Science 16.10.2020

CONTENTS INSIGHTS

16 OCTOBER 2020 • VOLUME 370 • ISSUE 6514 PERSPECTIVES

U.S. ELECTIONS 286 COVID-19 in children
and young people
F E AT U R E S ON THE COVER Children have a low risk of COVID-19
and are disproportionately
278 Weathering the storm Donald Trump’s presidency has been marked harmed by precautions
As president, Donald Trump has battered
science. But increased spending by by a dismissal of science and evidence. Now, By M. D. Snape and R. M. Viner
Congress and some supportive agency
heads have provided relief By J. Mervis voters are deciding who will occupy the White 288 Lubricating lipids in hydrogels
A self-renewing lipid layer substantially
283 Scientists and science are Slippery surfaces from lipid- The nucleus measures cell Metabolomics of healthy House amid a host of reduces friction and wear of a hydrogel
on the ballot By J. Mervis lubricated hydrogels pp. 288 & 335 confnement pp. 295, 310, & 311 and failing hearts p. 364 science-related crises, surface By T. A. Schmidt
including the COVID-19
284 What if Biden wins? $15 REPORT p. 335
A new president will have vast authority 16 OCTOBER 2020
to rapidly shift science policy, but 290 Advancing limb neural prostheses
will confront obstacles beyond his control sciencemag.org Neurotechnology can overcome
communication difficulties between
By D. Malakoff pandemic, forest fires prostheses and amputees

and climate change, and By S. Raspopovic

fierce debates over immi- 292 Reconstituting tissue patterning
A synthetic morphogen reveals quantitative
VOTING IN A gration and racial justice. principles of tissue patterning
See pages 267 and 278.
MAELSTROM By N. Barkai and B.-Z. Shilo
Science looms large in
RESEARCH ARTICLE p. 321; REPORT p. 327
crises facing U.S. voters pp. 267 & 278
294 Immiscible immunity
Illustration: Zoë van Dijk Mammalian metabolism meets
immunity at mitochondria-adjacent
SEE ALSO: EDITORIAL p. 267 lipid droplets By D. R. Green

PHOTO: BILL CLARK/CQ ROLL CALL NEWS 273 At last, room temperature RESEARCH ARTICLE p. 309
superconductivity achieved
IN BRIEF But the hydrogen-based material 295 A cellular sense of space
requires high pressure and pressure
268 News at a glance The nucleus measures cell confinement
By R. F. Service with a mechanosensitive phospholipase
IN DEPTH
274 Satellite swarm threatens By Z. Shen and P. Niethammer
270 Lava lake rises at dangerous radio array
African volcano “Megaconstellations” already RESEARCH ARTICLES pp. 310 & 311
Funding for volcano’s lone monitoring station bedevil optical telescopes.
lost as warning signs flash By R. Pease Now, radio astronomers are 297 Joe L. Martinez Jr. (1944–2020)
concerned By D. Clery Neuroscientist and advocate of inclusion
271 A cut above: pair that developed
CRISPR earns historic award 275 Found: genes that sway the By K. A. Trujillo et al.
Chemistry Nobel honors biology’s course of the coronavirus
powerful genome editor Host variants boost severity risk, POLICY FORUM
may point to drug options
By J. Cohen 298 COVID-19 recovery funds dwarf
By J. Kaiser clean energy investment needs
272 U.S. faculty job market tanks A modest fraction of current global
As COVID-19 upends university finances, 276 The United Kingdom’s mask stimulus funds can put the world on track
postdocs worry about their future crusader to achieve Paris Agreement goals
Trisha Greenhalgh argues COVID-19 shows
By K. Langin that health policy need not wait for perfect By M. Andrijevic et al.
evidence By E. Ruppel Shell
SCIENCE sciencemag.org BOOKS ET AL.
Published by AAAS
301 Experiments in creativity
Artists and engineers joined forces in the
1960s, blurring the line between art and
technology By I. Ockert

302 Tales from times long past
Field adventures and human origin stories
combine in a paleoanthropologist’s
compelling new memoir By B. J. King

16 OCTOBER 2020 • VOL 370 ISSUE 6514 263

CONTENTS

LETTERS 313 Neuroscience 360 Structural biology
Behavioral state coding by Structural and mechanistic bases
303 Save Kazakhstan’s shrinking molecularly defined paraventricular for a potent HIV-1 capsid inhibitor
Lake Balkhash hypothalamic cell type ensembles S. M. Bester et al.
S. Xu et al. 364 Physiology
By A. Ussenaliyeva Comprehensive quantification of fuel
RESEARCH ARTICLE SUMMARY; FOR FULL TEXT: use by the failing and nonfailing
303 Airborne transmission DX.DOI.ORG/10.1126/SCIENCE.ABB2494 human heart D. Murashige et al.
of SARS-CoV-2
314 Microbiota PODCAST
By K. A. Prather et al. Microbiota-modulated CART+ enteric
neurons autonomously regulate blood 288 & 335
304 Deliberate poisoning glucose P. A. Muller et al.
of Africa’s vultures D E PA R T M E N T S
321 Morphogens
By M. Henriques et al. Patterning and growth control in vivo 266 Editorial
by an engineered GFP gradient Not throwing away our shot
RESEARCH K. S. Stapornwongkul et al.
By H. Holden Thorp
IN BRIEF PERSPECTIVE p. 292; REPORT p. 327
267 Editorial
305 From Science and other journals REPORTS Speed and American elections

REVIEW 327 Morphogens By Jill Lepore
Engineering synthetic morphogen
308 Neurodevelopment systems that can program multicellular U.S. ELECTIONS SECTION p. 278
Transient cortical circuits match spontaneous patterning S. Toda et al.
and sensory-driven activity during 374 Working Life
development Z. Molnár et al. PERSPECTIVE p. 292; RESEARCH ARTICLE p. 321 My last drop

REVIEW SUMMARY; FOR FULL TEXT: 331 Ultracold chemistry By John C. Ayers
DX.DOI.ORG/10.1126/SCIENCE.ABB2153 Coherently forming a single molecule New Products............................................ 369
in an optical trap X. He et al. Science Careers .........................................370
RESEARCH ARTICLES
335 Hydrogels
309 Innate immunity Cartilage-inspired, lipid-based
Mammalian lipid droplets are innate immune boundary-lubricated hydrogels
hubs integrating cell metabolism and host W. Lin et al.
defense M. Bosch et al.
PERSPECTIVE p. 288
RESEARCH ARTICLE SUMMARY; FOR FULL TEXT:
DX.DOI.ORG/10.1126/SCIENCE.AAY8085 339 Spectroscopy
PERSPECTIVE p. 294 Zeptosecond birth time delay
in molecular photoionization
Cell biology S. Grundmann et al.
310 The nucleus acts as a ruler tailoring cell
342 Thermogalvanics
responses to spatial constraints Thermosensitive crystallization–boosted
A. J. Lomakin et al. liquid thermocells for low-grade heat
harvesting B. Yu et al.
RESEARCH ARTICLE SUMMARY;
FOR FULL TEXT: 346 Ecology
DX.DOI.ORG/10.1126/SCIENCE.ABA2894 Species richness and redundancy promote
persistence of exploited mutualisms in yeast
311 The nucleus measures shape M. C. Vidal et al.
changes for cellular proprioception
to control dynamic cell behavior 351 Signal transduction
V. Venturini et al. The GATOR–Rag GTPase pathway inhibits
mTORC1 activation by lysosome-derived
RESEARCH ARTICLE SUMMARY; amino acids G. G. Hesketh et al.
FOR FULL TEXT:
DX.DOI.ORG/10.1126/SCIENCE.ABA2644 356 Inorganic chemistry
PERSPECTIVE p. 295 Structural and spectroscopic
characterization of an Fe(VI) bis(imido)
312 Developmental biology complex J. L. Martinez et al.
Apical stress fibers enable a scaling between
cell mechanical response and area
in epithelial tissue J. M. López-Gay et al.

RESEARCH ARTICLE SUMMARY; FOR FULL TEXT:
DX.DOI.ORG/10.1126/SCIENCE.ABB2169

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SCIENCE sciencemag.org 16 OCTOBER 2020 • VOL 370 ISSUE 6514 265

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EDITORIAL

Not throwing away our shot

O ver the past few weeks, prominent scientif- first immunization. This meant that an EUA for a vac-
ic publications have condemned President cine would not be approved before the election. Trump
Donald Trump’s record on science. This is attacked Hahn and criticized this logical move for pa-
unprecedented. Although my predecessors at tient safety as being politically motivated. Surprisingly,
Science have always held elected U.S. officials a few days later, the White House agreed to the FDA
accountable (but could not make a formal po- guidelines. Hahn had stood up for science and stood up

litical endorsement because of the nonprofit to Trump. In an interview with Topol, Hahn pledged to

H. Holden Thorp status of the American Association for the Advance- stand up for sound scientific judgement.
Editor-in-Chief,
Science journals. ment of Science, the publisher of Science), many of The pressure put on Hahn by the scientific com-
[email protected];
@hholdenthorp these publications are now clearly denouncing the munity played a big role in stiffening his spine. Topol

U.S. president, administration, and federal agency told me that Hahn said he was “profoundly dejected”

leaders as the nation approaches a highly conse- after the convalescent plasma debacle and realized that

quential presidential election. To paraphrase lyrics the subsequent vaccine drama posed an “existential

by Lin-Manuel Miranda in “Hamilton” about anoth- crisis”—either he would be fired by Trump or perma-

er set of political essays, why do we write like we’re nently lose his standing in the scientific community.

running out of time? Because re- Ultimately, he decided that doing

cent events show that the voice of what was right for the success of the

the scientific community can lead “The pressure COVID-19 vaccine trials and the
to positive change. safety of the public—while also re-

I have been supportive and then put on Hahn pairing his reputation in medical
critical of Stephen Hahn, commis- science—was more important than

sioner of the U.S. Food and Drug by the scientific keeping his job at the FDA. We can
Administration (FDA). When he community hope that it’s too much trouble for
granted the emergency use authori- Trump to fire him this close to the
zation (EUA) for hydroxychloroquine played a big role election. I’m now back to support-
to treat coronavirus disease 2019 in stiffening ing Hahn knowing that scientists
(COVID-19), much of the biomedi- his spine.” will decide whether to approve the
cal community lost trust in him, but COVID-19 vaccines and provided he
I maintained that if he stuck to the continues to support science.
science on the COVID-19 vaccine, the
nation should support him. When With his apparent recovery from
he botched the announcement of COVID-19 due perhaps in part to re-
ceiving an experimental monoclonal

the EUA for convalescent plasma to antibody cocktail from Regeneron,

treat the disease, I lost confidence Trump’s attention has turned to tout-

in him again and wrote that society was on its own to ing this treatment as a “cure” and promising its avail-

tackle COVID-19 without help from the FDA. At the ability to all Americans. An antibody-based treatment

same time, Eric Topol, editor-in-chief of Medscape and does deserve more scientific attention, but a therapeutic

a prominent scientist and public health advocate, called is not a cure. If an EUA for this treatment is announced,

for Hahn to resign. the scientific community needs Hahn to resist Trump’s

Topol got Hahn’s attention. After Topol’s editorial ap- pressure to exaggerate and declare the pandemic over.

peared, the commissioner reached out to him, which, as These antibodies are helpful but currently in very lim-

Topol told me, started a series of conversations about ited supply and not something that will “get everybody

their differences. Hahn confirmed to Topol that he had out of the hospitals,” as Trump said recently. The sci-

been instructed by the White House to extoll the benefits entific community must keep the pressure on Hahn to

of convalescent plasma beyond his scientific judgment. state the science clearly.

Subsequently, the FDA proposed to the White House a Readers who don’t think Science and its publishing

more stringent protocol for approving a COVID-19 vac- peers should write about politics often tell us to “stick

cine. In the case of the two leading vaccine candidates to science.” We are sticking to science, but more impor-

(Moderna and Pfizer), a 2-month delay would be re- tantly, we’re sticking up for science. PHOTO: CAMERON DAVIDSON

quired for half of the volunteers that received a second

shot, which must be delivered 3 to 4 weeks after the –H. Holden Thorp

10.1126/science.abf2306

266 16 OCTOBER 2020 • VOL 370 ISSUE 6514 sciencemag.org SCIENCE

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EDITORIAL

Speed and American elections

“A s you love your country, fly to your polls,” the In 1960, all three television networks used comput-
Gazette of the United States urged voters in 1800, ers to make projections in the contest between John
in a presidential election that pitted Thomas Jef- F. Kennedy and Richard M. Nixon, which proved to be
ferson against John Adams. But voters hardly one of the closest elections in American history. On CBS,
raced to the polls that year: Balloting began in an IBM 7090 predicted a Kennedy victory at 8:12 p.m.
March and ended in November and the winner Eastern Standard Time, while polls remained open in

was declared only weeks before inauguration. In much of the country. Republicans pushed for a recount;

the centuries since, both voting and counting in the Unit- Nixon decided to concede. Afterward, IBM published a Jill Lepore
is the David Woods
ed States have gotten faster, if not always more fair, and promotional brochure called “The Fastest Reported Elec- Kemper ‘41 Professor
of American
this year, the communication of results long before they tion,” boasting, “For waiting millions on election night, History, Harvard
College Professor,
can possibly be known threatens to undermine not only the computer cut down the time of waiting.” Newspapers and Affiliate
Professor of Law at
the election but democracy itself. soon began commissioning computers, too. In 1962, The Harvard University,
Cambridge, MA, USA.
Republicans have raised alarms about old-fashioned, New York Times hired the Simulmatics Corporation, a

well-regulated technologies: the paper ballot and the post pioneering predictive analytics company. Simulmatics

office. But the real danger this election comes from new- promised that it could help the newspaper report the

fangled, unregulated social media companies. “What’s the results of the mid-term elections in “real time,” a term

Plan if Trump Tweets that He’s Won Re-election?” The that had been coined by the U.S. Department of Defense,

New York Times asked last month. at the height of the Cold War, to ex-

Twitter plans to slow down commu- plain how computers predicted, by

nications on its platform beginning “Haste...has also way of simulation, the path and ve-
20 October. That may be too little, locity of missiles.

too late. not infrequently Ballots aren’t bombs. Honestly,
The push for speed came, first, undermined what’s the hurry? Haste is not in
the democratic the public interest. It has also not
from newspapers. In 1852, The New process.” infrequently undermined the demo-
York Times promised that a new cratic process. In 1980, NBC Televi-
technology of communication, the sion News called Ronald Reagan
telegraph, would “enable the Press the presidential winner at 8:15 p.m.
of the entire country to announce At 10 p.m., Jimmy Carter conceded.
the result of the national election Polls hadn’t closed yet in the West,
on the morning after the closing

of the polls.” But as late as 1896, and down-ticket Democrats who lost

newspapers were still using homing their races blamed Carter. But, re-

pigeons to collect returns although, by 1904, electric- ally, NBC was to blame. As a consequence, television net-

ity allowed big-city newspapers headquartered in tall works adopted new rules, barring the calling of elections

buildings to speed results to the public by way of lights before the polls close. In 2000, every television network,

that could be seen for miles (that’s what’s meant by a relying on computer projections, called the presidential

“news flash”): Steady light to the west meant a Demo- election for George W. Bush over Al Gore, leading Gore

cratic victory; steady light to the east a Republican one. to concede, prematurely. Again, television networks es-

The emergence of radio in the 1920s and modern tablished new rules.

polling in the 1930s made election reporting more Media companies fix their mistakes. Journalists work

frantic and, equally, more prone to error. In 1948, the in the public interest. “We are not a media company,”

Chicago Daily Tribune famously went to press with the Mark Zuckerberg insisted after the 2016 election, deflect-

dead-wrong headline, DEWEY DEFEATS TRUMAN. ing blame. For 2020, Facebook has established a Voting

PHOTO: STEPHANIE MITCHELL/HARVARD UNIVERSITY But the real turn came in 1952 when CBS Television Information Center; one of its purposes, Zuckerberg says,

News brought in a UNIVAC computer to predict the is “to prepare people for the possibility that it may take a

outcome of the contest between Dwight Eisenhower while to get official results.” That might work. Or, it might

and Adlai Stevenson. With the introduction of “giant not. Either way, after the 3 November election, control of

electronic brains” into election-night television cov- the nation’s election reporting needs to be wrested out of

erage, Americans came to expect to learn of the out- Zuckerberg’s clutches and returned to journalists.

come of a presidential election before turning in for

the night. –Jill Lepore

10.1126/science.abf1768

SCIENCE sciencemag.org 16 OCTOBER 2020 • VOL 370 ISSUE 6514 267

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NEWS “ ”Allowing a dangerous virus that we don’t fully understand
to run free is simply unethical. It’s not an option.
Tedros Adhanom Ghebreyesus, head of the World Health Organization, on claims
that populations will develop “herd immunity” to the pandemic coronavirus if lockdowns end.

I N B R I E F Edited by Jeffrey Brainard China joins global vaccine plan

Scientists consider the skull of an auctioned Tyrannosaurus rex to be among the most pristine ever found. PU B L I C H E A LT H | China announced last
week it is joining a global initiative to
PA L E O N T O L O GY distribute COVID-19 vaccines fairly and
affordably. The country, which has developed
Top dino fetches top dollar at auction several vaccine candidates, was one of the
last big nations that had not signed on to the
A n unusually complete Tyrannosaurus rex fossil was sold last COVID-19 Vaccines Global Access (COVAX) PHOTO: MARY ALTAFFER/AP PHOTO
week for a record-breaking $31.8 million at an auction, dismay- Facility, developed by the World Health
ing many paleontologists. They worry such sales will encourage Organization (WHO) and partners. It aims to
more private trade of fossils, leaving important specimens off- shepherd approximately a dozen vaccines to
limits to researchers. The auctioned fossil, officially called BHI market and distribute 2 billion doses to par-
3033, is popularly known as Stan, after its discoverer, amateur ticipating countries by the end of 2021. Each
paleontologist Stan Sacrison, who found it in 1987 in South Dakota’s country would receive enough to inoculate
Hell Creek Formation. The sale price dwarfs the $8.4 million that at least 20% of its population. But China said
the Field Museum in Chicago paid in 1997 for the T. rex fossil named it will buy vaccines through COVAX for only
Sue. Stan’s buyer has not been identified. In September, the Society of 1% of its people, a pledge that could limit its
Vertebrate Paleontology asked Christie’s, the auction house, to sell Stan draw on the project’s vaccine supplies. A total
only to “institutions committed to curating specimens for the public of 180 countries representing approximately
good and in perpetuity, or those bidding on behalf of such institutions.” 90% of the world’s population have now
joined the plan, WHO said at a 12 October
268 16 OCTOBER 2020 • VOL 370 ISSUE 6514 press briefing. The United States is not one
of them.

Tasmanian devil reintroduced

CO N S E RVAT I O N | Though an icon of the
Down Under continent, the fierce-looking
Tasmanian devil had been missing from
Australia’s mainland for at least 3000 years,
probably wiped out by people. But a
comeback has begun: Between March and
September, Aussie Ark and two other con-
servation organizations released 26 of these
Boston terrier–size carnivorous marsupials
into a fenced 160-hectare preserve north of
Sydney. In modern times, the devil has been
endemic only to Tasmania, and since 1995,
lethal, transmissible cancers have reduced its
populations there by 90% to about 25,000.
The newly released animals come from a
group of almost 400 cancer-free devils raised
in captivity by Aussie Ark; it plans to place
40 more in two other mainland locations by
2023. The organization views the reintroduc-
tions as a step toward “rewilding” parts of
Australia with other native species as well.

Nobel honors auction theory

AWARDS | The Nobel Memorial Prize in
Economic Sciences was awarded on
12 October for research on auction formats
now used to sell goods and services such as

sciencemag.org SCIENCE

Published by AAAS

IN FOCUS An image of a juvenile zebrafish carrying an inserted
gene that makes its lymphatic system glow orange won first
place in the Nikon Small World Photomicrography Competition
this week. Researchers at the U.S. National Institutes
of Health, who made the image, this year reported
discovering lymphatic vessels in the nervous systems
of zebrafish, a commonly used lab animal. The
finding opened new avenues for studying
diseases of the human brain,
including Alzheimer’s.

PHOTO: DANIEL CASTRANOVA, BRANT WEINSTEIN, AND BAKARY SAMASA/NATIONAL INSTITUTES OF HEALTH/NIKON SMALL WORLD internet ads, fishing quotas, and electricity. chlorofluorocarbons (CFCs), supposedly inert BY THE NUMBERS
The prize is shared by Paul Milgrom and chemicals widely used in aerosol cans and
Robert Wilson, both of Stanford University. refrigeration, when they reached the upper $200,000
(Wilson delivered the news to Milgrom, his atmosphere. Chlorine freed by the reaction,
neighbor, via a doorbell camera because they showed, could destroy large amounts of Estimated loss on average for
Milgrom had ignored the early morning UV-blocking ozone. The insight, validated by a U.S. family of four from COVID-19
phone calls from Sweden.) In the 1960s and the discovery in 1985 of the ozone hole above
’70s, Wilson used game theory to show how Antarctica, led to the 1987 Montreal Protocol, during the next decade. About
the risk of the “winner’s curse”—winning an international agreement that required half is from lost income; the
an auction at too high a price—leads to low phasing out use of CFCs and similar pollut-
bids and lower revenue auctions. Milgrom, ants. Molina worked behind the scenes to rest reflects the costs of health
Wilson’s graduate student, showed how support its creation. Many of these products impairments and premature deaths.
auctions that give bidders more information are also potent greenhouse gases, which has The price of countering the pandemic by
about an item’s value are better at avoiding made the Montreal Protocol perhaps the testing people and tracing their contacts
the winner’s curse. In the 1990s, the U.S. most effective global step taken so far to
Federal Communications Commission (FCC) curb global warming. would be only one-thirtieth of those
put their theories to work in its allocation losses, economists estimate. (JAMA)
of radio spectrum to telecom companies. São Paulo science spared
FCC switched from giving away bandwidth $42,000
in a random lottery to an auction format FUNDING | The academic community in
designed by Milgrom and Wilson, raising Brazil’s São Paulo state breathed a sigh of Total cost of 51 disinformation ads
more than $120 billion over the next relief last week after its government aban- on Facebook, viewed at least
20 years. Other countries have used similar doned a plan to take control of the financial
auctions for other assets, such as carbon reserves of three state universities and the 8 million times this year in the United
emission allowances. São Paulo Research Foundation (FAPESP). States, that called findings
The move, part of a bill to balance state
Co-discoverer of ozone threat dies finances, would have crippled research in of climate change science a “hoax.”
São Paulo, which accounts for 40% of Brazil’s Facebook says it prohibits ads that
E N V I RO N M E N T | Mario Molina, an atmo- scientific output, scientists said (Science, include claims debunked by third-
spheric chemist and Nobel laureate who 4 September, p. 1152). But another threat is
helped identify and reduce threats to Earth’s looming for FAPESP. A new bill would allow party fact-checkers
ozone layer, died last week at age 77. With F. the government to withhold 30% of the and started a web page to connect
Sherwood Rowland, Molina showed in 1974 agency’s funds, which are a fixed share of the
that ultraviolet (UV) light could break down state’s tax revenues, in 2021. people with factual information
about climate science; critics call its
SCIENCE sciencemag.org efforts inadequate. (InfluenceMap)

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IN DEPTH

In a 2002 eruption,
a lava lake within
the crater of

Nyiragongo volcano
drained in hours.

NATURAL HAZARDS

Lava lake rises at dangerous African volcano

Funding for volcano’s lone monitoring station lost as warning signs flash

By Roland Pease advice on the dangers of the volcano, so he cury in a barometer. His model suggests PHOTO: CARSTEN PETER/NAT GEO IMAGE COLLECTION
monitored Nyiragongo’s moods in the years the internal pressure is 20 atmospheres,
I n 2002, the last time Nyiragongo volcano before the 2002 eruption. He is alarmed by well beyond the mechanical strength of the
erupted, lava raced down its flanks into parallels to today. volcano’s rocky flanks, Burgi and colleagues
the crowded city of Goma, on the border reported in August in Geophysical Research
between the Democratic Republic of the The 2002 eruption began after an earth- Letters. “This situation is unstable,” he says.
Congo and Rwanda. About 250 people quake opened up fissures in the southern “The danger is of a tremor opening up a
died, 20% of the city was destroyed, and flank of the volcano. The 200-meter-wide new fissure.”
hundreds of thousands fled. Since then, the lava lake, the largest in the world, drained in
at-risk population living in the shadow of a matter of hours, releasing low-silica, runny They believe the system may be reach-
the 3470-meter-tall volcano has more than lava that flowed as fast as 60 kilometers per ing a critical point, as it did before the 2002
doubled to 1.5 million. hour. The lava piled up in layers up to 2 me- eruption and an earlier one in 1977. In both
ters deep in Goma and created a new delta cases lava lake levels stabilized several years
Now, conditions are ripe for another disas- 800 meters wide in nearby Lake Kivu. before the eruption, they argue, as the mass
ter, says Dario Tedesco, a volcanologist at the of molten rock weighed down on the magma
Luigi Vanvitelli University of Campania, who As soon as the fissures healed, however, below. The eruptions lagged because magma
earlier this year led a campaign into the vol- fresh lava began to bubble up and refill the takes time to force open existing fractures,
cano’s roiling crater. He and his colleagues crater lake. Activity accelerated in 2016 when explains Andrew Bell, an expert on rock me-
found the lava lake there filling at an alarm- a second vent began to fountain within the chanics at the University of Edinburgh who
ing rate, raising the risk that the molten rock crater. In February, on their most recent in- developed a model to explain the collapse of
could burst through the crater walls once spection, Tedesco and his colleagues—flown Mount St. Helens in 1982. Burgi expects the
again. Their analysis suggests peak hazard in by U.N. peacekeepers to avoid the rebels lava lake to stop rising soon, in which case
will arrive in 4 years, although they believe active in the area—found the lake rising the period of peak danger for Goma would
an earthquake could trigger a crisis earlier. faster than ever. The second vent was gush- be from 2024 to 2027.
Adding to the concerns, the Goma Volcano ing an estimated 4 cubic meters of lava per
Observatory (GVO), the only monitoring second, enough to fill an Olympic swimming “They are right to be concerned,” Bell
station in the region, is losing its financial pool every 10 minutes. “As long as the vol- says. “Nyiragongo is dangerous in a way a
support from the World Bank. Tedesco’s as- ume is increasing, it increases the chances lot of volcanoes aren’t.” He adds, however,
sessment is blunt. “This is the most danger- of a volcanic eruption onto Goma,” says GVO that the behavior of the lava lake doesn’t say
ous volcano in the world!” Director General Katcho Karume, who also much about the immediate risk of eruption.
took part in the campaign. Swarms of small earthquakes or ground de-
Tedesco began to watch the volcano in formation are clearer warning signs of rest-
the mid-1990s, when refugees, fleeing the Pierre-Yves Burgi, a geophysical modeler less magma, he says. Cynthia Ebinger, an
genocide in nearby Rwanda, swelled Goma’s at the University of Geneva, says the lava expert on Rift Valley geology at Tulane Uni-
population. The United Nations sought his lake level is effectively a pressure gauge for versity, also has issues with Burgi’s model,
the volcano’s internal plumbing, like mer-

270 16 OCTOBER 2020 • VOL 370 ISSUE 6514 sciencemag.org SCIENCE

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NEWS

which assumes the magma plumbing feed- NOBEL PRIZES
ing Nyiragongo’s lava lake is the main fac-
tor controlling an eruption. She says the A cut above: pair that developed
stretching of tectonic plates in the region CRISPR earns historic award
leads to earthquakes and fresh intrusions of
magma that can also trigger eruptions. Chemistry Nobel honors biology’s powerful genome editor

PHOTOS: (LEFT TO RIGHT) © PETER RIGAUD C/O SHOTVIEW ARTISTS; DEANNE FITZMAURICE A network of seismometers around the By Jon Cohen Doudna and Charpentier, who is originally
volcano, operated by GVO and installed in from France and at the time of the discov-
recent years with assistance from research- D ecades typically pass before a discov- ery worked at Umeå University in Sweden,
ers in Belgium and Luxembourg, shows ery leads to a Nobel Prize, but the programmed a short “guide RNA” to carry a
high earthquake activity and several deep chemistry award last week celebrated bacterial CRISPR-associated enzyme to exact
swarms, says François Kervyn, director of two scientists who, a short 8 years DNA locations, allowing them to target spe-
the natural hazards division at the Royal ago, described how to transform an cific genes for the enzyme to cut. As the cell
Museum for Central Africa in Belgium. He obscure bacterial immune mechanism attempts to repair the damage, it often makes
doesn’t know how unusual the activity is into the most powerful genome editor ever mistakes, which can cripple a gene—an effec-
because his team lacks comparable, older devised: CRISPR. tive way to study its normal role or eliminate
data. But he says sustained, rumbling trem- a harmful mutant. CRISPR also makes it pos-
ors were recorded months before the 2002 The award, to Emmanuelle Charpentier of sible to insert a new stretch of DNA at the
eruption. “Nothing like that is detected for the Max Planck Unit for the Science of Patho- cut site.
the moment,” he wrote in an email. gens and Jennifer Doudna of the University
of California (UC), Berkeley, marks the first Many other groups soon built on the find-
Kervyn says the network requires constant time a Nobel Prize in science has gone to an ings, making CRISPR a common tool in labs
maintenance, because of vandalism, theft, all-female team. It also comes amid a high- around the world and spawning dozens of
and lightning damage. Several seismometers stakes patent fight over the revolutionary companies in agriculture and medicine pur-
are currently out of action. But the civil un- genetic “scissors”—which promise to have suing potential markets worth many billions
rest in the area makes repairs dangerous. an impact on medicine, crops, livestock, of dollars. One CRISPR application has al-
Earlier this year 13 park rangers were killed pest control, and even climate change. Few ready cured a person of sickle cell disease.
in an ambush in the surrounding Virunga doubted it would one day merit a Nobel, but
National Volcano Park. who would receive it, and when, was anyone’s Many scientists expected that Feng Zhang
bet. Both scientists said they were stunned by of the Broad Institute, whose team in Janu-
The threat of violence is only one of GVO’s the award. “I’m just floating,” Doudna said ary 2013 published the first evidence that
problems. Established in 1986, the observa- the next day. “It feels unreal.” CRISPR worked in mammalian cells, would
tory is set to lose the funding it has relied share the prize. The institutions of the three
on for the past 5 years. With a staff of about The pair built on other scientists’ discov- scientists are locked in a patent battle over
40, the observatory maintains the seismic ery that bacteria have distinctive stretches who deserves the intellectual property rights
stations and monitors the lake and the po- of DNA—so-called clustered regularly to CRISPR’s discovery, which could be worth
tentially deadly gases emitted by the volcano. interspaced short palindromic repeats, or billions of dollars. Zhang had not yet com-
It also plans for Goma’s evacuation, and will CRISPR—embedded in their genomes. Re- mented on the Nobel Prize as Science went
issue the alarm if an eruption occurs. tained from viruses that have infected the to press, but Erik Sontheimer, a CRISPR re-
microbes in the past, the DNA allows them searcher at the University of Massachusetts
Since 2015, the World Bank has given to recognize and defend themselves against Medical School, endorses the decision. “The
the observatory $2.3 million, as part of an future invasions. In a paper published online prize is not based on anything related to pat-
aid package primarily intended to rebuild in Science on 28 June 2012, they reconfigured ent law,” he says.
and protect the city airport, which was CRISPR to turn it into a tool that could edit
seriously damaged in the 2002 eruption. DNA in a cell-free system. Harvard University chemist George
But that project has ended. In an email, a Church published a study showing CRISPR
spokesperson for the World Bank Group
confirmed that “no follow-up activities are
envisioned by the WBG so far.”

The U.N. peacekeeping force is con-
cerned. At the end of September, it flew
Tedesco back to the city for more talks with
the World Bank and other development
agencies. A U.N. spokesperson says the
peacekeepers are considering supporting
GVO in the short term. “We are conscious
of the importance of keeping the volcanoes
monitored as a way to protect civilians and
save lives.”

As Science went to press, there was no
news of a resolution. Tedesco planned to
inspect Nyiragongo’s crater again, but bad
weather forced the cancellation of a helicop-
ter flight. “If things remain like this, there is
little to be optimistic about,” he says. j

Roland Pease is a journalist in Swindon, U.K. Emmanuelle Charpentier (left) and Jennifer Doudna were honored for changing how scientists edit DNA.

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NEWS | IN DEPTH

could edit mammalian cells at the same The coronavirus pandemic has further disrupted the already precarious academic employment landscape.
time as Zhang, who had been a postdoc
in his lab. But Church doesn’t think ei- WORKFORCE
ther of them was slighted. As he sees it,
Charpentier and Doudna made a discovery, U.S. faculty job market tanks
which is what the Nobel Committee prefers
to reward, and he and Zhang were inven- As COVID-19 upends university finances,
tors who showed how to apply it. “If any- postdocs worry about their future
one wants any tips on how not win a Nobel
Prize, it’s pretty easy,” Church says. “I’ve By Katie Langin Cumulative job postings Last year, 108 positions had been posted by
carefully avoided all this kind of brouhaha that time. It’s “depressing,” she says.
by focusing on inventions.” And, he says, I n February, Ashley Ingiosi was excited CREDITS: (PHOTO) GREGORY BULL/AP PHOTO; (GRAPHIC) N. DESAI/SCIENCE; (DATA) SCIENCE CAREERS
Zhang, who is 38, is young. “Feng Zhang is to finally interview for a faculty position The scarcity of academic jobs is a peren-
so full of creative ideas that I have no doubt after spending 10 years in training as a nial problem for U.S. science trainees. But
that he will get one or two in the future.” grad student and postdoc. “Then COVID this year, faculty job openings at U.S. insti-
came around,” the Washington State Uni- tutions are down 70% compared with last
Doudna would not directly address versity, Spokane, neuroscientist says, and year, according to an analysis of job adver-
whether the Broad scientist should have the job opening was eliminated. “That was tisements on the Science Careers job board.
shared the Nobel and dismissed the idea it the end of my job search last year.” (Science’s news team operates independently
might affect any patent decisions. “We could from the job board.) Only 173 U.S.-based jobs
see this prize as acknowledging the impor- Now, Ingiosi is preparing applications for were posted from July to September, com-
tance of the field overall,” she adds, noting the 2020–21 academic cycle and is encoun- pared with 571 during the same period last
many scientists developed the CRISPR tool. tering a new problem: a dearth of faculty job year. Non-U.S. job postings dropped by 8%.
openings. This year, the job posting website
The editor is both cheap and easy to use, she follows—NeuroRumblr—had only listed “It’s about double-worse than I imag-
stoking fears it could be misused in ways 50 faculty positions by the end of September. ined,” says Andrew Spaeth, an industrial
that threaten the environment or the hu- chemist and co-creator of a popular online
man species itself. CRISPR-powered “gene A slow start faculty job list for chemists. “I thought we’d
drives,” for example, can rapidly spread al- see a hit—maybe 30%,” he says, but his site
tered DNA through a species. Researchers U.S. faculty openings are down 70%, according lists roughly 70% fewer openings compared
have already shown how the technology to an analysis of the Science Careers job board. with last year. An ecology and evolution job
can sterilize and wipe out populations of (Gaps reflect days with no new postings.) list reveals a similar drop, with 65% fewer
disease-carrying mosquitoes—but critics openings this year.
worry that entirely eliminating an organ- 1200
ism from an ecosystem could have an un- 2017 2019 The dismal numbers reflect anxiety about
intended negative impact. 2018 2020 university finances amid the pandemic,
says Robert Zemsky, a professor of educa-
And in one of the most controversial bio- 1000 tion at the University of Pennsylvania who
medical experiments of the past decade, studies university finances. Big public uni-
researcher He Jiankui used CRISPR to edit 800 versities, in particular, are a “total mess,” he
the genomes of human embryos in China, says. “They are losing enrollment, they are
resulting in the birth of three babies. He 600 losing revenue, and they don’t know what
was widely condemned by the scientific to do, so they have hiring freezes every-
community and eventually jailed in China, 400 where.” Even universities that are finan-
a country that has become a leader in other cially stable now are concerned about the
areas of CRISPR research. 200 future. “Everybody is sitting on their hands
and nobody wants to make bets at all right
Doudna says her status as a Nobel laure- 0 now,” he says.
ate will allow her to become something of Jul. Aug. Sep. Oct. Nov. Dec.
an ambassador for science, and she plans to Given the hiring slowdown, many postdocs
devote the award money to a program her will probably try to stay in their positions
husband, UC Berkeley chemist Jamie Cate,
runs for science, technology, engineering,
and math students from underrepresented
groups. “I feel a real sense of responsibility
to making sure that girls and young women
in particular feel welcomed into our field
and that their work will be valued.”

Fyodor Urnov, a CRISPR researcher who
works with Doudna, calls it “the most de-
served Nobel Prize of the past 20 years.” The
discovery “changed everything for the bet-
ter,” says Urnov, who previously worked on
a more cumbersome gene editor called zinc
fingers. “We can improve the world around
us in extraordinary ways,” he says. “The 21st
century will be the age of CRISPR—thanks
to Jennifer and Emmanuelle.” j

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for longer than they would have otherwise, HIGH-PRESSURE PHYSICS
says Paula Stephan, an economics profes-
sor at Georgia State University who studies At last, room temperature
the scientific workforce. A letter in Science superconductivity achieved
(29 May, p. 957) argued that institutions
should take steps to extend postdoc ap- But the hydrogen-based material requires high pressure
pointments. But because postdoc salaries
are funded by a variety of mechanisms, co- By Robert F. Service or 4.2 K. In 1957, physicists John Bardeen,
author Amir Behbahani acknowledges, find- Leon Cooper, and Robert Schrieffer ex-
ing money to extend everyone’s salary would F ulfilling a decades-old quest, this week plained the phenomenon: Their “BCS the-
be challenging. “This is not an easy problem researchers report creating the first ory” suggested an electron zipping through
to fix,” says Behbahani, a postdoc at the Cali- superconductor that does not have to a superconductor temporarily deforms the
fornia Institute of Technology. be cooled for its electrical resistance material’s structure, pulling another elec-
to vanish. There’s a catch: The new tron behind in its wake without resistance.
Stephan notes, “There hasn’t been a huge room temperature superconductor
increase in funding, so it’s not clear where only works at a pressure equivalent to about In 1986, a pair of physicists found that
those dollars will come from, but maybe three-quarters of that at the center of Earth. in different materials, copper oxide ceram-
they’ll come from [principal investigators] But if researchers can stabilize the material ics, superconductivity set in at a higher
not taking on new postdocs.” Yet if postdoc at ambient pressure, dreamed-of applica- “critical temperature,” or Tc, of 30 K. Other
appointments are extended, she points out, tions of superconductivity could be within groups quickly cooked up related ceramic
that could lead to downstream impacts on reach, such as low-loss power lines and recipes; by 1994, they pushed the Tc up to
another group: soon-to-be Ph.D. graduates. ultrapowerful superconducting magnets 164 K in a mercury-based copper oxide un-
“It really worries me that if we help people that don’t need refrigeration, for MRI ma- der pressure. Electrons also pair up in cu-
stay on for … longer, it’s just going to kick chines and maglev trains. prate superconductors, but just how they
the can down the road and it doesn’t help superconduct remains murky.
people to get the message that there are not “This is a landmark,” says Chris Pickard,
a lot of [faculty] jobs out there.” But these are a physicist at the University of Cambridge. In 1968, Neil Ashcroft, a theorist at Cor-
exceptional times, she adds. “We really need But the extreme conditions of the experi- nell University, had suggested a different
to think about how to provide some kind of ment mean that even though it was “pretty type of material should display BCS super-
lifeline … and not lose a group of people that spectacular,” says Brian Maple, a physicist conductivity above room temperature: hy-
we put a lot of resources into training.” at the University of California, San Diego, drogen under intense pressure. Numerous
“this is certainly not going to be useful in groups have claimed to make such metallic
As tough as the situation is, it could serve making a device.” hydrogen, using diamond anvil cells, palm-
as an opportunity, says Cynthia Fuhrmann, size devices in which a target substance
an assistant dean of career and professional The announcement, by a team led by gets crushed to enormous pressure between
development at the University of Massachu- physicist Ranga Dias of the University of the tips of two diamonds. But the results
setts Medical School. “The reality is Ph.D. Rochester, culminates a long march up remain controversial, in part because the
scientists move on to many different career the thermometer. Superconductivity was pressures—exceeding those at the center of
paths and have for a long time,” she points first discovered in 1911 by Dutch physicist Earth—are so high they typically crack the
out. The academic hiring freezes could spur Heike Kamerlingh Onnes in a mercury diamonds (Science, 27 January 2017, p. 332).
more young scientists to look into non- wire chilled to 4.2° above absolute zero, In 2004, Ashcroft suggested binding hydro-
academic options, and Ph.D. and postdoc
PHOTO: ADAM FENSTER training programs to think more carefully Crushed between two diamonds, a compound of hydrogen, sulfur, and carbon superconducts at room temperature.
about “preparing scientists who can nim-
bly adapt across a breadth of roles and
across a breadth of sectors in science,”
Fuhrmann says.

If and when academic jobs rebound,
Fuhrmann hopes the way will be open
for scientists who took nonacademic jobs
and would like to return. Academic search
committees should be open to interview-
ing scientists “who have taken a different
route right now, out of necessity in part,
and to recognize what really interesting
perspectives … [they] could bring if they
move their science back into an academic
setting,” she says.

As for Ingiosi, she isn’t considering non-
academic positions just yet. She already has
one faculty job interview lined up this year
and is busy applying for other positions. But
if she doesn’t land a job offer during this ap-
plication cycle, her plans may change. “I al-
ways told myself that I wouldn’t do this to
myself 3 years in a row.” j

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gen to another element might add a sort of ASTRONOMY
“chemical precompression” that could make
higher temperature superconductivity pos- Satellite
sible at lower pressures. swarm
threatens
The strategy worked. In 2015, research- radio array
ers led by Mikhail Eremets at the Max
Planck Institute for Chemistry reported “Megaconstellations”
in Nature that they discovered super- already bedevil optical
conductivity at 203 K in H3S compressed telescopes. Now,
to 155 gigapascals (GPa), more than radio astronomers
1 million times Earth’s atmospheric pres- are concerned
sure. Over the next 3 years, Eremets and
others boosted the Tc as high as 250 K in By Daniel Clery
hydrogen-rich compounds containing lan-
thanum. But release the pressure, and all Companies hope to put tens of thousands of communications satellites in orbit.
those compounds disintegrate.
W hen complete, the 197 radio astron- Telecommunication Union (ITU), a U.N. or- IMAGE: ESA-SCIENCE OFFICE
Dias and his colleagues thought they omy dishes of the Square Kilometre ganization, will step in. “The radio spectrum
could push the Tc up even higher by add- Array (SKA) in South Africa will sit is a resource that is being consumed by pri-
ing a third element: carbon, which forms within a radio-quiet zone the size vate companies that typically have no regard
strong bonds with neighboring atoms. of Pennsylvania where even a cell- for science,” says radio astronomer Michael
“We were flying blind,” says team member phone is forbidden, to safeguard Garrett, director of the Jodrell Bank Centre
Ashkan Salamat, a physicist at the Univer- signals from the heavens. Yet that precaution for Astrophysics in the United Kingdom. “It’s
sity of Nevada, Las Vegas. won’t save the array, due to be completed only government intervention that can stop
in the late 2020s, from what may soon be this state of affairs in my view.”
They loaded their diamond anvil cell overhead: tens of thousands of communica-
with tiny solid particles of carbon and sul- tions satellites beaming radio signals straight So far, SpaceX has launched more than
fur milled together, and then piped in three down. “The sky will be full of these things,” 700 Starlinks out of an initial goal of 1440,
gases: hydrogen, hydrogen sulfide, and says SKA Director General Phil Diamond. and it has won approval for 12,000. Opera-
methane. They then shined a green laser tors such as OneWeb and Amazon’s Proj-
through the diamond, triggering a chemical The rocket company SpaceX has already ect Kuiper have similar ambitions. Studies
reaction that turned the mixture into trans- launched hundreds of Starlink satellites, the suggest wide-field optical surveys will be
parent crystals. first “megaconstellation” intended to provide worst affected, with satellite tracks marring
internet service to remote areas. The satel- most images. The team building the Vera
When they then cranked up the pressure lites have aroused the ire of optical astrono- C. Rubin Observatory, a survey telescope
to 148 GPa and checked the conductivity of mers because of the bright streaks they leave in Chile due to see first light next year, is
the sample via electrical leads, they found across telescopes’ fields of view. Now, radio working with SpaceX to reduce the impact.
that the crystals became superconduct- astronomers are worried, too. Last week, SKA The company has changed the orientation
ing at 147 K. By increasing the pressure to released an analysis of the impact that Star- of satellites as they rise in orbit, painted
267 GPa, the team reached a Tc of 287 K, link and other constellations would have on them darker, and fitted “visors” to reduce
the temperature of a chilly room or an ideal the array. It finds they would interfere with reflections. All Starlink satellites launched
wine cellar. Magnetic field measurements one of the radio channels SKA plans to use, since August have visors, SpaceX’s Patricia
also indicated the sample had become hampering searches for organic molecules in Cooper, vice president for satellite govern-
superconductive, Dias and his colleagues space as well as water molecules used as a ment affairs, told the UNOOSA workshop
report this week in Nature. key marker in cosmology. last week. “We’re trying to look for a path
where we can coexist,” she said.
“The results look believable,” Eremets says. SpaceX is promising to address the con-
He notes, however, that the Rochester team cern. But radio astronomers are also seeking The analysis from SKA, which when com-
has not yet been able to determine the pre- regulations. The United Nations Office for plete will be the world’s largest radio obser-
cise structure of the compound that’s super- Outer Space Affairs (UNOOSA), which dis- vatory, highlights the new concern. The band
conducting. Researchers will soon set to cussed the SKA analysis at a workshop last that Starlink uses to beam down internet
work on that question, and they will likely week, is considering ways to prevent pollu- signals takes up a sizable chunk of frequen-
also start to substitute other elements into tion of the night sky, for the benefit not just cies from 10.7 to 12.7 gigahertz, within a range
three-component hydrogen-based mixtures of astronomy, but also wildlife and the pub- known as band 5b that is one of seven bands
in hopes of even higher temperature super- lic. Astronomers also hope the International SKA’s South African dishes will target. The
conductors. “That’s the next thing everyone
is going to be doing,” says Eva Zurek, a theo-
rist at the University at Buffalo.

The ultimate aim, Eremets adds, is to
find a room temperature superconductor
that is stable when the pressure is released.
If researchers pull that off, the results could
transform daily life. Dias says: “I think this
is actually possible.” But theory doesn’t yet
suggest a way to make hydrogen-based ma-
terials work at ambient pressures. Zurek
adds, “We don’t necessarily have a clear
path forward.” j

274 16 OCTOBER 2020 • VOL 370 ISSUE 6514 Corrected 15 October 2020. See full text. sciencemag.org SCIENCE

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SKA analysis calculated the impact of 6400 COVID-19
satellites, taking into account both direct sig-
nals and leakage called “side lobes.” Found: genes that sway the
course of the coronavirus
The SKA team finds that satellite trans-
missions will lead to a 70% loss in sensitivity Host variants boost severity risk, may point to drug options
in the downlink band. If the number of satel-
lites in megaconstellations reaches 100,000, By Jocelyn Kaiser print on medRxiv, will speed treatments,
as predicted by many, the entire band 5b although he cautions that any clinical trial
would be unusable. SKA would lose its sensi- I t’s one of the pandemic’s puzzles: Most inspired by the findings should wait for
tivity to molecules such as glycine, a protein people infected by SARS-CoV-2 never the study’s acceptance in a peer-reviewed
component. “If it was detected in a plan- feel sick, whereas others develop seri- journal. “Because the epidemic is pro-
etary system that was forming, that would ous symptoms or even end up in an gressing at such an alarming rate, even a
be a very interesting piece of information,” intensive care unit clinging to life. Age few months of time saved will save lots of
Diamond says. “This is a new area that SKA and preexisting conditions, such as lives,” Baillie says.
is opening up.” The band could also contain obesity, account for much of the disparity.
the fingerprints of water molecules in dis- But geneticists have raced to see whether a In a standard approach to finding genes
tant galaxies, a tracer that cosmologists use person’s DNA also explains why some get that influence a condition, geneticists scan
to study how dark energy is accelerating the hit hard by the coronavirus, and they have the DNA of large numbers of people for mil-
expansion of the universe. uncovered tantalizing leads. lions of marker sequences, looking for asso-
ciations between specific markers and cases
Since 1959, ITU has protected a number Now, a U.K. group studying more than of the disease. In June, one such genome-
of narrow frequency bands for astronomy. 2200 COVID-19 patients has pinned down wide association study in The New England
But in recent decades, digital receivers common gene variants that are linked to Journal of Medicine (NEJM) found two
have allowed telescopes to “operate over the most severe cases of the disease, and “hits” linked to respiratory failure in 1600
the whole spectrum,” Diamond says. “We’ve that point to existing drugs that could be Italian and Spanish COVID-19 patients: a
learned to coexist with transmitters,” typi- repurposed to help. “It’s really exciting. marker within the ABO gene, which deter-
cally by excluding them from a radio quiet Each one provides a potential target” for mines a person’s blood type, and a stretch
zone or siting telescopes in remote areas. treatment, says genetic epidemiologist of chromosome 3 that holds a half-dozen
But they have no control over transmitters Priya Duggal of Johns Hopkins University. genes. Those two links have also emerged in
flying overhead. other groups’ data, including some from the
Kenneth Baillie of the University of DNA testing company 23andMe.
Radio astronomers want the satellite op- Edinburgh, an intensive care physician
erators to turn off their transmitters, move and geneticist, led the new study, which The new study confirmed the chromo-
to other bands, or point them away when he discussed on 2 October at an online some 3 region’s involvement. And because
they are flying over an observatory. Tony meeting of a data-pooling effort called the 74% of its patients were so sick that they
Beasley, director of the U.S. National Radio COVID-19 Host Genetics Initiative. He’s needed invasive ventilation, it had the
Astronomy Observatory, says they have been hoping the results, also posted as a pre- statistical strength to reveal other mark-
discussing these options with SpaceX. “In the
PHOTO: FABIO TEIXEIRA/ANADOLU AGENCY/GETTY IMAGES next year or two, we will be doing tests where A study of some of the sickest COVID-19 patients, such as those placed on ventilators, has identified gene
we’re going to be trying to coordinate in real variants that put people at greater risk of severe disease.
time, technically, with them.” Beasley says
this is a reflection of SpaceX’s corporate cul-
ture: “They want to do cool stuff; they don’t
want to do any harm.”

Other astronomers don’t want to count on
corporate goodwill. At the UNOOSA work-
shop, they pushed for two recommendations:
that all future satellites in low-Earth orbit
be designed to avoid beaming at radio tele-
scopes and radio quiet zones, and that satel-
lites control the leakage from their side lobes.
Those recommendations, along with others
that would protect optical observatories, will
be debated next year in U.N. subcommittees
before going to UNOOSA and, ultimately, the
U.N. General Assembly for approval.

Beasley is philosophical about the situa-
tion. “SpaceX is legally transmitting inside
one of their bands and there are going to be
impacts for anyone trying to do radio astron-
omy,” he says. “These spectrum allocations
represent the goals and intent of society. We
make [them] to enable commerce and to en-
able defense and all kinds of activities. We
have to come to a solution that satisfies all
these to some extent.” j

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ers, elsewhere in the genome, linked to se- anyone at this point has a clear understand- VOICES OF THE PANDEMIC

vere COVID-19. One find is a gene called ing of what are the underlying genes” for The United
Kingdom’s
IFNAR2 that codes for a cell receptor for the chromosome 3 link, says Andrea Ganna mask crusader

interferon, a powerful molecular messen- of the University of Helsinki, who co-leads Trisha Greenhalgh argues
COVID-19 shows that
ger that rallies the immune defenses when the COVID-19 Host Genetics Initiative. health policy need not
wait for perfect evidence
a virus invades a cell. A variant of IFNAR2 The U.K. genetics study did not confirm
By Ellen Ruppel Shell
found in one in four Europeans raised the that the ABO variants affect the odds of se-
I n May, when several prominent U.K. sci-
risk of severe COVID-19 by 30%. Baillie vere disease. Some studies looking directly entists pushed back against a Royal So-
ciety report recommending face masks
says the IFNAR2 hit is “entirely comple- at blood type, not genetic markers, have to help control the spread of COVID-19,
Trisha Greenhalgh was furious. The
mentary” to a finding reported in Science reported that type O blood protects against scientists argued there was insufficient
support in the scientific literature for the
last month: Very rare mutations that dis- COVID-19, whereas A blood makes a person efficacy of masks, and the U.K. government,
following their lead, declined to mandate
able IFNAR2 and seven other interferon more vulnerable. It may be that blood type masks for the general public.

genes may explain about 4% of severe influences whether a person gets infected, “The search for perfect evidence may be
the enemy of good policy,” Greenhalgh, a
COVID-19 cases (25 September, p. 155). but not how sick they get, says Stanford physician and expert in health care deliv-
ery at the University of Oxford, fumed in
Both studies raise hopes for ongoing trials University geneticist Manuel Rivas. In any the Boston Review. “As with parachutes for
jumping out of airplanes, it is time to act
of interferons as a COVID-19 treatment. case, O blood offers at best modest protec- without waiting for randomized controlled
trial evidence.”
A more surprising hit from the U.K. tion. “There are a lot of people with O blood
Greenhalgh is a firm believer in evidence-
study points to OAS genes, which code that have died of the disease. It doesn’t re- based medicine. She wrote a best-selling
book on the topic, and her research has
for proteins that activate an enzyme that ally help you,” says geneticist Andre Franke earned some of her nation’s highest hon-
ors. But in recent years, she has grown
breaks down viral RNA. A change in one of the Christian-Albrecht University of Kiel, critical of what she believes is the privileg-
ing of randomized controlled studies over
of those genes might impair this a co-leader of the NEJM study. clinical experience and close observation.
COVID-19, she argues, has revealed the
activation, allowing the virus to Researchers expect to pin down limits of evidence-based medicine—masks
being a potent case in point.
flourish. The U.K. data suggest Science’s more COVID-19 risk genes—
“The real tension in public health is, in the
there is a variant as common and COVID-19 already, after folding in the U.K. absence of strong evidence, whether it’s ap-
influential on COVID-19 as the in- reporting is data plumbed by Baillie’s team, propriate to take action,” says Tom Inglesby,
terferon genetic risk factor. supported by the the COVID-19 Host Genetics Ini- director of Johns Hopkins University’s Cen-
Pulitzer Center tiative has found another hit, a ter for Health Security. “And a large-scale
Other genes identified by Baillie’s gene called FOXP4 implicated in intervention like masks is extremely difficult
team could ramp up the inflamma- and the to study.” Yet the limited evidence available
Heising-Simons suggested masks could reduce the amount of
virus transmitted from one person to another
tory responses to lung damage trig- Foundation. lung cancer. And in a new med- by more than 90%. And that, Greenhalgh in-
sists, should have been enough to motivate
gered by SARS-CoV-2, reactions that Rxiv preprint posted last week, an inexpensive and largely risk-free public
health intervention. “Hundreds of thousands
can be lethal to some patients. One, DPP9, the company Ancestry.com reports that a of lives were lost before many governments
introduced mandatory masking,” she says.
codes for an enzyme known to be involved in gene previously connected to the effects of

lung disease; another, TYK2, encodes a signal- the flu may also boost COVID-19 suscepti-

ing protein involved in inflammation. Drugs bility only in men, who are more likely to

that target those two genes’ proteins are al- die of the disease than women.

ready in use—inhibitors of DPP9’s enzyme Geneticists have had little luck so far

for diabetes and baricitinib, which blocks identifying gene variants that explain

TYK2’s product, for arthritis. Baricitinib is in why COVID-19 has hit Black people in the

early clinical testing for COVID-19, and the United States and United Kingdom par-

new data could push it up the priority list, ticularly hard. The chromosome 3 vari-

Baillie says. ant is absent in most people of African

The chromosome 3 region still stands ancestry. Researchers suspect that socio-

out as the most powerful genetic actor: A economic factors and preexisting condi-

single copy of the disease-associated vari- tions may better explain the increased

ant more than doubles an infected person’s risks. But several projects, including

odds of developing severe COVID-19. Evo- Baillie’s, are recruiting more people of non-

lutionary biologists reported last month European backgrounds to bolster their

in Nature that this suspicious region ac- power to find COVID-19 gene links. And

tually came from Neanderthals, through in an abstract for an online talk later this

interbreeding with our species tens of month at the American Society of Human

thousands of years ago. It is now found Genetics annual meeting, the company

in about 16% of Europeans and 50% of Regeneron reports it has found a genome

South Asians. region that may raise the risk of severe dis-

But the specific chromosome 3 gene or ease mainly in people of African ancestry.

genes at play remain elusive. By analyzing Even as more genetic risk factors are

gene activity data from normal lung tissue identified, their overall effect on infected

of people with and without the variant, the people will be modest compared with other

U.K. team homed in on CCR2, a gene that COVID-19 factors, Duggal says. But stud-

encodes a receptor for cytokine proteins ies like the U.K. team’s could help reveal

that play a role in inflammation. But other the underlying biology of the disease and

data discussed at last week’s meeting point inspire better treatments. “I don’t think

to SLC6Z20, which codes for a protein that genetics will lead us out of this. I think

interacts with the main cell receptor used genetics may give us new opportunities,”

by SARS-CoV-2 to enter cells. “I don’t think Duggal says. j

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ILLUSTRATION: KATTY HUERTAS Even more lives might have been lost if she posed a hypothetical case of a 74-year- came up with the slogan ‘It’s a piece of cloth,
not for Greenhalgh’s tireless promotion of old woman prescribed a high dose of not a land mine,’ which drew attention to
masks, which ultimately helped win over statins to lower her cholesterol, who then the quite absurd framing that some anti-
policymakers, says Chas Bountra, a profes- suffers muscle pains—a common side ef- maskers had cooked up,” Greenhalgh says.
sor of translational medicine and pro vice- fect of statins—that interfere with her hob- After that, the media—and policymakers—
chancellor of innovation at Oxford. She bies and ability to exercise. Greenhalgh’s came calling.
faced powerful opposition, he says. “Not point was that the prescribing physician
every scientist would have had the courage.” had followed protocol but had not ac- In one TV appearance, a politician in-
counted for how the patient lived her life. sisted masks were unnecessary because
Greenhalgh says she was born with Such scenarios, Greenhalgh wrote, offer “a the best barrier to COVID-19 was a front
an insatiable appetite for academic good example of the evidence-based tail door. Greenhalgh agreed that was true, but
challenges—and a distaste for following wagging the clinical dog.”  added that if people don’t want to be on
the rules. “I nearly got kicked out of sec- lockdown forever, “I suggest we take that
ondary school for stealing a dog and bring- “She refutes any mechanical form of rea- front door, turn it on its side, shrink it
ing him to class,” she says. soning, be it an automatic use of guidelines down to the size of your hand, and make it
or a specific research design, as unscholarly,” out of a double layer of cloth.”
Warned by a teacher that the Univer- says philosopher Eivind Engebretsen of
sity of Cambridge did not admit out- the University of Oslo, who has collabo- Greenhalgh, whom one critic dubbed
spoken young women of “her sort,” she “the high priestess” of England’s masking
applied nonetheless and was “As scientists,our goal
granted an interview. “I didn’t must be to cut through the rubbish.” campaign, joined a World Health
have the proper clothes, so I Organization (WHO) committee
made myself a suit,” she recalls. Trisha Greenhalgh, University of Oxford studying the behavioral aspects
Her interlocutor, Tim Hunt, a bio- of mask wearing, such as whether
chemist who would go on to win rated with Greenhalgh for several years. it has an impact on other risky be-
the Nobel Prize in Physiology or “And she categorically opposes what she haviors. “What was apparent was
Medicine (and in 2015 became no- calls the most overused and underanalyzed that the people on the WHO com-
torious for disparaging comments statement in the academic vocabulary: mittee did not appear to under-
he made about women in sci- that ‘more research is needed.’ What we stand the full evidence base,” she
ence), didn’t seem to notice. “He need, she says, is more thinking.” says. But Greenhalgh persisted,
kept his head down and asked me and in early June, WHO, along
seven questions,” she says. When As the mask debate was raging late this with the U.S. Centers for Disease
he told Greenhalgh she’d gotten spring, Greenhalgh joined data scientist Control and Prevention and Pub-
every answer wrong, she asked Jeremy Howard at the University of San lic Health England, shifted from
him to explain, and together they Francisco to launch a website aimed at claiming masks are potentially
reviewed the problems one by turning the tide of public opinion around harmful to endorsing them. “I
one, until she fully understood the world (www.masks4all.co). Their ac- think the lesson here is don’t give
her errors. “I got my place at companying blog got millions of views and up,” she says.
Cambridge because research isn’t was translated into 21 languages. “Jeremy
knowing the right answers before Greenhalgh contends that
you start,” she says. “It’s about COVID-19 has made the collabo-
how you ask the questions and ration of science with the human-
how systematically you go about ities and social sciences all the
finding the answers.” more vital. Take vaccines, for ex-
ample. Greenhalgh has enrolled
After studying social and po- as a test subject for Oxford’s
litical science at Cambridge, promising vaccine candidate and
Greenhalgh qualified in medicine insists that carefully controlled
at Oxford and then embarked on studies are essential before any
a career in primary care, with a vaccine is released to the general
research focus in endocrinology public. Unlike masks, she notes,
and a passion for teaching. In vaccines and treatments can have
1999, noting that disadvantaged dangerous downsides.
students could not afford to attend her
course in international primary health But she’s well aware of the hu-
care, she designed—and, for 10 years, ran— man factor: Even the best vaccine will not
the United Kingdom’s first fully online work if people are too frightened to use
master’s degree program, attended by hun- it, and she is determined to help mitigate
dreds of doctors and nurses from all over that problem through advocacy and pub-
the world. “I was humbled by their passion lic speaking. Technological innovation, she
to improve quality of care in what are of- says, is not enough. Empathy, too, plays a
ten staggeringly difficult circumstances,” vital role. “Science sits awkwardly in a so-
she says. ciety where truth no longer matters,” she
says. “As scientists, our goal must be to cut
Greenhalgh has no fear of challenging through the rubbish.” j
conventional wisdom. For example, in a
2014 paper that became one of the most Ellen Ruppel Shell, professor of science journalism at
read and shared in the history of The BMJ, Boston University, is author most recently of The Job:
Work and Its Future in a Time of Radical Change.

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FEATURES

WEATHERING THE

STORM

As president, Donald Trump has battered science.
But increased spending by Congress and

some supportive agency heads have provided relief

By Jeffrey Mervis; with reporting by Adrian Cho,
Warren Cornwall, Jocelyn Kaiser, Robert F. Service, Erik Stokstad, and Paul Voosen

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NEWS | U.S. ELECTIONS

isastrous. Damaging. Catastrophic. gressive efforts to restrict immigration pose a rate. In a rare embrace of large spending
Those are just some of the more serious threat to the nation’s ability to attract increases, the Trump administration has
polite terms that many U.S. scien- scientific talent from around the world. thrown its weight behind a 2-year doubling
tists use to describe the policies of of those fields, which fuel what it calls “in-
President Donald Trump. His han- In the domestic arena, Trump’s efforts to dustries of the future.” And Congress seems
dling of the COVID-19 pandemic, impose new policies by executive order and amenable to the idea.
his repeated public dismissals of rewrite regulations have also drawn sharp
criticism from scientists. They say the admin- Assessing the president’s appointees is
D scientific expertise, and his disdain istration has routinely ignored or suppressed more complicated. Scientists have con-

for evidence have prompted many evidence that doesn’t support its efforts to demned some of Trump’s choices at agencies

researchers to label him the most antiscience roll back environmental regulations, includ- involved in environmental regulation or cli-

president in living memory. ing those aimed at limiting emissions of mate science, citing their meager scientific

Last month, that sense of betrayal led two greenhouse gases. Trump has also threatened credentials or views that are outside the

of the nation’s preeminent scientific bodies, the reliability of key demographic data by in- mainstream. The appointees are clustered at

the U.S. National Academy of Sciences and terfering with the orderly completion of the the Environmental Protection Agency (EPA),

the National Academy of Medicine, to issue 2020 census, and by telling the Department the National Oceanic and Atmospheric Ad-

an uncharacteristically harsh rebuke. Al- of Commerce to exclude undocumented resi- ministration (NOAA), and the Department of

though the 24 September statement did not dents from the final count. the Interior. The list also includes three re-

name Trump, it was clearly aimed at cently installed senior officials at the

the president. Census Bureau, which is embroiled

“Policymaking must be informed in controversy over its plans for com-

by the best available evidence with- pleting the 2020 census.

out it being distorted, concealed, At the same time, most scientists

or otherwise deliberately mis- give high marks to the officials who

communicated,” the leaders of the two lead agencies that hand out the bulk

academies wrote. “We find reports of federal research dollars (and are

and incidents of the politicization of generally not involved in hot-button

science, particularly the overriding regulatory issues). That list includes

of evidence and advice from public the heads of NIH—Obama-era hold-

health officials and derision of gov- over Francis Collins—and NSF, where

ernment scientists, to be alarming.” Sethuraman Panchanathan succeeded

Although many U.S. scientists Obama appointee France Córdova af-

share those sentiments, other aspects ter her 6-year term ended in March.

of the administration’s overall record Physical scientists also give good re-

elicit a more positive response. Ask views to Paul Dabbar and Chris Fall,

researchers how federal funding for who manage the science portfolio at

their fields has fared since Trump President Donald Trump has often ignored expert advice on COVID-19. the Department of Energy (DOE).

took office in January 2017, and they A third group of Trump science ap-

might acknowledge sustained support and Biomedical researchers, meanwhile, have pointees remains something of an enigma to

PHOTOS: JABIN BOTSFORD/THE WASHINGTON POST VIA GETTY IMAGES; (OPPOSITE PAGE) BILL CLARK/CQ ROLL CALL even mention new opportunities in some been appalled by what they say is a de facto the U.S. research community. They include

areas. Inquire about what they think of the ban on the use of tissue derived from elec- the president’s unofficial science adviser,

appointees leading the federal agencies that tive abortions in research, as well as orders Kelvin Droegemeier; Robert Redfield, head

fund their work, and they will offer some to cancel a grant that Trump disliked. Such of the Centers for Disease Control and Pre-

good—even glowing—reviews. moves, many researchers believe, are de- vention; and Stephen Hahn, head of the Food

Those seemingly contradictory responses signed to advance the president’s political and Drug Administration.

reflect the complexity of an $80-billion-a-year agenda at the expense of national interests. The trio are considered able scientists and

system that remains the envy of the world. Fewer scientists complain about the are generally respected by their peers. But

Any president trying to alter that behemoth Trump administration’s record on spend- Droegemeier, who leads the White House Of-

has three levers to press—policies, budget re- ing. But that’s largely because Congress has fice of Science and Technology Policy (OSTP),

quests, and leadership appointments. ignored the deep cuts the White House has has disappointed many science policy insid-

To analyze Trump’s record in each area, proposed in its annual budget requests to ers by failing to make good on promises to

Science has talked to dozens of researchers, Congress (see graphic, p. 280). better coordinate federal policies that affect

administrators, and lobbyists. Many asked For example, the National Institutes of universities. “I give him an A for effort, and

to remain anonymous because they have on- Health (NIH), the biggest federal supporter an F for performance,” one observer says. And

going interactions with the administration. of academic research, has seen its budget all three leaders have drawn complaints for

Most scientists give Trump exceedingly rise by 39% in the past 5 years despite deep their tepid responses when Trump has dis-

low marks in an arena where he has perhaps cuts proposed by Trump. The budget of the puted settled science or attacked their agen-

the greatest authority: foreign affairs. His National Science Foundation (NSF) has gone cies and the scientists who work for them.

unilateral decisions to pull out of the Paris up by 17% over the past 3 years, reversing But such broad strokes paint only a partial

climate treaty, the Iran nuclear deal, and the the downward direction that Trump has re- picture of how Trump has influenced the U.S.

World Health Organization are widely seen quested and rising more than twice as fast as research enterprise. In the following pages,

as damaging not just to global scientific co- it did under former President Barack Obama. Science looks at how federal science agencies

operation, but also to the continued health, Researchers working on artificial intelli- have fared under a president who has repeat-

safety, and prosperity of the planet. Similarly, gence (AI) and in quantum information sci- edly boasted of “draining the swamp” in the

most scientists think the administration’s ag- ence are enjoying an even more rapid growth nation’s capital.

SCIENCE sciencemag.org 16 OCTOBER 2020 • VOL 370 ISSUE 6514 279

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NEWS | FEATURES | U.S. ELECTIONS DOE stays strong

NIH grantees feel a chill Trump’s first energy secretary, Rick Perry,
had vowed to eliminate DOE when he ran
Trump’s arrival brought fears of upheaval, but NIH watchers say the agency has man- against Trump in 2016. But Perry surprised
aged to stay on course. Collins’s warm relationship with congressional leaders has helped the community by becoming a champion of
win generous budget increases. And Ned Sharpless, Trump’s choice to lead its largest the department’s science mission, and his
institute, the National Cancer Institute, has been “fantastic,” says Jon Retzlaff, chief policy successor, Dan Brouillette, has embraced
officer for the American Association for Cancer Research. that role since taking over in December 2019.
Observers also credit undersecretary Dabbar
In contrast, researchers say White House pressure caused NIH to launch a damaging for sustaining the political momentum behind
crackdown on scientists with foreign ties (p. 282). They also accuse Trump of political several big projects at DOE’s 17 national
meddling in two important issues—fetal tissue research and pandemic research. In June laboratories, including a new atom smasher to
2019, the White House ended funding for NIH’s in-house research using tissue from elective study nuclear physics at Brookhaven National
abortions and announced a new ethics review for extramural grants. This year, a 15-member Laboratory and a fast-neutron test reactor at
ethics panel dominated by abortion opponents recommended approval of only one of Idaho National Laboratory.
14 proposals that had passed review. And in April, NIH pulled a grant to the EcoHealth Al-
liance, a nonprofit organization working on bat viruses with the Chinese group that Trump Despite the Trump administration’s
accused—without evidence—of releasing the SARS-CoV-2 virus driving the pandemic. distaste for clean energy research and its
conviction that private industry is the real
Those actions “have sent a chilling message to scientists,” says molecular biologist engine of innovation, DOE’s $7 billion Office
Keith Yamamoto of the University of California, San Francisco. “If problems that you have of Science has fared well. It benefited hand-
a real passion to dig into are deemed politically unsound, you could be out of luck. So somely from the administration’s embrace of
watch out.” AI and quantum information science, where
physicists and engineers try to leverage
Smaller role for White House science office subtle quantum effects to develop more
powerful supercomputers and secure com-
Arriving 2 years into Trump’s 4-year term to head OSTP, Droegemeier promised to munication systems. In July, for example,
streamline and improve how the federal government manages academic research. But an DOE announced it would build a prototype
interagency panel he created to take on the task—the Joint Committee on the Research quantum network to connect Argonne Na-
Environment (JCORE)—has yet to reach consensus on any of the four areas Droegemeier tional Laboratory, Fermi National Accelerator
has targeted. Laboratory, and the University of Chicago.

“He came in all fired up, promising to make things happen,” one lobbyist says. “But so Fall, who was already working for the
far nothing has come out of JCORE, and the research community is very disappointed.” government when he became head of DOE’s
basic science shop in May 2019, thinks his of-
Research advocates do praise OSTP for helping focus more attention on AI and quan- fice has thrived by avoiding ideological battles
tum information science. But science lobbyists say the real driver of that initiative has over the proper role of government in creating
been Michael Kratsios, a scientific neophyte who was nominally in charge of OSTP before new technologies. “What we don’t do is policy,”
Droegemeier joined the administration. he says. “I’m doing my level best to keep the
Office of Science out of politics.”
Kratsios “came into the job knowing less about science than any previous OSTP head,”
one university lobbyist says. “But he was eager to learn, and he listens. He’s also figured
out how to use his connections to advance the administration’s agenda.”

Trump’s budget cuts dead on arrival CREDITS: (GRAPHIC) N. DESAI/SCIENCE; (DATA) AAAS/R&D BUDGET AND POLICY PROGRAM

President Donald Trump has repeatedly asked Congress to approve deep spending cuts at most federal research agencies. But lawmakers have generally
ignored his requests and have typically boosted science budgets—with some agencies getting hefty increases.

Trump request Final appropriation

2018 2019 2020

NIH –21.5% 8.7% –6.8% 5.4% –12.6% 6.5%

NSF –11% 3.9% –3.8% 4% –12.5% 2.5%

DOE Science –17.1% 16.1% –13.9% 5.2% –15.8% 6.3%

NASA Science –0.9% 7.9% –5.2% 11% –7.4% 3.4%

NOAA Science –31.9% 6.7% –41.4% 3.2% –40.8% 4.3%

USGS* –15% 5.8% –25.1% 1.1% –15.3% 9.5%
DARPA* 12%
EPA S&T* –44% 9.7% 0.9% 3.8%
6.3% 0% 11.7%
0% –40% –34% 1%

NIST Labs* –13% 5% –21% 0% –16% 4%

*U.S. Geological Survey (USGS), Defense Advanced Research Projects Agency (DARPA), Environmental Protection Agency Science & Technology (EPA S&T), National Institute of Standards and Technology (NIST Labs)

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Expert advice Hurricane forecast batters NOAA
under siege at EPA
Home to some of the country’s premier climate scientists, NOAA managed to operate mostly
Given candidate Trump’s rhetoric under the radar until August 2019, when Trump announced erroneously that Hurricane Dorian
opposing government regulation, his posed a threat to the state of Alabama and apparently used a marker to alter a National
affection for fossil fuels, and his denial Weather Service forecast showing its path. The White House and Commerce Department
of climate change, it’s no surprise that pushed NOAA’s acting administrator, Neil Jacobs, to reprimand weather forecasters for their
EPA has often disregarded science correction of the president’s map and tweets. That political flap, dubbed Sharpiegate, ulti-
in devising environmental policy. Its mately led to the arrival last month of two new senior political appointees, David Legates and
approach to regulating particulate air Ryan Maue, who have been dismissive of climate science.
pollution—often called PM2.5 (particu-
late matter smaller than 2.5 microns in “I have grave concerns around these appointments,” says Jonathan White, a retired Navy ad-
diameter)—contains all the hallmarks miral and CEO of the Consortium for Ocean Leadership. “NOAA has the best [climate] scientists
of that approach, including appointing in the government, and I’m very concerned these voices will be muzzled.”
people tied to polluting industries to key
posts, excluding experts from advisory A hurricane forecast map altered with a marker touched off controversy in September 2019.
roles, and using questionable methods
to tip the scales when balancing benefits Interior questions climate impacts
against costs.
PHOTO: TOM BRENNER/BLOOMBERG VIA GETTY IMAGES As custodian for more than 1.8 million square kilometers of federal land, the Department of
Soon after his appointment in 2017, the Interior has been a central player in the Trump administration’s push for more oil and gas
then–EPA Administrator Scott Pruitt drilling. But critics say department officials have often overlooked, disregarded, or altered the
launched several major changes that relevant science, enabling them to dismiss the climate impacts of that drilling and discount
would likely help ease regulations of potential harm to endangered species.
PM2.5, which is linked to increased
heart and lung diseases and premature One early target was calculations of the economic toll from greenhouse gas emissions. Shortly
deaths. He banned any EPA-funded after Trump took office, the department drastically reduced estimates by the Obama administra-
scientist from serving on advisory tion of such costs. It did so by considering only direct impacts in the United States and by reducing
boards that vet proposed regulations, the dollar value of impacts on future generations.
but kept the door open to people associ-
ated with polluting industries. (A federal The Trump administration has used the lower price tags to justify rolling back Obama-era limits
court overturned the ban earlier this on methane emissions from oil and gas wells, as well as carbon dioxide from cars and power
year.) Pruitt also installed an industry plants, which fall under the authority of the Department of Transportation and EPA, respectively.
consultant, Tony Cox, as chairman of But this year, a federal judge ruled the lower estimates were not defensible and that the Interior
the air pollution science committee Department had tried “to erase the scientific and economic facts” used in the previous estimates.
and abolished an expert panel, led by
Christopher Frey of North Carolina State The plight of endangered species has received little attention during the Trump administration,
University, that advised the committee with the number of new species being listed for federal protection at an all-time low. The Fish and
on the science of particulate matter. Wildlife Service, the branch of the Interior Department that decides whether a species is endan-
gered, “just doesn’t have the institutional support to really push back when politics gets in the way
Although Pruitt was forced out of the of science,” says Brett Hartl of the Center for Biological Diversity, which frequently sues federal
agency in mid-2018, his replacement, agencies over endangered species. “They’re kind of a forgotten agency.”
Andrew Wheeler, has followed a similar
path. He declined a recommendation 16 OCTOBER 2020 • VOL 370 ISSUE 6514 281
from agency scientists to tighten PM2.5
limits, citing a study by the reconsti-
tuted committee that found the science
behind such a reduction was uncertain.
The agency’s recent actions “just made
the whole thing a charade,” Frey says.

EPA officials have also proposed bar-
ring the agency from considering certain
scientific studies as it develops regula-
tions if the underlying data cannot be
made public because of concerns about
patient privacy or trade secrets. That’s
the case for some large studies on how
air pollution affects public health, and
for many industry-funded reviews of
toxic chemicals. Researchers say the
rule fails to recognize the legitimate
need to protect the confidentiality of
some data and will undermine the qual-
ity of EPA’s rulemaking.

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Relocation rattles USDA scientists

Agriculture Secretary Sonny Perdue upset scientists with his deci- they worried the departures of so many veteran staff would deprive
sion to move two of the agency’s research centers—the National USDA of institutional knowledge and expertise that would take years
Institute of Food and Agriculture (NIFA) and the Economic Research to replace.
Service (ERS)—from Washington, D.C., to Kansas City, Missouri. Ac-
cording to the Congressional Research Service, roughly 75% of the On the plus side, USDA’s decision this year to exempt certain
employees left the Department of Agriculture (USDA) rather than gene-edited crops from its biotechnology regulations, potentially
move, and many grants were delayed by several months. easing research, has been well received, says Karl Anderson, director
of government relations for the American Society of Agronomy, the
Perdue said the new location would bring NIFA and ERS closer Crop Science Society of America, and the Soil Science Society of
to their constituencies and save on rent. But many observers— America. Anderson also applauds the agency’s first ever set of long-
including congressional Democrats—saw the move as an excuse range goals, which aim to increase agricultural production by 40%
to shrink ERS and diminish its ability to provide objective monitoring by 2050 while cutting the industry’s environmental footprint in half.
of myriad agricultural trends through its surveys and reports. And “I think it’s a terrific effort,” he says.

Scrutiny of foreign ties intensifies

The Trump administration’s efforts to limit or been indicted and some have pleaded guilty, security. But NIH’s actions are widely re- PHOTO: BANDAR ALGALOUD/SAUDI ROYAL COUNCIL/HANDOUT/ANADOLU AGENCY/GETTY IMAGES
prohibit scientific collaborations with China although the charges typically involve making garded as the most aggressive and, thus, po-
and other countries deemed to pose national false statements to federal officials or cover- tentially the most harmful. NSF, for example,
security risks have set off alarms throughout ing up their foreign ties rather than passing insists on full disclosure but only occasionally
the academic community. Although separate along sensitive technologies. initiates an investigation, and DOE has told
from the president’s attempts to restrict its own scientists they cannot participate in
immigration, both efforts run counter to Several agencies have taken steps aimed foreign talent recruitment programs but has
the traditionally open environment that has at learning who else is funding research by not altered its rules for grantees.
propelled U.S. science since the end of World their grantees and then deciding whether
War II. Many researchers also regard them as those other sources pose a threat to national “Agencies are under tremendous pressure
exercises in racial and ethnic stereotyping. from the White House to find guilty people,”
Trump joined Middle Eastern leaders in 2017 at a new says Stanford University physicist Steven
The Obama administration pursued institute in Saudi Arabia studying terrorist threats. Chu, a Nobel Prize winner and former energy
a handful of investigations, some later secretary under Obama (and a past presi-
dropped, involving scientists with ties to dent of AAAS, Science’s publisher). “NSF
China. But in the summer of 2018, NIH has tried to push back, but NIH has almost
began to send letters to dozens of universi- completely folded.”
ties flagging nearly 200 faculty members
believed to have hidden research support The country needs to defend itself against
from Chinese entities. At the same time, military and economic espionage, scientists
university leaders heard themselves being say, but some worry the administration’s
accused of unwittingly handing over the actions to date have already damaged the
fruits of federally funded research to China, U.S. research enterprise and that additional
the United States’s chief rival as a scientific restrictions could be fatal.
and economic superpower.
“The potential loss is hard to estimate,”
In November 2018, the Department of Chu says. Noting the outsize contribution
Justice announced its China Initiative, making of foreign-born scientists to U.S. technical
it clear that NIH’s investigations were part of innovation in the past 30 years, he adds, “It’s
a broader campaign. Several scientists have scary to think [what would happen] if you
shut that off.”

A desire for new leadership

Looking ahead to such research-based challenges as the COVID-19 “At no time in our nation’s history has there been a greater need
pandemic and climate change, many scientists crave leadership that for our leaders to appreciate the value of science in formulating
respects science. On 2 September, for example, 81 Nobel laureates public policy,” they write in a public letter. “Joe Biden has consis-
announced their support for Trump’s opponent, Democrat Joe Biden. tently demonstrated his willingness to listen to experts, his under-
(So far, Trump has not received such an endorsement, although there standing of the value of international collaborations in research,
was a “Scientists for Trump” group during the 2016 contest.) and his respect for the contribution that immigrants make to the
intellectual life of our country.”
In their letter, the laureates don’t mention any specific policies
that Biden has championed over nearly a half-century in public More than a political endorsement, the letter reflects a sense that
office, including his 8 years as vice president under Obama. But the the federal government has turned its back on science in the past
statement makes clear that they think a Biden administration will 4 years and their hope that the next president will, in Obama’s
do a better job of interacting with the scientific community. memorable phrase, “restore science to its rightful place.” j

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Scientists and
science are
on the ballot

N ancy Goroff says she doesn’t mind Voters lined up last month in Fairfax, Virginia, to cast their ballots in this year’s elections.
that her opponent calls her a “radical
PHOTO: SARAH SILBIGER/BLOOMBERG VIA GETTY IMAGES professor.” In fact, Goroff, a New York Angeles, and came to Stony Brook in 1997. Unlike Goroff, Williams is playing down
Democrat running for a seat in the She studies the structure of semiconduct- any ties to the Democratic establishment.
U.S. House of Representatives, says ing polymers with the goal of improving Instead, she vows to break with her party
her scientific expertise is exactly what solar cells and other devices. when necessary to broker a deal with
Congress needs to deal effectively with Republicans. “Congress is broken” because
climate change, the COVID-19 pandemic, “Nancy isn’t someone who publishes of “hyperpartisanship,” she asserted dur-
and a host of other issues. a lot of papers. But her work is always ing the debate. Williams, a former state
very solid,” says Luis Echegoyen, a chem- legislator, lost her 2018 bid to win the seat,
A physical organic chemist and longtime ist at the University of Texas, El Paso, but prodigious fundraising has put her in a
faculty member at Stony Brook University, and current president of the American stronger position this year.
Goroff is one of several congressional Chemical Society.
candidates with scientific backgrounds on In Wyoming, wildlife ecologist Merav
the ballot next month. (Voters in four states Goroff, who stepped down as depart- Ben-David of the University of Wyoming is
will also weigh in on science-related ballot ment chair and went on leave when she the Democratic candidate for a seat in the
items.) Nonpartisan polls give her a chance launched her campaign in the spring of U.S. Senate. But she’s a decided underdog
of defeating the Republican incumbent, 2019, declines to place herself on the po- against Republican Cynthia Lummis, a
lawyer Lee Zeldin, and becoming the first litical spectrum. But her positions on most lawyer who has previously served four
female Ph.D. scientist to serve in Congress. issues align with those of the Democratic terms in the House.
presidential nominee, former Vice Presi-
Scientists running for Congress are no dent Joe Biden. “She’s no Bernie Sanders,” In four states, residents will be voting on
longer a novelty. But winning still is. A small says one longtime Stony Brook colleague, ballot initiatives with implications for U.S.
army of people with scientific training— Stephen Koch, referring to the Vermont researchers. California voters are being
almost all Democrats—ran in 2018, vowing senator and democratic socialist who lost asked to approve an additional $5.5 billion
to counter what they viewed as the anti- to Biden in the primaries. in bonds to fund the California Institute for
science message coming from President Regenerative Medicine, the state’s stem
Donald Trump and his administration. But That’s true even on climate change, cell research programs, which voters cre-
only a handful were successful. which Goroff has made a pillar of her cam- ated in 2004. Nevada could soon require
paign. Global warming is “the biggest threat the state’s electric utility companies to
This year, all those rookie legislators are to our way of life,” she says. But she has not double their use of renewable energy, to
running for reelection to the House, and endorsed the Green New Deal, an ambitious 50%. Voters approved the mandate in
most are favored to win. The list includes plan to cut greenhouse gas emissions and 2018, but the state constitution requires a
two Illinois Democrats, Sean Casten and create jobs being advocated by the party’s second affirmative vote.
Lauren Underwood. Casten, an engineer, progressive wing. “I have strong objections
has been a vocal advocate for clean en- to some provisions, while others are appro- Colorado voters are being asked to
ergy, while Underwood, a nurse and public priate,” she explains. support the reintroduction of gray wolves
health analyst, has been sharply critical of in portions of the state. The restoration
the administration’s response to the pan- In Montana, Democrat Kathleen Wil- effort would begin by the end of 2023. And
demic. The cohort also features Represen- liams, a water resources scientist running Oregon could become the first state to al-
tative Jim Baird (R–IN), who holds a Ph.D. for the state’s only House seat, is also low the use of so-called magic mushrooms
in animal nutrition. using climate change to differentiate in clinical research settings. The active
herself from her opponent, Republican ingredient, psilocybin, has been shown to
Goroff hopes her centrist positions will Matt Rosendale. Climate change “is real,” help those with depression, anxiety, and
appeal to voters in a Long Island district that she said in a recent debate in which she post-traumatic stress disorder. —J.M.
Trump carried easily in 2016. In contrast, accused Rosendale of “hiding his head
Zeldin, who is one of Trump’s most loyal in the sand” after he ducked a question With reporting by Rasha Aridi, Eli Cahan,
supporters, is following the president’s play- on the impact of human activity on the and Rebekah Tuchscherer.
book of painting Democrats as “radicals” planet’s climate.
whose policies pose a threat to the country.

Goroff waves off the criticism. “They say
that any Democrat is a communist or a
socialist,” she says. “And if they think that
using facts and scientific evidence as the
basis for making policy is radical, then that
says more about them than about us.”

Goroff earned her Ph.D. in organic chem-
istry from the University of California, Los

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NEWS | FEATURES | U.S. ELECTIONS

WHAT IF
BIDEN WINS?

A new president will have
vast authority to rapidly shift
science policy, but will confront
obstacles beyond his control

By David Malakoff

I f former Vice President Joe Biden wins promised to “stop the political theater and a vaccine or effective new treatments arrive PHOTO: CHIP SOMODEVILLA/GETTY IMAGES
the presidential election, he will face willful misinformation that has heightened is largely out of a president’s control. But a
high expectations from the U.S. scientific confusion and discrimination,” hold daily Biden administration could make headway
community. Its members will be count- briefings that “put scientists and public against the pandemic by encouraging and co-
ing on him to bring science and leader- health leaders front and center,” and ensure ordinating a wide range of tactics including
ship to the fight against COVID-19 while that government scientists “do not fear retri- mask wearing, physical distancing, testing,
reversing a host of moves by President bution or public disparagement for perform- contact tracing, and the development and
Donald Trump that many researchers ing their jobs.” He’s also pledged to rejoin the distribution of treatments and vaccines.
regard as disastrous (see story, p. 278). World Health Organization and boost fund-
A President Biden will have vast authority to ing for its pandemic efforts. Confront climate change.
move quickly to undo many Trump policies.
But he could be hampered by forces beyond At home, Biden says he’ll work with Biden advisers say climate change is one of
his control, including which party controls governors and local officials to encour- “the four crises” he will put a priority on ad-
the Senate, the ideological complexion of age greater use of physical distancing and dressing. (The others are the pandemic, the
the courts, and—when it comes to fighting masks—possibly even mandating their use economy, and racial injustice.) Biden says the
COVID-19—the progress of science itself. at federal facilities and on federal lands. And United States will rejoin the Paris climate ac-
he’s vowed to reverse the erosion of public cord on his first day in office—which he can
Here’s a look at some science-related ac- trust in two key health agencies, the Centers do with the stroke of a pen—and he will issue
tions Biden will likely pursue, and how for Disease Control and Prevention (CDC) executive orders to strengthen climate protec-
quickly he might be able to accomplish them. and the Food and Drug Administration tions. Advocates want him to roll back Trump
(FDA), by appointing new leadership and im- rules that weakened limits on power plant
Tackle the COVID-19 pandemic. proving the transparency of decision-making. emissions set by former President Barack
Obama, and to set even stiffer limits for cars
Biden has made confronting the pandemic Yet getting new agency leaders confirmed than Obama did. Overall, Biden wants the
the centerpiece of his presidential campaign. by the Senate could take months, observers United States to cease to be a net emitter of
The most dramatic immediate shift is likely say, and repairing the damage done to the greenhouse gases by 2050, and the federal
to be in the tone and consistency of messag- credibility of those agencies could be slow. Ef- government to invest at least $1.7 trillion over
ing coming from the Oval Office and federal forts to mandate mask wearing or limit gath- 10 years in clean energy technologies.
health agencies. On his first day, Biden has erings could face opposition, and how soon

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Achieving that ambitious agenda will be made public because of concerns about predicts Elgie Holstein, senior director for
likely require that Democrats control the U.S. patient privacy or trade secrets. strategic planning at the Environmental De-
Senate. Even with a Democrat-led Congress, fense Fund and a former DOE chief of staff.
however, Biden might only have a 2-year win- Conservation scientists, meanwhile, hope
dow, as the party in power often loses control he will block federal permits for several high- To pay for new spending, Biden is likely to
of one chamber of Congress in midterm elec- profile energy and mining projects, includ- propose restoring higher taxes on the wealthy
tions. Biden could also face pushback from ing proposed pits in Alaska and Minnesota and killing programs he sees as wasteful. One
conservative judges, especially on the Su- that threaten aquatic habitats. Paleonto- potential target is the Space Launch System
preme Court, if he relies heavily on executive logists are looking to Biden to restore fossil- (SLS), NASA’s troubled heavy-lift rocket for
authority to push his agenda. rich lands that Trump removed from several the human space program. The SLS has cost
national monuments in western states, while $20 billion so far and, after years of delays,
Change course on foreign policy. ocean scientists want him to reimpose fish- isn’t scheduled to launch until late 2021.
ing limits that Trump lifted at a marine mon- Many NASA observers argue that commer-
A president has great leeway in deciding how ument off the coast of New England. cial space firms, such as SpaceX, can do the
the United States interacts with other na- job for less.
tions, and research groups hope Biden will But many of Trump’s environmental poli-
move aggressively on several fronts. Many cies could take years to unwind because of Still, with budget experts warning that
want the country to re-engage with Iran to lawsuits and federal rules that require exten- the federal government’s debt is soaring to
revive the nuclear deal—from which Trump sive comment periods. Democratic control of record levels—it will soon exceed the size of
withdrew in 2018—that limited its ability to the Senate, however, could speed the process: the entire U.S. gross domestic product—the
produce nuclear weapons. Biden says he will Under a rarely used law, just a simple major- pressure to contain spending will grow. And
“offer Tehran a credible path back to diplo- ity of both houses is needed to cancel rules tax revenues may fall if the economy contin-
macy” if Iran “returns to strict compliance finalized near the end of the Trump adminis- ues to struggle, crippling Biden’s ability to
with the nuclear deal.” tration. (Republican lawmakers used the law advance his agenda.
to void many Obama-era rules at the start
Another tough challenge will be establish- of Trump’s term, when they controlled both Reinvigorate the scientific workforce.
ing the rules for U.S. research collaborations chambers of Congress.)
with China. Under Trump, law enforcement Under Trump, many researchers who work
agencies, the National Institutes of Health Insulate health agencies from politics. for the federal government have said they
(NIH), and other agencies have stepped up don’t feel valued or respected. Employee
investigations of scientists who failed to Biomedical researchers have been appalled surveys show job satisfaction at several sci-
disclose funding ties to foreign institutions, by the Trump administration’s baldly politi- ence agencies has taken a nosedive, and
leading to criminal, civil, and administrative cal moves to influence the work of NIH, CDC, there have been many anecdotal reports of
punishments. Many of the known cases in- and FDA. Those moves have included order- researchers leaving their jobs. Biden says
volve researchers who were born in China or ing NIH to cancel a grant that supported he wants to reverse that trend, starting by
had links to Chinese institutions. Critics say research into bat viruses in China, because replacing Trump appointees who have sus-
the effort has been racially tinged and has Trump alleged—without evidence—that the pect scientific credentials or hold views far
also hindered efforts to recruit foreign-born pandemic virus escaped from a laboratory in out of the mainstream. “The house cleaning
talent. They hope Biden will ease the scru- Wuhan involved in the project. Trump also could be remarkable; in some cases you are
tiny. But  Biden  has traditionally been a de- blocked or rewrote CDC and FDA policies going to see hacks who are flat-out science
fense hawk, and China’s harsh treatment of and guidance that contradicted his views on deniers replaced by appointees who not only
Uighurs and other religious minorities may the pandemic. And he instituted a de facto understand the science, but have done it
limit moves to ease tensions. ban on using fetal tissue from elective abor- themselves,” says one lobbyist who requested
tions in research. anonymity because he still interacts with the
On immigration, industry groups and Trump administration. Others speculate that
universities hope Biden follows through on Biden promises to “let science lead,” rais- Biden might raise the profile of science—and
promises to ease restrictions on visas for ing hopes that he will reverse these moves improve morale—by quickly filling the White
students and high-skill workers. And some and end political interference in the health House science adviser position. (Obama
have applauded Biden’s vow to protect the agencies. Researchers are also optimistic that named John Holdren to do the job the month
so-called Dreamers, undocumented im- Biden will select a stellar replacement for before he was sworn in.)
migrants who were brought to the United NIH Director Francis Collins, whom many
States as children, and end Trump’s de facto expect to depart after 11 years in the job. But it could take years to rebuild the ex-
ban on immigrants from many majority- pertise that some agencies have lost, a union
Muslim nations. Go big on spending. that represents public employees warned
earlier this year. And former government of-
Reverse Trump environmental policies. Keeping the economy afloat through the ficials say a Biden administration will also
pandemic will require massive federal need to strengthen current policies to protect
Environmental scientists have a long wish spending, Biden says, and he will likely ask researchers from political interference. Rick
list. They want Biden to undo changes in lawmakers to approve a host of spending Spinrad of Oregon State University, Corvallis,
how agencies review the environmental initiatives early in his term. Universities and a former chief scientist at the National Oce-
impacts of major projects and evaluate the research groups want some of the money, anic and Atmospheric Administration, says,
risks posed by toxic chemicals, which critics saying federal science agencies need tens of “What we have seen [under Trump] is abuse
say downplay the risks and inflate economic billions of dollars to help them recover from and violation of scientific integrity policies—
benefits. The Environmental Protection Net- the pandemic. And clean energy advocates with no consequences.” j
work, made up of former Environmental are hoping the stimulus package would make
Protection Agency officials, wants Biden to combating climate change a clear priority at With reporting from Adrian Cho, Jon Cohen,
kill a proposed rule that could bar the agency the Department of Energy (DOE). “We’ll see Warren Cornwall, Jocelyn Kaiser, Jefrey Mervis,
from using health and other data that can’t much more pressure on [DOE to do work] Erik Stokstad, Paul Voosen, and Meredith Wadman.
that might lead to reductions in emissions,”

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INSIGHTS

PERSPECTIVES

VIEWPOINT: COVID-19

COVID-19 in children and young people

Children have a low risk of COVID-19 and are disproportionately harmed by precautions

By Matthew D. Snape1,2 and Russell M. Viner3 to the pandemic reflected the reasonable by lockdown measures, and advocates of PHOTO:CHRIS MCGRATH/GETTY IMAGES
expectation from previous respiratory vi- child health need to ensure that children’s
T he severe acute respiratory syn- rus outbreaks that children would be a rights to health and social care, mental
drome coronavirus 2 (SARS-CoV-2) key component of the transmission chain. health support, and education are protected
pandemic has brought distinct chal- However, emerging evidence suggests that throughout subsequent pandemic waves.
lenges to the care of children and this is most likely not the case. A minority
adolescents globally. Unusually for a of children experience a postinfectious in- Evidence from contact-tracing studies
respiratory viral infection, children flammatory syndrome, the pathology and suggest that children and teenagers are
and adolescents are at much lower risk long-term outcomes of which are poorly less susceptible to SARS-CoV-2 infection
from symptomatic coronavirus disease 2019 understood. However, relative to their risk than adults; however, community swab-
(COVID-19) than any other age group. The of contracting disease, children and adoles- bing and seroprevalence studies conducted
near-global closure of schools in response cents have been disproportionately affected outside of outbreak settings suggest that
infection rates are similar to those in older

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Maintaining young people’s education and (in which an unknown trigger leads to an profile in adults is more complete. Given
wellbeing must remain an important priority inflammatory disease, resulting in coronary the low rates of disease in children, they
for society in the COVID-19 era. artery inflammation). However, a com- are likely to be a low priority to receive a
prehensive case series clearly delineated vaccine unless it is definitively shown that
age groups (1–3). Only half of children and PIMS-TS from Kawasaki disease, with chil- (i) children have an important role in the
teenagers with antibodies against SARS- dren who experience PIMS-TS being sub- transmission of the virus and (ii) the vac-
CoV-2 have experienced symptoms, and stantially older and with increased circulat- cine reduces viral shedding (and hence re-
there is growing evidence that there is a ing concentrations of ferritin (a marker of duces transmission).
broad range of presentations, emphasizing inflammation) and D-dimer and troponin
the limitations of community-based preva- (markers of cardiovascular damage), which To what extent do children transmit SARS-
lence studies based on testing only children are rarely seen in Kawasaki disease (8). A CoV-2? Recent reports that young children
with respiratory symptoms. Hospitalization dominant feature of PIMS-TS is myocardi- acutely unwell with COVID-19 have concen-
for severe acute COVID-19 in children is tis, transient myocardial dysfunction, and trations of viral RNA in nasal aspirates that
rare, but among these pediatric inpatients, shock, which are present in approximately are similar to, or higher, than adults (5) raised
respiratory symptoms are more apparent half of UK and U.S. case series (8, 9). concerns that their role in transmission may
than in infected children in the community have been underestimated. However, one of
(4). Case fatality in hospitalized children is, “...school closures should these studies compared children within the
fortunately, relatively low at 1% (compared be undertaken with first week of illness with adults with more
with 27% across all ages) (4). than 7 days of symptoms, when viral load
trepidation given the indirect is expected to be reduced (5). Such studies
The reason for the lower burden of harms that they incur.” need to be interpreted with consideration of
symptomatic disease in children is not yet the very low numbers of children with symp-
clear. Upper airway expression of angioten- In the UK, a Delphi national consensus tomatic COVID-19.
sin-converting enzyme 2 (ACE2), a receptor statement has recently been proposed (10)
for the SARS-CoV-2 spike protein, increases to guide investigation and management of Of greater concern is the possibility that
with age, and higher ACE2 expression cor- this condition, which focuses on supportive viral shedding could be occurring from
relates with being positive for SARS-CoV-2 care and enrolling patients into a specific asymptomatic children and that, given
genomic RNA in swabs of upper respiratory arm of the RECOVERY randomized con- schools “bridge” households, this could
tracts from symptomatic children, but not trolled trial to evaluate the use of corticos- create a pool of ongoing viral circulation
with viral load (5). An alternative proposal teroids and intravenous immunoglobulin in responsible for introductions of virus to the
is the absence in children of maladaptive patients with acute PIMS-TS. Fortunately, pupils’ homes and beyond. Understanding
immune responses that lead to acute res- fatalities are rare [occurring in 10 of the this issue is fundamental to resolving what
piratory distress syndrome (ARDS) in older 570 cases reported to the U.S. Centers for has been an unprecedented global disrup-
age groups (6), but there are likely other un- Disease Control and Prevention between tion to primary (children of ~5 to 11 years)
identified mechanisms. March and July 2020, and none of 52 cases and secondary (children aged 11 to 18 years)
in a UK series (4, 9)]. However, the long- education. Given the near universal closing
Understanding the nature of immune term consequences are unknown, and all of schools in conjunction with other lock-
responses in children is important given children and teenagers who experience down measures, it has been difficult to de-
the rare, but potentially severe, multisys- PIMS-TS require ongoing cardiac review. termine what benefit, if any, closing schools
tem inflammatory syndrome observed in Proposed mechanisms for this illness have has over other interventions. However,
more than 1000 children and adolescents focused on a maladaptive acquired immune there is some reassurance: Multiple studies
in multiple countries during the first wave response to SARS-CoV-2 infection, and a of contacts of primary and secondary school
of COVID-19 (7). Known variously as pedi- dysregulated humoral immune response is children with known SARS-CoV-2 infection
atric inflammatory multisystem syndrome suggested by increased antibodies against showed minimal onward transmission in
temporally associated with SARS-CoV-2 multiple, non–SARS-CoV-2, respiratory vi- schools (3). Furthermore, after the reopen-
(PIMS-TS), multisystem inflammatory syn- ruses in severe MIS-C but not mild MIS-C ing of primary schools in the UK, only 1
drome in children (MIS-C), or Kawasaki- or acute COVID-19 (5). of 23,358 nasal swabs taken from children
like disease, the illness presents with per- in June 2020 had detectable SARS-CoV-2,
sistent fever accompanied, to a variable Understanding this response is crucial giving an estimate of 3.9 cases per 100,000
extent, by gastrointestinal symptoms, rash, when considering the risks and benefits students (2). Looked at from another per-
and conjunctival inflammation. Laboratory of immunizing children against COVID-19, spective, when household outbreaks of
markers of inflammation are very high, and should a vaccine become available. Of the infection have occurred, it appears that
myocarditis is a distinct, and potentially fa- vaccines being tested in clinical trials, none children were responsible for only a small
tal, feature. Children and young people with have yet been administered to children, minority of household introductions of the
PIMS-TS are more likely to have antibodies with priority instead being given, appro- virus. Also, recent surveys found that reo-
to SARS-CoV-2 than evidence of virus from priately, to older age groups. The most pening of schools in a number of European
nasal swabs, with presentations usually 4 to advanced candidate, ChAdOX1-nCOV-19, countries in April and May had no clear
6 weeks after infection. The cardiac involve- is currently in phase 2 and 3 studies that impact on community transmission, with
ment initially led to this condition being include a pediatric arm for 5 to 12 year cases continuing to fall in most countries
described as a variant of Kawasaki disease olds (NCT04400838), receiving half the after reopening (11).
full adult dose in this study. However, this
1Oxford Vaccine Group, Department of Paediatrics, study arm is not currently active and will Nevertheless, recent experiences of sub-
University of Oxford, Oxford, UK. 2National Institute for commence enrolment only once the safety stantial outbreaks of COVID-19 related to
Health Research (NIHR), Oxford Biomedical Research children and teenagers show that there is
Centre, Oxford, UK. 3Great Ormond Street Institute for no room for complacency. In May, an Israeli
Child Health, University College London, London, UK. secondary school was shut shortly after a
Email: [email protected]; [email protected] postlockdown reopening after the identi-

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INSIGHTS | PERSPECTIVES

fication of two symptomatic students in- accidents at home increased markedly dur- HYDROGELS
dependently infected with SARS-CoV-2. A
subsequent schoolwide testing campaign ing the COVID-19 lockdown and potentially Lubricating
revealed that 153 (13.2%) students and 25 lipids in
(16.6%) staff had detectable SARS-CoV-2 posed a higher threat to children’s health hydrogels
infection, and contact tracing revealed a
further 87 cases in non–school attendees than COVID-19 (13). UK pediatricians report A self-renewing lipid
(12). Although formal studies were not con- layer substantially
ducted to definitively show school-based that delay in presentations to hospital or reduces friction and wear
transmission, potential contributory factors of a hydrogel surface
included a heat wave that led to extensive disrupted services contributed to the deaths
use of air-conditioning and exemptions By Tannin A. Schmidt
from face mask wearing, relatively crowded of equal numbers of children that were re-
classrooms (with 35 to 38 per class with 1.1 H ydrogels are hydrophilic polymer
to 1.3 m2 between students), and shared ported to have died with SARS-CoV-2 infec- chain networks that can absorb large
schoolyard and outdoor spaces. quantities of water or biological flu-
tion (14). Many countries are seeing evidence ids. In many of their biomedical and
As schools in the Northern Hemisphere other applications (1), hydrogels
reopen after summer holidays, risk mitiga- that mental health in young people has slide against another surface and
tion strategies adopted to variable degrees must be well lubricated. Hydrogel lubrica-
include creating separate cohorts (or “bub- been adversely affected by school closures tion is normally provided by fluid interfa-
bles”) within schools that interact mini- cial layers (2), but the long-lasting lubrica-
mally with each other, use of face masks in and lockdowns. For example, preliminary tion of articular cartilage in our joints (3–5)
crowded areas (if not the classroom itself), is partially the result of nonfluid, highly
and regular screening of students and staff. evidence suggests that deaths by suicide of hydrated head groups of exposed phospha-
The coming months will provide an invalu- tidylcholine lipids (6). On page 335 of this
able opportunity to identify which of these young people under 18 years old increased issue, Lin et al. (7) mimic and modify this
measures are most effective at minimizing mechanism in various synthetic hydrogels
transmission, to generate a standard “best during lockdown in England (15). by incorporating small concentrations of
practice” that balances young peoples’ rights lipids to create a self-renewing, molecularly
to an education with the need to protect the The role of children in transmission of thin lipid-based boundary layer. The results
broader community from further transmis- are striking, with substantial reduction of
sion. However, it is inevitable that there will SARS-CoV-2 remains unclear; however, ex- friction (and wear) observed by as much as
be students attending school while infected a factor of 100 relative to lipid-free hydro-
with SARS-CoV-2, and likely there will be isting evidence points to educational set- gels. Moreover, the effect remained even
some school outbreaks, with the frequency when gels were dried and rehydrated.
of these events reflecting levels of commu- tings playing only a limited role in transmis-
nity transmission. Regardless, it is hard to Articular cartilage is the lubricious, load-
support the opening of retail and hospital- sion when mitigation measures are in place, bearing tissue at the end of long bones in
ity sectors while schools remain shut, as oc- synovial joints that facilitates both low-
curred in many countries earlier this year. in marked contrast to other respiratory vi- friction and low-wear articulation. Although
the low friction of cartilage is attributed in
School closures and attendant loss of ruses. In the event of seemingly inevitable large part to fluid pressurization that can
other protective systems for children (such bear a substantial fraction of the load, lu-
as limited social care and health visiting) future waves of COVID-19, there is likely to bricant molecules also play an important
highlight the indirect, but very real, harms role in mediating friction, especially with
being disproportionately borne by children be further pressures to close schools. There surface-to-surface contact in the boundary
and teenagers as a result of measures to mode of lubrication. Synovial fluid constit-
mitigate the COVID-19 pandemic. In the is now an evidence base on which to make uents, which include hyaluronan, lubricin,
UK, it is estimated that the impact on ed- and surface-active phospholipids, all can
ucation thus far may lead to a quarter of decisions, and school closures should be un- and do contribute to the boundary lubrica-
the national workforce having lower skills tion of cartilage. Indeed, their independent
and attainment for a generation after the dertaken with trepidation given the indirect and synergistic function has been an active
mid-2020s, leading to the loss of billions of area of research and discussion (3, 8–11).
dollars in national wealth (11). Additionally, harms that they incur. Pandemic mitigation
there are a variety of other harms to chil- Biomedical Engineering Department, School of Dental
dren’s health, including the risk of reemer- measures that affect children’s wellbeing Medicine, University of Connecticut Health Center,
gence of vaccine-preventable diseases such Farmington, CT 06030, USA. Email: [email protected]
as measles because of disruptions to immu- should only happen if evidence exists that
nization programs.
they help because there is plenty of evi-
There are many other areas of potential
indirect harm to children, including an in- dence that they do harm. j
crease in home injuries (accidental and non-
accidental) when children have been less REFERENCES AND NOTES
visible to social protection systems because
of lockdowns. In Italy, hospitalizations for 1. What’s the STORY,“Serum testing of representative
youngsters”(2020); https://bit.ly/2H30aGa.

2. S. Ladhani, PHE publications gateway number:
GW-1599 (Public Health England, 2020); https://bit.
ly/35G0mVV.

3. R. M.Viner et al., medRxiv 20108126 [Preprint] 21
August 2020; 10.1101/2020.05.20.20108126.

4. O.V. Swann et al.; ISARIC4C Investigators, BMJ 370,
m3249 (2020).

5. L. M.Yonker et al., J. Pediatr. S0022-3476(20)31023-4
(2020). 10.1016/j.jpeds.2020.08.037

6. A. Fialkowski et al., Pediatr. Pulmonol. (2020). 10.1002/
ppul.24981

7. A. H. Rowley, Nat. Rev. Immunol. 20, 453 (2020).
8. E.Whittaker et al.; PIMS-TS Study Group and EUCLIDS

and PERFORM Consortia, JAMA 324, 259 (2020).
10.1001/jama.2020.10369
9. S. Godfred-Cato et al.; California MIS-C Response Team,
MMWR Morb. Mortal.Wkly. Rep. 69, 1074 (2020).
10. R. Horwood et al., medRxiv 20156075 [Preprint] 23 July
2020; 10.1101/2020.07.17.20156075.
11. The DELVE Initiative,“Balancing the risks of pupils
returning to schools”(Royal Society DELVE Initiative,
2020); https://bit.ly/3iy8Q5l.
12. C. Stein-Zamir et al., Euro Surveill. 25, (2020).
10.2807/1560-7917.ES.2020.25.29.2001352
13. S. Bressan, E. Gallo, F.Tirelli, D. Gregori, L. Da Dalt,Arch.
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Published online 21 September 2020

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Cartilage-inspired, lipid-based boundary-lubricated hydrogels lowed tuning of the lubricating ability and
duration of the hydrogels. A potential criti-
Liu et al. incorporated small concentrations of lipids to create a self-renewing, molecularly thin lipid-based cal consideration regarding the utility of
boundary layer. This discovery has potential applications in numerous fields relevant to biology and medicine. these hydrogels is that wear is required for
these hydrogels to function in their self-
Countersurface Newly exposed gel surface renewing manner. Although the authors
demonstrate that this wear is minimal and
Frictional wear that the materials can sustain many cycles,
this parameter could affect longevity and
Countersurface Driven by sliding would need to be taken into consideration
Sliding of the gel against a countersurface releases for different applications. Finally, one
lipid layers on the gel surface from the micro- amazing feature of these hydrogels that
reservoirs of lipid vesicles. This boundary lubricating could potentially open up many applica-
layer self-renews as the hydrogel wears under friction. tions is that they retain their self-sustain-
ing lubrication even after being fully dried
Reserves of lipids Hydration matters in an oven to 60°C and rehydrated. Indeed,
Microreservoirs of lipids embedded within Highly hydrated head groups of exposed phospha- this robust property has implications for
the hydrogel have a minimal efect on the tidylcholine lipids enable hydration lubrication. storage of hydrogels and potentially for
bulk mechanical properties, and their their utility in harsh conditions that would
concentration can be tuned. not be possible for many other materials.

GRAPHIC: KELLIE HOLOSKI/SCIENCE Although these molecules have been stud- orders of magnitude). A near-constant Lin et al. have demonstrated a simple yet
ied in the context of hydrogel lubrication in friction coefficient provided evidence that effective way of creating self-lubricating
the past, Lin et al. found that embedding boundary-mode lubrication is operative. hydrogels through incorporation of lipids,
lipids in microreservoirs within hydro- with minimal effect on the bulk mechani-
gels creates a material with self-renewing This last result highlights the importance cal properties. These materials may be
boundary lubrication. of incorporating lipids into a hydrogel to useful in biomedical applications where
provide self-renewing boundary lubrica- sustained and extreme friction and wear
Biotribology is the study of lubrica- tion. The authors further demonstrate that would occur, as well as various applica-
tion, friction, and wear when applied to sliding is the driving mechanism for lipid- tions of tissue engineering (13), biosensors,
biological systems or natural phenom- layer formation on the gel surface from the or even contact lenses. Given that hyaluro-
ena (12). Friction coefficients are systems microreservoirs of lipid vesicles, and that nan and lubricin were initially studied as
variables that depend on test variables, the self-renewal of this boundary lubricat- simple lubricants but were eventually ex-
surfaces, and geometries. With that depen- ing layer occurs as the hydrogel wears (ever amined more for their biological proper-
dence in mind, Lin et al. provide compel- so slightly) under friction (see the figure). ties (14, 15), these hydrogels could serve in
ling data demonstrating the robust and Moreover, lubrication by external applica- more complex biological functions beyond
effective lipid-based boundary lubrica- tion of lipids, either through soaking and pure lubrication, such as drug delivery
tion in their hydrogels. They examined washing hydrogels or by their presence in devices, anti-inflammatories, or immune-
a number of different hydrogels, both solution, is far less effective than when the response modulators. Indeed, this discov-
biological and synthetic polymers [some lipids are bulk-incorporated. Lipids from the ery has potential application in numerous
quite different from the commonly used surrounding solution had poorer access to fields relevant to biology and medicine,
poly(hydroxyethylmethacrylate), pHEMA], the gel/countersurface interface relative to and it will be of great interest to see where
and showed effective reduction of friction those incorporated into vesicles. Also, the in- future research and applications lead. j
with the lipid incorporation. They also corporation of lipid vesicles did not alter the
tested different test countersurfaces other mechanical properties of the hydrogel, which REFERENCES AND NOTES
than steel and again found effective friction may be relevant in various applications.
reduction. Finally, they examined a wide 1. N.A. Peppas,J.Z. Hilt,A. Khademhosseini, R. Langer,
range of sliding velocities (more than three Additionally, the concentration of incor- Adv. Mater. 18, 1345 (2006).
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41, 1800166 (2019).

10.1126/science.abd3831

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INSIGHTS | PERSPECTIVES

NEUROTECHNOLOGY and vibration) from specific areas of the limb.
Several neural interfaces with different ge-
Advancing limb neural prostheses ometries and placement have been developed
and preliminarily tested in upper-limb ampu-
Neurotechnology can overcome communication difficulties tees. The stimulation of residual median and
between prostheses and amputees ulnar nerves (which innervate fingers and
palm), through implanted transverse intra-
By Stanisa Raspopovic nerves grow into the new muscles and gain fascicular multichannel electrodes (TIMEs)
the capacity to excite the tissue. When users (6), restored tactile feedback from prosthe-
A lthough sophisticated upper- and attempt movement, neural signals contract ses in four upper-limb amputees. Relying on
lower-limb prostheses have been de- the chest muscles in the case of shoulder- the restored feedback, users controlled the
veloped, amputees cannot control level amputees (2) or residual thigh muscles amount of force exerted with the prosthesis
them intuitively nor perceive sensa- in the case of the above-knee amputation and distinguished between objects with dif-
tions from them. These deficiencies re- (3) (see the figure). Sensors placed over the ferent compliances and shapes.
sult in serious issues, including risk of skin capture the electrical signal produced
falls, decreased mobility, heart fatigue during by muscle activity, which is then transformed Other neurotechnologies that can restore
walking, and lower functionality while grasp- into movement of the robotic arm or leg. Yet, sensory information include Utah slanted
ing. Moreover, the prostheses are not per- control based on skin surface electrodes (2, electrode arrays (USEAs). These consist of a
ceived by the users as part of their own body 3) suffers from instability due to electrode grid of micrometric stimulating wires of dif-
(low embodiment), which increases cognitive movement or detachment. ferent length that are implanted in peripheral
burden during use or device abandonment. nerve fibers (7) and deliver spatially focused
An ideal man-machine interface should en- Further development of the muscle rein- (selective) feedback to hand amputees. In a
able effortless bidirectional communica- nervation concept led to the regenerative complementary approach, remarkable stabil-
tion between the user and the prosthesis. peripheral nerve interface approach (4). The ity of several years (in terms of functional-
Neural prostheses that provide bidirectional distal end of a transected peripheral nerve in ity and biocompatibility) was achieved with
interfacing with the residual nervous system the arm stump is sutured into a muscle graft, flat interface nerve electrode (FINE) (8) im-
exploit the persistence of the central and pe- which is implanted with recording wires. plants. FINEs enable a gentle nerve flatten-
ripheral neural pathways devoted to motor These wires are in turn connected to pros- ing, placing the active contacts in proximity
control and sensing (1). A combination of thesis controls via cables passing through the to the inner fascicles without penetrating the
neurotechnologies recently achieved previ- skin (which have the potential to become bro- nerve like TIMEs and USEAs do. Thus, FINEs
ously unseen capabilities of prosthesis ac- ken or induce infections). This creates a nat- are easier to implant and cause less nerve
tuation and sensory restoration, but several ural amplifier of neural signals of volitional damage, but at the cost of higher stimulation
hurdles need to be overcome before wide- control by transducing them into high-gain current to elicit sensations.
spread use of these devices. myoelectric signals. A high signal-to-noise ra-
tio of this biointerface enabled high-precision Stimulation of leg nerves is a differ-
Upper-limb amputees actuate opening control, even for single finger movements in ent challenge because they are bigger than
and closing of commercial hand prostheses two amputees (4). To overcome the prob- nerves in the arm, and skin receptors have
through the contraction of residual muscles, lems of skin electrodes and percutaneous different density over the foot-sole skin com-
with no possibility to control single digits. wires, tiny implantable myoelectric sensors pared with the palm. Through a meticulous
Above-knee amputees exploit their residual (IMESs), which capture the muscular signals surgery, multiple TIMEs were implanted in
hip movements to initiate protheses, which directly, were developed. These sensors were the sciatic nerve (which innervates the foot
then execute predefined patterns of motion. injected into the reinnervated muscles of and lower leg) and elicited selective foot and
Together with natural actuation, a physiolog- three above-elbow amputees and conferred leg sensations in three above-knee amputees,
ically plausible sensory feedback from pros- long-term functional use (5). Whenever the augmenting their confidence during walking
thesis to amputee is missing, forcing users to movement intention of an amputee activates (9). This improved their mobility on stairs,
continuously visually inspect their artificial the implanted muscles, IMESs capture and avoidance of falls, and embodiment of the
limbs. A key limitation of prostheses actua- amplify these electrical signals and send artificial leg while diminishing the cogni-
tion is that users must learn the nonintuitive them wirelessly to the receiving coil embed- tive load during use. Contrary to upper-limb
control strategies (for example, contracting ded into the prosthesis socket to control the amputation, leg amputation introduces addi-
the biceps to close the hand). motors of the prostheses. This proof of con- tional health complications such as increased
cept needs to be demonstrated in a bigger cardiovascular fatigue and decreased mo-
In the case of amputations closer to the cohort of patients and will hopefully increase bility. Two highly disabled, above-knee am-
hand or foot, the control signals can be ex- controllable movements. putees equipped with intraneural feedback
tracted from the residual muscles, but when from prostheses experienced several health
amputations are at the thigh or shoulder Alongside actuation, restoring sensory benefits, such as diminished cardiovascular
level, muscles that control the hand or foot information from the artificial limb to the fatigue and pain, increased mobility over un-
are lost. In these cases, a solution is surgical user is essential for functionality. Natural even terrains, and brain load decrease (10).
rerouting of nerves toward the other avail- sensations from the missing extremity can
able muscles, called targeted muscular rein- be restored to the brain, inducing so-called In these studies, different sensations were
nervation (TMR). After this intervention, the phantom sensations, through electrical stim- restored in amputees, but there is limited
ulation of the residual nerves proximal to the evidence for perceptions of limb position,
Neuroengineering Laboratory, Institute of Robotics amputation. Peripheral nerves contain par- speed, and torque, namely proprioceptive
and Intelligent Systems, Department of Health allel tubular structures, called fascicles, that sensations, which are essential for walking.
Sciences and Technology, ETH Zurich, Switzerland. transmit different sensations (such as touch To overcome this in below-knee amputees, a
Email: [email protected] surgical approach connecting in series two
opposing muscle-tendon ensembles (an ago-
nist and an antagonist) was developed (11).

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With this strategy, one muscle contracting otic and beneficial use of such a bidirectional Capturing information external to the
and shortening (volitional or electrically ac- approach needs to be proven. It needs to be limb is mandatory to trigger neurofeedback,
tivated) induces the stretching of the other explored whether artificial motor and sen- but prostheses do not have sensors in robotic
in the opposing direction. This linked mo- sory signals together could be intuitively fingers or under the prosthetic foot. Thus, re-
tion permits the natural body receptors em- handled by the brain, without sensorimotor search efforts are devoted to the development
bedded in the muscle-tendon to transmit conflicts or cognitive overload, hopefully re- of prosthetic electronic skin, which should be
information about muscle length, speed, and sulting in increased functionality. able to accommodate a high density of sen-
force, which is perceived by the brain as joint sors over flexible polymeric structures (15). In
proprioception and used for precise stair Neural prostheses for sensory feedback the future, these could be imagined as gloves
walking. However, transfer of this elegant so- restoration were connected to the stimulator, or socks, with robust and high-resolution
lution to more disabled above-knee amputees injecting electrical current into the nerves sensors, placed over the prostheses to trans-
could represent a considerable challenge. via percutaneous cables, which increases mit different sensory signals such as pres-
the probability of infections and has limited sure, movement, and temperature.
Sensations induced by these different robustness. Thus, fully implantable wireless
approaches are close to natural but can systems need to be developed. These systems To date, these studies are mainly proof of
be perceived as unpleasant electrical tin- should feature: long-term stability and safety concepts regarding an increase of quality of
life or technological viability of neural pros-
Bidirectional limb 1 2 theses, performed with their own metrics,
neural prostheses Muscle making it difficult to objectively compare
Amputated grafts outcomes. They are not clinical studies of
Residual motor and sensory neurons in arms limb safety and efficacy, which are important to
and legs of amputees can be used with implants 4 achieve the necessary medical certifications.
and surgery techniques to confer different Globally, the regulatory steps are demand-
sensations and precise motor control of ing and costly, and when accounting for in-
prostheses. Such bidirectional communication dividualization of devices and smaller vol-
and possibly combinations of approaches ume need, the economic cost is potentially
should improve the quality of life for amputees. high for end users. This could hinder the
widespread use of these technologies. Public
Residual nerve Muscle health care systems vary considerably, and
Sensors on skin Prosthetic device each carries out its own assessment of health
technology to support its decisions regard-
1 Targeted muscle reinnervation Nerve ing reimbursement, mainly by demonstrated
Nerves grow into new muscles, where they can implant cost-effectiveness and benefits that increase
excite the tissue. This is detected by sensors placed “quality-adjusted life-years.” Therefore, it is of
on the skin that then move the robotic prosthetic. 3 paramount importance to plan, from the first
steps of bidirectional neural prosthesis test-
2 Regenerative interface ing, how to demonstrate safety and health
Transected peripheral nerves are sutured into a gains because this would augment the likeli-
muscle graft and are implanted with myoelectric sensors hood of device approval. The future of neu-
that are connected to prosthesis motor controls. rotechnological intervention for amputees
will be in the personalized and combined
3 Sensory interfacing use of these technologies. Depending on the
Sensory information, such as tactile feedback, can amputation level and patients’ characteris-
be restored by using various implants that stimulate tics, the customized combination of mus-
electrically residual nerves. cular and sensory interventions is likely to
benefit amputees in the long term. j
4 Agonist-antagonist myoneural interface
Proprioceptive sensations, such as limb position and speed, REFERENCES AND NOTES
are important for walking and can be restored in amputees 1. G. S. Dhillon, K.W. Horch, IEEE Trans. Neural Syst.
through surgical connection of residual muscles. Rehabil. Eng. 13, 468 (2005).
2. T.A. Kuiken et al., JAMA 301, 619 (2009).
GRAPHIC: V. ALTOUNIAN/SCIENCE gling. Time-variable electrical stimulation, of the implants, high battery capacity, stable 3. L.J. Hargrove et al., N. Engl.J. Med. 369, 1237 (2013).
precisely defined by using computational leads (that currently are prone to breakage), 4. P. P.Vu et al., Sci.Transl. Med. 12, eaay2857 (2020).
modeling (12), that simulates in silico the and easy replacement of implants or their 5. S. Salminger et al., Sci. Robot. 4, eaaw6306 (2019).
responses of tactile neurons innervating the parts. Although typical implantable neuro- 6. S. Raspopovic et al., Sci.Transl. Med. 6, 222ra19 (2014).
glabrous (hairless) skin was preliminarily stimulators (such as pacemakers) have pre- 7. J.A. George et al., Sci. Robot. 4, eaax2352 (2019).
demonstrated to induce more natural sensa- programmed stimulation protocols, with no 8. D.W.Tan et al., Sci.Transl. Med. 6, 257ra138 (2014).
tions (7, 13) and could therefore potentially need for a continuous transcutaneous com- 9. F. M. Petrini et al., Sci.Transl. Med. 11, eaav8939 (2019).
increase acceptance of these technologies. munication, for prostheses a high burden of
Computational modeling could optimize im- information has to be wirelessly transmit- 10. F. M. Petrini et al., Nat. Med. 25, 1356 (2019).
plant geometry and electrical parameters to ted through the skin to enable bidirectional 11. T. R. Clites et al., Sci.Transl. Med. 10, eaap8373 (2018).
personalize devices in the future. communication. This demands high battery 12. H. Saal et al., Proc. Natl.Acad. Sci. U.S.A. 114, 28 (2017).
capacity while maintaining a limited implant 13. G.Valle et al., Neuron 100, 37 (2018).
Recently, muscular control implants and size for surgical placement, representing an 14. M. Ortiz-Catalan et al., N. Engl.J. Med. 382, 1732 (2020).
sensory stimulation were combined in four important technological challenge. Presently, 15. A. Chortos et al., Nat. Mater. 15, 937 (2016).
amputees, showing long-term stability and most implants require several hours-long
safety but with limited insights about sensory surgeries, and therefore minimally invasive ACKNOWLEDGMENTS
benefits or cognitive effects (14). The quanti- procedures should be developed.
fied long-term demonstration of the symbi- The author is supported by the European Research Council
2017-STG n.759998 (FeelAgain) and holds shares of SensArs
Neuroprosthetics. I thank F. Petrini and M. Capogrosso for
their thoughtful input.

10.1126/science.abb1073

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INSIGHTS | PERSPECTIVES

SYNTHETIC BIOLOGY nents in heterologous settings, however,

Reconstituting tissue patterning the synthetic approach is still limited by
the properties and complexity of the se-
lected pathway. This restricts the ability to
fully test or construct artificial morphogen-
A synthetic morphogen reveals based mechanisms. The studies by Toda et

quantitative principles of tissue patterning al. and Stapornwongkul et al. have over-
come these hurdles by converting an in-

ert molecule—green fluorescent protein

By Naama Barkai and Ben-Zion Shilo Moreover, in all systems studied, morpho- (GFP)—into a morphogen. This allowed

gen distribution depends on a myriad of tight control of the morphogen parameters

M ulticellular organisms develop feedback loops regulating its movement, and a broad examination of morphogen-
through a sequence of pattern- degradation, production, or downstream based mechanisms.
ing events, in which cells adopt activity. Perhaps surprisingly, although sys-
distinct cell fates. In many in- tems utilizing patterning by morphogens Toda et al. converted a secreted GFP into
stances, patterns are established are continuously discovered, the number a morphogen by adapting a paradigm they
previously established (10). In this system,

by morphogen gradients that de- of identified morphogens remains small: a synthetic Notch receptor carrying a GFP-

termine cell fates according to the position Systems representing different contexts or binding protein is activated to induce tar-

of cells within a uniform field. On pages organisms repeatedly employ the same few get genes of interest when presented with

327 and 321 of this issue, Toda et al. (1) and morphogen molecules. GFP that is anchored to a neighboring cell

Stapornwongkul et al. (2), respectively, use The potential of synthetic systems to membrane. To follow the distribution of

synthetic approaches to study morphogen disentangle the complexity of morphogen secreted GFP, the authors mixed receiving

gradients. Why are synthetic approaches systems and reveal their design principles cells, carrying the synthetic Notch receptor,

helpful? Patterning systems operate in was demonstrated with the Hedgehog (HH) with cells carrying a transmembrane pro-

complex biological settings, and synthetic morphogen (9). The HH pathway is distinct tein capable of binding GFP and anchoring

reconstitution isolates and defines the key

players. Because the features of such sys- L2 L2
tems depend directly on quantitative pa-

rameters, synthetic approaches allow re-

constituting systems in which parameters

can be precisely tuned and their effects

measured with precision. Additionally, the

regulation of patterning systems relies on

different feedback loops, and synthetic re- L5 L5
wiring highlights the logic of the critical cir-

cuits. Overall, the key parameters and play- An engineered green fluorescent protein (GFP) response reconstitutes patterning in the Drosophila melanogaster

ers can be examined from different angles. wing pouch. Stapornwongkul et al. reconstituted wing patterning in a dpp (decapentaplegic) mutant background.

The concept of morphogen gradients as Secreted GFP was expressed from a stripe of cells at the disc center. All cells in the wing pouch expressed

mediators of tissue patterning was pro- chimeric receptors carrying the GFP nanobody on the extracellular domain (left panel). Additional expression

posed by Wolpert in 1969, coined as the of an anchoring protein displaying a GFP nanobody led to more accurate patterning (right panel). The nested

“French-Flag” model (3). Morphogens are expression of sal (homeotic spalt-major) and omb (optomotor-blind) target genes was restored, as reflected in

molecules that can trigger cells to adopt dif- proper localization of L2 and L5 longitudinal wing veins.

ferent fates, depending on the morphogen

concentration the cells encounter. Localized from most morphogen signaling pathways it. GFP is then made to act as a morpho-

production of a morphogen at a restricted because it uses a “bifunctional-negative” gen: Diffusible GFP is released from a lo-

source creates a concentration gradient strategy within the same molecule: The HH calized source of secreting cells into a field

that accordingly confers a complex, posi- receptor Patched (PTCH) inhibits down- composed of a mixture of receiving cells

tion-dependent patterning of the receiving stream HH signaling and also sequesters carrying the synthetic Notch receptor, and

cells (4). Experiments over the past three external HH. Binding of HH to PTCH re- anchoring cells that capture the diffusible

decades confirmed the involvement of lieves the PTCH inhibitory activity and GFP and present it to the receiving cells.

morphogen gradients in a large number of induces the expression of PTCH as one of This system provides easy control of dif-

patterning events, such as specification of its downstream targets. What could be the ferent morphogen parameters. For example,

distinct neural fates within the spinal cord consequence of such a design? Motivated by changing the density of the anchor cells or

or positioning of veins in the fly wing (5–7). a mathematical model and using the abil- the affinity by which they bind GFP modu-

Yet, these experiments also revealed that ity to control parameters within a synthetic lated the range of GFP diffusion. Expression

the actual establishment and utilization of system, it was revealed that the double- of a secreted inhibitory molecule from an PHOTOS: STAPORNWONGKUL ET AL. (2)

morphogens are considerably more com- negative design promotes reliability: It ac- opposite pole provided another means for

plex than initially envisioned. celerates the approach to steady state and reducing the range and level of the gradi-

Questions arose as to whether the move- provides robustness to variation in ligand ent. Additionally, a positive feedback loop

ment of morphogen across the field de- production rates can be generated by making secreted GFP

pends on passive diffusion in the extra- Synthetic systems therefore enable flex-

cellular milieu or if more active processes ible control of parameters such as cell den- Department of Molecular Genetics, Weizmann Institute of
involving transport between cells through sity or availability of different molecules. Science, Rehovot 7610001, Israel. Email: naama.barkai@
specialized mechanisms play a role (8). When using the normal signaling compo- weizmann.ac.il; [email protected]

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Published by AAAS

a target gene for the synthetic re- Generating a synthetic morphogen essential clues regarding the genera-

ceptor. Combining these manipu- Toda et al. created a source of secreted green fluorescent protein (GFP). tion and maintenance of a stable

lations, Toda et al. generated a The response was marked by transcription factor (TF)–mediated morphogen gradient. Such proper-

propagating wave of patterning, induction of mCherry expression. When the cells carried a positive ties render these systems promising

akin to the movement of the mor- feedback loop by induction of GFP expression, the response was for addressing long-standing issues

phogenetic furrow in the develop- propagated. When the cells harbored a negative feedback loop, the that are seminal to morphogen pat-

ing Drosophila melanogaster (fruit- response was attenuated and steady state was reached faster. terning. For example, an important

fly) eye. Conversely, an engineered question is how sharp borders of

negative feedback response to the Morphogen feedback circuit Anti-GFP target-gene expression are created
pathway dampened the response between adjacent groups of cells.
amplitude and accelerated the ap- GFP inhibitor Difuse Although morphogen gradients are
proach to steady state, which is the Secretion continuous, sharp gene expression
state at which most morphogen or borders ensue, suggesting that cells

Input GFP-binding
synthetic Notch receptor

gradients function. Anchor TF can distinguish small differences
With this toolkit in hand, it was in morphogen concentration and
Target gene/mCherry translate them to a “yes or no” deci-
possible to generate elaborate pat-

terns. In their final demonstration, sion regarding gene expression. The

the authors combined one pole Positive feedback circuit systems described by Toda et al. did
that secreted the red fluorescent Anchor cell not give rise to such sharp borders,
protein mCherry as the morpho- suggesting that additional mecha-

gen, and an opposite pole that nisms are required.

secreted the inhibitor. The cells GFP Another intriguing topic involves
between the poles expressed syn- the ability of developmental sys-

thetic receptors for either mCherry tems to buffer morphogen gradients

or GFP and carried the positive against fluctuations (robustness)

feedback to express secreted GFP. and adjust the gradient with tissue

With this setting, three domains size (scaling). Several models have

of gene expression could be identi- been proposed to explain robust-

fied, mimicking an expected mor- Spatial propagation ness and scaling—for example, self-
phogen response (see the figure). regulated production of a diffus-

Stapornwongkul et al. took on the Negative feedback circuit ible molecule that impinges on the

additional challenge of examining Anchor cell global distribution of the morpho-

whether a secreted GFP can act as gen. When expression of such a mol-

a morphogen within the context of ecule depends on the morphogen, it

the whole organism. They focused GFP allows measurement of the morpho-
on the well-characterized Dpp (de- gen concentration at the edge of the

capentaplegic) gradient in the wing gradient, and adjusts the entire pro-

imaginal disc of D. melanogaster (5, file accordingly (11). It will be excit-

6), investigating whether a circuit ing to investigate whether synthetic

can be engineered that will imitate approaches could test such models

Dpp function in disc patterning. rigorously in the future. In the long

They tested diffusion properties of term, synthetic approaches may fa-

secreted GFP by releasing it from cilitate tissue engineering. With the

the stripe of cells normally secreting Dpp Nonsignaling receptors allow more stable capacity to manipulate the production, dif-

in vivo. Having established the properties trapping of the diffusible ligand, increasing fusion, and response to engineered proteins

of GFP distribution, the authors investi- the concentration of ligands presented to and pathways, it may be easier to execute in

gated whether GFP distribution can replace the signaling receptor. Such traps, however, culture developmental processes that will

the function of Dpp in patterning the wing also limit the diffusion of the morphogen. allow the formation of artificial tissues. j

disc. They engineered the normal Dpp re- This explains the need for fine-tuning their REFERENCES AND NOTES
ceptors Thickveins (Tkv) and Punt (Put), to expression, or alternatively, to allow non-
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tivation. A nested expression of the target represents an impressive technological feat. 7. A. Sagner,J. Briscoe, Development 146, dev182154
genes sal (homeotic spalt-major) and omb In addition to confirming previous ideas (2019).
(optomotor-blind) could be detected, but that were based on genetic manipulations,
with a profile that differed from normal. it allows detailed analysis of quantitative 8. P. Müller et al., Development 140, 1621 (2013).
However, when a nonsignaling membrane- parameters that are not approachable with 9. P. Li et al., Science 360, 543 (2018).
10. L. Morsut et al., Cell 164, 780 (2016).
11. B.Z. Shilo, N. Barkai, Dev. Cell 40, 429 (2017).

tethered protein that facilitated GFP trap- endogenous systems. Particularly informa- ACKNOWLEDGMENTS
ping was also expressed, the resulting gene tive is the ability to monitor, in time and
expression pattern was markedly similar space, the dynamics in which the system N.B. and B.-Z.S. are supported by grants from the US-Israel
Binational Science Foundation.

to the wild-type profile (see the images). reaches steady state. The dynamics provides 10.1126/science.abe4217

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INSIGHTS | PERSPECTIVES

IMMUNOLOGY response to LPS, including several PLIN
proteins as well as proteins with known
Immiscible immunity antiviral, antibacterial, and antiprotozoan
activity (see the figure). Coexpression anal-
Mammalian metabolism meets immunity at ysis revealed that expression of several of
mitochondria-adjacent lipid droplets the latter proteins correlated with that of
PLIN2, the major protein involved in the
By Douglas R. Green A century later, they received interest stabilization of LDs (7).
(and perhaps organelle status) with the
O il and water do not mix. This sim- discovery of perilipins (PLINs), proteins Among the antibacterial proteins in the
ple fact drives the formation of that function in the assembly and stability PLIN2 cluster was cathelicidin (CAMP), a
the lipid-based boundaries of cells, of LDs (3). A link to infection came with broadly active antimicrobial peptide with
nuclei, and most organelles that the discovery, by several authors of Bosch immune regulatory and chemotactic func-
make life possible. But a simpler et al., that microbial stimulation of mac- tions. Bosch et al. found that silencing
structure, the lipid droplet (LD), rophages in Drosophila induces formation CAMP expression in human macrophages
coalesces in the cell cytoplasm and com- of LDs with antimicrobial activity (4). This prevented their antimicrobial response to
prises a core of neutral fatty acids [mostly activity was dependent on a protein, Jabba, intracellular Escherichia coli. CAMP is pro-
triacylglycerides (TAGs) and sterol esters] that recruits histones to LDs, and flies lack- duced as a proprotein with an amino-ter-
surrounded by polar lipids (phospholipids ing Jabba displayed increased sensitivity to minal signal peptide that is cleaved before
and sterols) and associated proteins. An bacterial infection. Extranuclear histones CAMP is secreted. However, the authors
LD is, in essence, a drop of oil, but it has in flies and mammals are known to have found that LD-associated CAMP retained
the signal peptide, suggesting that the sig-
Double duty nal peptide of CAMP functions not only in
secretion but also in targeting CAMP to
Perilipin-5 (PLIN5) protein tethers lipid droplets (LDs) to mitochondria, and LDs. By directly steering CAMP to LDs, the
LDs provide fuel for b-oxidation (left). When the cells sense microbes, the LD proteome organelles acquired antimicrobial activity
changes, and LDs grow in number and size. PLIN2 stabilizes LDs, and antimicrobial against E. coli, Listeria monocytogenes,
proteins increase (right). PLIN5 and thus b-oxidation decrease. and methicillin-resistant Staphylococcus
aureus. LD-associated histones also in-
b-oxidation b-oxidation creased in LPS-treated cells but appeared
Triacylglyceride to play little to no role in antimicrobial ef-
Mitochondrion fects of LDs.

PLIN5 Ligation of cell surface TLRs on mouse
and human macrophages reduces mito-
Microbial sensing chondrial b-oxidation, an effect attributed
to down-regulation of adipose triglyceride
PLIN2 Antimicrobial lipase (ATGL) expression (6), and LPS-
protein treated macrophages shift to a Warburg ef-
fect–like oxidative glycolysis (8). However,
Sterol ester whereas Bosch et al. similarly found that
LD LPS treatment decreased mitochondrial
b-oxidation, they did not report substan-
properties that many proponents suggest antimicrobial activity (5), but no Jabba tial change in ATGL expression upon LPS GRAPHIC: A. KITTERMAN/SCIENCE
give it organelle status. As a rich energy homolog exists in mammals. Nevertheless, treatment of hepatocytes. They did ob-
reserve, LDs fuel b-oxidation in mitochon- activation of cell-surface Toll-like receptors serve reduced expression of PLIN5, the
dria and often physically associate with (TLRs), which are sensors of diverse mi- major protein responsible for tethering
these organelles. It follows, however, that crobial products, strongly stimulates TAG mitochondria to LD (9). Another protein
invading microorganisms similarly exploit uptake, synthesis, and retention in human suspected of mediating such tethering,
LDs as an energy source and, therefore, and mouse macrophages (6), suggesting a diacylglycerol O-acyltransferase 2 (10), was
that cells might “arm” LDs with innate similar antimicrobial role for LDs in mam- found by others to be up-regulated in LPS-
host defense mechanisms. On page 309 of malian cells. treated macrophages (6), but again, Bosch
this issue, Bosch et al. (1) explore the rela- et al. did not find this effect in hepatocytes.
tions between the antimicrobial activities Bosch et al. examined hepatocytes in mice Nevertheless, they observed that LPS treat-
of LDs and their function as a fuel depot injected with the TLR4 ligand lipopolysac- ment reduced contact between LDs and
for mitochondria. charide (LPS; a bacterial toxin) and ob- mitochondria, and enforced expression of
served an increase in LDs with heightened PLIN5 in cell lines increased the numbers
LDs were identified more than 130 years antimicrobial activity. They also observed and lengths of such contacts and prevented
ago and reside in all cells and cell types (2). similar effects in human monocyte-derived their reduction by LPS. These results sug-
macrophages treated with LPS. Using a gest that regulation of PLIN5 expression
Department of Immunology, St. Jude Children’s Research proteomic approach, the authors found controls the fueling of mitochondria by LD
Hospital, Memphis, TN 38139, USA. that 30% of the LD-associated proteome for b-oxidation.
Email: [email protected] changed (for the most part, increased) in
Enforced expression of PLIN5 reduced
the intracellular antimicrobial effects of
LPS treatment in cell lines. This suggests
that the uncoupling of mitochondria from

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LDs might be important for their anti- CELL BIOLOGY
microbial effects. But why? Because LD-
associated CAMP was the major factor A cellular sense of space
mediating LPS-induced antibacterial activ- and pressure
ity, it might be that mitochondria compete
with bacteria for LD binding or otherwise The nucleus measures cell confinement with
prevent the effects of CAMP on bacteria. a mechanosensitive phospholipase
Alternatively, the LPS-induced expression
of CAMP (and perhaps other antimicro- By Zhouyang Shen1,2 and Philipp Niethammer1 cantilever when confined to heights of less
bial effectors) might depend on the LPS- than 10 mm, which indicates the onset of cor-
induced metabolic shift to glycolysis. It D uring health or disease, cells traverse tical contractility and blebbing. Confining
would be useful to determine if enforced great distances along complex land- embryonic zebrafish cells in chambers of
PLIN5 expression affects metabolism in scapes of chemical and physical cues, similar heights, Venturini et al. observe rapid
LPS-treated cells and if this, in turn, affects for instance, to heal wounds or to cell polarization and migration.
expression of CAMP. seed cancer metastases in the body.
They navigate through tight, fluid- Cells can sense their physical environ-
Although LPS ligation of TLR4 directly filled tissue channels and squeeze through ment through their plasma membrane,
stimulates LD formation in macrophages narrow blood vessel pores. To choose the which harbors mechanosensitive ion chan-
(6), this effect in vivo depends in large part best path while avoiding entrapment, cells nels and adhesion molecules that connect
on the action of platelet-activating factor must gauge the space around them and the actin cortex to the cell’s exterior. The
(PAF) (11). To what extent the LPS-induced accommodate their movements to it. On plasma membrane, with its underlying
changes noted by Bosch et al. in 30% of the pages 310 and 311 of this issue, Lomakin et cortical meshwork, directly “touches” the
LD proteome might result from PAF or other al. (1) and Venturini et al. (2), respectively, walls of confined spaces. It is hence in-
LPS-induced cytokines remains unknown. find that embryonic, immune, and cancer tuitive to think that it may sense the con-
Nevertheless, the ability of LPs and presum- cells sense confinement through deforma- finement. Lomakin et al. and Venturini et
ably other TLR agonists to increase intra- tion of their nucleus. Stretch in the nuclear al. test this idea. Perturbing extracellular
cellular innate defenses against infection in membrane activates the enzyme cytosolic calcium (Ca2+), which is required for both
mammals and how this relates to the func- phospholipase A (cPLA ), which initiates cell adhesion and ion-channel mechano-
tions of LDs and their interactions with mito- transduction through the plasma mem-
chondria open new avenues for exploration. 22 brane, hardly affects confinement sens-
ing. Likewise, pharmacologic inhibition
“There is great and justifiable cell blebbing and movements that may of mechanosensitive channels has little
excitement regarding the help cells to crawl within or out of narrow effect. Even barely adherent, rounded cells
functions of LDs [lipid droplets] spaces. Both studies add to the emerging respond to confinement. Thus, some other
and other membraneless idea that the nucleus, besides its genetic mechanism must be involved.
organelles…” functions, directly senses the cell’s physical
environment. Two earlier studies (6, 7) revealed that
There is great and justifiable excite- cPLA senses nuclear swelling upon os-
ment regarding the functions of LDs and Previously, it was observed that different
other membraneless organelles and their cell types start to wobble or pace around 2
associated phase transitions in many cel- when confined (3, 4). This characteris-
lular processes. The studies by Bosch et al. tic behavior is caused by contractions of motic shock to initiate rapid immune cell
suggest that we have much to learn about their actin cortex, a meshwork of cytoskel- chemotaxis to zebrafish tail fin wounds (6).
these drops of oil in cells. j etal filaments that underpins the plasma Nuclear swelling activates cPLA , which
membrane. Once recruited to the actin
REFERENCES AND NOTES meshwork, the molecular motor protein 2
1. M. Bosch et al., Science 370, eaay8085 (2020). myosin II can slide actin filaments along
2. R.V. Farese Jr.,T. C.Walther, Cell 139, 855 (2009). each other to cause cortical contractions. then releases the unsaturated fatty acid
3. A. S. Greenberg et al., J. Biol. Chem. 266, 11341 (1991). These contractions pressurize the cellular arachidonic acid (AA) from nuclear mem-
4. P.Anand et al., eLife 1, e00003 (2012). fluid beneath, driving the formation of brane phospholipids. AA is converted into
5. M. Hoeksema, M. van Eijk, H. P. Haagsman, K. L. plasma membrane blebs (5). Within nar- hormone-like lipids, called eicosanoids,
Hartshorn, Future Microbiol. 11, 441 (2016). row spaces, this can produce cell move- which attract immune cells and control
6. Y. L. Huang et al., J. Biol. Chem. 289, 3001 (2014). ments (3, 4). Lomakin et al. and Venturini cell differentiation and survival, among
7. M. Fukushima et al., In Vitro Cell. Dev. Biol.Anim. 41, 321 et al. provide an explanation for how cells other functions. In the presence of Ca2+,
(2005). detect their confinement. cPLA was shown to sense nuclear swell-
8. L.A. O’Neill, E.J. Pearce, J. Exp. Med. 213, 15 (2016).
9. H.Wang et al., J. Lipid Res. 52, 2159 (2011). Lomakin et al. use atomic force micros- 2
copy to systematically squeeze cultured hu-
10. S.J. Stone et al., J. Biol. Chem. 284, 5352 (2009). man cancer cells with a flat cantilever. They ing and compression through stretch in
11. R. N. Gomes et al., Shock 26, 41 (2006). observe that cells actively push back on the the nuclear membrane (7). These studies
demonstrated that the nuclear membrane,
ACKNOWLEDGMENTS 1Cell Biology Program, Memorial Sloan Kettering Cancer much like the plasma membrane, rapidly
D.R.G. is supported by grants from the U.S. National Institutes Center, New York, NY 10065, USA. 2Louis V. Gerstner Jr. perceives physical cues from the cell envi-
of Health and by the ALSAC. Graduate School of Biomedical Sciences, Memorial Sloan ronment and converts them into chemical
Kettering Cancer Center, New York, NY 10065, USA. signals that drive inflammation in vivo.
10.1126/science.abe7891 Email: [email protected]
The confinement behaviors investigated
by Lomakin et al. and Venturini et al. are
rapid and reversible. They do not depend
on new protein synthesis but require an
intact nucleus: Enucleated and mitotic
cells do not show the response or do so

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INSIGHTS | PERSPECTIVES

at much higher compression. Through Lomakin et al. make nuclear membranes cleus. This would desensitize or inactivate

pharmacologic and genetic perturbations, floppier by depleting two lamina-stabilizing the nuclear gauge mechanism. If ER mem-

these studies identify intracellular Ca2+ components, lamin A and C. This reduces branes collapse into a stretched nucleus,

and cPLA as central regulators. cPLA the ability of the cell to sense confinement. the observations of Venturini et al. imply
22

releases AA into the cytoplasm or super- A floppier nuclear membrane may require that it must happen slowly. Investigating

natant of confined cells without causing more compression to fully unfold, stretch, whether and how membrane tension equil-

neighboring cells to bleb. This points to and activate cPLA . By contrast, it was pre- ibrates between the ER and the nucleus is
2

second-messenger or autocrine functions viously shown that lamina destabilization complicated by a lack of noninvasive meth-

of AA, or some other cPLA product. After promotes cPLA activation upon nuclear ods to directly measure organelle stretch
2 2 in intact cells in space and time. But
cell-permeable membrane-tension dyes
cPLA has cleaved AA from its preferred swelling after hypotonic shock (6). Perhaps
2
the regulation of nuclear membrane mech-
lipid substrate, phosphatidylcholine, the

remaining lysophosphatidylcholine can be anotransduction is stimulus-dependent. are under development (10), and a better

converted to lysophosphatidic acid (LPA) Venturini et al. describe another instance of understanding of how cPLA and related
2

by lysophospholipase D activity. LPA acti- stimulus dependence: Although hypotonic proteins detect membrane stretch should

vates the small guanosine triphosphatase cell swelling unfolds the nuclear mem- inform the design of genetically encoded

(GTPase) RhoA to cause cortical contrac- brane just like cell confinement, it pro- tension biosensors in the future.

tions and blebbing. Experiments carried duces less of an actin-myosin contraction The studies by Lomakin et al. and

out by Venturini et al. suggest Venturini et al. provide evi-

that the RhoA pathway is ac- dence for a mechanotransduc-

tivated downstream of cPLA . Nuclear membrane mechanotransduction tion paradigm in which the
2 nuclear membrane takes the
Cells sense critical confinement and swelling through stretch in their nuclear center stage (see the figure),
Future work may further de- membrane. Calcium (Ca2+) concentration and nuclear membrane stretch as proposed previously (7,
11). Cells may use the nuclear
fine the lipid(s) that mediate together activate cytosolic phospholipase A2 (cPLA2), which cleaves nuclear
membrane phospholipids into lysophospholipids and arachidonic acid (AA).
the confinement response.

Taking a careful look at the

changes in nuclear structure These cleavage products are further metabolized to bioactive lipids that “ruler” to detect their physical

upon confinement, Lomakin mediate cell-autonomous or paracrine effects. surroundings during confined

et al. and Venturini et al. ob- migration or sense and adjust

serve that nuclear membrane Confnement Swelling their “posture” in a three-
folds disappear, nuclear pore dimensional tissue matrix. A

distance increases, and cPLA Noncritical similar mechanism mediates
2 inflammatory lipid signal-
Stretch ing during wound detection
binds to the inner nuclear
membrane, consistent with the Ca2+ Critical

onset of nuclear membrane Stretch in zebrafish larvae (6). Recent
stretch. From these and other research suggests that the nu-

quantitative approaches, the Nuclear Ca2+ clear membrane also becomes
authors conclude that corti- membrane stretched during cell death
cal actin-myosin contraction stretch cPLA2 (12). Cell and nuclear swell-

and blebbing-mediated motil- Same cell Lysophospholipids Other cells ing are a hallmark of necrosis,
ity result from critical (that is, Cortical contraction and AA Chemotaxis but whether or how nuclear
membrane stretch–inducing) DiDerentiation membrane mechanotransduc-
nuclear deformation, which is Blebbing tion contributes to cell death
Movement Survival

transduced by cPLA into lipid signaling or tissue responses to
2

second messengers. Lomakin et al. show response. The authors identify intracellular necrosis is unclear. Revealing which physi-

that this mechanism allows immune and Ca2+ concentrations as a discriminating fac- ologies and pathologies are controlled by

cancer cells to rapidly move under confine- tor; these are higher during confinement the nuclear gauge will be an important

ment or efficiently traverse dense extracel- than upon osmotic swelling. Venturini et mission for future research. j

lular matrix networks in vitro. cPLA -defi- al. propose that cells distinguish different REFERENCES AND NOTES GRAPHIC: KELLIE HOLOSKI/SCIENCE
2 mechanical stimuli by their differential ef-
fect on Ca2+ concentration and membrane 1. A.J. Lomakin et al., Science 370, eaba2894 (2020).
cient mice (8) and people (9) exhibit several stretch. It will be important to understand 2. V.Venturini et al., Science 370, eaba2644 (2020).
how these two cues collaborate at mem- 3. V. Ruprecht et al., Cell 160, 673 (2015).
postdevelopmental phenotypes. These branes to activate cPLA . 4. Y.-J. Liu et al., Cell 160, 659 (2015).
5. G.T. Charras, J. Microsc. 231, 466 (2008).
have been mostly attributed to defects in 2 6. B. Enyedi, S. Kala,T. Nikolich-Zugich, P. Niethammer,

eicosanoid signaling, but some of them— Venturini et al. report that squeezed Nat. Cell Biol. 15, 1123 (2013).
nuclei maintain their unfolded, stretched 7. B. Enyedi, M.Jelcic, P. Niethammer, Cell 165, 1160
such as defective fertility, attenuated isch- state for at least an hour, which could al-
low cells to persistently detect their con- (2016).
emic tissue damage, and reduced allergic finement with little desensitization. Given 8. A. Saphirstein et al., Biochim. Biophys.Acta 1488, 139
the complex membrane topology of the
responses of cPLA -deficient mice—may nucleus, this observation is interesting and (2000).
2 perhaps unexpected. The outer nuclear 9. D. H.Adler et al., J. Clin. Invest. 118, 2121 (2008).
10. A. Goujon et al., J.Am. Chem. Soc. 141, 3380 (2019).
be revisited for potential cell-autonomous 11. B. Enyedi, P. Niethammer, Cell. Mol. Bioeng. 9, 247

contributions of nuclear membrane mech- (2016).
12. M. Riegman et al., Nat. Cell Biol. 22, 1042 (2020).
anotransduction by cPLA . It should also
2

be investigated whether or which other

phospholipases can substitute for cPLA in
2

its mechanosensory role.

Cells tune the sensitivity of their “nu- membrane connects to the endoplasmic ACKNOWLEDGMENTS
clear gauge” by altering the stability of reticulum (ER). Thus, perhaps the nuclear
their nuclear lamina, a dense filamentous membrane stretch is quickly dissipated Z.S. and P.N. are supported by U.S. National Institutes of
meshwork beneath the nuclear membrane. by membrane flow from the ER to the nu- Health grant GM127356.

10.1126/science.abe3881

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RETROSPECTIVE His work also showed that long-term poten-
tiation (LTP) is associative in nature, thereby
Joe L. Martinez Jr. (1944–2020) helping to establish LTP as a potential physi-
ological basis for associative learning.
Neuroscientist and advocate of inclusion
Joe’s relentless dedication to diversity,
PHOTO: THE UNIVERSITY OF TEXAS AT SAN ANTONIO By Keith A. Trujillo1, Alfredo Quiñones- of the Cajal Neuroscience Institute. At UTSA, equity, and inclusion by mentoring scien-
Hinojosa2, Kenira J. Thompson3 he worked with colleagues to obtain nearly tists around the country in career training
$18 million in funding for neuroscience re- programs made him stand out in the field.
J oe Louis Martinez Jr. died on 29 search and education. In 2012, he moved to Committed to offering extraordinary profes-
August at the age of 76. In addition the University of Illinois at Chicago where he sional development to students from under-
to making extraordinary contribu- served as professor and psychology depart- represented backgrounds, he was constantly
tions to the fields of neurobiology and ment head until his retirement in 2016. At seeking funding and developing programs
Chicano psychology, Joe was a tireless each institution, he embraced the opportu- in career awareness, lifelong mentorship,
advocate of diversity, equity, and inclu- nity to provide guidance and mentoring to and professional networking. He cofounded
sion in the sciences. He established profes- innumerable students, faculty, and staff. the American Psychological Association’s
sional development programs for individuals Diversity Program in Neuroscience and
from underrepresented groups and provided In 1976, upon realizing that the psycho- the Summer Program in Neuroscience,
lifelong mentoring as they pursued careers logical health and well-being of Hispanics Excellence and Success (SPINES) at the
in science and academia. Joe was passion- was being overlooked at CSUSB, Joe or- Marine Biological Laboratory in Woods Hole,
ately devoted to expanding opportunities in ganized the First Symposium on Chicano Massachusetts. Through these programs, for
the sciences well before diversity became a Psychology. The following year, he edited more than 20 years, he guided nearly 300
visible goal for scientific organizations and Chicano Psychology, a book highlighting pa- graduate students and postdoctoral fellows
academic institutions. to careers in neuroscience and academia. He
pers from the conference, which established was also a founding member of the National
Born in Albuquerque, New Mexico, on him as a founder of the field of Chicano Hispanic Science Network (NHSN), which
1 August 1944, Joe received his bachelor’s psychology. The book, rereleased in 1984, is dedicated to improving the health equity
degree in psychology from the University remains essential reading for both research- of Hispanics by increasing interdisciplinary
of San Diego in 1966; his master’s in ex- ers and health care providers. Joe’s work in translational research and fostering the de-
perimental psychology from New Mexico this area continues to influence thought on velopment of Hispanic scientists. Through
Highlands University in 1968; and his bilingual education and culturally sensitive the NHSN, Joe influenced the careers of hun-
Ph.D. in physiological psychology from the mental health services. dreds more young scientists.
University of Delaware in 1971. His faculty
career began in 1972 at California State Despite the success of his psychology Students would often walk away from
University, San Bernardino (CSUSB), shortly work, Joe yearned to return to the lab. His a pleasant conversation with Joe, only to
after the campus was established. He later preclinical research on the neurobiology of realize later that he had shared a profound
completed postdocs in the laboratory of neu- learning and memory had begun at the be- and inspiring message, as well as guidance
robiologist James McGaugh at the University havioral level, exploring the neurobiologi- that would serve them for years or decades
of California, Irvine, and with neurobiolo- cal substrates of learning and memory, and to come. We all appreciated his low-key,
gist Floyd Bloom at the Salk Institute for had moved into electrophysiological, neu- understated approach to mentoring. K.A.T.
Biological Studies in San Diego, California. rochemical, and molecular mechanisms. He met Joe in the 1980s, A.Q.-H. trained as an
was at the forefront of demonstrating that undergraduate researcher in Joe’s labora-
The University of California, Berkeley, drugs and neurotransmitters have the ability tory in the early 1990s, and K.J.T. began
recruited Joe in 1982, and he served as a to modulate memory processes by acting on as a postdoctoral fellow on Joe’s research
professor as well as the area head of bio- targets outside as well as inside the brain. He team in the late 1990s. Each of us remem-
psychology and faculty assistant to the vice contributed to the finding that endogenous bers Joe fondly, not only for his mentor-
chancellor for affirmative action. As the opioids are involved in learning and memory. ship and the opportunities he created for
highest-ranking Hispanic faculty member us, but also for his kind heart, extraordi-
in the University of California system, Joe nary intellect, and his inspiring friendship.
used his voice to help others from under- Joe made us all feel like family.
represented groups. However, he felt that he
could have a greater impact on diversity in Joe was an elected fellow of multiple sci-
the sciences by helping to build a university entific societies, including the American
with a high concentration of Hispanic stu- Association for the Advancement of Science
dents, so in 1995 he moved to the University (AAAS, the publisher of Science). He was on
of Texas, San Antonio (UTSA). He began as a the editorial board of 10 different psychology
professor of biology and went on to assume a and neuroscience journals and held senior
range of leadership roles, including director editorial positions for several others. Joe’s
accomplishments have been recognized with
1Department of Psychology and Office for Training, several prestigious awards, including the
Research, and Education in the Sciences, California State AAAS Lifetime Mentor Award in 1994. An
University San Marcos, San Marcos, CA, USA. 2Department extraordinary scientist, mentor, and activist,
of Neurologic Surgery, Mayo Clinic, Jacksonville, FL, Joe was devoted to scientific excellence and
USA. 3Ponce Research Institute, Ponce Health Sciences to providing guidance and opportunities to
University, Ponce, PR, USA. Email: [email protected] others. His quiet yet strong presence will not
be forgotten. j

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INSIGHTS

POLICY FORUM most governments have not yet signaled how
they intend to spend their money. This uncer-
CLIMATE AND ENERGY tainty notwithstanding, the massive influx of
support will be consequential in shaping the
COVID-19 recovery funds dwarf postpandemic global economy.
clean energy investment needs
We demonstrate the potential impact
A modest fraction of current global stimulus funds can that current stimulus could have for a
put the world on track to achieve Paris Agreement goals low-carbon energy system transformation.
Although such a transformation requires
By Marina Andrijevic1,2, Carl-Friedrich activity picks up again and could ultimately a wide array of policy measures to come to
Schleussner1,2, Matthew J. Gidden1,3, have a negligible impact on global warming fruition, the spending and liquidity support
David L. McCollum4,5, Joeri Rogelj3,6 over the longer term—unless COVID-19 re- being put forward can be a powerful cata-
covery also induces a longer-term structural lyst for a climate-positive recovery.
G overnments around the globe are re- change in the economy (4).
sponding to the coronavirus disease INVESTMENT CONSISTENT WITH 1.5°C
2019 (COVID-19)–related economic STIMULUS PACKAGES TO DATE Quantitative modeling studies of pathways
crisis with unprecedented economic Governments have announced a variety of compatible with the Paris Agreement agree
recovery packages (1), which at the policy responses aimed at alleviating the that a low-carbon transformation is predi-
time of writing surpassed USD 12 consequences of the COVID-19 crisis (1). We cated on decarbonizing the production and
trillion. Several influential voices, including focus on economic stimulus tools deployed use of energy (3, 5, 6), responsible for about
the United Nations (UN) secretary-general, explicitly through countries’ fiscal systems, two-thirds of economy-wide greenhouse gas
heads of state, companies, investors, and taking stock of the packages for 149 coun- emissions. To meet the Paris goals, energy
central banks, have called for post–COVID-19 tries [see table S1 in the supplementary supply would need to fully decarbonize by
economic recovery efforts to be used to cata- materials (SM)]. As of end of August 2020, mid-century, if not before (3, 5, 6). Aggregate
lyze the necessary longer-term transforma- our tracking framework showed aggregate stimulus estimates (1), green recovery sce-
tion toward a more sustainable and resilient fiscal stimuli amounting to USD 12.2 tril- narios (7), or suggestions for green recovery
society. Here we shine a light on the opportu- lion, 80% of which comes from countries in policy packages (8) have been published,
nity for these investments to support a green the Organization for Economic Cooperation among a plethora of analyses related to the
recovery by inventorying and classifying the and Development (see the figure and fig. pandemic. We compare the magnitude of
latest information on governments’ fiscal S1). The U.S. stimulus is the largest single COVID-19 recovery stimulus to the levels of
stimulus plans (1) and comparing the size of package to date, constituting a quarter of energy system investment required for put-
these measures to estimates of low-carbon all global commitments, although the Euro- ting the world on a path toward achieving
energy investment needs compatible with the pean Union (EU) as a bloc accounts for even the goals of the Paris Agreement (5), based
2015 UN Paris Agreement. We show that low- more (combining measures by national gov- on the average estimate across six energy-
carbon investments to put the world on an ernments and the European Commission). economy models that were included in the
ambitious track toward net zero carbon di- recent Special Report on Global Warming
oxide emissions by mid-century are dwarfed Our disaggregation of the packages for of 1.5°C by the Intergovernmental Panel on
by currently announced COVID-19 stimulus this analysis follows the approach of the Climate Change (IPCC) (3). Although indi-
funds. But marked differences across coun- International Monetary Fund (IMF), whose vidual model estimates can differ by up to
tries and regions at differing stages of de- COVID-19 Policy Tracker is the source for ±50%, the conclusions deriving from our
velopment emphasize the role that interna- our stimulus data (1). Stimulus packages analysis are nevertheless robust. Invest-
tional support and global partnership must are divided into two categories: “above-the- ments here refer to capital expenses for re-
play to create conditions that enable a global line” measures and liquidity support. The source extraction, their conversion, power
climate-positive recovery. former includes additional spending and generation, transmission, and storage, to-
forgone or deferred revenue, whereas the gether with efficiency improvements that
Current climate commitments by coun- latter includes instruments such as loans, reduce energy use in buildings, transport,
tries for the next decade remain woefully guarantees, and equity injections. About and industry (see SM for details).
inadequate to meet the climate goals spelled 70% of stimulus can be classified as “above-
out in the Paris Agreement (2). Decisive ac- the-line” measures, with 7% targeted for the The crucial insight emerging from this
tion in the coming decade would be needed health sector and 63% for other sectors. The comparison (see the figure) is the following:
to set the emissions of the most important remaining 30% is for liquidity support. Low-carbon investments over the next several
greenhouse gas—carbon dioxide—on a path years to put the world on track toward net
to net zero by mid-century (3) while ensur- The level of specification of countries’ zero carbon dioxide emissions by mid-century
ing that livelihoods of billions of people in stimulus packages varies widely, limiting are dwarfed by COVID-19 stimulus. Though
developing countries continue to improve. understanding of the explicit targets gov- impressive, a closer look at the numbers
The record decline in global greenhouse gas ernments will aim to achieve with their points to opportunities as well as challenges.
emissions in the first half of 2020 due to the plans. Although several governments have
COVID-19–related economic disruption will announced their intentions to earmark por- 1Climate Analytics, Berlin, Germany. 2Integrative Research
almost certainly rebound when economic tions of their packages for a “green recovery,” Institute on Transformations of Human-Environment
the exact details remain largely unclear, and Systems, Humboldt University, Berlin, Germany. 3Energy
Program, International Institute for Applied Systems Analysis,
Laxenburg, Austria. 4Electric Power Research Institute, Palo
Alto, CA, USA. 5Howard H. Baker Jr. Center for Public Policy,
University of Tennessee, Knoxville, TN, USA. 6Grantham
Institute for Climate Change and the Environment, Imperial
College London, London, UK. Email: marina.andrijevic@hu-
berlin.de; [email protected]

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Average annual low-carbon energy and tilting toward a rather weak, pre-COVID cli- globally. This represents a mere 0.2% of the

end-use energy efficiency investment needs mate policy environment worldwide (3, 5). total announced stimulus to date (compare

under a Paris-compatible pathway have been The additional investment needed to shift figs. S5 and S1), or 1% over the 2020–2024

estimated at about USD 1.4 trillion per year low-carbon energy investment onto a Paris- period. These numbers highlight that a cli-

globally over the near term between 2020 compatible pathway thus amounts to about mate-positive COVID-19 recovery relies as

and 2024 (3, 5). This yearly estimate of low- USD 300 billion per year globally over the much on supporting green investments as it

carbon energy investments amounts to some coming 5 years (see the figure and figs. S5 to does on avoiding lock-in in polluting ones.

10% of the total pledged COVID-19 stimulus S7), less than 3% of total pledged stimulus to Of course, not all stimulus should be ex-

to date (see the figure and figs. S3 and S4), date or 12% when considered over the entire pected to go into the energy transition. Our

or about half of stimulus when investments 2020–2024 period. Simply put, if even a frac- analysis indicates that, understandably, a sub-

are cumulated over the 5-year 2020–2024 tion of current government stimulus would stantial number of shares of “above-the-line”

period. Given that stimulus is expected to be directed in a responsible manner toward measures are earmarked for other sectors,

be spent over the course of a few fiscal years a green recovery, the marginal benefits for a such as health and financial relief for individ-

only and governments have traditionally low-carbon future could be considerable. uals and households. Moreover, governments

are typically responsible for only a

limited share of investment in low-

Economic stimulus and energy investments carbon energy across the world (10).
What governments can do, though, is
Liquidity support includes loans, guarantees, and quasi-fiscal operations. General spending reflects measures aimed mobilize private investment by chan-
at non–health sectors of the economy and which include supporting individuals, households, and businesses, as well as neling stimulus into dedicated public
forgone and deferred revenue. Energy investments are representative of average annual energy system investments financing mechanisms. For example,
over the near term (2020–2024) in a low-carbon pathway consistent with achieving the UN Paris Agreement. Annual

investment shifts represent the difference in fossil fuel and low-carbon investments between current policies and a low- liquidity measures for development

carbon pathway consistent with the Paris Agreement. In the absence of specific sectoral allocations, announced stimulus banks can help them to proactively

is classified as General spending, e.g., for China. Data and additional figures are available in the supplementary materials. support low-carbon investments, par-

Coronavirus disease 2019 (COVID-19) stimulus: Liquidity support Health sector General spending ticularly in developing countries, and
through that reduce perceived risks
Energy investments: Fossil fuels Low carbon faced by private investors (11).

European Union Today’s exceptional circumstances
could also give rise to low-carbon en-
Stimulus ergy and efficiency investment needs
or opportunities that exceed those
Global Energy investment estimated by earlier studies. For ex-
Investment shift ample, today’s historically low inter-
Total est rates support the competitiveness
COVID-19 United States
stimulus

Annual energy India of green technologies. Moreover, the
investments in investment estimates relied upon
Paris-compatible here derive from welfare-optimizing
pathway scenarios using neoclassical economic
theory that assess substantial, yet sus-

Annual Shift in cumulative China tained and gradual changes in invest-
investment shift investments over ment patterns over the long term in
relative to the 2020–2024 an otherwise stable socioeconomic
current policies period context (5). These assumptions are

in stark contrast with today’s real-

0 4000 8000 12000 0 5 10 15 20 25 30 ity. Nonequilibrium economic theory
USD billion
% Gross domestic product might be more adequate in a crisis

context and may suggest that sub-

played a minority role in energy investment Despite the order-of-magnitude difference stantially increasing green investments be-

globally, the potential for the current tranche in these numbers, there is an important ad- yond the estimates provided here could offer

of public funding to support a green recovery ditional part to this story: Increases in low- further benefits for growth (12).

over the next years is thus enormous. carbon investments have to be accompanied

The comparison between stimulus fund- by divestments from high-carbon fossil fuels NATIONAL AND REGIONAL DIFFERENCES

ing and low-carbon energy investment needs in the range of USD 280 billion per year over Beyond the global situation, we find that

becomes sharper when concentrating spe- the same near-term period. These divest- when looking more regionally, total stimu-

cifically on those investments above and ments are distinct from the possible removal lus in all cases exceeds annual low-carbon

beyond a non–Paris-compatible trajectory, of fossil-fuel subsidies, which also range in energy investment needs for an ambitious

like the one society has been on up to now. the hundreds of billions of USD but mainly Paris-compatible pathway (see figs. S8 and

GRAPHIC: N. CARY/SCIENCE About USD 1.1 trillion per year of low-carbon target consumption instead of production of S9; here we look at macro regions as de-

energy investment has been estimated for fossil fuels (9). Subtracting divestments from fined in table S2 and which are often used

such a non-Paris path, together with an ac- investments indicates that the overall in- in energy-economy modeling). However,

companying USD 1.1 trillion in fossil fuels. crease in net annual investments to achieve an clear differences exist between regions and

These amounts would ensure sufficient in- ambitious low-carbon transformation in the countries. The EU and United States have

frastructure and technology deployment for energy sector are notably small (see fig. S3): issued the largest stimulus packages glob-

global energy demand to be met, yet still about 20 additional billion USD per year ally, both in absolute terms and relative to

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INSIGHTS | POLICY FORUM

the size of their economies. Total stimulus ECONOMY-WIDE BENEFITS disruption and accompanying economic
exceeds average annual low-carbon energy In the context of a postcrisis recovery, gov-
investment needs by a factor of 20 in the ernments will be looking for stimulus mea- hardship in the medium term will remain
United States and by over 30 in the EU (see sures that can boost employment, scale
the figure and fig. S2). Even when consid- rapidly, and increase societies’ resilience high. All of these attributes make holistic
ering the entire 2020–2024 period, total to future shocks. Targeting a green trans-
stimulus remains several times larger than formation of the energy system as the pro- green policies attractive in the context of a
low-carbon energy investment needs. verbial engine of the economy can provide
such ancillary benefits. Investment in clean postcrisis recovery, and given the many an-
Developing economies are in a different energy has been identified as a driver of em-
situation. So far, the combined stimulus ployment (7, 14); it can also spur innovation cillary society-wide benefits, governments
available to low- and lower-middle income and diffusion of technologies across bor-
countries amounts to only a tiny fraction ders—an essential catalyst for low-carbon may even choose to adopt green recovery
(less than 4%) of total global stimulus and transformations of economies worldwide
even including upper-middle income econo- (15). Renewable energy investments have targets beyond those presented here.
mies raises this share to 14% only. These demonstrated a large potential for job cre-
numbers exclude potential international ation and often offer a more desirable risk In sum, a small fraction of announced
support, which to date remains negligibly profile for investors (14). Technologies like
small compared to the pledged domestic solar photovoltaics and wind turbines are of COVID-19 economic recovery packages
COVID-19 stimulus. This discrepancy will a small, modular size that allows for a more
not only affect developing countries’ ability rapid upscaling of production and much could provide the necessary financial
to recover from the COVID-19 crisis but also shorter project lead times.
the world’s collective ability to achieve the basis for a decided shift toward a Paris
Paris Agreement climate goals. At the same time, achieving a low-carbon
transformation involves more than just Agreement–compatible future. The dual
Despite recovery packages in developing investments in low-carbon energy. It re-
countries being smaller than in developed quires a broad range of reinforcing policy crises of COVID-19 and climate change are
countries [both in absolute terms and as a
share of gross domestic product (GDP)], an- “…a climate-positive global problems requiring bold govern-
nual low-carbon energy investment needs COVID-19 recovery relies as
are generally larger in these rapidly growing ment action, international cooperation,
economies in a relative sense (see the figure much on supporting
and fig. S8). For example, India’s total annual green investments as it and sustainable and inclusive solutions.
low-carbon energy investment needs relative does on avoiding lock-in in
to its GDP are about four times higher than Though challenging politically, our find-
those of the EU, and the country’s stimulus polluting ones.”
package relative to its GDP is about a quarter ings show that these solutions are well
the size of the EU’s. measures, including taxation and subsidy
reform, research and innovation, profes- within budget. j
Institutionalizing international support sional training, and education. It will also
within intergovernmental systems such require a variety of financial instruments, REFERENCES AND NOTES
as the Green Climate Fund of the United from direct infrastructural investments and
Nations Framework Convention on Climate capital spending to liquidity support and 1. IMF, Policy Responses to COVID-19 - Policy
Change or multilateral development banks loan guarantees for private sector invest- Tracker. International Monetary Fund (2020);
could help to solidify the partnerships needed ments. In the post–COVID-19 context, this www.imf.org/en/Topics/imf-and-covid19/
to enable a global climate-positive recovery. means that beyond the fiscal injections that Policy-Responses-to-COVID-19.
Furthermore, targeted financial instruments, governments can supply, recovery packages
like blended finance, have also been sug- should encompass incentives, policies, taxes 2. N. Höhne et al., Nature 579, 25 (2020).
gested as a means to increase low-carbon or rebates, mandates, and other supportive 3. J. Rogelj et al., in Global Warming of 1.5 °C.An IPCC
investment flows to developing countries (11, regulations that facilitate the achievement
13). Blended finance uses government, mul- of long-term climate goals. special report on the impacts of global warming of 1.5 °C
tilateral, or philanthropic money to lower above preindustrial levels and related global greenhouse
the risk for private investors and therewith By serving as a clear signal to investors, gas emission pathways, in the context of strengthening
mobilize additional private investments in green recovery packages also reduce the the global response to the threat of climate change, sus-
developing countries. International support likelihood of stranded assets. By contrast, tainable development, and efforts to eradicate poverty,
of only a small fraction of current COVID-19 polluting recovery packages that include G. Flato et al., Eds. (IPCC/WMO, Geneva, Switzerland,
stimulus could thus already provide a lever to unconditional oil and gas company bail- 2018; www.ipcc.ch/report/sr15/), pp. 93–174.
catalyze a low-carbon transformation in this outs may serve to increase the number 4. P. Forster et al., Nat. Clim. Chang. 10, 913 (2020).
first half of the decade. of assets that will someday be stranded. 5. D. L. McCollum et al., Nat. Energy 3, 589 (2018).
Unless governments embed their stimulus 6. L. Clarke et al., in Climate Change 2014: Mitigation of
As developing countries are struggling support in a coherent long-term vision—for Climate Change. Contribution of Working Group III to the
with the economic fallout of the COVID-19 example, by combining support to pollut- Fifth Assessment Report of the Intergovernmental Panel
crisis, mobilizing additional domestic re- ing sectors with a reorientation program on Climate Change, O. Edenhofer et al., Eds. (Cambridge
sources might seem challenging, both finan- for their workforce—the risk for additional Univ. Press, 2014), pp. 413–510.
cially and politically. To this end, a range of 7. IEA,“Sustainable Recovery”(International Energy
measures with both near-term economic ben- Agency, Paris, France, 2020); www.iea.org/reports/
efits and long-term climate-positive potential sustainable-recovery.
can prove effective (8). 8. C. Hepburn, B. O’Callaghan, N. Stern,J. Stiglitz, D.
Zenghelis, Oxf. Rev. Econ. Policy 36 (suppl. 1), S359
(2020).
9. J.Jewell et al., Nature 554, 229 (2018).
10. IRENA, CPI, “Global Landscape of Renewable Energy
Finance” (International Renewable Energy Agency,Abu
Dhabi, 2018), p. 44.
11. B. Steffen,T. S. Schmidt, Nat. Energy 4, 75 (2019).
12. H. Pollitt,J.-F. Mercure, Clim. Policy 18, 184 (2018).
13. B.Tonkonogy,J. Brown,V. Micale,X.Wang,A. Clark,
“Blended Finance in Clean Energy: Experiences and
Opportunities” (Climate Policy Initiative, 2018), p. 38.
14. C.Wilson et al., Science 368, 36 (2020).
15. D.Acemoglu et al., Am. Econ. Rev. 108, 3450 (2018).
16. M.Andrijevic et al., Climate-analytics/covid_recovery:
Data and analysis scripts,Zenodo (2020); https://doi.
org/10.5281/zenodo.4058546.

ACKNOWLEDGMENTS

We thank E. Campiglio and J.Tanaka for their feedback on
international financial support mechanisms, and acknowl-
edge the contributions of J. Kim, B.Yesil, and K. Lee ,who
provided excellent research assistance for the curation of the
data. M.A. and C.F.S. acknowledge support by the German
Federal Ministry of Education and Research (01LS1905A).The
views expressed in this paper are those of the authors and do
not necessarily reflect those of their institutions.All data and
codes are available at Zenodo (16).

SUPPLEMENTARY MATERIALS

science.sciencemag.org/content/370/6514/298/suppl/DC1

10.1126/science.abc9697

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Frank Malina works on Cosmos, a piece meant
to capture an astronaut’s vision of the planets.

Bell Laboratories established creative spaces

for their employees and served as patrons for

artistic collaborations, while universities pri-

oritized the provision of studio space where

engineering students could dabble in the arts.

McCray introduces the reader to two cen-

tral figures in the postwar movement that

blurred the lines between artist and scien-

tist: Frank Malina, an aeronautical engineer

turned kinetic sculptor turned journal edi-

tor, and Billy Klüver, a Swedish engineer at

Bell Laboratories. Individual artists and en-

gineers had their own reasons for pursuing

collaboration. Many of the engineers, in-

cluding Malina and Klüver, had been drawn

to careers in art before opting for more

practical pursuits. The artists who sought

out alliances, meanwhile, were often look-

BOOKS et al. ing for engineers’ expertise to help actual-
ize their creative visions. But participants

from both disciplines were often united by

a shared interest in processes.

HISTORY OF SCIENCE Many of the projects that resulted from

Experiments in creativity this movement illuminated how art could be
assembled and how technology could inspire
audiences. In 1965, for example, Malina de-

Artists and engineers joined forces in the 1960s, signed a stunning electrokinetic sculpture,
called Cosmos, that captured an astronaut’s

blurring the line between art and technology vision of the planets from space. In Grass
Field, artist Alex Hay and engineer Herb

Schneider designed a bodysuit embedded

By Ingrid Ockert ences collaborations of the past opened up with electronic sensors that would amplify

opportunities for today’s interdisciplinary re- the movements of Hay’s heart, brain, and eye

T he acronym “STEAM,” which stands lationships at universities and corporations. muscles and transmit them as sounds. View-
for science, technology, engineering, McCray has built his career examining the ers watched as Hay sat motionless while the
art, and math, came into popularity in walls around them reverberated with noise.
2011, as scientists and educators pon- intersections between scientists and non-
dered the question of how to get more scientists. Arguably the foremost scholar McCray suggests that today’s STEAM ini-
of interdisciplinary communities, his work tiatives often have a clear economic under-

students interested in pursuing careers illuminates the many contribu- pinning, with many proponents

in science. Part of the answer, they reasoned, tions nonscientists have made to believing that collaborations

would be to make science courses more holis- the creation of scientific culture. between the arts and sciences

tic by incorporating the arts—but how might In Making Art Work, he carefully will lead to more innovative

this be done? For inspiration, they need only blends oral histories with insights (and profitable) designs. This is

have looked to the 1960s, when a cadre of art- derived from print archives. a marked shift from the overall

ists and engineers worked together to create McCray tells the story of three intention of the collaborations

media that would blur the lines between in- venues where the arts and sci- of the 1960s, which were driven

dividuals, art, and technology. ences mix: an art collective Making Art Work by more philosophical concerns.
That historic movement is the subject of W. known as Experiments in Art and W. Patrick McCray The arts-and-technology com-
Technology (E.A.T.), the intersec- MIT Press, 2020. 384 pp. munity has also grown larger
Patrick McCray’s excellent new book, Making tional academic journal Leon- and more global over the past
PHOTO: COURTESY OF THE MALINA FAMILY ARCHIVE Art Work, which provides a comprehensive

history of postwar artistic and scientific col- ardo, and the Los Angeles County Museum 50 years. Much like 50 years ago, however,

laborations in the United States. Over nine of Art. But while these institutions form this new renaissance of art and culture has

chapters, McCray’s meticulous research chal- the book’s main threads, the story tran- prompted many unusual alliances. And,

lenges C. P. Snow’s controversial “two-cul- scends their specific endeavors, revealing once these artistic and scientific collabora-

tures” mode of thinking (1), which suggested much about the ways that scientists and tions are in place, they will take on a life of

that scientists and artists exist in different artists create their identities. their own. “The experiment,” notes McCray,

intellectual worlds. McCray’s research reveals The 1960s, we learn, was a period of ex- has “been switched on.” j

the ways in which experimental arts and sci- istential identity crisis for engineers. Influ- REFERENCES AND NOTES
enced by a barrage of popular articles and
The reviewer is a historian of science based in Berkeley, CA, studies claiming that they led dull lives, en- 1. C. P. Snow, The Two Cultures and the Scientific Revolution
USA. Email: [email protected] gineers pushed back. Corporations such as (Oxford Univ. Press, 1959).
10.1126/science.abe4099

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INSIGHTS | BOOKS

SCIENCE LIVES The Sediments
of Time: My Lifelong
Tales from times long past Search for the Past
Meave Leakey with
Field adventures and human origin stories combine Samira Leakey
in a paleoanthropologist’s compelling new memoir Houghton Mifin Harcourt,
2020. 400 pp.

By Barbara J. King famous Lucy—and, at the time, represented ing a vegetable garden and modern hu- PHOTO: BOB CAMPBELL/COURTESY OF THE LEAKEY FAMILY
the earliest known hominin bipedality. mans wrecking our planet, but she places
W hy, unlike other primates, did our blame for Earth’s most recent climate dis-
ancestors begin to walk upright? Meticulous cross-site research by paleo- ruption where it belongs. Our long evo-
What factors enabled Homo anthropologists, including Leakey herself, lutionary lineage is at a crisis point, she
erectus to develop new cultural has revealed a shift in habitat and diet that argues, and it is critical that we rein in
practices and, later, to give rise occurred before the time of australopith- consumerist greed and environmental de-
to our own species? As paleo- ecines, wherein many species moved from struction before it is too late.
anthropologist Meave Leakey explains woodlands to grasslands and changed
in The Sediments of Time, understanding from browsers to grazers. We now know The book shines in its descriptions of
climate change is key in answering such that an “inexorable drying trend” around 5 what it is like to set up base camp in remote,
questions. Reflecting on 50 years of re- to 7 million years ago led to a reduction in sometimes harsh conditions and to search
search, largely at field sites around Lake forest cover and an increase in grasslands, the landscape relentlessly for small frag-
Turkana in Kenya’s Great Rift Valley, the which created new foraging opportunities. ments of bone that are all but invisible to
book—co-written with Leakey’s daughter the untrained eye, and Leakey writes with
Samira Leakey—is an engaging memoir in Leakey, with husband Richard and daughter Louise, a fine sense of humor. The image she cre-
which fieldwork adventures appear along- inspects fossil fragments in 1972. ates of Louis and Richard Leakey stripping
side dense details of Ice Age cycles, ice core naked and carrying giraffe bones into the
technology, fossil anatomy, and geological In turn, new selection pressures and biped- Serengeti plains to experiment with scav-
research. It serves as an invitation to grasp alism, a form of locomotion that was effi- enging behavior is one not soon forgotten.
how climate cycles have driven human cient and freed up hominin hands to take Better yet, she writes with humility. Leakey
evolution and how anthropogenic global on fine manipulative tasks, emerged. frequently praises individual members of
warming now threatens our species (and a her team as well as other scientists, with
multitude of others). Again and again, Leakey’s attention re- evident admiration for their skills. There
turns to climate. Homo erectus, she writes, is a shadow biography of Richard in the
A university student in the 1960s who evolved in a “glacial-interglacial icehouse book’s pages, too, with tales ranging from
wished to become a marine biologist, world,” where endurance hunting and in- the plane crash that necessitated a double
Meave Leakey encountered rampant sex- creased social cooperation led to survival leg amputation to his conservation work as
ism that kept women off research ships. and migration out of Africa. Later, Homo the head of the Kenya Wildlife Service.
“Eventually, I came to the realization that sapiens had to cope with even greater ex-
my chances of finding a job on a boat were tremes of cold and heat. These considerable strengths offset the
terribly slim and that I would need to few places where the science takes a wrong
consider alternatives,” she writes. When a In the book’s epilogue, Leakey draws a turn. “At birth, a chimpanzee, like all other
friend alerted her to an advertisement for strange analogy between baboons destroy- primates, is already grown enough to func-
employment at a primate research center tion independently of its mother,” for ex-
in Kenya, Meave rang the listed phone ample, is a misleading statement about
number and soon found herself working an ape whose offspring depend on their
there for the paleoanthropologist Louis mothers for years. Meanwhile, Leakey’s
Leakey. Thus began her lifelong love af- openness to genomic analysis in paleo-
fair with East Africa, one that eventually anthropology is welcome in a fossil hunter,
included Leakey’s son Richard, whom she but she credits much more to genes than
married in 1970. most anthropologists would be comfort-
able with, from Richard Leakey’s punc-
Having joined a world-famous fossil- tuality to his prominent ears. And her
hunting family, Meave would go on to observation that “more and more people
make spectacular finds that have reshaped are abandoning their traditional lifestyles
how human evolution is understood and for the melting pot of the big city” comes
taught. In 1994, for instance, her team dis- off as insensitive to inequalities of global
covered an early hominin fossil at Kanapoi power, which I feel certain that, in reality,
that was subsequently named Australo- she is not.
pithecus anamensis and dated to between
3.9 and 4.2 million years ago. This find Overall, however, The Sediments of Time
extended the time range for australopith- is a marvelous account of what it is like for
ecines—the same genus of hominin as the a celebrated scientist to take on some of
the most vital and vexing questions regard-
The reviewer is emerita professor of anthropology at William ing human origins and to come up with
& Mary, Williamsburg, VA 23185, USA. Email: [email protected] biocultural answers. j

10.1126/science.abe4107

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LETTERS

Ecosystems supported by Lake Balkhash in Kazakhstan are in jeopardy as desertification increases.

PHOTO: PATRICK BAZ/AFP/GETTY IMAGES Edited by Jennifer Sills will have nowhere else to go if their water Airborne transmission
source disappears.
Save Kazakhstan’s of SARS-CoV-2
To protect Lake Balkhash, local legisla-
shrinking Lake Balkhash tion that regulates industrial exploitation of There is overwhelming evidence that inhala-
the lake water area should be updated and tion of severe acute respiratory syndrome
Kazakhstan is home to Lake Balkhash, enforced. The media should actively pro- coronavirus 2 (SARS-CoV-2) represents a
one of the largest inland drainless lakes mote environmental awareness among the major transmission route for coronavirus
in the world. Estimated to be more than population of Kazakhstan. Designating Lake disease 2019 (COVID-19). There is an urgent
35,000 years old (1), this lake has cultural, Balkhash a national treasure would increase need to harmonize discussions about modes
historical, and ecological value. However, the social significance of the lake in of virus transmission across disciplines to
since 1970, a substantial decrease in the Kazakhstan as well as abroad. Kazakhstan ensure the most effective control strategies
Ili river runoff has led to a drawdown of should monitor the lake and provide public and provide clear and consistent guidance
water reaching the lake [(2), p. 18], lead- access to up-to-date data on its parameters to the public. To do so, we must clarify the
ing to a decrease in water depth. Out of (especially the current volume of water). terminology to distinguish between aerosols
the original 16 lake systems around Lake The country should also clearly define and droplets using a size threshold of 100
Balkhash, only 5 remain (1). Preserving areas of responsibility among the states µm, not the historical 5 µm (1). This size
this lake ecosystem is crucial to halt- that are responsible for water resources more effectively separates their aerodynamic
ing the desertification process, which management. Given rising water security behavior, ability to be inhaled, and efficacy
has already claimed a third of the lake risks in Kazakhstan, Lake Balkhash needs of interventions.
and will have devastating effects on the an international collaboration to provide
diverse flora and fauna that depend on it. urgent and effective protection. It is crucial Viruses in droplets (larger than 100 µm)
that local and national policy-makers, law typically fall to the ground in seconds within
Lake Balkhash’s varying degrees of enforcement authorities, scientists, the pub- 2 m of the source and can be sprayed like
water mineralization support a wide lic sector, socially responsible businesses, tiny cannonballs onto nearby individuals.
variety of species; the western basin is and the world community work together to Because of their limited travel range, physi-
freshwater, whereas the eastern basin is protect this ancient lake. cal distancing reduces exposure to these
salty (3). The lake serves as a habitat for droplets. Viruses in aerosols (smaller than
20 species of fish, 6 of which live only in Aizhan Ussenaliyeva 100 µm) can remain suspended in the air
this lake (3), and 60 species of plants that Save Lake Balkhash Project, Almaty, Kazakhstan. for many seconds to hours, like smoke, and
don’t grow anywhere else [(4), pp. 304– Email: [email protected] be inhaled. They are highly concentrated
310]. More than 120 bird species rely on near an infected person, so they can infect
the lake [(2), pp. 24–26], 12 of which are REFERENCES AND NOTES people most easily in close proximity. But
listed in Kazakhstan’s Red Book of endan- aerosols containing infectious virus (2) can
gered species [(4), p. 305]. Because the 1. D.K.Nourgaliev et al.,Geophys.Res.Lett.30,1914 (2003). also travel more than 2 m and accumulate
lake is located in a desert area, without 2. V. N.Abrosov, Lake Balkhash (Nauka, 1973) [in Russian]. in poorly ventilated indoor air, leading to
runoff and with a dry continental climate 3. “Lake Balkhash,”Encyclopaedia Britannica (2020); superspreading events (3).
and very little precipitation, these species
www.britannica.com/place/Lake-Balkhash#ref189927. Individuals with COVID-19, many of
4. D.V. Sevastyanov, E. D. Mamedov,V.A. Rumyanzev, The

History of the Lakes Sevan, Issyk-Kul, Balkhash,Zai-san,
and Aral (Nauka, 1991) [in Russian].

10.1126/science.abe7828

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INSIGHTS | LETTERS

whom have no symptoms, release thousands is a member of the Science Advisory Board and holds stock This blow to vulture conservation
options for Phylagen and is a paid reviewer for the Alfred P.
of virus-laden aerosols and far fewer droplets Sloan Foundation. R.T.S. is a member of the Gilead Sciences requires urgent action. Local stakehold-
Scientific Advisory Board and chairs Data Safety and
when breathing and talking (4–6). Thus, one Monitoring Boards for VIR, Gilead, and Merck. Honoraria for ers need to be made aware of the loss of
these activities are paid to the Regents of the University of
is far more likely to inhale aerosols than be California. R.T.S. has served as a scientific consultant to Pfizer critical ecosystem functions, such as waste
and to AbbVie. M.A.M. is the unpaid Chair of the National
sprayed by a droplet (7), and so the balance Academy of Medicine Committee on Personal Protective removal and the likely control of disease
Equipment for Workplace Safety and Health.
of attention must be shifted to protecting (5, 12). African governments should raise
Published online 5 October 2020
against airborne transmission. In addition 10.1126/science.abf0521 awareness about existing anti-poisoning

to existing mandates of mask-wearing, social Deliberate poisoning legislation among residents, authorities, and

distancing, and hygiene efforts, we urge of Africa’s vultures police and invest the human and financial

public health officials to add clear guidance Between September 2019 and March 2020, resources required to effectively enforce
more than 2000 Critically Endangered (1)
about the importance of moving activities hooded vultures (Necrosyrtes monachus) these laws. In addition, the governments
were killed across eastern Guinea-Bissau.
outdoors, improving indoor air using ventila- Investigations revealed that the vultures should curb cross-border and local trade.
were intentionally poisoned to collect
tion and filtration, and improving protection their heads for belief-based use. Locals International partners must help West
sighted bait placed where vultures died
for high-risk workers (8). and reported a demand for vulture heads African countries develop and implement
in Senegal (2, 3). Toxicological analysis
Kimberly A. Prather1*, Linsey C. Marr2*, Robert T. of carcasses confirmed poisoning with national action plans to conserve vultures
Schooley3, Melissa A. McDiarmid4, Mary E. Wilson5,6, methiocarb (3), a carbamate pesticide
Donald K. Milton7 banned in Europe (4) but still used in and avoid their looming extinction.
1Scripps Institution of Oceanography, University Guinea-Bissau. If unchecked, these poi-
of California San Diego, La Jolla, CA 92037, USA. sonings are likely to continue, leading to Mohamed Henriques1*, Ralph Buij2,3, Hamilton
2Civil and Environmental Engineering, Virginia further declines in the population of this Monteiro4,5, Joãozinho Sá4,6, Francisco Wambar4,
Tech, Blacksburg, VA 24061, USA. 3Department imperiled species. José Pedro Tavares7, Andre Botha8, Geoffroy
of Medicine, University of California San Diego, La Citegetse9, Miguel Lecoq10, Paulo Catry11,
Jolla, CA 92093, USA. 4Division of Occupational & Old World vultures are among the most Darcy Ogada2,12
Environmental Medicine, University of Maryland threatened groups of birds worldwide (5). 1Centro de Estudos do Ambiente e do Mar (CESAM),
School of Medicine, Baltimore, MD 21201, USA. In Africa, the illicit trade in vulture parts Departamento de Biologia Animal, Faculdade
5School of Medicine, University of California, San accounts for 29% of reported vulture deaths de Ciências da Universidade de Lisboa, Lisboa,
Francisco, CA 94143, USA. 6Harvard T.H. Chan School (6). In West Africa, up to 61 and 70% (inside Portugal. 2The Peregrine Fund, Boise, ID 83709,
of Public Health, Boston, MA 02115, USA. 7Institute and outside parks, respectively) of vultures USA. 3Wageningen University & Research, 6708
for Applied Environmental Health, University of disappeared in just 30 years (7). Hundreds of PB Wageningen, Netherlands. 4Organização para
Maryland, College Park, MD 20742, USA. hooded vultures are traded yearly for belief- a Defesa e Desenvolvimento das Zonas Húmidas
*Corresponding author. Email: [email protected] based use, and their heads are considered (ODZH), Bairro de Belém, Bissau, Guinea-Bissau.
(K.A.P.); [email protected] (L.C.M.) good luck charms (8). Prices are rising as 5Instituto da Biodiversidade e Áreas Protegidas,
they become more rare (8, 9). Guinea-Bissau Bissau, Guinea-Bissau. 6Gabinete de Planificação
REFERENCES AND NOTES is home to about 22% of the world’s 197,000 Costeira (GPC), Bairro de Belém, Bissau, Guinea-
hooded vultures (10, 11). Bissau. 7Vulture Conservation Foundation, CH-8003
1. The National Academies of Sciences, Engineering, and Zürich, Switzerland. 8Endangered Wildlife Trust,
Medicine,“Video 31—CQ1 reflection and syntheses: Modderfontein, 1645, South Africa. 9BirdLife
Identifying opportunities and gaps on the path ahead International, Conservation of Migratory Birds
by Kim Prather”(Airborne Transmission of SARS- Project, Dakar, Senegal. 10Lisbon, 1900-087,
CoV-2: AVirtual Workshop, 26 to 27 August 2020); Portugal. 11Marine and Environmental Sciences
www.nationalacademies.org/event/08-26-2020/ Centre, Instituto Universitário, Lisbon, Portugal.
airborne-transmission-of-sars-cov-2-a-virtual-workshop. 12National Museums of Kenya, Nairobi, Kenya.
*Corresponding author.
2. J.A. Lednicky et al., Int.J. Infect. Dis., 10.1016/j. Email: [email protected]
ijid.2020.09.025 (2020).
REFERENCES AND NOTES
3. S. L. Miller et al., Indoor Air, 10.1111/ina.12751 (2020).
4. K.A. Prather, C. C.Wang, R.T. Schooley, Science 368, 1422 1. BirdLife International,“Necrosyrtes monachus
(amended version of 2017 assessment)”
(2020). (The IUCN Red List of Threatened Species, 2017).
5. V. Stadnytskyi, C. E. Bax,A. Bax, P.Anfinrud, Proc. Natl.
2. L.Kihumba,“Investigating the mystery behind Guinea-
Acad. Sci. U.S.A. 117, 11875 (2020). Bissau’s mass vulture deaths”(BirdLife International,
6. J.Ma et al.,Clin.Infect.Dis.,10.1093/cid/ciaa1283 (2020). 2020).
7. W. Chen et al. Build. Environ. 176, 106859 (2020).
8. L. Morawska et al., Environ. Int. 142, 105832 (2020). 3. “Lethal poisoning of 2000+ Critically Endangered vultures
in Guinea-Bissau— Update on the toxicology results and
COMPETING INTERESTS criminal investigation”(Vulture Conservation Foundation,
2020).
K.A.P. is Director of the National Science Foundation Center
for Aerosol Impacts on Chemistry of the Environment. L.C.M. 4. Regulation (EU) 2019/1606 (2019); http://data.europa.
eu/eli/reg_impl/2019/1606/oj.
Hooded vultures (Necrosyrtes monachus) in Guinea-Bissau could be driven to extinction. PHOTO: PEDRO NARRA/MINDEN PICTURES
5. E. R. Buechley, Ç. H. Şekercioğlu, Biol. Conserv. 198,
220 (2016).

6. D.Ogada et al.,Conserv.Lett.9,89 (2015).
7. J.-M.Thiollay,Ostrich 78,405 (2007).
8. G.Nikolaus,Malimbus 23,45 (2001).
9. G.Nikolaus,Vulture News 55,65 (2006).
10. M.Henriques et al.,PLOS One 13,e0190594 (2018).
11. D.L.Ogada,R.Buij,Ostrich 82,101 (2011).
12. P.I.Plaza,G.Blanco,S.A.Lambertucci,Ibis, 10.1111/

ibi.12865 (2020).

COMPETING INTERESTS

M.H., R.B.,J.P.T.,A.B., and D.O. are members of the IUCN
Species Survival Commission Vulture Specialist Group.
M.H. receives funding from Fundação para a Ciência e a
Tecnologia (FCT Portugal) through the strategic projects
UIDB/50017/2020 and UIDP/50017/2020 granted to
CESAM and from the doctoral grant SFRH/BD/131148/2017.
H.M. receives funding from the Institute for Biodiversity and
Protected Areas. F.W., H.M., and J.S. receive funding through
BirdLife International funds granted to ODZH.

10.1126/science.abd1862

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RESEARCH Colored scanning for a 6-month dosing interval
electron microscope and is in phase 2/3 clinical trials.
IN SCIENCE JOURNALS image of blood vessels Bester et al. describe structural
in kidney glomeruli, and biophysical studies that
Edited by Michael Funk which are structures provide a basis for the potent
antiviral activity of GS-6207. The
that produce HIV capsid is cone shaped, and
filtrate from the blood GS-6207 binds two neighboring
capsid subunits and stabilizes
the curved capsid. GS-6207 also
interferes with capsid binding
of cofactors that play a role in
viral infection. This insight into
GS-6207 activity provides a
platform for the rational develop-
ment of improved long-acting
therapies. —VV

Science, this issue p. 360

PHYSIOLOGY MUCOSAL IMMUNITY

Pressuring kidney cells A nose for inflammation
into endocytosis
Nasal-associated lymphoid
W hen the kidneys filter the blood tissues (NALTs) are lymphoid
through structures called glomeruli, organs in the nasal mucosa
circulating proteins such as albumin that are sites of inhaled antigen
are reabsorbed to limit proteinuria deposition. Bedford et al. stud-
(protein in the urine) and prevent ied the induction of immunity
damage to kidney cells. Gualdani et al. found in NALTs and identified a role
that mechanosensing induced by fluid flow for conventional dendritic cells
through the kidneys activated the cation (cDCs) in suppressing T cell
channel TRPV4 to promote the endocytosis responses during the steady
of albumin by kidney cells. Experimental state. Similar cDCs are found in
manipulations that impair glomerular filtra- human NALTs in adenoids and
tion exacerbated proteinuria in mice lacking tonsils and can also inhibit T cell
TRPV4. Thus, defects in TRPV4-mediated responses and prevent immune
endocytosis may underlie proteinuria, a activation. Inflammation in
symptom of many kidney diseases. —WW nasal mucosa caused by viral
infection induces local recruit-
Sci. Signal. 13, eabc6967 (2020). ment of monocyte-derived DCs,
which overrides the effects
IMAGE: SUSUMU NISHINAGA/CIENCE SOURCE T H E R M O G A LVA N I C S heat to be recovered. The STRUCTURAL BIOLOGY of cDCs and allows for T cell
authors added a component priming. These results pro-
Recovering low- that boosts the concentration Attacking HIV by vide mechanistic insight into
temperature heat gradient by forcing crystalliza- stabilizing its capsid steady-state and inflammatory
tion of the electrolyte at the responses in NALTs. —CNF
Low-temperature heat sources cold end, and these crystals Current HIV treatments require
are both abundant and largely then melt at the hot end. This drugs that must be taken daily, Sci. Immunol. 5, eabb5439 (2020).
dissipated into the environment. process boosts efficiency and is and care would be improved with
Yu et al. discovered a way to a potential method for recover- an effective drug that is long- INORGANIC CHEMISTRY
boost the concentration gradi- ing low-grade heat. —BG acting. GS-6207 (Lenacapavir)
ent in a liquid thermogalvanic is a drug developed by Gilead Nitrogen lifts iron
cell that allows low-temperature Science, this issue p. 342 Sciences that shows potential to hexavalence

The myriad ways that iron can
interact with oxygen have been
amply studied in biochemical
and geochemical contexts.
More recently, chemists have
explored the extent to which
nitrogen can likewise stabilize
iron in high oxidation states.
Martinez et al. now report that
an iron center coordinated
by carbene ligands can react

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RESEARCH | IN SCIENCE JOURNALS

with an organic azide to form a SPECTROSCOPY IN OTHER JOURNALS Edited by Caroline Ash
pentavalent bis(imido) com- and Jesse Smith
plex with two Fe=N bonds. The travel time of light
One-electron oxidation then in a molecule
accessed the Fe(VI) oxidation
state. Both compounds were There is currently considerable
sufficiently stable for crystallo- interest in experimental studies
graphic characterization. —JSY of various ultrafast processes. Of
particular interest are the real-
Science, this issue p. 356 time dynamics of photoionization,
one of the most fundamental
PHYSIOLOGY processes caused by the light-
matter interaction, in which the
Metabolomics, at the heart absorption of a photon leads to
the ejection of an electron and the
With heart failure a lead- formation of anion. Using an elec-
ing cause of death, a better tron interferometric technique,
understanding of metabolic Grundmann et al. report a birth
function in the heart is a time delay on the order of a few
welcome advance. Murashige hundred zeptoseconds between
et al. measured more than two electron emissions from the
270 metabolites using liq- two sides of molecular hydro-
uid chromatography–mass gen, which is interpreted as the
spectrometry in human blood travel time of the photon across
samples taken from an artery the molecule. The proposed
entering the heart and from technique is generally applicable
a vein leaving it. Differences to more complex systems, and
thus reflected the metabolic further studies are necessary to
processes at work in the heart. support this interpretation. —YS
Their results confirmed that
hearts voraciously consume Science, this issue p. 339
fatty acids. Hearts secreted,
rather than consumed, amino ECOLOGY PHYSIOLOGY IMAGES: (LEFT TO RIGHT) ALFRED PASIEKA/SCIENCE SOURCE; NHMLA COMMUNITY SCIENCE PROGRAM/CC BY-NC
acids, thus revealing active
proteolysis. In patients with Species richness Enduring muscular courtship
heart failure, ketone and lactate maintains mutualisms
consumption increased, as S everal species of male amphibians and reptiles hold
did proteolysis. These findings Mutualistic communities of tight to their partners, possibly to prevent them mating
could lead to strategies for species that benefit each other with their rivals. The southern alligator lizard (Elgaria
fighting heart disease by alter- are ubiquitous in ecosystems multicarinata) clamps its mate’s head in its jaws for
ing metabolism. —LBR and are important for ecosys- hours. This extreme muscular performance runs coun-
tem functioning. However, the ter to expectations of reptilian muscle resilience. Nguyen et
Science, this issue p. 364 relationship between the persis- al. tested the sustained bite force of the adductor muscles
tence of mutualisms and species of the lizard’s jaw for fatigue. Muscle fibers can specialize, in
Artistic rendering of the human heart richness has remained unclear. terms of performance, into fast-acting twitch fibers and into
featuring exterior blood vessels, Vidal et al. used a synthetic slow-acting tonic fibers that are capable of fatigue-resistant
which deliver nutrients and oxygen mutualism in brewer’s yeast to contraction. Tonic fibers also exhibit slow calcium fluxes and
to this energy-intensive organ experimentally test whether spe- relax slowly. The lizards’ jaw muscle appears to have evolved
cies richness buffers mutualistic to comprise fast-twitch fibers for eating and slow-tonic fibers
communities against exploita- that can sustain an extended courtship grip. —CA
tion by species that do not
provide benefits in return. They Proc. R. Soc. London Ser. B 287, 20201578 (2020).
showed that richer mutualist
communities survive exploita- The southern alligator lizard Elgaria multicarinata will grip the head
tion more often than pairwise of its mate for hours, thanks to specialized jaw muscle fbers.
mutualisms and that higher
species richness and functional SINGLE-CELL METHODS function of one of the world’s
redundancy allow mutualist major cities. Instead of human
communities to persist in the Watching information couriers, within our cells,
presence of exploiters. These flow inside cells messenger RNAs (mRNAs)
results provide experimental carry information. Thousands
support for the hypothesis that Each human cell has an infor- of mRNAs emerge from the
species richness is necessary for mation network like a subway cell’s nucleus with instructions
the function and maintenance of system underpinning the
mutualistic communities. —AMS

Science, this issue p. 346

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for cellular functions and M E TA L LU R GY using wild climbing plants to The authors show that the direc-
disappear into the cytoplasm make baskets and winnowers tion of current flow is dependent
when their duties are fulfilled. Nature’s guide for and using plastic containers and on the polarization state of the
Because of the development alloy design devices. The authors accounted light, and further control can
of single-cell sequencing for food security, potential for be achieved with back-gating
techniques, we are now very Metallic alloys composed of plastic pollution, and the con- and an in-plane electric field.
good at counting these mes- many different elements are servation status of 15 species of Combined with the possibility of
sengers, which are specific to often hard to identify and isolate climbing plants around Bwindi engineering the heterostructures
each cell type in our body. Qiu because of the large number of Impenetrable National Park, and the number of materials
et al. developed a new method potential combinations. Wei et Uganda. Families that had per- available with different proper-
to watch the movement of al. started with a nine-element mission to collect wild climbing ties, this work demonstrates that
mRNAs. The technique can mixture and assessed the plants had more food storage the monolayer transition metal
distinguish newly synthesized phase-separated zones that and processing devices than dichalcogenides can serve as
mRNAs from older ones and arose from natural mixing. They those who did not. Although a versatile platform for future
track each mRNA with a spe- used the phase composition for this study identified the risks of optoelectronic device technol-
cific tag. This method provides designing a titanium-vanadium- overharvesting one vulnerable ogy. —ISO
a picture of the information niobium-hafnium refractory climber species, it also showed
flow inside cells and shows alloy with attractive ductility. that families with access to Optica 7, 1204 (2020).
how they become disrupted by This strategy provides a method natural materials experienced
genetic perturbations that can for screening and isolating com- greater food security and less ARCTIC OZONE
cause cancer. —DJ plex element compositions that plastic use and waste. —SNV
may have outstanding proper- The hole truth
Nat. Methods 17, 991 (2020). ties. —BG Conserv. Sci. Pract. 2, e275 (2020).
Ozone loss in the Arctic strato-
IMMUNOLOGY Nat. Mater. 10.1038/ OPTOELECTRONICS sphere has never been as severe
s41563-020-0750-4 (2020). as that in the Antarctic ozone
Imaging antigen- Directing the flow hole, but during the past year, it
specific T cells C O N S E R VAT I O N of photocurrent declined to a level a bit closer to
that of its southern counterpart.
Positron emission tomog- Plastic trade-offs The next generation of infor- Wohltmann et al. report that dur-
raphy (PET) has previously mation-processing devices is ing the northern spring of 2020,
been exploited to trace In just over 100 years, plastics expected to be more energy Arctic stratospheric ozone levels
immune responses in living have become both a necessity efficient if the spin or valley fell to near zero in some places.
animals. However, its use has and a scourge, replacing natural degrees of freedom of a material This unprecedented depletion,
been largely limited to cells materials in a myriad of uses is used to encode and carry caused by unusually cold and
expressing surrogate markers and becoming a ubiquitous information. Rasmita et al. show stable conditions in the Arctic
recognized by radiolabeled contaminant both in ecosys- that circularly polarized light can stratosphere, could become
antibodies or cells genetically tems and within organisms. induce a directional photocur- more frequent or extensive if the
modified to take up radiola- For human populations in and rent in heterostructures of the recent trend toward colder Arctic
beled substrates. Woodham et around tropical forests, natural two-dimensional transition metal winters continues. —HJS
al. now report a nonintrusive, in materials are available to pro- dichalcogenides MoS2 and WSe2.
vivo method to track antigen- cess and store food. Bitariho et Geophys. Res Lett.
specific T cells that recognize al. looked at trade-offs between 10.1029/2020GL089547 (2020).
known antigens presented
PHOTO: ANDREW AITCHISON/ALAMY STOCK PHOTO by major histocompatibility The people who live around Bwindi Impenetrable Forest are skilled craftsfolk who select climbing plants for materials to make
complex (MHC) molecules. food-storage containers, thus avoiding the use of plastic alternatives that are not biodegradable.
The authors made a class of
radiolabeled peptide-bound
MHC dimers linked to antibody
Fc regions, which they called
“synTacs.” In a mouse model of
cancer, they were able to follow
CD8+ T cells within tumors that
recognized a particular oncop-
rotein. They could also detect
influenza virus (IAV) nucleopro-
tein–specific CD8+ T cells in the
lungs of IAV-infected mice. This
work may help pave the way for
future tools to noninvasively
track human T cell responses
during interventions such as
vaccination and cancer immu-
notherapy. —STS

Nat. Methods 17, 1025 (2020).

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RESEARCH

ALSO IN SCIENCE JOURNALS
Edited by Michael Funk

CORONAVIRUS many challenges to overcome to antibiotic resistance. —STS response with their area. This
ensure that such neurotechnolo- Science, this issue p. 309; work explains how cells of dif-
COVID-19 risks gies improve quality of life and see also p. 294 ferent sizes within an epithelial
for children can be tolerated. —GKA tissue collectively adapt their
CELL BIOLOGY mechanical response to control
There has been substantial Science, this issue p. 290 tissue shape and proliferation.
discourse about how children The nucleus makes Scaling of biological properties
are affected by severe acute NEURODEVELOPMENT the rules with size is a core property of
respiratory syndrome corona- other biological systems. —BAP
virus 2 (SARS-CoV-2) infection. A moment in time Single cells continuously experi-
A fraction of children develop a ence and react to mechanical Science, this issue p. 312
hyperinflammatory syndrome As the brain develops, it does not challenges in three-dimensional
that is clearly a cause for con- simply get bigger. Like a building tissues. Spatial constraints in NEUROSCIENCE
cern. However, many children that depends on temporary dense tissues, physical activity,
seem to develop mild or asymp- scaffolds as its structures are and injury all impose changes How neuron types encode
tomatic infections, yet they assembled, the developing in cell shape. How cells can behavioral states
are harmed by the lockdown brain sets up the circuits that measure shape deforma-
measures to prevent SARS- characterize the adult brain. tions to ensure correct tissue What is the contribution of
CoV-2 spread. In a Perspective, Molnár et al. review the current development and homeostasis molecularly defined cell types
Snape and Viner discuss what state of knowledge about how remains largely unknown (see to neural coding of stimuli
is known about coronavirus dis- brain connections are built and the Perspective by Shen and and states? Xu et al. aimed to
ease 2019 (COVID-19) in children how autonomously established Niethammer). Working inde- evaluate neural representation
and young adults and whether patterns are reshaped by activity pendently, Venturini et al. and of multiple behavioral states
they can spread the virus. from the sensory periphery. With Lomakin et al. now show that the in the mouse paraventricular
They discuss the impacts of the help of a transient popula- nucleus can act as an intracel- hypothalamus. To achieve this
lockdowns on education, social tion of neurons, the spontaneous lular ruler to measure cellular goal, they combined deep-brain
care, and mental health, as well activity of early circuits is shape variations. The nuclear two-photon imaging with post
as deleterious effects on child molded by increasing inputs envelope provides a gauge of hoc validation of gene expres-
health in terms of accidents at from the external world. When cell deformation and activates a sion in the imaged cells. The
home and maintaining vaccina- these normal developmental mechanotransduction pathway behavioral states could be well
tion programs. Although more interactions are disrupted, that controls actomyosin con- predicted by the neural response
research is needed, such harms consequent miswiring drives tractility and migration plasticity. of multiple neuronal clusters.
should be considered when dysfunction in the adult brain. The cell nucleus thereby allows Some clusters were broadly
evaluating control measures in —PJH cells to adapt their behavior to tuned and contributed strongly
the future. —GKA the local tissue microenviron- to the decoding of multiple
Science, this issue p. 308 ment. —SMH behavioral states, whereas oth-
Science, this issue p. 286 ers were more specifically tuned
INNATE IMMUNITY Science, this issue p. 311, p. 310; to certain behaviors or specific
NEUROSCIENCE see also p. 295 time windows of a behavioral
Cells drop a bomb state. —PRS
Improving prosthetics on pathogens DEVELOPMENTAL BIOLOGY
Science, this issue p. 313
People who use upper- and Lipid droplets (LDs) accumulate Fiber tension enables
lower-limb prosthetics face in cells to serve as lipid storage tissue scaling M I C R O B I O TA
numerous challenges caused organelles. They are also an
by limitations in the interface attractive source of nutrients Tissue development, homeo- Metabolic signals
between person and machine. for many pathogens. Bosch et stasis, and repair require cells from gut microbes
Ideally, prosthetics should have al. show that various proteins to sense mechanical forces.
bidirectional communication involved in innate immunity form Although many molecular actors The gut is a stretchy, glandu-
between the user and the device complexes on LDs in response implicated in cell mechanosen- lar, and highly innervated tube
so that people can easily and to bacterial lipopolysaccharide sitivity have been extensively packed at its distal end with
intuitively use their devices. (see the Perspective by Green). studied, the basis by which microorganisms. Disruption of
Key to bidirectional interfacing Upon activation, LDs became cells adapt their mechanical the microbial community can
is motor control and sensing. physically uncoupled from mito- responses to their geometry lead to metabolic disorders such
In a Perspective, Raspopovic chondria, driving a shift in cells remains poorly defined. López- as obesity and diabetes. Muller
discusses approaches to provid- from oxidative phosphorylation Gay et al. now identify how et al. investigated how the micro-
ing improved motor control and to aerobic glycolysis. This work two fundamental epithelial biota interacts with the enteric
sensing through various sensors highlights the ability of LDs both structures—stress fibers and nervous system to induce a
and implants. Recent studies to kill pathogens directly and to tricellular junctions—endow metabolic outcome. A population
suggest that motor control and establish a metabolic environ- Drosophila cells with an internal of autonomous enteric neu-
sensing can be combined to ment conducive to host defense. ruler to scale their mechanical rons called CART+ neurons are
improve the experience for users This may inform future antimi- enriched in the ileum and colon,
of prosthetics, but there are crobial strategies in the age of

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RESEARCH

where most of the microbiota ULTRACOLD CHEMISTRY SIGNAL TRANSDUCTION PLANETARY SCIENCE
resides. Stimulation or ablation
of the CART+ neurons alters Non-Feshbach ultracold Intricacies of amino Protecting Earth’s early
blood glucose levels, insulin, and molecules acid sensing atmosphere
feeding behavior. Furthermore,
by manipulating the microbiota, The formation of ultracold The way in which cells sense When planetary bodies form
the density of enteric neurons molecules has already had amino acids derived from with nascent atmospheres,
responds plastically in an induc- a profound impact on many external proteins taken up by those atmospheres are at risk
ible and reversible manner. —CA research areas of physics. micropinocytosis and then of being stripped away by solar
However, conventional methods degraded in the lysosome turns winds. However, a planet’s
Science, this issue p. 314 of producing such molecules out to be different from the way magnetic field, if sufficiently
are attainable only for a limited in which they sense external strong, can provide a shield
MORPHOGENS number of systems or they suf- amino acids taken up through against solar winds and preserve
fer for strong dephasing. He et transporters in the plasma mem- the atmosphere. Previous stud-
Engineering synthetic al. sought to pair atoms, through brane. Both sources of amino ies have shown that the early
morphogens coupling of their spins, to the acids end up activating the Earth had a geomagnetic field,
two-body relative motion medi- mechanistic target of rapamycin but its strength remains poorly
Morphogens provide positional ated by the inherent polarization complex 1 (mTORC1) protein understood and questions
information during tissue gradients in a strongly focused kinase complex. However, remain as to how Earth’s early
development. For this behavior trapping laser. They report a suc- Hesketh et al. found that cul- atmosphere survived. Green et
to occur, morphogens must cessful assembly of an ultracold tured human cells sense amino al. hypothesized that one part of
spread out and form a con- 87Rb-85Rb molecule in an optical acids derived from exogenous the answer may be the magnetic
centration gradient; however, tweezer and observed coher- proteins in late endosomes by a field of the nearby early Moon,
their mechanism of transport ent, long-lived atom-molecule mechanism independent of the for which there is evidence
remains a matter of debate. Rabi oscillations. They further Rag guanosine triphosphatases from paleomagnetic studies of
Stapornwongkul et al. now show demonstrate the full control of (GTPases) that control mTORC1 returned lunar samples. Models
that in the presence of extracel- the internal and external degrees activation in response to external of the coupled Earth and Moon
lular binding elements (binders), of freedom in the atom-molecule amino acids. Furthermore, the magnetospheres suggest that
the inert green fluorescent pro- system. —YS GATOR GTPase had an inhibitory they may have provided an effec-
tein (GFP) can form a detectable effect on mTORC1 activation in tive barrier to strong solar winds,
concentration gradient by diffu- Science, this issue p. 331 response to proteins processed protecting Earth’s atmosphere
sion in the developing fly wing through the lysosome, opposite until at least 2.5 billion years
(see the Perspective by Barkai HYDROGELS to its role in sensing amino acids ago. —KVH
and Shilo). When combining the taken up across the plasma
expression of nonsignaling bind- Slippery surfaces membrane. —LBR Sci. Adv. 10.1126/sciadv.abc0865
ers and receptors engineered using lipids
to respond to GFP, a synthetic Science, this issue p. 351 (2020).
GFP gradient can substitute In engineered systems, a
for a natural morphogen to reduction in friction can come M I C R O B I O TA
organize growth and patterning. from the use of lubricants or
In related work, Toda et al. also through surface coatings that A parasite’s bilious
show that GFP can be converted are inherently slippery. For most defense
into a morphogen by provid- hydrogels, which are cross-linked
ing anchoring interactions that polymers heavily swelled with The enteropathogenic parasite
tether the molecule, forming a water, surface lubrication typi- Giardia lamblia is a frequent
gradient that can be recognized cally comes from trapped liquids cause of self-limited diarrhea
by synthetic receptors that that help to form a slippery sur- in infected adult travelers. By
activate gene expression. These face. Drawing inspiration from contrast, parasitic infection of
synthetic morphogens can be articular cartilage that in part children in endemic areas is
used to program de novo multi- uses a lipid boundary layer, Lin et not associated with diarrheal
domain tissue patterns. These al. designed hydrogels with small disease but rather with reduced
results highlight core mecha- concentrations of lipids that are body weight gain and growth.
nisms of morphogen signaling continuously exuded toward Riba et al. established a G. lam-
and patterning and provide the surface to make a slippery blia infection model in neonatal
ways to program spatial tissue layer (see the Perspective by mice. Infected neonatal animals
organization independently Schmidt). Friction and wear of displayed reduced weight gain
from endogenous morphogen the hydrogels was reduced by and growth. Analysis of these
pathways. —BAP up to a factor of 100, and the animals showed that G. lamblia
effect was observed even after induced bile secretion and
Science, this issue p. 321, p. 327; the hydrogels were dried and that an altered gut microbiota
see also p. 292 rehydrated. —MSL composition, bile acid modifica-
tion by commensal bacteria, and
Science, this issue p. 335; subsequent alterations of lipid
see also p. 288 metabolism contributed to this
phenotype. —OMS
Sci. Transl. Med. 12, eaay7019 (2020).

SCIENCE sciencemag.org 16 OCTOBER 2020 • VOL 370 ISSUE 6514 307-C

Published by AAAS

RESEARCH

◥ works. These networks become established in
an autonomous fashion before the arrival of
REVIEW SUMMARY signals from the sensory periphery and before
the maturation of cortical circuits. The sub-
NEURODEVELOPMENT plate, which is a transient structure located
below the developing cortical plate, orches-
Transient cortical circuits match spontaneous and trates alignment of these autonomously estab-
sensory-driven activity during development lished pathways by integrating spontaneous
and sensory-driven activity patterns during
Zoltán Molnár*, Heiko J. Luhmann*, Patrick O. Kanold* critical stages of early development.

BACKGROUND: During early mammalian brain zontal layers and translaminar radial circuits ADVANCES: The subplate contains heteroge-
development, transient neurons and circuits (“cortical columns”). Patterns of spontaneous neous neuronal populations with distinct
form the scaffold for the development of neu- activity during early development synchronize characteristics, such as origin, birthdate, neuro-
ronal networks. In the immature cerebral cortex, local and large-scale cortical networks, which transmitters, receptor expression, morphology,
subplate neurons in the lower cortical layer and form the functional template for generation of projections, firing properties, and their partici-
Cajal-Retzius cells in the marginal zone lay the cortical architecture and guide establishment pation in specific intra- and extracortical con-
foundations for cortical organization in hori- of global thalamocortical and intracortical net- nectivity. The transformation of this early
subplate-driven circuit to the adult-like cortex
A requires patterned spontaneous activity and de-
pends on the awakening of silent synapses in
Section the cortical plate when thalamic inputs are pro-
gressively integrated. Moreover, a subpopulation
B Cortex of the glutamatergic and GABAergic (GABA,
g-aminobutyric acid) subplate neurons has wide-
Marginal zone G Normal cortex spread axonal projections that establish early
Cortical plate large-scale networks. The early circuits are re-
Subplate 1 modeled when Cajal-Retzius and subplate neu-
2 rons largely disappear by programmed cell death.
D Synchronized burst activity Both the programmed cell death and the re-
3 modeling of circuits may be also controlled by
III III IIII III IIII III the transition from spontaneous synchronized
III III IIII III IIII III 4 burst to sensory-driven activity.
III III IIII III IIII III
5 OUTLOOK: Functional impairments of these
C Preterm transient circuits (that include both transient
6 and more permanent cell types) have great clin-
MZ ical relevance. Genetic abnormalities or early
WM pathological conditions such as in utero infec-
E Asynchronized activity tion, inflammation, exposure to pharmacological
H Persistent neurons compounds, or hypoxia-ischemia induce func-
CP tional disturbances in early microcircuits, which
1 may lead to cortical miswiring at later stages
I I I I I I I II I I I I I I 2 and subsequent neurological and psychiatric con-
IIIIII IIIII IIIIIIIII ditions. A better understanding of the transition
I I I I I I I I I I I I I I II I I 3 from early transient to permanent neuronal
circuits will clarify mechanisms driving abnor-
SP F Reduced activity 4 Cortical miswiring mal distribution and persistence of subplate
II I I I I I causes neurons as interstitial white matter cells in pa-
I I I II I I thophysiological conditions. Exploring the transi-
I II I I I I 5 neurological or tion from transient to permanent circuits helps
psychiatric us to understand causal foundations of certain
in utero infection, inflammation, pharmaco-resistant epilepsies and psychiatric
drug exposure, or hypoxia-ischemia 6 conditions
▪conditions and to consider new therapeutic
WM
strategies to treat such disorders.
Early spontaneous synchronized neuronal activity sculpts cortical architecture. (A) Schematic outlines of
brain development from the embryonic stage to adult. (B and C) Prenatal cortical circuits are dominated by The list of author affiliations is available in the full article online.
early-generated, largely transient neurons in the subplate (SP) and marginal zone (MZ) before maturation of cortical *Corresponding author. Email: [email protected]
plate (CP) neurons. (D to H) Transformation of early subplate-driven circuits to the adult-like six-layered cortex (Z.M.); [email protected] (H.J.L.); [email protected]
requires spontaneous synchronized burst activity (D) that also controls programmed cell death (apoptosis), (P.O.K.)
arrangement of neurites and axons, and formation and awakening of synapses. Most subplate neurons disappear Cite this article as Z. Molnár et al., Science 370, eabb2153
with development; a few survive in rodents as layer (L) 6b neurons or in primates as interstitial white matter (2020). DOI: 10.1126/science.abb2153
(WM) cells (G). During prenatal and early postnatal stages, pathophysiological conditions such as hypoxia-ischemia,
drugs, infection or inflammation may alter spontaneous activity [(E) and (F)]. These altered activity patterns READ THE FULL ARTICLE AT
may disturb subsequent developmental programs, including apoptosis (H). Surviving subplate neurons that persist https://doi.org/10.1126/science.abb2153
in white matter or L6b may support altered circuits that could cause neurological or psychiatric disorders.

Molnár et al., Science 370, 308 (2020) 16 October 2020 1 of 1

RESEARCH

◥ have been mostly studied in animals, data from
preterm and newborn human babies indicate a
REVIEW similar sequence. At distinct developmental
periods, spontaneous activity influences or even
NEURODEVELOPMENT controls neurogenesis and neuronal migra-
tion, synaptogenesis, apoptosis, and myelination
Transient cortical circuits match spontaneous and (10, 11). In general, the sequence of spontaneous
sensory-driven activity during development activity in developing neuronal networks shows
four distinct phases (Fig. 2C).
Zoltán Molnár1*, Heiko J. Luhmann2*, Patrick O. Kanold3,4*
1) At early embryonic stages (labeled 1 in
At the earliest developmental stages, spontaneous activity synchronizes local and large-scale cortical Fig. 2C), spontaneous activity is sparse and
networks. These networks form the functional template for the establishment of global thalamocortical asynchronous because neurons are not con-
networks and cortical architecture. The earliest connections are established autonomously. However, nected yet. Neurons in isolation reveal long cal-
activity from the sensory periphery reshapes these circuits as soon as afferents reach the cortex. cium transients that appear stochastically and
The early-generated, largely transient neurons of the subplate play a key role in integrating spontaneous are influenced by ionotropic and metabotropic
and sensory-driven activity. Early pathological conditions—such as hypoxia, inflammation, or exposure receptors activated by ambient or paracrine
to pharmacological compounds—alter spontaneous activity patterns, which subsequently induce release of g-aminobutyric acid (GABA) and
disturbances in cortical network activity. This cortical dysfunction may lead to local and global miswiring glutamate. Subplate and Cajal-Retzius neurons
and, at later stages, can be associated with neurological and psychiatric conditions. already reveal relatively mature electrophysio-
logical properties, for example, faster action
I n the adult brain, neuronal communica- Before completion of neurogenesis and mi- potentials and higher discharge rates. Thalamic
tion is mediated primarily through chem- gration (Fig. 2. A and B), neocortical areas dis- stimulation elicits long responses in rodent
ical synapses, and neurons interact within play distinct spontaneous and sensory-driven subplate, which likely represent action poten-
a short time frame. The developing brain activity patterns, which can influence produc- tials followed by prolonged depolarizations
is not just a smaller version of the adult tion and release of growth factors, influence (Fig. 3A) (12). Subplate neurons in postcon-
brain but rather has different types of inter- maintenance of gap junctions, regulate trans- ception week (pcw) 17 to 23 fetal human cortex
actions between immature cells. These inter- mitter release, and guide the precise topogra- in vitro generate spontaneous depolarizations
actions are slower, are not as well stereotyped phy of developing projections (2). Overall levels that depend on gap junctional coupling (13)
and predicted, and rely more on spontaneous of activity can also contribute to cell survival,
activity patterns than interactions in the adult including of interneurons (3), Cajal-Retzius 2) In the next stage (labeled 2 in Fig. 2C),
brain. These early spontaneous activity pat- neurons (4), and thalamic neurons. bursts of correlated neuronal activity are gen-
terns are mediated through transient neuro- erated by intrinsic mechanisms or synaptic
nal networks that continue to exist during the Developing neurons often show transient interactions, including extrasynaptic recep-
gradual establishment of permanent networks. depolarizations, which can be transmitted to tors activated by ambient GABA or glutamate.
Transient alterations in activity during crucial other neurons through gap junctions. Sub- Active neurons are coupled in small networks
developmental periods can lead to persistent sequently, neurons become capable of releas- through electrical and/or chemical synapses
changes in functional connectivity and there- ing various neurotransmitters, depending on and generate synchronized burst activity, which
fore might underlie the manifestation of neu- the frequency and intensity of their firing. Sub- may be restricted to a local neuronal network,
rological and psychiatric conditions (1). Thus, plate and Cajal-Retzius neurons can also release propagating as a “wave” to neighboring cor-
fundamental knowledge on early steps of trophic factors and in this way directly influ- tical areas or activating remote cortical and
activity-dependent circuit formation has gen- ence cellular targets (5, 6). subcortical regions through axonal projections
eral biological, as well as practical clinical, (14). Highly synchronized spontaneous activ-
implications. Given the multitude of neuronal commu- ity in the form of calcium waves emerges as
nication pathways, we review progress in un- early as embryonic day 14.5 (E14.5) in mouse
The development of neural circuits starts derstanding the role of neuronal electrical thalamus and propagates among sensory tha-
early in embryogenesis. The preplate is the activity in the earliest neuronal networks of lamic relay nuclei, thereby coordinating pat-
first postmitotic cortical neuronal layer (1) the cerebral cortex. We focus on a critical de- terning of the cortical sensory area (15). At this
(Fig. 1) and is split into the marginal zone velopmental stage, when cortical networks con- age, the brainstem has not yet innervated the
and subplate by later-arriving cortical plate taining transient neurons begin to interact thalamus, indicating that this activity is gen-
neurons. Then, unfolding genetic programs of with the emerging inputs from the sensory pe- erated within the thalamus. Thalamocortical
neurogenesis and neuronal migration interact riphery, and on reciprocal connectivity between systems are already assembled when the first
with various forms of neuronal communica- the thalamus and cortex, as well as on connec- peripheral inputs reach them. Therefore, ini-
tion to establish the mature circuitry. tions within the cerebral cortex. tial thalamocortical loop formation occurs in
an autonomous fashion, and periphery-related
1Department of Physiology, Anatomy and Genetics, Spontaneous activity in early development activity from sensory organs can subsequently
Sherrington Building, University of Oxford, Parks Road, modify these connections (16).
Oxford OX1 3PT, UK. 2Institute of Physiology, University Spontaneous electrical activity, or electrical
Medical Center of the Johannes Gutenberg University Mainz, events occurring without apparent external 3) With maturation of intrinsic and synap-
Duesbergweg 6, Mainz 55128, Germany. 3Department of generation, is a general feature of all develop- tic electrophysiological properties, neurons
Biomedical Engineering, Johns Hopkins University, School of ing networks, but the cellular mechanisms fire in bursts and synchronize local networks
Medicine, 720 Rutland Avenue, MRB 379, Baltimore, MD underlying the various activity patterns may (labeled 3 in Fig. 2C). Spindle burst or delta
21205, USA. 4Johns Hopkins University Kavli Neuroscience differ and change profoundly during specific brush activity is a physiological hallmark
Discovery Institute, Baltimore, MD 21205, USA. stages of development (Fig. 2, A to C) (7–9). of this distinct period in human and rodent
*Corresponding author. Email: [email protected] Although the underlying mechanisms and development (Fig. 2B). Spindle bursts are trig-
(Z.M.); [email protected] (H.J.L.); [email protected] (P.O.K.) functional role of the various activity patterns gered by signals from the sensory periphery
(17), by endogenous thalamic activity (18), or

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RESEARCH | REVIEW

AB Cajal-Retzius cell F G

MZ CP neuron SYNAPSES GAP JUNCTION
VSZSVPZ/CIMPZZ Migrating channel
CP neuron H
CP GAP JUNCTIONS

IC THAL SP SP neuron VESICLE with
CL IZ GLUTAMATE
INS ST NMDA receptor
AMPA receptor
SVZ Outer radial glia E
progenitor cell
VZ
Intermediate
progenitor cell

Radial glia
progenitor cell

C AUTOCRINE

D

CSF PARACRINE SILENT SYNAPSE MATURE SYNAPSE

ENDOCRINE

Fig. 1. Cellular interactions in developing brain. (A) Cross section of in developing cortex (B). Dividing radial glial progenitors in VZ are in
human brain at 18 gestational weeks (5). Subplate (SP) and intermediate contact with cerebrospinal fluid and receive endocrine signals, some through
zone (IZ) are blue; germinal zones are pink (marginal zone, MZ; cortical plate, blood vessels (C). Immature neurons interact through paracrine (D) and
CP; subventricular zone, SVZ; ventricular zone, VZ). CL, claustrum; autocrine (E) mechanisms or couple into local networks through electrical (G)
INS, insula; ST, striatum; IC, internal capsula; THAL, thalamus. and chemical (H) synapses (F). These various forms of communications
(B to H) Schematic illustration of cellular cortical components present coexist in the developing brain.

by activity from other neocortical areas. Short indicating that circuits from periphery to cor- all contribute to the changing spontaneous
gamma bursts are present in rodent cortex tex are functional from early ages (26, 27). activity.
during the same developmental period and
also synchronize local radial neuronal net- Developing neurons do not oscillate at fre- 4) With further maturation of intrinsic mem-
works, functional precolumns (9, 19, 20). Sub- quencies of spindle bursts, and oscillations are brane and synaptic properties, spontaneous
plate neurons are required for this local burst abolished by manipulating thalamocortical activity becomes sparse and desynchronized (9)
activity, and subplate ablation causes disar- circuits and subplate neurons, suggesting that (labeled 4 in Fig. 2C). This gradual develop-
rangement in the cortical architecture (21). At oscillations are generated by specific circuits, mental shift from the dominant burst pattern
the embryonic and neonatal stages, this ac- rather than individually oscillating neurons to “adult-like” low-amplitude desynchronized
tivity originates in the thalamus and controls (21, 28–32). Death of neurons, changes in cir- activity is accompanied by a progressively stron-
the formation of the cortical map (18). The cuits or receptor composition, and changes in ger impact of the peripheral sensory input.
cholinergic system elicits some of these early (intracellular) ion composition could all con- However, sensory cortices can be activated by
activity patterns (7, 22, 23). tribute to the developmental changes in oscilla- external stimuli (light, sound, touch, and muscle
tions. Moreover, because early activity patterns twitches) at surprisingly early stages—for exam-
Cortical early network oscillations, develop- seem to be coordinated across the brain, the ple, in preterm human babies or early postnatal
mentally followed by cortical giant depolarizing above considerations point to a key role of the periods in altricial animals (35–39)—before the
potentials represent the two activity patterns in thalamus in relaying, integrating, and sculpting sensory organs are fully functional. In ferrets,
newborn rodents during further development early spontaneous and sensory-driven activ- primary auditory cortex (A1) responds to sounds
(9, 24). Endogenous activity in the somato- ity patterns. as early as postnatal day 21 (P21) (38), whereas
sensory system often arises from central pat- in mice, whisker stimulation elicits a cortical
tern generators in motor regions (8). However, In sensory systems, the periphery (7, 33) as response at E18.5 (18). During the first post-
because the somatosensory system is tightly well as central sources might initially inde- natal week in rodents, L4 neurons exhibit spon-
linked with the motor system, it is often not pendently generate spontaneous activity (14), taneous activity in a barrel map–like pattern,
possible to clearly separate “true” spontaneous but their interaction is unclear. Spontaneous which is driven by the periphery but largely
activity from sensory activity evoked by motor peripheral activity is relayed via the thalamus independent of self-generated whisker move-
action. Twitch-related activity is present in the to the developing cortex (34). Thus, it is not ments (26, 27, 40). This activity may be gen-
somatosensory cortex (25) shortly after birth, just a transient subplate, but rather a series erated by gap junction–coupled dorsal root
of transient networks and structures that

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