The treatment

The treatment - chubby boy who go on a bafiocm advcae‘...

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Unformatted text preview: chubby boy who go on a bafiocm advcae‘ rum? and, like other Rm: pmjects, it"s more literate anci suphisricated than most movies now being made for adulta. In the opening scene, we see the QM mam, Car}, as a boy, beginning to fail En love with Ema, a neighborhood girl. Then, in a wordless fourminum scene, we see a monmge 0mei and 33331165 fife mgether, ending with Ellie’s 313mm and death. “Like mamas eke, I burst into tears when I first saw the sequence,” Giaixfiino toié me, at a café in his neigh~ borlwod, a flew weeks aficr his Omar Win. “11: commtmimtes so strongky how life whizm by” He scored it in his usual Spare mama, writing a poignant wait:- éng meiody and favoring a baad of guitar, violin, simmer, and basg. As in “Lost,” he leaned on chords that fall} from major to mifior, and fixrtrher atom omized by telescoping them into em: binmweet, slightly dissonam harmany. His restraint makes the chumce 2.1} The more affecting. At tha next “Last” sassio'h, Gayk Levant—who, along with my other members ofthc Graham bad piayed on “Up”~—presenteé Giacchino with an enormous cake that bore the legcné “Cengmmiations, Michael1 W’s Love You." Gig-aching had brought in his Oscar and othcr amuds he had iatcly cofiectcd—w‘; Goiden Globe, a RAMA, anci two {3de the musicians rook W posing for pictures ufith them. Giacchino had to draw the fine, though, when the players smz’tcé asking if'flmy wulti take the awards home; Giacchim has hem Exmdering what to do mm. Some: Egan efhirn has aways wanted :1} p13): a larger mle ii‘i aha 1713m— making prmess, an& be has zalkcd to Abrams about the possibilities. He is taking the gamma: off'fmm film scaring ant} wifl try his hand at writing an ex- tended C0an piece, at: the invitation of the Dallas Symphony. He plans r0 stop writing for teicvi sionwrha mshed sched— ule has become we exhauztring, even for him. Ya”: he feds wistfizi at the presgaect afghng up the medium in which he has had singular success. “OfeVeryth-ing I’ve dam: in my career, or whatever you want to trail it, ‘Lost’ is the puma“: version of me musicaily,“ Giacchino amid, sipping iced tea. “I grew 1:1} with 51) many (ijffiimnt sounds, anti ins? 311mm me to exgress :11} if it, the makmfic and the atonah It‘s aisfi the put— esz versien of ma: smotionafiymi’m re- acting to these cimmcters thaz 1’ vs: spam so much time wid’z. It works because: I 30%: the showwi have rhe same attitude as some guy who carts up on his sefa cm Tuesday night to watch: I’m not making Calmlated decigionswoh, this cm: has to Saund Bin: :1 ninemenmventies thing, this has to sounci like an. mic Trajan War thing. it’s mach mom in'afitivc than that. it’s the music I won writt: if I were writing for myseif. In my Daflas piece, Til. see: how far I can ga in the same Aévertise men: gwww 823 THE HRS? 'Ftfi HEAR ABOUT EVENTS. PRQMOT§ON$ ANS 89EC3AL OFFER$ FROM NEW YORKER AQVEETEEERS. a 5 § 1 sungap re sess: ns (iimcriom without my ‘Lost’ {fiends- iu from ofmcf’ 1.}. Abrams is probably right whey: he 5 says that “Lost” might nave: have become a phemammon without Gmmixw's can» mbu’cion. ‘Whenl watched the pile: m - (361111}? as: DVD, 3 haw cffc: rflafigly the music ensnams thtz 3am In the first i two mimics, jam baa: a sinuousiy crccpy imp figue that (30:35 a fimery, four—note mm afid than {ism a feurrh. Giaechino 3 c2113 the thnme “the spirit fifths isiandf grid has used it thmughout the series. Th3 way such fiaggmms of themes keep dwaioping {mm episode to episofis cre— atm an overarchmg human. tmsion that: pluggeduin pop songs can’t match. Fa— mi§i3r music is a mmmlicnt Hutch, but, in the and, it wvers emotions in a péastic sheen, Unfimiiiar music gives the same i that somedxing new is Eaapgcning before QUI‘ eyw and cam. Mayhem is building :13 “Lost” moves tomtrd its canciuskoa, wt Siacchizm’s git}? {or piainspokm malociy will emerge i at the very end. On May 6th, Giacchim “ was complsfing the music for the fimi ‘ two egfisodas of this Show, which wifl air in a mowandmawhalflhour marathon. A (fouble remrdi-ng session was scheduied for the foflouflng 63y. "in mfidafiemoon, .1 rewivmi an e-mail containing a cue sn— titled “Parafltlgcam”—forz}r—foui bars in slew, (316332.: C major, with a piano play- . mg against a 80ft wash 0f smgs. Giac- chine’s chords ofpcrpemai ambivalence seemed to be 63ng toward some souifitl resoiufion. in the final twc bars, thong}, I saw a few, suiimxy C for the hag), which, like tbs best mysteries, amid be read my number ofmys. & NEWYORKEE.CDM IGOIOUTLOUB Alex Ross an Michsei (Hartman‘s: music. as A mm 53? mt- smsawxa sassmm s g} The premise is simpées. fake one i giobaé business chafié‘nge. Bring. different experts in diverse fieids to the tabfia. Thar; give them a platform to share {heir seiutions. “MWWW. «1.. Sessions was iné'tiatedwa multiwpfafiarm. mufiidiscipiinary approach that seeks to find me most insightfui sciatica?» to the most pressing chaflenges. of the day. incmding addrass'lng wnfici water needs and improving urban thoroughfares. E With this in mind; the Singapore 1 i I E i Wewanttokzmwhatymfllink. ; Join the gkabal conversaiion today at. fingapnmfiesfiom newycrfiemnthetowmcom 'E'HF. NEW YCX‘KER. MAY Fr. 2010 67 ANNALS OF lNNOVATlON THE TREATMENT Wby is it 59 dgfimlt [a daqu» dmgrjbr mam"? In the world of cancer research, there is something callezi a Kaplan—Meier mm, which tracks the health afpatienrs in the tzial gfem experimental 6mg. In its simplest version, it consism of two lines. The first follows the patients in the “central arm." the second the pa— rients in the “swarmith arm.” in mosr cases, zlmsc {we lines are Virmaély iclew tical. That is the sad fact 9f cancer re— search: nine times our often, there is :10 difference in. survival between theme who were given. the new dmg and Those who were nor. Bur every now and againfidfn tar millions ofdollzirs have been spent, and tens 01" thGi‘éSflfldfl of pages; of data collected, and patients fallowcd, and tomcologiml issues (namii’iirieri~ and safatj; issues refioivccl, and manufacturing pro- cessas finewt‘unedmthe patients in the matmenr arm will live longfir than the paiiesirs in the cantrol arm, aacl the we liaes on the Kaplanbhlleier will star? to diverge. Seven years ago. for example, a team from Gamma}: presented the resulrs of a ashram—saucer drug trial a: the 2m- mm] riteetirig (lithe Amalgam Society of Clinifial Oncologywa cerifcrcncc at' tender? by vimmlly every majrar gang‘ar researcher in {hit world. The lead Gem nemccli researcher wok the audicnce Ehmugh one Slicie afrcr anofiiewcfiré, dis/ls, cfké—laying out the design anci scape 0f the study. until. lie came to the crucial mommt: the Kaplan-Mcicr. Ar that point, what hr: said became irrele» mm. The mcrnbars of the audience saw daylight ban-veer: the two lines, for a par- timt yopulation in which rhat almost never happened, and thcyleaped to their feet and gave him an mailer}. Every drug mscsmthar in the world (ircams of standing in from OthOUSHndS ofpeopie at ASCO and clicking an 3 Kaplan-Mcier like that. “It its wh; we 1ch in this bus§~ mess," Sail Ballad} says. Once he though”: BY MALCOLM GLADW£LL that this dream would coma mic far him. It wag in the late mzrimer of 2006:, ané is aiming flu: greaicst moments; (if his; life. Bahcall is the (2.30. of Syma Pharmaceuticals, a small biotechnol— ogy company. it occupies a onewsmry brick Iiinetcen-‘vscvcntics building amt— :éirie Boston,just of? Roam 128, where: many lithe region’a high-tech compa- ziics have congregated, and that sum» mer Synta hari mm compoundg in dew V8i0§mefll. ODE W33 i1 cancer Elfilg called elcsclamal. The other was an immune modulator called apilimmi. Experimental drugs must pass through three 311121563 of testing before they can be: considered for government ap— proval. Phase 1 is asmall trial to deter mine at what (loge the thug can be taken gaf‘ely. Phase 2 is a larger trial in figure out ifi‘; has dilemma tic platen" rial, and Phase 3 is a definitive trial to see if‘it ammlly werks, rim-ally in com— pan witch slmdard treatments. files— clomol had progressed tn Phase 2 far scftwrissuc sarcamas anal for lung can» car, and had some up filled in both cases. A Phase 2 {rial for metastatic melanoma—a deadly farm :yf‘skjn can— ccrmwas also under way. Bur that was a limg Shot: anthng ever workari well fm- melanoma. in the prwious filmy five yam, than: had been. something like seventy large—scale Phase 2 rrials fbr memetatic—melanoma drugs, and if yam platted all the results on a single. Kapixn—Mcier there wouldn’t be much more than a ramr’s «lg-e of difference thEWCEU any m ofthe iinés. That left apilimmd. In animal stud— ies and early clinical $2215 for autoim— mune éisordm, it Seemed promising. But when Syntax went to Phase 2 with a trial fer psoriasis, the results were 1m» derwhclming. “It was ugly," Bahcall ‘We hail lung cancer Fail, smtnma maxi, and their: psoriasis. 'Wc had we more trial left, which was for Croimi‘s disease. I rcmembar my biogrars guy coming into my ofiicm saying, ‘I’vc got mam: good news and same bad news. The good news is tint apiliumd is safe. “We have the data. No taxidry. The bad news is that it"s not effective} lt was heartbreaking." Balacall is: a boyish man in his early fortiesg with a rouaci face and. dark, curly hair. He was aiming at me diningnmom table in his spamely filmished armr- ment in Manhattan, overlooking the Hudson River. Behind him, a bicycle: was leaning against a bare wall, giving rhe mr'im :1 postwcollegé feel. Bath his parems were asrmphysicists, and he, for}, was trained as a physicist, before leaving amicmia far the bufiiness world. He gmw up in the maim shim abstract and the tllmrctiu§l~wfitli theorems and mlmlations and precise measuremenrs. Bi}: drug :ievclopment was diil'crem, and wimr: he spoke about the failure 0f spill-mod there was a slight catch in his vows. Rahal] marred to rail: labour one 0% six: firs: patients ever {mated with elasw 1210:1101: a menrpfourwyearolcl Aliiczm- finiericaza mm. He'd had. Kapnsi’s gar» camel: tumors infirm} his lower £05530. l’iéd been a: Bath larael Dcaaoncgs Medical Center, in Boston, and Bahcail had flew“: up to see him. On a Momiay in january (Inf-2003, Baiicali 83.! by his bat} and they talked. The patient was fist our ofcollcgc. He had an LV, in his arm. You went :0 the hoespital and yau sat next tn some kicl whose only Wish was no? to die, and i: was impossible not to get emotionally inmlvcd. in physics, failure was disappointing. In drug de— velepmcnr, failure was; bearférméing. Elesclnmol wasn't much help against Kaposi’s sarcoma. Ami new apilimod didn’t work for Cmbn’s. “1 mean, wa'd Mam swam % r: g in: '2‘ w elegant m mfiwxa! drug dcrz'gii, (in! if pwvia’m £56 glam a) {afar rompfetc’ly w: expgrz‘cd :1 imagery: {lone charity Wink for the thn’s £3: Colitis medation,” Balieall went an. “I have relatives and friends with CIGl’lu’S (£56356, personal expciicmce with Crohn’s disease. W it had lein’s Imients come in and talk in meetings and tell their stow ties. W’c’d raised money for five years item investom. I felt ramble. Here We: wm with out ltatl tintgmd it lmé failed, It was the and of the line." That summer ufZQGt’i, in One pain- ful meeting after anorhet, Synra be- gan m doxmsim. “It was aVli’ednesday,” Bahcall said. ‘Vz’e were around a talble, and we wnre talking about pmnitig the hunger and lmw we’re going to contain mitts, one in a strict 0f tough discnsv sinus, and l noticed my chief medical affirm, lfiiricjacobson, at the and niche table, kind of lacking a little unusually parity for one of thesis kinds {if {lis- wssions." After the meeting, Bahcall pulled jacobson OVCFS “Is something up?" Jacobmn nodded. Half an lmur btfiite the meeting, he’d rammed some news. it wax about the melanoma trial fin: clcaclomel. the Stanly everyone had. given up on. ‘The consultant said she had new: seen data this grand,” jambw son told him. Enlicall called back this managttmnnt Emmi for a special meeting. He gem: the floor to Jambsnn. “Eric was, like, ‘Well, you know we’ve gnt this melanoma trial.’ " Salami}. began, “and it tonic a moment mpg pcnple’s memories. 136* mass we’é all been no focussed 0n Crnlin’s dlSCEESfi and tlm psoriasis trials. Ami Eric saicl, ‘W’efl. we got the insults. The clmg wwkedl It was a positive trial? " Cine pawn-n slammed the table, $1.0m} up, 21ml liellerml. Otlicn: pcph pared Eric with quesfions. “Erie: said, wall, the group analyzing the data is trying to disprove it, and they can’t dis— prove it.” And he said, "The cansultant handed me the data 011 W eclnesday morning, anti she said it was bninking gtmd.‘ And cvnryozit: said, 'Wrfiat?’ Be- cause Eric is the sweetest guy, who newer swcam. A bad word cannot arms his lips. Evcrymie matted yelling, ‘V‘Ilmt? What? What ciitl she say, Eric? Eric! End Say it? Say it!’ " Balm-all contacted Syntzi‘s board of diractors. Two clays later, l1€ sent out a climpzmywwidc €"mail saying that than: - would he: a meeting that afternmm. At four n’clock. all hundred and thirty '30 THE NW? YORKER. MAY W. 2010 employth amped irate the building’s lobby. lambson smod up. “Sc; the lights; go domt,” Bahcall command. “Clinical guys, when they present tiara, tend to do it in a very botmzns-up way this is the disease popiilatien, this is flit“ Ucnfmcnt, and this is the drug, and this is what was randomized, and this is El’ic (ii-3:110» graphic, and this is the patient pool, and this is who had toenail fungim, anti this is who was lavish. Tim}! go (in. anti an and on, and all anyone wants is, Show us the linking Kaplamllrleietl Emily he: said, ‘All right, now we can get to the efiicatjr.’ 1!: get}; reallysilem in the room. He clicks the slide. The twn lines scp~ mute out beautifullymmd a gasp gocs mt, acreazs a hundred anti thirty people, Eric starts: to continue, and one permit goes like this”—-Bah<:all started clap~ ping slowly—fund then a couple Clix-3w plnvioinecl in, and than soon the whole room is just going like this—clap, clap, clap. There were tears. ‘We all realized that out livfis lmd Changed, the lives of patients had changed, the way tif‘tmat— ing the disease had Changed. In that momma, everyone reallmd that this little nominally oi‘a haunted 21ml pimple had a chance to win. We had a drug that worlmd, in a disease where nething worked. That was the single most moving five minutcs tif'all my years at 83mm." In the Winter of 3955, El young decrm nanricd Emil Frcircich arrived at the National Cancer Institute. in Bethesda, Mainland. He had been (ital?th into the Army, and had been sent to fulfill iiis milimq nbligation in the publicwhcalth simian-3. He went to 806 Garden Ztibttxl, then the clinical (Erector for the: NC}. and later one (fiche majar figures in cam— mr teseatch. “I said, Trim :3. liernatolngist,‘ ” Fteémich recalls. “He: said, ‘l’ve got a good idea for ynu. Cure leukemiaf It was; a militia-1y assignment.” From that as“ signmcnt came, the fitst great break— through in the WM against cancer. Freireich’r: {new was on the com— monest form of childhotid leukemiam acute lymphoblnstie leukemia (ALL)- The diagnosis was a death sentence. “The children wtiulti come in blending,” Frciraich says. “They’d have infections. They woulrllie in pain. l‘t’lttdinn suwival was about eight weeks, and «Everyone was (land within the year." At the time, three {itugs were known tn lit: useful against ALL. One was zisethotttixate, which, the yetiiatric pathologist Sidney “Earlier had shown semen years earlier, could push the: disease inm remission- Cnrricostcmitls and 6—mercaptnpurina {ti—Ml”) had Slllé‘fii prnveci useful. But even though nicthotrnmtc and 6&4? muld kill a lot of cancer cellt, they Couldn’t kill them all, and that“: which smmived would tegmup and acljufl and multiply and return with it vengeanct. “These reinigsinns wm all. tempmmym mo or three mnnths,” Frcitcich, who now directs the adult—leukemia research prmgram at the M. D. .r‘méersnn Can— cer Cfifllfl, in Manama, gaysi “The num tlwtitles in litmntnlogy didn’t even want to use them in children. They felt itjuizt pmlongcd the agony, nmcle them tang-er, anti gave them side effects. That was the landscape.” In those year; tin: medical worlti lmd made great strides against mbcrwlosis, and treating til). am into the same 53ml)“ ktm as Treating cancer: il‘dntttnrs went after it with em: thug, the bacteria cvcw- rually tlcvclnpfid resistance. ’llieir salliw 6.011 was to 1532 multiple drugs; simulta— neouny that worked in very different ways. Fteitcich wondcmé about apply“ ing that model to leukemia. Manama—u are worked by (lisnigat'ing {tilicwacid up— take, which was. crucial in the division of walla; {inP shutdown the synthesis (if purine, which was also critical in cell iii— wisinn. Putting the two tngethet would be likn hitting the. cancer with :i left hank and a right hook. “inviting with a gmup that (Eventually included Torn Frai, affine: N.C.l., MECl limits Hellsnd, tithe meell Park Cancer lnttituft‘, in Bulfnlo, Ftciteici: started treating ALL patients with methotrcxatc and E—MP in continuation, each at mmthircis its regular dose to keep side elixir; in check. The mmissions grew more frequent. Fmireicli then added the steroici prtd~ nisone, which workcé by a mechanism iiifibrent from that ("if either {i—MP or methorrexaie; 116 could give it: at Full dam and not Witty about the side nfibcts; getting out ofcontml. Now he had a left book. a tight limit, anal an uppermt. “So things are looking gooé," Freiw midi went on- “But still everyan dies. The: rcmlSSlOI‘iS are short. And then out nftlii: blue came the from Element” mother drug, deriwd from pcnwirildc. that had been {fiscm’cred by Irving John— son, a msearchm at Eli “In order: :0 get two milligram ofdmg, it tmk some- fixmg like two man-ca; loads ofpcrivdn— Ede,” Freireich said. “It was exparmive. Bntfohnson was paralstent.” Lilly offered the new drug to Freircich. “Johnson had dame work in mice, and he Showeé me the results. I said, ‘Gce whiz, I’ve get: ten kids on the ward dying. l’fi give it to them tomorrow.’ Se l" went to Zubrm‘l. He said, 1 don’t think it’s a good idea? But I saici, "R1653 kids are dying. “’ha‘t’s the Macaw? He mid1 ‘O.K., I'll lctyou do a few children} The: response rate was fifty—five per cent. The kiés jumped wt of bed.” The drug was called vina'isztine, and‘ by itself, it was rm wonder drug. Like the othcm, it worked only {Cir 21 while. But the good news: was that it had a unique mechanism ofamjanmit inter» fared with cell division by binding to what is called the spinéle pmthnd its side effects were éifi‘ercm fiom {boss oftlm osher drugs: “30 I sat dawn at my desk one day and l thought: Gm, if 1 cm give 6»M‘P and math at nvo«:h.ir&s dam: and prednisone at full dese and vlncristine has different limiting toxici- tieg, I bet I can give a {£311 dam of thata :00. St) I dwiseé a uéal when: we weuld givfl all four in combination." The trial was called VM-JP. It was :a left hook, a right hook, an upyezcnt, and a jab1k and the lmgm was: {hm ifyou hit" laukcmia with that barrage it would never get“ up offthe canvas-:2. The firs? pa‘ricm mated under the experimental regime-1% was a young girl. .Fmi mich started Em offwkh a (lose that turned out to be :00 high. amid glue al— masc died. She was put on antibiotics and a respimzor. Freizcich saw her sigh: times a (lay, sitting 21% her bedside. She pulled through the chemca—indumd cri— sis; only to (Be lam ofan infection. But Freireich was learning. He tinkered with his protocol and started again. with patient No. 2. Her name was janice. She-was fifteen, and her rcmvcry was mathng share of miraculous. So was the recovery affine next patieat and the next anti the next, until nsariy every Child was in rcmiss'mn, without need of antibiot- ics er transfixskms. 1;: 1965, Frci and Fmimich published Gm: ofrhe most flan mans articles in the history ofimcology, “Progress and Perspective in the Che~ mothempy ofAcutc Leukemia,” in Adm “I see 50 mm»? Ewe réflectézz’ 5:2ch in 27%; adsmxfile {iféiéfizca " vamm in Chewaa‘éz’mpy. Almortt three decades later, a lmrfectly healthyjankzc gracccl the cover a)" the journal szcr?’ Resmmfi. What happeneé with ALL was a fimnafive exparifincc for an entire gem creation of cancer fighmrs. VAN]? proved that maximal: didn‘t need 3 magic balm letwd supertimg that conic? smp all can— cer in i2}; tracks. A drug aha: worked a little Mt (:01:le be combiawd with aa— wther that werkml 1!. little bit and an» other that Wflrkfl$ a litle bit, and, as long as all thm: worked in dificrent ways and had different side efibfis, the cambimtion could turn Out to biz spec» tamlar. To be valuable, a cancer drug éidn‘r have to be especially effective «in in; own; itjust had to be navel in the way it acted. Ami, from the beginning, this was what caugeé so much exciwmcm aboui elesdomol. Safi Bahcall’s panmr in the founding of 33mm was a cell biologist at Har— vard Mail‘in Schoal named Lam Bo Chen. Chm. wl‘m is in his mid—sixtieg, was born in Taiwan- He is a miss-Chic“ vous mm, with gluon—cwppsé straight black hair and \mriwa quirks—inch}ch mg a Mll‘zngncss to say whamver is on his mind. a skepticism :1be all things lap-mesa (mejapanesc anccupicci Taiwan during; thcwav, after all), and a keen ia- tcmst in the marital prawccts of hié‘. un- attached cwwarkcm. Bahmll, wlm is jaw/3513.3 dcscrlbes him afihmiamwiy as “the Eyes: gmd WOE‘SQf parts of a [lavish fa— :her. and the has! mil wom parts :3? a jcwish mother rolled into one.“ {Sam— ple e-mail from Chen: “Sufi is in Israel. How he finds: “fifefl Drug hunters like Chen {all into on: of awe broad Schools. The first schoal, {hat of “rational dcgign,” believes in starting with the ciissase and working backward—designing a cusmmizecl so- luzion based on the chammm‘istics ofthe problem. Herccptin, {me C)? the mom important of the saw generation of iareastwcanmr drugs, is a gmd example It was based on genetic detactive work showing that about a quarter ofall bicast cancers: were caused by the twerproduc~ {ion ofa pmmin called HERE. HIERZ kept causing cells to divide and divficlc, and THE NEW YORiiER, MAY IT, 20D Tl fl ' ' J} I cm: £76415 yea; guys form a 21mm. scientists set about: defiigning a drug :0 mm H £122 off The result 715:: drug that improved survival i5: {weary—five per cm: cf patients with advanced breast cani'er. {When Hemep-tiu’s Kaplan» Eider was ShGWfl at ASCO, there was? stunned ailment.) But working back» wzud m 2. soiution raciuirw a precise um dcmmnding 0f the problem, anti can» cer remains so mysterious and wmpiax that in most cases salemists don’t haw: that precist: understanding. 0: they think they do, and than, after they mm off one mechanism, they discover that the rumor has other éeaciiy tricks in reserve. The: oth'er appmach is to start with a drug candidata 252d than hunt for dis- eases that if. might attack This swateg, Imown 3.6111355 screening,” doesn’t in— voive a theory. Instfiad, it involves; a ran» dom search far matches between treat- mems and diseam. This was the schml > to whiChChtm belonged. In fact, he Eek that that: mm probiem with mass scream '4"? THE NEW YORKEEL MAY 17, 2010 mg was that it wasn’t 1119.33 enough. There were wtmtiL-ss companias eutsidc the drag busmcsswfiom industrial re— search labs to photography ginms iike Kodak-and thiifiimwchat had miilions of chemicais sitting in weir vaults. Yet most efthesc chemicais ind nave: ham testeci ta see if {he}; had porential as timgs. Chen cotflcin’t understand why. If the goai of drug ciiscovew was new elty, shmfidn’: the ham Fer new (imgs go as; far and wide as possibie? “In the early cighries,1 Eookcd into how Merck mé P5223: went about (hug discovexy,” Chm recalls. “How many campounds are they using? Are the}: doing the best they can? And} come up Mfih an incrtdiblc number. It turns out that Inmxkind had, at this point. made was of miflions efccmpounds. But Pfizer was gcmcning only six hunémd thousafid mmpounés, and Merck even fewm, 31301;: five hundred thousand. How could they screen far drugs and use only five hundreti thousand. when mafikind has already made so many mom?” An and}? fumuciai backer 9f Chea’s was Michael. Milken, 6hr: junkvbomi king of the nineteen—eighties who, after being treated for prostate cancer, be- came a major cancer phflamhmplst. “1 mid Nikkei: my story,” Chen 5335., “and very quickly he said, Tm going to give you {our miflion dofim‘s. Do “threw: you wmm’ Right away, Miiken thought 9f Russia. Someone had mid him that the Russians had had, for a 139g time, thansmds of chemists in (me city mak- ing cempounés, anti none ofthesc com? pounds had been disalesad.” Chen’s first purchase was a batch of twenty-two thaummi chemicais, gathered 5mm ail ever Russia and {finds/3e. 'lhw cost about ten dolim's each, and came in {in}! glass vials. With his money fiom Milken, Chm than bought a six—hundrafi-thcusand‘ doflm‘ statav—ofithevart {finsgwscreening machine. It was a. big, autcamated Rube Goidbarg contraption that couki test niaety~six campounds at a time: and do a huncired batches :2 day. A ro’bodc arm wwid dfiposit a few drops afcaflh Chen? ica} (mm 3. pine, fofiowcd. by a clump of (mace: cells and a touch beiuc ciyn. The mixturt: was left to sit for a waek, anti than refifxamined- If the cells were Stifi aiivc, they weuid shew as Mme. fifthe nhamicai killed the cancer 0:11st fluid woulci be dram: Cheri’s iaboratory began by testing his cempouués against prosmte-cmcer ceilfl, since that was the ciéseasa Miiken had. later, hrs screened dozens Mather came: cells as wtli. In Ehc first go— amtmd, his batch ofchemicals killed ev— aryfhiszg in sight. Bu: plenty 9f com~ pounds, including pestficjdes and 0’:th sorts of inéustz‘mi poisons, wili kill mm mar regs. Th6 trouble is that they’fl kiil hcakhy ccfis as wen. Chen was Racking fur serum-ling thaf was Sdade—that was more likely to kill mafignant cells than normal celis- He was also inter— ested in Sensitivity—in a chemicnl’s abil» Jury :0 kili at 30w concentrations. Chen reduced {he amount ofeach chemicai on the piate a. thousandfold, and {tied again. Now just: one chemical wwrked. He tied the same chemical on heaithy tails. 11: left them alone. Chen iowcreci the (1056 another rhousandfold. Ir saiii worked. The compound came 50111 the National T3335 Shevchmfizo Univcrsiry ot-Kiev. l: was 23. odd little chemical, the laboratory equivzlflnt afajm musi— cian’s riff. “I: was pure Chemist’s joy,” Chen saidw “Homemade, madam, anal clearly made for no particular gurpose. It was the only one that worked on ev— erything we rri .” Mass; screening wasn’r as elegant or as efficient as rational (ling {lesigrr But it provided a chance ofsatumbling across something by accidcmm'something so navel and unm’pected that no scientist woulrl have, dimmed it up. It }3rmfide§l {or sermdipity, and the history ofdmg discovery is {fill 13f starics efscrcndipity. Alexander illeming was 1003(ng far somathing to fight bacteria, but didn’t think the smawcr would be, provided by the: mold that grew on a perri dish be ac— cidentally lair out an his bench. That's where penicillin came from. Pfizer was locking for a new heart trsanncnt and realized that a drug cmrdimtte’s unfit“ peered side effect was more useful than its main affect, Tirat’s whgre Viagra came fmm. “The and of surprise would be the and (if science? the hismrian Robert Frieda} wrote in the 2001 essay “Serendipity ls Ne Accident," “lb this extent, the scientist mus: cmnstantly seek and hepe for surprises.” When Chen gathescri Chflmizral compounds from the fimhcst cormzrs cuf'thc earth and {tasted them against one cancer—call line after smasher, he was engineering smprlse. W’imt he fennel was exactly what he'd lioptd for when lrc started liifi hum: something he could waves have imagined or: his; own. W’hefi cancer. csilg came inm comma? Wii‘l’l the charm ical, rhey warmed it) go imam-351$ mode: They acm‘l as ifthcy had imam «marked with a blowmmh. The Ukrainian chem“ ical, elcsclomel, warktd by gathering up ccyper from the bloodstream and bringing it into cells’ mitochondria, sparking 2m electmchemical reaction; His: focus was on the toxic, oxygen-v based cempounds in the: cell called ROS, reactive oxygen specim Normal cells keep ROS in chch Many kinds ofcanccr cells, though, generate :20 much ROS that the cell's ability :0 keep fimctioning is stretched {0 {ha breaking paint, arid elesclomol cranked ROS up even firrther, to the point rim: the cam cer cells went up in flames. Researchers had long known rim hearing a? a cam cc: call was r: gnarl way of it, and there had been plenty of inmrcsr over the yam in achieving that effect with R08. But the idea: Musing COppfli‘ to set of}? an electmchcmical reaction was $0 weirdwancl so unlike tbs way cancer dmgfi normally worked—that it’s not an approach anyone would have tricé. by dwign. T313: was the serendigity. it £00k a bit (Jf “Clwmiat’sjoy,” constructed for m) partimfim reason by some bench scientists in Kiev, t0 show the: way. Elcsrlomel was wandmusly novel. “1 fell in lave,” Chen said. “I can't explain it. l just did.” hen Freiraich went to Zubmd with his idea for VAMP, Zubrori could easily have said rm. Drug prom» sols are typically rested in advance {or safety in animal medals. Thlfi 0m: wasn’t Fraireich freely admin: shat the wlmlr: idea 9f putting together Emisonv our: drugs in Such dasages was “imam,” and, afceurfie, the firs: patient in the trial had nmrly been killed by the toxic regimen. if she had died {‘er it, tl'u: whole trial could have bean cierajled. The: ALL success story provider? a hopeful road map for a genemtism of cancer fighters. But it also firm: with a warning: more who pursued the unex— pt‘cted imé to live with unexpected cen— sequcriccs. This was not the cleganm of rational drug design, where scientiats perfect :rheir sawing in the labamrory before waving limo the clinic. Work» ing from flag Marmgnr :0 tin: diseatse wan an exercise in warming? and trial anal mar, If you’re flying to put mgathcr a Comifination ofthree, an" {Our drugs rm: of an available {1001 sf dozens, how do ynu choose. whirl} :0 star: with? The number of permumtimm is vast. Ami, once y‘m‘ve srzrtled on a combifiatlon, how do 31m; atlminisrer it? A chilcl gets sick. Ymt meat her. She grist/s infra remis- sion, and than she rclapsm. VAN? es“ rablifimcl that the has: way to induce remission was to treat the child aggxes~ sively when she 61%: showed up with lrculccmia. But do yam treat during the remission :12; well, or (ml); when the child rclagyses? And, ifyou Heat Liming remissigm do yen mm: as aggressively as yet: did during mmissien inducrion, or at a lower: level? 130 you use the same dnzgs: in inducrirm 21$ you do in remis— sion and as yet: d0 in ralapse? How (10 3:08 give the drugs, scqumtially or in cambmation? Al what ($098? And how {rapicntly-wvcry day, or dc- }mu want to give the child's body a &w days to re- cmer between bums: ofchemo? Oncologists comparad daily (a—MP plus daily mcrhotmxm: with daily é—MP plus methormxme every fbur (law. They compared merlmrmxate followed by fi—MP, é-lN’lP Follawed by medicame— are, and both together. The): mmgareé prcdnisone fialloweci by full closes of "Strut: ngewnarr {are}??? an: 51:13:57.: 3' £215 sax €501" 1755122 1:55 I—mM—yau—m (391‘. " 6M3 methotmxam, and :2 new (bug, cyciophogphmnide {CTX}, with preci- nisom: followed by hali‘doacs i)f6«M§’, mcti‘zotrmmfe, and CTX. it was endless: vincristlne plus predaisone and then methotrflafe every {bur days or vlnmisu time, plus prednisane and than metho— traxatc daily? They tried Eww drugs, anci diflkrcm combinations. ’l‘hey tweaked and refined, am} gradually pushcci the care mm {mm forty per cent: to eighty five per can; A: Sulfide Children’s Kw scare?) Hesgiml. in Memphismwhich became :1 major center of ALL re» scarchmno fewer than sixteen clinical trialg, enmllifig 3011 children, have Mn conducted in the past .lbft}"C§ght years. And this was just childhwd leukenfia. Buginning in {he nineteenusevcntlcs, Lawrence Einham, at Indiana (,lnivczr- sity, pushed cure mtes for rcsticular can— cer above eighty pm? Gem with a ragi- men called 1515?: {lures to four rounds (3f lj-ieomycin, cmposide, and cisplatin. In the: nineteen—5w mties, Vinseng T, D?— Vim, at {he NCl.‘ tamt up with MGM” fin‘ advanfied Hofigkin's‘ disease: mus-n {algal}. oncovm, pmczubazine, and pred— nisone. DeVim want on to develop :1 combination tlicrasgy for breast canw car called C}??? Lyrlaphasphamicic, merlmtrexate, and S—flmmumcfi Each comhinafi (3:: was a variatimi on the com“ bimfion that came befere it, tailored m is targct fialuugh a Series of itcmfims. The Often asked qucsstion “W’lmn will we finé a cure for cancer?” implies that there: its some kincl (ifmasfer code be- himi flu: disease waiting to be cracked. But“ perhaps there isn’t a master mole. Perhaps there is only what can be an“ wvereci, one 559;: at a time} through trial and arm}: When elesclomol emergcci fi'om rim laboratory, than, all that was known ghoul it was; that it did semeshing novel to camcf calls in the labvmtory. Nobody imé any Rica what its best ta;th was. So Synm gave elesclomol m an oncologist at Beth Israel in 3233mm, who bcg‘m ramiomly testing it out on his patienm Tm comliirmfioa with padimxel, 21 Stan» elm} Cinematth drug. The «Edition ofclesclumol seemed to shrink the {timer of 3<>meone with melanama. A 2921:1323: whose advanced own-hm cancer had tidied multiplé rounds of previaus immanent bad game: rcspange. There was: dramatic activity agnins: szcsi’s sarmma. The}; «mid i1 ave gem: (in with Phase 13 indefinitely, ofcourse. Chen wanted to combine elcsciomul with. ra- diation therapy, and another gmup at Sfmm would later lolaby hart} r0 Si‘ild}? alcsclmmol‘s afflicts an 21mm mycleid iaukcmia (AML). the cemmcmezat fibrin of adult leukemia. But they had to {haw rite line gomwimie. {Dime 2 mafia he lung canccr, soft-635m sarcomas, and melanuma. New S‘ynm had ita mgetg. But with this munci oftasting came an even more difficult questing}. “513% the hem way to conduct a tesr ofa drug you barely undcrfit'and? To complicate tnan fin“- :imr, malanoma, the me that seem a} to be the best affix: three aptions, is among the most complicated ofail can- cers, Sometimes it confines itself to the surface 43f thc skit}, Sometimes it in- vades every urgim in the bady. Some kinda (if melanoma have a mutation in— volving a gem: {3311M 85ml“; others don’t. Sam: late-stage melanoma tumors pump (m: high levels (if an enzyme called LIX-“i. Snmctimex they gimp out only low levels ofLDH, and patients with low—LDH tumors lived so much longer that it" was as if they haci a difibrcm ($356238. Two patients could appear to have idmtlcal. (iiagmfises, and than (mt: wmtld be deaé in six menths and the mine: would be: fine. Tamers sometimes mysteriously disappeared. How did you mnciuct a (hug trial with a disease like this? it was'mfirely gmfigible that classle- mol wiittld work in EOW—LDH patients and not. in liigh~LDi~I patients, or in laigthDH patients and not in law— LDH ones. It might Wtiz'k well agfinst {he melanoma that confineé itself :0 iii“: skin, and not against $1116 kind that invadmi the liver and other secondary m‘g‘ms; i! migh: work in the early stages safazictastasis and mm in the later stages. Than there was: the prim—freatment question. Became of how quickly w: more; lmceme ragismm to {ii-123:5, new treatments sometimas work better on “naive” patients—«these who haven‘t been {reared with ether forms 0f the— methempy. So elesciamol might work on clicmomai'vc patients and not on prior—chemo patients. Ami, in any of thcsc situations, elegclemol might work bettcr or wame depending on which other drug or drugs it was cam- lJinecl with There was no emi m the possible combinatizms of patiem pop- ulatians anti dmgs than: 33mm. could have expimcd. A: the same time, 3mm had to make sure that whatever trial it ran was as big as passible. W’ith a discmc as vari able as melanoma, there was always the risk in a smell} swdy that what you thought Was a positive msuit was madly a mafia: of spontaneous mmissions, and {hat 3 neg— ative remit was just the: bad luck of hav— ing patients with an mmsmfly recalci— trant form of the disease. john Rifle wood, a melanoma. specialist at the UMchsity of Pittsburgh, haé done the mmh: in rude: m guard against some lucky 0r unlucky artifact, {he zraatment arm 0f :2 {31/3353 2 trial shmzlé have at £635? sevemy path-MS. 83mm was faced with a diiemma. Given melanozm’s variabiiity, {be com‘ pany would idcafly have dome $33153 dawn 0; more versions of its Phase 2 {r1311 low-LDH, higthDH, early~ sxage, iate»stage, grief—chemo, chenm- naive, maid—drug, gingh—dmg. There was no way, though, that they amid affin‘d to do that many trim with sew cant}: patients in each treatment arm. The American biotcch indusmjr is main: up oflots of companies like 3311mm" cause smafi starfqu are believed to bc those inlmvat‘: 'c and adventuhas than big pharmaceuticfi houses“ But not even big firms can d0 mankipk: Phase 2 triais on a giggle diseasewnot when, triaEs cost more than: a hundred Ehuusmd doilars pg: patiant and am what}, in the pursuit of Serendipity, they are simultaneously mistiag that same mpcrimenmi dmg (m two or three other kinds of cancer. So 53mm mmpmnfiseci. The company 361% {ME 05 one melanoma trial: fifiy—thm: patients were given eicsciomcfi piazs gaaxiitzmd, and Meaty—“eight, if} {be con" troi gmup, wear fivcn paaéinmci alone, rcpmsentiag evczy 50:: of Lifl'l Emmi, gage of‘discase, and priowsreatmmt smms. That’s a hug W3? {mm hzaif :1 dozen minis 0f sewnty each. Synta then went to Phase 3: six hun— dred and fifty-one chemowna‘ive pa- tienm, drama from a hundred and fifty hesgétaig, in fifteen countries. The trial was: éubbcd SYMMETRY. It was fundad by the pharmaceutical giant Giaxo Smith Kime. (Ham agreed to underwrite thc cos: {3? $116 11cm round of cfinécal trials andmfihould the drug be agpmved by the Feed and Drug Ad» ministmtjonuto split” the revenues with Sjs—‘nta. BUE was this: the perfecf triad? Not really. in the Phase 2 t‘rial, citsdosndi had been mixed with an orgama soak-“em allied Cremaphow 2.13:} than spun J/W’fig“ ¥ “It advancedz‘ég tecbnafagv, 5m! if; Imiagzzme changer. ” amund £11 a sonic-afar, whici’) is Eike a mini washing machéne. Eksdamal, which is rockwhard in its crysa'alline form, needed to be compictely dis— solvad if it was going to work as a dmg. For smrm-‘llfi’m‘f, though, sonicators wuldn’t be: useri “Many muntries '3an that it wouid be difficult, and some hospézsis even said, ‘VJc: don‘t afiow sanitation in the preparation mom; " Chm explained. “W’s got ail kinds <3? imbeiiemblfi fucaciback‘ In the end, we came up with something that, after; mixing, you we yen; hand t0 egémkc it." chalfi Emmi shaking be a probicm? No one kncw. Than 2?. Synta chemisz, Mitsunoré 0210‘ figured tau: how t0 make: a water— sniubic version of 61331110310} ‘Nhen the head of Synta's Chemistry team presented the: results, he “sang aJ'apau nest: drinking sang,” Chen saki. per— mitzing a smell} simile at the ec— cenrricitécss of the hpancse. “He was very happy.” It was a great aacompiishw men: The water~50§11b§¢ version maid be given in highgzr doses. Should they stop SYMMETRY and start again Wi‘ih elasclomol 2.6? They cauidn’c. A new mal wouid cost many mfilinns of (301- Im; more, and set the whole effort back two or three years. So they went ahead with a that didn’t dissom: casiiy, against a diffide target, with em assow men; of patients who may or 51121.}; me: have ham idealmmd crossed {ht}: fingers. SYMMETRY began in km: 290?. It was a d0ubi¢~b§ini randomized trial. No {me had any idea. who was getting eles'gciumol and wim “Emit, and m) {me woalé have any idea how walk the: 19:3: ticnts on elusciomol were daing untii the trial data were unhiindad. Day“ m—day management 0f flu: Study was Shasta} wiih a Ehirdwparry contmcmr. triai itselfwas suycn'iwd by an (mt- side group, kusawn as a dam-monitoring cannuittcc. MW“: send 3mm ail that data in same database fbnnat, zmci they plug {hm into their software package and then they type in the cutie ami press ’Enter,‘ ” Bahcai] mini. “And then this line”—he minted at the Kaplan—Meier in from 0f himw—“will, hopcfixlly, sepa- ratc Ems twa lines. They wiii find out in thirty seconds. It’s, lézcraily, {11056 guys press a button and for flat: next five years;, ten years, the fife: of the drug, that’s walk}; the oniy i312: chvidefice that matters.” It was 33mm; 2009, 3.36% the last of tin: 3i}: hundscd and fifty-One paticnzs were scheduled m be emailed in the trial in the next few weaks. Ac- cording to pmrocoi, when abs vaults began to some in, the datawmonitoring THE NEW’ YOKKEIk MAY 17, 2010 ?5 committee wcmld Call jncobson, and jacobson woulci call Bahczill. “ASCO starts May 29th,” Bahcall said. “If we get our data by early May. we could present at" ASCO this year.” :1 the course ofthfiz SYMME’l‘RY mat, Bahcafl’s diningwrmm—tabie talks grcw more refleetive. He drew Kaplan— l‘v-‘leicrs on the back awfzmpkms. He mlkecl about the: mists and Rams that tithe!“ him arch companies had encountered {m the road to the marketplace. fie mié my sto- ries abet}? Lag} Bo Chm, the Jewish mother ami )ewigh father roiled iutv onedancl, over 21ml War, he brought up the name ofjudnh Folkman. Folkman died in 2008, and he was a iegcnci. He was the @2123 ofangiogemsis—a wholly new way of attacking canch tumors. Avasrin, the dmg that everyone chcczmi at ASCC.) seven yam; ago, was flue result of Foikmazz’s wurk. Felkmzm’s gram” breakthrough hmi come while he was marking with mouse melanoma cellfi at the: National Naval Mcdical Caner: when tht: tumors couldn't set up a network of blood vessels to fired themselves. the}: woulci stop growing. Foikman realized that the body must have: its mm system far prmnming and 7F: VHF, NEW MKEK, MAY 17. 2010 halting blood—vessel formation. and that if 11:: could find a substance that prevented vesseis from being fanned ha woulfii have a patemialiy gmwarfifi can» cer drug. One ofth msearcimrs in M’dlunanfs labomrozy, M ichaei O’Reiliy, found what. seemed m be :1. potent §n~ lfibimr; angiosmtin. Q’Reilly than as» gambled a group of mice wlth an sag— gmssive lung cancer, :zml irritated half with a salim mluticm and halfwirl: 9m" gisssmtin. In the back “Dr. Foikman’s W’ar" {2001), Robert Cooke {lesarlbcs {he climacaic moment when flu: results ofchc Experiman came in: With a bards: of excited rescayclwss §am~ packcé into a small laboratory mum, FUllc» marl. euthanized all fifteen mica. rhm began handing them one in: (me It: O‘Rcéily w éia» O‘Rtéfly £00k {he first mouse, made an incészkm in its chest, and rcmnvcé {lac hmg. Tim orgma was? nverwhclmed by cancer. Folkmzm checked 2: nmchook to Her: which gmup {he mouw had Ewen in. it was mm of {laws that haci gmtcn (mils; saline. URL-ill}: wt inm the next mouse anti fumcwmi irs lung. it was pulsar. Whm treazmem had it gmmn? "file nombouk revealed E: was Lilsgiosmrin. I: wasn’t Folkman's triumph that Babe-all kept aiming back to, however. It was his; struggle. Folkmazl’s great in“ sight at the Naval Mmiiml Center oc— curred in 1960. O’Refillfs breakthrough exgerimmt occurred in 1%419 the. in— tervening years, Feihnan’a work was dismissed and atmekcd, and. conficmmd with away abstacle. A3: fimes, Bahcaii tried to sonvince himself th at elcsclomol’s path might be different. 53mm had thosa exciting Phase 2 results, and the ccfldarse-mcnt 0f the (31mm deal. "Fm the msulrs not m be real, ymu’d have to believe that it was; just a statistical fluke that the gum rimts who 3%.}? cimgs are getting lat:— ter,” Bahcal] said, in (me of those ciiw ing—room4able moments. “Yau’d have m fielieve shat the fact that than: were more responses in tha n'cafmmt gmup was also a smtistical fluke, along with the {act film: we’ve seen these signs if activity in Phase 1, and the that that the underlying biology sicrongly sayg that Wt: have an extremely active anti— cancer agent.” But then he: would remember Falk- 1mm. Angiosmtin am} a companion agent alga identified 503’ F 01141113sz lab— oramry, cudasmtin. were licensed lay a biotech company called EmmMed. And Knack/led never made a dime oil" either drug. The two drugs failed to Show any clinical effects in both I’imm E and Phase .2. Avastin was a completely different: wtifingiogmcsis agent, dis~ caveer and developed by another team entirely, amil hmught to market a decade after O’Rcilly's experiment. ‘vVhat‘s more, Avastin's colar'exrml—atanqer trialm the am: that received :1 stamimg ovation a? \5ifi.)mwas the drug’s: second gum around. A previous; lest‘c '3 trial, for breast cancer, had bat-:9, 9. crusthing {allw Life. Even Falkmzm’s bmutifizliy elab— orated theory about angiogmesis may not fill}? explain the: way Avasrin works. In addition to guitigzg of}. the flow Elf blood vessels; to the tumor, Avastin seems also to work by repairing some 0f the bland vessels feeding the tumor, so thin the drugs adminigmrcd if: combiw nation with Amati“ can get :0 the tumor men: efficiently. Bahcall finllmvcci the firmness ofothcr bietcch companies the: way a teenage boy foliast baseball. stadstics, and he Smew that nothing ever went smmt’hly. He could list, one by one, all {ht} bmak~ through dmgs that had filled their first Phase 3 or had failed muhiplc Phase 23, or that Eurnt‘d out mt {r3 wank the way they were suppaseci :0 W953:. In the wgrid of serenéipity am? of‘trial and. error3 failum was a csfiéition of discflvd any, bamuse, when something was new and worked in way}: that no one quite understooé, wary bit 9? kneawledge had to be Seamed, one experimem at a time. Yea caded u? with VAMP, which worked, but only after you compared dafiy 65M}? and dafiy methotrcxate with daiiy 6491? and methotmmte every four days, and $0 on, through a great Inme iterations, name. mfwhich worked very weii at all. You had {emits that looked “bfiinléng good,” but only after a triai with. a hundred compromfiaes. Chen had the same combination of mafiam and ideaiism that Bahcali did. He "was the invhcmsc skeptic at 33am. He was the one win; wonrfied the mast about the ham} shaking of the émgs in tin: SYMME’I’RY triai. He haé never been comfomtbie with the big push be~ hind melamma, “Everyone at Dana» Faxber”—~the car:ch hespitalat Harv ward—3mm me, ‘Dozit touch gmaiam- ma: 7’ Chm fiifiii. “ ‘1: is 30 hard. you save it as the. last, after you have rd— ready firearm! and tried evaqwhing else.’ " The scientists at Synm were getting her— tcr anti better at ufiderstanciing gust what it W93 that fiesdamal did when it mnfi’omed a cancer tel}. But hc knew that there was always a gap between what maid be learnad in the iaboratory and what happened in the clinic. “We jzfit don’t imam? what: happens in viva,” he said. “That’s why drug dm’filogment is; 51m 50 hard and $0 cxpcnsivc, because the ham bed}! is such a bad: box. We 21:: family shcafing in the dark.” Ht: shrugged. “Yea: have m have goat} sci“ cues, sure. But once you sham: rim drug in humans you g0 home and pray.” Chen was sitting in the room at Synta where Ericjacobson had revefiicd the “130ng good” news about ales» clemai's Phase 2 melanoma stuéy. Down the hall was a huge W—in freezer, fificci with thousands of chemicals from the Russian hall}. In another room was the Rube Goidberg drag-screening ma- chine, bought with Milkera‘s money. Chen began to £213; about cleaniomol’s earijest days, when he was still scavmgv mg ir‘nmugh tilt: libram’es of chamicai mmpanies for £33315 and 33112331 was still“ am cxwphysicéfl 30011ng to Stan a biotech wing-my. “I amid not comincc any-“One that eicmiomel had gotcmiai," Chen went: on. “Everyone mound me med. {9 stop it, including my research partner, who is 11 Nubel laureate. He. just hated it.” At one palm, Chen was working with yujifiim. The peopkt there ham elemdomel. He: WOI’kfid fer a whiic far the japanese: chemicai company Shie— n0gi.’1“he}apanesc hated it- “But yam know whc: I {band who bcfieved in it?“ Chen’s; eyes lit: up: “SafiE” as: year, am February 25th, Bahcafl and Chen were at z: Synta board meeting in midmm Manhattaa. Itwas fiveushirty in the afternoon. As the meeting was breaking up, Bahcaii got a. sail (m his mil phone. “I Investo take this,” he said to Chen. He (lacked into a nearby confemncc mom, ami Chen waited for him, with the company’s Chairman, Keith Goliust. Fiftem miw utcs passeci, thian Wang. “1 ref; Keith it must be the data—mam swing commit— we,“ Chen retains. “Hi: says, ‘No Waiy. T00 5mm. Haw couid the DMC . have any news just yet? I $3353., ‘E: has to be} $0 he stays with me and we wait. Arr other twenty minums. Finally Safi mums (mt. and I baked at 131m and I knew. He diciu’t have: to say anyihing. It was the cedar 0%? big face.” The call had bacn from Eric: jamir son. He had gust come back fmm $10:— ida. where he had met with the DMC, on iiht: SYMME'J‘RY trial. The: rtmits if the mi had beam Lanbiindcd. .hmbwn had Spent the £351: scveraE days gaing <3ch the (£11m, trying :0 answer every queaion 11:36. (iambic-check wary cart dusion. “1 have Some rem}! bad 1mm” he field 'Bahcail. The mafia} wauki have {a be halted: more pmpie were dying in the tramncnt arm than in die control arm. “it took me ahom a half hour to game out of primagr shock,” Bahcafl said. “I didn’t go hm‘flfi. I }usr grabbed my bag, got into a cab, want amighr to LaGu-ardia, tank the next flight to Logan, drove sunight to the OFFICE. The chick“ “26$an afiécm, the aziiaicai guys, smtisrical gays, npemicmi team wire 21%} there, and we essentiaily spent the rest affine night, unzil about one ear two in the morning, swimwing the: data.” it iookcd as if pattiems with high—LEE miners were the gxobicm: tilesdemoi seemed to fAil than completciy. It was heartbreaking. Giaxo, Balacafi knew, was certain to pal}. out QfIhe deal. That: wouid have to be many layoffs. Tim next day, Bahcmfl allad a meet:w ing efthe management team. They met in the Synm canference room. “Eric has same news,” Bahcadl saié. lawman stand 9;: and began. Em before he got very far he had to stsp. because he was overcame Md: situation, am? soon aw czyone clam in the warm “as, me, n Dccambar 7‘. 2909, 33mm re— ieased the fhl‘lnwing statement: Synm Pharmaceuticais Corp. éNAS- DAQ: SNTAE. a biapharmacemicai cam~ pan); focused on dismwcring, daveiuying. anti escrmmttrsiafizing smafi mulccnfe drugs in treat savers medicai conditions, mag}.- .mnuuaceé {he resairs of a study waltz-.2693; the nativity 0f eficsciumal against acme myeioid icukwnia {AML} 62%? Sims and wimm‘y buiaennic biasr ceiis :1er AM}. patients. pwscnwé m the Annual Meeting at" the American Sta-cm}; of Hamstrflugy {ASH} in New Orin-ans. . . . “The mmdmwm cenductcé .15 th'fl URL varsity of Tomma skewed eicmlomai was highiy acrive against AME. cell Hm and pri- mary bias? mils fmm AME.- pazicms at war centratians subscamfizzéiy 'iewcr than them Rim-my axhievcd in cancer patients in diam! minis," said Vuio \f‘ukovic. M .13., Phil, 5:“ aim Vim i’resiémt anti Chief Medical Offi— cer. Symiz. “0f particuiar iz'J‘iC’mq were the ex viw stuéics 0f prémar}: AME. Has: sells (rum parkway, recently :rcamé a: Tex-(mm. Wlwrc: 311 ii} saxnpies ofEcukcmir: mils mspimérd m exposu re m c‘iescksmnl. These resuéts provide :1 stmag mtkmaie for farmer mpiwéng {he pozcufiaf 6f ciesclomui in AME. :2 disease with high medics! nmci and fiimimd Optiims (a: gaiicms.” “l'wifl bet anything} haw, with any” body, that this wild be a drug out: day,” Chen saici. It was January. The early AEVIL results had just some in. (31ng was a: memory. “Now, maybe. we m- cmzy, we are romantic. But this kinci of characteristic you have K) have if you want to be a drug hunter. You haw m be aptimistic, you have to have su— preme confidexmc, because the odcis are so imrccfibly against you. I am a scicn— List. I gust hope that 1 would be so mu mantis that} bacome: deluded mough to limp hoping." 0 TH? NW YORKER. MAY 1?, 2010 77 ...
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The treatment - chubby boy who go on a bafiocm advcae‘...

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