Science 13.11.2020

CONTENTS

13 NOVEMBER 2020 • VOLUME 370 • ISSUE 6518

756

Larvae of the emerald ash borer, an introduced beetle, have killed millions of ash trees in North America by tunneling beneath their bark.

CREDITS: (PHOTO) MADDIE MCGARVEY; (GRAPHIC) C. BICKEL/SCIENCE NEWS 754 Pandemic dooms Danish mink— 765 Enhancing host cell infection
and mink research by SARS-CoV-2
IN BRIEF Mass culling ordered after discovery of Neuropilin-1 binds the furin-processed spike
mutations that may affect vaccine efficacy protein of SARS-CoV-2 to promote virus
746 News at a glance entry By M. Kielian
By C. Lesté-Lasserre
IN DEPTH REPORTS pp. 856 & 861
755 Dust storms on Mars propel
748 Effective vaccine offers shot water’s escape to space 767 Peptide synthesis at the origin of life
of hope for pandemic Orbiters spy potential ongoing Small-molecule organocatalysis
Pioneering RNA candidate seems to planetary “death spiral” By P. Voosen might have driven the emergence of peptide
work well, although its makers revealed biochemistry By K. B. Muchowska and J. Moran
scant data By J. Cohen RESEARCH ARTICLE p. 824
REPORT p. 865
749 A divided Congress could narrow F E AT U R E S
Biden’s ambitious plans 768 How to improve robotic touch
But president-elect has vowed to flex 756 Rising from the ashes Challenges for instrumenting
executive power By J. Mervis An effort to breed North American ash trees robotic hands to match
that can resist a deadly beetle could accelerate human performance
750 To tackle pandemic, Biden must the return of a forest icon By G. Popkin are outlined
overcome distrust and division
President-elect vows “bedrock of science” INSIGHTS By S. Sundaram
will drive his administration’s response to
worsening U.S. crisis POLICY FORUM 770 James S. Jackson (1944–2020)
Social psychologist who pioneered
By M. Wadman and W. Cornwall 760 What’s next for COVID-19 apps? the study of Black culture By T. A. Parham
Governance and oversight
751 New polio vaccine could boost Adaptive governance can help earn social BOOKS ET AL.
faltering eradication drive license By A. Blasimme and E. Vayena
Sabin’s oral vaccine has itself become a 771 Moving beyond the paradigm
source of polio outbreaks. A modern, stabler PERSPECTIVES A provocative 1975 call to leave behind
version may reduce the risk By L. Roberts dogmatic thinking could help scientists
763 Understanding COVID-19 strengthen ties with the public By J. Swift
752 India’s COVID-19 teacher vaccine efficacy
Kerala health minister K. K. Shailaja Vaccine efficacy in high-risk groups and 13 NOVEMBER 2020 • VOL 370 ISSUE 6518 743
has fought the pandemic with preparation, reduced viral shedding are important for
calm, and compassion By V. Chandrashekhar protection By M. Lipsitch and N. E. Dean

SCIENCE sciencemag.org Published by AAAS

CONTENTS

SPECIAL SECTION 772 Imaginary demons and 824 Martian atmosphere
scientific discoveries Hydrogen escape from Mars is driven
Cooling A new history acts as a field by seasonal and dust storm
technology guide to the fictional imps transport of water S. W. Stone et al.
invoked by scientific thinkers
INTRODUCTION NEWS STORY p. 755
By J. G. Michel
776 Cooling in a warming world REPORTS
LETTERS
NEWS 831 Metallurgy
778 Living with heat E. Pennisi 773 EcoHealth reframing Constrained minimal-interface structures
of disease monitoring in polycrystalline copper with
PODCAST extremely fine grains X. Y. Li et al.
By M. P. M. Vanhove et al.
PERSPECTIVES 837 Cosmochemistry
773 Build international Astronomical context of Solar System
782 Adapting to the biorepository capacity formation from molybdenum isotopes in
challenges of warming meteorite inclusions G. A. Brennecka et al.
S. C. Sherwood By J. P. Colella et al.
840 Optomechanics
783 Cooling our insatiable demand 774 Response Nano-acoustic resonator with ultralong
for data Amy S. Fleischer phonon lifetime G. S. MacCabe et al.
By M. Watsa and Wildlife Disease
784 Photon-engineered Surveillance Focus Group 844 Neuroscience
radiative cooling textiles A thalamocortical top-down circuit for
P.-C. Hsu and X. Li RESEARCH associative memory M. B. Pardi et al.

PODCAST IN BRIEF 848 Sensors
Stretchable distributed fiber-optic
REVIEWS 805 From Science and other journals sensors H. Bai et al.

786 Terrestrial radiative cooling: RESEARCH ARTICLES 853 Translation regulation
Using the cold universe as a A phosphorylation-regulated eIF3d
renewable and sustainable energy Human genomics translation switch mediates cellular
source X. Yin et al. 808 A human cell atlas of fetal gene adaptation to metabolic stress
A. M. Lamper et al.
791 New refrigerants and expression J. Cao et al.
system configurations for Coronavirus
vapor-compression refrigeration RESEARCH ARTICLE SUMMARY; 856 Neuropilin-1 facilitates SARS-CoV-2
M. O. McLinden et al. FOR FULL TEXT: DX.DOI.ORG/10.1126/
SCIENCE.ABA7721 cell entry and infectivity
797 Caloric materials for L. Cantuti-Castelvetri et al.
cooling and heating 809 A human cell atlas of fetal
X. Moya et al. chromatin accessibility 861 Neuropilin-1 is a host factor for
S. Domcke et al. SARS-CoV-2 infection J. L. Daly et al.
ON THE COVER
RESEARCH ARTICLE SUMMARY; FOR FULL PERSPECTIVE p. 765
Air-conditioning units TEXT: DX.DOI.ORG/10.1126/SCIENCE.
hang off the back side ABA7612 865 Prebiotic chemistry
of a row of buildings Prebiotic synthesis of cysteine
in Shenyang, Liaoning 810 Plant science peptides that catalyze peptide
province, China. Many Vascular transcription factors guide ligation in neutral water C. S. Foden et al.
Chinese people spend plant epidermal responses
sanfu, the hottest to limiting phosphate conditions PERSPECTIVE p. 767
period of the year, J. R. Wendrich et al.
in air-conditioned D E PA R T M E N T S
buildings. As the planet continues to warm, RESEARCH ARTICLE SUMMARY; FOR FULL TEXT:
the need for innovative and environmentally DX.DOI.ORG/10.1126/SCIENCE.AAY4970 745 Editorial
friendly cooling technologies becomes The disease of distrust By Reed V. Tuckson
more important. See page 776. 811 Coronavirus
Photo: Visual China Group via Getty Images Immune life history, vaccination, 874 Working Life
and the dynamics of Difficult conversations By Sasha McDowell
SARS-CoV-2 over the next
5 years C. M. Saad-Roy et al. New Products.............................................870
Science Careers ......................................... 871
819 Plant science
Cell wall remodeling and vesicle trafficking
mediate the root clock in Arabidopsis
G. Wachsman et al.

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744 13 NOVEMBER 2020 • VOL 370 ISSUE 6518 sciencemag.org SCIENCE

Published by AAAS

EDITORIAL

The disease of distrust

A n uncomfortable question has poked out from the etta Lacks, as the source of an invaluable research cell
chaos of the coronavirus disease 2019 (COVID-19) line. A statue across from the New York Academy of
crisis—why does health inequity still persist in Medicine honoring James Marion Sims, who achieved
the United States? American people of color have success through research on un-anesthetized enslaved
been disproportionately affected by the pandem- American persons, was another visible insult. Misper-
ic. This, sadly, is no surprise because socioeco- ceptions regarding the etiology of disease, the motives

nomic conditions, health care access challenges, of policy formulators, the veracity of health institu-

and distrust in health care systems have historically tions, and the trustworthiness of the research enter- Reed V. Tuckson
is the managing
prevented people of color from having healthier lives. prise have become almost as difficult to overcome as director of Tuckson
Health Connections,
As infections and deaths from COVID-19 continue to in- diseases themselves. LLC, a member of
the U.S. National
crease, effective treatments and vaccines are anxiously I am troubled by just how little the health profession Academy of Medicine,
and the former
expected to become available soon. Unfortunately, less has done to address the persistent misperceptions aris- Commissioner of
Public Health for the
attention is being paid to questions about their equita- ing from the nation’s history. Every aspect of the health District of Columbia,
USA. drreed@
ble distribution and uptake. This only contributes to the enterprise must build the relationship between patients tucksonhealth
connections.com
suspicion felt by minority groups in the United States— and health professionals. This includes facilitating in-

particularly people of color—of the medical community. clusive input by disenfranchised communities into

This barrier must come down. health policy formulation, rein-

Every level of the health enter- forcing the actual and perceived

prise should pledge to reclaim “Misperceptions… protections and benefits of clini-
the trust of all populations that cal research, and providing ac-

is demanded by its professional have become almost cessible scientific evidence to
oaths and missions. the public regarding therapeu-

This legacy of mistrust by as difficult to tics such as a COVID-19 vaccine.
people of color in health insti- overcome as diseases Let this be the moment when
tutions, health professionals,
researchers, and health policy– themselves.” the health community speaks
makers in the United States has to society in a manner that
existed for decades. This pain- reassures the disenfranchised
ful reality has been amplified of the strength of the bond
with them. When the human

by the actions of the Trump dignity of people is assaulted,

administration and state-level health outcomes are affected,

officials, and by the behaviors of law enforcement, thereby requiring health professionals to speak out

among others. It should be troubling to any health on matters of social concern. When patients receive

professional when thousands of African Americans care that deviates from best evidence because of bias

pour into the streets to strenuously assert that their or socioeconomic hurdles associated with structural

lives matter and that their humanity must be recog- racism, advocacy is required to recognize and address

nized. When people lose trust in the fundamental the problem. Whether through individual action or

institutions of their society, decisions regarding the the collective work of professional societies, disen-

conduct of their lives become altered in both obvious franchised people need to be assured that in matters

and nuanced ways that affect their well-being. pertaining to their health, there can be confidence in

I was privileged to serve as the Commissioner of scientific-based guidance and advice.

Public Health for Washington, DC, during the height We must all recognize this disease of distrust as the

of the HIV-AIDS epidemic. This agency’s work was scourge that it is and band together to reclaim this

substantially compromised by the legacy of the 40- essential characteristic of the health profession: the

year Tuskegee Syphilis Study, which began in 1932, preservation of the lives of all those who share our

where African American men were misled into partici- time and space. This should be the last time our so-

pating in research to find a cure for the disease. This ciety has to struggle against the legacy of the past as

mistrust has been compounded by other incidents, we fight persistent disparities in health outcomes and

including the failure of the biomedical community tackle this pandemic and the challenges to come.

PHOTO: REED TUCKSON to acknowledge an African American woman, Henri- –Reed V. Tuckson

SCIENCE sciencemag.org 10.1126/science.abf6109
13 NOVEMBER 2020 • VOL 370 ISSUE 6518 745

Published by AAAS

NEWS “ ”A mask remains the most potent weapon against the virus.
Today’s news does not change that urgent reality.
President-elect Joe Biden, on 9 November following
positive early results from a COVID-19 vaccine efficacy trial (see story, p. 748).

IN BRIEF

Edited by Kelly Servick

METEOROLOGY Hurricane Eta, which
caused flooding
2020 brings stormiest Atlantic on record
in Central America last
week, is among

29 named Atlantic Ocean
storms this season.

W ith the rise of subtropical storm “Theta” this week, continually improving methods of identifying cyclones via
the Atlantic Ocean broke the record for the satellite in the remote ocean, which makes the new record
most named storms in a season, with 29—surpassing relevant only for the past few decades. Though it’s unclear
a high set in 2005. Unusually warm Atlantic whether global warming is leading to higher incidence of trop-
waters and a La Niña event in the Pacific Ocean ical cyclones, climate change is boosting rains and flooding
contributed to the stormy season. Forecasters are left in the storms’ wake, and likely increasing their strength.

HIV shot proved for women Truvada became infected with HIV, just four committee convened to review its effec- PHOTO: ORLANDO SIERRA/AFP VIA GETTY IMAGES
receiving injections contracted the virus—a tiveness. Aducanumab, an antibody drug
PU B L I C H E A LT H | A long-lasting anti- result that prompted the team to halt the developed by Biogen, clears away buildup
viral injection is 89% more effective at trial early. Cabotegravir was previously in the brain of the protein beta amyloid,
preventing HIV infections in women than shown to prevent HIV infections in cis- thought to drive neuronal damage. In
a daily prophylactic pill, according to an gender men and transgender women who 2019, Biogen halted two large clini-
announcement this week from the clini- have sex with men. cal trials after it seemed neither would
cal trial network testing the approach. In a show that aducanumab slowed cognitive
randomized, double-blind trial that included Panel slams Alzheimer’s drug decline. Then, the company reversed
more than 3200 women across sub-Saharan course and sought FDA approval based
Africa, scientists compared the approved pill DRUG DEVELOPMENT | An experimen- on positive results in one of the trials. Of
marketed as Truvada—which many people tal Alzheimer’s disease treatment up the advisory panel’s 11 voting members,
struggle to take regularly—with an antiviral for approval by the U.S. Food and Drug 10 said the positive study did not provide
called cabotegravir, which was injected every Administration (FDA) took a beating enough evidence of effectiveness to sup-
2 months. Whereas 34 participants taking last week from an independent advisory port approval. (The 11th member voted

746 13 NOVEMBER 2020 • VOL 370 ISSUE 6518 sciencemag.org SCIENCE

Published by AAAS

“uncertain.”) FDA is expected to decide the risks of the GM salmon escaping 2020 ELECTION

about aducanumab by March 2021; it and interbreeding with wild salmon, Wins and losses for U.S. science

doesn’t have to follow the advice of its especially endangered populations. U.S. Most researchers hailed Joe Biden’s victory
in the race for U.S. president, but other
advisory committees, but it typically does. District Judge Vince Chhabria found the election results delivered a mixed message
about voter attitudes toward science.
agency had minimized risk by requir-
Newbies founder
Disputed replications fail again ing that AquaBounty raise the salmon in
land-based tanks. But he ruled that FDA Democrat Nancy Goroff’s bid to become
the first female science Ph.D. in Congress
PSYCHOLOGY | Ten high-profile psycho- must evaluate the possible consequence of appears doomed unless the Stony
Brook University chemist, vying for a
logy studies have failed to replicate for a escapes because approving more land- seat from New York in the U.S. House of
Representatives, can win an overwhelming
second time, suggesting the failure of the based facilities would increase escape risk. share of the votes not yet counted.

first replication effort can’t be explained The decision does not affect current com- University of Wyoming marine ecologist
Merav Ben-David, a Democrat, lost by almost
by poor research methods, as its critics mercial production of the salmon, which a three-to-one margin in her race for an
open U.S. Senate seat, and Democrat
have argued. A 2015 study led by Brian began this summer. Kathleen Williams, a water resources expert,
fell short in a second attempt to claim an
Nosek at the Center for Open Science at-large House seat from Montana.

replicated only one-third of 100 seminal Climate assessment turmoil Mixed fate for science fgures
psychology findings. Nosek and colleagues
Two House members with science Ph.D.s,
have now led a second multilab effort to G EOSC I E N C E | The Trump administra- physicist Bill Foster (D–IL) and animal
nutrition expert Jim Baird (R–IN), won by
repeat 10 of the replication attempts that tion has abruptly reassigned Michael comfortable margins. Both serve on the
House science committee, whose largely
had not been endorsed by the original Kuperberg, head of the U.S. Global Change intact leadership hopes to build on a
history of bipartisan legislation.
researchers. This time, the team had its Research Program, which coordinates
Most first-time House members with
research protocols peer reviewed—by federal climate change research, includ- science and medical backgrounds kept
their seats. But Joe Cunningham (D–SC),
those original researchers when possible— ing the National Climate Assessment an ocean engineer, was ousted, as was
Kendra Horn (D–OK), who chairs the
before launching its studies. Even though (NCA). Kuperberg, who will return to science committee’s space panel.

the revised protocols used study popula- the Department of Energy, will likely A narrow win by four-term Representative
Matt Cartwright (D–PA) keeps him in
tions and methods closer to the original be replaced by David Legates, a climate the running to lead a House spending
panel with jurisdiction over several
studies, they still didn’t uphold the contrarian the administration placed at science agencies.

original findings. Those results were most the National Oceanic and Atmospheric Colorado senator Cory Gardner, the chief
Republican sponsor of the 2016 American
likely unreliable, the team concludes in Administration in September, The New Innovation and Competitiveness Act that
reauthorized a host of science programs,
a paper published on 12 November in York Times reported. The move came days lost his seat to geologist and former
Governor John Hickenlooper (D). Gardner’s
Advances in Methods and Practices in after Elizabeth Weatherhead, a respected Democratic co-sponsor of the law, Senator
Gary Peters, eked out a victory in Michigan.
Psychological Science. atmospheric scientist who accepts the real-
State initiatives boost research
ity of human-driven climate change, was
California voters appear to have narrowly
FDA must reassess GM salmon named to lead the NCA, due in 2022. The approved $5.5 billion in stem cell research
incoming Biden administration can change funding for the California Institute
for Regenerative Medicine, pending
B I OT EC H N O LO GY | The U.S. Food and these appointments, but the moves could completion of the count. Colorado voters
gave the nod to planning the reintroduction
Drug Administration (FDA) must evalu- delay the congressionally mandated NCA, of gray wolves, while Oregonians said yes
to allowing researchers to test psilocybin,
ate the hazard that genetically modified used to guide climate policy. the active ingredient in so-called magic
mushrooms, in treating a range of illnesses.
(GM) salmon pose to their wild relatives
13 NOVEMBER 2020 • VOL 370 ISSUE 6518 747
before it can approve any new rearing New damage to Arecibo telescope
facilities, a U.S. district court ruled last

week. In 2015, the fast-growing Atlantic ASTRONOMY | The Arecibo Observatory

salmon developed by AquaBounty— was dealt a blow on 7 November, when

engineered to include genes from Pacific one of the radio telescope’s 12 main sup-

Chinook salmon and the eel-like ocean port cables snapped and damaged the

pout—became the first GM animal to 300-meter-wide main dish and other cables.

be FDA approved for human consump- The University of Central Florida, which

tion. Environmental groups sued FDA, leads a consortium managing the obser-

claiming it had not adequately assessed vatory on behalf of the National Science

Foundation, is already work-

ing to repair damage from

a previous cable break in

August. Researchers now fear

increased load on remaining

cables could lead to a cascade

of failures and the collapse of

the antenna platform that

is suspended over the dish.

The nearly 60-year-old tele-

scope, built into the hills of

PHOTO: AQUABOUNTY Puerto Rico, excels at study-

ing pulsing radio sources

in deep space and tracking

AquaBounty’s fast-growing salmon, approved in 2015, faces a further nearby asteroids that could

regulatory hurdle before production facilities can expand. threaten Earth.

SCIENCE sciencemag.org

Published by AAAS

IN DEPTH

A dose of Pfizer and BioNTech’s experimental COVID-19 vaccine is readied in October for a clinical trial participant in Turkey.

COVID-19

Effective vaccine offers shot of hope for pandemic

Pioneering RNA candidate seems to work well, although its makers revealed scant data

By Jon Cohen out the underlying data, says Hotez, who what you need to get the vaccine into den- PHOTO: DOGUKAN KESKINKILIC/ANADOLU AGENCY VIA GETTY IMAGES
is also part of a team making a vaccine dritic cells,” Sahin says. “That’s our key dif-
O n Sunday evening, standing beside against SARS-CoV-2, the virus that causes ferentiator.” The BioNTech team then chose
the Hudson river in upstate New COVID-19. He stresses, too, that the vast the mRNA that triggered the best immune
York, Kathrin Jansen was watching majority of the public will not have access responses in early human trials.
the sunset with her husband when to this or any other COVID-19 vaccine for
the head of Pfizer, Albert Bourla, several months. The subsequent efficacy trial, which has
called with the update she was ea- enrolled more than 44,000 people, quickly
gerly awaiting. Jansen, who heads vaccine “There are a lot of unanswered ques- yielded results because of the skyrocketing
R&D at Pfizer, had learned that morning a tions,” adds Georgetown University’s Jesse number of COVID-19 cases in the United
massive placebo-controlled trial of the com- Goodman, former chief scientist at FDA. States, home to the vast majority of the
pany’s candidate COVID-19 vaccine had a Nothing is known about how long the im- study’s 154 sites. The design called for an
positive efficacy signal, but it wasn’t clear munity triggered by the vaccine will last, independent panel to unblind the data if
just then how strong it was. Bourla told her whether it can prevent severe COVID-19, 62 participants had symptoms of COVID-19
an interim analysis found that the vaccine, and even whether it will slow transmission and tested positive for SARS-CoV-2. The
which uses a potentially revolutionary RNA rates if it’s used widely in a population. It’s trial hit the 62 case mark on 3 November,
technology, was more than 90% effective at unclear how well it works in the elderly, Jansen says, and the companies started to
preventing symptomatic cases of COVID-19. who suffer the most from SARS-CoV-2. carefully comb through the cases to pre-
“This is unbelievable,” she told Bourla. The vaccine, based on a simple strand of pare the data for the panel to evaluate Sun-
Jansen and her husband began to jump up messenger RNA (mRNA), has to be stored day morning, by which time the trial had
and down and soon had a champagne toast at –80°C to preserve the genetic material, 94 people with COVID-19.
with “some really good stuff.” and making and delivering enough for hun-
dreds of millions—if not billions—of people The company has not revealed how many
The rest of the world joined the celebra- remain huge challenges. of those cases were in the vaccine group
tion the next day as Pfizer and its Ger- versus the placebo group. So far, the trial
man partner BioNTech announced the BioNTech, a small company working on has found no major side effects. For safety
encouraging results of their candidate in mRNA vaccines to treat cancer, designed the reasons, FDA guidelines say before a com-
a press release. Pfizer says it may seek an COVID-19 vaccine and then partnered with pany can seek an EUA, 2 months must pass
emergency use authorization (EUA) for the Pfizer. Ugur Sahin, BioNTech’s CEO, says after at least half of the participants in a
vaccine from the U.S. Food and Drug Ad- they tested more than 20 different stretches vaccine trial have received all of their doses.
ministration (FDA) in a few weeks. But Peter of mRNA coding for portions of spike, the That point is about 2 weeks from now, and
Hotez, a vaccine researcher at Baylor Col- surface protein the coronavirus uses to bind Pfizer anticipates the trial will by then have
lege of Medicine, speaks for many scientists to human cells. They looked for mRNAs reached its planned endpoint of at least
when he says that despite the “apparently that were most likely to be taken up and ex- 164 accumulated COVID-19 cases.
good news,” he would keep the champagne pressed by dendritic cells, which “present”
corked. “It’s always hard to read the tea spike to the immune system to initiate anti- If Pfizer then files for an EUA, FDA has
leaves of a company press release,” with- body and T cell responses against the virus. promised to hold an open meeting of its
“We spent a lot of effort in understanding vaccine advisory board—a step commit-
tee members say is critical. “We all have

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Published by AAAS

NEWS

a healthy skepticism because companies 2020 U.S. ELECTION
clearly want to sell their vaccines,” says
Cody Meissner, a pediatrician at Tufts Uni- A divided Congress could
versity School of Medicine who is on the narrow Biden’s ambitious plans
committee and was nonetheless heartened
by the positive report. But president-elect has vowed to flex executive power

If the vaccine is given an EUA by FDA By Jeffrey Mervis To restore that confidence, Biden will
and regulators in other countries, or even
formally approved, an ethical dilemma likely populate his administration with
comes to the fore: whether to offer it to the
trial participants who received the placebo, M ost U.S. researchers and environ- well-respected researchers. Most science
which could compromise collecting more mental activists were ecstatic when agencies will be getting new leaders, al-
data on the durability of the vaccine’s im- Joe Biden emerged as the winner though Sethuraman Panchanathan is only
mune response and safety. Participants in of the U.S. presidential election on 5 months into a 6-year term as director
trials of other candidates might also drop Saturday. They expect him to re- of the National Science Foundation, and
out if they could access a 90% effective vac-
cine. “It could have a huge impact,” says bio- verse a host of Trump administra- Francis Collins may be asked to extend his
ethicist Christine Grady of the U.S. National
Institutes of Health, noting that fighting the tion policies they oppose and push for new 11 years at the helm of the National Insti-
pandemic may require multiple vaccines,
with known strengths and weaknesses. “Un- steps to fight climate change. tutes of Health until the coronavirus pan-
less we have good data, that’s going to be a
hard question to answer.” But when Biden is sworn in on 20 Janu- demic is controlled.

Pfizer and BioNTech developed their vac- ary 2021, his ability to advance an ambi- Biden’s choice of a science adviser and
cine without help from Operation Warp
Speed, a massive U.S. effort to fast-track tious agenda will be constrained by his head of the White House Office of Science
COVID-19 vaccines, although the com-
panies did agree to sell the government likely status as the first president in more and Technology Policy could send a key
100 million doses. Pfizer has cut deals with
several other countries as well. Each per- than 30 years to take office without his signal about the status of science in his
son requires two doses, and Pfizer and Bio-
NTech have produced only 500,000 doses, party controlling both chambers of Con- administration. The scope of that job, now
although they expect to have 50 million by
the end of the year. By 2021, the companies gress. Republicans are favored to preserve held by Kelvin Droegemeier, was greatly
project they can produce 1.3 billion doses.
their majority in the Senate diminished under Trump.
Still, initial supplies will be severely lim-
ited even in the United States and they will New appointeesby winning at least one of the A Republican majority in
remain short for most of the world next the Senate would pose a seri-
year. “If I look at the dose projections for two runoff contests in Geor-
2021, and I look at what’s now been spo-
ken for in bilateral deals around the world, gia, and Democrats will have a should end the ous obstacle to Biden’s cam-
it creates a fair amount of anxiety,” says narrower majority in the new “denigration paign promises aimed at
Nicole Lurie of the Coalition for Epidemic Pre- House of Representatives than combating climate change, in-
paredness Innovations, a nonprofit that aims
to improve equity and access to COVID-19 during the previous 2 years. of expertise” cluding a $2 trillion green in-
vaccines and drugs for all countries. Biden won’t need a Demo- frastructure initiative. Budget

Seth Berkley, who heads Gavi, the Vac- cratic Congress to undo an ar- under the Trump hawks in both parties are also
cine Alliance, says the positive vaccine data ray of executive orders issued administration. expected to put pressure on
bode well for the many other candidates in by President Donald Trump their leaders to rein in spend-
trials or development that also rely on the over the past 4 years. The David Hart, ing after pandemic relief pack-
SARS-CoV-2 spike protein, some of which president-elect has said he George Mason University ages caused the federal deficit
don’t need ultracold storage. It is also an en- will rejoin the Paris climate to skyrocket. Historically, how-
couraging sign for other vaccine candidates
using mRNA—one of which, from Moderna, pact on his first day in office ever, Congress has backed in-
could also have efficacy data this month.
and cancel orders that weakened environ- creases in federal research spending even
Lawrence Corey, a vaccine researcher
at the Fred Hutchinson Cancer Research mental regulations and barred immigrants during periods of austerity.
Center who heads a U.S. network that’s
testing several COVID-19 vaccines (but not from many majority-Muslim nations. His A first look at Biden’s priorities for sci-
the Pfizer/BioNTech candidate), calls it an
“amazing feat” that a vaccine has a clear new administration will also likely suspend ence will come when the administration
efficacy signal just 11 months after SARS-
CoV-2 was identified. “This is a revelation work on proposed regulations it opposes, rolls out its 2021 budget request in Febru-
of science,” Corey says. j
including several weakening pollution con- ary. Even before Biden is sworn in, how-

trols. The halt will effectively kill them, but ever, leaders of the House and Senate have

it could take years to reverse regulations said they want to pass another pandemic

that are already finalized. relief bill, which could include tens of bil-

Biden will also have substantial oppor- lions of dollars to help universities recover

tunity to reverse the “denigration of exper- from the losses caused by shutting down

tise” that permeated the Trump presidency, campus labs in the spring.

says science policy specialist David Hart of Lawmakers must also decide whether to

George Mason University. The outgoing complete work on this year’s annual bud-

administration’s disregard for evidence- get. In July, the House approved bills con-

based policy resulted in attempts to un- taining healthy boosts for several science

dermine the accuracy of this year’s census, agencies, and this week the Senate released

politicize climate and hurricane forecasts, its preliminary numbers. If the two bodies

and sideline scientific advisory panels. It can’t come to an agreement, the alternative

also triggered a “crisis of confidence” at is to continue the current freeze on federal

federal regulatory agencies, says Daniel spending and leave the dealmaking to the

Sarewitz of Arizona State University, Tempe. new president and Congress. j

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In October, then-candidate Joe Biden received a
COVID-19 briefing from public health experts.
He recently named many to a new advisory board.

2020 U.S. ELECTION fighting the pandemic. They were designed to
show he will mount a far more muscular fed-
To tackle pandemic, Biden must eral response than President Donald Trump,
overcome distrust and division who has largely left matters to state and lo-
cal officials. Among other things, Biden’s
President-elect vows “bedrock of science” will drive plan calls for standing up a 100,000-person
his administration’s response to worsening U.S. crisis corps to trace people who have been in con-
tact with an infected individual, massively
By Meredith Wadman and Warren Cornwall science” and “help shape my approach to increasing the availability of COVID-19 tests, PHOTO: DREW ANGERER/GETTY IMAGES
managing the surge in reported infections; and using the full power of the Defense Pro-
P resident-elect Joe Biden wasted little ensuring vaccines are safe, effective, and duction Act to replenish depleted stocks of
time this week in following through distributed efficiently, equitably, and free; personal protective equipment.
on his promise to put science first and protecting at-risk populations.” It has
in confronting the coronavirus three co-chairs: Marcella Nunez-Smith, an Once sworn in, Biden will be able to
pandemic, naming a 13-member internist and health equity researcher at the quickly realize some of these plans through
COVID-19 advisory board of promi- Yale University School of Medicine; former executive action. Other efforts, however, will
nent researchers and public health experts Obama administration Surgeon General require Congress to approve new funding
and unveiling new details of his evidence- Vivek Murthy; and David Kessler, who ran or pass legislation. And winning such ap-
based battle plan. the Food and Drug Administration under proval could take time, and prove difficult,
former Presidents George H. W. Bush and if Republicans maintain control of the Sen-
Many observers, however, say execut- Bill Clinton. ate. That will be decided by the results of
ing that plan will require not just technical two runoff elections in Georgia set for early
know-how, but also plenty of public persua- The same day, Biden’s transition team up- January 2021.
sion and political savvy. And they worry the dated its existing pandemic plan. It now says
pandemic will get much worse before Biden Biden will push every governor to require In the meantime, observers hope Biden’s
takes office on 20 January 2021, further com- people to wear face masks around anyone team will begin to correct one of the Trump
plicating efforts to end the crisis, which was outside their household and will work to administration’s biggest missteps: its chaotic,
growing by more than 100,000 cases a day provide an additional $25 billion in federal contradictory, and often false messaging,
and had killed at least 238,000 people in the funding to manufacture, distribute, and which has sown confusion about the course
United States as Science went to press. administer a free vaccine or vaccines. That of the pandemic, bolstered opposition to
pledge came as Pfizer announced that in- masks, and raised fears that vaccines would
“Biden’s got a bigger challenge than any terim data from a key clinical trial showed be rushed through the approval process. Pew
other country in the world,” says Nahid its vaccine is likely effective (see p. 748). Research Center polling, for example, has
Bhadelia, medical director of the Special found the number of Americans saying they
Pathogens Unit at Boston Medical Center. The moves came just 48 hours after news would be willing to take a vaccine fell from
networks declared Biden the winner of the 72% in May to 51% in September.
Biden said his advisory board, unveiled election and highlighted his emphasis on
on 9 November, will rely on a “bedrock of “The overarching issue is the need to re-
build trust” in what the federal government
is saying, says Tom Frieden, CEO of Resolve
to Save Lives, who directed the Centers for
Disease Control and Prevention (CDC) under
former President Barack Obama. “Social co-
hesion is essential to the control of infectious
diseases.” To build that cohesion, Biden’s
team should be enlisting messengers, includ-
ing public health experts, “who are trusted
by liberals and conservatives,” says Ellen
Peters, a social scientist at the University of
Oregon who has been surveying people’s per-
ceptions of the pandemic.

Biden’s effort to increase the use of masks
could prove an early test of whether his ad-
ministration can overcome the political and
cultural divides in a nation where more than
71 million people voted for Trump. Legal
experts have concluded that Biden cannot
impose a national mask mandate. He can,
however, require the use of masks on federal
property and during interstate transporta-
tion. But such mandates could flop without
a concerted effort to persuade people to em-
brace masks, says Harvard University health

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NEWS | IN DEPTH

care economist James Stock. If people are GLOBAL HEALTH
ordered to wear masks, they “just won’t do
it, it’s been so politicized.” New polio vaccine could boost
faltering eradication drive
Biden’s history of finding common
ground with political opponents could serve Sabin’s oral vaccine has itself become a source of polio
him well in this arena, noted Andy Slavitt, outbreaks. A modern, stabler version may reduce the risk
head of the Centers for Medicare and Med-
icaid Services during the Obama adminis- By Leslie Roberts up in just Pakistan and Afghanistan.
tration, during a 5 November presentation
at the University of California, San Fran- In places where immunization rates are
cisco (UCSF). During the transition, Biden
could “lean in hard on this, … doing listen- T he Global Polio Eradication Initiative low, however, OPV can continue to pass
ing tours” and meeting with governors to (GPEI) is about to roll out a brand- among susceptible children for several
firm up support for mitigation measures. “It new vaccine—one that its leaders des- weeks, mutating as it goes until it has re-
won’t work with all of them, but we don’t perately hope will turn the flagging gained its ability to paralyze and spread.
want to let the perfect be the enemy of the effort around. If it works as expected, This problem is especially acute for the type
good,” adds Eric Toner, an emergency physi-
cian and expert on pandemic preparedness the vaccine just might overcome one 2 virus, one of three polio serotypes. Scien-
at the Johns Hopkins University Center for
Health Security. of the biggest obstacles to polio eradication: tists realized long ago that this meant they

As president, Biden could use pressure out-of-control outbreaks caused by the polio would eventually have to stop using OPV. But
as well as persuasion, by requiring states to
follow CDC guidance if they want to qualify vaccine itself. If not, GPEI will be back to OPV is still the only vaccine that can quash
for certain kinds of federal funds. “The way
the CDC establishes trust and establishes dousing each outbreak with a vaccine that outbreaks in the poor, hot settings where the
its primacy is to begin to act more aggres-
sively, as long as it has a credible leader,” says risks starting another, as eradica- virus thrives.
Robert Wachter, an internist who chairs the
UCSF department of medicine. Biden could tion slips further from sight. “Hopefully, GPEI’s answer was to phase
name his nominees to head key pandemic- The new vaccine is so urgently we will stop OPV out one serotype at a time
fighting agencies, such as CDC and the De- lighting new after each was eradicated in the
partment of Health and Human Services, needed that the Bill & Melinda wild. Type 2, last seen in 1999,
before his inauguration, Ezekiel Emanuel Gates Foundation has paid for would be the first to go. In April
said at the 5 November UCSF event. Emanuel, nearly 200 million doses to be
a University of Pennsylvania oncologist, is
now a member of Biden’s new task force. produced by an Indonesian fires.That is 2016, all countries stopped us-
manufacturer “at risk,” even be- ing trivalent OPV and replaced
Observers differ on just how much em-
phasis the Biden administration should fore clinical trials are complete. the hope.” it with bivalent OPV, with the
place on contact tracing, given that the The World Health Organization type 2 component removed—a
rapidly rising number of infections could
overwhelm any contact tracing system. “Its (WHO) is ready to grant an emer- Mark Pallansch, trial run for the eventual ces-
value is limited unless everything else is go-
ing well, too,” says Harvard epidemiologist gency use listing, a new approval Centers for Disease sation of all OPV. The plan was
Marc Lipsitch, who compares tracing dur-
ing a massive outbreak to “trying to clean mechanism never before used for Control and Prevention to snuff out the few type 2 out-
up a tanker spill with a paper towel.”
a vaccine, as soon as Indonesia’s breaks that would inevitably
By the time Biden takes office, many ex-
perts fear the United States will be experi- regulatory authority gives the product the emerge from the last use of trivalent vaccine
encing unprecedented caseloads. Bhadelia
says she is particularly frightened by the nod. The first drops could be delivered in with a limited, emergency stockpile of a vac-
specter of overwhelmed hospitals and tens
of thousands of additional deaths by late several countries by the end of the year. cine effective against just type 2, known as
January 2021. She predicts “a huge surge
in the need for … everything from personal “All the early signs and data look pretty monovalent OPV2 (mOPV2).
protective equipment to health care workers
to medications.” Biden has vowed to marshal good,” says Jay Wenger, who leads polio eradi- The move worked in most places, but
the needed response, but, Bhadelia says: “The
trouble is, we need all those things now.” cation efforts at the Gates Foundation. But he mOPV2 spawned new outbreaks in some

Even if the Biden administration makes and others concede that clinical trials to date others. Twenty-three countries, most of them
all the right calls once it takes charge of the
pandemic fight, many experts expect the bat- have involved just 1200 people. The vaccine’s in Africa, are now battling vaccine-derived
tle to be lengthy and grueling. Turning the
pandemic around “is gonna be hard,” Toner full worth won’t be known until it is given to outbreaks, and the vaccine virus is paralyz-
says. “It’s gonna be slow.” j
millions of children under close scrutiny. ing more children than the wild type. The

The problem is Albert Sabin’s oral polio problem is rapidly getting worse, in part be-

vaccine (OPV), the workhorse of the eradi- cause children born after the switch no lon-

cation program. OPV is cheap, effective, ger have immunity to type 2. So far this year,

and easy to use, needing just two drops on more than 600 vaccine-derived cases have

a child’s tongue. It is made from a living vi- been recorded, five times as many as by this

rus, attenuated, or weakened, so it can’t par- point in 2019.

alyze but can still replicate in the gut. This The new vaccine, in the works since 2011

means children shed the vaccine virus in and known as novel OPV2 (nOPV2), is an

their stool for a few weeks after they receive improved version of Sabin’s vaccine, pains-

it, spreading it to others who are not vacci- takingly engineered to be more genetically

nated and protecting them, too. (The killed, stable. The Sabin vaccine was created in

injected vaccine adopted by most rich coun- the 1940s and ’50s by passaging the virus

tries protects against paralysis but does not through animal cells until scientists found

block circulation.) Massive OPV immuniza- a suitably weakened form. They now know

tion campaigns have driven the wild polio a few mutations at one end of the viral ge-

virus almost to extinction; it is now holed nome are key to weakening it.

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NEWS | IN DEPTH

To “tighten” or stabilize these Sabin nation might not work—“a very low prob- VOICES OF THE PANDEMIC

mutations, a global consortium of dozens ability, high-consequence event” that could India’s
COVID-19
of researchers introduced 18 nucleotide undermine faith in the eradication effort, teacher

changes at the so-called 5’ end of the viral he says. That’s why the rollout will be done Kerala health minister
K. K. Shailaja has fought the
genome. One change, explains the Gates with “an abundance of caution,” Zipursky pandemic with preparation,
calm, and compassion
Foundation’s Ananda Bandyopadhyay, says, “so if anything unexpected happens,
By Vaishnavi Chandrashekhar
who co-chairs the nOPV2 working group we will be able to identify it and respond
W hen the World Health Organiza-
at GPEI, was to block a single point muta- to it quickly.” tion (WHO) issued its first state-
ment on the spread of a novel
tion that seems to be the “gatekeeper,” pre- Because the new vaccine will be approved coronavirus in Wuhan, China, on
18 January, few local governments
ceding other events leading to virulence. for emergency use only, countries must have in India paid close attention. But K.
K. Shailaja, the diminutive woman running
Other tweaks aim to block another route an ongoing outbreak. But to meet WHO’s the health ministry in the southern state of
Kerala, immediately perked up her ears.
back to neurovirulence: recombination, in 27 strict criteria for the 3-month “initial-
Shailaja knew many students from Kerala
which the Sabin virus swaps genetic mate- use” period, they cannot have used mOPV2 were studying at Wuhan University, and she
understood the havoc an outbreak could
rial with related viruses and loses the mu- in the same area for the past 12 weeks, be- cause. In 2018, during her first stint as a
minister, she faced an outbreak of Nipah
tations that weaken it. cause that would make it harder to assess virus, another deadly pathogen spread from
animals to people. “We knew anything could
Data from preclinical research and phase how the vaccine is doing. The problem is happen at any time,” she says.

I and II studies in adults, children, and that countries don’t have the luxury of wait- By 24 January, Shailaja had called a meet-
ing of her rapid response team, set up a con-
infants in Belgium and Panama are “very, ing until the new vaccine is ready; when a trol room, and mobilized surveillance teams.
On 27 January, the first group of students
very reassuring,” Bandyopadhyay says: The new outbreak occurs, they must act imme- flew back from Wuhan. Three days later, one
of them tested positive for COVID-19, becom-
vaccine appears to be as safe and effective diately with mOPV2. This has resulted in ing India’s first confirmed case.

as the Sabin vaccine, and so far, extensive a changing cast of candidate countries as Kerala was ripe for the spread of the vi-
rus, with its large urban population, many
sequencing analyses have turned up no GPEI has waited for WHO’s emergency use residents living abroad (and traveling back
and forth), and high influx of migrant labor-
approval, originally expected ers. Yet with targeted testing, contact trac-
ing, and isolation measures, the leftist state
this summer. government brought the number of daily
new cases down to almost zero in the first
Countries must also ap- few months, flattening the curve far better
than the rest of India. As national lockdown
prove emergency use of measures eased, infections have risen again,
but the state seems prepared to keep things
the vaccine and be able to from going out of control. Only 0.36% of
confirmed cases have died, a mortality rate
monitor safety and efficacy, that is among the lowest in the world and
reflects both Kerala’s young population and
and they have to be able to high-quality health care. “In many ways,
[Kerala] got it right,” says virologist Shahid
transport type 2 isolates to a Jameel, director of Ashoka University’s
Trivedi School of Biosciences. “They possi-
lab for sequencing—fast—to

determine whether it arose

from the novel vaccine or

past use of the monovalent

vaccine. Liberia, the Republic

of Congo, Sudan, and Egypt

are now on the list, says

Michel Zaffran, who is step-

ping down as head of GPEI at

the end of the year.

If safety continues to look

good and nOPV2 seems to be

more stable, “those would be

positive signals to roll it out

A girl receives the oral polio vaccine in Egypt, a candidate country for in a bigger way,” says John

the introduction of a new vaccine less likely to cause outbreaks. Vertefeuille, who leads polio

efforts at the U.S. Centers

evidence of dangerous reversion. Now, the for Disease Control and Prevention (CDC).

“million-dollar question” is how stable the GPEI expects to ramp up production to

vaccine will be when used in a much larger 600 million doses a year.

population, says WHO’s Simona Zipursky, Even if nOPV2 works as planned, stop-

who co-chairs the nOPV2 working group. ping outbreaks will be just as hard as it is

Wenger hopes it will be hundreds of with mOPV2, says Mark Pallansch, a po- PHOTO: GIANLUIGI GUERCIA/AFP VIA GETTY IMAGES

times more stable. “But [even] a 10-fold lio expert at CDC. It depends on reaching

increase, which is not much, would be a enough children to boost population im-

huge change,” he says. “It doesn’t have to munity high enough so the virus can no lon-

be absolutely perfect to be useful. It could ger circulate—and countries with ongoing

be enough to let the program catch up.” outbreaks have, by definition, been falling

“I think it is indeed a much, much bet- short. But even if the new vaccine doesn’t

ter vaccine than monovalent OPV2,” says quash all vaccine-derived outbreaks,

WHO’s Ondrej Mach, GPEI’s team lead Pallansch says, “Hopefully, we will stop

for R&D. “But we simply have to be 100% lighting new fires. That is the hope.” j

sure.” There is a theoretical possibility that

the changes aimed at preventing recombi- Leslie Roberts is a journalist in Washington, D.C.

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bly got it right the most of any Indian state.” response was improvised and health per- infant mortality rates comparable to those

Much of the credit goes to Kerala’s calm sonnel were inadequately trained. The out- in many wealthier countries. Devolution of

and cheerful health minister, often called break was contained, however, by isolating power has also strengthened citizens’ par-

“Shailaja Teacher” because of her old job patients and tracing and quarantining more ticipation and public communication, Reddy

as a high school teacher. Although Kerala than 2000 contacts. In the end there were notes. “Despite political polarities, at the [vil-

benefited from historical advantages in- 19 confirmed cases and 17 deaths. And lage council] level, there is a great deal of so-

cluding the country’s highest literacy rates Shailaja and her team resolved to be better cial solidarity,” he says.

and arguably its best primary health care prepared for the next outbreak. They put in Shailaja built on those advantages, Reddy

system, experts say Shailaja’s leadership has place a raft of measures, including improved says, by engaging scientific advice, gener-

been critical. “She listens to people, she vis- surveillance and contact tracing systems, ating support across ministries, and com-

its hospitals privately, she talks to doctors,” standard operating procedures, and hospital municating with the public. “With a fairly

says K. Srinath Reddy, director of the Pub- protocols. “It’s important to build capacity educated and politically agile population, so

lic Health Foundation of India. “She comes in peacetime,” Jameel says, adding, “They’ve much depends on gaining citizen trust and

across as a person who is blessed both in done well in that.” cooperation, and she has been able to do that

ability and humility.” Shailaja also learned how to deal with the effectively,” he says.

Shailaja has a passion for science that goes thorny social aspects of an epidemic. In the Still, she has met with resistance from

back to her time as a physics and bio- political rivals seemingly resent-

logy teacher in the late 1970s. She and ful of her success as a woman. One

her students would read the science sarcastically called her “Nipah Prin-

section of local newspapers in class, cess,” especially after a film called

she recalls. “We would have the most Virus was made about the outbreak

interesting discussions about space, with a well-known actor playing

the Moon landing, so many things Shailaja heroically taking charge.

not on the syllabus,” she says. Politics, More recently, a politician called

however, eventually drew her in. her the “COVID Queen.” Opposition

In the 1950s, members of her fam- seems likely to increase with the re-

ily joined the growing communist cent surge in cases.

movement. Her grandmother took As India’s economy reopened and

part in local movements against travel increased, clusters of cases

untouchability (the persecution of cropped up in parts of Kerala, grow-

caste groups seen as lesser or “im- ing into a surge after the harvest fes-

pure”), sometimes taking young tival in late August. By October, the

Shailaja along to tumultuous pro- state was seeing some of the coun-

tests. Shailaja says her grandmother try’s largest daily increases in cases.

taught her to be brave, and not only Some observers say the government

in politics. Smallpox was once wide- became lax and did not test enough.

spread in Kerala, and the sick were Others point to the influx of migrant

often shunned; many people believed labor. “A lot of people also returned

patients were cursed by a goddess. from the Gulf [countries] after the

But not her grandmother. She would lockdown lifted,” Jameel notes.

visit patients in their homes and of- Fatigue with the early strict mea-

fer them clean water, good food, and “Untilwe get avaccine,all of uswill sures may have set in, especially
traditional herbal remedies. “She was among health workers, and the state’s

very bold,” Shailaja says. “Everybody governor, a federal appointee, sug-
gested the good health care and low
have to sacrifice some pleasures in our lives.”should have such a grandmother.”

After working her way up to K. K. Shailaja, Kerala state health minister death rates made people unafraid of

leadership positions in one of the the virus. When Shailaja spoke with

state’s communist parties, Shailaja was ap- Nipah outbreak, the government initially Science in August, she said she was preparing

pointed minister of health and social wel- cremated the dead—which was unaccept- for a possible second wave with an increase

fare in 2016. Memories of smallpox may able to Kerala’s many Muslims. One relative in hospital beds and recommendations to re-

have been in her mind in 2018 as she was called Shailaja in tears, and she asked her new some lockdown measures. “Until we get

grappling with the state’s first outbreak of team to find a solution. Finally, they settled a vaccine, all of us will have to sacrifice some

Nipah, a bat-borne virus with a human case on a burial technique: wrapping the body in pleasures in our lives,” she said. More re-

fatality rate of 50% to 75%. Ignoring warn- airtight plastic and burying it 3 meters deep. cently she acknowledged that festival gather-

ings, Shailaja visited the worst hit village to “We understood that we have to make our ings and political protests had contributed to

calm residents and explain that, although own protocols sometimes,” she says. the recent surge, and recommended stricter

person-to-person transmission can occur Kerala’s traditionally strong social services travel restrictions.

ILLUSTRATION: KATTY HUERTAS with Nipah, especially in hospitals, the risk have helped fight the new pandemic. During Now, more than ever, Kerala’s hard-

is low. Her visit was credited with helping the national lockdown early this year, Kerala working health minister will need to draw

prevent a mass flight from the area. provided migrant laborers with shelter and on all of her abilities—and her grandmoth-

WHO later concluded that Kerala’s early food to keep them from fleeing back to their er’s plucky spirit—to find new strategies

home states—and potentially spreading the against the virus. j

Science’s COVID-19 reporting is supported by the virus. The state started with some of the best

Pulitzer Center and the Heising-Simons Foundation. health indicators in the country, including Vaishnavi Chandrashekhar is a journalist in Mumbai.

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NEWS | IN DEPTH

COVID 19

Pandemic dooms Danish mink—and mink research

Mass culling ordered after discovery of mutations that may affect vaccine efficacy

By Christa Lesté-Lasserre pediting a complete ban on mink farming, enough to order the culling of all 12 mil-
originally planned for 2024 and now effec- lion remaining minks in Denmark, the
J ens Malmkvist’s life’s work came tive by March 2021. The explosive spread of world’s largest mink producer. About 80%
to a dramatic end this week. An the virus in mink and several documented of the animals were scheduled to meet
ethologist at Aarhus University, cases of mink-to-human transmission made their end this month anyway—and become
Malmkvist studies the behavior and the Dutch government fear farms might be- fur—but the decision means breeding and
welfare of farmed mink, with the aim come a permanent virus reservoir. laboratory stocks will be destroyed as well.
of giving them a better life as they are Mink farming will be banned at least until
raised for fur. But on 9 and 10 November, The Danish government has an even the end of 2021.
all 6350 minks at the Aarhus facility were more troubling concern. SARS-CoV-2 has
gassed as part of a nationwide cull ordered remained “quite stable” since its emergence Biologist David Kennedy of Pennsylvania
by the Danish government. in the human population, Ben Embarek State University, University Park, agrees
says, but spillovers into animals can trigger mutations in the spike protein “could
Denmark is seeking to stop the spread of mutations as the virus adapts to a new host. completely undermine” vaccine efficacy,
what it deems a dangerous strain of SARS- That has happened in mink. The report, especially if they occur in the part of the
protein that binds to the human receptor,
Mink farmer Henrik Nordgaard Hansen killed the entire herd at his farm near Næstved, Denmark, last week. as one of the four mutations in DFVI does.
He says more data are needed to document
CoV-2, the virus that causes COVID-19, posted online on 10 November by the Stat- the mutations’ impact, but in the mean- PHOTO: MADS CLAUS RASMUSSEN/RITZAU SCANPIX/AFP VIA GETTY IMAGES
that’s circulating in mink and infecting hu- ens Serum Institute, a government lab, re- time it’s important to keep the strain from
mans as well. Scientists say mutations in ported clusters of genetic mutations in the spreading. “If the human-to-human trans-
the virus, described this week in a short re- virus infecting the animals. One strain, now mission of this variant isn’t stopped, stop-
port, might reduce the efficacy of COVID-19 called the DFVI-spike mutant, has four mu- ping further introductions of this variant
vaccines. The cull was a “brave” and “dra- tations in the gene coding for the spike pro- from the mink won’t matter.”
matic” step, says Peter Ben Embarek, an tein, which helps the virus enter host cells.
expert in food safety and zoonoses at the Researchers in the Netherlands have also
World Health Organization. Malmkvist says Experiments with the DFVI strain studied SARS-CoV-2 evolution in mink. In
it may be the right decision, but mourns the showed plasma from recovered COVID-19 a paper published online by Science on
impact on research and the personal toll on patients or rabbits immunized with the vi- 10 November, they reported finding the mu-
his team. “It’s incredibly sad and shocking, rus did not neutralize it as efficiently as the tation affecting the receptor binding site—
just happening overnight like that,” he says. unmutated virus. Because many COVID-19 but not the other three present in DFVI—at
vaccines aim to elicit an immune response four farms. “It did not continue spreading,
The move reflects a growing concern to the spike protein, the worry is that those and we haven’t seen it since,” says vet-
about the spread of SARS-CoV-2 in mink, vaccines might not work well against the erinary epidemiologist Arjan Stegeman of
reported in six countries. Four—Spain, Swe- DFVI mutant, which so far has been found Utrecht University. (The team did find that
den, Italy, and the United States—have re- in 12 people in Denmark as well. 68% of farm workers and their contacts had
sponded by culling populations at affected antibodies to the virus, underscoring the
farms. The Netherlands went further by ex- The findings are preliminary, but the risk of mink-to-human transmission.)
government considered them serious
Although mink farming is controversial
in Europe, it is likely to survive the pan-
demic, Malmkvist says, so research into
mink welfare remains necessary. His stud-
ies have led to improved cage size and de-
sign, diets, and bedding materials. Work by
his team also influenced Danish legislation
that requires breeders to select for less fear-
ful animals and helped establish an animal
welfare certification system in the Euro-
pean Union, he says: “I felt part of a team,
making a difference.”

The fact that his research herd had not
seen outbreaks makes the mass slaughter all
the more painful. “But we cannot take any
risk regarding human health,” Malmkvist
says. “I must trust that the Danish leader-
ship has made the right decision.” j

Christa Lesté-Lasserre is a freelance journalist in Paris.

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In 2018, Mars was
enveloped by dust
storms (seen here in a
Mars Express image)
that helped water
escape the planet.

PLANETARY SCIENCE mosphere, driving winds that kick up more
dust, which in turn leads to more heat and
Dust storms on Mars propel more dust. A warmer atmosphere can hold
water’s escape to space more water vapor, and the dust itself likely
drags water along with it as it swirls into the
Orbiters spy potential ongoing planetary “death spiral” upper atmosphere.

PHOTO: ESA/DLR/FU BERLIN/CC BY-SA 3.0 IGO By Paul Voosen Arizona, was looking at data from MAVEN, The TGO observations showed water lev-
which has studied the planet’s upper atmo- els gradually increase through the southern
T wo years ago, Mars went undercover. sphere since 2014. One MAVEN instrument summer, but the MAVEN data suggest re-
Martian dust storms are common, directly samples the gossamer atmosphere as gional and global dust storms drive the larg-
but every decade or so, for reasons un- the probe dips to its lowest orbital altitude of est spikes. Over the course of 2 days near the
known, a monstrous one goes global, 150 kilometers, and Stone and his colleagues start of the 2018 storm, water abundance
veiling the planet. The storms can be a couldn’t believe what it was reporting: While in the upper atmosphere, normally about
mortal threat to exploration: The one the dust swirled at lower altitudes, a deluge 3 parts per million, more than doubled; by
in 2018 killed off NASA’s Opportunity rover of water was reaching the edge of space. summer’s peak, the storm and the overall
by coating its solar panels in dust. But now, “This was really a smack in the face,” Stone warming ultimately combined to push those
researchers say the storms may also be one says. “The global dust storm stands out in the levels to 60 parts per million. “It’s just a huge
of the culprits in the ultimate martian cold data like nothing else.” influx of water,” Stone says.
case: how the once-wet planet lost its water.
Earlier hints that dust storms might some- High in the atmosphere, UV light readily
Fossilized rivers and deltas etched across how be lofting water came in 2014, when two splits the water, allowing the hydrogen and
Mars suggest water flowed there billions of teams reported on UV observations made in oxygen to be lost to space. But Stone and
years ago. Most of it must have somehow es- 2007, after the last global dust storm, by the his colleagues believe another destructive
caped to space—yet researchers thought wa- Hubble Space Telescope and the Mars Ex- mechanism dominates. Their models suggest
ter vapor could not travel high in the frigid, press orbiter. The teams noticed a fluorescent carbon dioxide, ionized by particles in the
thin atmosphere without condensing into fog of hydrogen in the upper atmosphere, solar wind that bombards the atmosphere,
snow and falling back to the surface. New which faded as the southern hemisphere’s vigorously splits the water molecules apart.
data from NASA’s Mars Atmosphere and Vol- summer ended and the storm subsided. The “They’re making a good case,” though the
atile Evolution (MAVEN) orbiter, published only plausible source for that hydrogen was importance of the mechanism needs to be
this week in Science, show how churning dust water. “That was the first hint of something better quantified, says John Clarke, a plan-
storms may in effect pump water into space. weird going on,” says Michael Chaffin, a plan- etary astronomer at Boston University.
“These escape processes are an effective way etary scientist at the University of Colorado,
to make Mars dry,” says Anna Fedorova, a Boulder, who led the Mars Express work. The MAVEN team has calculated that if
planetary scientist at the Space Research In- the observed loss rates persisted throughout
stitute of the Russian Academy of Sciences. Since then researchers using instruments martian history, the planet would have lost a
on MAVEN and the European Space Agency’s global ocean more than 25 meters deep. But
One known escape process comes from the Trace Gas Orbiter (TGO) have found evidence how long this dust-driven destruction has
Sun’s ultraviolet (UV) light, which can split for water high in the atmosphere during the operated on Mars is anyone’s guess, Stone
small amounts of water near the surface of southern hemisphere’s summer, when solar adds. It could be recent, or it may have been
Mars, sending hydrogen and oxygen—both heating stirs up dust. That was true even key to drying out the planet billions of years
lighter than the planet’s mostly carbon diox- when there wasn’t a full-fledged dust storm, ago. Researchers believe the planet once
ide air—percolating to the top of the atmo- says Fedorova, who led the TGO work, pub- had a protective magnetic field that failed
sphere, where they are lost into space. But lished in January in Science. early in its history, allowing the solar wind
scientists assume water loss by this mecha- to penetrate deeper in the atmosphere,
nism is a trickle. Fedorova and colleagues believe dust where global dust storms were putting wa-
drives a positive feedback that pumps wa- ter in harm’s way. That could have caused
During the 2018 storm, however, Shane ter into the upper atmosphere. Sun-warmed water loss to surge, Chaffin says. “Maybe
Stone, a graduate student at the University of dust particles radiate heat into the lower at- you fall off a cliff and get this seasonal and
dust-driven loss,” he says. What MAVEN is
witnessing now, he adds, could be the end
of a “planetary death spiral.” j

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NEWS

FEATURES

RISING FROM

THE ASHES

An effort to breed North American ash trees that can resist

a deadly beetle could accelerate the return of a forest icon

By Gabriel Popkin, at the U.S. Forestry Sciences Laboratory in Delaware, Ohio;
Photography by Maddie McGarvey

O n a weekday morning in August, (Agrilus planipennis), the most devastating Forest geneticist team the most. Those
just one pickup truck sat in the insect ever to strike a North American tree.
sprawling visitors’ parking lot here Since the Asian beetle was first discovered Jennifer Koch finds signal trees that,
at this U.S. Department of Agricul- in Michigan in 2002, it has killed hundreds
ture (USDA) facility. A decadeslong of millions of ash trees across half the con- hopes her ash through genetic luck,
decline in research funding had tinent and caused tens of billions of dollars
been slowly quieting the place— of damage. breeding strategy can kill emerald ash
and then came the pandemic.
But in a narrow strip of grass “We have contests for who can success- could save other borers, rather than the
behind a homely, 1960s-era building, forest fully pull out the smallest larvae and the
geneticist Jennifer Koch was overseeing a biggest larvae,” Koch says. “People get threatened trees. other way around. Such
hive of activity. A team of seven technicians, pretty excited and competitive about it. You
researchers, and students—each masked have to do something, because it is very rare resistant trees could
and under their own blue pop-up tent— tedious—and [the larvae] are really gross.”
were systematically dissecting 3-meter-tall ultimately help Koch achieve her ambi-
ash trees in a strange sort of arboreal dis- The larvae kill ash trees by burrowing
assembly line. Over 5 weeks, the researchers into them to feed on bark and, fatally, the tious goal: using time-tested plant-breeding
would take apart some 400 saplings, peel- thin, pipelike tissues that transport water
ing wood back layer by layer in search of the and nutrients. They then transform into techniques to create ash varieties that can
maggotlike larvae of the emerald ash borer iridescent green beetles about the size of
a grain of rice that fly off to attack other fend off the borer and reclaim their historic
trees. Dead larvae excite Koch and her
place in North American forests.

Koch focuses mostly on the green ash,

one of at least 16 native ash species in North

America. “If we don’t intervene, there’s a

good chance that green ash will go extinct,”

she says. But she is also ramping up work

on other ash species; none is safe from the

borer. And ultimately, she hopes to expand

her approach to other trees brought low by a

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NEWS

foreign pest, in a bid to reverse the biological Ash borer invasion 7–13 mm
hollowing out of forests set in motion by the
transcontinental swapping of species. Since slipping into the United States around the Agrilus planipennis Cooked rice grain
turn of the millennium, probably on a container
Since a devastating fungal blight popped ship, the emerald ash borer (EAB) has spread to
up in the Bronx Zoo in 1904 and went on to 35 states and killed hundreds of millions of trees.
kill at least 3 billion chestnut trees, North Scientists have called it the most destructive forest
American forests have been swept by one pest ever introduced to North America.
plague after another, including a fungus
that kills elms and an aphidlike insect that A cornerstone tree
kills hemlocks. No tree has come back—but
Koch hopes her approach can usher in an Comprising at least 16 species native to North
unprecedented era of tree revival. “We don’t America, ash trees are key components of
think we have to lose any North American wetland, mountain, and savanna ecosystems.
tree species to invasive pests and disease,” They have also been heavily planted in cities.
says plant geneticist Jeanne Romero-
Severson of the University of Notre Dame, Adult EAB
one of Koch’s collaborators. feeds on leaves

Not all researchers share such faith in 1
tree breeding. Many researchers believe 2
identifying and releasing natural en-
emies of the ash borer, an approach 1–2 year Larva
called biological control, could cycle gallery
help ash sooner. And some won-
der whether, even if a better ash View at
emerges, the trees will be able to right
muscle their way back into pro-
foundly reshaped ecosystems. “It’s Frass
not like if we have a resistant
ash tree, everything is go- Cycle of destruction Larva
ing to be hunky dory,” says
Deborah McCullough, a for- The EAB completes its life cycle in 1 to 2 years. 3
est entomologist at Michigan Along the way it exploits multiple parts of the tree.
State University. Pupa 4
1 Mating
GRAPHIC: C. BICKEL/SCIENCE Koch, however, feels certain Adult EAB beetles feed on ash leaves and mate 5
that genes lurking among the billions of during the warmest parts of the summer. A female D-shaped
ash trees growing across the continent can can mate multiple times during her short life. exit hole
save the species. “Genetic variation,” she says,
“is a very powerful survival mechanism.” 2 Egg laying
Females lay eggs in crevices in ash bark. One female
KOCH’S QUEST HAS ITS ORIGINS in a humble can lay up to 100 eggs, which hatch in 7 to 10 days.
place: parking lots around Detroit. That’s
where, nearly 2 decades ago, experts gath- 3 Larva development
ered to examine ash trees that had suddenly Maggotlike larvae burrow into the tree and feed on
died. “It was pretty obvious right away this wood and tissues that trees use to transport water and
was not something anybody had ever seen nutrients, creating squiggly galleries up to half a meter
before,” recalls McCullough, who cut down long. Larval feeding is what kills trees.
some of those trees for study. “We just don’t
have native insects that do that kind of stuff.” 4 Adult development
In the fall, larvae create small chambers within the tree.
Eventually Eduard Jendek, an entomo- They overwinter there and pupate in the spring.
logist in Bratislava, Slovakia, identified the
culprit as the emerald ash borer, which 5 Escape
had lived mostly unnoticed in its east Asian Beetles bore out of the bark, creating characteristic
homeland. But the insect’s arrival in North D-shaped exit holes, and fly off in search of new trees to feed
America set off alarms. Ash is a key genus of on. Adult beetles live about 3 weeks. They can fly up to
temperate hardwood tree. Individuals soar 10 kilometers, but usually find a new tree much closer to home.
to 35 meters, and species anchor critical eco-
systems: black ash in soggy northern wet-
lands, green ash along Midwestern streams,
blue ash in open savannas of Kentucky, white
ash in dense mountain forests of Appalachia,
and a half-dozen species in the Southwest.
Resilient and stress-tolerant, ash was also
heavily planted in cities.

Adult borers, scientists soon learned, feed

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NEWS | FEATURES

on ash leaves and lay eggs on ash bark. Bur- in the plots fared. It was “kind of boring” at the breeding program. Carey moved down

rowing and feeding larvae eventually girdle first, Knight says, because almost all the ash a few centimeters along the tree trunk and

trees, killing them. North American trees, trees simply died. But over time, she found started a new dissection.

separated from their Asian cousins by an that about one in 1000 green and white ash In 2015, Koch’s team published its first

ocean and millions of years of evolution, trees—the most common species in Ohio— major paper on ash, reporting that lin-

had never been exposed to the borer, and produced flushes of new leaves even after gering green ash trees killed significantly

lacked chemicals to detect or defeat it. “It’s borers had killed neighboring trees. Start- more larvae than control trees. That, she

as if they don’t even know something is ing in 2008, Knight, Koch, and others cut says, convinced many who doubted that

boring into their vascular system and kill- branches from the biggest and healthiest of trees never exposed to an introduced insect

ing them,” Romero-Severson says. those trees, which they dubbed “lingering could still resist it. But even lingering trees

Michigan and USDA imposed quaran- ash,” and grafted them onto root stock of didn’t kill enough larvae to save themselves,

tines on moving ash trees in a bid to con- healthy trees. “We try to look for the best of the researchers found; they still died, just

tain the pest. But the beetle, an agile flier the best,” Knight says. more slowly. So in 2010, Koch started to

adept at sniffing out ash trees, slipped The researchers then developed a way to crossbreed her most resistant trees—the

through with ease; it has now same basic technique used by

reached 35 states and Washing- plant breeders for 10,000 years

ton, D.C. (see map, right). Many A beetle on the march to produce bigger grains, sweeter
Midwestern city streets became fruit, and countless other desired
denuded dystopias of dead trees. Since the emerald ash borer (EAB) was discovered in Michigan in 2002, traits. In essence, one of Koch’s
Some experts predicted the borer it has spread widely into areas where ash trees grow. colleagues joked, they created

could cause the extinction of ash “TreeHarmony”—a matchmaking

species in North America and be- service for durable trees. “We’re

gan to organize a response. CANADA kind of pushing Mother Nature

Koch, who had arrived at the along by putting these trees to-

USDA lab in the 1990s as a gradu- gether,” Koch says.

ate student and stayed on as a Such traditional breeding is a

staff scientist, was intrigued. UNITED STATES blunter tool than more fashionable

Gregarious and impatient with genetic engineering techniques

dogmatic thinking, Koch is more that can precisely transfer or alter

motivated by solving real-world single genes. But traits like insect

problems than by doing basic re- resistance are typically controlled
by many genes, not one—and in
search on model organisms. In Counties where the case of ash trees, researchers
EAB detected don’t know which genes are impor-
graduate school, she studied the tant. Some may code for chemicals
Range of ash that kill feeding larvae or make
genetics of air pollution resistance 0 1000 MEXICO in the
United States
in poplar trees but then moved on km and Canada
to trying to breed resistance to

a century-old debilitating bark wood less digestible; others may

disease of beech trees caused by a fungus- test for resistance under controlled condi- make leaves less detectable or palatable to

insect combination. tions. Starting in late spring, Koch’s team adults. Several generations of breeding and

In 2003, Koch attended an early meet- receives coffee filters containing thousands selection will allow these genes to stack up

ing on the forest pest du jour: the emer- of ash borer eggs reared by Forest Service over time, providing ever stronger defense,

ald ash borer. During the discussion, she entomologist Therese Poland in Lansing, Koch hopes.

wondered aloud whether some trees might Michigan. Researchers place 12 eggs on The efforts have borne some fruit. The

harbor natural resistance to the beetle. each stem of hundreds of ash saplings top-performing offspring of two lingering

“Everyone kind of looked at me like I was grown from cuttings. Eight weeks later, they ash trees kill up to four times as many lar-

nuts,” she recalls. “Back then the big head- dissect the trees and trace the fate of each vae as their parents, Koch and colleagues

line was: ‘Kiss your ash goodbye.’ People hatched borer. have found. “Our best tree so far was 11 out

just didn’t believe that there could be re- David Carey, a technician on Koch’s team, of 11” larvae killed, Koch says; the 12th egg

sistance within native species.” was performing that task in August. Sitting failed to hatch. Now, she’s planning to use

But Koch persisted. In cities, where the under his tent, he snapped green branches those top performers to breed an even more

plague first emerged, trees tend to lack di- off a sapling and saved them for future resistant generation. If those trees consis-

versity, she reasoned; urban foresters tend grafting onto other trees, in case the sapling tently kill 80% to 90% of larvae that attack

to plant genetically similar strains widely, proved resistant. Then he deftly shaved the them in field trials, Koch says they can be-

making street trees uniquely vulnerable to thin bark off the trunk, to expose evidence gin restoration efforts. She hopes restora-

invasive pests. Trees growing in forests, by of feeding: “galleries,” or winding tunnels tion plantings could start in about 10 years.

contrast, have had millions of years to mutate bored by the larvae that resemble a kinder- Such a timeline would be fast by tree-

and mix genes into countless combinations. gartner’s marker squiggles. breeding standards, but some fear it may be

The first step, Koch realized, was to sur- Soon, Carey found a little yellow head too slow to save the ash. Already, formerly GRAPHIC: A. CUADRA/SCIENCE

vey that genetic diversity before the borer poking out, the larva’s body still encased in ash-dominated sites now host other trees,

eliminated it. Starting in 2005, ecologist the tree. He pulled the larva out with twee- grasses, or invasive plants. So, to restore

Kathleen Knight of the U.S. Forest Ser- zers, placed it in a plastic tray with a grow- ash, those newcomers would first need to

vice and Koch set up 150 study plots in ing pile of its compatriots, and cataloged its be removed—a potentially expensive, labor-

infested forests in Ohio, and then repeat- size and location. The tree’s failure to kill intensive process, McCullough says. “Na-

edly revisited them, tracing how ash trees this larva was a strike against its future in ture doesn’t just sit there and wait for you

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to come along and plant a tree.” up samples from dissected saplings

McCullough and others are more and analyzes the chemicals in the

bullish on saving existing trees wood. This is no trivial task; ash,

through biological control: identify- like other trees, is a sophisticated

ing, rearing, and releasing insects chemical factory, producing hun-

or other species that kill unwanted dreds of compounds with structures

pests. The concept has a long history and functions unknown to science.

of success in managed landscapes, “Plants are just chemical geniuses,”

such as farm fields and orchards. Stanley says.

But its record in natural forests is Most of these compounds prob-

less sterling. For example, biocontrol ably provide no defense against ash

researchers have spent more than borers. But a handful show up dis-

3 decades seeking and rearing preda- proportionately in trees that kill the

tors to curb the hemlock woolly adel- most borer larvae, Stanley has found.

gid, which kills eastern and Carolina And if such compounds reliably pre-

hemlock trees; they’ve made prog- dict longer survival in the forest,

ress but are still far from declaring they could pave the way to rapid

victory (Science, 17 January, p. 238). testing of wild trees for borer resis-

Biocontrol researchers say the ash tance, potentially speeding breeding

borer might be easier to defeat. In efforts, Koch says. “We’re hoping for

the insect’s home range in Asia, re- some way we can quickly test a tree

searchers have found three species and say, ‘OK, that one’s a dog.’”

of tiny wasps that lay eggs inside ash Despite the progress she’s made,

borer larvae, and one wasp the size Koch says it sometimes “feels like the

of a grain of sand that parasitizes weight of the world is on us.” Hers

borer eggs. Parasitoids have often remains the sole U.S.-based effort to

proved to be more successful bio- revive ash trees through breeding.

control agents than predators, like (Breeders in the United Kingdom

those that might tame the woolly are seeking genetic resistance to a

adelgid, because parasitoids are fungus attacking ash trees there.)

more likely to target a single species, But she’s starting to recruit help by

causing less collateral damage. building a network of government

In recent years, researchers and nonprofit organizations to grow

have released wasps in forests in and plant resistant ash trees. The

30 states where the emerald ash Larvae of the emerald ash borer chew into trees, where they overwinter collaboration—which includes the

borer is present. Follow-up stud- beneath the bark before pupating in the spring. conservation organization American

ies have shown the wasps can find Forests; the Holden Arboretum in

beetles, parasitize them, and reproduce; in “Sometimes there’s an overexuberance Kirtland, Ohio; and Fender Musical Instru-

some trees, up to 80% of ash borer larvae towards the efficacy of biocontrol,” says ments, which has long used ash wood for

have wasps living inside them. “There’s a Koch, who feels she has had to meet a guitars—has plans to establish an ash tree

lot of data that suggest it’s promising,” says higher bar to get her breeding research nursery in Detroit. Some of Koch’s trees were

Poland, who leads the Forest Service’s re- funded. Still, she hopes the wasps succeed. supposed to be growing there by now, but the

search effort. Effective parasitoids could complement shipment was delayed by the pandemic and

Biocontrol is now the “cornerstone” of anti- her breeding efforts, she says, by lowering is now planned for spring.

borer efforts led by the Animal and Plant ash borer numbers enough to give partially Ash breeding may be just the beginning.

Health Inspection Service (APHIS), USDA’s resistant trees better odds of surviving to Koch believes her approach could save

primary agency for fighting plant pests. reproductive age. That’s what happens in other North American trees facing intro-

Through the end of 2019, APHIS had in- Asia, Koch notes, where genes and ash duced threats. Researchers at the Univer-

vested $13.2 million in emerald ash borer borer enemies conspire to protect trees. sity of Rhode Island and North Carolina

biocontrol research, versus $2.4 million in The ultimate goal, she says, is “to mimic State University, for example, have reared

breeding resistant trees. Whereas breeding what happens in nature.” lingering hemlock trees that may resist the

could pay off eventually, biocontrol may al- adelgid; Koch hopes to start breeding the

ready be protecting regrowing ash trees in IN THE MEANTIME, Koch worries her best performers. She’d also like to breed

some places, says Scott Pfister, director of funders—primarily USDA—will lose pa- beech trees that can beat the bark dis-

APHIS’s pest management division. “We tend tience with her breeding efforts. So she ease and eventually add butternut, which

to try to work towards shorter term solu- has embarked on several efforts to speed is threatened by a fungus, as well as elm

tions,” he says. “Breeding for resistance is a up the process. In one, she’s testing whether and chestnut trees. And she knows new

PHOTO: MADDIE MCGARVEY long-term research effort.” ash seedlings grown in containers under diseases and insects will arrive. “My goal,”

But biological control faces its own limi- artificial light and treated with hormones Koch says, “is that when I retire, I leave be-

tation: There have to be enough borers in produce seeds in less than the normal 3 to hind all the tools” that others might need

an area to sustain wasp populations. By the 4 years. Another seeks to identify the spe- to meet new threats to native trees. j

time borers have reached such densities, cific compounds that resistant ash trees use

they will have likely already killed almost to fight the borer. Robert Stanley, a graduate Gabriel Popkin is a journalist in Mount Rainier,

all large ash trees, experts say. student in Romero-Severson’s group, grinds Maryland.

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INSIGHTS

POLICY FORUM

TECHNOLOGY GOVERNANCE: COVID-19 adapt technological design to socially per-
ceived risks and expectations.
What’s next for COVID-19 apps?
Governance and oversight To date, both scholarly and policy debates
on DCT have largely overlooked the above
Adaptive governance can help earn social license dilemma, focusing instead on privacy-re-
lated issues as the pivotal element of DCT
By Alessandro Blasimme and Effy Vayena privacy risks, and the actual effectiveness governance (2). However, although preserv- ILLUSTRATION: DAVIDE BONAZZI/SALZMANART
of DCT, as well as public attitudes toward ing privacy is of the utmost importance,
M any governments have seen digital a potentially pervasive form of digital sur- technical safeguards such as encryption, de-
health technologies as a promising veillance. DCT thus appears to face a typi- centralized data architectures, and temporal
tool to address coronavirus dis- cal social control dilemma. On one hand, limits to data storage have not proved suf-
ease 2019 (COVID-19), particularly pending widespread uptake, assessing ficient for DCT apps to quickly diffuse at a
digital contact tracing (DCT) apps DCT effectiveness is extremely difficult; on population scale.
such as Bluetooth-based exposure the other hand, until DCT effectiveness is
notification apps that trace proximity to proven, its widespread use at a population Social license and trust depend on the ca-
other devices (1) and GPS-based apps that scale is hard to justify. Recognizing that pacity of either corporations or governments
collect geolocation data. But deploying technological uptake is an open-ended to meet societal expectations in relation to
these systems is fraught with challenges, process reliant upon social learning and a specific activity (3). Therefore, for DCT
and most national DCT apps have not yet the piecemeal creation of public trust, we to earn social license, such expectations, as
had the expected rate of uptake. This can suggest that policy-makers set up mecha- well as the factors that cause slow uptake
be attributed to a number of uncertainties nisms to test effectiveness, oversee the use on the part of the public, need to be probed.
regarding general awareness of DCT apps, of DCT apps, monitor public attitudes, and To increase public trust, the World Health
Organization has stressed the importance of

Health Ethics and Policy Lab, Department of Health Sciences
and Technology, ETH Zurich, Zurich, Switzerland. E-mail: effy.
[email protected]; [email protected]

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appropriate oversight for the governance of to do so could lead to premature dismissal be seen as a legitimation tool alone, but as a
DCT apps (4). Switzerland, for example, has of a potentially useful new technology. The fundamental component of the adaptation
involved the Federal Data Protection and Norwegian data protection authority, for in- process, a precondition for social learning
Information Commissioner and the Federal stance, stated that the known risks of DCT around both anticipated and unanticipated
Ethics Committee in the development of the surveillance outweigh its still unproven risks. Moreover, public engagement has the
Swiss national DCT app. The French govern- public health benefits—a position that potential to mitigate the threat posed by in-
ment has sought advice from eight high- caused the Norwegian government to put cumbent concentrations of power by state
profile national expert bodies. Such moves the system on hold (9). authorities or private companies involved
can contribute to the legitimation of a coun- in national DCT strategies.
try’s approach to DCT. Likewise, oversight ADAPTIVE GOVERNANCE
mechanisms of a DCT app can play a role When technologies come with known risks Technical aspects
in sustaining widespread and continued use but uncertainties about benefits persist, The effectiveness of DCT systems in break-
by the public. adaptive governance is a valuable policy ing transmission chains should be assessed
option. It has a long and respected pedi- against previously established public health
PUBLIC RELUCTANCE gree—both in academic scholarship and in objectives, such as app penetrance, ac-
Studies conducted in April and May 2020 policy-making—including in areas that re- curacy, and effectiveness in reducing the
showed that in countries like the United semble severe public health crises, such as health and social burden of the infection.
States, Switzerland, and Italy, between 55 natural hazards and disaster risk reduction. Failure to meet these objectives should lead
and 70% of adults in all age groups were In the case of DCT, we know that privacy- to reconsidering specific technical aspects
willing to download a contact tracing app related risks are present, alongside risks of existing DCT strategies.
(5). Yet these figures do not match the cur- linked to public surveillance and to techni-
rent DCT apps uptake. Even in countries cal failure in the presence of a global public Regular monitoring of technical param-
with robust privacy safeguards in place, health threat. At the same time, DCT ef- eters about the use and reliability of DCT
downloads of DCT apps have been below fectiveness in containing damage from CO- apps would inform specific strategies to be
expectations. At the time of writing, the VID-19 is still to be assessed. adopted to increase the rate of downloads
Australian DCT app has been downloaded and actual use of the apps, and to improve
by 6.5 million (26% of the population), the According to adaptive models, gover- their functioning. Most DCT apps are built
Italian one by 8 million (13.4%), and the nance should enable social learning and with a proactive commitment to privacy-
newly released French one by 1.5 million distribute oversight tasks across different preserving technological features (privacy
(2.3%). Ireland has about 1.3 million active actors (10). Collaboration between differ- by design) and only use strictly necessary
app users (24%), Switzerland 1.8 million ent stakeholders such as developers, health data (privacy by default). However, no
(21.5%), and Germany 16 million (19.3%). ministries, data protection authorities, ex- privacy-preserving system is perfect. Over-
As people keep downloading the app, at perts, and the involvement of lay publics sight bodies should thus regularly test the
some point, the desirable number of us- is a key element for an efficient adaptive robustness of adopted privacy-preserving
ers may be reached. Decades of research governance approach (11). In the face of the measures and define plans to continuously
in science and technology studies confirm above uncertainties, adaptive governance minimize harms.
that such a bell-shaped innovation diffu- urges national DCT initiatives to collect and
sion pattern is not particularly surpris- rapidly incorporate new knowledge into Legal aspects
ing, as technological uptake does not just their governance. DCT oversight should be able to clarify or,
rapidly happen by virtue of a technology’s as the case may be, suggest legal definitions
presumed usefulness (technological de- To effectively implement adaptive gov- for the kind of data collected by DCT apps
terminism), but owes instead to complex ernance of DCT, oversight activities should and the specific roles of all the actors—pri-
cycles of cultural and political adaptation focus on a number of specific adaptive fea- vate or public—involved in development
(social construction of technology) (6). tures (11, 12). and implementation. In particular, spe-
cific types of data like rotating Bluetooth
Members of the public cite unauthorized Public engagement IDs or associated metadata may not have
uses of their data beyond COVID-19 con- Owing to the exceptional circumstances of a clear legal status in a given jurisdiction.
tainment and access to personal data by IT the COVID-19 crisis, national DCT plans Ad hoc legislation may also be needed to
companies and state authorities as matters have been rolled out without engaging the set specific rules and safeguards around
of concern (7). Moreover, older people and public in any phase of the process (13). In voluntariness and misuses of DCT tools. In
people of lower socioeconomic conditions democratic countries, this is likely to un- Switzerland, for example, such legal provi-
are considerably less likely to download dermine trust in technological solutions, sions were introduced in an amendment to
DCT apps (8). Although the public’s reser- especially if they embody a pervasive sur- the Epidemics Act before the release of the
vations are understandable, efforts should veillance logic that may well appear at odds national DCT app.
be made to respond to those concerns with democratic ideals. DCT initiatives
and increase the rate of early adoption of should thus ensure that they offer regular Sanctions linked to unlawful handling of
DCT systems. Use of opt-out mechanisms opportunities of democratic input into the personal data are present in most jurisdic-
rather than opt-in, and large cohort stud- governance of DCT. This can be guaranteed tions. Increasing public awareness about
ies in which participants are incentivized to by including lay publics such as civil society such legal consequences of data misuse can
try out the app, could boost initial uptake representatives, advocacy groups, and non- support trust in DCT systems.
across demographics. This would help ad- governmental organizations in oversight
dress the dilemma discussed above, lead- bodies. Moreover, surveys, deliberative fo- DCT apps operate within national ter-
ing to a parallel increase in the capacity to rums, and notice-and-comment periods ritories. However, cross-border use would
assess effectiveness and, at the same time, should be regularly offered to increase pub- facilitate contact tracing while reinstat-
to exert control over such systems. Failure lic input into the governance of national ing global mobility. To achieve this objec-
DCT apps. Public engagement should not tive, technical interoperability and specific
legal safeguards about cross-border data

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INSIGHTS | POLICY FORUM

exchange must be adopted. The European benefits and burdens of DCT. To this aim, on digital platforms. We have argued that
Commission recently published the “Eu- it is advisable to include social scientists in
ropean Interoperability Certificate Gover- oversight bodies, with a mandate to monitor DCT governance should be focused on evi-
nance” specifying technical standards that how different social groups respond to and
will enable safe data exchange between na- are affected by DCT activities. dence collection and planned adaptation
tional apps (14).
REFLEXIVE ADAPTATION to address numerous uncertainties. In the
Moreover, DCT is not limited to state- In all of the above domains, oversight bod-
sponsored national apps. Private-sector ies should foster reflexive adaptation (11, context of a global crisis requiring rapid re-
employers and small businesses are al- 12) of DCT strategies based on real-world
ready developing their own internal con- data on actual use of DCT apps. Reflexive sponses, this approach has two further ad-
tact tracing systems, and they may make adaptation consists in regularly questioning
them mandatory for workers and custom- assumptions about design, risks, and users’ vantages: It allows governance structures to
ers. This is happening in the absence of attitudes to adapt technological features.
specific legal provisions. DCT oversight coevolve with technological solutions while
bodies should therefore suggest policy One way to proceed is to pay close at-
guidance to ensure that such private- tention to opportunity costs of new DCT they are already in use, and it can reduce
sector DCT is aligned with constitutional technologies. This implies assessing regu-
rights and freedoms and will not be used larly whether DCT complements or fore- the high cost of intervening in an already
to unduly monitor employees and private goes other containment strategies such as
citizens. Failure to deploy appropriate reg- manual tracing methods of established ef- widespread technology.
ulatory frameworks for private-sector DCT fectiveness—for example, on grounds of
may undermine trust in DCT broadly. representing a cheaper alternative. Whatever form, mandate, and composi-

Ethical aspects Moreover, reflexivity amounts to the ca- tion individual countries will establish, the
If DCT gains traction, ethically complex pacity to leverage social learning to detect
trade-offs between privacy and effective- emerging patterns of discrimination and creation of oversight structures around DCT
ness, or between users’ expectations and unfair treatment—faced, for instance, by
utility, may need to be addressed. For in- nonusers and people who do not possess the is of paramount importance and cannot
stance, as new clusters of infection emerge, latest smartphone models, or can only afford
DCT data may be used to study epidemic low–data-use contracts. A further element be delayed. Robust oversight will nurture
dynamics in real time. But this may require requiring reflexive capacity is the possible
lowering privacy safeguards to grant pub- normalization of digital surveillance within public trust and will contribute to stronger
lic health authorities access to DCT data. and beyond the realm of public health. For
Oversight bodies should thus have moni- instance, DCT apps could be developed to ethical safeguards and to the assessment of
toring and auditing capacity to ensure that incorporate functions, e.g., QR codes for en-
exhaustive information about the scope of try to facilities, that also enable contact trac- DCT’s contribution to a safer coexistence
data use and data protection safeguards is ing—as lately seen in China and the United
properly communicated to users through Kingdom. Unrolling such pervasive forms of with the virus until effective vaccines be-
a meaningful electronic informed consent control might generate habituation to their
process. Existing guidance on the use of use in other domains such as work, schools, come available.
electronic informed consent (15) should public transportation, and so on. Reflexive
be adapted to DCT, ensuring that ethical vigilance of these potential long-term effects COVID-19 found the world unprepared,
requirements are fulfilled and appropriate is of the utmost importance to prevent the
ethics review is conducted. Oversight bod- erosion of civil liberties and human rights. but now it is time for governments to care-
ies will also have to regularly probe public
attitudes and advise policy-makers as to A further hallmark of reflexive adaptation fully predispose all the necessary measures
ethically justified, socially accepted, and is the capacity to question basic assumptions
proportional solutions to such issues. of DCT models regarding, for instance, users’ to boost resilience and minimize future
risk-related behaviors. Although it is gener-
Notably, DCT runs the risk of exacerbating ally assumed that DCT alerts are empower- harms. This model will arguably be useful
health inequalities by missing out on people ing for individuals, different people have
who either do not have a smartphone, have different ways of making sense of risk. Ab- for other technologies and in case of future
contracts for limited data use, or are not sent appropriate user behaviors, the actual
proficient users. Frequently, elders are unfa- effectiveness of DCT will likely be limited. large-scale crises—in public health and pos-
miliar with advanced smartphone features It is therefore important to collect evidence
and may thus be excluded from the poten- that helps clarify how users act upon being sibly beyond. j
tial benefits of DCT—despite representing notified by a DCT app. This evidence can be
the most vulnerable social group in terms of used in efforts aimed at sensitizing users to REFERENCES AND NOTES
COVID-19–related mortality. Furthermore, follow best practices and recommendations
social groups that are more open to using about testing and self-isolation. 1. I. G. Cohen, L. O. Gostin, D.J.Weitzner, JAMA 323, 2371
DCT apps may be taking on a dispropor- (2020).
tionate burden in making themselves trace- ROBUST OVERSIGHT
able. DCT oversight bodies should be able The rapid deployment of DCT apps repre- 2. U. Gasser, M. Ienca,J. Scheibner,J. Sleigh, E.Vayena,
to monitor these risks and propose, where sents one of the largest experiments in pub- Lancet Digital Health 2, e425 (2020).
appropriate, an equitable distribution of the lic health surveillance ever attempted—and
certainly the first one relying so strongly 3. J. Morrison, The Social License (Palgrave MacMillan,
2014).

4. “Ethical considerations to guide the use of digital
proximity tracking technologies for COVID-19 contact
tracing”(2020); www.who.int/publications/i/item/
WHO-2019-nCoV-Ethics_Contact_tracing_apps-2020.1.

5. E. Hargittai, E. Redmiles, Sci.Am. (2020); https://blogs.
scientificamerican.com/observations/will-americans-
be-willing-to-install-covid-19-tracking-apps/.

6. W. E. Bijker,T. P. Hughes,T.J. Pinch, The Social
Construction of Technological Systems (MIT Press,
1987).

7. Ipsos MORI,“Survey on COVID-19 track and trace
smartphone app for The Health Foundation”(2020);
www.ipsos.com/ipsos-mori/en-uk/survey-covid-19-
track-and-trace-smartphone-app-health-foundation.

8. Ipsos MORI,“Demographic divide in likelihood to
download and report symptoms on the Government’s
contact tracing app”(2020); www.ipsos.com/ipsos-
mori/en-uk/demographic-divide-likelihood-download-
and-report-symptoms-governments-coronavirus-
contact-tracing-app.

9. G. Ursin, I. Skjesol,J.Tritter, Health Policy Technol.
(2020). 10.1016/j.hlpt.2020.08.004

10. C. Folke,T. Hahn, P. Olsson,J. Norberg, Annu. Rev.
Environ. Resour. 30, 441 (2005).

11. E.Vayena,A. Blasimme, J. Law Med. Ethics 46, 119
(2018).

12. A. Blasimme, E.Vayena, in Oxford Handbook of Ethics
of AI, F. Pasquale, M. Dubber, S. Das, Eds. (Oxford Univ.
Press, 2020), pp. 703–718.

13. M. M. Mello, C.J.Wang, Science 368, 951 (2020).
14. European Commission, European Interoperability

Certificate Governance: A security architecture for
contact tracing and warning apps; https://ec.europa.
eu/health/sites/health/files/ehealth/docs/
mobileapps_interop_certificate_governance_en.pdf.
15. Fed. Regist. 81, 90855 (2016).

10.1126/science.abd9006

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A 69-year old receives a COVID-19 vaccine in a Phase
3 trial. It is important to understand how different
groups respond to COVID-19 vaccines to establish the
most effective deployment strategy.

PERSPECTIVES indirect protection. Expanding ongoing ef-
forts or planning new studies may generate
VIEWPOINT: COVID-19 the data needed to address these questions.

Understanding COVID-19 For estimating subgroup-specific efficacy,
vaccine efficacy randomized controlled trials can provide
early estimates, yet these will have wide
Vaccine efficacy in high-risk groups and reduced confidence intervals, leaving substantial un-
viral shedding are important for protection certainty about true effects in high-risk sub-
groups. This uncertainty would be greater in
PHOTO: PAUL HENNESSY/NURPHOTO VIA GETTY IMAGES By Marc Lipsitch1 and Natalie E. Dean2 being used to explore different vaccination interim analyses that are based on the num-
plans (1, 2), with the recognition that vaccine ber of events across the whole trial popula-
T he elderly and people with comor- doses may be limited at first and so should tion and may be exacerbated if high-risk par-
bidities are at greatest risk of severe be deployed strategically. But as supplies ticipants are more cautious and have lower
coronavirus disease 2019 (COVID-19). grow large enough to contemplate an indi- exposure to infection, reducing their contri-
A safe and effective vaccine could rect protection strategy, the recommenda- bution to the efficacy estimates.
help to protect these groups in two tions of these models depend on the details
distinct ways: direct protection, of how, and how well, these vaccines work There are several strategies to address
where high-risk groups are vaccinated to and in which groups of people. How can the subgroup-specific efficacy, some of them
prevent disease, and indirect protection, evidence needed to inform strategic deci- already in place. Ensuring that high-risk
where those in contact with high-risk indi- sions be generated for COVID-19 vaccines? adults are well represented in the trial pop-
viduals are vaccinated to reduce transmis- ulation can be achieved by setting minimum
sion. Influenza vaccine campaigns initially Phase 3 vaccine trials are designed to enrollment targets for older adults and/or
targeted the elderly, in an effort at direct assess individual-level efficacy and safety. adults with comorbidities. Another consid-
protection, but more recently have focused These trials typically focus on a primary eration relates to the stopping rules for in-
on the general population, in part to en- endpoint of virologically confirmed, symp- terim analyses in trials. Vaccine trials with
hance indirect protection. Because influ- tomatic disease to capture the direct benefit early interim analyses that are planning to
enza vaccines induce weaker, shorter-lived of the vaccine that forms the basis for regu- discontinue randomization and vaccinate
immune responses in the elderly than in latory decisions. Secondary endpoints, such placebo participants after declaring efficacy
young adults, increasing indirect protec- as infection or viral shedding, provide sup- are most prone to subgroup uncertainty. To
tion may be a more effective strategy. It is porting data, along with analyses of vaccine improve the precision of efficacy estimates
unknown whether the same is true for CO- efficacy in subgroups. Nonetheless, unan- in high-risk subgroups, regulators could in-
VID-19 vaccines. swered questions about COVID-19 vaccine sist that interim analyses be performed only
characteristics are likely to remain even af- after a certain number of confirmed disease
For COVID-19, age-structured mathemati- ter trials are completed. First, trials are typ- cases occur in these subgroups, in addition
cal models with realistic contact patterns are ically not powered to establish subgroup- to existing monitoring of the overall num-
specific efficacy, yet the performance of the ber of events in the study.
1Center for Communicable Disease Dynamics, Department vaccine in high-risk groups affects the suc-
of Epidemiology, Harvard T.H. Chan School of Public Health, cess of a direct-protection strategy. Second, Trials that maintain blinded follow-up
Boston, MA 02115, USA. 2Department of Biostatistics, can vaccines prevent infection or reduce to assess long-term efficacy and safety may
University of Florida, Gainesville, FL 32611, USA. Email: mlip- contagiousness? This matters for achieving also generate more-reliable evidence on
[email protected]; [email protected] age-specific effects. For example, the World
Health Organization’s Solidarity Vaccines
Trial will preserve placebo-controlled follow-
up through month 12 or when an effective
vaccine is deployed locally (3). However, de-
pending on where the trials are being done
and whether the vaccine becomes rapidly
available in sufficient quantities after emer-
gency-use authorization in the population
undergoing the trial, it may become unethi-
cal and/or impractical to ask participants in
some subgroups to forego access to an avail-
able vaccine. For vaccine candidates evalu-
ated in multiple trials, such as the Oxford-
AstraZeneca vaccine being studied in the
United Kingdom, South Africa, Brazil, and
the United States, meta-analyses can synthe-
size results across locations to improve preci-
sion of subgroup-specific effect estimates.

Ideally, the phase 3 trials in progress will
identify more than one safe, effective vac-

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INSIGHTS | PERSPECTIVES

cine for regulatory approval and deployment. Vaccines that reduce disease severity can virus weekly regardless of symptoms, but

Postapproval studies will then take on an also reduce infectiousness by reducing viral not in other trials for which protocols have

important role for continued assessment of shedding and/or symptoms that increase been released. Even weekly testing will not

vaccine effectiveness. These may include in- viral spread (e.g., coughing and sneezing). give detailed information about the effect

dividual- or community-level randomized tri- A worst-case scenario is a vaccine that re- of the vaccine on viral shedding, and the

als to compare different active vaccines with- duces disease while permitting viral shed- relationship between viral loads and in-

out a control arm, as in the U.S. Department ding; this could fail to reduce transmission fectiousness is unknown; nonetheless, this

of Defense’s individually randomized or conceivably even increase transmission if approach is likely to provide some evidence

Pragmatic Assessment of Influenza Vaccine it suppressed symptoms. if viral loads are on average lower among

Effectiveness in the DoD (PAIVED) trial, To assess a vaccine’s impact on infec- vaccinated people. Human challenge vac-

which assesses the relative merits of three tiousness, some phase 3 trials examine the cine studies, in which individuals in a ran-

licensed influenza vaccines (NCT03734237). amount or duration of viral shedding in domized controlled trial are deliberately

Another approach to amass evidence on laboratory-confirmed, symptomatic partici- exposed to the virus, could generate high-

subgroup-specific efficacy is post- quality data on the effect of vaccines

approval observational studies. on viral shedding (9).

This includes active surveillance of Vaccine effects Other approaches exist to directly
high-priority cohorts from, for ex- estimate infectiousness without
ample, nursing homes or assisted Vaccines provide direct protection by reducing susceptibility to disease the need to extrapolate from viral
living facilities, as has been done or infection. Vaccines provide indirect protection by reducing the number load. Add-on household studies
for influenza. This also includes of people infected in a population or their infectiousness. These vaccine can supplement efficacy trials. In-
effects can be assessed in clinical trials by measuring the efficacy to

test-negative designs, which are prevent disease, to prevent infection, and to reduce infectiousness, as vestigators can follow household

routinely used to assess vaccine well as in studies to assess indirect effects of the vaccine (15). members or other close contacts of

effectiveness (4). Symptomatic infected participants to assess the

individuals that test negative for Individually randomized vaccine efcacy trial vaccine’s effect on infectiousness,
severe acute respiratory syndrome as has been implemented for the

coronavirus 2 (SARS-CoV-2) func- respiratory disease pertussis (also

tion as controls for test-positive called whooping cough) (10). Viral

cases, and their vaccination status Total primary infections sequencing could be used within the
is compared, adjusting for selected Symptomatic disease trial to link infector-infectee pairs
confounders. Test-negative designs Asymptomatic infections and better estimate indirect effects
can be integrated into outpatient Uninfected (11). Another strategy is to design
testing in the community (5) or Secondary infections cluster-randomized trials in which
use emergency department visits indirect effectiveness is a primary

to estimate vaccine effectiveness Vaccine (V) Placebo (P) outcome. In influenza vaccine tri-
against severe disease (6). To rap- als, health care workers at nursing

idly establish these systems, re- Vaccine efects homes were cluster-randomized to
searchers can leverage ongoing in- be offered vaccine or not, and the
fluenza surveillance. Conveniently, VP VP VP V P endpoints were mortality, influenza-

these programs can simultane- like illness, or influenza infection in

ously monitor more than one vac- the patients they cared for (12).

cine, enabling assessment of their Observational studies may also be

relative merits. Efcacy to Efcacy to Reduced Indirect vaccine helpful, but, in general, measuring
A key limitation of observational prevent prevent infectiousness efectiveness indirect effects of vaccines is even
disease infection of each harder than detecting direct effects.
studies is confounding. There may Primary Secondary breakthrough It is urgent, therefore, to obtain evi-
be many differences between indi- endpoint endpoint infection dence on how each candidate vac-
viduals who do and do not get vacci- cine affects infectiousness either
nated, which may create noncausal Not directly measured before approval or soon after, when
correlations between vaccine sta-

tus and outcomes. Although such scarcity may justify randomized dis-

biases can threaten any observational study pants by home collection of saliva samples tribution of a vaccine.

of vaccine effectiveness, there are some ap- and frequent polymerase chain reaction Other open questions about the rapidly

proaches to detect such biases and reduce (PCR) testing. However, this would not developed COVID-19 vaccines include long-

their magnitude (7, 8). capture any change in viral shedding for term safety (indicating the critical need for

The clearest evidence of indirect protec- asymptomatic participants. Moreover, se- pharmacovigilance activities), the duration

tion is from a vaccine that prevents infec- rology tests detect previous infection and of vaccine protection, the efficacy of a par-

tion entirely, thereby reducing transmis- cannot reconstruct shedding during active tial vaccination series or of lower doses (13),

sion. These data will be generated in efficacy infection. To measure viral load in both the vaccine’s level of protection against se- GRAPHIC: KELLIE HOLOSKI/SCIENCE

trials that include infection as a secondary symptomatic and asymptomatic partici- vere infection and death, efficacy by base-

endpoint. This endpoint is measured by pants, it is necessary to conduct frequent line serostatus, and the potential for the

a specialized assay to distinguish an in- (e.g., weekly) viral testing, irrespective of virus to evolve to escape vaccine-induced

fection-induced response from a vaccine- symptoms, to capture participants during immunity. The answers to such questions

induced antibody response. A vaccine can their period of acute infectiousness. The inform the optimal use of any vaccine.

provide indirect protection even if it does Oxford-AstraZeneca vaccine trial is testing Availability of a COVID-19 vaccine will

not fully prevent infection (see the figure). participants in the United Kingdom for the initially be limited, and so several expert

764 13 NOVEMBER 2020 • VOL 370 ISSUE 6518 sciencemag.org SCIENCE

Published by AAAS

committees are exploring strategic priori- CORONAVIRUS
tization plans. Health care workers are a
common first-tier group (14), which in turn Enhancing host cell infection
preserves health care systems by protecting by SARS-CoV-2
those who run them. A next priority is to di-
rectly protect those who are at highest risk Neuropilin-1 binds the furin-processed spike protein of
of death or hospitalization when infected: SARS-CoV-2 to promote virus entry
specifically, those over 65 and people with
certain comorbid conditions. This strategy By Margaret Kielian of influenza virus and HIV-1, inserts a hydro-
may be optimal for reducing mortality even phobic fusion peptide at its amino terminus
if the vaccine is somewhat less effective in T he current global pandemic of coro- into the cell membrane and then folds back
these groups (2). But if a vaccine offers little navirus disease 2019 (COVID-19) is to merge the host and virus membranes (7).
to no protection in high-risk groups yet is caused by severe acute respiratory syn- The S2 protein needs a further proteolytic
able to reduce infection or infectiousness in drome coronavirus 2 (SARS-CoV-2). A step to “liberate” its fusion peptide, and this
younger adults, an indirect strategy could critical initial step of infection is the is carried out by transmembrane protease
be preferred as vaccine supplies become interaction of the virus with receptors serine 2 (TMPRSS2) or other proteases (3).
large enough (1, 2). A worst-case scenario on host cells. In the case of SARS-CoV-2 and
for an effective vaccine is one that reduces other coronaviruses, this receptor binding A potentially important difference be-
disease in younger adults but provides nei- occurs through the spike (S) protein on the tween SARS-CoV-2 and SARS-CoV is the
ther direct nor indirect protection to high- virus surface. Both SARS-CoV-2 and the re- mechanism of S protein cleavage into S1
risk groups, leaving the most vulnerable at lated SARS-CoV, which caused an outbreak and S2. In SARS-CoV, this is caused by host
risk. Knowing these vaccine characteristics in 2003, bind to angiotensin-converting en- cell proteases called cathepsins, which are
is important when evaluating the relative zyme 2 (ACE2) on human cells. However, located within endocytic compartments.
merits of other products. Fortunately, there the observed differences in tissues that are However, the sequence of the SARS-CoV-2
are many vaccine candidates in develop- infected by these two viruses (tropism) sug- S protein contains a series of basic amino
ment that use a mixture of innovative and gests that additional host factors may be in- acids at the S1-S2 junction. Such polybasic
existing technologies. Although vaccines volved. On pages 861 and 856 of this issue, sites can be substrates for furin, a protease
may vary in their characteristics, having Daly et al. (1) and Cantuti-Castelvetri et al. that is present in the secretory pathway
reliable evidence on direct and indirect (2), respectively, show that the membrane and endocytic compartments (8). Studies
protection can help plan how to use these protein neuropilin-1 (NRP1) promotes SARS- with SARS-CoV-2 show that its S protein is
vaccines in a coordinated way. j CoV-2 entry and explain how NRP1 interacts cleaved by furin during virus production and
with the SARS-CoV-2 S protein. The results that this cleavage promotes subsequent virus
REFERENCES AND NOTES suggest the S protein–NRP1 interaction as a infection (3, 6). Thus, a notable difference
potential antiviral target. between the S proteins of these two corona-
1. L. Matrajt,J. Eaton,T. Leung, E. R. Brown, medRxiv viruses is the protease that carries out the S1-
10.1101/2020.08.14.20175257 (2020). Coronaviruses are enveloped RNA viruses S2 cleavage reaction. Furin cleavage also pro-
that can cause human diseases that range duces a potentially important remnant: the
2. K. M. Bubar et al., medRxiv from the common cold to severe and fatal polybasic site that remains at the carboxyl
10.1101/2020.09.08.20190629 (2020). respiratory infections. It is thought that both terminus of SARS-CoV-2 S1 after cleavage.
SARS-CoV-2 and SARS-CoV bind to ACE2
3. P. Krause et al., Lancet 10.1016/s0140-6736(20)31821-3 on the host cell surface, are internalized by Neuropilins are a family of membrane
(2020). endocytosis, and fuse with the endolyso- proteins that were originally identified be-
some membrane to deliver the viral genome cause of their involvement in angiogenesis
4. H. Chua et al., Epidemiology 31, 43 (2020). for replication in the host cell (3, 4) (see the (blood vessel formation) and axon guidance
5. Centers for Disease Control and Prevention (CDC), US figure). The viral S protein mediates this key (9). The neuropilins are co-receptors for mol-
membrane fusion reaction, but its activity ecules such as vascular endothelial growth
Flu VE Network (2020); www.cdc.gov/flu/vaccines- requires several processing steps. S is syn- factors (VEGFs) and semaphorins, and re-
work/us-flu-ve-network.htm. thesized as a large membrane protein that cent studies have demonstrated their up-
6. Q. Chen et al., J. Infect. Dis. 211, 1045 (2015). is cleaved into two components, S1 and S2, regulation during tumor angiogenesis and
7. M. Lipsitch,A.Jha, L. Simonsen, Int.J. Epidemiol. 45, which remain noncovalently associated (5, their potential as anticancer targets. Both
2060 (2016). 6). Cleavage is required for infection and can NRP1 and NRP2 can bind the carboxyl-ter-
8. N. E. Dean, M. E. Halloran, I. M. Longini Jr., Am.J. occur during virus particle production or vi- minal sequences generated by furin process-
Epidemiol. 10.1093/aje/kwaa084 (2020). rus entry into the target cell. The S1 protein ing of molecules such as VEGFs, with the
9. S. K. Shah et al., Science 368, 832 (2020). forms the “head” of the molecule and medi- sequences fitting into a pocket on the b1 do-
10. M. E. Halloran et al., J.Am. Stat.Assoc. 98, 38 (2003). ates binding to ACE2. The S2 protein is an- main of the NRP (9). Detailed studies of such
11. R. Kahn et al., medRxiv 10.1101/2020.09.14.20193789 chored in the virus membrane and mediates NRP1-peptide interactions show that binding
(2020). membrane fusion. S2, like the fusion proteins to the b1 pocket requires the sequence Arg/
12. W. F. Carman et al., Lancet 355, 93 (2000). Lys-X-X-Arg/Lys (R/K-XX-R/K, where X can
13. S. Riley,J.T.Wu, G. M. Leung, PLOS Med. 4, e218 (2007). Department of Cell Biology, Albert Einstein College be any amino acid) at the carboxyl terminus
14. National Academies of Sciences, Engineering, Medicine, of Medicine, Bronx, NY 10461, USA. of the protein or peptide (10). This “C-end
“Framework for equitable allocation of COVID-19 Email: [email protected] rule,” or CendR, can thus predict whether a
vaccine”(Consensus Study Report,The National protein is a candidate for binding to NRPs.
Academies Press,Washington, DC, 2020).
15. M. E. Halloran, I. M. Longini Jr., C.J. Struchiner, Design
and Analysis of Vaccine Studies (Springer, 2010).

ACKNOWLEDGMENTS

M.L. receives funding from cooperative agreement
1U01CA261277 from the U.S. National Institutes of Health.
N.E.D. receives funding from NIH/NIAID R01-AI139761.We
thank R.Venkayya and N. Grassly for helpful comments.
M.L. receives honoraria and consulting fees from Merck,
Affinivax, Sanofi Pasteur, and Antigen Discovery; receives
research funding (institutional) from Pfizer; and provides
unpaid scientific advice to Janssen,Astra-Zeneca, and Covaxx
(United Biomedical).

Published online 21 October 2020

10.1126/science.abe5938

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INSIGHTS | PERSPECTIVES

Daly et al. and Cantuti-Castelvetri et al. plex, which revealed that the peptide is po- teresting parallels and differences with the
found that the sequence of the S1-S2 junc- sitioned in the b1 pocket, similar to a VEGF roles of NRPs in infection by other viruses.
tion of virus isolates from human patients peptide that was crystallized with b1 (9). A For example, both the human T cell lym-
suggested that they fit the C-end rule, with small-molecule antagonist of NRP1 that in- photropic virus SU protein and the Epstein
Arg-Arg-Ala-Arg (RRAR) predicted to form hibits VEGF binding (11) also inhibited the Barr virus (EBV) gB protein are processed
the carboxyl-terminal sequence of the furin- b1-S1 peptide interaction and virus infection. by furin, and infection by these viruses is
cleaved S1. They showed that NRP1 pro- promoted by NRP1 (12, 13). EBV, which in-
moted infection of human cell lines by SARS- C-end rule peptides had previously been fects nasopharyngeal epithelial cells, shows
CoV-2 and by lentivirus pseudotypes that shown to mediate uptake of particles or bac- an apparent reciprocal effect in which NRP1
contained the SARS-CoV-2 S protein on their teriophages by cells and tissues (10). Cantuti- promotes infection, whereas NRP2 inhib-
surface. NRP1 was not the only host factor Castelvetri et al. conjugated the S1 peptide its it (13). Although Daly et al. showed that
that promoted SARS-CoV-2 infection, but onto nanoparticles and administered them S1 protein can also bind NRP2, its role in
even when both ACE2 and TMPRSS2 were intranasally to mice. The mouse olfactory SARS-CoV-2 infection is unknown. NRP2 is
present, NRP1 gave an additional increase. epithelium expresses NRP1, and the authors a receptor for Lujo virus, but this does not
observed significant uptake of the peptide- involve binding to the b1 pocket (14). These
and other examples indicate that a number
Model for SARS-CoV-2 processing and entry of viruses have evolved to use NRPs during
infection, but much remains unclear.
Proteolytic processing of SARS-CoV and SARS-CoV-2 S proteins facilitates virus entry. SARS-CoV and SARS-
CoV-2 bind to ACE2 at a region on S1. Furin cleavage at the S1-S2 junction exposes the C-end rule peptide on There is more to learn about the promo-
SARS-CoV-2 S1 and allows binding to NRP1. Subsequent processing by cathepsins and TMPRSS2 allows S2 tion of SARS-CoV-2 infection by NRP1. The
fusion peptide–mediated membrane insertion and merging of membranes. The absence of a furin cleavage site virus can propagate in the absence of furin
in SARS-CoV S1 and a SARS-CoV-2 S1 mutant prevents binding to NRP1 and limits virus entry and infection. cleavage in some cultured cells, where ca-
thepsin cleavage may be sufficient, but in
SARS-CoV-2 S protein SARS-CoV S protein vivo, the virus relies on furin processing,
which enhances viral pathogenesis in a ham-
S1 (Attachment) S2 (Fusion) S1 (Attachment) S2 (Fusion) ster model (15). How does NRP1 binding af-
S2′ fect the virus internalization pathway, and
ACE2 S1-S2 S2′ ACE2 S1-S2 Fusion peptide C does it act as a co-receptor with ACE2? C-end
N Fusion peptide Cathepsins rule peptide binding to NRP1 can promote
TMPRSS2 vascular leakage and tissue penetration, es-
NRP1 CN Transmembrane pecially when the peptides are presented
Furin domain on a multivalent particle (10). Does NRP1
TMPRSS2 similarly help to promote SARS-CoV-2 dis-
Transmembrane semination and spread? Together, Daly et al.
domain and Cantuti-Castelvetri et al. show that furin
processing, which has an important role in
SARS-CoV-2 SARS-CoV the maturation and fusion activity of the
SARS-CoV-2 S protein, also acts to generate
S2 Mutant ligands on the virus particle that bind NRP1.
b1 S1 SARS-CoV-2 The availability of small molecule inhibi-
tors of the NRP1-C-end rule peptide interac-
NRP1 ACE2 tion suggests a potential antiviral strategy.
Cell Defining the importance of this interaction
in vivo will be a vital next step. j
Infection Endosome Cathepsins,
TMPRSS2, fusion REFERENCES AND NOTES
TMPRSS2, fusion
1. J. L. Daly et al., Science 370, 861 (2020).
ACE2, angiotensin-converting enzyme 2; NRP1, neuropilin 1; S, spike; 2. L. Cantuti-Castelvetri et al., Science 370, 856 (2020).
SARS-CoV, severe acute respiratory syndrome coronavirus; TMPRSS2, transmembrane protease serine 2. 3. M. Hoffmann et al., Cell 181, 271 (2020).
4. X. Ou et al., Nat. Commun. 11, 1620 (2020).
This was due to an increase in virus uptake conjugated particles in this site. Similar to 5. D.Wrapp et al., Science 367, 1260 (2020). GRAPHIC: V. ALTOUNIAN/SCIENCE
into the cell rather than an increase in virus previous results (10), the S1 peptide–coated 6. A. C.Walls et al., Cell 181, 281 (2020).
binding to the cell surface. The promotion particles were observed to also travel into 7. S. C. Harrison, Virology 479-480C, 498 (2015).
of virus infection by NRP1 was inhibited by the neurons and blood vessels of the cortex. 8. S. S. Molloy et al., Trends Cell Biol. 9, 28 (1999).
the addition of a soluble NRP1 or by an an- To address the possible role of NRP1 in hu- 9. H. F. Guo, C.W.Vander Kooi, J. Biol. Chem. 290, 29120
tibody that mapped to the binding pocket man SARS-CoV-2 infection, the authors used
on NRP1. Further analyses revealed that S1 available data to confirm expression of both (2015).
or its carboxyl-terminal region interact with NRP1 and NRP2 RNA in human lung and 10. T.Teesalu et al., Proc. Natl.Acad. Sci. U.S.A. 106, 16157
NRP1, and this was inhibited by mutations olfactory epithelial tissue. They also showed
in the NRP b1 pocket. SARS-CoV-2 mutants that five out of six autopsy samples of olfac- (2009).
in which the polybasic cleavage site was de- tory epithelia from human COVID-19 pa- 11. A.Jarvis et al., J. Med. Chem. 53, 2215 (2010).
leted or S was made resistant to furin cleav- tients were positive for both S protein and 12. S. Lambert et al., Blood 113, 5176 (2009).
age were insensitive to NRP1 expression. NRP1. These results from mice and humans 13. H. B.Wang et al., Nat. Commun. 6, 6240 (2015).
are intriguing given that many COVID-19 pa- 14. M. Raaben et al., Cell Host Microbe 22, 688 (2017).
Daly et al. showed that a peptide derived tients lose their sense of smell. 15. S.Y. Lau et al., Emerg. Microbes Infect. 9, 837 (2020).
from the S1 carboxyl terminus binds to the
NRP1 b1 domain with micromolar affinity. Together, these papers establish NRP1 as ACKNOWLEDGMENTS
They solved the crystal structure of the com- a host factor for SARS-CoV-2 and suggest in-
The author is supported by National Institutes of Health
(R01-GM057454 and R01-AI075647).

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CHEMISTRY

Peptide synthesis at the origin of life

Small-molecule organocatalysis might have driven the emergence of peptide biochemistry

By Kamila B. Muchowska and Joseph Moran most amino acid polymerization occurs by protein (PCP). The resulting PCP-bound

translation, which requires ribosomes— amino acid thioesters undergo peptide

T he chemical origin of life is full a massive assembly of proteins and RNA. bond–forming reactions with one another,
of chicken-and-egg conundrums. Building a primordial ribosome under the leading to amino-to-carboxyl-terminal pep-
Among these is the origin of protein conditions of a lifeless planet is a hefty and, tide chain growth. The thiol moiety of phos-
synthesis. Nature’s protein-based en- as of now, unmet challenge. However, mi- phopanthetheine is supplied by cysteine,
zyme catalysts are built from the po- croorganisms use biological nonribosomal which is also the prevalent organic source

lymerization of amino acids, yet this peptide synthesis for the production of of sulfide in biochemistry (6). However,

process itself requires enzymes, adenosine peptide-based natural products. The nonri- most scientists do not believe that cysteine

triphosphate (ATP), and, most often, a ribo- bosomal peptide synthetases that perform commonly participated in prebiotic chem-

some. How were the first proteins formed this reaction are chemically much simpler istry at its earliest stages. Cysteine is often

on the path from chemistry to life? Despite than ribosomes. regarded as a late evolutionary addition to

more than 65 years of research into the Nonribosomal peptide synthesis begins the proteinogenic amino acid pool (7, 8).

chemical origins of life, there is still no clear with the activation of an amino acid’s car- Devising a plausible prebiotic route to cys-

answer (1). On page 865 of this issue, Foden boxy terminus by ATP-driven adenylation teine has proven to be challenging (9, 10). In

et al. (2) tackle the protein-synthesis conun- (see the figure). This is followed by nucleo- biology, cysteine synthesis starts from serine

drum from a new angle. philic attack on the adenylated amino acid and proceeds through a pyridoxal phosphate

Researchers who study prebiotic chem- by the thiol moiety of the phosphopantethe- cofactor-bound dehydroalanine, an inter-

istry have largely pursued two general ap- ine prosthetic group of a peptidyl carrier mediate that has a markedly short lifetime

proaches to make amino acids po- in the absence of the cofactor (6).

lymerize in the absence of biological Foden et al. proposed how this in-

polymers and ATP. Because the di- Building proteins in a prebiotic world herent instability might be over-
rect polymerization of amino acids come by beginning the prebiotic
requires the loss of water, the sim- Two nonribosomal peptide synthesis reactions highlight the pivotal synthesis of cysteine from a nonbio-
plest strategy is to drive the process roles that small-molecule organocatalysis and thiols might have logical nitrile analog of the amino
played in the emergence of biochemistry. AMP, adenosine monophosphate;

with wet-dry cycles (3). Although R and R1, amino acid side chain. acid serine. Proceeding through a
drying processes are plausible on a doubly acylated dehydroalanine, the

lifeless Earth, they are incompatible Nonribosomal peptide SH Phosphopantetheine acetylated cysteinyl nitrile was ob-
with other chemistries in a system synthetase (fragment) tained in near-neutral water. Given

containing more than just amino the centrality of cysteine in sulfur

acids. To make matters worse, po- PCP PCP PCP PCP PCP PCP biochemistry, the authors won-

lymerization under wet-dry cycles dered if a simpler prebiotic version

might be partially reversible, thus HS HS R S R1 S R SH of nonribosomal peptide synthesis
scrambling information contained S could have relied on this amino acid
in the specific peptide sequences O instead of its more complex bio-
(4). Retaining intact information NH2 NH2 ON synthetic successor, phosphopante-
would have been essential to life’s theine. Methods that use cysteine
further complexification. A sec- H2N O-AMP H2N O-AMP O O H NH2 moieties in peptide synthesis in-
R1
RO R1 O Amino acid
thioester Peptide elongation

ond major approach uses chemical Biochemistry of nonribosomal peptide synthesis clude cysteinyl thioester–based na-
condensing agents to drive amino tive chemical ligation (11). Although
acid polymerization. Some of these Adenylation of an amino acid C terminus is followed by nucleophilic attack popular, these methods start with a
condensing agents are known from on the adenylated amino acid by the thiol (−SH) moiety of the phosphopan- carboxy-terminal amino acid thioes-
synthetic chemistry but have no tetheine group (red). Peptidyl carrier protein (PCP)—bound amino acid ter. To make use of this strategy in
thioesters form peptide bonds, leading to peptide chain growth.

clear prebiotic source. Others are a prebiotic context, a robust route

plausible in the early Earth envi- O Catalyst to amino acid thioesters would be
ronment, but it is difficult to envi- needed—one that could operate
sion them being produced continu- Catalyst Catalyst H2N SH without the full toolkit of modern
ously in the needed quantities (1). OR HO synthetic chemistry (12).
O R SH OR R1
It is unsurprising, however, that NS NN A previously reported alterna-
GRAPHIC: A. KITTERMAN/SCIENCE nature provides a guide to its own N N H NH H NH R1 tive approach demonstrated sul-
beginnings (5). In biochemistry, H Peptide elongation fide-mediated oligomerization of
via peptidyl amidine amino nitriles to yield peptides
University of Strasbourg, Centre National de a-aminonitrile Amino acid thioimidate in water. The process began with
la Recherche Scientifique, Institut de Science amino nitriles, but under condi-
et d’Ingénierie Supramoléculaires, 67000 Catalytic aminonitrile-based peptide ligation tions of alternating reducing and
Strasbourg, France. Email: [email protected] oxidizing environments and ex-
The −SH group of the cysteine catalyst forms a bond with an aminonitrile,

(C;N) to form an amino acid thioimidate intermediate. An amino acid then
reacts with the intermediate, a peptidyl amidine bond is formed, and the

catalyst is released.

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INSIGHTS | PERSPECTIVES

cess quantities of sulfide (13). Such step- ROBOTICS
changes in reaction conditions pose a
problem for a realistic early Earth scenario. How to improve robotic touch
However, by exploiting the fact that thiols
reversibly add to a-amidonitriles, Foden Challenges for instrumenting robotic hands to match
et al. proposed a strategy for catalytic and human performance are outlined
redox-neutral oligopeptide synthesis pro-
ceeding via a thioimidate intermediate in By Subramanian Sundaram1,2 nels) and mechanoreceptors. Many families
neutral water (see the figure). The authors of mechanosensitive ion channels other than
subjected acetylated glycinyl nitrile and H uman hands are densely covered with PIEZOs are believed to contribute to touch
free glycine to acetylated cysteine (a hypo- touch receptors called mechanore- because PIEZOs alone do not account for
thetical phosphopantetheine precursor) at ceptors that provide us the sense of all human mechanosensation (6), but what
60oC in neutral water. Within 24 hours, an touch. This continuous tactile feed- these other families are, and how signals
acetylated Gly-Gly peptidyl amidine had back from objects we touch, and in- from these transducers are processed to-
formed, at a 60% yield, without the need formation on hand articulation and gether, are not known. Even if these trans-
for synthetic activating agents. This reac- movement—called proprioception—enable ducing channels were identified, it is not
tivity occurred with a variety of thiols and us to effortlessly handle diverse objects with clear what role they play in enabling the dis-
amino acids. Only amino-terminal serine, fine dexterity. Bell’s prescient treatise on the tinct mechanoreceptor types that respond to
threonine, and cysteine could be coupled hand, written in 1833, refers to the human specific stimuli. Mechanoreceptor responses
to a-amidonitriles stereoselectively, which hand as the “consummation of all perfection may encode signals from many diverse force
might have implications for the origins of as an instrument” (1). This sentiment echoes transducers, and a better understanding of
biological homochirality. stronger today, in part fueled by the steep the mammalian system may guide artificial
challenge of effectively instrumenting a ro- sensor design.
Foden et al. highlight the potential of botic hand to provide similar feedback with
small-molecule organocatalysis and the the goal of attaining human-level dexterity. First-order tactile neurons that collect sig-
pivotal role that thiols might have played Recent insights into the primate tactile sys- nals from mechanoreceptors have a branched
in the emergence of biochemistry. Could tem and advances in machine learning (ML) architecture, thereby integrating signals from
nature have made peptides this way before may offer new prospects for tackling this old multiple mechanoreceptors in distant points
the advent of enzymes or the ribosome? robotics challenge. of the skin known as the receptive field (3).
This exciting question reveals how much This complex spatial arrangement allows
we do not know about the rationale behind Roboticists have looked at all aspects of each first-order neuron to record object fea-
the shaping of life’s biochemical pathways human tactile physiology (ranging from tures during contact—like edges—as opposed
and the chemical structures used as cofac- mechanoreceptors to neural coding schemes to detecting forces at single points (7). As
tors and metabolites (6). If life did once to grasping strategies) for inspiration on de- a result, the signal carried by a first-order
use nitrile-based chemistry, it is unclear signing robotic touch systems. Most of the neuron captures many properties as seen
why it would have shifted to a biochemis- attention has focused on creating electronic through multiple transducers and from many
try where nitriles are rare. Also, why does sensors that mimic mechanoreceptors (see different locations. Furthermore, this signal
life—seemingly so wastefully—use the phos- the figure) (2). Four types of mechanorecep- may depend on material properties such as
phopantetheine moiety in nonribosomal tors—each responding to different types of hardness and surface texture. Prior to sens-
peptide synthesis, when it might have used tactile stimuli—innervate the skin: the fast ing by mechanoreceptors, object contact is
a much simpler thiol, such as cysteine? adapting receptors FA I and FA II, and slowly mediated by the skin, which modulates its
Experimental insights into these questions adapting receptors SA I and SA II (3). The own mechanical properties through skin hy-
will illuminate the currently opaque middle spatial coverage of these distinct mechanore- dration. Moisture secreted from sweat glands
ground between reactions that attempt to ceptor types in the human hand have been hydrates keratin in the skin and softens it.
recreate life’s earliest chemistry and the bio- systematically mapped since 1970, bringing This process changes the contact dynamics
chemistry we study today. j attention to their collective functional roles. between the fingertip and an object; junc-
However, the subcellular molecular transduc- tional contact area increases more slowly
REFERENCES AND NOTES ers of force have been harder to identify. The when touching a hard, smooth glass surface
mechanically activated ion channels PIEZO1 as compared to a soft rubber (8).
1. G. Danger, R. Plasson, R. Pascal, Chem. Soc. Rev. 41, and PIEZO2 were found to be force transduc-
5416 (2012). ers in mammalian cells (4), and evidence of Replicating all of the subtle features of
PIEZO2’s role in human tactile and proprio- mechanoreceptors and the skin in contempo-
2. C. S. Foden et al., Science 370, 865 (2020). ceptive function is enabling an understand- rary robots has remained daunting. However,
3. M. Rodriguez-Garcia et al., Nat. Commun. 6, 8385 ing of the initial signals involved in human substantial progress is being made in the
touch (5). PIEZO2 is known to be involved in creation of soft, stretchable electronic skins
(2015). many low-threshold mechanoreceptors. that can sense loads normal to the surface
4. J. G. Forsythe et al., Proc. Natl.Acad. Sci. U.S.A. 114, or shear forces against the surface; in both
Currently, there are many unknowns in cases, static or dynamic forces can be sensed
E7652 (2017). our understanding of the exact links between (2, 9). Creative new fabrication strategies
5. S.A. Harrison, N. Lane, Nat. Commun. 9, 5176 (2018). these initial transducers of force (ion chan- that use soft materials and high-performance
6. J. E. McMurry,T. P. Begley, The Organic Chemistry of organic electronics have also enabled neuro-
1Biological Design Center, Boston University, Boston, MA, USA. morphic sensors that produce action poten-
Biological Pathways (Roberts and Company Publishers, 2Wyss Institute for Biologically Inspired Engineering, Harvard tial–like voltage spikes in response to forces
Inc., ed. 2, 2016). University, Boston, MA, USA. Email: [email protected] (10). Neuromorphic tactile systems designed
7. A. Sauerwald et al., Science 307, 1969 (2005).
8. K. B. Muchowska, S.J.Varma,J. Moran, Chem. Rev. 120,
7708 (2020).
9. B. N. Khare, C. Sagan, Nature 232, 577 (1971).
10. I. Shalayel et al., Eur.J. Org. Chem. 2020, 3019 (2020).
11. P. E. Dawson,T.W. Muir, I. Clark-Lewis, S. B. Kent, Science
266, 776 (1994).
12. A. L.Weber, Orig. Life Evol. Biosph. 35, 421 (2005).
13. P. Canavelli, S. Islam, M.W. Powner, Nature 571, 546
(2019).

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for robots today are still nascent when com- use of exploratory and informative actions, to place. Achieving manual dexterity in robot
pared with architectures in humans. In hu- refine the sensory information acquired (11). manipulation with vision alone may prove
mans, the spatial distribution of receptors Thus, we can determine texture by sliding to be difficult in highly unstructured and
is typically 240 units/cm2 at fingertips, with our fingers, and reliably distinguish fabrics dynamic settings without continuous line-of-
over 17,000 receptors covering the hand (3). like velvet from wool. sight access, such as searching through piles
Contemporary robots lag by two to three of rubble in disaster response.
orders of magnitude, and the number of Although robotic manipulation of objects
levels of distributed processing need much with similar sensorimotor control is limited The success of robot vision–based object
improvement. However, this approach is by tactile hardware in robot hands, there has manipulation has many strong implications
promising because spike-based processing been exciting progress in using visual data. for robotic touch. It confirms that the emerg-
can efficiently encode temporal relationships, The ubiquity of cameras and the ability to ac- ing ML tools are effective at distilling infor-
motion, and other object properties with quire large datasets—which are critical for ef- mation from high-dimensional images into
high fidelity and energy efficiency. fectively utilizing deep convolutional neural actionable control policies. Many classes of
networks (CNNs) and reinforcement learning algorithms such as CNNs can be readily used
Passive touch is not the only way in which algorithms—are contributing to the success with tactile data (14), and vision-based ML
we acquire tactile information. To identify of visuomotor policies in manipulation tasks strategies can be used for grasp planning.
a grasped object, and simultaneously esti- (12, 13). Ultimately, relying too heavily on vi-
mate its material characteristics, texture, sion alone has its problems. This approach A roadmap for hardware advances in tac-
and weight—all without the aid of vision— works well in fixed settings without any vi- tile sensors may focus on at least three broad
humans often use active haptic sensing, the sual occlusions, such as robotic pick and themes. There should be renewed emphasis
on the reliability of tactile sensors over a
Human versus robotic touch robot’s lifetime (several years), and on pro-
ducing large amounts of high-quality data.
Human hands are covered with sensors (mechanoreceptors) that provide continuous touch-sensation Multimodal transducers that record light
feedback that allow us to identify and control objects. For example, we can exert the right amount touch, deformation, vibrations, and tempera-
of force to hold sharp and pointy fruits such as a horned melon (kiwano) with great poise and dexterity. tures using array architectures with increased
Robotic hands do not have these capabilities but continue to improve. distributed processing and reduced wiring
are needed. Robot hands specifically suitable
Human touch Skin Receptors for sensorimotor control will benefit from a
1 1 Meissner codesign of actuators and sensors with a high
Signal processing density of coverage (>100 sensors/cm2 over
Encoded tactile signals 2 corpuscle large areas). In addition, robust propriocep-
contain rich information tion will be needed in such applications for
about object contact, 4 2 Merkel cell- reliably localizing object contact.
timing, and movements 3 neurite
and collectively refect Neuromorphic tactile hardware (and
object properties. complex software) advances will strongly influence
the future of bionic prostheses—a compel-
3 Pacinian ling application of robotic hands. Adhering
corpuscle to encoding techniques that closely mirror
natural tactile coding schemes has been criti-
4 Rufni ending cal in providing users with realistic sensory
feedback through peripheral nerve interfaces
Mechanoreceptor architecture (15). In that regard, increasing the density of
Distinct types of mechanoreceptors are arranged in complex these connections will be crucial. j
architectures in the skin and record specifc types of touch stimuli.
Sweat can change the elasticity of skin and afect these signals. REFERENCES AND NOTES

Neural processing Distilled 1. C. Bell, The Hand: Its Mechanism and Vital Endowments
information as Evincing Design (The Bridgewater Treatises,William
Tactile signals and Pickering, London, UK, 1833), vol. 4.
proprioception Object identity
Weight 2. C. Bartolozzi, L. Natale, F. Nori, G. Metta, Nat. Mater. 15,
Touch signals encode timing Feedback control 921 (2016).
and object properties.
3. A. B.Vallbo, R. S.Johansson, Hum. Neurobiol. 3, 3 (1984).
Robotic touch Tactile Artifcial sensing 4. B. Coste et al., Science 330, 55 (2010).
inputs Advances in machine-learning 5. A.T. Chester et al., N. Engl.J. Med. 375, 1355 (2016).
Camera algorithms are helping robots add visual 6. F. Moehring, P. Halder, R. P. Seal, C. L. Stucky, Neuron
Visual information to augment tactile sensing.
inputs Tactile hardware breakthroughs are 100, 2 (2018).
needed to bridge the gap between the 7. J.A. Pruszynski, R. S.Johansson, Nat. Neurosci. 17, 1404
human and robot capabilities.
(2014).
GRAPHIC: C. BICKEL/SCIENCE Neural 8. B. Dzidek, S. Bochereau, S.A.Johnson,V. Hayward, M.J.
network
Adams, Proc. Natl.Acad. Sci. U.S.A. 114, 10864 (2017).
Output 9. A. Chortos,J. Liu,Z. Bao, Nat. Mater. 15, 937 (2016).
10. Y. Kim et al., Science 360, 998 (2018).
Object identity 11. S.J. Lederman, R. L. Klatzky, Cognit. Psychol. 19, 342
Weight
Feedback control (1987).
12. S. Levine et al., J. Mach. Learn. Res. 17, 1334 (2016).
13. M.Andrychowicz et al., Int.J. Robot. Res. 39, 3 (2020).
14. S. Sundaram et al., Nature 569, 698 (2019).
15. J.A. George et al., Sci. Robot. 4, 32 (2019).

ACKNOWLEDGMENTS

S.S. is supported by American Heart Association grant
20POST35210045.

10.1126/science.abd3643

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INSIGHTS | PERSPECTIVES

RETROSPECTIVE interest in persons of African descent knew
that Jackson’s work was a must-read. His per-
James S. Jackson (1944–2020) spectives were interesting and insightful, his
assertions compelling, and his theories com-
Social psychologist who pioneered the study of Black culture prehensive. I later met him at national meet-
ings of the Association of Black Psychologists
By Thomas A. Parham course. Rather, his initiatives penetrated and the American Psychological Association. PHOTO: UNIVERSITY OF MICHIGAN INSTITUTE FOR SOCIAL RESEARCH
communities across the country, yielding While his presence in the latter was an an-
J ames S. Jackson, beloved elder and population samples that few could match nual treat, it was his stature in the former
a light for Black culture in the field for their inclusive, decidedly Black diversity. that helped me truly understand the scope
of social psychology, joined the com- He also challenged the implicit and some- and impact of his work.
munity of Ancestors on 1 September times explicit bias in university courses and
at the age of 76. Jackson understood journal editorial review boards that Euro- I always appreciated Jackson’s orienta-
the need to explore the within-group American norms were the standard against tion to an African-centered view of reality.
variability of Black people’s lives and culture which Black people should be measured Like many Black psychologists of his era, he
rather than relying on simplistic between- and compared. His efforts to create a more embraced a strengths-based view of Black
group comparisons. His study of Black com- self-determined body of research on African culture. This perspective was important,
munities contributed a host of insights into American people, independent of their white as oftentimes Black life viewed through a
family composition, education, health status counterparts, revolutionized research en- Eurocentric lens was assumed to be deficient
and outcomes, aging, violence in the commu- deavors and data reporting in the 1980s and or pathological because it was different from
nity, religious and spirituality practices, help- beyond. His scholarship also helped entire what white people thought or how they be-
giving and help-seeking behaviors, law en- haved, according to their own psychological
forcement and policing, and experiences disciplines and a host of researchers under- experts. And yet, the salience of Jackson’s
with racism. He reframed the discourse on stand that there are always multiple factors work, in changing the focus on people of
people of African descent, giving Black peo- that explain a given phenomenon. African descent from telephoto to wide-
ple a voice on Black mental health. angle, allowed people throughout the coun-
For Jackson, advocacy on behalf of Black try to realize and embrace a more holistic
Born in Detroit, Michigan, on 30 July 1944, Americans extended beyond research. As a view of Black people’s humanity.
Jackson completed his bachelor’s degree in graduate student, he was a member of the
psychology at Michigan State University in Black Student Psychological Association, Jackson had a quiet demeanor, a sharp
1966, his master’s degree in psychology at the which sought to create a cultural comfort intellect, and keen insight. He was tough-
University of Toledo in 1970, and his Ph.D. in zone for students. Later, he was part of a con- minded when it came to rigorous research
social psychology at Wayne State University tingent of Black psychologists who confronted questions but tender and empathic when
in 1972. He then began his long career at the the American Psychological Association revealing and contextualizing the core of
University of Michigan, from which he re- about its lack of membership diversity, the Black people’s life experience. Although he
tired last year as a professor of psychology, standard theoretical models in which Black was averse to self-promotion, his work spoke
professor of Afro-American and African stud- people were invisible, and the testing and for itself through the impact it had on how
ies, and director and research professor at assessment protocols that inaccurately and Black people perceived themselves and were
the university’s Institute for Social Research. inappropriately claimed to assess the intellec- perceived by others.
His career included several stints on govern- tual capability and psychological stability of
mental advisory boards, including a position African American children and adults. Jackson’s awards and honors include
on the advisory council to the director of the his election as a fellow of the American
National Institutes of Health. I considered Jackson my respected elder, Association for the Advancement of Science
an mzee, as those of us of African descent re- (AAAS, the publisher of Science), the
In an effort to shed light on a group that fer to those whom we hold in high esteem. American Academy of Arts and Sciences, and
was mischaracterized in the research and I first encountered him on the pages of my the New York Academy of Medicine. He was
theories being presented at the time, Jackson textbooks. Any student of psychology with an recognized for outstanding contributions
established the Program for Research on to research in aging by the Gerontological
Black Americans in 1976. The following Society of America’s Robert W. Kleemeier
year, he began his groundbreaking National Award. In 2014, he was appointed to the
Survey of Black Americans—a dataset that National Science Board.
was arguably the largest and most com-
prehensive study of Black life and culture, Just as the Sun never truly sets, Jackson’s
as well as behavior patterns, in the coun- smile, ideas, and spirit will never truly leave
try. Jackson’s research methodology helped us. His identity, character, and humanity have
usher in a more authentic and realistic pic- been indelibly imprinted on those places he
ture of the Black experience, and his data traveled during his life, and his contribu-
samples provided the platform for countless tions have been permanently recorded in
investigatory endeavors. His subject samples the pages of numerous manuscripts, books,
were not restricted to a hundred students scholarly journals, advisory boards, scientific
enrolled in an introductory psychology meetings, and conference presentations. His
collective works have served as an intellec-
California State University Dominguez Hills, Carson, CA tual solvent, erasing profound misunder-
90747, USA. Email: [email protected] standings and biases about people of African
descent and revealing a rich and previously
unappreciated cultural tapestry. j

10.1126/science.abf0706

770 13 NOVEMBER 2020 • VOL 370 ISSUE 6518 sciencemag.org SCIENCE

Published by AAAS

BOOKS et al. Galileo’s paradigm-shattering theories went beyond
what is permitted by the scientific method.

CLASSICS REVISITED tionary, the practice of science in the 17th
century was largely entrusted to human
Moving beyond the paradigm perception. This meant that not being able
to feel Earth moving would have been con-
A provocative 1975 call to leave behind dogmatic thinking sidered by many to be sufficient to falsify
could help scientists strengthen ties with the public Galileo’s theory. Feyerabend asserted that
Galileo needed to break the existing scien-
By Joseph Swift understanding of the world around us. tific paradigm by presenting a new one and
that he only succeeded in doing so by going
Feyerabend did not think it was so simple. beyond what rational argument allowed,
drawing upon, for example, ad hoc hypoth-
A mid the turbulence of the 20th cen- He believed that within the landscape of eses and emotional language.
tury’s civil rights movement and all discoverable knowledge, the scientific
sexual revolution, the philosophy method offers a path leading to only a frac- Against Method was divisive. After publi-
of science was undergoing its own tion of all knowable facts. This is because cation, Feyerabend was called the “worst en-
radical transformation. Suspecting it encourages researchers to begin where emy of science” in Nature (1) and a “breath
of fresh air” in Science (2). Many scientists
that the scientific method was less well-established theories leave off, keeping thought that the book presented a type of
philosophy that could be easily weaponized
straightforward than scientists claimed, them aligned with existing scientific para- (3), not least because it provided a shield
for nonexperts promoting unsubstantiated
philosophers had started chal- digms. A path set forward by clas- or malicious arguments. Some also worried
that by weakening the boundaries of what
lenging the idea that deductive sical physics, he argued, will not counts as bona fide scientific research, sci-
ence itself might come to be considered just
logic was the best way to reveal Against Method lead to quantum mechanics. another type of cultural practice.
truths about the world. Against Paul Feyerabend Feyerabend thought that new
Method (1975), by philosopher of New Left Books, 1975. But this is not quite what Feyerabend
science Paul Feyerabend, played a scientific paradigms could only be sought to inspire. Instead, he wanted to
339 pp. reached by radical methods. In- generate curiosity about what happens
when we try to live within the rules of our
IMAGE: PICTORIAL PRESS LTD/ALAMY STOCK PHOTO key role in bringing such arguments to ma- deed, given that new paradigms sit outside current scientific paradigms. Is it always
desirable, for example, to treat mathemati-
turity. Forty-five years after its publication, existing knowledge structures, there cannot cal harmonies and statistical abstractions
as the best reflections of reality? Consider
the book continues to offer valuable in- be a predefined method on how to discover empirical research on the state of Ameri-
can democracy, which largely relies on ran-
sights to scientists confused by the public’s them. Anarchistic thinking, spiritualism, ir- dom sampling and quantitative metrics. By
discounting narratives of police injustice
ambivalence toward hard scientific truths. rationality—all must remain on the table. as anecdotal, some have argued that po-
litical scientists long remained blind to the
Most modern scientists would agree As proof of principle, Feyerabend ele- extent of racial authoritarianism (4).

that the scientific method provides the gantly demonstrated that a strict adherence Against Method hints that there must be
a middle ground between one extreme, in
best route toward an ever more cohesive to the scientific method would have forced which all views are equally valued, and the
other, in which the limits of current scientific
Galileo to give up his hypothesis that Earth paradigms are never tested. This casts the
role of today’s scientist as more ambiguous
The reviewer is at the Salk Institute for Biological Studies, orbits the Sun. Not only did the existing evi- than perhaps many would like, but such am-
La Jolla, CA 92037, USA. Email: [email protected] dence support the idea that Earth was sta- biguity could help scientists strengthen their
relationship with the public. By loosening the
framework within which scientists may op-
erate, Feyerabend gives them permission to
enter the political arena, a realm that many
researchers have historically deemed outside
their jurisdiction, but one in which their par-
ticipation is sorely needed. j

REFERENCES AND NOTES

1. T.Theocharis, M. Psimopoulos, Nature 329, 595 (1987).
2. W.J. Broad, Science 206, 534 (1979).
3. M. Kuntz, EMBO Rep. 13, 885 (2012).
4. V. M.Weaver, G. Prowse, Science 369, 1176 (2020).

10.1126/science.abe9322

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INSIGHTS | BOOKS

HISTORY OF SCIENCE

Imaginary demons and scientific discoveries

A new history acts as a field guide to the fictional imps invoked by scientific thinkers

By Jan G. Michel tematically presented us with a false re- Bedeviled: A Shadow

W hat role could imaginary creatures ality? If this were the case, we could not History of Demons
possibly play in the most ratio- trust our senses at all. There is, however, in Science
nal, systematic, and discovery- one feature of reality that such a demon Jimena Canales
oriented enterprise humanity has would be unable to manipulate. “Cogito, Princeton University Press,
ever created? Did the Enlighten- ergo sum,” reasoned Descartes, “I think, 2020. 416 pp.
therefore I am.” From this foundation, Des-

ment not teach us to dispense cartes constructed an approach to scientific

with the supernatural and provide us with knowledge that fundamentally influenced understanding any of the symbols it manip-

the power of reason to exorcise demons Western philosophy and modern science. ulates. But, asked Haugeland, what happens

from modern science? In her chapter on computer daemons, if “a superfast person”—Searle’s demon—

As Jimena Canales reveals in her thought- Canales discusses Searle’s demon, an imp took over an individual’s neural processing,

provoking and highly readable book Bedev- introduced by philosopher John Haugeland replicating that person’s exact responses?

iled, fictional imps that help us explore the in response to an assertion made by phi- What is then causally responsible for the

limits of what is possible pervade the his- losopher John Searle that computers do not person’s understanding—her neurons or

tory of scientific thinking, namely in the demon?

the form of thought experimentation. We learn a great deal about the

Although this is not a new topic of scientists who have used demons to

inquiry, Canales comes at it from a re- confront difficult challenges and ap-

freshingly original perspective, exam- proach apparent paradoxes. For in-

ining the ways that various scientific stance, along with her description of

thinkers throughout the centuries have the article in which Albert Einstein

made use of imaginary demons. invoked “ghosts” in order to question

In the book’s 10 chapters, Canales traditional notions of space (and,

recounts science’s most famous fiends, later, time), Canales includes details

including Laplace’s demon, a being about Einstein’s health problems, his

who could predict every occurrence broken marriage, and how Arthur

in the Universe, and Maxwell’s demon, Eddington helped to confirm his the-

who could violate the second law of ory of general relativity.

thermodynamics. More contemporary The reader also learns about the

examples are discussed in the book’s role that cultural factors played in

later chapters and include the self-pro- shaping scientific thought at differ-

gramming electronic circuits that Nor- ent times and in different contexts.

bert Wiener referred to as “demons” For example, we learn why Descartes

and the lines of code known as “dae- warned against the “dangers” of read-

mons” that are central to today’s com- ing novels like those that intrigued

puter communication infrastructure. Don Quixote and also about the role

At the outset of her scientific de- played by the Renaissance painter

monology, Canales presents a clas- Raphael in Erwin Schrödinger’s con-

sic example: Descartes’s demon. In Maxwell imagined a “very observant and neat fingered” demon who ceptions of life and negative entropy.

his Meditations on First Philosophy could detect and react to the motions of individual molecules. As Canales maintains, demons are

(1641), the French philosopher, math- “neither just psychological delusions

ematician, and scientist René Descartes at- understand the symbols they manipulate (1). or simplistic heuristic fictions nor simply IMAGE: REPRINTED BY PERMISSION FROM SPRINGER NATURE

tempted to establish a firm foundation for Searle argued that artificial intelligence is auxiliary midwives who help scientists de-

scientific knowledge. To do so, he used a comparable to a native English speaker with liver knowledge.” On the contrary, she ar-

method known as “Cartesian doubt,” which no knowledge of the Chinese language, who gues that the notion of a (scientific) demon

encouraged a skeptical approach to reality. is locked in a room and asked to provide should be regarded as akin to other, more

After arguing that our sensory experience is sensible responses in Chinese to inquiries established philosophical notions or tools,

often erroneous and also that we can never made in that language. Given an English “such as concepts, numbers, classes, and

be certain that we are not dreaming, Des- rule book that instructed the user how to categories”—a welcome contribution to the

cartes imagined an even worse scenario: correlate Chinese symbols with appropriate philosophy of scientific discovery that de-

What if a powerful and clever demon sys- responses, the person could convincingly serves further scholarly attention. j

The reviewer is at the Department of Philosophy of Religion convey that he understood the messages be- REFERENCES AND NOTES
and Science, Ruhr-Universität Bochum, 44801 Bochum, ing relayed without actually understanding 1. J. R. Searle, Behav. Brain Sci. 3, 417 (1980).
Germany. Email: [email protected] them. Similarly, argued Searle, the central 10.1126/science.abd9851
processor of a computer translates without

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Published by AAAS

LETTERS

Disease transmission can occur at live animal markets, but zoonotic disease research could benefit from an emphasis on humans’ and animals’ shared risk of infection.

PHOTO: AMILIA ROSO/THE SYDNEY MORNING HERALD/GETTY IMAGES Edited by Jennifer Sills approach that considers both pathogen Faculty of Medicine and Health Sciences, University
biodiversity and social-ecological drivers of Antwerp, Antwerp, Belgium. 12Operational
EcoHealth reframing (9). Prevention based on understanding Directorate Taxonomy and Phylogeny, Royal
of disease monitoring the transmission of pathogens through Belgian Institute for Natural Sciences, Brussels,
EcoHealth-based emerging infectious Belgium. 13University of Antwerp, Department of
Decade-old (1) and recent warnings for disease surveillance is a promising avenue Biology, Evolutionary Ecology, Antwerp, Belgium.
coronaviruses with zoonotic epidemic for sustainability science, orders of magni- 14Fundamental and Applied Research for Animals
potential (2) could have prevented the tude cheaper than mitigation in response and Health, Faculty of Veterinary Medicine,
emergence of coronavirus disease 2019 to a transfer to human hosts (10), and less University of Liège, 4000 Liège, Belgium.
(COVID-19) (3). We therefore agree with intrusive than current crisis responses. *Corresponding author.
Watsa and colleagues (“Rigorous wildlife Email: [email protected]
disease surveillance,” Perspective, 10 July, Maarten P.M. Vanhove1,2,3*, Jean Hugé4,5,6, Luc
p. 145) that wildlife biosurveillance should Janssens de Bisthoven7, Hans Keune8,9, Anne REFERENCES AND NOTES
increase. However, representing animals Laudisoit10, Séverine Thys11, Erik Verheyen12,13, 1. V. C. C. Cheng, S. K. P. Lau, P. C.Y.Woo, K.Yung Yuen, Clin.
as a threat to humans through disease Nicolas Antoine-Moussiaux14 Microbiol. Rev. 20, 660 (2007).
transmission leads to ill-conceived reac- 1Research Group Zoology: Biodiversity 2. Y. Fan et al., Viruses 11, 210 (2019).
tive policies (4). A perspective (5) in which and Toxicology, Centre for Environmental 3. European Environment Agency (EEA),“Late lessons
animals and humans share similar risks of Sciences, Hasselt University, Diepenbeek, from early warnings: Science, precaution, innovation—
pathogens and infections, making animals Belgium. 2Department of Botany and Zoology, Summary”(Report 1/2013, Publications Office of the
relevant disease models and sentinels, Faculty of Science, Masaryk University, Brno, European Union, Luxembourg, 2013); www.eea.europa.
would be more effective. Clarifying the con- Czech Republic. 3Laboratory of Biodiversity eu/publications/late-lessons-2.
nection between animal and human health and Evolutionary Genomics, Department 4. N.Antoine-Moussiaux et al., Sustain. Sci. 14, 1729 (2019).
could increase public support for research of Biology, University of Leuven, Leuven, 5. P. M. Rabinowitz, L. Odofin, F.J. Dein, EcoHealth 5,
seeking to understand host-switching in Belgium. 4Department of Environmental 224 (2008).
animals, such as the study of virus evolution Science, Open University of the Netherlands, 6. S.J.Anthony et al., Virus Evol. 3, vex012 (2017).
(6), interactions in pathogen communities Heerlen, Netherlands. 5Department of Biology, 7. W. de Souza, Parasitol. Res. 119, 2369 (2020).
(7), and pathogen discovery (8). Vrije Universiteit Brussel, Brussels, Belgium. 8. D. R. Brooks et al., WCSAJournal 1, 1 (2020).
6Research Group Environmental Biology, Centre 9. H. Lerner, C. Berg, Front.Vet. Sci. 4, 163 (2017).
A shared-risk perspective on emerg- for Environmental Sciences, Hasselt University,
ing infectious diseases mirrors the field Diepenbeek, Belgium. 7Capacities for Biodiversity 10. A. P. Dobson et al., Science 369, 379 (2020).
of EcoHealth, which explores the links and Sustainable Development, Royal Belgian
between ecosystem, animal, and human Institute for Natural Sciences, CEBioS program, 10.1126/science.abe8239
health. Such strategies place value in Brussels, Belgium. 8Belgian Biodiversity
healthy ecosystems through an integrative Platform–Research Institute Nature and Forest, Build international
Brussels, Belgium. 9Chair Care and the Natural
SCIENCE sciencemag.org Living Environment, Department of Primary and biorepository capacity
Interdisciplinary Care Antwerp, Faculty of Medical
and Health Sciences, University of Antwerp, In their Perspective “Rigorous wildlife
Antwerp, Belgium. 10Ecohealth Alliance, New York, disease surveillance” (10 July, p. 145), M.
NY 10018, USA. 11Department of Vaccinology, Watsa et al. underscore the value of One
Health approaches to stimulate integration
Published by AAAS
13 NOVEMBER 2020 • VOL 370 ISSUE 6518 773

INSIGHTS | LETTERS

across currently siloed efforts in zoo- Pontificia Universidad Catolica del Ecuador, Quito, emphasizing shared risk, such misinforma-
notic research and mitigation. To achieve Ecuador. 7Museum of Southwestern Biology and tion can be countered with well-researched
comprehensive decentralized pathogen Biology Department, University of New Mexico, messaging following a zoonotic outbreak.
surveillance, there is an urgent need to Albuquerque, NM 87131, USA. 8Department of Conservation social science has honed a
develop environmental and biodiversity Biological Sciences, Chicago State University, suite of tools to identify the often unpre-
infrastructure in biodiverse countries Chicago, IL 60628, USA. 9Department of Biology, dictable human motivations behind (8),
experiencing high rates of habitat Georgia Southern University, Statesboro, GA and the possible negative consequences of,
conversion, wildlife trafficking, and 30458, USA. 10Centre de Recherche en Sciences such communications (9).
human-wildlife interactions. Naturelles, Lwiro, Democratic Republic of
Congo. 11Facultad de Ciencias, Universidad de Colella et al. suggest that surveillance
Approximately one-third of One la República, Montevideo, Uruguay. 12Florida efforts should include natural history col-
Health networks lack an environmental Museum of Natural History and the University lections. Some natural history museums
component, fewer than half are active of Florida Biodiversity Institute, University of and zoos archive biobanked specimens,
in wildlife surveillance, and almost Florida, Gainesville, FL 32611, USA. 13Department cryopreserved viable cell cultures, disease
none is led by developing countries (1). of Ecology and Evolutionary Biology and the specimen banks, and histopathology
International support for development Museum of Zoology, University of Michigan, samples, but this highly effective practice
of natural history museums with frozen Ann Arbor, MI 48108, USA. 14Research Group (10) is limited by high costs. We agree
vertebrate tissue collections remains a Zoology: Biodiversity and Toxicology, Centre that devoting funding toward biodiver-
key component missing from the One for Environmental Sciences, Hasselt University, sity banking within countries at high
Health equation. Most pathogens causing Diepenbeek, Belgium. 15Department of Botany and risk for emerging infectious diseases
severe outbreaks in humans are zoonotic Zoology, Faculty of Science, Masaryk University, would improve conservation outcomes.
in origin (2); thus, understanding their Brno, Czech Republic. 16Laboratory of Biodiversity Taxonomically diverse biobanked tissues
evolution and that of their wild animal and Evolutionary Genomics, Department and live cell cultures could expand studies
hosts is imperative. of Biology, University of Leuven, Leuven, of host-pathogen relationships, clarify-
Belgium. 17Department of Forestry and Wildlife ing host range or affected tissues and
As was the case for coronavirus disease Management, Maasai Mara University, Narok, providing in vitro systems for infectivity
2019 (COVID-19) (3), identifying wild Kenya. 18Departamento de Vertebrados, Museu and pathogenicity investigations. Such
animal reservoirs can be challenging Nacional, Universidade Federal do Rio de Janeiro, collections could allow drug develop-
when biorepositories are lacking (4). In Rio de Janeiro, Brazil. ment for humans to expand beyond just
most countries, natural history biore- *Corresponding author. Email: [email protected] a few animal laboratory models, given
positories remain poorly supported and that relatively well-studied viruses such
largely disconnected from public health REFERENCES AND NOTES as SARS-CoV-2 are potentially broadly
initiatives. For example, most studies of infectious across taxonomic orders (11).
bat coronaviruses to date (5), including 1. M. S. Khan et al., Lancet Planet. Health 2, e264 (2018). Comparative genomics and transcrip-
the PREDICT animal surveys discussed 2. K. E.Jones et al., Nature 451, 990 (2008). tomics among nonmodel species are
in Watsa et al., did not preserve host 3. J. Cohen, Science 10.1126/science.abd7707 (2020). used infrequently in biomedical research
specimens or tissues, thus limiting the 4. S.A.J. Leendertz,J. F. Gogarten,A. Düx, S. Calvignac- programs but hold great potential for
potential for molecular host identification prioritizing species and gene targets with
or replication and extension of the science Spencer, F. H. Leendertz. EcoHealth 13, 18 (2016). alternative host defense mechanisms for
(6). Emerging infectious disease response 5. B. Hu et al., PLoS Path. 13, e1006698 (2017). laboratory study (12).
hinges on sampling depth across space, 6. J.A. Cook et al., Bioscience 70, 531 (2020).
time, and taxonomy, the very sampling 7. J. L. Dunnum et al., PLoS Negl.Trop. Dis. 11, 1 (2017). Mrinalini Watsa1,2* and Wildlife Disease
enabled by museum biorepositories. 8. O. Paknia, H. Sh Rajaei,A. Koch, Organ. Divers. Evol. 15, Surveillance Focus Group3
As primary biological infrastructure, 1Population Sustainability, San Diego Zoo Global,
in-country development of museum col- 619 (2015). San Diego, CA 92027, USA. 2Field Projects
lections that follow best practices (7), with International, San Diego, CA 92126, USA. 3Wildlife
specimen data freely available through 10.1126/science.abe4813 Disease Surveillance Focus Group authors and
the internet, should be an interna- affiliations are listed at science.sciencemag.org/
tional imperative (8) for effective global Response content/369/6500/145/suppl/DC1.
surveillance and mitigation of emerging *Corresponding author.
infectious diseases. We agree with Vanhove et al. that wildlife Email: [email protected]
conservation and emerging infectious
Jocelyn P. Colella1, Bernard Risky Agwanda2, disease screening are two sides of the REFERENCES AND NOTES
Faisal Ali Anwarali Khan3, John Bates4,5, Carlos A. same coin. Wildlife and humans can
Carrión Bonilla6,7, Noé U. de la Sancha4,8, Jonathan be vulnerable to spillover events by the 1. J. D. Negrey et al., Emerg. Microbes Infect. 8, 139 (2019).
L. Dunnum7, Adam W. Ferguson4, Stephen E. same pathogen. For example, respiratory 2. S.A.J. Leendertz et al., Mamm. Rev. 47, 98 (2017).
Greiman9, Prince Kaleme Kiswele10, Enrique P. diseases (1) and Ebola virus (2) outbreaks 3. R. E. Ricklefs, E. Bermingham, Glob. Ecol. Biogeogr. 11,
Lessa11, Pamela Soltis12, Cody W. Thompson13, have occurred simultaneously in great
Maarten P. M. Vanhove14,15,16, Paul W. Webala17, apes and humans. Pathogens also affect 353 (2002).
Marcelo Weksler18, Joseph A. Cook7* biogeographical species range expan- 4. P. M. Rabinowitz et al., Ecohealth 5, 224 (2008).
1Biodiversity Institute, University of Kansas, sions, contractions, and extinctions (3). 5. J. P. Kibambe et al.,“In Africa, wildlife raises the risk of
Lawrence, KS 66045 USA. 2National Museums Biosurveillance efforts should reflect that
of Kenya, Nairobi, Kenya. 3Faculty of Resource health risks are shared by humans and deadly diseases: It doesn’t have to”CNN (2020).
Science and Technology, Universiti Malaysia wildlife, a central tenet of the One Health 6. H.Zhao, Science 367, 1436 (2020).
Sarawak, Sarawak, Malaysia. 4Field Museum, framework (4). As Vanhove et al. point 7. H.Yan et al.,biorxiv 10.1101/2020.09.08.284737 (2020).
Chicago, IL 60605, USA. 5Natural Science out, wildlife can serve as the source for 8. K. E.Wallen, E. Daut, Nat. Conserv. 26, 55 (2018).
Collections Alliance, Washington, DC 20005, preventive solutions that mitigate spill- 9. H. N. Dang Vu, M. R. Nielsen, Hum. Dimensions Wildl. 23,
USA. 6Museo de Zoologiá, Escuela de Biología, over risks into humans and animals.
417 (2020).
A shared risk perspective could also 10. J. Radin, J. Cult. Econ. 8, 361 (2015).
combat the narratives that portray animals 11. J. Damas et al., Proc. Natl.Acad. Sci. U.S.A. 117, 22311
as dangerous pests or disposable commodi-
ties that endanger human health (5), as (2020).
in the case of bats (6), many of which are 12. L.Yurkovetskiy et al., Cell 183, 739 (2020).
likely not hosts for coronaviruses such as
severe acute respiratory syndrome coro- 10.1126/science.abe9392
navirus 2 (SARS-CoV-2) (7). In addition to

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SPECIAL SECTION

COOLING IN A

WARMING WORLD

NEWS PHOTO: GLENN ASAKAWA/UNIVERSITY OF COLORADO
Living with heat p. 778

PERSPECTIVES
Adapting to the challenges of warming p. 782
Cooling our insatiable demand for data p. 783
Photon-engineered radiative cooling textiles p. 784

REVIEWS
Terrestrial radiative cooling: Using the cold universe as a renewable and sustainable energy source p. 786

New refrigerants and system confgurations for vapor-compression refrigeration p. 791
Caloric materials for cooling and heating p. 797

RELATED ITEMS Podcast

776 13 NOVEMBER 2020 • VOL 370 ISSUE 6518 sciencemag.org SCIENCE

Published by AAAS

By Brent Grocholski

T he planet is warming from greenhouse gas emis- trade-o s between toxicity, flammability, and lower
sions, with increases in both peak and average efciency. An alternative approach involves the use
temperatures. Consequently, the demand for of caloric materials—i.e., solids that e ectively pump
cooling will intensify, driven by climate change heat as they are electrically, magnetically, or mechani-
as well as improving economic conditions. Cool- cally manipulated.
ing requirements for data centers and new tech-
nologies may also call for innovative solutions. A completely di erent cooling strategy is to use ma-
Developing a wide array of cooling strategies terials that regulate heat in the form of infrared ra-
diation. Passive radiative cooling materials take advan-

will be vital for human comfort and prevention tage of an atmosphere window for infrared radiation

of heat-induced medical emergencies. A growing number to eject heat into space. When deployed on rooftops,

of materials and methods are being designed to improve these systems can potentially cool buildings by a few

technologies, meet the temperature needs of data centers degrees, even in the daytime. Along the same lines,

and other facilities, and reduce harmful emissions. textiles may be modified so that heat can more ef-

Vapor compression systems supply much of the resi- ciently radiate through them, allowing people to be

dential and industrial cooling infrastructure. These more comfortable at higher thermostat set points.

systems rely on compressing gases, many of A large-area flm As the planet warms, keeping cool without
which contribute to the greenhouse e ect engineered to passively increasing greenhouse gas emissions will be a
if released into the atmosphere. Finding re- challenge, but new materials and technologies
placements is a priority but requires balancing radiate heat are poised to meet this goal.
away from the surface

SCIENCE sciencemag.org 13 NOVEMBER 2020 • VOL 370 ISSUE 6518 777

Published by AAAS

NEWS

LIVING
WITH
HEAT

Studies are probing
how heat threatens
health—and how to
lower the risks

By Elizabeth Pennisi

I t’s 5 a.m. and still dark at the Carlton digging a fire break, or burning vegetation Across the globe, researchers like PHOTO: PAUL JONES/UNIVERSITY OF WOLLONGONG
Complex fire camp in central Washing- to keep a larger fire away. It’s all part of a Domitrovich are working to pin down how
ton, except for the fire’s orange glow study to assess heat exposure in wildlands heat affects workers and vulnerable popu-
on a distant ridgeline. Wildlands fire- firefighters—the biggest ever to do so. From lations, such as the elderly. They are study-
fighter Bre Orcasitas, two colleagues, 2013 through 2016, more than 300 firefight- ing low-tech measures—sometimes nothing
and three volunteers suit up: heavy ers participated. more than a splash of cold water on the
duty fire-resistant pants, shirt, jacket, skin—to make people safer and more com-
and helmet. Their boots weigh 2 kilo- High body temperatures are inevitable fortable in hot conditions. And they are
grams; the backpacks they will haul to in firefighting: A study in 2013 uncovered exploring the body’s ability to adapt to the
the fire—loaded with 6 liters of water, food about 50 heat-related injuries across the heat. “Deaths and illnesses caused by heat
for a 16-hour shift, safety gear, and hand United States during that fire season. But are largely preventable,” says June Spector,
tools—can weigh 30 kilograms. Sometimes other data from their project have surprised an occupational and environmental health
the burden includes a 12-kilogram chain saw. Orcasitas and her colleagues. Warmth from physician-scientist at the University of
the firefighters’ physical exertion, not heat Washington, Seattle.
On this day in August 2014, the crew is from the fires, was the greatest danger, the
not just fighting flames, but also taking researchers found. Another surprise: “The The work has taken on urgency as global
part in research. Orcasitas outfits each per- assumption across the fire community was temperatures rise, heat waves become
son with a chest harness and sensors that that if somebody went down, it was be- more frequent and intense, and casual-
will record their heart rate, elevation gain, cause they just didn’t drink enough water,” ties mount. Between 1999 and 2010, the
distance traveled, carbon monoxide intake, Orcasitas says. But the team found other- U.S. Centers for Disease Control and Pre-
and skin temperature. Each swallows an in- wise. “You can’t drink yourself out of a vention logged 8081 heat-related deaths
gestible radio thermometer that relays deep heat-related injury,” explains project leader in the United States, one-third of them in
body temperature to the chest monitor ev- Joseph Domitrovich, an exercise physio- people age 65 or older. Already, about one-
ery 15 seconds via Bluetooth. Orcasitas and logist at the U.S. Forest Service’s National third of the world’s population experiences
her two colleagues will record each fire- Technology and Development Program. “It’s conditions that create heat stress, says
fighter’s activities, be it cutting down trees, not the magic bullet that people thought.” Nathan Bradley Morris, a human thermal

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COOLING TECHNOLOGY SPECIAL SECTION

Sweat plays an important logist from the Environmental Protection ing continues, the body can still cool itself
role in cooling the body, Agency. And much of the global population somewhat. But if a person gets too hot (this
is aging and getting heavier. tipping point varies, but hovers around
so researchers are capturing 42°C for exertional heat stress), sweating
and measuring it. By 2100, heat exposure will threaten the can stop and body temperature can sky-
health of an estimated 4 billion people, ac- rocket, sometimes even rising above 44°C.
physiologist at the University of Copenha- cording to an International Labour Orga- The brain falters; confusion, agitation,
gen. At high risk are construction workers nization report. The report forecasts that slurred speech, even coma can result.
and farm hands, respectively 13 times and the world’s productive working hours will
35 times as likely to die from heat as other decline 2.2% because of increasing heat, re- Even if people recover, heat can cause
workers. Farm hands in the United States sulting in $2.4 trillion in economic losses, problems. Some 15% of people exposed to
already face an average of 21 days in sum- concentrated in Southern Asia and Western chronic heat stress at work develop kid-
mer when humidity and temperature com- Africa. “There are inequities in who is ex- ney problems, possibly making it one of
bine to exceed recommended limits, and posed to heat,” Spector says. the first epidemics due to global warming,
the risks are growing. In the United States, a European consortium called Heat Shield
climate change will double the number of FOR CENTURIES, physiologists have studied reported in 2018 in The Lancet Planetary
unsafe days by 2050 and triple it by 2100, how the human body reacts to heat stress, Health. Moreover, studies have documented
Spector and colleagues reported on 25 Au- tracing its remarkable ability to keep its an increase in other injuries on hot days,
gust in Environmental Research Letters. core temperature at about 37°C even when possibly because heat and dehydration can
the outside air is many degrees hotter. impair thinking.
Amplifying the trends, the world’s popu- Sensory nerves on the skin respond to the
lation is moving to cities, which tend to be environment’s temperature, and internal At their worst, life-threatening tempera-
hotter than the countryside, says Lisa Leon, sensors keep tabs on heat gain, some of tures can damage the brain and cause or-
a research physiologist at the U.S. Army Re- which is generated by the body itself. In- gans to fail. Deprived of normal blood flow,
search Institute of Environmental Medicine. tense physical activity can turn the body the gut can leak, causing widespread in-
In Paris, about 12,000 people died in 1 week into a furnace, raising heat production 15- flammation. Blood vessels can get damaged
during a heat wave in 2003. Even those who fold. Whether the source is environmental and blood can coagulate. Cells can even fall
don’t work in the heat are vulnerable, espe- or internal, if heat is not dissipated, it can apart as their proteins break down.
cially people who are older and overweight strain and ultimately shut the body down.
or whose hearts may not be strong enough “Heat stroke is one of the three lead-
to cope with the physiological stress of heat, When internal sensors tell the brain the ing causes of death for athletes, soldiers in
says Christopher Gordon, a retired physio- body is warming, the hypothalamus sends training, and laborers,” says Douglas Casa,
signals that dilate blood vessels close to the an exercise physiologist at the University of
skin, causing more blood to circulate there Connecticut (UConn), Storrs.
and lose heat—provided the air is cooler
than the body. When it’s not, or if heat That’s what happened to Korey Stringer,
transfer to the air isn’t enough, the sweat an offensive lineman for the Minnesota Vi-
glands get to work. Another part of the kings. He collapsed on day two of spring
brain, the medulla oblongata, gets in touch training in 2001, but his heat stroke was not
with the heart, which increases its rate and treated aggressively, and he died the next
the amount of blood pumped per beat. The day. A professional athlete, he was fit—but
body’s fluids shift, redirecting blood to the not fit enough for such a strenuous workout
skin and helping fill sweat glands. early in the season. Motivation to exercise
may override the body’s signals to stop,
An active person can easily sweat out Leon says.
2 liters of water per hour, which cools the
body as it evaporates. It’s not the head, as Gatorade and the National Football
often believed, but the hands (with their League launched the Korey Stringer In-
high concentration of sweat glands) and the stitute at UConn in 2010, and now grants
torso (with its large surface area) that are and private support keep it going. As its
key sites for sweat-aided cooling. The fluid CEO, Casa has worked extensively with ath-
loss stimulates the release of hormones that letes and with the U.S. military to protect
enhance thirst and alter kidney function recruits from Stringer’s fate. For the most
to reduce urine production. These fluid- part, the military and sports trainers have
conserving measures help shore up blood “a good handle on treating heat stroke, but I
volume so the heart can maintain blood don’t think people are doing enough to pre-
pressure at safe levels. vent it from happening in the first place,”
Casa says.
Dehydration greatly adds to heat strain
and the risk of serious injury. Staying well- At the institute, suited up with heavy
hydrated can be protective, but it may not backpacks, rifles, and full military attire,
keep body temperature from rising if internal volunteers march around a lab warmed
or external heating is too great, Domitrovich to the temperature of a hot desert. Casa
and others have found. First comes heat ex- studies how bodies react to the stress of
haustion, characterized by cramps, fatigue, working in the heat and tests protective
headache, nausea, or dizziness—signals that measures, including new fabrics for hot
prompt most people to move out of the weather clothing, new safety and recovery
heat or stop exercising. As long as sweat- procedures, and wearable sensors that can
sound the alarm if conditions reach danger-
ous extremes.

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SPECIAL SECTION COOLING TECHNOLOGY

In a study last year, for example, some heat stroke,” Casa says. In fact, he says, because, even in the heat, heart rate doesn’t PHOTO: DAVID MCNEW/GETTY IMAGES
of the volunteers got thirsty during a bout the treatment guarantees recovery if used rise as much, and the heart pumps more
of fast walking on a treadmill in a room promptly and properly. blood per stroke. The body retains more
at 35°C with 30% humidity. Afterward, ex- FAR BETTER to avoid heat strain entirely, fluids and blood volume rises, increasing
perimenters allowed the subjects to drink says Nigel Taylor, a thermal physiologist water reserves for sweating and cooling.
enough to replace 25% of their lost fluids retired from the University of Wollongong. “The body has a really good capacity to
and asked whether they were still thirsty. That means adjusting to heat by avoiding acclimate,” says Daniel Gagnon, a human
They were not. Thirst was quenched well air conditioning, which Taylor says “pre- physiologist at the University of Montreal.
before they had enough water, Casa and vents us from adapting to our climate.” But “as long as you keep inserting air con-
his colleagues reported in November 2019 ditioning in that process, you delay ac-
in Nutrients. “The absence of thirst does Heat tolerance varies from person to per- climatization,” says Elizabeth Repasky, an
not mean the absence of dehydration,” he son, not just because of age and health, but immunologist at Roswell Park Comprehen-
warns. He recommends that elite athletes also because of genetic factors. One study of sive Cancer Center.
and others who exert themselves in hot 42,000 Indigenous miners in South Africa
conditions figure out their sweat rate and when they were first sent to work in the hot In the heat of summer, there may be other
adjust their drinking accordingly. mines found that about 15% could not han- ways to cool down, says Ollie Jay, a thermal
physiologist at the University of Sydney.
Long slogs and heavy clothing and gear dle the heat, whereas 25% coped just fine.
can put firefighters at even greater risk But Taylor and others have found that He has put octogenarians, chil-
of heat injury than the fire itself. dren, people with heart condi-
frequent exposure to heat also makes a big tions, even pregnant women
Casa has also field tested a strategy for difference to heat tolerance. If an individual into a heat chamber and has
runners suffering from exertional heat has a chance to get used to being hot—by found that fans can often be as
stroke. For decades, his team has pro- spending time in hot weather or exercising effective as air conditioning, at
vided medical care for a 12-kilometer race strenuously—the body modifies its physio- much lower environmental and
on Cape Cod in August. The race is short logy and becomes less vulnerable to heat financial costs. Jay and his team
enough that runners keep up a punishing stress. Athletes and workers can then work reported in November 2019 in
pace but long enough that their bodies can harder and longer despite the heat. the Annals of Internal Medicine
overheat; whereas about one in 10,000 that fans can be effective at up
marathon racers develops heat stroke, far He and others have studied adaptation to 40°C, particularly in humid
more—one in about 650—racers in this in detail. They find that after just 1 week conditions, where they help
event do so. At the Cape Cod race, his team spending 2 hours a day working outdoors in evaporate sweat that would oth-
treats up to 45 heat stroke victims a year a hot environment, the body begins to ad- erwise sit on the skin. (In dry
by immersing them in cold water. Getting just. Normal deep body temperature drops. environments, sweat evaporates
their body temperature below 40°C within The body sweats at a lower temperature, regardless of fan use.)
30 minutes is enough to ensure a full re- and there is less strain on the heart. That’s
covery, the team has found. “Most people Workers can be as productive
would be surprised to know we can treat and comfortable when cooled by
fans instead of air conditioners,
he and his colleagues reported
last year in Energy and Build-
ings. “In terms of increases in
work productivity, fan use in a
simulated Vietnamese working
environment of 30˚C with 70%
humidity is the equivalent of
7˚C of cooling with air condi-
tioning,” Jay says.

Splashing cold water on the
skin can also work well, his
studies show. “External dousing does the
job of sweat without having to sweat,” which
can lead to dehydration and strain the
heart, Jay says. His team evaluated dousing
and fans as alternatives to air condition-
ing during this summer’s U.S. heat wave.
In 80 of 105 cities—the exceptions being in
the Southwest—those alternative measures
would have been 100% effective, he and his
colleagues reported on 25 July in Science of
the Total Environment. “It’s getting hotter,
and heat waves are getting worse,” he says.
“What’s important is using these findings to
make changes in public policy.”
For outdoor workers, one simple—but
not always easy—fix is to move to the
shade. In a rural part of Indonesia, Spector,

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When cooling fails Yuta Masuda and Nicholas Wolff of the
Nature Conservancy, and colleagues ran-
The body works hard to keep its temperature stable. If deep body temperature rises, organs work together domly assigned 363 laborers to work in a
to drive heat to the skin. As heating continues, the heart, skin, brain, and other organs try to maintain the forest or a deforested area nearby. (Defor-
right body temperature and amount of fluids. But those systems can be overwhelmed. (Normal body temperature estation can increase local temperatures
and the danger threshold vary from person to person.) by up to 8°C.) The workers wore heart rate
monitors and had their oral temperatures
Body temperature 36.8˚C 1 Too warm taken regularly to calculate core body tem-
perature. During a 90-minute task in hot,
Fluid ratio Temperature sensors in the skin and deeper in humid, sunny conditions, people in open
Blood the body sense the environment is hot and the areas had temperatures above 38.5°C for
Organs body may need to take steps to cool itself. 3 minutes longer than those in the forested
area, Spector and her colleagues reported
Blood Blood and sweat last year in Environmental Research Let-
vessel When sensors notify the ters. The differences may seem small, but
brain, it stimulates blood over the course of a day, body temperatures
Sweat vessels to dilate and bring would likely keep climbing, putting these
gland heat to cooler surface workers at great risk of heat-related illness.
tissues. If that doesn’t cool Those who worked in deforested areas also
the body enough, sweat scored worse on cognition and memory
glands turn on. tests, perhaps because of dehydration or
discomfort, the team reports in a paper in
The heart’s role press in Environmental Research Letters.
To keep up with fluid flow demands, the heart
pumps faster and more vigorously. Blood volume Wildlands firefighters also work in an
initially increases, but can decrease if sweating exposed, hot environment. Yet it is not
drains too much fluid. sunshine or fire they need to worry about
most. “The heat from the fire almost never
38˚C has any effect on our core body tempera-
tures,” says William Knudsen, a wildlands
Adrenal 2 Getting thirsty firefighter based in Helena-Lewis and Clark
gland National Forest. Nor is it dehydration, once
When pressure sensors considered the biggest risk for these work-
Kidney detect enough water loss, ers. Orcasitas found, for example, that after
they activate the adrenal a particularly strenuous day’s work, a well-
gland to release a fluid- hydrated firefighter came back feeling “like
regulating hormone. The crap” and had a higher body temperature
body conserves dwindling than a colleague who started and ended the
water by reducing urine day more dehydrated. And fellow study co-
flow. Thirst develops. ordinator Knudsen saw firsthand how trou-
ble can arise even in temperate weather.
GRAPHIC: V. ALTOUNIAN/SCIENCE 39˚C 3 Heat strain His team recorded its highest body temper-
atures on a high-elevation site with an air
4 Heat stroke If intense exercise temperature of only about 21°C.
continues or outside
When the body temperatures Instead, Domitrovich says, “It’s the in-
gets hot and keep rising, water ternal heat production that’s most critical.”
dehydrated enough, loss continues. Big packs, heavy clothing, and a fast pace
sweating can cause body temperatures to spike. “And if
stop, the brain can Starting to fail you are less fit, you are going to generate
malfunction, With less fluid, the heart has to work ever more heat,” Orcasitas says. So now, when
and a person can harder to maintain blood pressure. As blood Knudsen takes out his crew, he’s mindful
lose consciousness. pressure sinks, cooling becomes increasingly of the weight they carry and how fast they
difficult. Deep body temperature climbs faster. hike, frequently taking a 2-minute break af-
ter 8 minutes of walking.
42˚C 39˚C
Orcasitas thinks the study will make a
5 Recovery difference for her and her firefighting col-
leagues. “These are all seemingly simple,
Cooling within but [the findings] are a pretty big deal,” she
30 minutes, such says, because they’re easy to act on.
as by immersion
in cool water, They could also help others stay cooler
can drive deep as global temperatures climb. “Heat stress
body temperatures is a very complex topic, so the more we can
to safe levels educate not just firefighters but everyone,
and restore the better,” Domitrovich says. “It will lead to
brain function. increased safety for all humans.” j

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SPECIAL SECTION COOLING TECHNOLOGY

PERSPECTIVE

Adapting to the challenges of warming

The impact of regional heat events is becoming more important to quantify

By Steven C. Sherwood emissions-reduction commitments and poli- ally warm more than oceans, a result of the

cies or carbon dioxide removal efforts, each difference in background humidity (6).

H eat extremes on Earth have reached presenting daunting sociopolitical, economic, Although early research focused on maxi-
a disturbing new level in recent and technological challenges. mum temperatures, additional factors have
years. The July 2020 temperatures come to the fore. Humidity is crucial to
soared across Siberia and reached A common saying is that people do not heat stress, for example, because it inhibits
a record-breaking 38°C inside the feel the average temperature. However, cli- evaporative cooling. Humidity is increasing
mate model projections do indicate that

Arctic Circle, continuing a line of in most regions, peak temperatures (see globally along with temperature. Regional

record heat events globally. “Event at- the figure) roughly track the annual mean variations in these variables tend to compen-

tribution” calculations, which are an en- in the same location (5). In some regions sate, so that areas like Western Europe and

deavor to apportion blame for South America that become drier also

extreme events through quantita- warm more (7). Thus, heat stress will

tive modeling, suggest that some Future rises in peak temperature increase relatively more uniformly
events would have been nearly im- and predictably, whereas moisture
possible without human-induced The increase in the maximum 20-year return value of maximum daytime stresses will change more variably, as
global warming. This includes the temperature late this century (2081–2100) relative to 1986–2005, based some regions warm and dry substan-
on the average of many climate models, is shown. Projections based on a

recent Siberian summer and the strong mitigation scenario [Representative Concentration Pathway (RCP) tially. Animals, including humans,

2018 heat wave in Japan, which 4.5] (top) and a high-emission scenario (RCP8.5) (bottom) are shown. and plants can be subject to either

killed more than a thousand people Mitigation stress independently. Anthropogenic
(1, 2). Rising heat is creating new warming has roughly tripled the size

challenges for humanity that will of the human population that experi-

require new adaptation and protec- ences dangerous humid heat annually

tion measures. Smart implementa- (8), and this heat is already approach-

tion requires careful calculation ing the limits of human tolerance in a

of how further global temperature few locations (9). Humidity increases

rises will translate into short-term not only thermal stress outdoors but

regional heat events and how these also the overall energy requirements

will translate into impacts on hu- of cooling systems, which already

man health and activities, food sup- account for a large fraction of total

ply, infrastructure, and ecosystems. power consumption in humid cli-

These enhanced heat extremes mates where air conditioning has be-

are the result of slightly more than No mitigation come widespread (10).
1°C of global-mean anthropogenic Another factor to consider is the du-

warming since the mid-19th cen- ration of heat events. More frequent

tury. The world has set a goal under or longer heat events tend to have

the Paris Agreement to keep global- greater impacts on human health (11),

mean anthropogenic warming be- and nighttime temperatures are more

low 2°C in the future, or 1.5°C if strongly correlated to heat-related

possible. Current national commit- mortality than daytime ones. These

ments, however, could well permit observations show that adequate

increases of up to 4°C or so by the physiological recovery from heat ex-

end of this century, with further in- posure is important. Wind systems,

creases thereafter (3). Even the ambi- such as the mid-latitude jet streams

tious Representative Concentration and associated weather systems, are

Pathway (RCP) 4.5 scenario consid- expected to slow in a warmer climate,

ered by the Intergovernmental Panel 0 0.5 1.5 1 2 3 4 5 7 9˚C potentially causing longer lasting pe-

on Climate Change in 2013 leaves riods of extreme weather. However, GRAPHIC: ADAPTED FROM COLLINS ET AL. (3)

only a 50% chance of remaining below 2.4°C such as Western Europe, extremes are pre- multiple factors are at work such that the net

by 2090, given the latest estimates of climate dicted to increase faster than the mean change remains unclear (12).

sensitivity (4). Limiting carbon dioxide to owing to greater variability. Moreover, the Because of the “urban heat island” effect,

meet the 2°C target will therefore require mean increases vary around the globe; one temperatures are higher in urban areas than

some combination of substantially stricter reason is that the upwelling of cold water in surrounding natural areas (13). The rela-

from the deep oceans will cause Southern tive lack of vegetation means that incoming

Climate Change Research Centre and ARC Centre of Excellence Hemisphere temperatures to lag behind solar energy goes into heating surfaces rather
for Climate Extremes, University of New South Wales, Sydney, those in the Northern Hemisphere for de- than canopies aloft, and less goes into evapo-
NSW 2052, Australia. Email: [email protected] cades or centuries. Also, land regions gener- rating water vapor. Human-made surfaces

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and urban canyons also retain heat better PERSPECTIVE
into the night. In addition, the energy used in
cities generates heat, which is negligible on Cooling our insatiable
a global scale but often important in urban demand for data
areas. Urban heat islands are not typically in-
cluded in climate calculations and are likely Hyperscale data centers provide challenges
to worsen anywhere that urbanizes further, and opportunities for energy use
adding to the warming delivered by the cli-
mate system. By Amy S. Fleischer Notably, these improvements in cooling
architecture are implemented mainly in
Although predicting the above factors is T he world is driven by constant access to hyperscale data centers and have coincided
challenging enough, quantifying their im- information. We have the entire world with a widespread shift away from small,
pacts is even harder. Quantitative models of at our fingertips wherever we are, and local, on-site data centers. In 2010, 79% of
heat-affected natural and human systems, if access to data in its various forms is all data center operations were executed in
used at all, are less advanced relative to the ubiquitous. The ability to retrieve this traditional data centers, including small on-
complexity involved than are weather and cli- information, much of it now stored site data centers, whereas in 2018, 89% of
mate models. Meanwhile, climate change is in the cloud, is supported by data centers compute instances were executed in cloud
creating conditions that lie outside the range of various sizes and scales. Although instant computing facilities (2). The economy of
of past experiences, limiting the reliability of access to data from anywhere is a benefit in scale in hyperscale data centers permits the
empirical studies. Current impact models di- many ways, part of the cost of this access is in use of advanced server designs and vastly
verge substantially in the predicted impacts of escalating energy demands, much of it from improved cooling technologies, and PUE can
climate changes (14) and almost surely suffer the cooling infrastructure needed to support now approach 1.1 to 1.2 (1). These massively
from systematic biases (15). Diverse impacts these data centers. scaled data centers have doubled in number
generally depend on the different aspects of in just the past 4 years, from just over 250
heat events, devaluing any one-size-fits-all The widespread movement to cloud- worldwide in 2015 to more than 540 today,
heat measure. We need to more rigorously based services over the past 14 years has with hundreds more in development (3).
quantify the links between meteorological transformed the data center industry. In
forecasts and practical consequences. 2006, 50% of all U.S. servers were located Data center cooling technology has
in small or medium-size data centers or come a long way from the server rooms of
Past studies do point to a couple of ro- in self-managed corporate data centers yore. Traditional designs often relied on
bust conclusions. One is that impacts will (1). These small data centers had an aver- air cooling and the overprovision of room
increase nonlinearly with mean warming, as age processor utilization of only 10 to 20% air conditioning, necessitating the use of a
extreme thresholds are crossed with rapidly and required a substantial energy invest- parka for technicians working in the space.
increasing frequency (8). This highlights the ment because of high power demands. Improvements in air-handling design thus
need for strong emissions mitigation to keep Inefficient cooling infrastructure for these were the first major steps forward in data
warming to a level that we can cope with. The servers, often located in closets or small center cooling. Raised floor designs with
other is that although no one will be spared, rooms, led to a total data center annual integrated air distribution plenums were
the world’s poor will be hit particularly hard energy demand of 70 terawatt hours in the implemented, with cold air distribution
(11). This highlights the need for low-cost ad- United States in 2014 or about 1.8% of all routed directly into the intake of the serv-
aptations and technologies as we seek suit- U.S. energy usage (1). ers by using perforated floor tiles in front of
able countermeasures to rising heat. j each rack or cabinet.
The total energy demand of data centers
REFERENCES AND NOTES includes both the energy demands of the IT Subsequent advances included arranging
equipment itself and the energy demand of servers into “hot aisle”–“cold aisle” configu-
1. World Weather Attribution Project, Siberian heatwave the supporting infrastructure, the vast major- rations to reduce the mixing of the exhaust
of 2020 almost impossible without climate change ity of which is for the cooling systems. A met- from one server with the intake of another;
(2020); www.worldweatherattribution.org/siberian- ric known as power usage effectiveness (PUE) detailed computational fluid dynamics
heatwave-of-2020-almost-impossible-without- represents the ratio of the total data center analysis of the floor tile designs to optimize
climate-change/. facility energy use to the energy use of the IT air flow and minimize pressure drop (4);
equipment. A data center with a PUE of 1.0 and the implementation of advanced sys-
2. Y. Imada, M.Watanabe, H. Kawase, H. Shiogama, M.Arai, would use no energy other than that used to tems and component-level control strate-
Sci. Online Lett.Atmos. 15A, 8 (2019). power the IT equipment. In 2007, when the gies for air handling. The benefit of some
metric was introduced by the Green Grid, the of these techniques is that they are suitable
3. M. Collins et al., in“Climate change 2013: The average data center PUE was 2.0, and this for retrofit into existing legacy data centers
physical science basis,”T. F. Stocker et al., Eds. average value had not changed appreciably (5) while also being relevant to new designs.
(Report, Intergovernmental Panel on Climate Change, by 2016 (1). However, an increased focus on Hyperscale data centers, which by nature
Cambridge Univ. Press, 2013), chap. 12. this metric in recent years has led to many have flexibility in their geographic location,
advances in cooling technology. can be located in cool and low-humidity cli-
4. S. C. Sherwood et al., Rev. Geophys. 58, mates in which both air-side economization
e2019RG000678 (2020). College of Engineering, California Polytechnic and water-side economization can be used
State University, San Luis Obispo, CA, USA. to reduce cooling costs. Air-side economiza-
5. A. Di Luca, R. de Elía, M. Bador, D.Argüeso, Weather Clim. Email: [email protected] tion features the mixing of outdoor air into
Extrem. 28, 100255 (2020).

6. M. P. Byrne, P.A. O’Gorman, Proc. Natl.Acad. Sci. U.S.A.
115, 4863 (2018).

7. E. M. Fischer, R. Knutti, Nat. Clim. Chang. 3, 126 (2013).
8. D. Li et al., Environ. Res. Lett. 15, 064003 (2020).
9. C. Raymond et al., Sci.Adv. 6, eaaw1838 (2020).
10. E. Morakinyo et al., Renew. Energy 142, 73 (2019).
11. A.Ahmadalipour, H. Moradkhani, M. Kumar, Clim.

Change 152, 569 (2019).
12. T. Shaw et al., Nat. Geosci. 9, 656 (2016).
13. K. Deilami, M. Kamruzzaman,Y. Liu, Int.J.Appl. Earth

Obs. Geoinf. 67, 30 (2018).
14. S. G.Yalew et al., Nat. Energy 5, 794 (2020).
15. J. Schewe et al., Nat. Commun. 10, 1005 (2019).

10.1126/science.abe4479

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SPECIAL SECTION COOLING TECHNOLOGY

the conditioned air and brings the same solutions for environmentally friendly and PERSPECTIVE

benefits as opening the windows when cool off-grid power production are of much inter- Photon-
engineered
outside. As such, the strategy is often re- est. Some hyperscale data center operators radiative
cooling textiles
ferred to as “free cooling.” Water-side econ- are exploring sourcing their own sustainable
Personal thermal
omization reduces the demand on the chill- power production using hydrogen fuel cells management offers
a path to reduce climate
ers that cool the conditioned air in many (13), and others are sourcing their energy control energy use

data centers, again by using outside air. from solar and wind farms. Future research By Po-Chun Hsu and Xiuqiang Li

Evaporative cooling techniques can reduce trends will include a focus on advanced cool- T ake a few seconds to look around and
list all the technologies that are indis-
the energy demand even further. By using ing techniques that feature energy recovery pensable for you. If your list does not
include textiles, try to live a typical day
such techniques, Google has dropped its av- and reuse. Both liquid and two-phase cooling without them. Textiles are arguably
one of the earliest human inventions.
erage trailing 12-month PUE to 1.10 (6). strategies produce a stream of heated liquid Without textiles to cover the human body
for warmth, our ancestors would not have
Future improvements in cooling strategies or vapor that can be used in various waste- been able to spread across the various cli-
mate zones of the Earth. Today, many textiles
will come from a shift in focus from air-cool- heat recovery systems, including straightfor- are made for social etiquette and aesthetic
purposes, but the pressing threat of global
ing strategies to a focus on embedded liquid ward techniques such as hot water produc- warming has created demand for innovative
textiles that help to better cool the person
and evaporative cooling techniques, which tion and plant or district heating (14) and who wears them.

take advantage of inherently higher heat more complex systems such as absorption The rationale behind linking textiles and
climate change is that wearing the cooler tex-
transfer coefficients. Direct liquid cooling refrigeration or the organic Rankine cycle, tiles for localized “personal thermal manage-
ment” may reduce the demand for air con-
features microchannel cold plates mounted which generates a source of electricity that ditioning. The impact of air conditioning is
considerable, given that it is not only respon-
directly on the heat-pro- can be fed back into the sible for 10% of U.S. electricity consumption
but that the refrigerants are also a source of
ducing chips. Reliability “As the demand data center (15). high global-warming-potential gasses (1, 2).
concerns related to the in- for data center The current technical Considering an indoor setting distinguishes
tegration of liquids in the capacity continues the new generation of cooling textiles from
server chassis initially af- limitation is the low quality textiles oriented for sports. On average, the
fected the implementation of the heat, and next-gen- metabolic heat rate of indoor light activities
eration advances will re- is 60 to 80 W/m2, balanced by the heat flux
from the skin to the environment. This flux
of this technology, but in- unabated, the quire much attention to the occurs through all viable heat transfer path-
creases in chip energy den- integration of the cooling ways: conduction, convection, radiation, and
evaporation. Because one of the criteria of
sity beyond the capabilities demand on the power technology and the energy thermal comfort is the absence of sensible
of air cooling, coupled with grid will continue generation technique to perspiration, evaporation only accounts for
technology advances such meet the growing demands ~5 W/m2. Using the American Society of
Heating, Refrigerating and Air-Conditioning
as optimized microchan- to escalate.” of our insatiable need for
nel designs (7) and detailed data. The past 5 years have Department of Mechanical Engineering and Materials
Science, Duke University, Durham, NC 27708, USA.
failure mode analysis and shown incredible advance- Email: [email protected]

mitigation (8), have led to wider adoption of ments in the technology used to cool data

embedded liquid cooling in hyperscale data center equipment, but much work remains

centers over the past few years. to be done to develop sustainable, environ-

However, advances in integrated chip de- mentally friendly solutions to the energy

signs with three-dimensional architecture demand required to power the cloud. j

are creating energy densities beyond even REFERENCES AND NOTES
that which can be controlled with direct liq-
uid cooling. Thus, next-generation cooling 1. A. Shehabi et al.,“United States Data Center Energy
research is investigating techniques such as Usage Report”(Lawrence Berkeley National Labs,
flow and pool boiling (9) and even direct im- LBNL-1005775, 2016).
mersion of the chips in dielectric fluids with
subsequent boiling at the chip interface (10). 2. E. Masanet,A. Shehabi, N. Lei, S. Smith,J. Koomey,
Thermosyphons, which feature gravity-fed Science 367, 984 (2020).
liquid-vapor systems, are the focus of much
attention (11), as they allow the high heat 3. www.srgresearch.com/articles/hyperscale-data-
transfer possible with flow boiling while center-count-reaches-541-mid-2020-another-
eliminating the reliability issues inherent 176-pipeline; accessed 10 October 2020.
with micropumps. In application, micro-
evaporators are located directly at each chip, 4. J.Athavale,Y.Joshi, M.Yoda, J. Electron. Packag. 140,
much like a cold plate; gravity-fed liquid 010902 (2018).
feeds the evaporator, and the resulting va-
por rises to a condenser located at the top of 5. R. Khalid,A. P.Wemhoff, J. Electron. Packag. 141, 041004
the server rack, where the loop begins again. (2019).
Much two-phase flow research focuses on
the use of environmentally friendly refriger- 6. www.google.com/about/datacenters/efficiency/;
ants such as HFC-245fa or HCFO-1233zd(E), accessed 15 October 2020.
adding the benefit that any leak will immedi-
ately vaporize, eliminating concerns around 7. B. Ramakrishnan,Y. Hadad, S.Alkharabsheh, P. R.
liquid leakage (12). Chiarot, B. Sammakia, J. Electron. Packag. 141, 041005
(2019).
As the demand for data center capac-
ity continues unabated, the demand on the 8. S.Alkharabsheh, U. L. N. Puvvadi, B. Ramakrishnan, K.
Ghose, B. Sammakia, J. Electron. Packag. 140, 020902
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9. H. Lee et al., J. Electron. Packag. 140, 020906 (2018).
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(2018).
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Therm. Eng. 180, 115757 (2020).
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power grid will continue to escalate. Thus, 10.1126/science.abe5318

784 13 NOVEMBER 2020 • VOL 370 ISSUE 6518 sciencemag.org SCIENCE

Published by AAAS

Engineers Standard 55 as the reference and (5), outdoor cooling textiles (6), and visibly the indoor scenario. A different strategy is to

assuming the clothing insulation is 1 clo colored cooling textiles (7, 8). Depending on use active cooling by devices such as Peltier

(0.155 m2K/W; clo is the industry unit for the types, these radiative cooling textiles can coolers that are either directly wearable or

thermal insulation), then the heat transfer have the cooling performance equivalent to connected with recirculating water (11, 12).

through textile conduction and natural con- more than a 2°C increase of indoor tempera- These systems have superior cooling power,

vection contributes ~40 W/m2, and radiation ture setpoint. One should not underestimate but the power consumption likely needs an

is responsible for ~25 W/m2. This calculation this amount of setpoint increase because it energy storage or supply breakthrough to

demonstrates the substantial role of radia- applies to the entire building space, which become part of daily clothing. A hybrid so-

tion in the human body heat balance. Unlike has orders of magnitude more thermal iner- lution is variable passive thermoregulation,

convective heat transfer, heat radiation is a tia and heat loss to manage compared with which uses energy to control the heat trans-

surface property and does not require any the occupants. Estimates of energy savings fer coefficients rather than supply the ther-

media or moving part, making it a perfect suggests the potential for a 20% reduction mal power. The tunable range is similar to

tool for personal thermal management. of heating, ventilation, and air conditioning the purely passive approach but can be ac-

Regardless of skin pigmentation, the hu- energy with this small setpoint increase (9). tively changed according to user preference

man skin is a nearly perfect black body that Looking ahead from the promise of en- and potentially other signal inputs from

emits thermal radiation through Planck’s law. ergy saving, challenges and opportuni- the environment or the human body (13,

This radiation transmits through the air gap ties exist for the radiative cooling textiles. 14). Ultimately, the radiative thermal engi-

and is absorbed by the textile, which contains Thousands of years of evolution have made neering can be combined with other textile

various types of resonating mo- heat-management mechanisms

lecular vibrational modes. The to accomplish multimodal con-

textile then reemits to the ambi- Designing more comfortable textiles trol. A radiative cooling textile
ence. Almost all clothing materi- with coupled dynamic evapora-
als are highly absorbing in the Heat transport through traditional textiles occurs by conduction or convection tive cooling can perform human
spectral region of human body (blue paths), but infrared (IR) radiation is blocked (red paths). Cooling textiles body cooling even when the
radiation. Although Kirchhoff’s improve radiative heat transfer between the skin and the environment. Adaptive ambient temperature is higher
textiles control the heat balance without working fluids or continuous energy input.

radiation law indicates that they than the skin.

are also good emitters, their in- Traditional textile Radiative cooling Adaptive textile Like many other renewable
frared (IR) opacity inevitably (IR-absorbing) textile (IR-transparent) (multimodal) energy technologies, radiative
results in the radiation shield- cooling textile was initially a ma-

ing effect. Therefore, rather than Convective/ Ambient terials science and nanophoton-
engineering the existing clothing Conductive ics effort for niche applications
materials, the key to radiative for energy-efficient buildings by

cooling is to re-invent the mate- accomplishing the localized per-

rial so that it is transparent in sonal cooling, and it will eventu-

mid-IR, allowing the thermal ra- Textile ally need to find the proper mar-

diation from the hot human skin ket position to be economically

to bypass the textile and directly sustainable. In particular, these

reach the ambience (see the fig- Radiative Air gap textiles will be joined by both
ure). By contrast, traditional IR- traditional textile engineering

absorbing textiles emit from the and the booming wearable tech-
cold outer surface with a much Skin nologies. Our ancestors invented

lower radiation power that is textiles as the “secondary skin”

proportional to the fourth power of tempera- the expectation for clothing design to be for thermal regulation. As textiles become an

ture, according to Stefan-Boltzmann’s law. complicated and often subjective in terms indispensable part of our lives, they hopefully

This design principle leads to polyethylene of what is considered necessary. Even for will move closer to being as smart, versatile,

(PE) textiles because of its simple chemi- simple energy-efficient thermal comfort, and natural as our actual skin. j

GRAPHIC: N. CARY/SCIENCE cal bonds and very few resonance peaks in psychological and environmental factors REFERENCES AND NOTES
mid-IR. In 2015, Tong et al. numerically pre- are in play that go beyond what might be
dicted that radiative cooling fabric could be ideal from a physical science perspective. 1. U.S. Department of Energy,“ARPA-E DELTA Program
achieved by controlling the PE fiber diameter The choices of IR-transparent polymers Overview”(2013); https://arpa-e.energy.gov/
and light-scattering mechanisms to obtain should be broadened to accommodate the sites/default/files/documents/files/DELTA_
both IR transparency and visible light opac- various needs for wearability, such as mois- ProgramOverview.pdf.
ity for wearability (3). One year later, Hsu et ture transport, skin touch comfort, scratch
al. experimentally demonstrated nanopo- durability, and laundering. A general rule is 2. U.S. Energy Information Administration,“Annual Energy
rous PE (nanoPE) radiative cooling fabric to search for materials with a high content Outlook 2020”(2020) https://www.eia.gov/outlooks/
(4). The nanoporous structure was designed of crystalline aliphatic segments, followed aeo/.
to achieve multifunctionality such as visible by quantitative measurement of absolute
opacity, breathability, and softness. Several extinction coefficient. Also, textiles should 3. J. K.Tong et al., ACS Photonics 2, 769 (2015).
efforts to enhance the wearability were also be adaptive. For example, the textile woven 4. P.-C. Hsu et al., Science 353, 1019 (2016).
conducted, including sweat-wicking and from carbon nanotube–coated bimorph 5. Y. Peng et al., Nat. Sustain. 1, 105 (2018).
wind permeability. Built on the intrinsic IR yarns can respond to sweat and modulate 6. L. Cai et al., Adv. Mater. 30, 1802152 (2018).
transmittance and nanoscale photonic engi- the mid-IR emissivity (10), which is energy 7. L. Cai et al., Joule 3, 1478 (2019).
neering, this concept was further developed free and effective for the outdoors, but 8. L. M. Lozano et al., Opt. Mater. Express 9, 1990 (2019).
9. T. Hoyt, E.Arens, H.Zhang, Build. Environ. 88, 89 (2015).
10. X.A.Zhang et al., Science 363, 619 (2019).
11. S. Hong et al., Sci.Adv. 5, eaaw0536 (2019).
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13. P.-C. Hsu et al., Sci.Adv. 3, e1700895 (2017).
14. E. M. Leung et al., Nat. Commun. 10, 1947 (2019).

into large-scale woven and knitted textiles needs to increase the trigger sensitivity for 10.1126/science.abe4476

SCIENCE sciencemag.org 13 NOVEMBER 2020 • VOL 370 ISSUE 6518 785

Published by AAAS

COOLING TECHNOLOGY

REVIEW ings, transportation, cold chain industries, and
personal comfort for outdoor activities. Inte-
Terrestrial radiative cooling: Using the cold universe grating radiative cooling with cold collection
as a renewable and sustainable energy source and storage can actively improve the efficiency
of air-conditioning (8, 9). Although the net
Xiaobo Yin1,2*, Ronggui Yang3*, Gang Tan4, Shanhui Fan5 cooling energy flux is limited, terrestrial radia-
tive cooling has emerged as a promising solu-
Photonic materials designed at wavelength scales have enabled a range of emerging energy tion for mitigating urban heat islands and for
technologies, from solid-state lighting to efficient photovoltaics that have transformed global energy potentially fighting against global warming if
landscapes. Daytime passive radiative cooling materials shed heat from the ground to the cold universe it can be implemented at a large scale (3). The
by taking advantage of the terrestrial thermal radiation that is as large as the renewable solar energy. transformative concept of using the universe as
Newly developed photonic materials permit subambient cooling under direct sunshine, and their a cold sink in an energy system redefines the
applications are expanding rapidly enabled by scalable manufacturing. We review here the recent thermodynamic limits for energy-harvesting
advancement of daytime subambient radiative cooling materials, which allow energy-efficient cooling processes on Earth (10) and has led to em-
and are paving the way toward technologies that harvest the coldness from the universe as a new erging effects such as generating light from
renewable energy source. darkness (11).

A ll materials at a temperature above ab- out solar heat, nighttime radiative cooling has Fundamentals of radiative cooling
solute 0 K continuously absorb and emit been exploited for cooling buildings and for
electromagnetic waves. Thermodynamics harvesting and purifying water, especially in The atmosphere sets the fundamental limit for
thus calls for a process of radiative heat tropical and subtropical regions (3). An under- terrestrial radiative cooling. It partially absorbs
exchange between objects of different standing of nocturnal radiative cooling is also and reflects the incident solar radiation. In ad-
temperatures by absorbing and emitting these crucial in applied meteorology and in agricul- dition, water vapor and a variety of other
energy-carrying electromagnetic waves. Look- ture to predict frost and to protect fruits or greenhouse gases such as carbon dioxide in
ing at radiative energy exchange on the planet- seedlings from freezing (4). the air strongly absorb the long-wavelength
ary scale, the Earth has a relatively stable terrestrial thermal radiation and prevent the
surface temperature near 300 K arising from “Terrestrial passive radiative heat from being directly released into the cold
the balanced radiative heat fluxes between the cooling harvests the coldness of space. By Kirchhoff’s law, such an absorption
incoming sunlight and the outgoing thermal results in a strong downward radiation from
radiation to the cold universe. The globally ab- the universe by exploiting the the atmosphere to the terrestrial surface. The
sorbed solar radiation has an immense power balance of radiative heat flow.” net energy flux from terrestrial surfaces is
of 100 PW, and the total outgoing thermal therefore the combination of the absorption
radiation is similarly enormous (1). Using the Daytime radiative cooling, however, poses a of solar radiation (during the day), the out-
coldness of the universe as a renewable energy fundamental material challenge. To achieve a going terrestrial thermal radiation, and the
source is therefore of great interest and could surface temperature below the ambient tem- absorption of the downward atmospheric ther-
be as important as solar energy utilization. perature under direct sunlight, it is necessary mal radiation (Fig. 1A). The large power den-
to ensure that the peak solar absorbance does sity mismatch between the terrestrial solar
Terrestrial passive radiative cooling harvests not exceed the energy amount emitted from irradiation and the infrared thermal radiation
the coldness of the universe by exploiting the the surface. Because of the large power density clearly requires a daytime radiative cooling
balance of radiative heat flow. The temperature mismatch between terrestrial solar irradiation material to have a very low solar absorptivity
of a sky-facing object can fall below the ambient and infrared thermal radiation from a surface (Fig. 1B). For a clear sky, the terrestrial radia-
air temperature by minimizing its heat gain with a temperature close to ambient, the mate- tion with wavelengths within the atmospheric
while maximizing the outgoing thermal radia- rial has to have a very low absorptivity for any window is highly transmissive to the entire
tion through the atmospheric window, i.e., 8 wavelengths at which solar energy is not neg- atmosphere, and the downward atmospheric
to 13 mm. This is the wavelength range at ligible (0.3 to 4 mm) while also having a high thermal radiation is insignificant at these wave-
which electromagnetic radiation penetrates absorptivity and emissivity at mid-infrared wave- lengths. Conversely, the terrestrial thermal rad-
the Earth’s atmosphere with low losses and a lengths, preferably within the atmospheric win- iation outside of the atmospheric window can
major channel through which the Earth dis- dow. This spectroscopic requirement is rather barely escape the atmosphere. The downward
sipates heat gained from solar to outer space. stringent because it requires tailoring of op- thermal radiation of the atmosphere is thus
Unlike almost all other available energy tech- tical properties of a material over a broad primarily at these wavelengths. Designing a
nologies, in which the waste heat is deposited range of wavelengths that span nearly two surface that absorbs neither solar radiation
into the surrounding ambient, passive radia- orders of magnitude. Natural materials are not nor downward atmospheric radiation is es-
tive cooling sends excessive heat to the outer readily available for effective daytime subam- sential to achieving efficient radiative cool-
space at no additional energy cost (2, 3). With- bient cooling. ing, for example, reaching a deep subambient
temperature.
1Department of Mechanical Engineering, University of Experimental demonstrations of daytime
Colorado, Boulder, CO 80309, USA. 2Materials Science and subambient cooling with engineered photonic The distinctive spectroscopic feature of the
Engineering Program, University of Colorado, Boulder, CO structures have therefore recently attracted atmospheric window and the possible absorp-
80309, USA. 3School of Energy and Power Engineering, great interest (5–7). Passive radiative cooling tion from the downward atmospheric radia-
Huazhong University of Science and Technology, Wuhan, at no cost of electricity offers vast opportu- tion led to two types of designs for daytime
Hubei 430074, China. 4Department of Civil and Architectural nities for energy-saving applications in build- radiative cooling materials: (i) a near black-
Engineering, University of Wyoming, Laramie, WY 82071, body broadband design with a close-to-unity
USA. 5Department of Electrical Engineering, Stanford emissivity for all infrared wavelengths and (ii)
University, Stanford, CA 94305, USA. a wavelength-selective design that has a high
*Corresponding author. Email: [email protected] (X.Y.); emissivity only within the atmospheric window.
[email protected] (R.Y.) For both cases, the absorptivity has to be near

Yin et al., Science 370, 786–791 (2020) 13 November 2020 1 of 6

zero in the entire solar spectrum. The broad- nonradiative heat transfer processes of con- heat off terrestrial surfaces at night. For ex-
band design emits strongly in all infrared vection and conduction occurring at surfaces ample, a millimeter-thick plate of magne-
wavelengths. However, because of the reci- also substantially affect the overall radiative sium oxide or lithium fluoride can achieve 20°C
procity of radiation and absorption, the large cooling performance. subambient cooling during a dry and clear
emissivity at the wavelengths outside of the night (15). Increasing solar albedo, i.e., specu-
atmospheric window leads to a strong absorp- The spectral power density of the down- lar or diffusive reflectance of sunlight, is the
tion of the downward atmospheric radiation. ward atmospheric radiation is highly sensitive key to achieving subambient daytime radia-
This adverse effect limits the lowest temper- to the geoclimatic conditions. Putting solar tive cooling. A wide range of materials with
ature that is achievable by a broadband emit- absorbance aside, ground temperature and high solar reflectivity have been explored over
ter. When a broadband emitter is located in a precipitable water in the air are the two most the past several decades. However, achieving
complex environment receiving radiation from important factors affecting the net radiative subambient cooling under direct sunlight has
surrounding structures such as the ground and cooling power (Fig. 1D). The transparency of been quite a challenge (5, 7). Since the experi-
buildings, the effectiveness of cooling will be the atmospheric window decreases with the mental demonstration of daytime subambient
further compromised (12). By contrast, the amount of precipitable water, and radiative cooling (4), a large number of materials have
wavelength-selective design has a low emis- cooling is therefore commonly considered to emerged, of which many are broadband emit-
sivity at wavelengths outside of the atmo- be more effective in hot and arid regions. Even ters (6, 16). For example, by further engineer-
spheric window. The low emissivity reduces under 100% relative humidity in humid areas, ing commercially available coextruded polyester
the overall power density of outgoing ther- experiments have demonstrated >5°C subam- multilayer mirrors and cool roof paints, a multi-
mal radiation but it also stops the absorption bient cooling using a wavelength-selective layer mirror achieved a 2°C subambient cooling
of the downward radiation from the atmo- radiative cooling surface (13). Other major without a convection shield (6), and the latter
sphere and its surroundings, allowing a lower greenhouse gases such as carbon dioxide could reach subambient temperature for most
achievable temperature below the ambient and ozone, along with atmospheric partic- of the day with a polyethylene convection
temperature. The inset of Fig. 1C shows a ulate matter with a diameter of <2.5 mm shield (16). While daytime subambient cooling
nearly linear response of the net radiative (PM2.5) from pollution or other processes, is not yet achievable in natural materials, sev-
cooling power for the two ideal emitters as a also affect the infrared absorption spectra eral examples of effective radiative cooling are
function of the temperature difference be- (Fig. 1D) (14). Radiative forcing factors such known. For instance, the nanostructured hairs
tween the emitter surfaces and their sur- as increasing greenhouse gas emissions and from silver ants of the Saharan desert have
roundings. Clearly, the broadband cooler has air pollutants clearly can strongly negate the relatively low solar absorbance (<40%) but also
a larger net cooling power when the surface transparency of the atmospheric window and have a high, broadband infrared emissivity
temperature is above or close to the surround- reduce the effectiveness of terrestrial radia- (Fig. 2A) (17). This allows the silver ant to shed
ing ambient temperature, which is particularly tive cooling. off solar radiation and body heat to thermo-
useful for applications with above-ambient regulate its temperature. White silk cocoons
temperature radiant surfaces. However, the Deep subambient daytime radiative cooling also have an average solar absorbance as low
wavelength-selective cooler allows achieving as 10% (Fig. 2A) (18, 19). Further processing of
a much lower subambient temperature. The A large variety of organic and inorganic mate- these natural materials can lead to synthetic
rials are broadband emissive in the infrared
wavelengths and are all capable of pumping

A the Universe 3 K C 1.0 Net cooling power (W/m2)

Sun Prad 0.8 Emissivity
5800 K Patm 0.6
Psolar 0.4 T (oC)
0.2
0.0 0.5 0.7 1 23 57 10 20
10 20
0.3

Wavelength (µm)

B D

Power density 100 Zero atmosphere 0.8Absorption (a.u.) Water vapor
(W/m2/nm) 10-1 (AM0) 0.6 Carbon dioxide
10-2 Ozone
PM 2.5
0.3
AM1.5 Terrestrial radiation at sea level 0.4
and atop the atmosphere

0.5 0.7 1 23 5 7 10 20 0.2 0.5 0.7 1 23 57

0.0
0.3

Wavelength (µm) Wavelength (µm)

Fig. 1. Fundamentals of terrestrial radiative cooling. (A) Schematic of temperature difference from the ambient assuming an overall heat transfer
radiative heat flows occurring at terrestrial surfaces. Psolar, absorption of solar coefficient of 3 W/m2•K, a ground ambient temperature of 20°C, and a total
radiation; Prad, outgoing terrestrial thermal radiation; Patm, absorption of downward precipitable water of 10 mm. Adapted from (3) with permission of AIP
atmospheric thermal radiation. (B) Solar spectra and terrestrial radiation spectra, Publishing. (D) Absorption spectra of the major greenhouse gases of water vapor
respectively, at sea level and atop the atmosphere. Adapted from (7). (C) Ideal (gray), carbon dioxide (red), and ozone (green), as well as the particulate
emissivity spectra of the broadband (red) and the wavelength-selective (blue) matters collected from air pollution. The spectrum for particulate matters was
radiative cooling surface. Inset shows the net cooling power as the function of the adapted from (14) with permission from Elsevier.

Yin et al., Science 370, 786–791 (2020) 13 November 2020 2 of 6

COOLING TECHNOLOGY

materials for daytime subambient cooling. Subambient cooling under direct sunlight materials’ electromagnetic properties. Demon-
For example, delignified natural wood has a poses a photonic design challenge. By tailoring strations involving photonic crystals and meta-
wavelength-dependent emissivity (Fig. 2A, blue structures at wavelength and subwavelength materials show how they can control the
curve) that allows >4°C subambient cooling scales, the rapidly evolving field of nanophoto- emissivity of a material or a device (21). By
during the middle of the day (20). nics provides a means to precisely manipulate stacking two thermally emitting photonic
crystals together, Rephaeli et al. introduced
A Silver ant skin a wavelength-selective emitter for deep sub-
Delignified wood ambient cooling (Fig. 2B, inset) (22). The top
0.8 Silk cocoon photonic crystal was designed to enhance the
infrared emissivity only within the atmospheric
0.6 Emissivity window while being transparent to the rest of
the spectrum (Fig. 2B). A broadband chirped
0.4 design was used for the photonic crystal under-
neath to maximize the reflectance over a wide
0.2 range of solar wavelengths. Both functions were
subsequently achieved to a certain extent using
0.0 0.7 1 23 5 7 10 20 a single photonic multilayer structure (Fig. 2C,
0.3 0.5 inset) made of alternative layers of silicon di-
Wavelength (µm) oxide (SiO2) and hafnium dioxide (HfO2) (5).
When back coated with a silver mirror, the multi-
B1 layer structure reflects nearly 97% of solar ra-
diation while maintaining a relatively strong
1.8µm emissivity within the atmospheric window (Fig.
2C). This design allows for an impressive sub-
Emissivity 0.5 ambient temperature of 4.9°C (Fig. 2D) when
Solar spectrum exposed to 850 W/m2 of direct sunlight. A variety
of photonic designs that resonantly enhance
0 1 4 Atmospheric 20 25 30 the light-matter interactions within the at-
0.3 0.5 Wavelength (µm) window mospheric window have subsequently been
developed. Most incorporate lossy dielectric
8 13 materials such as heavily doped semiconduc-
tors (2, 23) or materials with photon polariton
C1Emissivity/Absorptivity Exposed to sky 900 Solar irradiance (Wm–2) resonances within the atmospheric window
800 (e.g., SiO2 and silicon carbide) (3, 24). We high-
0.75 D light two photonic nanostructures with ex-
cellent wavelength-selective emissivity within
17.5 the atmospheric window (Fig. 2, E and F).
Computational methods that use learning and
0.5 Temperature (°C) 700 optimization algorithms have been adopted
15 Ambient air temperature for the automated design of radiative cooling
materials (24, 25). Unfortunately, many of these
500 outstanding photonic structures either re-
12.5 mained as theoretical designs or have not been
demonstrated at the large scales required for
0.25 10 Photonic radiative 250 the likely applications. The inherently low en-
cooler temperature ergy flux of daytime passive radiative cooling,
0 Atmospheric typically around 100 W/m2 or less, demands a
2.5 5 transmittance 7.5 0 macroscopic implementation of these micro-
20 10:00 11:00 12:00 13:00 14:00 15:00 fabricated and/or nanofabricated photonic
8 10 13 structures. The large-scale precision lithogra-
Time of day phy and the demanding process of depositing
Wavelength (µm) multiple dielectric films that are often involved
in these photonic designs clearly hinder their
EF wide deployment.

0.8 Scaling up for application

Emissivity 0.6 SiO , 277 nm To make an impact outside of a laboratory-
2 based setting, energy materials need to be
scalable. Structural relaxation of an originally
Si N 344 nm strictly defined photonic crystal or metamate-
34 rial does not necessarily degrade its perform-
ance and, in some cases, can potentially lead
0.4 AI O 1402 nm to more advantageous properties. Embracing
23 the amorphous nature of random photonic

Ag 192 nm

0.2

2 µm 0.0
2 4 6 8 10 12 14 16

Wavelength (µm)

Fig. 2. Photonic materials for radiative cooling. (A) Emissivity spectra of natural materials and synthetic
materials made from natural resources. Black, skins of silver ants (17); blue, silk cocoon (18); red, delignified
wood (20). (B) Emissivity spectrum of an optimized photonic structure with deep subambient radiative cooling
capacity (inset), which consists of two thermally emitting photonic crystals. Reprinted with permission from
(22). Copyright 2013 American Chemical Society. (C) Infrared emissivity spectrum of a multilayer radiative
emitter (inset) showing strong emissivity within the atmospheric window. Reprinted from (5) with permission
from Springer Nature. (D) Midday ambient temperature and surface temperature of the multilayer radiative
emitter when solar irradiance is between 800 and 870 W/m2. Reprinted from (5) with permission from Springer
Nature. (E) Wavelength-selective radiative emitter with multilayer conical pillar arrays of metal-dielectric
metamaterial. Reprinted from (23) with permission from John Wiley and Sons. (F) Multilayer radiative emitter
enabled by materials with phonon polariton resonances within the atmospheric window. Reprinted with
permission from (24). Copyright 2020 American Chemical Society.

Yin et al., Science 370, 786–791 (2020) 13 November 2020 3 of 6

structures has an obvious advantage in lever- A B
aging state-of-the-art manufacturing techniques.
For instance, random pyramidally textured Glass spheres
silicon surfaces allow high-efficiency light
trapping and have been widely adopted in embedded in
solar cells (26). Taking advantage of the well-
established roll-to-roll polymer extrusion process, a transparent and
Zhai et al. demonstrated a scalable-manufactured
metamaterial thin film for deep subambient flexible polymer
cooling by encapsulating randomly positioned
SiO2 microspheres in a visibly transparent Silver mirror Glass spheres constantly
matrix made of a polymethylpentene polymer backing reflects emit infrared light and
(Fig. 3A) (7). With the right size of dielectric visible light release heat
microspheres, the collective excitation of the
surface phonon polariton resonances of the C Temperature (°C) 1000 D
embedded microspheres resulted in a close-to- Solar irradiance (W/m2)800
unity emissivity for the atmospheric window. 40 600 25
When coated with a silver mirror underneath 35 Temperature (°C)
(Fig. 3B), the flexible metamaterial thin film 20 Ambient temperature
achieved a >8°C subambient cooling at noon Surface temperature
with >800 W/m2 of solar irradiance (Fig. 3C).
The temperature difference was as large as 30 > 8 °C 400 Solar irradiance > 15 °C
15°C when there was no direct sunlight im- 15
pinging onto the metamaterial surface (Fig.
3D). Scalable manufacturing of the deep sub- 200 10
ambient radiative cooling metamaterials rap- 25
idly enables the implementation of a 13.5-m2 16:30PM 16:40PM 16:50PM 17:00PM 17:10PM
kilowatt-scale system for cold collection and 0 Time of Day
storage (9). The introduction of polymers sub- 12:20PM 12:25PM 12:30PM 12:35PM 12:40PM 12:45PM
stantially improved the manufacturability and
applicability of radiative cooling materials. Time of Day
Polymer-based radiative cooling materials
have now received markedly increased inter- EF
est. In fact, polymers are understood to be
strongly emissive and absorptive in the in- PVDF/TEOS
frared because of vibrational excitations of frameworks
functional groups (28). For example, the polar
carbon-halogen bonds have their fingerprint GH
(bending) vibration frequencies well overlap-
ped with the atmospheric window, making 2 cm
many durable halogen compounds such as
polyvinylidene difluoride (PVDF) and polyte- 6 mm 10 µm
trafluoroethene (PTFE) or their blends great
candidates for outdoor use of passive radia- Fig. 3. Scale-up of the subambient radiative cooling materials. (A) Schematic of a radiative cooling
tive cooling (28–31). We show two polymer- polymer-inorganic metamaterial consisting of randomly distributed infrared microsphere resonators
based radiative cooling materials (Fig. 3, E (27). (B) Photos of the scalable-manufactured metamaterial thin films before (top) and after (bottom) silver
and F) and both have the potential to be coating. Reproduced from (3) with permission of AIP Publishing and from (7). The metamaterial thin film
scaled up in manufacturing. Instead of using shows >8°C subambient cooling at noon with >800 W/m2 solar irradiation (C) and >15°C subambient cooling
a reflective metallic mirror or a multilayer when there is no direct sunlight received (D). Two subambient cooling materials made of porous polymer
photonic structure to reject the full spectrum networks [(E) (30)] and fibrous structures [(F) Reprinted from (31) with permission from John Wiley and Sons].
solar radiation, highly hierarchical and ran- (G) Delignified and then condensed synthetic wood showing both high toughness and subambient cooling
dom porous networks (Fig. 3E) (30) and porous capacity (20). (H) A polyethylene aerogel serves as a solar reflector while providing thermal isolation (33).
fibrous structures (Fig. 3F) (31) were introduced
to reject sunlight through multiple scattering. vibrational frequencies that are well within parent material highly reflective in the solar
With further development of phase-inversion the atmospheric window. These have shown spectrum; however, most of these materials
chemistry using a more eco-friendly solvent, compelling advantages in scaling up the fab- are broadband emitters because of the inclu-
the approach can provide the versatility that rication process, and several prototype radiative sion of infrared emissive light scatters at high
is needed to apply radiative cooling materials cooling systems have already been deployed concentrations (6, 16, 32). Taking advantage
on existing surfaces and structures. for daytime use (8, 9). The stringent requirement of random photonics, multifunctional mate-
of high solar reflectance has been achieved by rials with daytime radiative cooling capabil-
Polymeric and random photonic materials backing the material with a reflecting metallic ity are of great interest. A densified radiative
(Fig. 3, A to F) achieve the needed wavelength mirror (Fig. 3, A and B) or by multiple scat- cooling structural material can be made from
selectivity by randomly incorporating the in- tering from low-loss porous networks (Fig. 3, E a delignified natural wood (20) (Fig. 3G). The
frared resonators with phonon polariton reso- and F). Facile synthesis or inclusion of random- processed wood has a toughness >10 times
nances and/or blending polymers with selected ly distributed light-scattering microparticles stronger than that of common natural wood
or nanoparticles such as titanium dioxide and while being capable of subambient cooling
aluminum oxide (Al2O3) also provides a ver- throughout the day. By contrast, we present
satile approach to render an originally trans- a lightweight material made of a polyethylene

Yin et al., Science 370, 786–791 (2020) 13 November 2020 4 of 6

COOLING TECHNOLOGY

A Thailand Philippines Nigeria Vietnam Pakistan environment for thermoelectric generation
4000 67 M 174 M 90 M 182 M (11) and other thermal cycles (37).
98 M
To identify the best climates for potential
3000 Indonesia India large-scale deployment of terrestrial radiative
2000 250 M 1,252 M cooling, in Fig. 4B we show a world map of
annual radiative cooling potential using an
Cooling degree days Bangladesh Brazil US ideal wavelength-selective radiative cooling
157 M 200 M 316 M material with a 5% solar absorbance. The as-
sessment is based on the global meteorological
Mexico China datasets collected between 2015 and 2019, in-
122 M 1,357 M cluding rainy and cloudy weather conditions
(38). The radiative cooling potentials are clear-
1000 ly geographically dependent because of re-
gional climates. Regions with a dry and hot
0 Cooling potential (W/m2) climate tend to have higher radiative cooling
power, up to 120 W/m2. By comparison, cold,
B highly humid, or cloudy regions tend to have
much lower radiative cooling potentials. Wide
120 adoption of radiative cooling materials in re-
100 gions with high radiative cooling potentials
80 can radically change building architectures
60 because the technology not only improves
40 building heat dissipation in both day and
20 night but also reduces the need for roof in-
0 sulation or solar shading structures often
Fig. 4. Air-conditioning potential in selected countries and worldwide radiative cooling potential. used in these areas.
(A) Twelve counties with large air-conditioning potentials (35). The populations of these countries are also
labeled. (B) Global radiative cooling potential. Finally, increasing the terrestrial albedo of
buildings alone could reduce the heat island
aerogel (33) (Fig. 3H). The high porosity makes velopes such as roofs, walls, and windows can effect by 33% for urban landscapes (39). Ap-
the aerogel highly solar reflective with ultra- result in substantial energy savings, especially plying passive radiative cooling materials at
low thermal conductivity. Moreover, the aero- for hot and/or arid climates. Active circula- an even larger scale over pavements and build-
gel is spectroscopically transparent in the tion of radiatively cooled air can better reg- ing roofs across a densely populated city offers
infrared. When applying the aerogel on a broad- ulate the indoor temperature for energy saving a transformative geoengineering tool for mit-
band emitter, the combined structure demon- in regions with hot summers but have a re- igating urban heat stress, potentially address-
strated a strong subambient cooling effect duced penalty of heating in cold winters by ing the crisis of global warming (40).
because the aerogel not only allows the in- simply shutting off the circulation (36). The
frared thermal radiation to transmit through wavelength-selective radiative cooling mate- Conclusion and Outlook
but also provides an excellent thermal isola- rials that allow deep subambient cooling are
tion for reducing heat loss from the emitter of particular advantage for the generation of Radiative cooling materials harvesting the cold-
surface. The same strategy of being spectrally cold water that can be used to reduce a cool- ness from the universe can be a game changer
reflective in solar wavelengths while being ing system’s condenser temperature for im- for reducing cooling demands, increasing power
transparent in infrared has also been recently proved efficiency; a 1°C reduction of condenser production, and even mitigating the urban heat
exploited to produce cooling textiles for per- temperature may lead to 3 to 5% electricity island effect. This rapidly evolving field has the
sonal thermal management (34). saving for a chiller (8, 9). Considering the potential to change the present global energy
tremendous freshwater withdrawal for power landscape. For wider adoptions of daytime
Enabling applications plant cooling, the coldness generated by rad- passive cooling materials and technologies,
iative cooling could reduce water use while however, substantial challenges remain that
Heat stress caused by high temperature is one increasing power plant efficiency if imple- should motivate research efforts. There is a
of the most severe climate threats to human mented at a scale that reduces the steam con- strong need for a reliable, cost-effective, self-
health and to the well-being of our society. densation temperature. Similarly, the potential adapting, and colorful radiative cooling mate-
The use of air-conditioning, along with the of passive radiative cooling has been inves- rial. Some progress has been made in this
associated energy consumptions and envi- tigated in photovoltaics to reduce operation direction. For example, to ensure that the
ronmental costs, is projected to increase sub- temperature and to increase efficiency; for cooling benefits in summer far exceed the pe-
stantially in the following decades (35) (Fig. example, this has been applied in electric auto- nalties in winter, especially in high-latitude
4A). The electricity needed for global air- mobiles to reduce air-conditioning use and pro- areas, switchable and self-adaptive radiative
conditioning is expected to triple over the long mileage and in consumer electronics for cooling materials were explored with electro-
next two decades, a trajectory that is not sus- thermal management (2, 3). Untapped cold- chromic and thermochromic materials (41, 42).
tainable. Direct and passive integrations of ness can also be used to build a low-temperature Radiative cooling materials with colors have
radiative cooling materials with building en- been recently explored by minimizing the ad-
verse solar absorbance from colorants (43, 44).
By using photocatalytic titanium dioxide as
a top coating to accelerate the degradation
of organic pollutants, self-cleaning radiative
cooling materials can potentially suppress soil-
ing and dust accumulations (45). Radiative

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COOLING TECHNOLOGY

REVIEW gas relative to that of carbon dioxide (CO2).
The value is calculated over some time horizon,
New refrigerants and system configurations for most commonly 100 years, which is denoted

vapor-compression refrigeration GWP100. Values for GWP100 vary from less than
1 for some of the new refrigerants to 23,500 (4)

Mark O. McLinden1*, Christopher J. Seeton2, Andy Pearson3 for SF6, an insulating gas used in electrical equip-
ment. The GWP100 for the most common CFCs

and HCFCs range from 1800 to 14,000.

The high global warming potential of current refrigerants in cooling equipment based on the vapor-compression cycle By the early 2000s, the potential climate im-

has triggered a major effort to find and implement more environmentally benign alternatives. Here, we review the pacts of the HFCs were beginning to be con-

basics of the vapor-compression cycle together with the safety, environmental, and thermodynamic constraints sidered. The HFCs generally have lower GWP

that have led to the current and next generation of refrigerants. The development of new fluids has focused on than the CFCs and HCFCs that they replaced,

fluorinated olefins, known as hydrofluoroolefins (HFOs), and blends that contain HFOs. Many of these are slightly and their introduction enabled a relatively rapid

flammable, presenting trade-offs between safety and environmental considerations. Engineers also have transition away from the CFCs, thus averting

options with a resurgence of the “natural refrigerants” (ammonia, carbon dioxide, propane, and isobutane). some climate impacts (5). Although current HFC

Innovative system designs that reduce the required quantity of refrigerant may allow a wider choice of refrigerants. emissions are estimated to contribute less than

0.02 K to warming at the surface, a business-

as-usual scenario with increasing emissions

R efrigeration and cooling are pervasive in ment of a class of halogenated compounds would lead to a more substantial climate im-
modern society, from the refrigerated known as chlorofluorocarbons (CFCs) and pact; one estimate by Velders et al. is from 0.3 to
cold chain that provides us fresh meats hydrochlorofluorocarbons (HCFCs), also called 0.5 K by the end of the century (6, 7).
and vegetables to the air conditioning of “freons.” These compounds are nonflammable
homes and offices and the cooling of data and have low toxicity, making them seemingly A further amendment to the Montreal Pro-

tocol, known as the Kigali Amendment, was

servers that enables the internet and global com- perfect refrigerants. However, they are long- negotiated in 2016. It phases down the high-

munications. Refrigeration is viewed by some lived in the atmosphere and transport chlorine GWP HFCs, calling for an eventual reduction

as one of the 20 most transformative engineer- to the stratosphere. They also have a high direct of 85% in GWP-weighted production by 2036 in

ing achievements of the 20th century (1). The global warming impact. The environmental con- developed countries, with later dates in other

demand for cooling will continue to increase for sequences of the CFCs and HCFCs began to be parts of the world. The details of this phase down

many years because of improving economic recognized in the 1970s, and chlorine from them are left to each country. These are promulgated

conditions globally along with changing re- was definitively linked to the depletion of strato- by the Environmental Protection Agency (EPA)

gional climate. spheric ozone in 1986 (3). In 1987, an interna- Significant New Alternatives Program (SNAP)

Heat normally flows from hot to cold, but ref- tional treaty, the Montreal Protocol, first phased regulations in the United States and the “F-Gas”

rigeration enables a reversal of that flow to either down and, with later revisions, ultimately phased regulations of the European Union (EU).

make something colder (such as refrigeration, out the CFC and HCFC refrigerants. Once again, the refrigeration industry is

air conditioning, or process cooling) or upgrade A related class of chemicals, the hydrofluoro- searching for replacements for the fluids vital

heat from a cold ambient source (heat pumps). carbons (HFCs), were brought to market in the to the operation of its equipment. We survey

A wide variety of methods and systems exist to 1990s as replacements. The HFCs contain no current developments to find and implement

provide refrigeration, and the most common type chlorine and thus have no ozone depletion po- replacement refrigerants, discuss the resur-

is based on the vapor-compression cycle. The key tential (ODP), but they retain the heat-trapping gence of long-known natural refrigerants, and

to these systems is the working fluid, the refriger- characteristics of the CFCs and HCFCs as quan- review system innovations that would allow

ant, that transports heat around the cycle through tified by the global warming potential (GWP), the use of alternative refrigerants or otherwise

phase changes (boiling and condensation). which is a measure of the climate impact of a reduce environmental impacts.

Although refrigeration provides tremendous

societal benefits, it comes with environmental A Heat rejected to ambient B
costs. Refrigeration accounts for 7.8% of total
global greenhouse gas emissions, with 63% 3 Condenser 2 Critical point
of that from “indirect” emissions (2) stemming
from the energy that drives the equipment. Expansion device Temperature Saturated
This value reflects the environmental impacts of Saturated liquid vapor
the largely fossil fuel–based energy sector. Focus- Compressor
ing on the refrigerant, the switch to fluids with 2
3

substantially lower direct global warming impact

could avert nearly 3% of global greenhouse emis- Evaporator Work 4 1
sions, with larger impacts in the future as the use input Entropy
of refrigeration and air-conditioning grows. 4 Heat absorbed from 1
conditioned space
At the turn of the 20th century, early refri-

gerants were flammable or toxic, so they were Fig. 1. Vapor-compression cycle. Vapor-compression refrigeration systems operate by boiling a working fluid (the

mainly used in industrial systems. Ammonia, refrigerant) in the evaporator (4 → 1) at a relatively low pressure, extracting heat from a low-temperature source

widely used in ice-making plants, is toxic and (such as the refrigerated space). The resulting vapor is compressed to a higher pressure (1 → 2). It is then

flammable, although difficult to ignite. Smaller condensed back to a liquid (2 → 3), with the heat of condensation rejected to a relatively high-temperature heat

systems used toxic sulfur dioxide or flamma- sink (ambient air for most refrigeration and air-conditioning systems). The refrigerant is then reduced back to

ble and toxic methyl chloride. The demand for the starting pressure to complete the cycle (3 → 4). (Right) The cycle on a thermodynamic diagram. The

safer refrigerants—suitable for use in homes condensation and evaporation processes are (ideally) at constant pressure and, thus, constant temperature

and public spaces—prompted the develop- (for a pure fluid); the ideal compression process is at constant entropy.

McLinden et al., Science 370, 791–796 (2020) 13 November 2020 1 of 6