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 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 & 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.

W hen y o u ﬁ rs t c a m e t o s e e m e, y o u h ad a b io psy t h at w as d one. A nd t h at b io psy s h ow ed t h at t h ere

w as c a nce r, c a nce r o n t h e r ig ht s id e. Y o u h ad y o ur c h em oth era py. S o t e ll m e h ow y o u'r e f e elin g,

[ IN AUD IB LE ].

W ell, I'v e b een r e ally p ra yin g o n it .

I h ope t h at m y p atie nts t a ke a w ay t h at e ve ry m om ent t h at t h ey s p end w it h m e, a nd e ve ry s te p t h at

t h ey t a ke w hile t h ey'r e in m y c a re -- t h at I'm c o m ple te ly t h ere f o r t h em . A nd e ve ry m om ent is n 't e asy.

T he la st M RI, t h e s iz e w as 3 .9 b y 2 .2 5 [ IN AUD IB LE ] 1 .6 .

A ll r ig ht.

S he's h ad h er c h em oth era py. S he's d one.

O K.

L e t's lo ok a t t h at. A nd t h at w as-- ju st a bout a m onth a go.

M y m oth er w as d ia gnose d w it h lu ng c a nce r ju st b efo re m y la st y e ar o f t r a in in g in g enera l s u rg ery

r e sid ency. T his is p rio r t o c h em oth era py.

M y r o le w as a s c a re ta ke r, f r ie nd, d aughte r. A nd t h e le sso n t h at I le arn ed f r o m m y m oth er w as h er

s tr e ngth , h er h um ilit y , h er a bilit y t o a llo w p eople t o c a re f o r h er.

B re ast m ass b efo re c h em oth era py, a nd t h is is t h e s a m e a re a a fte r c h em oth era py.

W ow . A m azin g.

I t 's a ll g one.

A nd s o c h em oth era py w as v e ry e ﬀ ectiv e .

T hat's g re at. T hat's g re at, t h at's g re at. I'm s o h appy f o r y o u.

I t h in k t h at t h at's o fte n d iﬃ cu lt , t o r e ally d epend o n s o m eone e ls e w hen w e a re m ost f r a gile .

N ow y o u h ave a n o pportu nit y t o t h in k a bout w heth er b re ast c o nse rv a tio n, o r w heth er a m aste cto m y.

A nd s o --

B eca use o f w hat c a nce r is , it b rin gs y o u in c o nta ct w it h a noth er h um an b ein g in a w ay t h at b are ly

a ny r e la tio nsh ip w ill. I m ean, it 's n ot a n e xtr a ord in ary r e la tio nsh ip , it is t h e e xtr a ord in ary r e la tio nsh ip .

[ M USIC P LA YIN G ]

F o r a s lo ng a s h um an b ein gs h ave liv e d, c a nce r h as a ﬄ ic te d u s. A d is e ase t h at d oes n ot s tr ik e f r o m

o uts id e, b ut c o nsu m es f r o m w it h in .

T he t h in g t h at w e'r e a ll c o nce rn ed a bout is t h e f a ct t h at t h is c o uld v e ry lik e ly b e c a nce r.

W hat c h ance is t h ere o f b ein g c u re d, r e ally c u re d?

W hat c h ance d o I r e ally h ave , d octo r?

I 'm s u re y o u r e aliz e t h at r e co ve ry is n ot a s u re t h in g.

T here 's n oth in g m ore h orrif y in g, n oth in g m ore e xtr a ord in ary o f a ll h um an [ ? a lit ie s ? ] a s c a nce r. It 's

u s k illin g o urs e lv e s. T here 's s o m eth in g p ro fo und, s o m eth in g p sy ch olo gic a l, s o m eth in g p rim it iv e ly

t e rrif y in g a bout it . I 'm lo okin g a t y o ur e ye .

W hen s h e ﬁ rs t t o ld m e I h ad c a nce r, I c o uld n't r e ally c o m pre hend w hat s h e h ad ju st s a id . A nd a fte r

s h e s a id c a nce r, s h e k e pt s p eakin g. B ut I c o uld n't h ear a nyth in g. I w as ju st in s h ock.

T here is n o a rc h ety p al r e sp onse t o c a nce r. P a tie nts h ave d iﬀ ere nt r e sp onse s. T his w om an's , t h is

m an's s tr u ggle , t h is c h ild 's s tr u ggle , is h is o r h er o w n. A s f a m ily m em bers , a s lo ve d o nes, a s

p hysic ia ns , w e m ig ht b e a ble t o w it n ess it . B ut it 's n ot o urs .

I t 's t h eir m ech anis m o f t r y in g t o e xp la in , t r y in g t o s tr u ggle w it h , t r y in g t o m ake p eace w it h , w hat's

h appenin g in t h eir o w n b odie s.

I t 's a r e al b attle . It 's a n in ner b attle . It 's p ain fu l in e ve ry w ay. A nd h ow a re y o u g oin g t o ﬁ nd p eace

a m id st t h e r a ge t h at's h appenin g in sid e y o ur b ody a nd y o ur o w n h eart?

T hro ughout h is to ry , c a nce r's t e nacit y h as in sp ir e d a n e ve n s tr o nger w ill t o u nders ta nd it . T o s u rv iv e it .

T o c u re it . If y o u c o uld ﬁ nd o ne g re at t h in g in c a nce r o ve r t h e la st 1 00 y e ars , it 's t h e m en a nd w om en

w ho h ave s a id , I'm n ot t a kin g t h is a nym ore . I'm g oin g t o t r y s o m eth in g e ls e .

A nd t h at's h ow s c ie nce a nd m edic in e a re a dva nce d. It 's b y p eople r e fu sin g t o t a ke t h e s ta tu s q uo. It 's

t h at w illin gness, t h at b ra ve ry , t h at h ero is m t o d o t h at, t h at h as, I t h in k, a dva nce d c a nce r t o t h e s ta te

w e a re n ow . A nd h opefu lly w ill a dva nce it f a r, f a r m ore in t h e y e ars t o c o m e.

T he P re sid ent o f t h e U nit e d S ta te s.

[ A PPLA USE]

I w ill a ls o a sk f o r a n a ppro pria tio n o f a n e xtr a $ 100 m illio n, t o la unch a n in te nsiv e c a m paig n f o r

ﬁ ndin g t h e c u re f o r c a nce r.

[ A PPLA USE]

H opes w ere h ig h in 1 971, w hen t h e U nit e d S ta te s d ecla re d w ar o n c a nce r. A m eric a ns h ad m ade it t o

t h e m oon. S ure ly , if t h ey s p ent e nough m oney a nd e m plo ye d e nough r e se arc h ers , t h ey c o uld

c o nquer c a nce r.

A fte r a ll, n ew s u rg ic a l a nd r a dia tio n t e ch niq ues, a nd n ew c o m bin atio ns o f c h em ic a ls , a lr e ady c u re d

s o m e f o rm s o f t h e d is e ase . C ure s f o r o th ers s e em ed s u re t o f o llo w . B ut p ro gre ss w ould p ro ve m addenin gly s lo w . N o o ne y e t u nders to od c a rc in ogenesis , t h e m yste rio us p ro ce ss b y w hic h n orm al

c e lls a re t r a nsfo rm ed in to c a nce r c e lls .

I t is n ot k n ow n w hy t h e c e lls c h ange a nd b eco m e a bnorm al. B ut t h ey b egin t o g ro w a nd a ﬀ ect t h ose

c e lls a ro und t h em , u ntil t h e v ic tim ﬁ nds h im se lf h opele ssly a ﬄ ic te d w it h c a nce r.

D ecla rin g w ar o n s o m eth in g t h at y o u d id n't u nders ta nd a t a ll w as n uts . It w asn 't lik e g oin g t o t h e

m oon. Y o u k n ew h ow f a r t h e m oon w as. Y o u k n ew w hat it t o ok t o g et t h ere . D ecla rin g w ar o n c a nce r--

w e d id n't k n ow w hat c a use d c a nce r.

T hat w as t h e h ubris -- T hat if y o u p ut e nough s c ie ntis ts in to a r o om t o geth er, if y o u g ave t h em e nough

m oney, a nd y o u t u rn ed t h e w heel a ro und a nd y o u ju ggle d t h e b ox, a nd y o u o pened t h e d oor, o ut

w ould p op a s o lu tio n t o t h is e ntir e s to ry.

U ntil t h e r id dle o f c a rc in ogenesis w as s o lv e d, t h e w ar o n c a nce r w ould b e b ase d o n t r ia l a nd e rro r.

A nd t h e '7 0s a nd '8 0s w ould t u rn o ut t o b e d eeply f r a ctu re d a nd c o nte ntio us d eca des in o nco lo gy.

S cie ntis ts f o ught a m ong t h em se lv e s. P a tie nts d em anded le ss p unis h in g a nd m ore e ﬀ ectiv e

t r e atm ents . A nd b asic a ssu m ptio ns w ere o ve rtu rn ed. T he w ar o n c a nce r s e em ed, a t t im es, t o b e a

w ar w it h in c a nce r.

B re ast c a nce r-- it 's e stim ate d t h at o ne o f e ve ry 1 3 A m eric a n w om en w ill d eve lo p b re ast c a nce r.

I f t h ere w as o ne c a nce r t h at r e ve ale d t h e a crim ony a nd t h e p ro m is e o f t h e e ra , it w as b re ast c a nce r.

B y t h e 1 970s, b re ast c a nce r w as o ne o f t h e le adin g c a use s o f d eath a m ong A m eric a n w om en, b ut

l it tle p ro gre ss h ad b een m ade in it s t r e atm ent. L ik e t h eir m oth ers a nd g ra ndm oth ers b efo re t h em ,

n early a ll b re ast c a nce r p atie nts s u bm it te d t o t h e s a m e e xtr e m e t h era py-- t h e r a dic a l m aste cto m y,

p io neere d b y D r. W illia m H als te d, a t Jo hns H opkin s, a t t h e t u rn o f t h e 2 0th c e ntu ry.

I t b eca m e a d ogm a. A nd if a s u rg eon, f o r e xa m ple , in a h osp it a l w ere t o d o s o m eth in g o th er t h an a

r a dic a l m aste cto m y, h e c o uld b e p ut o ﬀ t h e s ta ﬀ . T here w as n o t h ought o f d oin g a nyth in g e ls e .

I n a n e ra o f b ru ta l c a nce r t r e atm ents , t h e r a dic a l m aste cto m y s to od o ut.

B eca use t h ere w as d anger t h at t h e c a nce ro us c e lls in t h e b re ast h ad in va ded t h e p ecto ra l m usc le s,

t h ose m usc le s w ere r e m ove d. T he s u rg eon m ay le ave a b and o f t h e p ecto ra lis m ajo r, a t t h is p oin t, o r

t h e e ntir e m usc le m ay b e e xcis e d.

T he r a dic a l m aste cto m y w as b ase d o n t h e t h eory t h at c a nce r s p re ads o utw ard f r o m a c e ntr a l p oin t. G ettin g a ro und it a nd c u ttin g it o ut w as t h e o nly w ay t o s a ve t h e p atie nt.

T he u nderly in g p rin cip le o f t h e H als te d r a dic a l m aste cto m y is t h at c a nce r is a n o rd erly p ro ce ss-- t h at

i t s ta rts in a n o rg an, a nd t h en it s p re ads t o t h e ly m ph n odes. T he lo nger y o u w ait , t h e m ore lik e ly it is

t o g o t o d is ta nt o rg ans, a nd t h en w hen it h it s c rit ic a l a re as, it 's f a ta l.

F o r d eca des, w om en u nderw ent t h e p ro ce dure u nquestio nin gly .

W e w ere in t h e M arc u s W elb y w orld , b ack t h en. Y o u lis te ned t o y o ur d octo r, y o ur d octo r k n ew

e ve ry th in g, y o u d id n ot q uestio n y o ur d octo r.

B y 1 970, n early 4 0,0 00 A m eric a n w om en w ere u nderg oin g r a dic a l m aste cto m ie s e ve ry y e ar. T here

s e em ed t o b e n o a lt e rn ativ e .

B re ast c a nce r w as t h e o nly c a nce r t h at it w as f e lt y o u h ad t o d o t h e b io psy a nd t h e d eﬁnit iv e

t r e atm ent w it h in m in ute s o f e ach o th er. Y o u w ould g o t o s u rg ery. T he w om an w ould h ave t o s ig n a

c o nse nt t h at s a id if it w as f o und t o b e c a nce r, I w ould h ave a m aste cto m y r ig ht t h en a nd t h ere .

S o y o u w ould g o in to t h e o pera tin g r o om , a nd y o u w ould n't k n ow w heth er y o u w ere g oin g t o w ake u p

w it h a b re ast o r n ot. A nd y o u k n ow h ow y o u f o und o ut? Y o u lo oke d a t t h e c lo ck. If it w as t h re e h ours , it

w as c a nce r. A nd if it w as a n h our, y o u w ere b enig n. It w as ju st a ppallin g.

D esp it e t h e a ggre ssiv e ness o f t h e r a dic a l m aste cto m y, m ore t h an a t h ir d o f p atie nts r e la pse d. Y e t f e w

q uestio ned t h e o pera tio n.

W hen t h ey d id n't w ork , in ste ad o f s a yin g, H m m, m ayb e t h ere 's s o m eth in g w ro ng w it h t h is t h eory ,

t h ey s a id , o h, w e'r e ju st n ot c u ttin g e nough. A nd t h ey w ould m ake it b ig ger a nd b ig ger. B ut a ctu ally

t h ere w as s o m eth in g w ro ng w it h t h e t h eory.

I t w ould t a ke a n o bse rv a nt s u rg eon f r o m P it ts b urg h, n am ed B ern ard F is h er, t o ﬁ nally c h alle nge t h e

s c ie ntiﬁ c a ssu m ptio ns o n w hic h t h e r a dic a l m aste cto m y w as b ase d. F is h er h ad b een d oin g t h e

o pera tio n f o r y e ars , b ut h ad s e en lit tle b eneﬁt t o t h e w om en u nder h is c a re .

I b egan t o t h in k, w ell, w e r e ally d on't k n ow m uch a bout t h is d is e ase w e'r e t r e atin g. W hat, w hy a re w e

d oin g t h is ?

F is h er h ad t h ought h ard a bout h ow b re ast c a nce r a ctu ally s p re ads, o r m eta sta siz e s, f r o m o ne p art o f

t h e b ody t o a noth er. U nlik e m ost s u rg eons a t t h e t im e, h e d oubte d t h at c a nce r m ove s lik e a

s p re adin g s ta in a ro und t h e o rig in al s it e o f t h e t u m or. In ste ad, F is h er s u sp ecte d t h at s tr a y c a nce r c e lls d eta ch f r o m t h e o rig in al t u m or v e ry e arly a nd m ig ra te t h ro ugh t h e b lo odstr e am , o r ly m phatic s y ste m ,

t o f a r ﬂ ung s it e s in t h e b ody-- w here a s u rg eon's s c a lp el w ould n eve r ﬁ nd t h em .

I b egan t o o bta in in fo rm atio n in t h e la bora to ry t h at t h ere w as n o o rd erly p atte rn o f [ ? t u berc e ll ? ]

d is se m in atio n. T he id ea t h at c a nce r w as a lo ca l d is e ase w as n ot s o . It w as a s y ste m ic d is e ase , t h at's

w hat c a nce r w as.

I f ﬁ sh er w as r ig ht, it m eant t h at t h e r a dic a l m aste cto m y w as n ot e nough f o r w om en w hose b re ast

c a nce r h ad a lr e ady s p re ad, a nd t o o m uch f o r t h ose w hose c a nce r h ad r e m ain ed lo ca liz e d. F o r t h e

l a tte r, F is h er p ro pose d a m uch s m alle r o pera tio n c a lle d a lu m pecto m y, w hic h r e m ove d t h e t u m or, b ut

c o nse rv e d t h e b re ast.

F is h er r e so lv e d t o t e st h is t h eory w it h a f u ll- s c a le c lin ic a l t r ia l. H e w ould d iv id e b re ast c a nce r p atie nts

r a ndom ly in to t w o g ro ups-- o ne t o u nderg o t h e r a dic a l m aste cto m y, t h e o th er, t h e lu m pecto m y. T he

m edic a l e sta blis h m ent w as a ghast.

A r a ndom iz e d p ro ce dure , in w hic h t h e d octo r h im se lf a nd t h e p atie nt h ad n o c o ntr o l, w as t o ta lly

a bom in able t o t h e c o nsc ie nce o f t h e d octo rs a t t h at t im e. T hey w ere a bso lu te ly o ut t o d estr o y m e

a nd m y id eas. It w as t o ta lly a ntit h etic a l t o t h eir s .

W hen it 's a c h oic e b etw een lo sin g a b re ast a nd lo sin g y o ur lif e , I d on't t h in k t h ere 's m uch c h oic e

r e ally .

A nd h e w as t h e m ost h ate d s u rg eon in t h e h is to ry o f m ankin d. H is c o lle agues g ot t o t h e C ance r

I n stit u te . T hey v iliﬁ ed h im . I u se d t o g o t o m eetin gs a nd s it a nd lis te n t o t h em t e ar h im a part. I

s o m etim es w onder h ow w e s u rv iv e d it . W hat s tr u ck m e w as h e w as a t o ugh g uy.

F is h er r e sp onded t o h is c rit ic s w it h c h ara cte ris tic b lu ntn ess. " In G od w e t r u st," h e s a id . " A ll o th ers m ust

h ave d ata ."

B re ast c a nce r is a s c ie ntiﬁ c p ro ble m . It is n ot a n in te lle ctu al e xe rc is e o r a n e m otio nal p ro ble m . A nd

t h ere fo re , t h e d ata w hic h d ete rm in es w hat o r w hat n ot s h ould b e d one, m ust b e o bta in ed a nd

a naly ze d in a s c ie ntiﬁ c w ay.

H e w as t h ought t o b e a t r a it o r. H e w as t h ought t o b e h ackin g a w ay a t t h e v e ry f o undatio ns o f h is

d is c ip lin e. H e w as d enie d g ra nt f u ndin g. H e c o uld n't r e cru it s u rg eons a t t h e t r ia l.

T he p eople a t t h e a ca dem ic c e nte rs a nd t h e p eople t h at w ere r e ally h ard c o re , t h ey d id n't c h ange. T hey h ad p ut t h eir w hole lif e in to t h is , a nd t o s a y t h at t h ey w ere w ro ng, t o t h em se lv e s-- I d on't t h in k

t h ey c o uld a dm it it , e ve n t o t h em se lv e s.

F o rtu nate ly f o r F is h er, b re ast c a nce r p atie nts t h em se lv e s h ad ﬁ nally b egun t o q uestio n t h e r a dic a l

m aste cto m y.

T he w om en, b y t h is t im e, w ere g ettin g w in d o f t h is . T he w om en w ere t h e o nes t h at w ere ﬁ ndin g o ut

m ayb e t h ere w as a n a lt e rn ativ e . A nd it w as t h e w om en w ho r e ally d ro ve t h e c h ange a nd t h e s h if t t o

b re ast c o nse rv a tio n.

A t t h e h ead o f t h at m ove m ent w as a s c ie nce jo urn alis t n am ed R ose K u sh ner. A t t h e a ge o f 4 5,

K u sh ner h ad b een t o ld t h at s h e n eeded a r a dic a l m aste cto m y. A s s h e r e se arc h ed t h e p ro ce dure , s h e

b eca m e in fu ria te d b y h ow b lit h ely p hysic ia ns p re sc rib ed it . " N o m an is g oin g t o m ake a noth er

i m pote nt w it h out h is p erm is sio n," s h e w ro te . " B ut t h ere 's n o h esit a tio n if it 's a w om an's b re ast."

S he w ent t o t h e m edic a l m eetin gs, a nd s h e b era te d t h e s u rg eons. A nd s h e w as t h is lit tle , s h ort

w om an y e llin g a t t h em , a nd t h ey w ere a ll s h akin g in t h eir b oots .

I t h in k t h at t o day is t h e b egin nin g o f t h e e nd o f m aste cto m y f o r t h e r o utin e t r e atm ent o f a ll, a ll

b re ast c a nce r.

R allie d b y K u sh ner a nd o th ers , b re ast c a nce r p atie nts b egan ﬂ ockin g t o F is h er's s tu dy. T he t r ia l

c o m parin g t h e r a dic a l m aste cto m y t o t h e lu m pecto m y w ould t a ke a d eca de, b ut w hen t h e r e su lt s

w ere ﬁ nally r e le ase d in 1 985, t h ey w ere u nequiv o ca l.

W e h ave a r e port a bout b re ast c a nce r, t h is e ve nin g, w hic h is o f v it a l c o nce rn t o v ir tu ally e ve ry

w om an.

I t c o nclu des t h at w om en in w hom t h e b re ast is r e m ove d, d o n ot liv e a ny lo nger t h an w om en in w hom

o nly t h e t u m or is t a ke n o ut.

I t d id n't m ake a d iﬀ ere nce w heth er y o u a m puta te d t h e w hole b re ast o r ju st t o ok t h e t u m or o ut o f t h e

b re ast. T he s u rv iv a l w as t h e s a m e.

I t w asn 't t h e a m ount o f s u rg ery. It w as t h e k in d o f c a nce r t h at t h ey h ad. A nd p ro bably t h at s o m e

c a nce rs g ot o ut b efo re y o u g ot t h ere , b efo re t h e s u rg eon s h ow ed u p. A nd s o , y o u c o uld c u t a ll y o u

w ant, b ut t h e h ors e w as o ut o f t h e b arn a lr e ady.

W hat d oes t h is m ean f o r w om en w it h b re ast c a nce r? R adic a l m aste cto m y is n ow n o lo nger a v ia ble o pera tio n. R adic a l m aste cto m y is o ut.

A lt h ough m aste cto m ie s r e m ain ed c o m mon, t h e r a dic a l s u rg ery p io neere d b y D r. H als te d, t h at a ls o

r e m ove d a dja ce nt m usc le s a nd t is su e, w ould a ll b ut d is a ppear in t h e y e ars t o c o m e. F is h er h ad

o ve rth ro w n o ne o f t h e c e ntr a l d ogm as in c a nce r t h era py-- t h at c u ttin g m ore m eant c u rin g m ore .

A lm ost a s im porta ntly , h e h ad r e m in ded t h e ﬁ eld o f c a nce r m edic in e t h at t r e atm ent, w it h out

u nders ta ndin g t h e u nderly in g m ech anis m o f c a nce r, c o uld d o e norm ous d am age.

W hat h appens in m edic in e a nd in s c ie nce is w e c o m e u p w it h a s to ry t o e xp la in o ur o bse rv a tio ns. A nd

w e g et e nam oure d o f o ur s to ry. A nd t h en w e u se t h at s to ry t o k e ep g oin g o n, a nd it p ro pels t h e

r e se arc h , a nd it p ro pels t h e k in d o f t r e atm ents y o u d o. A nd it 's r e ally o nly w hen y o u ju st c a n't ju stif y

i t a nym ore , t h at w e s ta rt t o t h ro w it o ut. B ut it la sts a lo ng t im e, t h ese s to rie s.

I w as s ix o r s e ve n w hen I s a w t h e s h ow

Mash

. A nd it w as s o e xcit in g, a nd I f e lt t h at, t h at w as

s o m eth in g t h at I c o uld d o. A nd m y m om w as t h e p ers o n w ho t o ld m e t h at I c o uld d o a nyth in g. M y

m om a nd d ad d id n't g o t o c o lle ge, b ut w hen I s a id I w ante d t o b e a s u rg eon, a t s e ve n, t h ey w ere lik e ,

O K.

D on't w orry. D on't w orry.

I w ould s a y t h at I a m t h e ﬁ rs t g enera tio n t o t h e p ost S egre gatio n. It w as a t im e t h at m y p are nts f e lt

t h at t h ere w as o pportu nit y , a nd s o t h at t h ey h ad w ait e d a lo ng t im e. A nd s o it m eant f o r u s t h at t h ere

w as a lo t t o a cco m plis h .

D r. L o ri W ils o n is a s u rg ic a l o nco lo gis t, a nd t h e D ir e cto r o f t h e S urg ery R esid ency P ro gra m , a t H ow ard

U niv e rs it y .

T he f a ct t h at y o u c o uld m ake a d iﬀ ere nce in s o m eone's lif e , t h at a ctu ally c o uld s a ve t h e lif e , a nd t h at

b y f a r I t h ought w as o ne o f t h e m ost d ra m atic t h in gs a bout s u rg ic a l o nco lo gy.

D r. W ils o n s p ecia liz e s in b re ast c a nce r, in r e se arc h , a s w ell a s in h er p ra ctic e .

R ig ht n ow , t h e im porta nt t h in g is t o m ake s u re t h at y o u a re f e elin g w ell a nd t h at y o u'r e d oin g w ell.

E xcit e d.

Y o u'r e e xcit e d a nd y o u'r e n erv o us, a nd I k n ow t h at w e c a n d o t h at t o y o u.

D eep b re ath s. W heneve r w e k n ow t h at c a nce r is t h e d ia gnosis , w e a ls o w ant t o m ake s u re t h at w e g iv e a ll s id es, a nd

t h at y o u m ay n ot b e c u re d, a nd t h at y o ur c a nce r c o uld p ro gre ss t o s o m eth in g t h at c o uld e nd y o ur

l if e .

- -in t h e la st c o uple o f w eeks, t h at's ﬁ ne.

A ll r ig ht. I w ant t o g et a q uic k lo ok, ju st e xa m in e y o u r e al q uic k, t o s e e if I c a n f e el a nyth in g, s o t h at

w e c a n w atc h a s w e m ove f o rw ard .

A ll r ig ht.

I n Ju ly 2 013, D r. W ils o n h ers e lf w as d ia gnose d w it h b re ast c a nce r.

T he ﬁ rs t p ers o n t h at I c a lle d w as m y h usb and. I t o ld h im t h at t h e d ia gnosis w as c a nce r, a nd h e s a id ,

I 'll b e r ig ht h om e.

C an y o u f e el a nyth in g?

I t h in k t h e t h in g t h at c a ught m e o ﬀ g uard is t h at I n ot o nly h ave b re ast c a nce r o ne b re ast. I a ctu ally

h ave b re ast c a nce r in b oth b re asts , w hic h is a v e ry u nusu al w ay f o r p atie nts t o b e d ia gnose d.

A ll r ig ht. Y o u m ay g o a head a nd g et d re sse d, a nd w e'll g et y o u s ta rte d.

T o c o m plic a te m atte rs , L o ri h as a d iﬀ ere nt k in d o f c a nce r in e ach b re ast. O n t h e r ig ht, is a p artic u la rly

a ggre ssiv e t y p e c a lle d t r ip le n egativ e . O n t h e le ft, t h e c a nce r is a t y p e t h at m ay b e t r e ata ble b y

c h em oth era py, b ut it h as a lr e ady s p re ad t o h er ly m ph n odes.

I t m ake s it m ore d iﬃ cu lt t o t r e at, a nd s o t h e s ta tis tic s a re f a r w ors e .

Y o u O K? Y o u d on't lo ok t o o h appy t o day.

N o, I w as ju st a lit tle w eepy t o day.

I t 's t h e f e ar o f t h e u nkn ow n, a nd--

Y e ah, it is .

w onderin g w hat y o u'r e g ettin g in to .

I t h in k o ne o f t h e d iﬃ cu lt p arts I'm h avin g is w it h t h e t o ta lit y o f t h e d ia gnosis . I c a n p ro ce ss I h ave b re ast c a nce r. B ut w hat t h e lo ng-te rm im pact t h at m ay b e, I'm h avin g a d iﬃ cu lt t im e p ro ce ssin g t h at.

S o w e'r e g oin g t o d o a r ig ht t h yro id lo becto m y

S oon a fte r h er d ia gnosis , L o ri s h are d t h e n ew s w it h h er c o lle agues a nd s tu dents .

T his is o ne o f t h e a ssis ta nt c h ie fs t h at s e nt t h is t o m e. " 'W hy y o u?'" I in sta ntly a sk e d m yse lf. B ut I s o on

r e aliz e d t h at if t h ere is a nyo ne w ho c a n a tta ck t h e s it u atio n w it h t h e t y p e o f s tr e ngth a nd f a it h t h at is

n eeded, it is y o u. Y o u g iv e e ach a nd e ve ry r e sid ent t h at y o u t o uch h ope-- a h ope t h at is n eeded t o

r e sis t t h e u rg e t o q uit , a nd t o ju st k e ep ﬁ ghtin g a lit tle m ore .

I k n ow y o u w ould d o a nyth in g f o r u s, b ut n ow t h e t a ble 's t u rn ed. It 's t im e f o r y o u t o w atc h y o ur

c o m mit m ent p ay o ﬀ . W e'll b e y o ur s o ld ie rs t h ro ugh t h is b attle , f r o m t a kin g a g re ate r r o le w it h [ ?

m am o ? ] d ay, t o e xtr a w ork o f a ny s o rt. T o b eco m e-- t ill b eco m in g t h e le ader t h at y o u m ake u s

b elie ve w e c a n b e is d one."

T his is t h e p ro ble m o f c a nce r. W hy d oes t h is c e ll, in ste ad o f d iv id in g in to t w o n orm al a nd e qual p arts ,

d iv id e in to t h re e, f o ur, o r e ve n ﬁ ve , u nequal p arts ?

T he f a ilu re o f r a dic a l m aste cto m y, w hic h c o uld b e t r a ce d d ir e ctly t o a m is ta ke n u nders ta ndin g o f h ow

c a nce r s p re ads, h ave p ro vid ed f u rth er p ro of t h at t o m ake p ro gre ss in t r e atm ent, o nco lo gis ts h ad t o

s o lv e t h e f u ndam enta l m yste ry o f t h e d is e ase . W hat c a use s h ealt h y c e lls t o s u ddenly b egin d iv id in g

w it h out r e str a in t.

F o r m any y e ars , w e h ad n o id ea w hat c a use d c a nce r, w hy it g re w , w hy it w as a s n asty a nd d iﬃ cu lt a s

i t w as. A nd w it h out u nders ta ndin g t h e m ole cu la r u nderp in nin gs o f c a nce r, w e r e ally w ere a t a lo ss t o

d eve lo p a ppro ach es t h at w ould b e m uch m ore t a rg ete d a nd m uch m ore e ﬀ ectiv e .

A lo t o f t h e w ork t h at w as p erfo rm ed, u p u ntil t h e 1 970s, w as a n e m pir ic a l a ppro ach . S in ce c a nce r is

a d is e ase o f a bnorm al c e llu la r g ro w th , le t's t r y t o u se in hib it o rs o f c e llu la r g ro w th t o k ill c a nce r c e lls .

T hat s a ys, I'm n ot r e ally s u re w hat is c a usin g, w hat's d riv in g, t h e g ro w th . B ut le t's ju st u se t h in gs t h at

k ill g ro w in g c e lls , a nd le t's h ope a nd p ra y t h at w e'll ju st k ill c a nce r c e lls a lit tle b it m ore t h an n orm al

c e lls .

A nd it w as s ta rtlin g s u cce ssfu l in t h e c a se o f c h ild hood le uke m ia s a nd s o m e o th er c a nce rs . B ut n ow ,

b y t h e 1 970s, t h ere is a s o rt o f, a lm ost a t e rro r in t h e ﬁ eld t h at, u nle ss w e u nders ta nd w hat's g oin g o n

d eep in sid e, w e w on't b e a ble t o g et t h e n ext g enera tio n o f m edic in es. W e h ave m ade m ajo r p ro gre ss. B ut it 's im porta nt t o a ppre cia te t h at m ost o f t h ese a ppro ach es h ave

b een m ade w it h out a b asic k n ow le dge o f w hat c a nce r is a ll a bout.

M ost r e se arc h ers b elie ve d t h ere w ould t u rn o ut t o b e a s in gle c a use o f a ll c a nce rs a nd, t h ere fo re , a

s in gle c u re . B eyo nd t h at, t h ey w ere h opele ssly d iv id ed. T here w ere t h re e c o m petin g t h eorie s a bout

w hat c a use s n orm al c e lls t o t u rn b ad. E ach w as b ase d o n s e em in gly s o lid e vid ence . E ach h ad z e alo us

a dvo ca te s. A nd e ach s e em ed u tte rly in co m patib le w it h t h e o th ers .

T here w ere m eetin gs o n v ir u se s a nd c a nce r, c h em ic a ls a nd c a nce r, g enes a nd c a nce r. A nd n o o ne

w ent t o e ach o th ers ' m eetin gs. T hey w ere r e ally s ilo s in a ﬁ eld c a lle d c a nce r r e se arc h .

T he m ost w id ely h eld t h eory w as t h at c a nce r w as c a use d b y v ir u se s. T hey a re v e ry s m all, b ut

n eve rth ele ss v ir u se s a re r e sp onsib le f o r c o ld s, in ﬂuenza , m easle s, p olio , a nd m any o th er ills . A nd

n ow , r e se arc h s c ie ntis ts t h in k t h ey m ay b e in vo lv e d in c a nce r, a s w ell.

T he id ea o f v ir a l c a rc in ogenesis t r a ce d b ack t o 1 908, a nd a y o ung r e se arc h er a t R ocke fe lle r

U niv e rs it y , n am ed P e yto n R ous.

T he id ea w as in t h e a ir in t h e e arly 1 900s t h at v ir u se s c a use h um an d is e ase . B ut t h e o nly h um an

d is e ase t h ey'd b een im plic a te d in w ere s o -c a lle d in fe ctio us d is e ase s. P e yto n R ous, a y o ung s c ie ntis t,

h ad it in m in d t h at m ayb e v ir u se s m ig ht c a use c a nce r. A nd h e w as p re se nte d w it h a n o pportu nit y t o

t e st t h is id ea b y a L o ng Is la nd c h ic ke n f a rm er.

T he f a rm er b ro ught R ous a p riz e d P ly m outh R ock h en, w hic h h ad d eve lo ped a r a re t u m or in it s

b re ast. R ous id entiﬁ ed t h e t u m or a s a s a rc o m a, c a nce r o f t h e t is su e, a nd t r ie d t o u nders ta nd w hat

c a use d it .

T he ﬁ rs t e xp erim ent h e d id w as t o t a ke t h e t u m or a nd d is ru pt it in to m ore o r le ss s in gle c e lls . A nd

t h en t r a nsp la nt t h at in to a noth er c h ic ke n. A nd lo a nd b ehold , t h at c h ic ke n w ould g et a t u m or.

H avin g p ro ve d t h at h e c o uld s p re ad c a nce r lik e a n in fe ctio us d is e ase , R ous t r ie d t o id entif y w hat

i n sid e t h e m alig nant c e lls w as r e sp onsib le . H e b ro ke t h e c e lls o pen a nd ﬁ lt e re d o ut t h e c o nte nts , u ntil

h e w as le ft w it h s o m eth in g v e ry , v e ry s m all, t h at c o uld s till s p re ad c a nce r f r o m c h ic ke n t o c h ic ke n. T o

R ous, t h e lik e lie st e xp la natio n w as a v ir u s.

H e p ublis h ed a o ne-p age p aper in t h e Jo urn al o f t h e A m eric a n M edic a l A sso cia tio n, a nnouncin g t h at

h e h ad f o und a ﬁ lt e ra ble a gent, p re su m ably a v ir u s, a n in fe ctio us a gent t h at c o uld c a use c a nce r.

W ell, a ll h ell b ro ke lo ose . T his h ad a r e vo lu tio nary e ﬀ ect o n o ur u nders ta ndin g o f c a nce r, b eca use it w as v e ry c le ar. T here w as

a n a gent, t h ere w as a c a use , a nd t h ere w as a n e ﬀ ect. A v ir u s, c a nce r. A nd t h ere fo re , t h e c la im w as

b ein g m ade t h at c a nce r w as a v ir a l d is e ase .

T im e w ill s h ow t h at v ir u se s, o r a t le ast a v ir u s-lik e p ro ce ss, w ill b e f o und t o b e o ne o f t h e m ajo r

c a use s o f c a nce r.

F o r s e ve ra l d eca des a fte r R ous's d is c o ve ry , v ir o lo gis ts s e arc h ed f o r a c a nce r v ir u s in h um ans, b ut

f o und n one.

P e ople w ere lo okin g f o r o th er e xa m ple s o f t h e v ir u s, a nd t h en t h ey w ere t r y in g t o ﬁ gure o ut w ays t o

u nders ta nd h ow t h e v ir u s w ork e d. A nd f r a nkly , t h e t o ols f o r d oin g t h at w ere n't t h ere . It w as h ard t o

p ush t h at c o nce pt b eyo nd w hat R ous d id in t h ose ﬁ rs t e xp erim ents .

T hen in 1 957, in a d usty ﬁ eld h osp it a l, in U ganda, a n Ir is h s u rg eon n am ed D enis B urk it t o bse rv e d

s tr a nge o ra l a nd a bdom in al t u m ors o ccu rrin g in a la rg e n um ber o f c h ild re n in h is c lin ic .

T hese u nfo rtu nate c h ild re n, u su ally u nder t h e a ge o f 1 2, w it h e norm ous s w ellin gs o f t h eir ja w a nd

s o m etim es t h e a bdom en. It is u nfo rtu nate ly u nbeara bly f a ta l.

N ot o nly w as t h is a p re vio usly u nkn ow n c a nce r, b ut it s e em ed t o s p re ad t h ro ugh t h e p opula tio n in a

b ro ad b and, a s if it w as c o nta gio us.

T he d is tr ib utio n o f t h is t u m or s y n dro m e w as lim it e d t o c e rta in a re as a cro ss t r o pic a l A fr ic a .

B urk it t b ro ught s a m ple s b ack t o t w o v ir o lo gis ts in L o ndon-- M ic h ael A nth ony E pste in a nd Y vo nne B arr.

U nder a m ic ro sc o pe, t h e r e se arc h ers d is c o ve re d v ir u s p artic le s in t h e t u m or c e lls . T he E pste in -B arr

v ir u s w as t h e ﬁ rs t d eﬁnit iv e ly lin ke d t o a h um an c a nce r.

T he n ew s t h at v ir u se s m ig ht t r a nsm it t h e d is e ase t e rriﬁ ed t h e p ublic . T here w as t a lk o f q uara ntin es

a nd m ass g ra ve s. B ut a s t h e p ublic b ra ce d f o r p ossib le c a nce r e pid em ic s, s c ie ntis ts b egan

e xp erim entin g w it h v a ccin es t o p re ve nt t h em .

" T he v ir a l t h eory is t h e m ost h opefu l o ne f o r m an," o ne r e se arc h er w ro te . " If it is a v ir u s, w e c a n

h andle it . W e c a n ﬁ nd a w ay t o c o ntr o l, p erh aps, t o p re ve nt c a nce r."

M any v ir u s d is e ase s c a n n ow b e p re ve nte d. P o lio w as c o nquere d. P e rh aps c a nce r m ig ht b e t o o.

D oes t h at m ean t h at w e c a n e xp ect a v a ccin e a gain st c a nce r? A gain st s o m e t y p es o f c a nce r, p ro bably y e s.

F in din g c a nce r-c a usin g v ir u se s b eca m e a c o nsu m in g f o cu s o f t h e r e se arc h c o m munit y in t h e 1 960s

a nd '7 0s. T he N atio nal C ance r In stit u te p oure d u p t o h alf it s b udget in to a S pecia l C ance r V ir u s

D is c o ve ry P ro gra m .

H undre ds o f m illio ns o f d olla rs w ere b ein g s p ent o n a s in gle id ea, a nd t h at w as t h at h um an c a nce rs

w ere c a use d b y v ir u se s. T here w as s c a nt s u pport f o r a ny s c ie ntis t w ho w ante d t o lo ok a t o th er

p ote ntia l c a use s.

F o rt D ie tr ic h , M ary la nd, a b io lo gic a l w eapons la bora to ry , w as c o nve rte d in to a s ta te -o f- th e-a rt f a cilit y

d evo te d t o h untin g f o r c a nce r v ir u se s.

I t h in k a ll o f u s a re v e ry h appy t h at w e h ave h ere a n in dic a tio n o f h ow t h e g eniu s o f m an, w hic h c o uld

b e u se d t o d estr o y lif e , t h at s a m e g eniu s c a n b ette r b e u se d t o s a ve lif e .

A nd y e t, d esp it e y e ars o f w ork a nd t e ns o f m illio ns o f d olla rs , t h e S pecia l V ir u s C ance r P ro gra m d id

n ot d is c o ve r a ny v ir u se s t h at c a use t h e m ajo r k ille rs , a m ong t h em lu ng, c o lo n, a nd b re ast c a nce r.

E ve ntu ally , in la te r y e ars , a s ig niﬁ ca nt n um ber o f h um an c a nce r v ir u se s w ould b e f o und, in clu din g

h um an p apillo m avir u s, a m ajo r c a use o f c e rv ic a l c a nce r, a nd h epatit is B a nd B , m ajo r c a use s o f liv e r

c a nce r. T hese d is c o ve rie s w ould p ave t h e w ay f o r e ﬀ ectiv e v a ccin es. B ut v ir u se s w ere n ot t h e

s in gula r c a use o f c a nce r s o m any h ad b een lo okin g f o r.

I n t h e m id 1 970s, t h e c o ntin ued r e peate d f a ilu re s t o ﬁ nd h um an c a nce r v ir u se s b egan t o p ush c a nce r

v ir u se s o ﬀ s ta ge a s c re dib le a gents f o r t r ig gerin g h um an c a nce r.

A noth er w ell e sta blis h ed h yp oth esis n ow m ove d f r o nt a nd c e nte r-- t h at c a nce r is c a use d b y c h em ic a ls

i n t h e e nvir o nm ent.

I f w e d on't k n ow t h e c a use s o f m ost c a nce rs , w e d o k n ow w hat d oesn 't c a use it . C ance r is n ot c a use d

b y t o m ato es, t ig ht c o rs e ts , a p unch o n t h e n ose , e atin g m eat, m akin g lo ve , o r ly in g o n t h e g ro und in

W ale s. O n t h e o th er h and, t h ere is e vid ence t h at s o m e t h in gs in o ur e nvir o nm ent d o s e em t o c a use

s o m e c a nce rs .

T he c h em ic a l t h eory w as e ve n o ld er t h an t h e v ir a l t h eory. In 1 775, a L o ndon d octo r n am ed P e rc iv a ll

P o tt n otic e d a la rg e n um ber o f s c ro ta l c a nce rs a m ong y o ung m en in h is c lin ic . H is p atie nts h ad b een

c h im ney s w eeps w ho w ere in dentu re d s e rv a nts a nd s p ent d ay a fte r d ay c a ke d in a sh . E xa m in in g t h em , P o tt o bse rv e d t h at m ost o f t h em h ad p artic le s o f s o ot lo dged u nder t h eir s k in . H e s u sp ecte d

t h at it m ust b e t h e c a use o f t h eir c a nce r.

O ve r t h e c e ntu rie s, e vid ence o f e nvir o nm enta l c a rc in ogens m ounte d. E pid em io lo gis ts lin ke d c a nce r

t o c o al m in in g a nd t o t h e c o nsu m ptio n o f s n uﬀ . B ut it w as a m uch m ore c o m mon e xp osu re t h at

u lt im ate ly p ro ve d t h e t h eory o f c h em ic a l c a rc in ogenesis .

T he lin k b etw een c ig are tte s a nd lu ng c a nce r w as u nkn ow n in t h e e arly 2 0th c e ntu ry. C ig are tte

s m okin g w as r a re , a nd lu ng c a nce r w as n early u nheard o f.

I f y o u h ad a p atie nt o n t h e w ard w it h lu ng c a nce r in t h ose d ays, y o u m ade s u re t h at a ll t h e m edic a l

s tu dents g ath ere d a ro und t o s e e t h is u nusu al d is e ase .

W orld W ar I c h anged e ve ry th in g. S old ie rs in t h e t r e nch es w ere g iv e n c ig are tte s t o r e lie ve s tr e ss,

b eco m in g a ddic te d. W hen t h e s o ld ie rs r e tu rn ed h om e, t h ey b ro ught t h eir h abit w it h t h em . S uddenly ,

s m okin g w as s o cia lly a cce pta ble . P ro pelle d b y t h e m ass m edia , it q uic kly s p re ad t h ro ugh t h e

p opula tio n-- a s y m bol o f s ta tu s a nd s ty le .

A ny w ay y o u lo ok a t it , y o u'll f e el b ette r a bout s m okin g w it h t h e t a ste o f K e nt.

A s m ore p eople s m oke d, lu ng c a nce r c la im ed a g re ate r p erc e nta ge o f n ew c a nce r c a se s. In 1 900,

l u ng c a nce r a cco unte d f o r le ss t h an 1 % o f a ll c a nce rs . B y 1 930, it w as 1 5% . B y 1 945, it w as 2 0% a nd

r is in g. S till, t h e lin k b etw een s m okin g a nd c a nce r w as a lit tle u nders to od.

C ance r in a m oth er o r f a th er d oesn 't m ean t h at a s o n o r d aughte r w ill d eve lo p c a nce r. It m eans o nly

t h at t h e s o n o r d aughte r s h ould b e a le rt f o r s ig ns o f c a nce r, b eca use t h ey m ay b e m ore lik e ly t o f o rm

c a nce r t h an o th ers .

T hat's m ost r e assu rin g, d octo r. T here 's s o m uch m ore I w ant t o k n ow , I d on't k n ow w here t o b egin .

I n t h e a bse nce o f h ard e vid ence a bout c ig are tte s, a h ost o f o th er e xp la natio ns w ere o ﬀ ere d t o

a cco unt f o r t h e r is e in lu ng c a nce r.

T here w as s u sp ic io n t h at e xp osu re t o p ois o n g as in t h e ﬁ rs t W orld W ar w as c a usin g c a nce r, t h at t h e

i n ﬂuenza p andem ic o f 1 918-1 9 m ig ht h ave c re ate d s c a rs t h at w ould la te r g ro w in to c a nce r. It w as t h e

i d ea t h at r o ad d ust f r o m n ew ly t a rre d r o ads w as c a usin g c a nce r.

G ra dually , a f e w s c ie ntis ts b egan t o s u sp ect a d ir e ct lin k b etw een c ig are tte s m okin g a nd lu ng c a nce r. P e ople w ere t h in kin g, w ell, t h ere m ust b e s o m eth in g in t h e a ir -- a s it w ere -- t h at's c a usin g t h is

a lt e ra tio n in t h e b ehavio r o f a f o rm ally r a re f o rm o f c a nce r.

I n t h e la te 1 940s, t w o B rit is h e pid em io lo gis ts , B ra dfo rd H ill a nd R ic h ard D oll, in te rv ie w ed m ore t h an

1 50 lu ng c a nce r p atie nts in L o ndon h osp it a ls , a sk in g t h em d oze ns o f q uestio ns a bout t h eir d ie t,

h abit s , a nd liv in g c o ndit io ns. A m ong t h em , w as o ne a bout s m okin g. A fte r a ll t h e a nsw ers w ere t a llie d,

o nly o ne c o m mon a sso cia tio n lin ke d t h e c a nce r p atie nts -- c ig are tte s.

A t t h e s a m e t im e, in U nit e d S ta te s, a y o ung G erm an b orn m edic a l s tu dent n am ed E rn est W in der

b eca m e in te re ste d in t h e p ossib le lin k b etw een s m okin g a nd c a nce r. W it h t h e h elp o f o ne o f h is

p ro fe sso rs , a r e now ned s u rg eon n am ed E va rts G ra ham , W in der e m bark e d o n h is o w n s tu dy,

i n te rv ie w in g h undre ds o f lu ng c a nce r p atie nts , a sk in g t h em if t h ey'd e ve r s m oke d. D r. G ra ham , a

h eavy s m oke r h im se lf , w as in it ia lly s k e ptic a l t h at h e a nd W in der w ould ﬁ nd a c o rre la tio n. T o h is

s u rp ris e , t h e r e su lt s le ft lit tle r o om f o r d oubt.

W e p urs u ed it u ntil w e h ad m ade a n e xa m in atio n o f m ore t h an 6 00 p atie nts . A nd w e f o und t h at it w as

e xtr e m ely r a re t o ﬁ nd a nyo ne w ho w as n ot a n e xce ssiv e c ig are tte s m oke r.

W in der w ent o n t o c o nduct e xp erim ents e xtr a ctin g t h e c h em ic a ls f r o m c ig are tte s m oke , a nd f o und

t h em t o b e p ote nt c a rc in ogens.

T hat b ottle c o nta in s t h e a m ount o f t a r t o w hic h t h e a ve ra ge h eavy c ig are tte s m oke r is e xp ose d t o

o ve r a g iv e n y e ar's p erio d o f t im e. T he p re se nt e vid ence v e ry s tr o ngly in dic a te s t h at t o bacco

s m okin g, a nd p artic u la rly c ig are tte s m okin g, is a m ajo r c a use o f lu ng c a nce r.

T he r e ve la tio n c a m e t o o la te f o r E va rts G ra ham . T hough h e im media te ly q uit s m okin g, h e w ould d ie

o f lu ng c a nce r in Ju ne 1 957.

I n m edic in e, a s in a ll o th er p hase s o f lif e , w e c a nnot o ve rc o m e a p ro ble m b y d enyin g it s e xis te nce .

T o geth er, t h e t r a nsa tla ntic s tu die s w ere c o nvin cin g p ro of o f a lin k b etw een s m okin g a nd c a nce r. B ut

c ig are tte c o m panie s h id t h e e vid ence f r o m t h e p ublic b ehin d a b arra ge o f p se udosc ie nce a nd

m is le adin g a dve rtis in g.

T he t o bacco in dustr y r e ally d eve lo ps t h is s tr a te gy o f c re atin g d oubt. It 's r e ally q uit e b rillia nt, b eca use

i t 's n ot s o o fte n t h at t h ey w ould s a y t h at s m okin g d oes n ot c a use d is e ase . T hey w ould s a y it 's a n o pen

q uestio n. W e n eed t o k e ep a n o pen m in d. T he in dustr y 's p osit io n is t h at t h e o rig in o f lu ng c a nce r is c o m ple x a nd s till o bsc u re . A nd t h at-- in

a ddit io n t o t o bacco s m oke -- m any o th er f a cto rs d ese rv e f u rth er s tu dy, s u ch a s t h e e ﬀ ects o f c h ro nic

a nd a cu te lu ng in fe ctio n, a ir p ollu tio n, g enetic f a cto rs , s tr e ss--

T his b eco m es t h e lo ngest-r u nnin g s c ie ntiﬁ c f r a ud in t h e h is to ry o f h um an c iv iliz a tio n.

I m agin e t h ese t w o o ra nge b lo cks a s r e pre se ntin g a ll t h e c ig are tte s s m oke in 1 910.

I n t h e y e ars t o c o m e, t h e r a te o f s m okin g c o ntin ue t o c lim b.

H ere a re t h e a m ounts w hic h h ave b een s m oke d s in ce t h en, u p t o 1 960.

A nd a lo ng w it h it , t h e r a te o f lu ng c a nce r.

C om pare t h is w it h t h e n um bers o f d eath s f r o m lu ng c a nce r d urin g t h e s a m e y e ars . T here in

t h ousa nds, b ut s till g oin g u p, a nd c lo se ly f o llo w in g t h e r is in g c ig are tte s a le s.

F in ally , in Ja nuary 1 964, a b lu e r ib bon c o m mis sio n o f s c ie ntis ts , p harm aco lo gis ts , a nd s ta tis tic ia ns,

a ppoin te d b y P re sid ent K e nnedy a nd le d b y t h e S urg eon G enera l, is su ed a lo ng-a w ait e d r e port

e va lu atin g t h e s c ie nce b ehin d c ig are tte s a nd c a nce r.

O ut o f it s lo ng a nd e xh austiv e d elib era tio n, t h e c o m mit te e h as r e ach ed t h e o ve ra ll ju dgm ent t h at

c ig are tte s m okin g is a h ealt h h aza rd o f s u ﬃ cie nt im porta nce t o t h e U nit e d S ta te s t o w arra nt r e m edia l

a ctio n.

T he S urg eon G enera l's r e port le nt s tr o ng s u pport t o t h e t h eory t h at c h em ic a ls s u ch a s t h ose in

c ig are tte s m oke c o uld c a use c a nce r. F u rth er p ro of w as a dded o ve r t h e n ext d eca de w it h t h e

d is c o ve ry t h at f a cto ry c h em ic a ls , lik e b enze ne, c h lo ro fo rm , a nd f o rm ald ehyd e, w ere a ls o

c a rc in ogens.

B ut t h ough t h e c h em ic a l t h eory w as g ain in g m om entu m , it t o o w ould p ro ve in adequate t o f u lly

e xp la in c a rc in ogenesis . T he f u ll a nsw er w ould a w ait a d eeper u nders ta ndin g o f t h e c a nce r c e ll it s e lf.

[ L A UG HS]

A t le ast h e t a ste d it .

Y o u'r e a f u nny b oy, Y o u k n ow t h at?

M om my lik e s c h errie s. I t 's b een a m onth s in ce L o ri's d ia gnosis a nd h er 2 0-w eek r e gim en o f c h em oth era py h as b egun.

L ik e s o m e. Y u m , y u m , y u m , y u m . I g ot y o u! Y e s.

A nd m y w if e , L o ri.

Y e ah, h ow y o u d oin g? N ic e t o m eet y o u.

G ood t o m eet y o u. T hank y o u f o r c o m in g. W e a ppre cia te it .

I 'll g o ﬁ rs t, y e ah.

M y h usb and a ctu ally is g oin g t o s h ave h is h ead w it h m e. A nd s o u ntil m y h air g ro w s b ack, w e'll b oth

b e b ald t o geth er. H e's m y r o ck. H e's b een t h ere f o r e ve ry th in g.

H e's lo okin g g ood.

Y o u a ll f o rg et I'v e b ald h eaded b efo re , 2 0 y e ars a go, b efo re L o ri a nd I g ot t o geth er. In t h e ﬁ rs t w in te r

w hen I g re w m y h air . A nd t h en L o ri lik e d m y h air , a nd I h ave n't s h ave d it s in ce .

O h, is n 't t h at s w eet.

A ll r ig ht. N ext.

[ A PPLA USE]

Y e ah.

[ IN AUD IB LE ]

Y o u c a n t a ke it a ll.

O h, O K.

Y o u O K?

Y e ah, I'll b e O K.

[ M USIC P LA YIN G ]

I d on't b uy in to t h e W hy m e? B eca use s o m uch o f c a nce r is n ot p re dic ta ble . It 's n ot s e t o n f a m ily h is to ry o r a ny f e atu re . A nd s o a bso lu te ly c o uld b e m e.

H ey, n ig ht-n ig ht. Y o u r e co gniz e M om my? W e h ave a 1 9-m onth -o ld , a nd I w ant t o s e e m y s o n g ro w u p,

s e e m y s o n g et m arrie d a nd g o t o g ra d s c h ool, a nd a ll t h e g ood s tu ﬀ t h at e xp ect f o r f a m ily . A nd w it h

t h is d ia gnosis , t h at's m ore d iﬃ cu lt a t h in g t o s e e.

C ance r s tr ik e s n early e ve ry liv in g t h in g o n t h is p la net. It c a nnot b e f u lly c u re d u ntil w e u nders ta nd it ,

a nd t o u nders ta nd it , w e m ay h ave t o s o lv e t h e m ost c o m ple x p uzzle o f a ll- - t h e n atu re o f lif e it s e lf.

T he d iﬃ cu lt y w it h h andlin g c a nce r is t h at it 's a c e llu la r d is e ase . It 's a d is e ase w hic h is o f a d iﬀ ere nt

t y p e t h an a ny d is e ase w e'v e s o lv e d t h us f a r.

B y t h e m id 1 970s, s c ie ntis ts h ad m ade lit tle p ro gre ss t o w ard s o lv in g t h e m yste ry o f w hat c a use s

c a nce r.

W e o nly k n ew t h re e f a cts a bout c a nce r. T he ﬁ rs t f a ct w as t h at v ir u se s c o uld c a use c a nce r. B ut w e

a ls o k n ew t h at c h em ic a ls c o uld c a use c a nce r. N ow , w hat v ir u se s a nd c h em ic a ls h ad t o d o w it h e ach

o th er in c a usin g c a nce r, w e d id n't k n ow . B ut h ere w ere t w o in dependent c a use s. A nd t h en, w e h ad a

c lu e t h at g enes m ig ht b e in vo lv e d in c a usin g c a nce r.

T hese t in y s tr u ctu re s s e en u nder t h e m ic ro sc o pe a re c a lle d c h ro m oso m es. In e ach c e ll o f t h e b ody is

a ﬁ xe d a nd c o nsta nt n um ber o f t h ese c h ro m oso m es, c o nsis tin g o f a ﬁ xe d a nd o rd erly a rra ngem ent

o f g enes.

T here w ere c lu es t h at it w ould in vo lv e g enes, a nd t h ey w ere c lu es t h at w ere la rg ely ig nore d. F ir s t

c lu e w ould b e s im ply t h at t h e c a nce r c e ll g iv e s r is e t o m ore c a nce r c e lls , w hic h g iv e s r is e t o m ore

c a nce r c e lls . T hat d oesn 't h appen u nle ss t h ere a re g enes in vo lv e d. C lu e t w o w as t h at s o m e c a nce rs

a re in herit e d in a lim it e d n um ber o f c a se s. T hat s c re ens g enes.

T he id ea t h at c a nce r is a d is e ase o f t h e g enom e is a ctu ally a p re tty o ld id ea. Y o u g o b ack t o t h e v e ry

b egin nin g o f t h e 2 0th c e ntu ry , a nd it w as p ro pose d b y a s c ie ntis t, B ove ri, t h at c a nce r w as r e ally d ue

t o c h ro m oso m al d efe cts . N ow , t h at r e ally d id n't h ave a lo t o f t r a ctio n t h en, b eca use w e d id n't k n ow

a nyth in g a bout t h e s tr u ctu re o f D NA. B ut t h e id ea t h at c h ro m oso m es g ettin g b ro ke n in d iﬀ ere nt w ays

c o uld b e t h e b asis o f c a nce r w as a n o ld n otio n.

T he g enetic t h eory h ad la rg ely b een f o rg otte n, u ntil 1 967, w hen a b io ch em is t a t t h e U niv e rs it y o f

C alif o rn ia a t B erk e le y, n am ed B ru ce A m es, m ade w hat p ro ve d t o b e a m om ento us d is c o ve ry. I w as t h in kin g a lit tle d iﬀ ere ntly t h an o th er p eople , b eca use I w as t r a in ed a s a b io ch em is t, a nd a ls o a s

a g enetic is t.

A m es h ad s e t o ut t o in ve nt a t e st t o d ete rm in e w hic h c h em ic a ls h ad t h e a bilit y t o m uta te g enes.

O ne d ay, I w as r e adin g t o o m any la bels o n p ota to c h ip p acka ge, o r w hate ve r it w as, a bout t h is

c h em ic a l a ddit iv e , t h at c h em ic a l a ddit iv e . A nd t h en I t h ought, g ee, w e o ught t o h ave a n e asy t e st f o r

t e stin g t h in gs t o s e e if t h ey'r e m uta gens.

A m es t e ste d a v a rie ty o f c h em ic a ls a nd c a m e t o a n im porta nt c o nclu sio n. T hose a gents t h at s h ow ed

t h e g re ate st p ow er t o m uta te g enes w ere t h e s a m e o nes k n ow n t o c a use c a nce r.

I a lw ays k n ew in m y b ones t h at m uta tio n h ad t o h ave s o m eth in g t o d o w it h c a nce r. Y o u w ere t a kin g a

n orm al c e ll, a nd m uta tin g, a nd m akin g it d iﬀ ere nt.

W hat A m es d is c o ve re d is t h at, in f a ct, t h in gs t h at c a use c a nce r a re c o nnecte d b y a s in gle c o m mon

p ro perty , a nd t h at is t h at t h ey c a use m uta tio ns in g enes.

S o v ir u se s? C hem ic a ls ? G enes? W e c o uld n't ﬁ gure t h at o ut. W e b elie ve d in e ve ry o ne o f t h em , b ut

w hat t h e r e la tio nsh ip w as b etw een t h ese , w e h ad n o id ea.

T he m ost im porta nt t h in g is t h at e ve ry o ne t h in ks t h ere h as t o b e a r e so lu tio n. S o in o th er w ord s,

t h ese t h re e t h eorie s h ave t o h ave a c e ntr a l e xp la natio n. It 's t h e g ra nd u niﬁ ed t h eory o f c a nce r.

T he ﬁ nal p ie ce o f t h e p uzzle o f c a rc in ogenesis c a m e f r o m a noth er W est C oast la b a t t h e U niv e rs it y o f

C alif o rn ia a t S an F ra ncis c o , r u n b y a y o ung v ir o lo gis t n am ed M ic h ael B is h op. W hen I a rriv e d a t U CSF

i n F e bru ary 1 968, t h ere w as n o c le ar s in gle t h eory a bout w hat m ake s a c a nce r c e ll. A nd, in f a ct,

n oth in g a ll t h at t a ngib le . It w as a b la ck b ox.

I w as w ork in g o n p olio v ir u s a t t h e t im e. A nd t h en I w as in tr o duce d t o t h e R ous S arc o m a v ir u s o f

c h ic ke ns, a nd o ve rn ig ht b eca m e a c a nce r s c ie ntis t.

B is h op w as s o on jo in ed in h is la b b y a y o ung r e se arc h er n am ed H aro ld V arm us.

I w as a y o ung d oc w ho h ad a ctu ally s p ent m ore t im e s tu dyin g E nglis h lit e ra tu re t h an s c ie nce . B ut I

s ta rte d t a lk in g w it h M ik e , w ho h ad b een t r a in ed m uch a s I h ad, a s a d oc, a nd t h en h ad le arn ed

s o m eth in g a bout n ew t e ch nolo gie s b y w ork in g w it h p olio v ir u s. T he t w o o f u s r e aliz e d w e h ad t h e

s a m e o bje ctiv e in m in d. I t t o ok a bout 1 0 m in ute s f o r m e t o r e co gniz e t h at h e h ad a la se r-lik e in te llig ence , a nd t h at w e c o uld

w ork t o geth er, a nd p ro bably h ave a g ood t im e d oin g it .

T o geth er, B is h op a nd V arm us d ecid ed t o t a ckle t h e r id dle o f c a rc in ogenesis b y s tu dyin g t h e s tr a nge

v ir u s ﬁ rs t f o und in c h ic ke n t u m or c e lls -- t h e R ous S arc o m a v ir u s. T he r e m ark a ble t h in g a bout t h is

v ir u s w as t h at y o u c o uld in fe ct c e lls in a t e st t u be, a nd t h en t h e n ext d ay, t h ose c e lls w ould a ll b e

c a nce r c e lls . It w as a n e xtr a ord in ary t r a nsfo rm atio n, a nd h ow t h at w ork e d, h ow it h appened, w as

a bso lu te m yste ry.

T he n asc e nt d is c ip lin e o f m ole cu la r b io lo gy w as d eve lo pin g. A nd s o f o r t h e ﬁ rs t t im e, t h ere w ere t h e

e xp erim enta l in str u m ents w it h w hic h o ne c o uld a tta ck t h is p ro ble m , lo ok in sid e c a nce r c e lls , p eer

i n to t h e n ucle i o f t h ese c e lls , a nd p eer in sid e t h e g enes t h at t h ese c e lls c a rrie d in t h eir D NA.

T he R ous S arc o m a v ir u s p re se nte d a r a re o pportu nit y t o w atc h c a rc in ogenesis u p c lo se .

W e w ere n't s tu dyin g v ir u se s a s a c a use o f c a nce r. W e w ere s tu dyin g v ir u se s a s a w ay t o ﬁ nd o ut h ow

c a nce r a ris e s, w hat's t h e m ech anis m o f t h e d is e ase . V ir u se s a re u su ally v e ry s im ple . T his p artic u la r

v ir u s h as o nly f o ur g enes, a nd w e h ave t e ns o f t h ousa nds o f t h em . T o u nders ta nd h ow ju st f o ur g enes

c a n g iv e r is e t o c a nce r r e ally s im pliﬁ ed t h e p ro ble m im mense ly .

T hro ugh a p ro ce ss o f e lim in atio n, a f e w la bs, in clu din g B is h op a nd V arm us's , z e ro ed in o n o ne o f t h e

v ir u s's g enes.

T his v ir u s t h at c a use s c a nce r h as f o ur g enes. A nd t h ey ﬁ nd t h at a c lo se ly r e la te d v ir u s-- t h at d oesn 't

c a use c a nce r-- h as t h re e g enes. A nd t h at's a v e ry in te re stin g d iﬀ ere nce . W hat's t h is e xtr a g ene?

A nd t h en t h e e vid ence b egin s t o m ount. T his g ene c a rrie d b y t h e v ir u s, t h e e xtr a g ene, c a n c a use t h e

c a nce r. It w as c a lle d a n o nco gene, a c a nce r c a usin g g ene in t h e v ir u s.

A nd t h en w e b egan t o t h in k a bout a p uzzle . A nd t h e p uzzle w as, w hy d oes t h e v ir u s h ave t h is c a nce r

g ene? T his g ene w e c a lle d S RC , t h e o nly t h in g it d oes is t o c o nve rt t h e c e ll t o a c a nce r s ta te . S o t h e

c a nce r g ene s e em ed a lm ost s u perﬂ uous.

W ell, t h e v ir u s d oesn 't a ctu ally n eed t h e g ene. W hy d oes it h ave it ? W here d id it c o m e f r o m ?

M ayb e-- t h ey t h ought-- t h e c a nce r c a usin g g ene d id n ot o rig in ate in t h e v ir u s a t a ll. M ayb e it

o rig in ate d in t h e c h ic ke n.

T o m y a sto nis h m ent, w hen w e lo oke d in n orm al c h ic ke ns, w e f o und s o m eth in g t h at r e se m ble d t h e S RC c a nce r g ene in R ous S arc o m a v ir u s. It w as a r iv e tin g m om ent.

E ve ry b ody e xp ecte d t h at t h e S RC -- t h e S RC o nco gene, t h e c a nce r g ene-- w as a n atu ra l r e sid ent

w it h in t h e g enom e o f R ous S arc o m a v ir u s. B ut, in f a ct, t h e p ro fo und d is c o ve ry t h ey m ade w as t h at

R ous S arc o m a v ir u s h ad a ctu ally s to le n, h ad k id napped, t h at g ene f r o m t h e r e perto ir e o f n orm al

g enes t h at a re n orm ally s to re d in t h e g enom e o f a n orm al c h ic ke n c e ll.

I f t h e S RC o nco gene h ad a ctu ally d esc e nded f r o m a n orm al g ene in c h ic ke ns, w here e ls e m ig ht it b e

f o und? W e lo oke d a t d ucks. W e lo oke d a t e m us a nd r h eas, w hic h a re t h e m ost p rim it iv e b ir d s liv in g.

A nd t h en e ve ntu ally , b y ﬁ ddlin g w it h t h e t e ch nolo gy, w e c o uld s h ow t h at it w as e ve n in h um ans.

T he f a ct t h at S RC e xis te d in a ll o rg anis m s-- n ot ju st in v ir u se s, b ut in c h ic ke n, a nd g eese , a nd in

h um ans-- t h at f a ct g ave a v e ry c ru cia l t o ol, b eca use t h at m eant t h at g enes t h at a re c a pable o f

c a usin g c a nce r a re a lr e ady e xis tin g in sid e a nim al g enom es. I m ean, im agin e h ow e xcit in g t h at w ould

h ave b een. N ow , a ll o f a s u dden, y o u b egin t o s e e t h ro ugh t h e d ark n ess a g lim pse o f w hat t h e c le ar

t h eory o f c a nce r is . T here a re g enes in y o ur b ody t h at c o ntr o l n orm al c e llu la r g ro w th , a nd if y o u

d is ru pt t h ese g enes, y o u e sse ntia lly b egin t o u nle ash c a nce r.

F in ally , t h e m yste ry o f c a rc in ogenesis h ad a s in gle e xp la natio n-- t h e o nco gene.

T he im porta nt t h in g is t h at t h e v ir a l t h eory w as n ot w ro ng. T he e nvir o nm enta l t h eory w as n ot w ro ng.

T he h ere dit y t h eory w as n ot w ro ng. T hey w ere ju st in su ﬃ cie nt. It w as lik e t h e b lin d m en a nd t h e

e le phant-- t h ey w ere c a tc h in g p arts o f t h e w hole , a nd t h en a ll o f a s u dden, if y o u s te pped b ack, y o u

s a w t h e w hole e le phant.

T he d is c o ve ry o f t h e S RC o nco gene b y B is h op a nd V arm us e le ctr iﬁ ed t h e ﬁ eld a nd w ould w in t h em

t h e N obel P riz e . B ut t h ere w as a noth er m yste ry le ft t o s o lv e . S o f a r, t h e o nly a ctu al o nco gene

d is c o ve re d w as in a v ir u s t h at c a use d c a nce r in a c h ic ke n. N o o ne h ad y e t f o und o ne in a h um an.

B ut t h e t a nta liz in g s u ggestio n f r o m B is h op a nd V arm us's w ork w as t h at t h ere w ere h um an g enes t h at

c o uld c a use c a nce r. It w as a g re at s u ggestio n. It w as a c o ol id ea-- k in d o f h ad t o b e r ig ht. B ut t o k n ow

t h at it r e ally w as r ig ht r e quir e d ﬁ ndin g a h um an c a nce r-c a usin g g ene in a h um an c e ll.

B y t h e la te 1 970s, a w orld w id e h unt w as o n f o r a h um an o nco gene. O ne o f t h ose jo in in g t h e s e arc h

w as R obert W ein berg , t h e y o ung c a nce r r e se arc h er a t t h e M assa ch use tts In stit u te o f T e ch nolo gy.

T hough o nly 3 6, W ein berg h ad s p ent m any f r u it fu l a nd f r u str a tin g y e ars in t h e t r e nch es o f c a nce r

r e se arc h . S cie nce is a p ro fe ssio n f o r m anic d epre ssiv e s, b eca use t h ere 's o cca sio nal h ig hs w here y o u m ake a

d is c o ve ry , a nd t h en 9 0% o r 9 5% o f t h e t im e, t h ere 's f r u str a tin g d iﬃ cu lt ie s, a nd n oth in g h appens.

W hat d riv e s o ne is o ne's o ngoin g c u rio sit y a nd t h e o ptim is m t h at if y o u p ush h ard e nough a nd y o u

l o ok u nder e nough s to nes, y o u'r e g oin g t o t u rn u p s o m e r e ally in te re stin g t h in gs.

I n F e bru ary 1 978, t h e w ors t b liz za rd in B osto n's h is to ry s tr u ck t h e c it y , u nle ash in g h urric a ne-fo rc e

w in ds a nd m ore t h an 3 0 in ch es o f s n ow . B ut W ein berg w as d ete rm in ed t o g et t o h is la b a t M IT . A s h e

t r u dged t h ro ugh t h e d rif ts a cro ss t h e L o ngfe llo w B rid ge, h e t h ought a bout t h e e lu siv e h um an

o nco gene. " Is o la tin g s u ch a g ene," h e'd o nce w rit te n, " w ould b e lik e w alk in g o ut o f t h e c a ve o f

s h adow s."

M any b elie ve d t h at e ve n t h ough t h e V arm us-B is h op w ork w as in te re stin g in it s o w n r ig ht, s o m ehow it

d id n ot s h ed a ny lig ht o n w hat h appens in sid e t h e h um an b ody. A nd t h at's w hat p ro vo ke d m y o w n

r e se arc h , s ta rtin g in 1 978, t o t r y t o ﬁ nd s u ch g enes.

W hen B ob w ent lo okin g t o ﬁ nd t h is h um an c a nce r g ene, in w hat w as t h en a n a lm ost in ﬁnit e s e em in g

h um an g enom e, it w as in cre dib ly h ard .

T here a re t e ns o f t h ousa nds o f g enes in a h um an c e ll. F in din g o ne t h at c a use d c a nce r w ould b e lik e

ﬁ ndin g a p artic u la r s n ow ﬂake in t h e m id st o f a b liz za rd . T he id ea o f h ow t o d o t h at c a m e t o W ein berg ,

a s w e c ro sse d t h e L o ngfe llo w B rid ge o n t h at s n ow y F e bru ary d ay. H e c o uld is o la te t h e in div id ual

g enes in a h um an c a nce r c e ll a nd s p rin kle t h em , o ne b y o ne, o nto n orm al c e lls in a P e tr i d is h , u ntil

o ne o f t h e g enes t u rn s t h e c e lls m alig nant. It w ould t a ke a y e ar, b ut it w ork e d.

S o if y o u h ad a n orm al c e ll, a nd y o u in tr o duce d t h at o nco gene, t h at c e ll b eca m e c a nce r. T hat's v e ry

p ow erfu l. Y o u h ave 2 0,0 00 g enes, a nd y o u ju st in tr o duce o ne in to a c e ll, a nd t h at c e ll w ill c h ange. A nd

t h at c e ll t h at is a n orm al c e ll, a g ood c it iz e n, g ood b ehavio r, w ill b eco m e a f u ll c a nce r.

W ein berg h ad d is c o ve re d t h e ﬁ rs t h um an o nco gene. It w as c a lle d R A S.

I t w as, a nd it r e m ain s a d ete ctiv e s to ry , c a n w e ﬁ nd a ll t h e g enes t h at a re r e sp onsib le f o r t h e

a bnorm al b ehavio r o f c a nce r c e lls ? D oin g s o , w it h t h e f a it h t h at s o m e o f o ur ﬁ ndin gs m ay e ve ntu ally

p ro ve u se fu l, f o r t h ose w ho a re in te re ste d in d eve lo pin g n ew k in ds o f t h era py.

I n t h e y e ars t h at f o llo w ed, la bs a ro und t h e w orld d is c o ve re d d oze ns o f o th er g enes s im ply a w ait in g a

m uta tio n t o t r a nsfo rm t h em in to o nco genes.

I t is a d is c o ve ry o f g re at p ro portio ns-- t h e id ea t h at a g ene c a n b e s w it c h ed o n t o p ro duce a bnorm al p ro te in s a nd, t h us, c a nce r. It c o uld m ean t h at a ll t h in gs w e a sso cia te w it h c a nce r-- r a dia tio n,

h ere dit a ry d efe cts , c h em ic a ls , r a re v ir u se s, s m okin g-- a ll w ork b y t o uch in g t h e s a m e t r ig ger-- t h e

o nco gene.

I t h in k, f o r t h e ﬁ rs t t im e, t h ere w as a m ech anis tic e xp la natio n o n w hy c a nce r w as o ccu rrin g. A nd it

w as a t o ta l r e vo lu tio n-- t h e p ro m is e t h at p erh aps, if t h e o nco genes w ere r e sp onsib le f o r t h e

d eve lo pm ent o f c a nce r, t h en, if w e w ere s m art e nough, w e o ught t o b e a ble t o a tta ck t h em a nd t h en

t o t u rn a nd c u re t h e c a nce r.

W e a ll h ad a f e elin g t h at e ve ry th in g w as a bout t o c h ange, t h at w e w ere p la yin g o ut t h e e ra o f t r ia l

a nd e rro r, o f e m pir ic is m . A nd w e w ere b egin nin g t o m ove t o a n ew e ra o f d esig n, w here w e

u nders to od e nough o f t h e s c ie nce a bout c a nce r, t h at w e c o uld im agin e t h e d is c o ve ry a nd

d eve lo pm ent o f d ru gs t h at w ould s e le ctiv e ly t a rg et w hat w as w ro ng, w hat w as d iﬀ ere nt a bout a

c a nce r c e ll t h an a n orm al c e ll. It w as a v e ry h eady a nd h opefu l t im e.

B ut e ve n in t h e m id st o f t h eir e uphoria , t h ose w ho h ad d is c o ve re d t h e o nco gene w ere a w are o f t h e

c h alle nges t h at la y a head. " W e h ave n ot s la in o ur e nem y-- t h e c a nce r c e ll," H aro ld V arm us w ould s a y,

w hen h e r e ce iv e d t h e N obel P riz e . " W e h ave o nly s e en o ur m onste r m ore c le arly a nd in n ew w ays,

w ays t h at r e ve al a c a nce r c e ll t o b e a d is to rte d v e rs io n o f o ur n orm al s e lv e s."

T he v u ln era bilit y is a lr e ady w it h in u s. T he v e ry g enes t h at m ake y o u g ro w -- t h e v e ry g enes t h at k e ep

y o u a liv e -- w ill, u nder d iﬀ ere nt c ir c u m sta nce s, k ill y o u.

D r. L o ri W ils o n h as b een u nderg oin g c h em oth era py f o r ﬁ ve m onth s. B eca use o f t h e t y p e a nd s iz e o f

h er c a nce rs , s h e h as c h ose n t o h ave a d ouble m aste cto m y, t h ough n ot t h e k in d o f r a dic a l s u rg ery

d one in t h e p ast.

H i, L o ri. It 's n ic e t o s e e y o u. H ow a re y o u?

W e s e e le ss in va siv e s u rg erie s t o day. W hen I s ta rte d m y t r a in in g, I w ould s till s e e, o cca sio nally , a

w om an w ho h ad a r a dic a l m aste cto m y. T o day, I c a n't e ve n t h in k o f t h e la st t im e I'v e s e en t h at.

H ave y o u b een o pera tin g?

I h ave . I h ave . [ IN AUD IB LE ]

S o, in g enera l, w hen w e w ent a head w it h m aste cto m ie s--

B eca use o f t h e s iz e a nd t y p e o f b re ast c a nce r t h at I h ave , m aste cto m y is m y c h oic e , o n b oth s id es. R ig ht n ow , I a bso lu te ly w ant t o b e b ette r. I w ant n ot t o h ave it c o m e b ack. A nd s o if t h at m eans

m aste cto m y, a nd t h at m eans n ot d oin g a lu m pecto m y a nd b re ast c o nse rv a tio n, I'm O K w it h t h at.

O n t h e le ft s id e, it is s o ft, b ut s till a lit tle --

T he m ain c o nce rn w hen o ne is d ia gnose d w it h c a nce r, is t o t r y t o e stim ate w hat t h e r is k o f

o ccu rre nce is in o th er p arts o f t h e b ody. W hen w e in it ia lly m et, a r is k o f c a nce r c o m in g b ack w as

m ore t h an 5 0% . S o w e'r e d eﬁnit e ly a tta ckin g t h e c a nce r f r o m e ve ry p ossib le d ir e ctio n. W e'v e d ecid ed

t h at t h e b est a ppro ach w ould b e t o s ta rt w it h c h em oth era py ﬁ rs t, t o t r y a nd s h rin k t h e c a nce r a s

m uch a s p ossib le , b efo re p ro ce edin g w it h s u rg ery.

M y f e ar is t h at t h e c h em oth era py's n ot a s e ﬀ ectiv e , t h at it d oesn 't t r e at t h e c a nce r c o m ple te ly , t h at

t h e c a nce r g ro w s d urin g t r e atm ent-- w hic h w ould n ot b e a g ood p ro gnosis f o r m e.

I f t h e c e lls c o ntin ue t o b e p re se nt d esp it e t h e t r e atm ents , t h ey c a n g ro w in o th er p arts o f t h e b ody.

T hat's w hen c a nce r b eco m es lif e t h re ate nin g.

S ay g ood-b ye t o y o ur la st c h em oth era py.

Y a y!

Y a y.

T he b ig gest r is k a fte r s u rg ery w ould b e h avin g ly m phedem a, o r s w ellin g o f m y a rm . If I h ad

l y m phedem a, I p ro bably w ould n't b e a s u rg eon a ny lo nger. O f c o urs e , t h at m ake s m e s a d, b eca use

t h ere 's s o m e t h in gs t h at y o u ju st a re . I ju st t h in k t h at b ein g a s u rg ic a l o nco lo gis t, t h at's o ne o f t h e

t h in gs t h at I a m .

W hen t h e p atie nt is a p hysic ia n h ers e lf- - s o m eone w ho's in t h e ﬁ eld , w ho h as s e en w om en s tr u ggle ,

a nd d ie o f t h e b re ast c a nce r-- y o u k n ow h ow t h e s to ry c a n e nd.

F o urte en y e ars a go, P re sid ent N ix o n s ig ned a b ill d ecla rin g a n o ﬃ cia l w ar o n c a nce r.

W e'r e s p endin g a bout $ 1 b illio n a y e ar o n c a nce r r e se arc h in t h is c o untr y , a nd w hat a re w e g ettin g

f o r it ?

A m eric a ns a re lo sin g t h e w ar a gain st c a nce r. I n 1 986, t h e w ar o n c a nce r h ad b een g oin g o n f o r 1 5 y e ars . B illio ns o f d olla rs h ad b een s p ent, a nd

g re at p ro gre ss h ad b een m ade in t h e b asic s c ie nce o f t h e d is e ase .

H ow c lo se d oes t h is b rin g u s t o a c u re w hic h t h e w hole w orld is w ait in g o n?

T hat's a n im pondera ble a t t h e m om ent.

I t w as a n in cre dib le t im e, s c ie ntiﬁ ca lly . B ut t h ere w as t h is d eep c h asm b etw een t h e la b a nd t h e c lin ic ,

t h at n obody h ad b rid ged. P e ople b egan t o b eco m e s o m ew hat d is illu sio ned. W e'r e u nders ta ndin g

m uch m ore a bout c a nce r, b ut w here a re t h e t r e atm ents ?

A n ew s tu dy s a ys t h at y o ur c h ance s o f d yin g f r o m c a nce r a re g re ate r t o day t h an t h ey w ere 3 0 y e ars

a go.

A 1 986 s tu dy a ppeare d w hic h , f o r t h e ﬁ rs t t im e, s y ste m atic a lly a naly ze d h ow p atie nts w ere f a rin g in

t h e w ar o n c a nce r. O ne o f t h e c o -a uth ors o f t h e s tu dy w as a r e sp ecte d s ta tis tic ia n n am ed Jo hn B aila r.

D r. B aila r, a re w e b ein g m is le d b y s o -c a lle d s u rv iv a l s ta tis tic s?

W ell, f o r y e ars a nd y e ars , w e'v e b een h earin g m arv e lo us s to rie s a bout p ro gre ss a gain st c a nce r. A nd

a t t h e s a m e t im e, m any p eople a re n't a w are t h at m orta lit y r a te s a re g oin g u p. E ve ry y e ar, s o m e

8 000, 1 0,0 00 m ore p eople d ie o f c a nce r t h an d ie d t h e y e ar b efo re . It 's u p t o 4 50,0 00 t h is y e ar. H ow

d o w e m atc h t h is u p w it h t h ese s to rie s a bout w onderfu l p ro gre ss?

T hat w as t h e ﬁ rs t s h ot a cro ss t h e b ow , w here c re dib le n um bers -b ase d s c ie ntis ts s to od u p a nd s a id ,

w hat h ave w e r e ally a cco m plis h ed, a nd a re w e o n t h e r ig ht t r a ck? T here w as ﬁ rs t a s e nse t h at t h is

c a n't b e r ig ht. A nd t h en, I m ust s a y, it w as a s e nse o f r a ge in s o m e p la ce s, t h at a nyb ody w ould d are

t o s a y t h ese t h in gs.

A ny t im e in t h e la st 2 0 o r 3 0 y e ars , w e c o uld h ave g one t o t h e le aders o f t h e w ar a gain st c a nce r a nd

h eard t h e s a m e s to ry a bout h ow s u cce ss is ju st a ro und t h e c o rn er. I s im ply d on't b elie ve it a nym ore .

T he A m eric a n C ance r S ocie ty d is p ute d t h is s tu dy's c o nclu sio n. A s p oke sm an s a id , a nd I q uote , " W e'r e

m akin g g re at p ro gre ss." H e s a id , " C ance r is r e ally a lo t o f d iﬀ ere nt t y p es o f d is e ase s. If y o u lu m p

t h em t o geth er, y o u g et a d is to rte d p ic tu re ." U nquote .

I t h in k t h ere w as a g enera l s e nse in t h e p ublic -- c e rta in ly , a g enera l s e nse in C ongre ss, t h at c o ntr o lle d

a lo t o f t h e m oney f o r c a nce r r e se arc h . A g enera l s e nse , e ve n, a m ong s o m e o f t h e le aders in t h e

c a nce r e ﬀ ort, t h at t h in gs m ust b e g ettin g b ette r. A nd w e h ad, t h en, t h is s o lid d ocu m enta tio n t h at t h at w as n ot t h e c a se .

B aila r h ad a s o lu tio n-- t o s h if t p rio rit ie s in t h e w ar o n c a nce r, f r o m n ew t r e atm ents t o p re ve ntio n.

A dvis e t o p eople w atc h in g D r. B aila r t h is m orn in g.

S to p s m okin g. S to p s m okin g. S to p s m okin g. T hat is t h e ﬁ rs t a nd m ost im porta nt t h in g w e c a n t e ll

p eople t o day.

B ut n ot m any in t h e c a nce r c o m munit y w ere p ayin g a tte ntio n t o B aila r's p le as f o r c a nce r p re ve ntio n.

T hose w ho h ad d ole d o ut b illio ns o f d olla rs in t a xp aye r m oney e xp ectin g n ew c u re s t o b e d is c o ve re d,

n ow d em anded t o k n ow w here t h e m oney h ad g one.

I m ean, y o u'r e n ot r u nnin g s o m e lit tle k it ty g am e h ere . Y o u'r e r u nnin g a $ 1 b illio n a y e ar, v e ry

i m porta nt p ro je ct. A nd it w orrie s m e t h at y o u d on't u nders ta nd t h e d iﬀ ere nce b etw een h ow

i m porta nt it is t o m anage, a nd h ow im porta nt it is t o r e ach t h e ﬁ nal r e su lt s .

W it h out n ew t r e atm ents t o t r y , d octo rs h ad f e w o ptio ns f o r t h eir s ic ke st p atie nts . S om e d ecid ed t o

r a is e t h e d ose s o f t h eir d ru gs t o h ig her a nd h ig her le ve ls . Ju st a s r a dic a l s u rg eons h ad o nce p ush ed

t h eir d is c ip lin es t o t e rrif y in g lim it s , n ow r a dic a l c h em oth era pis ts d id t h e s a m e.

I n t h e la te s u m mer o f 1 981, a d octo r n am ed W illia m P e te rs a rriv e d a t D ana-F a rb er C ance r In stit u te ,

i n B osto n. P e te rs h ad c o m e t o t h e h osp it a l t o w ork u nder T o m F ry , o ne o f t h e p io neers o f h ig h d ose

c h em oth era py.

T o m F ry 's a r e m ark a ble in div id ual, w ho's a ﬀ ectio nate ly k n ow n b y e ve ry b ody a s B ig B ir d -- t a ll, la nky

m an, w it h a n in cre dib le e ncyclo pedic k n ow le dge o f t h e d is e ase a nd a ppro ach t o t r e atm ent t h at

d ro ve e ve ry b ody t o t h in k o uts id e t h e b ox.

F ry b elie ve d h e c o uld t r a nsla te t h e s u cce ss h e'd h ad w it h h ig h d ose c h em oth era py in c h ild hood

l e uke m ia , t o s o lid t u m ors -- e sp ecia lly t o b re ast c a nce r.

B re ast c a nce r h ad b egun t o c a ptu re t h e m in dse t o f t h e c o m munit y . P e ople w ere lo okin g f o r a w ay in

w hic h y o u w ould r e vo lu tio niz e t h is d is e ase -- m ake t h e w ar o n c a nce r ﬁ nally s u cce ssfu l. A nd it b eca m e

a r e al r a lly in g p oin t f o r g ettin g t r e atm ents d one.

T o geth er, F ry a nd P e te rs d ecid ed t h at t h e w ay t o a tta ck b re ast c a nce r w as t o v a stly in cre ase t h e

d ose s o f c h em oth era py d ru gs. T he f a ct is t h at if a t w o-fo ld d iﬀ ere nce in d ose m ake s a d iﬀ ere nce , a ﬁ ve -fo ld f o ld d iﬀ ere nce in d ose ,

m ade p ossib le b y b one m arro w t r a nsp la nta tio n, m ig ht b e e xp ecte d t o m ake a b ig ger d iﬀ ere nce .

B one m arro w h ad a lw ays b een t h e lim it in g f a cto r f o r c h em oth era py. A s t h e s o urc e o f w hit e b lo od

c e lls t h at p ro te ct t h e b ody f r o m in fe ctio n, b one m arro w w as e sse ntia l. If y o u d estr o ye d it , t h e p atie nt

w ould d ie .

Y o u h ad t o ﬁ gure o ut a t r ic k t o g et a ro und t h e b one m arro w . A nd t h e c o nce pt b eca m e, w hy n ot t a ke

s o m e o f t h e b one m arro w o ut, f r e eze it in t h e la bora to ry , t r e at t h e p atie nt w it h a s h ig h a d ose a s y o u

c o uld t o le ra te , a nd t h en p ut t h e m arro w b ack. A nd lik e s e ed o n a n ew la w n, t h e m arro w w ould r e -

p opula te .

T he p ro ce dure h ad b een t r ie d, w it h s o m e s u cce ss, in c h ild re n w it h a dva nce d le uke m ia . B ut n o o ne

k n ew h ow a dult w om en w it h b re ast c a nce r w ould t o le ra te it . In t h e s u m mer o f 1 983, P e te rs a nd F ry

b egan a c lin ic a l t r ia l, w hic h t h ey n am ed t h e S olid T u m or A uto lo gous M arro w P ro gra m , o r S TA M P.

I s a id , T o m , if w e'r e d oin g t h is , w e'r e g oin g t o p ush t h e d ose s t o t h e lim it . W e'r e g oin g t o d o it o nce . I

d on't w ant, a t t h e e nd o f it , s o m ebody t o c o m e b ack a nd s a y, if y o u o nly h ad d one a lit tle b it m ore ,

y o u'd g otte n t h e r ig ht a nsw er.

T he r e se arc h ers in fu se d p atie nts w it h d ose s o f d ru gs ﬁ ve t im es h ig her t h an n orm al, b rin gin g t h em t o

t h e b rin k o f d eath , b efo re s a vin g t h em w it h t h eir o w n b one m arro w c e lls . A lm ost im media te ly , t h ey

s a w a r e sp onse in a p atie nt.

S he h ad a r e m ark a ble r e sp onse . T he t u m or, w it h in a w eek, b egan t o r e gre ss a w ay, s u ch t h at t h ere

w as a lm ost n oth in g b y t h e e nd o f a w eek, t o t w o.

T hough t h e S TA M P t r ia l w as s till y e ars a w ay f r o m c o m ple tio n, w ord o f d ra m atic r e m is sio ns b egan

l e akin g o ut t o d esp era te p atie nts a nd t h eir f a m ilie s.

P a tie nts w ere d em andin g a cce ss t o it . T hey w ere lo bbyin g in su ra nce c o m panie s a nd d oin g a lo t o f

p re ss t o s h am e in su ra nce c o m panie s in to p ayin g f o r t h is u npro ve n in te rv e ntio n. A nd it g ot t o t h e

p oin t w here w e c o uld n't g et p eople t o c o m e in to t h e c lin ic a l t r ia ls t o p ro ve w heth er t h ey w ere

e ﬀ ectiv e o r n ot, b eca use t h ey w ante d a cce ss t o it r e gard le ss.

I f s o m ebody t o ld y o u t h at y o u p ro bably w ere o nly g oin g t o liv e t w o m ore y e ars , a nd y o u h ad n o id ea

h ow y o u w ere g oin g t o d ie -- it m ig ht b e e asy , o r it m ig ht b e r e ally lo usy -- I m ean, I t h in k y o u w ould

s a y, y o u w ould r e ach f o r a nyth in g t h at s e em ed p ro m is in g. M any d octo rs w ere a s e ager t o t r y t h e p ro ce dure a s t h eir p atie nts . N ot o nly w as t h e b one m arro w

t r a nsp la nt s c ie ntiﬁ ca lly e xcit in g, it w as e xtr e m ely lu cra tiv e .

T ra nsp la nt b eca m e a b usin ess. H osp it a ls f o und t h at if t h ey u se d t h is t y p e o f t r e atm ent a ppro ach , it

c o uld s ig niﬁ ca ntly im pro ve t h e b otto m lin e. S uddenly , t h e d oors o pened. C om munit y h osp it a ls ,

d octo rs in p riv a te p ra ctic e , e ve ry a ca dem ic in stit u tio n, n ow h ad t o h ave it s o w n h ig h d oes

c h em oth era py p ro gra m .

4 3-y e ar-o ld A nn G ra nt w as o ne o f t h ose w om en w ho u nderw ent t h e t r e atm ent o uts id e o f a c lin ic a l

t r ia l. D ia gnose d w it h m eta sta tic b re ast c a nce r, s h e f e lt s h e h ad lit tle c h oic e .

A lm ost a ll t h e d octo rs w e in te rv ie w ed s u ggeste d t h at w e c o nsid er h ig h d ose c h em oth era py, w it h a

s te m c e ll t r a nsp la nt. T he t r e atm ent w as p re se nte d a s, t h is is t h e w ay it 's d one, t h is is t h e g old

s ta ndard o f t r e atm ent, a nd t h is is w hat w e d o. I w as t h ere , I b elie ve , 2 1 d ays. A nd it w as ju st e ve ry d ay

b le nded in to a noth er. I n eve r k n ew if it w as d ay o r n ig ht. E ve ry th in g w as p ain fu l, a nd y o u'r e s o s ic k,

y o u c a n't d o a nyth in g. Y o u'r e d yin g, I m ean, y o u'r e f e elin g y o urs e lf d yin g.

P e te rs w as s e ein g t h e s a m e h orriﬁ c s id e e ﬀ ects w it h in h is c lin ic a l t r ia l. O ne in ﬁ ve w om en w ere d yin g

f r o m t h e t r e atm ent.

Y o u h ad t o s it a nd a sk y o urs e lf , c a n w e g o o n? A re y o u r e ally a m adm an, d oin g t h is t y p e o f a ppro ach ?

A re y o u r e ally o uts id e t h e b ounds o f w hat y o u s h ould e th ic a lly b e g oin g? Y o u w ere w orrie d a bout it .

I 'd b e a lia r if I d id n't s a y t h at I d id n't t h in k lo ng a nd h ard a bout t h e d iﬃ cu lt ie s t h at w e h ad in t h ose

t h in gs.

A fte r a d eca de o f s tu dy, P e te r's o w n c lin ic a l t r ia l r e ve ale d t h at t h e p ro ce dure h ad b een n o m ore

b eneﬁcia l t h an r e gula r d ose s o f c h em oth era py. In 1 999, h e p re se nte d h is ﬁ ndin gs t o a s h ocke d a nd

d is a ppoin te d c a nce r c o m munit y .

T he r a ndom iz e d c o ntr o l t r ia l s h ow ed t h at t h ere w as n o d iﬀ ere nce in t h e s u rv iv a l, b ut t h e p eople w ho

g ot t h e t r a nsp la nts h ad a h ig her c h ance o f d yin g f r o m t h e t r a nsp la nts . A nd s o t h e id ea t h at t h is w as

t h e a nsw er t o b re ast c a nce r, ju st d id n't w ork -- t h at m ore w asn 't b ette r. It w asn 't b ette r in s u rg ery , a nd

i t w asn 't b ette r in c h em o.

E ve ry p atie nt d ie d o f t h eir d is e ase . A nd if w e c o uld c h ange t h at, w e n eeded t o d o it . If it w ork e d, w e'd

b e f a m ous, O K? If it d oesn 't w ork , w ell, a ll r ig ht. Y o u'v e m ade a c o ntr ib utio n, a nd t h at's t h e w ay

m edic in e m ove s f o rw ard . B efo re h ig h d ose c h em oth era py f o r b re ast c a nce r w as ﬁ nally a bandoned, it h ad b een p erfo rm ed o n

t h ousa nds o f w om en. F o llo w -u p s tu die s c o nﬁrm ed t h at t h ese p atie nts h ad r e ce iv e d lit tle o r n o

b eneﬁt, a nd m any h ad lo st t h eir liv e s a s a r e su lt o f t h e p ro ce dure .

W e d id t h is in t h e U nit e d S ta te s f o r 1 5 y e ars , t r a nsp la nte d m ore t h an 1 5,0 00 w om en, d id it w it h out

c lin ic a l t r ia ls t h at a ctu ally s h ow ed t h at it w as b eneﬁcia l. T his is a n e xa m ple o f h ow m edic a l o nco lo gy

a nd m edic in e ju st g ot t o ta lly o ut o f h and.

T here a re t im es w hen y o u d o e ve ry th in g t o t h e m axim um , a nd y o u h ave a s c ie ntiﬁ c f o undatio n t o

j u stif y t h at. B ut t h en t h ere a re t im es w hen y o u n eed t o s te p b ack a nd s a y, a m I r e ally d oin g w hat is

b est f o r t h e p ers o n? A nd h ow d o I b ala nce t h is e ﬀ ort t o e xte nd lif e , v e rs u s t h e im pact t h at y o ur

t h era pie s h ave in w ors e nin g t h at lif e ?

I n t h e e nd, e ve n t h ose w ho s u rv iv e d, p aid a t e rrib le p ric e f o r h ig h d ose c h em oth era py. I h ave

t r e m endous c o gnit iv e p ro ble m s t h at c a use a lo t o f f r u str a tio n in m y lif e . A nd I'm n ot b it te r. I ju st g et

f r u str a te d w hen I c a n't d o s o m eth in g. A nd I w is h I c o uld g et m y w ord s a ll t h e t im e, a nd I w is h I c o uld

r e m em ber s h ort-te rm m em ory t h in gs, a nd I w is h t h at I d id n't h ave t h ese p ause s.

T he f a ilu re o f h ig h d ose c h em oth era py m ark e d t h e e nd o f a n e ra in c a nce r t r e atm ent, in w hic h t h e

g uid in g p rin cip le h ad b een m ore is b ette r. F e w d oubte d t h at a n ew , m ore r a tio nal s tr a te gy w as

n eeded-- o ne t h at w ould b rin g t h e in sig hts g ain ed in t h e la b, t o p atie nts in t h e c lin ic .

T his w as a c ris is o f f a it h . It w as a t im e w hen, a ll o f a s u dden, t h e d is c ip lin e h ad t o lo ok b ack o n it s o w n

h is to ry -- o n it s e lf- - a nd t o a sk q uestio ns a bout w here it w as g oin g, w here h ad it c o m e f r o m , a nd w hat

w as g oin g t o h appen n ext?

D r. L o ri W ils o n a nd h er f a m ily h ave c o m e t o L o s A ngele s, t o t h e C edars -S in ai M edic a l C ente r, w here

s h e w ill h ave h er s u rg ery p erfo rm ed.

Y e ah, O K. S ay g ood-b ye t o M om my.

I lo ve y o u. S ee y o u la te r.

U lt im ate ly , w e a re g oin g t o ﬁ nd o ut f r o m t h e s u rg ery t h e ﬁ nal r e su lt f r o m g oin g t h ro ugh

c h em oth era py r e gim en t h at I h ad. A nd t h en, m akin g d ecis io ns a bout m y lif e f r o m t h ere .

O K. N ow , I'm g oin g t o w eig h y o u, if y o u c o uld s te p o n t h e s c a le . A nd t h en w e'll p ut y o ur e arrin gs h ere ,

a nd t h en w e c o uld g iv e it t o y o ur h usb and. C an I c a ll y o u b y y o ur ﬁ rs t n am e L o ri? I w ould p re fe r t h at.

O r d o y o u w ant D r.?

I w ould p re fe r y o u c a ll m e L o ri.

O K. C an t e ll m e w hat s u rg ery w e'r e d oin g f o r y o u t o day?

I 'm h avin g m aste cto m ie s o n b oth s id es. I'm h avin g m y ly m ph n odes d one c o m ple te ly , o n t h e le ft. A nd

a s e ntin el n ode d one o n t h e r ig ht.

A nd w ho's g oin g t o b e y o ur s u rg eon f o r t h at?

D r. G iu lia no.

M orn in g. W here ' L o ri?

A rm ando G iu lia no is t h e d octo r L o ri t r a in ed u nder a s a F e llo w 1 3 y e ars a go.

D id n't e xp ect t o b e w ork in g t o geth er a gain lik e t h is .

N o, n o. N ot lik e t h is . B ut--

W e s a y in s u rg ery , o nce a F e llo w , a lw ays a F e llo w . T hat r e la tio nsh ip d oesn 't c h ange. A nd h ere w as t h is

y o ung w om an I r e m em ber in h er e arly 3 0s, w ho n ow c o m es w it h b ila te ra l b re ast c a nce r.

W e'll t a ke g ood c a re o f y o u.

I k n ow y o u w ill. T hank y o u. A ppre cia te it .

G et t h in gs r o llin g, a s w e s a y in s u rg ery.

W e a ll lo ve d L o ri, a s a F e llo w . S he w as v e ry h ard w ork in g, v e ry s m art, f u n t o b e w it h , t o ta lly r e lia ble ,

a nd v e ry in quis it iv e . Y o u c o uld s e e t h at s h e h ad a c e rta in s p ark , t h at L o ri w ould d o s o m eth in g w it h h er

l if e , a nd w it h h er c a re er.

H i. Y o u r e ady? W e o nly n eed o ne s e tu p. W e'll d o t h e r ig ht s id e ﬁ rs t. O K. L e t m e h ave a m ark in g p ad.

R ais e t h e t a ble a b it f o r m e, L o ri.

L o ri h as t w o c a nce rs , o ne in e ach b re ast, b oth o f w hic h a re v e ry d is tu rb in g t o m e, f o r d iﬀ ere nt

r e aso ns. S o o n t h is s id e, h er n odes w ere n egativ e . W e'll s e e if t h ey a re n egativ e t o day. H ow 's t h at lo ok? P re tty

g ood, h uh? A nd t h en w e'll p ut t h e c e ntr a l n ode in cis io n h ere .

D r. G iu lia no w ill b egin t h e s u rg ery b y r e m ovin g t h e s e ntin el ly m ph n ode, w hic h w ill b e im media te ly

b io psie d. If it t e sts p osit iv e , it w ill s ig nal t h at L o ri's c a nce r h as s p re ad b eyo nd h er b re ast.

O K. B lu e d ye , p le ase , E ile en. Y o u c a n id entif y t h e ﬁ rs t ly m ph n ode t h at's b een h it b y t h e c a nce r a nd,

t h ere fo re , t h e o ne m ost lik e ly t o h ave m alig nancy. If y o u t a ke t h at o ut, a nd t h ere 's n o c a nce r in t h at,

t h en t h ere 's n ot g oin g t o b e c a nce r in a ny o f t h e o th er ly m ph n odes. A nd w hat h appened is , w e

d ecid ed t h at, w ell, w hy r e m ove n egativ e ly m ph n odes?

G iu lia no is o ne o f t h e d octo rs w ho p io neere d t h is p ro ce dure 2 0 y e ars a go, a s p art o f t h e m ove m ent

t o s a ve w om en f r o m u nnece ssa ry s u rg ery.

P e ople d id n't b elie ve it , o f c o urs e , in it ia lly . S urg eons w ould s e e it o r s a y, it d oesn 't m ake s e nse . W e'v e

c re ate d a m agic ly m ph n ode. T here 's n oth in g m agic a bout it . It w as ju st r e co gnis in g t h e a nato m y o f

t h e ly m phatic s.

S o t h at's t h e ly m phatic t h at is t a kin g t h e c a nce r c e lls a nd t h e b lu e d ye f r o m t h e b re ast, r ig ht t o t h at

l y m ph n ode. F ro ze n s e ctio n, p le ase , [ IN AUD IB LE ] m e.

I t w as a E ure ka m om ent, t h e ﬁ rs t t im e w e s a w a b lu e ly m ph n ode.

F e els O K [ IN AUD IB LE ].

A nd w e w ould t a ke t h at o ut, a nd it in va ria bly p re dic te d w heth er t h e c a nce r h ad s p re ad o r n ot. S o y o u

c a n n ow d o a m uch le ss r a dic a l o pera tio n.

A gain , it 's L o ri W ils o n. L o ri W ils o n.

P a th olo gy is o n t h e p hone. Y o u w ant it o n s p eake r?

P le ase .

R egard in g f r o ze n s e ctio n r e su lt s o n p atie nt, L o ri W ils o n.

O K. G o a head.

N o c a rc in om a s e en. A ll r ig ht. T hank y o u.

T hank y o u v e ry m uch .

G ood n ew s. S he g ets a b re ak.

L o ri's d octo rs s e e n o s ig n o f h er c a nce r h avin g s p re ad. B ut t h ey w ill h ave t o w ait f o r t h e r e su lt s o f a

m ore t h oro ugh p ath olo gy t o k n ow f o r s u re .

I t h in k w hen y o u t r e at c a nce r, it 's im porta nt t o k n ow y o ur lim it a tio ns, a nd u nders ta nd w hat y o u c a n

b e s u re o f a nd w hat y o u a re n ot s u re o f. S o m uch o f w hat w e d o is u nce rta in . W e c a n't p re dic t t h e

f u tu re .

L o ri, y o u a w ake ? It w ent g re at. It r e ally w ent v e ry w ell. C entr a l n ode w as n egativ e o n t h e r ig ht. R eally ,

I 'm v e ry p le ase d.

A nd t h at's v e ry h ard f o r p atie nts .

A ll r ig ht. S ee y o u la te r.

I t h in k u nce rta in ty is p art o f t r e atin g c a nce r.

H ope is a f u nny t h in g. Y o u h ave t o b ase h ope o n s o m eth in g. S o w hen m y c a nce r c a m e b ack, a nd I

r e ally -- w hen y o u h ave 1 6 t u m ors in y o ur lu ngs, y o u'r e n ot t h in kin g s u rv iv a l. S o I d id n't h ave h ope a t

t h at p oin t. B arb ara B ra dﬁeld w as ju st 4 8, w hen h er b re ast c a nce r r e la pse d in 1 992. A lr e ady, s h e'd

e ndure d a m aste cto m y a nd r o und a fte r r o und o f r a dia tio n a nd c h em oth era py.

T he o nco lo gis t s a ys, w ell, w e'r e g oin g t o h it it w it h a s tr o nger c h em o. A nd I s a id , n o, w e'r e n ot. If it

d id n't w ork t h e ﬁ rs t t im e, it 's n ot g oin g t o w ork t h is t im e. I'm n ot d oin g t h at. If I'm g oin g t o d ie , I d on't

w ant t o d ie b ald a nd t h ro w in g u p.

T he d octo r s a id , w ell, I k n ow t h is d octo r o ve r a t U CLA w ho's d oin g s tu die s o f o nco genes. C an I s e nd

y o ur s lid es o ve r t o h im ? A nd I s a id , I d on't c a re . F in e. W hate ve r y o u w ant.

T his o ne is r e sis ta nt, o r t h is o ne's r e sis ta nt.

B ra dﬁeld 's s lid es w ere s e nt t o D r. D ennis S la m on, a n o nco lo gis t w ork in g a t t h e U CLA M edic a l C ente r.

T he s o n o f a W est V ir g in ia c o al m in er, S la m on h ad g ro w n u p w atc h in g lu ng c a nce r r a va ge h is

c o m munit y , d eve lo pin g, w hat h e c a lle d, a m urd ero us r e so lv e t o ﬁ nd a c u re . H e w as t h e ﬁ rs t in h is

f a m ily t o g o t o c o lle ge, a nd t h en m edic a l s c h ool, c o m ple tin g h is t r a in in g t h e s a m e y e ar a s B is h op a nd V arm us's g ro undbre akin g d is c o ve ry o f t h e o nco gene. L ik e m any o th er r e se arc h ers o f h is g enera tio n,

S la m on b elie ve d t h at t h e d is c o ve ry o f t h e o nco gene o ﬀ ere d a n o pportu nit y t o a tta ck t h e d is e ase in

n ew w ays, b y c re atin g s m arte r d ru gs t h at c o uld d is c rim in ate b etw een h ealt h y c e lls a nd c a nce r c e lls .

C an w e u nders ta nd w hat's b ro ke n in a n orm al c e ll t h at m ake s it a c a nce r c e ll? A nd if w e u nders ta nd

w hat's b ro ke n, t a rg et t h at s p eciﬁ ca lly . A nd if w e'r e a ble t o s u cce ssfu lly d o t h at, in t h eory , w e s h ould

h ave t r e atm ents t h at a re A , m ore e ﬀ ectiv e a nd B , le ss t o xic . A nd b y n o m eans w as I a lo ne in t h at

o bse rv a tio n.

W e a lw ays w ere lo okin g f o r t h in gs t h at c o uld t a rg et t h e c a nce r c e ll, le ave t h e n orm al c e lls a lo ne, a nd

t r y t o s e para te t h e n orm al b ody f r o m , a s it w ere , t h is d is to rte d v e rs io n o f t h e b ody, t h e c a nce r in t h e

b ody.

A lr e ady, t h e ﬁ rs t t a rg ete d t h era py a gain st c a nce r h ad b een d is c o ve re d. In t h e e arly 1 970s, a d ru g

c a lle d t a m oxif e n w as s h ow n t o a rre st t h e p ro gre ss o f c e rta in t y p es o f b re ast c a nce r b y s ta rv in g t h em

o f t h e h orm one e str o gen. D ennis S la m on a nd o th er y o unger r e se arc h ers w ante d t o r e ﬁne t a rg ete d

t h era pie s s till f u rth er, b y g oin g a fte r t h e s p eciﬁ c o nco genes t h at g iv e r is e t o s p eciﬁ c c a nce rs .

S cie ntis ts lik e S la m on c a m e o f a ge a t a t im e w hen t h e o nco gene w as d is c o ve re d. S o t h eir q uestio n

w as n o lo nger, w hat is t h e o nco gene? T heir q uestio n is , h ow d o w e k ill a c a nce r c e ll b y u nders ta ndin g

w hat a n o nco gene is . S o, w hat is a n o nco gene s p eciﬁ c t h era py?

B y t h e 1 990s, d oze ns o f t h ese n ew c a nce r c a usin g g enes h ad b een d is c o ve re d. O ne in p artic u la r

i n tr ig ued S la m on. It w as c a lle d H er2 . In it s r e gula r f o rm , t h e H er2 g ene is v it a l t o n orm al c e ll d iv is io n.

I t c re ate s a nte nna-lik e s tr u ctu re s c a lle d r e ce pto rs , t h at s e nd a nd r e ce iv e s ig nals t e llin g t h e c e ll t o

d iv id e. B ut in it s m alig nant f o rm , t h e H er2 o nco gene c o pie s it s e lf o ve r a nd o ve r, a nd t h ese d uplic a te

g enes c re ate a d ense f o re st o f r e ce pto rs .

T he c e ll g oes c ra zy , b eca use t h ere a re s o m any r e ce pto rs , t h at t h e o nly t h in g t h e c e ll c a n d o, a nd

k n ow s t o d o, is t o g ro w in a t o ta lly u nco ntr o lle d f a sh io n. It is n ot d is sim ila r t o h avin g a v e ry p ow erfu l

c a r-- a P o rs c h e, a F e rra ri- - t h at h as t h e g as p edal s tu ck. T hat t h in g is g oin g t o c o ntin ue t o g o v e ry ,

v e ry f a st, u ntil it c ra sh es.

H er2 w as a lr e ady b ein g s tu die d b y r e se arc h ers in t h e S an F ra ncis c o b io te ch c o m pany, G enente ch .

U sin g t h e o nco gene, t h e G enente ch s c ie ntis ts h ad in duce d c a nce r in m ic e , b ut t h ey h ad n o id ea if it

w as r e sp onsib le f o r a ny h um an c a nce rs . T he o nly w ay t o ﬁ nd o ut w ould b e t o s e arc h f o r it in

h undre ds o f d iﬀ ere nt t y p es o f t u m or s a m ple s. T hey a sk e d S la m on t o h elp . W e h ad a b ank-- it s o unds s tr a nge-- b ut a b ank o f t u m or t is su es t h at h ad b een r e m ove d f o r

t h era peutic p urp ose s f o r p atie nts . A nd a s w e w ere w ork in g o ur w ay t h ro ugh o ur t u m or b ank w it h a ll

t h e v a rio us c a nce rs -- w e w ere lo okin g f o r t h e g ene c a lle d H er2 -- w hen w e g ot t o t h e b re ast c a nce r

p art o f t h e b ank, w e f o und a p re tty g ro ss a lt e ra tio n t h at w as o ccu rrin g in a bout 2 0% t o 2 5% o f t h e

p atie nts ' t u m ors .

T here a re t u m ors t h at h ave m ult ip le [ IN AUD IB LE ]. T hey h ave m uch h ig her s ig nals , s o t h ey'r e m uch

m ore in te nse b ands, h ere . S o t h is b and r e pre se nts w hat t h e g ene lo oks lik e in t h is a naly sis .

I f t h is is a b re ast c a nce r c e ll, s o m e b re ast c a nce r c e lls w ould n't h ave a ny H er2 p okin g t h ro ugh t h e

s u rfa ce , o r m ayb e t h ey'd h ave o ne o r t w o. B ut t h ere w ere b re ast c a nce r c e lls w here t h e s u rfa ce o f

t h e c e lls w as s tu ﬀ ed w it h H er2 , t o ns o f it .

W hat r e ally b eca m e e xcit in g is , w hen w e w ent b ack a nd lo oke d a t t h e c lin ic a l d ata , w e f o und t h at

t h ose w om en w hose t u m ors c o nta in ed t h is a lt e ra tio n, h ad a m uch d iﬀ ere nt o utc o m e. T hey w ere

a m ong t h e w om en w ho h ad t h e v e ry w ors t o utc o m es. S o t h ey w ould h ave r e cu rre nce s m uch m ore

q uic kly . A nd t h at w as t h e ﬁ rs t a re a w here w e s ta rte d t o s e e t h ere w as s m oke h ere . T here w as a

g enetic a lt e ra tio n t h at w as a sso cia te d w it h t h e m ost a ggre ssiv e h um an b re ast m alig nancie s.

S o n ow y o u h ave t w o p ie ce s o f in fo rm atio n t h at a re c rit ic a l. O ne, t h at o nco gene is p re se nt, a nd if it 's

p re se nt, t h e t u m or is v e ry , v e ry a ggre ssiv e . A nd t h e n ext q uestio n is h ow t o t a rg et t h is .

B oth S la m on a nd s o m e G enente ch s c ie ntis ts b elie ve d t h ere w as a lr e ady a w eapon a va ila ble w it h

w hic h t o t a rg et t h e o nco gene. It w as c a lle d a n a ntib ody, a nd it e xis ts w it h in t h e h um an im mune

s y ste m .

Y o u c o uld t h in k o f a ntib odie s a s in te nse ly , e xq uis it e ly , t a rg ete d m is sile s m ade in t h e b ody, t o t a rg et

v ir u se s, b acte ria , o r o th er c e lls .

S cie ntis ts a lr e ady k n ew h ow t o g enetic a lly e ngin eer a ntib odie s o uts id e t h e h um an b ody. T he t r ic k

w ould b e t o ﬁ nd o ne t h at c o uld t a rg et t h e H er2 o nco gene. W it h in a c o uple o f y e ars , G enente ch

r e se arc h ers h ad d eve lo ped a n um ber o f c u sto m a ntib odie s t h ey t h ought m ig ht w ork .

S o w e t o ok a ntib odie s t h at G enente ch h ad m ade a nd f o und t h at t h ere w ere s e ve ra l o f t h em t h at

c o uld in hib it t h e g ro w th o f t h ese h um an b re ast c a nce r c e lls in c u lt u re , if t h ey h ad t h e H er2 a lt e ra tio n.

A nd if t h ey d id n't h ave t h e H er2 a lt e ra tio n, t h e a ntib odie s h ad a bso lu te ly n o e ﬀ ect o n t h em . S o n ow

w e h ad s o m eth in g t h at w as m ore , e ve n, t h an a s m okin g g un. T he m ost p ro m is in g o f t h ese n ew a ntib odie s w as n am ed H erc e ptin . S la m on w as e ager t o t r y it in

H er2 p osit iv e p atie nts . B ut G enente ch e xe cu tiv e s w ere w ary.

A t t h e t im e, w e w ere a s m all c o m pany. R eso urc e s w ere e xtr e m ely p re cio us, a nd t h ere w ere c e rta in

p eople t h at t h ought t h is w as ju st n onse nsic a l, e ve n a fte r t h at p ro of o f c o nce pt w as d em onstr a te d.

A nd o th er p eople t h ought t h at t h is c o uld b e t h e f u tu re o f c a nce r t h era py.

A nd it w as t h at c o re o f s c ie ntis ts w ho k e pt t h e p ro je ct a liv e , w ho r e ally b elie ve d t h at t h e d ata m eant

s o m eth in g. I w ould g o u p a lo t a nd t r y t o lo bby t h e n on-b elie ve rs , t h at t h is w as s o m eth in g t h at w as

r e al. In f a ct, I s o rt o f g ot a m onik e r w it h in G enente ch , I w as b ein g c a lle d D ennis t h e M enace .

S la m on b utto nhole d c o m pany e xe cu tiv e s in t h e h allw ay, b eggin g t h em t o f u nd a s m all c lin ic a l t r ia l.

F in ally , G enente ch a gre ed. H e im media te ly s e t a bout r e cru it in g w om en w it h la te s ta ge b re ast c a nce r.

B arb ara B ra dﬁeld 's s lid es a rriv e d ju st in t im e.

W e t e ste d h er t u m or, a nd it t u rn ed o ut t o b e o ne o f t h e m ost p osit iv e w e'd s e en. S he p ro bably w ould

n ot h ave s u rv iv e d m ore t h an t h re e o r f o ur m onth s.

I w as h opin g I c o uld d ie w it h d ig nit y . T hat w as r e ally w here I w as a t t h at p oin t. A nd I g ot t h is c a ll f r o m

D r. S la m on a t U CLA . H e s a id t h at I c o uld q ualif y . H e'd lo ve t o h ave m e in t h e s tu dy. A nd I s a id , w ell, is

t h ere c h em o? A nd h e s a id , y e s, it w ill b e c h em o a nd t h en t h is d ru g. A nd I s a id , n o t h ank y o u, I'm n ot

d oin g t h at.

S o w e s a id g oodbye , g ood n ig ht. T he n ext m orn in g v e ry e arly , h e c a lle d m e b ack. A nd h e s a id , I'v e

b een t h in kin g a bout y o u a ll n ig ht.

I s a id , I r e aliz e y o u m ay h ave m ade a d ecis io n, a nd I d on't w ant t o t r y t o u nduly in ﬂuence y o u. B ut I

w ant t o t e ll y o u, I r e ally t h in k t h is is s o m eth in g y o u s h ould r e co nsid er.

B y t h e t im e h e w as h alf w ay t h ro ugh it , I w as t h in kin g, I d on't h ave a nyth in g t o lo se . S o t h at w as t h e

s ta rt o f t h e H erc e ptin t r ia ls .

B ra dﬁeld jo in ed S la m on's t r ia l in O cto ber 1 992, a lo ng w it h 1 4 o th er w om en. A ll o f t h em h ad

e xh auste d e ve ry s ta ndard t r e atm ent f o r b re ast c a nce r.

T hey w ere a s m uch a p art o f t h e s to ry a nd, in f a ct, c o lle agues, a s a nyb ody w ho w as in vo lv e d in t h e

s c ie nce . W e w ere e xcit e d a bout t h e s c ie nce c o m in g f r o m t h e la bora to ry. T hey h ad a b ig ger d og in t h is

ﬁ ght. I t 's a v e ry p ecu lia rly in tim ate s e ttin g. T hey a ctu ally g et t o k n ow e ach o th ers ' s to rie s. T his is a y o ung

w om an w ho's u nderg one a v e ry t o ugh b one m arro w t r a nsp la nt. T here 's a C hin ese w om an w ho's

b ro ught in a s ta sh o f h erb s. A nd s h e s a ys, I'll t a ke t h e la te st d ru g, if y o u le t m e t a ke t h e o ld est d ru gs.

W e h ad o ne g al t h at c a m e a ll t h e w ay f r o m B osto n. H er n am e w as B ev, a nd s h e w as a lo t o f f u n-- v e ry

r a uco us. S he b ro ught t h is lo ve ly c a ke t h at h ad b re asts o n it , a nd it s a id , B re ast W is h es, D r. S la m on.

M y t u m or in m y n eck w as t h e t o uch sto ne o f t h e s tu dy, b eca use f r o m t h e v e ry b egin nin g, it w as t h e

o nly t u m or t h at c o uld b e f e lt . A nd s o y o u c o uld s e e it -- it w as r ig ht h ere . A nd s o e ve ry w eek,

e ve ry b ody w ould c o m e in a nd f e el it .

W ell, w it h in t h e ﬁ rs t t w o w eeks, it g ot s m alle r. A nd s o t h at w as t h e m ost e xcit in g t h in g. E ve ry b ody

w ould c o m e in a nd f e el it , a nd g o, if y o urs is g ettin g s m alle r, t h at m eans m in e is , t o o.

B ut f o r m any o f t h e w om en, t h e t h era py w asn 't w ork in g. O ne b y o ne, t h ey b egan t o d ro p o ut o f t h e

t r ia l, t o o ill t o c o ntin ue. H alf w ay t h ro ugh t h e t r ia l, t h ere w ere o nly ﬁ ve p atie nts le ft, in clu din g

B ra dﬁeld .

I t 's lik e a s is te rh ood o f h opefu ls -- e ve ry o ne's w atc h in g e ve ry o ne e ls e , a nd t h ere 's a d esp era tio n. A nd

y e t, o nly s o m e p eople a re r e sp ondin g, a nd s o m e p eople a re n ot.

A s S la m on a nxio usly a w ait e d t h e t r ia l r e su lt s o f H erc e ptin , o th er r e se arc h ers b egan lo okin g f o r n ew

o nco genes t o t a rg et. O ne o f t h em w as B ria n D ru ke r, a y o ung d octo r, w ho h ad le ft t h e D ana F a rb er

C ance r In stit u te f o r a r e se arc h la b in O re gon.

W hen I w as d oin g m y o nco lo gy t r a in in g, le arn in g h ow t o t a ke c a re o f c a nce r p atie nts , it w as lik e t h ey

h ad p ut m e in to a r o om w it h a lig ht b ulb t h at w as s tu ck o n, a nd g ave m e a b ase ball b at. A nd t h ey s a id

t o m e, k n ock o ut t h at lig ht b ulb , a nd h ere 's y o ur b ase ball b at. A nd if t h at d oesn 't w ork , w e'r e g oin g t o

u se a b ig ger b at-- h ig h d ose c h em oth era py. A nd I s a id , w hy d on't w e ﬁ gure o ut w hy t h e lig ht's s tu ck

o n a nd ﬁ x it t h at w ay.

D ru ke r h ad b eco m e in te re ste d in a r a re a nd f a ta l b lo od c a nce r c a lle d C M L-- c h ro nic m ye lo id

l e uke m ia . In 1 973, a r e se arc h er a t t h e U niv e rs it y o f C hic a go, n am ed Ja net R ow le y, h ad id entiﬁ ed t h e

s p eciﬁ c g enetic m uta tio n in C M L c e lls . T he e nds o f t w o d iﬀ ere nt c h ro m oso m es a ccid enta lly s w it c h

p la ce s. In t h is n ew f o rm , t h e g ene s u ddenly t r ig gers h yp era ctiv e g ro w th o f c e lls .

I w as in m edic a l s c h ool in t h e la te '7 0s. W e k n ew a bout Ja net R ow le y's p io neerin g w ork id entif y in g e xch ange o f m ate ria l b etw een t h e e nds o f t w o c h ro m oso m es. B ut it w asn 't u ntil I a ctu ally g ot b ack in

t h e la bora to ry , t h at w e r e ally c o uld u nders ta nd w hat t h e c o nse quence s o f t h at s w ap o f c h ro m oso m e

m ate ria l w as. A nd it a ctu ally w as a n o nco gene t h at c a use d t h e u nre str a in ed g ro w th o f w hit e b lo od

c e lls in t h is le uke m ia c a lle d c h ro nic m ye lo id le uke m ia .

I t h appened t h at c h em is ts a t t h e S w is s p harm ace utic a l c o m pany, C ib a-G eig y, la te r n am ed N ova rtis ,

w ere lo okin g a t a c la ss o f d ru gs t h at s e em ed a ctiv e a gain st t h e k in d o f o nco gene t h at c a use s C M L.

H earin g o f t h is , B ria n D ru ke r a nd h is c o lle ague C harle s S aw ye rs a ppro ach ed t h e c o m pany a nd a sk e d

i f t h ey c o uld t e st t h e c o m pounds in t h eir la bs.

T his w as n ot a p ro je ct t h at h ad a t im elin e a nd a p la n w hen it w as ﬁ rs t h atc h ed. N eit h er o ne o f u s

e xp ecte d t h e d ru g t o r e ally w ork a t t h e le ve l t h at it e nded u p w ork in g.

T here w as t h is o ne c o m pound t h at s to od o ut, h ead a nd s h ould ers a bove t h e o th ers . It 'd k ill t h e

l e uke m ia c e lls a nd n ot h arm a ny n orm al c e lls .

D ru ke r c a lle d h is d ru g Im atin ib , la te r k n ow n b y it s t r a de n am e G le eve c. F ir s t, in a P e tr i d is h , t h en in

m ic e , t h e d ru g s e em ed t o w ip e o ut a ny t r a ce o f C M L c e lls .

N ow , w e h ad a lo t m ore e xp erim ents t o d o, b ut it w as r e ally e xcit in g t o a ctu ally s e e a c o m pound t h at

w as d oin g w hat I h ad h oped a c o m pound c o uld d o. T hat w as a lm ost t o o g ood t o b e t r u e.

B ria n a nd I t o ok it u pon o urs e lv e s t o c o nvin ce N ova rtis t h at t h is d ru g h ad t o b e t e ste d in p atie nts .

T hat w as t w o o r t h re e y e ars h am merin g a t g ettin g t h is d ru g in to c lin ic a l t r ia ls . A nd it w as a n u phill

b attle . I h ad s o m eth in g t h at m ig ht b e a ble t o w ork f o r t h em . It n eeded t o g et a t r y. If it d oesn 't w ork ,

ﬁ ne. I'll g o a w ay, y o u'll n eve r h ear f r o m m e a gain , b ut g iv e it a c h ance .

B ria n D ru ke r a nd D ennis S la m on w ere in t h e v a nguard o f a n ew g enera tio n o f d octo r r e se arc h ers

w hose p ers is te nce b ro ke t h e b arrie r b etw een r e se arc h a nd t r e atm ent.

B ein g in vo lv e d in t h ose e arly s tu die s, t h at s h ow ed u s t h at y o u c o uld t a ke t h is r e ally b asic s c ie nce

r e se arc h a nd t r a nsla te it f r o m a la b in to t h e c lin ic , a nd t a ke c lin ic a l q uestio ns a nd b rin g it in to t h e la b

a nd y o u'd g et a nsw ers , w as r e ally t h e w hole p ro m is e o f t h is n ew a ppro ach .

B y t h e s p rin g o f 1 993, t h e in it ia l t r ia l o f t h e b re ast c a nce r d ru g H erc e ptin h ad e nded, a nd S la m on w as

r e ady t o s h are B arb ara B ra dﬁeld 's r e su lt s w it h h er.

T he d oor s u ddenly ﬂ ew o pen, a nd h e a nd h is a ssis ta nt c a m e w alk in g in , w it h t h e b ig gest g rin s o n t h eir f a ce s, a nd s a id , t h ere is n o m ore c a nce r. M y h usb and a nd I lo oke d a t e ach o th er a nd w e s a id , t h ere 's

n o m ore c a nce r. A nd D ennis s a id , c o m e o n, I'll t a ke y o u d ow n t o r a dio lo gy, a nd y o u c a n lo ok a t t h e

s lid es.

S o w e w ent d ow n, a nd w e lo oke d a t t h e s c re ens. A nd h e p oin te d o ut, h ere 's t h e 1 6 t u m ors in y o ur

l u ngs. N ow lo ok o ve r h ere . N ot t h ere . W e d id n't q uit e k n ow w hat t o d o w it h t h at in fo rm atio n, a nd

n eit h er d id D r. S la m on. H e s a id , t h is is n ew g ro und f o r u s. W e d on't k n ow if y o ur c a nce r w ill b e b ack in

t h re e m onth s. W e d on't k n ow if it 's r e ally c u re d. Ju st g o h om e, a nd e njo y lif e .

B arb ara B ra dﬁeld 's r e m is sio n w as a ﬁ rs t in t h e h is to ry o f c a nce r t h era py. N eve r b efo re h ad a c a nce r

c a usin g o nco gene b een id entiﬁ ed a nd s u cce ssfu lly t a rg ete d. B ut t h is w as o nly a ﬁ rs t s te p, a s m all

s ta ge o ne c lin ic a l t r ia l. G enente ch a nd S la m on w ould n eed t o t r y H erc e ptin in m any m ore p atie nts ,

b efo re t h ey c o uld b e s u re it w as w ork in g.

O f c o urs e , y o u a lw ays w orry , is t h is t h e o ne o ﬀ e xa m ple , a nd it w on't b e r e peate d w hen y o u g o t o a

l a rg er p hase t w o t r ia ls .

A s S la m on a nd G enente ch p re pare d f o r a w id er c lin ic a l t r ia l, n ew s o f H erc e ptin 's e arly s u cce ss h ad

a lr e ady le ake d o ut.

D octo rs a re c a llin g it a b re akth ro ugh.

A p ro m is in g, b ut s till u npro ve n d ru g.

A d ru g t h at c o uld m ean a s ta y f o r s o m e w om en f a cin g a p ossib le d eath s e nte nce .

S oon G enente ch w as in undate d w it h c a lls a nd le tte rs f r o m w om en w ho w ante d t h e d ru g.

T his w as a bso lu te ly a v a lid q uestio n, w hic h is , lo ok, w e'r e d yin g o ut h ere . T his is a s e rio us illn ess, a nd

y o u h ave a m edic in e t h at c o uld h elp m e.

T he d ru g r a is e s h opes f o r t h e f u tu re , b ut h elp s o nly a h andfu l o f t h e w om en w ho n eed it n ow .

B eca use t h ey n eeded t o d o a w id er t r ia l ﬁ rs t, t h e c o m pany r e fu se d.

T he c o m pany w ante d t o f o cu s o n t h e c lin ic a l t r ia ls , a nd t h ey w ante d p atie nts t o e nro ll in t h e t r ia ls , n ot

t o g et t h e d ru g o uts id e o f t h e t r ia ls .

I f y o u d on't c a rry o ut t h at v e ry c a re fu l c lin ic a l p ro ce ss, y o u c a n't lo ok b ack a t t h e e nd a nd s a y, w it h

a ny c o nﬁdence , t h at I k n ow t h is d ru g w ork s. I t 's a t e rrib le r e alit y t h at m edic in e, w hic h is t h e m ost h um an o f a ll t h e s c ie nce s, is c a ught p erfo rm in g

t h e le ast h um an o f a ll e xp erim ents -- w hic h is t o d eny p atie nts m edic in es, e ve n w hen t h ey s e em t o b e

s u cce ssfu l in s m all t r ia ls . B ut it 's t h e r e alit y , a nd t h at is t h at t h ere h ave b een s o m any f a ls e le ads, t h at

d oin g s o m eth in g t o o e arly is a lw ays a f o rm ula f o r d is a ste r.

T he is su e c a m e t o a h ead a fte r a y o ung g yn eco lo gis t n am ed M arti N els o n r e la pse d w it h b re ast

c a nce r. N els o n w ante d t o e nro ll in t h e w id er c lin ic a l t r ia l o f H erc e ptin , b ut s h e w as r e peate dly d enie d.

W e k e pt g ettin g t h e r u naro und, g ettin g o ne p ers o n b la m in g a noth er. T im e w as g oin g o n. S he w as

g ettin g s ic ke r a nd s ic ke r. B ut w e c o ntin ued t o a sk f o r t h e d ru g, a nd t h en M arti d ie d w it h out o ur e ve r

g ettin g a n a nsw er.

T he d eath o f M arti N els o n g alv a niz e d t h e b re ast c a nce r c o m munit y . In 1 994, d oze ns o f a ctiv is ts

c o nve rg ed o n G enente ch 's c a m pus.

T hey d ecid e t h at a s p art o f t h eir p ro te st, t h ey'r e g oin g t o h old a f u nera l p ro ce ssio n f o r M arti N els o n.

I t a bso lu te ly t o ok G enente ch b y s u rp ris e . If t h ey d id n't k n ow w ho w e w ere b efo re , a nd w hat t h e

b re adth o f o ur w illin gness t o e ngage in t h is is su e w as, t h ey c e rta in ly k n ew it a fte r t h at.

T he a ctiv is m t h at h ad b egun w it h R ose K u sh ner's o pposit io n t o r a dic a l m aste cto m y, a nd c o ntin ued in

t h e S TA M P t r ia ls , n ow r e ach ed a b oilin g p oin t.

F o r t h e ﬁ rs t t im e, y o u h ad a c o m pany t h at w as e ngaged in c a nce r r e se arc h , h avin g t o d eal w it h

p eople c h ain in g t h em se lv e s t o c a rs in t h e p ark in g lo t, a nd d em andin g a cce ss, a nd b ein g in f r o nt o f

t h e n ig htly n ew s. T hat ju st h ad n ot h appened in c a nce r.

D esp era te t o r e so lv e t h is im passe , G enente ch e xe cu tiv e s s a t d ow n w it h b re ast c a nce r a ctiv is ts in

1 995. T he n egotia tio n e nded w it h a c o m pro m is e . T he c o m pany a gre ed t o p ro vid e s m all a m ounts o f

H erc e ptin t o w om en o uts id e t h eir t r ia l o n t h e b asis o f a lo tte ry. It w asn 't a p erfe ct s o lu tio n, b ut it

b ro ught a n e nd t o t h e p ro te sts .

I n 1 997, t h e t r ia ls w ere ﬁ nally c o m ple te . S usa n D esm ond-H ellm ann w as o ne o f t h e ﬁ rs t G enente ch

e xe cu tiv e s t o h ear t h e r e su lt s .

I h ung u p t h e p hone a nd lit e ra lly r a n a s f a st a s I c o uld , d ow n t h e h ill, t o t h e b uild in g w here A rt's o ﬃ ce

w as, r a n u p t h e s ta ir s , r a n in h is o ﬃ ce , c lo se d t h e d oor. A nd I g ot o n t h e b oard -- h e h ad a w hit e b oard

i n h is o ﬃ ce -- a nd I d re w t h e s u rv iv a l c u rv e o f t h e p atie nts in t h e t r ia l, a nd s h ow ed h im t h e d ata t h at p atie nts h ad liv e d lo nger.

I n f a ct, H erc e ptin h ad e xte nded t h e liv e s o f w om en w ho h ad t a ke n t h e d ru g b y a n a ve ra ge o f 5 0%

o ve r t h ose w ho h ad n ot, w it h h ard ly a ny s id e e ﬀ ects . It w as o ne o f t h e m ost s ig niﬁ ca nt r e su lt s in t h e

h is to ry o f c a nce r m edic in e.

W hat g ets y o u t h ro ugh w ork is t h e d ata . W e t a lk a bout h ow d o y o u ﬁ ght w hat m ay b e a n u phill b attle ,

o r lo ok lik e a n u phill b attle . It 's ju st a n u nﬂaggin g b elie f in t h e d ata . A nd I t h in k y o u h ave t o b e y o ur

o w n w ors t c rit ic , b ut if t h e d ata k e eps c o m in g b ack t e llin g y o u t h is is r e al, t h is is r ig ht, t h is is t h e w ay

t o g o, t h en y o u h ave t o b elie ve it .

T he n ext y e ar, w e d id t e sts a gain , a nd m y c a nce r w as s till a ll g one. A nd it 's n eve r c o m e b ack.

C ance r's a f u nny t h in g, b eca use o nce y o u h ave it , it s it s lik e a lit tle m onke y o n y o ur s h ould er. It n eve r

g oes a w ay. It 's b een 2 0 y e ars , a nd it 's s till p art o f m y p sy ch e. A nd it c h anges w ho y o u a re . T here 's a

l it tle e le m ent o f f e ar t h at n eve r g oes a w ay.

S o t h is is t h e ﬁ rs t v is it s in ce s u rg ery , r ig ht? If y o u c a n c o m e o n u p o n t h e b ed, h ere .

O h, s o m eth in g s w eet.

S o g o a head a nd r e m ove e ve ry th in g f r o m t h e w ais t u p o ﬀ , p ut t h e g ow n t h at's b ehin d y o u o n--

o penin g t o w ard s t h e f r o nt, a nd t h en D r. G iu lia no w ill b e r ig ht in .

A w eek a fte r h er s u rg ery , L o ri is m eetin g w it h D r. G iu lia no t o r e ce iv e t h e p ath olo gy r e su lt s . T hey w ill

s h ow w heth er t h e c h em oth era py a nd s u rg ery h ave c o m ple te ly e ra dic a te d t h e c a nce r f r o m h er b ody.

I w as c h om pin g a t t h e b it t o g et t h e p ath olo gy. A nd I c a lle d t h e p ath olo gis t, a nd h e w as v e ry e xcit e d,

a nd t o ld m e t h at w e h ad a c o m ple te r e sp onse .

O n t h e r ig ht, n o t u m or a t a ll.

O h m y g osh .

A nd o n t h e le ft, a ll t h e ly m ph n odes w ere f r e e, a nd t h at b ig g ia nt t u m or w as d ow n t o t h re e

m illim ete rs .

O h m y g oodness.

T he t h ought t h at it w ould w ork f o r a ll o f t h e b re ast c a nce r t h at I h ad, o n b oth s id es, a nd t h at w e'd h ave n o r e sid ual d is e ase o n o ne s id e, a nd m in im al r e sid ual d is e ase o nly in t h e b re ast o n t h e o th er

s id e, m akin g it a s u cce ss. T his w as n ot in a ny o f t h e s c e nario s t h at I t h ought o ut in m y m in d, t h at I

c o uld h ave a c o m ple te r e sp onse , o r t h at I- -

F a nta stic . A ll t h e ly m ph n odes w ere f r e e.

T hank y o u. T hank y o u s o m uch . I a ppre cia te it .

C om e o n o ut. G et d re sse d.

O K.

T hank y o u.

I t 's n ot w hat I e xp ecte d, b ut I w ill t a ke it . I w ill a bso lu te ly t a ke g re at n ew s lik e t h at.

O nce I h ad m y s u rg ery a nd h ad m y p ath olo gy, t h en t h at h elp ed m e s o lid if y a p ro gnosis . B ut in a ll

t h at, t h ere a re n o g uara nte es. A nd s o t h at's t h e g ra y a re a f o r m e. E ach t im e I h ave s o m eth in g t h at

m ayb e p op u p t h at p ro bably w ould n't h ave b een a n is su e a y e ar a go, I'll t h in k a bout, w ell, is t h is t h e

m om ent t h at I ﬁ nd o ut? Is t h is t h e m om ent t h at I p ote ntia lly c o uld h ave r e cu rre d?

I n Ju ne 1 998, B ria n D ru ke r w as ﬁ nally g iv e n t h e g o a head t o b egin c lin ic a l t r ia ls o n a d ru g f o r c h ro nic

m ye lo id le uke m ia . E ve ry s in gle p atie nt w e e nro lle d h ad t h eir b lo od c o unts r e tu rn t o n orm al. In t h e

c o nte xt o f t h e h is to ry o f c a nce r, w e e xp ect a 1 0% o r 2 0% r e sp onse r a te . T o s e e 1 00% r e sp onse r a te

w as u nheard o f, a bso lu te ly u nheard o f.

A t t h at p oin t, I k n ew w e h ad s o m eth in g t h at w as f u ndam enta lly d iﬀ ere nt t h an a ny o th er d ru g f o r t h is

l e uke m ia , b eca use it w as t r e atin g s o m ebody t h at n o o th er d ru g w as a ble t o c o ntr o l, a nd it d id it

r a pid ly a nd w it h out s id e e ﬀ ects , a nd it w as a o nce a d ay p ill. T hat w as a bso lu te ly a m azin g t o s e e.

T here 's a lo ve ly d esc rip tio n o f H erc e ptin a nd G le eve c a s t h e f o ur-m in ute m ile . B efo re R oger

B annis te r r a n t h e f o ur-m in ute m ile , t h ere w as a g ro up o f p eople w ho s a id , it 's n ot p ossib le t o r u n t h e

f o ur-m in ute m ile , b eca use h um an p hysio lo gy ju st is n 't b uilt t h at w ay.

A nd B annis te r h as d one it -- t h e m ile in t h re e m in ute s 5 9.4 s e co nds.

W hat h appens w hen y o u b re ak a r e co rd lik e t h at, is n ot t h at y o u b re ak t h e lim it . It 's t h at y o u b re ak

t h e o f a lim it . A nd in o nco lo gy, t h e id ea o f t h e lim it w as y o u c o uld n ot d esig n a d ru g t h at w as s p eciﬁ c f o r a c a nce r c e ll.

I n t h e e nd, t h is v a lid ate s t h e 2 5-y e ar s e arc h . It 's t h e b egin nin g o f t a rg ete d t h era py, it 's t h e b egin nin g

o f c h angin g t h era py c o m ple te ly in c a nce r. A nd it s a ys t h at a ll t h at r e se arc h t h at w as d one f o r 2 5

y e ars o n h am ste rs , a nd m ic e , a nd t h e t is su e c u lt u re c e lls , a nd t h en t r a nsit io n t o h um ans, a nd a ll t h e

i n fo rm atio n w e g ot, is n ow b ein g u se d t o m ake d ru gs, is n ow b ein g u se d t o h elp p eople .

I t w as t h e p ro of o f p rin cip le t h at, y e s, t h is is g oin g t o w ork . T a rg etin g o nco genes is w ork in g. A nd w e'll

m ake a d is e ase t h at is le th al t o d is e ase t h at is c u ra ble .

F o ur, t h re e, t w o, o ne. H appy 2 000.

A s t h e 2 0th c e ntu ry c a m e t o a n e nd, g re at s tr id es h ad b een m ade in t h e c e ntu rie s-o ld s tr u ggle

a gain st c a nce r. T he n ew d ru gs H erc e ptin a nd G le eve c s h ow ed t h at t h e d is e ase m ig ht b e s to pped b y

t a rg etin g s p eciﬁ c o nco genes. R ese arc h ers a ls o n ow k n ew t h at d iﬀ ere nt t y p es o f c a nce r w ere c a use d

b y g enetic m uta tio ns. A nd it s e em ed p ossib le a c u re c o uld s o on b e f o und f o r e ach .

A nd t h ere w as s till a noth er r e aso n f o r h ope. S cie ntis ts f r o m a ro und t h e w orld w ere a lr e ady

c o lla bora tin g o n w hat w ould b eco m e o ne o f t h e la rg est s c ie ntiﬁ c p ro je cts in h is to ry , w it h m ajo r

i m plic a tio ns f o r c a nce r r e se arc h -- t h e m appin g o f a ll t h e g enes in t h e h um an b ody. B ut lim it e d

s u cce ss d id n ot g uara nte e u lt im ate t r iu m ph.

I n m edic in e, t h ere 's a lw ays s e lf- d elu sio n. T his is it s g re ate st s tr e ngth , a nd it s o ld est s in . Y o u a lw ays

w ant t o b elie ve . If y o u b eco m e t o o in ure d t o t h e p ossib ilit y o f s u cce ss, t h en y o u lo se a ll y o ur p assio n--

y o u b eco m e a r o bot. O n t h e o th er h and, if y o u b elie ve t o o m uch , y o u b eco m e a m onste r, r ig ht? A nd

s o m ew here in b etw een lie s t h e r e al w is d om o f c lin ic a l m edic in e.

S cie ntis ts h oped t h ey h ad ﬁ nally f o und t h e r o ad t o v ic to ry. B ut n o o ne c o uld im agin e t h e n um ber o f

t w is ts a nd t u rn s t h at s till la y a head.

[ 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.