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Published by norazilakhalid, 2020-12-21 15:49:53

SCIENCE_21_August_2020.pdf

SCIENCE_21_August_2020.pdf

CONTENTS INSIGHTS

21 AUGUST 2020 • VOLUME 369 ISSUE 6506 POLICY FORUM

SPECIAL SECTION 906 A DAM BIG PROBLEM 912 Knowledge transfer for large-scale
A string of catastrophic failures vaccine manufacturing
MUD has raised alarm about dams meant Massive, rapid production will require
to contain muddy mine wastes firms to share know-how not just about
894 INTRODUCTION what to make but how to make it
By W. Cornwall
By D. Malakoff By W. Nicholson Price II et al.
910 RED ALERT
896 MUD ON THE MOVE Researchers are working to find new PERSPECTIVES
uses for red mud, the caustic byproduct
By D. Malakoff, N. Desai, and X. Liu of aluminum production By R. F. Service 915 The foundation
of efficient robot learning
898 A MUDDY LEGACY ON THE COVER Innate structure reduces data requirements
A dozen years after two scientists showed and improves robustness By L. P. Kaelbling
how centuries-old mud has smothered The muddy
many U.S. streams, their ideas are guiding Markarfljót River 917 A glycoprotein in urine binds
restoration efforts By P. Voosen in Iceland carries bacteria and blocks infections
a heavy load of Direct imaging of a human fluid illuminates
902 THE MUD IS ELECTRIC sediment to the the molecular basis of urinary tract
Bacteria that conduct electricity are sea. Throughout the protection from disease By W. Kukulski
transforming how we see sediments world, mud—a mix
of fine sediment REPORT p. 1005
By E. Pennisi and water—is one
of the most common and consequential 918 When the smallest details count
904 Next up: a phone powered by substances. For better and worse, humans The type of liquid crystals formed by
microbial wires? By E. Pennisi are now heavily influencing how mud forms smooth colloidal rods depends on their
and where it piles up. See page 894. degree of curvature By M. H. Godinho
PODCAST Photo: Arctic-Images/Getty Images
RESEARCH ARTICLE p. 950
NEWS 890 Coronavirus creates a flu PHOTO: DOUGLAS MAGNO/AFP VIA GETTY IMAGES
season guessing game 919 Remodeling vasculature
IN BRIEF SARS-CoV-2’s interactions with other to avoid blindness
pathogens remain unknown as winter looms Pathological vasculature marks itself for
886 News at a glance repair by deploying neutrophil extracellular
By K. Servick traps By E. A. Podrez and T. V. Byzova
IN DEPTH
892 Pandemic’s fallout on RESEARCH ARTICLE p. 934
888 Critics question whether novel malaria control appears limited so far
reactor is ‘walk-away safe’ Countries avert disaster by resuming 921 Immunotherapy with a sting
Design approval nears for NuScale Power’s bed net campaigns By L. Roberts New agonists of an innate immune pathway
small modular reactors, but deployment induce antitumor immunity in mice
plans slip 3 years By A. Cho 893 Pandemic lockdown stirs up
ecological research By T. F. Gajewski and E. F. Higgs
889 Paradox puts objectivity Biologists launch studies of how
on shaky footing wildlife around the world RESEARCH ARTICLE p. 935; REPORT p. 993
Quantum test of venerable thought responded to the “anthropause”
experiment suggests facts are relative 923 Past, present, and future
By E. Stokstad of lead–acid batteries
By G. Musser Improvements could increase energy density
PODCAST and enable power-grid storage applications
882 21 AUGUST 2020 • VOL 369 ISSUE 6506
Published by AAAS By P. P. Lopes and V. R. Stamenkovic

925 James G. Townsel (1935–2020)
Neuroscientist and devoted mentor
of diverse scientists By R. Nishi et al.

BOOKS ET AL.

926 One step forward, two steps back
Interest groups and state-level political
inertia have stalled many of America’s clean
energy initiatives By S. H. Ali

927 Ray Bradbury, luminary
of the space age, at 100
A new biography chronicles the golden
years of Earth’s first martian

By I. Ockert

sciencemag.org SCIENCE

LETTERS Ice core drilled at Concordia Station in 1000
Antarctica suggests fast, pulse-like jumps
928 Baer’s pochard duck in atmospheric CO2 of the distant past.
at risk of extinction

By X. Tong

928 Waterbirds’ coastal
habitat in danger

By Y. Wu et al.

929 Protect the giant ibis
through the pandemic

By H. Yang et al.

929 Errata

RESEARCH

PHOTO: THIBAUT VERGOZ, INSTITUT POLAIRE FRANÇAIS IN BRIEF 956 Coronavirus 1000 Global carbon cycle
Isolation of potent SARS-CoV-2 neutralizing Abrupt CO2 release to the atmosphere
930 From Science and other journals antibodies and protection from disease in a under glacial and early interglacial
small animal model T. F. Rogers et al. climate conditions
REVIEW C. Nehrbass-Ahles et al.
963 Global climate change
933 Photosynthesis Synchronous timing of abrupt climate 1005 Microbiology
Light harvesting in oxygenic photosynthesis: changes during the last glacial period Architecture and function of
Structural biology meets spectroscopy E. C. Corrick et al. human uromodulin filaments in
urinary tract infections
R. Croce and H. van Amerongen REPORTS G. L. Weiss et al.

REVIEW SUMMARY; FOR FULL TEXT: 970 Organic chemistry PERSPECTIVE p. 917
DX.DOI.ORG/10.1126/SCIENCE.AAY2058 Asymmetric remote C–H borylation of
aliphatic amides and esters with a modular Coronavirus
RESEARCH ARTICLES iridium catalyst R. L. Reyes et al. 1010 Studies in humanized mice and

934 Biomedicine 974 Chemical physics convalescent humans yield a
Neutrophil extracellular traps target Attosecond spectroscopy of liquid water SARS-CoV-2 antibody cocktail
senescent vasculature for tissue remodeling I. Jordan et al. J. Hansen et al.
in retinopathy F. Binet et al.
979 Surface chemistry 1014 Antibody cocktail to SARS-CoV-2
RESEARCH ARTICLE SUMMARY; FOR FULL TEXT: Covalent surface modifications and spike protein prevents rapid
DX.DOI.ORG/10.1126/SCIENCE.AAY5356 superconductivity of two-dimensional metal mutational escape seen with
PERSPECTIVE p. 919 carbide MXenes V. Kamysbayev et al. individual antibodies A. Baum et al.

935 Drug development 984 Immunology D E PA R T M E N T S
An orally available non-nucleotide STING SOSTDC1-producing follicular helper T
agonist with antitumor activity B.-S. Pan et al. cells promote regulatory follicular T cell 884 Editorial
differentiation X. Wu et al. Black scientists matter
RESEARCH ARTICLE SUMMARY; FOR FULL TEXT:
DX.DOI.ORG/10.1126/SCIENCE.ABA6098 988 Neuroscience By Malegapuru William Makgoba
PERSPECTIVE p. 921; REPORT p. 993 Julich-Brain: A 3D probabilistic atlas of the
human brain’s cytoarchitecture K.Amunts et al. 885 Editorial
936 Cancer immunology A dangerous rush for vaccines
Cross-reactivity between tumor MHC class 993 Drug development
I–restricted antigens and an enterococcal Antitumor activity of a systemic STING- By H. Holden Thorp
bacteriophage A. Fluckiger et al. activating non-nucleotide cGAMP mimetic
E. N. Chin et al. 1026 Working Life
942 Cancer immunology Choose your adviser wisely
BTN3A1 governs antitumor responses by PERSPECTIVE p. 921; RESEARCH ARTICLE p. 935
coordinating ab and gd T cells K. K. Payne et al. By Akshata Naik

950 Liquid crystals Science Careers ....................................... 1019
Shaping colloidal bananas to reveal biaxial,
splay-bend nematic, and smectic phases
C. Fernández-Rico et al.

PERSPECTIVE p. 918

SCIENCE (ISSN 0036-8075) is published weekly on Friday, except last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue, NW, Washington, DC 20005. Periodicals mail
postage (publication No. 484460) paid at Washington, DC, and additional mailing offices. Copyright © 2020 by the American Association for the Advancement of Science. The title SCIENCE is a registered trademark of the AAAS. Domestic
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SCIENCE sciencemag.org 21 AUGUST 2020 • VOL 369 ISSUE 6506 883

Published by AAAS

EDITORIAL

Black scientists matter

T he recent murder of George Floyd by police in scientists fail to adapt to and cope with the discipline,
the United States, the Black Lives Matter pro- standards, and work ethic demands of the science
tests around the world, and racial inequali- establishment. White scientists may think that they
ties everywhere that have been exposed by know what racism is and that they can better explain
the coronavirus disease 2019 (COVID-19) pan- to Black scientists the experiences that those Black
demic—such as the disproportionately high vul- individuals have endured. This dismissive attitude ig-

nerability and mortality in African-American, nores the reality of discrimination and alienation ex-

Malegapuru William Afro-Caribbean, and Afro-Latin communities—are a perienced by Black scientists. These realities include
Makgoba
is the Health Ombud of wake-up call for humankind to recalibrate, restruc- differences in the way young people are encouraged
the Republic of South
Africa, Pretoria, South ture, and reimagine its beliefs and behaviors. It’s im- (or discouraged) to pursue scientific careers, the lack
Africa. [email protected]
ohsc.org.za portant to recognize that beneath overt racism are of role models, not having access to meaningful career

subtle forms of structural and institutionalized rac- guidance and mentorship, and not being plugged into

ism that have existed for a very long time, unabated, influential career networks. Consequently, even the

across communities—in homes, hospitals, churches, best and brightest can fail to be recognized and admit-

schools, governments, and so many other institu- ted into top scientific programs.

tions—throughout the Western world. Research and academic institutions,

Now, societies are being provoked to scholarly academies, and scientific pub-

ponder fundamental questions about “...Black lications in the Western world all show
racism. What about the scientific a paucity of Black scientists in leader-

world? Do Black scientists matter? scientists ship positions, on editorial boards, and
My perspective is based on my expe- as authors. And although the Western

riences as a Black and African scientist have felt like scientific establishment has several
in South Africa, the United Kingdom, recognition systems for meritorious

and the United States, as well as in aliens of the scientific discoveries, rarely are Black
African nations through the African scientists represented among the

AIDS Vaccine Program. I’ve had the scientific awardees. In fact, some young Black Af-
opportunity to interact with a range enterprise.” rican scientists have told me that their
of Black African colleagues, from research was credited to their superiors
young African scientists to African and even patented and sold without
scientific leaders in their fields or in their involvement. Sadly, Black scien-

their institutions. We often discussed tists who do not assimilate or conform,

our dreams, aspirations, and passions or who abandon their African or Carib-

as well as work environments in the Western world bean or Latin American identity altogether in exchange

where Black scientists (African or otherwise) are not for the so-called superior white Western identity, can

well-represented or valued—where Black scientists become intellectually and socially isolated. Identity

have felt like aliens of the scientific enterprise. changes and health crises can cause some Black scien-

One problem in the Western world is that the sci- tists to suffer alienation even within Black communities

entific enterprise is in denial about its inherent rac- in these Western nations.

ism. Black scientists encounter discrimination when Racism in science has a long history throughout the

they embark on a science career in Western countries. world and manifests largely through systems of evalua-

The overwhelming message from their experiences tion, recognition, funding, and promotion. The scientific

is that the culture of academic science where Black community can postpone confronting this pernicious

scientists are underrepresented is riddled with deeply reality, but it cannot stop the train of change—it has left

entrenched racism of various forms and subtleties. the station. For equality in the global scientific enter-

For example, although science is supposed to be ob- prise to be addressed, meaningful change should start

jective, many white scientists who are part of the en- in the Western world’s scientific system, where a new

terprise refuse to believe and acknowledge the racism environment must be created in which not only Black

and alienation that is articulated by Black scientists scientists but all scientists can thrive—one that values

regarding their work and career. I have experienced, human dignity, equity, and social justice.

and have heard of, some white scientific leaders who

feel that the problem is not the system, but how Black –Malegapuru William Makgoba PHOTO: VAL ADAMSON

10.1126/science.abe3234

884 21 AUGUST 2020 • VOL 369 ISSUE 6506 sciencemag.org SCIENCE

Published by AAAS

EDITORIAL

A dangerous rush for vaccines

T he chasm between science and politics con- a Vaccines and Related Biological Products Advisory
tinues to grow, with Russian President Putin Committee to consult on the approval of vaccines and
announcing this week that a fast-tracked vac- any associated emergency use authorizations. There
cine for coronavirus disease 2019 (COVID-19) is are calls for assurances that there will not be any such
ready for use, and President Trump indicating authorization for COVID-19; the only emergency use
days earlier that a vaccine could be ready in authorization ever granted for a vaccine was for one

the United States before the 3 November presi- against anthrax because of the purported threat of bio-

dential election. There’s been a dangerous rush to get logical warfare involving this agent. In any event, the H. Holden Thorp
Editor-in-Chief,
to the vaccine finish line first. In a race of “Sputnik” scientific community in the United States must insist Science journals.
[email protected];
proportions (as Putin puts it), quick approval by regu- that approvals of an emergency use authorization or for @hholdenthorp

latory agencies is needed to “win.” This is dangerous a COVID-19 vaccine itself should be made in consulta-

thinking, driven by political goals and instant gratifi- tion with the FDA’s Committee—and actions around the

cation: Shortcuts in testing for vaccine safety and ef- world should involve similar scientific oversight.

ficacy endanger millions of lives in the short term and Premature approval of a vaccine in the United States

will damage public confidence in vaccines and in sci- (or anywhere) could be a disastrous replay of the hy-

ence for a long time to come. droxychloroquine fiasco but with

The Russian vaccine remains much higher stakes. Approval of a

shrouded in mystery—there is no “...Shortcuts vaccine that is harmful or isn’t ef-
published information about it, and fective could be leveraged by polit-

what has been touted comes from in testing ical forces that already propagate
the mouths of politicians. In the vaccine fears.

United States, the pressure applied for vaccine safety So far, U.S. government scien-
to government scientists by the ad- and efficacy tists are holding strong. Francis
ministration on any aspect of the Collins, director of the National
pandemic is becoming increasingly endanger millions Institutes of Health, emphatically
palpable, as they have been criti- of lives…” called for phase 3 trials of vac-
cized or quieted in plain sight by the cines, and FDA director Stephen
administration and Trump. Anthony Hahn also has stated that he will
Fauci, the nation’s foremost leader follow the science. There’s a lot
on infectious diseases and a mem- riding on Hahn, and as long as

ber of the White House Coronavirus he holds firm with the science,

Task Force, has been the most will- the scientific community should

ing to state things clearly, but he has had to deal with support him. He made a mistake in granting an emer-

muzzling and outright abuse from Trump and White gency use authorization for hydroxychloroquine but

House adviser Peter Navarro (not to mention shameful withdrew it once he saw the data—randomized clinical

threats of violence against him and his family). trials showing that the drug was useless against CO-

The majority of epidemiologists worldwide who work VID-19. Now the other faces of the U.S. government’s

on infectious diseases are firmly committed to random- science apparatus—Robert Redfield (director of the

ized controlled trials (“phase 3”) for all interventions, Centers for Disease Control and Prevention), Deborah

but especially for vaccines to be given to healthy people. Birx (response coordinator of the White House Coro-

This method allows comparison to a control group that navirus Task Force), and Brett Giroir (assistant sec-

receives a placebo. The phase 3 studies now under way retary for Health)—need to push all their chips onto

on promising COVID-19 vaccine candidates involve ap- the table in favor of a phase 3 randomized controlled

proximately 30,000 patients. A randomized controlled trial on any COVID-19 vaccine. Despite their periodic

trial is particularly important for determining the ef- squirming and equivocation, these leaders all deserve

fectiveness of the vaccine, and the trial must continue and need the nation’s support as long as they continue

until individuals in the control group become infected. to respect the science on this issue.

It is impossible to predict how long that will take. Physi- Countless lives are at stake—no compromises on

PHOTO: CAMERON DAVIDSON cians who seek to advise healthy patients on taking the the vaccine.

vaccine will rightfully require these data.

The U.S. Food and Drug Administration (FDA) has –H. Holden Thorp

Published online 13 August 2020; 10.1126/science.abe3147

SCIENCE sciencemag.org 21 AUGUST 2020 • VOL 369 ISSUE 6506 885

Published by AAAS

NEWS “ ”We have tried to make this work, but it is not working.
Barbara Rimer, dean of public health at the University of
North Carolina, Chapel Hill, as it moved to online-only instruction, just 1 week
after in-person classes resumed, because campus COVID-19 cases surged.

I N B R I E F Edited by Jeffrey Brainard Africa halts wild poliovirus

Arecibo’s dish lost 250 of its 40,000 panels when a cable broke—less damage than this view suggests. I N F ECT I O US D I S E AS ES | After a long fight,
Africa has wiped out the wild poliovirus.
ASTRONOMY The last case occurred 4 years ago, and on
25 August, the independent Africa Regional
Arecibo telescope damage assessed Certification Commission, acting on behalf
of the World Health Organization, is
T he iconic Arecibo radio telescope in Puerto Rico was damaged expected to officially declare the continent PHOTO: ARECIBO OBSERVATORY
on 10 August when a snapped steel cable smashed into a receiver free of the wild virus. Africa came close
and tore a 30-meter gash in its 307-meter-wide dish. No one was before, going 2 years without a case until
injured during the early morning incident. The damage to the 2016, when the wild virus appeared seem-
dish is not critical, but the broken cable has destabilized a plat- ingly out of the blue in Borno state in
form holding receiver antennas high above the dish. Managers northeastern Nigeria, where the militant
have halted observations for at least 2 weeks while investigations are group Boko Haram reigns, and paralyzed
carried out, and no cost estimate or restart schedule will be available four children. Polioviruses derived from
before then, says Ramon Lugo of the University of Central Florida, the oral polio vaccine continue to circulate
which manages the observatory for the National Science Foundation. and cause paralysis across Africa; wiping
Engineers are examining what went wrong with the 23-year-old cable, them out has proved extremely difficult.
whether a temporary replacement can be rigged up, and what damage Pakistan and Afghanistan are now the last
was done to the antennas. Set in a depression in the hills, Arecibo was bastions of the wild virus.
the world’s largest single dish for 5 decades until a Chinese telescope
surpassed it in 2016 and is still widely used for astronomy, planetary U.K. replaces health agency
science, and atmospheric research.
COVID-19 | Facing criticism over its
886 21 AUGUST 2020 • VOL 369 ISSUE 6506 response to the COVID-19 pandemic,
the U.K. government announced on
18 August that it will replace England’s
disease-control agency with a United
Kingdom–wide one focused on infectious
diseases. The move merges Public Health
England (PHE) with England’s contact
tracing program, NHS Test and Trace, and
the U.K. Joint Biosecurity Centre, to create
the new agency, the National Institute for
Health Protection. Its interim leader will be
businesswoman and Conservative parlia-
mentarian Dido Harding, who had headed
NHS Test and Trace. PHE’s work on obesity
and other noncommunicable health condi-
tions will be shifted to local authorities, but
the government has not yet clarified how.
Critics said the change was poorly conceived
and questioned whether the new agency
is set up to succeed, citing a need for close
coordination with the National Health
Service’s hospital-based scientists.

Redo for radiocarbon dates

G EO C H RO N O LO GY | The first update of
carbon dating in nearly a decade, published
last week, allows scientists to probe 5000
years further into the past and revises the
timing of big events in human history.

sciencemag.org SCIENCE

Published by AAAS

Living things incorporate radioactive TRUMP TRACKER
carbon-14 from the environment, and the
decay of this carbon after death provides a Trump environmental plans spark new controversies
clock for dating specimens from the recent
past. The update extends the technique’s The White House this month announced it will move ahead with controversial changes
use to about 55,000 years ago. The recali- to two major environmental policies, but suffered a legal setback on a third.
brated timeline shows that Homo sapiens
and Neanderthals overlapped in Europe for Arctic drilling OK’d
centuries longer than once thought. It also
shows the volcanic eruption that devastated The U.S. Interior Department on 17 August announced it will move ahead with plans to
the island of Thera in Greece may have sell leases to drill for oil in Alaska’s Arctic National Wildlife Refuge. The decision followed
occurred as recently as 1544 B.C.E., in line an environmental review that concluded drilling on much of the refuge’s 6300-square-
with archaeological evidence. kilometer coastal plain wouldn’t endanger caribou or polar bears, or exacerbate climate
change. Scientists have warned the effects of oil drilling could harm the animals, and
Mathematician’s sentence delayed environmental groups swiftly vowed legal challenges.

C R I M I N A L J UST I C E | Eva Lee, an applied Methane rule relaxed
mathematician at the Georgia Institute
of Technology who admitted to making Several state governments and environmental groups are preparing court challenges
false statements related to a U.S. National to a new Trump administration rule, finalized last week, that gives oil and gas companies
Science Foundation (NSF) grant, won’t greater leeway to allow leaks of methane, a potent climate-warming gas, from their
begin to serve her sentence until next spring facilities. Critics say the rule has fatal flaws, including how it calculates costs and benefits,
so she can continue to build models to and many larger firms opposed the change, saying it would create uncertainty and
help control the COVID-19 pandemic. On discourage efficiency improvements. If Democrats win control of the Senate and the White
12 August, U.S. District Court Judge Steve House in January 2021, they could overturn this and other recent regulatory decisions.
Jones rejected the government’s request
for 8 months of immediate home confine- Bird protections upheld
ment, saying the country “needs her” talents
now. Instead, he ordered Lee confined A federal judge on 11 August overturned an administration reinterpretation of the 1918 Migra-
for 2 months starting in April 2021 and said tory Bird Treaty Act that had helped companies avoid fines for inadvertently killing birds. “It is
that schedule could be further modified. not only a sin to kill a mockingbird,” U.S. District Court Judge Valerie Caproni wrote in her deci-
Lee pleaded guilty in December 2019 to mis- sion, quoting To Kill a Mockingbird, “it is also a crime” under federal law. Conservationists had
representing information to NSF in a report objected to the reinterpretation, because it meant businesses could not be fined for failing to
related to the $40,000 grant and then lying protect birds from foreseeable fatal hazards, such as oil spills and uncovered oil waste pits.
to federal agents investigating her actions.
PHOTO: GERALD HERBERT/AP PHOTO She told Jones she didn’t understand the A worker aids a pelican
reporting requirements and that her univer- covered in oil from the 2010
sity withheld the necessary administrative Deepwater Horizon accident. 21 AUGUST 2020 • VOL 369 ISSUE 6506 887
support for her grant, which it has disputed.
Published by AAAS
U.S. academies to study racism

RAC I A L J UST I C E | The National Academies
of Sciences, Engineering, and Medicine
(NASEM) is gearing up for an in-depth study
of systemic racism in U.S. academic research.
Representative Eddie Bernice Johnson
(D–TX), who leads the science committee in
the U.S. House of Representatives, has asked
it to analyze “the extent to which the U.S.
scientific enterprise perpetuates systemic
inequities to the detriment of society as a
whole, as well as how those inequities are
manifested.” National Academy of Sciences
President Marcia McNutt says such a study
could set the table for needed changes in
the same way that a 2018 NASEM report
on sexual harassment catalyzed discussion
and action. Structural racism in academia
is “hindering our ability to deal with some
of our biggest challenges, including the
current COVID-19 pandemic,” says Freeman
Hrabowski, president of the University of
Maryland, Baltimore County.

SCIENCE sciencemag.org

NEWS | IN DEPTH

IN DEPTH E ngineers at NuScale Power believe
they can revive the moribund U.S.
NUCLEAR POWER nuclear industry by thinking small.
Spun out of Oregon State University
Critics question whether novel in 2007, the company is striving to win
reactor is ‘walk-away safe’ approval from the U.S. Nuclear Regu-
latory Commission (NRC) for the design of
Design approval nears for NuScale Power’s small modular a new factory-built, modular fission reac-
reactors, but deployment plans slip 3 years tor meant to be smaller, safer, and cheaper
than the gigawatt behemoths operating
By Adrian Cho today (Science, 22 February 2019, p. 806).
But even as that 4-year process culminates,
2.5 m reviewers have unearthed design problems,
including one that critics say undermines
Relief Reactor pool NuScale’s claim that in an emergency, its
valve small modular reactor (SMR) would shut
Cooling water Steam itself down without operator intervention.
Containment
vessel Condensing The issues are typical of the snags new reac-
Reactor vessel water tor designs run into on the road to approval,
says Michael Corradini, a nuclear engineer
Convection Recirculation at the University of Wisconsin, Madison. “I
valve don’t think these things are show-stoppers.”
Core However, M. V. Ramana, a physicist who
Boron-defcient studies public policy at the University of
water British Columbia, Vancouver, and has been
critical of NuScale, says the problems show
PASSIVE SAFETY? Normally, convection circulates water—laced with boron to tune the nuclear the company has oversold the claim that its GRAPHIC: C. BICKEL/SCIENCE
reaction—through the core of NuScale’s reactor (left). If the reactor overheats, it shuts down and valves SMRs are “walk-away safe.” “They have given
release steam into the containment vessel, where it conducts heat to a surrounding pool and condenses you the standard by which to evaluate them
(center). The water flows back into the core, keeping it safely submerged (right). But the condensed and they’re failing,” Ramana says.
water can be low in boron, and reviewers worried it could cause the reactor to spring back to life.
Even critics expect that next month NRC
888 28 AUGUST 2020 • VOL 369 ISSUE 6506 will issue a safety evaluation report approv-
ing the NuScale design, which will be a
major milestone, says José Reyes, NuScale’s
co-founder and chief technology officer.
“This is the document that says, ‘This de-
sign is safe,’” says Reyes, who hatched the
idea for the reactor in 1999. NuScale will
resolve the lingering technical issues before
anything gets built, he says.

However, NuScale’s likely first customer,
Utah Associated Municipal Power Systems
(UAMPS), has delayed plans to build a Nu-
Scale plant, which would include a dozen
of the reactors, at the Department of En-
ergy’s (DOE’s) Idaho National Laboratory.
The $6.1 billion plant would now be com-
pleted by 2030, 3 years later than previ-
ously planned, says UAMPS spokesperson
LaVarr Webb. “UAMPS is still very commit-
ted to the project,” Webb says. “Our members
really want to decarbonize their electric
supply and replace coal.” The delay will give
UAMPS more time to develop its applica-
tion for an NRC license to build and operate
the plant, Webb says. The deal depends on
DOE contributing $1.4 billion to the cost of
the plant, he adds.

A nuclear reactor is essentially a boiler. In
its core, uranium atoms split, releasing heat
and neutrons, which split other uranium
atoms in a chain reaction. Highly pressur-
ized cooling water circulates through the
core and carries heat to a steam generator,

sciencemag.org SCIENCE

Published by AAAS

where it boils water in a separate circuit to cording to the meeting transcript. “I don’t QUANTUM THEORY

drive turbines and generate electricity. The see a calculation that proves it wrong.” Paradox puts
objectivity on
cooling water also slows the speeding neu- Ultimately, whoever applies for a license shaky footing

trons, increasing the probability that they to build and operate a NuScale plant— Quantum test of venerable
thought experiment
will split the uranium atoms. presumably UAMPS—must devise an op- suggests facts are relative

Expense and safety worries have stalled erating procedure that ensures such a sce- By George Musser

nuclear power despite increasing demand nario never occurs. But NuScale should N early 60 years ago, Nobel Prize–
winning physicist Eugene Wigner
for carbon-free electricity. NuScale’s remedy provide guidance, Vesna Dimitrijevic´, a nu- captured one of the many oddities of
quantum mechanics in a thought ex-
is a radically new design. A conventional clear engineer and ACRS member, argued periment. He imagined a friend of his,
sealed in a lab, measuring a particle
reactor relies on huge pumps and pipes to at the meeting. The issue demonstrates how such as an atom while Wigner stood out-
side. Quantum mechanics famously allows
drive the cooling water through its core and slippery a seemingly black-and-white tech- particles to occupy many locations at once—
a so-called superposition—but the friend’s
ferry it to the steam generator. A NuScale nical issue can be. “The applicant thinks observation “collapses” the particle to just
one spot. Yet for Wigner, the superposition
reactor—which would be less than 25 me- there isn’t a problem here,” Corradini says. remains: The collapse occurs only when
he makes a measurement sometime later.
ters high, hold about one-eighth as much “The ACRS isn’t so sure and want the staff Worse, Wigner also sees the friend in a super-
position. Their experiences directly conflict.
fuel as a large power reactor, and gener- and the applicant to think through the steps
Now, researchers in Australia and Taiwan
ate less than one-tenth as much electric to make sure this isn’t a problem.” The NRC offer perhaps the sharpest demonstration
that Wigner’s paradox is real. In a study
power—would rely on natural convection staff, which writes the safety evaluation re- published this week in Nature Physics, they
transform the thought experiment into a
to circulate the water (see diagram, p. 888). port, thinks it can be dealt with in the oper- mathematical theorem that confirms the ir-
reconcilable contradiction at the heart of the
It is also designed to shut itself down in ating license, he adds. scenario. The team also tests the theorem
with an experiment, using photons as prox-
a pinch. Each reactor fits within a steel con- The issue pokes a hole in NuScale’s credi- ies for the humans. Whereas Wigner believed
resolving the paradox requires quantum me-
tainment vessel, which in turn sits in a pool bility, says Edwin Lyman, a physicist with the chanics to break down for large systems such
as human observers, some of the new study’s
of water holding up to a dozen modules. Or- Union of Concerned Scientists. “This is a case authors believe something just as fundamen-
tal is on thin ice: objectivity. The puzzle could
dinarily, the space between the reactor and of the public relations driving the science mean there is no such thing as an absolute
fact, one that is as true for me as it is for you.
containment vessel remains evacuated, like instead of the other way around,” he says.
“It’s a bit disconcerting,” says co-author
the vacuum jacket in a thermos bottle. Should Sarah Fields, program director of the en- Nora Tischler of Griffith University. “A mea-
surement outcome is what science is based
the core overheat or the reac- vironmental group Uranium on. If somehow that’s not absolute, it’s hard
to imagine.”
tor leak, relief valves would “If there reallywas Watch, says the safety ques-
vent steam into the evacu- a fatal flaw, tions argue against NuScale’s Some physicists dismiss thought experi-
ated space, where it would request to operate without ments like Wigner’s as interpretive navel
conduct heat to the pool and ACRS would not an emergency planning zone. gazing. But the study shows that the con-
condense into the bottom of “That’s a crazy thing to do for tradictions emerge in actual experiments,
says Dustin Lazarovici, a physicist and phi-
the containment vessel. When have published a reactor design that’s totally losopher at the University of Lausanne who
enough water had accumu- new and with which you have was not part of the team. “The paper goes to
great lengths to speak the language of those
a positive report.”lated, it would flow back into no operating experience.”

the reactor to keep the core Reyes says the company’s

safely submerged. NuScale José Reyes, NuScale Power analysis justifies that request.

is so confident in the design NuScale’s studies show that

that it has asked NRC to allow its plants to under any credible scenario, the radiation at

run without the standard 32-kilometer-wide the plant periphery will not exceed NRC’s lim-

emergency planning zone. its for the edge of the traditional emergency

In March, however, a panel of independent planning zone, he says. Permission to forgo

experts found a potential flaw in that scheme. the buffer zone could help NuScale market its

To help control the chain reaction, the reac- plants where space is tight, he says.

tor’s cooling water contains boron, which, un- ACRS found a few other problems, in-

like water, absorbs neutrons. But the steam cluding one with NuScale’s novel steam

leaves the boron behind, so the element will generator, which sits within the reactor ves-

be missing from the water condensing in sel and could be prone to damaging vibra-

the reactor and containment vessel, NRC’s tions. Still, on 29 July, ACRS recommended

Advisory Committee on Reactor Safeguards that NRC issue the safety evaluation report

(ACRS) noted. When the boron-poor water and certify NuScale’s design. “If there really

re-enters the core, it could conceivably re- was a fatal flaw, ACRS would not have pub-

vive the chain reaction and possibly melt lished a positive report,” Reyes says.

the core, ACRS concluded in a report on its NRC plans to publish its safety evaluation

5–6 March meeting. report next month, and by year’s end it is ex-

NuScale modified its design to ensure that pected to issue draft “rules” that would es-

more boron would spread to the returning sentially approve the design. But that won’t

water. The small changes eliminated any end the regulatory odyssey. The current de-

potential problem, Reyes says. However, sign specifies a reactor output of 50 mega-

at a 21 July meeting, ACRS concluded that watts of electricity, whereas the UAMPS plan

operators could still inadvertently drive calls for 60 megawatts. The change requires

deborated water into the core when trying a separate NRC approval, Reyes says, during

to recover from an accident. “I’m not say- which NuScale will resolve the outstand-

ing that this [scenario] is going to happen,” ing technical issues. That additional 2-year

ACRS member Jose March-Leuba said, ac- review should start in 2022. j

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NEWS | IN DEPTH

who have tried to merely discuss founda- top experiment, in which it made pairs of en- COVID-19
tional issues away and may thus compel at tangled photons, also backs up the paradox.
least some to face up to them,” he says. Optical elements steered each photon onto a Coronavirus
path that depended on its polarization: the creates a
Wigner’s thought experiment has seen equivalent of the friends’ observations. The flu season
renewed attention in recent years. In 2015, photon then entered a second set of elements guessing game
Cˇaslav Brukner of the University of Vienna and detectors that played the role of the
tested the most intuitive way around the Wigners. The team found, again, a mismatch SARS-CoV-2’s interactions
paradox: that the friend inside the lab has in between the observations of the friends and with other pathogens remain
fact seen the particle in one place or another, the Wigners. What is more, when they var- unknown as winter looms
and Wigner just doesn’t know where it is yet. ied exactly how entangled the photons were,
In the jargon of quantum theory, the friend’s they found that the mismatch occurs for dif- By Kelly Servick
result is a hidden variable. ferent conditions than in Brukner’s scenario.
“That shows that we really have something I n March, as the Southern Hemisphere
Brukner sought to rule out that conclusion new here,” Tischler says. braced for winter flu season while fight-
in a thought experiment of his own, using a ing COVID-19, epidemiologist Cheryl
trick—based on quantum entanglement—to It also indicates that one of the four as- Cohen and colleagues at South Africa’s
bring the hidden variable out into the open. sumptions has to give. Few physicists be- National Institute for Communicable
He imagined setting up two friend-Wigner lieve superdeterminism could be to blame. Diseases (NICD) set up a plan to learn
pairs and giving each a particle, entangled Locality is already under fire in quantum from the double whammy. They hoped to
with its partner in such a way that their theory, but a failure in this case would imply study interactions between seasonal respira-
attributes, upon measurement, are corre- an especially potent form of nonlocality. So tory viruses and SARS-CoV-2, which causes
lated. Each friend measures the particle, some are questioning the tenet that observ- COVID-19. Does infection with one change a
each Wigner measures the friend measuring ers can pool their measurements empiri- person’s risk of catching the other? How do
the particle, and the two Wigners compare cally. “It could be that there are facts for one people fare when they have both?
notes. The process repeats. If the friends saw observer, and facts for another; they need
definite results—as you might suspect—the not mesh,” says study co-author and Griffith But the flu season—and the answers—
Wigners’ own findings would show only physicist Howard Wiseman. It is a radical never came. NICD’s Centre for Respiratory
weak correlations. But instead they find a relativism, still jarring to many. “From a Disease and Meningitis, which Cohen leads,
pattern of strong correlations. “You run into classical perspective, what everyone sees is has logged only a single flu case since the
contradictions,” Brukner says. considered objective, independent of what end of March. In previous years, the coun-
anyone else sees,” says Olimpia Lombardi, a try’s surveillance platforms, which capture
In 2018, Richard Healey, a philosopher of philosopher of physics at the University of a sampling of flu cases from doctors offices,
physics at the University of Arizona, pointed Buenos Aires. hospitals, and clinics, have documented, on
out a loophole in Brukner’s argument, which average, about 700 cases during that period,
Tischler and her colleagues have now closed. And then there is Wigner’s verdict: that Cohen says. “We’ve been doing flu surveil-
In their new scenario they make four as- quantum mechanics itself breaks down. Of lance since 1984, and it’s unprecedented.”
sumptions. One is that the results the friends all the assumptions, it is the most testable,
obtain are real: They can be combined with by efforts to probe quantum mechanics on Some cases probably got overlooked as
other measurements to form a shared body ever larger scales. But the one position that clinics temporarily closed and people with
of knowledge. The researchers also assume doesn’t survive the analysis is having no po- mild symptoms avoided medical care, Cohen
quantum mechanics is universal, as valid for sition, says Eric Cavalcanti, a co-author at says. “But I don’t believe it possible that we’ve
observers as for particles; that the choices Griffith. “Most physicists, they think: ‘That’s entirely missed the flu season with all of our
the observers make are free of peculiar bi- just philosophical mumbo-jumbo.’” Now, he [surveillance] programs.” Apparently, travel
ases induced by a godlike superdeterminism; says, “They will have a hard time.” j restrictions, school closures, social distanc-
and that physics is local, so that one observ- ing, and mask wearing have all but stopped
er’s choices do not affect another’s results. George Musser is a journalist based in New Jersey flu from spreading in South Africa. Similar
and author of Spooky Action at a Distance. stories have emerged from Australia, New
Yet the analysis shows the contradictions Zealand, and parts of South America.
of Wigner’s paradox persist. The team’s table-
The Northern Hemisphere hopes to be so
lucky. Few cases in the south might mean ILLUSTRATION: DAVIDE BONAZZI/SALZMANART
little infection spreading north, says Pasi
Penttinen, head of the influenza and re-
spiratory illness program at the European
Centre for Disease Prevention and Control

When observers observe observers, a quantum paradox persists, suggesting measurements are relative. Science’s COVID-19 reporting is supported by the
Pulitzer Center and the Heising-Simons Foundation.
890 28 AUGUST 2020 • VOL 369 ISSUE 6506
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Published by AAAS

Australia stepped up flu vaccination efforts
to reduce strain on hospitals during its winter.

(ECDC). But if lockdowns and social dis- pathogen, most often rhinoviruses and tests will be important for both research
and treatment decisions, says Benjamin
tancing measures aren’t in place in October, enteroviruses that cause cold symptoms, as Singer, a pulmonary and critical care phy-
sician at Northwestern University. The U.S.
November, and December, flu will spread well as RSV. Only one of the patients had Food and Drug Administration has issued
emergency use authorizations for three flu–
much more readily than it has in the south, influenza, although there likely wasn’t much COVID-19 combination tests, developed by
two companies and the U.S. Centers for Dis-
warns virologist John McCauley, director flu circulating so late in the season, says ease Control and Prevention (CDC).

of the Worldwide Influenza Centre at the Stanford pathologist Benjamin Pinsky, a co- Meanwhile, health authorities preparing
for the Northern Hemisphere winter are hop-
Francis Crick Institute. author. The study didn’t find a difference in ing flu vaccines can help keep hospital admis-
sions down as health systems grapple with
The prospect of a flu season during the outcomes between COVID-19 patients with the pandemic. Flu vaccine manufacturers
including GlaxoSmithKline and AstraZeneca
coronavirus pandemic is chilling to health and without other infections. But it was too have announced production increases for
the 2020–21 season. CDC expects to have a
experts. Hospitals and clinics already under small to draw broad conclusions. record-setting 194 million to 198 million
doses—a 20 million–dose increase from last
strain dread a pileup of new respiratory in- To make things more complicated, hav- year. Last month, the United Kingdom’s Na-
tional Health Service announced it would ex-
fections, including influenza and respira- ing one virus can change a person’s chance pand the age groups eligible for a free flu shot
among both children and adults.
tory syncytial virus (RSV), of getting infected with an-
But what if the flu season is minor? Pour-
another seasonal pathogen other. Epidemiologist Sema ing resources into an immunization cam-
paign necessarily subtracts from COVID-19
that can cause serious ill- The flu season Nickbakhsh and her team responses, says Penttinen, whose team pro-
ness in young children and that wasn’t at the University of Glasgow vides guidance to European member states
the elderly. In the United have studied interactions on flu vaccination. Still, rates of vaccination
States, where some areas COVID-19 control measures between different pairs of have long been “suboptimal” in Europe, he
already face long waits for dramatically reduced transmission respiratory viruses, adjust- adds. (Rates among older adults—the tar-
COVID-19 test results, the of flu in many Southern Hemisphere ing for confounding fac- get population for the flu vaccine in many
delays could grow as flu countries (documented cases, tors that would cause two countries—range from 2% to 72.8%, de-
symptoms boost demand. April through mid-August). viruses to show up concur- pending on the country, according to the
most recent ECDC data, released in 2018.) “I
“The need to try to rule out COUNTRY 2018 2019 2020 rently or at separate times, think the tendency is to say, ‘We should err
on the side of caution—putting efforts into
SARS-CoV-2 will be intense,” Argentina 1517 4623 53 such as tendencies to wax at least maintaining if not increasing the
influenza vaccine coverage,’” Penttinen says.
says Marc Lipsitch of the Chile 2439 5007 12 and wane with the seasons.
Harvard T.H. Chan School Australia 925 9933 33 Coinfections with flu and The dearth of flu in the Southern Hemi-
of Public Health. sphere could complicate efforts to develop its
other respiratory viruses next influenza vaccine. Less circulating influ-
enza virus means fewer clues about which ge-
Because flu has largely South Africa 711 1094 6 are relatively rare, Nick- netic variants are most prevalent and likely
to contribute to a new season. The current
CREDITS: (PHOTO) SPEED MEDIA/ICON SPORTSWIRE/NEWSCOM; (DATA) FLUNET; spared the Southern Hemi- bakhsh says, and the inter- record-low season creates a genetic bottle-
GLOBAL INFLUENZA SURVEILLANCE AND RESPONSE SYSTEM neck, McCauley says, and the flu variants that
sphere, researchers have little evidence actions her group has documented suggest survive “will be presumably the fittest ones.”
It’s not clear what variants will dominate
about how COVID-19 might influence the some protective effects. For example, being when flu, inevitably, rears its head again.

course of a flu outbreak. One big concern is infected with influenza A seemed to reduce Barr and McCauley, whose institutions
are two of the six that collect and analyze
coinfection—people getting COVID-19 and the chance of also having a rhinovirus, the flu samples to decide the composition of the
annual vaccine, say they’ve received fewer
flu at once, says Ian Barr, deputy director researchers reported in 2019. (The mecha- patient samples than in previous years. In-
sufficient data could lead to a less effective
of the World Health Organization Collabo- nism behind this effect isn’t yet clear.) vaccine for the Southern Hemisphere in 2021.
The contents of that cocktail must be decided
rating Centre for Reference and Research Nickbakhsh is more concerned about by the end of September. “It’s a little un-
settling,” Barr says, “but we’ll do the best we
on Influenza in Melbourne, Australia. “Two RSV, which her team found to have positive can with the viruses that we have.” j

or three viruses infecting you are normally interactions with CoV-OC43, a coronavirus

worse than one,” he says. species of the same genus as SARS-CoV-2.

But the consequences of coinfections It’s possible, she says, that having COVID-19

with SARS-CoV-2 haven’t been thoroughly could increase a person’s susceptibility to

studied. In April, a team at Stanford Uni- RSV, or vice versa. Pinning down inter-

versity found that among 116 people in actions between COVID-19 and other infec-

Northern California who tested positive for tions requires a large number of patient

the coronavirus in March, 24 also tested samples tested for SARS-CoV-2 and other

positive for at least one other respiratory respiratory viruses. Rapid, dual diagnostic

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A malaria worker distributes bed nets
on 28 April in Cotonou, Benin.

GLOBAL HEALTH and Red Crescent Societies. “Crowds can be
very difficult to control,” she says, making
Pandemic’s fallout on malaria physical distancing all but impossible.
control appears limited so far
“We all knew if Benin did not go ahead,
Countries avert disaster by resuming bed net campaigns there would be a massive domino effect” on
other countries, Erskine says. So GMP and its
By Leslie Roberts they were very, very sick, Alonso says. But a partners—including the Global Fund to Fight PHOTO: YANICK FOLLY/AFP/GETTY IMAGES
broad lockdown would be “a bullet straight AIDS, Tuberculosis and Malaria; the U.S.
B ack in March when COVID-19 hit, to the heart of the malaria program,” he President’s Malaria Initiative; and the Alli-
Pedro Alonso became alarmed about a says. “For the past 40 years we have been ance for Malaria Prevention (AMP)—started
different infectious disease. “I thought saying that malaria can kill within hours. If to lobby leaders in Benin and elsewhere, she
I would be witnessing the biggest ma- a child has fever … go straight to the clinic.” says, armed with models. AMP advised coun-
laria disaster in 20 years,” says Alonso, tries on how to reduce COVID-19 risks—for
a malaria scientist at the World Health By 25 March, WHO had issued guidance instance, by distributing nets door to door
Organization (WHO). African countries went telling countries they should proceed with instead of from a central point.
on lockdown to curtail COVID-19; worried malaria prevention and treatment—and
about mass gatherings, they suspended cam- could do so safely. “WHO was very effective Benin agreed, distributing 8 million nets
paigns to distribute mosquito-fighting bed in getting the message out,” says Thomas in April and setting an example for other
nets. Fears abounded that with clinics over- Churcher of Imperial College London (ICL), governments, says Sussann Nasr of the
whelmed by COVID-19, patients would be who published an alarming model about Global Fund: “In the end, every country
unable to get treatment for malaria, which the effects of scaling back malaria interven- said yes.” Still, “We don’t want to get a false
kills an estimated 405,000 per year, mostly tions in Nature Medicine on 7 August. sense of security,” Nasr says. “We have to be
African children. In the worst case scenario, sure that the 2021 countries do their cam-
models projected, malaria deaths could more The distribution of insecticide-treated paigns, too,” says Hannah Slater, a modeler
than double this year. bed nets was GMP’s first concern. Malaria at PATH, a global health nonprofit in Seat-
deaths plunged from an estimated 839,000 tle. The same holds for indoor spraying with
“It does not seem to be happening,” Alonso in 2000 to 405,000 in 2018 largely thanks insecticides and seasonal chemoprevention,
says. Lobbied hard by WHO’s Global Malaria to the massive net rollout across Africa. But in which children are given antimalaria
Programme (GMP), which he heads, and its bed nets need to be replaced every 3 years, drugs during the disease’s high season.
partners, countries resumed bed net cam- as the insecticide wears off and nets tear.
paigns. Rapid diagnostic tests and effective Twenty-six African countries had scheduled Even if preventive interventions continue,
malaria drugs remain available. The situa- mass distribution campaigns this year—but malaria deaths could soar if sick children
tion could still go south as the COVID-19 epi- in March, many were wary of proceeding. don’t receive effective treatment—for in-
demic accelerates, but for now, Alonso says, stance, because frightened mothers keep
“We probably stopped the first big blow.” Benin was the most urgent priority. It had them home. The ICL model projects that if ac-
already completed the first phase of its cam- cess to treatment drops by 50% for 6 months,
In March, WHO recommended that coun- paign, distributing vouchers door to door that 129,000 additional malaria deaths would oc-
tries halt mass vaccination campaigns for families could use to pick up their bed nets cur between May 2020 and May 2021.
measles and other diseases, fearing they from a central point 1 month later. But the
might spread COVID-19 (Science, 10 April, government had canceled the second phase. Getting a fix on how many children are
p. 116). Like other health agencies, the Af- The concern was that people, worried about being treated is tough, Alonso says. But
rica Centres for Disease Control and Pre- supplies, would rush to distribution centers there are ominous hints. Antenatal visits
vention advised people to stay home unless to pick up their nets, says Marcy Erskine of are down in some places, and that’s where
the International Federation of the Red Cross pregnant women, who are very vulnerable
to severe malaria, receive chemoprevention
and bed nets along with regular checkups.
And routine immunizations for diseases such
as measles have fallen off. “What I really
worry about is a child who won’t be treated
and deaths will go uncounted,” says Regina
Rabinovich of the Harvard T.H. Chan School
of Public Health—a problem even before the
pandemic. Undercounting probably explains
the “paradoxical” finding that reported ma-
laria cases are down this year, Alonso says.

Churcher fears some countries may see
COVID-19 peak during the high malaria
season, leaving fragile health systems deal-
ing with simultaneous epidemics. Even
countries that go into strict lockdown must
continue malaria services, he says: “It’s not
a trade-off. You have to do both.” j

Leslie Roberts is a journalist in Washington, D.C.

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COVID-19

Pandemic lockdown stirs up ecological research

Biologists launch studies of how wildlife around the world responded to the “anthropause”

By Erik Stokstad from eBird, a citizen science project run by In the Society Islands of French Polynesia,

the Cornell Lab of Ornithology, the research- researchers are probing how coral reefs are

A fter a COVID-19 lockdown earlier this ers are examining bird communities in faring now that hotels have gone dark. On
year prevented biologist Eduardo 95 U.S. and Canadian counties. They wonder, one hand, local residents appear to be re-
Silva-Rodríguez from visiting his field for example, whether species that don’t like turning to subsistence fishing to make ends
sites in rural Chile, he moved his re- noise, such as yellow-rumped warblers, be- meet. That could mean trouble for reefs by
search closer to home. He and other came more abundant around airports. And removing herbivorous fish, which control

Chilean researchers set up automated they are checking whether low-flying species algae that can blanket and kill coral. But

cameras to monitor wildlife in urban settings, became more common near roads, suggest- empty hotels could help reefs if it means less

including on his own campus at the Austral ing fewer were dying in collisions with cars. nutrient pollution from wastewater, which

University of Chile, Isla Teja. The cameras At popular destinations such as national stimulates algae growth. It’s “a once-in-a-

soon captured surprises: rare animals, in- parks, the tourism standstill has created re- lifetime opportunity to better understand the

cluding endangered southern river otters and search opportunities. In Ecuador’s Galápa- links between humans and coral reefs,” says

a wild cat called the güiña, roaming through gos Marine Reserve, the decline in visitors ecologist Sally Holbrook of the University of

pandemic-quieted cities where they’d never has been “unlike anything that would ever California (UC), Santa Barbara, who works at

been documented before. the Moorea Coral Reef Long Term

The snapshots are just one ex- Ecological Research site.

ample of how wildlife is responding In Italy, ecologist Francesca

to what scientists are calling the Cagnacci also got a rare chance

“anthropause”—the dramatic slow- to see how the absence of moun-

down in human activity caused tain bikers, hunters, and traffic

by the pandemic. Some research- affected wildlife in the forests

ers are tracking how animals and surrounding Trentino, where she

ecosystems are reacting to steep is tracking deer and other ani-

declines in tourism. Others are mals with radio collars. In March,

pooling data on animal movements Cagnacci saw something very un-

to probe large-scale responses to usual in the hushed woods: deer

emptier roads and airports. The and birds wandering during day-

unique natural experiment is al- light. “I won’t forget this for my en-

lowing scientists to compare how tire life,” says Cagnacci, who works

animals behaved before, during, at the Edmund Mach Foundation’s

and after the pandemic—and per- Research and Innovation Centre.

haps glean insights into how to Normally timid jackals wandered in Tel Aviv, Israel, during an April lockdown. The anthropause has quieted the

better protect wildlife once human oceans, too. In California’s Mon-

activity resumes full speed. “The lockdown happen, short of a world war,” says ecologist terey Bay, marine ecologist Ari Friedlaender

has given us the capacity to find where we Jon Witman of Brown University. He and his of UC Santa Cruz took to the water with col-

can optimize conservation,” says Amanda colleagues are studying, among other things, leagues in March and early April, when lock-

Bates, an ecologist at Memorial University. whether shy marine fish become bolder now downs reduced boat traffic. Equipped with a

In one collaboration led by the Interna- that recreational divers aren’t around, a be- crossbow and special arrows, they collected

tional Bio-Logging Society, researchers are havioral change that could alter how the eco- blubber samples from 45 humpback whales.

contributing tracking data collected by satel- system functions. Witman is heading to the When they can return to the lab, they’ll mea-

lite tags, radio collars, and other tools from Galápagos this week: “We’re chasing a fleet- sure levels of cortisol, a stress hormone. They

some 180 species of birds, mammals, reptiles, ing moment,” he says. plan to collect new samples over the next

and fish from all continents and oceans. In the Bahamas, researchers are examining year, when boat traffic is expected to pick up,

“There is a gold mine of data,” says ecologist how the tourism crash is affecting critically in an effort to discover just how much addi-

Christian Rutz of the University of St. An- endangered rock iguanas. Visitors routinely tional stress—if any—the vessel noise creates

drews. Among other things, researchers will feed the iguanas bread, meat, fruit, and vege- for whales.

be investigating whether animals changed tables; now the change in diet “could have re- Scientists acknowledge that the oppor-

PHOTO: AP PHOTO/ODED BALILTY their movements during the anthropause— ally profound effects,” says Susannah French, tunity to study the anthropause is coming

crossing roads more frequently, for example, a physiological ecologist at Utah State Uni- at the expense of much human death and

or venturing out at unusual times of day. versity. Researchers hope to sail to the Baha- suffering. “It’s our sincere hope that no

A separate team of 16 researchers, orga- mas soon to weigh the animals, take blood one ever gets a chance to study this again,”

nized by conservation biologist Nicola Koper samples, and check their gut microbiota. The Witman says. “But incredible things are

at the University of Manitoba, is exploring data could help local officials better manage happening in natural ecosystems.” j

similar questions for 85 bird species in Can- tourists once they return, says Chuck Knapp,

ada and the United States. Working with data a biologist at the Shedd Aquarium. With reporting by Rasha Aridi.

SCIENCE sciencemag.org 28 AUGUST 2020 • VOL 369 ISSUE 6506 893

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FEATURES

MUD
By David Malakof

894

Published by AAAS

NEWS

Waterlogged sediment can be PHOTO: DOUGLAS MAGNO/AFP VIA GETTY IMAGES lop. Mire. Ooze. Cohesive sediment. Call
vital for life, but also poses a it what you want, mud—a mixture of fine
threat. Torrents of mud, such as sediment and water—is one of the most
this one unleashed by the failure common and consequential substances
of a mine tailings dam in Brazil, on Earth. Not quite a solid, not quite
periodically kill people, bury a liquid, mud coats the bottoms of our
communities, and pollute rivers. lakes, rivers, and seas. It helps form mas-

G sive floodplains, river deltas, and tidal
flats that store vast quantities of carbon
and nutrients, and support vibrant communities of
people, flora, and fauna. But mud is also a killer:
Mudslides bury thousands of people each year.

Earth has been a muddy planet for 4 billion
years, ever since water became abundant. But how
it forms and moves have changed dramatically.
About 3 billion years ago, the arrival of land plants
boosted the breakdown of rock into fine particles,
slowed runoff, and stabilized sediments, enabling
thick layers of mud to pile up in river valleys. Tec-
tonic shifts that gave rise to mountains, as well as
climate changes that enhanced precipitation, accel-
erated erosion, and helped blanket sea floors with
mud hundreds of meters thick. Over time, many
mud deposits hardened into mudrock, the most
abundant rock in the geologic record, accounting
for roughly half of all sedimentary formations.

Now, humans are a dominant force in the world
of mud. Starting about 5000 years ago, erosion
rates shot up in many parts of the world as our
ancestors began to clear forests and plant crops.
Even more sediment filled rivers and valleys, al-
tering landscapes beyond recognition (see p. 898.)
In some places dams and dykes trapped that mud,
preventing fresh sediment from nourishing flood-
plains, deltas, and tidal flats and causing them to
shrink (see p. 896). And industrial processes be-
gan to produce massive quantities of new forms of
mud—mine and factory waste—that is laden with
toxic compounds and often stored behind dams
that can fail, unleashing deadly torrents (see pp.
906, 910).

Despite its ubiquity, mud still harbors mysteries.
Biologists, for example, are just beginning to grasp
the vast menagerie of organisms that live in mud,
and unravel the remarkable adaptations that al-
low them to cope with special challenges, such as a
lack of oxygen (see p. 902). And biogeochemists are
still grappling with the immense role mud plays in
cycling carbon, and hence influencing global cli-
mate. Such issues, as the cliché goes, are still just
clear as mud.

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NEWS | FEATURES | MUD

Copper

MUD ON THE MOVE

By David Malakoff; Graphics by Nirja Desai and Xing Liu

Humans are reshaping the world’s mud supply, altering where—and how fast—it Mississippi The (less) muddy
piles up. Thousands of years ago, our ancestors caused erosion rates to surge by Mississippi
starting to clear forests and plant crops, muddying lakes and rivers. Today, North America’s
deforestation and urbanization are causing some rivers to carry more sediment, biggest river has seen
even as dams and efforts to curb erosion choke off sediment supplies to other sediment loads drop,
waterways. Such changes, together with precipitation shifts driven by climate change, accelerating the loss of
are leading to sometimes dramatic transformations in river deltas, coastal its delta in Louisiana.
mud flats, and the amount of mud that ultimately collects at the bottom of the sea.

Cleared Sediment Floodplain

Dam forest fow sediment Deltas

Magdalena

Trapped Plowed Tidal Ocean foor Amazon
sediment feld fats

Water moves vast quantities of sediment eroded Deforestation
in highlands to the ocean, but human activities leads to larger deltas
can greatly boost or reduce sediment flows. Deforestation has increased
sediment loads in the
The human imprint 1 Amazon and other South
American rivers in recent
Around the world, mud cores drilled decades, helping expand the
from lake bottoms show a pattern continent’s river deltas by
similar to that found in Lake Dojran some 16 kilometers per year.
in Greece and Macedonia (right): Erosion rate (relative scale)0
Sedimentation rates rose sharply about Change in annual sediment fux in tons (2000–10)
4000 years ago as humans began to Parana
clear landscapes. At Lake Dojran, Amazon
researchers used sediment levels of a Jhuo-shuei–1
lithium isotope as a proxy for erosion.
LenaBiobío
Ob
–2
Biobío
Yellow–32000Present
Yangtze6000 4000
Indusyears
Mississippiago
Xijiang
Roll on, muddy rivers Clearer waters
CREDITS: (RIVERS MAP) HYDROSHEDS/NASA SHUTTLE RADAR TOPOGRAPHY MISSION; (TIDAL FLATS MAP) MURRAY ET AL., NATURE, 565, 222 (2019); (EROSION
The Amazon currently tops the list of the world’s 10 largest transporters of PROXY DATA) ROTHACKER ET AL., SCIENTIFIC REPORTS, 8, 247 (2018); (SEDIMENTS DATA) LI ET AL., SCIENCE BULLETIN, 65, 1, 62 (2020); JINREN NIDeforestation and farming increased sediment in some large rivers
sediment to the sea. Other large muddy rivers help make Bangladesh and from 2000 to 2010, particularly in South America. But dams have cut
China major suppliers of sediment. loads elsewhere, especially in Asia. A 2019 study of 193 large rivers
estimated a 20.8% overall decline in sediment load. Here are the top
Amazon Bangladesh sediment gainers and losers.
755.28 1094.96
200
Tons annually
0
Brahmaputra
739.51

Yellow China Total annual sediment –200
706.7 1083.03 load of top 10 rivers –400
3860 –600
Yangtze Brazil –800
376.33 755.28

Ganga United States
355.45 479.53

Mississippi Egypt
261.33 180
Copper
218.2 Colombia
Nile 143.59
180
Pakistan
Magdalena 123.56
143.59
Indus
123.56

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Lena
Ob

Rhine Volga Big barriers
Indus Asian rivers were once
Yellow among the world’s
muddiest, nourishing
Brahmaputra Yangtze huge deltas and tidal
flats. But those features
Nile are now threatened by
a phalanx of huge dams
Ganga that prevent sediment
from reaching the sea.

Senegal Xijiang
Mekong
Niger

A decadal decline Congo 0 10 20 30
Although the Nile Zambezi
carries one of the
world’s largest Tidal fat area, in square
sediment loads to kilometers (km2). Each dot
the sea, dams across represents a 1° grid cell
Africa now block for the period 2014–16.
up to two-thirds of
the sediment that ~200,000 ~0
flowed downstream
just decades ago.

River fow, in cubic meters per
second (m3/s), based on
average long-term discharge

Deltas of change Shifting tides

Muddy deltas that form where rivers meet the sea support rich farmlands Tidal flats, vast banks of mud that flank many coasts, are key habitats
and ecosystems. A 2020 study of 11,000 deltas found that 9% lost for marine organisms and seabirds, as well as important players in
land from 1985 to 2015, whereas 14% added area. Globally, deltas grew by the global processing and storage of carbon and nutrients. Asian nations
54 square kilometers (km2) per year over that period, mostly in South boast the largest total expanses (below), but other regions have
America and Asia. The leading land gainers and losers. extensive flats (above). Reductions in sediment flows imperil some
flats; one recent global study estimated flats have shrunk by at least
10 20,000 km2 since 1984.
DATA: (DELTA) NIEHUIS ET AL., NATURE, 577, 514 (2020); (TIDAL FLATS) MURRAY ET AL., NATURE, 565, 222, (2019)
5 Indonesia China
0Net delta land change (km2/year) 14,416 12,049
Parana
–5 Lena Australia Canada India
–10 8866 6477 5788
SCIENCE sciencemag.org Rhine-Meuse
Godavari United States Brazil
6622 5389
Ganga-Brahmaputra
Volga Published by AAAS
Mekong
Senegal
Niger
Mississippi
Nile
Copper River
Yellow

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NEWS | FEATURES | MUD

A MUDDY

LEGACY

A dozen years after two scientists showed how
centuries-old mud has smothered many

U.S. streams, their ideas are guiding restoration efforts

By Paul Voosen, on Big Spring Run in Pennsylvania

C enturies ago, parts of the east- fail if planners didn’t figure out how to pre- geomorphologist Jim Knox and hydrologist PHOTO: NICHOLAS HERTZLER
ern United States were drowned vent massive slugs of legacy sediment, which Stanley Trimble—documented thick beds
in mud. Now, Robert Walter also carries harmful nutrients, from sloshing of legacy sediments beneath waterways in
was dancing in it. The geo- down the bay’s many tributaries. “It was un- Georgia and the Upper Midwest.
chemist stood calf deep in this comfortable,” Merritts says, “because I knew
small stream 100 kilometers that my colleagues had other ideas.” “Agricultural erosion in parts of this coun-
west of Philadelphia, thick curli- try was far more severe” than many geo-
cues of chocolate sediment flow- Now, a dozen years later, new research is logists realized, says Trimble, who recently
ing around his legs. Walter did a settling many of the debates that Merritts’s retired from the University of California,
little jig as his colleague and spouse, geo- and Walter’s paper touched off. Although Los Angeles. “We are talking about buried
morphologist Dorothy Merritts, watched. dams are not solely to blame for legacy sedi- farms and villages.” Beaver, a small town in
More mud stirred, heading downstream. ment, it’s now clear colonial-era erosion did Minnesota, had been smothered by nearly
dramatically alter streams in much of the 5 meters of eroded silt from uphill farms
Brown water might not hold much in- continent’s tectonically quiet eastern half, that reached the second floors of homes.
terest for many researchers. But a dozen says Ellen Wohl, a geomorphologist at Colo- Port Tobacco, Maryland, once a boomtown,
years ago, it catapulted Merritts and Walter rado State University, Fort Collins. “There’s faded after its wharfs silted up. But these
to scientific prominence. The pair, profes- been an accelerated recognition of how ubiq-
sors at Franklin & Marshall College (F&M), uitous this sediment is,” she says. And that
showed that Big Spring Run and many other recognition has been driven by Walter and
meandering, high-banked streams in the Merritts, says Noah Snyder, a geomorpho-
eastern United States look nothing like the logist at Boston College. Their study is “one
low-banked, marshy waterways that existed of the most influential papers I’ve seen.”
when European explorers first arrived nearly
500 years ago. The original streams, Merritts Now, the duo is hoping to inspire a new
and Walter argued in an influential 2008 pa- approach to stream restoration by turning
per published in Science, are now buried be- back the clock at Big Spring Run. By remov-
neath millions of tons of “legacy sediment” ing centuries of mud, they have returned the
that was released by colonial-era farming stream to its marshy, precolonial glory, and
and logging, and then trapped behind count- are now demonstrating the environmental
less dams built to power flour, timber, and payoff such strategies can deliver.
textile mills. “We realized,” Walter says, “that
the [streams] had been completely manufac- MERRITTS AND WALTER weren’t the first to
tured and altered.” realize that erosion has clogged many U.S.
stream valleys with sediment. In 1917, Grove
The finding challenged decades of conven- Karl Gilbert, a storied geologist who studied
tional scientific wisdom and sparked push- western North America, revealed that gold
back from researchers who said the pair had mining in the late 1800s had caused sedi-
overstated its case. It called into question ment to fill and reshape deep river valleys in
expensive efforts to restore rivers by using the California Sierra Nevadas. In the 1940s,
heavy equipment to resculpt them into what Stafford Happ, a soil scientist at the U.S. De-
practitioners believed had been their natu- partment of Agriculture, documented how
ral shapes. And the work raised concerns silt eroded over centuries had buried and
that a massive, multibillion-dollar effort to transformed Wisconsin waterways. In the
clean up the nearby Chesapeake Bay would following decades, two other researchers—

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NEWS

As the result of a restoration project that
removed 22,000 tons of colonial-era

sediment, Big Spring Run in Pennsylvania
now snakes through lush wetlands.

pioneering studies never quite persuaded the land around them. As part of their recalls. “I wanted to be able to understand
scientists that some waterways had been work, they showed the importance of rivers everywhere around me.”
utterly transformed. frequently spilling over their banks during
floods and depositing sediment on adjacent After earning a doctorate in geomorpho-
Much of our understanding of how riv- floodplains; such overbank deposition, they logy from the University of Arizona in 1987,
ers behave and evolve comes from two geo- found, was a fundamental part of a natural, Merritts joined the F&M faculty. She became
morphologists, Luna Leopold and Gordon healthy waterway. a field junkie, spending much of her career
“Reds” Wolman. While working together deciphering how plate tectonics had reshaped
at the U.S. Geological Survey (USGS) in the Merritts, 62, says she grew up wanting landscapes around the Pacific Rim by looking
1950s, they studied streams in Virginia, to tell her own stories about the landscape. at how rivers had shifted over time. The work
Maryland, and Pennsylvania—all easily ac- Raised in central Pennsylvania, she spent often took her to hazardous spots, including
cessible from USGS headquarters in Reston, her childhood outdoors, climbing and hik- East Timor, where she needed a bodyguard
Virginia. Using quantitative techniques rare ing with packs of kids. Her grandfather, a because of a civil war, and Humboldt county
at the time, they developed an influential conductor on the Pennsylvania Railroad, in California, where she was threatened at
explanation for how rivers form stable, told her of the wonders he saw in the state’s gunpoint by cannabis growers. Until recently,
braided, meandering channels and sculpt valleys. “That’s what I wanted to do,” she Merritts carried two life insurance policies.

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NEWS | FEATURES | MUD

These hazards prompted her, in 2002, to towering bank of finely laminated mud midable team, say those who know them.
look for a safer project closer to home. She they found the remains of a colonial-era Merritts is meticulous, Wohl says, “just
had heard concerns about silt eroding from milldam. That’s when Walter made a leap. thorough and detailed and comprehensive.”
the banks of rivers flowing through farms in “These are everywhere,” he said. “I bet all Walter is more of a provocateur and disci-
Pennsylvania, so she and her students began these streams come from these old dams.” pline jumper. Their qualities are comple-
to survey local waterways. They appeared mentary, says Kathy Boomer, a river scientist
to behave in the ways that Leopold and Merritts was doubtful. “I thought it was at the Foundation for Food and Agriculture
Wolman had laid out. But the traditional kind of crazy that you could [make that] Research. “They’re the most collaborative
model of river evolution couldn’t fully ex- leap from one outcrop,” she recalls. But and open-minded scientists I know.”
plain a picture that a student showed Mer- subsequent trips to Lancaster’s historical
ritts one day; it displayed a nearly vertical, society, along with reviews of other records, In January 2008, Merritts and Walter un-
6-meter-high wall of layered sediments confirmed the dams had, indeed, been seem- veiled their ideas in Science. “The modern,
along the Little Conestoga River. ingly everywhere. On some rivers, settlers incised, meandering stream is an artifact of
had built one every few kilometers. “It was,” the rise and fall of mid-Atlantic streams in
As it happened, Walter, who had recently Merritt says, “just astonishing.” response to human manipulation of stream
arrived at F&M, was visiting as Merritts and valleys for water power,” they wrote. Ulti-
the student discussed the photo. Now 69, It was also disconcerting. The ubiqui- mately, they concluded, the findings “imply
Walter was born and raised in Lancaster, tous dams could mean many of the riv- the need to reconsider current procedures
Pennsylvania, where F&M is located, and ers that Leopold and Wolman had used to for stream restoration” that rest on “the
had spent days fishing nearby streams, but draw their conclusions had this unrecog- assumption that eroding channel banks
nized backstory, and so sat atop far more are natural and replenishable.” The paper
quickly became the most influential of their
careers, with some 750 citations.

landscape evolution was not his focus. A spe- Dorothy Merritts and Robert Walter put NOT ALL THE ATTENTION was positive. “What PHOTO: SAMUEL FEIBEL
cialist in the chemistry of volcanic rocks, he their research on rivers to a real-world surprised me was the resistance they met,”
began his career dating the terrain surround- test by helping restore Big Spring Run. Wohl says. “People really had a hard time ac-
ing the skeleton known as Lucy, the famed cepting this.”
human ancestor discovered in Ethiopia. Still, anthropogenic sediment than realized. It
one look at the student’s photo was enough suggested that efforts to restore streams to In critiques later published in Science
to persuade him that the layers of sediment meandering, high-banked single channels and elsewhere, some researchers faulted
it showed had been deposited in still—not were misguided. And it implied that mas- Walter and Merritts for implying that their
moving—water. “There has to be a dam sive blankets of stored sediment could be findings, based largely on rivers in eastern
there,” he said. There’s only one way to get a major source of nutrient pollution that Pennsylvania, where colonial mill dams were
that kind of deposit, Merritts adds. “A lake.” would run downriver for decades to come. common, could be applied widely through-
out the eastern United States. “I thought
CURIOUS, the next day the two research- The duo spent the next several years the conclusions far exceeded the evidence,”
ers journeyed to the Little Conestoga. building its case, driving to dam sites and Trimble recalls. Other research, he and oth-
Sure enough, just downstream from the documenting and dating sediments. The col- ers noted, had found that legacy sediments
laboration also became a courtship, as the had piled up even along river reaches that
two scientists found they made both a scien- didn’t have dams. But until the couple’s pa-
tific and personal match. They were married per came out, those studies had failed to gain
next to an old mill in 2004. broad traction.

Together, Merritts and Walter make a for- Other scientists were irked by the sug-
gestion that Leopold and Wolman’s iconic
theoretical framework was flawed. “To say
channel morphology is dependent on his-
toric milldams is incorrect,” says Martin
Doyle, a river ecologist at Duke University.
“The classic understanding of how rivers
work is still true.”

The real-world implications raised the
stakes. River restoration specialists risked
wasting heaps of cash on projects that might
be quickly undone if floods pushed piles of
old sediment into newly carved streams.
State and federal agencies had to decide how
to account for legacy sediments as they set
water quality guidelines and environmental
cleanup goals. And efforts to curb the sup-
ply of silt washing into the Chesapeake Bay
might have to contend with far more of it
than planners had counted on. “This is the
900-pound gorilla for how we restore our
streams,” says Gregory Noe, a USGS ecologist
who studies mid-Atlantic streams.

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AS THE DEBATE swirled, Merritts and restored area declined drastically, by 85%, ac- lonial dams did trap sediment, they found,

Walter decided to put their ideas into prac- cording to a USGS report published this year. the glaciated landscapes provided far less

tice. During their research, they had met Polluting phosphorus, which hitches a ride grist than those farther south. The thick

Joe Sweeney, a farmer who owned land that on silt particles, dropped 79%. Ken Forshay, beds of legacy sediment seen in the mid-

encompassed Big Spring Run, and Ward a research ecologist with EPA based in Ada, Atlantic are “not going to be seen everywhere,”

Oberholtzer, an engineer at LandStudies, a Oklahoma, says he was skeptical he’d see such Merritts says. And “not every place had that

river restoration firm. Sweeney had hired improvements. But the data have “turned a many milldams.”

Oberholtzer to examine why trees he had nonbeliever into a believer,” he says. Noe found similar variation in a massive

planted on Big Spring Run’s high banks to Even before all the results were in, the Big study of 68 river sites in the mid-Atlantic,

prevent erosion were dying. The conclusion: Spring Run project prompted similar resto- now nearing publication. “There’s more

Their roots couldn’t reach the groundwater; rations in Pennsylvania and Maryland, with nuance now,” Noe says. “Milldams are very

trenches dug by Merritts, Walter, and their 20 now completed and 10 more underway. important” in understanding sediment in

students suggested several meters of legacy It’s simple to see why: Though the project some watersheds, he says, “but they’re not

sediment caked over the site. To restore such would have cost $1 million in today’s dol- necessarily the causative factor everywhere.”

connections, the team proposed re-creating lars to restore its 800 meters, it was at least Noe’s study will also provide the first de-

the kind of languid wetland that Walter and 16 times more cost effective at reducing pol- tailed, large-scale accounting of sediment

Merritts believed had once existed on the lution than other techniques, found Patrick sources and sinks for the region. The good

spot. But first they would monitor it for sev- Fleming, an agricultural economist at F&M. news is that, at nearly all the rivers his

eral years, to establish a baseline that could “This practice blew the other ones away.” team studied, the floodplains downstream

be used to evaluate any post- were capturing as much sedi-

restoration changes. ment as was eroding upstream,

In 2011, after more than potentially curbing pollution.

2 years of planning and assis- The floodplains are acting as

tance from the Pennsylvania kidneys, he says, and are “water

Department of Environmental quality superheroes.”

Protection, the National Science But Noe adds that if those

Foundation, the Environmental floodplains weren’t busy cap-

Protection Agency (EPA), USGS, turing colonial silt, they could

and others, bulldozers began to instead be a greater sink for the

remove 22,000 tons of legacy sediment runoff from farms and

sediment along 4 square kilo- cities. And the further removal of

meters of the valley. (The silt dams, as many states are pursu-

was trucked to F&M and used as ing, will only free up new slugs

fill beneath a new building.) A of mud. So legacy sediment prob-

layer of rich, black, precolonial lems aren’t going away, says Karl

soil emerged from beneath the Wegmann, a geomorphologist at

legacy sediment. In it, research- North Carolina State University.

ers found seeds that provided “It’s like Chernobyl. We’re going

PHOTOS: (TOP TO BOTTOM) ROBERT WALTER AND DOROTHY MERRITTS/FRANKLIN & MARSHALL COLLEGE; LANDSTUDIES an archive of the wetland plants to be living with it for centuries.”

that had once grown along the The question now is what to

stream. Although federal regu- do about it. The Chesapeake Bay

lations required the restora- Commission, which leads the

tion team to carve a single new cleanup of the bay, is evaluating

channel, they built low banks how to credit legacy sediment

and installed stumps and other restorations for their pollution re-

obstacles that would encourage ductions, based on long-term data

high waters to jump the banks, Meters of mud had buried the rich, black soil that typified Big Spring Run before from project like Big Spring Run.

transforming the stream into a Europeans arrived (top). It took heavy machines to remove the legacy sediment. It’s “been tremendously valuable,”

multithreaded wetland. says David Wood of the Chesa-

Within 1 year, the banks bloomed with TWELVE YEARS AFTER their Science paper peake Stormwater Network, a nonprofit

sedges like a Chia pet. Today, bog turtles scut- appeared, a clearer picture is emerging of that coordinates restoration practices. This

tle and geese nest in thick native vegetation how far beyond Big Spring Run the ideas is “the type of research that is needed else-

that has put down roots that hold sediment floated by Merritts and Walter can be ap- where across the watershed,” he says.

in place. There’s room for floodwaters to slow plied. Evidence that precolonial streams of- For their part, Merritts and Walter are

down and spread out, instead of sweeping ten resembled wetlands has popped up in pragmatic, not environmental romantics.

away bankside trees and plants. “The biology more places—in Kentucky, for example, says They may have revealed a prehuman base-

does not have to re-establish itself” after ev- Arthur Parola, a stream scientist at the Uni- line for many waterways, but they know

ery severe storm, Oberholtzer says. versity of Louisville. “The more we look, the change is a constant of geology. Many riv-

Monitoring shows the restoration has also more we’re finding,” he says. “These wetland ers are so drowned in silt that they can-

altered the stream’s biogeochemistry. Storage systems were maybe the common types of not be redeemed. The world is not pristine.

of organic carbon tripled in the restored area streams in the eastern United States.” But only by acknowledging and accounting

and levels of nitrate, a key pollutant, dropped In New England, however, Merritts and for the legacy of the past, they say, can we

sharply, soaked up by the wetland plants. The Walter found a different picture when they take a first step toward solving the prob-

load of sediment swept downstream from the surveyed streams with Snyder. Although co- lems of today. j

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Published by AAAS

THE MUD IS or Lars Peter Nielsen, it all began
with the mysterious disappearance
ELECTRIC of hydrogen sulfide. The microbio-
Bacteria that conduct electricity are logist had collected black, stinky
transforming how we see sediments mud from the bottom of Aarhus
Harbor in Denmark, dropped it
By Elizabeth Pennisi into big glass beakers, and inserted

Threads of electron-conducting F custom microsensors that detected PHOTO: LARS RIIS-DAMGAARD AND STEFFEN LARSEN
cable bacteria can stretch changes in the mud’s chemistry.
902 At the start of the experiment, the muck
up to 5 centimeters from deeper was saturated with hydrogen sulfide—the
mud, where oxygen is scarce and source of the sediment’s stink and color. But
30 days later, one band of mud had become
hydrogen sulfide is common, paler, suggesting some hydrogen sulfide
to surface layers richer in oxygen. had gone missing. Eventually, the micro-
sensors indicated that all of the compound
Published by AAAS had disappeared. Given what scientists
knew about the biogeochemistry of mud,
recalls Nielsen, who works at Aarhus Uni-
versity, “This didn’t make sense at all.”

The first explanation, he says, was that
the sensors were wrong. But the cause
turned out to be far stranger: bacteria that
join cells end to end to build electrical
cables able to carry current up to 5 centi-
meters through mud. The adaptation, never
seen before in a microbe, allows these so-
called cable bacteria to overcome a major
challenge facing many organisms that live
in mud: a lack of oxygen. Its absence would
normally keep bacteria from metabolizing
compounds, such as hydrogen sulfide, as
food. But the cables, by linking the microbes
to sediments richer in oxygen, allow them
to carry out the reaction long distance.

When Nielsen first described the discov-
ery in 2009, colleagues were skeptical. Filip
Meysman, a chemical engineer at the Uni-
versity of Antwerp, recalls thinking, “This is
complete nonsense.” Yes, researchers knew
bacteria could conduct electricity, but not
over the distances Nielsen was suggesting.
It was “as if our own metabolic processes
would have an effect 18 kilometers away,”
says microbiologist Andreas Teske of the
University of North Carolina, Chapel Hill.

But the more researchers have looked
for “electrified” mud, the more they have
found it, in both saltwater and fresh. They
have also identified a second kind of mud-
loving electric microbe: nanowire bacteria,
individual cells that grow protein structures
capable of moving electrons over shorter
distances (see graphic, p. 903). These nano-
wire microbes live seemingly everywhere—
including in the human mouth.

The discoveries are forcing researchers to
rewrite textbooks; rethink the role that mud
bacteria play in recycling key elements such as
carbon, nitrogen, and phosphorus; and recon-
sider how they influence aquatic ecosystems
and climate change. Scientists are also pur-
suing practical applications, exploring the
potential of cable and nanowire bacteria to

sciencemag.org SCIENCE

NEWS | FEATURES | MUD

battle pollution and power electronic devices Mud’s electric microbes
(see sidebar, p. 904). “We are seeing way more
interactions within microbes and between At least two kinds of bacteria have evolved electric solutions to gaining energy. These microbes, first discovered
microbes being done by electricity,” Meysman in mud, separate the reduction and oxidation reactions that release the energy needed to fuel life. To enable
says. “I call it the electrical biosphere.” these reactions, nanowire bacteria move electrons just micrometers between cells, particles, or other electron
acceptors. Cable bacteria move electrons farther: up to 5 centimeters to oxygen-rich sediments.

MOST CELLS THRIVE by robbing electrons A challenging Oxygen (O2) Littorella
from one molecule, a process called oxida- environment Hydrogen sulfde unifora
tion, and donating them to another mol- In ocean and freshwater
ecule, usually oxygen—so-called reduction. sediments, the oxygen Water
Energy harvested from these reactions needed for metabolism
drives the other processes of life. In eukary- is typically restricted 3
otic cells, including our own, such “redox” to surface layers or near
reactions take place on the inner membrane plant roots. In deeper
of the mitochondria, and the distances in- layers, toxic hydrogen
volved are tiny—just micrometers. That is sulfide accumulates as
why so many researchers were skeptical organic matter decays.
of Nielsen’s claim that cable bacteria were
moving electrons across a span of mud 1 Protein wire 1 cm 2 Bacterium
equivalent to the width of a golf ball. Bacterium Iron oxide (Fe+3) 1
Wire
The vanishing hydrogen sulfide was key 23
to proving it. Bacteria produce the com- Cable bacteria
pound in mud by breaking down plant de- Nanowire bacteria e– 3 e– These bacteria
bris and other organic material; in deeper Found almost REDUCTION
sediments, hydrogen sulfide builds up be- everywhere e– Reactions such as create a cylinder
cause there is little oxygen to help other microbiologists e– O2 + Hydrogen e– Water of conducting
bacteria break it down. Yet, in Nielsen’s lab- have looked, these e– Fe+3 e– Fe+2 wires that encases
oratory beakers, the hydrogen sulfide was bacteria shuttle a chain of cells.
disappearing anyway. Moreover, a rusty hue electrons gained 2 e– The wires enable
appeared on the mud’s surface, indicating through oxidation of the microbes to
that an iron oxide had formed. organic compounds ELECTRON TRANSFER transfer electrons
along protein Electrons travel along e– gained by oxidizing
One night, waking from his sleep, Nielsen nanowires to nanowires or bacterial cables. hydrogen sulfide
came up with a bizarre explanation: What if electron-accepting to oxygen-rich
bacteria buried in the mud were completing substances or cells. 1 e– sediment, where
the redox reaction by somehow bypassing Sometimes these OXIDATION the electrons are
the oxygen-poor layers? What if, instead, wires are used Reactions such as used to make water.
they used the ample supplies of hydrogen to grab electrons Sulfde Sulfate + e–
sulfide as an electron donor, then shuttled instead. Acetate Carbon dioxide + e– e–
the electrons upward to the oxygen-rich free up electrons.
surface? There, the oxidation process would
GRAPHIC: V. ALTOUNIAN/SCIENCE produce rust if iron was present. terial filaments that appeared in the layer in the sediment that he saw,” Meysman re-
of glass beads inserted in the beakers filled calls. “It was an instruction from Mother
Finding what was carrying these electrons with the Aarhus Harbor mud. Each fila- Nature to take this more seriously.”
proved complicated. First, Nils Risgaard- ment was composed of a stack of cells—up
Petersen on Nielsen’s team had to rule out a to 2000—encased in a ridged outer mem- His team began to develop tools and tech-
simpler possibility: that metallic particles in brane. In the space between that membrane niques for investigating the microbes, some-
the sediment were shuttling electrons to the and the stacked cells, many parallel “wires” times working collaboratively with Nielsen’s
surface and causing the oxidation. He ac- stretched the length of the filament. The group. It was tough going. The bacterial
complished that by inserting a layer of glass cablelike appearance inspired the microbe’s filaments tended to degrade quickly once
beads, which don’t conduct electricity, into common name. isolated, and standard electrodes for mea-
a column of mud. Despite that obstacle, the suring currents in small conductors didn’t
researchers still detected an electric current Meysman, the one-time skeptic, quickly work. But once the researchers learned how
moving through the mud, suggesting metal- became a convert. Not long after Nielsen to pick out a single filament and quickly at-
lic particles were not the conductor. announced his discovery, Meysman decided tach a customized electrode, “We saw really
to examine one of his own marine mud high conductivity,” Meysman says. The liv-
To see whether some kind of cable or wire samples. “I noticed the same color changes ing cables don’t rival copper wires, he says,
was ferrying electrons, the researchers next
used a tungsten wire to make a horizontal
slice through a column of mud. The current
flickered out, as if a wire had been snipped.
Other work narrowed down the conductor’s
size, suggesting it had to be at least 1 micro-
meter in diameter. “That’s the conventional
size for bacteria,” Nielsen says.

Ultimately, electron micrographs re-
vealed a likely candidate: long, thin, bac-

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NEWS | FEATURES | MUD

Next up: a phone powered by microbial wires? cables sprout protein wires spanning 20 to
50 nanometers from each cell.
T he discoverers of electric microbes have been quick to think about how these
bacteria could be put to work. “Now that we have found out that evolution has As with cable bacteria, some puzzling
managed to make electrical wires, it would be a shame if we didn’t use them,” says sediment chemistry led to the discovery
Lars Peter Nielsen, a microbiologist at the University of Aarhus. of nanowire microbes. In 1987, microbio-
One potential use is to detect and control pollutants. Cable microbes seem to logist Derek Lovley, now at the University
thrive in the presence of organic compounds, such as petroleum, and Nielsen and of Massachusetts, Amherst, was trying to
his team are testing the possibility that an abundance of cable bacteria signals the understand how phosphate from fertil-
presence of undetected pollution in aquifers. The bacteria don’t degrade the oil izer runoff—a nutrient that promotes algal
directly, but they may oxidize sulfide produced by other oil-eating bacteria. They might blooms—is released from sediments be-
also aid cleanup; sediments recover faster from crude oil contamination when they neath the Potomac River in Washington,
are colonized by cable bacteria, a different research team reported in January in Water D.C. He suspected microbes were at work
Research. In Spain, a third team is exploring whether nanowire bacteria can speed the and began to sieve them from the mud.
cleanup of polluted wetlands. And even before nanowire bacteria were shown to be After growing one, now called Geobacter
electric, they showed promise for decontaminating nuclear waste sites and aquifers metallireducens, he noticed (under an elec-
contaminated with aromatic hydrocarbons such as benzene or naphthalene. tron microscope) that the bacteria sprouted
connections to nearby iron minerals. He
Fighting climate change is another target. Lab tests have demonstrated that cable suspected these wires were transporting
bacteria can reduce the amount of methane—a major contributor to global warming— electrons, and eventually figured out that
generated by rice cultivation by 93%, researchers reported on 20 April in Nature Com- Geobacter orchestrates chemical reactions
munications. They do this by helping break down substances that methane-producing in mud by oxidizing organic compounds
bacteria rely on. and transferring the electrons to minerals.
Those reduced minerals then release their
Electric bacteria could also give rise to new technologies. They can be genetically hold on phosphorus and other elements.
modified to alter their nanowires, which could then be sheared off to form the basis of
sensitive, wearable sensors, says Derek Lovley, a microbiologist the University of Mas- Like Nielsen, Lovley faced skepticism
sachusetts (UMass), Amherst. “We can design nanowires and tailor them to specifi- when he first described his electrical mi-
cally bind compounds of interest.” For example, in the 11 May issue of Nano Research, crobe. Today, however, he and others have
Lovely, UMass engineer Jun Yao, and their colleagues described a nanowire sensor that documented almost a dozen kinds of nano-
detects ammonia at concentrations relevant for agricultural, industrial, environmental, wire microbes, finding them in a variety of
and biomedical applications. environments besides mud. Many shuttle
electrons to and from particles in sediment.
Fashioned into a film, nanowires can generate electricity from the moisture in But some rely on other microbes to obtain
the air. The film generates power, researchers believe, when a moisture gradient de- or store electrons. Such biological partner-
velops between the film’s upper and lower edges. (The upper edge is more exposed ships allow both microbes to “do new types
to moisture.) As the water’s hydrogen and oxygen atoms separate because of of chemistry that neither organism can do
the gradient, a charge develops and electrons flow. Yao and his team reported on on their own,” says Victoria Orphan, a geo-
17 February in Nature that such a film can create enough power to light a light-emitting biologist at the California Institute of Tech-
diode, and 17 such devices connected together can power a cellphone. The approach nology. Whereas cable bacteria solve their
is “a revolutionary technology to get renewable, green, and cheap energy,” says Qu redox requirements by long-distance trans-
Liangti, a materials scientist at Tsinghua University. (Others are more cautious, port to oxygenated mud, these microbes de-
noting that past attempts to wring energy from moisture, using graphene or poly- pend on each other’s metabolisms to satisfy
mers, have not panned out.) their redox needs.

Ultimately, researchers hope to exploit the bacteria’s electrical talents without having to Some researchers are still debating how
deal with the finicky microbes themselves. Lovley, for example, has coaxed a common lab the bacterial nanowires conduct electrons.
and industrial bacterium, Escherichia coli, to make nanowires. That should make it easier Lovley and his colleagues are convinced that
for researchers to mass produce the structures and explore practical applications. –E.P. chains of proteins called pilins, which consist
of ring-shaped amino acids, are key. When
but they are on par with conductors used in the Danish government. Among the chal- he and his colleagues reduced the number
solar panels and cellphone screens, as well lenges the center is tackling is mass pro- of ringed amino acids in pilin, the nanowires
as the best organic semiconductors. ducing the microbes in culture. “If we had became poorer conductors. “That was really
a pure culture, it would be a lot easier” to surprising,” Lovley says, because proteins are
The researchers also dissected the cable test ideas about cell metabolism and envi- generally thought to be insulators. But others
bacteria’s anatomy. Using chemical baths, ronmental influences on conductance, says think the issue is far from settled. Orphan, for
they isolated the cylindrical sheath, finding the center’s Andreas Schramm. Cultured one, says that although “there is some com-
it holds 17 to 60 parallel fibers, glued along bacteria would also make it easier to isolate pelling evidence … I still don’t think [nano-
the inside. The sheath is the source of the the cable’s wires and test potential applica- wire conductance] is well understood.”
conductance, Meysman and colleagues re- tions for bioremediation and biotechnology.
ported last year in Nature Communications. WHAT IS CLEAR is that electrical bacteria are
Its exact composition is still unknown, but EVEN AS RESEARCHERS puzzle over cable everywhere. In 2014, for example, scientists
could be protein-based. bacteria, others have been studying another found cable bacteria in three very differ-
big player in electric mud: nanowire bac- ent habitats in the North Sea: an inter-
“It’s a complicated organism,” says teria, which instead of stacking cells into tidal salt marsh, a seafloor basin where
Nielsen, who now heads a Center for oxygen levels drop to near zero at some
Electromicrobiology, established in 2017 by times of the year, and a submerged mud

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Derek Lovley (left) discovered mud bacteria that sprout electron-transporting nanowires, while Lars Peter Nielsen (right) described microbes that build conducting cables.

PHOTOS: (LEFT TO RIGHT) VOLKER STEGER/SCIENCE SOURCE; LARS KRUSE/AU FOTO plain just off the coast. (They didn’t find systems. By preventing the buildup of hy- tidal oyster reefs, she has found, a single
them in a sandy area populated by worms drogen sulfide, for example, cable bacteria cubic centimeter of mud can contain 2859
that stir up the sediments and disrupt the are likely making mud more habitable for meters of cables, which cements particles
cables.) Elsewhere, researchers have found other life forms. Meckenstock, Nielsen, and in place, possibly making sediment more
DNA evidence of cable bacteria in deep, others have found them on or near the roots stable for marine organisms.
oxygen-poor ocean basins, hydrothermal of seagrasses and other aquatic plants,
vent areas, and cold seeps, as well as man- which bubble off oxygen that the bacte- The bacteria also alter the mud’s chemis-
grove and tidal flats in both temperate and ria likely exploit to break down hydrogen try, making layers closer to the surface more
subtropical regions. sulfide. That, in turn, protects the plants alkaline and deeper layers more acidic,
from toxic gas. The partnership “seems to Malkin has found. Such pH gradients can
Cable bacteria have also shown up in be a very generic property of water plants,” affect “numerous geochemical cycles,” she
freshwater environments. After reading Meckenstock says. says, including those involving arsenic,
Nielsen’s papers in 2010 and 2012, a team manganese, and iron, creating opportuni-
led by microbiologist Rainer Meckenstock Robert Aller, a marine biogeochemist at ties for other microbes.
re-examined sediment cores drilled during Stony Brook University, thinks the bacteria
a study of groundwater pollution in Dus- may also aid many undersea invertebrates, With vast swaths of the planet covered
seldorf, Germany. “We found [cable bac- including worms that build burrows that al- by mud, cable and nanowire bacteria are
teria] exactly where we thought we would low oxygenated water to flow into the mud. likely having an influence on global cli-
find them,” at depths where oxygen was de- He has discovered cable bacteria sticking mate, researchers say. Nanowire bacteria,
pleted, recalls Meckenstock, who works at out the sides of worm tubes, likely so they for example, can strip electrons from or-
the University of Duisburg-Essen. can tap that oxygen for electron storage. In ganic materials, such as dead diatoms, then
return, those worms are kept safe from the shuttle them to other bacteria that produce
Nanowire bacteria are even more broadly toxic hydrogen sulfide. “The bacteria make methane—a potent greenhouse gas. Under
distributed. Researchers have found them [the burrow] more livable,” says Aller, who different circumstances, cable bacteria can
in soils, rice paddies, the deep subsurface, described these connections in a July 2019 reduce methane production.
and even sewage treatment plants, as well paper in Science Advances.
as freshwater and marine sediments. They In coming years, “We are going to see a
may exist wherever biofilms form, and The microbes also alter the properties broad acceptance of the importance of these
the ubiquity of biofilms provides further of mud, says Sairah Malkin, an ecologist at microbes to the biosphere,” Malkin says.
evidence of the big role these bacteria may the University of Maryland Center for En- Just over a decade after Nielsen noticed
play in nature. vironmental Science. “They are particularly the mysterious disappearance of hydrogen
efficient … ecosystem engineers.” Cable bac- sulfide from the Aarhus mud, he says, “It is
The broad range of electric mud bacteria teria “grow like wildfire,” she says; on inter- dizzying to think about what we’re dealing
also suggest they are a major force in eco- with here.” j

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906

Published by AAAS

NEWS | FEATURES | MUD

A DAM BIG

PROBLEM
A string of catastrophic failures
has raised alarm about dams meant
to contain muddy mine wastes

By Warren Cornwall

PHOTO: WASHINGTON ALVES/REUTERS T he dam, a 40-meter wall of rocks quences of a failure are getting much bigger,”
and dirt, gave way without warn- says Priscilla Nelson, a geotechnical engineer
ing, unleashing a torrent of mud. at the Colorado School of Mines.
Within a day, some 21 million cu-
bic meters of gray goo and water— In response, scientists, governments, en-
the tailings waste left behind by vironmentalists, and miners are searching
16 years of copper and gold min- for safer ways to handle the tainted mud.
ing at the Mount Polley mine in Some are trying to simply inventory the
western Canada—escaped from world’s tailings dams—estimates of the num-
a holding pond behind the dam, buried a ber range from 3500 to 21,000—and iden-
creek, and poured into Quesnel Lake, home tify those most at risk of failure. A few have
to one-third of British Columbia’s legendary called for a ban on one common but failure-
Fraser River sockeye salmon. prone design. Others are working on regu-
latory and management fixes. “The mining
The 2014 Mount Polley disaster shocked industry,” says Joseph Scalia, a geotechnical
mining engineers around the world. Many engineer at Colorado State University, “is re-
considered Canada a leader in developing alizing they can’t just spend as little as pos-
rules aimed at preventing the failure of such sible and the problem is going to go away.”
tailings dams, and respected the mine’s
owner, Imperial Metals. “That wasn’t sup- TAILINGS ARE THE TRASH of the mining world.
posed to be able to happen,” Jim Kuipers, To extract most metals, from iron to gold,
an engineer and former tailings dam man- miners often mix pulverized rock with water,
ager who now consults for environmental creating a milkshake of silt and gravel. As
groups, recalls a colleague telling him. higher quality mineral deposits run out, min-
ers are turning to lower grade sources that
Since then, the sense of crisis has deepened. generate more waste. Worldwide, the metal
In 2015, a tailings dam in Brazil collapsed, content of copper ore has fallen by nearly
unleashing a mammoth mud spill that killed half since the mid–20th century. Extracting
19 people, contaminated 668 kilometers of a single kilogram of copper can now produce
river, and reached the Atlantic Ocean. In 200 kilograms of sludge. The muck is often con-
2018, a dam failed at a major mine in Aus- taminated with toxic metals or minerals that
tralia; luckily, a second barrier prevented produce sulfuric acid when exposed to air.
disaster. Last year, a dam disintegrated at a
decommissioned Brazilian iron mine, releas- Tailings dams, unlike those built to store
ing a torrent that killed 270 people. water or generate power, don’t earn reve-
nue, creating an incentive for mine owners
Engineers fear more catastrophes await, to minimize costs. Many are built piece-
as the world confronts a swelling volume of meal throughout the life of a mine. And
muddy mine tailings, contained by more and the barriers are often made from a mixture
larger dams. Some rise to nearly the height of of rock and the tailings themselves, rather
the Eiffel Tower and hold back enough waste than a more uniform and predictable ma-
to fill Australia’s Sydney Harbor. “The conse- terial such as concrete. Those factors con-
tribute to a failure rate that, over the past
Mud released by a burst tailings dam at an iron mine century, was more than 100 times higher
near Brumadinho, Brazil, killed 270 people in 2019.

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Why mining dams fail Pooled water

Basins filled with leftover sludge from mining can grow to half the
size of Manhattan. Historically, dams containing tailings have failed at

more than 100 times the rate of water-holding dams. In just the
past decade, failures have killed hundreds and contaminated ecosystems

with toxic mud. Many failures have common culprits.

Pipe releasing
mine waste

1 Mine Tailings
tailings beach

2 Inconsistent 4
construction

Starter dam

3

Prebuild site survey

Dam face

1 Liquefaction 2 A risky design 3 Shaky ground 4 Piecemeal changes
Infiltration of water into the dam Upstream construction is a common Geologic weaknesses in the ground Unlike water dams, tailings dams
is a chief source of failures. In but failure-prone approach. The dam is below a dam can leave it vulnerable. evolve. They are built bit by bit over
extreme cases, water combined raised gradually, as tailings accumulate. In one of the biggest recent failures, decades as mine waste piles up.
with stress such as an earthquake With each new level, the dam tilts dam builders didn’t drill deep enough This creates more potential for errors.
can cause an earthen dam to upstream, relying on tailings below to discover a weak layer left by
suddenly turn to liquid. to help carry the load. receding glaciers. Original construction

Solid tailings Pipes releasing Soil
mine waste Core sample
Next upstream Weak layer of
dam layer soil below Starter dam
sample level
Time Built-up
tailings
Stress
Liquefed tailings
Dam
face Dam modifed
over time in
Tailings problematic
ways
Weight of dam bearing
Water Suspended Starter dam down on tailings
dam material

than that of reservoir and power dams, ac- and shoveled up much of the mud that had ries of seemingly small risks that snowball GRAPHIC: C. BICKEL/SCIENCE
cording to one estimate. buried the creek. (The company says the into a catastrophe.
spill didn’t cause long-term harm to the
Each disaster has its own constellation of Quesnel Lake ecosystem, but some eco- There is an unwritten covenant that
causes, but some arise from seemingly trivial logists say it’s still too early to tell.) regulators and mine owners can count on
errors. At Mount Polley, investigators led by engineers to design a safe tailings system,
Norbert Morgenstern, a geotechnical engi- Morgenstern, who also led the investiga- Morgenstern told a gathering of Brazilian
neer at the University of Alberta concluded tions into the 2015 Brazilian incident and geotechnical engineers in 2018. “That cov-
that part of the dam was built on a weak the 2018 Australia failure, has found that enant,” he said, “has been broken.”
patch of silt and clay. Exploratory boreholes faulty engineering, including inadequate
drilled prior to construction were too shallow scrutiny of the underlying geology, was at THE SEARCH IS ON for fixes. Some mining
to find the problem. Builders further weak- the heart of all but two of 15 major incidents watchdogs are calling for replacing one
ened the dam by making its walls steeper between 1980 and 2015. common type of dam, called an upstream
than planned, after the company ran short dam, and banning future use of the design.
of rock. One night, the weight of the sludge One major problem, he says, is the Upstream dams are built in stairlike stages,
became more than the dam could bear. “normalization of deviance.” The phrase, heading upstream over the accumulating
coined after the 1986 explosion of the tailings (see graphic, above). Part of the
It could have been much worse. No one space shuttle Challenger, describes how weight of each added step is borne by the
died. Workers ultimately repaired the dam engineers can be lulled into accepting a se-

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PHOTO: DIEGO BARAVELLI/FOTOARENA/SIPA/AP IMAGES tailings below. This approach is often the are already equipped with radar or lasers that dams for Klohn Crippen Berger, a private
cheapest, because the tailings serve as con- watch for worrying bulges. Momayez’s goal is firm. It’s also an enormous challenge to
struction material. to integrate streams of data in a computer process tailings at big mines churning out
system that can spot problems that might 100,000 tons of waste per day, particularly
More than 40% of major tailings dams escape periodic inspections. “We have a in wet climates. “It’s easier said than done,”
are the upstream design, according to pretty good idea how these tailing dams fail,” McLeod says.
a global inventory of more than 1700 Momayez says. “The question is, can we pre- MANY GROUPS are also pushing for regula-
dams recently launched by pension funds dict that, can we get ahead of the curve?” tory and management reforms. After the
of Sweden and the Church of England, 2019 Brazilian disaster, investment funds
which have pressed the mining industry Some engineers would like to simply worth more than $10 trillion helped bring
to strengthen environmental and safety eliminate the need for massive dams. together officials from industry, govern-
measures. A study of 8000 tailings dams “The best tailings dam is no dam at all,” ment, and the investor group Principles for
in China found that 95% were upstream Nelson says. She is studying whether Responsible Investment to create a set of
dams. And such dams are involved in mine waste can be melted into glasslike global guidelines for tailings dam construc-
three-quarters of tailings dam failures, ac- fibers that could be used for textiles or
cording to one estimate. reinforcing concrete. In June, mining gi- tion. Earlier this month, the coalition issued
its plan, calling for stiffer engineering stan-
The problem is that tailings aren’t a pre- Firefighters search for survivors dards for new dams. It also urges top min-
dictable building material, and they are of- in the mud unleashed by a ing executives, rather than lower level staff,
ten waterlogged. The water can act like a 2019 tailings dam failure in Brazil. to be responsible for tailings safety, and for
lubricant, reducing the friction that binds independent experts to review companies’
an earthen dam together. Engineering flaws ant BHP said it would spend $10 million waste plans. But it doesn’t push for a ban on
such as poor drainage can exacerbate the to study such reuse of copper tailings. upstream dams.
problem. In extreme cases—such as the
2019 disaster at the Brazilian iron mine— A more mature approach is to wring Morgenstern notes that similar reforms
dam sections simply liquefy. the water from tailings, creating waste the he and others suggested in the late 1990s,
consistency of damp earth, which can be after an earlier string of dam disasters, were
In Chile, where earthquakes make up- sculpted into mountains. The leftovers can never fully embraced. He expects it won’t be-
stream dams even riskier, the government still be toxic, but there’s less danger of a come clear until the end of the year whether
has forbidden the design since 1970. Brazil devastating flood, says Jan Morrill of Earth- the new proposals will fare better. Still, he’s
banned them in the wake of the 2019 acci- works. “Filtered tailings should be consid- heartened that, after the recent tragedies,
dent, and has ordered the mothballing of all ered the industry standard,” Morrill says. muddy mine waste is again in the spotlight.
upstream dams by 2027. Worldwide, such a “The tree,” he says, “has been shaken.” j
policy could mean the demise of thousands Although the approach has been around
of mines and tailings dams (which could be for decades, it’s rarely used, representing
replaced by dams with different designs). just 4% of tailings systems in the pension
Although such a change might be expensive funds’ inventory. Filtered tailings systems
for companies, right now communities near can cost five to 10 times more than a con-
dams are bearing the costs of cheaper con- ventional dam, says Harvey McLeod, a
struction, says Payal Sampat of Earthworks, geological engineer who designs tailings
a nonprofit group that promotes mining re-
forms. “That is unacceptable.”

Some experts caution against a one-size-
fits-all approach. Upstream dams can per-
form safely, particularly in places with dry
climates and few earthquakes, says David
Williams, a geotechnical engineer at the
University of Queensland, St. Lucia. “You
can construct [an upstream dam] to be
perfectly safe. You can also build it in a not
so good way.”

One knowledge gap is an understand-
ing of the forces that can suddenly turn an
earthen dam into a liquid river of mud. At
the Georgia Institute of Technology, geo-
technical engineer Jorge Macedo is stress
testing tailings in his lab to document the
conditions that trigger liquefaction, par-
ticularly in silt, a little-studied material
that is common in tailings used to build
upstream dams.

Other researchers are looking at bet-
ter ways to spot dams on the verge of
failure. Moe Momayez, an engineer and geo-
physicist at the University of Arizona, is test-
ing sensors on an Arizona dam that track
temperature and moisture levels. Some dams

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RED ALERT

Researchers are working to find new
uses for red mud, the caustic byproduct
of aluminum production

By Robert F. Service

P ractical and glamorous, aluminum an additional 150 million tons each year. metals, whereas others turn the mud into ce- PHOTO: BELA SZANDELSZKY/AP PHOTO
is prized for making products from Red mud has become trouble looking for ment or bricks.
kitchen foil and beverage cans
to Tesla Roadsters and aircraft. a place to happen. In 2010, an earthen dam “There is hope here,” says Yiannis
But the silvery metal—abundant, at one waste pond in Hungary gave way, un- Pontikes, a mechanical engineer at the
cheap, lightweight, and corrosion leashing a 2-meter-high wall of red mud that Catholic University of Leuven. But eco-
resistant—has a dark side: red buried the town of Ajka, killing 10 people and nomic and marketing hurdles remain, and
mud. This brownish red slurry, a giving 150 severe chemical burns. (For more “the clock is ticking” as regulators consider
caustic mishmash of metal- and on the dangers posed by waste dams, see p. new controls, says Efthymios Balomenos, a
silicon-rich oxides, often with a dash of ra- 907.) Even when red mud remains contained, metallurgical engineer at the National Tech-
dioactive and rare earth elements, is what’s its extreme alkalinity can leach out, poison nical University of Athens. “At some point
left after aluminum is extracted from ore. groundwater, and contaminate nearby rivers we will not be able to produce waste. So,
And it is piling up. Globally, some 3 billion and ecosystems. Such liabilities, as well as there is an urgent need to make changes.”
tons of red mud are now stored in massive growing regulatory pressure on industry to
waste ponds or dried mounds, making it develop sustainable practices, have catalyzed ALUMINUM IS ONE of the most commonly
one of the most abundant industrial wastes global efforts to find ways to recycle and re- recycled materials, with 75% of all alumi-
on the planet. Aluminum plants generate use red mud. Some researchers are develop- num ever produced still in use. But there
ing ways to extract the valuable rare earth is an ever-burgeoning demand. Aluminum

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NEWS | FEATURES | MUD

A worker inspects ponds dium, a rare earth metal used to strengthen and bake the mixture in a furnace, they can
holding 30 million tons of red metal alloys. Researchers have recently make bricks able to withstand 80 megapas-
shown that scandium-aluminum alloys are cals of compressive force, 40 times more
mud at an aluminum plant as much as 40% stronger than pure alumi- than conventional bricks. They’re now look-
in Hungary. A 2010 spill from num. That has manufacturers eagerly eye- ing to scale up the technique, which could
ing the alloy; aircraft manufacturers, for be used to make everything from roofing
the ponds killed 10 people. instance, could use it to build planes that tiles to sidewalk pavers.
have lighter aluminum framing and burn
production starts with mining bauxite, a less fuel. But scandium currently costs Because of its chemistry, red mud can also
rock rich in aluminum oxide that also con- $3500 per kilogram, so there’s plenty of in- capture and lock away carbon dioxide (CO ),
tains a wealth of other elements, includ- centive to find new, cheaper sources.
ing silicon, iron, and titanium. Workers 2
extract the aluminum with a combination Scientists have come up with several
of treatments, including caustic chemicals, ways to purify scandium from red mud. the major climate warming gas. In Australia,
heat, and electricity. What remains is usu- Balomenos’s group, for example, has shown aluminum producer Alcoa bubbles CO into
ally red, because of the iron, but its exact it can use both sulfuric acid and compounds
makeup can vary from region to region, de- called ionic liquids to extract the rare earth. 2
pending on the ore, making it still harder Ultimately, red mud could meet 10% of Eu-
to contend with. “The composition of [red rope’s demand for scandium, Balomenos red mud, creating a mild acid that reacts
mud] varies so much it means one [type says. Rusal, one of the largest aluminum with the alkaline waste, forming carbon-
of solution] will not work,” says Brajendra producers in the world, is already building ate minerals that turn the red mud into red
Mishra, a materials scientist at the Worces- a pilot plant that uses related methods to sand that can be used to level road beds. The
ter Polytechnic Institute. extract scandium from red mud at one of company estimates that the red mud from a
its facilities in the Ural Mountains of Rus- single aluminum refinery can lock up 70,000
One approach that does seem to be work- sia. But scandium makes up only about 140 tons of CO per year, equivalent to taking
ing is tapping red mud as a source of scan- parts per million of red mud, Pontikes notes,
so “99.99% of the residue” still remains. 2

OTHER APPROACHES aim to use more of more than 15,000 cars off the road.
the waste. One idea is to harness red mud,
which is typically 40% to 70% iron oxide, YET THESE GLIMMERS of progress could fade,
to make iron-rich cements. The world uses Balomenos says, just as earlier hopes have.
more than 4 billion tons of cement per year, Since 1964, he notes, researchers have pat-
mostly as the binder in concrete. The most ented some 700 uses for red mud, includ-
common version is Portland cement, made ing tapping it to make decorative ceramics,
from calcium silicates that react with water dyes, and even fertilizer. Yet just 3% of red
to make create a tough, hard matrix. mud is currently recycled.

But in 2015, researchers in New Zealand One major reason is that many schemes
reported that by adding a common cement envision using red mud to make commodi-
additive called silica fume to red mud, ties that are already cheap and produced
together with a modest amount of iron, with methods that have been optimized
they could create a cement with roughly over a century or more. In addition, red
the same hardness as Portland cement. mud isn’t easy to handle. The iron industry
Pontikes and his colleagues are working to has shied away from extracting the metal
extend these findings, by developing recipes from it, for example, because the caustic
that would enable manufacturers to make waste destroys key components in their
cement from a wide range of red muds smelters. “The industry has iron ore avail-
with varying iron concentrations. The team able with much better quality,” Mishra says.
hopes red mud could become a source of
both the extra iron added to their cements Balomenos argues that countries could
and the alkaline compounds needed to cata- push progress by establishing zero waste
lyze the hardening reactions. mandates for aluminum makers, or other in-
centives that force companies to recycle red
In the meantime, Pontikes’s lab is already mud instead of letting it pile up. The Euro-
producing about 1000 kilograms of iron- pean Union has considered instituting a tax
rich cements per day. They’ve even used on waste deposited in landfills, for example.
their product for demonstration projects, But it hasn’t done so, and there appears to
such as a 2-ton staircase made with ultra– be little appetite elsewhere for similar ideas.
high-strength concrete. “This is no longer a
lab-scale endeavor,” Pontikes says. He’s be- Another obstacle, Balomenos says, is in-
gun to talk with companies about making ternational opposition to allowing hazard-
the cement on an industrial scale. ous materials to cross borders. As a result,
it can be cumbersome and costly to move
Red mud could form the basis for other red mud that contains even trace amounts
construction materials. Pontikes and his of heavy metals or radioactivity. For now, he
team have found that if they add about says, simply putting the waste in a landfill is
10% clay and silicate minerals to red mud both cheaper and far simpler.

Finally, there is the question of con-
sumer acceptance. Even if scientists and
engineers manage to come up with a suite
of practical uses for red mud, consumers
still have the final say in whether they will
buy products with such a noxious start-
ing point. “Will you use roofing tiles made
with red mud?” Pontikes asks. “It’s up to
the market to say ‘yes.’” j

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POLICY FORUM

VACCINES: COVID-19 be critical for the current crisis but could also
create the foundation for fewer siloes, im-
Knowledge transfer for large- proved standardization, and less secrecy over
scale vaccine manufacturing manufacturing information in the future.

Massive, rapid production will require firms to share METHODS, KNOW-HOW, AND SECRECY
know-how not just about what to make but how to make it Knowledge transfer can facilitate manufac-
turing scale-up in multiple contexts. Most
By W. Nicholson Price II1,2, Arti K. Rai3, cess to knowledge not contained in patents straightforwardly, other firms may need to PHOTO:BAY ISMOYO/AFP VIA GETTY IMAGES
Timo Minssen2 or in other public disclosures; one reason for manufacture the “winning” vaccine of an
the expense and delay historically associated originator firm under some form of license
A s the world rushes to identify safe and with entry of biosimilars into the market that encompasses transfer of know-how.
effective vaccines and therapeutics to has been the cost and time associated with Knowledge of one firm’s processes can also
counter the coronavirus disease 2019 reverse engineering originator firms’ manu- facilitate the manufacturing efforts of firms
(COVID-19) pandemic, attention is facturing processes (2). But a change may with other vaccines, particularly if the vac-
turning to the next step: manufactur- be coming. A group of six biopharmaceuti- cines use the same manufacturing platform.
ing these products at enormous scale. cal firms researching monoclonal antibody And sometimes, a firm may even need knowl-
To speed up the process, firms are even es- (mAb) candidates recently sought [and the edge held by others to make its own prod-
tablishing manufacturing capacity “at risk,” U.S. Department of Justice (DOJ) granted] uct in large quantities. For example, Inovio
before products receive regulatory approval permission under antitrust law to exchange claimed in a June court filing that its own ex-
(1). Yet for at least some complex COVID-19 “technical information” on each other’s man- perimental vaccine is being held “hostage” by
vaccines and biological therapeutics, fast ufacturing processes and platforms (but not a contract manufacturer that refuses to share
manufacturing, particularly of products information on cost or price) (3). A focus on manufacturing details (4).
originally developed by other firms, will re- rapid information exchange of the sort re-
quire not only physical capacity but also ac- cently encouraged by the DOJ will not only One might reasonably ask why robust
dissemination of manufacturing knowledge
for complex biologics is only beginning to
emerge, given the longstanding dominance
of patenting in biopharmaceutical innova-
tion and the legal requirement that patents

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Workers prepare a production line at the Bio Farma specific stocks of knowledge about how to typically requires the extensive codification
Pharmacy in West Java to produce a COVID-19 make products. of tacit manufacturing knowledge.
coronavirus vaccine. Sharing of manufacturing
know-how across firms will be critical. Greater sharing of firm-specific manufac- Where knowledge is already explicit
turing knowledge—as well as firm-specific and codified, whether in regulatory filings
disclose how to make the products they and otherwise secret manufacturing precur- or elsewhere, that knowledge should be
cover. Regrettably, for reasons related to the sors, such as cell lines and production soft- shared, at least as a club good within the
early timing of when patent applications are ware—help the information ecosystem gener- universe of major industry players working
filed and failure on the part of patent offices ally. Especially for more established platforms, to develop COVID-19 vaccines or, ideally,
to enforce disclosure obligations, patents on knowledge transfer could promote standard- even more broadly. If explicit knowledge is
biologic products often fail to disclose neces- ized best practices across the industry. Newer codified in patents, pooling of those patent
sary manufacturing information (2). technologies could also benefit from greater rights or other licenses should also be pur-
background or case-specific knowledge. For sued, although patents surrounding manu-
Reliance on manufacturing secrecy (in- example, even mRNA vaccines, which should facturing processes generally reveal little
cluding secrecy that improperly overlaps be simpler to make than traditional vaccines information and are therefore particularly
with patent protection over the manufac- (7), appear to have involved technology trans- unhelpful as a vehicle of knowledge trans-
tured products) is not specific to the phar- fer—that is, transfer of both knowledge and fer for manufacturing (2). And where tacit
maceutical industry. But secrecy in other material—to other firms (8). And nongov- knowledge has not been codified at all, col-
industries has generally been more time- ernmental organizations (NGOs) such as the laboration should include efforts to explore
limited than it has been with complex bio- Coalition for Epidemic Preparedness (CEPI) and share such tacit knowledge.
logics. In the latter case, the combination of appear to build into their funding contracts
tight regulatory control over biologic prod- provisions for technology transfer to addi- INCENTIVES, ACTORS, AND REALPOLITIK
ucts and complex and sometimes idiosyn- tional parties that may be needed to perform Several entities might facilitate this type of
cratic manufacturing methods has slowed manufacturing (1). Similarly, an 11 August knowledge transfer, at least if they could pro-
both competition and innovation. 2020 Securities and Exchange Commission vide the right incentives and potentially the
filing by the firm Moderna indicates that administrative infrastructure for such shar-
To be sure, product lines differ, and cri- at least some U.S. government contracts ing to occur. In determining the best facili-
ses can be valuable catalysts. As noted, in build in provisions for technology transfer tators, international aspects are key because
the case of mAbs and the COVID-19 crisis, in the event of the firm’s decision to termi- knowledge transfer will necessarily occur
large biopharmaceutical firms are now nate production. across borders.
willing to share—and perhaps ultimately
standardize on the basis of—information Although individual contracts that antici- Existing international organizations are
that they might previously have viewed as pate technology transfer are important, when one set of candidates. WHO is currently pro-
providing at least some competitive advan- the products that will ultimately be made at moting the idea of a COVID-19 intellectual
tage (5). The available evidence suggests, scale are as-yet unidentified, broader efforts property (IP) pool (10). Although patents
however, that vaccine manufacturing still to ensure their eventual scalability should seem not to be the key barrier to successful
lacks standardization, even within manu- happen as quickly as possible so that all scale-up, the pool as organized does include
facturing platforms (6). And some new vac- potential manufacturers are prepared once provisions related to nonpatent knowledge
cine technology platforms, such as mRNA, the right candidates are identified. This is transfer. Under the proposal, any govern-
have never been manufactured at scale. particularly true given U.S. government pro- ment, pharmaceutical company, or organiza-
Given this variation, the persistence of se- nouncements that capacity established dur- tion developing COVID-19 vaccines or tests
crecy is unsurprising. ing the scale-up for potential vaccines will be could transfer its IP to WHO on a voluntary,
used regardless of which firm has developed uncompensated basis. It is unclear how
But maintaining pervasive secrecy for capacity, requiring the ability to retrofit and much uncompensated transfer of know-how
manufacturing COVID-19 vaccines during adapt facilities to products different from this pool will receive, and there appears to be
the pandemic could cause dramatic failure. their initial design parameters. some industry resistance (11).
Relevant information for quick and effective
scale-up must be readily available. Vaccines As with mAbs, we see signs in the vac- National governments can and should
are being developed in a massively paral- cine context that some firms are open to also address issues of knowledge transfer.
lel fashion; the World Health Organization more collaboration and knowledge-sharing Although the rhetoric of war on the virus
(WHO) reports that as of 31 July 2020, there than in the ordinary course. Sanofi and might suggest all-out government coordina-
are 26 candidates in clinical evaluation and GlaxoSmithKline have entered a collabora- tion along the lines of the U.S. government’s
139 candidates in preclinical evaluation. tion for the development of a joint vaccine, mass production of penicillin during World
Preparations for manufacturing scale-up of which likely requires at least some technol- War II (12), it is unclear how broadly the cur-
vaccines are taking place before a single ef- ogy transfer about production of the under- rent federal government will invoke its more
fective vaccine has been identified, let alone lying vaccine elements (9). Robust knowl- coercive powers. At the moment, the U.S.
multiple vaccines (1). Along the way, firms edge-sharing across platforms and products government, operating primarily through
are developing information about manufac- should be commonplace during the pan- Operation Warp Speed, appears focused on
turing, both of the specific product at issue demic response. using the lure of very substantial funding to
and of vaccine manufacture more generally. secure future supply of various vaccine candi-
This information is added to existing firm- Transferring such knowledge may not be dates. Specifically, the United States has com-
trivial. Aside from the competitive concerns, mitted billions of dollars to multiple vaccine
1University of Michigan Law School, Ann Arbor, MI, USA. some knowledge may be tacit—that is, more manufacturers (Astra-Zeneca, J&J, Novavax,
2Centre for Advanced Studies in Biomedical Innovation Law, context-specific, based on experience, and Moderna, Pfizer, and Sanofi/GSK), with each
University of Copenhagen, Copenhagen, Denmark. 3Duke more difficult to codify. The tacit knowledge contract aiming to secure hundreds of mil-
University Law School and Center for Innovation Policy, concern may be less acute for biopharmaceu- lions of doses and manufacturing platforms
Durham, NC, USA.4University of Copenhagen Faculty of Law, tical products than other goods, however, for ranging from viral vectors (AstraZeneca and
Copenhagen, Denmark. Email: [email protected] the simple reason that regulatory approval

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INSIGHTS | POLICY FORUM

J&J) to RNA (Moderna and Pfizer) to protein which seems more feasible, would leave con- more on its own and confronting the free-
subunit (Novavax and Sanofi/GSK). trol with the originator firm but use the lure
of funds to require early knowledge transfer rider dilemma directly.
Particularly given the U.S. government’s and licensing to third parties necessary for
commitment to use all capacity available, adequate scale-up and production—knowl- Of course, transformation is easy to call
regardless of the winner vaccine(s), a gov- edge transfer that occurred even before the
ernment commitment could usefully require product was a clear success. for and difficult to achieve. Even without
transfer of manufacturing know-how across
firms with which it has contracted. A con- It is possible, perhaps even likely, that transformation—that is, in the scenario in
tract manufacturing firm to which the U.S. some or all of the ongoing efforts to facili-
government has given hundreds of millions tate product development and manufactur- which pharmaceutical companies main-
of dollars, Emergent Biosolutions, is already ing may already include provisions to foster
committed to manufacturing for J&J, Astra- knowledge transfer, including codification tain secrecy over manufacturing informa-
Zeneca, and Novavax and could therefore of tacit knowledge and the sharing of other-
serve as a natural locus for such knowledge wise-secret manufacturing process informa- tion that does not relate to COVID-19 vac-
transfer. Of course, like the exchange of tion. Certainly, the recent activity by manu-
mAb manufacturing information recently facturers of mAbs suggests a recognition that cines and therapeutics—one-time sharing
approved by DOJ, such transfer would be knowledge transfer is important. However,
limited to a few firms. And unlike the DOJ unlike the business review letter from DOJ, of knowledge could still advance the field’s
process, any process that may be occurring the contracts that have been executed by
through Warp Speed is not transparent (13), Warp Speed are not public. Although the collective understanding. Such an outcome
which might be highly problematic from a NGO Knowledge Ecology International has
competition and antitrust law perspective. used Freedom of Information Act requests to would be a missed opportunity for long-
secure outlines of a few contracts, almost all
Regional organizations could also facili- key information is redacted as commercially term broader change but would still carry
tate knowledge transfer. For example, given confidential. Ironically, this may include in-
the substantial resources that the European formation on knowledge sharing. substantial benefits, even outside those
Union (EU) has committed to a vaccine and
the EU’s demonstrated commitment to data BROADER IMPLICATIONS arising from improved manufacturing dur-
sharing and willingness to allow some phar- Although the issues described here apply
maceutical sector cooperation under EU most directly to COVID-19 vaccines and ing the pandemic.
competition law, the EU might be well suited therapeutics, a push for information shar-
to using the lure of funding to nudge firms ing of manufacturing know-how could have Whatever the long-term effects on indus-
toward knowledge transfer (14). Ideally, this broader positive effects across the industry.
would be done through a transparent process Where highly complementary skill sets and try innovation, the most important goal is
such as the DOJ review letter. know-how are brought to the table and more
problematic collaborations on costs and to make high-quality vaccines for COVID-19
NGOs could also be an option for facili- prices are excluded, as specified in the recent
tating knowledge transfer. NGOs such as DOJ letter, this can also have a positive effect available as quickly and broadly as possible.
CEPI are providing funding for some vaccine on competition in the sector. However, where
candidates; they could condition receipt of the know-how of foreign companies is part of To pursue that goal and to promote global
funds on the contribution of manufacturing the deal, such as in the recent U.S. mAb agree-
knowledge to a central pool of information. ment, the long-term effects on fair global solidarity and reciprocity, the policy-makers
Even if NGOs were not able to bargain for competition and international sensitivities
such general sharing, if each agreement in- should also be considered very carefully. and companies jointly engaged in the world-
cludes a requirement to provide knowledge
transfer to other manufacturers funded by In the most transformative scenario, ro- wide race to develop CoVID-19 drugs and
the NGO, such provisions would widen the bust sharing of manufacturing information
base of available knowledge. This approach in the current crisis could drive more robust vaccines should share information about how
has worked in the past in the semiconduc- sharing of such information more gener-
tor industry, where the U.S. government–led ally. Rather than relying on secrecy to limit to actually make them. j
partnership SEMATECH increased knowl- competition in the underlying products,
edge transfer across the industry (15). firms could share basic information about REFERENCES AND NOTES
manufacturing processes, enabling greater
Whatever the facilitator, the knowledge innovation, flexibility, and quality. Outside 1. N. Lurie, M. Saville, R. Hatchett,J. Halton, N. Engl.J. Med.
transfer could take different forms. One the COVID-19 context, the current levers for 382, 1969 (2020).
model would provide open access to essen- maintaining exclusivity in the underlying
tial information—including patents, know- products—patents and regulatory market 2. W. N. Price 2nd,A. K. Rai, Science 348, 188 (2015).
how, and critical components—to all com- and data exclusivity—could still shape com- 3. “U.S. clears way for drugmakers to share COVID anti-
ers, without need of licensing. This would petition rather than manufacturing secrecy,
maximize access but decrease private sector which impedes any transfer of information body capacity,”New York Times, 23 July 2020.
incentives and strikes us as politically chal- outside firms. Sharing in the pandemic could 4. C. Koons, S. Decker,“Inovio tells court supplier is holding
lenging. Another would leave all knowledge catalyze an industry-wide move to a high-
transfer to purely private mechanisms (if information, high-innovation state of manu- covid vaccine‘hostage,’”Bloomberg, 3 June 2020; www.
permitted by antitrust authorities). But his- facturing, overcoming the collective action bloomberg.com/news/articles/2020-06-03/inovio-
tory suggests that purely private mecha- problem inherent in any one firm disclosing tells-court-supplier-is-holding-covid-vaccine-hostage.
nisms are unlikely to transfer enough knowl- 5. B. Kelley, Nat. Biotechnol. 38, 540 (2020).
edge quickly. An intermediate position, 6. D. Hosangadi et al., Vaccine 38, 4167 (2020).
7. N.A. C.Jackson, K. E. Kester, D. Casimiro, S. Gurunathan,
F. DeRosa npj, Vaccines 5, 11 (2020).
8. “Moderna and Lonza announce worldwide strategic
collaboration to manufacture Moderna’s vaccine
(mRNA-1273) against novel coronavirus,”press release,
1 May 2020; https://investors.modernatx.com/
news-releases/news-release-details/moderna-and-
lonza-announce-worldwide-strategic-collaboration.
9. D. Roland,“GlaxoSmithKline, Sanofi team up for corona-
virus vaccine,”Wall Street Journal 14 April 2020.
10. E. Silverman WHO embraces plan for Covid-19
intellectual property pool, Stat 15 May 2020;
www.statnews.com/pharmalot/2020/05/15/
who-covid19-coronavirus-patents-intellectual-property.
11. E. Silverman Pharma leaders shoot down
WHO voluntary pool for patent rights on
Covid-19 products, Stat 28 May 2020; www.
statnews.com/pharmalot/2020/05/28/
who-voluntary-pool-patents-pfizer.
12. P. Neushul, J. Hist. Med. 48, 371 (1993).
13. K. Blankenship,“Warp Speed initiative aims for COVID-
19 vaccine production within 6 weeks,”Fierce Pharma
14 July 2020; www.fiercepharma.com/manufacturing/
trump-administration-hopes-for-covid-19-shot-manu-
facturing-to-start-within-6-weeks.
14. E. U. Commission,“EU vaccines strategy,”
31 July 2020; https://ec.europa.eu/info/
live-work-travel-eu/health/coronavirus-response/
public-health_en#eu-vaccines-strategy.
15. L. D. Browning,J. M. Beyer,J. C. Shetler, Acad. Manage.J.
38, 113 (1995).

ACKNOWLEDGMENTS

W.N.P. and T.M. were supported by the Novo Nordisk
Foundation (NNF17SA0027784).We thank J. Barnes-Weise of
the Global Health Innovation Alliances Accelerator for com-
ments on an earlier draft.

Published online 13 August 2020

10.1126/science.abc9588

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PERSPECTIVES

ARTIFICIAL INTELLIGENCE

The foundation
of efficient
robot learning

Innate structure reduces General-purpose robots are being designed to help with domestic tasks. However, developing the learning
data requirements applications needed to allow robots to undertake even simple tasks is extremely challenging.
and improves robustness

By Leslie Pack Kaelbling

PHOTO: MICHAEL BAHLO/EPA/SHUTTERSTOCK T he past 10 years have seen enormous The original inspirations for RL were mod- enabled in an intelligent system? Modern
breakthroughs in machine learn- els of animal behavior learning through re- neural networks have been shown to be ef-
ing, resulting in game-changing ap- ward and punishment. If RL is to be applied fective at interpolating: Given a large num-
plications in computer vision and to interesting real-world problems, it must ber of parameters, they are able to remember
language processing. The field of be extended to handle very large spaces of the training data and make reliable predic-
intelligent robotics, which aspires to inputs and actions and to work when the re- tions on similar examples (4). To obtain
construct robots that can perform a broad wards may arrive long after the critical action generalization, it is necessary to provide “in-
range of tasks in a variety of environments was chosen. New “deep” RL (DRL) methods, ductive bias,” in the form of built-in knowl-
with general human-level intelligence, has which use complex neural networks with edge or structure, to the learning algorithm.
not yet been revolutionized by these break- many layers, have met these challenges and As an example, consider an autonomous
throughs. A critical difficulty is that the nec- have resulted in stunning performance, in- car with an inductive bias that its braking
essary learning depends on data that can cluding solving the games of chess and Go strategy need only depend on cars within
only come from acting in a variety of real- (2) and physically solving Rubik’s Cube with a bounded distance of it. Such a car’s intel-
world environments. Such data are costly to a robot hand (3). They have also seen use- ligence could learn from relatively few ex-
acquire because there is enormous variabil- ful applications, including energy efficiency amples because of the limited set of possible
ity in the situations a general-purpose robot improvement in computer installations. On strategies that would fit well with the data
must cope with. It will take a combination the basis of these successes, it is tempting to it has observed. Inductive bias, in general,
of new algorithmic techniques, inspiration imagine that RL might completely replace increases sample efficiency and generaliz-
from natural systems, and multiple levels of traditional methods of engineering for robots ability. Compositionality and incrementality
machine learning to revolutionize robotics and other systems with complex behavior in can be obtained by building in particular
with general-purpose intelligence. the physical world. types of structured inductive bias, in which
the “knowledge” acquired through learning
Most of the successes in deep-learning There are technical reasons to resist this is decomposed into factors with independent
applications have been in supervised ma- temptation. Consider a robot that is designed semantics that can be combined to address
chine learning, a setting in which the learn- to help in an older person’s household. The exponentially more new problems (5).
ing algorithm is given paired examples of robot would have to be shipped with a con-
an input and a desired output and it learns siderable amount of prior knowledge and The idea of building in prior knowledge
to associate them. For robots that execute ability, but it would also need to be able to or structure is somewhat fraught. Richard
sequences of actions in the world, a more learn on the job. This learning would have to Sutton, a pioneer of RL, asserted (6) that
appropriate framing of the learning prob- be sample efficient (requiring relatively few humans should not try to build any prior
lem is reinforcement learning (RL) (1), in training examples), generalizable [applicable knowledge into a learning system because,
which an “agent” learns to select actions to many situations other than the one(s) it historically, whenever we try to build some-
to take within its environment in response learned], compositional (represented in a thing in, it has been wrong. His essay incited
to a “reward” signal that tells it when it is form that allows it to be combined with pre- strong reactions (7), but it identified the criti-
behaving well or poorly. One essential dif- vious knowledge), and incremental (capable cal question in the design of a system that
ference between supervised learning and of adding new knowledge and abilities over learns: What kinds of inductive bias can be
RL is that the agent’s actions have substan- time). Most current DRL approaches do not built into a learning system that will give it
tial influence over the data it acquires; the have these properties: They can learn surpris- the leverage it needs to learn generalizable
agent’s ability to control its own exploration ing new abilities, but generally they require a knowledge from a reasonable amount of data
is critical to its overall success. lot of experience, do not generalize well, and while not incapacitating it through inaccu-
are monolithic during training and execution racy or overconstraint?
Computer Science and Artificial Intelligence Laboratory (i.e., neither incremental nor compositional).
and Center for Brains, Minds, and Machines, There are two intellectually coherent strat-
Massachusetts Institute of Technology, Cambridge, MA, How can sample efficiency, generalizabil- egies for finding an appropriate bias, with
USA. Email: [email protected] ity, compositionality, and incrementality be different time scales and trade-offs, that can

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INSIGHTS | PERSPECTIVES

be used together to discover powerful and ing” (MAML), has been reported (10). MAML requires a much smaller number of param-
flexible prior structures for learning agents. is a nested optimization framework in which eters, and hence much less training, than do-
One strategy is to use the techniques of ma- the outer optimization selects initial values ing so without convolutional structure. The
chine learning at the “meta” level—that is, to of some internal neural network weights idea of image convolution comes from both
use machine learning offline at system design that will be further adjusted by a standard engineers and nature. It was a foundational
time (in the robot “factory”) to discover the gradient-descent optimization method in the concept in early signal processing and com-
structures, algorithms, and prior knowledge wild. The RL2 algorithm (11) uses DRL in the puter vision (14), and it has long been under-
that will enable it to learn efficiently online factory to learn a general small program that stood that there are cells in the mammalian
when it is deployed (in the “wild”). runs in the wild but does not necessarily have visual cortex that seem to be performing a
the form of a machine-learning program. similar kind of computation (15).
The basic idea of meta-learning has been Another variation (12) seeks to discover, in
present in machine learning and statistics the factory, modular building blocks (such as It is necessary to discover more ideas like
since at least the 1980s (8). The fundamental small neural networks) that can be combined convolution—that is, fundamental structural
idea is that in the factory, the meta-learning to solve problems presented in the wild. or algorithmic constraints that provide sub-
process has access to many samples of pos- stantial leverage for learning but will not pre-
sible tasks or environments that the system The process of evolution in nature can vent robots from reaching their potential for
might be confronted with in the wild. Rather be considered an extreme version of meta- generally intelligent behavior. Some candi-
than trying to learn strategies that are good learning, in which nature searches a highly date ideas include the ability to do some form
for an individual environment, or even a unconstrained space of possible learning al- of forward search using a “mental model” of
single strategy that works well in all the gorithms for an animal. (Of course, in nature, the effects of actions, similar to planning or
environments, a meta-learner tries to learn the physiology of the agent can change as reasoning; the ability to learn and represent
a learning algorithm that, when faced with well.) The more flexibility there is in the in- knowledge that is abstracted away from indi-
a new task or environment in the wild, will ner optimization problem solved during a ro- vidual objects but can be applied much more
learn as efficiently and effectively as possible. bot’s lifetime, the more resources—including generally (e.g., for all A and B, if A is on top
It can do this by inducing the commonalities example environments in the factory, broken of B and I move B, then A will probably move
among the training tasks and using them to robots in the wild, and computing capacity too); and the ability to reason about three-
form a strong prior or inductive bias that al- in both phases—are needed to learn robustly. dimensional space, including planning and
lows the agent in the wild to learn only the In some ways, this returns us to the initial executing motions through it as well as us-
aspects that differentiate the new task from problem. Standard RL was rejected because, ing it as an organizing principle for memory.
the training tasks. although it is a general-purpose learning There are likely many other such plausible
method, it requires an enormous amount of candidate principles. Many other problems
Meta-learning can be very beautifully and experience in the wild. However, meta-RL re- will also need to be addressed, including how
generally formalized as a type of hierarchi- quires substantial experience in the factory, to develop infrastructure for training both in
cal Bayesian (probabilistic) inference (9) in which could make development infeasibly the factory and in the wild, as well as meth-
which the training tasks can be seen as pro- slow and costly. Thus, perhaps meta-learning odologies for helping humans to specify the
viding evidence about what the task in the is not a good solution, either. rewards and for maintaining safety. It will
wild will be like, and using that evidence be through a combination of engineering
to leverage data obtained in the wild. The What is left? There are a variety of good principles, biological inspiration, learning
Bayesian view can be computationally diffi- directions to turn, including teaching by in the factory, and ultimately learning in
cult to realize, however, because it requires humans, collaborative learning with other the wild that generally intelligent robots
reasoning over the large ensemble of tasks robots, and changing the robot hardware can finally be created. j
experienced in the factory that might poten- along with the software. In all these cases,
tially include the actual task in the wild. it remains important to design an effective REFERENCES AND NOTES
methodology for developing robot software.
Another approach is to explicitly character- Applying insights gained from computer 1. A.Barto,R.S.Sutton,C.W.Anderson,IEEETrans.Syst.
ize meta-learning as two nested optimization science and engineering together with in- Man Cybern.13,834 (1983).
problems. The inner optimization happens in spiration from cognitive neuroscience can
the wild: The agent tries to find the hypoth- help to find algorithms and structures that 2. D.Silver et al.,Science 362,1140 (2018).
esis from some set of hypotheses generated can be built into learning agents and pro- 3. OpenAI,arXiv 1910.07113 (2019).
in the factory that has the best “score” on the vide leverage to learning both in the factory 4. M.Belkin,D.Hsu,S.Ma,S.Mandal,Proc.Natl.Acad.Sci.
data it has in the wild. This inner optimiza- and in the wild.
tion is characterized by the hypothesis space, U.S.A.116,15849 (2019).
the scoring metric, and the computer algo- A paradigmatic example of this approach 5. P.W.Battaglia et al.,arXiv 1806.01261 (2018).
rithm that will be used to search for the best has been the development of convolutional 6. R.Sutton,“The bitter lesson”; www.incompleteideas.net/
hypothesis. In traditional machine learning, neural networks (13). The idea is to design a
these ingredients are supplied by a human neural network for processing images in such IncIdeas/BitterLesson.html.
engineer. In meta-learning, at least some as- a way that it performs “convolutions”—local 7. R.Brooks,“Abetter lesson”; https://rodneybrooks.
pects are instead supplied by an outer “meta” processing of patches of the image using the
optimization process that takes place in the same computational pattern across the whole com/a-better-lesson/.
factory. Meta-optimization tries to find pa- image. This design simultaneously encodes 8. J.Schmidhuber,Evolutionary Principles in Self-Referential
rameters of the inner learning process itself the prior knowledge that objects have basi-
that will enable the learning to work well in cally the same appearance no matter where Learning (Technische Universität München,1987).
new environments that were drawn from the they are in an image (translation invariance) 9. D.Lindley,A.F.M.Smith,J.R.Stat.Soc.B 34,1 (1972).
same distribution as the ones that were used and the knowledge that groups of nearby 10. C.Finn,P.Abbeel,S.Levine,in Proceedings of the 34th
for meta-learning. pixels are jointly informative about the con-
tent of the image (spatial locality). Designing International Conference on Machine Learning (2017),pp.
Recently, a useful formulation of meta- a neural network in this way means that it 1126–1135.
learning, called “model-agnostic meta-learn- 11. Y.Duan et al.,arXiv 1611.02779 (2016).
12. F.Alet et al.,Proc.Mach.Learn.Res.87,856 (2018).
13. Y.Lecun,L.Bottou,Y.Bengio,P.Haffner,Proc.IEEE 86,
2278 (1998).
14. A.Rosenfeld,ACM Comput.Surv.1,147 (1969).
15. D.H.Hubel,T.N.Wiesel,J.Physiol.195,215 (1968).

ACKNOWLEDGMENTS

The author is supported by NSF, ONR,AFOSR, Honda
Research, and IBM. I thank T. Lozano-Perez and students and
colleagues in the CSAIL Embodied Intelligence group
for insightful discussions.

10.1126/science.aaz7597

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BIOMEDICINE bacterium can have several pili. Therefore,

A glycoprotein in urine binds this multitude of interactions causes bac-
terial aggregation, effectively preventing
individual bacterial cells from attaching to

bacteria and blocks infections and infecting the urinary tract. In case of
the E. coli strain studied by Weiss et al.,
the interaction between UMOD and bacte-

Direct imaging of a human fluid illuminates the molecular rial cells occurs through specific binding of
FimH to a glycan at asparagine 275 of the

basis of urinary tract protection from disease UMOD protein (see the figure).
However, UMOD contains several other

complex glycosylation sites whose func-

By Wanda Kukulski The authors show that the armlike struc- tions have not yet been dissected. A com-

tures extending from UMOD filaments in- pelling possibility is that these serve as

H uman urinary tracts are highly teract with FimH. The interaction between binding sites for proteins of other uro-
susceptible to bacterial infections. UMOD and FimH is biochemically strong pathogenic bacteria. In line with this idea,
Pathogenic bacteria initiate infec- and likely leads to stable binding. Indeed, when Weiss et al. imaged urine from pa-
tions by attaching to sugar chains Weiss et al. show that through this bind- tients infected with different bacteria,
(glycans) exposed on the surface of ing, UMOD mediates the stable formation namely Klebsiella, Pseudomonas, and

the urinary tract epithelium (1). It of clumps of bacteria. Streptococcus, the authors found similarly

has long been suspected that uromodu- The suggested mechanism of UMOD- aggregated bacterial cells embedded in

lin (UMOD)—the most abundant protein based defense is notably simple and robust: UMOD filaments. Given its implication

in human urine—prevents bacteria from The abundant UMOD filaments outcom- in various aspects of kidney function (7),

binding to urinary tract glycans, thus de- pete receptors on the urinary tract walls in UMOD might have other molecular roles

fending the organism from such infections binding to bacterial pili. Each flexible fila- that rely on its distinct glycosylation pat-

(2). However, the mechanism underly- ment has multiple binding sites, and each tern or its adoption of a filamentous struc-

ing this protection has remained ture, besides protection from bac-

elusive. Now, on page 1005 of this terial infections.

issue, Weiss et al. reveal, at the Filaments fight infection What has enabled this break-
molecular level, how UMOD fila- through in understanding of the
ments interact with uropathogenic Uromodulin (UMOD) forms filaments that compete with the adhesion association between UMOD and
Escherichia coli cells in human of uropathogens to the urinary tract epithelium. By binding to bacterial uropathogenic bacteria? The care-
pili, UMOD filaments corral uropathogens, block bacterial adhesion

urine (3). These results provide a in the urinary tract, and permit pathogen clearance through urination. ful and systematic mass spectrom-

structural basis for understanding FimH, type 1 fimbrin D-mannose specific adhesin. etry data for the glycosylation map

the protective function of UMOD. Urinary tract laid the foundation for resolving
UMOD forms filaments first visu- this mystery. The key, however,
UMOD flament was the integration of these data
alized by electron microscopy more architecture with cryo–electron tomography
than 60 years ago (4). Despite these

early images, the filaments’ struc- Bacterial (cryo-ET). This electron micros-
tural organization is unknown, pili copy (EM)–based method allows

which is, in part, why the protective UMOD FimH–UMOD one to visualize three-dimensional
role of UMOD has eluded scien- flament interaction architectures of near-natively pre-
tists. An important hint regarding served samples at a resolution
UMOD function came from the fact high enough to see individual

that myriad glycans decorate the Competitive Asn275 FimH macromolecules. Cryo-ET can be
filaments, possibly presenting bac- binding applied to samples that are too ir-
teria with binding opportunities regular, large, or heterogenous for

that compete with glycan receptors cryo-EM, which allows cryo-ET

on the urinary tract walls (5). UMOD to span the range from purified
Weiss et al. deciphered a compre- samples to complex reconstitu-

hensive map of the glycosylation Aggregation tions with diverse components and
pattern of UMOD, the structure of even undisturbed cellular samples.

UMOD filaments, and the nature Bacteria entangled Similar to cryo-EM data, cryo-ET
of bacteria–filament interaction. by UMOD data can be processed by averaging

Infective E. coli cells attach to the structures in subvolumes, thereby

urinary tract epithelium through further increasing the resolution

GRAPHIC: JOSHUA BIRD/SCIENCE needlelike structures called pili. At (8). Whereas cryo-EM is currently

their tip, E. coli type I pili consist Removal revolutionizing structural biology
of the protein FimH (type 1 fimbrin with urine by visualizing protein structures
D-mannose specific adhesin) (6). at atomic resolution (9), cryo-ET
Urinary tract Infection lags behind in terms of resolution,
Institute of Biochemistry and Molecular Medicine, epithelium although for certain structures a
University of Bern, Bühlstrasse 28, 3012 Bern, resolution better than 5 Å can be
Switzerland. Email: [email protected] achieved (10, 11).

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INSIGHTS | PERSPECTIVES

A singular asset of cryo-ET, however, is LIQUID CRYSTALS
its ability to seamlessly investigate a struc-
ture across multiple scales of complexity. When the smallest details count
The power of this approach is demon-
strated impressively in this study. The The type of liquid crystals formed by smooth colloidal rods
authors used cryo-ET followed by subto- depends on their degree of curvature
mogram averaging to determine the archi-
tecture of purified native UMOD filaments By Maria Helena Godinho nematics were also reported. Bent colloidal
and the interaction region between UMOD particles have also been reported to produce
filaments and FimH. They also used cryo- N atural and synthetic micro- and liquid crystalline solutions. Yang et al. (7)
ET to image the binding of bacterial cells nanoparticles—in an appropriate generated suspensions of silica particles that
to UMOD. The visualization of entangled solvent and within a given range of exhibited different smectic structures, includ-
bacteria is particularly notable, as it in- concentration, pressure, and tempera- ing a twisted smectic phase, by controlling
volved direct imaging of unprocessed urine ture—can form colloidal liquid crystal- the bending angle and aspect ratio of the par-
from patients diagnosed with urinary tract line systems that combine the optical ticles, which were different from the curved
infections. properties of crystals (anisotropy) and the systems Fernández-Rico et al. produced.
fluidity of liquids. The particles are largely
Although cryo-ET continues to provide anisotropic, with one or two characteristic Curved filaments are common in nature
unprecedented views of large macromolec- dimensions much larger than the third. The and have inspired theoretical investiga-
particles can also be bent or curved or, if de- tions and functional applications. A straight
“...directly imaging a human rived from natural materials, can have chi- filament converted into a curved shape can
fluid...represents a milestone by ral interactions, all of which can affect how sometimes coil into a helix even when the
demonstrating the potential the particles self-assemble and form liquid filament lacks chirality (8, 9). The intrinsic
of cryo–electron tomography crystalline phases. On page 950 of this issue, curvature was attributed to the existence
for biomedical imaging.” Fernández-Rico et al. (1) report on a simple across the filament of materials with differ-
method allowing the production of large ent mechanical characteristics that contract
ular assemblies and cellular architecture quantities of polydisperse colloidal synthetic asymmetrically. The resulting shapes of the
(12, 13), its application to primary samples rods from a viscous photoresin. They im- filaments depend on diameter, length, and
of human origin is thus far scarce (14). The posed a well-controlled curvature on these boundary conditions at extremities. Long fil-
approach taken by Weiss et al.—to assess rods by fine-tuning the cross-link density of aments tend to generate spirals, if supported
the molecular basis of disease by directly the resin and the temperature. They show by one end, or helical structures, if clamped
imaging a human fluid—is conceptually that curvature has pronounced effects on the at both ends. In the latter case, left- and right-
simple, yet represents a milestone by dem- liquid crystalline phase behavior. handed helices, separated by straight seg-
onstrating the potential of cryo-ET for bio- ments, were observed, so the overall system
medical imaging. Future studies likely will Bawden et al. (2) first reported the forma- was still achiral (see the figure, bottom left).
expand the use of cryo-ET to explore fun- tion of colloidal liquid crystals in aqueous
damental questions on the role of supra- solutions of rodlike tobacco mosaic virus. The tuning of the curvature can be pre-
molecular architecture in human health Later, Onsager (3) used entropic arguments cisely controlled by varying the asymmetric
and disease. j to explain the formation of parallel align- characteristics of the materials existing along
ment (nematic phase) of long, hard rods from the filament. Similar mechanisms imposed
REFERENCES AND NOTES a disorder phase. For ellipsoidal particles, in by asymmetric cross-linking should be at
addition to the nematic phase, helicoidal work in the formation of the curved sphero-
1. G.Zhou et al., J. Cell Sci. 114, 4095 (2001). structures (chiral nematic order), which are cylinders that Fernández-Rico et al. made by
2. F. Serafini-Cessi,A. Monti, D. Cavallone, Glycoconj.J. 22, characterized by the existence of successive cross-linking and heating photoresin rods.
pseudonematic layers that are rotated by a The particles were stiffened by further cross-
383 (2005). small angle about an axis perpendicular to linking, which fixed their curved shapes be-
3. G. L.Weiss et al., Science 369, 1005 (2020). the plane of the layers, were also reported. fore creating colloidal suspensions.
4. K. R. Porter, I.Tamm, J. Biol. Chem. 212, 135 (1955). Colloidal solutions of cellulose nanorods (4)
5. J. Pak,Y. Pu,Z.T.Zhang, D. L. Hasty,X. R.Wu, J. Biol. have a chiral nematic structure that can be Fernández-Rico et al. used confocal mi-
frozen-in (see the figure, top), by removing croscopy to image a series of different liquid
Chem. 276, 9924 (2001). the solvent so that scanning electron micros- crystalline phases obtained from three types
6. E. Hahn et al., J. Mol. Biol. 323, 845 (2002). copy can reveal the layers of the precursor of curved particles. The most interesting
7. O. Devuyst, E. Olinger, L. Rampoldi, Nat. Rev. Nephrol. 13, liquid crystalline phase (5). This helicoidal finding was the first experimental evidence
structure is often found in animals and plants of the nematic splay-bend phase, in which
525 (2017). and is interpreted by a twisted plywood the less-curved polydisperse particles were
8. S. Pfeffer,J. Mahamid, Trends Cell Biol. 21, 11 (2018). model proposed by Bouligand (6). Similarly, organized in a serpentine undulated struc-
9. E. Callaway, Nature 582, 156 (2020). for spherocylinders (cylinders capped with ture (see the figure, bottom right). Only the
10. F. K. Schur et al., Science 353, 506 (2016). a hemisphere on both ends), smectic phases less curved particles are at the origin of the
11. A. von Kügelgen et al., Cell 180, 348 (2020). with layered structures more ordered than splay-bend phase. More curved particles
12. J. Mahamid et al., Science 351, 969 (2016). generate liquid crystalline phases described
13. M.A.Jordan, D. R. Diener, L. Stepanek, G. Pigino, Nat. Cell Centro de Investigação de Materiais–I3N (CENIMAT/I3N), previously for molecular banana-shaped mol-
Department of Materials Science, Faculty of Science and ecules (10) and colloidal rods. Thus, small
Biol. 20, 1250 (2018). Technology, University NOVA of Lisbon, Campus da Caparica, details had large effects on the packing of
14. A.Al-Amoudi, D. C. Díez, M.J. Betts,A. S. Frangakis, 2829-516 Caparica, Portugal. Email: [email protected] the particles, in accord with theoretical pre-
dictions (11). Indeed, the smectic phase was
Nature 450, 832 (2007).

ACKNOWLEDGMENTS
W.K. is supported by the National Centre of Competence in
Research (NCCR) TransCure and the University of Bern.

10.1126/science.abd7124

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predicted to be destabilized if polydisperse, liquid crystals, including the twist-bend nem- MEDICINE
smooth curved particles were used to pro-
duce the colloidal suspensions. However, in atic. Chiral particles could further enhance Remodeling
the work of Fernández-Rico et al., there was vasculature to
no evidence for the twist-bend nematic phase this class of smooth curved colloidal particles avoid blindness
(see the figure, bottom right). This phase is
characterized by the simultaneous assembly and generate new phases. The optical proper- Pathological vasculature
of curved particles into right and left helices marks itself for repair
to form an achiral system, as has been seen in ties and response to external fields of these by deploying neutrophil
thermotropic molecular liquid crystals (12). extracellular traps
phases may form the basis for future studies
Through precise control of the curvature By Eugene A. Podrez and Tatiana V. Byzova
of the particles, Fernández-Rico et al. could that cannot be carried out for molecular liq-
tune the sequence of phases that includes not V ascular remodeling is essential for
only the splay-bend phase but also the biaxial uid crystalline phases. j building hierarchically structured
nematic and smectic phases. For small cur- vascular networks, which in turn
vature, the microparticles self-assemble into REFERENCES AND NOTES support proper organ function (1).
nematic and smectic phases as the concentra- The retina is particularly depen-
tion of the solvent decreases. As the value of 1. C. Fernández-Rico et al., Science 369, 950 (2020). dent on optimal blood supply, and
the curvature increases, the splay-bend nem- 2. F. C. Bawden, N.W. Pirie,J. D. Bernal, I. Fankuchen, insufficient or excessive vasculature often
atic phase disappears. At the highest curva- leads to blindness. The process of vascular
ture (almost circular arcs), only the isotropic Nature 138, 1051 (1936). regression reduces blood vessel density, fa-
phase develops. 3. L. Onsager, Ann. N.Y.Acad. Sci. 51, 627 (1949). cilitating normalization of vasculature and
4. J. F. Revol et al., Liq. Cryst. 16, 127 (1994). subsequent tissue repair (2). Regression is
The study of Fernández-Rico et al. makes 5. A. P. C.Almeida et al., Adv. Mater. 30, 1703655 (2018). either caused by the withdrawal of essential
possible the production of a range of nematic 6. Y. Bouligand, C. R.Acad. Sci. Hebd. Seances Acad. Sci. D vascular growth factors or by triggering en-
colloidal liquid crystals. Theoretical predic- dothelial apoptosis and subsequent pruning
tions suggest that tuning the curvature and 261, 4864 (1965). of vasculature (3). However, it is unknown
the interactions with the boundaries could 7. Y.Yang et al., J.Am. Chem. Soc. 138, 68 (2016). how dysfunctional and excessive retinal
lead to phases not yet observed for colloidal 8. S.J. Gerbode,J. R. Puzey,A. G. McCormick, L. blood vessels are selected and marked for
pruning. On page 934 of this issue, Binet et
Mahadevan, Science 337, 1087 (2012). al. (4) reveal that pathological vasculature
9. P. E. S. Silva, F.Vistulo de Abreu, M. H. Godinho, Soft in the retina of mice and humans orches-
trates its own remodeling by promoting the
Matter 13, 6678 (2017). extrusion of neutrophil extracellular traps
10. A.Jákli, O. D. Lavrentovich,J.V. Selinger, Rev. Mod. Phys. (NETs). This mechanism might be applied
to other pathologies that require vascular
90, 045004 (2018). remodeling, such as cancer, pulmonary hy-
11. I. Dozov, Europhys. Lett. 56, 247 (2001). pertension, and heart disease (3).
12. D.A. Paterson et al., Soft Matter 12, 6827 (2016).
Retinal ischemic diseases, such as reti-
ACKNOWLEDGMENTS nopathy of prematurity and diabetic reti-
nopathy, are triggered by insufficient vascu-
M.H.G. is supported by the Portuguese Foundation lature, leading to ischemia (lack of oxygen),
for Science and Technology under project nos. UID/ which is compensated for by excessive
CTM/50025/2019 and M-ERA-NET2/0007/2016 (CellColor) production of vascular growth factors, pri-
and by the European Topology Interdisciplinary Action marily vascular endothelial growth factor
(EUTOPIA CA17139). (VEGF). This leads to overgrowth of misdi-
rected and leaky vasculature, with signs of
10.1126/science.abd3548 vascular deterioration and senescence (in
which cells stop dividing and become dys-
Liquid crystals from smooth curved colloidal systems functional) stimulated by aging or stress,
similar to processes observed in tumors (3).
Fernández-Rico et al. found that different liquid crystals form from microrods with different degrees Regression of this excessive and pathologi-
of curvature. Natural systems such as cellulose nanorods form liquid crystals but have a chiral nature. cal vasculature is a necessary step to avoid

Cellulose-nanorod chiral nematics Lerner Research Institute, Cleveland Clinic, Cleveland, OH,
USA. Email: [email protected]
Solutions of cellulose nanorods form a nematic liquid crystalline phase that has a chiral twist.

1 mm 400 nm

Scanning electron microscopy images Helicoidal structure
Curved solid lines are equidistant twisted layers and arcs The twisted plywood model, proposed
(red, left), and the “peaks” (right) can be attributed to the by Bouligand (6), accounts for the
fracture of the twisted layers. helicoidal nature of the layers and arcs.

GRAPHIC: C. BICKEL/SCIENCE; (PHOTOS) M. H. GODINHO Long-curved flaments

Similar structures are formed in certain liquid crystal phases.

Curved phases NTB

Left-handed Slightly curved rods Right
twist twist
organize in a nematic
Right-
handed twist splay-bend (NSB) phase Plane
(right). No microrod

studied (1) led to the

Curved structures nematic twist bend (NTB) Left
Long flaments can exhibit left- and phase that can switch twist
right-handed helices or spirals.
from right- to left- NSB

handed helices (left).

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INSIGHTS | PERSPECTIVES

chronic inflammation and to en- Vascular senescence facilitates tissue repair the SASP signature includes pro-
sure tissue repair. Thus, a pre- angiogenic factors that promote
cise understanding of the exact Dysfunctional senescent retinal vasculature produces senescence- vascularization in tumors (9) and
molecular mechanisms governing associated secretory phenotype (SASP) components, attracts in age-related diseases, including
vascular regression in retinal and neutrophils, and stimulates the extrusion of neutrophil extracellular retinopathy (11). In tumors, SASP
traps (NETosis, see photo below). This causes endothelial cell

other diseases is of the utmost apoptosis and vascular pruning, which is essential for vascular repair facilitates drug delivery, thus mak-

clinical importance. and tissue recovery in ischemic retinopathy. ing tumors vulnerable to chemo-

Using high-resolution droplet- NETosis therapy (9). In proliferative dia-
based RNA sequencing and sophis- betic retinopathy, however, SASP

ticated bioinformatics approaches Neutrophil cytokines such as IL-6, IL-8, and
in animal models of retinopathy, VEGF directly promote pathologi-

Binet et al. were able to effectively NETS cal vascular growth, delaying tis-
tease out the main players of vas- sue repair (11). However, similar to
cular regression at the molecular, Endothelial apoptosis Binet et al., studies found benefi-

cellular, and tissue levels. They cial roles of SASP in tissue growth

showed in mice and humans that SASP (8) and wound healing (12) as in-
the entire process relies on the ducers of stem-like characteristics
Vascular normalization

innate immune system, namely Senescent of keratinocytes, driving epithelial
neutrophils, which are deployed vasculature regeneration (13).
during the late phase of retinal
It is notable that the retinal

disease, which is associated with vasculature activates a “self-cor-

vascular regression rather than recting” program by acquiring the

vascular growth. SASP. Binet et al. demonstrate that

Neutrophils serve as a first line Tissue repair the SASP signature is associated
of innate immunity against patho- with activation of RAS pathways

gens by means of oxidative burst, within a population of senescent

phagocytosis, and release of web- retinal endothelial cells. In cancer,

like DNA and protein structures proangiogenic SASP components

called NETs. Besides their origi- are the result of inhibition rather

nally defined role in pathogen de- than activation of the KRAS path-

fense (5), NETs also mediate severe way (9). Nevertheless, even in can-

inflammatory reactions of primar- cer, SASP promotes therapeutically

ily a destructive nature, such as beneficial vascular remodeling.

cancer metastasis and tissue and Together, these results support the CREDITS: (PHOTO) SCIENCE PHOTO LIBRARY/SCIENCE SOURCE; (GRAPHIC) ADAPTED FROM T. V. BYZOVA BY MELISSA THOMAS BAUM/SCIENCE

organ damage within the vascu- concept that cellular senescence

lar, pulmonary, and renal systems has substantial value as a therapeu-

(6). Most recently, NETs have been tic target in a variety of disorders

implicated in organ damage and associated with vascular dysfunc-

other complications of coronavi- tion, and that induction of vascu-

rus disease 2019 (COVID-19) (7). lar senescence is a prerequisite for

Binet et al. show that during the vascular remodeling and optimi-

process of retinal vascular repair, zation. Moreover, because most of

NETs perform a very different the vasculature requires active and

function of marking senescent vas- uninterrupted maintenance, this

cular branches for pruning (see the figure). not only in aging but also during develop- senescence-induced regression and remod-

Under different circumstances, this tag- ment (8) and in actively growing tissues eling aided by neutrophils might also be ap-

ging for destruction might lead to impaired such as tumors (9). In diseased retinas, this plicable to vascular homeostasis. j

blood supply and eventually to organ fail- senescence-associated secretory phenotype REFERENCE AND NOTES
ure; however, in ischemic retinopathy, this (SASP) is observed in endothelial cells, peri-
process serves an essential prerequisite for cytes, astrocytes, and Müller glia but not in 1. A. R. Pries,T.W. Secomb, Physiol. 29, 446 (2014).
tissue repair. It remains to be determined retinal ganglion cells (which connect pho- 2. E. C.Watson,Z. L. Grant, L. Coultas, Cell. Mol. Life Sci. 74,
whether this role of NETs is restricted only tosensitive cells in the retina to the optic
to tissues of primarily postmitotic nature, nerve), which are also known to undergo se- 4387 (2017).
such as the retina and central nervous sys- nescence. Together, these findings indicate 3. C. Korn, H. G.Augustin, Dev. Cell 34, 5 (2015).
tem, or whether it also operates in other that various types of senescent cells might 4. F. Binet et al., Science 369, eaay5356 (2020).
pathologies, such as neoplasms, or even be able to attract neutrophils and deploy 5. V. Brinkmann et al., Science 303, 1532 (2004).
whether it might underlie developmental NETs. It will be interesting to explore why 6. V. Papayannopoulos, Nat. Rev. Immunol. 18, 134 (2018).
vascular restructuring. only certain types of senescent cells pro- 7. B.J. Barnes et al., J. Exp. Med. 217, e20200652 (2020).
mote NETs. 8. D. Muñoz-Espín et al., Cell 155, 1104 (2013).
Involvement of NETs in other patholo- 9. M. Ruscetti et al., Cell 181, 424 (2020).
gies seems to be likely because NETosis is Acquisition of a SASP signature is be- 10. J. Sabbatinelli et al., Front. Physiol. 10, 1523 (2019).
11. M. Oubaha et al., Sci.Transl. Med. 8, 362ra144 (2016).
12. M. Demaria et al., Dev. Cell 31, 722 (2014).
13. B. Ritschka et al., Genes Dev. 31, 172 (2017).

stimulated by a specific combination of fac- lieved to be mainly detrimental because ACKNOWLEDGMENTS

tors, including interleukin-1b (IL-1b) and of its contribution to inflammation, oxida- The authors are supported by National Institutes of Health
C-X-C motif chemokine 1 (CXCL1), which tive stress, thrombosis (blood clotting), and (HL142772 and HL145536).

are secreted by senescent cells and found metabolic imbalance (10). In endothelium, 10.1126/science. abd7063

920 21 AUGUST 2020 • VOL 369 ISSUE 6506 sciencemag.org SCIENCE

Published by AAAS

CANCER

Immunotherapy with a sting

New agonists of an innate immune pathway induce antitumor immunity in mice

By Thomas F. Gajewski and Emily F. Higgs when it does occur, with the aim of mim- STING molecule but not human STING

icking or reproducing those steps in the (11). The first generation of human STING

T umor antigen-specific CD8+ T cells cases when it does not occur. In general, agonists, including MIW815 (ADU-S100)
are a critical component of the anti- an adaptive immune response (i.e., induc- and MK-1454, have been investigated in
tumor immune response. Many can- tion of a T cell or antibody response) first early-phase clinical trials alone and in
cer patients display evidence of an requires activation of the innate immune combination with anti–PD-1. So far, some
endogenous T cell response against system, which nonspecifically signals the clinical responses to these agonists have

their tumors, yet fail to eliminate presence of “danger” or an outside threat. been observed, but only in a minority of

tumors unaided. The failure of spontane- Preclinical tumor models revealed that en- patients (12, 13). Several biological consid-

ous immune-mediated tumor rejection is dogenous CD8+ T cell priming (activation) erations are being explored to understand

thought to be partially due to the action of by innate antigen-presenting cells (APCs) mechanisms of response versus resistance.

negative regulatory mechanisms (immune was markedly reduced in mice deficient for These include deciphering which immune

checkpoints) that inhibit key functional STING (stimulator of interferon genes) (8). cells in the tumor microenvironment must

properties of tumor-infiltrating T cells (1). Mice lacking STING also showed reduced be present for STING agonists to induce

Checkpoint blockade immunotherapies cytokine production, including interferon- downstream T cell priming, understanding

have demonstrated notable therapeutic b (IFN-b), in response to tumor implan- the optimal dose and schedule of STING

success by overcoming tumor-induced T tation and failed to reject highly immu- agonists to avoid overstimulation and

cell inhibition; however, their ef- negative regulation, and identi-

ficacy is poor when patients lack “Understanding which innate immune pathway fying predictive biomarkers for
evidence of a spontaneous T cell is functionallyrelevant...will be paramount clinical activity.
response (2, 3). Innate immune
agonists may promote priming toward optimization of innate immune agonist The metabolic instability of
and recruitment of tumor-specific cyclic dinucleotide–based STING
agonists requires them to be ad-

CD8+ T cells and are gaining trac- ministered intratumorally. The
constraint for intratumoral ad-
combinations with existing immunotherapies.”tion as a cancer immunotherapy

approach. On page 935 and 993 ministration itself has limitations,

of this issue, Pan et al. (4) and Chin et al. nogenic tumors. These defects were not because physical issues such as increased

(5), respectively, describe innate immune observed in mice deficient in other innate intratumoral pressure, restraints on diffu-

agonists that show antitumor activity in immune pathways, such as specific Toll- sion of the injected agent, and the impos-

preclinical cancer models. like receptors (TLRs). sibility of injecting all metastatic lesions

Antibodies targeting the immune check- The STING pathway is a cytosolic DNA- in an advanced cancer patient are all po-

point receptor, programmed cell death sensing pathway, and tumor-derived DNA tential barriers to therapeutic efficacy.

protein 1 (PD-1), or its major ligand, PD- could be found within the cytosol of tu- A small number of intravenous STING

L1, have been approved by the U.S. Food mor-infiltrating APCs. Cytosolic DNA is agonists have begun evaluation in clini-

and Drug Administration for clinical use detected within cells when it binds to cal trials (NCT03843359, NCT04420884,

in ~15 different cancer entities (6). Clinical cGAS [cyclic guanosine monophosphate and NCT04096638), and the next focus

benefit has been correlated with the pres- (GMP)–adenosine monophosphate (AMP) of STING agonist development will likely

ence of an activated T cell gene signature (cGAMP) synthase], which generates be on agonists formulated for systemic

prior to treatment (2), and following anti– cGAMP, which in turn engages and acti- administration, such as those reported by

PD-1 administration, a marked expansion vates STING (9). Signaling downstream Pan et al. and Chin et al. (see the figure).

of tumor-infiltrating CD8+ T cells has of STING leads to APC activation and in- Clinical development of systemically

been observed (3). Despite clinical suc- flammatory cytokine production, which administered STING agonists needs to

cesses, a major subset of cancer patients subsequently promotes T cell priming and account for several important consider-

lack sufficient T cell inflammation, and recruitment (10). Together, these observa- ations. One is that systemic administra-

these patients generally do not respond to tions led to the hypothesis that exogenous tion may lead to greater toxicity, because

checkpoint blockade immunotherapy (7). agonists of the STING pathway may have engaging APCs outside the tumor micro-

It is thought that triggering productive the potential to trigger de novo innate environment may release high amounts

T cell–based inflammation within the tu- immune activation, leading to an adap- of IFN-b and other inflammatory cyto-

mor microenvironment may offer the po- tive immune response that can control tu- kines. Chin et al. report that efficacious

tential to expand the fraction of patients mor growth alone or in combination with doses of SR-717 led to significantly lower

benefiting from anti–PD-1 treatment and checkpoint blockade immunotherapy. concentrations of serum IFN-b than an-

other immunotherapies. The first STING agonist investigated other recently developed systemic STING

One strategy toward this goal has been for immunotherapy was the molecule agonist, diABZI-2. Systemic administration

to gain an understanding of the fundamen- DMXAA, which had antitumor activity in of diABZI-2 also promoted tumor control;

tal mechanistic steps involved in spontane- preclinical models and was subsequently however, diABZI-2 stabilizes STING in its

ous T cell activation and tumor infiltration determined to interact with the mouse open conformation, similar to the bacterial

SCIENCE sciencemag.org 21 AUGUST 2020 • VOL 369 ISSUE 6506 921

Published by AAAS

INSIGHTS | PERSPECTIVES

New innate immune agonists

The non-nucleotide stimulator of interferon genes (STING) agonists MSA-2 and SR-717 reported by Pan et al. and Chin et al., respectively, stabilize STING in its closed
conformation. STING activation induces downstream signaling events that culminate in the expression of inflammatory cytokines such as interferon-b (IFN-b) and
interleukin-6 (IL-6). Secretion of these cytokines in the tumor microenvironment promotes the maturation and activation of cDC1 dendritic cells, which then promote
antitumor immunity by priming tumor antigen–specific CD8+ T cells in the tumor-draining lymph node.

Tumor shrinkage

MSA-2 O O O O OO
O O SS O
O
STING S
Open O SO
conformation OO
O
O
STING GRAPHIC: MELISSA THOMAS BAUM/SCIENCE
Closed
conformation

F NN N IFN-b CD80 CD86
N IL-6
FN
SR-717 NN
O
O N N NN
NNN

N N cDC1 dendritic cell activation CD8+ T cell cross-priming
O O
FF
F O
OF
F

product cyclic di-GMP but unlike endoge- events in relevant cell subpopulations mune agonist combinations with existing
nous cGAMP (14). The agonists presented within the tumor microenvironment will immunotherapies.
by Pan et al. and Chin et al. both stabi- be critical. Antitumor efficacy of SR-717
lize the closed conformation of STING. was not improved by either anti–PD-1 or The compounds reported by Chin et al.
Further study is necessary to tease apart anti–PD-L1 treatment in a mouse model of and Pan et al. illustrate how distinctive mo-
the biological consequences of stabilizing melanoma, which is in contrast to MSA-2, lecular properties of STING agonists can
STING in its open versus closed confor- which did show improved tumor shrinkage determine the balance of activity in the
mations. The MSA-2 compound described when combined with anti–PD-1 therapy. tumor versus systemically. Non-nucleotide
by Pan et al. also demonstrated limited These differences could be due to differ- small-molecule STING agonists that can be
toxicity in mice despite systemic adminis- ent molecular properties of these STING administered systemically may represent an
tration, owing to its preferential bioactiv- agonists, differences in dose and schedule attractive approach for targeting this path-
ity within the acidic milieu of the tumor of administration in combination with im- way and have the potential to transform the
microenvironment. mune checkpoint blockade, or distinctions therapeutic landscape once optimized. j
between the experimental models used.
A second important consideration is REFERENCES AND NOTES
the effect of systemic STING agonists on A third consideration for clinical devel-
specific immune cell subpopulations. Chin opment is the dose and schedule of admin- 1. G.J. Freeman et al., J. Exp. Med. 192, 1027 (2000).
et al. noted that SR-717 induced expres- istered drug. These need to be optimized 2. M.Ayers et al., J. Clin. Invest. 127, 2930 (2017).
sion of the immunosuppressive molecules carefully, because systemic administra- 3. P. C.Tumeh et al., Nature 515, 568 (2014).
PD-L1 and indoleamine 2,3-dioxygenase 1 tion also may give rise to a bell-shaped 4. B.-S. Pan et al., Science 369, aba6098 (2020).
(IDO1) in primary human peripheral blood efficacy curve. Probing pharmacodynamic 5. E. N. Chin et al., Science 369, 993 (2020).
mononuclear cells in vitro. Additionally, endpoints within the tumor microenviron- 6. R. K.Vaddepally, P. Kharel, R. Pandey, R. Garje,A. B.
intraperitoneal injection of SR-717 in a ment associated with activity should guide
melanoma mouse model led to increased selection of therapeutic dosing. Fourth, Chandra, Cancers (Basel) 12, 738 (2020).
PD-L1 expression on CD11c+CD8– dendritic the consideration of which tumor types 7. J.A.Trujillo, R. F. Sweis, R. Bao,J.J. Luke, Cancer
cells but not on CD8+ dendritic cells iso- and which patients have the potential to
lated from tumor-draining lymph nodes. respond to these agents also needs to be Immunol. Res. 6, 990 (2018).
Although CD8+ dendritic cells are thought addressed, so predictive biomarkers for ap- 8. S.-R.Woo et al., Immunity 41, 830 (2014).
to be the key APC subset for inducing tu- propriate patient selection also need to be 9. L. Sun,J.Wu, F. Du,X. Chen,Z.J. Chen, Science 339, 786
mor-specific CD8+ T cell priming, it is nota- pursued. A final consideration is that other
ble that SR-717 affected these dendritic cell innate immune agonists are advancing (2013).
subtypes differently. Further characteriza- in clinical development, including agents 10. L. Corrales et al., Cell Rep. 11, 1018 (2015).
tion of the ways by which STING agonists targeting TLR pathways, such as TLR9 11. J. Conlon et al., J. Immunol. 190, 5216 (2013).
induce both stimulatory and suppressive (15). Understanding which innate im- 12. F. Meric-Bernstam et al., J. Clin. Oncol. 37 (15_suppl.),
mune pathway is functionally relevant in
Department of Pathology, University of Chicago, Chicago, distinct patient populations will be para- 2507 (2019).
IL, USA. Email: [email protected] mount toward optimization of innate im- 13. K.J. Harrington et al., Ann. Oncol. 29, viii712 (2018).
14. J. M. Ramanjulu et al., Nature 564, 439 (2018).
15. M. Reilley et al., J. Clin. Oncol. 37 (15_suppl.),TPS2669

(2019).

ACKNOWLEDGMENTS

The authors are funded by the National Institutes of Health
(grants F30CA250255 to E.F.H. and R35CA210098 to T.F.G.).
T.F.G. reports a licensing agreement and receives research
support and consultancy fees from Aduro Biotech.

10.1126/science.abc6622

922 21 AUGUST 2020 • VOL 369 ISSUE 6506 sciencemag.org SCIENCE

Published by AAAS

B AT T E R I E S

Past, present, and future of lead–acid batteries

Improvements could increase energy density and enable power-grid storage applications

By Pietro P. Lopes and electrodes and active components mainly for Pb and PbO2, which is a thermodynamically
Vojislav R. Stamenkovic application in vehicles. Future performance and kinetically more demanding process

W hen Gaston Planté invented the goals include enhanced material utilization given the poor solubility of the PbSO4 crys-
lead–acid battery more than 160 through more effective access of the active tals. The intricate relationship between acid
years ago, he could not have fore- materials, achieving faster recharging rates concentration gradients within the electrode
seen it spurring a multibillion-dol- to further extend both the cycle life and cal- pores and lead sulfate dissolution rates un-
lar industry. Despite an apparently endar life and to reduce their overall life cycle derscores the challenge of improving the bat-
cost with a direct impact on the implementa- tery’s ability to recharge at fast rates.

low energy density—30 to 40% of tion of grid storage systems. All of these processes occur in competition

the theoretical limit versus 90% for lithium- The constant dissolution and redeposi- with the thermodynamically favored but un-

ion batteries (LIBs)—lead–acid batteries are tion of the cell’s active materials, over each desired water-splitting reactions that evolve

made from abundant low-cost materials and charge–discharge cycle, creates a situation O2 and H2 gases. Lead and lead dioxide are
nonflammable water-based electrolyte, while where both positive and negative electrode poor catalysts for these reactions and have

manufacturing practices that operate at 99% morphology and microstructure are con- high overpotentials that kinetically limit

recycling rates substantially minimize envi- stantly changing (see first the figure). These these processes unless fast charging occurs

ronmental impact (1). Nevertheless, forecasts structural changes enable the corrosion of with high voltages. However, metal and ionic

of the demise of lead–acid batteries (2) have electrode grids typically made of pure lead impurities in electrodes and electrolyte fa-

focused on the health effects of lead and the or of lead-calcium or lead-antimony alloys cilitate electrolysis of water and its loss (5).

rise of LIBs (2). A large gap in technologi- and affect the battery cycle life and mate- The requirement for a small yet constant

cal advancements should be charging of idling batter-

seen as an opportunity for ies to ensure full charging

scientific engagement to ex- Morphological changes (trickle charging) mitigates
pand the scope of lead–acid water losses by promoting
batteries into power grid ap- Both electrodes form surface PbSO4 during discharging. Scanning electron microscopy the oxygen reduction reac-
plications, which currently images of Pb/PbSO4 electrodes show marked surface morphology changes for distinct tion, a key process present
lack a single energy stor- charge and discharge protocols. in valve-regulated lead–acid

age technology with opti- batteries that do not require

mal technical and economic adding water to the battery,

performance. which was a common prac-

In principle, lead–acid tice in the past.
2 mm 2 mm 2 mm Some of the issues fac-
rechargeable batteries are

relatively simple energy stor- A charged Pb electrode First discharge at a slow rate First discharge at a faster rate ing lead–acid batteries dis-
age devices based on the lead cussed here are being ad-

electrodes that operate in aqueous electro- rial utilization efficiency. Because such mor- dressed by introduction of new component

lytes with sulfuric acid, while the details of phological evolution is integral to lead–acid and cell designs (6) and alternative flow

the charging and discharging processes are battery operation, discovering its governing chemistries (7), but mainly by using car-

complex and pose a number of challenges to principles at the atomic scale may open ex- bon additives and scaffolds at the negative

efforts to improve their performance. This citing new directions in science in the areas electrode of the battery (4), which enables

technology accounts for 70% of the global of materials design, surface electrochemistry, different complementary modes of charge

PHOTOS: MILENA ZORKO/CENTER FOR NANOSCALE MATERIALS AT ARGONNE energy storage market, with a revenue of 80 high-precision synthesis, and dynamic man- storage (supercapacitor plus faradaic Pb

billion USD and about 600 gigawatt-hours agement of energy materials at electrochemi- charge–discharge). These electrodes also of-

(GWh) of total production in 2018 (3). Lead– cal interfaces. This understanding could have fer a rigid, unreactive, and conductive elec-

acid batteries are currently used in uninter- a direct impact on battery life, as preserving trode backbone that prolongs cycle life.

rupted power modules, electric grid, and the overall electrode surface area ensures ef- At the positive electrode, identification of a

automotive applications (4, 5), including all fective charge–discharge processes. material that can withstand the high electrode

hybrid and LIB-powered vehicles, as an in- These efforts must take into account the potentials and harsh acidic environment re-

dependent 12-V supply to support starting, complex interplay of electrochemical and mains a problem to be solved. Utilization of

lighting, and ignition modules, as well as crit- chemical processes that occur at multiple bipolar electrodes can reduce the amount of

ical systems, under cold conditions and in the length scales with particles from 10 nm to 10 lead used for structural components (elec-

event of a high-voltage battery disconnect (3). µm (see the second figure) (5). The active ma- trode grid), immediately improving material

Although the principle of operation has not terials, Pb and PbO2, are traditionally packed utilization, but challenges with corrosion and
changed, manufacturers have improved this as a self-structured porous electrode. When cost-effective manufacturing are still a limit-

technology by optimizing performance of the discharged, Pb2+ ions quickly react with the ing factor. Implementation of battery man-

available sulfuric acid in the electrolyte and agement systems, a key component of every

Materials Science Division, Argonne National Laboratory, nucleate insoluble PbSO4 crystals. During LIB system, could improve lead–acid battery
Lemont, IL 60439, USA. Email: [email protected] charging, PbSO4 must be converted back to operation, efficiency, and cycle life.

SCIENCE sciencemag.org 21 AUGUST 2020 • VOL 369 ISSUE 6506 923

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INSIGHTS | PERSPECTIVES

Perhaps the best prospect for the unuti- As with any technology, many of the as- tion from discarded LIB systems. Accidental

lized potential of lead–acid batteries is elec- sociated risks can be limited with proper inclusion of LIBs in lead battery recycling has

tric grid storage, for which the future market management of materials, good manufactur- proven hazardous, and better safety and recy-

is estimated to be on the order of trillions ing practices, and committed waste manage- clinge protocols are needed.

of dollars. For that reason, the low cost of ment. The 99% recycling rate of lead–acid The range of tools and methods developed

production and materials, reduced concerns batteries (12) and stringent regulations on Pb over the past 30 years, both experimentally

about battery weight, raw material abun- environmental emissions greatly minimize and theoretically, are readily applicable to

dance, recyclability, and ease of manufactur- the risk of Pb release to the environment. further develop and elucidate the science

ing make it an attractive solution if technical Alternatively, the lack of economically fea- of lead–acid batteries. These topics would

barriers can be addressed. At a current spot sible recycling solutions to LIB technology in greatly benefit from further engagement

price below $2/kg and an average theoretical the short term, combined with the expected from U.S. National Laboratories and across

capacity of 83 ampere hours (Ah)/kg (which increase in the number of battery cells that academia (15). Leveraging our current sci-

includes H2SO4 weight and the average con- are approaching their end of life, aggravate entific knowledge and an established manu-
tribution from Pb and PbO2 active materials) the potential for environmental contamina- facturing industry with admirable safety and
that rivals the theoretical capac-
recycling records would ensure

ity of many LIB cathode materi- strong economic, technical, and

als (8), lead–acid batteries have Multiscale electrochemistry environmental support for lead–
the baseline economic potential acid batteries to continue serv-
to provide energy storage well The technical challenges facing lead–acid batteries are a consequence of the ing as part of a future portfolio
within a $20/kWh value (9). complex interplay of electrochemical and chemical processes that occur at of energy storage technologies. j
multiple length scales. Atomic-scale insight into the processes that are taking

Despite perceived competition place at electrodes will provide the path toward increased efficiency, lifetime, and REFERENCES AND NOTES
between lead–acid and LIB tech- capacity of lead–acid batteries.
nologies based on energy density 1. I.Feldman et al.,Environ.Law Rep.46
metrics that favor LIB in por- Macroscopic Negative electrode Separator Positive electrode (2016).
table applications where size is components panel
an issue (10), lead–acid batteries (centimeters) 2. R.Rapier,Forbes 27,1 ; www.
are often better suited to energy The Pb anode and Pb+C Pb-alloy forbes.com/search/?q=lead%20
storage applications where cost is PbO2 cathode grid grid battery#6227d028279f (2020).
the main concern. In reality, LIB electrodes and
technology has been more detri- separator are Pb paste PbO2 paste 3. C.Pillot,in 11th InternationalAdvanced
mental to nickel–metal hydride illustrated. Charging Detail below Automotive Battery Conference (2020),
and nickel-cadmium battery mar- regenerates these pp.1–111; www.avicenne.com/pdf/
kets (3). The increased cost, small materials. e– Fort_Lauderdale_Tutorial_C_Pillot_
production rates, and reliance on March2015.pdf.
scarce materials have limited the Microstructural H2SO4 Electrode
penetration of LIBs in many en- and fuid fows dilution grid Mber 4. G.J.May,A.Davidson,B.Monahov,
ergy storage applications. (10 µm to 1 mm) H2SO4 J.Energy Storage 15,145 (2018).
Charge and discharge Pb/PbO concentration
The inherent concern sur- 2 PbSO4 5. D.Pavlov,Lead-Acid Batteries: Science
rounding lead–acid batteries cycles form complex andTechnology (Elsevier Science,2011).
is related to the adverse health H2O H2O
and environmental effects of particle interfaces dilution concentration 6. D.Rand,Batter.Int.(no.100),pp.25–27
lead (11). More effective mitiga- (2017); www.batteriesinternational.
tion is feasible with application between Pb and PbSO4 or com/back-issues-3/.
of known practices, strict gov- PbO2 and PbSO4 on the
ernment regulations, and im- micrometer scale. These 7. A.Hazza,D.Pletcher,R.Wills,Phys.
proved training and engineering Chem.Chem.Phys.6,1773 (2004).
controls, which would further self-structured porous
increase the already impressive 8. D.Doughty,E.P.Roth,Electrochem.Soc.
recycling rate of 99% (12). Also, networks create acid and Interface 21,37 (2012).
many serious safety and health
concerns exist as part of LIB water concentration 9. M.S.Ziegler et al.,Joule 3,2134 (2019).
manufacturing and operation, 10. A.J.Bard,R.Parsons,J.Jordan,Standard
including the carcinogenic po- gradients at the
tential of Ni and Co oxide com- Potentials inAqueous Solution (Taylor &
ponents of cathode materials, electrochemical Francis, 1985).
the production of highly toxic or- 11. G.Flora,D.Gupta,A.Tiwari,Interdiscip.
ganofluorophosphate neurotox- interfaces. Toxicol.5,47 (2012).
ins as a consequence of thermal 12. SmithBucklin Statistics Group,“National
runaway events (battery fire and Nanostructural Pb (negative) Discharge Recycling Rate Study”(2019).
explosion) (8, 13) and potential crystal formation H2SO4 13. W.Weber et al.,J.Chromatogr.A 1394,
contamination of the environ- 128 (2015).
ment with toxic organofluorine (~10 nm to ~10 µm) 14. K.Liu,Y.Liu,D.Lin,A.Pei,Y.Cui,Sci.Adv.
by-products arising from electro- 4,eaas9820 (2018).
lytes and additives (14). Continuous dissolution 15. A.Davidson,Consort.Batter.Innov.
(2019); https://batteryinnovation.org/
and redeposition of lead-battery-innovation-and-the-year-
ahead/.
active materials occur 2e–
ACKNOWLEDGMENTS
at the surface of PbO2 (positive) H0
particles and drive 2 The approach applied to develop structure-
function correlations was funded by the U.S.
changes in Detail Charge PbSO4 Department of Energy, Office of Science, GRAPHIC: MELISSA THOMAS BAUM/SCIENCE
microstructure. below Office of Basic Energy Sciences, Materials
Sciences and Engineering Division. The
Water-splitting 2H+ H2 2H2O O2 research efforts were supported by the Lead
2e– 4H+ + 4e– Battery Science Research Program through
reactions M a Cooperative Research and Development
Pb Agreement. Use of the Center for Nanoscale
(0.1 to 1 nm) Materials, an Office of Science user facility,
Charging can also split was supported by the U.S. Department
water into H2 and O2 during of Energy, Office of Science, Office of
overcharging or at impurity Basic Energy Sciences, under contract
metal (M) atom. no. DE-AC02-06CH11357.We thank E.
Coleman, D. Strmcnik, M.Zorko, C. Ferels, N.
Chaudhari, and in memoriam Stefan Djokic
for support in experiments.

10.1126/science.abd3352

924 21 AUGUST 2020 • VOL 369 ISSUE 6506 sciencemag.org SCIENCE

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RETROSPECTIVE a training stipend, offered mentorship, an-
nual monitoring, and enrichment activities.
James G. Townsel (1935–2020) For 23 years, DPN supported almost 300
trainees from underrepresented groups.
Neuroscientist and devoted mentor of diverse scientists The enrichment program, codirected by
Jim and Joseph Martinez, consisted of a
PHOTO: MEHARRY MEDICAL COLLEGE LIBRARY AND ARCHIVES By Rae Nishi1, Byron D. Ford2, and built a strong research program that monthlong experience encompassing pro-
John G. Hildebrand3 made substantial contributions to the fields fessional development, lectures in neuro-
of neurotransmitter biochemistry and traf- science, mentoring, and networking at the
J ames “Jim” Garfield Townsel, a neuro- ficking of proteins involved in neurotransmis- Marine Biological Laboratory in Woods
scientist who devoted his life to diver- sion. When he returned to Meharry as chair Hole, Massachusetts. Although DPN lost its
sifying the field, died on 22 June. He in 1984, he drew upon his early experiences funding, the enrichment component lives
was 84. Jim made valuable contribu- to create a culture of research that benefited on as the Summer Program in Neuroscience,
tions to the field of neurotransmission students. He hired two active neuroscientists, Excellence, and Success (SPINES).
through his research, but he is best secured competitive federal funding for re-
known for his unwavering focus on eliminat- search, created a multidisciplinary graduate All three of us worked closely with Jim
ing racial health disparities by mentoring program that earned an NIH training grant, as he spearheaded these diversity programs
underrepresented trainees and supporting and developed an NIH-funded collaborative and saw firsthand his passion for further-
their scientific advancement. program with Vanderbilt University for pre- ing the careers of underrepresented train-
doctoral trainees. ees in neuroscience. He did not believe in
Born on 9 September 1935 in Albemarle, giving handouts, and he sought to instill in
North Carolina, Jim grew up in the inner Devoted to training his students to be- all trainees the qualities necessary to suc-
city of Harrisburg, Pennsylvania. He gradu- come effective scientists, Jim mentored ceed in science. He was truly frustrated to
ated in 1958 with high honors from Virginia with tough love. Each day, he would walk discover mentors who thought they were
State University (VSU), where he majored through the lab and grill his trainees about supporting their trainees of color by put-
in biology and participated in the Reserve ting them on papers as honorary authors.
Officers’ Training Corps. After working in the their research. He expected productivity but For Jim, what mattered was an earned first
U.S. Army Medical Service Corps, he began also emphasized rigor and reproducibility, authorship, because that would lead to ad-
graduate school, a transition made possible qualities that were not yet fully appreciated vancement and research grants.
by Richard Dunn, a botanist at VSU who, as by the scientific community. He always de-
Jim put it, “rolled boulders out of my way and manded intellectual accountability. As his Jim was deeply disturbed by racial dispari-
was committed to my success.” Ph.D. student, I (B.D.F.) understood that it ties in health. He recognized that diversifying
was acceptable not to know something, but the scientific workforce is essential to mitigat-
After earning his Ph.D. in physiology at that I had best learn it before I was asked ing such disparities. It was therefore critically
Purdue University in 1968, Jim was recruited about it again. Jim’s view was that Black sci- important to him that trainees of color stay
immediately to the faculty of VSU. In 1971, entists had to be better than scientists from in science, get research grants, and advance
he accepted a postdoctoral traineeship at more commonly represented backgrounds in the field. He knew that to ensure this result,
Harvard Medical School in the laboratory order to succeed in academia. He prepared the students he trained would have to carry
of neurobiologist Edward Kravitz. Jim’s ex- these scientists well and continued to sup- on in his footsteps, becoming mentors them-
perience at Harvard galvanized his passion port them throughout their careers. selves and remaining lifelong supporters of
for neuroscience. In 1973, he accepted an their trainees, and that those trainees would
assistant professorship at Meharry Medical Jim collaborated with neuroscientists have to become mentors in turn, bringing
College, a historically Black medical school in Joseph Martinez and James Jones to lead ever more diverse scientists into academia.
Nashville, Tennessee. He later moved to the the Diversity Program in Neuroscience
University of Illinois at Chicago to adminis- (DPN), a diversity-focused training program In DPN advisory committee meetings,
ter its Urban Health Program. In 1984, he re- funded by the NIH and supported by the Jim was always very serious, but when
turned to Meharry, where he was a professor American Psychological Association. DPN we worked with him at SPINES, he was
and chair of the physiology department until began in 1988 and, in addition to providing friendly and supportive, often giving every
his retirement in 2010. participant a hug at the end of his teach-
ing session. During a lively discussion with
When he arrived at Meharry in 1973, Jim one of us (R.N.) last summer, he emphasized
quickly secured research grants from the the long-term commitments that true men-
National Institutes of Health (NIH) and the torship requires and expressed disappoint-
National Science Foundation, but the lack of ment that such emotional investment is
research culture at the college hindered his often overlooked. He concluded, “There are
work. He would later recall that the summary many books about mentoring, but none of
statement of his first NIH research project them tell you how to have a heart, which is
grant application expressed admiration for what you need to succeed.”
him as an applicant but considered his chance
of success in the school’s environment to be Jim had that heart. Most of his train-
vanishingly small. Nonetheless, Jim persisted ees from the lab as well as hundreds from
SPINES remain in research and are now
1Falmouth, MA 02540, USA. 2Biomedical Sciences faculty members at research universities.
Division, University of California, Riverside, CA 92521, They serve as role models, carrying his
USA. 3Department of Neuroscience, University of Arizona, legacy forward and continuing to fulfill his
Tucson, AZ 85721, USA. Email: [email protected] vision of a more equitable scientific land-
scape and world. j

10.1126/science.abd8380

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BOOKS et al. Wind turbines loom behind an oil pump in Texas,
illustrating the enduring tension between clean
energy and fossil fuels.

ENERGY POLICY with a politician on a particular issue, they
often take cues from them on unrelated is-
One step forward, two steps back sues, including energy policy.

Interest groups and state-level political inertia have stalled The environment was once a unifying
many of America’s clean energy initiatives cause in American politics. In 2007, former
Speaker of the House Newt Gingrich, an
By Saleem H. Ali echoed in economist Mancur Olson’s 1965 otherwise polarizing Republican, co-wrote a
book called A Contract with the Earth to re-
book, The Logic of Collective Action, which mind conservatives of as much, referencing
the party’s environmental legacy (2). How-
W hy is it that America has not been laid out a theory of how concentrated ben- ever, Stokes shows that a carefully curated
able to achieve science-based efits can trump diffuse cost factors. Stokes campaign advanced by conservative groups
targets for carbon emissions re- convincingly argues that climate change such as the American Legislative Exchange
ductions despite the availability fits this paradigm perfectly. She reveals how Council, the State Policy Network, and
of numerous economically and successful green energy policies are eroded Americans for Prosperity—sensing ambiva-
lence toward green policies from core Re-
ecologically rational solutions? through a process she refers to as retrench- publican Party supporters—began targeting
the base with messaging against renewable
This question is often framed in terms of ment, and how renewable energy infrastruc- energy in the late 20th century. Such cam-
paigns gained momentum between 2000
job losses or energy security arguments. In ture development has succumbed to a series and 2010. The impact of this anti-environ-
mentalist miasma continues to this day.
Short Circuiting Policy, a timely of negative feedback loops that
Using the heuristic of what she calls a
political ethnography of U.S. have kept progress on a treadmill “narwhal curve,” Stokes provides a useful
visual primer for how steep a rise in re-
energy policy, Leah Cardamore of policy inertia. newable energy transition is needed. She is
also more sympathetic to nuclear power in
Stokes argues that clean energy Drawing on more than a hun- her analysis, noting that the retirement of
nuclear plants is making our task of transi-
programs initially gained trac- dred interviews with key decision- tion even more challenging. On this point,
I had hoped that Stokes would have been
tion as potential opportunities to makers and stakeholders, as well more willing to critique environmentalist
organizations as another sort of special in-
create green jobs and reduce car- as detailed document and me- terest group. Many of the pathologies that
she identifies in fossil fuel and electric util-
bon footprints but then waned, dia analysis, Stokes explores the ity interests also apply to the anti-nuclear
movement, which derailed any potential
even as the economics increas- consequences of stalled environ- for economies of scale being realized from
this clean technology. [Extreme risk aver-
ingly favored their success. Focus- Short Circuiting Policy mental policies at length. She sion and a misapplication of the precau-
ing on state-level politics, Stokes Leah Cardamore Stokes discusses the usual mechanisms tionary principle trumped hard data in
carefully lays out how Arizona, Oxford University Press, of influence, such as political lob- this regard as well (3).] She could have also
Kansas, Texas, and Ohio struggled bying and advertising campaigns, engaged with some of the literature that
2020. 338 pp. challenges the dominance of the interest
group hypothesis in explaining political
to contain the power of the fossil fuel and but also reveals more pernicious phenom- influence, for example, the work of Gunnar
Trumbull (4). Despite these minor misses,
electric utilities industries and, in doing so, ena, including “astroturfing,” wherein the Stokes has written a highly readable and
compelling book that will be of interest to
failed to sustain a clean energy trajectory. entity advancing a particular policy is con- environmental policy scholars and the gen-
eral public alike. j
The book’s title is a reference to a passage cealed by an ostensibly grassroots campaign.
REFERENCES AND NOTES
from political scientist E. E. Schattschnei- Such efforts, she argues, create a “fog of PHOTO: JIM WEST/SCIENCE SOURCE
1. N. Oreskes, E. M. Conway, Merchants of Doubt
der’s 1942 book, Party Government, which enactment”—a gap between interest groups’ (Bloomsbury, 2010).

reads: “Pressure politics is a method of short- expectations of a given policy and its actual 2. N. Gingrich,T. L. Maple, A Contract with the Earth (Johns
Hopkins Univ. Press, 2007).
circuiting the majority.” This sentiment is implementation—comparable to what others
3. S. L. Montgomery,T. Graham Jr., Seeing the Light
have documented in tobacco legislation (1). (Cambridge Univ. Press, 2017).

The reviewer is at the College of Earth, Ocean The democratic process is fragile, reveals 4. G.Trumbull, Strength in Numbers (Harvard Univ.
and Environment, University of Delaware, Newark, Stokes, and highly vulnerable to powerful Press, 2012).
DE 19716, USA. Email: [email protected] interests. What’s more, when citizens agree
10.1126/science.abc8702

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INSIGHTS

SCIENCE LIVES

Ray Bradbury, luminary of the space age, at 100

A new biography chronicles the golden years of Earth’s first martian

By Ingrid Ockert and worked with Disney’s “imagineers” on Bradbury Beyond Apollo
several projects before their partnership Jonathan R. Eller
O ne hundred years ago this month, bore fruit, namely in the form of Epcot’s University of Illinois Press,
the poet laureate of Mars was born ride Spaceship Earth and Walt Disney Pro- 2020. 376 pp.
in sleepy Waukegan, Illinois. To a duction’s film Something Wicked This Way
generation of baby boomers, Ray Comes (1982) based on Bradbury’s novel world of postwar science communication.
Bradbury was best known for his of the same name. Similarly, Eller reveals

masterpiece The Martian Chronicles how Bradbury helped Bruce Murray and Equally valuable is the full picture of

(1950), a lyrical collection of stories that others at the Planetary Society promote Bradbury’s career as a public speaker that

wondered how humans might adapt to life space travel and planetary exploration. Eller provides readers. Bradbury appeared

on the red planet. His poetic descriptions While not all of the writer’s projects came regularly on television and in auditoriums

captured the world’s collective imagina- to fruition, he continued to dream up new across the United States, strengthening

tion, spurring the development of space films, books, exhibits, and other projects his relationships with fans and helping to

technologies, including Mars-bound satel- and collaborations. establish him as a leading voice for space-

lites and rovers. As Norman Cor- flight. Although some biographers

win noted in 1971, “[Bradbury] got might have omitted discussion of

to Mars before the scientists…No Bradbury’s public lectures, Eller’s

amount of scientific data, no logs decision to include a detailed re-

and extrapolations of computer counting of the author’s outreach

codes, will ever dislodge him from efforts proves vital to understand-

that planet.” ing his continued influence within

To mark the centennial of Brad- the scientific community.

bury’s birth, Jonathan Eller, a Even as Bradbury established a

professor of English at Indiana Uni- persona as a martian luminary, he

versity and director of the Center for continued to write stories in other

Ray Bradbury Studies, has written genres—strange tales of haunted

Bradbury Beyond Apollo, the final crypts, hard-boiled noirs, and sweet

biography in a trilogy that explores musings of childhood innocence.

Bradbury’s life. Eller’s thoughtful Eller documents the continued de-

narrative is meticulous, offering velopment of Bradbury’s writing

more than 300 pages of analysis prowess, describing how the author

and snippets from Bradbury’s un- experimented with poetry and with

published letters and manuscripts more realistic stories.

to document every moment of the Bradbury was careful to delineate

PHOTO: © LISL STEINER, ALL RIGHTS RESERVED. COURTESY OF RAY BRADBURY LITERARY WORKS, LLC. writer’s golden years, starting with his expertise as that of a writer, not

the launch of Apollo 15 in 1971 and a scientist, when speaking alongside

ending with his final days in 2012. professionals at NASA symposiums.

Along the way, Eller offers readers But his popularity demonstrated

insights into how Bradbury estab- that inspiration, not just education,

lished his legacy as a luminary of was an important dimension of sci-

the space age. ence communication. Today, many

Throughout his career, Eller Surrounded by Disney and NASA mementos, Bradbury writes in 1981. successful scientists recognize that

explains, Bradbury looked for op- effective communication weaves to-

portunities to collaborate, to strengthen For a historian of science like myself, gether awe and information.

his connection with fans, and to grow as a Eller’s careful analysis of Bradbury’s pro- Bradbury’s lectures offered audiences

writer. Bradbury Beyond Apollo dives deep fessional networks is invaluable. Too of- opportunities to connect with him, and

into the writer’s expansive personal and ten, the files of influential public figures with each other, over a positive vision of

professional network of scientists, film- remain closed, reinforcing their enigmatic, human spaceflight. As he explained in

makers, writers, and artists. Bradbury, we two-dimensional public image. The care- a letter to officials at the Smithsonian in

learn, established friendships early on with ful detail of this biography paints a rich 1981, “[I am] in the business of shaking

key players and looked for projects that portrait of Bradbury as a talented conver- people up and rousing their blood so they

would allow them to work together. He sationalist and gifted collaborator and al- go out of the show half-mad with love and

met Walt Disney in the 1960s, for example, lows readers to understand the nuances of stunned with the beauties of space. If we

his professional relationships. The writer’s do that, the rest will follow.” j

The reviewer is a historian of science based in Berkeley, CA, correspondence, meanwhile, offers incred- 10.1126/science.abc2948
USA. Email: [email protected] ible perspective into the interconnected

SCIENCE sciencemag.org 21 AUGUST 2020 • VOL 369 ISSUE 6506 927

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LETTERS

Human activities threaten the
dwindling Baer’s pochard population.

Edited by Jennifer Sills National Key-protected Species List, 8. The National People’s Congress of the People’s Republic PHOTO: WANG DUBAO/BARCROFT MEDIA VIA GETTY IMAGES
where the Baer’s pochard is still listed of China,“The Wildlife Protection Law of China”(2018);
Baer’s pochard duck as a lower-priority class III protected www.npc.gov.cn/npc/c12435/201811/
species (6, 7). Local governments must f4d2b7a3024b41ee8ea0ce54ac117daa.shtml
at risk of extinction strictly enforce the Wildlife Protection [in Chinese].
Law of China to stop illegal hunting and
The Baer’s pochard (Aythya baeri), a trade (8) and increase the investigation 9. The Department of Forestry and Grassland,
migratory duck, used to be widespread in and monitoring of the Baer’s pochard “International Workshop of the Baer’s Pochard
northeast China and eastern Russia, where population, distribution, and habitats (9). Conservation” (2018); www.forestry.gov.cn/portal/
it would breed, and in central and south- China should also promote the protection xdly/s/5188/content-1086081.html [in Chinese].
east Asia, where it would migrate for the and restoration of the inland freshwater
winter (1). However, in recent years, the wetlands that serve as the duck’s primary 10. L.Zhang et al., Bird Conserv. Int. 27, 2 (2017).
Baer’s pochard population has decreased to habitats by strengthening the manage-
between 150 and 700 Critically Endangered ment of wetland nature reserves and 10.1126/science.abd2087
individuals (2, 3). China, as the primary resi- improving the infrastructure of wetland
dence of Baer’s pochard (3), must take more parks. The government, scientists, and Waterbirds’ coastal
protective measures to alleviate the threats the public must work together to control
to the species and prevent their extinction. China’s pollution (10). Finally, the govern- habitat in danger
ment should work to raise the public’s
Anthropogenic activities have exac- awareness of wildlife protection. Migratory waterbirds, especially shore-
erbated the rapid decline of the Baer’s birds, depend on China’s coastal wetlands
pochard population. Wetlands are the Xin Tong (1). China’s plans to reclaim the coastal
duck’s primary habitats and breeding College of Environmental Science and region for industry, aquaculture, and
grounds, but 33% of wetlands in China Engineering, Nankai University, Tianjin 300350, other infrastructure could destroy the last
were lost between 1978 and 2008 (4). China. Email: [email protected] remaining habitat of many vulnerable spe-
Environmental pollution has killed Baer’s cies (2, 3). From 2000 to 2010, the local
pochards and further restricted their hab- REFERENCES AND NOTES governments of China’s coastal areas, moti-
itats (5). Human activities such as fishing, vated by rapid urbanization and economic
illegal hunting, and picking up bird eggs 1. X.Wang et al., Bird Conserv. Int. 22, 2 (2012). development, have reclaimed more than
have disrupted Baer’s pochard popula- 2. BirdLife International, Baer’s Pochard (Aythya baeri) 320,000 ha of coastal wetlands (4). In 2012,
tions and threatened their breeding (5). China approved plans to reclaim 246,900
(IUCN Red List Threatened Species, 2019). ha of coastal wetlands for construction by
The Baer’s pochard is an important 3. A. U. Chowdhury et al., FORKTAIL 28, 57 (2012). 2020 (4). The largest reclamation project—
species in the biosphere and vital for 4. Z. G. Niu et al., Nature 471, 7338 (2011). the Oufei Project in Wenzhou Bay—spans
maintaining biodiversity and freshwa- 5. X. F.Wang et al., Chin.J.Wildl. 40, 1 (2019) [in Chinese]. an area of 8854 ha (5) and threatens a
ter ecosystems. Urgent and coordinated 6. The Department of Forestry and Grassland,“The National crucial waterbird habitat. China should
action from government and the public halt reclamation plans until environmental
is required to protect this species. The Key-protected Species List”(2018); www.forestry.gov.cn/ needs are addressed.
Chinese government should update the main/3954/content-1063883.html [in Chinese].
7. The Department of Forestry and Grassland,“List of Wenzhou Bay is an important stopover
National Protected Terrestrial Wildlife Beneficial to site for birds migrating along the East Asian-
Economic or Scientific Value” (2000); http://www. Australasian flyway. More than 100,000
forestry.gov.cn/main/3954/content-959027.html
[in Chinese].

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INSIGHTS

waterbirds rest in the area (6), including the remain, constrained to the northeastern the infrastructure they will need to host
region of Cambodia (1). The small popula- future domestic and international tour-
Endangered black-faced spoonbill (Platalea tion suffers from habitat loss and distur- ists. By preparing to provide eco-tourism
bance caused by human activities, and services, these communities can benefit
minor) and spoon-billed sandpiper (Calidris tensions between humans and wildlife from alternative income sources once
have escalated during the coronavirus dis- tourism resumes, thereby allowing them
pygmaea) (7, 8). There is no other suitable ease 2019 (COVID-19) pandemic. In April, to continue their support for the conser-
3 giant ibises and more than 100 other vation of the giant ibis and the region’s
waterbird habitat that could serve as an birds were poached in Cambodia’s Chhep other endangered species.
Wildlife Sanctuary (2). To save the giant
alternative resting area (9). To protect rare ibis, conservation efforts must continue, Hong Yang1,2*, Mingguo Ma1, Julian R. Thompson3,
even during the pandemic. Roger J. Flower3
waterbirds, we must protect their habitats 1Chongqing Engineering Research Center for
Giant ibises nest in forests and frequent Remote Sensing Big Data Application, School of
from reclamation. nearby wetlands, where they prey on Geographical Sciences, Southwest University,
frogs, insects, and larvae (3), all histori- Chongqing 400715, China. 2Department of
China’s coastal wetland protection cally plentiful in their habitats. However, Geography and Environmental Science, University
extensive clearance of Cambodia’s lowland of Reading, Reading RG6 6AB, UK. 3Department
contains substantial gaps (10). Of the 110 dry forest for agro-industry, coupled with of Geography, University College London, London,
widespread wetland agricultural drain- WC1E 6BT, UK.
waterbird priority conservation sites, 67 age, has disrupted the ecosystems on *Corresponding author.
which the ibises depend. Under China’s Email: [email protected]
are located outside the protected area (11). Belt and Road Initiative (4), new roads
are planned to run through the Siem REFERENCES AND NOTES
The Chinese government must take bio- Pang District in northeast Cambodia, as
well as protected forests in the Keo Seima 1. BirdLife International,Thaumatibis gigantea
diversity conservation needs into account Wildlife Sanctuary in eastern Cambodia, (The IUCN Red List ofThreatened Species,2018).
further disrupting the ibis’s habitats (5).
before proceeding with reclamation projects. Hydroelectric dams on the Mekong River 2. Wildlife Conservation Society,“COVID-19 fueling an
and its tributaries will change water levels uptick in poaching: Three critically endangered giant
National parks, nature reserves, and other in riverine wetlands, potentially decreas- ibis—Cambodia’s national bird—killed in protected
ing habitat quality and affecting ibis prey area” (2020).
protections should be designated to fill the species (6, 7).
3. O.Keo,BirdingAsia 9,100 (2008).
gaps in the current system. The addition of As their habitats diminish, ibises are 4. A.M.Lechner,F.K.S.Chan,A.Campos-Arceiz,Nat.Ecol.
also vulnerable to climate fluctuations.
the Yellow Sea-Bohai Gulf (Phase I) to the Prolonged drought in the 2009–2010 dry Evol.2,408 (2018).
seasons decreased ibis breeding rates 5. R.Loveridge,S.Ty,“Ten-year species action plan for the
World Heritage List in 2019 is a step in the by about 50% (4). Potential increases in
drought severity due to climate change giant ibis (Thaumatibis gigantea) in Cambodia 2015–
right direction (12). To further strengthen could replicate these declines (8). 2025”(BirdLife International Cambodia Programme,
Cambodia, 2015).
protections, China should fund the investi- To conserve the giant ibis population, 6. J.E.Chastant,D.E.Gawlik,Waterbirds 41,35 (2018).
we must protect key habitats, enforce 7. A.H.Claassen,“Abundance,distribution,and reproductive
gation and monitoring of migratory birds on environmental regulations, and reconcile success of sandbar nesting birds below theYali Falls hydro-
conservation and agricultural develop- power dam on the Sesan River,Northeastern Cambodia”
coastal wetlands (4) and carry out ecosystem ment through trade-offs between land- (WorldWildlife Foundation/Danida/Wildlife Conservation
sparing, wildlife-friendly farming and Society/BirdLife International,Cambodia,2004).
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Peng Cui* efit from conservation, especially during 1289 (2011).
Key Laboratory of Biosafety, State Environmental uncertain times such as the COVID-19 10. Wildfowl andWetlandsTrust,“Cambodia:The kingdom of
Protection Scientific Observation and Research pandemic. International tourists spent wetlands”(2019); www.wwt.org.uk/news/2019/09/20/
Station for Ecology and Environment of Wuyi more than US$100,000 visiting Cambodia cambodia-the-land-of-wetlands/17652#.
Mountains, Nanjing Institute of Environmental to view giant ibises in the past decade
Sciences, Ministry of Ecology and Environment, (2). With global tourism in decline for 10.1126/science.abd0141
Nanjing 210042, China. an indeterminate period of time, this
*Corresponding author. income will decrease, and pressure on E R R ATA
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for the return of tourists should focus at Fukushima” by K. O. Buesseler, Science 369,
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1. Q.Bai et al.,Avian Res.6,12 (2015). Cambodian wetland protected areas (10).
2. H.Yang et al.,Proc.Natl.Acad.Sci.U.S.A.114, With financial and institutional support Erratum for the Report: “Anti-Markovnikov alcohols
from international nongovernmental orga- via epoxide hydrogenation through cooperative
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coastal wetland conservation and management in China Erratum for the Report: “Widely tunable compact
(Higher Education Press,Beijing,2017),pp.227–239 terahertz gas lasers” by P. Chevalier et al., Science
[in Chinese]. 368, eabc5418 (2020). Published online 8 May 2020;
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Manag.31,65 (2014) [in Chinese].
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[in Chinese]. 2020; 10.1126/science.abc4034
7. BirdLife International,Platalea minor (The IUCN Red List
ofThreatened Species,2017).
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List ofThreatened Species,2018).
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10.1126/science.abc9000

Protect the giant ibis

through the pandemic

The giant ibis (Thaumatibis gigantea),

Cambodia’s national bird, is edging toward

extinction. The ibis’s historical range

stretched across Southeast Asia, but only

194 Critically Endangered individuals

SCIENCE sciencemag.org 21 AUGUST 2020 • VOL 369 ISSUE 6506 929

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RESEARCH Remote C–H borylation by
a modular iridium catalyst

Reyes et al., p. 970

IN SCIENCE JOURNALS
Edited by Michael Funk

GLOBAL CARBON CYCLE

Pulses of the past

B ursts of carbon dioxide, released into the atmo-
sphere and occurring on centennial time scales,
were seen during the cold periods of the last
glacial cycle but not in older or warmer condi-
tions. Nehrbass-Ahles et al. present a record of
atmospheric carbon dioxide concentrations retrieved
from the European Project for Ice Coring in Antarctica
Dome C ice core showing that these carbon dioxide
jumps occurred during both cold and warm periods
between 330,000 and 450,000 years ago. They relate
these pulses to disruptions of the Atlantic meridi-
onal overturning circulation caused by freshwater
discharge from ice sheets. Such rapid carbon dioxide
increases could occur in the future if global warming
also disrupts this ocean circulation pattern. —HJS
Science, this issue p. 1000

Tiny gas bubbles visible in a freshly drilled ice core provide evidence
of atmospheric composition 330,000 to 450,000 years ago.

MICROBIOLOGY excreted. This innate protec- alterations in the T cell recep- repair-mediated degrada- CREDITS (FROM TOP): REYES ET AL.; CHRISTOPH NEHRBASS-AHLES, UNIVERSITY OF CAMBRIDGE
tion against UTIs is likely to be tor repertoire, which could then tion of stalled forks. The TET2
How uromodulin helps particularly important in infants be detected. They designed a product 5-hydroxymethyl-
flush out bacteria and children. —SMH deep-learning method for dis- cytosine at stalled replication
tinguishing the T cell repertoires forks recruited a base excision
Urinary tract infections (UTIs) Science, this issue p. 1005; in the blood of patients with and repair–associated endonucle-
are one of the most frequent see also p. 917 without cancer, which they vali- ase. Without TET2, stalled
bacterial infections in humans. dated in samples from multiple replication forks were stabilized
The glycoprotein uromodulin CANCER clinical cohorts. —YN instead of degraded, thereby
is the most abundant urinary Sci. Transl. Med. 12, eaaz3738 (2020). reducing PARP inhibitor sensi-
protein and can provide some A deeper look at cancer tivity. —LKF
protection from UTIs, but the immunity MOLECULAR BIOLOGY
precise mechanism has been Sci. Signal. 13, eaba8091 (2020).
unclear. Weiss et al. found that A key goal in oncology is diag- A fork in the road for drug
uromodulin forms stacked, nosing cancer early, when it is resistance CANCER IMMUNOLOGY
fishbone-like filaments that more treatable. Despite decades
act as a multivalent decoy of progress, early diagnosis Inhibitors of the enzyme Phages and cancer
for bacterial pathogens with of asymptomatic patients poly(ADP-ribose) polymerase immunity
adhesive pili that attach to the remains a major challenge. (PARP) block the repair and
uromodulin glycans (see the Most methods involve detecting restart of stalled replication Gut bacteria are involved in
Perspective by Kukulski). The cancer cells or their DNA, but forks, which eventually kills the education of T cell immune
resulting uromodulin-pathogen Beshnova et al. suggest a differ- cancer cells. Kharat et al. found responses, and the intestinal
aggregates prevent bacterial ent approach that is focused on that the DNA demethylase TET2 ecosystem influences antican-
adhesion to glycoproteins of the the body’s immune response. was critical for sensitivity to cer immunity. Fluckiger et al.
urinary epithelium and promote The authors reasoned that the PARP inhibitors by promoting report microbial antigens that
pathogen clearance as urine is presence of cancer may cause might cross-react with antigens

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