17 OCTOBER 2014 • VOL 346 ISSUE 6207 291SCIENCE sciencemag.org

lular organelles, and viruses—to looking at

best blurry and indistinct in visible light

micrographs. The three new Nobelists over-

came that limit through fluorescence, coax-

ing objects to reveal details by emitting their

own light.

In the late 1980s, Moerner, then at IBM’s

Almaden Research Center in San Jose, Cali-

fornia, was trying to develop a novel opti-

cal data storage technique. Along the way,

he and his colleagues improved their lasers

and detection equipment enough to track the

light absorption spectra and fluorescence of

single molecules. Those studies revealed that

the wavelength of light given off by individ-

ual molecules can shift as molecules dance

around, an insight that made possible later

imaging developments.

Hell developed his technique, called

stimulated emission deple tion micro scopy,

in 2000. It uses a laser beam to excite mol-

ecules to glow and a second beam to cancel

out all fluorescence except within a volume

just nano meters across—hundreds of times

smaller than a wavelength of light.

Shortly thereafter, Betzig

developed a different method

known as single-molecule local-

ization microscopy. Instead of

turning off unwanted fluores-

cence, his technique excites it se-

lectively, using a precisely tuned

laser to tickle just a single kind

of biological molecule at a time.

By separately imaging molecules

that have different distributions

in a sample, then superimposing the sepa-

rate images, the technique can build up a

complete picture of the structure. Betzig

demonstrated the method for the first time

in 2006 and described it in a paper in Science

(11 August 2006, p. 748).

Hell told the Nobel press conference on

8 October by phone from Germany that he be-

gan working on the problem when he became

bored by the conventional

problems of microscopy

and wondered if this seem-

ingly unbreakable limit

could be breached. “I was

attracted to the problem.

I eventually realized there

was a way,” he said. At first,

Hell added, other scientists

couldn’t believe his new

approach had cracked a

problem that had vexed

researchers since Abbe’s

work in 1873. “I realized

you don’t overcome the

limit by changing the

waves of light; you over-

come it by playing with

the molecules.”

The implications were revolutionary. Us-

ing electron microscopes, researchers had

been able to observe only specially prepared

dead specimens. The ability to produce vis-

ible light images at a resolution of tens of

nanometers meant they could now study

biological molecules in living organisms. “I

am thrilled by this,” says Catherine Lewis,

director of the cell biology and biophysics

division at the National Institute of General

Medical Sciences in Bethesda, Maryland.

“Because these techniques allow research-

ers to monitor molecular movements over

time, they are becoming very important for

understanding things such as metastasis in

cancer, and the way viruses enter cells and

where they go.”

Some researchers noted that, coming so

soon after the techniques’ discovery, the

award contrasted with the Nobels’ usual

stately pace. “It’s still quite new. It’s only

just starting to be adopted in the lab,” says

Leeds’ Peckham. Susan Cox, a biologist at

King’s College London, agrees. “These three

people are very worthy recipi-

ents,” she says. “But we’re still at

the start. It’s a little messy, and

the technological development

is happening as the scientific re-

sults are coming in.”

Microscopists were quick to

develop variants of the Nobel-

winning techniques, with a

bewildering array of acronyms—

SPDM, SPDMphymod, STORM,

PALM, dSTORM, fPALM, SOFI,

and SIM—but they remained too expensive

and technically difficult for many biology

labs, Cox says. In recent years, however,

major optics manufacturers have begun

producing off-the-shelf systems. “That’s the

critical thing,” Cox says: “being able to push

the button, and it just works.” ■

With reporting by Robert F. Service.

Setting specimens aglow makes

possible extreme close-ups such as

this image of mouse nuclei.

Regulating industry’s big boysFrench economist Jean Tirole is honored for his analyses of oligopolies

NOBEL PRIZES

By Tania Rabesandratana

Big companies make their own rules—

but they can still be regulated. That

insight earned Jean Tirole, scientific

director at the Industrial Economic

Institute at the Toulouse School of

Economics in France, the 2014 Nobel

Prize in economics. Tirole’s influential anal-

yses of oligopolies, industries dominated by

a few large firms, helps answer the question:

“What sort of regulations and competition

policy do you want

in place so that large

and mighty firms will

act in society’s best

interest?” said Tore

Ellingsen, chair of the

prize committee.

Until the 1980s,

regulation researchers sought simple rules

that could apply to every industry. They

often dealt with two extreme situations:

single monopolies or perfect competition.

Tirole instead used mathematical model-

ing from game theory and contract theory

to describe how giant firms react and in-

teract under various conditions. He also

provided tools to deal with so-called asym-

metric information, when public authori-

ties have less information than the firms

they are trying to regulate.

Tirole has never shied away from giv-

ing practical policy recommendations, says

Reinhilde Veugelers, an economics profes-

sor at the University of Leuven in Belgium

and senior fellow at the Bruegel think tank

in Brussels, adding that his work is highly

relevant to current debates on the regulation

of telecoms, banking, and energy markets.

Indeed, Joaquín Almunia, the European

commissioner for competition, praised

Tirole’s influence on the regulation of com-

pany mergers, among other topics, in a

statement on Monday. “We owe Jean Tirole

so much,” Almunia said.

For a longer version of this story, see

http://scim.ag/econNobel. ■

“for the development of super-resolved fluorescence microscopy”

Eric Betzig

Stefan W. Hell

William E. Moerner

CHEMISTRY NOBEL

“for his analysis of market power and regulation”

Jean Tirole

ECONOMICS NOBEL

Published by AAAS

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