on the shelves behind me, dating back to the days of Koda- chrome and before, at the age of 84 I doubted that renewing my annual subscription would still inspire my photographic and world interests. Then your October Photo Issue arrived. Thank you for a new lease of life. HARRY BARKER Lancashire, England Before the Civil War, when the art form was still in its infancy, photographs were seen as inherently unsuitable for record- ing events because of the mere split second of captured time. Lithographs were far more popular because they could be crafted to suit current tastes in public memory. The modern mentality is far different. BRIAN DOLPHIN Columbia, South Carolina To Robert Draper: I’m sorry. You are wrong. You are not “just one of the writers.” Your article on the power of photog- raphy moved me as much as the photographs themselves. FAITH PARKER Saratoga Springs, New York 125Years of Photos As a college junior in 1976, I was an avid photographer. (How I miss my Pentax SP1000!) I wrote to National Geographic asking the requirements to be a staff photographer. I re- ceived a personal reply stating I would need to have a college degree and five years’ experience on a photo-oriented news- paper, and I probably should know another language. It also stated that “the average Geographic photographer spends far more time being a traveler, diplomat, making arrangements, and coping with a myriad of problems that can arise when he or she is working alone in a strange land.” NANCY J. BUSHNELL North Mankato, Minnesota EMAIL comments to ngsforum@ ngm.com; for subscription help, ngsline@customersvc.com. TWITTER @NatGeoMag WRITE National Geographic Magazine, PO Box 98199, Washington, DC 20090-8199. Letters may be edited for clarity and length. ART: DANIELA SANTAMARINA, NGM STAFF BASED ON A PHOTO BY STEVE MCCURRY LETTERS
  • 10.  national geographic February  SURVIVAL GUIDE ART: ISTVAN BANYAI. PHOTO: MICHAEL WELLS Border Lines My team studies what happens to undocumented migrants crossing the border from Mexico to the U.S. Many don’t make it. So the archaeology and anthropology we do are often unpleasant—uncovering death and physical and emotional suffering. We hope the research that we do can aid immigration law reform. On a trip to study a four-year- old migrant site where the traffic had slowed, we found the body of a 41-year-old woman. She was just south of Tucson, Arizona, in the So- noran Desert, only 30 miles from the Mexican border. The area is mountain- ous. She had been cresting a steep hill. It was July, and the temperatures there averaged 100°F or more. Finding a person meant the team had to navigate between gathering scientific data and feeling empathy. And we had to call the police. She’d been dead about four days, and there were already birds circling overhead. We knew what animals did to bodies in the desert, so we needed to collect what data we could—without disturb- ing the body—then and there. There were seven of us on the team, and we were all struggling. It was easier when we had seen other migrants’ bodies that were fragment- ed, a collection of bones. No one wanted to take this woman’s pho- tograph because we could see her humanity. We called her Marisol. Before we found her, we had come across some items buried under a tree nearby, including a backpack with a new, very vibrant Mexican blanket inside. When we finished logging the data—what she carried with her, her clothing, the GPS coordinates—we used the blanket to cover Marisol up and waited for the police. It was a temporary gesture. Jason De León National Geographic Emerging Explorer EXPERTISE Cultural Anthropologist LOCATION Arizona
  • 11. In Ancient Rome this necklace could have been the end of you. Tyrian purple was a color reserved for the Emperor alone. Back then, breaking the law to make a fashion statement meant risking your life. But today, you’re free to flaunt this strand without fear of repercussion. And thanks to a very special offer, you don’t even have to be afraid of the price. Today, you can bring home this stunning 100-ctw Tyrian Amethyst Necklace for ONLY $39! History’s luxury law repealed. The Emperor’s ban no longer applies. It’s now safe to be seen in this royal hue. Purple belongs to the people! And what better way to indulge yourself than with our Tyrian Amethyst Necklace? This spectacular 18” strand boasts 100 carats of polished, genuine amethyst beads paired with elegant, gold-finished spacers. Time is running out. The appeal of amethyst has endured for centuries, but these necklaces won’t stick around forever. Independently appraised at $445, this necklace was initially priced at $299. That's good, but we prefer great. That's why, for a limited time, you can own this stunning necklace for only $39! Your satisfaction is guaranteed. Wear the necklace for a few weeks and see for yourself. If you’re not completely satisfied by the Tyrian Amethyst Neck- lace, send it back within 30 days and we’ll refund 100% of your purchase price. But if history is any indication, once you experience this breathtaking color up close, you’ll do everything you can to keep it from getting away! Smart Luxuries—Surprising Prices™ 14101 Southcross Drive W., Dept. TAN167-01, Burnsville, Minnesota 55337 www.stauer.com Stauer® Rating of A+ Necklace enlarged to show luxurious detail. 100 carats of genuine amethyst • Gold-finished spacers 18" length necklace Banned Gemstone Now 100% Legal Get 100 carats of historically dangerous amethyst for under $40! Independently Appraised at $445* * For more information concerning the appraisal, visit http://www.stauer.com/appraisedvalues.asp. Amazing Amethyst Offer! Order now to get this $299 necklace for only $39! Tyrian Amethyst Necklace Promotional Code Price Only $39+ S&P Save $260 Order now to take advantage of this fantastic low price. 1-888-870-9512 Your Promotional Code: TAN167-01 Please use this code when you order to receive your discount. TAKE 87% OFF INSTANTLY! When you use your PROMOTIONAL CODE
  • 12. AND KRIS HARTMAN AT MT. ST. HELEN’S NATIONAL PARK WHEN TIM MEDVETZ SHATTERED HIS BODY AND CRACKED HIS SKULL IN A NEAR-FATAL MOTOR- CYCLE ACCIDENT IN 2001, HE WAS NOT EXPECTED TO WALK AGAIN. A YEAR LATER, HE WAS CLIMBING MT. EVEREST. NOW, ON “GOING WILD,” TIM IS TAKING EVERY- DAY AMERICANS ON A RIGOROUS JOURNEY, TRANSPORTING THEM TO PLACES OTHERS CAN ONLY DREAM OF REACHING WHERE THEY CAN EXPLORE THE WONDERS OF THE WORLD— AND REDISCOVER THEMSELVES. IN THIS EPISODE, WE MEET KRIS HARTMAN, WHO’S BEEN DEALING WITH THE DEATH OF HIS SISTER SEVEN YEARS AGO BY IMMERSING HIMSELF IN HIS JOB AND NIGHTLY TV- WATCHING BINGES. HIS WIFE WORRIES THAT’S HE’S MISSING OUT ON HIS SON’S CHILDHOOD. “HE NEEDS A WAKE-UP CALL —a little dose of Mother Nature,” says Tim. Together, they’ll take a treacherous three-day journey up the summit of Mt. St. Helen’s, an 8,300-foot active volcano in Washington State. Its snowy peaks and dense forests are teeming with dangerous wildlife, including cougars, elk, and bears. Tim knows this deadly environment is just the place to kick Kris into gear. “I’m going to put you through hell,” Tim tells him—and does. Will Kris reach the peak—and muster the courage to dig deep within and find the strength to LIVE LIFE TO THE FULLEST? JEEP IS A SPONSOR OF “GOING WILD,” WHICH PREMIERES MARCH 2014 ON NAT GEO WILD. THE ALL-NEW 2014 JEEP CHEROKEE GIVES YOU THE FREEDOM TO CHASE NEW HORIZONS. FIND OUT MORE ABOUT THE ALL-NEW 2014 JEEP CHEROKEE AT JEEP.COM/CHEROKEE.
  • 13. RIGHT HERE, THE NEW STANDARD OF ITS CLASS EMERGES FEATURING A BOLD EXTERIOR DESIGN WITH THE SMOOTH RIDE AND UP TO 31 MPG HWY DELIVERED BY ITS CLASS-EXCLUSIVE NINE-SPEED TRANSMISSION. WITH AVAILABLE NAPPA LEATHER-TRIMMED INTERIOR INSPIRED BY NATURAL HUES FROM AROUND THE WORLD, BEST-IN-CLASS 4X4 CAPABILITY AND 8.4" TOUCH SCREEN COMMAND CENTER, THE 2014 JEEP CHEROKEE IS READY FOR ANY JOURNEY THAT YOU’RE READY TO BEGIN. J E E P. C O M /C H E R O K E E 2.4L I4 FWD Models: EPA est. 22 city/31 hwy MPG. Actual mileage may vary. Jeep “Mid-Size SUV”sub-segmentation based on 13MY cross-shop activity. Excludes vehicles with third-row seating. Jeep is a registered trademark of Chrysler Group LLC. INTRODUCING THE ALL-NEW 2014 CHEROKEE SEE THE WORLD ONE HORIZON AT A TIME ,
  • 14. United States Behind a theater window at Florida’s Weeki Wachee Springs State Park, Nikki Chickonski swims through swirling bubbles. Strategi- cally placed air hoses allow the mermaids to take in lungfuls of air, then perform unencumbered by scuba tanks. PHOTO: CRISTINA GARCIA RODERO, MAGNUM PHOTOS VISIONS 
  • 15. Iceland The colorful rhyolite mountains of the Land- mannalaugar highlands are a popular hiking destination in Iceland’s southern interior. Getting there can be hard: Local roads aren’t paved, and rivers run across them. They must be forded using four-wheel drive. PHOTO: HANS STRAND
  • 16. O Order prints of select National Geographic photos online at NationalGeographicArt.com.O Order prints of select National Geographic photos online at NationalGeographicArt.com.
  • 17. Bhutan Robes fly as monks practice a traditional dance in the court- yard of the Rinpung Dzong, a fortress and monastery complex dating from 1646—and now a seat of district government—located in Bhutan’s Paro Valley. PHOTO: DAVID BUTOW
  • 18. VISIONS | YOUR SHOT This page features two photographs: one chosen by our editors and one chosen by our readers via online voting. For more information, go to yourshot.nationalgeographic.com.  national geographic february  EDITORS’ CHOICE Hong Ng CK Kuala Lumpur, Malaysia In the Dang district of Nepal, Hong was working with an organization that holds free art classes for young students. During a break, a girl began jumping rope, sending dust from the floor into the air as the sun shone in through a window behind her. READERS’ CHOICE Aleš Umek Celje, Slovenia Umek rode his bike 55 miles to take landscape shots of Slovenia’s picturesque Logar Valley. “I wanted to make a dream landscape,” he says. At the top of one hill he found a view of a small homestead that looked as if it belonged in a fairy tale.
  • 19. For people with a higher risk of stroke due to Atrial Fibrillation (AFib) not caused by a heart valve problem IMPORTANT SAFETY INFORMATION: Do not stop taking ELIQUIS without talking to the doctor who prescribed it for you. Stopping ELIQUIS increases your risk of having a stroke. ELIQUIS may need to be stopped, prior to surgery or a medical or dental procedure. Your doctor will tell you when you should stop taking ELIQUIS and when you may start taking it again. If you have to stop taking ELIQUIS, your doctor may prescribe another medicine to help prevent a blood clot from forming. ELIQUIS can cause bleeding which can be serious, and rarely may lead to death. You may have a higher risk of bleeding if you take ELIQUIS and take other medicines that increase your risk of bleeding, such as aspirin, NSAIDs, warfarin (COUMADIN® ), heparin, SSRIs or SNRIs, and other blood thinners. Tell your doctor about all medicines, vitamins and supplements you take. While taking ELIQUIS, you may bruise more easily and it may take longer than usual for any bleeding to stop. Get medical help right away if you have any of these signs or symptoms of bleeding: - unexpected bleeding, or bleeding that lasts a long time, such as unusual bleeding from the gums; nosebleeds that happen often, or menstrual or vaginal bleeding that is heavier than normal - bleeding that is severe or you cannot control - red, pink, or brown urine; red or black stools (looks like tar) - coughing up or vomiting blood or vomit that looks like coffee grounds - unexpected pain, swelling, or joint pain; headaches, feeling dizzy or weak ELIQUIS is not for patients with artificial heart valves. Before you take ELIQUIS, tell your doctor if you have: kidney or liver problems, any other medical condition, or ever had bleeding problems. Tell your doctor if you are pregnant or breastfeeding, or plan to become pregnant or breastfeed. Do not take ELIQUIS if you currently have certain types of abnormal bleeding or have had a serious allergic reaction to ELIQUIS. A reaction to ELIQUIS can cause hives, rash, itching, and possibly trouble breathing. Get medical help right away if you have sudden chest pain or chest tightness, have sudden swelling of your face or tongue, have trouble breathing, wheezing, or feeling dizzy or faint. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/ medwatch, or call 1-800-FDA-1088. PleaseseeadditionalImportant Product Information on the adjacent page. Individual results may vary. Visit ELIQUIS.COM or call 1-855-ELIQUIS ELIQUIS is a prescription medicine used to reduce the risk of stroke and blood clots in people who have atrial fibrillation, a type of irregular heartbeat, not caused by a heart valve problem. Ask your doctor if ELIQUIS is right for you. ©2013 Bristol-Myers Squibb Company 432US13BR01723-09-01 09/13 I was taking warfarin. But I wondered, could I shoot for something better? NOW I TAKE ELIQUIS® (apixaban) FOR 3 GOOD REASONS: 1 ELIQUIS reduced the risk of stroke better than warfarin. 2 ELIQUIS had less major bleeding than warfarin. 3 Unlike warfarin, there’s no routine blood testing. ELIQUIS and other blood thinners increase the risk of bleeding which can be serious, and rarely may lead to death.
  • 20. What is the most important information I should know about ELIQUIS (apixaban)? Do not stop taking ELIQUIS without talking to the doctor who prescribed it for you. Stopping ELIQUIS increases your risk of having a stroke. ELIQUIS may need to be stopped, prior to surgery or a medical or dental procedure. Your doctor will tell you when you should stop taking ELIQUIS and when you may start taking it again. If you have to stop taking ELIQUIS, your doctor may prescribe another medicine to help prevent a blood clot from forming. ELIQUIS can cause bleeding which can be serious, and rarely may lead to death. This is because ELIQUIS is a blood thinner medicine that reduces blood clotting. You may have a higher risk of bleeding if you take ELIQUIS and take other medicines that increase your risk of bleeding, such as aspirin, nonsteroidal anti-inflammatory drugs (called NSAIDs), warfarin (COUMADIN®), heparin, selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs), and other medicines to help prevent or treat blood clots. Tell your doctor if you take any of these medicines. Ask your doctor or pharmacist if you are not sure if your medicine is one listed above. While taking ELIQUIS: • you may bruise more easily • it may take longer than usual for any bleeding to stop Call your doctor or get medical help right away if you have any of these signs or symptoms of bleeding when taking ELIQUIS: • unexpected bleeding, or bleeding that lasts a long time, such as: • unusual bleeding from the gums • nosebleeds that happen often • menstrual bleeding or vaginal bleeding that is heavier than normal • bleeding that is severe or you cannot control • red, pink, or brown urine • red or black stools (looks like tar) • cough up blood or blood clots • vomit blood or your vomit looks like coffee grounds • unexpected pain, swelling, or joint pain • headaches, feeling dizzy or weak ELIQUIS (apixaban) is not for patients with artificial heart valves. What is ELIQUIS? ELIQUIS is a prescription medicine used to reduce the risk of stroke and blood clots in people who have atrial fibrillation. It is not known if ELIQUIS is safe and effective in children. Who should not take ELIQUIS? Do not take ELIQUIS if you: • currently have certain types of abnormal bleeding • have had a serious allergic reaction to ELIQUIS. Ask your doctor if you are not sure What should I tell my doctor before taking ELIQUIS? Before you take ELIQUIS, tell your doctor if you: • have kidney or liver problems • have any other medical condition • have ever had bleeding problems • are pregnant or plan to become pregnant. It is not known if ELIQUIS will harm your unborn baby • are breastfeeding or plan to breastfeed. It is not known if ELIQUIS passes into your breast milk. You and your doctor should decide if you will take ELIQUIS or breastfeed. You should not do both Tell all of your doctors and dentists that you are taking ELIQUIS. They should talk to the doctor who prescribed ELIQUIS for you, before you have any surgery, medical or dental procedure. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some of your other medicines may affect the way ELIQUIS works. Certain medicines may increase your risk of bleeding or stroke when taken with ELIQUIS. HowshouldItakeELIQUIS(apixaban)? Take ELIQUIS exactly as prescribed by your doctor. Take ELIQUIS twice every day with or without food, and do not change your dose or stop taking it unless your doctor tells you to. If you miss a dose of ELIQUIS, take it as soon as you remember, and do not take more than one dose at the same time. Do not run out of ELIQUIS. Refill your prescription before you run out. Stopping ELIQUIS may increase your risk of having a stroke. What are the possible side effects of ELIQUIS? • See “What is the most important information I should know about ELIQUIS?” • ELIQUIS can cause a skin rash or severe allergic reaction. Call your doctor or get medical help right away if you have any of the following symptoms: • chest pain or tightness • swelling of your face or tongue • trouble breathing or wheezing • feeling dizzy or faint Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of ELIQUIS. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. This is a brief summary of the most important information about ELIQUIS. For more information, talk with your doctor or pharmacist, call 1-855-ELIQUIS (1-855-354-7847), or go to www.ELIQUIS.com. Manufactured by: Bristol-Myers Squibb Company Princeton, New Jersey 08543 USA Marketed by: Bristol-Myers Squibb Company Princeton, New Jersey 08543 USA and Pfizer Inc New York, New York 10017 USA COUMADIN® is a trademark of Bristol-Myers Squibb Pharma Company © 2013 Bristol-Myers Squibb Company ELIQUIS and the ELIQUIS logo are trademarks of Bristol-Myers Squibb Company. Based on 1289808 / 1298500 / 1289807 / 1295958 December 2012 432US13CBS03604 This independent, non-profit organization provides assistance to qualifying patients with financial hardship who generally have no prescription insurance. Contact 1-800-736-0003 or visit www.bmspaf.org for more information. IMPORTANT FACTS /The information below does not take the place of talking with your healthcare professional. Only your healthcare professional knows the specifics of your condition and how ELIQUIS® may fit into your overall therapy. Talk to your healthcare professional if you have any questions about ELIQUIS (pronounced ELL eh kwiss).
  • 21. Millions Demand America’s Purest Silver Dollar. Shouldn’t You? Secure Your New 2014 Eagle Silver Dollars Now! Millions of people collect the American Eagle Silver Dollar. In fact it’s been the country’s most popular Silver Dollar for over two decades. Try as they might, that makes it a very hard “secret” to keep quiet. And right now, many of those same people are lining up to secure the brand new 2014 U.S. Eagle Silver Dollars — placing their orders now to ensure that they get America’s newest Silver Dollar —in stunning Brilliant Uncirculated condition — before millions of others beat you to it. America’s Brand New Silver Dollar This is a strictly limited release of one of the most beautiful silver coins in the world. Today you have the opportunity to secure these massive, hefty one full Troy ounce U.S. Silver Dollars in Brilliant Uncirculated condition. The nearly 100-year-old design features walking Lady Liberty draped in a U.S. flag, while the other side depicts a majestic U.S. eagle, thirteen stars, and an American shield. But the clock is ticking... The Most Affordable Precious Metal— GOVERNMENT GUARANTEED Silver is by far the most affordable of all precious metals — and each full Troy ounce American Eagle Silver Dollar is government-guaranteed for its 99.9% purity, authenticity, and legal tender status. A Coin Flip You Can’t Afford to Lose Why are we releasing the most popular Silver Dollar in America for a remarkably affordable price? We’re doing it to introduce you to what hundreds of thousands of smart collectors and satisfied customers have known since 1984 — GovMint.com is the place to find the world’s finest coins. Timing is Everything Our advice? Keep this to yourself. The more people who know about this offer, the worse for you. Demand for Silver Eagles in recent years has shattered records. Experts predict that 2014 Silver Eagles may break them once again. Our sup- plies are limited and there is a strict limit of 40 per household. 30-Day Money-Back Guarantee You must be 100% satisfied with your 2014 American Eagle Silver Dollars or return them within 30 days of receipt for a prompt refund (less all s/h). Don’t miss out on this exclusive release. Call immediately to secure these American Eagle Silver Dollars ahead of the crowd. 2014 American Eagle Silver Dollar BU Your cost 1-4 Coins - $27.95 each + s/h 5-9 Coins - $27.75 each + s/h 10-19 Coins - $27.50 each + s/h 20-40 Coins - $27.25 each + s/h Offer Limited to 40 per Household For fastest service, call toll-free 24 hours a day 1-800-910-7267 Offer Code PSE192-04 Please mention this code when you call. Prices and availability subject to change without notice. Past performance is not a predictor of future performance. NOTE: GovMint.com® is a private distributor of worldwide government coin and currency issues and privately issued licensed collectibles and is not affiliated with the United States government. Facts and figures deemed accurate as of December 2013 ©2013 GovMint.com. 14101 Southcross Drive W., Dept. PSE192-04 Burnsville, Minnesota 55337 www.GovMint.com Actual size is 40.6 mm JUST RELEASED: 2014 SILVER!
  • 22. How long will an elephant live? Look to its teeth. NEXT WILDLIFE Area enlarged PHOTOS: HUGH TURVEY. GRAPHIC: JOSÉ MIGUEL MAYO. SOURCE: DAVID FAGAN, THE COLYER INSTITUTE
  • 23. TEETH MAY BE the most essential organ elephants have, says veterinary dentist David Fagan. The reason is appetite. An African savanna elephant consumes between 400 and 600 pounds of vegetation a day, an Asian elephant about 300. To process that quantity of food, elephants need to chew constantly. They wear down each tooth until it’s no longer useful. Then it falls out. Most other mammals have two sets of teeth in their lifetimes. Elephants go through six. Each set—one tooth on the top, one on the bottom—lasts about three years when an African savanna ele- phant is young but can be good for more than ten years later in life. Unlike human teeth, which sprout from the gum line, elephants’ start at the back of the mouth and move forward like a conveyor belt. It’s an effective system until there aren’t any teeth left. Elephants that live to old age—about 70 years in captivity—often succumb to starvation, unable to chew. —Daniel Stone Replacement molar begins forming. Tooth emerges. Worn teeth are dislodged by roughage. How it works Teeth develop at the back of the mouth and move forward. Unlike chewing teeth, tusks are not replaced. An x-ray of an Asian elephant’s jaw reveals teeth that can reach the size of a phone book. 
  • 24. NEXT 105 105 0 mi 200 0 km 200 North Cove PACIFIC OCEAN South Bay North Cove Westport Cohassett Beach Grayland Heather Bay City OCOSTA ELEMENTARY SCHOOL (FUTURE TSUNAMI SHELTER) A subduction zone—where one plate slides under another—like Cascadia can produce an earthquake strong enough to trigger a tsunami. Cascadiasubductionzone Seattle WASHINGTON OREGON CANADA U.S. CALIF. AREA ENLARGEDJUAN DE FUCA PLATE PACIFIC PLATE GORDA PLATE NORTH AMERICAN PLATE Cascadiasubductionzone MAP: JEROME N. COOKSON, NGM STAFF. SOURCES: NATHAN WOOD, USGS; MATHEW SCHMIDTLEIN, CALIFORNIA STATE UNIVERSITY, SACRAMENTO. PHOTO: N EISELE-HEIN, GETTY IMAGES Rooftop RefugeUp to 5,000 people are in Westport, Washington, on a summer day. About a fifth could be too close to the coast and too far from high ground to escape on foot from a tsunami, which experts say would follow an earthquake there by 25 minutes. The city is forging a safe haven, building on state plans. Last April it approved a bond for the first vertical tsunami refuge in the U.S.—on top of a school and able to withstand a 9.2 magnitude earthquake. “Japan’s 2011 tsunami was a transitional moment in moving Westport from planning to implementation,” says emer- gency manager John Schelling. Westport residents saw parallels between the Japanese towns and their own area: both in a potential tsunami path, both flat. So when Westport needed a new school, a tsunami plan became part of it. Rising a little taller than 55 feet, the building will allow water to pass through without compromising the structure, which can shelter 700. Planners hope that this first successful idea spawns other refuge options. —Johnna Rizzo 0 mi 1 0 km 1 Pedestrian travel time to tsunami safety zone 0-9 minutes 10-19 20-29 30-39 40-49 50+ Proposed tsunami shelter location Tsunami safety zone
  • 25. What are the breakthroughs and new technologies that will enter the energy mix? Energy is an issue that touches every person on the planet. greatenergychallenge.com Everything you need to stay current on the big picture of energy— and what it means for you—can be found at is a National Geographic initiative in partnership with Shell that convenes and engages influential citizens and key energy stakeholders in solutions-based thinking and dialogue about our shared energy future. It’s a call-to-action to become actively involved, to learn more and do more—to change how we think about and consume energy so that we can all help tackle the big energy questions. Let’s start now. Be part of the solution. Take part in the challenge. Stay informed with up-to-the-minute news and insights ENERGY NEWS ` Trusted, balanced, independent global reporting with a scope and scale that stands apart. Test Your Energy I.Q. ENERGY QUIZZES ` Featuring amazing facts and energy-saving tips. Join the debate and move the conversation forward THE BIG ENERGY QUESTION ` Encouraging solutions through diverse conversations. Engage with the world’s experts ENERGY BLOG ` A fascinating forum where experts keep issues front and center. Do rapidly growing cities offer a blueprint for energy sustainability? How will we drive change for smarter mobility? As we move to a population of 9 billion by mid-century, how do we manage the stress on the intersection of food, water, and energy?
  • 26. NEXT PHOTOS: ANAND VARMA (LEFT); PHOO CHAN, FLICKR/GETTY IMAGES. ART: MAAYAN HAREL Silent Flight German engineers have a flight plan: mimic barn owls’ quiet aerial maneuvering to make less noisy airfoils for hu- man aviation. Nocturnal hunters, barn owls use acoustics to locate prey, so they can’t be distracted by noises of their own making. Key to a barn owl’s stealth is flying slowly, with very little flapping. Its steep wing curve is a particular asset: It’s especially good at creating the low pres- sure on the top side that sucks the wings upward, says lead researcher Thomas Bachmann. Plumage plays a part too. Owls have extreme- ly dense coats, and their feathers’ soft texture muffles sound. Fringes on the edges of feathers may also lead to ways to downplay turbulence. —Johnna Rizzo Solid Grasp Linger in the bathtub long enough, and fingers and toes will prune. Those wrinkles may seem insignifi- cant, but they could be rooted in evolution. Puckered digits were once thought to be just the bloated result of water absorption. Then Newcastle University evolutionary biologist Tom Smulders heard about another theory—that the lines promote water runoff and aid adhesion, like treads on a tire. Smulders con- firmed that pruney fingers have the advantage in wet conditions. He’s only just scratched the surface of how the wrinkles work. For now, though, his findings could boost the theory that a million years ago the ancestors of modern humans went through a semiaquatic state, when skin folds might have helped toes cling to slick rocks and fingers catch wriggling fish. —Catherine Zuckerman Fingertips grip wet objects, like this marble, better when they’re “pruney.” In some wasp species, such as yellow jackets and hornets, females have 12 antennal segments. The males have 13. 1312
  • 27. Prescription Lyrica is not for everyone. Tell your doctor right away about any serious allergic reaction that causes swelling of the face, mouth, lips, gums, tongue, throat, or neck or any trouble breathing, rash, hives or blisters. Lyrica may cause suicidal thoughts or actions in a very small number of people. Patients, family members or caregivers should call the doctor right away if they notice suicidal thoughts or actions, thoughts of self harm, or any unusual changes in mood or behavior. These changes may include new or worsening depression, anxiety, restlessness, trouble sleeping, panic attacks, anger, irritability, agitation, aggression, dangerous impulses or violence, or extreme increases in activity or talking. If you have suicidal thoughts or actions, do not stop Lyrica without first talking to your doctor. Lyrica may cause swelling of your hands, legs and feet. Some of the most common side effects of Lyrica are dizziness and sleepiness. Do not drive or work with machines until you know how Lyrica affects you. Other common side effects are blurry vision, weight gain, trouble concentrating, dry mouth, and feeling “high.” Also, tell your doctor right away about muscle pain along with feeling sick and feverish, or any changes in your eyesight including blurry vision or any skin sores if you have diabetes. You may have a higher chance of swelling, hives or gaining weight if you are also taking certain diabetes or high blood pressure medicines. Do not drink alcohol while taking Lyrica. You may have more dizziness and sleepiness if you take Lyrica with alcohol, narcotic pain medicines, or medicines for anxiety. If you have had a drug or alcohol problem, you may be more likely to misuse Lyrica. Tell your doctor if you are planning to father a child. Talk with your doctor before you stop taking Lyrica or any other prescription medication. Please see Important Risk Information for Lyrica on the following page. To learn more visit www.lyrica.com or call toll-free 1-888-9-LYRICA (1-888-959-7422). You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088. Artist depiction Get specific treatment for Diabetic Nerve Pain. Lyrica is FDA approved to treat Diabetic Nerve Pain. Diabetes damages nerves which may cause pain. Diabetic Nerve Pain (or pain from Diabetic Peripheral Neuropathy) is characterized by shooting, burning, pins and needles symptoms. Lyrica provides effective pain relief so patients feel better.* Some patients also had a significant reduction of pain in as early as one week. And, Lyrica is not a narcotic.** Ask your doctor about Lyrica today. *Individual results may vary. **Those who have had a drug or alcohol problem may be more likely to misuse Lyrica. We asked Phyllis to tell us about her experience with Lyrica. To hear Phyllis’s story visit Lyrica.com. PBP537409-02 ©2013 Pfizer Inc. All rights reserved. March 2013 “HAVING LESS DIABETIC NERVE PAIN... IT’S A WONDERFUL FEELING.” —PHYLLIS, RETIRED SCHOOL BUS DRIVER DIAGNOSED WITH DIABETIC NERVE PAIN.
  • 28. IMPORTANT FACTS =?=;7B8CBB8C9B:1C1@5?=4C2AC2?%B 3B8?6?=B;C2?%BC9@;C1A4@3;C9@ 6@=C9B:1,C@::C1-866-706-2400 AC+?;? 000,2?%BB:127:)=;0B;,6A3, )$ )( -C?+?;?A=CA2C2?%BC(=6,-CB0C'A*-C'C C2?%BC(=6, )::C?49;CB;B+B8, ?=B8C?=C9BC ), B;?A=CA+B3.BC )+@=8?@C@=8C)+@=8@3BC@BCB4?;BB8C@8B3@*;CA2C:@A 3?9 :?=B, )6A;C?;C@CB4?;BB8C@8B3@*CA2C!@*B8@C9B3?6@:;C(=87;?B;-C#8,-C@=8 ?;C7;B8C7=8BC:?6B=;BC.5C!@*B8@C9@3@6B7?6@:;CA2C)3B?6@-C(=6,-C@=8C :?C#?::5C@=8CA, Rx only NEED MORE INFORMATION? / );*C5A7C8A6ACAC19@3@6?;,C!9?;C?;CA=:5C@C.?B2C;733@5C A2C?31A@=C?=2A3@?A=, /CACACwww.lyrica.com AC6@::C 1-866-459-7422 (1-866-4LYRICA). HOWTOTAKE LYRICA Do: /C!@*BC#'$()CB@6:5C@;C5A7C8A6ACB::;C5A7,C'A7 8A6AC0?::CB::C5A7C9A0C3769CAC@*BC@=8C09B=CAC@*BC?, !@*BC#'$()C@C9BC;@3BC?3B;CB@69C8@5, /C!@*BC#'$()C0?9CAC0?9A7C2AA8, Don’t: /C?+BC@C6@CAC7;BC3@69?=B;C?2C5A7C2BB:C8?%%5CAC;:BB15 09?:BC@*?=4C#'$(), /C?=*C@:6A9A:CAC7;BCA9BC3B8?6?=B;C9@C3@*BC5A7C ;:BB15C09?:BC@*?=4C#'$(), /C9@=4BC9BC8A;BCAC;A1C#'$()C;788B=:5, (2C5A7C;A1C@*?=4C#'$()C;788B=:5-C5A7C3@5C9@+BC9B@8@69B;- =@7;B@-C8?@9B@-CA7.:BC;:BB1?=4-C?=6B@;B8C;0B@?=4-CAC5A7 3@5C2BB:C@=?A7;,C(2C5A7C9@+BCB1?:B1;5-C5A7C3@5C9@+B ;B?%7B;C3ABCA2B=, /C @C@=5C=B0C3B8?6?=B;C0?9A7C2?;C@:*?=4CAC5A7C8A6A, POSSIBLE SIDE EFFECTS OF LYRICAC LYRICA may cause serious side effects, including: /C BBC(31A@=C @2B5C(=2A3@?A=C).A7C#'$(), /C7;6:BC1A.:B3;-C1@?=-C;AB=B;;CAC0B@*=B;;C@:A=4C0?9 2BB:?=4C;?6*C@=8C2B+BC /C5B;?49C1A.:B3;C?=6:78?=4C.:75C+?;?A= /CB?49C4@?=,CB?49C4@?=C3@5C@22B6C6A=A:CA2C8?@.BB;C@=8 6@=C.BC;B?A7;C2AC1BA1:BC0?9C9B@C1A.:B3;, /C
  • 29. BB:?=4C9?49 (2C5A7C9@+BC@=5CA2C9B;BC;531A3;-CB::C5A7C8A6AC?49C@0@5, The most common side effects of LYRICA are: /C?%%?=B;;CCCCCCCCCCCCCCCCCCCCCC/C!A7.:BC6A=6B=@?=4 /C:75C+?;?A= CCCCCCCCCCCCCCCC/C 0B::?=4CA2C9@=8;C@=8C2BB /CB?49C4@?= CCCCCCCCCCCCCCCCCC/C5C3A79 /C :BB1?=B;;CCCCCCCCCCCCCCCCCCCCC (2C5A7C9@+BC8?@.BB;-C5A7C;9A7:8C1@5CB@C@B=?A=CAC5A7C ;*?=C09?:BC@*?=4C#'$(), BEFORE STARTING LYRICA, continued /C)=4?AB=;?=C6A=+B?=4CB=%53BC)C?=9?.?A;,C'A7C3@5 9@+BC@C9?49BC69@=6BC2AC;0B::?=4C@=8C9?+B;, /C)+@=8?@ A;?4:?@%A=B-C)+@=8@3B A;?4:?@%A=BC@=8 3B2A3?=CAC)6A; 1?A4:?@%A=BC2AC8?@.BB;,C'A7 3@5C9@+BC@C9?49BC69@=6BCA2C0B?49C4@?=CAC;0B::?=4CA2 5A7C9@=8;CAC2BB, /C@6A?6C1@?=C3B8?6?=B;C;769C@;CA56A8A=B-C@=7?:?%B;CA 3B8?6?=B;C2AC@=?B5C;769C@;C:A@%B1@3,C'A7C3@5C9@+BC@ 9?49BC69@=6BC2AC8?%%?=B;;C@=8C;:BB1?=B;;,C /C)=5C3B8?6?=B;C9@C3@*BC5A7C;:BB15, BEFORE STARTING LYRICA !B::C5A7C8A6AC@.A7C@::C5A7C3B8?6@:C6A=8??A=;-C?=6:78?=4C?2C5A7 /C@+BC9@8C8B1B;;?A=-C3AA8C1A.:B3;CAC;7?6?8@:C9A749;CA .B9@+?A /C@+BCAC9@8C*?8=B5C1A.:B3;CAC8?@:5;?; /C@+BC9B@C1A.:B3;-C?=6:78?=4C9B@C2@?:7B /C@+BC@C.:BB8?=4C1A.:B3CAC@C:A0C.:AA8C1:@B:BC6A7= /C@+BC@.7;B8C1B;6?1?A=C3B8?6?=B;-C;BBC874;CAC@:6A9A:C ?=C9BC1@; /C@+BCB+BC9@8C;0B::?=4CA2C5A7C2@6B-C3A79-CA=47B-C:?1;-C 473;-C=B6*-CAC9A@C@=4?AB8B3@ /C:@=CAC2@9BC@C69?:8,C(C?;C=AC*=A0=C?2C1A.:B3;C;BB=C?= @=?3@:C;78?B;C6@=C9@11B=C?=C973@=;, /C)BC1B4=@=-C1:@=CAC.B6A3BC1B4=@=CAC@BC.B@;2BB8?=4, (C?;C=AC*=A0=C?2C#'$()C0?::C9@3C5A7C7=.A=C.@.5,C 'A7C@=8C5A7C8A6AC;9A7:8C8B6?8BC09B9BC5A7C;9A7:8C@*B #'$()CAC.B@;2BB8-C.7C5A7C;9A7:8C=AC8AC.A9,C !B::C5A7C8A6AC@.A7C@::C5A7C3B8?6?=B;,C(=6:78BCA+B9B 6A7=BC3B8?6?=B;-C+?@3?=;-C@=8C9B.@:C;711:B3B=;, #'$()C@=8CA9BC3B8?6?=B;C3@5C@22B6CB@69CA9BC6@7;?=4 ;?8BCB22B6;,C;1B6?@::5CB::C5A7C8A6AC?2C5A7C@*B IMPORTANT SAFETY INFORMATION ABOUT LYRICA LYRICA may cause serious, even life threatening, allergic reactions. A1C@*?=4C#'$()C@=8C6@::C5A7C8A6AC?49C@0@5C?2C5A7 9@+BC@=5C;?4=;CA2C@C;B?A7;C@::B4?6CB@6?A= /C 0B::?=4CA2C5A7C2@6B-C3A79-C:?1;-C473;-CA=47B-C9A@CAC=B6*CC /C@+BC@=5CA7.:BC.B@9?=4 /C$@;9-C9?+B;C@?;B8C.731;CAC.:?;B; Like other antiepileptic drugs, LYRICA may cause suicidal thoughts or actions in a very small number of people, about 1 in 500. @::C5A7C8A6AC?49C@0@5C?2C5A7C9@+BC@=5C;531A3;- B;1B6?@::5C?2C9B5C@BC=B0-C0A;BCAC0A5C5A7-C?=6:78?=4 /C;7?6?8@:C9A749;CAC@6?A=; /C=B0CAC0A;BC8B1B;;?A= /C=B0CAC0A;BC@=?B5 /C2BB:?=4C@4?@B8CACB;:B;; /C1@=?6C@@6*; /CA7.:BC;:BB1?=4C /C=B0CAC0A;BC??@.?:?5 /C@6?=4C@44B;;?+B-C.B?=4C@=45-CAC+?A:B= /C@6?=4CA=C8@=4BA7;C?317:;B; /C@=CBB3BC?=6B@;BC?=C@6?+?5C@=8C@:*?=4C /CA9BC7=7;7@:C69@=4B;C?=C.B9@+?ACAC3AA8
  • 30. LYRICA may cause swelling of your hands, legs and feet. !9?;C;0B::?=4C6@=C.BC@C;B?A7;C1A.:B3C0?9C1BA1:BC0?9 9B@C1A.:B3;, LYRICA may cause dizziness or sleepiness. AC=AC8?+BC@C6@-C0A*C0?9C3@69?=B;-CAC8ACA9B 8@=4BA7;C9?=4;C7=?:C5A7C*=A0C9A0C#'$()C@22B6;C5A7, );*C5A7C8A6AC09B=C?C?;CA*@5CAC8AC9B;BC9?=4;, ABOUT LYRICA LYRICA is a prescription medicine used in adults 18 years and older to treat: /C@?=C2A3C8@3@4B8C=B+B;C9@C9@11B=;C0?9C8?@.BB;CAC 9@C2A::A0;C9B@:?=4CA2C;9?=4:B;-CAC;1?=@:C6A8C?=75 /C@?@:C;B?%7B;C09B=C@*B=CA4B9BC0?9CA9BC;B?%7BC3B8?6?=B; /C
  • 31. ?.A35@:4?@C1@?=C@::CA+BC5A7C.A85 Who should NOT take LYRICA: /C)=5A=BC09AC?;C@::B4?6CAC@=59?=4C?=C#'$()
  • 32. Mr. Bigshot rolled up in a roaring high-performance Italian sports car, dropping attitude like his $14,000 watch made it okay for him to be rude. That’s when I decided to roll up my sleeves and teach him a lesson. “Nice watch,” I said, pointing to his and holding up mine. He nodded like we belonged to the same club. We did, but he literally paid 100 times more for his membership. Bigshot bragged about his five-figure purchase, a luxury heavyweight from the titan of high- priced timepieces. I told him that mine was the Stauer Corso, a 27-jewel automatic classic now available for only $179. And just like that, the man was at a loss for words. The Stauer Corso is proof that the worth of a watch doesn’t depend on the size of its price tag. Our factory spent over $40 million on Swiss-made machinery to insure the highest quality parts. Each timepiece takes six months and over 200 individual precision parts to create the complex assembly. Peer through the exhibition back to see the 27-jeweled automatic movement in action and you’ll understand why we can only offer the Corso in a limited edition. Our specialty is vintage automatic movements. The Corso is driven by a self-winding design, inspired by a 1923 patent. Your watch will never need batteries. Every second of power is generated by the movement of your body. The dial features a trio of complications including a graphic day/night display. The Corso secures with a two-toned stainless steel bracelet and is water-resistant to 3 ATM. Your satisfaction is 100% guaranteed. Test drive the Stauer Corso. If you don’t love it, send it back within 30 days and we’ll refund every dollar of your purchase price. And you’re welcome to keep the $99 sunglasses as our gift! Spending more doesn’t make you smarter. But saving thousands on a watch this stunning will leave you feeling (and looking) like a genius! 27-jeweled Vertex automatic movement - Interior dials - Transparent caseback - Dual-toned stainless steel case and bracelet band fits wrists 6 ½–9 Only the “Robin Hood of Watchmakers” can steal the spotlight from a luxury legend for under $200! How to Outsmart a Millionaire Exclusive OFFER! Order the Stauer Corso and these Stauer Flyboy Optics™ Sunglasses (a $99 value) are yours FREE! Flyboy Optics™ Sunglasses with UV protection Limited Edition… Order Today! A Stauer Exclusive Not Sold in Stores Ostentatious Overpriced Competitors Price Stauer’s Corso Timepiece — PLUS Free $99 Stauer Flyboy Optics™ Sunglasses — only $179 +SP Call now to take advantage of this fantastic offer with our 30-day money back guarantee. 1-800-859-1626 Promotional Code CSW457-06 Please mention this code when you call. 14101 Southcross Drive W., Dept. CSW457-06 Burnsville, Minnesota 55337 www.stauer.com Stauer® Rating of A+
  • 33. PHOTOS: MARK THIESSEN, NGM STAFF. NGM MAPS. SOURCE: DIDIER BAZILE, CIRAD, FRANCE NEXT Keen on Quinoa Quinoa’s reputation is blossoming. The seed of a goosefoot species that originated in Peru and Bolivia around Lake Titicaca, it’s been a staple of Andean cuisine for millennia. Over the past decade other cul- tures have developed a taste for it too. Since 2007 U.S. imports have risen from 7 million to more than 70 million pounds a year. This growing appetite is affecting South America. Farmers are struggling to meet demand, and some urban populations can’t afford the resulting price increases. To cash in on the crop’s popularity, countries on other continents have begun moving from consumer to cultivator. There are now quinoa farms in 56 countries, including France, Thailand, Australia, and the U.S. Quinoa is also being grown in Africa, where the UN hopes its high protein content will help fight hunger. The long-term objective is diversity, says Kevin Murphy, a plant breeder at Washington State University. “There are hundreds of varieties of quinoa, and our goal is to develop the ideal one for different climates.” For now most retail stores in the U.S. remain stocked with Andean quinoa. With continued crop experimentation, though, Murphy adds, it won’t be long before locally grown—and less expensive— becomes an everyday option. —Catherine Zuckerman Quinoa’s cultivation range is expanding. NORTH AMERICA AFRICA ASIA EUROPE AUSTRALIA SOUTH AMERICA Lake Titicaca Quinoa introduction Before 1975 1975-2000 After 2000 Native Goosefoot (right) and its edible seeds (above)
  • 34. NEXT PHOTO (TOP): JOHN WEINSTEIN, FIELD MUSEUM. SOURCE: LANCE GRANDE, THE LOST WORLD OF FOSSIL LAKE. PHOTO (BOTTOM): VISUAL DEVELOPMENT LAB, MCMASTER UNIVERSITY. GRAPHIC: MARGARET NG. ART (TOP): ÁLVARO VALIÑO. SOURCE: AMADEUS Early BirdThere’s a new branch on the avian family tree. A 50-million-year-old fossilized bird found in Wyoming is thought to be an extinct cousin of modern hummingbirds and swifts. Based on the fossil’s well-preserved plumage, paleontologist Daniel Ksepka believes Eocypselus rowei—four inches from head to tail—would have been a conventional flier. Its descendants’ feathers specialized, growing long so swifts could stay aloft all day and short so hum- mingbirds could hover. —Catherine Zuckerman The discovery of this fossil helps explain the evolution of swifts and humming- birds in North America. EYE SPY Dots represent instances—observed over the course of five seconds—when each gender fixated on a facial feature. Face-to-Face Women have long been shown to be better than men at remem- bering faces. New research from Canada’s McMaster University helps explain why. Kinesiologist Jennifer Heisz tracked the way men and women moved their eyes as they scanned pictures of faces (right). Both gen- ders started at the center and looked at the same features—eyes, nose, mouth—but wom- en made more eye movements between the features. “More frequent scanning generates a more vivid picture in your mind,” says Heisz. Understanding how the brain memorizes vi- sual information could lead to improvements in how memory loss is treated. —Daniel Stone Start Women 17 10Men 10 seconds 2 3 4 5 Seoul Jeju The world’s busiest air route connects Jeju and Seoul, South Korea. It saw 10.1 million passengers in 2012.
  • 35. 
  • 36. MIND MACHINE An engineer wears a helmet of sensors at the Martinos Center for Biomedical Imaging—part of a brain scanner requiring almost as much power as a nuclear submarine. Antennas pick up signals produced when the scanner’s magnetic field excites water molecules in the brain. Computers convert this data into brain maps like the one on pages -.
  • 37. SECRETS OF THE New technologies are shedding light on biology’s greatest unsolved mystery: how the brain really works. 1.
  • 38. 1. Frontal cortex 2. Motor cortex 3. Parietal lobe 4. Corpus callosum 5. Thalamus 6. Occipital lobe 7. Temporal lobe 8. Brain stem 9. Cerebellum BRAIN PREPARATION PERFORMED AT ALLEN INSTITUTE FOR BRAIN SCIENCE 4. 5. 7. 9. 6. 3. 2. 8.
  • 39. THE COLOR OF THOUGHT The brain’s many regions are connected by some , miles of fibers called white matter— enough to circle the Earth four times. Images like this, taken at the Martinos Center, reveal for the first time the specific pathways underlying cognitive functions. The pink and orange bundles, for example, transmit signals critical for language. VAN WEDEEN AND L. L. WALD, MARTINOS CENTER FOR BIOMEDICAL IMAGING, HUMAN CONNECTOME PROJECT 
  • 40.  would be close enough to my brain to pick up the radio waves it was about to emit. As the slab glided into the cylindrical maw of the scanner, I thought of The Man in the Iron Mask. The magnets that now surrounded me began to rumble and beep. For an hour I lay still, eyes closed, and tried to keep myself calm with my own thoughts. It wasn’t easy. To squeeze as much resolution as possible out of the scanner, Wedeen and his colleagues had designed the device with barely enough room for a person of my build to fit inside. To tamp down the panic, I breathed smoothly and transported myself to places in my memory, at one point recalling how I had once walked my nine-year-old daughter to school through piles of blizzard snow. As I lay there, I reflected on the fact that all of these thoughts and emotions were the creation of the three-pound loaf of flesh that was under scrutiny: my fear, carried by electrical impulses converging in an almond-shaped chunk of tissue in my brain called the amygdala, and the calm- ing response to it, marshaled in regions of my frontal cortex. My memory of my walk with my daughter was coordinated by a seahorse-shaped fold of neurons called the hippocampus, which reactivated a vast web of links throughout my brain that had first fired when I had clambered over the snowbanks and formed those memories. I was submitting to this procedure as part of my cross-country reporting to chronicle one of the great scientific revolutions of our times: the stunning advances in understanding the work- ings of the human brain. Some neuroscientists are zooming in on the fine structure of individ- ual nerve cells, or neurons. Others are charting the biochemistry of the brain, surveying how our billions of neurons produce and employ thousands of different kinds of proteins. Still others, Wedeen among them, are creating in un- precedented detail representations of the brain’s wiring: the network of some 100,000 miles of nerve fibers, called white matter, that connects the various components of the mind, giving rise to everything we think, feel, and perceive. The U.S. government is throwing its weight be- hind this research through the Brain Research an Wedeen strokes his half- gray beard and leans toward his computer screen, scroll- ing through a cascade of files. We’re sitting in a win- dowless library, surrounded by speckled boxes of old letters, curling issues of sci- entific journals, and an old slide projector that no one has gotten around to throwing out. “It’ll take me a moment to locate your brain,” he says. On a hard drive Wedeen has stored hundreds of brains—exquisitely detailed 3-D images from monkeys, rats, and humans, including me. Wedeen has offered to take me on a journey through my own head. “We’ll hit all the tourist spots,” he promises, smiling. This is my second trip to the Martinos Center for Biomedical Imaging, located in a former ship-rope factory on Boston Harbor. The first time, a few weeks ago, I offered myself as a neuroscientific guinea pig to Wedeen and his colleagues. In a scanning room I lay down on a slab, the back of my head resting in an open plastic box. A radiologist lowered a white plastic helmet over my face. I looked up at him through two eyeholes as he screwed the helmet tight, so that the 96 miniature antennas it contained V BY CARL ZIMMER PHOTOGRAPHS BY ROBERT CLARK VAN WEDEEN AND L. L. WALD, MARTINOS CENTER FOR BIOMEDICAL IMAGING, HUMAN CONNECTOME PROJECT (ABOVE); TASCHEN GMBH
  • 41. ANATOMY OF A MYSTERY Scientists have studied the brain for centuries, but by the s they could still make out only the regions visible to the naked eye, as shown in this illustration. New technologies let scientists peer deep into the hidden structure of the brain. A high-resolution view of the image on the previous two pages reveals white matter fibers arranged in a mysterious grid structure (opposite), like longitude and latitude lines on a map. 
  • 42.  national geographic February  through Advancing Innovative Neurotechnolo- gies (BRAIN) Initiative. In an announcement last spring President Barack Obama said that the large-scale project aimed to speed up the map- ping of our neural circuitry, “giving scientists the tools they need to get a dynamic picture of the brain in action.” As they see the brain in action, neuroscien- tists can also see its flaws. They are starting to identify differences in the structure of ordinary brains and brains of people with disorders such as schizophrenia, autism, and Alzheimer’s dis- ease. As they map the brain in greater detail, they may learn how to diagnose disorders by their effect on anatomy, and perhaps even un- derstand how those disorders arise. On my return trip to his lab Wedeen finally locates the image from my session in the scanner. My brain appears on his screen. His technique, called diffusion spectrum imaging, translates ra- dio signals given off by the white matter into a high-resolution atlas of that neurological Internet. His scanner maps bundles of nerve fibers that form hundreds of thousands of pathways carrying information from one part of my brain to another. Wedeen paints each path a rainbow of colors, so that my brain appears as an explosion of colorful fur, like a psychedelic Persian cat. Wedeen focuses in on particular pathways, showing me some of the circuitry important to language and other kinds of thought. Then he pares away most of the pathways in my brain, so that I can more easily see how they’re organized. As he increases the magnification, something astonishing takes shape before me. In spite of the dizzying complexity of the circuits, they all intersect at right angles, like the lines on a sheet of graph paper. “It’s all grids,” says Wedeen. When Wedeen first unveiled the grid struc- ture of the brain, in , some scientists were skeptical, wondering if he’d uncovered only part of a much more tangled anatomy. But Wedeen is more convinced than ever that the pattern is meaningful. Wherever he looks—in the brains of humans, monkeys, rats—he finds the grid. He notes that the earliest nervous systems in Cambrian worms were simple grids—just a pair of nerve cords running from head to tail, with runglike links between them. In our own lineage the nerves at the head end exploded into billions but still retained that gridlike structure. It’s pos- sible that our thoughts run like streetcars along these white matter tracks as signals travel from one region of the brain to another. “There’s zero chance that there are not prin- ciples lurking in this,” says Wedeen, peering intently at the image of my brain. “We’re just not yet in a position to see the simplicity.” Scientists are learning so much about the brain now that it’s easy to forget that for much of history we had no idea at all how it worked or even what it was. In the ancient world physicians believed that the brain was made of phlegm. Aristotle looked on it as a refrigerator, cooling off the fiery heart. From his time through the Renaissance, anatomists declared with great authority that our perceptions, emotions, rea- soning, and actions were all the result of “animal spirits”—mysterious, unknowable vapors that swirled through cavities in our head and trav- eled through our bodies. The scientific revolution in the th century began to change that. The British physician Thomas Willis recognized that the custardlike tissue of the brain was where our mental world existed. To understand how it worked, he dissect- ed brains of sheep, dogs, and expired patients, producing the first accurate maps of the organ. It would take another century for researchers to grasp that the brain is an electric organ. Instead of animal spirits, voltage spikes travel through it and out into the body’s nervous system. Still, even in the th century scientists knew little about the paths those spikes followed. The Italian phy- sician Camillo Golgi argued that the brain was a seamless connected web. Building on Golgi’s research, the Spanish scientist Santiago Ramón y Cajal tested new ways of staining individual BURROWING DOWN TO SINGLE NERVE CELLS MAY FINALLY PROVIDE ANSWERS TO BASIC QUESTIONS ABOUT THE BRAIN. Carl Zimmer wrote on bringing back extinct species in the April  issue. Robert Clark’s previous story, on sugar, was in the August  issue.
  • 43. Seeing the Brain  for the rules that organize the brain’s seeming chaos. Recently Lichtman’s postdoctoral re- searcher Narayanan Kasthuri set out to analyze every detail in a cylinder of mouse brain tissue measuring just a thousand cubic microns—a volume /, the size of a grain of salt. He selected a region surrounding a short segment of a single axon, seeking to identify every neuron that passed through it. That minuscule patch of brain turned out to be like a barrel of seething snakes. Kasthuri found a thousand axons and about 80 dendrites, each making about 600 connections with other neurons inside the cylinder. “It’s a wake-up call to how much more complicated brains are than the way we think about them,” says Lichtman. neurons to trace their tangled branches. Cajal recognized what Golgi did not: that each neuron is a distinct cell, separate from every other one. A neuron sends signals down tendrils known as ax- ons. A tiny gap separates the ends of axons from the receiving ends of neurons, called dendrites. Scientists would later discover that axons dump a cocktail of chemicals into the gap to trigger a signal in the neighboring neuron. Jeff Lichtman, a neuroscientist, is the current Ramón y Cajal Professor of Arts and Sciences at Harvard, carrying Cajal’s project into the st century. Instead of making pen-and-ink drawings of neurons stained by hand, he and his colleagues are creating extremely detailed three-dimensional images of neurons, revealing every bump and stalk branching from them. By burrowing down to the fine structure of individual nerve cells, they may finally get answers to some of the most ba- sic questions about the nature of the brain. Each neuron has on average , synapses. Is there some order to their connections to other neurons, or are they random? Do they prefer linking to one type of neuron over others? To produce the images, Lichtman and his col- leagues load pieces of preserved mouse brain into a neuroanatomical version of a deli meat slicer, which pares off layers of tissue, each less than a thousandth the thickness of a strand of human hair. The scientists use an electron mi- croscope to take a picture of each cross section, then use a computer to order them into a stack. Slowly a three-dimensional image takes shape— one that the scientists can explore as if they were in a submarine traveling through an underwater kelp forest. “Everything is revealed,” says Lichtman. The only problem is the sheer enormity of “everything.” So far the largest volume of a mouse’s brain that Lichtman and his colleagues have managed to re-create is about the size of a grain of salt. Its data alone total a hundred terabytes, the amount of data in about 25,000 high-definition movies. Once the scientists have gathered this infor- mation, the really hard work begins: looking THE GLOW OF MEMORY When you form a memory, “there’s a physical change in the brain,” says Don Arnold, of the University of Southern California. Red and green dots on the branches extending from this rat neuron show where it contacts other neurons. As the rat forms new memories, new dots appear and old ones vanish. GARRETT GROSS AND DON ARNOLD, UNIVERSITY OF SOUTHERN CALIFORNIA
  • 44. JENNIFER ON THE BRAIN Caltech and UCLA scientists use pictures of celebrities to study how the brain processes what the eyes see. In  they found an individual nerve cell that fired only when subjects were shown pictures of Jennifer Aniston. Another neuron responded only to pictures of Halle Berry—even when she was masked as Catwoman. Follow-up studies suggest that relatively few neurons are involved in representing any given person, place, or concept, making the brain stagger- ingly efficient at storing information. IMAGE CREDITS AT NGM.COM/BRAIN
  • 45.  LISTENING IN How did scientists discover the “Jennifer Aniston neuron”? At UCLA’s Medical Center for Neuroscience electrodes are implanted in the brains of epileptic patients such as Crystal Hawkins. The next time she has a seizure, the electrodes will pinpoint its source, allowing neurosurgeons to target what brain tissue to remove. The electrodes also provide a rare opportunity to eavesdrop on neurons functioning normally, which led to the discovery of nerve cells that respond to specific faces. ERIC BEHNKE AND ANDREW FREW, UCLA (BOTTOM)
  • 46. Seeing the Brain  Complicated, but not random. Lichtman and Kasthuri discovered that every neuron made nearly all its connections with just one other one, scrupulously avoiding a connection with almost all the other neurons packed tightly around it. “They seem to care who they’re connected to,” Lichtman says. Lichtman can’t say yet whether this fastidious pattern is a general rule or a feature of just the tiny area of mouse brain he sampled. Even as they scale up the technology, he and his colleagues will need another two years to complete a scan of all 70 million neurons in a mouse. I ask about scanning an entire human brain, which contains a thousand times more neurons than a mouse’s. “I don’t dwell on that,” he says, with a laugh. “It’s too painful.” When and if Lichtman completes his three- dimensional portrait of the brain, it will reveal much—but it will still be only an exquisitely de- tailed sculpture. His imaged neurons are hollow models; real neurons are crammed with living DNA, proteins, and other molecules. Each type of neuron uses a distinct set of genes to build the molecular machinery it needs to do its own job. Light-sensitive neurons in the eyes produce photon-catching proteins, for example, and neurons in a region called the substantia nigra produce a protein called dopamine, crucial to our sense of reward. The geography of proteins is essential to understanding how the brain works— and how it goes awry. In Parkinson’s disease the substantia nigra neurons produce less dopamine than normal, for reasons that aren’t yet clear. Alzheimer’s disease scatters tangles of protein through the brain, although scientists have yet to firmly settle on how those tangles give rise to the devastating dementia the disease causes. A map of the brain’s molecular machinery called the Allen Brain Atlas has been generated at the Allen Institute for Brain Science in Seattle, founded ten years ago with funds from Micro- soft co-founder Paul Allen. Using the brains of recently deceased people, donated by their families, researchers there use a high-resolution magnetic resonance imaging (MRI) scan of each brain as a three-dimensional road map, then slice it into microscopically thin sections that are mounted on glass slides. They then douse the sections with chemicals that reveal the presence of active genes harbored in the neurons. So far the researchers have mapped the brains of six people, charting the activity of 20,000 protein-coding genes at 700 sites within each brain. It’s a colossal amount of data, and they’ve only begun to make sense of it. The scientists estimate that 84 percent of all the genes in our DNA become active somewhere in the adult brain. (A simpler organ like the heart or pan- creas requires far fewer genes to work.) In each of the 700 sites the scientists studied, the neurons switch on a distinct collection of genes. In a pre- liminary survey of two regions of the brain, the scientists compared a thousand genes that were already known to be important for neuron func- tion. From one person to the next, the areas of the brain where each of those genes was active were practically identical. It looks as if the brain has a finely grained genetic landscape, with spe- cial combinations of genes carrying out tasks in different locations. The secret to many diseases of the brain may be hiding in that landscape, as certain genes shut down or switch on abnormally. All the information from the Allen Brain At- las is posted online, where other scientists can navigate through the data with custom-made software. Already they’re making new discover- ies. A team of Brazilian scientists, for instance, has used it to study a devastating brain disor- der called Fahr’s disease, which calcifies regions deep inside the brain, leading to dementia. Some cases of Fahr’s disease had already been linked to a mutation in the gene SLCA. In the atlas the scientists found that SLCA is most ac- tive in precisely the regions that are targeted by the disease. They also found a network of other genes that is most active in the same areas, and now they’re trying to find out whether they’re involved in Fahr’s disease as well. Of all the new ways of visualizing the brain, perhaps the most remarkable is one invented by Stanford neuroscientist and psychiatrist THE SECRET TO MANY DISEASES MAY BE HIDING IN THE BRAIN’S GENES, AS THEY SHUT DOWN OR SWITCH ON ABNORMALLY.
  • 47. INTIMATE VIEW Two hundred sections of a piece of mouse brain, each less than /, the thickness of a human hair, are readied to be imaged by an electron microscope. Arranged in stacks, , such photomicrographs form a -D model no larger than a grain of salt (in tweezers). A human brain visualized at this level of detail would require an amount of data equal to all the written material in all the libraries of the world.
  • 48. AVOYAGE INTO THE Thought, feeling, sense, action—all derive from unimaginably complex interactions among billions of nerve cells. A section of mouse brain (above) no larger than a grain of salt serves as a window into this hidden world.
  • 49. JASON TREAT AND KURT MUTCHLER, NGM STAFF; ANTHONY SCHICK. ART: BRYAN CHRISTIE Global digital storage, 2012: 2.7 billion terabytes Storage capacity needed to produce human brain image 1.3 billion terabytes Storage capacity needed to produce mouse brain image 450,000 terabytes 1mm=1,000microns* 100microns 10microns Blood vessels ANATOMY OF A NERVE CELL JASON TREAT AND KURT MUTCHLER, NGM STAFF; ANTHONY SCHICK. ART: BRYAN CHRISTIE PHOTO (FLAP): JOSH L. MORGAN, HARVARD UNIVERSITY; ARTHUR WETZEL, PITTSBURGH SUPERCOMPUTING CENTER SOURCES: JEFF LICHTMAN, HARVARD UNIVERSITY; DANIEL BERGER, MASSACHUSETTS INSTITUTE OF TE *The 1-mm image is from a different data set than the other images. DEEPBRAINDIVE For the first time scientists can visualize how neurons actually connect with one another. The three blocks at right have been colorized but are not an artist’s conception: They show, at increasing levels of magnification, real neurons in part of a mouse’s brain receiving signals from the face. Technology may soon make possible a similar reconstruction of an entire mouse brain—and eventually of the vastly more complicated architecture of the human brain, opening the way for advances in understanding schizophrenia, depression, and other mental diseases. Cell body The neuron’s power- house, responsible for generating energy and synthesizing proteins An image a millimeter high—less than four- hundredths of an inch—shows nerve cells arranged in orderly layers and columns. A section a hundredth the size reveals blood vessels among pink cell bodies and a tangle of their axons and dendrites. Ma this sho de de info cel cal HALF THE WORLD’S HARD DRIVES Visualizing neurons at the level of detail shown in these images requires unprecedented computing power. Producing an image of an entire human brain at the same resolution would consume nearly half the world’s current digital storage capacity. Dendrites Branching projections that pick up signals from other neurons
  • 50. 3microns 1micron ECHNOLOGY; INTERNATIONAL DATA CORPORATION agnified again by 100, s section more clearly ows axons (blue) and ndrites (yellow). Budlike ndritic spines receive ormation from other lls’ axons across gaps lled synapses. Magnified yet again, this section reveals synaptic vesicles (yellow grains) containing neurotrans- mitters, which carry chemical messages across synapses, signaling the receiving nerve cell to fire or stop firing. Axon A long nerve fiber that conducts information from the cell body in the form of an electrical impulse Glial cells The glue of the nervous system, supporting, feeding, and protecting neurons Axonal terminal End point of an axon’s branches, where electrical impulses are discharged; releases neurotransmitters that carry chemical messages to other cells’ dendrites
  • 51. A CLEAR VIEW Scientists at Stanford University bathe a mouse brain (far left) in chemicals that remove fats and other molecules, rendering it transparent (left). Proteins can then be added that bind only to certain neurons. Below, a green-glowing protein reveals the ubiquity of a type of neuron that accounts for just one percent of a mouse’s brain. KWANGHUN CHUNG AND KARL DEISSEROTH, STANFORD UNIVERSITY (ALL)
  • 52. Seeing the Brain  Karl Deisseroth and his colleagues. To see the brain, they begin by making it disappear. On my visit to Deisseroth’s lab, undergradu- ate Jenelle Wallace led me to a bench where half a dozen beakers rested in a plastic-foam base. She pulled one out and pointed to a grape-size mouse brain resting at the bottom. I didn’t look at the brain so much as through it. It was nearly as transparent as a glass marble. Needless to say, a normal human or mouse brain is decidedly opaque, its cells swathed in fat and other compounds that block light. That’s why Cajal had to dye neurons in order to see them and why Lichtman’s group and the Allen Insti- tute scientists slice the brain into thin sections to gain access to its inner depths. The advantage of a transparent brain is that it allows us to peer into its workings while the organ is still intact. Along with postdoctoral researcher Kwanghun Chung, Deisseroth came up with a recipe to replace the light-scattering compounds in the brain with transparent molecules. After making a mouse brain transparent in this way, they can then douse the brain with glowing chemical labels that latch on to only certain proteins or trace a specific pathway connecting neurons in distant regions of the brain. The scientists can then wash out one set of chemicals and add another that re- veals the location and structure of a different type of neuron—in effect untangling the Gordian knot of neural circuits one by one. “You don’t have to take it apart to show the wiring,” says Deisseroth. It’s not easy to dazzle neuroscientists, but Deisseroth’s method, dubbed CLARITY, has left his colleagues awestruck. “It’s pretty badass,” says Christof Koch, the chief scientific officer at the Allen Institute. Wedeen has called the research “spectacular…unlike anything else in the field.” Because of our shared evolutionary heritage, a clarified mouse brain can reveal a great deal about human brain function. But Deisseroth’s ultimate goal is to perform the same transforma- tion with a human brain—a far more difficult task, not least because a human brain is 3,000 times as large as that of a mouse. A CLARITY picture showing the location of just one type of protein in just one human brain would create a monstrous heap of data—about two petabytes, or the equivalent of several hun- dred thousand high-def movies. Deisseroth anticipates that CLARITY may someday help the sort of people he treats in his psychiatric practice, by revealing hidden features of disor- ders like autism and depression. But for now he’s keeping those hopes in check. “We have so far to go before we can affect treatments that I tell people, Don’t even think about that yet,” he says. “It’s just a voyage of dis- covery for now.” As revealing as a transparent brain may prove to be, it will still be dead. Scientists need differ- ent tools to explore the terrain of living brains. The scanners Wedeen uses to trace white mat- ter patterns can, with different programming, record the brain in action. Functional magnetic resonance imaging (fMRI) pinpoints regions of the brain recruited during a mental task. Over the past couple of decades fMRI has helped re- veal networks involved in all manner of thought processes, from recognizing faces to enjoying a cup of coffee to remembering a traumatic event. It’s easy to be dazzled by fMRI images, which festoon the brain with rainbow blobs. But it’s im- portant to bear in mind that those images are actually quite coarse. The most powerful scanners can record activity only down to the scale of a cubic millimeter—a sesame seed’s worth of tissue. Within that space, hundreds of thousands of neu- rons are firing in synchronized patterns, trading signals. How those signals give rise to the larger patterns revealed by fMRI remains mysterious. “There are ridiculously simple questions about the cortex that we can’t answer at all,” says Clay Reid, a former colleague of Jeff Lichtman’s at Har- vard who moved to the Allen Institute in . Reid has come to Seattle hoping to answer some of those questions with a grand series of experiments he and his colleagues call Mind- Scope. Their goal is to understand how a large TO SEE THE BRAIN, SCIENTISTS AT STANFORD UNIVERSITY BEGIN BY MAKING IT AS TRANSPARENT AS A GLASS MARBLE. For more on the mind, tune in to the third season of Brain Games, premiering in January on the National Geographic Channel. Check local listings.
  • 53. NO ROOM FOR ERROR Removing brain tumors is a risky procedure— surgeons need to excise as much of a tumor as possible without destroying neurons essential for functions such as speech, sight, and memory or the connective fibers between them. David Fortin (at center right), a neurosurgeon at the Université de Sherbrooke in Canada, relies on a high-resolution map of a patient’s brain to avoid mishaps.
  • 54. A GUIDED HAND Scans of one of Fortin’s patients revealed that a tumor (red, above) had grown into a region controlling the movement of hands and feet. As he removed parts of the tumor (left), Fortin applied current to the region to determine if neighboring neurons were critical for move- ment. “There was a lot of motor function still active in this patient,” says Maxime Descoteaux, one of the Université de Sherbrooke scientists who made the brain scan. “So the surgeon in this case was more conservative than aggressive.” MAXIME DESCOTEAUX AND MAXIME CHAMBERLAND, SHERBROOKE CONNECTIVITY IMAGING LAB, UNIVERSITÉ DE SHERBROOKE (TOP) 
  • 55. Seeing the Brain  number of neurons carry out a complex task. The function Reid and his colleagues have chosen to decipher is vision. Scientists have been investigating how we see for decades, but they’ve been able to study it only piecemeal. A neuro- scientist might place an electrode in the region of a mouse’s brain involved in visual perception and then note whether nearby neurons fire when the animal sees a particular image. This approach has allowed scientists to map regions of the visual brain that specialize in dif- ferent tasks, such as detecting the edges of an object or perceiving brightness. But scientists haven’t been able to see all those regions work together at once—to learn how the million or so neurons in the visual regions of a mouse’s brain instantly put information together into the image of a cat. Reid and his colleagues are setting out to solve that problem by engineering mice so that their visual neurons will release flashes of light when they fire. The flashes record the neural activity when a mouse sees a specific object, be it a cat, a snake, or an appealing piece of cheese. The scien- tists can then compile the data to create massive mathematical models of vision. If the models are accurate, the researchers will be able to literally read the mind of a mouse. “Our goal is to reconstruct what the mouse sees,” says Reid. “And I think we can do it.” Reid’s research on mouse vision is another step toward neuroscience’s ultimate goal: a com- prehensive view of how this vastly complicated organ really works—what the scientists I talked to call a theory of the brain. Such a grand vision is still a long way off, and for the most part, the search for it has yet to change the way doctors treat patients. But there is one line of research— brain-machine interfaces—where the mapping of the mind has started to change people’s lives. When she was 43 years old, Cathy Hutchin- son suffered a massive stroke, leaving her unable to move or speak. Lying in her bed in Massachu- setts General Hospital, she gradually figured out that her doctors didn’t know if she was brain- dead or still aware. Her sister asked Hutchinson if she could understand her. She managed to answer by moving her eyes up on command. “It gave me such a relief,” Hutchinson tells me  years later, “because everybody talked about me as if I was dying.” It is a chilly winter day at her home in eastern Massachusetts, and she’s sitting in a wheelchair in the middle of the living room, dressed in a dark green jogging suit and sneakers. Still almost completely paralyzed and unable to speak, she communicates by looking at letters arrayed on a computer monitor bolted to her wheelchair, a camera tracking the movement of a tiny metal disk attached to the center of her eyeglasses. Near the top of the brain is a region called the motor cortex, where we generate commands to move our muscles. For more than a century we’ve known that each part of the cortex corresponds to a particular area of the body. When people like Hutchinson become paralyzed, the motor cortex often remains intact, but it can’t communicate with the rest of the body, because its connections have been destroyed. John Donoghue, a neuro- scientist at Brown University, wanted to find a way to help people with paralysis by tapping into the signals from their motor cortex. Perhaps they could eventually learn to type on a computer or operate a machine merely with their thoughts. Donoghue spent years developing an implant and testing the device on monkeys. Once he and his colleagues knew it was safe, they were ready to start working with human patients. One of them was Hutchinson. In 2005 sur- geons at Rhode Island Hospital drilled a hole the size of a poker chip in her skull and inserted the sensor for Donoghue’s device. About the size of a ladybug, the sensor contained a hundred min- iature needles, which, pressing into Hutchinson’s motor cortex, recorded the signals from nearby neurons. A set of wires anchored to this device passed through the hole in her skull and led to a metal connector sitting on her scalp. After her surgery had healed, the Brown Uni- versity researchers plugged Hutchinson’s implant into a cable that relayed signal patterns from her brain to a cart of computers they wheeled into her room. As a first step, the scientists trained IF THEIR MODELS ARE ACCURATE, THE RESEARCHERS WILL BE ABLE TO LITERALLY READ THE MIND OF A MOUSE.
  • 56.  national geographic February  “Cathy’s smile when she put down that drink— that’s everything,” Donoghue says. Today Donoghue and other scientists are building on that success, hoping to create human-machine interfaces that will be power- ful, safe, and easy. At Duke University Miguel Nicolelis has been experimenting with exoskel- etons that strap on to the body. Signals from the brain control each limb. Already he has gotten monkeys to control full-body exoskeletons. If all goes well, a paraplegic wearing a simpler version of the device will deliver the open- ing kick at the  World Cup in Nicolelis’s native Brazil. “Eventually brain implants will become as common as heart implants,” says Nicolelis. “I have no doubt about that.” When it comes to the brain, predicting the fu- ture is a tricky game. Advances in the past have inspired giddy expectations that in many cases have not been met. “We can’t tell a schizophren- ic brain from an autistic brain from a normal brain,” says Christof Koch. But the research that’s going on now, he believes, is moving neurosci- ence to a remarkable new stage. “I think we can begin to put the pieces together.” j the computers to recognize signals in her motor cortex and use them to move a computer cursor around a screen. This was achieved the first time she tried because they had learned how to trans- late patterns of brain activity into movements. Two years later they coupled a robotic arm to the computers, refining a program that could inter- pret Hutchinson’s brain signals to move the arm forward and back, to raise it up and down, and to open its robotic fingers and squeeze them shut. After just a few sessions Hutchinson, the com- puter, and the robotic arm had become a team. “It felt natural,” she tells me. So natural that one day she reached out for a cinnamon latte, grabbed it, and brought it to her lips to drink. BY THOUGHT ALONE A rhesus macaque walks with the aid of a pneumatically powered exoskeleton controlled by a computer reading signals from electrodes implanted in the monkey’s motor cortex. Miguel Nicolelis and colleagues at Duke University are developing similar devices that could allow paralyzed humans to walk again.