The New York Times Magazine - May 15, 2016

T H E H E A LT H I S S U E
May 15, 2016
THE NEW
1900 S
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OF
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CANC E R
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A WAVE OF NEW
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IN THE PAST DECADE,

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May 15, 2016 T H E H E A L T H I S S U E
T HE NEW ANATOM Y O F
CANCER
42
SECTION PA G E
DOCTOR WITHOUT BORDERS 1 42

For an oncologist in an era of rapidly proliferating, precisely targeted treatments, every case is an improvisation.
By Siddhartha Mukherjee
THE LAZARUS EFFECT 2 48

Most clinical trials for cancer drugs are failures. But for a handful of patients, a drug proves to be profoundly
effective. What can science learn from these exceptional responders? By Gareth Cook
W R I T T E N O N T H E B O DY 3 54
For decades, science has classified cancers by the organ or system in which they begin. That taxonomy is slowly
being replaced but its still the indispensable way to understand the odds. By Ryan Bradley
T H E S H A R K A N D T H E L I G H T N I NG 4 60
Andrew Levys parents knew that the rare and deadly cancer in his blood could not be beaten, so they began
to prepare for the worst. Then something mysterious happened. By Melanie Thernstrom
STA RV I NG T H E B E A ST 5 64
In the early 20th century, the German biochemist Otto Warburg believed that tumors could be treated
by disrupting their source of energy. His idea was dismissed for decades until now. By Sam Apple
STA N DA R D O F C A R E 6 68
At a Catholic nursing home in New York, the sisters who treat the untreatable. Photographs by Gillian Laub
6 Continued on Page 10

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May 15, 2016 T H E H E A L T H I S S U E
17 20 26
FIRST WORDS ON MONEY WELL

Online, we present ourselves in Venture capitalists still deny theyre
It may be better to give up
ever-more-numerous guises across a variety in a bubble. But the signs
your bad habits all at once, rather
of platforms. What does the avatar and the potential consequences are
than one at a time.
we choose say about who we really are? becoming harder to ignore.
BY GRETCHEN REYNOLDS
B Y A M A N DA H E S S B Y G I D E O N L E W I S - K R AU S
28 32 34
LETTER OF
THE ETHICIST E AT
R E C O M M E N D AT I O N
Is it O.K. to get a dog
Think of them not as A roasted salad that is
from a breeder, not a shelter?
topographical maps, but as incredibly crisp and yielding all at once.
B Y K WA M E
aordable Pollocks. BY SAM SIFTON
ANTHONY APPIAH
B Y T O M VA N D E R B I LT
36 39 82
DIAGNOSIS LIVES TA L K
His pounding head and tight chest The hip-hop producer and
Feeling the eects of alcohol,
were so painful that the patient didnt record-label executive DJ Khaled is
and of breaking all the rules, in Tehran.
pay enough attention to the extra careful around Beyonc.
most important symptom of all. ELLIE H., AS TOLD
I N T E RV I E W
TO NARGES BA JOGHLI
BY LISA SANDERS, M.D. B Y A N A M A R I E C OX
Previous page: Photograph of the infusion area, where patients undergo CONTRIBUTORS 12
chemotherapy, in the Herbert Irving Cancer Center at NewYork-Presbyterian/ THREAD 14
Columbia by Kirsten Luce for The New York Times. Cover and Page 41: POEM 24
JUDGE JOHN HODGMAN 28
Cancer cell from National Cancer Institute. Cover timeline photographs, top
TIP 33
to bottom: Hulton Archive/Getty Images; Scimat Scimat/Getty Images; U.S.
PUZZLES 78, 80
National Library of Medicine; National Cancer Institute. PUZZLE ANSWERS 76
10 Copyright 2016 The New York Times

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When one didnt exist,
Dana-Farber
created a pathway
to treat children with
rare brain cancers.
Researchers at Dana-Farber have been studying some of the rarest and most dangerous childhood brain cancers, hoping
to develop new, more effective approaches to treatment. Our work with cancers like DIPG, a brain stem glioma that affects
only 200 children each year and AT/RT, a lethal brain tumor that affects 100 annually, is creating a better understanding
of how to attack these diseases. Taking on rare childhood cancers has helped us open new pathways in the study of
many adult cancers as well, including ovarian, breast, colon and possibly pancreatic cancer. While the biology of cancer
remains complex, we believe even small steps can lead to giant leaps forward toward a brighter future for our children,
and for everyone.
See videos, whitepapers and more at DiscoverCareBelieve.org/DIPG.
2015 Dana-Farber Cancer Institute

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Contributors
Siddhartha Doctor Without Borders, Editor in Chief JAKE SILVERSTEIN
Mukherjee Page 42 Deputy Editors JESSICA LUSTIG,

BILL WASIK
Managing Editor ERIKA SOMMER
Siddhartha Mukherjee, a cancer physician
Design Director GAIL BICHLER
and scientist at Columbia University, won the
Director of Photography KATHY RYAN
2011 Pulitzer Prize for nonfiction for his book
Features Editor ILENA SILVERMAN
The Emperor of All Maladies: A Biography of Politics Editor CHARLES HOMANS
Cancer. His new book, The Gene: An Story Editors NITSUH ABEBE,
Intimate History, will be published this month. MICHAEL BENOIST,
In this issue, Mukherjee writes about how SHEILA GLASER,
cancer treatments are becoming more tailored CLAIRE GUTIERREZ,
to the individual patient. While writing this, LUKE MITCHELL,

DEAN ROBINSON,
I began to remember what it was like to train
WILLY STALEY,
as an oncologist a decade and a half earlier,
SASHA WEISS
when we were learning such surprising things
Associate Editors JEANNIE CHOI,
about cancer, Mukherjee said. And then
JAZMINE HUGHES
there was a shiver of delight, thinking about Chief National Correspondent MARK LEIBOVICH
Photographed by Kathy Ryan at The New York Times on May 4, how, perhaps a decade from now, a new Staff Writers SAM ANDERSON,
2016, at 3:13 p.m. group of doctors and scientists will read this EMILY BAZELON,
article and wonder about our time. SUSAN DOMINUS,
MAUREEN DOWD,
Sam Apple Starving the Beast, Sam Apple is the author of the memoir American NIKOLE HANNAH-JONES,
Page 64 Parent and teaches journalism at the University WESLEY MORRIS,

JENNA WORTHAM
of Pennsylvania.
Writers at Large C. J. CHIVERS,
JIM RUTENBERG
Ryan Bradley Written on the Body, Ryan Bradley is a writer based in Los Angeles.
David Carr Fellow GREG HOWARD
Page 54 He last wrote for the magazine about how Art Director MATT WILLEY
experts predict the future. Deputy Art Director JASON SFETKO
Designers FRANK AUGUGLIARO,
Gareth Cook The Lazarus Eect, Gareth Cook is a contributing writer for the BEN GRANDGENETT
Page 48 magazine and a Pulitzer Prize-winning journalist. Digital Designer LINSEY FIELDS
He last wrote about the mathematician Terry Tao. Associate Photo Editors STACEY BAKER,
AMY KELLNER,
CHRISTINE WALSH
Cristiana Couceiro Written on the Body, Cristiana Couceiro is an illustrator based
Page 54 Virtual-Reality Editor JENNA PIROG
in Lisbon.
Photo Assistant KAREN HANLEY
Copy Chief ROB HOERBURGER
Lucas Foglia The Shark Lucas Foglia is a photographer based in San Copy Editors HARVEY DICKSON,
and the Lightning, Francisco. His second book, Frontcountry, was DANIEL FROMSON,
Page 60
published by Nazraeli Press. MARGARET PREBULA,
ANDREW WILLETT
Brooke Jarvis Standard of Care, Brooke Jarvis is a contributing writer for The Head of Research NANDI RODRIGO
Page 68 California Sunday Magazine and a finalist for the Research Editors NANA ASFOUR,
2016 Livingston Award for International Reporting. DAN KAUFMAN,

ROBERT LIGUORI,
RENE MICHAEL,
Gillian Laub Standard of Care, Gillian Laub is a photographer based in New
LIA MILLER,
Page 68 York. Her documentary on race relations in Georgia,
STEVEN STERN,
Southern Rites, recently premiered on HBO.
MARK VAN DE WALLE
Production Chief ANICK PLEVEN
Melanie Thernstrom The Shark Melanie Thernstrom is a contributing writer for Production Editors PATTY RUSH,
and the Lightning, the magazine and the author, most recently, of HILARY SHANAHAN
Page 60
The Pain Chronicles. Editorial Assistant LIZ GERECITANO BRINN
Publisher: ANDY WRIGHT Associate Publisher: DOUG LATINO Advertising Directors: JACQUELYN L. CAMERON (Advocacy) MICHAEL GILBRIDE (Fashion and Luxury) SHARI KAPLAN (Live Entertainment and Books)
NANCY KARPF (Fine Arts) MAGGIE KISELICK (Automotive, Technology and Telecom) SCOTT M. KUNZ (International Fashion) SHERRY MAHER (Department Stores, Beauty and American Fashion) CHRISTOPHER
REAM (Studios) JASON RHYNE (Recruitment) JOHN RIGGIO (Legal Branding) JOSH SCHANEN (Media and Travel) SARAH THORPE (Corporate, Health Care, Education, Liquor and Packaged Goods) BRENDAN
WALSH (Finance and Real Estate) National Sales Office Advertising Directors: KYLE AMICK (Atlanta/Southeast) JACQUELYN L. CAMERON (Washington) LAUREN FUNKE (Florida/Southeast) DOUG LATINO (Detroit)
CHRISTOPHER REAM (Los Angeles/San Francisco/Northwest) JEAN ROBERTS (Boston/Northeast) JIMMY SAUNDERS (Chicago/Midwest) KAREN FARINA (Magazine Director) LAURA BOURGEOIS (Marketing
Director, Advertising) MICHAEL ANTHONY VILLASEOR (Creative Director, Advertising) MARILYN M C CAULEY (Managing Director, Specialty Printing) THOMAS GILLESPIE (Manager, Magazine Layout) CHRIS RISO
(Publishers Assistant). To advertise, email karen.farina@nytimes.com.
12 5.15.16

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The Thread
Readers respond to the 5.1.2016 issue. has no such intention of surrendering to collective bargaining, Worcester was in
foreign economic competitors? the forefront of cities that suppressed it.
RE: THE OBAMA RECOVERY Andrea Economos, Scarsdale, N.Y. Tom Reney, Holyoke, Mass.
Andrew Ross Sorkin interviewed President
Barack Obama about his economic legacy. I was excited by the cover question: Why As leaders investing in the future of our
Do So Many Voters Feel Left Behind? city and its residents, we read with great
It takes far too much eort to follow the I opened the magazine to begin to interest the history of the author Adam
dots for the vast majority of Americans. learn the answer. The rst eight pages of THE STORY, ON
Davidsons ancestors. We know Worces-
Those who feel a general uneasiness, even the issue were a glossy spread describing TWITTER ter today as a college town and a hub for
as they know it is not as bad as it was, the Hudson Yards residences in Manhat- innovation, education and jobs in health
A mobile alert that
believe it is not as good as it used to be tan, inviting your readers to Be a part @andrewrsorkin
and biotech, robotics, advanced manufac-
and blame the president for what they of it. Why do so many voters feel left got an interview with turing and data science, among others, as
sense is a far too tepid recovery. out? An ad asking, Hey, want to buy a Obama? I dont well as a vibrant arts and cultural scene.
It matters not that the Republicans $16,000,000 four-bedroom apartment? think so, New York With a steady approach to private
Times. Thats
orchestrated much of the slowness, that on Page 1 might be part of the answer. not a news alert. and public redevelopment, our city has
they forced austerity measures upon a Brad Robertson, Portland, Ore. Thats an ad. become a bright spot in New England,
nation crying out for an infusion of cap- @jayrosen_nyu and it is poised for future economic
ital. It is seemingly almost forgotten that growth. Hard work and opportunity
President Obama inherited an absolute will never go out of style in Worcester.
economic disaster and was called upon, Dreamers are welcome here, too.
in the face of unrelenting Republican Laurie A. Leshin, president of Worcester Poly-
obstructionism, to right a sinking ship. technic Institute, and Timothy P. Murray,
History will be the ultimate arbiter chairman of the Worcester Regional Chamber
for this president. It is a harsh and often of Commerce and former lieutenant governor
unfair image being portrayed, but it is of Massachusetts
almost impossible for the president to ask
the public to grasp that what he avoided
is, to a large degree, a measure of what
he accomplished.
Robert S. Nussbaum, Fort Lee, N.J.
President Obamas implication that the

oshoring of American jobs is irrevers- RE: WORCESTER, MASS.
ible demonstrates a surprising absence Adam Davidson investigated what happened
of appreciation for American economic to Worcester, a city that was once a haven
ingenuity. His lack of business experi- for people to experience the good life of the
ence and extensive experience in gov- middle class.
ernment sent him down a path of trying
to change other nations labor and envi- Adam Davidsons parallel tales of Worces-
ronmental standards instead of trans- ters legacy as an industrial powerhouse
forming our own domestic approach to and his own familys lineage in the city
business development. left me wanting more detail about the CORRECTIONS:
Is it any wonder that Americans are place that lies at the heart of the com- An introduction to the Money Issue on May
ocking to a presidential candidate who monwealth. Davidson says that, during 1 referred incorrectly to Websters dictio-
its boom years as a manufacturing cen- nary. It was Noah Webster who created it,
ter, just about anybody willing to put not Daniel Webster.
in a hard days work could get a job
on the shop oor. My understanding, An article on May 1 about the representation of
though, is that Worcester factories paid the middle class on TV misspelled the surname
enough to foster a middle class because It is almost of an actress featured in an episode of Horace
they required a skilled work force. To this forgotten and Pete. She is Laurie Metcalf, not Metcalfe.
end, Worcester was a leader in establish- that President
Photograph by Katy Grannan
ing trade schools to train mechanics and Because of an editing error, a tweet featured in
machinists, and Worcester Polytechnic Obama the mail column on May 1 carried an incor-
Institute, the citys prestigious science inherited rect handle for a reader who commented on
and engineering school, was founded an absolute a recent article on Minecraft. It is @chaykak,
by local manufacturers. They also paid not @chayak.
enough to keep labor unions at bay. economic
During the century that saw the rise of disaster. Send your thoughts to magazine@nytimes.com.
14 5.15.16 Illustrations by Tom Gauld

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First Words
Online, we present ourselves in ever-more-numerous guises across a variety of platforms.

What does the avatar we choose say about who we really are? By Amanda Hess
Self Portrait
Every time I send an email, I see myself staring back at me. I always
have a slight, knowing smile on my face, even if the content of my email
is confused, distressed or brimming with unrestrained glee. I chose
the image (maybe unconsciously) because it seemed professional and
direct, and also because my hair looked good. Smug email me is not
my only online incarnation. There are dozens more of my avatars
scattered across the web. The word avatar originates in Hinduism,
where it refers to a god descending to the earth in mortal form. In
Hindu theology, Vishnu assumes various earthbound avatars
among them a sh; a tortoise; a half-man, half-lion in an eort
to restore order at times when humanity has descended into chaos.
Now were the gods, reinventing ourselves online in the hope of
bringing order to a realm we cant quite keep under our control.
Our avatars represent a self-image thats fractured across dozens
of sites and text bubbles and email chains. We present ourselves
dierently on Twitter and Tumblr and Slack depending on the
norms built into each space. On Facebook, Im posed by a professional
5.15.16 17

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First Words
photographer, waist contorted into a

slimmed line, eyes peering up out the
window of a skyscraper. On Snapchat,
Im burrowed into my oce chair, blankly
blinking my eyes open and closed. On
Candy Crush, Im a cartoon man-otter. I
dont particularly know why Ive selected
these avatars as my representatives; its
some combination of my read on the plat-
forms sensibility, my emotional state at
the time of upload and the suite of photos
I had on my phone at that moment.
But as I traverse the Web, I naturally
scan for subtle clues in the avatars cho-
sen by friends and strangers, reading
their U.S.A.-themed scrapbooks and
cat GIFs like leaves at the bottom of a
teacup. On Twitter, an avatar ipped to
Beyonc in Lemonade or Prince reads
like a pledge to a newly materialized
online club; a bizarre cartoon points to a
person who tweets frequently and with
open self-loathing; an unhatched egg
that appears automatically upon prole
creation has become its own anti-avatar
avatar. The latest avatar trend turns you
into a cartoon character in your own life.
With the Bitmoji app, you can conjure a
comic-strip image of yourself to emote
over email, Twitter and text. And Mii-
tomo, a new mobile game from Ninten-
do, makes the gamication of our social
lives explicit in it, when your impish
avatar socializes, you win piles and piles
of digital coins for your trouble.
Before avatars became a technological, and Neal Stephensons breakout novel, If an avatar for Habitat, the early online community
almost bureaucratic form of self-presenta- Snow Crash, in 1992, about a futuristic, was billed as a place full of drama and
tion, avatar was used to single out a rarer anarcho-capitalist Los Angeles in which was once adventure, where each user could seize
embodiment of culture and art. As Britain people projected themselves into a virtual a projection of the rare opportunity to reect his real
colonized the Indian subcontinent in the public square called the Metaverse. the human self-image, from toe to head. A player
19th century, the Hindu word became a The coincidence of a bunch of Ameri- could literally snap o his avatars head
fashionable metaphorical ourish among can video-game, fantasy and science-c- body and human and pop a new one on.
the British literati. In The Life of John Mil- tion authors cribbing from Hinduism values, as the The technological co-opting of the
ton, a seven-volume work published from 101 speaks to the need to describe a truly Internet grew word replicated the power dynamic in the
1859 to 1894, the literary critic David Mas- novel phenomenon. But it also hints at original avatar myth the avatar helps a
son conjured avatar to anoint poets who a similar worldview among the men in popularity higher being interact with a lesser realm,
embodied the spirit of the time, elevating and they were all men who came to it was flattened one he or she controls. But it also retained
them into something like gods among dene it. As Stephenson told me, That into a mask. the idea of the avatars task of delivering
men. A century later, the word jumped was a time when people had more ide- righteousness to a lawless world. Richard
from writers who captured the spirit of alistic notions of what digital technol- Garriott, creator of the Ultima games, said
the age to geeks who did the same. ogy was going to do for us, sometimes he came across the Hindu concept while
The technological use of avatar bordering on the mystical. For socially looking for a way to encourage moral
emerged via a spontaneous burst of coin- marginalized science-ction fans and behavior in gaming. He was disturbed by
ages in the late 1980s and early 90s, at the computer geeks, the virtual world could players who took the easiest possible route
dawn of personal computing. It appeared help people enjoy a level of social status to win the game. They werent acting like
in the video game Ultima IV: Quest of and acceptance they lacked at home. heroes, Garriott told me. They would kill
the Avatar in 1985; the dial-up computer Using a computer granted them a level all the local villagers if it meant gaining
community Habitat in 1986; the tabletop of godlike power, because they had skills enough power to kill the bad guy. So Gar-
role-playing game Shadowrun in 1989; most people lacked. In advertisements riott started framing his hero as an avatar
18 5.15.16 Illustration by Javier Jan

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instead of a character. He served players
with a personality test to imbue the ava-
tar with the players own attributes and
build elements of personal accountability
into the gameplay. In James Camerons
2009 lm Avatar, another avatar injects
human empathy into a virtual interaction.
In the lm, an ex-Marine sent to colonize
the planet Pandora grows to identify with
its native people through his occupation
of a body that looks and feels like theirs.
But if an avatar was once a projection
of the human body and human values, as
the Internet grew in popularity it was at-
tened into a mask. It became the standard
term for a simple image that accompa-
nied a screen name in a chat room or dis-
cussion group. In discrete gaming worlds,
value systems were strangely authentic:
Everyone was building his or her mini-me
in the same system and playing by the
same rules. But in the mixed-use spaces
of the Internet where some people
were playing themselves and others were
hoping to play tricks avatars became
ambiguous. Bad actors could sulk under
the cover of the Web while they pasted
reputation-killing content on a message
board or terrifying threats on Twitter.
Avatars became tools for stoking chaos
instead of enforcing order.
When social networking arose, mam-
moth platforms like Facebook and Linked-
In chose to strip the mask away. The idea of
the avatar doesnt factor into their self-con-
ception, and the word doesnt appear in
their promotional copy. These are plat-
forms with proles and accounts.
On Facebook, youre supposed to just be
you no particular technological prow-
ess required, and no avatar necessary to
translate yourself to the new medium.
Thats the new tech fantasy, anyway. But
of course, on Facebook, our prole pic-
tures are avatars, too: emblems of our suc-
cess, our good grooming, our unappable
happiness. In fact, proliferating online
platforms have prompted us to create
more and more conceptions of ourselves
to send o into the world. Showing up,
looking good, being clever and seeming
like you really care in all these dierent
spaces can feel like a video game set to
the hardest level, except you only get one
life. In Sanskrit, avatar is related not only
to descending; it also means to make
an appearance. When that becomes too
much, your avatar a being who is end-
lessly malleable takes over.

P r e s s R e a d e r. c o m +1 604 278 4604
On Money By Gideon Lewis-Kraus
When Silicon Valley venture capitalists

Venture capitalists still deny theyre get themselves into image trouble, its
usually because theyve been too candid
in a bubble. But the signs and with their low estimate of other peo-
ples intelligence. For example, after
India recently prevented Facebook
the potential consequences are from offering free Internet service
there, Marc Andreessen suggested in
becoming harder to ignore. a tweet that the subcontinent might be

better off had it remained under colo-
nial administration. Its much less com-
mon for V.C.s to soil their own nests
in public. So it came as something of a
surprise when Chamath Palihapitiya
Sri Lankan war refugee, early Facebook
employee, investor in Slack and Box,
part owner of the Golden State War-
riors told Vanity Fair in March that
if we are in fact in the early stages of a
second tech collapse, venture capitalists
have only their own mediocre, clubby
selves to blame. They should, he said,
focus on using capital as a way to take
really big bets on things that just seem
totally audacious. Right now we havent
done enough of that, and the result is
that most of the things weve funded
are mostly crap and largely worthless.
It was a striking admission. This large-
ly worthless start-up scene, according to
the research rm CB Insights, has raised
an estimated $238 billion over the last ve
years a remarkable bull run in private
technology stocks. Forbes reports that
there are now close to 200 unicorns,
to use the Valley term of art for private
companies worth more than a billion dol-
lars on paper. Since the nancial crisis,
these companies, along with their more
established public predecessors, have
been seen by many Americans as the
last redoubt of condence and produc-
tivity in an otherwise uneven recovery.
V.C.s have spent years dismissing spec-
ulation about a private-equity bubble as
merely an expression, by know-nothing
spectators, of resentment and alarmism;
media onlookers, they argue, should talk
instead about the triumphal progress of
the genuinely great start-ups as they try
to solve our most dicult problems. Over
the past year, however, as allegations of
mismanagement and unsustainability
have grown Square went public for
approximately half its last private val-
uation; Fidelity and other large mutual
funds wrote down their positions in
Dropbox, MongoDB, and Snapchat; and
both Zenets and Theranos were accused
20 5.15.16 Illustrations by Andrew Rae Next Week: On Technology, by Jenna Wortham

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On Money
of deceptive practices that condence Where they diered from the naysay- a limited-edition private oer to join the
has come to look more like hubris. ers, however, was in their rating of the scarce ranks in a special purpose vehicle
This past January, after a long autumn causes and consequences; the fault, they that bears all the risks of one company
of minor misfortune left the market in a said, didnt belong to the technological with none of the hedging benets of a
stall, I spent a week loitering in the com- elite but to everybody else: What has portfolio. Dumb money is those pinkish
mand concourse of American V.C., Sand driven inated valuations, in a time of guys with bull necks in Zegna suits. The
Hill Road in Menlo Park, Calif., where extremely low interest rates and meager weird thing about dumb money, unfor-
the soft, spruce-ltered sunlight falls returns elsewhere, is dumb money, all tunately, is that it can act with endish
through plate glass into quiet oces of the alien capital that has owed into the intelligence, insisting on stipulations that
beige on beige. There was some selec- Valley in recent years. Dumb money is a guarantee returns at the expense of found-
tion bias at work, as all my introductions hedge-funder whos jealous of a V.C. Dumb ers, employees and other investors.
were brokered by a smart and thoughtful money is sovereign wealth. Dumb money Luckily for the American economy, the
friend, but not a single investor I talked is an Emirati home oce. Dumb money is dumb money this time around is no longer
to t the description of the supercilious a Facebook millionaire in a Maserati who a mob of deluded pensioners waist-deep
techno-optimist and most, in private, wants to look like a player. Dumb money in Webvan. (Its also, the V.C.s noted, a lot
didnt hesitate to concede Palihapitiyas wants to get in on tech because its a box less money in total, and at least in theory
point. Of course they believed private to check o. Dumb money isnt in it for the its coming from people who can aord the
valuations had become preposterous; long run. Dumb money doesnt actually losses; the last dot-com crash erased an esti-
of course the run in private tech stocks care about the technology. Dumb money mated $6.2 trillion in household wealth.) So
couldnt possibly last; and of course, doesnt create value. Dumb money thinks Gideon Lewis-Kraus the coming correction will allow the smart
is a contributing writer
many start-ups, especially those of the what you lose on the margin youll make money to roll up its brushed-microber
for the magazine.
Uber for garden-gnome rearrangement up for in volume. Dumb money wants to Adam Davidson will sleeves and get back to basics. A lot of $10
variety, are in fact largely worthless. get in on Uber at any price, and will accept return next month. billion companies will become $1 billion
22 5.15.16 Illustration by Andrew Rae

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On Money
companies, and $1 billion companies will Venture capital a share in the wealth theyve created. Per- exploded bubble could very well mean
be acquired for $100 million, and the dumb haps worst of all, it betrays a callow belief that those totally audacious bets will go
money will slink away. Operating expens- increasingly that the genuinely transformative long- unfunded entirely. That might seem like a
es and burn rates will come way down, represents a term endeavors that V.C.s have come to satisfying comeuppance for the imperious
and companies that didnt worry about closed system support erstwhile academic research Valley, but its not something to be smug
protability or unit economics will. There into articial intelligence, bioengineering about. Smart money convinces itself of its
will be layos, sure, but the only serious a system where and sustainable energy will be somehow highly dierentiated intelligence at what
eects will be that the trac on I-280 will it is no longer insulated from an industry downturn. An might prove to be all of our expense.
no longer back up three exits, itll be easier so easy to
to get a table at the Village Pub and engi-
neers three minutes out of Stanford will no distinguish good Poem Selected by Matthew Zapruder
longer expect $150,000 a year and backlit money from bad.
fountains of complimentary fruit water. In a poem, it is possible to talk to someone who is dead, and maybe even to reach some
The main thing that has changed since kind of tentative, hard-won reconciliation or understanding. This poem is the nal entry
January is that very little seems to have of Sally Keiths collection about the loss of her mother.
changed. V.C. investment over the rst
quarter of the year has remained at, at
about $12 billion, from the nal quarter of
2015, though a ight to perceived quality
has caused both a drop in the total number
of deals and a concentration at the top. The
total number of tech I.P.O.s, however, was
zero. Yet the ood of money to the Valley
has not abated: according to The Wall Street
Journal, this has been the single biggest
fund-raising quarter for venture capital
since the (in retrospect) ominous year 2000. 63.
Bill Gurley, a partner in the rm Bench- By Sally Keith
mark Capital, recently published a blog
post in which he reminded his colleagues, I hear my mother on the phone. She says the moon is far away.
in a tone of exaggerated mildness, that The moon is white and full and underneath the water is black.
table stakes in the industry have perhaps The arc of light once marking the water by now is pared to a eck.
become too high. Loose capital allows
the less qualied to participate in each The moon is almost full, I correct, looking up
market. This less qualied player brings Where the moon hangs beside the untextured black of the branch.
more reckless execution, which drags even
The sky is dug. It deepens, a deepening blue.
the best entrepreneur onto an especially
sloppy playing eld. Despite warnings
When she tells me there is wind at the river, I know
like these, companies and V.C. rms have
continued to court as much of that loose The motorboat knocks at the dock.
capital as they still can; almost a decade
of aggressive growth strategy, by even the Where I am, it is still. The edge of the moon closest to the earth
most prudent, demands it. With an utterly Translucent, as if the smallest piece has been shaved from the back.
dead I.P.O. market, and no appetite among
the big public tech companies to acquire Between our two points, the land is long.
companies with bad balance sheets, ven- Her hair that was gray is almost all white.
ture capital is less liquid than ever, and thus
increasingly represents a closed system However deep the water is depends on the pull of the tide, depends
a system where it is no longer so easy to On the laws of the moon. It is barely dusk where I walk.
distinguish good money from bad. Silver glows on the antelope backs. The trees curl up around the creek.
Defenders of that system argue that all
they really need are the expected half-doz-
She is the mother. I explain the moon to her and she explains it back.
en mega-I.P.O.s (Slack, Palantir, Snapchat,
Uber, Airbnb) to make enough cash returns
to oset the losses. But that fantasy math
holds for only a tiny cohort of V.C. rms.
Matthew Zapruder is the author of four collections of poetry, most recently Sun Bear. He teaches at Saint
It also overlooks the well-being of tens of
Marys College of California and is editor at large at Wave Books. Sally Keith, an associate professor at
thousands of employees, especially sup- George Mason University, is the author of four collections of poetry, including, most recently, River House,
port sta, who have worked for years for published by Milkweed Editions in 2015.
24 5.15.16 Illustration by R. O. Blechman

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Well By Gretchen Reynolds
Out With the Old

It may be better to give up your bad habits all
at once, rather than one at time.
Experiments involving health and well-

being typically require their subjects to
change just one aspect of their lives. Focus-
ing on a single variable like diet or exer-
cise makes it simpler to collect data and
draw conclusions. But some researchers
at the University of California, Santa Bar-
bara, recently wondered if this minimalist
approach might be shortchanging peo-
ples potential to improve their health.
Maybe its better to address all of our bad
habits at once rather than try to make
incremental changes to our lives.
For their study, published in March in the
journal Frontiers in Human Neuroscience,
the researchers put 31 college students,
who tend to have exible daily schedules,
through a series of physical, cognitive
and emotional tests and gave them brain
scans. Roughly half the students served as
a control group and continued their daily
routines; the other half overhauled their
lives completely. Every morning, they
visited the school for an hour of supervised
stretching, resistance training and balance
exercises, followed by an hour of training
in mindfulness and stress reduction, which
included quiet walks and meditation. In the
afternoon, they exercised for an additional
90 minutes. Twice a week they completed
two interval-style endurance workouts on
their own. They attended lectures about
nutrition and sleep and kept daily logs
detailing their exercise, diets, sleep pat- generally exceeded by a great deal what One kind of measures of tness, mood, thinking skills
terns and moods. had been seen in many past experiments and well-being, even though none of them
After six weeks, the students retook the whose subjects altered only one behavior. change, like were still exercising or meditating as much
original tests. Those in the control group The studys authors suggest that one kind starting an as they did during the experiment.
showed no changes. But the others were of change, like starting an exercise regi- exercise Of course, this study couldnt isolate
substantially stronger, tter and more men, may amplify the eects of another, which elements of the lifestyle makeover
exible. They performed much better like taking up meditation. Whats more, regimen, may were essential, or how the various changes
on tests of thinking, focus and working the improvements persisted: According to amplify the inuenced one another. There were too
memory. They also reported feeling hap- Michael Mrazek, the director of research effects of many moving parts. Mrazek says that he
pier and calmer; their self-esteem was at the Center for Mindfulness & Human and his colleagues plan to tackle these
much higher. Their brain scans showed Potential at U.C.S.B. and the studys lead another, like issues in future experiments. For now, he
a pattern of activity believed to indicate author, another set of tests six weeks after taking up says, the results suggest that the limits
a greatly enhanced ability to stay focused. the experiments end showed that the meditation. of the human capacity for change may be
These improvements, especially on change-everything students still scored much greater than we, as scientists, have
measures of mood and stress reduction, much higher than they originally had on given people credit for.
26 5.15.16 Illustration by Sam Island

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P r e s s R e a d e r. c o m +1 604 278 4604
The Ethicist By Kwame Anthony Appiah
Is It O.K. to Get
and 1.2 million of them are euthanized. dogs may be a prejudice that would yield
Breeders kill shelter dogs chances is to a more careful exploration of the facts.
a message you see on signs and T-shirts. Settling that question requires more than
A Dog From
There is much to be said for adopting ethical expertise. But there is one ethical
a shelter dog; if every canine companion point here worth noting: Having a pref-
that died or ran away were replaced with erence for one kind of dog (or person) is
A Breeder, Not
one, the shelters would be pretty much not morally equivalent to being hostile
empty. But given that you are morally free to all others.
not to have a dog, you are morally free not
A Shelter?
to have a shelter dog. Though we should Having lived in Cameroon for two years
all support laws and policies that reduce and in Ghana for one year, I know that
animal suering, taking on a pet you dont you bargain for most purchases in those
want isnt the way to do it. Nor are you spe- countries. I learned that most items have no
cically responsible for the practices that real price and that bargaining is, at its
lead to so many animals being abandoned. heart, at least as much a social interaction as
Are you killing a shelter dog when you an economic interaction. Soon I became
buy a pet from a breeder? Not in your case: quite good at getting a low price, although
The alternative for you would be to not not as good as the locals. When American
get a dog at all. Among the 50 or 60 mil- friends visited, they were appalled at my
lion dog-owning American households, driving a hard bargain, thinking I was
there are other people who share your unethical because of my being (relatively)
preferences. And so a role remains for a quite wealthy and not willing to share
responsible breeder. But as a dog lover my wealth with someone who was obviously
who worries about abandoned animals, quite poor. Was I being unethical?
you probably should contribute to orga-
I got my wonderful, loving dog from nizations that may reduce their numbers. Edwin Kay
a reputable breeder about eight years ago, Dont think of this as the canine equivalent
but sometimes I feel guilty that I didnt of a carbon-oset program. The reason Unlike you, Ive never lived in Cameroon.
adopt a shelter dog instead. When I consider to contribute is not that doing business But I spent much of my childhood and
that her life span is already more than with a breeder automatically makes you early adulthood in Ghana, and everyone
half over, I suspect that I will eventually get culpable but that its a way to support a I know there would have been puzzled
another dog. When I do, Im sure I will cause about which you care deeply. by the attitude of your American friends.
go to a breeder again. (I wont get into the Still, its worth pointing out that many Bargaining is how prices are set, and no
reasons for this, although there are many.) of the dogs in shelters are purebreds sane seller starts with the price she wants
Is this ethical? Is it relevant that I have some, no doubt, originally from respon- to get. Indeed, trade is enlivened, in part,
taken in strays in the past and given them sible breeders (even though one sign of by the fact that each sale is a negotiation.
a loving home for the rest of their lives? Is such a breeder is a willingness to take Life would be as dull as a supermarket
it relevant that I have never abandoned or back a dog from a buyer who wants to checkout line otherwise. Its also a little
failed to neuter or spay a pet? Is it relevant return it). So your opposition to shelter condescending to think that people will
that, given a choice between a shelter dog
and no dog, I would choose no dog at all?
What if I give money to shelters for neutering
stray dogs? What if I give money for Bonus Advice From Judge John Hodgman
education to prevent people from adopting
puppies without properly training or Steve writes: My wife and I were watching Mad Max,
socializing them, thus preventing those dogs and she became very upset after Maxs dog was killed. We
from ending up in shelters? How much discovered a website, doesthedogdie.com, and learned that
money must I give to justify getting a dog a dog also dies in the sequel. I want to watch the full series,
from a breeder? Or should breeders but my wife insists that would be supporting dog murder.
donate a certain amount for each puppy
To submit a query: sold either to shelters or to education Obviously you are not supporting actual dog murder any more
Send an email to programs? Is such a trade-o ethical? than you are supporting postapocalyptic gasoline-hoarding
ethicist@nytimes biker gangs (wait youre not, are you?), or for that matter
Illustration by Kyle Hilton
.com; or send mail Name Withheld

to The Ethicist, The human murder. I trust your wife understands this and that
New York Times even fictional dog murder makes her upset. I feel you are
Magazine, 620 Many dog lovers worry about bringing obliged to respect her wishes and skip ahead to Mad Max:
Eighth Avenue, New
puppies into a world that seems to have Fury Road, which, according to your incredible website,
York, N.Y. 10018.
(Include a daytime too many. Each year in this country, some- features only the eating of a live two-headed C.G.I. lizard
phone number.) thing like four million dogs enter shelters, something we can all get behind.
28 5.15.16 Illustration by Tomi Um

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The Ethicist
take a price that they think exploitative. As Why didnt We nalized a stepparent adoption in parentage. Certainly by the time your son
Adam Smith pointed out long ago, when 2011, which included a name change and leaves high school, hes entitled to know
two people come together in the market you tell me? a new birth certicate listing my husband that his stepfather is not his biological
and agree on a price, without coercion, is always a as my sons father. My husband and father and something of the story of why.
deception or the pressure of necessity, harder question I then had two children together. My son But why wait? As you note, theres a risk
both end up better o. The seller gets the holds no memory of my husband not being that your sons biological father will con-
money she wanted and hands over the to answer than in his life; he is his father, and thats that. tact your son online, and the boy would
goods she was trying to unload; the buyer Why are you The fear I have is that his biological father be upset that you werent forthright with
acquires the goods she desired for a price telling me? may try to contact him in the future. He him. Trust is morally central to family
she was willing to pay. Against the right randomly sends Facebook messages to me relationships; when its lost, it can often
background, market exchanges improve or family members asking about my son be recovered, but its better not to have
things for everybody. Bargain away! and expressing frustration that he isnt to. Why didnt you tell me? is always a
allowed to see him. I dont want my son to harder question to answer than Why are
I have a 9-year-old son. His biological hear the facts from anyone but me, but you telling me?
father was my boyfriend, who, toward the I also have no desire to tell him about his The dicult task here, of course, is to
end of my pregnancy, cut o contact with biological father. Legally, theres no reason explain why his biological father isnt in
me and expressed little or no interest in he would have to be told. The records are his life. It involves admitting that he let
the child. He signed away his rights, at my sealed, and as I stated, he has a new birth you and your son down. Still, you know
request, when my son was 6 months old. certicate. What should I do? your son. Youll have a sense of what
We had sporadic contact over the next year. information he can handle now. And if
He saw my son once at his rst birthday. Name Withheld you want advice, there are child psychol-
When my son was 2, I met my future ogists and therapists who can help you
husband. Our family t together from the Secrets like these often undermine rela- gure out exactly how to tell him. My eth-
start, and he and my son bonded without tionships, which is why most experts now ical advice, though, is that hes entitled to
any coaxing. I married this man in March think that its a good idea to bring chil- know these things just as soon as he can
2010, and my son attended the wedding. dren up knowing the truth about their absorb them. Which might be today.

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Letter of Recommendation
U.S.G.S. Topographical Maps

By Tom Vanderbilt
At the close of the Second World War, the the name of every last desert wash, old Think of them stunning dualism, the rugged bathymetry
not as maps, but
United States government embarked on mine or gloried goat track was exhaus- as incredibly
of the Pacic Ocean against the rolling hills
an enormous artistic enterprise. It is esti- tively cataloged. This 54,000-tile mosaic affordable Pollocks. of Humboldt Countys redwood forests.
mated to have cost nearly $3 billion and, was not, of course, done in the cause of Some are more abstract. Take, for exam-
at its height, employed more than 2,000 aesthetics, but it nevertheless represents ple, Item 41017 in the U.S.G.S. online store.
people. I am talking about the topograph- as gorgeous and complete a depiction of For $12, you will be treated to an oversize,
Prop stylist: Emily Mullin
ic mapping program of the United States the country as any ever made. plastic-coated, shaded-relief map of the
Geological Survey. It was an opus of Whit- For the past number of years, I have Grand Canyon National Park and Vicin-
manesque proportion, a heroic render- been collecting the U.S.G.S.s maps, treat- ity, a sprawling, muscular and gorgeous
ing of the American landscape; every ing them as eminently aordable pieces sweep of brown and russet that looks less
last whorl and hachure and dotted line of American art. A favorite is the 1977 like the birds-eye view of the canyon itself
of actual topography not to mention map of Eureka, Calif., which contrasts, in and more like the fractal, spidery spread
32 5.15.16 Photograph by Hannah Whitaker

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Letter of Recommendation
of frost across a window pane. In a way, Some enigmatically the pinnacle of both cartographic and map was the product, and every map was
named U.S.G.S.
it calls to mind the work of Jackson Pol- artistic achievement. It is simple to place drawn by hand, he said. There was an
places and their
lock, in particular his painting Enchant- rough coordinates: in deepest shadow those steep slopes that assumption that every map would only
ed Forest. Perhaps Pollock was a kind of are turned away from the light, he writes. be made once or twice in a century, so
Popcorn Cave: 41,
topographer himself, charting some inner -121.366 It is simple, also, to leave, completely we went to extraordinary expense to
territory until he gave up on the project unshaded, the steep slopes that face the make them not only correct but beau-
Kookooligit volcanic
of representation altogether. field: 63.599, light. The critical part, however, is what tiful. The Geological Survey has a new
Most of my maps lie rolled up in tubes, -170.433 lies between the two. It is hardly surpris- mapping program, called U.S. Topo,
tucked away like books to be perused at Bacchus Pit: 40.639, ing that Leonardo da Vinci, that master which, with its numerous layers of
some future date. On some gray after- -112.041 of the liminal techniques of sfumato and sophisticated data, is probably more
noons, sequestered in my Brooklyn apart- Printer Boy Hill: chiaroscuro, produced some early topo- precise but less aesthetically pleasing.
ment, I will pull out, say, a map of Arches 30.216, -106.233 graphical maps. The older is a at map or a globe
National Park, spread it over my kitch- The beauty intrinsic to these maps is map, the geographer Arthur Robinson
en table and trace imaginary pathways the byproduct of an entirely dierent once observed, the more likely it is to be
across airbrushed depictions of reddish mode of production, the last gasp of called an art object. There might be an
sandstone with my nger. I take in the tiny an antiquated way of representing the echo of Kant here: Precisely because the
names of features, a matter-of-fact proces- world. Larry Moore, a longtime cartog- historical topo maps are no longer nec-
sion of gravel pits and drill holes. Then rapher with the U.S.G.S., told me, in a essary objects, they can be purely viewed
my eye hooks upon more oridly named phone call, that the printed maps I so as aesthetic objects. Any old iPhone will
features, each unlocking the imagination: treasure are no longer made (and exist these days reliably tell you where you are,
Cactus Rat Mine, Bootlegger Canyon mainly in the ever-shrinking warehouses to within 10 feet or so, but only a well-
or The Poison Strip (so named because of the U.S.G.S.). Back in the old days, the made map can take you somewhere.
of naturally occurring arsenic in the area
that killed o sheep).
Sometimes I will pick up a map because
of some other interest in an area. I bought Tip By Malia Wollan slipping. A blow to the face looks bad.
a circa-1968 orthophoto map (an aerial Even if it doesnt hurt, such a punch cre-
photograph with topographic overlays) of How to Take a Punch ates the perception that youre losing,
Rozel Point, on the shores of Utahs Great particularly if you bleed or your head ies
Salt Lake, simply because it would be, two backward. Avoid that whiplash action by
years later, the site of Robert Smithsons strengthening your neck muscles.
Spiral Jetty, the countrys most celebrat- Whatever you do, dont get angry.
ed piece of land art. I like to imagine that Dont let yourself be overtaken by fear,
Smithson who was obsessed with geolo- spite or rage. Never ght from emotion,
gy visited Rozel with the very same map says Shields, who wasnt much of a talk-
in hand. (I checked; he probably didnt.) er as a child; as early as second grade,
Smithson said that he picked sites like she was ghting her classmates. I used
Rozel because he wanted them to be free my sts to explain myself, she says. She
of scenic meaning; indeed, having been started boxing at 11 in Flint, Mich., and
there, I can say that it is the sort of place in the gym she learned to control her
that arguably looks better on an orthopho- temper, to stay in the present moment,
to map. In person, it just seems like rocky to endure. If you get hit, tell yourself:
wastes and a dead lake. But the map, from Its just one punch, she says.
above, captivates a tempestuous burst of Dont close your eyes, says Clares- Also, dont get distracted. Shields
almost extraplanetary rust-colored desert sa Shields, who at 17 became the rst keeps her focus on her opponents chest
strikingly oset by the pale blue lake. (Not American woman to win an Olympic gold so she can see the precursory muscle
all nearby maps are so exciting. One quad- medal in boxing, in 2012. Squeezing your movements that indicate a nascent jab
rant south is an entirely blue panel labeled, eyes shut wont lessen the pain. Try to or hook. She avoids eye contact. Some-
simply, Great Salt Lake.) avoid even blinking. Watch the st come times in the ring an adversary will wink
The connection between the beauty of in and learn from it. at Shields, blow a kiss, grin wildly or
the territory and the beauty of the map is Deect the impact by keeping your stick out her tongue. (She likes to say
typically more direct; my home quadrant elbows in close to your sides and shifting that 80 percent of boxing is mental.)
in Brooklyn, for example, is hardly sub- your body so the advancing st grazes your If youre hitting or being hit in a psy-
lime. This is because topo maps measure elbow or bicep rather than slamming into chologically messy, fervid state, stop.
change, which I suspect is the key to their your ribs or belly. Keep in constant motion You may hit me with one good shot,
visual appeal. In his 1965 book Carto- but maintain a centered stance. Dont do says Shields, who will compete in the
graphic Relief Presentation, the great a big move to get out of the way, Shields Olympics again this summer in Rio de
Swiss authority Eduard Imhof suggests says. To counter a swing to the face, duck Janeiro, but Im patient. Ill wait, and
that the transition from light to dark was your head to the side, a tactic boxers call then Ill land three or four.
Illustration by Radio 33

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Eat By Sam Sifton
Grace Notes
A roasted salad that is crisp and yielding all at once.
It looked like the makings of dinner at a

yoga retreat. There was a sheet pan lled
with cherry tomatoes, glistening with olive
oil, dusted in lime zest, showered in salt and
pepper. Beside it, another pan: a soy-driz-
zled mound of ripped kale and dried
shaved coconut. There were the ingredi-
ents for a dressing as well: miso paste from
Japan; tahini from the Levant; local honey;
a knob of ginger; a bright red pepper. All of
this was very beautiful. But I didnt see how
it was going to come together.
It did. Those tomatoes were roasted,
along with the kale, and they converged
under the dressing to create an excel-
lent, powerfully avorful dish exactly
the sort of salad to raise a dinner party
or family meal high. You could serve it
as a starter course, in advance of some
grains, or soup, or a roast. On a weekend,
it could be a terric lunch. You may want
to make it all the time. (I do.)
The recipe comes from Anna Jones, a
British food stylist who worked for Jamie
Oliver before striking out on her own. It
appears in her rst cookbook, A Modern
Way to Eat, a collection of recipes that,
if you spend as much time as I do snoop-
ing around peoples kitchens, seems to be
shaping up as a kind of new-era Silver
Palate Cookbook. (This salad could be
Joness chicken Marbella.)
When I write a recipe or cobble
something together for dinner, Jones
writes in the books introduction, I
always have three things in the back of
my mind that shape my cooking: How
will this taste? How can I make it more
interesting to eat by layering up the tex-
tures? And how can I make it look the
most beautiful on the plate?
These are good questions, in their
way. Of course the rst is what the
34 5.15.16 Photograph by Davide Luciano Food stylist: Maggie Ruggiero. Prop stylist: Gozde Eker.

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In salads, the entrepreneurial class calls table stakes; Warm Kale, Coconut and Tomato Salad
your cooking had better taste good. And Time: 40 minutes
layering of the third is perhaps more a symptom
textures is what of a world obsessed with photograph- 12 ounces cherry tomatoes, approximately
ic documentation than one concerned 1 pint basket
separates the 3 to 4 tablespoons extra-virgin olive oil
with deliciousness. But Joness second
great from the question is vitally important, partic- Kosher salt and freshly cracked black
merely good. ularly in salads, where the layering of pepper to taste
textures is what dierentiates the great 2 to 3 limes, well scrubbed if waxed
from the merely good. You want crisp 12 ounces green or purple kale,
and yielding, slick and crunchy and soft, approximately 2 heads, lower stalks
removed and leaves torn into pieces
all at once.
cup unsweetened dehydrated
So I roasted the tomatoes until they
shaved coconut
were almost but not quite melting. The
1 tablespoon soy sauce
heat concentrated their flavor, and the
lime accented it beautifully. The kale 1 inch fresh ginger root, peeled and
grated, approximately 1 tablespoon
joined them in the oven for the last 10
1 tablespoon white miso paste
minutes or so. Cooked without oil, the
greens went soft in parts and crunchy in 1 tablespoon tahini
others, and the soy and coconut brack- 1 tablespoon honey

eted their pure mineral intensity. For 1 red serrano or jalapeo pepper,
the dressing, I whipped together the nely chopped
ginger, miso, tahini, honey, olive oil,
lime juice and chopped hot pepper to 1. Heat oven to 425. Rinse the tomatoes
create a mixture far thicker than vin- well, dry with paper towels and cut them
in half, then place on a sheet pan. Dress with
aigrette one that lent itself better to 1 to 2 tablespoons of olive oil, salt, pepper,
drizzling over the bowl than using as the zest of 2 limes and the juice of 1 of them.
something to slick every green. It is Roast the tomatoes until just blistered and
dressing as paint, perhaps, both creamy beginning to take on color, approximately 15
to 20 minutes.
and bold. (You can thin it out a little with
extra lime juice.) 2. Meanwhile, mix together the kale, coconut
The combination the layering up, shavings and soy sauce, and place on another
in Joness phrase is sublime. You could sheet pan. Roast these in the oven next to or
certainly toss everything together, but below the tomatoes for approximately 5 to 10
minutes, or until the kale has begun to crisp at
I think the dish works better as a kind
its edges.
of tableau: the greens assembled across
the bottom of a bowl or platter, with 3. Make the dressing in a small bowl,
the tomatoes dotted across them along combining the grated ginger root, the miso,
with the strips of shaved coconut, and the tahini, the honey, the pepper, the juice
of the second lime and the remaining olive
the whole thing dressed simply, without
oil. Adjust seasonings to your liking you
tossing, the miso-tahini mixture added may wish to increase the amount of lime juice
as you might apply pieces of mozzarella with a third lime, to thin the dressing.
to a pizza. People will mix everything
together on their own, on their own 4. Put the tomatoes and kale into a large
serving bowl, and drizzle the dressing over
plates, as they eat. the top, a few tablespoons at a time; you
Regardless, and pleasantly, there is may not need all the dressing if the tomatoes
no need to rush the preparation. You are particularly juicy. Serve warm.
can assemble the recipe serially, slow-
Serves 4. Adapted from Anna Jones.
ly. The greens and the tomatoes come
out of the oven hot. They can be served
merely warm, and indeed should be.
I know that food cooked with calm-
ness and a little grace, Jones told The
Guardian a few weeks ago, tastes, to
me, a little better than when Im run-
ning around doing 10 million different
things. Which is true as north, though
generally hard to achieve. Here is a
chance now. Take it.
Comment: nytimes.com/magazine 35

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Diagnosis By Lisa Sanders, M.D.
His pounding head and tight chest Either you are getting in the car with me
to go back to the hospital, or Im calling
an ambulance, the woman announced to
were so painful that the patient her 38-year-old husband. Hed been home
from the hospital for a day, but he looked
sicker than ever.
didnt pay enough attention to the
most important symptom of all. Wedding Illness
It started at his younger brothers wed-
ding about a week before a destina-
tion event in Colorado. Almost from the
moment he stepped o the plane, he
felt awful. His head throbbed. His body
ached. His eyes felt puy, and his whole
face looked swollen. When he went
to bed that rst night, he tossed and
turned, sleepless. In the morning, when
he pulled himself out of bed, the sheets
were soaked with sweat.
At rst he wrote it o to altitude sick-
ness. The resort was in the mountains,
high above sea level, and he had never
been up at that altitude. Though his wife
and two children felt ne, others in the
wedding party were feeling the eects of
the elevation. One bridesmaid fainted at
the reception; an elderly aunt from Texas
had to leave early.
The afternoon wedding service seemed
to last forever. His tuxedo felt like a strait-
jacket; his chest felt tight; and he could
barely breathe. By the time the reception
dinner started, he felt terrible. He shook
with violent chills, and his head was
pounding. His neck hurt, and he could
hardly swallow. His wife asked the host
to change the order of the toasts so that
he could give his early. Then he went to
the hotel and climbed into bed.

Sick at Sea Level
He gured he would feel better when they
got down to Denver. But he didnt. And
back in Boston, at sea level, he still felt
awful. His wife reluctantly left him in the
city, where he had a ight to catch early
the next day, and drove to their home,
an hour away.
When he was alone in his hotel room,
his symptoms seemed even scarier, and
late that night he took a taxi to Massa-
chusetts General Hospital. Because of
his chest tightness, he had an EKG. To
his surprise, it was abnormal, and he
was rushed to the cardiac-care unit. The
doctors were sure he hadnt had a heart
attack. But something had damaged his
36 5.15.16 Illustration by Anna Parini

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DANNY HAD A FAMILY
HISTORY OF CANCER.
WE DIDNT LET IT
DEFINE HIS FUTURE.
As a firefighter, Danny Soto faced danger every day. But what
scared him most was the disease that had taken the life of
his father, and now threatened his: an aggressive form of colon
cancer. At Memorial Sloan Kettering, Dr. Martin Weiser and a team
of physicians helped Danny gain more control over his treatment
with a precise surgery and intraoperative radiation. Their unique
treatment plan allowed Danny to get back to saving the lives of
others, including his fellow firefighters many of whom were
inspired to get colonoscopies after his return.
See Dannys story at MSKCC.ORG/MORESCIENCE
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P r e s s R e a d e r. c o m +1 604 278 4604
Diagnosis
heart. After dozens of tests, they told him READERS Only the headache, the sore neck and the bacteria that caused the infection would
RESPONSES
he had myocarditis, an inamed heart painful throat. The doctor quickly exam- carry the bug to other parts of the body,
muscle, but they werent sure why. They More than 400 ined him. The patients skin was warm mostly the lungs but occasionally bone,
searched for a cause. Myocarditis often readers oered possible and sweaty, and his neck was sti and brain or other organs. Typically, this infec-
diagnoses after
stems from a viral infection. But bacteria tender, especially on the right. Martinello tion is caused by an unusual bacterium
the case was posted
can also infect and injure the heart; they on The Timess Well was going to approach this systematically, called Fusobacterium necrophorum. No
looked for strep and other possible culprits blog on May 5. he told the couple. First he would get a matter which bug caused it, Lemierres
but didnt nd them. They were worried head CT scan, then a scan of the neck. was almost a death sentence in the pre-
Ellen,
that he had picked up a tick-borne infec- Vancouver
Then he would do a lumbar puncture antibiotics era. Even now, up to 18 percent
tion in rural Colorado. None of the tests Rubella. a spinal tap. He felt optimistic that one of patients with Lemierres will die.
were positive, but after four days they sent of those tests would provide an answer.
him home to nish up a week of an antibi- Stephanie P.,
Tel Aviv
otic called doxycycline, just in case. Decompression sickness The Dangers of Strep
At home, he went to bed, hoping he (caisson disease). A Pain in the Neck In this case, blood cultures suggested
was on the mend. His wife wasnt so The head scan was normal. There was that the infection had started with a dis-
M.N.K.,
sure. The next day, when she looked in Philadelphia
no tumor, no blood clot and no sign ease that is far more common and much
on him, she was frightened by how very Acute Kawasaki disease. of increased pressure. Because of the less feared: strep throat. There are mil-
sick he looked. He was pale and sweaty, patients tender neck, Martinello won- lions of cases of streptococcal infection
the way hed been in the mountains. The Dave, New York dered whether he had an abscess there. It in this country every year, usually in the
Epstein-Barr-caused
shaking and fever were back. His head- meningitis. was the right question, though the result throat or on the skin. A tiny fraction of
ache was terrible; the day before it was was not what Martinello expected. There the time, these bugs can invade the sur-
so bad that hed cried with pain some- was a small abscess. More worrisome, rounding tissues and cause a life-threat-
thing shed never seen before. The pros- there was a blood clot in the patients ening illness, as they had in this patient.
pect of an hourlong drive back to Mass internal jugular vein on the right side. It Both the Lemierres and the myocarditis
General seemed daunting. Thats when was a sign of Lemierres disease, a rare were caused by this strep throat gone
she told him he had to go to the hos- infection that Martinello had seen only wild. This kind of invasive infection must
pital and decided to drive him to Anna once before. be treated with antibiotics, but the anti-
Jaques Hospital, a community hospital Lemierres was best described in the biotic the patient was taking for a possi-
one town over in Newburyport, Mass. 1930s by Andr Lemierre, who reported ble tick bite, doxycycline, isnt eective
Lisa Sanders, M.D. 20 cases of this previously undiagnosed against strep. When he was tested for
is a contributing writer condition. The patients started o with a strep at Mass General, the result was
Searching for Answers for the magazine sore throat and subsequently developed negative, but it was unclear why. But by
and the author of Every
It was late by the time they arrived at a clot in the jugular vein. Then the clot the time the patient came to Anna Jaques
Patient Tells a Story:
Anna Jaques, and the emergency room Medical Mysteries and would frequently break apart, and the Hospital, the bacteria was in his blood
was quiet. Dr. Domenic Martinello the Art of Diagnosis. pieces each containing some of the and was easily found.
knocked at the entrance to the cubicle Now that Martinello knew what was
where the patient had been directed. making this man so sick, he was worried
His wife looked up expectantly, her face that his small community hospital was not
tight with exhaustion. The patient lay prepared to care for him. They didnt have
motionless on a stretcher; his eyes were the kind of specialists he needed on call
sunken, and his skin hung o his face 24/7. Martinello arranged for the patient
as if he hadnt eaten much recently. His to be transferred to a sister hospital, the
voice was soft but raspy, and every time Beth Israel Deaconess hospital in Boston.
he swallowed, his lips tightened in a gri- At Beth Israel, the patient was closely
mace of pain. Together husband and wife monitored by infectious-disease special-
recounted the events of the past few days: ists and ear-nose-and-throat surgeons. He
the wedding, the fevers, headaches, pain continued on antibiotics for six weeks and
in his neck and throat, the four days in started a course of a blood thinner to keep
the hospital in Boston. the clot from growing or spreading.
It was certainly a confusing picture, That was a year ago. The patient has
and Martinello wasnt sure what to make completely recovered. Looking back, he
of the diagnosis of myocarditis. In any remembers that his throat was painful, but,
case, the man had no chest pain now. he told me, it seemed insignicant com-
pared with the shaking chills, fever and
And the Winners Are: Hediyeh Baradaran, headache. I thought of it as kind of a side-
a radiologist at Weill Cornell in Manhattan, bar, when in fact it was the main event, he
and Ariaratnam Gobikrishna, a cardiologist says. Since then, he and his wife have read
at Monteore Medical Center in the Bronx, were up on the illness. Their new family motto
the rst people to make the correct diagnosis. is: Take strep seriously.
38 5.15.16 Illustration by Anna Parini

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Lives
Tipsy in Tehran
I always knew I wanted to try alcohol. It told me to meet him at 3 in the afternoon.
represented independence and sophistica- I had butteries all morning and couldnt
tion. It was about breaking the rules and concentrate in any of my classes. We met
having fun, and as a teenager, I wanted up and walked to the park next to the uni-
Feeling the eects of alcohol, and nothing else. But I had never even seen versity. After we found a secluded bench
alcohol in real life. I had only seen a photo far from the guards, A. pulled out a Sprite
of breaking all the rules. of an alcoholic drink in a frayed photo bottle from his book bag; he had lled it
album: It was of my father, with a big with moonshine in the dormitory the night
As told to Narges Bajoghli
smile on his face, in a cabaret in Tehran before. The mens dorm was always less
before the revolution. strict than ours. They werent checked by
By the time I was born, long after the the guards at the doors, so they smuggled
establishment of the Islamic republic in in alcohol, cigarettes, weed, hash, opium,
Iran and the prohibition of alcohol, my anything you can imagine. It was safer to
father had joined the Iranian military, and drink and do drugs there because no one
it was impossible to have alcohol in our would tell the guards. But women were
home. So it wasnt until I was 19 and in checked when they entered their dorms,
school at the University of Tehran that I and my hall mates constantly ratted out my
had my rst drink. friends and me just for smoking cigarettes.
At the university, it seemed to me that A. pulled out a disposable cup and
most of the students there had already poured. He took a few sips before oering
started drinking. And in that typical way of it to me. I kept looking around to make sure
a teenager, I felt left out. I knew I wanted to no guards were walking by. I nervously took
drink; I just didnt know how it would hap- a very small sip and then waited. I thought
pen. I wasnt friends with the students who something would happen to me right away.
could freely drink at home with their par- But nothing did, and so I drank a bit more.
ents, and I hadnt yet been invited to the I took an even bigger gulp, until A. told me
house parties where alcohol was served. to slow down. By that point, I knew he had
Then one spring day, my boyfriend, A., gured out that this was my rst time.
asked me if I wanted to drink with him. I We drank the bottle together that after-
was very much in love with him and didnt noon, and we had a blast. We joked and
want him to think I was nave, so I tried told each other stories until the guards told
to act casual when I said yes. us with sour faces to leave so they could
Great! he said, promising to bring close the university gates. We were so tipsy
something to school the next week. and in such a good mood that we didnt
At the university? I asked him in even mind their bad attitude. A. often
disbelief. snapped back at the guards he hated
But it made sense. A. didnt have his how stern they were with all of us but
own place, and our parents wouldnt he laughed that day, throwing his arms
have allowed us to have each other over up triumphantly and saying: Take it easy,
(throughout our ve-year relationship, my man. Its not that serious. Were leaving.
parents never knew he existed). Like many I leaned into him, resting my head on his
couples of our generation in Iran, we shoulder, and we went o arm in arm as
struggled to nd time alone. The universi- if nothing were amiss.
ty was the only place we could be together After giggling all the way to our usual
for long periods. A. said we would nd a spot to get something to eat, A. walked
place to drink together in the park next to me back to my dorm before our curfew
our main building, where my girlfriends at 9. A block away, he squeezed my hand
and I often hid to smoke cigarettes. and gave me a wink. Looking back on it
Even though I tried to act cool, I wor- now, I know that we didnt even have that
ried about handling the eects of alcohol. much to drink, but I felt so lightheaded
I was scared that the university guards and giddy and free.
would catch us and that wed be expelled, After that, A. brought alcohol to cam-
maybe much worse a lashing is the pus a few more times, and I befriended
punishment under Islamic law. And yet a classmate who had her own apartment
Name: Ellie H. Ellie H. received to Narges Bajoghli there was something about being at the and great parties with lots of alcohol. But
Age: 30
a bachelors degree in Persian. university, with all those rules, that made that rst time is etched in my memory
and a masters
such brashly illegal acts so very desirable. doing it in such a public way on the
Location: Tehran degree from the
University of Tehran. One day the next week, A. whispered university grounds. I would never do that
She told her story to me with a big smile that he had it. He today. I was much less fearful then.
Illustration by Melinda Josie 39

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Cognitive oncology is here.
Watson for Oncology uses cognitive technologies
to help doctors analyze medical information shared
by patients against a variety of data, both structured
and unstructured. Combined with clinical expertise
and external research, IBM Watson can help identify
potential treatment options for individuals. When
Watson thinks with us, we can outthink.
outthink
cancer
at ibm.com/trademark. Other product and service names might be trademarks of IBM or other companies. International Business Machines Corp. 2016.
IBM and its logo, ibm.com and Watson are trademarks of International Business Machines Corp., registered in many jurisdictions worldwide. See current list
ibm.com/outthink

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+1 604 278 4604
May 15, 2016
THE NEW
ANATOMY
OF
CAN C E R
Its not one disease, or even many diseases. In the past decade, our deepening
understanding of genetics has revealed cancer as an innitude a foe as persistent and mutable as evolution itself,
with as many avenues of attack as there are genes in our bodies. The fantasy of a single illness with a single
cure may be gone, but new research has pointed toward a future in which cancers innumerable assaults can be countered
in kind, with fast, personalized, hypertargeted forms of treatment. In a special Health Issue of
The New York Times Magazine, we map out this new way of thinking, and tell the stories of patients and
caregivers as they navigate cancers strange frontier.
A SPECIAL REPORT
P H O T O I L L U S T R AT I O N B Y C R I S T I A N A C O U C E I R O
41

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Credit by Name Surname
42 0.00.16 Credit by Name Surname

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1.
DOCTOR
WITHOUT BORDERS
For an oncologist in an
era of rapidly proliferating,
precisely targeted treatments, every
case is an improvisation.
he bone-marrow biopsy took about 20 min- I had been treating Donna in collaboration
utes. It was 10 oclock on an unusually chilly with my colleague Azra Raza for six years. Donna
morning in New York in April, and Donna M., a has a preleukemic syndrome called myelodys-
self-possessed 78-year-old woman, had own in plastic syndrome, or MDS, which aects the bone
from Chicago to see me in my oce at Colum- marrow and blood. It is a mysterious disease with
Photograph by Ansel Adams, via the National Archives, College Park, Md.
bia University Medical Center. She had treated few known treatments. Human bone marrow is
herself to orchestra seats for The Humans normally a site for the genesis of most of our
the night before, and was now waiting in the blood cells a white-walled nursery for young
room as no one should be asked to wait: pants blood. In MDS, the bone-marrow cells acquire
down, spine curled, knees lifted to her chest a genetic mutations, which force them to grow
grown woman curled like a fetus. I snapped on uncontrollably but the cells also fail to mature
sterile gloves while the nurse pulled out a bar into blood, instead dying in droves. It is a dual
cart containing a steel needle the length of an curse. In most cancers, the main problem is cells
index nger. The rim of Donnas pelvic bone that refuse to stop growing. In Donnas marrow,
BY SIDDHARTHA MUKHER JEE was numbed with a pulse of anesthetic, and I this problem is compounded by cells that refuse
drove the needle, as gently as I could, into the to grow up.
I L L U S T R AT I O N S B Y outer furl of bone. A corkscrew of pain spiraled Though there are commonalities among can-
CRISTIANA COUCEIRO through her body as the marrow was pulled, and cers, of course, every tumor behaves and moves
then a few milliliters of red, bone-ecked sludge thinks, even dierently. Trying to nd a
lled the syringe. It was slightly viscous, halfway drug that ts Donnas cancer, Raza and I have
between liquid and gel, like the crushed pulp of administered a gamut of medicines. Throughout
an overripe strawberry. all this, Donna has been a formidable patient:
The New York Times Magazine 43

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1
When a cell divides, it reproduces
perennially resourceful, optimistic and willing its own genetic instructions for
how to perform its basic functions,
to try anything. (Every time I encounter her in including when next to divide and
the clinic, awaiting her biopsy with her char- when to die.
acteristic fortitude, it is the doctor, not the 2
patient, who feels curled and small.) She has When these instructions are
mutated that is, reproduced
moved nomadically from one trial to another, inaccurately the cell normally
shuttling from city to city, and from one drug will self-destruct, but sometimes
to the next, through a landscape more desolate the self-destruct message
itself is garbled.
and exhilarating than most of us can imagine;
Donna calls it her serial monogamy with dier-
ent medicines. Some of these drugs have worked
for weeks, some for months but the transient
responses have given way to inevitable relapses.
Donna is getting exhausted.
3
Her biopsy that morning was thus part routine Then the cells divide
and part experiment. Minutes after the marrow unchecked.
was drawn into the syringe, a technician rushed
the specimen to the lab. There he extracted the
cells from the mixture and pipetted them into
tiny grain-size wells, 500 cells to a well. To each
well about 1,000 in total he will add a tiny
4
dab of an individual drug: prednisone, say, to Healthy cells divide a finite
one well, procarbazine to the next and so forth. number of times. A cancer cell can,
in theory, keep dividing forever.
The experiment will test about 300 medicines 5
(many not even meant for cancer) at three dif- When the mutated cells reach
an unusual level of growth, they
ferent doses to assess the eects of the drugs on form a tumor. When that tumor grows
Donnas cells. unchecked and is able to
Bathed in a nutrient-rich broth suused with spread to different, surrounding
tissues, it is malignant.
growth factors, the cells will double and redou-
ble in an incubator over the course of the fol-
lowing two weeks, forming a lush outgrowth of
malignant cells cancer abstracted in a dish. A
computer, taught to count and evaluate cells, will
then determine whether any of the drugs killed
the cancerous cells or forced them to mature into
nearly normal blood. Far from relying on data
from other trials, or patients, the experiment will
test Donnas own cancer for its reactivity against
a panel of medicines. Cells, not bodies, entered
this preclinical trial, and the results will guide
her future treatment.
I explained all this to Donna. Still, she had a
question: What would happen if the drug that
6
appeared to be the most promising proved Sometimes the mutated cells in
unsuccessful? a malignant tumor break away and
travel through the bloodstream
Then well try the next one, I told her. The to take hold of other parts of the
experiment, hopefully, will yield more than one body. That is metastasis.
candidate, and well go down the list.
Will the medicine be like chemotherapy?
It might, or it might not. The drug that we end
up using might be borrowed from some other CANCER DEVELOPMENT
disease. It might be an anti-inammatory pill,
or an asthma drug. It might be aspirin, for all Cancer works the same way all life works, through the process of cell division and mutation. All
we know. living things grow and heal through cell division, and all living things evolve and change through
the occasional mutations that occur as the cells divide. But some mutations can be deadly,
My conversation with Donna reected how
leading to the unchecked growth that defines cancer. More than 14 million Americans have a
much cancer treatment has changed in the last
history of cancer; it is expected to kill 600,000 Americans this year.
decade. I grew up as an oncologist in an era of
standardized protocols. Cancers were lumped
into categories based on their anatomical site of
44 5.15.16 Illustration by Christiana Couceiro

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1.
origin (breast cancer, lung cancer, lymphoma, require a specic individualized treatment can be who had ovarian cancer recalled the bewilder-
leukemia), and chemotherapy treatment, often profoundly unsettling. Michael Lerner, a writer ing language of those trials by making up non-
a combination of toxic drugs, was dictated by who worked with cancer patients, once likened sensical names for chemotherapy drugs that had
those anatomical classications. The combi- the experience of being diagnosed with cancer been pumped into her body: I have survived
nations Adriamycin, bleomycin, vinblastine to being parachuted out of a plane without a map eight treatments of hexamethophosphacil and
and dacarbazine, for instance, to treat Hodgkins or compass; now it is the oncologist who feels vinplatin at the full dose, ladies and gentlemen.
disease were rarely changed for individual parachuted onto a strange landscape, with no I have broken the record.
patients. The prospect of personalizing thera- idea which way to go. There are often no previ- To be fair, important lessons were garnered
py was frowned upon: The more you departed ous probabilities, and even fewer certainties. The from the trials. Using combinations of chemo-
from the standard, the theory ran, the more like- stakes feel higher, the successes more surprising therapy, we learned to treat particular cancers:
ly the patient would end up being undertreated and the failures more personal. Earlier, I could aggressive lymphomas and some variants of
or improperly managed, risking recurrence. In draw curtain upon curtain of blame around a breast, testicular and colon cancers. But for
hospitals and clinics, computerized systems patient. When she did not respond to chemother- most men and women with cancer, the clinical
were set up to monitor an oncologists compli- apy, it was her fault: She failed. Now if I cannot achievements were abysmal disappointments.
ance with standard therapy. If you chose to make nd a tool in the growing kit of drugs to target a Records were not broken but patients were.
an exception for a particular patient, you had to cancers vulnerabilities, the vector feels reversed: A breakthrough came in the 2000s, soon after
justify the choice with an adequate excuse. Big It is the doctor who has failed. the Human Genome Project, when scientists
Chemo was watching you. Yet the mapless moment that we are now in learned to sequence the genomes of cancer
I memorized the abbreviated names of combi- may also hold more promise for patients than any cells. Cancer is, of course, a genetic disease at
nation chemo the rst letter of each drug for that has come before even if we nd the known its core. In cancer cells, mutated genes corrupt
my board exams, and I spouted them back to my world shifting under our feet. We no longer have the normal physiology of growth and ultimately
patients during my clinic hours. There was some- to treat cancer only with the blunt response of set loose malignant proliferation. This charac-
thing magical and shamanic about the multiletter standard protocols, in which the disease is imag- teristic sits at the heart of all forms of cancer:
contractions. They were mantras imbued with ined as a uniform, if faceless, opponent. Instead Unlike normal cells, cancer cells have forgotten
promise and peril: A.B.V.D. for Hodgkins, C.M.F. we are trying to assess the particular personality how to stop dividing (or occasionally, have for-
for breast cancer, B.E.P. for testicular cancer. The and temperament of an individual illness, so that gotten how to die). But once we could sequence
lingo of chemotherapists was like a secret code or we can tailor a response with extreme precision. tens of thousands of genes in individual cancer
handshake; even the capacity to call such baleful Its the idiosyncratic mind of each cancer that we specimens, it became clear that uniqueness dom-
poisons by name made me feel powerful. When are so desperately trying to capture. inates. Say two identical-looking breast cancers
my patients asked me for statistical data, I had arise at the same moment in identical twins; are
numbers at my ngertips. I could summon the Cancer and its treatment once seemed the mutations themselves in the two cancers
precise chance of survival, the probability of simpler. In December 1969, a group of cancer identical? Its unlikely: By sequencing the muta-
relapse, the chance that the chemo would make advocates led by the philanthropist Mary Lask- tions in one twins breast cancer, we might nd,
them infertile or cause them to lose their hair. I er splashed their demand for a national war say, 74 mutated genes (of the roughly 22,000 total
felt omniscient. on cancer in a full-page ad in The New York genes in humans). In her sisters, we might nd
Yet as I spoke to Donna that morning, I real- Times: Mr. Nixon: You Can Cure Cancer. This 42 mutations, and if we looked at a third, unre-
ized how much that omniscience has begun epitomized the fantasy of a single solution to lated woman with breast cancer, we might nd
to wane unleashing a more experimental or a single monumental illness. For a while, the 18. Among the three cases, there might be a mere
even artisanal approach in oncology. Most can- centerpiece of that solution was thought to be ve genes that overlap. The rest are mutations
cer patients are still treated with those hoary surgery, radiation and chemotherapy, a strategy particular to each womans cancer.
standardized protocols, still governed by the colloquially known as slash and burn. Using No other human disease is known to possess
anatomical lumping of cancer. But for patients combination chemotherapy, men and women this degree of genetic heterogeneity. Adult-onset
like Donna, for whom the usual treatments fail were dragged to the very brink of physiological diabetes, for example, is a complex genetic dis-
to work, oncologists must use their knowledge, tolerability but then pulled back just in time ease, but it appears to be dominated by variations
wit and imagination to devise individualized to send the cancer, but not its host, careering in only about a dozen genes. Cancer, by contrast,
therapies. Increasingly, we are approaching o the edge. has potentially unlimited variations. Like faces,
each patient as a unique problem to solve. Throughout the 1980s and 1990s, tens of like ngerprints like selves every cancer is
Toxic, indiscriminate, cell-killing drugs have thousands of people took part in clinical trials, characterized by its distinctive marks: a set of indi-
given way to nimbler, finer-fingered molecules which compared subjects on standard chemo vidual scars stamped on an individual genome.
that can activate or deactivate complex path- combinations with others administered slightly The iconic illness of the 20th century seems to
ways in cells, cut off growth factors, accelerate dierent combinations of those drugs. Some reect our cultures obsession with individuality.
or decelerate the immune response or choke responded well, but for many others, relapses If each individual cancer has an individu-
the supply of nutrients and oxygen. More and recurrences were routine and gains were al combination of gene mutations, perhaps
and more, we must come up with ways to use small and incremental for most cancers. Few this variability explains the extraordinary
drugs as precision tools to jam cogs and turn eorts were made to distinguish the patients; divergences in responses to treatment. Gene
off selective switches in particular cancer cells. instead, when the promised cures for most sequencing allows us to identify the genetic
Trained to follow rules, oncologists are now advanced malignancies failed to appear, the changes that are particular to a given cancer.
being asked to reinvent them. doses were intensied and doubled. In the We can use that information to guide cancer
The thought that every individual cancer might Margaret Edson play Wit, an English professor treatment in eect, matching the treatment
Source photograph from Getty Images The New York Times Magazine 45

P r e s s R e a d e r. c o m +1 604 278 4604
to an individual patients cancer. spurred by science, yes, but also a sense for the nodes melt away. She had received azacitidine
Many of the remarkable successes of cancer art of medicine. as part of another trial before moving on to the
treatments of the last decades are instances of Oncologists are also practicing this art in areas immunotherapy. A man, with a similar stage of
drugs that were matched to the singular vulner- that rely less on genes and mutations. A week cancer, had not been pretreated. He had only
abilities of individual cancers. The drug Gleevec, after Donnas biopsy, I went to see Owen OCon- a partial response, and his disease grew back
for instance, can kill leukemia cells but only if nor, an oncologist who directs Columbias lym- shortly thereafter.
the patients cancer cells happen to carry a gene phoma center. OConnor, in his 50s, reminds me Falchi and OConnor will use this small train-
mutation called BCR-ABL. Tarceva, a targeted of an amphibious all-terrain vehicle capable of ing set to begin a miniature trial of patients with
therapy for lung cancer, works powerfully if the navigating across any ground. We sat in his oce, relapsed Hodgkins disease. We will try it on
patients cancer cells happen to possess a par- with large, sunlit windows overlooking Rockefel- just two or three patients, Falchi told me. Well
ticular mutant form of a gene; for lung-cancer ler Plaza. For decades, he explained, oncologists rst use azacitidine intentionally, this time
patients lacking that mutation, it may be no dif- had treated relapsed Hodgkins lymphoma in a and then chase it with the immune activators. I
ferent from taking a placebo. Because the med- standard manner. There were limited options, suspect that well reproduce the responses that
icines target mutations or behaviors that are OConnor said. We gave some patients more weve seen in our retrospective studies. In lung
specic to cancer cells (but not normal cells), chemotherapy, with higher doses and more toxic cancer too, doctors have noted that pretreating
many of these drugs have surprisingly minimal drugs, hoping for a response. For some, we tried patients with azacitidine can make them more
toxicities a far cry from combination chemo- to cure the disease using bone-marrow trans- responsive to immunological therapy. Falchi and
therapies of the past. plantation. But the failure rate was high: About OConnor are trying to gure out why patients
30 percent of patients didnt respond, and half respond if they are pretreated with a drug that
A few days after Donnas visit to the clinic, I went of them died. seems, at face value, to have nothing to do with
to my weekly meeting with Raza on the ninth Then a year or two ago, he tried something the immune system. Perhaps azacitidine makes
oor of the hospital. The patient that morning new. He began to use immunological therapy to the cancer cells more recognizably foreign, or
was K.C., a 79-year-old woman with blood can- treat relapsed, refractory Hodgkins lymphoma. perhaps it forces immune cells to become more
cer. Raza has been following her disease and Immunological therapies come in various forms. aggressive hunters.
keeping her alive for a decade. There are antibodies: missile-like proteins, made Falchi and OConnor are mixing and matching
Her tumor is evolving into acute leukemia, by our own immune systems, that are designed unexpected combinations of medicines based
Raza said. This, too, is a distinctive behavior of to attack and destroy foreign microbes (anti- on previous responses departing from the
some cancers that we can now witness using bodies can also be made articially through known world of chemotherapy. Even with the
biopsies, CT scans and powerful new techniques genetic engineering, armed with toxins and new combination, Falchi suspects, there will be
like gene sequencing: We can see the cancers used as drugs to kill cancer cells). And there resistant patients, and so he will divide these into
morphing from smoldering variants into more are drugs that incite a patients own immune subsets, and root through their previous respons-
aggressive types before our eyes. system to recognize and kill tumor cells, a mode es, to determine what might make these patients
Was the tumor sequenced? I asked. of treatment that lay fallow for decades before resistant grinding the data into ner and ner
Yes, theres a sequence, Raza said, as we being revived. OConnor used both therapies grains until hes down to individualized therapy
leaned toward a screen to examine it. P53, and found that they worked in patients with for every variant of lymphoma.
DNMT3a and Tet2, she read from the list of Hodgkins disease. We began to see spectac-
mutant genes. And a deletion in Chromosome ular responses, he said. Suppose every cancer is, indeed, unique, with
5. In K.C.s cancer, an entire segment of the Yet even though many men and women with its own permutation of genes and vulnerabili-
genome had been lopped o and gone missing relapsed Hodgkins lymphoma responded to ties a sole, idiosyncratic mind. Its obviously
one of the crudest mutations that a tumor immunological treatments, there were some absurd to imagine that well nd an individual
can acquire. who remained deeply resistant. These patients medicine to treat each one: There are 14 mil-
How about ATRA? I asked. We had treated were the hardest to treat, OConnor continued. lion new cases of cancer in the world every
a few patients carrying some of K.C.s mutations Their tumors seemed to be unique a category year, and several million of those patients will
with this drug and noted a few striking responses. of their own. present with advanced disease, requiring more
No. Id rather try Revlimid, but at a higher Lorenzo Falchi, a fellow training with OCon- than local or surgical treatment. Trying to indi-
dose. Shes responded to it in the past, and the nor and me, was intrigued by these resistant vidualize treatment for those cases would shatter
mutations remain the same. I have a hunch that patients. Falchi came to our hospital from Italy, every ceiling of cost.
it might work. where he specialized in treating leukemias and But while the medical costs of personalized
As Raza and I returned to K.C.s room to lymphomas; his particular skill, gleaned from therapy are being debated in national forums in
inform her of the plan, I couldnt help thinking his experience with thousands of patients, is to Washington, the patients in my modest waiting
that this is what it had come down to: inklings, look for patterns behind seemingly random bits room in New York are focused on its personal
observations, instincts. Medicine based on pre- of data. Rooting about in Columbias medical costs. Insurance will not pay for o-label uses
monitions. Chemo by hunch. The discussion databases, Falchi made an astonishing discov- of medicines: It isnt easy to convince an insur-
might have sounded ad hoc to an outsider, but ery: The men and women who responded most ance company that you intend to use Lipitor to
there was nothing cavalier about it. We parsed powerfully to the immune-boosting therapies treat a woman with pre-leukemia not because
these possibilities with utmost seriousness. We had invariably been pretreated with another she has high cholesterol but because the can-
studied sequences, considered past responses, drug called azacitidine, rarely used in lympho- cer cells depend on cholesterol metabolism for
a patients recent history and then charged ma patients. A 35-year-old woman from New their growth (in one study of a leukemia subtype,
forward with our best guess. Our decisions were York with relapsed lymphoma saw her bulky the increasing cells were highly dependent on
46 5.15.16 Sources: The Cancer Genome Atlas, Nature Genetics

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1.
cholesterol, suggesting that high doses of Lip-
itor-like drugs might be an eective treatment).
In exceptional cases, doctors can requisition
pharmaceutical companies to provide the med-
icines free for compassionate use, to use the
language of the pharma world but this process
is unpredictable and time-consuming. I used to
ll out such requests once every few months.
Now it seems I ask for such exceptions on a
weekly basis. Some are approved. A majority,
unfortunately, are denied.
So doctors like Falchi and OConnor do what
they can using their wiles not just against can-
cer but against a system that can resist innova-
tion. They create minuscule, original clinical tri-
als involving just 10 or 20 patients, a far cry from
the hundred-thousand-patient trials of the 80s
and 90s. They study these patients with monastic
concentration, drawing out a cosmos of precious
data from just that small group. Occasionally, a
patient may choose to pay for the drugs out of
his or her own pockets but its a rare patient
who can aord the tens of thousands of dollars
that the drugs cost.
But could there be some minimal number
of treatments that could be deployed to treat
a majority of these cancers eectively and less
expensively? More than any other scientist, per-
haps, Bert Vogelstein, a cancer geneticist at Johns
Hopkins University, has tackled that conundrum.
The combination of genetic mutations in any
individual cancer is singular, Vogelstein acknowl-
edges. But these genetic mutations can still act
through common pathways. Targeting pathways,
rather than individual genes, might reorganize
the way we perceive and treat cancer.
Imagine, again, the cell as a complex machine,
with thousands of wheels, levers and pulleys
organized into systems. The machine malfunc-
tions in the cancer: Some set of levers and pul-
leys gets jammed or broken, resulting in a cell
that continues to divide without control. If we
focus on the individual parts that are jammed
and snapped, the permutations are seemingly
innite: Every instance of a broken machine
seems to have a distinct ngerprint of broken
cogs. But if we focus, instead, on systems that
malfunction, then the seeming diversity begins
to collapse into patterns of unity. Ten compo-
nents function, say, in an interconnected loop to
CANCER BY GENES keep the machine from tipping over on its side.
Snap any part of this loop, and the end result
Researchers have discovered that cancers they once assumed were quite different might
is the same: a tipped-over machine. Another
be similar genetically, which means a treatment that used to work for only a small group of
20 components control the machines internal
patients now might help a much larger group. Mutations in the gene E2F3, for example, are
thermostat. Break any of these 20 components,
found in breast, lung, bladder and prostate cancers, among others. Knowing this, its possible
and the system overheats. The number of com-
to develop similar drugs that target the gene across different cancers.
ponents 10 and 20 are deceptive in their
complexity, and can have endless permutations.
But viewed from afar, only (Continued on Page 75)
Illustration by Cristiana Couceiro The New York Times Magazine 47

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F
or years, Grace Silva had experienced odd epi-

sodes with her throat bouts of swelling and
radiating pain that seemed to resolve with anti-
biotics but her doctors couldnt explain what
was wrong. Finally, after a are-up in the summer
of 2010, Grace was referred to a specialist, an ear
doctor who felt something amiss on the left side
of her throat: a lump. The Silva family agreed
that it was time to get Grace, then 54, to a thy-
roid specialist. Graces daughter Melanie tracked
down the name of one at Brigham and Womens
Hospital, a 90-minute drive from Graces brown
clapboard split-level near New Bedford, Mass.
In September 2010, the specialist delivered the
diagnosis: anaplastic thyroid cancer. It was bad,
he warned her, and she would need surgery.
Graces other daughter, Karrie, was marrying in
a few weeks. Cant it wait? Grace asked. It could
not. And whatever you do, the specialist said,
please dont look it up on the Internet.
Medical texts describe the prognosis
for anaplastic thyroid cancer as poor,
THE LAZARUS but that hardly captures it. If every cancer
EFFECT has a personality, this one is notoriously
aggressive. Its tendrils of tissue are so
invasive that by the time of diagnosis, it is
Most clinical trials for cancer often too late to operate safely. Radiation
drugs are failures. But for a handful or chemotherapy rarely buy much time,
of patients, a drug proves and even when all traces of the tumor
to be profoundly effective. What are eliminated, it usually reappears. Ana-
can science learn from plastic thyroid tumors are also known
these exceptional responders? for their aberrant rmness, more akin
to wood than esh. As they bloom, the
tumors can tighten like a noose, constrict-
ing the windpipe and giving their victims a sen-
BY GARETH COOK sation of perpetual drowning. This panicky air
hunger can be mitigated with escalating doses
PHOTOGRAPHS BY of morphine, but its a miserable, desperate end
PHYLLIS DOONEY that, once witnessed, is not easily forgotten. The
oncologist Grace was sent to, Dr. Jochen Lorch
of the nearby Dana-Farber Cancer Institute, had
48 5.15.16

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2.

P r e s s R e a d e r. c o m +1 604 278 4604
watched a patient die this way during medical under one counter, and explained that all the it would be time to begin the work of getting
school, and it lled him with such horror, such standard treatments had been exhausted. He told her aairs in order. But the scan results, plain
helplessness, that for years he felt sure he would them about an experimental trial for aggressive to even an untrained eye, were shocking: The
never pursue a career in cancer treatment. thyroid cancers that hadnt responded to stan- largest mass had shrunk to half its previous size.
Of course nobody dreamed of saying these dard treatments, and Grace agreed to enroll. The Everywhere there were signs of retreat. Lorch
things to Grace at the time. A surgeon removed drug, everolimus, was used in transplant surgery said he had never seen such a rout. All six of
her tumor, and she was able to attend her to prevent rejection, and it had been approved the other anaplastic thyroid patients on the trial
daughters wedding. She then withstood a long for some use in cancer. Lorch had seen indica- eventually died, but Graces tumors shrank until
stretch of radiation, every weekday for more tions that the drug could work in the thyroid, they barely registered.
than a month vomiting into a bag as her hus- but he didnt have high hopes for the anaplastic Graces case became the subject of intense
band, Joe, did his best behind the wheel of their cases its long track record had been too dis- scientic scrutiny. How could such a notoriously
brown Chrysler. Her doctors knew they had to mal. Partly we were motivated, Lorch told me, recalcitrant cancer simply collapse? Why had
hit the cancer with everything they had. By the by the fact that we didnt have anything else. she alone responded so extremely? Nobody
end of her treatment in December 2010, Grace, In the days after starting the trial, Grace found was claiming that she was cured. But by the end
of 2011, Grace felt this much was
sure: Having asked for a sign, she
had become a walking miracle.
What happened to Grace is some-

times called by another biblical
name: the Lazarus eect, after the
story in which Jesus stands outside
the tomb of Lazarus of Bethany and
summons him back to life. Many
veteran oncologists have seen cases
like Graces, and the stories of these
unlikely recoveries, shared online or
by word of mouth, have become a
source of hope for patients. Yet for
the eld itself, the Lazarus eect has
been a source of persistent frustra-
tion. In 2011, for example, the Food
and Drug Administration withdrew
its support for the treatment of
breast cancer with Avastin, a drug
with proven ecacy on tumors in
other organs. Some breast-cancer
patients had experienced powerful
responses and owed their lives to
the drug but most patients werent
helped and were instead exposed to
unnecessary side eects. With no
S HARON K. , WHOS E BLADDER CANCER HAS
BEEN IN REMIS S ION S INCE 2 0 1 0. PREVIOU S PAGE: way to predict the results, the drug
GRACE S ILVA AT HOME IN MAS SACHU S ETTS. was as good as useless.
Today patients like Grace have
a once-vivacious Portuguese woman with dark herself standing in front of the mirror in her come to be known as exceptional responders, and
eyes and raven hair, had lost more than 30 pounds bedroom, taking in her diminished reection, cancer researchers have nally begun to unravel
and could barely eat or talk. beseeching God to give her some kind of sign. If the puzzles they pose. In a cancer, some of the
In March 2011, Joe drove Grace back to her time had come, she wanted to know, for the bodys cells develop genetic aberrations, grow-
Dana-Farber. She had started to recover some sake of her husband and three children. If Im ing and spreading uncontrollably, and there are
of her strength, and the day had come to learn going to die, I need time to prepare, she recalled myriad variations on this theme. While physicians
the results of her rst follow-up scan. The news thinking at the time. Either way, she felt sure that recognize hundreds of types of the disease, genetic
wasnt good. Less than three months since her God would hold her by her right hand, as in one analyses suggest that the true number is far high-
last radiation treatment, the cancer had already of her most cherished lines from the book of Isaiah. er. The closer that scientists look at tumors, the
spread to her lungs. The largest mass, on her right Two months later, in May, Joe drove Grace more mutations they nd, to the point where it
lung, was more than an inch in diameter. This is to Dana-Farber for her follow-up scan. Lying may be impossible to count the types of cancer.
the way with anaplastic thyroid cancer. motionless as the CT scanner began its inquiries, Really, every patient suers her own personal can-
Lorch sat with Grace and Joe in a cream- she thought of Isaiah and prayed. If the evero- cer, and when a drug is perfectly aligned to it to
colored exam room, a red biohazard box nestled limus had failed to slow the cancers advance, the exact set of mutations driving the tumor the
50 5.15.16 Photograph by Phyllis Dooney for The New York Times

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result is an exceptional response. In such a case, the tumors various mutations, the researchers them. The dream is to go much deeper, to give
if scientists could catalog the tumors mutations, settled on a prime suspect, a gene called TSC1. an oncologist a listing of all a tumors key muta-
they would have a shot at reconstructing a play- When they re-examined the failed clinical trial, tions and their biological signicance, making
by-play how the conagration began, how the they discovered that the bladder-cancer patients it possible to put aside the rough typology that
drug smothered it and, from this, gain insights genetically similar to Sharon had done noticeably currently reigns and understand each patients
that could help others. better, staying in the trial substantially longer. The personal cancer. Every patient, in this future situa- 2.
The power of this approach was rst demon- problem hadnt been the drug, but knowing exact- tion, could then be matched to the ideal treatment
strated a few years ago, at Memorial Sloan Ketter- ly who should receive it. and, with luck, all responses would be exceptional.
ing Cancer Center in Manhattan. In April 2009, When Sharons doctors published a paper on This idea, more broadly, has been called pre-
Sharon K., who was 68 at the time, had been told their ndings in the journal Science, research- cision medicine: the hope that doctors will be
by her local doctor that her bladder cancer had ers at the National Cancer Institute in Bethes- able to come to a far more exact understanding
morphed into a muscle-invasive form: It had da, Md., immediately understood the broader of each patients disease, informed by genetics,
become aggressive and dicult to contain. At implications. They sifted through a decade of and treat it accordingly. It is in cancer where this
Sloan Kettering, she was given chemotherapy, failed clinical trials, thousands of cases, and has advanced the furthest, and the exceptional
followed by a cystectomy, which involved remov- found that more than 100 patients had experi- responders provide a glimpse of what precision
ing the bladder and fashioning a new one out of enced impressive positive eects. More Shar- medicine might mean. When Graces tumor was
a portion of small intestine. I felt like my insides ons were out there, each potentially harboring sequenced, scientists found a mutation in TSC2,
were going to fall out, said Sharon, who asked a secret about how to defeat cancer. a sister gene to TSC1, the one mutated in Sha-
that her last name not be used to protect her pri- In 2014, the institute started the Exceptional rons cancer. Sharon, like Grace, had responded
vacy. Still, a few months later, the cancer returned. Responders Initiative, and since then the case to everolimus, and so the genetic similarity sug-
In February 2010, running out of alternatives, reports have come in, each a tantalizing mys- gested that their cases were not ukes, that their
Sharon joined a clinical trial at the center, with tery. What explains the patient with a Stage 4 seemingly dierent cancers shared a deep con-
instructions to take two pills every morning and esophageal cancer that spread to the liver but nection. In this sense, Graces anaplastic thyroid
return for regular checkups. Thousands of trials then disappeared three years ago? Or the Stage 4 cancer more closely resembled Sharons bladder
are open in the United States on any given day, adenocarcinoma patient who experienced a com- cancer than other thyroid cancers. A more precise
and for people like Sharon, who traveled from plete remission? What can we learn, from each oncology would have assigned both to everolimus
Florida to take part, they are an opportunity to Lazarus, about how to save the lives of others? on purpose, not by chance.
take advantage of the latest scientic ideas. But Still, the two womens tumors were not identi-
the odds are generally long: Historically, less than cal: While Sharons cancer vanished, Graces still
T
7 percent of cancer drugs tested in humans even- lingered, even if it was harder to discern. Graces
tually win F.D.A. approval. disease barely showed on the scans, and she
At Sharons rst follow-up scan, the tumors looked healthy; friends and family found them-
were in recession; within months, they were gone. selves forgetting, from time to time, how seriously
Her doctors were thrilled. And yet the trial Sharon ill she was. Dr. Nikhil Wagle, a Dana-Farber physi-
had joined was a failure. Of the 44 other patients, cian and scientist who worked on the genetic anal-
just one saw his tumor shrink in a meaningful ysis of her tumor, was once involved in the case
way. Dr. David Solit, a researcher at Sloan Ketter- of a 38-year-old man with metastatic melanoma.
ing, joined a meeting with his colleagues there to A photo, taken when he joined a trial for the drug
discuss the trials results, and he remembers the vemurafenib, shows the mans chest, pale with a
feeling in the room, familiar to anyone in the eld. greenish cast, covered in large, oblong tumorous
O.K., weve had no new eective bladder cancer he rst surviving record of treating cancer dates bumps. Cancer derives from the Greek for crab,
treatments for 30 years, and we did yet another to around 1600 B.C., in an ancient Egyptian papy- and in this case, it was easy to see how the ancients
clinical trial that was [based on] a reasonable idea, rus: tumors of the breast, excised and cauterized imagined crab claws in cancers eruptions. After
he recalled. This is a disappointment. Now lets with what is described as a re drill. In the centu- 15 weeks, though, another photo shows the mans
give up and move on to the next thing. ries since, oncology has retained something of this chest almost completely smooth, its healthy color
But before they did, they wanted to look into elemental character. It is a bodily assault, brutal restored. Lazarus, touched by vemurafenib. Then,
Sharons exceptional response. In the previous but necessary, guided largely by trial and error. two months later, the mans chest is wan and ban-
few years, a new technique called next-generation The Boston hospital where Grace was treated daged, with protrusions so substantial that they
sequencing had made reading an entire genetic takes its name from the cancer researcher Sidney are visible in prole at his neck. He died in hospice.
code exponentially faster and cheaper. Curious Farber, who pioneered a treatment for childhood In June 2012, a year after Graces miraculous
to see what the technology was capable of, Solit leukemia in the 1940s using aminopterin, a poison recovery, Maddox, the rst of her three grandchil-
and his colleagues sent Sharons tissue to Illumi- that racked his young charges but held the disease dren, was born. The happy beginning of the next
na, a sequencing company with headquarters in at bay, at least for a time. What works and what generation was all the more meaningful for Grace
California. Three months later, Illumina sent back does not with one generation of patients is used because she had not expected to witness it. But
what amounted to two Human Genome Projects: to guide treatment for the next. cancer doesnt rest, and Graces doctors knew she
a complete readout of her DNA, totaling some Today, a better understanding of cancers faced the same threat as the man with metastatic
three billion base pairs of code, and then another, workings is transforming treatment, as oncolo- melanoma. If a tumor cannot be eliminated, drug
equally large, for her tumor. After months of inves- gists learn to attack tumors not according to their resistance is the rule. As the biological machinery
tigation, considering the potential signicance of place of origin but by the mutations that drive goes awry inside a cancerous mass, reproducing

P r e s s R e a d e r. c o m +1 604 278 4604
cells make more errors copying their DNA, releas- Grace used to be a standout in the choir, and roared to life. It sounds like truly extraordinary bad
ing a stream of mutants. The everolimus had made one of her favorite hymns had always been It luck a one-in-three-billion shot but the power
conditions harsh, but if a mutant should arise that Is Well With My Soul, but since the radiation of evolution means that its entirely predictable:
could thrive despite the drug, it would divide, and damaged her vocal cords, she had been unable Inside the tumor, cancer rolls a pair of dice, over
divide again, eventually taking over and spreading. to sing. A few months passed, and the temsiroli- and over, until they come up snake eyes.
Darwins survival of the ttest governs inside a mus wasnt working. Lorch tried another drug; Often cancer appears to reverse the natural
tumor, selecting for a crueler version of the dis- it didnt work either. course of things, by taking mature cells, disci-
ease. The cancer was looking for a new way out. plined in form and function, and returning them
to a more fevered, inchoate state. Anaplastic can-
O
Grace is a pioneer, which means that others cers like Graces are those in which the cells have
might learn from her. But it also means that lost their characteristic form. Seen on a pathol-
her doctor, Jochen Lorch, has no precedents ogy slide, normal thyroid follicular cells have a
to guide him, because her case is without prec- smooth, rounded look, like uncracked eggs, and
edent. Within months of Maddoxs birth, he they are arranged in neat circles. With anaplas-
had to tell Grace that a substantial mass had tic thyroid cancer, the cells swell up into a mess
appeared near her right lung and that sever- of irregular shapes, as if theyd all been melted
al smaller nodules had taken root nearby. The together. They are reproducing so often that its
tumor was progressing surely one of med- not unusual for a pathology slide to show a cell in
icines most perverse coinages. the middle of doubling, caught in the act.
When Grace became resistant to the evero- Cancer is a monster, but in its erce evolution-
limus, Lorch decided to try a pharmaceutical ne of the more grotesque insights yielded by ary tendencies, it is grasping, as with anything
cousin, temsirolimus. (Resistant tumors some- cancer genetics is that many of the genes impli- else in nature, for a way to be in the world. Life on
times stick to the same basic escape plan.) Lorch cated in the disease are the same genes that earth has invaded the air, the deep sea, the bed-
also asked if she would be willing to undergo guide early human development. All of us begin rock. Over eons, it has suered meteor storms,
a biopsy, so that the resistant tumor could be as a relatively formless embryo, and from there volcanic dystopias, shifting continents and depri-
sequenced and compared with the original. This, the cells follow an elaborate program. They vations beyond counting, and yet it always comes
he explained, might help future patients who grow rapidly. They migrate and specialize, tak- back stronger. With cancer, biologys erce insis-
faced everolimus resistance. ing on roles like nerve or skin or the production tence its resilience, its ceaseless creativity, its
To understand that cancer is genetic is of hormones in the thyroid. Cells that are no sheer generative capacity is the enemy. With
also to realize that the disease lurks with- longer needed die willingly. All of this activity cancer, the opponent is life.
in a biological system that has about 20,000 is ordained in our DNA and orchestrated by an As Lorch considered other ways to help
genes, each vulnerable in many ways. Some elaborate system of cellular communication in Grace, he knew that one option might come
day, researchers hope to be able to develop which genes activate and deactivate one another from the pharmaceutical company Millennium,
a comprehensive resistance map for cancer, as needed. It is hard to imagine, but this coop- in Cambridge, Mass., which was working on a
a full accounting of the ways that the disease, erative dance is what allows an unshaped mass next-generation mTOR inhibitor, a drug that,
in all its varieties, defeats different therapies. of cells to become something as perfect and like everolimus, targets the mTOR gene. By the
The sequence of Graces resistant tumor could graceful as a babys tiny hand, with each nger- summer of 2013, Wagles colleagues at the Broad
fill in one tiny part of such a map. Eventually, nail sculpted just so. Institute of M.I.T. and Harvard, where he has a
some scientists believe, treatments for most In Graces body, cancer hijacked this system and position, had made some progress. After cre-
cancers could come in the form of multiple turned it to its own ends. For example, the gene ating a proxy cancer, a collection of cells with
advanced therapeutics, applied in parallel. One that mutated in Graces original cancer, TSC2, is the specic mutation found in Graces resistant
would be aimed at containing the tumors cur- part of whats called the mTOR pathway, which tumor, they applied a compound that mimicked
rent mutations, while the others would target helps direct cellular growth. Normally the TSC2 the activity of the drug by Millennium, which is
its favorite backups. Hemmed in and blocked gene acts as a brake, sending cease-and-desist now called Takeda Oncology. The drug should
from shifting to Plans B or C or D, the insur- orders to the mTOR gene when its time for the work, they concluded. The company told Lorch
rection would collapse. cellular engines to ease. The mutation trashed the that it would support a clinical trial as soon as the
When Lorch suggested the biopsy, Grace was brakes, locking the cells in overdrive. Everolimus, drug was ready. Grace had agreed to the biopsy
preparing for her grandson Maddoxs dedica- however, acts on the mTOR gene directly, limiting to help future patients, and now she had a chance
tion ceremony, and she knew that any surgical its ability to emit growth signals an emergency to become one of them.
complications might put her attendance at risk. brake. When Grace took it, her cancer faltered.
But her faith assured her that there was a reason Early in 2013, Graces team received the For Lorch, the challenge was to keep Grace
she had happened into Lorchs care that any sequence of her resistant tumor, and its trick was alive long enough to join the trial. He knew her
adversities she faced would eventually lead to a revealed: A single letter of DNA had changed in the tumor was always in motion. Under the long
greater good. She is deeply convinced that what mTOR gene. This solitary substitution meant that a press of everolimus, it had mutated, allowing it
we are doing here, and what is happening with lone amino acid, part of a long chain that makes up to resurge. The tumor then shook o two other
her, is all part of a plan, Lorch says. the mTOR protein, was dierent. Because of this, drugs, including temsirolimus. Lorch decided to
At Maddoxs ceremony in November 2012, the mTOR protein assumed a slightly deformed go with a traditional chemotherapy combination:
Graces ribs ared with every breath. The biopsy shape, and this meant that the everolimus could carboplatin plus paclitaxel. In July 2013, he start-
had gone smoothly, but the area was still tender. no longer grab hold and do its work. The cancer ed Grace on the new therapy. As fall arrived, hair
52 5.15.16

P r e s s R e a d e r. c o m +1 604 278 4604
was slipping from her scalp, but the cancer had mutation fails because it is only one of many driv- on his chair, leaning back with his hand a loose st
gone quiet, pharmaceutically stunned. ing the tumor, or because the mutation occurred on his forehead, as if he were bracing for impact.
For all the excitement surrounding precision at random in the genetic chaos, a passenger, while When her time comes, it is going to be hard to
medicine, it is humbling to see how distant a goal other mutations do the driving. Future basket tri- speak with her husband and all the people whove
it remains, even in cancer. There was nothing als could help doctors tease out the distinctions. come in with her over the years. He paused. Am
especially precise about the chemotherapy Lorch Many such trials are now underway, including a I dreading this? Yes. Does it motivate me to try 2.
prescribed for Grace, and this, for most patients, large federally supported eort called NCI-Match. harder to keep her around? Yes, absolutely.
is the reality today. Despite all of oncologys recent Sharon and Graces cases even helped inspire
successes, our understanding of the human cells an everolimus basket trial. Carole Arenson, an President Obamas $202 million Precision Med-
vast genetic machinery cancers playground 80-year-old Illinois woman, has metastatic sarco- icine Initiative, announced during his 2015 State
remains modest. The original Illumina sequence of ma with a mutation in TSC2, the same troublesome of the Union address, seeks to study one million
Sharons tumor revealed a total of 17,136 mutations. gene implicated in Graces disease. Carole joined American volunteers to learn how genetic and
Pick any one and inquire about its signicance, the everolimus basket trial and, in November, she other data might be used to tailor treatments.
and the answer will most likely be: Who knows? learned that the tumors were shrinking. In this, the The initiative aims for progress in many ailments,
To make the shift to precision oncology, can- scientic investigations can be seen coming full including heart disease, diabetes, obesity and
cer researchers have invented a novel means to circle, from a pair of Lazarus miracles to practical depression, but initially the focus is cancer. In Jan-
evaluate new treatments. Called a basket trial, it medicine that, to Carole, has felt like salvation. uary, in his nal State of the Union address, Obama
is a trial for which patients are recruited by the When I met Lorch in his oce last year, he was announced that he was putting Vice President
tumors genetic signature, not its point of origin optimistic. Grace had just started on the Takeda Joseph R. Biden Jr. in charge of a moonshot to
in the body; a drug is thus tested against a basket Oncology drug, and the initial signs pointed to cure cancer. Beau Biden, the vice presidents son,
of many cancer types. Last August, an interna- considerable shrinkage. Back in the fall of 2010, died in May 2015, at age 46, of brain cancer. The
tional team led by researchers at Sloan Ketter- when she rst received her diagnosis, her life presidents mother died of uterine and ovarian
ing published some of the rst results of such a expectancy could be measured in months. We cancer. For the loved ones weve all lost, Obama
trial, for cancers with a mutation in a gene called are trying to turn [cancer] into a chronic disease, said before the joint session of Congress, for the
BRAF. The doctors saw a good response in lung Lorch said. Right now, to have someone still alive families that we can still save, lets make America
cancer and two rare cancers, showing the power ve years after they were diagnosed and enjoying the country that cures cancer once and for all.
of selecting drugs based on tumor genetics. For her grandkids is the best that we can do. As we Two days after the presidents moonshot
other cancer types in the trial, though, the drug spoke, though, on his computer screen was a scan speech, I was on the eighth oor of the Charles
was less eective, or there were too few patients with spots: masses of Graces tumor cells, within A. Dana Building in Boston to visit Wagle at
to draw conclusions, showing how much more which, concealed from him, the cancer was surely Dana-Farber. Last October, Wagle unveiled
remains to be learned. Sometimes targeting a plotting its next escape. Lorch sat a bit sideways the Metastatic Breast Cancer Project, inspired
partly by his involvement in Graces
GRACE S ILVA AT HER BEDROOM MIRROR.
case and partly by frustration over
the way cancer research works
today. Its quite dicult to track
down patients with intriguing case
histories, scattered as they are across
the country and protected by blan-
kets of privacy. So instead of going
through doctors or hospitals, the
project makes its appeal to patients
directly. Through the projects web-
site, they can enter their medical
histories and grant Wagles team
access to their records, their DNA
and tumor samples. Participants
have started recruiting others to the
project, solving a central challenge
facing the scientic study of any rare
phenomenon. In six months, more
than 1,800 patients with metastatic
breast cancer have joined, including
hundreds of exceptional responders.
In return, the project involves them
in its decision-making and promises
to share its data with any scientist
who asks. A lot of patients feel like
the research-industrial complex is
about making (Continued on Page 77)
Photograph by Phyllis Dooney for The New York Times The New York Times Magazine 53

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8
10
4 7
54 5.15.16

P r e s s R e a d e r. c o m +1 604 278 4604
W R I T T EN 3.
ON
T HE B ODY
FOR DECADES, SCIENCE HAS CLASSIFIED CANCERS BY THE
ORGAN OR SYSTEM IN WHICH THEY BEGIN. THAT
TAXONOMY IS SLOWLY BEING REPLACED BUT ITS STILL
THE INDISPENSABLE WAY TO UNDERSTAND THE ODDS.
according to its point of origin within a specic list cancers in order of occurrence the most fre-
organ or system grew from decades of steady dis- quently occurring rst along with an estimate
coveries made by researchers staring at stained of the number of deaths that the cancer will cause
slides under a microscope. The shape of cancer this year, and its ve-year relative survival rate (as
B Y R YA N B R A D L E Y
cells, they found, would often give clues about a compared with people without cancer).
I L L U S T R AT I O N S B Y cancers behavior. Broken down and sorted by As we get better at screening for cancers,
CRISTIANA COUCIERO appearance some cells might be atter, some survival rates improve the ve-year relative
are shaped like rings, some look more like oats survival rate for all cancers diagnosed from
cancers were treated dierently, and treatment 1975 to 1977 was 49 percent in the United
improved. Even as doctors move to the precision States; from 2006 to 2010, it was 68 percent.
I N T H E M I D ST OF a genetic revolution that of genetic research, the knowledge gained by star- But numbers dont tell the whole story. Because
promises to scramble everything we know ing at cells continues to be crucial to treatment. doctors are better at nding cancer, treatment
about cancer and how to treat it, our experience Just 10 cancers in eight organs, the blood improves, but so do incidence rates. And of
of the disease today still begins with a single and the lymphatic system will account for more course, as doctors become better at curing
question: Where did it start? than 70 percent of new cancer cases in the United other ills, they allow cancer the enemy that
That, it turns out, remains a very useful ques- States this year, according to estimates from the lurks within the bodys own processes many
tion to ask. The practice of categorizing cancer American Cancer Society. The following pages more years to strike.

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1. L I K E L I HO OD OF 30%
R E C E I V I NG A CA NC E R
DI AG NO S I S BY AG E
MEN WOM E N
BREAST
CASES: 249,260 DEATHS: 40,890
SURVIVAL: 90%
LUMPS IN BREASTS are common, and caused by

a variety of factors, including tumors. Most often,
tumors begin in the lobules (the cells that produce
milk) and the ducts connecting the lobules to the
nipple. The tumors are usually benign, meaning
that they will remain in situ (stably surrounded
by the tissue in which they were rst formed) and
cause no harm. Some tumors continue to expand,
10%
though, invading neighboring tissue. These are
malignant. Breast cells, like all cells, use receptors
to convert chemical signals into actions within the
cell. These receptors are now seen as dening fea-
tures of breast cancer, and how they behave is a key
factor in determining the most eective treatment.
ER- or PR-positive: Normal breast cells and some

breast-cancer cells contain receptors that attach to BIRTH 49 50 59 60 69 70+
the hormones estrogen and progesterone, which
can fuel the growth of a tumor. Breast cancers that
are ER- (estrogen receptor) or PR- (progesterone Non-small-cell: As many as 90 percent of all
2.
receptor) positive will respond to hormone treat- lung cancers are non-small-cell, and about 40
ment, which can block the estrogen or proges- percent of those are adenocarcinomas, a type
terone receptors. About 74 percent of all breast of carcinoma (the most common type of can-
cancers are ER- and/or PR-positive. cer) that starts in cells that secrete mucus and
other substances (adeno is from the Greek
HER2: Another receptor, for a protein called HER2 for gland). About 25 to 30 percent of non-
(for human epidermal growth factor receptor 2) small-cell lung cancers are in the at cells of the
also spurs cell growth. HER2-positive cancers are LUNG bronchis epidermoid lining squamous-cell
more aggressive than HER2-negative ones, but CASES: 224,390 DEATHS: 158,080 carcinomas. Most of the rest are lumped into a
they are also more sensitive to certain drugs that SURVIVAL: 18% category called large-cell carcinomas.
block the HER2 protein. (In cancer, sensitivity is
a good thing. The more sensitive the cancer is, LU NG CA NC E R AC C O U N T S for one in four 3.
the more likely it is to respond to the treatment.) United States cancer deaths, in large part
because the complex structure of lungs makes
Triple negative: Researchers call cancers with tumors both hard to detect and more likely to
none of the above receptors triple negative. spread. Only about 16 percent of the tumors are
Such cancers, about 12 percent of all breast can- found before metastasis, when their cells have
cers in the United States last year, tend to spread entered the bloodstream or lymphatic system
quickly and are harder to treat. They are also nearly and taken root somewhere else. P R O S TAT E
two times as common in black women as white CASES: 180,890 DEATHS: 26,120
women, and more common in women with muta- Small-cell: Sometimes called oat-cell, because SURVIVAL: 99%
tions along the BRCA1 tumor-suppressor gene. the cells appear attened (they contain very little
cytoplasm, the liquid inside cells), small-cell lung CATCHING PROSTATE cancer early can save
Sources, estimated new cases and deaths in the United States cancers usually form inside bronchi (the lungs lives, but early detection also presents com-
in 2016: American Cancer Society. Five-year relative survival branching airways) and are notably aggressive, plicated questions about how to weigh the
rates: National Cancer Institute. Charts, Pages 56-58: National
Cancer Institute. Chart, Page 59: American Cancer Society. metastasizing with alarming speed. They appear risk of cancer against the risks posed by treat-
Chart estimates based on United States population in 2016. almost exclusively in the lungs of smokers. ment. Many prostate cancers grow slowly and
56 Chart illustrations by Cristiana Couceiro. Organ drawings by Joe McKendry.

P r e s s R e a d e r. c o m +1 604 278 4604
might never cause any signicant harm; the cells called polyps, found in the mucus-producing 5.
treatment for prostate cancer, for its part, can gland cells that line the colon. About a third to
cause several undesirable side eects, including half of all individuals worldwide have polyps in
incontinence and impotence. There are no clear their colons, but fewer than 10 percent of those
answers or well-dened lines, so the American polyps will become invasive cancer adeno-
Cancer Society recommends that beginning at carcinomas. Doctors typically determine how
age 50, men should have a conversation with advanced the adenocarcinoma is based on dif-
their doctors about prostate screening, and that ferentiation. Dierentiation in biology is the
those at higher risk black men or men with process of immature cells maturing, and cancer LY M P H AT I C S Y S T E M
a close relative whose cancer was diagnosed cells often look like younger versions of healthy CASES: 81,080 DEATHS: 21,270
before age 65 should have this discussion cells: The more poorly dierentiated the tumor SURVIVAL: 73% 3.
beginning at age 45. cells are, the more advanced the cancer. Some
of the drug therapies used to attack cancer push LYMPHOMA IS ANY cancer that begins some-
Adenocarcinomas: More than 95 percent of these younger-looking cells into maturity. where in the lymphatic system often the
all prostate cancers form in the gland cells of lymph nodes, which are little oval organs that
the prostate, but even within this subcategory, Vascular invasion: Cancer cells that have act as lters for invasive particles like viruses,
the cancer cells can take dierent forms. Some moved into the colons veins or arteries are a bacteria and cancer. Connecting the nodes are
are described as foamy, others as colloid, still vascular invasion; a lymphatic invasion occurs lymphatic vessels, which are like veins but,
others as signet-ring, because their nuclei are when the tumor has entered the lymphatic sys- instead of carrying blood, circulate lymph, a
pushed to the periphery in a way that makes tem. When cancer cells move into these sys- uid lled with white blood cells called lym-
them look like the face of a ring. Pathologists tems, which circulate throughout the body, its phocytes. The lymphatic system collects uids,
use a grading system to determine how well much more likely that the cancer will spread to wastes and invasive particles from the parts of
or poorly dierentiated the cancer cells look a new part of the body. our body outside the bloodstream; lymphomas
under a microscope (as with many other can- weaken the immune system, and increase the
cers). Well-dierentiated cancer cells get a low Mucinous tumors: These tumors spread quick- odds of a bad infection. The interconnected
grade they look more like healthy cells. Poorly ly and exist in pools of excess mucus. In sig- whole-body systems of lymph and blood are
dierentiated cells score higher and tend to net-ring tumor cells, its mucus that pushes the also the pathways cancer uses to spread during
spread more aggressively. cells nucleus over to one side and gives the cell metastasis. Our lymph system is incredibly com-
its distinctive shape. While all cancers learn how plicated, and so are lymphomas: There are doz-
Small-cell carcinoma: An aggressive form of to better hide over time, this is especially true ens and dozens of categories and subcategories,
prostate cancer that is dicult to detect because, of solid tumors like these. A type of cancer vac- each quite dierent from the next.
unlike adenocarcinomas, it does not usually aect cine in trials now uses a patients dendritic cells,
the production of a certain protein (called PSA) which are blood cells that act like messengers in Hodgkin lymphomas: These begin in lympho-
that shows up in blood samples. Its made up of the immune system: The blood cells are trained cytes. As many as 95 percent of all patients with
small, round cells hence the name. in a lab to activate other cancer-ghting cells, Hodgkin have a form called classical Hodgkin,
Source photographs, Page 54: Getty Images and the Texas State Library and Archives Commission.
then reintroduced into the patient. with enlarged, cancerous lymphocytes called
Squamous-cell carcinoma: This type of prostate Reed-Sternberg cells; the other 5 percent have
cancer is nonglandular it aects the lining DE A DL I E ST CA NC E R S cells that look like popcorn and are called pop-
Page 56: National Library of Norway. Page 57: Australian National Maritime Museum.
of the prostate, and it, too, is hard to detect, ( R A N K E D BY 5 - Y E A R S U RV I VA L R AT E ) corn cells. Most cancer cells are sensitive to
because PSA levels typically remain the same. DNA damage, which is how most chemotherapy
It is very aggressive, with a median survival rate ESOPHAGEAL works: by using agents that attack the bonds that
18% BRAIN
after diagnosis of just 14 months, but also quite form DNAs double helix, breaking the strands,
31%
rare (less than 1 percent). STOMACH
stopping the cancer cells from multiplying and
30% killing them. The rst F.D.A.-approved chemo-
4. therapy was a nitrogen mustard (similar to mus-
PANCREATIC
8% tard gas) for Hodgkin lymphoma, in 1949.
LIVER
18% Non-Hodgkin lymphomas: The remaining forms
LUNG of lymphoma are far more common and can
18%
be divided into many more subgroups, some
of which are considerably more aggressive
COLORECTUM than Hodgkin lymphomas. If the cells appear
CASES: 134,490 DEATHS: 49,190 grouped together in structures called follicles,
SURVIVAL: 65% its a follicular type; or it might be spread out,
making it a diuse type; low-grade or indolent
COLON CANCERS NEARLY always grow slowly, lymphomas grow slowly; high-grade or aggres-
over the course of 15 or 20 years, and usually sive lymphomas grow quickly. A promising
emerge out of small, already-formed clumps of new form of treatment for lymphomas takes

P r e s s R e a d e r. c o m +1 604 278 4604
a patients T cells, a type of immune cell found 7.

patch that has irregular borders and is somewhat
in blood, and genetically engineers them in the asymmetrical in form. It can begin in what was
lab to produce special receptors on their surface previously a benign mole.
called chimeric antigen receptors (CARs). These
CAR-T cells can recognize proteins on tumor cells Lentigo maligna: Similar to supercial spreading
that had masked the cancer from the patients melanoma, it stays close to the skin surface and
immune system. The underlying principle of a shows discoloration, but is most common in the
lot of immunotherapies is similar: to unmask the SKIN (MELANOMA) elderly and chronically sun-exposed (its the most
cancer, so the immune system will attack it. CASES: 76,380 DEATHS: 10,130 common form of melanoma in Hawaii).
SURVIVAL: 92%
6. Acral lentiginous: Usually appearing as a black
SKIN CANCER IS the most commonly diagnosed or brown discoloration under the nails or on
form of cancer in the United States, but the most the soles of the feet or palms of the hands, it is
common types basal-cell and squamous-cell the most common form of melanoma in Afri-
skin cancer (also called nonmelanoma skin can- can-Americans and Asians.
cer) are found so early and so often that they are
not required to be reported to cancer registries Nodular: A very aggressive melanoma, it is usu-
in North America. The best way to detect skin ally invasive at the time of diagnosis.
BLADDER cancer early is to recognize new or changing
CASES: 76,960 DEATHS: 16,390 skin growths, particularly those that look dier- 8.
SURVIVAL: 78% ent from other moles. Use the ABCDE rules: A
is for asymmetry (one half of the mole does not
BLOOD IN URINE is by far the most common match the other half); B is for border irregular-
symptom of bladder cancer, and usually the rst ity (ragged, notched, or blurred edges); C is for
to be detected. It occurs in about eight out of color (not uniform, with shades of tan, brown,
10 people who have bladder cancer, which is or black in one mole); D is for diameter greater
far more common in men, especially white than 6 millimeters (about the size of a pencil THYROID
men. Bladder cancer often spreads, even after eraser); and E is for evolution (in other words, CASES: 64,300 DEATHS: 1,980
treatment, to dierent parts of the urinary tract, change). Melanomas represent about 1 percent SURVIVAL: 98%
including the linings of the kidney, ureter and of all skin-cancer cases but nearly all skin-cancer
urethra. Researchers are nding, though, that deaths, because they grow and metastasize so T H Y R O I D C A N C E R S A R E among the most
there is a window of opportunity between treat- much faster than other forms of skin cancer. treatable cancers. In some cases, theyre diag-
ments. While the cancer is developing resis- nosed after a lump in the neck is found; in others,
tance to previous treatments, its especially Superficial spreading: The most common form when a patient feels tightness in the throat or
vulnerable to new ones. One gene therapy of melanoma (about 70 percent of all cases), it hoarseness or has a hard time breathing or swal-
uses modied viruses to infect bladder-can- rst appears as a at or slightly raised discolored lowing. Only about 5 percent of thyroid cancers
cer cells, marking them with a hormone that grow aggressively and present a risk of spread-
sends a chemical signal to the immune system MO ST - S U RV I VA B L E CA NC E R S ing to other organs. Many thyroid tumors are so
to attack them. ( R A N K E D BY 5 - Y E A R S U RV I VA L R AT E ) slow-growing that earlier this year, an interna-
tional panel of pathologists decided that a whole
Urethral: About 95 percent of bladder cancers category of thyroid tumors (about one-sixth of
THYROID
develop in the bladders innermost lining, 98% the 64,300 cases cited above) would no longer
called the urothelium. These cells bunch and MELANOMA be considered cancer. Most thyroid cancers do
92% HODGKIN
stretch, depending on whether or not the blad- PROSTATE LYMPHOMA not respond well to chemotherapy, but some
99% TESTICULAR 86%
der is empty or full. In so doing, they come 95% newer targeted drugs show incredible promise.
into contact with urine and, more important, BREAST One class, known as kinase inhibitors, helps block
90%
chemicals carried in the urine that may cause certain enzymes common to thyroid cancer, and
cancer. (Chemicals from tobacco smoke are a also blocks the growth of blood vessels. (Cancer
possible cause of bladder cancer, as are arsenic tumors often survive by getting the body to form
and diesel exhaust.) new blood vessels, a process called angiogenesis.)
Non-muscle invasive: Also called supercial Differentiated: Nearly 90 percent of thyroid can-
or early bladder cancer, it can appear as small cer cases involve dierentiated thyroid cancers
growths that look like cauliower in the lining (D.T.C.), in which the cancer mutation doesn't
of the organ. The cancer might later move from look all that dierent from a typical thyroid cell.
its supercial or early designation to become But D.T.C. is itself divided into four groups. A
invasive, at which point it has a high chance of variant of one of them, papillary thyroid cancer,
metastasizing. is the kind that was downgraded this year. It is
58 Chart illustrations by Cristiana Couceiro. Organ drawings by Joe McKendry.

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21% P RO STAT E
more common in women and younger people
and is fairly treatable.
OT H E R 34%
Medullary thyroid: This sometimes comes from
having an inherited abnormality in a specic gene MEN
called RET. Patients with the abnormal RET gene 14% LU NG
that causes medullary thyroid cancer often have
their thyroid removed as a preventive step.
K I DN E Y 5%
8% C OL ON
9. LY M P HOM A 5%
M E L A NOM A 6% 7% B L A DDE R
3.
B R E A ST 29% 30% OT H E R
KIDNEY
CASES: 62,700 DEATHS: 14,240 WOM E N
SURVIVAL: 74%
3% M E L A NOM A
K I D N E Y S F I LT E R B L O O D , transforming LU NG 13%
excess water, salt and other waste into urine. 4% LY M P HOM A
Blood enters them through the renal arteries; 6% T H Y ROI D
C OL ON 8%
urine exits through ureters at the renal pelvis. 7% B L A DDE R
The renal cells lining the tubes in and out of the
kidney are where nearly all kidney cancers rst
appear. Kidney cancer has long been resistant
to chemotherapy, but researchers are nding L O CAT ION OF N E W CA NC E R CA S E S
more success with targeted drug treatments
(called adjuvant therapy) delivered after surgery,
which attack the genetic mutations underlying a 10. Chronic lymphocytic: A cancer of the lympho-
tumors growth. Until recently most pathology cytes, which are white blood cells that ght
reports for kidney cancer listed it simply as renal infections, its the most common form of leu-
cell carcinoma (R.C.C.), but now they more often kemia in the United States. Relapsed chronic
break it into subcategories. lymphocytic leukemia (C.L.L.) is harder to treat:
The tumors are more likely to be resistant to
Clear-cell: Also known as conventional R.C.C., it previous treatments (chemotherapy in partic-
accounts for nearly 75 percent of all cases. Like ular). One new class of drugs targets a specic
Source photograph, Page 58: Australian National Maritime Museum. Page 59: National
many other kidney cancers, its dicult to diag- BLOOD (LEUKEMIA) genetic mutation associated with chemoresis-
Library of Norway and the U.S. Department of Energy Genomic Science Program.
nose at an early stage, but a few signs include CASES: 60,140 DEATHS: 24,400 tance to slow the cancers spread.
blood in urine or a lump in the abdomen. SURVIVAL: 60%
Acute lymphoblastic: This is the most com-
Papillary R.C.C.: This category is divided further, MOST TYPES OF leukemia start in immature blood mon type of leukemia in young children. The
into Type I (5 percent of all cases) and Type II (10 stem cells, which are found in bone marrow. Stem standard treatment for acute lymphoblastic leu-
percent). Type I is usually hereditary, meaning cells develop into dierent types of cells that have kemia (A.L.L.) is usually chemotherapy, and the
a gene in this case one called MET passed dierent jobs. Blood stem cells develop into either survival rate tends to be much higher in chil-
down from a parent can greatly increase the risk lymphoid stem cells or myeloid stem cells. Lym- dren than adults (85 percent versus 50 percent).
of this cancer. These inherited genetics appear phoid stem cells develop into lymphocytes, a type One challenge of all leukemias all cancers,
in germline cells, or reproductive cells, which of white blood cell; myeloid stem cells sometimes really is knowing just how many cancerous
are dierent from adult cells, also called somatic develop into bone-marrow-based blood cells, like cells remain in the body after treatment, espe-
cells. About 85 to 90 percent of all cancers come platelets. Cancer has stem cells, too, which were cially since even a few can give rise to a relapse.
from sporadic mutations in somatic cells, and the rst discovered in acute myeloid leukemia, in A polymerase chain reaction (P.C.R.) test can
rest are related to inherited mutations in germ- 1994. Leukemia is either acute or chronic. Acute is identify trace amounts of cancer cells based
line cells. When researchers talk about geneti- fast-growing; chronic is not. Many types of chronic on the cancers gene mutations its genetic
cally sequencing cancer, they are talking about leukemia can be controlled and lived with for years ngerprint. Cancers ability to mutate is what
sequencing somatic cells. But some cancers, like and even decades something also increasingly makes it a tricky, ever-changing foe; but the
Type II Papillary R.C.C., carry distinct inherited true of many other cancers. More people are living more we understand these genetics, the more
risks, which germline cell sequencing can reveal. with cancer today than ever before in history. we can take advantage of them.

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THE SHARK
AND THE
LIGHTNING
Andrew Levy's parents knew

that the rare and deadly cancer in his blood
could not be beaten, so they
began to prepare for the worst. Then
something mysterious happened.
BY MELANIE THERNSTROM
PHOTOGRAPHS BY
LUCAS FOGLIA

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4.
61

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diagnosis, Esther and Dan say, they were among They decided that when Andrew was well
them. When Andrew got sick, they were in their enough, they would not return to their old home but
mid-30s and energetic, optimistic and extroverted. begin a new life. They found a house in the nearby
W
They had both attended Stanford Dan majored town of Atherton in the style of an English country
in industrial engineering, Esther in human biolo- manor, encircled by hedges and white rose bushes,
gy, with a minor in dance before going on to that suggested privacy and safety. Andrew was too
successful careers. Dan founded a sports-related vulnerable to leave the apartment, so Esther could
start-up, then became vice president of small busi- not go to see the house in person, but they bought it
ness at Facebook, while Esther worked at Kurbo, a anyway, and she made plans with a decorator friend
start-up focused on weight management for kids, to create an airplane-themed room for Andrew.
and taught spin classes at a Jewish community But on June 19, the medical team told Esther
center for fun. Their own families were stable and and Dan that there was bad news again: Andrews
close-knit; to recall any true adversity in either cancer had returned. The number of cells was
family, they had to think back to a grandmother small but would inevitably grow, the doctors
hen Esther and Dan Levys son Andrew was 14 of Dans whose family perished in the Holocaust. explained. The team presented a new plan: They
months old, he received a diagnosis of a kind Once Andrews illness was diagnosed, he would begin chemotherapy again in preparation
of leukemia so rare that their medical team said needed a bone-marrow transplant as swiftly as for a second bone-marrow transplant, perhaps
getting it was like being bitten by a shark and possible. First the doctors had to kill the leuke- using cord blood this time.
struck by lightning at the same time. mic cells in Andrews bone marrow with chemo- Oh, God, Esther said, putting her head in
Leukemia, a cancer of those cells in the bone therapy, then replace them with a donors cells. her hands. She felt she could not go through it
marrow that produce new blood cells, has many Andrews 3-year-old sister, Lea, and his 5-year-old all again. And there was no reason to think it
varieties, but the most common type in children, brother, Wills, were tested, and in the familys would work. The odds of success during the rst
acute lymphocytic leukemia, is largely curable. rst bit of luck since the diagnosis, Wills turned transplant had been long; in a second attempt,
Andrews cancer, however, a subtype of acute out to be a perfect donor match. Andrew under- they would be much more so. But the odds that
megakaryoblastic leukemia (AMKL), aects only went two rounds of chemotherapy, but there it would cause all of us more suering were 100
about 45 children a year nationwide and is much were still traces of cancer when the transplant percent, she told me.
more dicult to treat. The odds of surviving this was performed in February 2015, putting the From the initial diagnosis, Dan had determined
type of AMKL are roughly even unless the child outcome at high risk of failure. that their goal was not simply to help Andrew sur-
is one of a handful who happen to have a particu- The Levys had created a Helping Hands web- vive but to keep the family intact. To choose to
lar genotype, in which case these odds plummet site, where friends signed up to host play dates move back into the hospital, where they believed
to a mere one in 10. Genetic analysis revealed that or deliver meals (as did our family because our Andrew would die, was a fundamental violation
Andrew was in this tiny group. children were in the same school as Wills), and a of every promise we made to ourselves and our
There was more bad news. Two weeks after the Facebook group for updates on Andrews illness, kids that we would be together again, he told me.
diagnosis, Andrews doctor, Norman Lacayo, an which 1,700 people joined. But despite all the He felt the family had just started to heal from
oncologist at Lucile Packard Childrens Hospital support, Esther felt deeply alone with the expe- the months of separation. The emotional scars
at Stanford University, received an urgent call rience, she says. Her former life had vanished: of the experience, he said, would be irreparable
from Michael Loken, the president of Hematolog- She was living in Andrews hospital room, sleep- if we ripped them open and split our family apart
ics Inc., a Seattle lab that was analyzing Andrews ing on a sofa that opened into a hard bed. She had again. They decided to stop treatment. They
cells. Loken had recently discovered that a small left her job and the rest of her family while Dan would move to their new house, where Andrew
percentage of children with AMKL had a specic continued to work and live at home with Wills would spend whatever time he had splashing in
phenotype a pattern of proteins on the surface and Lea. Her nights were punctured by Andrews their swimming pool and playing in the grass
of the leukemia cell he called R.A.M. (a former cries; her days were spent frantically trying to with Wills and Lea.
patients initials) that independently predicted distract him from his pain and nausea, cleaning The doctors were stunned. We love you, and
a terrible outcome, with a survival rate of about up his vomit, holding him down during blood we love Andrew and were not ready to give
one in six. Andrew had this phenotype too. draws and making stressful medical decisions. up, Jennifer Willert, the pediatric oncologist
Has anyone ever survived this kind of can- He screamed if she left him for a few minutes, in charge of the transplant, blurted out. Lacayo
cer? Dan asked Lacayo. All I wanted to know even to use the bathroom or shower. and Willert argued for at least trying some pal-
is that it was not impossible, Dan recalls. Lacayo After Esther and Andrew spent three months in liative chemotherapy to prolong Andrews life.
said yes, but Dan felt his answer was foggy. The the hospital, the entire family moved into a nearby Esther and Dan hesitated but ultimately declined.
truth was that the team couldnt nd a single apartment, in order to live in a smaller space they They called their decorator friend and told her to
equivalent case in the literature. could keep immaculately clean while waiting for return the furniture for Andrews new room. She
Beginning on that December morning in 2014 Andrews new immune system to develop. Esther was one of the rst people to whom they told the
when Esther took Andrew to the E.R., she recalls, remained Andrews full-time nurse, responsible news: Andrew was going to die.
she felt as if they had stepped into a horror movie, for a dizzyingly complex regimen of medications
the unfolding events both surreal and evil. Up to and sterile changes of the IV. A bone-marrow test The Levys posted the news of their decision
that point, Esther and Dan had led, in her words, that April showed no traces of cancer, and Andrew on June 22. They explained their thinking and
charmed lives picture perfect. Only a small was considered to be in remission. They posted asked their friends not to question their choices,
subset of people would sincerely say that nothing videos of him banging on his drums and singing recommend new treatment options, tell them
truly bad has ever happened to them; before the with his toy Elmo and pretending to play golf. about Gods plan or insist that there was hope.
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I truly believe that I have a new way of looking the bone-marrow tests to see if the cancer was death. They called a rabbi, and thinking about
at parenting it is not about the length of life gone. Now there are no more diagnoses, Dan how Andrew loved airplanes, they picked a Jewish
that matters, but the quality of life, Esther wrote. wrote on Facebook. No more tests. And no more cemetery near the airport. Not wanting him to be
We are going to focus on quality. milestones. But there is waiting. Maybe hours, or buried alone, they purchased grave sites for them-
But quality time with a doomed child turned days, or weeks. This was the most agonizing of selves as well. They established an Andrew Levy
out to be impossible. The cancer cells were few all: the wait for Andrews death. Memorial Fund to raise money for music therapy
enough that they were not yet making Andrew On July 1, they moved into their new house, at the Lucile Packard Childrens Hospital.
sick, but, Esther posted, I cant think of any- and Andrew became sick. By the holiday week- The members of their medical team visited
thing more painful than spending time with your end, he was moaning or screaming in pain when- their home to say goodbye. Andrew had stopped
precious baby knowing that he is going to die ever he was awake. Dan took a leave of absence eating. He was barely moving, his breathing raspy
soon. Parenting is teleological; parents rear a from work. Esther held Andrew at all times, his and his complexion sallow, with the particular
child to become an adult. What were their goals body draped over hers on the couch or the bed. look the team knew from other dying children.
for Andrew now? I am no longer raising him to Dan took food to her because she couldnt hold Sometimes he stopped breathing momentarily,
grow up to be a wonderful human being, Esther him and sit up at the dinner table. Her hair began and his body would become rigid, and his face
wrote. Should she let him eat junk food or watch to fall out because of the stress. It was unbear- turn blue. Its O.K. for you to go, Esther told him.
videos on the iPad all day? Did it matter? able for him and for us, she says. All she wanted now was for this to end quickly.
Their older kids asked tormenting questions. The hospice team began to come every day to They called Wills and Lea into the living room
Lea wanted to know whether they could buy try to control the pain with high doses of opioids. a room the kids rarely entered. Esther pulled
4.
Andrew a certain toy when he was 4 years old like Harvey Cohen, an oncologist and the medical them close to her on the couch, and Dan sat on a
her. Wills wanted to know why they had Andrew director of the hospitals palliative-care program, cushion on the oor. They had rehearsed what they
if they knew he was going to be sick all the time. explained to them that as the disease progressed, were going to say with Barbara Sourkes, a hospital
Dan read them Mo Willemss book Waiting Andrew would not have enough platelets for his psychiatrist with whom they had grown close, and
Is Not Easy! about an impatient elephant. As blood to clot. A hospice nurse told them to buy they made an audio recording of this moment in
he read, he thought about the waiting that had dark towels for Andrews crib, so that if he started case they needed to discuss it with her later.
engulfed them over the previous nine months. to bleed uncontrollably, the sight would be less Dan told the children that the transplant had
They had waited to get the right diagnosis; they frightening for his siblings and for them. been a success, and that Willss cells had done a
had waited 100 days for the transplanted cells During the second week of July, the hospice great job, but that Andrews cells needed to work
to grow; they had waited for the results from team told them to prepare for Andrews imminent on their own at some point, and they werent.
His body is just not working, he
BACK HOME: PREVIOUS PAGES, ESTHER LEVY
FOLLOWS ANDREW IN THEIR YARD; BELOW, ANDREW
said, as straightforwardly as he could
WRESTLES WITH HIS OLDER BROTHER, WILLS. manage.
Is Andrew going to get better?
Wills asked.
The doctors dont think so, Wills.
No.
Sourkes had advised them to tell
the children only what they needed to
know so as not to overwhelm them,
because the children needed emotion-
al space to process things their own
way. So Andrew Andrew is going
to die at some point, Dan said. We
dont know when.
I dont like that Andrew is going to
die! Lea exclaimed and started crying.
Wills pulled the hood of his sweat-
shirt over his face and said he didnt
want to talk about it.
Andrew is going to die, so that
means we are only going to have
four people in our family, Lea said
unhappily. She asked if they could
get a new baby to replace Andrew,
and she and Wills began to fantasize
about a new baby who would make
everything all better.
Esther returned to Andrew. I prom-
ise, I promise you, we are not going
to forget him, (Continued on Page 72)
Photograph by Lucas Foglia for The New York Times The New York Times Magazine 63

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he story of modern cancer research begins,

somewhat improbably, with the sea urchin. In
the rst decade of the 20th century, the German
biologist Theodor Boveri discovered that if he
fertilized sea-urchin eggs with two sperm rather
than one, some of the cells would end up with
the wrong number of chromosomes and fail to
develop properly. It was the era before modern
genetics, but Boveri was aware that cancer cells,
like the deformed sea urchin cells, had abnormal
chromosomes; whatever caused cancer, he sur-
mised, had something to do with chromosomes.
Today Boveri is celebrated for discovering the
origins of cancer, but another German scientist,
Otto Warburg, was studying sea-urchin eggs
around the same time as Boveri. His research,
too, was hailed as a major breakthrough in our
understanding of cancer. But in the following
decades, Warburgs discovery would largely
disappear from the cancer narrative, his contri-
butions considered so negligible that they were
left out of textbooks altogether.
Unlike Boveri, Warburg wasnt interest-
S TA R V I N G ed in the chromosomes of sea-urchin eggs.
Rather, Warburg was focused on energy,
THE BEAST specically on how the eggs fueled their
growth. By the time Warburg turned his
In the early 20th century, attention from sea-urchin cells to the
the German biochemist Otto Warburg cells of a rat tumor, in 1923, he knew that
believed that tumors could be sea-urchin eggs increased their oxygen
Source photographs from Getty Images and Wikimedia Commons
treated by disrupting their source consumption signicantly as they grew,

of energy. His idea was so he expected to see a similar need for
dismissed for decades until now. extra oxygen in the rat tumor. Instead, the
cancer cells fueled their growth by swal-
lowing up enormous amounts of glucose
(blood sugar) and breaking it down without oxy-
gen. The result made no sense. Oxygen-fueled
reactions are a much more ecient way of turn-
BY SAM APPLE
ing food into energy, and there was plenty of oxy-
gen available for the cancer cells to use. But when
P H O T O I L L U S T R AT I O N S B Y
Warburg tested additional tumors, including ones
CRISTIANA COUCEIRO
from humans, he saw the same eect every time.
The cancer cells were ravenous for glucose.
Warburgs discovery, later named the Warburg
eect, is estimated to occur in up to 80 percent
of cancers. It is so fundamental to most cancers
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5.

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that a positron emission tomography (PET) scan, There are typically many mutations in a sin- said, he would study biochemistry rather than
which has emerged as an important tool in the gle cancer. But there are a limited number of molecular biology.
staging and diagnosis of cancer, works simply ways that the body can produce energy and I never thought, until about two months ago,
by revealing the places in the body where cells support rapid growth. Cancer cells rely on Id ever have to learn the Krebs cycle, he said,
are consuming extra glucose. In many cases, the these fuels in a way that healthy cells dont. referring to the reactions, familiar to most high-
more glucose a tumor consumes, the worse a The hope of scientists at the forefront of the school biology students, by which a cell powers
patients prognosis. Warburg revival is that they will be able to slow itself. Now I realize I have to.
In the years following his breakthrough, War- or even stop tumors by disrupting one
burg became convinced that the Warburg eect or more of the many chemical reactions a cell
occurs because cells are unable to use oxygen uses to proliferate, and, in the process, starve
B
properly and that this damaged
respiration is, in eect, the start-
ing point of cancer. Well into
the 1950s, this theory which
Warburg believed in until his
death in 1970 but never proved
remained an important sub-
ject of debate within the eld.
And then, more quickly than
anyone could have anticipated,
the debate ended. In 1953, James orn in 1883 into the illustrious
Watson and Francis Crick pieced Warburg family, Otto Warburg
together the structure of the DNA was raised to be a science prod-
molecule and set the stage for the igy. His father, Emil, was one of
triumph of molecular biologys Germanys leading physicists,
gene-centered approach to can- and many of the worlds greatest
cer. In the following decades, physicists and chemists, including
scientists came to regard cancer Albert Einstein and Max Planck,
as a disease governed by mutat- were friends of the family. (When
ed genes, which drive cells into Warburg enlisted in the military
a state of relentless division and during World War I, Einstein sent
proliferation. The metabolic him a letter urging him to come
catalysts that Warburg spent home for the sake of science.)
his career analyzing began to Those men had explained the
be referred to as housekeeping mysteries of the universe with
enzymes necessary to keep a a handful of fundamental laws,
cell going but largely irrelevant and the young Warburg came to
to the deeper story of cancer. believe he could bring that same
It was a stampede, says elegant simplicity and clarity
Thomas Seyfried, a biologist at to the workings of life. Long
Boston College, of the move to before his death, Warburg was
molecular biology. Warburg considered perhaps the greatest
was dropped like a hot potato. WARBU RGS WORKS HOP: THE KAIS ER WILHELM biochemist of the 20th century,
Source photograph from Archives of the Max Planck Society, Berlin
INSTITUTE FOR CELL PHYSIOLOGY (NOW PART OF

There was every reason to think THE MAX PLANCK S OCIETY) IN BERLIN, 1 93 1 . a man whose research was vital
that Warburg would remain at to our understanding not only of
best a footnote in the history of cancer research. cancer cells of the nutrients they desperately cancer but also of respiration and photosynthesis.
(As Dominic DAgostino, an associate professor need to grow. In 1931 he won the Nobel Prize for his work on
at the University of South Florida Morsani Col- Even James Watson, one of the fathers of respiration, and he was considered for the award
lege of Medicine, told me, The book that my stu- molecular biology, is convinced that target- on two other occasions each time for a dif-
dents have to use for their cancer biology course ing metabolism is a more promising avenue ferent discovery. Records indicate that he would
has no mention of cancer metabolism.) But over in current cancer research than gene-centered have won in 1944, had the Nazis not forbidden
the past decade, and the past ve years in par- approaches. At his oce at the Cold Spring Har- the acceptance of the Nobel by German citizens.
ticular, something unexpected happened: Those bor Laboratory in Long Island, Watson, 88, sat That Warburg was able to live in Germany and
housekeeping enzymes have again become one beneath one of the original sketches of the DNA continue his research throughout World War II,
of the most promising areas of cancer research. molecule and told me that locating the genes despite having Jewish ancestry and most likely
Scientists now wonder if metabolism could prove that cause cancer has been remarkably unhelp- being gay, speaks to the German obsession with
to be the long-sought Achilles heel of cancer, a ful the belief that sequencing your DNA is cancer in the rst half of the 20th century. At
common weak point in a disease that manifests going to extend your life a cruel illusion. If he the time, cancer was more prevalent in Germany
itself in so many dierent forms. were going into cancer research today, Watson than in almost any other nation. According to the
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Stanford historian Robert Proctor, by the 1920s a country manor and built specically for him. Cancer Center, has been among the most out-
Germanys escalating cancer rates had become a After the war, the Russians approached Warburg spoken proponents of this renewed focus on
major scandal. A number of top Nazis, including and oered to erect a new institute in Moscow. metabolism. In Thompsons analogy, the War-
Hitler, are believed to have harbored a particular Klein recalls that Warburg told them with great burg eect can be thought of as a social failure:
dread of the disease; Hitler and Joseph Goebbels pride that both Hitler and Stalin had failed to a breakdown of the nutrient-sharing agreement
took the time to discuss new advances in cancer move him. As Warburg explained to his sister: that single-celled organisms signed when they
research in the hours leading up to the Nazi inva- Ich war vor Hitler da I was here before Hitler. joined forces to become multicellular organ-
sion of the Soviet Union. Whether Hitler was per- isms. His research showed that cells need to
sonally aware of Warburgs research is unknown, receive instructions from other cells to eat, just
but one of Warburgs former colleagues wrote as they require instructions from other cells to
I
that several sources told him that Hitlers divide. Thompson hypothesized that if he could
entourage became convinced that Warburg identify the mutations that lead a cell to eat
was the only scientist who oered a serious hope more glucose than it should, it would go a long
of producing a cure for cancer one day. way toward explaining how the Warburg eect
Although many Jewish scientists ed Ger- and cancer begin. But Thompsons search for
many during the 1930s, Warburg chose to those mutations didnt lead to an entirely new
remain. According to his biographer, the discovery. Instead, it led him to AKT, a gene
Nobel Prize-winning biochemist Hans Krebs, already well known to molecular biologists for
who worked in Warburgs lab, science was the its role in promoting cell division. Thompson
dominant emotion of Warburgs adult life, vir- now believes AKT plays an even more funda-
tually subjugating all other emotions. In Krebss magine two engines, the one being driven by mental role in metabolism.
telling, Warburg spent years building a small complete and the other by incomplete combus- The protein created by AKT is part of a chain
team of specially trained technicians who knew tion of coal, Warburg wrote in 1956, responding of signaling proteins that is mutated in up to 80
how to run his experiments, and he feared that to a criticism of his hypothesis that cancer is a percent of all cancers. Thompson says that once
his mission to defeat cancer would be set back problem of energy. A man who knows nothing these proteins go into overdrive, a cell no longer 5.
signicantly if he had to start over. But after the at all about engines, their structure and their worries about signals from other cells to eat; it
war, Warburg red all the technicians, suspecting purpose may discover the dierence. He may, instead stus itself with glucose. Thompson dis-
that they had reported his criticisms of the Third for example, smell it. covered he could induce the full Warburg eect
Reich to the Gestapo. Warburgs reckless deci- The complete combustion, in Warburgs anal- simply by placing an activated AKT protein into a
sion to stay in Nazi Germany most likely came ogy, is respiration. The incomplete combustion, normal cell. When that happens, Thompson says,
down to his astonishing ego. (Upon learning he turning nutrients into energy without oxygen, is the cells begin to do what every single-celled
had won the Nobel Prize, Warburgs response known as fermentation. Fermentation provides organism will do in the presence of food: eat
was, Its high time.) a useful backup when oxygen cant reach cells as much as it can and make as many copies of
Modesty was not a virtue of Otto Warburg, quickly enough to keep up with demand. (Our itself as possible. When Thompson presents his
says George Klein, a 90-year-old cancer research- muscle cells turn to fermentation during intense research to high-school students, he shows them
er at the Karolinska Institute in Sweden. As a exercise.) Warburg thought that defects prevent a slide of mold spreading across a piece of bread.
young man, Klein was asked to send cancer cells cancer cells from being able to use respiration, but The slides heading Everyones rst cancer
to Warburgs lab. A number of years later, Kleins scientists now widely agree that this is wrong. A experiment recalls Warburgs observation
boss approached Warburg for a recommendation growing tumor can be thought of as a construc- that cancer cells will carry out fermentation at
on Kleins behalf. George Klein has made a very tion site, and as todays researchers explain it, the almost the same rate of wildly growing yeasts.
important contribution to cancer research, War- Warburg eect opens the gates for more and more Just as Thompson has redened the role of
burg wrote. He has sent me the cells with which I trucks to deliver building materials (in the form AKT, Chi Van Dang, director of the Abramson
have solved the cancer problem. Klein also recalls of glucose molecules) to make daughter cells. Cancer Center at the University of Pennsylvania,
the lecture Warburg gave in Stockholm in 1950 at If this theory can explain the why of the has helped lead the cancer world to an appreci-
the 50th anniversary of the Nobel Prize. Warburg Warburg eect, it still leaves the more pressing ation of how one widely studied gene can pro-
drew four diagrams on a blackboard explaining question of what, exactly, sets a cell on the path foundly inuence a tumors metabolism. In 1997,
the Warburg eect, and then told the members to the Warburg eect and cancer. Scientists at Dang became one of the rst scientists to con-
of the audience that they represented all that they several of the nations top cancer hospitals have nect molecular biology to the science of cellular
needed to know about the biochemistry of cancer. spearheaded the Warburg revival, in hopes of metabolism when he demonstrated that MYC a
Warburg was so monumentally stubborn that nding the answer. These researchers, typical- so-called regulator gene well known for its role
he refused to use the word mitochondria, even ly molecular biologists by training, have turned in cell proliferation directly targets an enzyme
after it had been widely accepted as the name to metabolism and the Warburg eect because that can turn on the Warburg eect. Dang recalls
for the tiny structures that power cells. Instead their own research led each of them to the same that other researchers were skeptical of his inter-
Warburg persisted in calling them grana, the conclusion: A number of the cancer-causing est in a housekeeping enzyme, but he stuck with it
term he came up with when he identied those genes that have long been known for their role because he came to appreciate something critical:
structures as the site of cellular respiration. Few in cell division also regulate cells consumption Cancer cells cant stop eating.
things would have been more upsetting to him of nutrients. Unlike healthy cells, growing cancer cells
than the thought of Nazi thugs chasing him out Craig Thompson, the president and chief are missing the internal feedback loops that are
of the beautiful Berlin institute, modeled after executive of the Memorial Sloan Kettering designed to conserve (Continued on Page 74)

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S TA N D A R D
OF CARE
At a Catholic nursing home

in New York, the sisters who treat
the untreatable.
PHOTO G R A PH S BY G I L L I A N L AU B
That began to change with the broad accep- mother-in-law was Jewish and live by the pre-
tance of hospice, which spread in the United States scient words of its founder, Rose Hawthorne
during the 1970s and 1980s and turned the innova- Lathrop, a daughter of Nathaniel Hawthorne:
tions of modern medicine toward helping those We cannot cure our patients, but we can assure
whose cures were beyond its reach. The physician the dignity and value of their nal days, and keep
Dame Cicely Saunders founded the rst modern them comfortable and free of pain. (The Haw-
clinic in London; the term hospice had rst been thorne Dominicans also operate similar homes
used by old sanctuaries for weary travelers. in Atlanta and Philadelphia.)
Sanctuary, says the photographer Gillian Laub, As the nuns cared for their guests, Laub fol-
is what she and her family found at Rosary Hill lowed them with her camera its her way.
Home in Hawthorne, N.Y., a hamlet in Westches- Then, even after her mother-in-law died in late
ter County. Laubs mother-in-law was suering September, she found herself returning to Rosa-
from terminal cancer, and her insurance would ry again and again, still wanting to capture some-
not cover the 24-hour care she required. So they thing of the kindness that her family had found
took her to Rosary, which is run by Catholic nuns there. She asked the nuns to sit for portraits,
and accepts no payment from the families of those in which she stripped away the background to
t the beginning of the 20th century, sick Ameri- they treat all of them with incurable cancer. show their eyes and faces in clear focus. I want-
cans typically died at home. By the middle of it, Rosary, which sits on a hill above the town, ed them to be quiet, she said, so their power
they mostly died in hospitals. And yet this great was founded in 1901, long before the mainstream could come through.
transformation in the geography of death was, at medical community embraced hospice care and The nuns in particular had moved her. She
rst, of little interest to medical providers: In the during a time when some doctors still thought was struck by their tenderness with the dying,
1960s, some doctors routinely chose not to inform cancer was contagious. Although it still treats only how they painted womens ngernails and
terminal patients of their fate. Studies found the terminally ill, Rosary is not technically consid- combed their hair, changed them into fresh
hospitals stashing dying people at the ends of ered a hospice in New York because, among other nightgowns and arranged owers in their
halls and largely ignoring them. Medicine, it was things, it accepts patients too early. The nuns, who rooms. This is how dying should be, Laub says.
said, was about healing people. It had nothing are members of the Dominican order, care for It doesnt feel like a place of death. It feels like
to oer the already dying. those of all religions and backgrounds Laubs a place of living. BROOKE JARV IS
68 5.15.16

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6.

P r e s s R e a d e r. c o m +1 604 278 4604
SISTE R JOAN
M A RIE , 66: 24 YE ARS WITH
THE HAWTHORNE
DOMINICANS. PREVIOUS
PAGE : SISTER REGINA
MARIE, 31: SIX YEARS.

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SI STE R KE V IN, 88: 6 4 Y EAR S. SISTER MARIA GIANNA, 32: FOUR YEARS.
6.
Photographs by Gillian Laub
SI STE R STE L L A MARY, 4 4 : 10 Y EAR S. S IST ER CAR MEL A M A R I E , 4 0 : 1 0 Y E A R S.
The Caregivers: Additional portraits are at nytimes.com/magazine. 71

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Leukemia is hell, and it sucks. He is still going to die, so from Stanfords protocol to increase Andrews
(Continued from Page 63) there is nothing joyous about this time. chances of getting a robust graft versus leuke-
When they rst got Andrews diagnosis, she mia eect. Typically, a leukemia patient receives
she said. You are always going to have a brother told a night nurse that she just wanted to get her immune-suppressing drugs for at least 100 days
named Andrew because he is always your brother, happy-go-lucky little boy back for a single hour. (and often much longer) in order to avoid a seri-
now and forever. She had not understood then that any reprieve ous side eect called graft versus host disease,
Andrews pieces of love will always be in our would only mean that they would have to go in which new T cells attack not only the cancer
heart, Lea said, and then they all agreed to watch through losing him all over again and each cells but also the patients skin, liver and gas-
Mickey Mouse together. return will be harder than the last as Andrew trointestinal tract. The art of a transplant is said
grows and bonds with us, she wrote in a post. to be maximizing graft versus leukemia while
The vigil stretched on through the summer, and By October, Andrew was healthier than he had minimizing graft versus host.
what they called mirages began to appear. In been in a year, running and playing ball with his Willert, who is now at the University of Cali-
late July, Esther was sitting outside with Bar- siblings. None of the doctors had ever seen this fornia, San Francisco, Benio Childrens Hospital,
bara Sourkes, holding Andrew and watching kind of recovery before. They decided to bring had advocated a rapid early taper of Andrews
Wills shoot baskets. Suddenly Andrew sat up him back to the hospital for a bone-marrow test. immune-suppressing drugs on Day 60, as is the
and reached for a ball and managed to throw Michael Loken, who had analyzed Andrews practice at U.C.S.F. and other places, because she
it through his own little basketball hoop. Esther blood work, had not been surprised that felt that the benets outweighed the risk of graft
and Barbara were speechless. Andrews cancer returned. He had been working versus host. I fought for it because I have seen
At rst the mirages were brief Andrew on a paper about R.A.M., the genetic marker that the power of getting rid of immune suppressants
would laugh when Lea showed him her bellybut- Andrew had. He had tracked 19 other cases of and letting the cells do their job, she says. After
ton or would stack blocks for 10 minutes and children with the phenotype; three years after the all, thats the whole point of a transplant!
then he would lapse back into pained lethargy diagnosis, only two were still alive and healthy. The nal, critical decision was made against
for the rest of the day. But soon these episodes When he examined Andrews marrow this time, medical advice: Esther and Dans resolution to
began to lengthen. For Esther, the mirages did using a sample of 200,000 cells, he got goose stop treatment and let Andrew die. Had they
not feel like miracles but evil tricks. She went bumps. He repeated the test with 500,000 cells. permitted more chemotherapy, the treatment
through intense surges of anger. I felt like, How Then he called Lacayo with the news. The cancer would have killed Willss cells, which were what
many trials are we going to have to endure? she had disappeared. ultimately enabled Andrew to live.
says. Are we being spared nothing?
Esther started sending the medical team vid- How could cancer spontaneously disappear? When you have a child with a life-threatening
eos. Andrew is eating pizza, Andrew is sitting It does feel a bit like a miracle, says Jennifer illness, you have an irrevocably altered exis-
up, Andrew is laughing, Lacayo, their oncologist, Willert, the transplant doctor, echoing the sentence, Barbara Sourkes had told the Levys, and
recounts. And we are like, What? timents of others. Noting the rare evocation of a Esther feels that is true. She had always felt in
In August, as the team struggled to account concept that stands outside science, Loken says: control of her fate, but now she believes this to
for what was happening, they theorized that in It certainly deed our expectations with no dis- be a ction. She nds it dicult to reconcile bit-
July, when everyone assumed Andrew was dying cernible basis of happening. I guess this may be terness over the blight of Andrews illness with
of cancer, he must have had a terrible infection the denition of a miracle. gratitude for the reprieve. We are the luckiest
instead, which passed. It didnt change the prog- The medical team grasped for a scientic of the unluckiest people in the world, she says.
nosis: The doctors stressed that, while Andrew explanation. Because Andrew had received no I truly believe that. The story presents itself to
might continue to recover from that infection as treatment over the summer, the answer had her as a riddle that cannot be resolved. She recalls
his new immune system took hold, the cancer to lie in the bone-marrow transplant of Willss her anger when others told them to hope. Is the
cells were also growing and would eventually cells. Their main theory was that the infection lesson that their friends were right and there is
overwhelm him. that nearly killed Andrew in July had triggered a always hope? Yet it was only by letting go of hope
After a blood test showed that his platelets huge increase in his new white blood cells and and accepting Andrews death that he lived.
were low, Cohen, the palliative-care doctor, that heightened immune response had attacked She has not returned to work. My full-time
urged them to accept transfusions to increase not only the infection but the cancer cells as well. job is to help the kids feel safe again, she says. But
Andrews platelets so that, even though he was The doctors theorized that the response it is hard for her to feel safe. The two years after a
going to die, it would not be from bleeding to was partly a product of timing: The cancer had transplant are the riskiest time for a relapse; after
death. But at the hospital, it turned out, myste- returned just as Andrews new immune system two years that likelihood plummets, and after ve
riously, that Andrew had more platelets than at grew strong enough to destroy the cancer cells. years, a patient is considered cured. The two-year
his last blood test, so there was no need for a A critical part of why transplants work is that mark is still nine months away.
transfusion that day. When Dan suggested giving some of the white blood cells, the T cells, that There are only two states after such a diag-
him vitamins, Esther snapped at him. He seemed grow from the transplanted bone marrow will nosis: disease and uncertainty, Cohen had told
to be taking the anomalous blood test to mean attack any lingering cancer cells, an eect them. Either he will die soon, and thats certain
Andrew was getting better, when, she says, I had known as graft versus leukemia. Chemother- or he will continue on, and you will live with
no hope, and I needed not to have hope in order apy rarely kills every last cancer cell, so it is that constant balance of hope and fear. But the
to function. And then they both apologized. believed that without graft versus leukemia, the balance will change as time goes on.
In September, Andrew began to walk again, cancer will eventually grow back. This is often Only in the past few weeks, Esther says, has
and his appetite and energy and dark curls grew. spoken of as a model of so-called immunother- she been able to feel that she isnt testing fate by
Dan decided to return to work. Andrew turned apy stimulating the patients own immune scheduling a dentist appointment for Andrew six
2 a birthday his parents had never thought he system to attack cancer cells which is widely months out or by feeling moments of joy watch-
would reach and knew would be his last. Esther regarded as one of the most promising avenues ing him without being shadowed by fear of the
recalls how friends urged them to enjoy every for cancer treatment. future. Day by day, she says, we are allowing
moment, and how she would tell them: No, this Willert had made a key decision to depart ourselves to celebrate a little more.
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Warburg to another primary fuel used by cancers. You insulin, which is released by the pancreas and tells
(Continued from Page 67) block glucose and glutamine, they might be able cells to take up glucose, inuences what happens
to use fatty acids. We dont know yet. inside a cell. Cantley now refers to insulin and a
resources when food isnt available. Theyre Given Warburgs own story of historical closely related hormone, IGF-1 (insulinlike growth
addicted to nutrients, Dang says; when they cant neglect, its tting that what may turn out to be one factor 1), as the champion activators of meta-
consume enough, they begin to die. The addiction of the most promising cancer metabolism drugs bolic proteins linked to cancer. Hes beginning to
to nutrients explains why changes to metabolic has been sitting in plain sight for decades. That see evidence, he says, that in some cases, it really
pathways are so common and tend to arise rst as drug, metformin, is already widely prescribed to is insulin itself thats getting the tumor started.
a cell progresses toward cancer: Its not that other decrease the glucose in the blood of diabetics One way to think about the Warburg eect, says
types of alterations cant arise rst, but rather that, (76.9 million metformin prescriptions were lled Cantley, is as the insulin, or IGF-1, signaling path-
when they do, the incipient tumors lack the access in the United States in 2014). In the years ahead, way gone awry its cells behaving as though
to the nutrients they need to grow. Dang uses the its likely to be used to treat or at least to pre- insulin were telling it to take up glucose all the
analogy of a work crew trying to put up a build- vent some cancers. Because metformin can time and to grow. Cantley, who avoids eating
ing. If you dont have enough cement, and you inuence a number of metabolic pathways, the sugar as much as he can, is currently studying
try to put a lot of bricks precise mechanism by the eects of diet on mice that have the mutations
together, youre going to which it achieves its anti- that are commonly found in colorectal and other
collapse, he says. cancer eects remains a cancers. He says that the eects of a sugary diet on
Metabolism-centered source of debate. But colorectal, breast and other cancer models looks
therapies have produced the results of numerous very impressive and rather scary.
some tantalizing suc- METABOLISM COULD epidemiological studies Elevated insulin is also strongly associated
cesses. Agios Pharma- BE THE LONG-SOUGHT have been striking. Dia- with obesity, which is expected soon to over-
ceuticals, a company ACHILLES HEEL betics taking metformin take smoking as the leading cause of preventable
co-founded by Thomp- OF CANCER, A COMMON seem to be signicantly cancer. Cancers linked to obesity and diabetes
son, is now testing a WEAK POINT IN A less likely to develop can- have more receptors for insulin and IGF-1, and
drug that treats cases of DISEASE THAT MANIFESTS cer than diabetics who people with defective IGF-1 receptors appear
acute myelogenous leu- IN SO MANY dont and signicantly to be nearly immune to cancer. Retrospective
kemia that have been DIFFERENT FORMS. less likely to die from the studies, which look back at patient histories, sug-
resistant to other ther- disease when they do. gest that many people who develop colorectal,
apies by inhibiting the pancreatic or breast cancer have elevated insulin
mutated versions of the levels before diagnosis. Its perhaps not entire-
metabolic enzyme IDH ly surprising, then, that when researchers want
N
2. In clinical trials of the to grow breast-cancer cells in the lab, they add
Agios drug, nearly 40 percent of patients who insulin to the tissue culture. When they remove
carry these mutations are experiencing at least the insulin, the cancer cells die.
partial remissions. I think theres no doubt that insulin is
Researchers working in a lab run by Peter pro-cancer, Watson says, with respect to the
Pedersen, a professor of biochemistry at Johns link between obesity, diabetes and cancer. Its
Hopkins, discovered that a compound known as as good a hypothesis as we have now. Watson
3-bromopyruvate can block energy production in takes metformin for cancer prevention; among
cancer cells and, at least in rats and rabbits, wipe its many eects, metformin works to lower insu-
out advanced liver cancer. (Trials of the drug have lin levels. Not every cancer researcher, howev-
yet to begin.) At Penn, Dang and his colleagues er, is convinced of the role of insulin and IGF-1
are now trying to block multiple metabolic path- ear the end of his life, Warburg grew obsessed in cancer. Robert Weinberg, a researcher at
ways at the same time. In mice, this two-pronged with his diet. He believed that most cancer was M.I.T.s Whitehead Institute who pioneered the
approach has been able to shrink some tumors preventable and thought that chemicals added to discovery of cancer-causing genes in the 80s,
without debilitating side eects. Dang says the food and used in agriculture could cause tumors has remained somewhat cool to certain aspects
hope is not necessarily to nd a cure but rather to by interfering with respiration. He stopped eating of the cancer-metabolism revival. Weinberg says
keep cancer at bay in a smoldering quiet state, bread unless it was baked in his own home. He that there isnt yet enough evidence to know
much as patients treat their hypertension. would drink milk only if it came from a special whether the levels of insulin and IGF-1 present
Warburg, too, appreciated that a tumors herd of cows, and used a centrifuge at his lab to in obese people are sucient to trigger the War-
dependence upon a steady ow of nutrients make his cream and butter. burg eect. Its a hypothesis, Weinberg says.
might eventually prove to be its fatal weakness. Warburgs personal diet is unlikely to become I dont know if its right or wrong.
Long after his initial discovery of the Warburg a path to prevention. But the Warburg revival has During Warburgs lifetime, insulins eects on
eect, he continued to research the enzymes allowed researchers to develop a hypothesis for metabolic pathways were even less well under-
involved in fermentation and to explore the pos- how the diets that are linked to our obesity and stood. But given his ego, its highly unlikely that
sibility of blocking the process in cancer cells. diabetes epidemics specically, sugar-heavy he would have considered the possibility that
The challenge Warburg faced then is the same diets that can result in permanently elevated lev- anything other than damaged respiration could
one that metabolism researchers face today: Can- els of the hormone insulin may also be driving cause cancer. He died sure that he was right about
cer is an incredibly persistent foe. Blocking one cells to the Warburg eect and cancer. the disease. Warburg framed a quote from Max
metabolic pathway has been shown to slow down The insulin hypothesis can be traced to the Planck and hung it above his desk: A new sci-
and even stop tumor growth in some cases, but research of Lewis Cantley, the director of the entic truth does not triumph by convincing its
tumors tend to nd another way. You block glu- Meyer Cancer Center at Weill Cornell Medical opponents and making them see the light, but
cose, they use glutamine, Dang says, in reference College. In the 1980s, Cantley discovered how rather because its opponents eventually die.
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Oncologist
(Continued from Page 47)
two systems in this machine are aected: stability

and temperature.
Cancer, Vogelstein argues, is analogous. Most
of the genes that are mutated in cancer also func-
tion in loops and circuits pathways. Super-
cially, the permutations of genetic aws might
be boundless, but lumped into pathways, the
complexity can be organized along the arche-
typal, core aws. Perhaps these cancer pathways
are like Hollywood movies; at rst glance, there
seems to be an innite array of plot lines in an
innite array of settings gold-rush California,
the Upper West Side, a galaxy far, far away. But
closer examination yields only a handful of arche-
typal narratives: boy meets girl, stranger comes
to town, son searches for father.
How many such pathways, or systems, oper-
ate across a subtype of cancer? Looking at one
cancer, pancreatic, and mapping the variations
in mutated genes across hundreds of specimens,
Vogelsteins team proposed a staggeringly sim-
ple answer: 12. (One such core pathway, for
instance, involves genes that enable cells to
invade other tissues. These genes normally allow
cells to migrate through parts of the body but
in cancer, migration becomes distorted into
invasion.) If we could nd medicines that could
target these 12 core pathways, we might be able
to attack most pancreatic cancers, despite their
genetic diversity. But that means inventing 12
potential ways to block these core paths an
immense creative challenge for scientists, con-
sidering that they havent yet gured out how to
target more than, at best, one or two.
Immunological therapies provide a second
solution to the impasse of unlimited diversity.
One advantage of deploying a patients own
immune system against cancer is that immuno-
logical cells are generally agnostic to the muta-
tions that cause a particular cancers growth. The
immune system was designed to spot dierences
in the supercial features of a diseased or foreign
cell, thereby identifying and killing it. It cares as
little about genes as an intercontinental ballis-
tic missile cares about the email addresses, or
dietary preferences, of the population that it has
been sent to destroy.
A few years ago, in writing a history of cancer,

I interviewed Emil Freireich. Freireich, working
with Emil Frei at the National Cancer Institute
in the 1960s and 70s, stumbled on the idea of
deploying multiple toxic drugs simultaneously
to treat cancer combination chemotherapy.
They devised one of the rst standard protocols
vincristine, Adriamycin, methotrexate and
prednisone, known as VAMP to treat pediat-
ric leukemias. Virtually nothing about the VAMP
protocol was individualized (although doses
could be reduced if needed). In fact, doctors

P r e s s R e a d e r. c o m +1 604 278 4604
were discouraged from trying alternatives to Answers to puzzles of 5.8.16
the formula.
Yet as Freireich recalled, long before they TRAPPED MOISTURE
came up with the idea for a protocol, there were S A G E S H A D A J A R F A S T
Reach for the stars small, brave experiments; before trials, there was A T R I A B I T E S U R E I N T E R
this summer
S W O R N A G R A S L I C E S E R V E
trial and error. VAMP was brought into existence H A W E D C H A N G E Y O U R H2O W A Y S
A R T C H O O R A T T R I O W E T
through grit, instinct and inspired lunges into H2O M A I N C O U R S E S K I M
the unknown. Vincent T. DeVita Jr., who worked K A R A T E T O S S W O W S C A L E
R E M I D R A N K D I D I T I T I S
with Freireich in the 1960s, wrote a book, The O R O N O A N A S O N A T A N S E C
F I N E L I N E D O G G Y H2O B A G
Death of Cancer, with his daughter, Elizabeth T E E I N C M O L E S N O B J A S
DeVita-Raeburn. In it, he recalled a time when H O T H2O W I R E S T O O L B E L T
S O S O R U I N E D I R R Y O W I E
the leukemic children in Freireichs trial were A B E T O S L I N R O A S T A I N T
dying of bacterial meningitis during treatment. D I N E R
S L U R
E E N
G O
S E
O D
W
A
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S
H O R S
G O L D H2O
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The deaths threatened the entire trial: If Freire- E Y E S E A S B R R I E R E L A B

S A L T H2O O F T H E E A R T H A N I T A
To learn about our variety ich couldnt keep the children alive during the T H E H U S T L E R F A I R N A D A L
of unique summer camps call therapy, there would be no possibility of remis- H O S E R E E R O T R O Y N E A L S
O S O S R O A N S E N A S Y L A
305.367.6516 or visit sion. They had an antibiotic that could kill the
OceanReefClubSummerCamps.com microbe, but the medicine wouldnt penetrate
the blood-brain barrier. So Freireich decided to KENKEN
try something that pushed the bounds of stan-

dard practice. He ordered DeVita, his junior,
to inject it directly into the spinal cords of his
patients. It was an extreme example of o-label
use of the drug: The medicine was not meant for
use in the cord. DeVita writes:
The rst time Freireich told me to do it, I
held up the vial and showed him the label, think- CRYPTIC
Breuer Classic. Natural, ing that hed possibly missed something. It says C R U M P E T S ACROSS:1. anag. spectrum 5.
C L O G U P
honey, teak, walnut, black, or c(log)up 9. gig + antic 10. rev.
white with blonde cane. right on there, Do not use intrathecally, I said. O N A R A A A
One piece chrome

G I G A N T I C
hidden presumably 11. no rah 12.
A M U S E R
Freireich glowered at me and pointed a long, E I T C E P A
anag. repeating some letters roles
frame. Floor glides. N O R A H E R R O R L E S S
Side Chair $159 bony nger in my face. Do it! he barked. I did it, T D E R A D I 14. anag. repeating some letters
Back $44 though I was terried. But it worked every time. I N A N I N S T A N T saint 18. anag. repeating some
request brochure K A S T S I L E letters notes 21. anag. repeating
When I asked Freireich about that episode N O N E T O O S O O N some letters dares 23. a(do)R.N.
Arm Chair
and about what he would change in the current E O P
A D D R E S S E D
N G G K
A D O R N
24. winning w 25. str(O.K.)ing
$ landscape of cancer therapy, he pointed to its 26. G + usted 27. serge + ant
169 D Y R
I N N I N G
E L D
S T R O K I N G
I
DOWN: 1. co-gent 2. anag. during
extreme cautiousness. We would never have N E I R N V H 3. pant heist 4. trice + Ra + tops 6.
$
44 achieved anything in this atmosphere, he said.
The pioneer of protocols pined for a time before
G U S T E D S E R G E A N T two meanings 7. gasped Al 8. par
+ a + site 13. anag. Senator Reid 15.
sin + gal + on + G 16. homophone needing 17. anag. yes and no 19. go
Breuer replacement seat. there were any protocols. + diva 20. k + night 22. hidden her niece
16 3/8 x18 3/8w. Medicine needs standards, of course, oth-
National Ordering: 800-616-3667
10-5 M-F (ET) . VISA . MC . AE erwise it can ramble into dangerous realms, FILM RE-VIEWS BATTLESHIPS
www.homewardfurniture.com +shipping.
compromising safety and reliability. But cancer
1. Id always 6. Han Solo 0 2 0 2 1 4 1
medicine also needs a healthy dose of Freireich: assumed snapped at
the desire to read between the (guide)lines, to Academy Award Princess Leia 3 . . . . . . .
winners . . . 7. . . . production of 1 . . . . . . .
reimagine the outer boundaries, to perform the 2. Casino Royale a play Al Pacino
features a is starring in. 2 . . . . . . .
experiments that become the standards of the horrific car 8. If youre taking 1 . . . . . . .
future. In January, President Obama introduced accident . . . your date to the
3. I dont think movies, pick a
0 . . . . . . .
an enormous campaign for precision medicine. there was ever more romantic 0 . . . . . . .
Cancer is its molten centerpiece: Using huge an Abbott 9. . . . film version of
3 . . . < . . .
troves of data, including gene sequences of and Costello Auntie Mame,
werewolf movie I thought the
hundreds of thousands of specimens and exper- ... stage version
4. In New York was better.
iments performed in laboratories nationwide, City tickets for 10. . . . would earn
the projects goal is to nd individualized med- movies . . . it a rating of X
5. If you enjoy when it was first
icines for every patients cancer. But as we wait hearing the released.
for that decades-long project to be completed, name Stella
called . . .
oncologists still have to treat patients now. To
Award-Winning Photography understand the minds of individual cancers, we Answers to puzzle on Page 78
From The New York Times
are learning to mix and match these two kinds
SPELLING BEE
of learning the standard and the idiosyncrat-
ic in unusual and creative ways. Its the kind Moratorium (3 points). Also: Amour, armor, aroma, atrium, automat,
888.669.2709 of medicine that so many of us went to medical
automata, imitator, marmot, mirror, momma (or mamma), moratoria,
mortar, motor, motto, murmur, muumuu, rumor, tatami, tomato,
nytimes.com/store school to learn, the kind that wed almost forgot- trauma, tritium, tumor, umami. If you found other legitimate dictionary
ten how to practice. words in the beehive, feel free to include them in your score.
76 5.15.16

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Lazarus Effect
(Continued from Page 53)
discoveries and competing for grants, and in

many ways they are right, Wagle said. I get it.
The project cuts against the grain of a medi-
cal system that was not designed to learn from
patients. Every day in this country, doctors treat
people for all kinds of disorders, and some do
surprisingly well, or surprisingly poorly and
virtually all of this information is lost to science.
Eric Lander, the founding director of the Broad
Institute and co-chairman of the Presidents
Council of Advisors on Science and Technology,
has begun laying the groundwork for a national
project he calls Count Me In, which would allow
anyone to make their medical records, and DNA,
available to researchers. In my opinion, Lander
said, its a crime to let valuable information go
to waste when a patient wants to share it.
Wagles project is Count Me Ins rst under-
taking. Next, Count Me In is beginning a similar
eort on angiosarcoma, an understudied cancer,
and two more eorts are planned this year. Preci-
sion oncology has been driven by advances in two
areas: automation, responsible for the plummet-
ing cost of genetic sequencing, and information
technology, which allows the data to be recorded
and interpreted. Projects like Count Me In are
built on the premise that a third disruptive tech-
nology can also be brought to bear: social media.
The campaign by American political leaders
to cure cancer goes back decades, including Nix-
ons war on cancer. But these latest federal calls
for action which bring to mind images of the
best and brightest, backed by brute force risk
mistaking the nature of the opponent and mis-
understanding the potential of the weapons now
available. Ask almost any specialist about a cure
for cancer, and she will cringe, because there is
no one cancer to be cured. We face an enemy that
is resourceful, changeable and merciless, but we
have a population that wants to help. Instead of a
war (or a moonshot), what is required probably
looks more like a counterinsurgency operation.
The people are tired of being victimized, unable
to have a say in their own fates. Almost any one
of them would tell you: If you are going to die,
its better to die with a purpose.
The patients enlisted so far, however, have
joined almost by accident. Sharon, who contin-
ues to live in Florida without any sign of cancer,
explained how thoroughly her good fortune has
depended on her circumstances. Her son-in-law,
an oncologist, pointed her to Sloan Kettering,
and she could aord to y up every four weeks to
participate in the trial. I think about the people
who would have trouble with funds, and it breaks
my heart, she said. If Grace had not happened to
live near Boston, the odds that she could have laid
eyes on any of her grandchildren or contribut-
ed to science are long indeed. Carole Arenson,
who has continued to do (Continued on Page 79)

P r e s s R e a d e r. c o m +1 604 278 4604
Puzzles
SPELLING BEE PROJECTORS BATTLESHIPS

By Frank Longo By Patrick Berry By Wei-Hwa Huang
How many common words of 5 or more letters can Answer the clues for 8 words 4 across and 4 down This is a puzzle version of the classic pencil-and-
you spell using the letters in the hive? Every answer to be entered in the grid. Each answer is 1 letter paper game. Place 1 cruiser (3 grid cells, as shown),
must use the center letter at least once. Letters may too long to fit, though, so either the first or last letter 2 destroyers (2 cells) and 3 submarines (1 cell) in the
be reused in a word. At least 1 word will use all 7 will project outside the grid. The clues are in no grid horizontally and vertically so that no 2 vessels
letters. Proper names and hyphenated words are not particular order. One letter has been placed for you touch, not even diagonally. The numbers at the side of
allowed. Score 1 point for each answer, and 3 points as a starting help. When the puzzle is done, start at the grid tell you how many cells in the corresponding
for a word that uses all 7 letters. the upper left and read the projecting letters rows and columns are occupied by vessels.
clockwise to get the name of a famous film (like BEN-
Ex. Fleet
Rating: 8 = good; 15 = excellent; 22 = genius HUR in the example below).
0 2 0 2 1 4 1
B E 3 . . . . . . .
1 . . . . . . .
R U B Y 2 . . . . . . .
1 . . . . . . .
S E E N
0 . . . . . . .
A H A
U
S H 0
3
.
.
.
.
.
.
.
<
.
.
.
.
.
.
Clues: Funny bones location Eliots ___ Marner

U I Dumpster emanations Legendary firefighter Red
Nuns wear Boots, as from office Edit, as a voice-over
3 1 1 2 1 2 0
Three-note chord 1 o . . . . . .
M 1 . . . . . . .
T O 2 . . . . . . .
B 1 . . . . . . .
R 3 . . . . . . .
1 . . . . . . .
Our list of words, worth 26 points, appears with last weeks answers. 1 . . . . . . .
ACROSTIC
1 Y 2 C 3 M 4 T 5 D 6 X 7 U 8 L 9 W 10 S 11 F 12 A 13 I 14 B 15 R 16 N 17 J 18 K 19 O 20 H 21 P 22 E 23 V 24 T
25 Q 26 Y 27 D 28 L 29 M 30 A 31 N 32 X 33 F 34 W 35 B 36 R 37 I 38 O 39 V 40 C 41 G 42 E 43 H 44 L 45 X 46 T
By Emily Cox & Henry Rathvon 47 D 48 P 49 R 50 K 51 B 52 M 53 N 54 F 55 V 56 J 57 C 58 A 59 E 60 Q 61 L 62 G 63 R 64 K 65 S 66 U 67 O 68 B
Guess the words defined below and 69 Y 70 X 71 N 72 T 73 P 74 Q 75 C 76 I 77 W 78 V 79 J 80 H 81 G 82 F 83 Y 84 S 85 E 86 X 87 M 88 B 89 W

write them over their numbered
dashes. Then transfer each letter to 90 A 91 L 92 P 93 I 94 V 95 D 96 H 97 Q 98 O 99 K 100 X 101 J 102 S 103 W 104 U 105 Y 106 T 107 M 108 C 109 H 110 A
the correspondingly numbered square
in the pattern. Black squares indicate 111 B 112 K 113 Q 114 E 115 G 116 D 117 S 118 I 119 X 120 N 121 R 122 P 123 H 124 U 125 O 126 A 127 T 128 K 129 E 130 C 131 J 132 I
where words end. The filled pattern will

133 D 134 V 135 G 136 M 137 X 138 W 139 R 140 U 141 O 142 T 143 F 144 B 145 N 146 A 147 P 148 G 149 S 150 H 151 Y 152 Q 153 J
contain a quotation reading from left
to right. The first letters of the guessed
154 E 155 W 156 R 157 K 158 V 159 U 160 P 161 I 162 N 163 C 164 Y 165 G 166 L 167 S 168 B 169 J 170 Q 171 D 172 K 173 M
words will form an acrostic giving the
authors name and the title of the work.
A. Streaks made by falling rocks G. Hedy Lamarr role opposite Victor M. Insult T. Lack of ideas or substance
____ ____ ____ ____ ____ ____ ____ Mature ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____
12 30 146 58 110 126 90 ____ ____ ____ ____ ____ ____ ____ 107 52 136 173 3 87 29 24 142 106 72 127 4 46
B. Disinclined to do work 41 148 135 81 62 165 115 N. Altered by permeation U. Consummate, thoroughgoing,
H. Illustrious; noteworthy ____ ____ ____ ____ ____ ____ ____ complete
____ ____ ____ ____ ____ ____ ____ ____ 53 31 71 162 145 120 16
68 14 51 88 144 35 168 111 ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____
O. Musical set at Rydell High 159 140 7 66 124 104
C. In a light and fluffy form 96 20 123 80 150 109 43
____ ____ ____ ____ ____ ____ V. Things feared by aichmophobes
____ ____ ____ ____ ____ ____ ____ I. Leave confounded 125 98 141 38 67 19
163 57 40 130 2 75 108 ____ ____ ____ ____ ____ ____ ____ P. Bad news on the bottom line (2 wds.)
____ ____ ____ ____ ____ ____ ____
78 94 158 55 23 134 39
D. Swill 161 132 93 118 13 76 37
____ ____ ____ ____ ____ ____ ____ W. Crashers opposite
____ ____ ____ ____ ____ ____ ____ J. Item akin to a tuffet 92 147 122 73 48 160 21
Q. Discriminatory sort, snob ____ ____ ____ ____ ____ ____ ____
171 116 95 47 27 133 5 ____ ____ ____ ____ ____ ____ ____ 103 89 34 77 155 138 9
E. ____ recollected in tranquility 101 17 56 169 131 79 153 ____ ____ ____ ____ ____ ____ ____
25 74 113 97 152 60 170 X. Like a rapier but not a scimitar
(Wordsworth words on poetry) K. World capital designed by British (hyph.)
architects (2 wds.) R. Release an oocyte
____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____
____ ____ ____ ____ ____ ____ ____
22 59 42 114 154 129 85 ____ ____ ____ ____ ____ ____ ____ ____ 156 63 49 36 139 121 15 32 137 70 6 86 119 45 100
F. What almost half of U.S. state 157 64 112 128 172 50 18 99
S. Slurping or burping at the table, e.g. Y. Language in which goodbye is
mottoes are in L. Projects by seekers of degrees (2 wds.) zay gezunt
____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____ ____
143 11 82 33 54 28 44 61 8 91 166 102 167 117 10 149 84 65 83 1 69 151 105 26 164
78

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Lazarus Effect Initiative has accumulated about 50 conrmed next to Grace, enraptured as the scene unfolded,
(Continued from Page 77) cases from around the country. Fifty exceptional a hand resting on her grandmothers leg.
responders is a large number, but it is also small. Sitting there, I found myself wondering if
well on everolimus, found a place in the basket The same could be said of 20,000 cancer cases, something happened during one of Simaos
trial only because she had Foundation Medicine, annotated with genetic and clinical information: storm runs. I imagined a gravely ill man, tied
a company in Cambridge, Mass., sequence her large, unprecedented and also not nearly enough. down for safety, the sea enraged. The man would
tumor, revealing the crucial mutation. Im as For thousands of years, deep thinkers about have been praying, and he would have known
happy to see you, Carole recalled telling a doc- military strategy have understood that wars are that his only earthly hope was Simao, up in the
tor involved with the trial, as you are to see me. not won in the way the public imagines. Gen. cockpit, refusing to panic as the marine glass
This haphazard approach has led to a chicken- Robert H. Barrow, who served four years as com- shattered in his face. Was there a moment when
and-egg problem that is among the most obvious mandant of the United States Marine Corps, is this was somehow noted when some benef-
obstacles to progress in precision oncology. In credited with saying that amateurs talk about icence was granted to Simaos youngest, little
order to run basket trials, researchers must nd tactics, but professionals study logistics. Science Grace, who always took his lunch to the docks?
patients with the right mutations. But this has has revealed the nature of cancer, and also creat- The trailing tug began pumping ocean water,
proved dicult, because most patients arent hav- ed new means to gather intelligence on the foe. two celebratory arches in the air. Water! Jae-
ing sequences done: Insurance generally doesnt Solitary engagements can reveal new weaknesses lynn shouted. I know, I know, Grace said. Look,
cover it. The reason? Because, insurance compa- to exploit. Does anyone truly imagine prevailing its so pretty. The boats circled. You want to go
nies point out, there is not yet enough evidence without bringing the ght everywhere without someday on a ship? Grace asked. Jaelynns eyes
that it will be clinically useful. The way to gather matching cancer in its inventiveness, its nimble- kept to the screen. It was morning in the Azores,
this evidence? Basket trials. ness, its sheer relentlessness? and the light hit low. Yeah, she said.
Jos Baselga, the physician in chief and chief A few months later, Grace began coughing up
medical ocer at Sloan Kettering, told me that his On a bitter morning in January, I visited Grace blood. Joe rushed her to the emergency room: A
hospital has a number of quite promising basket at home. When I stepped into the entryway, she tumor in her lung was growing again. The Takeda
trials running but is struggling to nd enough stood at the top of some steps, wearing a purple Oncology drug had been good for six months.
patients. One analysis published last year found top, black leggings and a pair of comfy black slip- Grace went through a round of radiation on the
that patients in genetically targeted trials are see- pers. From a television, I made out a voice that lung and then started nivolumab, a therapy that
ing better outcomes than those in traditional trials. could be only Elmo. Grace smiled. helps the immune system attack tumors. Earlier
Yet if patients who would qualify arent fortunate She took a seat on a sofa with Jaelynn, her this month, though, she went to the hospital with
enough to be at cancer centers like Sloan Ketter- 2-year-old granddaughter, who sat in an o- dizziness and a severe headache. Scans showed
ing or Dana-Farber that run sequencing programs white cable-knit sweater watching the TV and metastasis to the brain.
supported by philanthropic money, they either occasionally pushing her ne black hair from her Lying at in a bed on the 12th oor of Brigham
need to pay for it themselves or they are out of face. On the wall hung a photograph of Faial, and Womens Hospital, Grace assured Lorch that
luck and so is cancer research. Baselga, in con- the Portuguese island where Graces father, who her minister was praying for him too, as he pon-
versations with Biden, has argued for a change in went by Mestre Simao, had been a ferry captain. dered his options: for her but also for what science
policy: If Medicare covered sequencing, private Simao was beloved for braving severe storms might still learn from her remarkable case. The
insurance would follow, opening up precision to fetch people in distress from a nearby island nivolumab was out, but Lorch did notice that the
medicine to many more people. and deliver them to the Faial hospital. He would drug seemed to have been working around her
Its a problem of scale. Sloan Kettering, Dana- tie himself to the wheel. Sometimes he returned lung several tumors shrank which is signi-
Farber and several other top cancer hospitals are with a cockpit window blown out. cant because doctors dont know who will respond
pooling their ndings so that oncologists can Grace showed me a video on her phone from to the drug. He and his colleagues plan to take
search through cases, about 20,000 so far, to see 2013, when a new ferry arrived at the island: The what theyve learned about the genetics of Graces
what mutations were found, what drugs were Mestre Simao, named for her father. With its lime cancer and compare it with evidence, from her
tried and how patients responded. The Nation- green and dark blue bow, the boat made its way blood, of the drugs activity. This might help the
al Cancer Institutes Exceptional Responders in from the ocean, trailed by a tug. Jaelynn stood next patient. Grace may have yet more to give.

P r e s s R e a d e r. c o m +1 604 278 4604
Puzzles Edited by Will Shortz
EXHIBIT A 1
19
2 3 4
20
5 6 7 8 9 10
21
11 12 13 14
22
15 16 17 18
By Patrick Berry
23 24 25 26
ACROSS 55 Tag line? 96 ____ Body? (rst

27 28 29
1 Tired runner? 56 Inedible Peter Wimsey
4 Hard to nd 57 La Scala premiere novel) 30 31 32
10 Production Code of 1887 98 Its symbol is a star
org. 58 Show signs of age and crescent 33 34 35 36 37 38 39 40 41
14 Prayer ____ 59 Associates 102 Quarters
104 Hand makeup 42 43 44 45 46 47 48 49
19 Singer with a 60 Erwin of 1950s TV
palindromic name 61 Bring along 107 What Carrie
50 51 52 53 54 55
20 Taphouse needed after the
63 Pound
21 Magazine with a prom? 56 57 58 59
65 Whirlybird whose
palindromic name 112 1980s-90s
paint job is aking Olympian Jackie
22 Out of bounds o ? 60 61 62 63 64
23 Repeatedly cried, Joyner-____
70 Christian in 113 Maker of Caplio 65 66 67 68 69
Land ho! with Hollywood
no land in sight, cameras
71 Supply 114 Major shopping 70 71 72
maybe?
72 ____ All Too Much centers arent
26 Inames
(Beatles song) among the prizes! 73 74 75 76 77 78 79 80 81 82
27 Rains pellets
73 Cuba ____ 116 Wild and woolly?
28 Fighting o 83 84 85 86
drowsiness? 74 Dethrone 117 Ligurian Sea feeder
30 Like tweets 78 Track down 118 Stun with sound 87 88 89 90 91
31 One of the cities 80 Something just 119 GameCube
of the plain occurred to me successor 92 93 94 95 96 97
32 Internal pump 83 Correct copy 120 Signed over

98 99 100 101 102 103 104 105 106
33 Belarussian capital 84 Down-lled 121 Lacking excess
35 Lose it garment 122 Divines 107 108 109 110 111 112
37 Peanuts girl 85 Adversary who 123 Lose rigidity
42 2016 campaigner shows up at 113 114 115
44 Jack ____ (member

romantic dinners? DOWN
of the Royal Navy) 87 Finally, I can buy
116 117 118 119
1 Land line?
5/15/16
46 Conger eel? Au that house! 2 Trig term 120 121 122 123
contraire! 90 Cut (o ) 3 Substitute anchor
50 Stuck to the 91 Scong reply during Walter
corkboard? 92 Company that sold Cronkites tenure
Spirographs at CBS 9 Finishes with 12 Kates partner of 51 Exchange 84 Break down
54 Not with a bang
93 Santa Baby 10 Predicament old TV cyclically 86 Take heat from?
but a whimper 4 ____ Island (home of
poet singer Wagner College) 13 Hartford-based 52 Body, 88 Spoke horsely?
11 Poet who wrote, I metaphorically
5 Cleveland team,
Fortune 100 89 Something t for a
took a deep breath company 53 Author of the 1984 queen
Puzzles Online: Todays puzzle and more
informally
and listened to 14 Layer memoir Mayor 94 Fashion editors
than 9,000 past puzzles, nytimes.com/crosswords 6 Ex Machina robot
the old brag of my 15 Head locks 59 Owner of Fisher- predictions
($39.95 a year). For the daily puzzle commentary: 7 Evocative of
heart. I am, I am, 16 Good at ones job Price 95 Experiment
nytimes.com/wordplay. yesteryear
17 Reasons to 60 Lacking creature subject
Mobile crosswords: nytimes.com/mxword 8 Belief systems I am
despair comforts 97 Continental
18 In need of a steer 62 Party purchase divides?
KENKEN 24 Shrink or enlarge 64 It often contains 99 Unswerving

lies 100 Ere
25 Target
65 Ireland : Erin :: 101 Start of several
29 Highly regarded
Fill the grid with digits so as not to repeat a digit in any row or column, and so that the digits within each Britain : ____ Hawaiian place
31 Glide eortlessly
heavily outlined box will produce the target number shown, by using addition, subtraction, multiplication 66 Dalmatian, e.g. names
or division, as indicated in the box. A 5x5 grid will use the digits 15. A 7x7 grid will use 17. 34 Act
67 Kedrova of Torn 103 City near Lake
36 That was sure Curtain Nasser
close! 68 ____ Novello Award 105 Screenwriter
38 Contributes to (songwriters Ephron
a GoFundMe honor) 106 Baseball
campaign 69 Rhodes of Rhodes commissioner
39 Stumper? scholar fame after Giamatti and
40 Food sometimes 70 Move through a Vincent
sold with a avor crowd, maybe 107 Shoe with holes
packet 73 Ceiling stains 108 Colonial home,
41 Those in favor cause you might say
42 Predator to be 75 Browser-bar text 109 Stomach stu
43 Codon carrier 76 Jamaican genre 110 Lowest possible
45 Lord of the Flies 77 Undertaking turnout
protagonist 79 Arms 111 Rodent-control
47 Hoppy drink 80 Tools used for brand
48 Actress Carrere cutting curves 112 Housemaids ____
49 Kevin who played 81 Put away (bursitis)
Hercules on TV 82 Even so 115 Hypotheticals
KenKen is a registered trademark of Nextoy, LLC. 2016 www.KENKEN.com. All rights reserved.
80

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P r e s s R e a d e r. c o m +1 604 278 4604
Talk
DJ Khaled You also show o your incredible garden

on Snapchat. Do you keep it yourself? I
have a landscaper, but Ive always loved
Is Extra gardening. Its cheaper and also better

to execute your vision and just go get it
Careful Around
yourself and then have somebody put
it in for you. If Im stressed out, I go sit
there and just embrace it and play some
Beyonc
nice reggae music in the background. You
should try it one day. Im addicted to my
owers. Sometimes, I overdo it. My girl
is like, What are you doing?
Interview by Ana Marie Cox The one person who seems to get
annoyed by your constant Snapchats is
your ance. No, actually, she loves me.
Do you have a favorite kind of ower? I
do. I dont know how to pronounce the
name. Theyre amazing. When the sun is
Youre a prolic hip-hop multihyphenate: out, they wake up just smiling, and then
producer, radio host and record-label when the sun is down, they just go down.
executive. But you also make your own Thats why I water them and take care of
albums, and it seems as if one of your them, because Im planting my seeds of
many gifts is persuading other rappers success. I show them love. When you show
to appear on your albums. How does that the owers love, you see the love.
work? I put the right people in the room What else is on the horizon for you?
together to make magic. Basically, Im Well, my life goal is to do everything
one of the greatest producers ever. And forever. My life goal is called live life. I
Im also one of the greatest D.J.s ever. And want to do movies. I want to work with
Im also one of the best executives ever. Denzel Washington.
What people really know you for is your Earlier this year, you gave Jeb Bush some
Snapchat, where you disseminate keys advice on Jimmy Kimmel Live! but it
to success. Exactly how many keys to obviously didnt work out. Do you think
success are there? The keys can never he didnt follow your advice? He replied,
run out, you know what Im saying? so at least hes starting to embrace the
Sometimes when you get a key, it gets keys, you know what I mean? You cant
you another key, and gets you another put a timer on your success. Patience is a
key. One of my major keys is actually the talent. Thats another key.
master keys: God. In my life, theyve hid What are the top keys of success? No. 1
the keys from me, so Ive overcome and key is God. Thats the master key. Another
weathered a lot of storms. key is never give up.
You just mentioned they, a recurring All right. Another key is never quit.
villain in a lot of your videos. Who are Uh-huh. Another key is never surrender.
they? They is the people that dont O.K. Another key is give thanks to life
believe in you, dont support you. at all times.
What do you do when you encounter Now, you realize that three of those are
a they? Sometimes you might meet almost exactly the same, right? Its not:
somebody that you love thats turning giving up is when youre thinking about
into a they. My key is invite them to giving up. Quitting is quitting. Never
Miami and take them to the ocean and surrendering means you got to ght
Interview has been condensed and edited.
let them jump o the boat in the ocean, everything to make sure you dont fall
on the sand bar, and cleanse o and pray for none of them jive artists.
and then go take a shower and hopefully Right now, youre on tour with Beyonc.
Age: 40 DJ Khaled is the chief His Top Five
the they is out of you. executive of We Types of Flowers: Do you ever talk to her? Im very quiet.
Occupation:
Youve said that both having a lot of pil- the Best Music Group, 1. Hydrangea Every time Ive ever seen her is when
Record producer,
lows and cocoa butter are keys. Which a hip-hop record 2. Bougainvillea Im with my brother Jay Z, and I just say,
D.J. and record-label
label. His Snapchat 3. Orchid
is more important? Cocoa butter. I put executive
is djkhaled305. 4. Geranium
Hi, and I look the other way so fast,
cocoa butter all over my face and my Hometown: 5. Birds of paradise and I kind of run. I just dont want to
iconic belly and my arms and legs. Why Miami say nothing too much. Im not messing
live rough? Live smooth. that up.
82 5.15.16 Photograph by Stephen Voss

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P r e s s R e a d e r. c o m +1 604 278 4604
John Whitney lost his son to cancer, so when he tumors have shrunk and his outlook is bright, thanks to
discovered a lump in his own shoulder, he was rightfully the groundbreaking work being done at the Tisch Cancer
w o r r i e d . H e w a s d i a g n o s e d w i t h n o n - H o d g k i n s Institute, a National Cancer Institute (NCI)designated
lymphoma and caught the attention of experts at the cancer center at the Mount Sinai Health System.
Lymphoma Immunotherapy Program at the Icahn School For you. For life.
of Medicine at Mount Sinai. They treated John with an
individualized technique that teaches immune cells to 1- 8 0 0 -MD-SINA I
attack cancer as they would bacteria or a virus. Today, Johns mountsinai.org/mscancer
WERE
A TEACHING HOSPITAL.
OUR DOCTORS
TAUGHT JOHNS IMMUNE SYSTEM
HOW TO FIGHT CANCER.

P r e s s R e a d e r. c o m +1 604 278 4604

The New York Times Magazine - May 15, 2016

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T H E H E A LT H I S S U E

May 15, 2016

IN THE PAST DECADE,

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Interior 3,503 Square Feet

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JIM SURVIVED ESOPHAGEAL CANCER NICOLE SURVIVED LEUKEMIA

KOMMAH SURVIVED BREAST CANCER GUS SURVIVED LEUKEMIA

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DOESNT SEE COMING

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DOCTOR WITHOUT BORDERS 1 42

THE LAZARUS EFFECT 2 48

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THE COMPLETE OFFERING TERMS ARE IN AN

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FIRST WORDS ON MONEY WELL

10 Copyright 2016 The New York Times

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See videos, whitepapers and more at DiscoverCareBelieve.org/DIPG.

2015 Dana-Farber Cancer Institute

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Siddhartha Doctor Without Borders, Editor in Chief JAKE SILVERSTEIN

Mukherjee Page 42 Deputy Editors JESSICA LUSTIG,

cancer treatments are becoming more tailored CLAIRE GUTIERREZ,

to the individual patient. While writing this, LUKE MITCHELL,

Page 64 Parent and teaches journalism at the University WESLEY MORRIS,

2016 Livingston Award for International Reporting. DAN KAUFMAN,

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But our guests feel it every day.

THE ORIGINAL, ALL-INCLUSIVE WELLNESS RESORT

Tucson, Arizona Lenox, Massachusetts

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President Obamas implication that the

14 5.15.16 Illustrations by Tom Gauld

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Online, we present ourselves in ever-more-numerous guises across a variety of platforms.

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photographer, waist contorted into a

18 5.15.16 Illustration by Javier Jan

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When Silicon Valley venture capitalists

becoming harder to ignore. a tweet that the subcontinent might be

20 5.15.16 Illustrations by Andrew Rae Next Week: On Technology, by Jenna Wortham

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The best returns arent just measured in dollars.

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22 5.15.16 Illustration by Andrew Rae

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24 5.15.16 Illustration by R. O. Blechman

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Retirement plans built for ever-changing conditions.

prepared for nearly every situation. downpour without an umbrella.

forecast may show nothing but James f inancial advisor, theyll

financial outlook is infinitely more for you complete with thoroughly

thoughtful approach is always recommended. s er v ing t he ir cl i ent s dif f erent l y. Go t o

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Out With the Old

Experiments involving health and well-