FIRST ASSIGNMENT:Watch the PBS documentary series The Emperor of All Maladies pdf and answers to questions for Part 2 & 3. The Emperor of All Maladies - Part 2 Blind Men and the ElephantLinks to an ex

T he f o llo w in g p ro gra m c o nta in s m atu re c o nte nt w hic h m ay n ot b e s u it a ble f o r a ll a udie nce s. V ie w er

d is c re tio n is a dvis e d. T his p ro gra m is m ade p ossib le b y G enente ch , d edic a te d t o m akin g a d iﬀ ere nce

i n p atie nts ' liv e s a ro und t h e w orld . A nd b y C ance r T re atm ent C ente rs o f A m eric a , p ro vid in g

i n te gra tiv e t r e atm ent f o r o ve r 2 5 y e ars . B y S ie m ens, a h erit a ge o f in nova tio n, a p assio n f o r lif e . B y

D avid H . K o ch .

B y B ris to l- M ye rs S quib b, c o m mit te d t o t h e s c ie nce o f im muno-o nco lo gy. B y t h e A lf r e d P . S lo an

F o undatio n p ro gra m t o e nhance p ublic u nders ta ndin g o f s c ie nce t e ch nolo gy a nd e co nom ic s. B y t h e

K o vle r F u nd, p urs u in g s o lu tio ns f o r A m eric a 's n egle cte d n eeds. B y t h e A rth ur V in in g D avis

F o undatio ns.

A nd b y t h e A m eric a n A sso cia tio n f o r C ance r R ese arc h , b y A m eric a n C ance r S ocie ty , b y t h e L e uke m ia

a nd L y m phom a S ocie ty . B y t h e E nte rta in m ent In dustr y F o undatio n, b y S ta nd U p T o C ance r. B y t h e

C orp ora tio n f o r P u blic B ro adca stin g, a nd b y t h e g enero us c o ntr ib utio ns t o t h is P B S s ta tio n f r o m

v ie w ers lik e y o u. T hank y o u.

I s in ce re ly b elie ve t h at t h e t im e w ill c o m e in m y lif e tim e w hen

we g et c o ntr o l o f f o rm s o f c a nce r

w hic h a re c u rre ntly u nco ntr o lla ble .

I t r y n ot t o e xa ggera te t h at w e h ave f o und t h e r ig ht k e y. N ow , w heth er it w ill o pen t h e g ate in to t h e

s e cre cy o f c a nce r, t h at r e m ain s t o b e s e en.

I f w e c a n h arn ess t h e b uilt -in im munolo gic a l s y ste m , I t h in k w e c a n lic k c a nce r.

A gain a nd a gain d urin g t h e 2 0th c e ntu ry , s c ie ntis ts h ad c o nvin ce d t h em se lv e s t h at t h ey w ere o n t h e

v e rg e o f a s in gle c u re f o r t h e m any d is e ase s c a lle d c a nce r. B ut w it h e ach b re akth ro ugh, c a nce r

r e ve ale d n ew la ye rs o f c o m ple xit y . A nd la stin g c u re s r e m ain ed t a nta liz in gly o ut o f r e ach .

I t 's lik e s o m any d re am s t h at w e h ave , w here w e c a n't q uit e r e ach s o m eth in g, w here e ve ry t im e w e

g ra b s o m eth in g, it ﬂ ie s o ﬀ lik e a b all in a p ool. B eca use it 's c o nsta ntly o ne s te p o ut o f o ur r e ach , o ne

s te p o ut o f o ur r e ach . T hat is w hy c a nce r is lik e n o o th er d is e ase .

T he n ew m ille nniu m w ould w it n ess m ore f r u str a tio n, m ore d ebate a m ong r e se arc h ers . B ut it w ould

a ls o s e e s te adily d eepenin g u nders ta ndin g o f t h e w ays c a nce r d eve lo ps, o f h ow it c a n b e p re dic te d

a nd p re ve nte d, o f h ow t h e b ody's o w n d efe nse s c a n b e a rra ye d a gain st it -- s o m any d is c o ve rie s in s o

m any ﬁ eld s t h at r e se arc h ers h ave c o m e t o b elie ve t h at r e al, d ura ble c u re s a re n ot o nly f o re se eable , b ut in evit a ble .

T he c ycle o f d is c o ve ry o ve r t h e la st f e w d eca des h as b een in cre dib le . A nd w e'r e b egin nin g t o g et a

c lu e a s t o w hat t h e f u ndam enta l n atu re o f t h e c a nce r c e ll is . A nd w e a re b egin nin g t o a sk t h e

q uestio n, c a n w e n ow u se t h at k n ow le dge t o la unch a s e co nd a tta ck, a m ore s o phis tic a te d a tta ck

t h ro ugh p re ve ntio n t o t r e atm ent t o t a rg ete d t r e atm ents a gain st c a nce r?

A nd 1 0, 9 , 8 , 7 , 6 , 5 , 4 , 3 , 2 , 1 . H appy 2 000!

T he 2 1st c e ntu ry b egan w it h t h e p ro m is e o f a n ew g old en a ge o f s c ie nce a s e norm ous p ro gre ss w as

b ein g m ade t o w ard s o lv in g s o m e o f t h e m ost c h alle ngin g p ro ble m s, f r o m t h e A ID S v ir u s t o t h e o rig in s

o f t h e u niv e rs e . N o r e alm o f s c ie nce s e em ed p ois e d t o m ake g re ate r s tr id es t h an c a nce r r e se arc h .

T he d is c o ve ry t h at c a nce r w as a g enetic d is e ase in t h e m id -1 970s h ad le d t o t h e ﬁ rs t t a rg ete d d ru gs,

w hic h c o uld , w it h p in poin t a ccu ra cy, s tr ik e a t t h e v e ry a bnorm alit ie s t h at c a use c a nce r. H erc e ptin

h oned in o n t h e e ﬀ ects o f a s in gle m uta tio n, a ctiv e in a bout a q uarte r o f a ll b re ast c a nce rs .

B ut it w as t h e n ext n ew d ru g, G le eve c, t h at e sp ecia lly c a ught t h e p opula r im agin atio n-- a s im ple p ill

a ctiv e a g ene t h at c a use s C M L, a d eadly t y p e o f le uke m ia . G le eve c w as t h e c u re t h e c a nce r w orld

h ad b een w ait in g f o r.

Y o u c o uld t a ke p eople w it h h undre ds o f t h ousa nds o f m alig nant w hit e b lo od c e lls , g iv e t h em t h is

d ru g, a nd w it h in w eeks, t h e d is e ase w as d is a ppearin g. M any p eople in t h e c a nce r c o m munit y w ere

s a yin g, O K, c a nce r is g oin g t o b e c u re d.

T here is s o m e n ew h ope t o day in t h e b attle a gain st c a nce r.

T his d ru g o pens t h e d oor t o t h e f u tu re .

C ould t h is b e t h e b egin nin g o f a r e vo lu tio n in a ll k in ds o f c a nce r t r e atm ent?

G le eve c b eco m es t h e n ew r e lig io n. It b eco m es t h e n orth s ta r o f t h e c a nce r g ala xy. A nd e ve ry b ody,

a nd I m ean e ve ry b ody, is s u ddenly f o cu se d o n t r y in g t o r e plic a te t h e G le eve c m odel.

I f y o u lo ok a t t h e p erio d b etw een 2 000 a nd 2 005, it w as t r u ly e xtr a ord in ary. W e f e lt lik e w e w ere in

t h is g old en a ge f o r c a nce r t h era py. M ajo r in ve stm ents b y p harm a, b y b io te ch , a nd it ju st f e lt lik e w e

w ere g oin g t o b e o ﬀ t o t h e r a ce s.

B ut lik e s o m any p ro m is e d r e vo lu tio ns in c a nce r t r e atm ent b efo re , t a rg ete d t h era py w ould h ave t o o ve rc o m e t h e c a nce r c e lls u nca nny r e silie nce .

W ell, e xtr e m ely q uic kly , t h e q uestio n b eca m e w ere t h ose g old en e ra d ru gs-- H erc e ptin , G le eve c--

o utlie rs ? W ere t h e e xce ptio n a nd n ot t h e r u le .

T he d is c o ve ry t h at g enes c a use d c a nce r in t h e m id -1 970s in sp ir e d a g enera tio n o f s c ie ntis ts w ho

d ecid ed t o d evo te t h eir c a re ers t o t r a nsla tin g t h is in sig ht in to u se fu l a pplic a tio ns f o r p atie nts . O ne o f

t h em w as a y o ung r e se arc h er a t Jo hns H opkin s U niv e rs it y n am ed B urt V ogels te in , w ho s e t o ut t o

l e arn m ore a bout t h e m uta te d g enes t h at g ave r is e t o t h e d is e ase . V ogels te in c h ose t o f o cu s o n c o lo n

c a nce r, a s lo w -m ovin g d is e ase t h at w ould b e e asy t o m onit o r o ve r t im e.

O ur id ea w as v e ry s im ple . Y o u ju st c o m pare t h e D NA o f a c a nce r c e ll t o t h e D NA o f a n orm al c e ll f r o m

t h e s a m e in div id ual, a nd s e e w here a nd if it 's d iﬀ ere nt.

O K, t h at's n orm al c o lo n. T his is w hat it s h ould lo ok lik e . A nd h ere 's a c o lo n c a nce r.

I f t h e D NA is d iﬀ ere nt, t h en t h at's a v e ry c o m pellin g a rg um ent t h at t h ose a lt e ra tio ns a re r e sp onsib le

f o r t h e d is e ase .

W hen V ogels te in , b egan lo okin g f o r m uta te d g enes, t h e t e ch nolo gy w as p rim it iv e a nd t h e g oin g w as

s lo w .

L o gis tic a lly , o ne h as t o lo ok t h ro ugh t h e lit e ra lly b illio ns o f b ase p air s in a c a nce r c e ll g enom e t o s e e

w hat t h ose d iﬀ ere nce s a re . A nd t h at w as r e ally t h e c h alle nge b ack t h en.

B y t h e e nd o f t h e 1 980s, a fte r y e ars o f a rd uous w ork , V ogels te in h ad m anaged t o id entif y n ot o ne

g enetic m uta tio n in c o lo n c a nce r c e lls , b ut s e ve ra l. H e h ad a ls o ﬁ gure d o ut t h e e xa ct s e quence in

w hic h t h ese a bnorm alit ie s o ccu rre d, a t im elin e o f t h e c a nce r's e vo lu tio n f r o m o ne g enetic m uta tio n

t o t h e n ext.

I n t h e p arla nce o f c a nce r r e se arc h ers , h e c re ate d w hat w e c a ll t h e V ogelg ra m , a s e quence o f lik e ly

e ve nts t h at c o ntr ib ute t o t h e d eve lo pm ent o f c a nce r. A nd it 's n ot ju st o ne e ve nt. A nd y o u c o uld b egin

t o t h in k a bout c a nce r a s h avin g a h is to ry.

V ogels te in 's w ork r e ally p in ned d ow n t h e id ea t h at c a nce r, g enetic a lly s p eakin g, is a m ult i- s te p

p ro ce ss-- n ot o ne g ene f o r m ost c a nce rs , b ut m ult ip le g enes t h at le ad t o c a nce r.

V ogels te in 's r e su lt s p ose d a s e rie s o f c h alle ngin g q uestio ns. Ju st h ow c o m ple x w ould t t u rn o ut t o b e?

H ow m any m uta tio ns w ould b e f o und w it h in t h e g enom es o f t h e m ajo r c a nce rs , lik e t h ose o f t h e lu ng, b re ast, a nd p ancre as? A nd h ow lo ng w ould it t a ke t o ﬁ nd t h em a ll? T he a nsw ers w ould b egin t o

e m erg e f r o m t h e c o m ple tio n o f o ne o f t h e m ost a m bit io us s c ie ntiﬁ c p ro je cts e ve r u nderta ke n-- t h e

m appin g o f e ve ry g ene in t h e h um an b ody.

T o day, t h e w orld is jo in in g u s t o c e le bra te t h e c o m ple tio n o f t h e ﬁ rs t s u rv e y o f t h e e ntir e h um an

g enom e. W it h out a d oubt, t h is is t h e m ost im porta nt m ost, w ondro us m ap e ve r p ro duce d b y

h um ankin d.

T he a nnounce m ent o f t h e s u cce ssfu l c o m ple tio n o f t h e h um an g enom e p ro je ct w as a t u rn in g p oin t

f o r c a nce r r e se arc h ers .

T he h um an g enom e p ro je ct ﬁ nally g ave u s a c a ta lo g o f a ll t h e g enes. T he z ip c o des w ere a ll la id o ut.

W e h ad a c o m ple te G oogle M aps o f t h e g enom es, s o w e c o uld n avig ate a nyw here . A nd t h en w hen w e

h ad t h at, w e c o uld g o s e arc h in g s y ste m atic a lly f o r t h e g enes t h at c a use c a nce r.

N ow t h at t h ey h ad s e quence d t h e D NA o f n orm al c e lls , r e se arc h ers b elie ve d t h ey c o uld d o t h e s a m e

f o r c a nce r c e lls . T hen t o ﬁ nd t h e m uta te d g enes t h at t r ig ger c a nce r, a ll t h at w ould b e n eeded w ould

b e a s id e-b y-s id e c o m paris o n, t h e g enes o f n orm al c e lls n ext t o t h e g enes o f c a nce r c e lls .

U nlik e in t h e p ast w here y o u w ere lo okin g g ene b y g ene, o ne b y o ne b y o ne, y o u c a n n ow lo ok a t t h e

e ntir e s p ectr u m . Y o u c a n lo ok a t t h e la ndsc a pe, a s it w ere , o f c a nce r. A nd y o u c o m pare , w it h in t h e

s a m e in div id ual, t h e n orm al g enom e-- n ot o ne g ene, b ut e ve ry s in gle g ene-- w it h e ve ry s in gle g ene

t h at's a lt e re d in c a nce r.

T hough it s e em ed s im ple . T his id ea w ould s p ark a m assiv e in te rn atio nal e ﬀ ort b egin nin g in 2 005 t o

c o lle ct, s e quence , a nd a naly ze t h ousa nds o f s a m ple s o f t h e m ost c o m mon c a nce rs . It w as c a lle d T he

C ance r G enom e A tla s.

T he c a nce r g enom e a tla s w as a n in cre dib le t e am s c ie nce e ﬀ ort, w here t h is g ro up g ot t o geth er a nd

s a id , w e n eed t o u nders ta nd t h e a tla s, t h e la ndsc a pe, o f a ll o f t h e g enetic c h anges t h at c a n h appen in

c a nce r t o u nders ta nd w hat is t h e p ossib ilit y o f w hat c a n g o w ro ng.

B y t h e s p rin g o f 2 008, t h e ﬁ rs t r e su lt s f r o m t h e A tla s w ere r e ady.

T he m ost e xcit in g m eetin g w as t h at ﬁ rs t t im e w here t h ere w ere e nough s a m ple s f r o m b ra in t u m ors

t o b e a ble t o b egin t o s a y, O K, w hat's n ew h ere ? P re vio usly , y o u'v e h ad o nly a b lu rry v ie w t h ro ugh t h e

f o g, a nd y o u c o uld m ake o ut s o m e o f t h e m ost d ra m atic f e atu re s. B ut n ow t h e f o g h as b lo w n a w ay.

Y o u c a n s e e t h e w hole la ndsc a pe o f w hat's t h ere a nd in fe r t r u th a bout h ow t h ose c a nce rs h appened. B ut a s m ore a nd m ore r e su lt s p oure d in , s o m e o f t h e in it ia l e xcit e m ent w as r e pla ce d b y a nxie ty .

T here c o uld b e n o d oubt t h at w hat V ogels te in h ad g lim pse d in c o lo n c a nce r w as ju st t h e b egin nin g.

T he p ro fo undly s u rp ris in g t h in g a bout T he C ance r G enom e A tla s is it p oin te d o ut t h at c a nce rs a re

m uch m ore g enetic a lly c o m ple x t h an t h re e, f o ur, ﬁ ve g enes. T here c a n b e 1 0 g enes t h at a re a lt e re d,

2 0 g enes. In o ne b re ast c a nce r s p ecim en, 1 10 g enes w ere a lt e re d.

E ve n m ore c o nfo undin g, t h e m ajo rit y o f g enetic a bnorm alit ie s d is c o ve re d w ere n ot f a m ilia r

o nco genes, b ut a noth er t y p e o f g ene c a lle d a t u m or s u ppre sso r g ene. U nlik e o nco genes, w hic h

t ip ped c e lls in to a f r e nzy o f c e ll d iv is io n, t u m or s u ppre sso r g enes w hen d am aged f a il t o s to p c e lls

f r o m d iv id in g.

T u m or s u ppre sso r g enes a re in a s e nse t h e o pposit e o nco genes. O nco genes k in d o f w ork lik e a n

a cce le ra to r in a c a r. T hey d riv e t h e c e lls ' g ro w th . A nd t h e t u m or s u ppre sso r g enes a re t h e b ra ke s.

A nd in m any c a se s, t h e b ra ke s a re s im ply g one f r o m t h e c e ll.

W e n ow r e aliz e t h at v ir tu ally a ll h um an c a nce r c e lls h ave b oth d efe cts -- s tu ck a cce le ra to r p edals --

h yp era ctiv e o nco genes-- a nd d efe ctiv e t u m our s u ppre sso r g enes-- d efe ctiv e b ra ke lin in gs. A nd

t o geth er, t h ose t w o d efe cts c o nsp ir e t o m ake t h e f u ll p anoply o f a bnorm al b ehavio rs t h at w e

a sso cia te w it h m alig nant c e lls .

I n t h e s p an o f a f e w y e ars , a s t h e t r u e c o m ple xit y o f t h e c a nce r c e ll b eca m e c le ar, a ny h ope t h at

t a rg ete d t h era pie s w ould w in a q uic k v ic to ry o ve r t h e d is e ase w as d is p elle d.

T he c a nce r g enom e is e xce edin gly c o m ple x. E ach c a nce r t y p e c o nta in s a nyw here f r o m 5 0 t o 1 00

r e cu rre nt a m pliﬁ ca tio ns a nd d ele tio ns. S o w hile t h e p ro gre ss o f t h e p ast 2 0 y e ars h as b een

i m pre ssiv e , it 's a ls o c le ar t h at w e a re d ealin g w it h t h e t ip o f t h e ic e berg .

T he d is c o ve ry o f c a nce r's c o m ple xit y d urin g t h e c e ntu ry 's ﬁ rs t d eca de s e em ed t o p ush c u re s e ve n

f u rth er a w ay. D ru g d eve lo pers c o uld n ow s e e t h e g enetic la ndsc a pe o f c a nce r m ore c le arly , b ut t h e

p ic tu re w as o ne o f in tim id atin g c h aos. H ow eve r, t h ere w ere s till a f e w c a nce rs t h at s e em ed t o b e

c a use d b y ju st o ne o r t w o m uta te d g enes. It w as o n t h ese t h at d ru g m ake rs b egan t o f o cu s m ost

i n te ntly .

I n 2 003, s c ie ntis ts w ork in g f o r t h e S w is s g ia nt N ova rtis b elie ve d t h ey h ad f o und a lik e ly t a rg et, a r a re

o nco genes c a lle d A LK . Ja panese r e se arc h ers h ad s h ow n t h at a m uta tio n in t h e A LK g ene s e em ed t o

b e t h e c a use o f a t y p e o f lu ng c a nce r t h at a ﬀ ects a ro und 4 0,0 00 p eople a y e ar w orld w id e. T hough

t h e m ark e t w ould b e r e la tiv e ly s m all, N ova rtis d ecid ed t o p urs u e a d ru g t a rg ete d a gain st t h is m uta tio n. T heir s c ie ntis ts b egan b y m anip ula tin g v a rio us c o m pounds t o t r y t o b lo ck t h e e ﬀ ects o f t h e

g ene. A fte r s e ve n y e ars o f t r ia l a nd e rro r, t h ey b elie ve d t h ey h ad o ne t h at m ig ht w ork .

D o y o u s e e? Y e ah, it r e ally lo oks lik e t h is . W e h ave r o om h ere , r ig ht, t o p ut s o m eth in g t h at c o uld ﬁ ll

t h e p ocke t b ette r, s o m eth in g--

T he d ru g, c a lle d L D K, w ork s b y ﬁ llin g a p ocke t in a p ro te in in sid e t h e c a nce r c e ll, b lo ckin g t h e s tr e am

o f g ro w th s ig nals p ro duce d b y t h e m uta te d g ene. It 's lik e ja m min g a lo ck w it h a b ro ke n k e y.

I t 's a b eautif u l c o m pound. It 's a ctu ally b eautif u l w hen y o u s e e it ﬁ t in to t h e p ocke t. It 's r e ally d esig ned

t o t h e jo b it 's d oin g.

E ve ry b ody t h in ks t h eir b aby is b eautif u l.

[ L A UG HTER ]

T he m edic in al c h em is ts h ave a v e ry t o ugh c h alle nge. N ot o nly d o t h ey h ave t o ﬁ nd a m ole cu le t h at

ﬁ ts t h at p ocke t p erfe ctly , t h ey a ls o h ave t o s im ult a neously b e m akin g s u re t h at t h e c h anges t h ey

m ake in t h e m ole cu le d on't c a use it t o b in d t o s o m eth in g e ls e a nd c a use t o xic it y . A nd s o t h e b est

a nalo gy I c a n t h in k o f is it 's lik e a R ubik 's c u be. Y o u c a n s o lv e o ne s id e o f t h e R ubik 's c u be, a nd it 's a ll

b lu e, a nd it ﬁ ts in to t h e e nzy m e p erfe ctly . B ut y o u'v e m esse d u p a ll k in ds o f o th er t h in gs, a nd m ayb e

i t b in ds t o s o m eth in g e ls e t h at c a use s t o xic it y .

C hem is ts n eed t o b e e te rn al o ptim is ts , b eca use 9 9.9 % o f w hat y o u d o f a ils . A nd a fte r y e ars o f w ork o f

h undre ds o f s c ie ntis ts , it a ll c a m e d ow n t o o ne p ow der r ig ht h ere in t h e v ia l.

S o I t a ke f o ur o f t h ese e ve ry d ay. A nd t h is is w hat's k e epin g m e a liv e , lit e ra lly .

I n 2 013, D r. Ju anm anuel G om ez, h im se lf a p hysic ia n, b eca m e o ne o f t h e ﬁ rs t p atie nts e ve r t o t a ke

L D K.

J u anm anuel G .?

O h, t h ey a re c a llin g f o r m e.

H i.

T his w ay?

Y u p. G re at.

W e'r e g oin g t o t a ke a le ft.

G om ez h ad b een t o ld t h at h is p ro gnosis w as d ir e . H is lu ng c a nce r w as in opera ble , a nd c h em oth era py

w as n o lo nger a n o ptio n. W it h n oth in g e ls e t o t r y , h is d octo rs u rg ed h im t o jo in a n e arly t r ia l o f t h e

L D K d ru g.

R em ove y o ur s h oes, a nd s te p r ig ht u p o n t h e s c a le .

A ll r ig ht.

I t w as v e ry c le ar t o m e if I d id n't d o a nyth in g d iﬀ ere nt, I w as n ot g oin g t o b e h ere . A nd I w as d yin g. I

w as. I k n ew . I c o uld f e el it .

T he d ru g h ad a n im media te im pact. W it h in w eeks, D r. G om ez's t u m ors b egan t o s h rin k a nd h e w as

a ble t o r e su m e a n orm al lif e .

T he a dve nt o f t h ese t a rg ete d t h era pie s r e ally h as b een m ir a cu lo us f o r s o m e o f o ur p atie nts .

S o c a n y o u u nbutto n t h at t o p b utto n f o r m e?

T he d is e ase m elt s a w ay s o m eth in g t h at c h em oth era py c o uld r e ally n eve r d o.

C ouple d eep b re ath s.

A nd w hen I'm s a yin g a m azin g r e sp onse , I'm t a lk in g a bout t h ese im ages f u ll o f c a nce r, w it h b lo tc h es

p re tty m uch t h ro ughout t h e lu ngs, a nd t h ese p atie nts w ould b e t r e ate d w it h t h is d ru g. A nd n ow a ll

t h ese p atc h es w ould n ow ju st d is a ppear. E ve n m ore , I t h in k, s tu nnin g f o r u s a s o nco lo gis ts is t h at

p atie nts w ould f e el b ette r v e ry , v e ry q uic kly .

W ell, y o ur la bs lo ok p erfe ct t o day. S o t h at's g re at.

Y e s.

A nd y o ur s c a ns lo ok g re at, t o o. S o I lo oke d a t t h e c h est a nd t h e a bdom en a nd t h e b ra in , a nd t h ey

l o ok b eautif u l.

G re at. R eally , I t h in k y o u'r e d oin g g re at, s id e e ﬀ ect-w is e .

B ut e ve n w it h d ru gs lik e L D K t h at s h ow e arly p ro m is e in c lin ic a l t r ia ls , t h ere is a p ro ble m . M ost s o on

s to p w ork in g. T he r e aso n w hy c o m es d ow n t o a c o nce pt f a m ilia r f r o m in fe ctio us d is e ase s-- r e sis ta nce .

E ve n if a d ru g c a n s h ut d ow n t h e o ne k e y m uta tio n in a c a nce r c e ll, t h e c e ll o fte n m uta te s a gain a nd

i s n o lo nger v u ln era ble t o t h e e ﬀ ects o f t h e d ru g.

C ance r c e lls a re c o nsta ntly m uta tin g. In f a ct, t h e c a nce r it s e lf is e vo lv in g in sid e y o ur b ody o ve r t im e,

s o t h at t h e g enetic d iv e rs it y o f c a nce r a t w eek z e ro is n ot t h e s a m e a s t h e g enetic d iv e rs it y o f c a nce r

5 y e ars o r 1 0 y e ars f r o m n ow . It t r a nsfo rm s t h e id ea o f t r e atm ent f r o m a s ta tic id ea t o a d yn am ic

i d ea.

S cie ntis ts h ad lo ng u nders to od t h at c a nce r w as n ot t h e s a m e d is e ase in e ve ry o ne. B ut w it h t h e

r e aliz a tio n o f c a nce r's m uta bilit y , t h ey n ow f e are d it m ig ht n ot b e t h e s a m e d is e ase in a nyo ne.

W hat w e k n ow t o day is t h at e ach c a nce r is a m ovin g t a rg et. A nd v e ry f e w d ru gs, e ve n w hen t h ey'r e

h avin g f a nta stic c lin ic a l r e su lt s , e nd u p c u rin g p eople . B eca use c a nce r b eco m es r e sis ta nt t o t h e

d ru gs t h at w e'r e u sin g in a lm ost e ve ry c a se .

A s a d octo r h im se lf , Ju anm anuel G om ez w as a w are o f t h e p ossib ilit y t h at h is c a nce r w ould b eco m e

r e sis ta nt t o L D K.

I t is a g am ble . T hey d on't k n ow . T hey p ro bably h ave s e en s o m e r e su lt s in s o m e a nim al m odels a nd

t h ey k n ow t h e d ru g w ork s. Is t h at g oin g t o n ece ssa rily t r a nsla te in to a h um an b ein g? N o o ne k n ow s.

I n f a ct, ju st s ix a nd a h alf m onth s a fte r e nro llin g in t h e c lin ic a l t r ia l, G om ez's c a nce r d id b eco m e

r e sis ta nt t o t h e d ru g, a nd h e w as f o rc e d t o t r y a noth er e xp erim enta l t h era py. T hat t h era py a ls o

s to pped w ork in g. A nd D r. G om ez p asse d a w ay in O cto ber 2 014.

G om ez's e xp erie nce o n t h e L D K t r ia l w as n ot e xce ptio nal. W hen a ll t h e r e su lt s w ere t a bula te d, t h e

d ru g h ad e xte nded t h e liv e s o f a ll 1 60 p atie nts b y a n a ve ra ge o f ju st s e ve n m onth s.

T he s u cce sse s o f t h e ﬁ rs t d eca de o f t a rg ete d t h era py w ere s o e norm ous t h at w hen t h e s e co nd

d eca de s ta rte d r o llin g a ro und, a ll o f a s u dden w e f e lt d is a ppoin te d. B eca use r a th er t h an h avin g

G le eve c, w e w ere g ettin g in cre m enta l a dva nce s.

I n t h e la st d eca de, a n a ve ra ge o f o nly f o ur n ew t a rg ete d t h era pie s h ave b een a ppro ve d f o r u se in

p atie nts e ach y e ar, m ost o f w hic h h ave e xte nded p atie nts ' liv e s b y ju st a f e w m onth s. 9 o f 1 0 n ew e xp erim enta l c o m pounds f a il. T his in cre m enta l p ro gre ss h as c o m e a t a h ig h p ric e -- b illio ns o f d olla rs

i n r e se arc h a nd d eve lo pm ent. T o r e co up t h ese c o sts , p harm ace utic a l c o m panie s h ave p ric e d t h eir

s u cce ssfu l c a nce r d ru gs a t u npre ce dente d le ve ls .

T he r e alit y is f o r t h e o ve rw helm in g m ajo rit y o f p atie nts a nd o nco lo gis ts , t h is is o ne o f t h e b ig gest

p ro ble m s in c a nce r c a re . If y o u lo ok a t t h e p ric e s o f c a nce r d ru gs b efo re t h e y e ar 2 000, t h e a ve ra ge

p ric e w as a bout m ayb e a bout $ 5,0 00, $ 10,0 00 a y e ar. A nd t h en in t h e y e ar 2 012, 1 2 o f t h e 1 3 d ru gs

t h at w ere F D A a ppro ve d c a m e a t a p ric e o f $ 100,0 00 o r m ore .

A t t h e C harle sto n A re a M edic a l C ente r in W est V ir g in ia , s ta ﬀ o nco lo gis t D r. S uza nne C ole s e es t h e

i m pact o f t h e h ig h c o st o f c a nce r c a re e ve ry d ay.

H ello .

H i.

H ow a re t o day?

I 'm d oin g g re at. A nd I d id n't k n ow y o u w ere --

Y e s, I'm h avin g a b aby.

W ell, c o ngra tu la tio ns.

Y e ah. It 's n ot g oin g t o b e t o o lo ng f r o m n ow .

S om e o f o ur p atie nts w ho a re m id dle c la ss A m eric a ns w ork in g n orm al jo bs w it h a w eso m e in su ra nce --

s o m etim es t h at in su ra nce d oesn 't c o ve r e ve ry th in g t h at's n ece ssa ry a nd t h ere a re s ig niﬁ ca nt

m edic a l b ills m onth t o m onth t o m onth t o m onth .

A ll r ig ht. S o w hat I'm g oin g t o d o is g iv e y o u a s ta ndin g o rd er f o r la bs. A nd I ju st w ant t o k e ep t h is in

y o ur p urs e .

A nd if y o u'r e o n a m edic a tio n t h at y o u n eed t o s ta y a liv e , a nd y o ur c o -p ay o n t h at m edic a tio n is $ 700

a m onth , t h at's r e nt. T hat's c a r p aym ent. T hat's a c ra zy a m ount o f m oney t o b e f o rk in g o ve r e ve ry

m onth ju st t o h ave a cce ss t o t h e t h in g t h at's g oin g t o k e ep y o u a liv e .

M s. C arrin gto n, t h is is Je nnif e r B ass.

H i, t h ere . N ic e t o m eet y o u. H i, Je nnif e r. N ic e m eetin g y o u.

S he is o ur ﬁ nancia l n avig ato r, a nd s h e h elp s p eople in y o ur s it u atio n g et b ack o n t r a ck w it h t h eir

i n su ra nce s o t h at t h ey c a n g et t h eir c a nce r t r e atm ent.

O K.

A t t h e C harle sto n h osp it a l, a f u ll t im e e m plo ye e h elp s p atie nts w ho h ave n o a bilit y t o p ay t h eir

m edic a l b ills .

I a ppre cia te it .

Y e s, m a'a m . I'm g oin g t o g iv e y o u a ll o f t h is . Y o u ﬁ ll o ut. O nce y o u s ta rt g ettin g b ills , d on't p ay a ny o f

t h em .

I c a n't .

D on't p ay a ny o f t h ose .

I 'm n ot w ork in g n ow .

T his is t h is y e ar's p atie nts . T his is w hat I h ave w ork e d w it h t h is y e ar o n s o m e f o rm o f ﬁ nancia l

a ssis ta nce . It is c o m ple te ly f u ll. W e h ave o sto m y s u pplie s u p h ere . I h ave m aste cto m y b ra s a nd t h e

m aste cto m y p ro sth esis u p h ere . T his is a b lo od t h in ner. I t h in k t h ere 's a w ig u nder m y d esk . Y e ah, I

s tic k t h in gs e ve ry w here . W ig s, w hate ve r it is , I w ill t a ke it .

G ettin g c a nce r is o ne o f t h e w ors t e co nom ic t h in gs t h at c a n h appen t o y o u in t h e U nit e d S ta te s. It

c a use s t h e a ccu m ula tio n o f e norm ous a m ounts o f d ebt. It f u ndam enta lly s h if ts t h e ﬁ nance s o f

f a m ilie s. A nd w hat's v e ry c h alle ngin g f o r a lo t o f p atie nts is t h at it c a n o fte n b e a d is e ase t h at e nds

y o ur lif e . A nd s o t h e r e so urc e s y o u'v e a ccu m ula te d t h at y o u h ope t o p ass o n t o y o ur h eir s o r y o ur

s u rv iv in g s p ouse o r s o m eone e ls e e nd u p b ein g c o nsu m ed in t h e t r e atm ent o f a c o ndit io n t h at in

s o m e c a se s is in cu ra ble .

T he im pact o f t h e h ig h c o st o f d ru gs is m ost a cu te in t h e U nit e d S ta te s, w here d ru g c o m panie s s e t

t h eir p ric e s. In c o untr ie s w here t h e g ove rn m ent n egotia te s t h ose p ric e s, f e w er p atie nts c h oose t o

f o rg o t h eir m edic a tio ns r a th er t h an p ay f o r t h em . In t h e d eve lo pin g w orld , n ew c a nce r d ru gs a re o fte n

n ot e ve n a va ila ble b eca use t h eir c o st is s o h ig h.

T his is a m ora l is su e. T here 's a 1 0% t o 1 5% lo w er ﬁ ve -y e ar s u rv iv a l in c a nce r in p eople w ho a re u nin su re d a nd in p eople w ho a re p oor a nd in p eople w ho a re b la ck. P e ople s h ould n ot d ie b eca use

t h ey'r e p oor. P e ople s h ould n ot d ie b eca use t h ey'r e u nin su re d.

T he s o lu tio n t o t h e p ro ble m o f c o st, m any b elie ve , lie s in u nders ta ndin g e ve n m ore a bout t h e

m ech anis m s o f c a nce r, s o t h at s o m uch m oney is n ot w aste d in p urs u in g ﬂ aw ed d ru gs.

T his w hole s y ste m is e xtr e m ely in eﬃ cie nt. W e a re n ot u sin g t h e t a rg ets a ppro pria te ly o r w is e ly . A nd

t h ere fo re , a ll o f t h ese m edic in es a re f a ilin g. S o w hat w e r e ally n eed t o d o is t o p erfo rm m ore e ﬃ cie nt

r e se arc h . A nd r e ally , it m eans t o p erfo rm m ore e ﬃ cie nt b asic r e se arc h . A nd t h at's w hat's g oin g t o

d riv e d ow n t h e p ric e o f c a nce r d ru gs.

A nd y e t f u ndin g f o r t h e m ost p ro m is in g b asic r e se arc h h as n ot b een s o t ig ht s in ce t h e N atio nal

C ance r A ct w as p asse d in 1 971.

A s t h e d ir e cto r o f t h e N atio nal In stit u te s o f H ealt h , I liv e w it h t h e r e alit y t h at w e'r e n ot lim it e d b y

i d eas, w e'r e lim it e d b y r e so urc e s. A nd w e'r e n ot g oin g a s f a st a s w e c o uld . W e a re n ow a bout 2 5%

b elo w w here w e w ere 1 0 y e ars a go in t e rm s o f r e so urc e s t o d o t h is w ork . W e'v e g ot t o ﬁ gure o ut h ow

t o t u rn t h at a ro und.

I t 's g oin g t o b e $ 511.5 3.

U ntil b ette r a nd c h eaper t h era pie s a re d is c o ve re d, m any p atie nts a nd t h eir f a m ilie s a re f o rc e d t o

m ake a d iﬃ cu lt c a lc u la tio n.

W hat a m I w illin g t o p ay m e f o r h ow m any m onth s o f lif e ? H ow d o I t h in k o f t h at? W hat e quatio n

g ove rn s t h re e m onth s o f lif e f o r x -th ousa nd d olla rs ?

M ayb e it a llo w s s o m ebody t o s e e a g ra ndso n's b ir th day p arty o r g o t o a w eddin g. T hose a re g re at

m om ents o f lif e . S o m ayb e t h at's e nough. I t h in k it 's n ot e nough f o r m ost p eople , a nd e sp ecia lly

g iv e n t h e a m ount o f e ﬀ ort t h at w e'v e p ut in to t h is p ro ble m .

W it h s o f e w n ew t a rg ete d t h era pie s, t r e atm ents a t m ost c a nce r h osp it a ls a ro und t h e c o untr y r e m ain s

m uch a s it h as b een f o r t h e la st 2 0 y e ars .

E ve ry b ody is s o e xcit e d a bout a ll o f t h ese n ew t a rg ete d t h era pie s. B ut w hen it c o m es d ow n t o it , t h e

v a st m ajo rit y o f m ost o f t h e c a nce rs t h at w e t a ke c a re o f, t h ey a re s till p rim arily t r e ate d w it h

c h em oth era py. T here a re c a nce r s u rg eons. T here a re r a dia tio n o nco lo gis ts . B ut t h e b ackb one o f

w hat w e d o is w e g iv e c h em oth era py. C hem oth era py h as g otte n b ette r o ve r t h e y e ars . B y u sin g t h ese d ru gs in c o m bin atio n a nd t a ilo rin g

t h em m ore e ﬀ ectiv e ly t o e ach p atie nt, d octo rs h ave m ade in ro ads a gain st m any c a nce rs . O f a ll

p atie nts w ho w ill b e d ia gnose d t h is y e ar, s o m e 2 /3 w ill s u rv iv e o ve r ﬁ ve y e ars . A nd o f t h ose , m any w ill

g o o n t o liv e n orm al lif e s p ans.

T here a re a lo t o f t u m ors t h at w e t a ke c a re o f t h at a re c u re d-- e arly s ta ge b re ast c a nce r, e arly s ta ge

c o lo n c a nce rs , e arly s ta ge p ro sta te c a nce r. M any o f t h ose p atie nts w ill liv e t h e w hole r e st o f t h eir

l iv e s a nd n eve r h ave a ny p ro ble m s e ve r a gain .

H ey. H ow 's it g oin g?

D r. C ole s e es u p t o 2 5 p atie nts a d ay. M any w ill b e a ble t o liv e w it h t h eir c a nce rs f o r y e ars o r s e e t h em

d is a ppear e ntir e ly .

D a d a d un. It 's 8 .2 .

O h, m y g od.

8 .2 !

Y e ah, I k n ow . T hat's lik e t h e b est it 's b een.

B ut t h ose s h e s p ends m ost t im e w it h h ave r e la pse d o r b een d ia gnose d w it h m eta sta tic d is e ase .

A re y o u b ette r t h an y e ste rd ay?

O h, g osh , y e s. A nd f o r t h em , s h e m ust o ﬀ er a v e ry d iﬀ ere nt k in d o f c a re .

I k n ow , I k n ow g oin g in to t h is t h at t h e v a st m ajo rit y o f m y p atie nts w ho c o m e t o m e w it h s ta ge f o ur

d is e ase a re g oin g t o d ie . A nd t h ere 's n oth in g t h at I c a n d o a bout t h at, e nd f a ct, b eca use it 's t h e

n atu re o f t h e d is e ase t h at t h ey h ave in t h e t im es t h at w e liv e w it h t h e t o ols t h at w e h ave .

A ny w eir d h eadach es, b lu rre d v is io n?

I t 's v e ry h ard t o t a lk a bout d eath t o s o m ebody w ho's in r e la tiv e ly g ood h ealt h . Y o u k n ow s o m ebody

w ho's ju st b een d ia gnose d w it h a c a nce r, t h ey m ay n ot e ve n f e el it in sid e o f t h em .

A nd y o u h ave s w olle n ly m ph n odes a ll a lo ng t h at a re a. A nd t h ere 's o ne t h at's k in d o f h ig her u p t h at

I 'm w orrie d a bout.

B ut if t h ey'r e in a s it u atio n w here it c o uld h appen, t h ey n eed t o k n ow t h at t h at's a p ossib ilit y . A nd I j u st b elie ve in t h at c o re p rin cip le s o d eeply t h at it r e ally g uid es m e in h ow I t a lk t o e ve ry s in gle o ne o f

m y p atie nts .

T e ll m e w hat y o u k n ow a bout y o ur lu ng c a nce r.

I h ave ju st r e ally k n ow n f o r t h re e d ays t h at I h ave c a nce r.

O K.

I w as ju st d ia gnose d.

S o w hat w as w ro ng--

I r e m em ber a s a r e sid ent r o undin g w it h lo ts o f f a nta stic p hysic ia ns, w ho w ould w alk in to a r o om w it h

a p atie nt. T hey w ould s a y, e ve ry th in g is ﬁ ne. Y o u'r e g ettin g b ette r. Y o u'll b e g ettin g o ut o f t h e h osp it a l

s o on.

A nd t h en w e w alk in to t h e h all. W e w alk a f e w s te ps a w ay f r o m t h e d oor. A nd v e ry c a su ally , o h, t h at

g uy's n ot lo ng f o r t h e w orld . A nd w hy s h ould w e a s p hysic ia ns h ave a ll o f t h is in fo rm atio n a bout t h e

p atie nt? It 's t h e p atie nt's in fo rm atio n.

A re y o u in te re ste d in k n ow in g n um bers a bout y o ur p ro gnosis ? A re y o u in te re ste d in t h at k in d o f

t h in g? O r a re y o u t o o o ve rw helm ed w it h a ll o f it t o --

Y e s, I'm t h e t y p e o f p ers o n t h at lik e s t o k n ow a s m uch in fo rm atio n a s p ossib le . W hen w e'r e d ealin g

w it h a s ta ge f o ur lu ng c a nce r, w e k n ow t h at it is n ot a c u ra ble s it u atio n. It is t r e ata ble . A nd w e c a n d o

t h in gs t o in te rv e ne a nd h elp y o u liv e a s lo ng a s p ossib le . B ut b eca use t h is c a nce r h as s p re ad t h ro ugh

t h e b ody, it 's m uch m ore lik e ly t h at t h is c a nce r is g oin g t o b e t h e t h in g t h at t a ke s y o ur lif e r a th er t h an

s o m eth in g e ls e .

W ow , y o u g ave a d eeper e xp la natio n t h an I h ad h eard e arlie r t o day, s o it 's p re tty --

I t 's r e ally in cre dib ly h ard t o s it d ow n w it h a noth er h um an b ein g a nd lo ok t h em in t h e e ye a nd s a y, I'm

s o rry , b ut t h ere 's n oth in g m ore t h at m edic a l s c ie nce c a n d o t o m ake y o u liv e lo nger o r b ette r.

I w is h t h at w e h ad s o m e m agic m edic a tio n t h at w ould m ake t h is a ll d is a ppear. A ll o f t h e t r e atm ents

a re t o g iv e y o u a s m uch t im e a s p ossib le .

M ost c a nce r is v e ry p re dic ta ble . O nce it c o m es b ack-- u nle ss it 's a c u ra ble , o f w hic h t h ere a re a n um ber-- it 's g oin g t o b e t h e e nd o f t h at p ers o n. A nd t h ere a re c e rta in t a sk s t h at t h e p ers o n s h ould d o

b efo re t h ey d ie .

A nd t h at's ju st b ein g a s s tr a ig ht a bout it , s o t h at--

W hic h I a ppre cia te .

- -y o u h ave a g ood s e nse o f w hat y o u'r e r e ally d ealin g w it h , a nd y o u c a n m ake t h e b est c h oic e s in t h e

c o nte xt o f y o ur lif e k n ow in g t h at w e m ig ht b e o n lim it e d t im e.

W ell, t h is ju st r e ally s u cks.

I t d oes. A nd I'm s o rry.

Y e ah, m e t o o.

I f y o u'r e h earin g a bout t h at f o ur w eeks b efo re y o u d ie , y o u'r e p ro bably n ot g oin g t o h ave a c h ance t o

g o t o L A a nd m ake u p w it h y o ur b ro th er o ut t h ere . Y o u m ay n ot h ave a c h ance t o t a lk t o y o ur p rie st o r

a r a bbi a t a t im e w hen y o u'r e r e ally w ell. A nd a ll o f t h at c a n b e h elp ed b y ju st b ein g m ore h onest w it h

p eople d urin g t h e c o urs e o f t h eir illn ess.

I ju st h adn't b een f o cu sin g o n--

A ll t h e d ata s u ggests t h at d ir e ctly a ddre ssin g s y m pto m s, r e lie vin g t h eir p ain , k e epin g t h em m ore

f u nctio nal a llo w s t h em t o liv e a lo nger p erio d o f t im e a s w ell a s a b ette r p erio d o f t im e.

I 'v e b een t r y in g t o d o w hat I w ant t o d o a nd liv e lif e t o it s f u lle st a nd t o e njo y it . W ell, it h as a d iﬀ ere nt

l o ok o n it f o r t h e n ext c o uple y e ars , I t h in k.

Y e s.

D r. C ole 's a ppro ach is r e la tiv e ly n ew . F o r d eca des, s o -c a lle d p allia tiv e c a re w as a lm ost t a boo in

o nco lo gy. T he f o cu s o f c a nce r t r e atm ent w as o n e ra dic a tin g t u m ors a t a ll c o sts . D octo rs d id lit tle t o

a lle via te t h e p ain o r a ddre ss t h e p sy ch olo gic a l n eeds o f d yin g p atie nts .

T o m any d octo rs , t h e w ord p allia tiv e c a re w as a w ord t h at t h ey w ere a lle rg ic t o , b eca use it m eant

t h at t e llin g t h e p atie nt-- o r p erh aps t e llin g t h em se lv e s, m ore t h an a nyth in g e ls e -- t h at t h is w as d efe at.

O bse sse d w it h c u re , t h is v o ic e o f p allia tiv e c a re , r e sto rin g p atie nt a uto nom y, r e sto rin g p atie nt d ig nit y ,

i t w as p ush ed a w ay in to t h e b ackg ro und. T he m ove m ent t o w ard p allia tiv e c a re b egan in t h e 1 960s in L o ndon, w here a B rit is h n un n am ed

C ic e ly S aunders s e t u p a c lin ic t o c a re f o r p atie nts a t t h e e nd o f t h eir liv e s.

W e c e rta in ly o w e a lo t t o C ecily S aunders . S he s h ow ed t h at o ne c o uld m ake t h e lif e o f p eople w ho

a re d yin g m uch m ore c o m fo rta ble w it h a dequate p ain m edic a tio n a nd w it h a dequate e m otio nal

s u pport. A nd s h e b egan t o t a lk a cro ss t h e c o untr y t o n urs e s, o nco lo gy c e nte rs , a nd h ad a r e al im pact

o n p allia tiv e c a re b egin nin g in t h is c o untr y.

T o day, p allia tiv e c a re is p art o f t h e m edic a l t r a in in g a nd e ve ry d ay w ork o f m ore a nd m ore

o nco lo gis ts a nd o nco lo gy n urs e s in t h e U nit e d S ta te s.

D o y o u f e el lik e a t t h is p oin t, a fte r e ve ry th in g t h at y o u'v e g one t h ro ugh in t h e la st c o uple m onth s, a nd

w e w ere t o h ave t o r e ally t h in k a bout c h em oth era py, y o u'd b e w antin g t o d o t h at a gain ? O r y o u'r e

n ot s u re ?

I 'd p ro bably b e w antin g t o .

Y o u'd b e w illin g t o t r y it .

Y e ah.

O K, g ood t o k n ow .

S om e p eople , t h ey n eed t o d o e ve ry th in g t h at t h ey c a n d o t h at is p ossib le t o b e d one t o s ta y o n t h is

e arth . T hey c a n s till s a y, I lo ve t h is lif e . I lo ve b ein g a liv e . I lo ve b ein g h ere . A nd I w ill d o a nyth in g t o

s ta y.

F o r s o m e p atie nts , it is a w ar. T heir e xp erie nce o f it is a w ar. A nd t o s a y t h at it is n 't is t o d eny t h em

t h eir r e alit y . It is a w ar f o r t h em . A nd y e t f o r o th er p atie nts , t h ey d on't w ant t o ﬁ ght. B ut it 's n ot t h e

l a nguage o f d efe at. It is t h e la nguage o f n egotia tio n. It is t h e la nguage o f w hat t o d o n ext g iv e n t h e

c ir c u m sta nce s.

S o y o u'v e b een in t h e h osp it a l f o r a c o uple o f d ays. A nd o ne t h in g t h at I ju st w ante d t o m ake s u re w as

t h at y o u w ere u nders ta ndin g w hat w as g oin g o n w it h y o ur c a nce r. W e'v e d one s o m e c h em o, a nd it

s e em s lik e it 's n ot r e ally h elp in g u s s lo w d ow n t h e c a nce r. A nd s o w e'r e g oin g t o h ave t o m ake a

c h oic e a bout w heth er y o u w ant t o t r y t o d o m ore t r e atm ent, o r w heth er w e s h ould s to p.

H e w ants t o d o w hate ve r y o u t h in k is b est, r ig ht? B eca use y o u t r u st h er 1 00% w it h e ve ry th in g. A nd w e

d on't k n ow . S o w e'll le ave it in y o ur h ands. R ig ht n ow , y o ur b ody is in a s it u atio n w here w e'v e g ot t o g et y o u b ette r b efo re w e c o uld e ve n t h in k

a bout d oin g m ore t r e atm ent. B ut it 's n ot a b ad c h oic e t o s o m etim es s a y n o t o t h e c h em oth era py a nd

t a ke w hat t im e t h at y o u h ave le ft a nd e njo y it a nd n ot b e s ic k a nd c o m in g b ack a nd f o rth .

O h, [ IN AUD IB LE ]. [ C O UG H] I s e e t h e t im e c o m in g. B ut t h e lif e y o u'v e g iv e n m e a lr e ady is b ette r.

[ IN AUD IB LE ]. T hanks, [ IN AUD IB LE ].

I ju st r e ally w ant w hat is b est f o r y o u. I w ant y o u t o f e el w ell f o r a s lo ng a s p ossib le . Y o u k n ow I w ant

y o u t o b e f r e e o f p ain . A nd I d on't w ant y o u t o s tr u ggle a t a ll. W e'r e g oin g t o ju st f o cu s o n t r y in g t o

h elp y o u g et s tr o nger s o t h at y o u c a n g et o ut o f t h e h osp it a l.

Y e ah, t h anks.

A nd o nce y o u'r e h om e, w e c a n t a lk a bout w heth er it m ake s s e nse t o d o a ny m ore t r e atm ent o r n ot.

A nd if w e d ecid e n ot t o d o it , t h en I'm g oin g t o h ave h osp ic e c o m e a nd b e w it h y o u, O K?

O K. Y o u'r e d oin g g ood. Y o u'r e h angin g in t h ere .

I d on't k n ow if e ve ry b ody h as t h e s a m e o pin io n o f w hat is a g ood d eath .

A ll r ig ht, s w eetie . I'll c h eck o n y o u t o m orro w .

B ut I t h in k t h at it m ig ht b e b ette r f o r s o m eone t o m ayb e b e in a p la ce t h at t h ey'r e c o m fo rta ble ,

s u rro unded b y p eople t h at t h ey lo ve . If y o u d ecid e t o p ull b ack f r o m t r e atm ent a nd g o o n h osp ic e ,

t h en y o u h ave s o m e s a y a bout h ow y o u d ie a nd w here y o u d ie a nd w ho's w it h y o u. A s o nco lo gis ts , w e

m ay n ot b e c u rin g e ve ry b ody. B ut w e a re h elp in g p eople in a v e ry im porta nt w ay.

A ll r ig ht. Y o u g ood r ig ht n ow ?

Y e ah.

O K.

H ealin g is n ot a lw ays e te rn al lif e . H ealin g is s o m etim es h elp in g p eople h ave a g ood d eath . T here 's

s o m e k in d o f h ealin g in t h at, t o o.

T here 's a n o fte n-n ote d p ara dox t h at w e m ust n ow h onestly c o nfr o nt, n am ely d esp it e t h e

e xtr a ord in ary p ro gre ss w e'v e m ade in u nders ta ndin g t h e u nderly in g d efe cts in c a nce r c e lls , it h as t o

b e a ckn ow le dged t h at w e h ave n ot s u cce eded in c o ntr o llin g c a nce r a s a h um an d is e ase t o t h e e xte nt t h at I b elie ve is p ossib le . N ow , I k n ow o th er--

A s t h e ﬁ rs t d eca de o f t h e 2 000s p asse d w it h out t h e e xp ecte d r e vo lu tio n in t a rg ete d t h era py, s o m e

p ro m in ent v o ic e s in t h e c a nce r c o m munit y b egan t o c a ll f o r a s h if t in p rio rit ie s, f r o m t h e c o stly h unt

f o r n ew d ru gs t o c a nce r p re ve ntio n.

I f y o u d on't g et c a nce r, y o u'r e n ot g oin g t o d ie f r o m it . A nd t h at's a s im ple t r u th t h at w e s o m etim es

o ve rlo ok, b eca use it 's in te lle ctu ally n ot v e ry s tim ula tin g a nd e xcit in g. P e rs u adin g s o m ebody t o q uit

s m okin g is u lt im ate ly a b ehavio ra l o r p sy ch olo gic a l e xe rc is e . It h as n oth in g t o d o w it h m ole cu le s a nd

g enes a nd c e lls . A nd s o p eople lik e m e a re e sse ntia lly u nin te re ste d in it , in s p it e o f t h e f a ct t h at

s to ppin g p eople s m okin g w ill h ave v a stly m ore e ﬀ ect o n c a nce r m orta lit y t h an a nyth in g I c o uld h ope

t o d o in m y o w n lif e tim e.

P re ve ntio n, b lo ckin g t h e f a cto rs t h at c a use t h e d is e ase in t h e ﬁ rs t p la ce , h ad lo ng b een t h e f o rg otte n

f r o nt in t h e w ar o n c a nce r. B ut a s p re ve ntio n a dvo ca te s b egan t o g ain a s tr o nger v o ic e , t h ey c o uld

p oin t t o s o m e im porta nt s u cce sse s, n one m ore s o t h an t h e c a m paig n t o s to p s m okin g.

C ig are tte s m okin g c o ntr ib ute s s u bsta ntia lly t o m orta lit y f r o m c e rta in s p eciﬁ c d is e ase s a nd t o t h e

o ve ra ll d eath r a te .

T he a nti- s m okin g c a m paig n b egan in 1 964, w hen t h e s u rg eon g enera l d eﬁnit iv e ly lin ke d s m okin g a nd

l u ng c a nce r. A t ﬁ rs t, t h e ﬁ ndin g h ad lit tle e ﬀ ect. T he r a te o f s m okin g in cre ase d in 1 964, '6 5, '6 6, a nd

' 6 7.

T e ll m e, s ir . It 's b een f o ur y e ars s in ce t h e s u rg eon g enera l's r e port c a m e o ut a bout s m okin g a nd

c a nce r, a nd y o u'r e s till s m okin g. W hy?

B eca use t h is is a lo ngsta ndin g h abit o f m in e. Ir re gard le ss w hat t h ese d octo rs s a y, a lo t o f p eople w ill

n ot p ay m uch a tte ntio n. T here 's o th er t h in gs m ore d angero us t h an s m okin g.

I t w ould t a ke a m uch m ore im agin ativ e s tr a te gy t o ﬁ nally b egin t o c u rb A m eric a 's a ddic tio n t o

c ig are tte s. T he id ea w as t h e b ra in ch ild o f a 2 6-y e ar-o ld p ate nt a tto rn ey n am ed Jo hn B anzh af. It

i n vo lv e d t u rn in g c ig are tte c o m panie s' r e lia nce o n t e le vis io n a dve rtis in g a gain st t h em .

M arlb oro , t h e c ig are tte w it h b ette r [ IN AUD IB LE ], b rin gs y o u p ro f o otb all.

I t w as T hanksg iv in g D ay. I'm s it tin g t h ere w it h m y f a th er. W e w ere w atc h in g a ll o f t h e f o otb all g am es.

A nd ju st o ve r a nd o ve r a nd o ve r a gain , y o u s e e c ig are tte c o m merc ia l, c ig are tte c o m merc ia l, c ig are tte c o m merc ia l. N ow , I'd s e en h undre ds, t h ousa nds, t e ns o f t h ousa nds g ro w in g u p, b ut ju st

s o m eth in g c lic ke d.

T here 's a lw ays t im e f o r a M arlb oro .

S om eth in g o ccu rre d t o m e, s o m eth in g I h ad le arn ed in la w s c h ool, w hic h is c a lle d t h e f a ir n ess

d octr in e, w hic h s a id t h at if y o u p re se nt o ne s id e o f a , q uote , " c o ntr o ve rs ia l" is su e o f p ublic

i m porta nce , y o u m ust m ake r e aso nable t im e a va ila ble f o r t h e o th er s id e. A nd it o ccu rre d t o m e,

c o uld t h at p ossib ly a pply t o c ig are tte c o m merc ia ls ?

B anzh af w ro te a le tte r t o t h e F e dera l C om munic a tio ns C om mis sio n, d em andin g t h at t h e t e le vis io n

n etw ork s a ir a ntis m okin g m essa ges a lo ngsid e c ig are tte a dve rtis e m ents . T o h is s u rp ris e , t h e F C C

a gre ed.

S o t h e A m eric a n C ance r S ocie ty p ro duce s a s e t o f s tr ik in g a nti- to bacco a ds in t h e la te 1 960s, e arly

1 970s.

I t 's a ll y o urs . Y o ur t o ta l c o nsu m ptio n o f c ig are tte s s o f a r, G eorg e-- h alf a m illio n.

A nd a lt h ough t h ey'r e o fte n s h ow n b y n etw ork s la te a t n ig ht, t h ey b egin t o h ave a n im pact o n r a te s o f

s m okin g.

[ C O UG H] [ IN AUD IB LE ] h ere . [ C O UG HIN G ]

T here w ere p eople c o m in g u p t o m e a nd s a yin g, I q uit s m okin g. M y f a th er q uit s m okin g. A nd t h en

s u ddenly , t h eir a ds b eco m e a lia bilit y . T he m ore t h ey a dve rtis e d, t h e m ore p eople s to p s m okin g. T hey

h ad t o g et o ﬀ t h e a ir .

I n Ja nuary 1 971, t h e la st s m okin g a d a ppeare d o n A m eric a n t e le vis io n. A nti- s m okin g a dvo ca te s w ould

e ve ntu ally p ers u ade a ll 5 0 s ta te s t o r e gula te c ig are tte s m ore h eavily a nd s u e t o bacco c o m panie s f o r

t h e h ealt h c a re c o sts o f s m okin g.

W e p aid a q uarte r o f a t r illio n d olla rs . W e k ille d o ﬀ Jo e C am el. W e g ot r id o f c ig are tte b illb oard s. W e'r e

t h e m odel. W e'r e t h e e xa m ple . W e d id it , a nd w e d id it a gain st t h ese t r e m endous o dds.

F ro m it s h eig ht in t h e la te 1 960s, c ig are tte s m okin g h as d eclin ed b y n early h alf. A s a r e su lt , lu ng

c a nce r h as a ls o b egun t o t r e nd d ow nw ard .

A lm ost n oth in g h as s a ve d a s m any liv e s, r e duce d a s m uch s u ﬀ erin g, a s a r e co gnit io n o f t h e f a ct t h at s m okin g c a use s c a nce r.

A noth er p re ve nta ble e pid em ic n ow t h re ate ns t o s p re ad t h e d is e ase . T hough n o o ne is c e rta in o f t h e

m ech anis m , o besit y c le arly c o nve ys a h ig her r is k o f c o lo n, b re ast, a nd k id ney c a nce rs a m ong o th ers .

I t 's p re dic te d t h at a s s m okin g r a te s c o ntin ue t o s lo w ly d eclin e a nd a s o besit y r a te s c o ntin ue t o

e xp lo de, b efo re t h e e nd o f t h is d eca de, t h at o besit y w ill p ass t o bacco u se a s t h e le adin g p re ve nta ble

c a use o f c a nce r. A nti- s m okin g c a m paig ns h ave b een a ro und f o r a w hile a nd h ave b een v e ry

s u cce ssfu l. B ut w e s till h ave n ot t u rn ed a ro und t h e o besit y e pid em ic , w hic h a t s o m e p oin t w e'r e g oin g

t o h ave t o f a ce s q uare o n a nd ﬁ x.

A fte r s m okin g a nd o besit y , h ow eve r, t h e k n ow n p re ve nta ble c a use s o f c a nce r h ave b een m uch

h ard er t o ﬁ nd. R adia tio n, s u nlig ht, a sb esto s, a f e w v ir u se s-- a ll h ave b een p ro ve n t o t r ig ger t h e

g enetic m uta tio ns t h at g iv e r is e t o c a nce r. S till, it is e stim ate d t h at s o m e 4 0% o f c a nce r c a se s h ave

n o k n ow n c a use a t a ll.

T he w ork o n w hat c a use s c a nce r is t h e m ost d iﬃ cu lt f o rm o f c a nce r r e se arc h a t t h e m om ent. W e

d on't k n ow t h e c a use o f m ost o f t h e m ajo r k ille rs . W e r e ally d on't k n ow w hat c a use s b re ast c a nce r,

p ancre as c a nce r, c o lo n c a nce r, p ro sta te c a nce r. W e d on't k n ow w hat c a use s t h em t h e w ay w e k n ow

t h at if y o u s to p s m okin g c ig are tte s, y o u c a n r e duce y o ur r is k o f lu ng c a nce r.

M any o f t h e m uta tio ns t h at c a use c a nce r a re p ro bably t h e r e su lt o f a ccid enta l c o pyin g e rro rs a m ong

b illio ns o f c e lls t h at d iv id e e ve ry d ay. B ut f o r d eca des, s c ie ntis ts h ave s e arc h ed f o r h id den t r ig gers in

t h e e nvir o nm ent t h at m ig ht e xp la in t h ose c a nce rs t h at y e t h ave n o e xp la natio n.

W e liv e in a n in cre asin gly c a rc in ogenic e nvir o nm ent. T his c o uld b e c a usin g m any c a nce r d eath s.

S cie ntis ts h ave b een t e stin g n early e ve ry s u bsta nce k n ow n t o m an t o t r a ck d ow n c a rc in ogens.

W it h s o m uch m yste ry s till s u rro undin g t h e d is e ase , a s e rie s o f u npro ve n t h eorie s a bout w hat c a use s

c a nce r h ad b een p ara ded t h ro ugh t h e m edia , e ve ry th in g f r o m s u gar t o p la stic s, h ig h t e nsio n p ow er

l in es t o c e llp hones. B ut p ro vin g a c a usa l lin k b etw een a ny a gent a nd c a nce r is d iﬃ cu lt . A nd t h is f a ct

h as g re atly in cre ase d a nxie ty a nd f e ar.

C ance r is f r ig hte nin g, b ew ild erin g, f r u str a tin g. M any p eople a re ju st e ndle ssly t r a w lin g o ve r, t r y in g t o

ﬁ gure o ut w hat d id I d o? W here d id I g o? S hould I h ave t a ke n t h at v a ca tio n? W as I n ear a n ucle ar

r e acto r?

D id I d rin k s o m e w ate r w ate r? D id I n ot e at o rg anic f o ods? A nd w e'r e s a yin g, lo ok a t a ll t h ese s c ie ntis ts w ho c la im t o k n ow s o m uch , a nd t h ey c a n't e xp la in t o m e w hy m e, I, t h is in div id ual,

d eve lo ped ly m phom a, le uke m ia , o r b re ast c a nce r.

U nable t o id entif y t h e c a use s o f m any c a nce rs in t h e la bora to ry , a b ra nch o f s c ie nce c a lle d

e pid em io lo gy h as a ppro ach ed t h e p ro ble m f r o m t h e o th er e nd b y s tu dyin g t h e in cid ents o f c a nce r in

c o nta in ed p opula tio ns a nd w ork in g b ackw ard s t o w ard a c o m mon c a use .

I t is v e ry m uch lik e c ir c u m sta ntia l e vid ence in a c o urt c a se . A n e pid em io lo gis t, m uch lik e a la w ye r, is

t r y in g t o ﬁ gure o ut, o fte n b ase d o n r e tr o sp ectiv e d ata , o n r e co nstr u ctio n, w hat t h e t r u e s e t o f e ve nts

m ig ht h ave b een t h at c a use d c a nce r.

O ne o f t h e ﬁ rs t e pid em io lo gis ts w as a n It a lia n p hysic ia n B ern adin i R am azzin i, w ho, in 1 700,

a sso cia te d m any d is e ase s w it h o ccu patio ns. G old sm it h s d eve lo ped m erc u ry p ois o nin g. C oal m in ers

s u ﬀ ere d lu ng d is e ase . R am azzin i's o bse rv a tio n t h at c h ild le ss n uns h ad h ig her r a te s o f b re ast c a nce r

l a id t h e g ro undw ork f o r u nders ta ndin g t h e r o le o f h orm ones in t h e d is e ase .

I n t h e 1 8th c e ntu ry , d octo rs n otic e d t h at h abit u al u se rs o f s n uﬀ h ad h ig her t h an n orm al r a te s o f n asa l

c a nce r. In t h e 1 950s, a c o nce ntr a tio n o f r a re lu ng c a nce rs in s h ip build ers w ould le ad r e se arc h ers t o

a sb esto s. B ut m ore o fte n, e pid em io lo gis ts h ave s tr u ggle d t o u nders ta nd t h e b ehavio r o f c a nce r. W hy

d o s o m e c a nce rs a ppear m ore o fte n in s o m e c o untr ie s t h an in o th ers , e ve n a m ong p eople w ho

r e ce ntly m ove d t h ere ? W hy d o c a nce rs s o m etim es s e em t o a ct lik e in fe ctio us d is e ase s, b re akin g o ut

i n s m all p opula tio ns c a lle d c lu ste rs ?

C ance r c lu ste rs h ave b een p artic u la rly c o ntr o ve rs ia l. F a m ous e xa m ple s, lik e t h ose a t T o m 's R iv e r,

N ew Je rs e y; W oburn , M assa ch use tts ; a nd a lo ng L o ve C anal in u psta te N ew Y o rk , h ave f r u str a te d

i n ve stig ato rs a nd le d s o m e t o d oubt t h at t h ey w ere a nyth in g m ore t h an a s ta tis tic a l m ir a ge.

C ance r c lu ste rs a re e xtr e m ely d iﬃ cu lt b eca use t h e n um bers a re v e ry s m all. Y o u o fte n g o t o

i n ve stig ate t h e c lu ste r s o m e y e ars a fte r it 's h appened. N ow it 's g one. C ir c u m sta nce s m ay h ave

c h anged. T he p oin t s o urc e o f w hate ve r it w as, if t h ere w as s o m eth in g, m ay h ave d is a ppeare d. S o it 's

a n in cre dib ly -- t o d o t h e d ete ctiv e w ork h ere is r e ally e xtr e m ely d iﬃ cu lt .

N obody k n ow s h ow m any c lu ste rs t h ere a re a nd h ow m any o f t h em a re r e ally r e la te d t o s o m e

c o m mon c a use . O ur t o ols ju st a re n't p ow erfu l e nough, a re n't g ood e nough. It 's s o rt o f lik e g oin g in to

a g ig antic d ark w are house f u ll o f d angero us o bje cts w it h t h is t in y lit tle m in er's la m p o n y o ur h ead,

a nd g oin g in a nd lo okin g a ro und a nd s a y, g ee, I d on't s e e a nyth in g, r ig ht, a nd t h en g oin g o ut a gain . B ut e ve n a s n ew c h em ic a ls t h at c a use c a nce r h ave b een d iﬃ cu lt t o ﬁ nd, a n o ld s u sp ect h as

r e em erg ed-- v ir u se s.

F o r a n um ber o f c a nce rs , s o m e v e ry c o m mon o nes, lik e liv e r c a nce r a nd c e rv ic a l c a nce r, v ir u se s a re

f r o nt a nd c e nte r in t h e m ajo r c a use s o f t h ose c a nce rs . H appily , w e h ave d eve lo ped v a ccin es t h at c a n

p re ve nt in fe ctio ns f o r s o m e o f t h ose a gents . A nd t h at h as r e duce d t h e in cid ents o f c a nce r

d ra m atic a lly .

T o nig ht w e h ave s o m e n ew s w e d o n ot g et t o r e port o fte n e nough in t h e b attle a gain st c a nce r. T he

ﬁ rs t la rg e-s c a le t e st o f a v a ccin e f o r c e rv ic a l c a nce r f o und t h e F D A 1 00% e ﬀ ectiv e in b lo ckin g t h e

v ir u s t h at c a use s t h e d is e ase .

A v a ccin e a ppro ve d b y t h e F D A in 2 006, a ctiv e a gain st t h e h um an p apillo m a v ir u s, t h e le adin g c a use

o f c e rv ic a l c a nce r, p ro m is e s t o a ll b ut e ra dic a te t h e d is e ase if c h ild re n c a n b e in ocu la te d b efo re t h ey

b eco m e s e xu ally a ctiv e .

W hen I w as a r e sid ent, if y o u h ad a n a bnorm al p ap s m ear, y o u h ad a t o ta l h yste re cto m y, b eca use w e

d id n't k n ow w hat e ls e t o d o. Y o u lo st y o ur f e rtilit y . A nd t h en w e ﬁ gure d o ut t h at it w as c a use d b y a

v ir u s. A nd n ow w e h ave a v a ccin e. S o m y d aughte r's b een v a ccin ate d.

N ow , t h at's a m azin g. T hat's p re tty a m azin g. W e e sse ntia lly c a n w ip e o ut c a nce r o f t h e c e rv ix b y t h e

H PV v a ccin e.

T he s c ie nce o f c a nce r p re ve ntio n is s till y o ung a nd d ependent o n im perfe ct k n ow le dge o f w hat

c a use s c a nce r. B ut e ve n if it s u cce eded o nly in c u rta ilin g s m okin g, o besit y , a nd t h e k n ow n c a nce r-

c a usin g v ir u se s, it w ould h ave a p ro fo und im pact o n m orta lit y .

I t h as b een e stim ate d t h at t o day, if s o cie ty w ere t o im ple m ent w hat's k n ow n a bout p re ve ntio n, t h en

c a nce r d eath s c o uld b e r e duce d b y 5 0% . A nd t h at's w it h out a ny n ew r e se arc h o r a ny n ew d is c o ve rie s.

T hat's ju st im ple m entin g w hat is a lr e ady w ell- k n ow n.

H ere 's m y c h erry -ﬂ avo re d N uLY TELY. L o okin g f o rw ard t o d rin kin g t h is in t h e n ext s e ve ra l h ours .

E ve n w hen c a nce rs c a n't b e p re ve nte d, t h ey c a n s till b e s to pped, if t h ey a re d ete cte d e arly e nough.

B otto m s u p, s o t o s p eak. H eh.

I n M arc h 2 000, t w o y e ars a fte r h er h usb and's d eath f r o m c o lo n c a nce r, T V a nch or K atie C ouric b egan

a w ell p ublic iz e d c ru sa de t o in cre ase t h e n um ber o f p eople g ettin g r o utin e c o lo nosc o pie s, w hic h c a n d ete ct t h e d is e ase in it s e arlie st s ta ges.

S o f a r, I'm lo okin g p re tty c le an, h uh?

S o f a r, y o u'r e v e ry c le an.

P e ople d on't w ake u p o ne d ay a nd a ll o f a s u dden h ave a c a nce r. Y o u h ave t h is g ia nt w in dow o f

o pportu nit y , 2 0 o r 3 0 y e ars , t o c a tc h a c a nce r b efo re t h e ﬁ nal s ta ges, w hic h o nly o ccu rs in t h e la st

f e w y e ars o f t h is lo ng lif e tim e o f t h e c a nce r. A nd t h ey c a n a lm ost a lw ays b e c u re d b y s u rg ery a lo ne if

t h ey'r e c a ught e arly .

O K, K atie . T hat's it .

T hat w asn 't b ad a t a ll.

N o.

I n t h e la st d eca de, p artia lly a s a r e su lt o f C ouric 's e ﬀ orts , c o lo n c a nce r s c re enin g is u p s h arp ly , a nd

m orta lit y f r o m t h e d is e ase is d ow n n early 1 0% .

T he f u ll e xa m in atio n r e quir e s t h re e v ie w s-- t h e c ra nio ca udad v ie w , t h e m edio la te ra l v ie w , a nd a xilla ry

v ie w .

I n t h e 1 950s, a d octo r a t t h e M D

Anders o n C ance r C ente r in H ousto n in ve nte d a m eth od o f t a kin g

d eta ile d im ages o f t h e in sid e o f t h e b re ast.

T he h ead is t u rn ed t o t h e c o ntr a la te ra l s id e. T he t u be is in [ IN AUD IB LE ] in to p la ce .

T he m am mogra m w as h aile d a s a m ajo r b re akth ro ugh in t h e ﬁ ght a gain st b re ast c a nce r. T his is a

ﬁ nis h ed [ ? p ro duct. ? ] N ote t h e s e co nd c a rc in om a w as in t h is b re ast, n ot a ppre cia te d c lin ic a lly .

O ve r t h e y e ars , w it h t h e h elp o f a n a ctiv is t b re ast c a nce r c o m munit y , t h e t e st b eca m e p art o f m illio ns

o f w om en's a nnual c h ecku p.

E ve ry w om an in A m eric a o ve r 3 5 s h ould k n ow t h is w ord -- m am mogra phy. It 's a f a st a nd s im ple

p ro ce dure t h at c a n d ete ct b re ast c a nce r e arly , w hile it 's h ig hly c u ra ble .

[ C H EER IN G ]

W e h ave p ush ed f o r m am mogra phy s c re enin g f o r o nce a y e ar f o r a lif e tim e. E arly d ete ctio n s a ve s

l iv e s. W hole o rg aniz a tio ns w ere b uilt a ro und t h at c o nce pt. T he b re ast c a nce r in dustr y w as b uilt a ro und t h at c o nce pt.

B ut lik e s o m any c a nce r t h era pie s o r p re ve ntio n m eth ods, t h e m am mogra m h as t u rn ed o ut t o b e t o o

b lu nt a n in str u m ent f o r t h e c o m ple xit y o f c a nce r. A b evy o f r e ce nt s tu die s h ave s h ow n t h at w hile

a nnual m am mogra m s r e su lt in a c le ar r e ductio n in m orta lit y f o r w om en o ve r t h e a ge o f 5 0, t h e

b eneﬁt t o y o unger w om en is n eglig ib le . In t h ese e arlie r y e ars , t h e t e st is t o o im pre cis e t o d is tin guis h

a r e al c a nce r f r o m a h arm le ss g ro w th . M eanw hile , f a ls e p osit iv e d ia gnose s h ave le d t h ousa nds o f

w om en t o u nderg o p ain fu l, e xp ensiv e , a nd d is ﬁ gurin g t r e atm ents , lik e m aste cto m y.

I n b re ast c a nce r, w e'r e s o a fr a id o f m is sin g t h at o ne p atie nt in 1 ,0 00 t h at w ill d ie o f t h e d is e ase , w e

e nd u p t r e atin g a ll t h ousa nd. S o t h at t r ig gers e norm ous a m ount o f p ro ce dure s, t r e atm ents ,

i n te rv e ntio ns. T hat is d iﬃ cu lt t o s to p. It 's e th ic a lly d iﬃ cu lt t o s to p. A nd e co nom ic a lly , it 's d iﬃ cu lt t o

s to p, b eca use t h e in ce ntiv e s a re t o s u sta in it .

M en h ave n ot b een s p are d t h e c o lla te ra l d am age c a use d b y a n im pre cis e m eth od o f e arly d ete ctio n.

L ik e t h e m am mogra m , t h e t e st f o r p ro sta te c a nce r, t h e p ro sta te -s p eciﬁ c a ntig en, o r P S A , is o fte n

m is in te rp re te d, le adin g t o h ig h r a te s o f f a ls e p osit iv e s a nd u nnece ssa ry s u rg erie s.

T he d iﬃ cu lt y t h at's f a ce d b y t h e p atie nt is s a yin g, is m y e arly a bnorm alit y h arm le ss, o r is it g oin g t o

b e h arm fu l? W ill I r e gre t n ot p ro ce edin g? A nd t h at's a v e ry d iﬃ cu lt c h oic e , b eca use t h e

c o nse quence s o f b ein g w ro ng c a n b e d eva sta tin g.

T here w e g o. R ig ht t h ere .

W hat w e'r e a ll lo okin g f o r is c a n w e ﬁ nd m ark e rs t h at s a y y e s, t h ere is s o m e a bnorm alit y . B ut t h e

l ik e lih ood o f t h is d eve lo pin g in to a f r a nk c a nce r is e xtr e m ely lo w .

T hese m ark e rs , o r c lu es t o t h e p re se nce o f c a nce r, m ig ht c o m e in t h e f o rm o f m uta tio ns t h at t u rn u p

i n r o utin e g enetic s c re enin gs.

I t 's o ur h ope, m ayb e o ur d re am , t h at o ne d ay w hen p eople g o t o t h eir y e arly o ﬃ ce v is it a nd d eposit

s a m ple s o f b lo od a nd u rin e, e t c e te ra , t h ese s p ecim ens w ill b e t e ste d f o r m uta tio ns. T hey w ill b e

a le rte d t o t h e p re se nce o f a c a nce r w hic h t h ey w ould n't y e t k n ow a bout, b eca use it h asn 't c a use d

s y m pto m s. A nd t h ey c a n t h en b e h andle d t h ro ugh s u rg ery , a nd t h e c a nce rs a re g one. T hat's t h e

h ope.

C , C , C , T , C , T , C , A . A lr e ady, t h ere a re a f e w t e sts t h at c a n d ete ct g enetic m uta tio ns t h at w ill lik e ly g iv e r is e t o c a nce r

b efo re a s in gle c a nce r c e ll h as e ve n a ppeare d in t h e b ody. T he ﬁ rs t g re w o ut o f t h e w ork o f a y o ung

b io lo gis t n am ed M ary C la ir e K in g, w ho in t h e m id -1 970s, b egan in ve stig atin g w hy t h ere w ere s o m e

f a m ilie s in w hic h b re ast c a nce r w as m uch m ore p re va le nt t h an in o th ers .

I s a id , t h is is a c o m mon illn ess. H ow m uch b re ast c a nce r w ould w e e xp ect t o s e e c lu ste rin g in f a m ilie s

j u st b y c h ance , b eca use it 's c o m mon? A nd t h en h ow m uch m ore o r le ss t h an t h at d o w e a ctu ally s e e?

K in g d is c o ve re d t h at in s o m e f a m ilie s, t h e r a te o f b re ast c a nce r w as s o h ig h it c o uld n ot b e b y

c h ance . S he h yp oth esiz e d t h at t h ese f a m ilie s m ust c a rry a g enetic m uta tio n t h at t h ey p asse d d ow n

f r o m o ne g enera tio n t o t h e n ext. T o p ro ve t h at t h ere w as a g ene a nd t h en t o ﬁ nd it , K in g w as g oin g t o

h ave t o w ork c lo se ly w it h a ﬀ ecte d f a m ilie s.

I n eeded f a m ilie s w ho w ould b e p art o f t h is , w ho w ould b e p atie nt, a nd w ho w ould b e w illin g t o h ave

m e c o m e b ack t o t h em a nd t a lk t o t h em o ve r a nd o ve r, a nd t a ke b lo od s a m ple s a nd a sk t o c o lle ct

t h e t u m our s a m ple s w hen t h ey h ad s u rg erie s, a nd w ould lis te n t o m y h yp oth ese s a nd t a lk t o m e

f o re ve r.

T here w as o ne m an s h e k n ew w ho c o uld h elp h er ﬁ nd s u ch f a m ilie s. D r. B ern ard F is h er w as b y t h at

t im e in t h e m id st o f h is g ro undbre akin g s tu dy o n t h e e ﬀ ectiv e ness o f t h e r a dic a l m aste cto m y. If

a nyo ne c o uld in tr o duce K in g t o f a m ilie s w it h in herit e d b re ast c a nce r, it w as h e.

M eetin g B ern ie F is h er c h anged m y lif e . H e k n ew f r o m h is p ra ctic e t h at t h ese f a m ilie s s h ow u p f r o m

t im e t o t im e. A nd h e k n ew t h at w hen h e w as w ork in g w it h a f a m ily t h at h ad h ad, h is to ric a lly in

g enera tio ns, f o ur o r ﬁ ve , s ix c a nce rs , h e w as s u re t h at in t h e n ext g enera tio n it w ould s h ow u p a gain .

S o w hen I a sk e d h im if h e w ould h elp m e id entif y f a m ilie s, h e s a id , w ell, o f c o urs e .

O n t h is p edig re e o r f a m ily t r e e, c ir c le s r e pre se nt w om en, s q uare s r e pre se nt m en, a nd ﬁ lle d s y m bols

r e pre se nt c a nce r.

W ork in g in t h is w ay, f a m ily b y f a m ily , K in g w as a ble t o id entif y t h e s e ctio n o f D NA a lo ng c h ro m oso m e

1 7, w here t h e m uta te d g ene w as f o und. T he g ene w as c a lle d B RC A. W om en w ho c a rry t h e B RC A

m uta tio n, w hic h c a n b e d ete cte d b y a s im ple b lo od t e st, k n ow t h ey h ave u p t o a 7 0% c h ance o f

c o ntr a ctin g b re ast c a nce r a nd a 3 0% c h ance o f d eve lo pin g o va ria n c a nce r.

W it h t h is f o re w arn in g, t h ey c a n t a ke p re ve nta tiv e m easu re s. T hey c a n w atc h t h em se lv e s m ore c lo se ly

o r c h oose t o h ave t h eir b re asts r e m ove d b efo re c a nce r e ve r a ppears . B y k n ow in g m uch m ore a bout

h ow c a nce r d eve lo ps, d octo rs m ay b e a ble t o a sse ss t h e r is k s f o r e ach p ers o n lo ng b efo re h e o r s h e c o ntr a cts t h e d is e ase a nd d eve lo p s tr a te gie s t o p re ve nt it o r d ete ct it e arly .

I t h in k t h e t im e w ill c o m e w here y o ur o w n in div id ual r is k s a re g oin g t o b e b ette r p re dic te d b y u sin g

y o ur f a m ily h is to ry , b y u sin g y o ur o w n e nvir o nm enta l e xp osu re s a nd y o ur lif e sty le , a nd b y u sin g y o ur

D NA. S o h ere it 's n ot lo okin g a t a c a nce r g enom e h ere , lo okin g a t y o ur c o nstit u tio nal g enom e a nd

s a yin g O K, f o r y o u, y o ur r is k s o f t h is d is e ase a re h ig her t h an t h e a ve ra ge, f o r t h at d is e ase a re lo w er.

C le arly , if w e'r e t a lk in g p re ve ntio n in a w ay t h at's g oin g t o w ork , it c a n't b e o ne s iz e ﬁ ts a ll. It 's g ot t o

b e f o cu se d o n t h at in div id ual.

T he c o m bin atio n o f p re ve ntio n, e arly d ete ctio n, a nd s o m e n ew t a rg ete d t h era pie s h ave m ade a

s ig niﬁ ca nt d iﬀ ere nce in t h e ﬁ ght a gain st c a nce r. In t h e U nit e d S ta te s, c a nce r m orta lit y h as b een

s lo w ly d eclin in g, d ow n 2 0% o ve r t h e la st t w o d eca des. A nd t h ere is o ptim is m t h at t h is t r e nd w ill

a cce le ra te . O ne m ajo r r e aso n is t h at r e se arc h ers h ave b egun t o d is c e rn p atte rn s w it h in t h e

c o m ple xit y o f t h e c a nce r c e ll t h at o nce h ad s e em ed s o d auntin g. T he ﬁ rs t s te p w as u nders ta ndin g

t h at n ot a ll t h e m uta tio ns in c a nce r c e lls a re e qually s ig niﬁ ca nt.

M ost m uta tio ns in a c a nce r c e ll a re r a ndom , u nim porta nt m uta tio ns. T here 's a lim it e d n um ber o f

t h ose c h anges t h at r e ally c o nfe r t h e p ro pertie s o n t h e c a nce r. W hat w e h ave r ig ht n ow is a s if tin g

p ro ce ss t o ﬁ nd, b y c o m parin g m any d iﬀ ere nt c a nce rs , w hic h o nes a re t h e r e cu rre nt t a rg ets t h at

r e ally m atte r a nd g iv e t h e c a nce r it s p ro pertie s.

T hose m uta tio ns t h at a re s ig niﬁ ca nt, it t u rn s o ut, o fte n p la y a k e y r o le in m any d iﬀ ere nt c a nce rs .

I n f a ct, b re ast c a nce r a nd le uke m ia , w hic h lo ok c o m ple te ly d iﬀ ere nt u nder t h e m ic ro sc o pe, m ay

a ctu ally s h are s o m e a lt e re d g enetic c o m ponents . S o t h ere fo re , t h e w orld o f c a nce r, h avin g b een

d iv e rs iﬁ ed, n ow b egin s t o ﬁ nd t h ese , a nd I c a n o nly d esc rib e t h em a s s o rt o f g enetic w orm hole s, f r o m

o ne c a nce r t o a noth er.

T hese f r e sh in sig hts h ave r e ju ve nate d t h e ﬁ eld o f t a rg ete d t h era py. If t h e m any m uta tio ns in a c a nce r

c e ll c a n b e n arro w ed d ow n t o ju st a f e w , b lo ckin g t h eir e ﬀ ects m ig ht b e p ossib le w it h a t e ch niq ue

a lr e ady u se d in a m uch le ss p re cis e w ay in c h em oth era py-- c o m bin atio ns o f d ru gs.

T he k e y is t o h it a c a nce r w it h m ult ip le d ru gs s im ult a neously . W hen a c a nce r m uta te s, it g ain s s o m e

n ew p ro pertie s. B ut v e ry o fte n, it g ain s a n ew v u ln era bilit y a s w ell. It g ain s a p ow er, a nd it g ain s a n

A ch ille s' h eel. S o w hat's e xcit in g r ig ht n ow is t h e c a ta lo gin g f o r e ve ry m uta tio n t h e A ch ille s' h eels it

c re ate s-- if m uta tio n h ere , v u ln era bilit y t h ere . A tta ck t h ere . It m ig ht m uta te , b ut y o u'v e a ls o g ot o ve r

h ere t o h it . Y o u'r e la yin g o ut, e sse ntia lly , a w ay t o d eplo y y o ur a rm ie s, k n ow in g t h at c a nce r is g oin g t o t r y t o e sc a pe d ow n t h is p ath , a nd y o u'v e g ot s o m eth in g w ait in g f o r it .

N ot o nly h ave c a nce r r e se arc h ers n arro w ed d ow n t h e n um ber o f o nco genes a nd t u m or s u ppre sso r

g enes t h at a ctu ally c a use c a nce rs , t h ey'v e a ls o d is c o ve re d t h at n one o f t h ese g enes o pera te s in

i s o la tio n. In ste ad, t h ey w ork a s p art o f g ro ups c a lle d p ath w ays t o a cco m plis h s p eciﬁ c t a sk s.

T here a re o nly a bout 2 00 g enes w hic h a re r e sp onsib le f o r t h e v a st m ajo rit y o f c a nce rs . T hen t h ese

2 00 g enes f u nnel d ow n in to o nly a bout 1 2 p ath w ays. If y o u c a n ﬁ gure o ut a w ay t o t a rg et t h ese

p ath w ays, y o u w ill h ave a t h era py t h at's u se fu l f o r m any d iﬀ ere nt k in ds o f c a nce rs .

Y o u c a n t h in k o f a p ath w ay lik e a c ir c u it o r a b ucke t b rig ade. If y o u d is ru pt t h e b ucke t b rig ade a t a ny

o ne n um ber o f p osit io ns, y o u c o uld d is ru pt t h e e ntir e ty o f t h e b rig ade. W hat w e'r e le arn in g n ow is

t h at t h ere m ay b e m ult ip le d iﬀ ere nt w ays t o a ctiv a te t h is b ucke t b rig ade c a usin g c a nce r. B ut it a ls o

m eans t h at t h ere a re m ult ip le p la ce s t o in te rv e ne a nd d is ru pt it .

M ake n o m is ta ke , t h is is c o m plic a te d. It 's a t le ast a s e la bora te a s t h e m ost c o m plic a te d e le ctr o nic

c ir c u it d ia gra m t h at y o u h ave e ve r s e en. B y g ettin g o ur m in ds a ro und t h at, e ve n if it 's s o m ew hat

i m perfe ct, o ﬀ ers a lo t o f o pportu nit ie s.

W it h t h e c o st o f g enetic s e quencin g p lu m metin g, it m ay b e o nly a m atte r o f t im e b efo re d octo rs c a n

m ap a ll t h e g enes a nd p ath w ays in sid e e ve r p atie nt's c a nce r, a nd t r e at e ach o f t h em w it h a

p ers o naliz e d c o m bin atio n o f d ru gs.

W here w e'r e g oin g is t h is m uch m ore in div id ualiz e d a ppro ach , ju st lik e in fe ctio us d is e ase s. If y o u

h ave a v e ry b ad in fe ctio n, v e ry b ad, y o ur d octo r w ill t a ke a s a m ple o f t h e b ug, g ro w it , a nd p ic k a n

a ntib io tic o r t w o o r s o m etim es t h re e, m ix t h em t o geth er, a nd h opefu lly c u re y o u. A nd t h at's w hat

w e'r e t r y in g t o d o in o nco lo gy n ow .

N o m atte r h ow p ow erfu l o r p re cis e , h ow eve r, c o m bin atio n t a rg ete d t h era pie s s till m ust c o nfr o nt

c a nce r's c o m ple xit y a nd it s r e le ntle ss d riv e t o a dapt a nd s u rv iv e .

T o m e, t h e b est w ay t o t h in k a bout c a nce r is t h at it is lit e ra lly e vo lu tio n in a b ottle . It 's lik e t a kin g t h e

e norm it y o f t h e p ow er o f t h re e b illio n y e ars , u nim agin able t im e f r a m es t h at h ave c re ate d t h e

u nim agin able d iv e rs it y o f lif e . Im agin e c a ptu rin g a ll o f t h ose f o rc e s w it h in a s in gle c e ll a nd p uttin g

t h at in sid e s o m eone's b ody. T hat is , t o m e, t h e m eta phor o f c a nce r. It is a ll o f t h e h is to ry o f lif e t h at

p la ys o ut a t a b illio n t im es t h e s p eed o f e vo lu tio n.

I f c a nce r e xp lo it s t h e p ow er o f e vo lu tio n t o s u rv iv e , p erh aps o nly a c o m mensu ra te w eapon, e qually a dapta ble a nd a ls o p erfe cte d o ve r m illio ns o f y e ars , c a n o ve rc o m e it . T hat w eapon, m any s c ie ntis ts

b elie ve , is t h e h um an im mune s y ste m .

T he im mune s y ste m is a n e xtr a ord in ary s e t o f d efe nse s, a n in tr ic a te in te rp la y o f c e lls a nd p ro te in s.

T hey'r e c ir c u la tin g t h ro ugh o ur b lo od s tr e am . T hey h ave t h ese s u rfa ce s t h at k e ep lo okin g a nd s a yin g,

i s t h ere s o m eth in g f o re ig n? Is t h ere s o m eth in g c h anged? Is t h is s o m eth in g d iﬀ ere nt? B eca use I h ave

t o k e ep t h at o ut.

T he id ea t h at t h e im mune s y ste m m ig ht e ﬀ ectiv e ly t r e at c a nce r is n ot n ew . It w as ﬁ rs t e xp lo re d b y a

1 9th -c e ntu ry s u rg eon, W illia m C ole y. W hile w ork in g a t M em oria l H osp it a l in N ew Y o rk C it y , C ole y

c a m e a cro ss a s tr a nge c a se -- a p atie nt w hose t u m or s e em ed t o v a nis h o f it s o w n a cco rd a fte r a

s e rio us in fe ctio n.

C ole y t h ought, t h ere 's a p ow er h ere . W e d on't k n ow q uit e h ow t o h arn ess it , b ut I'm g oin g t o t r y t o

i n fe ct p eople w ho m ay h ave t h is d ir e , in opera ble f o rm o f c a nce r a nd s e e if w e c a n d o a nyth in g a bout

i t . A nd t h at, in a m essy a nd u nsc ie ntiﬁ c w ay, w as t h e b ir th o f c a nce r im munoth era py.

C ole y m ade a c o m pound o f in fe ctio us b acte ria a nd in je cte d it d ir e ctly in to t h e t u m ors o f p atie nts ,

h opin g t o t r ig ger a f e ve r t h at w ould s o m ehow o ve rw helm t h e c a nce r. S om e o f h is p atie nts w ere

c u re d, b ut n o o ne w as a ble t o d uplic a te h is r e su lt s . A nd f o r d eca des, im munoth era py r e m ain ed o n

t h e f r in ges o f c a nce r r e se arc h , e ve n w hen s c ie ntis ts w ere a ble t o d ete ct m yste rio us p artic le s t h at

a ppeare d t o b e ﬁ ghtin g c a nce r c e lls .

W e n otic e d t h ese p ecu lia r lit tle b odie s w it h t h e c a nce r c e lls . W e d on't k n ow ju st w hat t h ey a re . A nd

w e d on't k n ow w hat it m eans, b ut o nce t h e c a nce r c e lls d eve lo p t h ese s p ots , t h ey g o o n t o

d is in te gra te a nd d ie . W ell, t h at's it . T hat's w hat w e h ave b een s e ein g. T he lit tle d ots m ay b e e vid ence

o f a n im munolo gic a l m ech anis m , o r t h ey m ay b e s o m eth in g n on-s p eciﬁ c. A nd w e h ope w e c a n ﬁ nd

o ut w it h f u rth er s tu dy.

I m munoth era py r e m ain ed a b ackw ate r. B ut a f e w s c ie ntis ts , c e rta in t h at t h ere w as s o m eth in g t o it ,

k e pt t h e ﬁ eld a liv e . O ne o f t h em w as S te ve n R ose nberg , w ho, s in ce t h e 1 970s, h as b een e xp lo rin g

i m munoth era py t r e atm ents a t t h e N atio nal C ance r In stit u te . A s u rg eon lik e C ole y, h e t o o h ad h ad a

p atie nt w hose c a nce r h ad m ir a cu lo usly d is a ppeare d.

A ll a sp ects o f h is c a nce r w ere g one. H e h ad u nderg one o ne o f t h e m ost r a re e ve nts in a ll o f

m edic in e. H e h ad h ad a s p onta neous r e gre ssio n o f a ll o f h is m eta sta tic c a nce r.

R ose nberg b elie ve d t h at t h e e xp la natio n h ad t o lie in t h e p atie nt's o w n im mune s y ste m . H e d ecid ed t h en a nd t h ere t o f o cu s h is r e se arc h o n im mune c e lls , o r ly m phocyte s.

O K, le t's t a lk a bout a dm is sio ns f o r t h is w eek. T he b ody h as h undre ds o f b illio ns o f ly m phocyte s. A nd

s o m ew here in t h e b ody o f a c a nce r p atie nt, t h ere a re ly m phocyte s, w e h yp oth esiz e , t h at c o uld

r e co gniz e w hat w as d iﬀ ere nt a bout t h e c a nce r.

S o M ark , le t's h ear a bout c e lls .

W e h ave [ IN AUD IB LE ] o n t h e [ ? N M AR ? ] w it h t h e r a ndom iz e d p ro to co l. It 's d ue t o s ta rt in fu sio n o n t h e

7 th .

I t w as t h at h yp oth esis , it w as t h at d re am t h at t h en le d u s t o t r y t o id entif y t h e a ctu al c e lls t h at w ere

a tta ckin g t h e c a nce r a nd u se t h em t o a ctu ally d eve lo p a c a nce r t r e atm ent.

R ose nberg is o la te d v a rio us t y p es o f im mune c e lls in h is la b, a nd in a s e rie s o f c lin ic a l t r ia ls , in je cte d

t h em in to p atie nts . B ut p ro gre ss w as p ain fu lly s lo w . In t h e ﬁ rs t 6 6 p atie nts , h is t h era py s h ow ed n o

s ig ns o f w ork in g. T hen, in 1 984, h e t r e ate d t h e 6 7th , a N avy o ﬃ ce r n am ed L in da T a ylo r, w it h a f a r

h ig her d ose . T hre e d eca des la te r, s h e is s till in p erfe ct h ealt h .

I t e ll y o u, I n eve r c ry e xce pt a ro und y o u.

I k n ow .

I t w as a n im porta nt e ve nt in t h e d eve lo pm ent o f c a nce r t r e atm ents , b eca use it s h ow ed p eople t h at it

w as p ossib le -- a t t h at p oin t, in a v e ry t in y p erc e nta ge o f p atie nts -- t o c a use t h e im mune s y ste m t o

m ake a c a nce r d is a ppear.

T he h ope f r o m t h ose e arly e xp erim ents w as t h at if y o u c o uld s o m ehow a ctiv a te s p eciﬁ c a sp ects o f

t h e im mune s y ste m , c o uld y o u n ow e duca te it t o a tta ck a c a nce r c e ll a nd n ot a tta ck a n orm al c e ll?

R ose nberg w ent o n t o d is c o ve r t h at a s p eciﬁ c t y p e o f im mune c e ll c a lle d a T c e ll. W as a ctiv e a gain st

s o m e c a nce rs , b ut w hen g re atly o utn um bere d w as t o o w eak t o d efe at t h em . T hro ugh d oze ns o f

e xp erim enta l t r ia ls , h e le arn ed t o e xtr a ct t h ese c a nce r-ﬁ ghtin g T c e lls f r o m a p atie nt's o w n b ody;

g ro w t h em in t h e la b in to a v a st a rm y, b illio ns o f c e lls s tr o ng; a nd t h en in fu se t h em b ack in to t h e

p atie nt's b ody t o ﬁ ght h is o r h er c a nce r.

S o n ow y o u h ave 6 8.6 b illio n c e lls .

[ A PPLA USE] M ore t h an w hat y o u t h ought.

R ose nberg is r u nnin g s e ve ra l c lin ic a l t r ia ls f o r m ela nom a p atie nts u sin g t h is a ppro ach . A ll r ig ht, t h ere .

R ig ht h ere , lit tle b uggers , r ig ht in t h is a re a. C hew , c h ew , c h ew .

E ve ry w eek, h e s e es a n ew g ro up o f p atie nts , a ll w it h a dva nce d c a nce rs , m ost o f w hom h ave

e xh auste d e ve ry o th er t r e atm ent.

M r. R ogers , I'm D r. R ose nberg .

H i.

D elig hte d t o m eet y o u. G ood. P le ase s ta y r ig ht w here a re y o u?

I 'm Ja n.

H i, Ja n. D elig hte d t o m eet y o u. T e ll m e, w hen d id y o u ﬁ rs t n otic e a p ro ble m

S epte m ber o f 2 011.

W hat d id y o u n otic e ?

A m ole .

D oug R ogers is 6 0-y e ar-o ld o ld r e tir e d N ASC AR m ech anic f r o m S outh C aro lin a. H e f o und o ut h e h ad

m eta sta tic m ela nom a w hen h e h ad a b la ck m ole o n h is le g c h ecke d in 2 011.

A nd t h en r ig ht in t h e c o nca ve a re a w here t h e m ole w as, a lit tle b la ck c ru sty p la ce c a m e b ack u p.

T he c a nce r s o on s ta rte d t a kin g o ve r h is b ody.

S o s h ow m e w here t h e w here t h e t u m or o rig in ally s ta rte d. W here w as t h e o rig in al m ole t h at y o u h ad?

R ig ht u p h ere . S ee, t h e s c a r [ IN AUD IB LE ]--

I s e e. I s u re ly d o. Y e s, O K. G ood. Y o u c a n lie b ack.

W hat w e h ave t o d o t o p erfo rm t h is t r e atm ent is w e h ave t o t a ke o ﬀ o ne o f t h e t u m ors . O f c o urs e , w e

h ave t o is o la te t h e im mune c e lls t h at a re a ctu ally a tta ckin g t h e c a nce r. A nd w hat b ette r p la ce t o ﬁ nd

t h em t h en w it h in t h e c a nce r it s e lf ? A nd w e g ro w t h em u p, a nd t h en w e g iv e t h em b ack t o y o u. A nd in o th er p atie nts , w e'v e s e en v e ry r e m ark a ble d is a ppeara nce o f c a nce r.

S o t h at's w hat w e h ave p la nned. I'v e g one o ve r y o ur x -r a ys. Y o u s e em t o b e a g ood p atie nt f o r t h is .

N ow , t h is m ig ht b e a lit tle c h illy . I'm s o rry a bout t h at.

T w o d ays la te r, t h e t e am p re pare d f o r a n o pera tio n t o r e m ove o ne o f R oger's t u m ors s o t h ey c a n ﬁ nd

t h e T c e lls t h at m ay b e t r y in g t o ﬁ ght it .

S o t h is o pera tio n is g oin g t o b e p re tty s im ple , a s f a r a s a naesth esia is c o nce rn ed. D o y o u g ot a ny

q uestio ns f o r m e?

N o, s ir .

A ll r ig ht. W here a re y o u f r o m ? I d ete ct a lit tle a cce nt.

B ro okly n , N ew Y o rk .

[ L A UG HS]

T hat's n o a cce nt. T hat's a d ra w l.

S outh C aro lin a.

W e'v e b een t o geth er s in ce I w as 1 8, a nd I'm 5 5 n ow . W e'v e t r a ve le d d ow n a lo t o f r o ads. S o w e'v e ju st

g ot a lo t le ft t o d o t o geth er. W e g ot t o b eat t h is .

I s t h is h ow [ IN AUD IB LE ]? Y o u m ig ht n ot r e m em ber t h is p art.

T his m ay le ngth en h is lif e , o r e ve n c u re h im . I c a n't w ra p m y b ra in a ro und b ein g w it h out h im . I c a n't

d o it . H e d riv e s m e c ra zy , ju st lik e a ny h usb and d riv e s a w if e c ra zy. B ut I c a n't lif e w it h out h im .

W it h R ogers s till in t h e o pera tin g r o om , R ose nberg 's t e am d eliv e re d a s a m ple o f h is t u m or t o t h e la b.

I n t h e la bora to ry , o ne o f o ur t e ch nic ia ns is w ait in g t o d is se ct t h e t u m or in to t in y f r a gm ents , p ut t h ose

f r a gm ents in to in div id ual c u lt u re w ells , a nd le t t h e ly m phocyte s g ro w o ut o f t h em .

O ve r t h e n ext f o ur w eeks, R ose nberg 's w ill n urtu re R oger's im mune c e lls , t r y in g t o t u rn a f e w c a nce r-

ﬁ ghtin g T c e lls in to a n a rm y, b illio ns s tr o ng.

R ose nberg h as n ot b een t h e o nly s c ie ntis t in ve stig atin g t h e im mune s y ste m a nd c a nce r. In t h e e arly 1 980s, a s c ie ntis t a t t h e U niv e rs it y o f T e xa s, Jim A llis o n, b egan w ork in t h e ﬁ eld , e ve n t h ough h e w as

t o ld it w ould s ta ll h is c a re er.

T here w as s u ch s k e ptic is m a bout im munoth era py in g enera l. I r e m em ber a s r e ce ntly a s 2 004 g oin g

t o a m eetin g o f c a nce r b io lo gis ts , a nd f e elin g I s h ould p ro bably s h ould w ear a h elm et a nd a

b odyg uard a nd e ve ry th in g t o a vo id b ein g a buse d f o r h avin g t h e a udacit y t o s a y I t h in k t h e im mune

s y ste m c a n t a ke c a re o f c a nce r.

A llis o n's id ea w as v e ry d iﬀ ere nt f r o m R ose nberg 's . In ste ad o f t r y in g t o b oost t h e im mune s y ste m , h e

t h ought t h e im mune s y ste m m ig ht s o m ehow b e h old in g it s e lf b ack f r o m a tta ckin g c a nce r c e lls .

E ve ry o ne w as lo okin g a t w ays t o s tim ula te t h e im mune s y ste m . N o o ne r e aliz e d t h at t h ere w ere

r e str a in ts o r b ra ke s. A llis o n f o und t h at a c e rta in p ro te in a cte d lik e a b ra ke . S o y o u c a n r e m ove t h e

b ra ke s, a nd t h en t h e n ew s y ste m g oes t o w ork .

I n 1 996, A llis o n d eve lo ped a c o m pound t h at c o uld f r e e t h e im mune s y ste m t o a tta ck c a nce r. It t o ok

h im y e ars t o ﬁ nd a c o m pany t h at w ould h elp h im p ro duce h is d ru g. B ut w hen Y e rv o y ﬁ nally c a m e t o

m ark e t in 2 011, t h e w hole p harm ace utic a l in dustr y q uic kly t o ok n ote . S in ce t h en, s e ve ra l n ew d ru gs

h ave b een d eve lo ped b ase d o n t h e s a m e p rin cip le -- r e m ovin g t h e c o nstr a in ts t h at p re ve nt t h e

i m mune s y ste m f r o m a tta ckin g c a nce r.

C ance r is a d yn am ic in te rp la y b etw een p atie nt a nd t u m or. A nd f o r m any d eca des, w e h ave

c o nce ntr a te d a ll o f o ur e ﬀ orts o n t h e t u m or p art o f t h at in te rp la y. A nd n ow I t h in k w e r e co gniz e t h at

t h ere is a r o le t o b e p la ye d b y f o cu sin g o n t h e p atie nt, a nd h ow t h is h ost im mune r e sp onse c a n b e

t u ned t o t r y a nd c o ntr o l t h e c a nce r.

W hat m ake s t h ese n ew im munoth era py d ru gs s o e xcit in g is t h at u nlik e R ose nberg 's h ig hly

c u sto m iz e d t r e atm ent, t h ey c a n b e m ass p ro duce d a nd a dm in is te re d a t a ny h osp it a l.

T he f r u it s o f Jim A llis o n's w ork m ove t h e ﬁ eld o f im mune t h era py t o m ake it g eneric . A nd t h at h as

t r e m endous im pact f r o m a ﬁ nancia l p oin t o f v ie w . Y o u d on't n eed t o in div id ualiz e . Y o u h ave t h e s a m e

v ia l f o r e ve ry o ne.

F o r r e aso ns n ot w holly u nders to od, im munoth era py h as s o f a r b een m ost s u cce ssfu l in ﬁ ghtin g a

s m all g ro up o f c a nce rs , m ain ly m ela nom a a nd k id ney c a nce r. F o r m ost o th er t y p es, t h e c e lls in t h e

i m mune s y ste m s till s e em u nable t o ﬁ nd a nd ﬁ ght t h e c a nce r. B ut a noth er n ove l a ppro ach m ay

g re atly e xp and im munoth era py's r e ach . I n P h ila delp hia , a t t h e U niv e rs it y o f P e nnsy lv a nia , D r. C arl Ju ne h as u se d g enetic e ngin eerin g t o g iv e

t h e T c e lls in t h e im mune s y ste m a k in d o f h om in g d evic e .

W e k n ow t h e im mune s y ste m c a n b e a ro und a s a f o rm o f s u rv e illa nce a nd c a ll o ut t h e e arly t u m ors .

B ut in m ost c a se s, it f a ils , a nd it c a n't r e ally d is tin guis h b etw een a t u m or c e ll a nd n orm al c e lls .

T he T c e lls c a n't s e e c a nce r c e lls . T hey a re c o m ple te ly b lin d. T hey'll w ander r ig ht b y. Y o u c a n a ctu ally

s e e t h is u nder t h e m ic ro sc o pe. T hey d on't r e co gniz e t h e c e ll a s b ein g b ad.

S o w e h ave t o r e dir e ct t h at T c e ll. W e p ut in a n ew g ene in to t h e c e ll. A nd t h at n ew g ene f o rc e s t h e T

c e ll t o s e e t h e c a nce r c e ll. S o it 's v e ry m uch t a kin g o ﬀ t h e b lin dfo ld a nd a llo w in g t h e T c e ll t o s e e t h e

c a nce r c e ll.

B y r e -e ngin eerin g T c e lls t h is w ay, Ju ne is c re atin g a liv in g d ru g a ttu ned t o e ach p atie nt's c a nce r. H e

r e ce iv e d a ppro va l t o t r y t h e t e ch niq ue in a c lin ic a l t r ia l o f s e rio usly ill le uke m ia p atie nts . A t t h e s a m e

t im e, a s ix -y e ar-o ld g ir l n am ed E m ily W hit e head, w ho w as b ein g t r e ate d f o r le uke m ia , in a n earb y

h osp it a l t o ok a s u dden t u rn f o r t h e w ors e .

O ur d octo r c a m e in a nd s a id , s h e h as a f u ll r e la pse . It 's v e ry d iﬀ ere nt n ow . S urv iv a l is le ss t h an 3 0% .

W e f o und o ut t h at s h e d oes h ave a s p eciﬁ c m uta tio n. A nd t h e d octo r t o ld m e n ot t o G oogle it , n ot t o

l o ok u p a ny in fo rm atio n o n it . A nd s o o f c o urs e I d id r ig ht a w ay. A nd I s a w t h at v e ry f e w p eople w it h

t h at s p eciﬁ c m uta tio n s u rv iv e -- I m ean, v e ry f e w .

E m ily 's h ealt h w ors e ned b y t h e d ay. A nd w hen t h e p ossib ilit y o f a b one m arro w t r a nsp la nt f e ll

t h ro ugh, t h e W hit e heads le aped a t t h e c h ance t o e nro ll t h eir d aughte r in D r. Ju ne's n ew t r ia l.

Y o u k n ow , if a nyth in g w as g oin g t o w ork , t h is w as g oin g t o b e it , b eca use t h ere w asn 't a nyth in g e ls e

l e ft f o r h er. If it d id n't w ork , w e p ro bably o nly h ad a f e w w eeks le ft w it h h er.

W hile E m ily 's f a m ily w ait e d f o r h er im mune c e lls t o b e p re pare d, D oug R ogers r e tu rn ed t o t h e N CI t o

c o ntin ue h is t r e atm ent w it h D r. S te ve n R ose nberg .

Y o u g uys w ant t o c o m e o ve r a nd s e e t h e la b?

Y e s, w e'r e lo okin g f o rw ard t o it .

S ee s o m e c e lls ?

Y e ah, w e'r e e xcit e d. A ll r ig ht.

A m onth a fte r t h e o pera tio n in w hic h h is im mune c e lls w ere e xtr a cte d, t h ey w ere n early r e ady t o b e

r e in fu se d in to h is b ody.

T o m orro w , w e'r e g oin g t o g iv e y o u e xa ctly o ne b illio n c e lls . A nd a bout t w elv e h ours a fte r y o u h ave

t h ose c e lls , t h ey'r e g oin g t o b e g ro w in g in y o u. A nd y o u'r e g oin g t o h ave t w o b illio n c e lls .

I n 1 2 h ours , m y b ody w ill d ouble t h em .

I t h ought it w as t r u ly a m azin g.

Y e ah, it w as.

I m ean, it w as s o in te re stin g. A nd t h en le ttin g m e lo ok a t m y c e lls u nder t h e m ic ro sc o pe, it w as

e xtr a ord in ary.

T here t h ey a re .

I t w as r e ally e m otio nal, t o o. I c a ught m yse lf ju st ﬁ ghtin g b ack t e ars . I d id n't w ant t o e m barra ss

m yse lf c ry in g o ve r a lit tle t h in g o f D ougie 's c e lls . B ut it c o uld m ean e ve ry th in g t o u s.

I f y o u c o uld h ave lo oke d u nder t h e m ic ro sc o pe, a ll t h e m ela nom a d ots w ere g one. It w as r e pla ce d b y

h ealt h y c e lls . A nd t h en w hen h e a ctu ally le t m e h old t h em --

I 'm s h akin g.

L o ok, y o u c a n s e e t h em a ll in t h ere , if y o u lo ok c a re fu lly . S ee t h em a ll?

Y o u'r e h old in g y o ur c e lls in y o ur h and t h at m ig ht s a ve y o ur lif e . It w as e xtr a ord in ary.

T hat's a lo t o f c e lls . F e el it ?

O K, lo ok t h is w ay, D ougie .

I 'm a fr a id I'm g oin g t o d ro p.

D on't d ro p it . G ot it .

I f e el s o e xcit e d t o g et t h em in t h ere a nd le t t h e c e lls -- D o t h eir t h in g, h uh?

- -d o t h eir w ork t h at t h e d octo r's d esig ned t h em t o d o, h opefu lly .

T he n ext d ay, h ow eve r, t h ere is a p ro ble m w it h R oger's c e lls . A v ir u s h as c o nta m in ate d t h em a nd t h ey

a re n o lo nger s a fe f o r in fu sio n.

S om eth in g v e ry u nusu al h appened t o y o ur c e lls . A nd t h at is in t h e la st d ay, it lo oks lik e t h ey'r e

i n fe cte d. A nd s o o ur p la n is t o a bort t h e c e ll in fu sio n t o day, o f c o urs e , a nd p re pare a n ew b atc h f o r

y o u f o r n ext w eek. T hat's t h e b ad n ew s. T he g ood n ew s is t h at w e h ave t h in gs in r e se rv e .

C an y o u g ro w t h em a nd p re pare t h em in s ix d ays?

W e c a n. F ro m e ve ry th in g I u nders ta nd a bout w hat w ent w ro ng, w e s h ould b e a ble t o g et y o u g ood

c e lls ﬁ ve o r s ix d ays f r o m n ow . O K.

O bvio usly , w e w ere d is a ppoin te d. B ut y o u c a n't d o a nyth in g a bout it , s o y o u ju st m ove o n.

Y o u h ave t o d ig d ow n d eep a nd ﬁ nd y o ur s tr e ngth , a nd ju st b e p ra ye rfu l t h at h e'll s ta y h ealt h y f o r t h e

n ext w eek w hile t h ey'r e g ro w in g.

A nd t h ey w ere s u ch g ood, h ealt h y c e lls , t o o. [ IN AUD IB LE ]. B ut t h ese w ill b e a ls o , b eca use t h ey c a m e

o ut o f t h e s a m e b atc h . S o t h ey'll b e ﬁ ne. T hey m ig ht e ve n b e b ette r.

F o ur w eeks a fte r a rriv in g a t C hild re n's H osp it a l, E m ily 's c e lls w ere r e ady. S he w ould b e t h e ﬁ rs t c h ild

a nd o nly t h e f o urth p ers o n e ve r t o r e ce iv e t h is t r e atm ent. A nd h er d octo r, S te ve n G ru pp, p re pare d t o

g iv e h er t h e ﬁ rs t o f t h re e in fu sio ns.

O K.

Y e ah.

E m ily W hit e head, 5 -5 -4 .

T his is t h e s tu ﬀ t h at w e'r e a ctu ally t a lk in g a bout. A nd e ach d ay t h e v o lu m e g oes u p.

W e'v e o nly d one t h is in a v e ry s m all n um ber o f a dult p atie nts . B ut h ow a ctu ally w ell it w ill w ork in k id s

i s o nly p ossib le t o k n ow b y a ctu ally d oin g it . W e'r e g oin g t o g et s ta rte d h ere . [ IN AUD IB LE ].

W hat is it d oin g?

Y o u'r e s e ein g [ IN AUD IB LE ]. It 's a ll r ig ht. O K, w e'r e d one. T hat's t h e w hole t h in g.

[ C LA PPIN G ]

Y a y.

S o w e ﬁ nally g ot t h ere .

Y e ah.

I t 's a lit tle b it le ss t h an w e u su ally g iv e , b ut t h ey s h ould b e e nough. A nd t h ey'r e v e ry h ig hly p ote nt.

A w eek a fte r D oug R ogers ' o rig in al b atc h o f T c e lls w as in fe cte d, h e w as g iv e n a n in fu sio n d ra w n f r o m

a m uch s m alle r b atc h k e pt f r o ze n in r e se rv e . It w as t h e ﬁ rs t t im e R ose nberg h ad e ve r t r ie d t h is .

I 'd b e ju st ly in g if I d id n't s a y I'm n ot t e rriﬁ ed.

W e a ll k n ow [ IN AUD IB LE ].

S om etim es w e h ave t h ose h ard c o nve rs a tio ns n ow . A nd I d o ﬁ ne w it h it u ntil n ig ht c o m es. A nd t h en

i t 's h ard .

H opefu lly , I g ot a n ew le ase o n lif e . M y c e lls a re s a yin g, le t's g et t o w ork . T hey'r e r o llin g t h eir s le eve s

u p, s e e. T hey'v e g ot a v o ra cio us a ppetit e , h opefu lly . W e e nvis io n t h em a s P a c-M an. T hey'r e g oin g t o

g o t o t h ose m ela nom a c e lls .

[ W HIM PE R ]

Y o u O K?

[ W HIM PE R ]

W hat's t h e m atte r?

N ause ous I ju st w ant t o [ IN AUD IB LE ].

D ay t w o w e w ent in a nd g ot 3 0% t h en. T he ﬁ rs t d ay w as 1 0% . A nd w e w ent h om e. S he w as o n m y

b ack, d oin g h ors e y b ack r id es, a nd it f e lt g ood. [ L A UG HTER ]

A nd t h en a t m id nig ht, s h e s p ik e d a f e ve r, s o w e d ro ve b ack t o t h e E R . T hen t h in gs ju st s p un o ut o f

c o ntr o l. A nd t h ey p ut h er t o s le ep, a nd t h at w as t o ugh. B eca use a t t h at p oin t, D r. L e xa s a id , t h is is a s

s e rio us a s it c a n g et.

A nd t h en t h ey h ad a w hole t e am . A s s o on a s t h ey h ad h er u nder, a w hole t e am o f d octo rs c o m e in .

A nd I s u it e d u p w it h t h em a nd p ut t h e m ask o n e ve ry th in g. A nd t h en w atc h in g t h em c u t a rte ry lin es in

b oth w ris ts a nd t h en in h er t h ig h. A nd t h ey c u t a n a rte ry lin e in h er n eck. A nd t h en w hen t h ey w ere

d one, t h ere w as 1 7 IV p um ps k e epin g h er a liv e .

T hey c a m e t o u s a nd s a id t h at t h ey d id n't t h in k t h at s h e w as g oin g t o m ake it t h ro ugh t h e n ig ht. I

r e m em ber s it tin g b y h er b ed, w atc h in g h er o n t h e v e ntila to r. A nd I ju st k e pt t h in kin g t h at t h is c a n't b e

t h e e nd. T his is n 't h ow it 's g oin g t o e nd. It c a n't b e it .

S he's a s s ic k a s a h um an b ein g c a n p ossib ly b e. T he IC U s ta ﬀ a re w ork in g ﬂ at o ut t o t r y t o k e ep h er

a liv e . W e o bvio usly t h in k t h is is a t o xic it y o f t h e T c e lls , b ut w e d on't r e ally k n ow w hat's h appenin g.

A nd s o n ow w hat?

W it h E m ily 's lif e s lip pin g a w ay, Ju ne's t e am f r a ntic a lly r a n a noth er b atc h o f b lo od t e sts , h opin g t o

u nco ve r p re cis e ly w hy h er n ew im mune c e lls h ad t u rn ed o n h er a nd m ade h er s o s ic k. T he t e sts c a m e

b ack s h ow in g s k yro cke tin g le ve ls o f a n im mune p ro te in c a lle d IL -6 .

W hen t h ose le ve ls c a m e b ack, t h ey w ere lit e ra lly o ﬀ t h e c h arts . A nd s o t h en I s u ggeste d a d ru g t h at

c a n b lo ck IL -6 . T hat's n eve r b een g iv e n t o c a nce r p atie nts b efo re , b ut it is a n F D A a ppro ve d d ru g f o r

j u ve nile a rth rit is . A nd it ju st h appens t h at m y d aughte r h as t h at d is e ase .

D r. G ru pp s a id , I'm g oin g t o t e ll y o u, w e'r e g ra sp in g f o r s tr a w s. B ut if w e g iv e h er t h is a rth rit is d ru g, it

c o uld h elp . B eca use s h e c a n't g et a ny s ic ke r, o r s h e w on't b e w it h u s.

T here is a n e norm ous r o le o f lu ck a nd h appensta nce in t h ese k in d o f s it u atio ns. W e g ave t h at d ru g.

A nd h er r e sp onse w as a sto nis h in g. I m ean, t h e IC U s ta ﬀ t h at w ere o n t h at n ig ht s a y t h ey h ave n eve r

s e en a p atie nt t h at s ic k g et b ette r t h at q uic kly .

E m ily ﬁ nally w oke u p in t h e in te nsiv e c a re u nit o n h er s e ve nth b ir th day. A fte r h er b ru sh w it h d eath ,

t h e d octo rs s till d id n't k n ow if t h e T c e ll t h era py w as w ork in g. T hre e w eeks la te r, t h ey d id a b one

m arro w t e st. It c a m e b ack n egativ e . E m ily 's le uke m ia h ad v a nis h ed. [ M USIC

- T A IO C RUZ, " D YN AM IT E"]

[ S IN G IN G ] I w ant t o c e le bra te a nd liv e m y lif e . S ayin g a yo , b aby, le t's g o. B eca use w e--

E m ily 's c lo se c a ll h ad t h re ate ned t h e c lin ic a l t r ia l. B ut in t h e e nd, d oze ns o f o th er c h ild re n w it h

l e uke m ia w ere t r e ate d. A nd t h e a rth rit is d ru g t h at s a ve d E m ily 's lif e b eca m e a s ta ndard p art o f t h e

t h era py.

E m ily w as t h ro ugh t h e w ors t. B ut s h e w as e nte rin g u nch arte d t e rrit o ry. A s t h e ﬁ rs t c h ild e ve r t o g et

t h is t r e atm ent, h er m edic a l t e am h ad n o id ea h ow lo ng h er n ew im mune c e lls w ould b e a ble t o k e ep

h er c a nce r a t b ay.

S o in o ur la st s ix o f t h e v a lu able p atie nts , t h ere a re f o ur c o m ple te r e gre ssio ns a nd t w o p artia l

r e gre ssio ns. S o t h at p ro to co l is --

W e'r e in t h e b egin nin gs o f a v e ry lo ng a nd h opefu lly e xcit in g r o ad w it h im munolo gic a l t h era pie s.

T here a re p eople w ho d edic a te d t h eir liv e s t o t h is . A nd ﬁ nally , w e'r e b egin nin g t o s e e in te re stin g

g lim mers in w hic h t h e im mune s y ste m c a n b e e duca te d t o s ta rt t o s e e c a nce rs a nd t o k ill t h ose

c a nce rs .

R ig ht n ow , im munoth era py r e m ain s s o m eth in g o f a r o ule tte w heel.

T his la rg e o ne is a lm ost g one a w ay c o m ple te ly , r ig ht? W hat is it , lik e --

D octo rs a re n ot s u re w hy it w ork s in s o m e p atie nts a nd in s o m e c a nce rs a nd n ot in o th ers .

W ow , s h e's h avin g a f a bulo us r e sp onse , is n 't s h e?

H i. N ic e t o s e e y o u.

G ood t o s e e y o u.

I t lo oks lik e e ve ry th in g is v ir tu ally d is a ppeare d. S o w e'r e t h rille d f o r y o u.

A lit tle o ve r a y e ar a go, I t h ought I w as g oin g t o d ie . B ut y o u'v e s a ve d m y lif e . A nd I ju st c a n't t e ll y o u

e nough, t o t h ank y o u f o r ju st e ve ry th in g.

I n R ose nberg 's m ost r e ce nt t r ia l o f 2 5 m ela nom a p atie nts , 1 8 s a w t h eir t u m ors s h rin k. A nd n in e w ere

s till a liv e a fte r ﬁ ve y e ars . B ut f o r t h e o th ers , t h ere w as o fte n n o f u rth er t r e atm ent h e c o uld o ﬀ er. W hy d on't y o u m easu re it ? W ould y o u?

S ure .

I t 's la rg er.

T hat o ne d oes lo ok la rg er. It w as 4 0 m illim ete rs , u p t o 4 8.

T he p atie nt c o m es f o r t h is f o llo w -u p s c a n. A nd f o r t h em , t h is is a lif e a nd d eath v is it . If t h e t r e atm ent

h as n ot w ork e d, v e ry o fte n t h ere is n oth in g le ft t o d o f o r t h ese p atie nts .

A ll r ig ht, le t's g o s e e.

A m onth a fte r g ettin g h is c e lls , D oug R ogers is b ack t o s e e if t h ey w ere w ork in g.

W ell, h ello a gain . S o n ic e t o s e e y o u. C om e o ve r h ere a nd s it d ow n.

H i. G ood t o s e e y o u.

W ell, h ow h ave y o u b een d oin g?

I 'v e b een g ood-- r e al g ood, m atte r o f f a ct.

T e ll m e w hat y o u'v e n otic e d a bout y o ur--

W ell, it ju st lo oks s o m uch b ette r. B ut m ain ly it ju st f e els b ette r. It f e els p re tty m uch lik e m y r ig ht le g

d oes.

I 'v e b een lo okin g a t y o ur x -r a ys. A nd t h e x -r a ys s h ow m ore t h an h alf o f a ll t h e c a nce r g one. It 's a t

l e ast a 5 5% d ecre ase c o m pare d t o t h e s ta rt o n t h e x -r a ys, b oth in t h e g ro in a s w ell a s in t h ese t is su es.

T hat's a m azin g.

W e'r e r e ally e xcit e d a bout it . S o y o u h ad t h ese t w o b ig o nes.

R ig ht, m hm .

A nd t h ose t w o b ig le sio ns w ere t h ese t w o t h at a re n ow w ay, w ay d ow n.

Y e ah.

W ell, t h at's r e ally a g ood s ig n t h at t h in gs a re h appenin g s o q uic kly . I t w as f o r m e. B ut f r o m y o ur s ta ndpoin t, a re y o u p le ase d w it h t h e w ay e ve ry th in g h as g one?

Y o u c a n s it u p n ow . A gain , w hen w e s e e t h is k in d o f r e gre ssio n a t o ne m onth , it v e ry o fte n c o ntin ues

u ntil e ve ry th in g d is a ppears . B ut n ot a lw ays, s o w e'r e g oin g t o h ave t o f o llo w it c a re fu lly t o b e s u re it

d oesn 't s ta rt c o m in g b ack. S o I ju st c o uld n't b e m ore t h rille d w it h h ow t h in gs a re g oin g.

W ell, h ey.

W e a re t o o.

T hank y o u v e ry m uch .

V ery e xcit in g.

O K. N ow w ait h ere , b eca use D r. [ IN AUD IB LE ] a nd D r. [ IN AUD IB LE ] c o m e in a nd ju st g o o ve r y o u a lit tle

m ore c a re fu lly .

O K.

S o n ic e t o s e e y o u a gain .

T hank y o u s o m uch .

W e'll s e e y o u in a m onth .

O K. I'll s e e y o u in a m onth .

I 'm h ere .

O K.

A bso lu te ly .

A ll r ig ht.

T hank y o u v e ry m uch .

T hanks. W ow , t h at is f a bulo us n ew s. 5 5% !

Y e ah. T hat's p re tty g ood n ew s.

G ood n ew s. Y o u'v e g ot t o t h ank t h e m an u psta ir s ﬁ rs t.

T hat's r ig ht. 5 5% , t h at's a m azin g.

Y e s.

J u st t h in k if it c o ntin ues lik e t h at, D ougie .

I n A pril 2 014, t w o y e ars a fte r s h e r e ce iv e d C arl Ju ne's r is k y g ene t h era py t r e atm ent f o r h er c a nce r,

E m ily W hit e head r e tu rn ed t o c h ild re n's h osp it a l in P h ila delp hia f o r a c h ecku p.

L e t's

hope t h is s tu ﬀ 's q uic k.

W ell, t o day is E m ily 's t w o y e ars s in ce t r e atm ent. S o w e'r e g oin g t o g et h er b lo od w ork c h ecke d. S o it 's

a b ig d ay f o r u s.

W e'r e a lw ays a lit tle b it n erv o us, b eca use ju st w alk in g in to t h e h osp it a l a nd y o u h ear t h e s o unds t h at

w e h eard f o r t h re e m onth s. T here 's t h at b ig s tr u ctu re . A nd t h ere 's lik e a d in gin g. A nd a ll o f a s u dden,

i t 'll h it u s a ll o ve r a gain .

T here 's b een t o o m any t im es w hen w e d id n't g et t h e r ig ht o utc o m e, s o it d oes m ake u s n erv o us. B ut

w e d on't e xp ect a nyth in g b ut g ood r e su lt s . H ow a bout, E m ? W hat d o y o u t h in k?

S o h ow y o u f e elin g?

G ood.

A ny p ro ble m s?

N o.

N one w hats o eve r?

N o.

Y o u g o t o s c h ool e ve ry d ay?

Y e s.

D o y o u lis te n t o y o ur t e ach ers ? Y e s.

O K. H ow a re y o ur g ra des?

G ood.

W hen w e w ro te t h is t r ia l, w e s a id w e w ould f o llo w p atie nts f o r t w o y e ars . W e n eve r im agin ed t h at w e

w ould a ctu ally b e a ble t o f o llo w p atie nts f o r t w o y e ars . B ut w e s a id t h at's w hat w e w ould d o. A nd n ow

w e'v e r e ach ed t h at p oin t.

N ic e , d eep b re ath s.

W e'll c o ntin ue t o m onit o r h er s it u atio n. W e'll c o ntin ue t o w atc h f o r t h e p ossib ilit y o f h er d is e ase

c o m in g b ack. B ut s h e h as c o m ple te d t h e t r e atm ent.

T he q uestio n y o u'r e r e ally a sk in g m e is , h ow lo ng d o y o u n eed t h e c e lls t o s ta y in r e m is sio n f o re ve r?

A nd t h e a nsw er is I d on't k n ow .

Y e ah.

W e'r e s u per e xcit e d t h at s h e's a t t h is p oin t.

W e a re t o o.

B ut e ve ry d ay t h at s h e g oes o ut f r o m h er c e ll t h era py m ake s h er u niq ue. S o t h e a m azin g t h in g is t h at

s h e's d oin g a s w ell a s s h e's d oin g. T he n erv e -w ra ckin g t h in g is w e d on't r e ally h ave t h e a nsw ers o n

w hat t h e n ext y e ar o r t w o y e ars o r 1 0 y e ars lo ok lik e . W e d on't k n ow , b eca use s h e is p lo w in g n ew

g ro und h ere . N obody t h ought w e w ould b e in t h is p osit io n w hen w e s ta rte d.

I h ave a d og, a b unny, a nd a ﬁ sh .

O h, m y g osh . Y o u lo ve a nim als , d on't y o u?

Y e ah.

S he is a bso lu te ly a p io neer. S he w as t h e ﬁ rs t k id . S he w as t h e ﬁ rs t p atie nt w it h A LL. S he w as t h e ﬁ rs t

p atie nt w ho g ot s o t e rrib ly ill. S he t a ught u s a bout t h e t o xic it y c o ntr o l t r e atm ent, w hic h h as s a ve d t h is

t h era py.

A ll r ig ht. S o le t m e s e t t h is u p r e al q uic k. T u rn o n t h e lig ht. W e'v e n ow t r e ate d 3 0 c h ild re n. A nd 2 7 o f t h em h ave c o m ple te r e sp onse s. T hey'r e n ot la stin g in a ll o f

t h em , b ut it lo oks v e ry h opefu l t h at t h ere 's g oin g t o b e m any m ore c h ild re n lik e E m ily . W e c a n't s a y

t h e C w ord , c u re , y e t. W e d on't k n ow . It 's o nly w it h m ore t im e w ill w e k n ow if e ve ry la st c a nce r c e ll's

g one.

W e g ot s o m e r e su lt s b ack. A nd C BC lo oks g ood. W hit e c o unt's 4 .5 . H em ogoblin 's 1 2.9 . A nd h er

p la te le ts a re 1 71. A nd t h e d iﬀ ere ntia l's O K. S o t h e p re lim in ary lo ok is t w o y e ars c a nce r f r e e.

I t 's a g ood d ay.

I t 's a g re at d ay, y e ah.

S o m any p ro m is in g c a nce r c u re s h ave c o m e a nd g one o ve r t h e y e ars t h at m any r e se arc h ers r e m ain

c a utio us a bout t h e m eanin g o f t h is la te st d eve lo pm ent. B ut r e su lt s lik e E m ily 's h ave m ade

i m munoth era py t h e t a lk o f t h e c a nce r w orld .

E arly r e su lt s a re r a is in g t h e t a nta liz in g p ossib ilit y t h at w e m ay a ctu ally b e s e ein g c u re . It 's t o o e arly t o

t e ll. B eca use t o k n ow y o u h ave a c u re , y o u'r e g oin g t o h ave t o w ait . B ut it h as t h at f e elin g. A nd I t h in k

t h at's w hy t h ere 's t h is lit e ra lly a t h rill g oin g t h ro ugh t h e e ntir e o nco lo gy c o m munit y t o s e e s o m e o f

t h ese c lin ic a l r e sp onse s t o t h ese n ew im munoth era pie s.

W hat w as u niq ue in o ur e xp erie nce w as t h at m ost o f t h ese r e sp ondin g p atie nts a ch ie ve d d eep o r

c o m ple te r e sp onse s, w it h m any s h ow in g--

W e h ave s e en t h at w it h t a rg ete d t h era pie s, r e sis ta nce o ccu rs . B ut h ere is d iﬀ ere nt. T his im mune

s y ste m is n ot t a kin g a ny v a ca tio n. T hat im mune s y ste m is t h ere f o r t h e w hole t r ip . T he p atie nts t h at

r e sp ond t o im mune t h era py, t h ey r e sp ond f o r a lo ng t im e. A nd I t h in k t h at p ie ce w ill c h ange, c le arly ,

t h e w ay w e t r e at c a nce r f o re ve r.

I t s e em s u nlik e ly t h at a ny o ne t r e atm ent o r m eth od o f p re ve ntio n, o r a ll o f t h em w ork in g t o geth er,

w ill e ve r e lim in ate c a nce r c o m ple te ly . T he h is to ry o f t h e s tr u ggle a gain st t h e d is e ase , f r o m m edie va l

a poth eca rie s t o m odern o pera tin g t h eatr e s, f r o m r a dia tio n t o c h em oth era py, t o t a rg ete d t h era py a nd

a dva nce s in p re ve ntio n a nd e arly d ete ctio n, a ll h ave t a ught t h e c a nce r w orld o f t e m pere d o ptim is m .

B ut n o o ne d oubts t h at t h e g re at b arrie r t o a ll c a nce r t h era pie s, t h e m yste ry o f h ow c a nce r w ork s, is

ﬁ nally b ein g b ro ke n d ow n b y t h e c o nce rte d w orld w id e e ﬀ orts o f r e se arc h ers a nd d octo rs a nd n urs e s,

a nd b y p atie nts .

F re sh in sig hts f r o m T he C ance r G enom e A tla s a re r e ve alin g in e ve r g re ate r d eta il t h e n atu re o f c a nce r's c o m ple xit y , e nablin g r e se arc h ers t o u nco ve r p atte rn s in t h e w ays it e vo lv e s, in te ra cts w it h

t h e im mune s y ste m , a nd t h riv e s in sid e t h e h um an b ody. T his p ro fu sio n o f k n ow le dge is in sp ir in g n ew

i d eas f o r t r e atm ent a nd p re ve ntio n. W hile s c ie ntis ts a re r e lu cta nt t o u se t h e w ord " c u re ," m any

b elie ve t h at it is o nly a m atte r o f t im e b efo re m ost t y p es o f c a nce r b eco m e m anageable , n o m ore

t e rrif y in g o r d estr u ctiv e t h an a ny o f t h e o th er c h ro nic d is e ase s t h at a ﬄ ic t h um anit y .

R eady, s e t, g o! [ IN AUD IB LE ].

W e h ave e nte re d a t h at is in cre dib le .

O ne, t w o, t h re e!

O ur u nders ta ndin g o f c a nce r is r e ally a t a p oin t w here w e h ave t h e o pportu nit y t o m ake p ro gre ss a t a

r a te a nd a le ve l t h at w e'v e n eve r s e en b efo re .

H ands t o geth er. B at r ig ht h ere . L e t y o ur a rm s c o m e s tr a ig ht o ut w hen y o u s w in g. S ee, s e e t h ere .

T here h as b een o ne r e vo lu tio n. T hat's t h e r e vo lu tio n in u nders ta ndin g t h e d is e ase .

P o ps g ets a n a t-b at.

T he s e co nd r e vo lu tio n, w hic h is t a kin g t h at u nders ta ndin g a nd p uttin g it t o w ork f o r u s in c a nce r

p atie nts , is a w ork in p ro gre ss. It 's n ot g oin g t o c o m e q uic kly . It 's n ot g oin g t o c o m e w it h out r e se arc h .

B ut it 's g oin g t o c o m e.

Y o u lo ok s o p re tty . W here a re t h ose h ands?

[ G IG GLE ]

O h, t h ere t h ey a re .

W hen y o u lo ok a t w hat's g oin g o n w it h c a nce r r ig ht n ow , it 's s tu nnin g. It is e xh ila ra tin g.

[ C O OIN G ]

I 'm a m aze d t h at w e c a n in t h e c o urs e o f h alf a c e ntu ry g o f r o m k n ow in g n oth in g t o u nders ta ndin g a

p ro ble m , t o d eve lo pin g r u dim enta ry s o lu tio ns, t o b ette r s o lu tio ns, t o w hole a rm am enta riu m o f

s o lu tio ns. If it t a ke s h alf a c e ntu ry a nd if it t a ke s a c e ntu ry , t h at w ill s till b e a n a m azin g t r iu m ph. A nd

i f it 's t h ere f o r m y g ra ndch ild re n, t h at's n oth in g w e s h ould b e a polo giz in g f o r.

W hat I'd lik e t o s e e y o u d o is ﬁ rs t t o lo ca liz e y o ur le sio n. T here a re c rit ic s w ho'v e s a id t h at w e'r e c a ught in t h is p erp etu al c ycle in w hic h w e h ope a nd d esp air .

B ut t h ese c ycle s h ave m ove d u s f o rw ard .

C om e b ack.

T he w ay t h at w e'v e u nders to od a nd t r e ate d c a nce r a s a b io lo gic a l e ntit y , a s a s o cia l p henom enon, a s

a c u lt u ra l p henom enon h as t r a nsfo rm ed o ve r t h e la st f e w d eca des a nd w ill c o ntin ue t o t r a nsfo rm in

t h e f u tu re .

F a nta stic . W onderfu l.

I f t h e c a nce r c e ll is e vo lv in g, t h en s o a re w e.

[ M USIC P LA YIN G ]

T his p ro gra m is m ade p ossib le b y G enente ch , d edic a te d t o m akin g a d iﬀ ere nce in p atie nts ' liv e s

a ro und t h e w orld . A nd b y C ance r T re atm ent C ente rs o f A m eric a , p ro vid in g in te gra tiv e t r e atm ent f o r

o ve r 2 5 y e ars . B y S ie m ens, a h erit a ge o f in nova tio n, a p assio n f o r lif e . B y D avid H . K o ch .

B y B ris to l- M ye rs S quib b, c o m mit te d t o t h e s c ie nce o f im muno-o nco lo gy. B y t h e A lf r e d P . S lo an

f o undatio n p ro gra m t o e nhance p ublic u nders ta ndin g o f s c ie nce , t e ch nolo gy, a nd e co nom ic s. B y t h e

K o vle r F u nd, p urs u in g s o lu tio ns f o r A m eric a 's n egle cte d n eeds. B y t h e A rth ur V in in g D avis

F o undatio ns.

A nd b y t h e A m eric a n A sso cia tio n f o r C ance r R ese arc h , b y A m eric a n C ance r S ocie ty b y t h e L e uke m ia

a nd L y m phom a S ocie ty . B y t h e E nte rta in m ent In dustr y F o undatio n, b y S ta nd U p T o C ance r. B y t h e

C orp ora tio n f o r P u blic B ro adca stin g a nd b y t h e g enero us c o ntr ib utio ns t o t h is P B S s ta tio n f r o m

v ie w ers lik e y o u.