PICKS BOOKS lt's not ove r ye t September's comingsoon. Here are three beach-vacation clas- sics fO 「 the precious last weeks ofsummer. —Sarah Begley Everyday people, extraordinary b00 s TOM PERROTTA HAS DOCUMENTED DECADES' WORTH OF social issues in deceptively domestic novels. He addressed modern parenting ⅲ 2004 ' s 田 e Children, the Christian right ⅲ 2007 ' s The Abstinence Teacher and the response tO grief in 2011 ' s The Leftovers. AII those works take place in suburban America and have at their centers workaday folks living against the b ackdrop Of sweeping change. ln examining the national intere st by way Of dinner-table conversation, perrotta has created some of the most memorably human drama ofhis era. His new novel, Mrs. Fletcher, about a mother and son, is the latest example. "I never feel like l'm writing about the suburbs,: ” says perrotta. "I feel like l'm writing about people wh0 live in the suburbs, and people are a subject Of inexhaustible interest. ” Mrs. Fletcher is a look at two kinds Of sexual revolution: the breakdown ofbarriers created by lnternet porn and the new manner oftalking about sex on campus. lt will spark plenty 0f conversations before college drop-offbegins ⅲ August ・ TO Perrotta, lnternet porn—the sort that comes tO Obsess empty-nester Eve Fletcher—has been a democratizing force: "I certainly don't want t0 be the person defending porn, but one of the things it's done is show that real people are not as sexually picky as American commercial culture might lead us tO believe. There's a place in porn for older people, people 0f different races. ” Meanwhile, new cultural wokeness—and rigidity— creates confusion and resentment for Brendan, Eve's blithely self-assured, unsophisticated son. Perrotta demonstrates hO 、 the conversation around re-envisioning sex and gender, one that occurs entirely above Brendan's head, has consequences. ln the author's telling, it "leads tO a kind ofpuritanical calling-out ofpeople wh0 have sinned against these goals. ” This may be the latest Of perrotta's works tO be adapted by Hollywood. HBO, which broadcast the grand-scale ad 叩 tation The Leftovers, has optioned Mrs. Fletcher, following film versions of Perrotta novels Election and Little Children. But the in- demand author's wading intO the contemporary campus comes from a prosaic place: chats with his college-age children, wh0 also helped inspire his previous b00ks. (LittIe ChiIdren came out when they were just that. ) The parent and his children have had very different experiences. "1100ked at college as this place 0f freedom and liberation and ん n , ” says perrotta (Yale ' 83 ). "And now a 10t 0f people experience it as a kind 0f minefield, where you have t0 watch what you say. Maybe that's not a bad thing, but I think the sense Of it as a fun place or a place where the world gets bigger has become much more complicated. " perceptive 0f slight shifts in the SOCial current but never condemning hiS sinning characters' souls, perrotta proves an amiable guide through it all. —D. D. Tom Perr tta F SCOTT FITZGERALD T E N D E 」 5 TENDER THE NIGHT ( 1934 ) By F. Scott 日 ge ′ a Acouple'stenuous marriage begins tO unravel on the French Riviera, surrounded by temptation and danger. lnspired in partbyhis own life, it was thelast novel Fitzgerald would complete. Flctehcr COMPLEX CHARACTER NewIy liberated Eve is the latest memorable Perrotta heroine. Says the author: "l'm really interested in tellingthe story Of women Of my generation. " PHILISTINES AT THE HEDGEROW ( 1998 ) By Steven Gaines The journalist's pop history examines passion and property in the Hamptons," where the rich and the famous behave badly and compete over real estate with long-entrenched locals. MeM 計一 0 齢 HOW STELLA GOT HER GROOVE BACK ( 1996 ) By Terry McMiIIan A divorced investment analysttakes a break from her life as a single mom and heads on vacation tO 」 amaica, where shefalls fora man halfherage. 49

WILL SHE BE MARRIED 0 ドド AT 15 ′ 14 靆 3 ′ Every year, more than 1 5 million girls end 叩 in early marriage, some as young as age 12. fact, in the developing world, one in seven girls is married before her 1 5th birthday. For these girls, it's an end t0 their education and their childhood. ■ But ChildFund lnternational educates communities about the damage caused by child marriage and even steps in tO prevent or undO such marriages. SO 訓 girls have the chance t0 fulfill their potential. ■旧 27 countries, ChildFund is improving the lives 0f more than 19 million children and family members. Learn more at ChiIdFund.org chi\dFunn4 HeIping children ⅲ need worldwide achieve their potential.

す U R N ー N G 1 H E B 0 DY ー N 10 A C A N C E R 日 G H す E R A breakthrough new approach, awaiting FDA approval, has the potentialto transform cancer treatment by converting the bOdy's own cells intO cancer-destroying agents. Here's hOW it works: WITH THE USUAL MIX OFANTICIPATION and apprehension, Kaitlyn J0hnson is etting ready tO go t0 her first summer camp. She's looking forward t0 meeting new friends and being able to ride horses, swim and hOSt tea parties. She's alSO a little nervous and a little scared, like any 7-year-01d facing her first sleepaway camp. But the wonder is that Kaitlyn is leaving the house for anything but a medical facility. Diagnosed with leukemia when she was 18 months old, her life has been consumed With cancer treatments, doctors' visits and hospital stays. Acute lymphoblastic leukemia is the most common cancer among young children, accounting for a quarter of all cancer cases in kids, and it has no cure. For about 85 % t0 90 % 0f children, the leukemia can, however, be effectively treated through chemother 叩 y. lfit is not eliminated and comes back, it is, more Often than not, fatal. Rounds of chemotherapy can buy patients time , but as the disease progresses, the periods Of remission get shorter and shorter. "The options for these patients are not very good at all; ” says Dr. Theodore Laetsch, a pediatrician at the University Of Texas Southwestern Medical Center. When Kaitlyn's cancer wasn't con- trolled after three years and round after round of chemotherapy drugs, her doc- tors had little else to 0 飛 r. "They said, 'This did nothing, it didn't touch it,' ” to ChiIdren's HospitaI of PhiIadeIphia says Kaitlyn's mother Mandy, a dental (CHOP), where they stayed in a hotel for assistant from Royce City, Texas. "My eight weeks while Kaitlyn received the stomach just dropped. " Kaitlyn could therapy and recovered. "The thought receive a bone-marrow transplant, but crossed my mind that Kaitlyn might only about half of those procedures are not come home again; ” says Mandy. successful, and there was a good chance "I couldn't tell you how many times I that she would reject the donor cells. If would be ⅲ the bathroom at the hospital, that happened, her chances 0f surviving spending an hour in the shower just Kaitlyn 砒 age 5 , after receiving her were very small. crying, thinking, What are we going t0 ow 〃 genetically modified immune cells ln a calculated gamble, her doctors do if this doesn't help her? ” sugge sted a radical new option : becoming a revolutionary approach tO cancer But it did. After receiving the therapy a test subject in a trial Ofan experimental treatment that uses a series Of precision in 2015 , the cancer cells in Kaitlyn's body therapy that would, for the first time, use strikes tO dis integrate cancer from within melted away. Test after test, including gene therapy tO train a patient's immune the body itself. Joining the trial was risky, one that picks up one cancer cell in a system tO recognize and destroy their since Other attempts tO activate the million, still can't detect any malignant cancer in the same way it dispatches immune system hadn't really worked in cells lurking in KaitIyn's blood. What ま bacteria and viruses. The strategy is the the past. Mandy, her husband James and saved Kaitlyn was an infusion Of her late st develop me nt in immunotherapy, Kaitlyn traveled from their home ⅲ Texas own immune cells that were genetically 30 TIME August 21 , 2017 Cancer- cell dea TOXins Cancer ce 〃 0 The CAR T-cell rece ptors recogn ize unique proteins on the cancer cells. They latch ontO the proteins, triggering the T cell tO destroy the cancer cell Cancer protein T ce ″

らイ EVERY LAST " CHILD DESERVES に ~ A FUTURE Save the Children Meet 5- year• -0 旧 Amena. Seeing her safe inside 0 hospital, リ ou wouldn't know that she's 0 child refugee from Syria, recently rescued at sea from certain death. At save the Children, we dO whatever it takes ー every da リ and in times Of crisis ー t0 ensure children likeAmena grow up healthy, learning and safe. NO matter wh0 they are or where they're born. Because every child deserves 0 future. Every st child. SavetheChiIdren.org/Amena WatCh Amena's dramatic rescue and recovery. *ChiId's name changed for protection. ◎ 2017 , Save the Children. AII rights reserved. Ph0to: Louis Leeson.

he stepped on a land mine in Afghanistan, ⅲ 2010. KeIIybecame the highest-ranking U. S. military offcer to lose a child in Afghanistan or lraq since 9 / 11. When retirement finally came in 2016 , it seemed like a blessing. Kelly took a lucrative j0b working for DynCorp, a defense contractor, and steered clear Of what he described as "the cesspool of domestic politics. ” ()e also made clear that he was willing tO serve for either Hillary Clinton or Trump. ) Kelly was watching college football on a Saturday ⅲ Novemberwhen Reince Priebus called tO sound him out about a jOb in the new Administration. Kelly at first thought the call was a prank, the work 0f some other retired Marines. Once he was convinced it was Priebus, he asked his wife Karenwhat she thought. Her reply: "lfthey think they day, and then j oined the Merchant Ma- need you, you can't get out Of it. Besides, l'm really tired ofthis quality retired time rine t0 see the world (his first ship deliv- we're spending together. ” ered 10 , 000 tons Ofbeer tO Vietnam). ln Kelly had never met Trump and was 1970 , he enlisted in the Marines—a move surprised when the President-elect 0f- that would endear him tO many recruits fered him the job as Secretary of Home- he would one day lead—but that only land Security ⅲ the first five minutes 0f got him as far as Camp Lgeune. "I was his "interview ” at Trump's Bedminster, a grunt,: ” he recalled. wasn't commit- N. J. , golf resort. The post intrigued him ted tO a career. I wanted tO go tO college from the start—so did the red flags. AI- and come back and be an 0 伍 cer. ” So after most immediately, Trump aides tried tO tWO years at Lejeune, he entered the Uni- install as Kelly's NO. 2 Kansas secretary versity ofMassachusetts in Boston, grad- Of state Kris Kobach, whose theories uated in 1976 as a commissioned Offcer about widespread voter fraud made him and began t0 climb the Corps' small but a Trump favorite. Kelly resisted and won fiercely competitive leadership ladder. that battle, but he lost the fight t0 bring in lt was a legendary run. He served on a deputy ofhis own choosing. This quickly carriers and did stints at Quantico, Camp because the pattern. Aides he wanted on PendIeton, the NationaI War COIIege ⅲ his team were 0ften vetoed by political Washington and the Marine Corps' head- types around the President. And Kelly, quarters in Arlington, Va. He served three whO in his post at Southern Command tours in lraq and alSO tOOk on more po- was responsible for a variety Of issues litical posts, including congressional li- ranging 仕 om drug cartels t0 Latin refu- aison for the Marines as well as senior gee flows, bristled at the coaching Trump aide tO Defense Secretaries Robert Gates aides tried tO give him in advance Of his and Leon Panetta, both ofwhom worked confirmation hearing. ⅲ multiple White Houses. "This is a guy Then c ame the hastily drafted travel and the Caribbean. Kelly won wide praise WhO iS focused on the mission; ” Panetta ban. when Kelly first learned 0f the for his work there, but he drew attention told TIME. "You tell him to take the hill Executive Order, he asked about White when he criticized President Obama's and he will take the hill. Then he'll tell House talking points for the embassies you there's a smart way and a dumb way decision tO open combat POStS tO women and Congress. The answer: there were and his desire tO close the military prison tO dO it. none. The incident le 仕 Kelly stunned by at Guantanamo Bay. Kelly could be He was sharp and salty, but the Trump team's lack of preparation. But famously blunt. Asked about the rise of also collegial and adaptable t0 any he appeared before cameras t0 SLIPP0rt ISIS in 2016 , he said, "As a military guy, environment. After at least 45 years and the ban and promised t0 carry it out. That it's simple for me. My part 0fthis equation 29 moves, he completed hiS Marine career angered Democrats who had backed his is tO kill as many ofthem as we can. ” as head of Southern Command, a four- nomination. lt alSO endeared him tO the KeIIy knows the cost of war too well. Star POSt that covers more than countries president, who found himself defending His son Robert was killed at age 29 when spanning Central America, South America 25 TRUMP'S GENERALS H.R. MCMASTER NATIONAL SECURITY ADVISER BACKGROUND A West POint graduate and cavalry officer, McMaster authored a scathing rebuke Ofthe militaryleadership during the Vietnam War as part Of his Ph. D. from the University Of North Carolina at ChapeI HiII.Itformed the basis for his best-selling 1997 bOOk DereIiction ofDuty. A000 0E5 Known as the lconoclast General, McMaster's efforts tO rewrite military doctrine stalled his rise through the ranks. He earned a Silver Starforvalor duringthe first GulfWar and served multiple deployments tO lraq and Afghanistan. NOTABLE 000 す E "OurIeaders can'tfeel compelled tO tell their bosses what they want tO hear. ” 物

Time 0 竈 "IT'S BEAUTIFUL. SHOULD I TAKE APICTURE FORMY lnstagram?" Aubrey plaza stands up t0 snap an iPhone ph0t0 ofthe avocado toast that's just arrived at our table. She care- fully moves ourwater glasses t0 declutter the shot, which she says she'll post the week her new movie, lngrid Goes West, hits theaters. ln the 61m , her character also uploads a perfect portrait Ofthe overpriced green grub t0 her lnstagram, with the aim ofimpressing a social-media influencer She wants tO befriend. Now PIaza shakes her head and laughs, saying, "This is stupid." She's humoring me, because l've asked her tO meet me—in honor ofthe film's theme ofmillennial social-media obsession—at lower Manhattan's Café Gitane, the birthplace ofthe fOOd trend that's become an lnstagram cliche. Plaza, 33 , hates social media. But she's willing t0 gram and tweet as much as necessary tO get people tO see the film, which she also co-produced. Directed and co-written by newcomer Matt Spicer, lngrid follows a lonely young woman who, after the death ofher mother, uses her inheritance tO move across the country, make herself over and befriend an lnsta-celebrity (Elizabeth Olsen) who's famous because she eats the right toast and wears the right floppy hats. Plaza is brilliant, playing lngrid with a teetering balance of fragility and derangement. lngrid is alSO a window intO a phenomenon with which Plaza is familiar: the gulfbetween who people are and who Others perceive them tO be. lt's been tWO years since she said goodbye t0 April Ludgate, the enthus iastically apathetic municipal cog she played for seven seasons on NBC's Parks 0 d Recreation. But many of Plaza's fans hold fast to the notion that Aubrey is April and April is Aubrey. Plaza cops t0 being complicit ⅲ the confusion. "I have a wh01e cycle 0f feeding this persona that has been projected onto me,: ” she says. "My reaction tO it as a people pleaser is tO give that back, which isn't always authentic to who I really am. ' PLAZA HAS WANTED tO be an actor since her first acting workshop around the age of10. At her all-girls Catholic school in Wilmingt0 n, D el. , she was both a type -A student running for president ofevery student organization and a class clown. Like April, she loved Halloween, but not for its celebration ofthe macabre. She loved that it allowed her to dress up in costumes and play characters—in Other words, tO act. When she wasn't in school, her life revolved around movies: making them, watching them and checking them out tO customers at a video-rental shop. She worked there alongside her aunt, who introduced her to independent films like Christopher Guest's Waitingfor Guffman andJohn waters' SeriaIMom. She also fondly remembers watchingJurassic 20r た and anything that ended with a kiss between TO m Hanks and Meg Ryan. "lt wasn't like I was watching FeIIini," she says. Her 61m education continued when she went to New York University's Tisch School ofthe Arts and honed her comedy 44 TIME August 21 , 2017 skills at the Upright Citizens Brigade, co-founded by future Parks co-star Amy Poehler. She hoped to have a career like Adam Sandler's: join S 砒肝 d Night Live, make her own movies and take on the occasional dramatic role. But before she got the chance t0 emulate Sandler, she was cast opposite him inJudd Apatow's 血 Pe 叩厄 , after which she began her gig on Parks. Since then, Plaza has proved that she can do much more than roll her chestnut eyes. ln The TO DO List, her virgin valedictorian brings a Poindexter- tinged mania t0 completing a Trapper Keeper んⅡ ofsexual ventures before college. ln the raunch-fest Mike 0 れ d Dave Need WeddingDates, she played a crass manipulator WhO smokes weed out ofapples and eats leering bros for breakfast (metaphorically speaking— the zombie she played in LifeAfter Beth literally does eat dudes). lfthere's a common denominator, it's a smidge ofsociopathy—which makes PIaza perfect to play lngrid. The character's behavior in the film's opening scene—crashing a wedding and pepper- spraying the hashtag-h 叩 py bride—could easily be classified as crazy. But Plaza grappled with whether or not lngrid was actually mentally ill. "Borderline personality kept coming up when I was trying to understand what 加 lngrid Goes West, 2 20 ' S character seeks connections 0 〃れ e as 0 reprievefrom loneliness INGRID GOES WEST ( 2 ) 】 2E0 PARKS AND RECREATION 】 GETTY IMAGES; DIRTY GRANDPA 】 LIONSGATE; LEGION 】 FX: MIKE AND DAVE NEED WEDDING DATES. T 工 E TO DO LIST 】 EVERETT

0 0 Presley autographing phOtOS in Houston ⅲ 1956 0 0 3 ◆ 82.6 % Rating Of PresIey's first appearance on The Ed Su 〃 ivan Show, on Sept. 9 , 1956. He later played on the program tWO more times. He was paid $ 50 , 000 for the shows, a huge sum atthattime. ⅲ 1956. "I just fell into it, really. My daddy and I maestro ofSun Records whO recorded artists such as were laughing about it the other day. He looked at B. B. King and lke Turner in a still-segregated South, me and said, 'What h 叩 pened, E? The last thing I understood the underlying realities 0f Jim Crow can remember iS I was working in a can factory and America. Chuck Berry and Little Richard would be you were drivin' a truck' ... lt Just caught us up. early breakout stars across the color line, but Phillips believed that would not be enough to integrate the Ⅱ . THESURGE cultural and commercial markets. "I knew that for Presley emerged at the moment the machinery 0f black music to come to its rightful place in this post—World War Ⅱ mass culture began t0 hum. The country, we had tO have some White singers come world was on the move; 01d barriers were under over and dO black music—not copy it, not change, siege; new possibilities were opening up. lt was the not sweeten it. Just dO it," he said. With presley's age 0f the GI Bill and Brown v. Board 0fEducation, emergence ()s well as Bill Haley's and Jerry Lee suburbs and television, interstate highways and Lewis', among others), Phillips' prophecy came true, fast fOOd. Material prosperity in Eisenhower's but not without resentment from the architects Of America was startling. Families whose forebears the tradition Presley was drawing on. "I was making had struggled on the fringes of farming and of everybody rich, and I was poor; ” said Crudup, wh0 debilitating manufacturing work suddenly had originally recorded "That's AII Right. " "I was born more money (and more things, ranging from TVS tO poor, I live poor, and l'm going t0 die poor. ” washing machine s ) than they could have imagined ln the white mainstream, Presley's story was two decades before, in the depths Of an economic quinte S sentially American— a striver rising tO riches crash that seemed to go on forever. When J0hn from largely impoverished obscurity (his family Maynard Keynes was asked whether there had lived ⅲ a federal housing project ⅲ Memphis after ever been anything like the Great Depression, he moving tO Tennessee) on the strength Of his talent, had replied, "Yes. lt was called the Dark Ages, and not on the circumstances Ofhis birth. "I don't know it lasted 400 years. ” One unexpected benefit from what it is; ” Presley told the Saturday Evening Post THE ONCE AND FUTURE KING PresIey makes one Of his 升 t public performances, at the Mississippi-AIabama Fair and Dairy ShOW. His song earns him a fifth-place prize, and months ね t he begins playing guitar. EIvis PresIey is born in TupeIO, Miss. tO GIadys and Vernon く PresIey Signs with RCA in a deal worth S40 , 000. The PresIey family moves tO Memphis. PresIey soon becomes interested in the 0 blues scene. PresIey. 》 NOV. 1955 NOV. 1948 OCT. 3 , 1945 JAN. 8 , 1935

3 0 物。第 = を第敷三当を気 ツ , を第ニ iS a weakened immune system; because meticulously SO that we develop this in the treatment wipes out a category of the right way. ” his immune cells—the ones that turned For now, CAR T cells are expensive— cancerous —he returns tO the University some analysts estimate that each patient's ofpennsylvania every seven weekS for an batch of cells would cost hundreds of infus ion Of immunoglobulins tO protect thousands of dollars—because they him from pneumonia and colds. Olson, require a bespoke production process. tOO, is still cancer-free. If approved, Novartis, which licensed WhiIe the number ofpeople who have the technology from the University of received CAR T cell therapy is still small, Pennsylvania, will provide the therapy the majority are in remission. That'S in about 35 cancer centers in the U. S. by especially encouraging for children, the end ofthe year. Other companies are whose lives are permanently disrupted already workmg toward universal T cells Ludwig with his prized 必 by the repeated cycles oftreatments that that could be created for off-the-shelfuse above, d in 2010 receiving the currently are their only option. "lt's a revolutionary CAR T cell 市 era 〃ツ in any patient with cancer. "This is just chance for these kids to have a normal the beginning, ' s ays June. life and a normal childhood that doesn't advanced—perhaps as a replacement for Since Ludwig's cancer has been in involve constant infusions, transfusions, or in combination With Other treatments. remission, he and his wife have packed infections and being away from their The severe immune reaction triggered their RV and taken the vacations they home, family and school,: ” says Dr. Gwen by the therapy remains a big concern. missed While he was a slave tO hiS cancer Nichols, chief medical offlcer of the While it can be monitored in the hospital and chemotherapy schedule. This year, Leukemia and Lymphoma Society. and managed with steroids or antibodies they 're visiting Mount Rushmore , Grand The hope is that while CAR T cell that fight inflammation, there have been Teton National Park and Yellowstone ther 叩 y will at first be reserved for people deaths in other trials involving CAR NationaI Park before taking their who have failed to respond to 砠 standard T cells. One drug company put one of granddaughter t0 Disney World in the を treatments, eventually they won't have its studies on hOld due tO the toxic side fall. "When they told me I was cancer- t0 wait that long. As doctors learn from effects. "I am excited by CAR T therapy, free, it was just like someone said, 'You pioneers like Kaitlyn, Ludwig and but l'm also worried that some people won the lottery,' ” he says. "lf somebody Olson, they will have more confidence might get tOO excited,: ” says the American else with this disease has the chance tO 箋 in pushing the therapy earlier, when Cancer Society's Brawley. "lt's important walk in my shoes and live past it, that patients are stronger and the cancer is less that we proceed slowly and d0 this would be the greatest gift for me. ' 33 物ー第マ

immune cells turned out tO be more Of a hit-or-miss endeavor than a reliable road tO rem1SSion. After spending nearly three decades on the problem, June zeroed in 0 Ⅱ a malignant fingerprint that could be exploited tO stack the deck Of a cancer patient's immune system with the right destructive cells tO destroy the cancer. ln the case Of leukemias, that marker turned out t0 be CD19, a protein that all cancerous blOOd cells sprout on their surface. June repurposed immune cells tO carry a protein that would stick tO CD19, along with another marker that would activate the immune cells tO start attacking the cancer more aggressively once they found their malignant marks. Using a design initially developed by researchers at St. Jude Children's Research Hospital for such a combination, June and his colleague Bruce Levine perfected a way to genetically modify and grow thes e cancer-fighting cells ⅲ abundance in the lab and to test them ⅲ animals with leukemia. The resulting immune platoon of CAR T cells is uniquely equipped to ferret out and destroy cancer cells. But getting them intO patients is a complex process. Doctors first remove a patient's immune cells from the blood, genetically tweak them in the lab to carry June's cancer-targeting combination and then infuse the modified cells back into the patient using an IV. Because these repurposed immune cells continue tO survive and divide, the therapy continues tO work for months, years and, doctors hope, perhaps a life- time. Similar tO the way vaccines prompt the body to produce immune cells that can provide lifelong protection against viruses and bacteria, CAR T cell therapy could be a way tO immunize agamst can- cer. "The word vaccination would not be inappropriate; ” says Dr. Otis Brawley, chief medical offcer of the American Cancer Society. June's therapy worked surprisingly well in mice, shrinking tumors and, in some cases, eliminating them altogether. He 叩 plied for a grant at the National Cancer lnstitute at the National lnstitutes of Health to study the therapy in people from 2010 tO 2011. But the idea was still SO new that many scientists believed that testing it ⅲ people was t00 risky ln 1999 , a teenager died days after receivlng an 32 TIME August 21 , 2017 experimental dose ofgenes tO correct an inherited disorder, and anything involving gene therapy was viewed suspiciously. WhiIe such deaths aren't entirely unusual ⅲ experimental studies, there were ethical questions about whether the teenager and his family were adequately informed of the risks and concerns that the doctor ⅲ charge of the study had a financial conflict Of interest in seeing the therapy develop. 0 伍 c s ⅲ charge ofthe program acknowledged that important questions were raised by the trial and said theytook the questions and concerns very seriously. But the entire gene-therapy programwas shut down. AII of that occurred at the University Of pennsylvania—where June was. His grant application was rejected. lt would take two more years before private funders—the Leukemia and Lymphoma Society and an alumnus ofthe umversity WhO was eager tO support Ⅱ e 、 cancer treatments—donated $ 5 million tO give June the chance t0 bring his therapy tO the first human patients. THE DATE JULY 31 has always been a milestone for Bill Ludwig, a retired cor- rections 0ffcer in NewJersey. lt's the day that he joined the Marines as an 18-year- old, and the day, 30 years later, that he married his wife Darla. lt was alSO the day he went t0 the hospital tO become the first person ever tO receive the combination gene and CAR T cell therapy, in 2010. For Ludwig, the experimental ther 叩 y was his only remaining option. Like many people with leukemia, Ludwig had been living on borrowed time for a decade, counting the days between the chemotherapy treatments that would hOld the cancer in his blood cells atbay for a time. lnevitably, like weeds in an untended garden, the leukemia cells would grow and take over his blood system again. But the periods Of reprieve were get- ting dangerously short. "I was running out oftreatments; ” says Ludwig. SO when his doctor mentioned the trial conducted by June and Porter at the University 0f Pennsylvania, he didn't hesitate. "I never thought that the clinical trial was going tO cure me,: ” he says. "I just wanted tO live and t0 continue t0 fight. lfthere was something that would put me intO the next month, still breathing, then that's what I was looking for. ” When LudW1g signed the consent form for the treatment, he wasn't even tOld what tO expect in terms Of side effects or advers e reactions. The scientists had no way 0f predicting what would happen. "They explained that I was the first and that they obviously had no case law, so t0 spealg ” he says. SO when he was hit with a severe fever, had difflculty breathing, showed signs of kidney failure and was admitted tO the intensive care unit, he as- sumed that the treatmentwasn'tworking. His condition deteriorated SO quickly and SO intensely that doctors tOld him tO call his family to his bedside, just four days after he received the modified cells. "I told my family I loved them and that I knew why they were there,: ” he says. "I had already gone and had a cemetery plot, and already paid for my funeral. ” Rather than signaling the end, Lud- wig's severe illness turned out tO be evi- dence that the immune cells he received were furiously at work, eliminating and sweeping away the huge burden 0f can- cer cells choking up his bloodstream. But his doctors did not realize it at the time. lt wasn't until the second patient, Doug Olson, who received his CAR T cells about six weeks after Ludwig, that Porter had a eureka 1 れ 0 Ⅱ lent. When he received the call that Olson was also running a high fever, having trouble breathing and showing abnormal lab results, Porter realized that these were signs that the treatment was working. "lt happens when you kill huge amounts of cancer cells all at the same time; ” Porter says. What threw him off initially is that it's rare for anything tO wipe out that much cancer in people with Ludwig's and Olson's disease. June and porter have since calculated that the T cells obliterated anywhere from 2. 引 b. to 7 lb. ofcancer in Ludwig's and Olson's bodies. "I couldn't fathom that this is why they both were so sick' ” says Porter. "But I realized this is the cells: they were working, and working rapidly. ltwas not something we see with chemotherapy or anything else we have to treat thiS cancer. ” LUDWIG HAS NO 、 been in remiSS10n for seven years, and hiS success led tO the larger study of CAR T cell therapy ⅲ children like KaitIyn, who no longer respond tO existing treatments for their cancer. The only side effect Ludwig has

引 00d - cancer cells T cells—which can seek and destroy cancer cells—are extracted from a patient's bIOOd ② 0 T cell antigen chimeric produce modified to genetically are the T cells ②旧 the lab, DNA ー cell T ce[ls 3 The CAR T cells are grown in ね e numbers in the lab and are infused back intO the patient ceptO (CARs) that make them better cancer fighte rs receptor antigen Chimeric modified to destroy her leukemia. "You take someone whO essentially has no possibility for a cure—almost every single one Of these patients dies—and with [this] therapy, 90 % go into remission,' says Dr. David Porter, director of blood and bone-marrow transplantation at the University of PennsyIvania. Such radical immune-based approaches were launched in 2011 with the success Of intravenous drugs that loosen the brakes on the immune SYStem SO it can see cancer cell s and de stroy them with the s ame vigor with which they attack bacteria and viruses. Now, with the genetically engineered immune cells known as chimeric antigen receptor (CAR) T cells that were used ⅲ Kaitlyn's study, doctors are crippling cancer in more precise and targeted ways than surgery, chemotherapy and radiation ever could. While the first cancer immunotherapies were broadly aimed at any cancer, experts are now repurposing the immune system intO a personalized precision treatment that can not only recognize but also eliminate the cancer cells unique tO e ach individual patient. What makes immune-based therapies like CAR T cell therapy so promising— and SO powerful—is that they are a living drug churned out by the p atients themselves. The treatment isn't a pill or a liquid that has to be taken regularly, but a one-hit wonder that, when given a single time, trains the bOdy tO keep on treating, ideally for a lifetime. "This therapy is utterly transformative for this kind of leukemia and also lym- phoma; ” says Stephan Grupp, director 0f the cancer immunotherapy program at CHOP and one of the lead doctors treat- ing patients in the study in which Kaitlyn participated. Eager to bring this groundbreaking option tO more patients , including those With Other types Of cancers, an advisory panel for the F00d and Drug Administra- tion voted unanimously in July to move the ther 叩 y beyond the testing phase, during which several hundred people Often does, and it iS expected tO announce obligated to follow the panel's advice, it ments have failed. While the FDA isn't with certain leukemias if all other treat- become a standard ther 叩 y for children have been able to take advantage ofit, to 31 Trial after trial failed as reinfusions of cancer and battled skin cancer himself. cancer, having lost his first wife tO ovarian familiar with the devastating effects Of ofthe U. S. NavaI Academy, June is all too wh0 pioneered the therapy. A graduate Abramson Cancer Center and the scientist at the University Of Pennsylvania's 0f the Center for CeIIuIar lmmunotherapy the research,: ” says Dr. CarlJune, director "Only a handful ofpeople were doing its own cells. and the immune system is loath tO target cells that mutate and grow out ofcontrol, the body, cancer cells start out as healthy and viruses that are distinctly foreign tO ing. Unlike infection-causing bacteria the practical reality had proved daunt- cancer has been around for a long time, ofusing the body's immune cells against ever, almost didn't h 叩 pen. WhiIe the idea THIS REVOLUTIONARY THERAPY, hOW- in the U. S. , as well as untold suffering. currently spent each year on cancer care cant drop ⅲ the more than $ 120 billion treating them, would result in a signifi- patients. Curing cancers, rather than may even lead tO a cure for some ofthese tO e ntertain the ide a that this living drug are even cautiously allowing themselves benefit from this novel approach. They hundreds of trials to see if they, too, will diagnosed ⅲ Senator JOhn McCain—in sarcoma and brain, including the kind breast, prostate, pancreatic, ovarian, ing tO enroll people with Other cancers— Across the country, doctors are rac- itS decision in a matter ofweeks.