THE NEW YORK TIMES INTERNATIONALTUESDAY, OCTOBER 8, 2019 N AThe Nobel Prize in Physiology
or Medicine was jointly awarded
to three scientists — William G.
Kaelin Jr., Peter J. Ratcliffe and
Gregg L. Semenza — for their
work on how cells sense and adapt
to oxygen availability.
The Nobel Assembly an-
nounced the prize at the Karolin-
ska Institute in Stockholm on
Monday.
Their work established the ge-
netic mechanisms that allow cells
to respond to changes in oxygen
levels. The findings have implica-
tions for treating a variety of dis-
eases, including cancer, anemia,
heart attacks and strokes.
Why were they honored?
“Oxygen is the lifeblood of liv-
ing organisms,” said Dr. George
Daley, dean of Harvard Medical
School. “Without oxygen, cells
can’t survive.”
But too much or too little oxy-
gen also can be deadly. The three
researchers tried to answer this
question: How do cells regulate
their responses?
The investigators uncovered
detailed genetic responses to
changing oxygen levels that allow
cells in the bodies of humans and
other animals to sense and re-
spond to fluctuations, increasing
and decreasing how much oxygen
they receive.
Why is the work important?
The discoveries reveal the cel-
lular mechanisms that control
such things as adaptation to high
altitudes and how cancer cells
manage to hijack oxygen.
Randall Johnson, a member of
the Nobel Assembly, described
the work as a “textbook discov-
ery” and said it would be some-
thing students would start learn-
ing at the most basic levels of biol-
ogy education.
“This is a basic aspect of how a
cell works, and I think from that
standpoint alone, it’s a very excit-
ing thing,” Mr. Johnson said.
The research also has implica-
tions for treating various diseases
in which oxygen is in short supply
— including anemia, heart attacks
and strokes — as well as for treat-
ment of cancers that are fed by
and seek out oxygen.
Who are the winners?
WILLIAM G. KAELIN JR., professor
of medicine at Dana-Farber Can-
cer Institute and Brigham & Wom-
en’s Hospital Harvard Medical
School, was drawn to science for
its objectivity.
“Like any scientist, I like solv-
ing puzzles,” he said in an inter-
view on Monday morning.
But he had an unprepossessing
start. When he was a pre-med stu-
dent hoping to become a physi-
cian researcher, a professor
wrote, “Mr. Kaelin appears to be a
bright young man whose future
lies outside of the laboratory.”
Eventually, he became in-
trigued by a rare, genetic cancer,
von Hippel-Lindau disease, that is
characterized by a profusion of
extra blood vessels and overpro-
duction of erythropoietin, or EPO,
a hormone that stimulates pro-
duction of the red blood cells that
carry oxygen.
The cancer “was really fasci-
nating,” Dr. Kaelin said. It had un-
usual features, like causing the
body to make a substance, vegF,
that stimulates the formation of
blood vessels. And the cancer can
cause the body to make too many
red blood cells by increasing the
production of EPO.He had a hunch about what was
going awry: “I thought it had
something to do with oxygen
sensing.”
As it turned out, he was right.
“It is one of the great stories of
biomedical science,” Dr. Daley
said. “Bill is the consummate phy-
sician-scientist. He took a clinical
problem and through incredibly
rigorous science figured it out.”
Dr. Kaelin said he knew, of
course, that the Nobel Prize would
be awarded on Monday. But his
chances were “so astronomically
small” that he stuck with this usu-
al routine and did not stay up the
night before.
He had a dream, though, that he
had not received the 5 a.m. call
from Sweden. He woke up and
looked at the time; in fact, it was
just 1:30 a.m.
He went back to sleep, and
when it really was 5 a.m., his
phone rang.
GREGG L. SEMENZA, professor of
genetic medicine at Johns Hop-
kins, said his life was changed by a
high school teacher, Rose Nelson,
who taught biology at Sleepy Hol-
low High School in Tarrytown,
N.Y.
“She was unbelievable,” Dr. Se-
menza said in an interview. “Shetransmitted the wonder and joy of
science and scientific discovery.
She set me on a course to science.”
In college, at Harvard, he
thought he would earn a Ph.D. and
do research in genetics. But then a
family he was close to had a child
with Down syndrome.
“That shifted me from being in-
terested in genetics as kind of a
scientific discipline to thinking
about the impacts of genetics on
people,” he said.
After attending medical school
at the University of Pennsylvania,
Dr. Semenza set out to understand
what cancer cells are searching
for when they spread into sur-
rounding tissues, and then into
blood vessels that carry them
around the body.
His guess was that cancer cells
are searching for oxygen.
Dr. Semenza turned his atten-
tion to the gene that guides pro-
duction of EPO. Once it is activat-
ed, the body makes more oxygen
carrying red blood cells. But how
is that switch turned on when the
body is deprived of oxygen?
As a geneticist, he was trained
to study rare genetic diseases. But
his work on cellular responses to
oxygen led him to study such com-
mon diseases as heart disease and
cancer.At first, he divided his attention
between the two conditions. More
recently, Dr. Semenza said, he has
focused on cancer, looking for
ways to use what he has learned to
find new ways to attack tumors.
Dr. Semenza was asleep when
the call from Sweden came on
Monday morning, and did not get
to his phone in time to answer it.
The phone rang again a few min-
utes later.
“I heard this very distinguished
gentleman tell me I was going to
receive the Nobel Prize,” he said.
“I was shocked, of course. And I
was kind of in a daze. I’ve been in a
daze ever since.”
But, he added, “It’s been won-
derful.”
PETER J. RATCLIFFE, the third No-
belist, is the director of clinical re-
search at the Francis Crick Insti-
tute in London and director of the
Target Discovery Institute at Ox-
ford.
He became a medical re-
searcher almost by chance. “I was
a tolerable schoolboy chemist and
intent on a career in industrial
chemistry,” he said in a speech in- “The ethereal but formida-
ble headmaster appeared one
morning in the chemistry class-
room. ‘Peter,’ he said with unnerv-
ing serenity, ‘I think you should
study medicine’. And without fur-
ther thought, my university appli-
cation forms were changed.”
He became a kidney specialist,
fascinated by the way organs reg-
ulate production of EPO in re-
sponse to the amount of oxygen
available. Some colleagues, he
said, thought this was not very im-
portant.
But he persisted, intrigued by
the scientific puzzle. “We set
about the problem of EPO regula-
tion, which might have been seen,
and some did see, as a niche area,”
he said in a telephone interview
posted by the Nobel Committee on
Twitter.
“But I believed it was tractable,
it could be solved by someone.
The impact of that became evi-
dent later.”
The research is an illustration
of the value of basic research, he
added: “We make knowledge,
That’s what I do as a publicly
funded scientist. It is good knowl-
edge. It is true. It is correct.”
But, he added, “We set out on a
journey without a clear under-
standing of the value of that
knowledge.”
When the call from Sweden
came, Dr. Ratcliffe was writing a
grant proposal. Now, he will con-
tinue working on it.
“I’m happy about it,” he said of
the Nobel Prize. But he was not
enthusiastic about being thrust
into the public eye.
“I’ll do my duty, I hope,” he said.
“It’s a tribute to the lab, to those
who helped me set it up and
worked with me on the project
over the years, to many others in
the field, and not least to my fam-
ily for their forbearance of all the
up and downs,” he said in a state-
ment released by Oxford.Who won the 2018 Nobel for medi-
cine?
The prize last year went to
James P. Allison of the United
States and Tasuku Honjo of Japan
for their work on immunotherapy,
for unleashing the body’s immune
system to attack cancer. This
breakthrough has resulted in an
entirely new class of drugs and
brought lasting remissions to
many patients who had run out of
options.When will the other Nobel Prizes be
announced?■The Nobel Prize in Physics will
be announced on Tuesday in Swe-
den. Last year’s winners were Ar-
thur Ashkin, Gérard Mourou and
Donna Strickland.■The Nobel Prize in Chemistry
will be announced on Wednesday
in Sweden. Last year’s winners
were Frances H. Arnold, George P.
Smith and Gregory P. Winter.■The 2018 and 2019 Nobel Prizes
in Literature will be announced on
Thursday in Sweden. The prize
last year was postponed after the
husband of an academy member
was accused, and ultimately con-
victed, of rape — a crisis that led to
the departure of several board
members and required the inter-
vention of the King of Sweden.
The 2017 winner was Kazuo Ishi-
guro.■The Nobel Peace Prize will be
announced on Friday in Norway.
Last year’s winners were Nadia
Murad and Denis Mukwege.■The Nobel Memorial Prize in
Economic Science will be an-
nounced Monday next week in
Sweden. Last year’s winners were
William Nordhaus and Paul
Romer.By GINA KOLATA
and MEGAN SPECIAThe Nobel Prize in Physiology or Medicine was jointly awarded to Gregg L. Semenza, Peter J. Rat-
cliffe and William G. Kaelin Jr. for their work on how cells sense and adapt to oxygen availability.JONATHAN NACKSTRAND/AGENCE FRANCE-PRESSE — GETTY IMAGESMichael Wolgelenter contributed
reporting.
2019 NOBEL PRIZE MEDICINE3 Scientists Who Laid Groundwork for Helping Cells Fight Disease
KABUL, Afghanistan — Eleven
Taliban commanders have been
released from a high-security
prison in Afghanistan, according
to Taliban officials, in an apparent
deal that included a prominent re-
gional leader caught five years
ago personally escorting a ship-
ment of nearly a ton of opium.
Afghan and American officials
have remained silent about the re-
leases from the prison, near the
Bagram Air Base outside Kabul. A
senior Afghan official said the 11
Taliban prisoners had been re-
leased in return for three Indian
engineers after months of negoti-
ations with local Taliban com-
manders in northern Baghlan
Province, where the engineers
were kidnapped last year. The In-
dian Embassy in Afghanistan de-
clined to comment.
The releases, which took place
on Sunday, came just days after
Zalmay Khalilzad, the United
States diplomat and chief negotia-
tor with the Taliban, went to Is-
lamabad, Pakistan, and met with
Taliban representatives. It was
Mr. Khalilzad’s first meeting with
them since President Trump
called off negotiations with the in-
surgents on the eve of a potential
breakthrough.
The potential release of thou-
sands of Taliban prisoners was
part of those negotiations. But
that issue was a main point of con-
tention with Afghan officials who
were furious that their govern-
ment was excluded from those
talks, and that the United States
was negotiating the release of
prisoners being held under Af-
ghan authority.
It was unclear whether the re-
leases on Sunday had anything to
do with negotiations between the
United States and the Taliban. In
Afghanistan, however, rumors
were rife — not only among Af-
ghan and Taliban officials, but also
some diplomats — that a separate
prisoner exchange had been a ma-
jor topic of discussion in the Islam-
abad meeting between the Mr.
Khalilzad and the Taliban.
The insurgents have been hold-
ing three American University of
Afghanistan professors since Au-
gust 2016, one of them an Ameri-
can said to be in poor health. In re-
turn for their release, the Taliban
have demanded the release of
Anas Haqqani, a member of the
feared Haqqani network, a wing of
the Taliban. He is a stepbrother of
the network’s leader and is one of
the most prized prisoners of the
Afghan government.
Some Afghan and Taliban offi-
cials suggested the two sides
might have reached an agreement
on the swap, possibly as a trust
building measure that could help
revive the broader peace negotia-
tions.
The release of prisoners in itself
was not unusual, with the Afghan
government on occasions of reli-
gious festivals often pardoning
dozens whose prison terms are
near completion.
But what has drawn attention tothis latest release is the notoriety
of one Taliban figure in particular:
Abdul Rashid Baluch, who was on
the United States Treasury De-
partment’s “Specially Designated
Global Terrorist” list and was ar-
rested in a narcotics raid five
years ago.
Mr. Baluch was a Taliban shad-
ow governor, a regional official in
charge of military and political op-
erations in the southwestern
province of Nimroz, when he was
caught with a huge shipment of
opium. The drug bust was held up
as a major revelation in how the
line between Taliban insurgents
and the narcotics mafia had
blurred in Afghanistan. (Taliban
officials have denied that Mr.
Baluch was involved in drug traf-
ficking.)
Despite evidence of Mr.
Baluch’s involvement in terrorist
attacks, Afghan prosecutors delib-
erately tried him on stricter coun-
ternarcotics charges. They feared
that the counterterrorism process
was vulnerable to political deal-
making.
Now, the release of Mr. Baluch,
especially if it is tied to the United
States peace talks with the Tal-iban, once again brings to the fore
the concern that the American ne-
gotiations did not address the
complexity of the conflict — and
particularly how to consider the
Taliban’s increasing hold on the
massive drug trade in the country.
If his release was a unilateral
Afghan government decision, it is
unlikely that the Afghan govern-
ment would decide on the fate of a
United States-designated terror-
ist figure without first consulting
the Americans.
Mr. Baluch was arrested in
Nimroz, a smuggling hub on the
border with Iran, in July 2014. An
Afghan special forces helicopter
swooped down on two vehicles
racing through the desert, seizing
nearly a metric ton of opium, light
and heavy weapons, ammunition
and satellite phones. The main
person they detained had insisted
he was a carpet seller, but investi-
gators confirmed his identity as
Abdul Rashid Baluch when he was
transferred to Kabul, the Afghan
capital.
Both Afghan and Western offi-
cials at the time played up his
case, and his arrest in a coun-
ternarcotics operation rather than
a counterterrorism raid. He was
tried in the country’s high-securi-
ty drug court and given an 18-year
sentence.
His release now, under circum-
stances lacking transparency, is
the latest instance of a major drug
smuggler going free.
Late in 2014, Hajji Lal Jan
Ishaqzai, another major kingpin,
bribed his way out of prison by
paying millions of dollars. Long
among wanted international
smugglers, he had been arrested
in 2012 after a shootout and sen-
tenced to 20 years in prison.
The United States has spent
more than $8 billion on narcotics
operations in Afghanistan, ac-
cording to the United States Spe-
cial Inspector General for Afghan-
istan Reconstruction. Throughout
the course of the war, American
officials have shifted antidrug
strategies several times.
Earlier this year, the American-
led mission in Afghanistan called
off its latest attempt to cut off the
Taliban’s revenue stream from
drugs: a concerted bombing cam-
paign that targeted drug labs,
mostly in the country’s volatile
south where much of the opium is
grown. In 2018, the total opium
poppy cultivation area in Afghani-
stan was estimated at between
242,000 to 283,000 hectares, ac-
cording to a United Nations re-
port, the second-highest meas-
urement since it started monitor-
ing the crop in 1994.Taliban Leader’s Release Spurs Questions
By MUJIB MASHALJailed Afghans arrested on
suspicion of smuggling opium.BRYAN DENTON FOR THE NEW YORK TIMESTaimoor Shah contributed report-
ing from Kandahar, Afghanistan,
and Fahim Abed and Thomas Gib-
bons-Neff from Kabul.
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