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Published by norazilakhalid, 2020-12-15 17:42:58

Science 2020_08_14.pdf

Science 2020_08_14.pdf


14 AUGUST 2020 • VOLUME 369 • ISSUE 6505

NEWS 758 Don’t crush that ant—it could 756 PHOTO: AP PHOTO/BRIAN INGANGA
plant a wildflower
IN BRIEF New findings show how ants choose and 770 Marine food webs destabilized
protect the seeds they disperse A combination of warming and
750 News at a glance acidification threaten marine biomass
By E. Pennisi and productivity By S. L. Chown
F E AT U R E S REPORT p. 829
752 Antibodies may curb pandemic
before vaccines 760 Lucky strike 771 An early start to Huntington’s disease
Now in efficacy trials, monoclonal antibodies Last year, an unusual meteorite crashed in a The huntingtin gene mutation interferes
promise to both prevent and treat disease Costa Rican rainforest. Rich in the building with neurogenesis in human fetal cortex
blocks of life, it has captivated collectors and
By J. Cohen researchers By J. Sokol By M. DiFiglia

753 For science in Latin America, INSIGHTS RESEARCH ARTICLE p. 787
‘a fascinating challenge’
Pandemic shows benefits of investments in POLICY FORUM 773 Designing a wider superelastic window
research but also poses grave threats Adding chromium to an iron alloy enables
766 Distorting science, shape recovery over a wide temperature range
By R. Pérez Ortega and L. Wessel putting water at risk
A recent rule is inconsistent with science By P. La Roca and M. Sade
755 Looking for the light in Haiti and will compromise the integrity
For physician Marie Marcelle Deschamps, of U.S. waters By S. M. P. Sullivan et al. REPORT p. 855
COVID-19 is just the latest challenge By R. Bazell
PERSPECTIVES 774 The importins of pain
756 Africa’s pandemic puzzle: why so A nuclear protein importer modulates gene
few cases and deaths? 769 Can playing together help expression to control the persistence of
Antibody surveys tell a different story than us live together? neuropathic pain By M. S. Yousuf and T. J. Price
official tolls By L. Nordling A field experiment in Iraq shows that
having Muslim teammates reduced REPORT p. 842
757 Fed-up archaeologists aim to fix field Christian soccer players’ prejudice
schools’ party culture 775 A coexistence that CuO2
Drinking and harassment spur experiments, By E. L. Paluck and C. S. Clark planes can see
including local projects and student stipends, Antiferromagnetism and superconductivity
for core training course By L. Wade REPORT p. 866 are not at odds in a quintuple-layer cuprate

744 14 AUGUST 2020 • VOL 369 ISSUE 6505 Published by AAAS By I. Vishik

REPORT p. 833

777 Michael Soulé (1936–2020)
Founder of conservation biology

By D. W. Inouye and P. R. Ehrlich SCIENCE

A mathematical model reveals the influence
778 How it all ends 787 Neurodevelopment of population heterogeneity on herd
A light-hearted exploration of the death of the Huntington’s disease alters human immunity to SARS-CoV-2 T. Britton et al.
Universe serves as an effective antidote for neurodevelopment M. Barnat et al.
everyday worries By P. Halpern 850 Electrochemistry
PERSPECTIVE p. 771 A molecular mediator for reductive
779 Science meets politics concerted proton-electron transfers
A passion for promoting the public good 793 Structural biology via electrocatalysis M. J. Chalkley et al.
guided geneticist J. B. S. Haldane’s Binding mechanisms of therapeutic
scholarship By P. W. Hughes antibodies to human CD20 855 Metallurgy
A. Kumar et al. Iron-based superelastic alloys with
LETTERS near-constant critical stress temperature
799 Organic chemistry dependence J. Xia et al.
780 Retraction Divergent synthesis of complex
diterpenes through a hybrid PERSPECTIVE p. 773
By S. Licht et al. oxidative approach X. Zhang et al.
858 Neurodevelopment
780 Controlling the COVID-19 narrative Coronavirus Mitochondrial dynamics in postmitotic
806 DNA vaccine protection against cells regulate neurogenesis R. Iwata et al.
By N. Bharti
SARS-CoV-2 in rhesus macaques 863 Paleoanthropology
780 Dismantling systemic racism J. Yu et al. Fire and grass-bedding construction
in science 200 thousand years ago at Border Cave,
812 SARS-CoV-2 infection protects South Africa L. Wadley et al.
By E. A. Odekunle against rechallenge in rhesus macaques
A. Chandrashekar et al. 866 Intergroup relations
781 Untapped resources for Building social cohesion between
medical research REPORT p. 818 Christians and Muslims through soccer
in post-ISIS Iraq S. Mousa
By O. A. Pérez-Escobar et al. REPORTS
RESEARCH 818 Coronavirus
Primary exposure to SARS-CoV-2 protects D E PA R T M E N T S
IN BRIEF against reinfection in rhesus macaques
W. Deng et al. 749 Editorial
783 From Science and other journals Vaccine nationalism’s politics
REVIEW By David P. Fidler
823 Immunology
786 Catalysis BAF restricts cGAS on nuclear DNA to prevent 874 Working Life
Using nature’s blueprint to expand catalysis innate immune activation B. Guey et al. Interrupted—again By Kathy Gillen
with Earth-abundant metals R. M. Bullock et al.
829 Trophic resilience ON THE COVER
REVIEW SUMMARY; FOR FULL TEXT: Trophic pyramids reorganize when
DX.DOI.ORG/10.1126/SCIENCE.ABC3183 food web architecture fails to adjust to A soccer game at Khazir
ocean change I. Nagelkerken et al. refugee camp outside
771 & 787 Erbil, northern Iraq.
PERSPECTIVE p. 770 A randomized study
assigned displaced
833 Superconductivity Christians to a soccer
Observation of small Fermi team with displaced
pockets protected by clean CuO2 sheets Muslims or to an all-
of a high-Tc superconductor Christian team. Playing
S. Kunisada et al. on a mixed team improved Christians’ behaviors
toward Muslim peers, but not toward Muslims
PERSPECTIVE p. 775 more broadly. The results highlight the potential
and limitations of intergroup contact after war.
838 Tropical forest See pages 769 and 866. Photo: Associated Press
Active restoration accelerates
the carbon recovery of human-modified Science Staff ..............................................746
tropical forests C. D. Philipson et al. New Products............................................. 871
Science Careers .........................................872
842 Neuroscience
Importin a3 regulates chronic
pain pathways in peripheral sensory
neurons L. Marvaldi et al.


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SCIENCE 14 AUGUST 2020 • VOL 369 ISSUE 6505 745

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746 14 AUGUST 2020 • VOL 369 ISSUE 6505 SCIENCE

Published by AAAS


Vaccine nationalism’s politics

B efore coronavirus disease 2019 (COVID-19) struck, With COVID-19, history is repeating itself. Countries
cooperation on global health—especially for pan- with the resources to obtain vaccines have not subordi-
demic preparedness and response—would, we nated their needs and capacities to the objective of global,
told ourselves, enhance national security, support equitable access. And the worldwide spread of the coro-
economic wealth, protect human rights, and facil- navirus eliminates leverage that viral sovereignty might
itate humanitarian assistance around the world. have provided countries without such means. Interna-

However, the politics of the coronavirus catastro- tional and nongovernmental organizations launched

phe do not reflect such national interests or international an ad hoc effort—the COVID-19 Vaccines Global Access David P. Fidler
is an adjunct senior
solidarity. “Vaccine nationalism” is more evidence that ef- (COVAX) Facility—to achieve equitable access. But with fellow at the Council
on Foreign Relations,
forts to elevate health cooperation—and the sciences that no serious participation by major states so far, COVAX Washington, DC,
USA. [email protected]
inform it—have produced more rhetoric than political lacks game-changing support. In keeping with the long-

roots within countries and the international community. standing pattern of political behavior during pandemics,

Concerns about vaccine nationalism were escalating vaccines will eventually reach most populations, but only

even before the United States announced on 31 July its after powerful countries have protected themselves.

largest deal to date with pharmaceutical companies to Further, changes in domestic and global politics

secure COVID-19 vaccines. Other countries—including have made matters worse. Domestically, the extent to

China, India, the United Kingdom, which governments have ignored

and members of the European science, denigrated health experts,

Union—are pursuing similar strat- “…access supported quack remedies and
egies. To critics, this scramble to policies, peddled disinformation,

secure vaccine supplies is one of to coronavirus and botched social distancing and
many decisions by governments other nonpharmaceutical interven-

that have failed to control spread vaccines tions has been astonishing. This
of the virus, destroyed economic travesty flows from the traction

activity, and damaged international has become that populist, nationalist, antiglo-
cooperation. Ineffective national- a priority in power balist, and authoritarian attitudes
istic policies appear to create a have gained around the world.
gap between science and politics politics…”
that makes the pandemic worse Globally, balance-of-power poli-
and undermines what science and tics has returned to world affairs.
health diplomacy could achieve. In Geopolitical calculations have
shaped national responses to CO-

fact, vaccine nationalism reflects VID-19, with the United States and

“business as usual” in global health. China treating the pandemic as

Historically, health diplomacy has struggled with another front in their rivalry for power and influence.

global, equitable access to drugs and vaccines during seri- National access to coronavirus vaccines has become a

ous disease events. Countries did not achieve this goal, priority in power politics, especially as a means to re-

for example, during the 2009 H1N1 influenza pandemic. cover from the economic damage at home, in export

International access typically happened only after devel- markets, and within regions of strategic importance in

oped countries secured pharmaceuticals for use at home, the balance of power.

as happened with vaccines for smallpox and polio and These changes in politics have generated ferocious

drugs for HIV/AIDS. Developing countries, such as China headwinds against global, equitable vaccine access—an

and India, tried to break out of this pattern by building objective only approached with great difficulty when

their own pharmaceutical innovation and production political waters were less turbulent. Reorienting health

capabilities. More recently, developing countries have policy and diplomacy will require root-and-branch re-

asserted sovereignty over pathogenic samples. This ap- construction of political interests on infectious diseases.

proach conditions access to samples on the source coun- Perhaps the mounting desperation for scientists to de-

try receiving benefits from research and development, liver a vaccine against COVID-19 will provide an incen-

including drugs and vaccines. This “viral sovereignty” tive for leaders to rebuild health policies sufficiently so

SOURCE: INDIANA UNIVERSITY strategy produced the virus-and-benefit sharing regime that, when the next pandemic hits, politicians and citi-

in the World Health Organization’s Pandemic Influenza zens will be less likely to drink the hydroxychloroquine.

Preparedness Framework in 2011. –David P. Fidler


SCIENCE 14 AUGUST 2020 • VOL 369 ISSUE 6505 749

Published by AAAS


Edited by Jeffrey Brainard

Fishermen use a hose
(left) to suck up netted

menhaden into a ship
in Virginia’s portion of

the Chesapeake Bay.


New fisheries regulation considers predators’ needs

W hen fisheries regulators decide how many fish as prey for Atlantic striped bass, a species especially prized by
humans can kill, they rarely consider whether the recreational fishers. The move—one of the first like it in the
quota affects other predators. But last week manag- world—is “a major step forward for management of marine
ers overseeing fisheries off the U.S. east coast took resources and conservation science,” the Pew Charitable Trusts
that broader view in deciding how they will set said in a statement. The decision should also help other fish,
catch limits for menhaden, a small, oily fish that is whales, and birds that feed heavily on menhaden, the commis-
the basis for the second largest fishery in the United States by sion said. Conservationists had long pushed for the change, ar-
weight harvested. Ending a yearslong conservation battle, guing that menhaden, which are mostly sold for animal feed,
the Atlantic States Marine Fisheries Commission unanimously fish oil pills, and bait, play a key role in marine food webs and
voted to set new menhaden limits designed to leave enough needed to be managed more sustainably.

Russia OKs COVID-19 vaccine use ministry spokesperson. (China earlier of Russia’s move said it was politically PHOTO: ANDREW CABALLERO-REYNOLDS/AFP VIA GETTY IMAGES
approved use of an experimental COVID- motivated and meant to prop up the
PU B L I C H E A LT H | In a move that startled 19 vaccine for its military, but it’s unclear stature of its scientific community.
and confused researchers worldwide, whether any troops have received it.)
Russia’s Ministry of Health on 11 August The certificate says the vaccine cannot A call for antibody treatments
issued a “registration certificate” for be used widely until 1 January 2021, but
a COVID-19 vaccine—even though it does not explain the rationale. Vaccine D RU G D E V E LO P M E N T | Companies,
has been tested in only 76 people. The researchers and public health specialists academia, and governments should work
certificate allows the vaccine, made by the immediately denounced the certification to make monoclonal antibodies against
Gamaleya Research Institute in Moscow, as premature and inappropriate because many diseases more widely available
to be used by “a small number of citizens the vaccine has yet to complete an efficacy to people across the globe, a report
from vulnerable groups,” including medical trial that convincingly shows it is safe and says. Antibody treatments have had an
staff and older people, according to a effective in a large group of people. Critics immense impact on treating several

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types of cancer as well as autoimmune signaled major shifts in vegetation. When Committee. In Nature Genetics, it
diseases and are increasingly used to the last ice age ended roughly 11,000 years published revised naming guidelines that
fight infectious diseases like Ebola and ago, forests and grasslands regrew across call for, among other updates, tweaking
HIV. But people in low- and middle- North America, creating a landscape that symbols known to autoconvert to dates.
income countries hardly have any access remained largely stable for thousands of For example, DEC1, an abbreviation for
to these expensive drugs, according to years. But recently, humans have changed “deleted in esophageal cancer 1,” was
the report by the International AIDS the landscape even more than melting renamed DELEC1; SEPT1 is now SEPTIN1.
Vaccine Initiative, a nonprofit research glaciers, she reported, lending further The committee, which considers such
organization, and the Wellcome Trust, one support for the notion of a new epoch changes case by case, has altered 27 such
of the world’s biggest research funders. in geological history, the Anthropocene, symbols this year, reported The Verge, a
Academic researchers and governments defined by human activity. news website.
can improve access, the report says, by
supporting new technologies to make Number of abrupt ecosystem changes per every HIV-positive to join vaccine trials
antibody treatments cheaper and clarify- 250 years for every 100 sites studied
ing and harmonizing regulations so that C L I N I CA L T R I A LS | In response to lob-
more countries can register the therapies. 15 10 20 bying by AIDS activists and scientists,
The report’s authors also tout the poten- companies running two large clinical
tial for monoclonal antibodies to treat 13,000 to 11,000 11,000 years 1700 C.E. studies of COVID-19 vaccines have agreed
COVID-19 (see p. 752). to include people with HIV. Vaccine trials
years ago ago to to often exclude HIV-positive people because
of concerns their infection would impair
(glacial shifts) 1700 C.E. 1950 C.E. their responses to immunization. But the
Infectious Diseases Society of America
Pollen reveals human footprint Gene renaming eases headaches and AIDS activists argued that most HIV-
infected people on antiviral treatment
ECOLOGY | Agriculture and other human DATA M A N AG E M E N T | It was driving don’t have suppressed immune systems
activities have caused abrupt changes in geneticists mad: When they entered the and that leaving this group out would be
North America’s ecosystems more often standardized symbols of certain human wrong. Moderna and Pfizer, which each
in the past 250 years than the previ- genes, such as MARCH1, into Microsoft launched a 30,000-person U.S. phase III
ous 11,000—more even than during a Excel, the software program automatically trial in late July, both announced last
relatively short period of glacial advance converted them into dates, such as 1-Mar. week that they plan to amend their pro-
and retreat from 13,000 to 11,000 years Scientists could reformat columns to tocols to include people with stable HIV.
ago. At last week’s virtual annual meet- avoid the common problem, but many Lynda Dee of AIDS Action Baltimore says
ing of the Ecological Society of America, didn’t, allowing errors to propagate in AstraZeneca plans to include HIV-positive
Stanford University paleoecologist M. data sets and scholarly papers based on people when it begins enrollment in a
Allison Stegner described her team’s them. Last week, a fix was announced phase III vaccine trial at U.S. sites; a
analysis of fossil pollen in 400 well-dated by an international group that manages company spokesperson declined to con-
mud cores sampled from lakes across the symbols, the Human Genome firm this.
North America. Big shifts in pollen types Organization’s Gene Nomenclature
Neuroscience meeting axed
CO M M U N I T Y | Organizers of one of
The Milky Way’s distant cousin the world’s largest scientific meetings
announced last week it will not take place
A stronomers were surprised to find that a online or in person this year because of
galaxy formed just 1.4 billion years after COVID-19. Many scientific organizations
the big bang looks remarkably like our have replaced in-person meetings with
well-ordered, disk-shaped Milky Way— virtual ones this year, but the Society for
a challenge to the conventional Neuroscience (SFN) canceled its meeting
view that galaxies in the early universe altogether, citing risks and restrictions from
were chaotic and unstructured. the pandemic. About 30,000 neuroscientists
In Nature this week, a team of had once planned to convene in Washington,
astronomers describes processing D.C., in October. Some scientists criticized
archival data from Chile’s Atacama SFN’s decision. “So you have $70M [mil-
Large Millimeter/submillimeter Array lion] sitting in your bank account and you’re
of the distant galaxy SPT0418–47; telling us that can’t organize an amazing
observations captured it in its youth virtual meeting with 6+ months notice?”
12 billion years ago, when the universe computational neuroscientist Gunnar
was just 10% of its current age. The Blohm of Queen’s University in Kingston,
gravity of another galaxy between Earth Canada, wrote on Twitter. Others, including
and SPT0418–47 focused its rays, creating neuroscientist Kay Tye of the Salk Institute
a circular image (right). But subsequent for Biological Studies, said it was the right
computer modeling revealed a rotating call. “It would have been a pretty sad virtual
disk and central bulge, features thought to experience,” she tweeted.
form much later in galactic evolution.

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IN DEPTH COVID-19 hopes are riding on antibodies
that bind to a key surface protein of the new
coronavirus (orange in an artist’s concept).


Antibodies may curb pandemic before vaccines

Now in efficacy trials, monoclonal antibodies promise to both prevent and treat disease

By Jon Cohen lines of B cells that make the proteins, rais- in three large-scale, placebo-controlled tri-

W hile the world is transfixed by ing concerns they could be scarce and expen- als. A prevention trial run in coordination
the high-stakes race to develop a
COVID-19 vaccine, an equally cru- sive. On 15 July, Lilly, AbCellera, AstraZeneca, with NIAID’s COVID-19 Prevention Trials
cial competition is heating up to
produce targeted antibodies that GlaxoSmithKline, Genentech, and Amgen Network (CoVPN), an arm of the Trump ad-
could provide an instant immune
boost against the virus. Clinical trials of these jointly asked the U.S. Department of Justice ministration’s Operation Warp Speed, will
monoclonal antibodies, which may both pre-
vent and treat the disease, are already under- (DOJ) whether they could share informa- recruit 2000 people who live in a house with
way and could produce signs of efficacy in the
next few months, perhaps ahead of vaccine tion about manufacturing their monoclonals a confirmed COVID-19 case. One treatment
trials. “If you were going to put your money
down, you would bet that you get the answer without violating antitrust laws “to expand study run by the company aims to enroll
with the monoclonal before you get the an-
swer with a vaccine,” says Anthony Fauci, and expedite production.” nearly 2600 hospitalized people with severe
head of the National Institute of Allergy and
Infectious Diseases (NIAID). Soon after the pandemic began, research- COVID-19, whereas another, about half that

“Antibodies have the potential to be an im- ers in industry and academia began to iden- size, will test the antibodies in infected people
portant bridge until the vaccine is available,”
says Ajay Nirula, a vice president at Eli Lilly, tify, design, tweak, and conduct with mild or moderate symptoms.
one of several large companies investing in
them. Likely to be more effective than rem- lab tests of monoclonal antibodies Science’s Lilly has launched its own trials,
desivir and dexamethasone, the repurposed against SARS-CoV-2, the virus that including a phase III, placebo-
drugs shown to help against COVID-19, anti- causes COVID-19. Most bind to COVID-19 controlled study in 2400 residents
bodies could protect the highest risk health and “neutralize” the viral surface reporting is or staff of long-term care facilities,
care workers from becoming infected while protein, or spike, that initiates an supported by the run with the help of CoVPN.
also lessening the severity of the disease in infection. On 29 May, Lilly, work- Pulitzer Center
hospitalized patients. But producing mono- ing with AbCellera, launched the “We should be able to see an effi-
clonals involves using bioreactors to grow and the cacy signal very quickly” from these

first human study of a monoclonal Foundation. trials, says Amy Jenkins, who heads

antibody—a phase I trial testing the Pandemic Prevention Platform

its safety and tolerability in hospitalized (P3) program at the Defense Advanced Re- IMAGE: JUAN GAERTNER/SCIENCE SOURCE

COVID-19 patients. Other safety trials fol- search Projects Agency, which for 2 years

lowed, from Lilly’s Chinese partner Junshi has invested in speeding the development

Biosciences and Regeneron, which devel- of monoclonal antibodies. Although Jenkins

oped a cocktail of three monoclonals that hesitates to make a firm prediction, she says

works against Ebola. the November-December time frame is “real-

Regeneron is now testing the efficacy of its istic and conservative.” That is likely earlier

COVID-19 cocktail, which combines a spike than any vaccine will prove safe and effective,

antibody from a person who recovered and researchers predict. “I would be reluctant to

one from a mouse given the spike protein, say [that] would be any earlier than the end

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of the year,” Fauci said at a press conference next year for prevention and treatment. COVID 19

about the launch of NIAID’s first COVID-19 “Unlike with vaccines, it is hard to project For science in
Latin America,
efficacy vaccine trial on 27 July. the number of treatment courses that will ‘a fascinating
Regeneron’s Christos Kyratsous notes be available,” Woodcock says. Prevention,
Pandemic shows benefits
that vaccine trials must wait a few weeks which would be a single intramuscular of investments in research
but also poses grave threats
for a person’s immune system to develop shot, requires less product than the intra-
By Rodrigo Pérez Ortega and Lindzi Wessel
appropriate responses to shots and further venous infusions used in treatment, she
A s the COVID-19 pandemic surged
weeks for “the event”—a chance exposure notes, but the amount needed depends on across the United States and Europe
in February, scientists at Mexico’s
to SARS-CoV-2. This means those trials re- a person’s weight. Center for Research and Advanced
Studies (Cinvestav) sprang into ac-
quire time and many people. In contrast, for Although how to prioritize vaccine dis- tion. They quickly converted one of
their research labs into a diagnostic clinic,
the antibody treatment trials, “your event tribution has already sparked extensive and by mid-March, as cases began to mount
in Mexico, they had launched seven other
has already happened,” Kyratsous says. And debate, no such discussion has yet taken COVID-19–related projects.

in the prevention studies, the household place about monoclonal antibodies. But Then a second crisis hit. On 2 April,
Mexican President Andrés Manuel López
contacts of COVID-19 cases will be much DOJ acknowledged the supply concerns on Obrador ordered the termination of pub-
lic trust funds, which pay for special and
more likely to be exposed than people who 23 July, giving the six companies that had long-term projects at Cinvestav—a public
institute with nine campuses that employs
typically join a vaccine efficacy study. petitioned it the green light to share pro- 7500 people—and other institutions. Three
weeks later, he announced a 75% cut for
Immunologist Dennis Burton, whose duction information. some federal institutions’ operating bud-
gets, including Cinvestav’s, that would have
group at Scripps Research has isolated Regeneron is not part of that group, yet forced the institute to shut down, says Cin-
vestav Director José Mustre de León.
highly potent monoclonal antibodies Kyratsous is optimistic about meeting the
Another blow followed on 14 May, when
against SARS-CoV-2 that it hopes to move need. “The good thing with some of these the National Council of Science and Tech-
nology (Conacyt) asked scientists to donate
into human studies (Science, 15 June, DOI: biologics is you can ramp up production their monthly federal supplement, a typi-
cal part of Mexican researchers’ income,
10.1126/science.abc8511), says he is opti- fairly fast,” he says. Nirula agrees. “If we to the nation’s health system to support
the COVID-19 response. “Not only would
mistic that monoclonals will have success in these clinical we not have any money, but we’ll have to
take money out of our own pockets,” says
protect people from infection “Antibodies trials, we will have a lot of drug Gabriela Olmedo, a genetic engineer and di-
for months with a single shot. available,” he says. rector of Cinvestav’s Irapuato campus.

“It’s much easier to take care have the The cost of monoclonals, Mexican scientists aren’t alone in feeling
of a few incoming virus par- potential to be especially for the higher doses conflicting pressures from the pandemic.
ticles than to try and resolve an important needed for treatment, could Across Latin America, researchers have
or cure an ongoing infection.” split the world into the haves raced to contribute their expertise to the
The same logic holds for treat- and have-nots. “It’s unlikely worst public health crisis in a century and
demonstrate that several decades of invest-
ment. “Hit the virus hard and bridge until that that treatment will get ment in research—including the capacity to
early,” Burton says. down to a price point in the run large clinical trials—has paid off. “We
basically showed that we have knowledge
Kyratsous says even if the vaccine is near future that it would be in the country that can be put to work for
monoclonal antibodies don’t available.” easily affordable globally,”
beat vaccines to the finish line, says Seth Berkley, who leads

they still might have a role to Ajay Nirula, Eli Lilly Gavi, the Vaccine Alliance,
play against COVID-19. “We’re and heads an international

going to need both approaches COVID-19 vaccine effort.

in the long run,” Kyratsous suggests. Vac- Jenkins says a key aim of the P3 proj-

cines are rarely 100% effective, and many ect, which has provided four groups with

people may decline a vaccine or skip im- $96 million in seed money, has been to de-

munization for other reasons. What’s more, velop monoclonal antibodies that can be

he notes, the elderly or people who are im- made by the body itself, instead of in large

mune compromised may not mount robust fermentation tanks. The idea, which has not

immune responses after being vaccinated. yet been tested in humans for COVID-19, is

Supplies of monoclonal antibodies may to inject people with DNA or messenger

be limited, however, in part because of RNA that encodes a desired antibody, al-

modest investment. Operation Warp Speed, lowing their own cells to make it. “We think

for example, has committed $8 billion to we can bring down the cost of monoclonal

six different COVID-19 vaccines; for mono- antibodies,” Jenkins says.

clonals, the government has invested about Regardless of cost, evidence that mono-

$750 million, much of it in Regeneron, clonals work as preventives could benefit

which will produce somewhere between everyone by giving vaccinemakers a clear

70,000 and 300,000 doses before it even sign that antibodies against the surface pro-

has efficacy data. Lilly says it will have tein of SARS-CoV-2 are enough to protect a

100,000 doses by the end of the year. person. This, in turn, could provide a strong

But no one knows how far those doses indicator for evaluating the worth of a can-

would stretch, says Janet Woodcock, who is didate vaccine short of actual efficacy data.

on leave from the Food and Drug Admin- “It will be earthshaking to the vaccine field

istration to lead Warp Speed’s therapeutic in a positive way,” says Myron Cohen of the

effort. If the antibodies work, a study from University of North Carolina, Chapel Hill,

the Duke University Margolis Center for who leads testing of monoclonal antibodies

Health Policy estimates the United States for CoVPN. “It provides a thousand oppor-

alone could require nearly 40 million doses tunities to move forward faster.” j

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Students protest against a cut in the education budget at the Central University of Ecuador on 5 May. Technological Innovation (CONCYTEC). This
year, the government paused certain funding
the benefit of the society as a whole,” says In Argentina and Chile, science’s political programs; by July’s close, CONCYTEC had PHOTO: RODRIGO BUENDIA/AFP/GETTY IMAGES
Aisén Etcheverry, who heads Chile’s National standing has risen in the crisis. Argentine spent just 16% of its 2020 budget.
Agency for Research and Development. At President Alberto Fernández, elected in
the same time, the pandemic has created 2019, was already taking a science-friendly In neighboring Ecuador, new threats of
deep economic and financial problems for approach, generally heeding his science ad- cuts to higher education and the economic
the region, which faces a projected 5.3% con- visers and promising more funding—a shift crisis have led scientists to ramp up efforts
traction in gross domestic product this year. from his predecessor, who implemented to secure funding by collaborating with re-
The resulting cuts are hitting science hard devastating budget cuts and demoted the searchers from the United States and the
and threatening hard-won gains. science ministry to a subsection of the Min- European Union, says Diego Quiroga, dean of
istry of Education. Now, the public sees research at San Francisco de Quito University.
Latin America comprises less than 10% that prioritizing science helps Argentina re- “If we don’t look abroad for funding, we’ll
of the global population yet accounts for spond to the pandemic, argues Juan Pablo have nothing,” says Quiroga, who predicts
nearly one-third of reported COVID-19 Paz, secretary of scientific and technological the pandemic will cause an exodus of young
deaths. In deaths and case counts, Brazil coordination. “I think science will remain in scientists. As Mustre de León puts it: “We’re
ranks second only to the United States; Co- a stronger position than before.” losing an entire generation of scientists.”
lombia, Chile, Peru, and Mexico have been
hard hit as well. The fallout could push an In Chile, Etcheverry redirected her In Mexico, after an outcry from research-
additional 16 million residents of the region agency—part of a new science ministry ers, students, and the media, the president
into extreme poverty, according to a report and only 3 months old when the pandemic ordered Conacyt officials to drop their plea
from the United Nations. struck—to provide COVID-19 testing and for donations. Cinvestav was allowed to keep
other aid to the pandemic response and its public trust funds for now and is negoti-
Latin America’s growth in basic research, made money available to track societal im- ating a smaller budget cut. But other federal
achieved through decades of investment in pacts of the crisis, such as increases in do- institutions will still see cuts, and the epi-
many countries, has put the region in a bet- mestic violence. Showing that science could sode left scientists shaken and worried. “If
ter position to fight back, says Hernando help “generated a conversation inside the we hadn’t had this budget cut environment,
García Martínez, director of the Alexander government that never had happened be- we could have done much more,” Mustre de
von Humboldt Biological Resources Re- fore,” Etcheverry says. “It’s definitely a turn- León says. And the pandemic has worsened
search Institute in Bogotá, Colombia. “We ing point on how the sector is perceived.” an already-tense relationship between the
wouldn’t have had the capacity to respond scientific community and Conacyt Director
to such a direct and real problem for society Still, the economic crisis has not spared and developmental biologist María Elena
as COVID-19,” says García Martínez, who de- Chilean science. Becas Chile, a scholarship Álvarez-Buylla Roces, whose response to the
scribes the crisis as a “fascinating challenge.” program that funds international study for pandemic they have criticized.
aspiring researchers and has boosted growth
In early April, Colombian researchers of many scientific fields in Chile, has been Elsewhere, too, the pandemic has deep-
were among the first to start a clinical trial partly suspended. “Having that frozen or put ened rifts between scientists and politi-
of convalescent plasma—antibody-rich se- into question just because we’re in a crisis is cians. Brazilian President Jair Bolsonaro
rum from people who have recovered—for not the right decision because these are the has repeatedly called into question scientific
COVID-19 patients. More than 190 other kinds of things that prepare you for the next expertise, downplaying the severity of the
clinical trials are ongoing in Latin America. one,” says César Fuentes, an astronomer at pandemic and promoting treatments lack-
Researchers in Brazil, Mexico, and Argen- the University of Chile. ing evidence. In Venezuela, scientists’ alarms
tina have joined the race to develop their prompted threats from high-level govern-
own vaccines and are partners in phase The picture is darker in Peru, says Gisella ment officials. And in Colombia, seven sena-
II and III trials of international vaccine Orjeda, former president of the country’s tors sent President Iván Duque Márquez a
front-runners. National Council of Science, Technology and letter on 27 July complaining about a lack
of leadership during the pandemic by Mabel
Torres Torres, who leads the new Ministry
of Science, Technology and Innovation and
was previously engulfed in scandals over her
promotion of an untested cancer treatment.
“It’s an absent ministry,” says immunologist
Gabriela Delgado Murcia of the National
University of Colombia, Bogotá. “We feel
desolate.” Two days later, the Ministry of Fi-
nance proposed a 35% cut for the country’s
2021 science budget.

Despite the challenges that the pandemic
has brought, García Martínez remains hope-
ful. Years of scarce funding have taught Latin
American researchers to do a lot with very
little, he says—an especially helpful skill
these days. “We are very adaptive.” j

Rodrigo Pérez Ortega is a science journalist
in Washington, D.C. Lindzi Wessel is a journalist
in the San Francisco Bay Area.

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Looking for the light in Haiti

For physician Marie Marcelle Deschamps, COVID-19 is just the latest challenge

By Robert Bazell sire to become a good doctor,” she says. The a tiny building across the street from an

beginning of her career coincided with the enormous slum known as City of God into

M arie Marcelle Deschamps remem- huge outbreak in Haiti of the disease that a health organization that now treats more
bers the first patient with COVID-19 came to be called HIV/AIDS, before there Haitians with HIV/AIDS and tuberculosis
to visit a clinic she runs in Port- were meaningful treatments. She recalls than any other group in Haiti, as well as car-
au-Prince, Haiti. It was late March. telling her husband, “I am signing so many ing for people with myriad other maladies.
His blood oxygen saturation, nor- death certificates I hope that one day peo-
Deschamps sees COVID-19 as just the lat-

mally above 90%, was 35%. The ple won’t judge me for being a bad doctor.” est chapter in the Haitian saga. “Every time

45-year-old man died within 1 hour. “Oh In the early days of the HIV/AIDS crisis, you make progress, finding the solutions,

my God,” she recalls telling her you are pushed back by either a

colleagues. “It’s here.” natural or political catastrophe,”

As the director of a major she says. “You are always in a situa-

health care organization in Haiti, tion of crisis where you have to act

Deschamps was already stretched rapidly.” After the devastating 2010

thin by the struggles of providing earthquake, Deschamps’s clinic

medical help in one of the poorest allowed hundreds of slum dwell-

nations on Earth. Her clinic was ers whose shacks had collapsed to

soon seeing thousands of COVID-19 camp on its property. She and her

cases per week, and her days became colleagues circulated among the

consumed with treating patients, injured treating horrible fractures

supervising the other doctors, and and other injuries.

dispatching teams to provide care Soon after the earthquake,

and counseling to people in Haiti’s U.N. troops from Nepal unknow-

urban slums and countryside. ingly brought a cholera epidemic

Those who have met Deschamps to Haiti that sickened more than

(including this reporter) know her 800,000 and killed more than

as amazingly warm, bright, and 10,000 over several years, putting

charming. Clinic staff, patients, enormous additional stress on

and even strangers greet her fondly all of Haiti’s health facilities, in-

as she rushes past. The need for cluding Deschamps’s clinics. “The

women to take an increasing role country has been very vulnerable,”

in Haiti’s health care has long been Deschamps says, citing threats as

identified as a key to economic diverse as political destabilization,

development, and after 4 decades impacts of deforestation on farm-

of practicing medicine in her na- land and drinking water sources,

tive country, Deschamps is seen by hurricanes, and a never-ending pro-

many as an icon and a role model. cession of infectious diseases. “Now

“She is inspiring,” says Sandra COVID,” she says with a laugh. “So,

Lamarque, head of mission in Haiti I said to my myself, what is it we

for Doctors Without Borders. “Every time you make progress ... have not seen finally.”
Jean William Pape, founding you are pushed back by either a natural Until Deschamps saw her first

director of GHESKIO, the private or political catastrophe.” COVID-19 patient in late March,
nonprofit health organization Haiti’s poverty and isolation had
Deschamps now heads, credits her kept it relatively safe from the pan-

for introducing multiple programs Marie Marcelle Deschamps, GHESKIO demic. The government had taken
that have improved women’s health precautions, closing the interna-

and wellbeing, including ones that tional airport and shutting down

care for victims of sexual assault, guide poor a group of senior Haitian and U.S. doctors businesses. Two infected travelers, one from

women in obtaining microcredit loans to chose Deschamps to study in the United the United States and one from Europe, had

ILLUSTRATION: KATTY HUERTAS start businesses, or help them get their chil- States, where she did fellowships in An- been discovered and quickly isolated.

dren into schools. “When she sets out to solve thony Fauci’s lab at the National Institute But the patient in her clinic—and others

a problem, it gets solved,” says Pape, who now of Allergy and Infectious Diseases, Walter who quickly followed—had been working

co-directs Haiti’s response to COVID-19. Reed military hospital, and the Centers for at hotels in the Dominican Republic, which

Deschamps decided on a career in medi- Disease Control and Prevention. On her shares a porous border with Haiti on the is-

cine after witnessing her father die a slow return to Haiti, she and Pape expanded land of Hispaniola. Because it is a popular

death from kidney failure. “I had such a de- GHESKIO. It grew from humble origins in winter tourist destination for people from

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the northeastern United States and Europe, Children run past a mural warning about COVID-19 in Nairobi. Kenya has reported relatively few cases so far.
the Dominican Republic got hit hard and
early with COVID-19. More than 30,000 Hai- COVID 19
tians lost their jobs there and were either
forced out or fled home—some bringing the Africa’s pandemic puzzle:
virus with them. Another 300,000 had com- why so few cases and deaths?
muted back and forth for occasional work.
Antibody surveys tell a different story than official tolls
For several weeks, Haiti saw large num-
bers of COVID-19 cases, often overwhelm- By Linda Nordling Blantyre, Malawi, immunologist Kondwani PHOTO: AP PHOTO/BRIAN INGANGA
ing the relatively few available hospital Jambo of the Malawi–Liverpool Wellcome
beds. Because many Haitians lack shelter, A lthough Africa reported its mil- Trust Clinical Research Programme and col-
food, and medical care, the United Na- lionth official COVID-19 case last leagues concluded that up to 12.3% of them
tions Economic and Social Council warned week, it seems to have weathered had been exposed to the coronavirus. Based
that COVID-19 could trigger a humanitar- the pandemic relatively well so far, on those findings and mortality ratios for
ian catastrophe, a theme echoed in a letter with fewer than one confirmed case COVID-19 elsewhere, they estimated that re-
co-authored by Deschamps and published for every thousand people and just ported number of deaths in Blantyre at the
on 16 June in The New England Journal of 23,000 deaths. Yet several antibody sur- time, 17, was eight times lower than expected.
Medicine titled Facing the Monster in Haiti. veys suggest far more Africans have been
infected with the coronavirus—a discrep- Scientists who surveyed about 10,000
The letter warned that stigmatization— ancy that is puzzling scientists around the people in two cities in Mozambique, Nam-
once directed against those with HIV— continent. “We do not have an answer,” says pula and Pemba, found antibodies to
was now impeding care for those with immunologist Sophie Uyoga of the Kenya SARS-CoV-2 in 3% to 10% of participants,
COVID-19. Health care workers have en- Medical Research Institute–Wellcome Trust depending on their occupation; market
dured threats and had stones thrown at Research Programme. vendors had the highest rates, followed by
them. Some patients have been driven from health workers. Yet in Nampula, a city of
their homes and shunned by relatives, forc- After testing more than 3000 blood do- approximately 750,000, a mere 300 infec-
ing them to live on the streets. Deschamps nors, Uyoga and colleagues estimated in a tions had been confirmed at the time. Mo-
has directed community health workers to preprint last month that one in 20 Kenyans zambique only has 16 confirmed COVID-19
try to combat stigma and educate people aged 15 to 64—or 1.6 million people—has deaths. Yap Boum of Epicentre Africa, the
about safety measures, but she acknowl- antibodies to SARS-CoV-2, an indication of research and training arm of Doctors With-
edges it isn’t easy. “How can you ask some- past infection. That would put Kenya on a out Borders, says many people in Cameroon
one to adopt proper distancing measures par with Spain in mid-May, when that coun- have COVID-19 antibodies as well.
when five people are living in one room?” try had 27,000 official COVID-19 deaths.
Kenya’s official toll stood at 100 when the So what explains the huge gap between
So far, however, the worst predictions study ended. And Kenya’s hospitals are not antibody data and the official toll? Part of
haven’t come to pass. Although testing and reporting huge numbers of people with the reason may be that Africa misses many
surveillance is limited, the official number COVID-19 symptoms. more cases than other parts of the world
of confirmed cases declined from almost because it tests far less. Kenya tests about
300 per day in mid-June to about 100 in mid- Other antibody studies have yielded simi- one in every 10,000 inhabitants daily for
July. As of 9 August, Haiti had reported only larly surprising findings. From a survey of active SARS-CoV-2 infections, one-tenth of
183 COVID-19 deaths in its population of 500 asymptomatic health care workers in
11.2 million. Deschamps says that even at
current levels COVID-19 represents a huge
burden, but she is “hopeful and skeptical at
the same time” about the future.

Some other resource-poor countries
have reported similar declines in cases.
Global health experts have speculated that
those countries may benefit from relatively
younger populations, shanties that though
crowded are well-ventilated, or a more ef-
fective early immune response to COVID-19
because of the many other infections people
face. “We just don’t know the reasons for this
but it is a very intriguing question,” says im-
munologist Barry Bloom, former dean of the
Harvard T.H. Chan School of Public Health.

Although she could live and practice
medicine anywhere, Deschamps insists she’ll
never leave Haiti. “This is my place,” she says.
Haitians are resilient, she says, in spite of all
they’ve endured. “It’s not that we forget …
[but] we are always looking for the light.” j

Robert Bazell, an adjunct professor at Yale University,
is a journalist based in New Haven, Connecticut.

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the rate in Spain or Canada. Nigeria tests CAREERS
one out of every 50,000 people per day.
Even many people who die from COVID-19 Fed-up archaeologists aim
may not get a proper diagnosis. But in that to fix field schools’ party culture
case, you would still expect an overall rise
in mortality, which Kenya has not seen, says Drinking and harassment spur experiments, including
pathologist Anne Barasa of the University of local projects and student stipends, for core training course
Nairobi. Uyoga cautions that the pandemic
has hamstrung Kenya’s mortality surveil- By Lizzie Wade researchers say it’s more important than
lance system, however.
ever for academic archaeologists to take
Marina Pollán of the Carlos III Health In-
stitute in Madrid, who led Spain’s antibody E ach year, archaeologist Carol Colaninno the lead in making such schools safe. New
survey, says Africa’s youthfulness may protect guides undergraduates through a con- regulations under Title IX, the U.S. federal
it. Spain’s median age is 45; in Kenya and Ma- sequential choice: Where should they law governing sexual harassment in higher
lawi, it’s 20 and 18, respectively. Young people go to field school? Every budding U.S. education, no longer require universities to
around the world are far less likely to get se- archaeologist must attend one to learn investigate incidents that happen in their
verely ill or die from the virus. And the popu-
lation in Kenya’s cities, where the pandemic hands-on skills such as excavation, and programs abroad.
first took hold, skews even younger than the
country as a whole, says Thumbi Mwangi, an to have any hope of landing a job or entering Although anecdotes of sexual harassment
epidemiologist at the University of Nairobi.
grad school for archaeology. in field schools are plentiful, data on such
Jambo is exploring the hypothesis that
Africans have had more exposure to other The undergrads can choose from hun- episodes are limited. But studies show they
coronaviruses that cause little more than
colds in humans, which may provide some dreds of field schools, many in remote areas. are common in archaeology, as they are in
defense against COVID-19. Another possi-
bility is that regular exposure to malaria or But Colaninno, who teaches at Southern Il- other field-based disciplines. In a survey by
other infectious diseases could prime the im-
mune system to fight new pathogens, includ- linois University, Edwardsville, knows from the Southeastern Archaeological Confer-
ing SARS-CoV-2, Boum adds. Barasa, on the
other hand, suspects genetic factors protect former students and information passed ence, 68% of 244 respondents of all genders
the Kenyan population from severe disease.
privately among others in her reported inappropriate remarks
More antibody surveys may help fill out
the picture. A French-funded study will test whisper network that some field “The in the field; another 13% re-
thousands for antibodies in Guinea, Senegal, schools have a reputation for ported unwanted sexual contact.
Benin, Ghana, Cameroon, and the Demo-
cratic Republic of the Congo. And 13 labs in 11 faculty who sexually harass with archaeology Remote sites and field schools
African countries are participating in a global impunity. Many schools are also cowboy have been considered “an al-
SARS-CoV-2 antibody survey coordinated by famed for heavy drinking. ternative space where different
the World Health Organization. mentality … rules applied,” Baxter says.
Traditional field schools foster
If tens of millions of Africans have al- “the archaeology cowboy mental- The current culture at such
ready been infected, that raises the ques-
tion of whether the continent should try for ity … working really hard during devolves into sites and schools may drive some
“herd immunity” without a vaccine, Boum the day but playing really hard a frat party.” students out of the profession, ac-
says—the controversial idea of letting the at night—and drinking a ton,” cording to a paper published last
virus run its course to allow the popula- says Katrina Eichner, an archaeo- Katrina Eichner, month in American Anthropo-
tion to become immune, perhaps while logist at the University of Idaho. logist. An atmosphere of in-
shielding the most vulnerable. That might
be preferable over control measures that If directors of these field schools University of Idaho formality, including frequent
cripple economies and could harm public
health more in the long run. encourage that atmosphere, she drinking, undermined expec-

“Maybe Africa can afford it,” given the adds, “it devolves into a frat party.” Over tations of professionalism and excluded
apparent low death rate, he says. But
Glenda Gray, president of the South African time, that cowboy culture gets perpetuated people who weren’t willing or able to
Medical Research Council, says it could be
dangerous to base COVID-19 policies on anti- across academic generations. navigate the unspoken rules, according
body surveys. It’s not at all clear whether
antibodies actually confer immunity, and if Now, Colaninno, Eichner, and other ar- to the paper’s analysis of archaeological
so, how long it lasts, Gray notes—in which
case, she asks, “What do these numbers re- chaeologists are trying to change the script. field sites and an anonymous field school
ally tell us?” j
With the help of a National Science Founda- in Chile. “It weeds out people,” says author
Linda Nordling is a journalist in Cape Town,
South Africa. tion (NSF) grant, Colaninno is studying, and Mary Leighton, an anthropologist at the

plans to implement, best practices for pre- University of Michigan, Ann Arbor. “The

venting sexual harassment at field schools. people who love it, stay [in archaeology].

And some archaeologists, aware that remote And the people who don’t like it leave.”

summer courses can cost thousands of dol- To create a more welcoming and profes-

lars and keep students of modest means out sional culture, Colaninno’s team recently

of the field altogether, are rethinking the offered recommendations from the first

whole model: They teach field skills at local phase of its research. The suggestions in-

sites during the regular semester. “We don’t clude: Create an environment that doesn’t

have to create the same environment that we trivialize harassment, offer multiple ways

didn’t want to be in when we were students,” to report harassment other than going to

says Jane Eva Baxter, an archaeologist at De- the field director, and reflect weekly on

Paul University and the author of a respected what’s working and what isn’t. The team,

guide for field school instructors. which published its guidance in May in Ad-

Although field schools are on hold this vances in Archaeological Practice, plans to

year because of the COVID-19 pandemic, implement those policies at eight U.S. field

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schools as part of its NSF-funded project, most afraid of. Together, the team comes up ECOLOGY
and study outcomes over 2 years. with principles to “minimize those fears and
maximize that excitement,” Gonzalez says. Don’t crush
In April, a study in Advances in Archaeo- that ant—it
logical Practice addressed another way field To boost access to archaeology, Eichner could plant
schools weed out students: cost. Among found grant funding so that students at the a wildflower
more than 200 field schools, the average cost Texas field school she ran paid only for room
for 4 weeks was just over $4000, not includ- and board. She also surveyed students so she New findings show how
ing airfare, the study found. Field school also could accommodate diverse gender identi- ants choose and protect
interferes with summer jobs. ties, disabilities, and more. She estimates the seeds they disperse
that 20% to 30% of students belonged to
Archaeologists need to “think of ways to the LGBTQ+ community. “This is not extra By Elizabeth Pennisi
train students that are more in line with the work,” she says. “This is the work.”
realities of their lives,” Baxter says. Her de- T rilliums, bloodroot, violets—many
partment no longer requires anthropology Justin Dunnavant of Vanderbilt University, wildflowers of spring in eastern
majors to attend a summer field school. In- co-founder of the Society of Black Archaeo- North America bloom thanks to ants.
stead, they take a field methods course that logists, is particularly aware of how field The tiny six-legged gardeners have
runs 1 day per week during the school year. schools shape the culture of his discipline. partnered with those plants as well as
The society interviewed established Black about 11,000 others to disperse their
Similarly, for three recent semesters, archaeologists and found that attending seeds. The plants, in turn, “pay” for the ser-
Sarah Rowe, an archaeologist at the Uni- field school together had helped them forge vice by attaching a calorie-laden appendage
versity of Texas, Rio Grande Valley, ran a a strong, supportive community in a major- to each seed, much like fleshy fruits reward
class that trained students in archaeological ity white discipline. (Just 0.3% of members birds and mammals that discard seeds
survey, data collection, and community en- of the Society for American Archaeology are or poop them out. But there’s more to the
gagement as they investigated their county’s Black, according to a 2015 survey.) “If we’re ant-seed relationship than that exchange,
public cemetery. She also runs a field school going to seriously build out a pipeline of researchers reported last week at the an-
in Ecuador, which offers several weeks of im- Black archaeologists, we need to have a field nual meeting of the Ecological Society of
mersive training in excavation. “We need to school that is racially diverse and support- America, which was held online.
focus on a constellation of options” for train- ive,” Dunnavant says.
ing students, she says. Far from just transporting the seeds, the
He keeps that in mind at the field school ants are active gardeners, preferring some
Well-managed, immersive field schools he co-directs, where students help study the seeds over others and possibly keeping their
can build powerful and lasting bonds, says lives of enslaved Africans on a former plan- charges safe from disease. “It’s becoming
Sara Gonzalez, an archaeologist at the Uni- tation on St. Croix in the U.S. Virgin Islands clear that it’s not a simple two-way inter-
versity of Washington, Seattle. She co-directs (Science, 8 November 2019, p. 678). A grant action,” says Douglas Levey, an ecologist at
a field school with the Historic Preservation covers the costs of students from historically the National Science Foundation.
Office of the Confederated Tribes of Grand Black colleges and universities and pays them
Ronde Community of Oregon on their res- a stipend. The team could excavate faster if it The importance of this partnership is com-
ervation. “It’s an opportunity for students focused less on training, Dunnavant says. But ing into focus as well. In forests disturbed
to learn directly from the tribe how to do sprinting for results is not his goal. “If we’re by human activity, where ants can be scarce,
archaeology.” The school prohibits alcohol not actually building capacity for people to seeds may not find their way to fertile ground,
and emphasizes inclusivity and respect. take over in these spaces and beyond, it’s go- and ecosystems can suffer. “If ants are lost,
Each summer begins with discussions of ing to be a very short-term gain.” j then there’s a real chance that we will lose
what students are most excited about—and plants, as well as the other species that de-
pend upon ants and plants,” says Judith
Students and instructors at an archaeological field school in St. Croix forge ties for the future as they learn. Bronstein, an evolutionary ecologist at the PHOTO: M. CANTWELL/SCIENCE
University of Arizona.

Many ants eat seeds, but in deciduous
forests in Europe and North America, Aus-
tralian dry woodlands, and South African
shrublands called fynbos, a few dozen ant
species spare the seeds in favor of some-
thing better. Certain plants attach a nutri-
tive glob called an elaiosome to their seed
coats, which serves as lunch for the ants’
young and gives ants a handle on seeds that
can be bigger than their head. Until now,
researchers assumed the ants simply carry

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In return for these Aphaenogaster ants dispersing its seeds, bloodroot attaches a tasty “handle” that gives the ants a reward and a way to carry the seed to their nest.

PHOTO: ALEX WILD the seeds to their nests, feed the elaiosome while leaving others to rot, Miller told the why secondary forests lack dense under-
to their broods, and deposit the seed either meeting. “So being less preferred really has growth, and why plants that rely on ants to
outside or inside at the colony’s “garbage consequences,” Bronstein says. disperse their seeds are scarce there.
dump,” which provides a fertile environ-
ment for sprouting. But Charles Kwit, an To find out how ants make their choices, At the meeting, Prior and her student
ecologist at the University of Tennessee, Miller and Susan Whitehead at the Virginia Carmela Buono reported that a survey of
Knoxville, thought ants might help seeds Polytechnic Institute and State University 20 sites in northeastern North America
with more than just transportation. (Virginia Tech) used mass spectroscopy showed a similar trend. Compared with
and other techniques to analyze the chemi- never-cleared forests, secondary forests had
The common seed-dispersing ants in the cal makeup of elaiosomes. They found that fewer Aphaenogaster ants, which disperse
genus Aphaenogaster, like others, secrete ants pick seeds based on the specific combi- up to 70% of seeds in a deciduous forest,
antimicrobial chemicals to clean themselves nation and concentrations of oleic acid and Buono said. The secondary forests had less
and fellow ants. Kwit wondered how those other compounds made by the plant, 20 of leaf litter and fewer decaying logs for ants
disinfectants might affect the seeds’ micro- which are unique to trilliums. The ants’ to colonize. They also had more invasive
bial communities—and their health. He and tastes may affect plant species’ distributions, slugs, which compete with ants by eating
his graduate student Chloe Lash teamed up says Kirsten Prior, an ecologist at Bingham- the elaiosomes—and leaving seeds behind,
with Melissa Cregger of Oak Ridge National ton University: “Widespread trillium species rather than dispersing them. The loss of
Laboratory to isolate and sequence DNA from [are] preferred by seed-dispersing ants com- seed-carrying ants “has major implications
microbes on the seed coats of three common pared to rare trillium species.” for forest communities and restoration,”
ant-dependent plants: wild ginger, bloodroot, Prior says. “To restore understory plant
and twinleaf. To start, each species’ seed had Human activities, too, can influence ant- communities, we might also need to think
a complex and unique microbiome—its com- seed partnerships. Many researchers as- about having to restore this important spe-
munity of bacteria and fungi. But after an sumed ants survive disruptions such as forest cies interaction.” For example, it might help
ant handled a seed, its microbiome shrank clearing and quickly move back into dis- to ensure there are plenty of decaying logs
and became more similar to those of other turbed areas. But Katie Stuble, an ecologist and leaf litter for the ants to thrive in.
handled seeds of different species, Lash re- at the Holden Arboretum in Kirtland, Ohio,
ported at the meeting—apparently because of found otherwise. “Land-use history impacts Bronstein notes that in the past, eco-
the antimicrobial treatment. Wild ginger and ant communities,” she said at the meeting. logists deciphered ants’ role as gardeners
twinleaf also harbored fewer plant patho- Her arboretum covers 1416 hectares, much of through painstaking observations. Now, she
gens. The microbiome changes, Levey says, it cleared for farmland at different times over says, “There are exciting testable hypoth-
“could affect postdispersal seed predation, the past century before the trees regrew. eses, well-designed experiments, serious
dormancy, seed viability, timing of germina- phytochemical analyses, and sophisticated
tion, and health of the resulting seedlings.” Even in areas cleared decades ago, her statistical approaches,” as well as genome se-
team found higher concentrations of inva- quencing and fine-scale chemical analyses.
Kwit’s lab has also found that when it sive earthworms and lower concentrations of
comes to seeds, ants have preferences that seed-dispersing ants than in forests that were Melissa Burt, an ecologist at Virginia
may influence the plants’ success. In both never cleared. Earthworms break down fallen Tech, hopes these studies bring ants new re-
the field and the lab, his student Chelsea leaves and organic debris, possibly leaving too spect. “Many people that I talk to about ants
Miller presented ants with seeds from vari- little cover for ants. “This suggests that there only know them as pests that are taking over
ous trillium species and found the ants are huge impacts of past land use that proba- their kitchens, but many ants perform im-
were quick to pick up some species’ seeds bly run deeper than we previously suspected,” portant functions in ecosystems,” she says.
Stuble says. Those impacts could explain “Seed dispersal is just one of those.” j

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Last year, an unusual meteorite crashed in a Costa Rican rainforest.
Rich in the building blocks of life, it has captivated collectors and researchers

By Joshua Sokol


Published by AAAS


s the fiery emissary streaked how chemical reactions in space give rise confirmed in a meteorite. And if they were
across the skies of Costa Rica, to complex precursors for life; some scien- clean and careful, they could hedge against
an unearthly mix of orange and tists even believe rocks like Aguas Zarcas a perennial criticism of the Murchison finds
green, Marcia Campos Muñoz was gave life a nudge when they crashed into a by ensuring the molecules discovered inside
in her pajamas, watching TV on barren Earth 4.5 billion years ago. were native, and not contamination from
the couch. It was 23 April 2019, a Earth’s own microbes.
bit past 9 p.m., when she heard a From the beginning, the inky Aguas
Zarcas resembled a legendary carbona- “If I had to start a new museum collec-
A foreboding rumble. Heart racing, ceous chondrite that exploded in 1969 tion for meteorites, and I could only select
she tiptoed outside to calm her over Murchison, an Australian cattle town. two, I would choose Murchison and Aguas
Geology students helped collect about Zarcas,” says Philipp Heck, who curates the
barking dog, Perry, and to check on the cow 100 kilograms of Murchison, and a lo- meteorite collection at Chicago’s Field Mu-
cal postmaster mailed pieces of it to labs seum. “If I could choose only one, I would
pastures ringing her small house in Aguas across the world. To date, scientists have choose Aguas Zarcas.”
recognized nearly 100 different amino ac-
Zarcas, a village carved out of Costa Rica’s ids in it, many used by organisms on Earth FROM THE INSTANT the rock entered the
and many others rare or nonexistent in atmosphere, however, the clock began to
tropical rainforest. Nothing. She ducked known life. Hundreds more amino acids tick. Clays—its major constituent—soak up
have been inferred but not yet identified. surrounding air and water like a sponge;
back inside, just before a blast on the back

terrace rattled the house to its bones.

Campos Muñoz phoned her father,

brother, and oldest son, who rushed to

the house. On the terrace, they found a

grapefruit-size hole in the corrugated

zinc roof and a smashed-up plastic table,

last used for the quinceañera of Campos Carbon footprints Meteorite fragments
Muñoz’s daughter. The culprit was scattered On 23 April 2019, an asteroid km
the size of a washing machine Pérez Huertas
She picked up the biggest fragment, still chock full of primordial carbon, Valerio Díaz house
landed along a 6-kilometer-long Campos Muñoz house
warm to the touch. Already, her phone was swath between the villages of
La Palmera and Aguas Zarcas. Aguas Zarcas
chiming with WhatsApp messages from

friends telling of blazing fireballs and rocks

raining down on farms and fields. The fam-

ily added its own viral messages to the mix:

photos of Campos Muñoz and her son hold-

ing the big stone that crashed through her

roof. Within hours, a local journalist visited Area
the house and streamed videos of the damage
San José
on Facebook Live. COSTA RICA

It was only the beginning. A space rock the La Marina

size of a washing machine had broken up in

the skies over the village, and the excitement

was about to spread globally.

Meteorites are not uncommon: Every year, Juan Castro Blanco
National Park
tens of thousands survive the plunge through

Earth’s atmosphere. More than 60,000 have

been found and classified by scientists. But

meteorite falls, witnessed strikes that take Murchison also contained nucleobases, earthly amino acids and other organic com-
the building blocks of genetic molecules such pounds intrude, layer by layer, followed by
their name from where they land, are rare— as RNA, and in November 2019, researchers the microbes that produced them. Each sec-
found a major component of RNA’s backbone: ond in contact with moist rainforest soil or
just 1196 have been documented. And even the sugar molecule ribose. This half-century human hands destroys more information.
parade of discoveries jump-started the now- “Ideally we pluck it from the air while it’s
among that exclusive group, there was some- flourishing field of astrobiology. “We’re not coming down,” says Ashley King, a plan-
detecting life itself, but the components are etary scientist at London’s Natural History
thing extraordinary about this particular all there,” says Daniel Glavin, an astrobio- Museum, “whilst wearing gloves.”
logist at NASA’s Goddard Space Flight Center.
meteorite, something anyone with the right “I wouldn’t have a job without Murchison.” For billions of years, Aguas Zarcas had
avoided such contaminating influences.
knowledge could know from the first pic- The 30 kilograms of primordial leftovers If it could stay that way just a little lon-
from Aguas Zarcas hold similar promise. ger, scientists would be able to recover in-
tures. The dull stone was, as far as rocks go, But these new pieces are 50 years fresher formation from three ancient, otherwise
than Murchison, allowing scientists to apply inaccessible periods.
practically alive. modern techniques to preserve and probe
what amounts to fragile lumps of unspeak- The first predates the Solar System. Some
Aguas Zarcas, as the fragments would ably old clay. They could sniff out delicate 7 billion or 8 billion years ago, specks of star-
organic compounds long evaporated from dust were ejected from supernovae and the
soon collectively be called, is a carbona- Murchison. They could hunt not just for outer atmospheres of aging stars, some made
amino acids and sugars, but also proteins, of hardy materials such as graphite, dia-
ceous chondrite, a pristine remnant of which have long been suspected but never mond, and silicon carbide. The size of smoke
particles, they drifted in space, settling in a
the early Solar System. The vast majority

of meteorites are lumps of stone or metal.

But true to their name, carbonaceous

chondrites are rich in carbon—and not just

boring, inorganic car-

Clays in an Aguas bon, but also organic

Zarcas fragment molecules as complex

may hold amino acids as amino acids, the

and stardust that building blocks of pro-

predates the Sun. teins. They illustrate

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nameless interstellar cloud. to sweep them up, but the future meteorite Many carbonaceous chondrites crashed
In the next phase, that formless cloud col- avoided that fate, remaining part of a small into early Earth, perhaps delivering not just
asteroid in the cold void beyond Jupiter. In a sprinkling of organics, but also a portion of
lapsed into a disk swirling around the new- that early home, it avoided being melted by the planet’s inventory of water. Aguas Zarcas
born Sun, generating frictional heat that the Sun or in the hot interior of a planet. itself endured several billion more years of
roasted everything but those presolar grains solitude, save for occasional smashups with
into a seething vapor. As the disk cooled, the Instead the asteroid grew modestly, amass- other wayward space rocks. Based on its fi-
first solids condensed out like frost on a win- ing specks of ice and carbon, the latter already ery trajectory through Earth’s atmosphere,
dow-pane: crystalline clumps of aluminum morphing as sunlight drove chemical reac- caught on dashcams and volcano-monitoring
and calcium as big as poppy seeds. These tions. In its interior, the presolar stardust, the cameras, researchers believe the unknown
fragments date back 4.56 billion years, defin- first solid minerals, the glassy spheres, and body ended up in the asteroid belt between
ing the age of the Solar System. Within a few the carbon compounds all crowded together. Mars and Jupiter. Then one last collision
million years, molten drops of rock cooled Heat from the radioactive aluminum melted splintered off a chunk, which spiraled in to-
into glassy spheres—the “chondrules” that the ices. Liquid water gushed out, kicking off ward Earth, nearing the rotating globe just as
give chondrites their name. another wave of chemistry that would go on Costa Rica spun into view on 23 April 2019.
for a few million years more. Simple com-
Then, in the third phase, these small par- pounds such as hydrogen cyanide and am- Surviving its passage through the at-
ticles started to stick together into boulders, monia dissolved and were transformed into mosphere was one test, but now another
among them the hodgepodge of rocks that amino acids and other complex forms. threat loomed: the country’s formidable
would become Aguas Zarcas. Planets began rainy season, which could erode and con-
taminate much of that preserved history.
Heavenly messenger The most important meteorite in half a
century had landed on one of the last dry
Aguas Zarcas belongs to a rare class of meteorites, rich in complex organic molecules, including amino acids. nights of the year.
Some scientists believe they gave life a nudge when they slammed into a barren Earth 4.5 billion years ago.
Nobody knew it then, but the first hard
100 micrometers (µm) Mix and match rain was 5 days away.

2 The meteorite is a breccia—a mashup of different ON 24 APRIL 2019, the day after the Aguas
3 primordial bodies. A close-up of a cross section Zarcas fall, meteorite dealer Mike Farmer
reveals key ingredients. wasn’t planning on doing much, maybe re-
1 laxing with his son or doing some yardwork
1 Calcium-aluminum– 3 Calcite outside his house in a Tucson, Arizona, gated
community. His bags were already packed for
rich inclusions (CAIs) Crystals of calcite are a a flight the next day to hunt for a meteorite
that fell in Cuba. But soon after he woke up,
Dates from 4.56-billion- sign of aqueous alteration— the Facebook picture from Campos Muñoz
flashed across his screen. “It was like, oh,
year-old CAIs, the first the watery chemistry Jesus Christ,” he says. “I knew immediately
what it was.” So much for Cuba.
solids to condense from that drove the creation of
He quickly packed $50,000 in cash into
a disk of hot gas, define complex organic molecules. the liner pockets of a safari vest, along with
more clothes for what would now be a jun-
System. Isotopes in the 4 Matrix flight to Costa Rica. As the plane taxied for
clumps record the early The dark, surrounding takeoff after a layover in Dallas, Farmer’s
matrix is made of clay and phone dinged. It was another message from
Sun’s activity levels. Costa Rica with a photo. Would he like to
3 holds the organic molecules. buy some meteorites? “I about had a heart
2 Chondrules It may also contain a precious attack,” Farmer says.

Soon after the CAIs, few presolar grains: hardy That message came from the family of
Ronald Pérez Huertas, who lives a few kilo-
glassy spheres specks of stardust that meters from Campos Muñoz outside of the
village of La Palmera. On the night of the
solidified. Chondrules predate the Solar System. fall, Pérez Huertas was leaving his job at a
cheese factory when the fireball flashed over-
were first described head. At home, his wife, Virginia Argüello
Arias, heard a sound like thunder—the sonic
4 as “droplets of fiery Presolar booms of the atmospheric breakup. When
rain” in 1877, but grain she looked outside, the neighbor’s German
shepherd, Rocky, was cowering and trem-
theorists cannot agree bling. Later, they learned that a fragment
had crashed through Rocky’s doghouse.
on how they formed. 3 µm
The next morning, Argüello Arias walked
Time capsule to her front gate. She spotted a small stone
coated in an iridescent sheen: the fusion
Aguas Zarcas holds minerals and molecules forged billions of years ago in three distinct periods.
Light, heat, and water drove chemical reactions that created increasingly complex organic molecules.

Interstellar cloud Solar System formation Parent asteroid Earth delivery

~7 billion years ago 4.56 billion years ago Present day

Key Presolar grains CAIs, Carbonates
minerals (silicon carbide, graphite) chondrules

Key Water, methanol, hydrogen Alcohols, carboxylic acids, Amino acids,
molecules cyanide, formaldehyde
hydrocarbons purines, sugars
Chemical Starlight,
driver cosmic rays Sunlight, Radioactive heat,
heat water

Increasing complexity

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Marcia Campos Muñoz held off selling her largest meteorite chunk, even as values surpassed gold. Mike Farmer bought everything he could, including a punctured doghouse.

PHOTOS: (LEFT TO RIGHT) ANDREA SOLANO BENAVIDES; MICHAEL FARMER crust that forms in the heat of descent. That one meteorite is known to have landed in Meteoritics & Planetary Science. “Some coun-
afternoon, her son and daughters joined in Costa Rica before—in 1857. For Gerardo tries have lost valuable material,” he says. “I
a family hunt through pastures and stands Soto, the geologist who called her back, it suppose over time more of these regulations
of mango and soursop trees. They found was a “dream come true.” When Soto and will be developed.”
enough fragments to cover a table and snap his colleagues Pilar Madrigal and Oscar
a tempting photo. After Googling meteorite Lücke drove up from San José the next day, Costa Rica may soon restrict the trade,
dealers, they sent the photo to someone they carrying microscopes and scales, a quick in- as well. “I consider it necessary to generate
thought might be willing to pay. To their spection eliminated their doubts. “I can die a policy regarding objects from outer space
amazement, he was already en route. now because I saw it,” Soto says. that fall into Costa Rican territory,” says
Ileana Boschini López, head of the country’s
The following morning Farmer showed Madrigal, a UCR geochemist, put a piece Directorate of Geology and Mines.
up in person, along with Robert Ward, a under a magnifying glass. Her eyes sparkled
competitor and sometimes collaborator in when she saw the glassy, extraterrestrial In Oman vague guidelines meant for his-
the meteorite business who had arrived on chondrules. “It is really meaningful to hold torical artifacts snared Farmer and Ward,
the same flight. Counting out cash, they a meteorite like this in one’s hands: It is at who were arrested there with a carful of
bought those initial stones—much too least 4.5 billion years old,” she says. Campos meteorites in 2011 and sentenced, after a
cheaply, the family now realizes. Muñoz says she got goosebumps watching brief trial, to 6 months in prison. Condi-
the scientists work. “It seemed like they were tions were brutal, with rioting in nearby cell
Farmer also bought the fragment that hit about to burst into tears,” she says. For hours blocks and meager meals. They got out half-
Rocky’s doghouse. And, for good measure, Campos Muñoz and her family sat rapt with way through after an appeal. But by then
the doghouse, too. For the next 4 days Farmer attention as the scientists explained what Farmer had lost almost 20 kilograms and
and Ward bunked together at a nearby coffee they could see within the rock. was having recurring nightmares.
plantation and set up shop each day on the
family’s front lawn, offering to do business By the time the foreign collectors arrived, That episode and other close scrapes have
with anyone in town who trekked over. the scientists had already left with photo- cemented a strange relationship for the
graphs and a few tiny pieces of the rock. duo, who share a love of seat-of-the-pants
A gold rush began. On the first of May, Without the institutional funding to com- adventuring—but have trouble sharing the
a public holiday, the village was crammed pete, they kept out of the commercial fray. limelight and the sums of money at stake.
with cars as treasure hunters combed the “Unfortunately, many people sold their frag- “Sometimes they absolutely hate each other,”
surrounding land. Buses carrying out-of- ments to private individuals, and they left the says Laurence Garvie, meteorite curator at
towners parked on a nearby hill. Ronald country,” Madrigal says. Arizona State University (ASU), Tempe. But
Pérez Huertas began to patrol his property, other times they get together and laugh about
blocking access to anyone but the Ameri- Around the world, meteorites are subject it. “They are like an old married couple.”
cans. His son had a friend cover his shift at to a patchwork of laws, often those governing
the gas station one day so he could go out antiques; Denmark, for example, classifies The experience in Oman did not seem to
and search, returning with a bulky chunk them as “fossil troves” that belong to the state. diminish the duo’s hard-charging instincts.
weighing almost 1 kilogram. Australia, Canada, Chile, France, Mexico, and Around Aguas Zarcas, tensions were rising,
New Zealand consider meteorites cultural along with prices. Stones could fetch $200,
By this time as many as 30 collectors from treasures that can’t be exported without per- even $400 per gram. Bidding wars ensued. “I
Russia, Germany, Belgium, and the United mission. But in many places, including Costa came close to sinking a shovel in one guy’s
States had set up their own bases under the Rica and the United States, meteorites can be skull,” Farmer says.
path of the fireball, which had strewn frag- freely bought, sold, and exported.
ments across 6 kilometers. Demand grew. That guy was Jay Piatek, a wealthy doctor
Prices skyrocketed from the few dollars per Meteoriticists are largely content with that and obsessive collector who runs a weight
gram Farmer had first offered to $50, even arrangement, because the market drives peo- loss clinic in Indianapolis (Science, 28 No-
$100 per gram, passing the price of gold. ple to scour fields and deserts for rare finds, vember 2014, p. 1044). He had shown up
and the collectors often share samples with with his girlfriend, gunning to add to his
Campos Muñoz, meanwhile, had called scientists. But attitudes are shifting, says A. collection of rare meteorites. With a piece
scientists at the University of Costa Rica J. Timothy Jull, editor-in-chief of the journal of Murchison already displayed at home,
(UCR) on the morning after the fall. Only Piatek knew exactly what he was looking

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at—and the prices it could com- merger or a deluge of fresh gas.

mand. “He’s screaming, ‘I’ll pay The Field Museum team has

more!’” Farmer says. “I had a also been combing through

guy rip a bag of rocks out of my Aguas Zarcas for the calcium-

hand and rush to him.” Piatek and aluminum-rich inclu-

remembers it differently. “To sions, the earliest minerals to

me, they were taking advantage condense out of the protosolar

of people,” he says. disk. Drifting around the disk,

As more collectors swarmed they gathered a record of the

the town and fresh material young Sun’s unruly outbursts,

kept flowing in, other conflicts as surges of particle radiation

erupted. Then the first rains left telltale signatures of he-

fell. Water-logged pieces be- lium and neon in each grain.

gan to crumble. They emitted a “They are like flight recorders,”

sulfurous reek as the moisture Heck says. “We can just count

liberated sulfur compounds those elements that form and

previously trapped in pores, learn about the activity of the

making remaining fragments Sun.”

easier to find but less precious. Several other teams are go-

After blowing through his ing after the meteorite’s com-

$50,000 in 4 days, Farmer plex organic compounds. They

flew back to Tucson, and drove formed millions of years later,

north toward ASU. In the desert as basic carbon molecules re-

midway between the two cities, acted in the warm, wet inte-

he handed over his samples to rior of Aguas Zarcas’s parent

Garvie. ASU would store some, In fresh samples of the Aguas Zarcas meteorite, researchers have identified salts, asteroid. Some of the products

like the doghouse smasher, on easily washed away by rain. Several are recrystallized on glass, including halite. of that early chemistry are

Farmer’s behalf. Others were volatiles—compounds, frozen

straight donations, Garvie says, eventually artificial edge reminiscent of permanent in pockets when the meteorite floated in cold

totaling a few hundred grams. marker. Garvie’s official report describes a space, that are unstable at room tempera-

Farmer was eager for Garvie to classify “Murchison-like” odor with “notes of com- ture on Earth and escape with their telltale

Aguas Zarcas scientifically, because getting post.” Others compare it to Brussels sprouts, smells. Using electronic “noses” designed for

an official designation was sure to buoy or describe something sweet and organic, the purpose, researchers at Brown University

prices. Feeling “nerve-wracking” pressure like diesel, cooking gas, even vanilla. Farmer, and ASU are hoping to capture the fleeting

that a rival institution had obtained its own who has a long-standing tradition of eating a chemicals before they fade.

fragments, Garvie raced to combine the data little bit of his finds, says it’s the nastiest rock Other carbon compounds are sturdier. At

obtained by Soto’s team in Costa Rica with he’s ever tasted. “Laurence got mad at me,” NASA Goddard, for example, Glavin’s team

his own mineral descriptions and an analy- Farmer says. “He said, ‘That’s pretty stupid, ground up bits of Aguas Zarcas with a mor-

sis of the object’s trajectory from a group in we don’t know what’s in this!’” tar and pestle, mixed them in pure water,

Brazil. Isotopic tests by geochemist Karen Few papers have been published on the heated the mixture to almost boiling, and,

Ziegler at the University of New Mexico, meteorite so far—but they are coming. At using a mass spectrometer, analyzed the

Albuquerque, sealed its place in the same the Field Museum, Heck is analyzing an al- compounds rising off.

narrow class of carbonaceous chondrites as most 2-kilogram piece, donated by a retired The process spat out a graph crowded

Murchison. Garvie submitted a write-up to health care executive, to probe the time be- with unknown organic molecules of differ-

the Meteoritical Society, which maintains fore the Solar System took shape. He says ent weights. “It’s like, oh my God, there’s

the world’s official space rock database. his team has found a handful of candidate likely hundreds of different amino acids in

The report was accepted and published by grains of silicon carbide, likely specks of this meteorite,” Glavin says. “Murchison, for

the end of May, just 5 weeks after the fall. dust scattered by aging giant stars that were 50 years, has been the gold standard. Aguas

Now “Aguas Zarcas” was formally Aguas later swept up in the protosolar disk. If con- is comparable.” The team is now working

Zarcas, and the world’s exemplar specimens, firmed and dated, those grains could add to on a lower temperature technique to hunt IMAGE: LAURENCE GARVIE/CENTER FOR METEORITE STUDIES/ASU

about 40 grams worth, would reside at ASU. an emerging picture of galactic conditions in for peptides: multiple amino acids bound

“Does it really matter that you got first the distant past. together. If found, they would illustrate an-

place?” Garvie says. “No, of course not.” He A few similar grains from the Murchison other level of prebiological space chemistry,

pauses. “But it does matter.” meteorite are as much as 7.5 billion years suspected but never seen.

old. But most of its grains were forged just In a recent twist, though, ASU researchers

ONE DAY in November 2019, outside ASU’s a few hundred million years before the Solar report they’ve struggled to find any amino

meteorite lab, Garvie approaches me gin- System. If Heck finds a similar age cluster- acids in their fragments. “It’s strange,” says

gerly with a tiny glass beaker filled with ing in Aguas Zarcas grains, it could point to Maitrayee Bose, an ASU cosmochemist. Bose

water and powdered Aguas Zarcas, leftover a generation of stars all born about 7 billion suggests one explanation for the contradic-

from a test. He swirls the gray-black mix- years ago, giving them a few billion years tory results: Each piece samples a different

ture like a sommelier to release its bouquet. to grow old and seed the Solar System with bit of a heterogenous rock, which may have

I sniff cautiously. “You just smelled some- dust. Some astronomers believe the Milky experienced different levels of alteration by

thing that’s 4.5 billion years old,” he says. Way went through a wave of starbirth at that water and heat. “It’s like the human body,”

I pick up the smell of moist soil, with an earlier epoch, perhaps triggered by a galactic she says. “Every part is slightly different.”

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Looking close at isovaline, an amino acid These asteroid scraps will be truly pristine, meteorite proceeds to repaint the house, re-

that occurs in space but is almost never having never touched the atmosphere or sat place the roof, expand their dairy barn, and

found in earthly life, the NASA team has atop rainforest soil. Aguas Zarcas—precious buy new furniture and a car. Once prices

uncovered hints of a deeper pattern. Amino but not space-mission precious—is a good started to climb, Farmer—now a family

acids can occur in two mirror-image mo- material for trial runs: The OSIRIS-REx team friend—gave them more money to compen-

lecular forms, differing like right and left bought 60 grams of it to refine its analysis sate for his initial lowball purchases, plus

hands. Chemical reactions have no prefer- pipeline in advance of the Bennu material. bonuses for acting as his fixers. For Argüello

ence for either form, so left alone, nature Expecting two chunks of prehistoric car- Arias’s 50th birthday, the women of the fam-

should produce half-and-half mixtures. But bon, scientists find themselves with three. ily all took a trip to Panama.

organisms on Earth seem to build them- “It wasn’t a million- or a billion-dollar mis- Having sold all the putrid fragments

selves out of only left-handed amino acids. sion to go collect it. It just fell,” says Jessica harvested after the rains, Farmer said he’s

That bias could reflect a roll of the dice by Barnes, a team member at the University hoarding five intact kilograms, out of seven

the first life, a random choice that descen- of Arizona. “So, thank you to the cosmos total kilograms he obtained. Some are at

dants preserved. Another theory, published for that.” home, in the same Ziploc bags they went

in May, suggests the left-hand bias arose on into the instant he bought them; other

Earth: After life emerged in a mix of mirror- ONE DAY IN MAY, once again on the cusp of pieces are being stored on his behalf at ASU

image forms, the radiation of cosmic ray Costa Rica’s rainy season, Ruddy Valerio in sealed boxes filled with nitrogen instead

showers in the atmosphere, which has its Díaz sat enjoying the open air at his res- of air. Right now, there’s still too much avail-

own inherent handedness, offered an evo- taurant next to a freshwater tank teeming able online and at rock and mineral exhibi-

lutionary advantage to organisms with left- with tilapia. Butterflies fluttered through tions for him to sell his collection. “I have

handed proteins. the majority of it in the world, and all

But Aguas Zarcas has up to 15% pristine,” Farmer says. “Ten, 20 years

more left-handed than right-handed down the road, when me or my son or

isovaline, underscoring similar find- somebody opens that box, you’ve got

ings from Murchison and other car- a very important asset there.”

bonaceous chondrites. The persistent Little of Aguas Zarcas remains in

pattern suggests the lefty bias may Aguas Zarcas—or in Costa Rica. UCR

have arisen in space. Perhaps, another is now home to a few fragments, each

camp argues, the polarized light from weighing a few tenths of a gram. San

nearby stars imparted a slight bias to José’s National Museum has a little

meteoritic organic molecules that was more. Madrigal says she hopes some

incorporated by life. “I think the me- of the pieces sold overseas might

teorites are telling us the story that eventually be donated back to Costa

we were destined to evolve left hand– Rican institutions.

based protein life,” Glavin says. Campos Muñoz is still a holdout,

Other labs are examining Aguas maybe the last. She still has the big

Zarcas for clues to a later stage of chunk that fell through her roof,

Earth’s evolution. Models predict which she hopes will end up in an ex-

carbonaceous asteroids crashing With the money from meteorite stones he sold, Ruddy Valerio DÍaz hibition. She wants more for it—she

down on early Earth would have pro- paid off his debts, built a butterfly farm, and started a restaurant. won’t say exactly how much—than

duced an ancient atmosphere rich dealers have offered.

in water vapor and carbon dioxide. At the an adjacent breeding garden. COVID-19 The hole in the roof remains. She had

University of California, Santa Cruz, cosmo- had cleared the place of customers, leaving meant to fix it, but first came the meteorite

chemist Myriam Telus wanted to test the an empty patio, but at least he had a finan- hunting frenzy, then the rainy season, and

idea with real data. She reached out to a cial cushion. When the rocks rained down, now the pandemic. Plus, she knows these

dealer for samples, which she then would Valerio Díaz had been skipping between bits of collateral damage are valuable to

destroy by baking them to dust and measur- temp jobs, dreaming of opening a busi- collectors, too. “This hole in the roof and

ing the emitted gases. “It can be very hard to ness. No bank would give him a loan. “Our the damaged tables are part of our family

convince people this is worthwhile for some- economic situation was so tough,” he says. now,” she says.

thing that is precious,” she says. But soon she “This money literally rained from the sky.” Neighbors suspect her family are all mil-

had 2 grams—enough to proceed with the Valerio Díaz waited 2 months to sell lionaires, winners of a cosmic lottery, she

experiment. the 300 grams of stones he found along says. Strangers still show up from time to

For still other scientists, Aguas Zarcas roads, under electrical towers, and on his time and dawdle out front, looking for the

landed at a fortuitous moment. own land. Farmer wouldn’t pay enough. “house of the meteorite.” She stays in touch

Right now, Japan’s Hayabusa2 spacecraft But someone else agreed to $50 per gram, with the Costa Rican scientists to follow

PHOTO: ANDREA SOLANO BENAVIDES is hurtling back toward Earth bearing dust enough to pay off all his debts, build his their research and reads every paper they

from Ryugu, an asteroid with asphalt-black wife, Rosibel, the butterfly farm, and start send her way.

patches that resemble carbonaceous chon- the restaurant. The only problem was what “I feel very proud that such an important

drites. Those samples are scheduled to para- to call the place. They came up with a long event for history and science took place in

chute down to Australia on 6 December. And list of punning titles: Manna from Heaven, my country,” she says, “and in my house.” j

in 2023, NASA’s OSIRIS-REx mission will Cosmos Restaurant, Black Stones. Now, it’s

deliver about 60 grams of material from the Tilapias Rancho El Meteorito—Meteorite Joshua Sokol is a journalist in Raleigh, North Carolina.

carbon-rich asteroid Bennu, also thought to Tilapia Ranch. Andrea Solano Benavides, a journalist in San José,

be a close relative of Aguas Zarcas. Nearby, Pérez Huertas and his family used Costa Rica, contributed reporting.

SCIENCE 14 AUGUST 2020 • VOL 369 ISSUE 6505 765

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INSIGHTS Ephemeral streams, such
as this one in western
South Dakota, have
lost federal protection
under the Navigable

Waters Protection Rule.



Distorting science, putting water at risk

A recent rule is inconsistent with science and will compromise the integrity of U.S. waters.

By S. Mažeika Patricio Sullivan1, ing water quality and healthy watersheds in water protections, which went into effect PHOTO: S. M. P. SULLIVAN
Mark C. Rains2, Amanda D. Rodewald3,4, (3) (see the figure). Although the Agencies nationwide on 22 June, will require coordi-
William W. Buzbee5, Amy D. Rosemond6 claim to have “looked to scientific princi- nated efforts among scientists, lawmakers,
ples to inform” the NWPR, science has been and resource managers.
T he Navigable Waters Protection Rule largely ignored and oversimplified. These
(NWPR) (1), which was published new exclusions are based on selective pars- Clearly articulated in the CWA is the in-
in April by the U.S. Environmental ing of statutory language and earlier case tention “to restore and maintain the chemi-
Protection Agency (EPA) and the law, rather than on previously established, cal, physical, and biological integrity of the
Department of the Army (“the science-based interpretations of the U.S. Nation’s waters” (4). The CWA was explicit
Agencies”), has redefined “waters of Federal Water Pollution Control Act, com- in protecting “navigable waters,” which
the U.S.” (WOTUS) to restrict federal pro- monly known as the Clean Water Act (CWA) Congress defined broadly as WOTUS; how-
tection of vulnerable waters (2). With its (4). The EPA’s own Science Advisory Board ever, the extent to which waters other than
emphasis on “continuous surface connec- (SAB) found sufficient evidence to conclude navigable rivers, lakes, and territorial seas
tions” and “permanen[ce],” the NWPR re- that “…the proposed Rule lacks a scientific [traditional navigable waters (TNWs)] are
moves or reduces protection for U.S. waters, justification, while potentially introduc- protected has repeatedly provoked legal
including millions of miles of streams and ing new risks to human and environmen- skirmishing. Particularly contentious are
acres of wetlands, many of which comprise tal health” (5). Responding to this unprec- determinations about which nontraditional
headwaters that are critical for sustain- edented distortion of science and rollback waters, such as wetlands and small tributary
streams, contribute to the integrity of TNWs.

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The NWPR functionally ends the debate by derstanding recognizes as critical to services Because these wetlands and streams will
elevating state over federal regulatory author- derived from freshwater ecosystems gradi- summarily lose federal protection, they will
ity. Without federal law as a protective regu- ents of connectivity (versus a binary prop- be vulnerable to outright destruction, fill, or
latory floor, states can and often do choose erty: connected, not connected) that oper- unpermitted industrial pollution discharges
to leave waterbodies unprotected, making ate as a function of frequency, magnitude, that risk transporting pollutants throughout
waters vulnerable to unregulated pollution, timing, and duration of biological, chemical, watersheds. Losses of nonfloodplain wet-
dredging, filling, and other activities that and physical connections among waterbod- lands could include particularly vulnerable
may profoundly erode water quality (3). ies (10). By disregarding or misinterpreting and often valuable waters (2), including
the science of waterbody connectivity, the some playa lakes, prairie potholes, Carolina
The NWPR downplays science by redefin- NWPR draws scientifically unsupported and Delmarva Bays, pocosins, and vernal
ing protected “waters” and explicitly states boundaries to distinguish WOTUS, reaches pools. A preliminary analysis predicts wide-
that “science cannot dictate where to draw conclusions contrary to current science, and spread losses of wetland functions, with
the line between Federal and State waters.” asserts legal and scientific views substan- particularly high impacts on wetlands in
The NWPR relies overwhelmingly (and ar- tially different from those of the Agencies arid and semi-arid regions. For example,
guably arbitrarily) upon the 2006 Supreme under previous administrations of both po- the CWR protected 72%, whereas the NWPR
Court opinion by Justice Scalia in Rapanos litical parties going back to the 1970s. The will only protect 28% of wetland acres, in
v. United States, Carabell v. United States NWPR promotes regulations contrary to New Mexico’s Río Peñasco watershed (11).
Army Corps of Engineers that lacked major- what science shows about effective water
ity support. A more scientifically nuanced protection. Although agencies often have The NWPR also categorically excludes
position was articulated by Justice Kennedy latitude to adjust regulatory choices when subsurface hydrologic connectivity. To dis-
on the same case; the four dissenting implementing longstanding statutes, they regard groundwater connectivity is to dis-
Justices agreed with Kennedy’s rationales cannot do so arbitrarily and without rea- regard the scientific understanding of how
for protecting waters, but would have pro- soned justification and rationales in light of natural waters function. The Agencies justify
tected even more. relevant law, facts, and science. this exclusion by claiming that “A ground-
water or subsurface connection could also
The realized impacts are likely to be In contrast to the CWR’s recognition of be confusing and difficult to implement.”
worse than projected, as ephemeral streams biological, chemical, and physical connectiv- Although implementation may be challeng-
and nonfloodplain wetlands are usually ity, the NWPR relies solely on direct hydro- ing in some cases, claimed implementation
underestimated by remotely sensed data logic surface connectivity to determine wet- ease under the NWPR should not supersede
(3). The economic analysis filed with the land jurisdiction. Nonfloodplain wetlands an evidence-based determination of connec-
NWPR was largely silent about impacts, and ephemeral streams are categorically tivity given the potential for economic and
simply acknowledging that “the [A]gencies excluded on the basis of lack of hydrologi- environmental harm.
are unable to quantify [the scope] of these cal connectivity irrespective of their degree
changes with any reliable accuracy” owing of biological or chemical connectivity. Also A PATH FORWARD IN UNCERTAIN TIMES
to geospatial data issues and uncertainty excluded are floodplain wetlands lacking a The NWPR directly conflicts with a growing
about government responses (6). Yet, in direct surface water connection to TNWs “in body of scientific evidence and with input
spite of this uncertainty and the potential a typical year,” and intermittent tributaries and review by federal and nonfederal scien-
for harm, the Agencies proceeded with a re- lacking relatively permanent surface flows. tists. The rule narrows WOTUS in ways that
strictive and risky rule. are inconsistent with longstanding views
Such exclusions are inconsistent with evi- about the CWA’s mandate to safeguard
CONNECTIVITY AND QUALITY dence demonstrating that these waters are access to clean water. The NWPR opens
Connectivity is a cornerstone in under- functionally connected to and support the previously protected waters to filling, im-
standing how freshwater ecosystem func- integrity of downstream waters. Removal pairment, and industrial pollution, and will
tions are sustained. In 2015, the Obama of federal protection is likely to diminish undermine decades of investments restoring
administration promulgated the Clean Wa- numerous ecosystem services, such as safe- water quality across the United States and
ter Rule (CWR) that included all tributaries guarding water quality and quantity, re- lead to profound loss or impairment of eco-
and most wetlands as WOTUS (7). The sci- ducing or mitigating flood risk, conserving systems and the services they provide. For
entific rationale for the CWR was reviewed biodiversity, and maintaining recreationally context, the economic value of ecosystem
in the EPA Connectivity Report (8), which and commercially valuable fisheries (3). services provisioned by nonfloodplain wet-
synthesized >1200 peer-reviewed scientific lands alone has been estimated at $673 bil-
publications and input from 49 technical EPHEMERAL, ISOLATED lion per year (2).
experts. After a public review process, the Just as tiny capillaries play critical roles
25-member EPA SAB confirmed the scien- in the human body, nonfloodplain wet- Congress has the power to strengthen the
tific underpinnings of both the Connectivity lands (so-called “isolated”) and ephemeral CWA by enacting new legislation to replace
Report and the CWR. streams (that flow only after precipitation or repeal the NWPR. Future administrations
events) support an extensive suite of eco- can reassess and act to restore protections
Since then, the body of supporting evi- system services. Because nonfloodplain through new rulemaking, without the need
dence has grown (3, 9), enhancing our un- wetlands and ephemeral streams are con- for new legislation. Toward these ends, the
derstanding of how the integrity of freshwa- nected to one another and downstream wa- scientific community has already spoken
ter ecosystems within a watershed relates to ters along a gradient of connectivity, they on the matter, proposing three frameworks
the biological, chemical, and hydrological also provide substantial cumulative or ag- for the development of renewed protections
connectivity among waterbodies, including gregate ecosystem services (10). based on sound scientific merits (2).
wetlands and ephemeral streams. This un-

1Schiermeier Olentangy River Wetland Research Park, School of Environment and Natural Resources, The Ohio State University, Columbus, OH, USA.2School of Geosciences, University of South
Florida, Tampa, FL, USA.3Cornell Lab of Ornithology, Cornell University, Ithaca, NY, USA.4Department of Natural Resources, Cornell University, Ithaca, NY, USA.5Georgetown University Law
Center, Georgetown University, Washington, DC, USA.6Odum School of Ecology, University of Georgia, Athens, GA, USA. Email: [email protected]

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Meanwhile, litigation may present chal- Research-based evidence on the impacts exploitation of water resources. Although
lenges to and perhaps enjoin implementa- of climate change were notably absent in the
tion of the NWPR. The April 2020 County NWPR and will also be critical in challeng- federal statutes grant latitude to state, tribal,
of Maui v. Hawaii Wildlife Fund may help. ing the rule. Under current human-use and
In that case, the U.S. Supreme Court rejected water-management schemes, many stream and local governments to provide additional,
an argument that would have eliminated flows are declining, such that intermittent
federal CWA protections. The Court instead and perennial streams are increasingly be- more protective regulation, many states do
called for a functional and context-sensitive ing replaced with ephemeral streams that
analysis of the disputed activities and their will lose protection. For example, the Upper not do so, and many even prohibit regula-
effects to determine federal jurisdiction over Kansas River Basin lost 558 km (21%) of
intentional pollution discharges into ground- stream length between 1950 and 1980, pre- tions more stringent than federally required
water that predictably flows into WOTUS. In sumably as a result of groundwater pumping
that 6 to 3 decision, the Court laid out a clear exacerbated by climate change, with a cu- (2, 14). Thus, absent federal protections,
scientific basis for closing a loophole in the mulative loss of 844 km (32%) predicted by
CWA, affirming for the first time that pollut- 2060 (12). Reduced mountain snowpack and many waterbodies will go unprotected.
ants that travel through groundwater and increased evaporation have been implicated
If the NWPR remains in place, local and
Protected versus unprotected waters
grassroots approaches to water conserva-
Multiple waterbody types were initially under consideration for protection as “waters of the United States”
under the Navigable Waters Protection Rule. Ephemeral streams flow only after precipitation events, tion, including watershed councils and coali-
intermittent streams flow periodically or seasonally, and perennial streams flow continuously. There are many
types of nonfloodplain, or “isolated” wetlands, including prairie potholes and vernal pools, as illustrated here. tions, information and educational plans to

Protected Prairie potholes Unprotected reduce pollution, and university extension

Perennial streams Vernal Nonfoodplain programs, will need to further mobilize to fill
pools wetlands
Intermittent (“isolated”) the vacuum created by the new rule. Such ef-
streams (individual and
(with relatively aggregate) forts would require additional resources and
surface fows) Intermittent heightened stakeholder coordination. j
Floodplain wetlands (lacking relatively REFERENCES AND NOTES
(abutting TNWs through permanent
surface hydrologic surface fows) 1. U.S.Environmental ProtectionAgency and Department
connection of Defense,Department of theArmy,Corps of Engineers,
“in a typical year”) Ephemeral The NavigableWaters Protection Rule: Definition of
streams “Waters of the United States,” 85 Fed.Reg.22250
Traditional (individual and (A2020).
navigable aggregate)
waters (TNWs) 2. I.F.Creed et al.,Nat.Geosci.10,809 (2017).
Floodplain wetlands 3. S.AR.Colvin et al.,Fisheries (Bethesda,MD) 44,73
(not abutting TNWs
through surface (2019).
hydrologic connection 4. FederalWater Pollution ControlAct,33 U.S.C.1251 et seq.,
“in a typical year”)
Sec.101,p.3 (1972).
Groundwater 5. U.S.EPA,Letter toAndrewWheeler,27 February 2020,

then emerge into surface waters are in fact in the ~20% decline in the Colorado River’s SAB commentary on the proposed rule defining the GRAPHIC: MELISSA THOMAS BAUM/SCIENCE
covered by the CWA.  mean annual flow in comparison to the pre- scope of waters federally regulated under the CleanWater
vious century; the Upper Colorado River Act,EPA-SAB-20-002 (Environmental ProtectionAgency,
Redoubled research efforts also can help basin supplies water to around 40 million 2020).
address knowledge gaps critical for effec- people and supports ~16 million jobs (13). 6. U.S.Environmental ProtectionAgency and Department
tive water policy. Quantifying the potential of theArmy,Economic analysis for the NavigableWaters
“harm” to clean water that will be caused Adoption of the NWPR is an indicator that Protection Rule: Definition of“Waters of the United
by the NWPR is critical for both litigation the federal government is at least in part States” (EPA, 2020).
and future rulemaking. Thus, the scientific shedding the use of science and responsibility 7. U.S.Environmental ProtectionAgency and Department
community will be challenged to further for water protection. Additional federal roll- of Defense,Department of theArmy,Corps of Engineers,
demonstrate the consequences of changes backs of environmental protection, such as CleanWater Rule: Definition of“Waters of the United
to physical, chemical, and biological con- the Update to the Regulations Implementing States”80 Fed.Reg.37054 (EPA,2015).
nectivity on water quality—especially in the the Procedural Provisions of the National 8. U.S.Environmental ProtectionAgency,Connectivity of
context of nonperennial streams and non- Environmental Policy Act, a rule finalized streams and wetlands to downstream waters: a review
floodplain wetlands. on 15 July, could create a perfect storm for and synthesis of the scientific evidence technical report,
EPA/600/R-14/475F (EPA, 2015).
9. S.M.P.Sullivan,M.C.Rains,A.D.Rodewald,Proc.Natl.
Acad.Sci.U.S.A. 116,11558 (2019).
10. U.S.Environmental ProtectionAgency,Letter to Gina
McCarthy,17 October 2014.SAB review of the draft EPA
report Connectivity of streams and wetlands to down-
stream waters:Areview and synthesis of the scientific
evidence (EPA,2014).
11. R.Meyer,A.Robertson,NavigableWaters Protection Rule
spatial analysis:AGIS based scenario model for compara-
tive analysis of the potential spatial extent of jurisdictional
and non-jurisdictional waters and wetlands (Saint Mary’s
University of Minnesota,Winona,MN,2020).
12. J.S.Perkin et al.,Proc.Natl.Acad.Sci.U.S.A.114,7373
13. P.C.D.Milly,K.A.Dunne,Science 367,1252 (2020).
14. State constraints: State-imposed limitations on the
authority of agencies to regulate waters beyond the
scope of the federal CleanWaterAct (Environmental Law
Institute, 2013).


We thank the many individuals who contributed to previous
and related documents concerning the proposed replace-
ment rule that helped inform this paper, including letters to
the Federal Register (Docket ID No. EPAHQ-OW-2018-0149)
and Public Input on the SAB Commentary on the Proposed
Rule Defining the Scope of Waters Federally Regulated under
the Clean Water Act (84 FR 4154).We also thank L. Poff,W.
Kleindl, and three anonymous reviewers for their critiques
and suggestions in earlier drafts. R. B. Keast and S.M.P.S.
developed the figure. S.M.P.S. is currently providing advisory
and expert consulting services to ongoing litigation regarding
the NWPR.


768 14 AUGUST 2020 • VOL 369 ISSUE 6505 SCIENCE

Published by AAAS

Displaced Iraqis play soccer. Christian players’
prejudice decreased toward Muslim teammates
but not toward Muslim strangers.

PERSPECTIVES 5), which counters both lay and scientific no-
tions that attitudes guide behavior. One could
INTERGROUP RELATIONS argue that between attitudes and behaviors,
it is better to change behavior because preju-
Can playing together help dicial action is worse than harboring prejudi-
us live together? cial attitudes. Additionally, public behaviors
may cause more downstream change because
A field experiment in Iraq shows that having Muslim they are more easily observable than private
teammates reduced Christian soccer players’ prejudice attitudes (6). More work is needed to mea-
sure these kinds of spillover effects, following
PHOTO: SPENCER PLATT/GETTY IMAGES By Elizabeth Levy Paluck and Chelsey S. Clark Given its relevance for policy (Mousa notes on Mousa’s finding that community members
that $877 million was allocated in 2020 to- who attended more games were more likely
T he contact hypothesis in psychology ward “social cohesion” programming by the to view religious and ethnic divisions as ar-
predicts that prejudice can be reduced U.S. Agency for International Development) bitrary. Future work can also disentangle
when rival groups come together under and that the contact hypothesis has been whether attitudes are simply more difficult
optimal circumstances of cooperation studied for many years, some may classify to change or whether current research is not
and equal status. To date, the weight this research as an application of a well- measuring the correct attitudes.
of real-world evidence for this hypoth- known finding. This would be inaccurate.
esis comes from self-reported attitudes after Previous research has not demonstrated Perhaps the nature of intergroup contact is
self-initiated contact, not from preregistered cause and effect with real-world interven- useful for changing a more limited range of
randomized trials that take intergroup con- tions or measured behaviors or otherwise attitudes than those measured in the present
tact as seriously as one would take a potential leveraged the most robust research method- study. Mousa observes one instance of atti-
vaccine for conflict (1, 2). Consequently, on ologies. These methods are crucial, given that tude change among players: the item regard-
page 866 of this issue, the results of Mousa’s the anticipated effects of contact range from ing arbitrary religious and ethnic divisions.
(3) new field experiment are breaking news. positive change to backlash, in which contact She points out that it represents a change in
Mousa intervened in amateur Christian soc- stirs latent resentments. This makes Mousa’s “abstract attitudes rather than concrete pol-
cer leagues across Northern Iraqi cities af- research more similar to basic science that icy positions.” As it was originally conceived,
fected by ISIS violence. To assess the impact makes progress toward fundamental evi- the contact hypothesis was a salve for preju-
of this ambitious real-world intervention, she dence than to applied research that tests pol- dice or animus, not for antagonistic political
randomly assigned Muslim players to half of icy interventions based on a robust founda- opinion or behavior (7). Since then, psycho-
the teams, measured players’ behavior up to tion of scientific evidence. Work in the field, logical evidence has grown, suggesting that
6 months later, and posted her preregistered which is often mistaken for applied research prejudice-reduction interventions have in-
analysis plan and data alongside the report. because of its location outside the laboratory, consistent and even unintended effects on
Mousa finds that having Muslim teammates performs the function of basic science when related political attitudes (8). Mousa defines
causes Christian players to change their be- it comes to the question of whether inter- and measures the target of her intervention,
havior for the better toward Muslim players, group contact increases social cohesion. social cohesion, as a more compound concept
by including them, working with them, and than prejudice, involving intergroup coopera-
awarding them material signs of respect. The study presents a fundamental theo- tion and policy attitudes. Interventions such
Team-based contact with minority group retical puzzle: Why don’t the positive behav- as contact that are intended to soften atti-
members reduced prejudiced behavior to- ioral effects generalize out of context, or to tudes toward outgroups may need to be com-
ward other minority group players. positive intergroup attitudes? The first piece bined with additional activities to channel
of the puzzle is that the observed changes newfound goodwill into a political or policy
Department of Psychology and Policy, School of Public and are limited to behaviors and not attitudes. position. Early work on interracial contact in
International Affairs, Princeton University, Princeton, NJ, A growing number of field experiments on the United States recognized this point. For
USA. Email: [email protected] prejudice reduction uncover this pattern (4, example, in addition to creating ideal contact
conditions for Black and White individuals
working in teams, one study using Black ac-
tors to mention instances of discrimination
and race-based hardship helped White par-
ticipants connect their experience to larger
societal issues (9).

The second piece of the theoretical
puzzle is that changes in behavior toward
other Muslim players in the league did not
generalize to changes in behavior toward
Muslim strangers. Mousa offers possible
explanations, including ongoing threat
from recent anti-Christian violence, the
fragile quality of the contact with other
players, and the possibility that behavior
change takes longer to manifest. Another

SCIENCE 14 AUGUST 2020 • VOL 369 ISSUE 6505 769

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possibility rests in the basic math of the MARINE ECOLOGY
league’s intergroup contact: Christian lead-
ers allowed a maximum of three Muslim Marine food webs destabilized
players on treatment teams. This limita-
tion represents a hard-won insight about A combination of warming and acidification threaten
the difficulty of implementing intergroup marine biomass and productivity
contact interventions in post-conflict set-
tings but may have limited the generaliz- By Steven L. Chown (fish, crabs) consumers were represented
ability of behavioral effects. by the species included in the mesocosms,
F orecasting the ecological consequences as were typical feeding interactions among
Psychological theory predicts that indi- of climate change requires both ob- species and trophic levels. The 1800-liter
viduals can make positive generalizations servations and experiments. Among mesocosms were then either exposed to
from one prototypical group member to the most informative experiments are conditions typical of those along the South
the rest of the group (10). The handful of manipulations of ecosystems, either Australian coast (a control setting) or ex-
Muslim players may have been seen as ex- through large outdoor interventions posed to increased temperature, simulated
ceptional, not prototypical, in the eyes of or through the construction of mesocosms acidification, or a combination of the two,
the Christian players, similar to other con- (1)—replicas of the natural world that en- as expected at the end of this century un-
texts with a token number of outgroup indi- able conditions to be carefully controlled. der the Intergovernmental Panel on Climate
viduals. If the Muslim players were consid- Mesocosms typically mimic the complexity Change’s Representative Concentration
ered an exception to the rule, psychological of natural ecosystems, enabling researchers Pathway 8.5 (RCP8.5) scenario. RCP8.5 is
theory would not predict that positive im- to disentangle how these systems work now based on an extreme anthropogenic green-
pressions of Muslim players would general- and what path they might follow as future house gas emissions scenario, but one that
ize to their group. conditions change. They can also be repli- continues to be plausible (3). Nagelkerken et
cated, enabling signal to be distinguished al. then investigated food web structure in
Another consequence of the small number from the variability that is an inherent fea- the form of feeding interactions and the way
of Muslim players is that it inhibits the re- ture of natural systems. On page 829 of this in which biomass and productivity change
search from exploring effects on both sides of issue, Nagelkerken et al. (2) report on their among trophic groups.
the intergroup contact. Mousa’s data suggest use of mesocosms to better understand the
that Muslim players’ prejudice did not change future of marine systems and the ecological Simulated ocean acidification had little
over time, but there are too few Muslims and services they deliver. They find that marine effect, except for a benefit from bottom-up
no Muslim control group to rigorously test benthic ecosystems have limited capacity to resource enrichment. By contrast, although
this claim. Leaving out the perspectives of respond to a future combination of warming food web structure was relatively insensi-
minority group members, who are often in- and acidification, with considerable degra- tive to temperature and to the combination
strumentalized for the purpose of attitude dation a potential outcome. of temperature and acidification, both bio-
change among the majority, is a pattern in mass and productivity were greatly reorga-
intergroup contact research. There is much Nagelkerken et al. address several key nized among trophic groups (see the figure,
to learn by studying reactions to intergroup questions. Their experiments explore the center). In effect, and especially under com-
contact among minority group participants. way that ecological interactions will play bined warming and acidification, primary
out under end-of-century temperature and producer and secondary consumer biomass
This landmark study cuts a clear path for ocean acidification conditions compared and productivity increased, whereas sub-
future scholarship. Generalized answers with those now. They assess how species with stantial declines occurred among primary
will only emerge after more experimental similar functions, but different responses to consumers. As Nagelkerken et al. point out,
work that may seem like policy applica- changing physical conditions, replace each such trophic imbalance is unlikely to be sta-
tion but is actually basic science, working other, thus preserving the form of ecologi- ble in the long term. Rather, it represents
systematically toward robust conclusions. cal interactions (especially feeding) among a transitory state, with one likely outcome
Mousa is one of a cohort (2) of young scien- community members. They also aim to de- the collapse of the system such that primary
tists who are leading the way. j termine whether the trophic structure of producers dominate and secondary con-
present-day marine systems (see the figure, sumers, such as fish, are largely lost (see the
REFERENCES AND NOTES left)—with a high biomass of primary pro- figure, right). Less extreme outcomes might
ducers and lower biomasses of primary and result if species are capable of adapting to
1. E. L. Paluck, S.A. Green, D. P. Green, Behav. Pub. Pol. 3, secondary consumers—will be maintained as the combination of warmer temperatures
129 (2019). physical conditions change. and higher acidity.

2. E. L. Paluck, Harvard Dataverse (2020); doi:10.7910/ Nagelkerken et al. constructed replicas The outcomes from these mesocosm ex-
DVN/ODACR5. of Australian marine benthic systems, in- periments are worrying. Secondary marine
cluding all of the major groups of organ- consumers, such as fish and larger inverte-
3. S. Mousa, Science 369, 866 (2020). isms that might be expected: cyanobacteria, brates, are an important nutritional source
4. A. Scacco, S. S.Warren, Am. Polit. Sci. Rev. 112, 654 algae, copepods, shrimps, crabs, molluscs, for people (4). Indeed, demersal and small
polychaetes, brittle stars, sponges, and fish. pelagic fish now dominate global fisheries
(2018). Primary producers (such as algae) and catch (5). Yet these important marine re-
5. E. L. Paluck, J. Pers. Soc. Psychol. 96, 574 (2009). both primary (molluscs) and secondary sources are under pressure because of fishing
6. T. Kuran, Private Truths, Public Lies (Harvard Univ. Press, for human consumption (6) or the produc-
School of Biological Sciences, Monash University, Victoria tion of fish meal for aquaculture (7). These
1997). 3800, Australia. Email: [email protected] mesocosm trials suggest that this direct
7. G.Allport, The Nature of Prejudice (Addison Wesley,

8. J. Dixon, M. Levine, S. Reicher, K. Durrheim, Behav. Brain

Sci. 35, 411 (2012).
9. S.W. Cook, J. Res. Dev. Educ. 55, 647 (1978).
10. J. C.Turner, M.A. Hogg, P.J. Oakes, S. D. Reicher, M.

S.Wetherell, Rediscovering the Social Group, A Self-
Categorization Theory (Basil Blackwell, 1987).


The authors thank the Rita Allen Foundation for funding and
R. Porat and D. Green for comments.


770 14 AUGUST 2020 • VOL 369 ISSUE 6505 SCIENCE

Published by AAAS

pressure, which includes increased benthic results, which show an absence under future NEUROSCIENCE
trawling (5), will further be compounded by conditions of important stabilizing processes
the combination of warming and acidifica- that include species substitution, functional An early start
tion. These local-scale conclusions are well redundancy, and trophic compensation, ap- to Huntington’s
aligned with global models forecasting con- ply as much to other settings as they do to disease
tinual declines in global ocean animal bio- the system they investigated is far from clear.
mass, especially at higher trophic levels, as Indeed, replication in other ways and other The huntingtin gene
climates change (8). Beyond the end of this settings of this work is critical because me- mutation interferes with
century, these impacts are expected to be es- socosm outcomes can be quite variable (1). neurogenesis in
pecially severe in some regions (9). human fetal cortex
If the trajectory documented by
Human futures are not the only ones that Nagelkerken et al. is found elsewhere, ad-
are at stake. Other species, and ecosystems, ditional early warning indicators, such as
also depend on what’s happening in the sea. initial declines in primary consumer bio-
Marine secondary consumers, such as fish, mass and productivity, will have been made
are not the end of the trophic line. Rather, available. These are indicators that could
they are also food for seabird and marine help detect and perhaps prevent the tran-
mammal species, which are themselves now sition of marine systems to states that are

Expected changes to future marine trophic structure By Marian DiFiglia

Currently, marine nearshore systems have high primary producer biomass and productivity, which declines H untington’s disease (HD) is a rare,
moderately with increasing trophic level. Mesocosm experiments reveal a sharp decline in primary—but not inherited brain disorder that causes
secondary—consumer biomass and productivity in response to expected end-of-century temperature and progressive degeneration of neurons,
acidification conditions. Such trophic structure is unstable. In the absence of adaptation, systems are expected impaired movement and cognition,
to collapse to those with few secondary consumers and a dominance of primary producers. and death ~15 years after onset.
Most carriers of the pathogenic mu-
Present conditions Mesocosm outcome Ultimate expectation tation in the huntingtin (HTT) gene develop
symptoms in midlife, but abnormalities in
Secondary the brain can occur a decade earlier. On
consumers page 787 of this issue, Barnat et al. (1) de-
scribe anomalies in neuronal precursors
Primary destined for the cortex of human fetal brain
consumers and embryonic mouse brain harboring
HD-associated mutations in the HTT gene.
Primary These findings prompt questions about the
producers impact of these events on early develop-
ment, the emergence of disease, and the
Biomass/productivity Biomass/productivity Biomass/productivity timing of therapeutic interventions.

GRAPHIC: JOSHUA BIRD/SCIENCE under pressure from changing climates and much less rich and productive than they are The genetic mutation in HTT causes
human activity (10). Moreover, these verte- now. Overall, the message from these marine an increase in the number of consecutive
brates play a role in the transfer of marine mesocosm trials is clear: Destabilization of DNA triplets of CAG, which encodes gluta-
nutrients to terrestrial areas, thus contribut- marine food webs can only be mitigated if mine. This results in 39 or more glutamine
ing to the functioning of coastal margin and further concerted action is taken to reduce residues in the mutant huntingtin protein
island ecosystems (11). greenhouse gas emissions. j (mHTT) (2). Most of the affected individu-
als are heterozygous for the mutation, have
One finding from Nagelkerken et al.’s REFERENCES AND NOTES an average of 42 CAG repeats in the mutant
experiments that might seem unusual is HTT allele, and experience onset of the dis-
the limited impact of acidification alone. 1. R. I.A. Stewart et al., Adv. Ecol. Res. 48, 71 (2013). ease in midlife. Human embryos studied by
Acidification’s effects on animals—such as 2. I. Nagelkerken, S. U. Goldenberg, C. M. Ferreira, H. Ullah, Barnat et al. had CAG repeat numbers in
influences on embryonic development, adult this range. Ten percent of HTT carriers have
reproduction, and energetics—are now prov- S. D. Connell, Science 369, 829 (2020). 55 or more CAG repeats and suffer juvenile
ing in many cases to be less severe than 3. Z. Hausfather, G. P. Peters, Nature 577, 618 (2020). onset with progressive cognitive decline
feared (12). But the effects of interactions 4. C. C. Hicks et al., Nature 574, 95 (2019). but more rigid postures instead of the cho-
between stressors are not yet well character- 5. R.A.Watson,A.Tidd, Mar. Policy 93, 171 (2018). reiform (rapid, jerky) movements that are
ized. Rich opportunity exists to determine 6. D.A. Kroodsma et al., Science 359, 904 (2018). typical of adult onset HD. Thus, CAG repeat
just how general Nagelkerken et al.’s find- 7. D. Pauly, Nature 574, 41 (2019). length inversely correlates with the age of
ings are, by exploring the outcomes of in- 8. H. K. Lotze et al., Proc. Natl.Acad. Sci. U.S.A. 116, 12907 disease onset. The CAG repeat is also unsta-
teractions among multiple stressors such as ble and continues to expand in postmitotic
increased temperature, increased carbon di- (2019). neurons, likely instigating greater harm.
oxide, and changing salinity. Whether their 9. J. K. Moore et al., Science 359, 1139 (2018).
10. M.A. Hindell et al., Nature 580, 87 (2020). In the postmortem brain of HTT gene
11. B. Moss, J. Exp. Mar. Biol. Ecol. 492, 63 (2017).
12. L. S. Peck, Oceanogr. Mar. Biol.Annu. Rev. 56, 105 Laboratory of Cellular Neurobiology, Department of
Neurology, Massachusetts General Hospital and Harvard
(2018). Medical School, Charlestown MA, USA.
Email: [email protected]

SCIENCE 14 AUGUST 2020 • VOL 369 ISSUE 6505 771

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carriers, there is marked atrophy of HD patients (11). In HD mice,

of the cortex and the neostriatum the expression of genes involved in

(which comprises the caudate nu- synaptic function decreases early,

cleus and putamen in the human whereas the expression of genes

brain); the neostriatum is a region involved in responses to DNA dam-

heavily innervated by the cortex age and cell death increases later

(3). Thinning of the cortex can be (12). Stem cells seem to accumu-

detected by brain imaging a decade late in the subependymal region,

before disease onset (4). The loss of adjacent to the caudate nucleus, of

projections from neurons in the cor- HD postmortem human brain, sug-

tex to neurons in the neostriatum gesting increased neurogenesis (13).

contributes to early signs of dis- Moreover, medium spiny neurons in

ease, including slight involuntary the neostriatum of HD postmortem

movements, decreased executive human brain can grow longer pro-

functions, and emotional changes. cesses and sprout more spines, in-

Most HD mouse models, including dicative of neuronal plasticity (14).

the one studied by Barnat et al., The aggregates of mHTT formed

are engineered with an expanded in nuclei of cortical and neostriatal

CAG repeat (Q111) in the mouse Htt neurons are not linked to neuron

gene; as these mice become adults, death and may even facilitate neu-

they do not develop the severe neu- ron survival by sequestering the

ropathological features and motor mutant protein and limiting abnor-

deficits seen in the human disorder mal protein interactions (5, 15).

(3). One neuropathological feature The unequivocal evidence offered

shared between human and mouse by Barnat et al. that the mutation

HD is the presence of aggregates of in HD has effects on cortical neu-

mHTT that form in the nucleus and rogenesis in the human fetal brain

cytoplasm of cortical and neostria- stirs the question of how much

tal neurons (3, 5). this contributes to cortical changes

Barnat et al. found that mHTT The developing human fetal brain is produced from apical progenitors that affect dysfunction. Identifying

in 13-week-old human fetal brain (magenta) and basal progenitors (green) that generate neurons and are targets for therapy that specifi-

and 13.5-day-old mouse embryonic altered in carriers of the huntingtin gene mutation. cally address neurodevelopmental

brain had impaired the processes milestones could be challenging.

that regulate interkinetic nuclear migration to interfere with many functions includ- The primary therapeutic approach today

of progenitors and caused premature com- ing membrane trafficking, cytoskeleton- is to reduce the expression of HTT and the

mitment of neuronal precursors to their dependent transport of synaptic vesicles, mutant protein it encodes. With these new

differentiated cell fate. mHTT and other and synaptic activation. These altered func- findings in hand, it will be important to

proteins were mislocalized and engaged in tions can in turn disrupt synaptic connec- consider when treatment to lower expres-

abnormal protein interactions that led to tions between the cortex and other regions, sion of the mutant HTT gene should begin

dysfunction. Cultured embryonic stem cells thereby contributing to disease. and whether such a therapy can attenuate

derived from the same HD mouse model Studies support an influence of mHTT potential deficits arising at an early stage in

(Q111) also exhibit “premature” neurogen- on cortical neurodevelopment. HD gene neurodevelopment. j

esis caused by imbalance between progeni- carriers have a subtle reduction in head REFERENCES AND NOTES
tor and neural induction states (6). If this circumference and lower body mass in-
occurred throughout neurogenesis in in- dex decades before predicted onset (8). 1. M. Barnat et al., Science 369, 787 (2020).
dividuals with HD, it could affect neuron Moreover, human cortical neurons derived 2. Huntington’s Disease Collaborative Research Group,

Cell 72, 971 (1993).

density and distribution and cause smaller from stem cells of juvenile-onset HD pa- 3. J.-P. G.Vonsattel, Acta Neuropathol. 115, 55 (2008).
brain size. However, knowledge of other tients are delayed in neurite growth and 4. H. D. Rosas et al., Brain 131, 1057 (2008).
events in the embryonic and early postna- firing action potentials, and they express 5. M. DiFiglia et al., Science 277, 1990 (1997).
6. G. D. Nguyen, S. Gokhan,A. E. Molero, M. F. Mehler,

tal periods—including generation of astro- lower levels of genes involved in synap- PLOS ONE 8, e64368 (2013).
cytes, synapse formation and pruning, and tic functions (9). In the same HD model 7. P. G. Bhide et al., J. Neurosci. 16, 5523 (1996).
programmed cell death—is necessary to dis- (Q111) used by Barnat et al., young mice 8. J. K. Lee et al., Neurology 79, 668 (2012).
cern the impact of the mutant HD gene on had altered electrophysiological properties 9. S. R. Mehta et al., Cell Rep. 25, 1081 (2018).
human cortex formation. in neurons of the neostriatum, and older 10. M. Kovalenko et al., J. Huntingtons Dis. 7, 17 (2018).
mice displayed subtle reductions in corti- 11. J. M. Dubinsky, J. Huntingtons Dis. 6, 267 (2017).
Wild-type HTT is expressed throughout 12. S.A.Ament et al., Mol. Syst. Biol. 14, e7435 (2018).
13. M.A. Curtis et al., Proc. Natl.Acad. Sci. U.S.A. 100, 9023

the developing and adult mouse brain, and cal volume and thickness (10). (2003). PHOTO: BARNAT ET AL. (1)
it is highly expressed in neurons (7). The The lasting effects of mHTT on neuro- 14. G.A. Graveland, R. S.Williams, M. DiFiglia, Science 227,
protein reaches its highest expression lev-
els in the developing mouse brain between genesis and on postnatal and early adult 770 (1985).
brain development could be forestalled for 15. F. Saudou, S. Finkbeiner, D. Devys, M. E. Greenberg, Cell

95, 55 (1998).

postnatal days 2 and 7, when astrocytes decades by compensatory homeostatic pro- ACKNOWLEDGMENTS
populate the cortex and neurons start to cesses. For example, molecular pathways
extend branches and form synaptic connec- are activated in human and mouse HD to The author is supported by NINDS 1U01NS114098, CHDI
tions. In this period, aberrant interactions cope with the oxidative stress and altered Foundation, and Dake Family Fund.

by mHTT with other proteins are known energy metabolism that occur in neurons 10.1126/science.abd6215

772 14 AUGUST 2020 • VOL 369 ISSUE 6505 SCIENCE

Published by AAAS


Designing a wider superelastic window

Adding chromium to an iron alloy enables shape recovery over a wide temperature range

By Paulo La Roca1 and Marcos Sade2 are independent of temperature over the a critical value s , a first martensitic plate
largest superelastic window reported, from T
C onventional metal alloys can only re- 10 to 473 K.
cover their original shape if subjected forms (shown in blue).
to very small elastic deformations. Superelasticity is explained by the pres- A constant-stress plateau in the curve
Superelastic alloys (also named pseu- ence of a stress-induced martensitic trans-
doelastic alloys) can recover their formation. In this solid-solid displacive characterizes both the direct and inverse
shape after deformations as great as transition between two crystal structures, transitions, usually named transformation
20% (1) just by unloading the force on the usually named austenite and martensite af- and retransformation, respectively. The end
material. They are part of the larger group ter the phases originally described in steel, of the transformation plateau corresponds
of shape-memory alloys but do not require much harder martensite forms by rapid to the sample completely transformed to
a temperature change for recovery, and they quenching of austenite. This transition does martensite. The inverse path is also shown
have found applications in areas including not require diffusion because the atoms until the material recovers the form when
robotics, structural engineering of build- move over distances much smaller than the it reaches the original austenitic state. The
ings, and aerospace engineering (2, 3). A interatomic distance. The structure of these functional properties of a superelastic al-
superelastic alloy usually exhibits this prop- phases depends on the specific material (5). loy that determine its performance are the
erty only over a well-determined and often A schematic plot of a stress-deformation critical stress to induce the martensitic
small temperature range normally called a cycle corresponding to a martensitic stress- transformation s , the retransformation
“superelastic window.” On page 855 of this induced transition obtained at constant
issue, Xia et al. (4) describe superelastic “in- temperature (see the figure, left) is accom- T
var” alloys with functional properties that panied by a schematic of the evolution of
a material sample as the transformation stress s , the hysteresis width H , and the
1Centro Atómico Bariloche (CNEA), 8400 Bariloche, cycle goes on. The sample is initially fully Rs
Argentina. 2Instituto Balseiro (Universidad Nacional de austenitic (shown in gray). After a tensile
Cuyo–CNEA), CONICET, Bariloche, Argentina. stress is applied, the sample is elastically maximum recoverable strain . The dissi-
Email: [email protected] deformed; when the applied stress reaches max

pated energy in each transformation cycle,
determined by the enclosed area of the
cycle, increases as the hysteresis width and
maximum recoverable deformation enlarge.
This energy dissipation makes these alloys
potential candidates as damping materials
in devices to be used in buildings or aero-
space structures (2, 3).

Widening the superelastic window

Superelastic alloys can recover their shape after deformation over a small temperature range. Xia et al. now report an almost temperature-independent response
for a superelastic iron alloy.

Snapping back from strain A wider temperature range

Pulling on an austenite sample transforms it to martensite at a constant stress σT and Stress-induced transformations for a conventional superelastic material
reaches a maximum elongation at a strain εmax. When strain is released, the austenite (blue curves) are limited at hysteresis (red cross) and by plastic
phase and original shape are recovered but at a lower stress σR. deformation. The temperature range is for a Cu-Mn-Al shape-memory
alloy (7). A very large superelastic window was reported by Xia et al.
σT σT σT for a Fe-Mn-Al-Cr-Ni alloy (red curves).

Transformation Full martensite 180 K 350 K
4 σ

σT Other Plastic
alloys deformation
Stress Dissipated energy Hσ ε
0 473 K

σR Superelastic window
1 temperature

σR σR 10 K
6 5 σ

GRAPHIC: C. BICKEL/SCIENCE Retransformation Fe-Mn-Al-Cr-Ni

Full austenite Strain 0ε Superelastic window temperature
0 εmax 14 AUGUST 2020 • VOL 369 ISSUE 6505 773
Published by AAAS


The variation of functional properties with NEUROSCIENCE
temperature can be strongly detrimental for
several types of applications, such as damp- The importins of pain
ing devices in platforms that operate over
a wide temperature range. Finding new al- A nuclear protein importer modulates gene expression
loys with functional properties independent to control the persistence of neuropathic pain
of temperature variations would strongly
increase the benefit of using superelastic By Muhammad Saad Yousuf and Typically, researchers follow neuropathic
alloys. For example, devices in space appli- Theodore J. Price pain in animal models for 20 to 30 days af-
cations must function over a wide range of ter induction with an injury to DRG neurons.
temperature variations (2, 6). Unlike a more N europathic pain, which is pain that The phenotype identified by Marvaldi et al.
conventional shape-memory alloy (7), the arises from injury or disease affecting in mice lacking importin a3 does not emerge
superelastic response of the Fe-Mn-Al-Cr-Ni the somatosensory nervous system, af- until 60 days after peripheral nerve injury,
alloy reported by Xia et al. can be considered fects millions of people with devastat- a time point that is rarely explored in such
independent of temperature (see the figure, ing consequences to their well-being. studies. Specifically, reducing importin a3
right). The family of iron-nickel–based invar Available therapeutics have limited expression in sensory neurons also resolved
alloys already exhibits very low thermal ex- efficacy, and the underlying mechanisms neuropathic pain 60 days after nerve injury,
pansion. The addition of Cr led to superelas- governing the persistence of this disorder are as did interfering with AP1 transcription fac-
tic alloys in which this mechanical response mysterious. On page 842 of this issue, Mar- tor signaling using a variety of drugs. Notably,
was independent of temperature. valdi et al. (1) reveal that the nuclear import the authors demonstrate that reduction of
protein, importin a3, plays a crucial role in AP1 signaling in sensory neurons of the DRG
It is known from thermodynamic concepts maintaining neuropathic pain months af- is the locus of this effect, in agreement with
related to martensitic transformations (first- ter a peripheral nerve injury in mice. Their their importin a3 findings. This strongly
order transitions) that the variation with findings demonstrate that activator protein supports the conclusion that a late wave of
temperature of the critical transformation 1 (AP1) family transcription factors require importin a3–facilitated, AP1-driven gene ex-
stress needed to induce the martensite phase this nuclear transport complex for entrance pression in DRG neurons is responsible for
linearly depends on the entropy change be- to the sensory neuronal nucleus, pointing to persistent neuropathic pain (see the figure).
tween the involved phases. Thus, there is a a defined set of drug targets for the potential One such gene that appears to be regulated
thermodynamic magnitude that controls the disruption of persistent neuropathic pain. An by this late wave of AP1 activity is Syngap1,
effect of temperature on the most important implication of the findings is that even very which encodes a synaptic protein that might
parameter that characterizes the superelastic long-lasting neuropathic pain can be dis- increase the strength of connections between
effect—that is, s . If a specific superelastic al- rupted with disease-modifying therapeutics. the injured peripheral neurons and the first
synapses in the pain pathway in the dorsal
T An important advance in the work of horn of the spinal cord in the central ner-
Marvaldi et al. is the demonstration of a vous system (CNS). This importin a3–driven
loy is designed to have a negligible amount mechanism that may be responsible for the facilitation of gene expression could presyn-
of entropy change between the austenite and transition to chronic neuropathic pain. The aptically enhance signaling efficacy between
martensite phases, superelasticity indepen- idea of an acute-to-chronic pain transition DRG neurons and their targets in the CNS in
dent of temperature should result. has received a lot of attention because clini- neuropathic pain, representing an exciting
cal trials and clinical experience suggest that candidate mechanism to explain the transi-
Xia et al. showed that it is possible to con- drugs used for acute pain are rarely effec- tion from acute to chronic neuropathic pain.
trol the entropy change with the addition of tive for chronic pain (2). Acute pain typically
Cr to an Fe-Mn-Al-Ni alloy, and in this way, has a clear cause, and the amount of pain A critical insight from this work is a recon-
a composition was found where the entropy is usually proportional to the injury or the ceptualization of the acute-to-chronic neuro-
change was nearly zero. This remarkable re- stimulus. Chronic pain does not always have pathic pain transition. It is broadly accepted
sult may be connected with magnetic order a clear cause, often persists after an injury that neuropathic pain is initially driven by
transitions that are present in both austen- has healed, and may be disproportionate to the emergence of spontaneous or ectopic
ite and martensite phases, and this aspect the original injury or to the apparent stim- activity in DRG sensory neurons, including
deserves more attention in future research. ulus. These properties of chronic pain are pain-sensing neurons called nociceptors (3–
Finally, Xia et al. show that the search for particularly relevant in chronic neuropathic 5). However, once neuropathic pain becomes
superelastic alloys with tunable entropy pain, which is often not recognized until it chronic, it is widely thought that there is a
changes between austenite and martensite is chronic, because diagnostics to identify pe- shift from changes in the peripheral nervous
phases—for example, by varying composi- ripheral nerve damage are lacking, and treat- system toward independent CNS-mediated
tion—constitutes a powerful tool for design- ment options are ineffective and limited. The mechanisms, suggesting a “centralization” of
ing alloys with remarkable properties. j neurons that are most commonly affected in neuropathic pain when it becomes chronic.
neuropathic pain are sensory neurons in the The study of Marvaldi et al. does not upend
REFERENCES AND NOTES dorsal root ganglion (DRG, which connects to this concept, but it places focus back on DRG
1. F. C. Bubani, M. Sade, F. Lovey, Mater. Sci. Eng.A 543, 88 the spinal cord); injury to these sensory DRG neurons in the peripheral nervous system as
(2012). neurons was studied by Marvaldi et al. the key drivers of chronic neuropathic pain.
2. J. Mohd Jani et al., Mater. Des. 56, 1078 (2014).
3. P. La Roca,A. Baruj, M. Sade, Shape Memory University of Texas at Dallas, Center for Advanced Pain This work persuasively demonstrates that
Superelasticity 3, 37 (2016). Studies, Richardson, TX, USA. Email: [email protected] there are likely distinct transcriptional pro-
4. J.Xia et al., Science 369, 855 (2020).; [email protected] grams in DRG sensory neurons that are re-
5. K. Otsuka, C. M.Wayman, Shape Memory Materials sponsible for different phases of neuropathic
(Cambridge Univ. Press, rev. ed., 1999).
6. T. Omori et al., Science 333, 68 (2011).
7. Y. Sutou, N. Koeda,T. Omori, R. Kainuma, K. Ishida, Acta
Mater. 57, 5759 (2009).


Supported by ANPCyT (PICT 2017-2198 and PICT 2017-4518),
CONICET (PIP 2017-0634), and U.N.Cuyo (06/C588).


774 14 AUGUST 2020 • VOL 369 ISSUE 6505 SCIENCE

Published by AAAS

pain. This complexity may contribute to why importin a3 and AP1 transcription factors, SUPERCONDUCTIVITY
the disease is so challenging to treat, espe- FOS and JUN. Sequencing of DRGs taken
cially because most researchers have focused from humans with neuropathic pain demon- A coexistence
on the acute phase of injury. The work also strate up-regulation in the expression of FOS that CuO2
parallels recent clinical findings demonstrat- and JUN in a subset of male neuropathic pain planes can see
ing that peripheral nerve block with regional patients (5). This clinical parallel emphasizes
injection of lidocaine or lidocaine derivatives the translational value of these findings. Antiferromagnetism
is almost always effective for alleviating neu- and superconductivity
ropathic pain, even in people who have suf- Marvaldi et al. lay a new foundation for are not at odds in a
fered for long periods of time (6, 7). Bringing thinking about neuropathic pain. Focusing quintuple-layer cuprate
our understanding of mechanisms in line on the therapeutic potential of these
with clinical observations is promising from mechanistic insights has potential for de-
the view of developing better therapeutics. velopment of long sought-after disease-
modifying therapeutics in this clinical
Injury to peripheral nerves turns on a re- space. The work demonstrates that drugs
generation program that is frequently accom- targeting AP1 transcription factors can
panied by emergence of neuropathic pain. be effective in reducing neuropathic pain
One of the earliest signaling events at the in mice. Some of these drugs are already

By Inna Vishik

Importin a3 regulates persistent pain following nerve injury S uperconductivity is a zero-resistance
quantum-coherent state with appli-
Different combinations of activator protein 1 (AP1) transcription factors and importins are likely cations to sensing, powerful elec-
responsible for early versus chronic phases of neuropathic pain. tromagnets, and computing. Some
materials have mysterious reasons
Growth Cytokines Early

for becoming superconducting,

Axon Soma which continues to drive interest in the

topic. Cuprates exhibit the highest super-

mTOR Importin a3 Nuclear conducting transition temperature (T ) of
pore c
a complex
b known materials under ambient pressure,
AP1 Importins exceeding the boiling point of liquid nitro-
Microtubule AAAAA
gen in many compounds. On page 833 of

this issue, Kunisada et al. (1) show how a

seldom-studied quintuple-layer cuprate,

Ba Ca Cu O (F,O) , can help uncover the
2 4 5 10 2

elusive superconductivity mechanism in

Target Target these high-temperature superconductors.
Promoter gene Chronic Promoter gene
Early responses to nerve injury include local Early Superconductivity is not found by itself
translation and activation of mammalian target
of rapamycin (mTOR), which induces local in cuprates. Instead, interrelationships be-
translation of transcription factors, such as
AP1 family members, and nuclear transporters, In chronic neuropathic pain, importin a3 selectively mediates tween multiple competing, coexisting, and
such as importins. These proteins then nuclear translocation of AP1 transcription factors. Once in the
undergo retrograde transport to the nucleus. nucleus, they regulate gene transcription and subsequent changes intertwined electronic phases may be key
in protein synthesis that maintain the chronic pain state.
to formulating a mechanism for cuprate

superconductivity (2, 3). Despite this com-

plexity, most experimental studies on cu-

site of DRG axon injury is the local transla- in existence and could be repurposed for prates have focused on a small handful of
tion of the protein kinase mammalian target pain treatment. Indeed, Marvaldi et al. in-
of rapamycin (mTOR), which then drives re- tentionally considered drug repurposing compounds (4, 5), even though hundreds
programming of translational capacity in the when choosing AP1 inhibitors to study.
axon (8). These events are critical for regen- Therefore, Marvaldi et al. have identified of different cuprate superconductors have
eration, but they also lead to local synthesis some excellent candidates for future study,
of transcription factors, such as cyclic adeno- namely sulmazole and sulfamethizole. j been identified. Key insights can be over-
sine monophosphate response element-bind-
ing protein (CREB) (9), and nuclear import REFERENCES AND NOTES looked by studying compounds that mani-
factors, such as importin b1 (10), which then 1. L. Marvaldi et al., Science 369, 842 (2020).
act as positive, retrograde signals linking axo- 2. T.J. Price et al., Nat. Rev. Neurosci. 19, 383 (2018). fest a particular phenomenon only weakly.
nal injury to transcriptional changes in the 3. L. Djouhri et al., J. Neurosci. 26, 1281 (2006).
neuronal nucleus, paving the way for neuro- 4. J. Serra et al., Pain 153, 42 (2012). In this context, seldom-studied cuprate
pathic pain. The study of Marvaldi et al. sug- 5. R.Y. North et al., Brain 142, 1215 (2019).
gests that these transcriptional changes may 6. A.Vaso et al., Pain 155, 1384 (2014). compounds give a fresh perspective on a
be coordinated in temporal waves that are 7. S. Haroutounian et al., Pain 155, 1272 (2014).
ultimately controlled by a nuclear membrane 8. M.Terenzio et al., Science 359, 1416 (2018). long-standing problem, especially if they
gatekeeper (importin a3). Early signals may 9. O. K. Melemedjian et al., Mol. Pain 15, S45 (2014).
be mediated by CREB or other transcription are compatible with both surface spectros-
factors, whereas late signals are controlled by 10. S. Hanz et al., Neuron 40, 1095 (2003).
copies and bulk transport measurements.
The authors are supported by NIH grant NS065926. Cuprate properties can be tuned by modi-

GRAPHIC: KELLIE HOLOSKI/SCIENCE 10.1126/science.abd4196 fying the number of charge carriers with a

process called doping. Hole-doped cuprates

involve introducing positive charge and

achieve the highest T . The parent com-

pound with no doping is an electrical insu-

Department of Physics, University of California Davis,
Davis, CA 95616, USA. Email: [email protected]

SCIENCE 14 AUGUST 2020 • VOL 369 ISSUE 6505 775

Published by AAAS


lator, owing to strong electron- Superconducting five-layer cuprate energy electronic excitations.

electron repulsion, and the spins The Ba2Ca4Cu5O10(F,O)2 superconductor has two outer CuO2 planes (OP), This surface is also important
on adjacent copper sites point and two inner CuO2 planes (IP1) that sandwich a fifth CuO2 layer (IP0). for circumscribing the origin of
in opposite directions, making Each layer has properties that combine to allow the compound to have both superconductivity.

it an antiferromagnet. The an- antiferromagnetism and superconductivity. The superconducting gap is

tiferromagnetism is diminished an excitation tied to the Fermi
by hole-doping, allowing su-
perconductivity to emerge. The F Charge reservoir surface and reflects the energy
relationship between the anti- layer (CRL),
ferromagnetic electronic phase Ba dopants required to break a Cooper pair,
and the mechanism of super- the bound pair of electrons
Doping OP
that forms the charge carrier
CuO2 plane unit in a superconductor. In

conductivity has driven cuprate Ca O Cu Ba Ca Cu O (F,O) , Kunisada
research. Moreover, other fami- 2 4 5 10 2
lies of unconventional super-
IP1 et al. observed a superconduct-

ing gap on the outer IPs. The

conductors—including heavy magnitude of the supercon-

fermion materials, organic su- IPO Magnetic ducting gap is large enough to
perconductors, and iron-based moment suggest that superconductivity

superconductors—have similar Clean on these IPs is not a conse-

phenomenology in which su- quence of simply being near

perconductivity appears proxi- IP1 to the superconducting outer
mate to the demise of antiferro- planes but instead that the

magnetic order. This has led to IPs themselves are favorable

proposals of a common mecha- OP Cooper pair for superconductivity while si-
nism of superconductivity be- CuO2 plane multaneously hosting antifer-
tween these different super- romagnetism. Moreover, the IP

conductors, invoking dynamic Doping superconducting gap does not

excitations related to antiferro- extend to the antinodal regions

magnetism in joining electrons CRL of the Brillouin zone, where
into Cooper pairs (6). Despite the superconducting gap is at

this, the electronic and super- a maximum in other cuprates,

conducting properties inherent A look inside disputing proposals that super-
conductivity originates there.
to lightly hole-doped cuprates A top-down view of IP1 AF order These results indicate that cu-
shows the antiferromagnetic prate superconductivity can ro-
are still poorly understood. bustly coexist with long-range
(AF) order and creation of
Ba Ca Cu O (F,O) offers a
2 4 5 10 2 a Cooper pair, which is

distinct perspective by per-

mitting access to the doping needed for superconducting antiferromagnetism. Further,

regime where superconductiv- behavior. Unlike other cuprates, Cooper pair this study helps disentangle
ity is in closest proximity to the AF order is retained doping from chemical disor-
long-range antiferromagnet- when the material becomes der to highlight how the latter
ism while minimizing disorder. superconducting. may play a greater role in more

All cuprates share a structural commonly studied cuprates.

unit of copper oxide (CuO ) planes, which that there are two types of IPs: one in the Understanding how superconductivity

participate most heavily in superconduc- middle of the stack and two equivalently develops from an antiferromagnetic insu-

tivity. Doped electrons or holes are trans- in the second and fourth positions. In lator may be key to uncovering the elusive

ferred to the CuO planes, but the elemen- Ba Ca Cu O (F,O) , each of the structurally mechanism of superconductivity in cu-
2 2 4 5 10 2 prate high-temperature superconductors.
The high-quality surface-sensitive ARPES
tal substitution actually happens in the inequivalent CuO planes tells a distinct
portion of the crystal structure between
story (see the figure). The outer planes

blocks of CuO planes called the charge- yield information consistent with com- and bulk-sensitive quantum oscillation ob-
2 monly studied single- and double-layer
cuprates, whereas the two types of IPs re- servations on Ba Ca Cu O (F,O) move the
reservoir layers (CRLs). The composition 2 4 5 10 2

of the CRLs distinguishes different cu- field closer to this goal while highlighting

prate compounds. Cuprates can have one veal two CuO planes that are lightly hole- the importance of continued investigation
2 of cuprates with three or more adjacent
or more CuO planes in a structural block CuO layers. j
2 doped and still superconducting and one
IP which is very lightly hole-doped and not 2
close to one another, separated by inter- superconducting.
vening CRLs. Kunisada et al. first confirmed long-
range antiferromagnetism in the IPs using 1. S. Kunisada et al., Science 369, 833 (2020).
The highest T is typically found in com- two techniques: quantum oscillations and 2. M. Hashimoto, I. M.Vishik, R.-H. He,T. P. Devereaux,Z.-X.
c angle-resolved photoemission spectros-
copy (ARPES). This multitechnique ap- Shen, Nat. Phys. 10, 483 (2014).
pounds with three or more adjacent CuO proach indicated a common ground state 3. E. Fradkin, S.A. Kivelson,J. M.Tranquada, Rev. Mod.
2 in high magnetic field and zero magnetic
field. Evidence for antiferromagnetism was Phys. 87, 457 (2015).
planes (7), making such materials highly observed using the size and location of the 4. S. Hüfner, M.A. Hossain,A. Damascelli, G.A. Sawatzky,
Fermi surface, which is the locus of zero-
promising for understanding factors that Rep. Prog. Phys. 71, 062501 (2008). GRAPHIC: C. BICKEL/SCIENCE
5. C. C. Homes et al., Nature 430, 539 (2004).
enhance T . In such compounds, one or 6. D.J. Scalapino, Rev. Mod. Phys. 84, 1383 (2012).
c 7. A. Iyo et al., J. Phys. Soc.Jpn. 76, 094711 (2007).

more inner CuO planes (IPs) are not di- 10.1126/science.aba9482

rectly adjacent to the CRL. Because of this

distance, IPs tend to have smaller dop-

ing and less disorder. Ba Ca Cu O (F,O)
2 4 5 10 2

is a quintuple-layer cuprate, meaning

776 14 AUGUST 2020 • VOL 369 ISSUE 6505 SCIENCE

Published by AAAS

RETROSPECTIVE the state. His love of nature was profound,
and he was always willing to share his
Michael Soulé (1936–2020) knowledge of natural history. He was eager
to participate in river trips, including an 18-
Founder of conservation biology day raft trip I (D.W.I.) led through the Grand
Canyon, where Michael rowed his own raft
PHOTO: UC SANTA CRUZ By David W. Inouye1,2 and Paul R. Ehrlich3 In 1978, Michael helped convene the and shared his expertise about local amphib-
First International Conference on Research ians and reptiles.
M ichael Soulé, widely credited with in Conservation Biology, and in 1980, he
starting the field of conservation coauthored with Bruce Wilcox the field’s Michael was an inspiring speaker.
biology, died on 17 June at age 84. first textbook. He was a cofounder and At the 2000 meeting of the Society for
Michael’s research laid the intellec- president of the Wildlands Network, co- Conservation Biology, he ended his talk
tual groundwork for a new avenue of chair of the science council for Australia’s with a plea for contributions to fund the
study, and he cofounded the Society WildCountry Project, and a council member society’s programs. In response, many hun-
for Conservation Biology in 1985 to ensure of RewildingEarth. In 1998, he and conser- dreds of dollar bills fluttered down from the
that the nascent field had the resources and vation biologist Reed Noss wrote the first balcony into the audience below, as Michael
organization to address the critical environ- paper about restoring habitat at a continen- watched with surprise and delight.
tal scale, a strategy they called “rewilding,”
mental issues we face today. Michael’s vision which is now an international movement. After retiring in 1998, Michael contrib-
uted his expertise to local nongovernmental
of a better world, in which nature holds a Another example of Michael’s character- environmental organizations and promoted
central place, has inspired scientists and na- istic foresight was his biological mosquito control. He consulted
ture enthusiasts across the globe. decision to begin sam- on wildlands conservation for governments
pling insect populations in Romania, Australia, and the Republic of
Born on 28 May 1936, Michael grew up at the Rocky Mountain
in San Diego, California. His free-ranging Biological Laboratory Georgia, as well as the
childhood, spent exploring tide pools and in 1984. This ongoing United States. In the
collecting abalones and lobsters, sparked his project recently served rural town of Paonia,
lifelong love of natural history and helped as the source for reports Colorado, located in an
shape his interest in ecosystems. Michael ob- that climate change agricultural valley flush
tained his undergraduate degree in biology has caused substantial with small farms, or-
at San Diego State College and his Ph.D. in insect decline in that chards, and vineyards,
biology in 1964 from Stanford University in undisturbed habitat. Michael and June, his
Stanford, California. Michael’s childhood fa- wife, enjoyed kayaking
miliarity with the chap- and rafting. Despite his
After joining the biology faculty at the arral canyons of San Buddhist bent, Michael
University of California (UC) San Diego in Diego contributed to was an occasional car-
1967, Michael became troubled by the rapid his insights about the nivore and hunter of big
loss of natural habitats in Southern California. effects of coyotes as game, especially species
He resigned from the university in 1979 to be- predators and the con- numerous enough to
come director of the Kuroda Institute for the sequences of their disappearance. In their cause overgrazing, such
Study of Buddhism at the Zen Center of Los groundbreaking 1999 Nature paper, he and as introduced caribou
Angeles. In 1984, he returned to academia, his graduate student Kevin Crooks intro- in Alaska.
first teaching at the University of Michigan duced the idea that coyotes flourish in the
and then, in 1989, moving to UC Santa Cruz, absence of larger predators and in turn re- A fellow of the
where he served as chair of the environmen- duce small-predator populations, allowing American Academy of Arts and Sciences,
tal studies department and helped start the prey populations to increase. Michael was also awarded a Guggenheim
environmental studies Ph.D. program, one of Fellowship, the Archie Carr Medal, and the
the first in the United States. I (P.R.E.) met Michael when he became one Edward O. Wilson Biodiversity Technology
of my first grad students in 1959. He showed Pioneer Award. Audubon magazine named
Michael’s research spanned conservation, his independence and humor from the very him as one of the 100 Champions of
evolutionary biology, population genetics, start. At the end of a seminar, eminent biolo- Conservation of the 20th Century. He re-
island biogeography, environmental stud- gist Ernst Mayr—our invited guest—said, “I ceived the National Wildlife Federation’s
ies, biodiversity policy, and ethics. His work always instruct my grad students to tell me National Conservation Achievement Award
helped distinguish conservation biology as if they think I’m mistaken.” Michael quipped, for Science in 1998 and the Zoological Society
a field with a mission (conserving biodiver- “Does that go for grad students at other uni- of San Diego’s Conservation Medal in 2007.
sity), an urgency (species are going extinct), versities, too?” Ernst laughed, but our de-
and a need for a broad focus (including eco- partment chair, sitting next to me, thought it His gentle demeanor, sense of humor, sci-
nomics, policy, and ecology). Although his a terrible insult and whispered that I should entific expertise, and visionary leadership,
fieldwork provided new insights, Michael’s get rid of Michael. I disagreed, and Michael tempered by a Buddhist perspective, made
greatest contribution was to introduce, and and I became lifelong friends and colleagues. Michael approachable, collegial, and memo-
argue for, big ideas in developing the field. rable. Leading the development of a field
The recent appearance of a wolf pack in in which science must be combined with
1Department of Biology,University of Maryland, College Colorado cheered Michael, who hoped he policy and economics to produce successful
Park, MD 20742, USA. 2Rocky Mountain Biological might also see the return of grizzly bears to outcomes required foresight and commit-
Laboratory, Crested Butte, CO 81224, USA. 3Department ment, which will be carried on by the gen-
of Biology, Stanford University, Stanford, CA 94305, USA. erations of conservation biologists inspired
Email: [email protected] by Michael’s example. j


SCIENCE 14 AUGUST 2020 • VOL 369 ISSUE 6505 777

Published by AAAS

BOOKS et al. An artistic rendering shows the predicted merger
of the Milky Way and Andromeda galaxies.

of an expanding Universe, Einstein decided

to eliminate the term. However, Einstein

may have been right to include such a con-

stant after all. Although dark energy could

well be volatile, most astronomical obser-

vations indicate that it is relatively steady,

conveying a rate of accelerated expansion

that is comparable to what is predicted

when a cosmological constant is retained in

the relativity equations.

If the Universe were to succumb to dark

energy–induced expansion, an increasingly

rapid stretching of space would eventually

isolate us from the bulk of the Universe.

Over the eons, all stars would burn out, re-

sulting in a lack of usable energy, a scenario

called “heat death.” But what if dark energy

turns out to be even more potent than a

cosmological constant, overcoming every

possible form of attraction and rendering

everything unstable? Mack devotes perhaps

ASTROPHYSICS the most frightening chapter of all to this

How it all ends scenario, known as “the Big Rip,” in which
everything—including space itself—is torn
into shreds.

A light-hearted exploration of the death of the Universe In the chapter that follows, she explores
yet another kind of cosmic catastrophe, this

serves as an effective antidote for everyday worries one triggered by changes, on the quantum
level, of the vacuum state of the Universe.

Like a frozen river that permits skaters to

By Paul Halpern many such collisions will occur between frolic on its surface, the vacuum state sup-

numerous other galaxies, until all of space ports the particle dynamics that make life

I n these challenging times for Earth, has been condensed back down to a single possible. But, just as rising temperatures
the notion of exploring and inhabiting highly compressed, potentially infinitely might cause chunks of ice to break off and
other worlds is enticing. After all, if dense glob. Scary? Very much so. She re- melt, unexpected cosmic conditions might
someday humanity’s existence on this assures us, however, that mounting astro- suddenly disrupt the vacuum state, alter the
planet appears threatened, we might nomical evidence indicates that
masses of elementary particles,

continue civilization elsewhere—assum- cosmic collapse is very unlikely. and sink the particle world.

ing we have the technology to do so. Yet, as Before we can breathe a sigh The final and presumably

astrophysicist and popular science commu- of relief, Mack reveals a second most optimistic scenario that

nicator Katie Mack shows in her excellent, scenario that might be even Mack describes is a “cosmic

far-reaching debut book, The End of Every- worse for the Universe than bounce,” which at least permits IMAGE: NASA; ESA; Z. LEVAY AND R. VAN DER MAREL, STSCI; T. HALLAS; AND A. MELLINGER

thing (Astrophysically Speaking), at some the first: the space-stretching the prospect of new worlds after

point the entire Universe’s luck will run out. effect of dark energy. An abun- an interval of universal destruc-

In clear, succinct prose, Mack details five dance of observational data in- The End of Everything tion. The basic idea is that the
different ways the cosmos might end. For dicates that an unknown agent (Astrophysically Speaking) cosmos would experience end-
the first possibility, “the Big Crunch,” she is accelerating the expansion less cycles of devastation and
posits that the Universe’s expansion will of the Universe, driving distant Katie Mack rebirth. Having completed her
reverse itself into a lethal crush that mani- galaxies farther away from our Scribner, 2020. 240 pp. Ph.D. thesis under Paul Stein-

fests as collisions between neighboring gal- own at a faster and faster rate. What is not hardt, the co-originator of one such model

axies. In this scenario, she argues, the Milky known yet is how that dark energy behaves (called the ekpyrotic universe), she is the

Way will crash together with Andromeda, over time. Some models endow it with ideal writer to convey this theory’s premise.

and old stars will suddenly be jolted from greater potency than others. And describe it well she does, drawing upon

their orbits, while, elsewhere, hydrogen gas Albert Einstein once added a fudge factor, a clever analogy that involves hands clap-

coalesces and ignites to form new stars. The known as the cosmological constant, to the ping together and drawing apart.

Sun, by then a swollen red giant, will have equations of general relativity to artificially All in all, The End of Everything serves

subsumed our mother planet. Meanwhile, induce stable solutions. At that time, he as an outstanding, levelheaded guide to a

did not believe in cosmic growth or shrink- horrific medley of ways the Universe might

The reviewer is at the Department of Mathematics, Physics, age. Once Edwin Hubble revealed evidence expire. The book is the perfect antidote to
and Statistics, University of the Sciences, Philadelphia, of the recession of galaxies, which was in the malaise of mundane worries. j
PA 19104, USA. Email: [email protected] agreement with Georges Lemaître’s theory

778 14 AUGUST 2020 • VOL 369 ISSUE 6505 SCIENCE

Published by AAAS


SCIENCE LIVES A Dominant Character:
The Radical Science
Science meets politics and Restless Politics
of J. B. S. Haldane
A passion for promoting the public good guided Samanth Subramanian
geneticist J. B. S. Haldane’s scholarship Norton, 2020. 400 pp.

By P. William Hughes Artificial Selection. During this time, he also Subramanian explains that Haldane
viewed science as the most effective tool
formulated two eponymous hypotheses: Hal- for promoting the public good. He designed
safer bomb shelters for Blitz-affected Lon-
I n 1906, 13-year-old Jack Haldane stood on dane’s rule, which predicted that the hetero- don and better mineshaft ventilation, and,
the floor of Loch Striven, 40 meters under gametic sex (i.e., the XY male or ZW female) like many others of this era, he advocated
the sea. His father had sent him down to of a species hybrid is more likely to be sterile methods of eugenic family planning. Hal-
test whether decompression sickness— than the homogametic sex; and Haldane’s dane’s interest in genetics was motivated
caused by nitrogen bubble formation in dilemma, which asserted that the rate of by a similar concern for human welfare.
He wrote, for example, that “a satisfactory
divers’ blood—could be avoided by con- adaptive evolution is limited because advan- theory of natural selection must be quan-
titative,” but he also felt that it should be
trolling the rate of ascent. In his leaky suit, tageous alleles rarely cosegregate efficiently.
useful: Accurate quantification of artifi-
Jack knew that each dive carried a risk of Haldane wrote prolifically. He published cial selection could assist plant breeders
throughout the world.
drowning. Still, the data they collected was one of the first textbooks on enzyme func-
Haldane’s tempestuous relationship
invaluable. A risk-chasing and industrious tion; discussed chemical warfare, religious with authority led him to leave Eng-
land for India in 1956. There, Haldane
scientist, his father was developing pro- spent the twilight of his career, first at
the Indian Statistical Institute (ISI) in
tocols that would benefit many people. Kolkata and later at a special research
unit in Bhubaneswar. He explained
It would be absurd—even immoral, Jack that this move was his way of protest-
ing the United Kingdom’s repressive
believed—to refuse to be his guinea pig. actions during the Suez crisis, and he
argued that Jawaharlal Nehru’s newly
Despite holding no formal science de- established Indian state was more con-
ducive to scientific freedom. Nearing
gree, the younger Haldane would himself retirement, Haldane confined himself
to simple but insightful breeding and
go on to have an extraordinary scientific biometry experiments and continued to
write about science in the popular press.
career, becoming one of the founders of
Subramanian admonishes Haldane’s
modern evolutionary synthesis and a fa- belated rejection of Lysenkoism, sug-
gesting that he demurred because he
mous writer of popular science books. In was reluctant to criticize fellow commu-
nists. This criticism lands awkwardly,
a new biography, A Dominant Character, mostly because Haldane did disown
Lysenko—although not as quickly as his
Samanth Subramanian highlights Hal- anticommunist peers—and eventually
left the CPGB, disillusioned by its rejection
dane’s many accomplishments and con- of “bourgeois genetics.” However, Haldane
clearly admired Stalin and tried to reconcile
siders how his strong moral and political Darwinian evolution with Soviet dialectical
materialism (“diamat”) pseudoscience. Sub-
beliefs influenced his scientific work. ramanian suggests that these mistakes were
the predictable result of the political views
After recounting his early experi- that motivated Haldane’s best work.
Ultimately, Subramanian’s depiction
ments with his father, the book follows of Haldane is balanced and modern and
should prove engaging to readers interested
young John Burdon Sanderson Haldane in the birth of genetics and in the intersec-
tion of science and political belief. j
(nicknamed “Jack” or “JBS”) from his
aristocratic origins in North Oxford to

Eton College and then Oxford University,

where he graduated in 1912 with first-

class honors in classics and mathematics.

His first great scientific success, we learn,

was a 1915 paper on genetic linkage in

mice, coauthored with his sister, Naomi. Haldane, shown holding a model air raid shelter, never lost

Although Haldane had always been inter- the sense of public duty he learned as a young aristocrat.

ested in genetics, the positive reception of

this paper, which Haldane completed while faith, and air raid precautions in newspapers;

serving in the British Army during World argued with racist propagandists in eugen-

War I, intensified his focus. ics journals; and even authored a futuristic

PHOTO: ARTHUR TANNER/FOX PHOTOS/GETTY IMAGES Between World Wars I and II, Haldane manifesto (“Daedalus; or, Science and the Fu-

constructed mathematical formalizations of ture”) that argued that advancements in biol-

the laws of Mendelian inheritance and their ogy would permit the abolition of disease and

impact on evolution by natural selection, cul- the self-direction of human evolution.

minating in his best-known work, a series Haldane never lost the sense of public

of 10 papers written between 1924 and 1934 duty that he had learned as a young aristo-

called A Mathematical Theory of Natural and crat, and in 1942, he joined the Communist

Party of Great Britain (CPGB) and the edito-

The reviewer is at the Department of Ecology, Environment, rial board of its newspaper, the Daily Worker.
and Plant Sciences, Stockholm University, Stockholm, This came at a cost: MI5 kept a file on him for
Sweden, and the Science for Life Laboratory, Stockholm, more than 30 years, and he was barred from
Sweden. Email: [email protected] speaking at certain American universities.

SCIENCE 14 AUGUST 2020 • VOL 369 ISSUE 6505 779

Published by AAAS



Edited by Jennifer Sills when preliminary evidence suggests they with the public. In the meantime, scientists PHOTO: IRA L. BLACK/CORBIS/GETTY IMAGES
were not a substantial factor (5). To combat who have the capacity, seniority, and job
Retraction this new misinformation, scientists must security should help value and amplify
communicate clearly and dispute inaccu- the messages and motivations of those
We have obtained new evidence, 6 years rate, politically motivated narratives. who are willing to participate in public
after the publication of our Report engagement, often at the expense of career
“Ammonia synthesis by N2 and steam elec- Black, Native, and Latinx Americans advancement. It is essential for scientists
trolysis in molten hydroxide suspensions have shouldered the greatest burden of the to work across disciplines and integrate
of nanoscale Fe2O3” (1), that there is a trace unscientific COVID-19 mismanagement multiple communication strategies to make
NOx– impurity in the nanoscale Fe2O3 that in the United States (6). Protests against scientific evidence understandable, engag-
was unknown at the time. We no longer police brutality have been dismissed as ing, and approachable.
have the original nanoscale Fe2O3, and nonurgent or unnecessary, despite evidence
manufacturers’ content levels of impurities that systemic racial injustice disproportion- Nita Bharti
in chemicals may vary over time. However, ately kills Black Americans (7). Scientific Biology Department, Center for Infectious
recently purchased nanoscale Fe2O3 per evidence, which should be at the forefront Disease Dynamics, The Pennsylvania State
gram contains 0.0005 g N as NOx–, and of public discussions and policy on health University, University Park, PA 16802, USA.
an 15N2 isotopic tracer analysis conducted and civil rights, has been drowned out by Email: [email protected]
by Wenzhen Li, Yifu Chen, and Hengzhou political arguments.
Liu at Iowa State University; Shuang Gu at REFERENCES AND NOTES
Wichita State University; and author S.L. Scientists cautiously explain uncertainties
suggests that this trace impurity, rather while politicians and politically motivated 1. B.Deese,R.A.Klain,“Another deadly consequence of
than N2, is the major nitrogen reactant media outlets emphatically cast blame and climate change:The spread of dangerous diseases,”
in the observed ammonia synthesis. We misappropriate scientific evidence. Scientists TheWashington Post (2017).
are retracting the original Report, and we cannot allow propagandists to spread
encourage exploration of an N2 to NOx– lies that dismantle a reasoned response 2. W.C.Tucker,Ecol.Law Quart.39,831 (2012).
intermediate to ammonia pathway, rather to COVID-19 or urgently needed progress 3. O.Benecke,S.E.DeYoung,Glob.Pediatr.Health 6,
than direct elemental nitrogen pathway, to toward health equity and social justice for
ammonia synthesis. All observed stimulation Black Americans. Informed scientists must 2333794X19862949 (2019).
of ammonia generation with these (likely take a strong public stance on complex 4. E.Lipton et al.,“He could have seen what was coming:
NOx–-containing) nanoscale Fe2O3 materials, issues, emphasizing evidence to clearly com-
as well as all thermodynamic calculation municate and contextualize scientific results BehindTrump’s failure on the virus,”The NewYorkTimes
results, remain accurate as documented in to the public, not just to other scientists. (2020).
the original Report. Institutions must recognize that the current 5. D.M.Dave,A.I.Friedson,K.Matsuzawa,J.J.Sabia,S.
system of promotion and tenure devalues Safford,“Black Lives Matter protests,social distancing,
Stuart Licht1*, Baochen Cui1, Baohui Wang1, Fang- such communication, at a huge societal cost. and COVID-19,”National Bureau of Economic Research
Fang Li1, Jason Lau2, Shuzhi Liu1 Working Paper No.27408 (2020);
1Department of Chemistry, George Washington Irresponsible, unscientific voices have papers/w27408.
University, Washington, DC 20502, USA. killed too many because of their reach 6. “Health equity considerations and racial and ethnic
2Department of Chemistry, Contra Costa College, and efficacy. Academic incentives must be minority groups”(Centers for Disease Control and
San Pablo, CA 94806, USA. updated to meaningfully reward outreach Prevention, 2020).
*Corresponding author. Email: [email protected] efforts, and scientific training should 7. L.Peeples,Nature 573,24 (2019).
prepare scientists to discuss their findings
REFERENCES AND NOTES 10.1126/science.abd3662
1. S. Licht et al., Science 345, 637 (2014).
Dismantling systemic
racism in science
Controlling the
In his Editorial “Time to look in the mir-
coronavirus narrative ror” (12 June, p. 1161), H. H. Thorp calls
on scientists to recognize systemic racism
The corruption of scientific results has
serious consequences for human health.
Climate change deniers (1, 2) and people
who amplify anti-vaccine messages (3) have
created dangerous, enduring myths, giving
rise to new problems for which scientists
must now find solutions. Now, politicians
are undermining the response to coronavi-
rus disease 2019 (COVID-19) by disregarding
scientific facts and the guidance of epidemi-
ologists (4). Simultaneously, nonscientists
have asserted that Black Lives Matter
protests caused increases in COVID-19 cases,

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Published by AAAS

Preliminary evidence indicates (9). A majority of these leaders claimed to 4. Petersen et al., MMWR Morb. Mortal.Wkly. Rep. 68,
that protests demanding justice be committed to diversity and inclusion, but 423 (2019).
diversity and inclusion training or programs
for Black Americans, such existed in only half of the organizations 5. S.Yaya, BMJ Glob. Health 5, e002913 (2020).
as this one, have not caused a surveyed, and 41% of organizations did not 6. Higher Education Statistics Agency,“Who’s working in
monitor diversity (such as employee demo-
spike in COVID-19 infections. graphics) or discrepancies in performance HE?: Personal characteristics”(2019);
rankings, pay, and promotion (9). data-and-analysis/staff/working-in-he/characteristics.
within the science community. As part To view the number of Black professors compared with
of this self-reflection, scientists should Unfortunately, scientists from under- the total number of professors, in the“Personal char-
consider the many ways that inequality represented groups are often the ones who acteristics by occupational classification”table, select
manifests in science, including science’s take on the responsibility (often coupled “Show: Ethnicity”and“Contract levels: Professor.”
historical contributions to discrimina- with additional labor and minimal recogni- 7. N. Rollock,“Staying Power”(University and College
tion, the lack of representation in science, tion) of trying to change a racist system Union, 2019);
and the extra burden placed on minority (10). To lighten their burden, white col- Power/pdf/UCU_Rollock_February_2019.pdf.
scientists to fix issues relating to diversity leagues should also take responsibility for 8. S.Wood et al., Proc. R. Soc. Ser. B Biol. Sci. 287,
and inclusion. Understanding the scope of dismantling systemic racism in the science 20200877 (2020).
systemic inequality in science will enable community. Although there is no single 9. Biotechnology Innovation Organization,“Measuring
genuine and sustainable efforts to make “one size fits all” approach to addressing diversity in the biotech industry: Building an inclusive
scientific institutions fair for all. inequality, there are common themes and workforce”(Center for Talent Innovation and BIO,
actions that can be implemented in scien- 2020);
Racial categories historically developed tific institutions. Measuring_Diversity_in_the_Biotech_Industry_
and endorsed by scientists led to a hierar- Building_an_Inclusive_Workforce.pdf.10.
chy of groups seen as superior or inferior. Scientists involved in hiring should 10. M. F.Jimenez et al., Nat. Ecol. Evol. 3, 1030 (2019).
Although unsupported by biological implement advertising strategies, espe-
evidence, these categories have had devas- cially at leadership levels, that attract 10.1126/science.abd7531
tating effects on non-white communities diverse applicant pools, and they should
throughout history. The myth that racial facilitate fair decisions by forming diverse Untapped resources
groups were fundamentally different was recruitment panels. To retain diverse
used to justify colonialism, slavery, geno- individuals, leaders should promote an for medical research
cide, and eugenics (1), and it still governs inclusive environment. To do so, they must
policies today. The intersectionality of rac- develop training material on understand- A therapeutic solution to the coronavirus
ism and modern society has left a legacy of ing and tackling bias and create safe disease 2019 (COVID-19) pandemic is
racial disparities in socioeconomic status spaces for professionals to speak freely and urgently needed, but new drug discovery
(2), education (3), and health (4, 5). honestly. All departments should develop and development are lengthy processes.
zero-tolerance, anti-racism policies and put Pharmaceuticals derived from plants and
The lack of diversity in scientific institu- procedures in place that effectively handle fungi remain important in our armory
tions reveals ongoing systemic racism in the complaints about racism and race-related against numerous diseases (1, 2), yet much
field. As of 2019, less than 1% of UK profes- aggression. Mentoring schemes should be of plant and fungal biodiversity remains
sors were Black (6). Black female professors embedded into departments to address the unexplored for drug discovery (3). Of
in the United Kingdom experience bully- neglect that Black, Indigenous, and people about 350,000 known plant species, 7%
ing, racial discrimination, and institutional of color often experience when navigating have medicinal uses (1, 4), and the wider
neglect (7). Systemic racism has also contrib- their career. Underrepresented individuals potential of the world’s flora to yield new
uted to the lack of diverse representation. (many of whom are already used as unpaid medicines has been discussed by conserva-
Even textbooks currently lack representation consultants) should be given the power to tion biologists for decades (5). We urgently
of Black female scientists (8). According to make important decisions. need a comprehensive scientific study of
a recent report, leadership positions such biodiversity to inspire, accelerate, and
as CEO or executive in the biotech industry All scientists should recognize the innovate medicinal discovery.
are largely occupied by white professionals achievements of diverse individuals.
Recognition includes citing their work, Acquiring usable plant and fungal
referring them for opportunities, nominat- material is resource-consuming, but a
ing them for awards, and teaching their partial solution lies in specimens already
work in classes. Appropriately recognizing housed in herbaria, botanic gardens (6),
the work of underrepresented individu- and fungal biological resource centers.
als will enable them (rightly) to be as Herbaria host about 380 million specimens
competitive as their white counterparts from all described plant species (7), and
when looking to progress professionally. By botanic gardens maintain about one-third
taking these steps, scientists of all back- of all known land plant species (8). Fungal
grounds can help create a more inclusive, collections currently host about 860,000
diverse, and fair community. strains worldwide (9). These collections are
invaluable resources representing unparal-
Esther A. Odekunle leled chemical diversity.
GlaxoSmithKline, Stevenage, Hertfordshire SG1
2NY, UK. Email: [email protected] Evolutionary relationships inferred
from DNA could be used to guide selec-
REFERENCES AND NOTES tion of species with medicinal potential.
Just a few milligrams from specimens
1. R.J. Cottrol, J. Social Hist. 49, 740 (2015). enable comprehensive chemical profiling,
2. D. R.Williams et al., Health Psychol. 35, 407 (2016). uncovering new chemical entities that
3. K.Weir, Monitor Psychol. 47, 42 (2016). share chemical or physical characteristics
with drug molecules, potentially with novel
modes of action (1). Artificial intelligence
and emerging technologies could reveal

SCIENCE 14 AUGUST 2020 • VOL 369 ISSUE 6505 781

Published by AAAS

compounds with mechanistic effects rel-
Gets evant to diseases threatening humanity (1,
Social. 10). Furthermore, collections are increas-
ingly used to generate genomic data, which
AAAS.ORG/COMMUNITY could be used to identify members of gene
families known to be involved in the syn-
AAAS’ Member Community is a one-stop destination thesis of useful compounds (11).
for scientists and STEM enthusiasts alike. It’s “Where
Investing in a new era of large-scale
Science Gets Social”: a community where facts exploration of therapeutic candidates
matter, ideas are big and there’s always a reason to from nature could help humanity prepare
for future health challenges. Scientists,
come hang out, share, discuss and explore. governments, and other stakeholders must
establish functional and equitable agree-
Published by AAAS ments to ensure that this work complies
with the Nagoya Protocol and associated
access and benefit sharing legislation and
reflects the value and origins of specimens
collected during the colonial era (12). It is
also critical that benefits are shared with
the nations and Indigenous peoples from
where these resources derive.

Oscar A. Pérez-Escobar1, James E. Richardson2,3,
Melanie-Jayne R. Howes1,4*, Eve Lucas1, Noelia
Álvarez de Róman5, Jérôme Collemare6, Ian A.
Graham7, Joachim Gratzfeld5, Paul J. Kersey1, Ilia
J. Leitch1, Alan Paton1, Peter M. Hollingsworth3,
Alexandre Antonelli1,8
1Royal Botanic Gardens, Kew, TW9 3AE,
UK. 2Department of Biology, Faculty of
Natural Sciences, Universidad del Rosario,
Bogotá, Colombia. 3Royal Botanic Garden
Edinburgh, Edinburgh, EH3 5LR, UK. 4Institute
of Pharmaceutical Science, Faculty of Life
Sciences & Medicine, King’s College London,
SE1 9NH, UK. 5Botanic Gardens Conservation
International, Richmond, TW9 3BW, UK.
6Westerdijk Fungal Biodiversity Institute, Utrecht,
Netherlands. 7Department of Biology, Centre
for Novel Agricultural Products, University of
York, York, YO10 5DD, UK. 8Gothenburg Global
Biodiversity Centre and University of Gothenburg,
Gothenburg, Sweden.
*Corresponding author: Email: [email protected]


1. M.-J. R. Howes et al., Plants, People, Planet. 10.1002/
ppp3.10138 (2020).

2. D.J. Newman, G. M. Cragg, J. Natural Prod. 83, 770

3. J.W. H. Li,J. C.Vederas, Science 325, 161 (2009).
4. K.J.Willis, Ed.,“State of the World’s Plants 2017”

(Royal Botanic Gardens, Kew, UK, 2017); https://
5. W. F. Laurance et al., Science 278, 1117 (1997).
6. E. K. Meineke et al., Ecol. Monographs 88, 505 (2018).
7. A.James et al., Appl. Plant. Sci. 6, e1024 (2018).
8. R. Mounce et al., Nat. Plants 3, 795 (2017).
9. World Data Centre for Microorganisms (WDCM) Culture
Collections Information Worldwide (
10. J. M. Stokes et al., Cell 180, 688 (2020).
11. R. D. Kersten,J.-K.Wenig, Proc. Natl.Acad. Sci. U.S.A.
115, E10961 (2018).
12. S. Das, M. Lowe, J. Natural Sci. Collect. 6, 4 (2018).


O.A.P.-E. receives financial support from the Swiss
Orchid Foundation and the Sainsbury Orchid
Trust. I.A.G. is Director of the United Kingdom
Research and Innovation–Biotechnology and
Biological Sciences Research Council (UKRI-
BBRSC) High Value Biorenewables Network.
A.A. receives financial support from the Swedish
Research Council, the Swedish Foundation for
Strategic Research, the Knut and Alice Wallenberg
Foundation, and the Royal Botanic Gardens, Kew.

10.1126/science.abc8085 SCIENCE


Edited by Michael Funk

TROPICAL FOREST Efforts to restore tropical
forests in Sabah, Malaysia,
The carbon gain in restored logged forest
can accelerate carbon
T here is currently great interest in the capacity of global forest to storage but require
store carbon and hence contribute to the mitigation of climate
change in the coming decades. In a study of Southeast Asian tropi- high prices on carbon.
cal forest, Philipson et al. show that active restoration of logged
forests generates higher rates of carbon accumulation than naturally
regenerating forest. To estimate the economic feasibility of restoration
treatments, they modeled the carbon price required to offset the cost
of restoration, finding that the highest prices seen in recent years would
be needed to approach those that could offset restoration costs. These
results are important for tropical forest policy, establishing the impor-
tance of restoration for the carbon recovery potential of tropical forests.
—AMS Science, this issue p. 838

ORGANIC CHEMISTRY synthetic schemes for divergent of BAF. This work suggests that on malignant B cells and
synthesis. —MAF the regulation of DNA detection is the target of therapeutic
Trio of enzymes power by the innate immune system antibodies used in cancer
divergent synthesis Science, this issue p. 799 relies on more complex mecha- immunotherapy. Kumar et al.
nisms than simple physical now present structures that
Diterpene natural products are IMMUNOLOGY separation alone. —STS explain why so-called type I
built from a 20-carbon build- antibodies efficiently activate
ing block, with a huge range of A loose BAF puts its foot Science, this issue p. 823 the complement pathway to
possible structures and modi- on the cGAS kill cells, whereas type II
fications. Chemical synthesis STRUCTURAL BIOLOGY antibodies do not. Type I
of specific molecules, some of A signaling pathway in ver- antibodies each bind to two
which have valuable biological tebrates called cGAS-STING Strength in numbers CD20 dimers and form clus-
activities, is tricky because of detects the presence of intra- ters that facilitate binding to a
the need for selective oxida- cellular DNA as a surrogate Human cluster of differentia-
tions and rearrangements for both cellular damage and tion 20 (CD20) is expressed
when starting from widely viral infection. At the same
CREDITS (FROM TOP): © FACE THE FUTURE; KUMAR ET AL. available scaffolds. Zhang et time, sensing of self-DNA must Hexameric assembly models illustrate potential differences in compactness
al. characterized selectivities be suppressed to prevent the between therapeutic antibodies (rituximab, left; ofatumumab, right).
for three oxidative enzymes development of autoimmune
that each attack different responses. Guey et al. identify
positions on a common scaf- barrier-to-autointegration factor
fold. They then seamlessly 1 (BAF) as a protein that intrin-
combined chemical transfor- sically competes with the cGAS
mations with the enzymatic component of this pathway for
oxidations to produce nine dis- binding to genomic self-DNA.
tinct compounds across three When there is a breakdown in
families of diterpenes. These nuclear compartmentaliza-
results highlight the potential tion, cytosolic cGAS enzymatic
of hybrid organic-biocatalytic activity is prevented because

SCIENCE 14 AUGUST 2020 • VOL 369 ISSUE 6505 783

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component of the complement ECOLOGY IN OTHER JOURNALS
pathway. The second-generation
type I antibody ofatumumab Ozone pollution Edited by Caroline Ash
has molecular features that threatens biodiversity and Jesse Smith
make it more efficient at
clustering than first-generation Terrestrial ecosystem com- Mare’s milk has a high lactose
rituximab. By contrast, the type position and biodiversity are content and rapidly ferments
II antibody obinutuzumab inter- tightly linked to environmental into products that are digestible
acts with just one CD20 dimer factors, and there are concerns by lactose intolerant Central
and cannot form higher-order that they may be at risk from Asian herdspeople.
assemblies. Understanding anthropogenic ozone pollution.
these mechanisms will inform In a Review, Agathokleous et SIGNAL TRANSDUCTION cannot bind calcium, and thus an PHOTO: PAUL'S LADY/SHUTTERSTOCK
the design of next-generation al. synthesize widespread evi- enhanced immune response can
immunotherapies. —VV dence that ozone pollution can Plants take the be triggered. —LBR
affect key ecological processes splice to the fight
Science, this issue p. 793 and functions of terrestrial Nat. Plants 6, 1008 (2020).
ecosystems and alter the Plants transiently activate
NEURODEVELOPMENT diversity of plants, insects, and immune responses using IMMUNOLOGY
soil microorganisms. They also layers of diverse regulatory
Mitochondrial dynamics identify areas of high endemic mechanisms. This strategy The thymus X factor
and cell fate richness throughout the world minimizes any potential damage
that will also be at high ozone from an overly active protec- The thymus is an organ that
Radial ganglia cells, the stem risk by the end of the century. tive response. Dressano et al. facilitates the maturation of
cells of early brain develop- These advances in our under- discovered in the model plant thymocytes into T cells and
ment, can generate more standing of ozone pollution and Arabidopsis that when an is notable for its variable size
of themselves or generate its effects present new chal- immune response was activated, and composition. It is largest
differentiating neurons. Iwata lenges for the preservation of the plant’s immunoregula- during early life, then it shrinks
et al. now show that these terrestrial biodiversity. —YL tory RNA binding protein (IRR) with age and in response to
fate decisions involve the became dephosphorylated. injury and infection. Thymic
mitochondria. Cells that have Sci. Adv. 10.1126/ Dephosphorylation altered IRR’s development also affects T
fragmented mitochondria sciadv.abc1176 (2020). interaction with messenger RNA cell output but remains poorly
shortly after mitosis are more transcripts, including that of cal- understood. Chan et al. report
likely to become neurons, CELL TRANSPLANTATION cium-dependent protein kinase that liver X receptors (LXRs),
whereas cells that are undergo- 28 (CPK28), a key negative nuclear receptors important for
ing mitochondrial fusion are A second transplant for regulator of pattern recognition immunity and metabolism, play
likely to continue being stem intestinal disease receptor signaling complexes. an important role in thymus
cells. —PJH CPK28 is acutely regulated by dynamics. In mice, thymic
Allogeneic hematopoietic cell changes in calcium concentra- epithelial cells use LXRab
Science, this issue p. 858 transplantation (HCT) is a tion and its own phosphorylation for self-renewal and thymic
beneficial treatment for blood state. However, altered splicing regeneration. Meanwhile,
M E TA L LU R GY and bone marrow cancers. results in the expression of a LXRab makes thymocytes more
However, HCT can lead to truncated CPK28 protein that resistant to negative selection,
Temperature-stable graft-versus-host disease thereby boosting the production
superelasticity (GvHD), which affects vari-
ous organs, including the gut.
Shape memory alloys are Fecal microbial transplantation
superelastic, which means that (FMT) from a healthy donor has
they can recover their original successfully treated intestinal
shape after a large amount of disorders such as Clostridium
strain. However, in most alloys, difficile infection and ulcerative
this behavior tends to only colitis. Van Lier et al. conducted
work well for a small range a single-arm clinical trial to
of temperatures. Xia et al. investigate whether such FMTs
identified an iron-manganese- could ameliorate symptoms
aluminum-chromium-nickel of intestinal GvHD in 15 HCT
alloy for which superelasticity is recipients. Within a month of
virtually temperature indepen- treatment, intestinal GvHD
dent (see the Perspective by La resolved and gut microbial
Roca and Sade). This distinc- diversity was restored in 10 of
tive property is attractive for a 15 study participants. Although
variety of applications in which confirmation is required in
large temperature variations larger trials, FMT may be a
are normal, such as in space promising treatment for intesti-
exploration. —BG nal GvHD. —MN

Science, this issue p. 855; Sci. Transl. Med. 12,
see also p. 773 eaaz8926 (2020).

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FOLLOW THE MONEY motion. In the weeks after the

HUMAN GENETICS Philanthropy—or eyes open, the visual cortex
tax-exempt lobbying? acquires this ability. Roy et al.
Fermenting coevolution studied the newborn ferret to
Major corporations appear determine how synaptic and
T he dogma is that lactase persistence is a to fund their charitable cell-intrinsic properties enable
recent human adaptation to the domes- foundations in part to cater the development of direction
tication of dairy animals. Paradoxically, to politicians who are selectivity. Receptive fields of
retaining the ability to digest lactose important to the firm’s profit- mature neurons were more
beyond infancy is not universal among ability. Integrating corporate tax elongated along the temporal
pastoralists. Questioning the fitness advan- returns, lobbying data, and data axis and narrower along the
tage of lactase persistence, Segurel et al. on U.S. congressional commit- space-time axis compared
genotyped more than 900 people from 13 tee assignments, Bertrand et with the receptive fields for
ethnic groups and confirmed a low frequency al. show that donations from a neurons before visual stimu-
of the persistence allele among Central given corporate-funded founda- lus. With visual experience,
Asians. Since the emergence of the mutation tion to charities in a particular neurons improved their short-
in modern-day Ukraine almost 6000 years congressional representa- latency responses but also
ago, and after extensive migrations across the tive’s district, or for which a became more selective in their
steppes, the persistence mutation became congressional representative responses. —PJH
strongly represented in European popula- is a board member, ebb and
tions but was lost among Central Asians. The flow according to whether the eLife 9, e58509 (2020).
authors suggest that Central Asian herdspeo- representative sits on a com-
ple adapted to milk consumption either by mittee that is of interest to the MATERIALS SCIENCE
fermenting it, which was accompanied by the corporation. The patterns paral-
ingestion of helpful lactobacilli, or as a result lel spending by political action An uncuttable foam
of the selection of lactose-digesting bifido- committees (PACs). Around
bacteria in their gut microbiota. The question 7% of charitable giving (~$1.2 Designing structures across
is why these exogenous strategies are more billion annually) appears to be many different length scales
advantageous to Central Asians than the politically motivated, amounting provides flexibility in optimiz-
mutation is to Europeans. —CA to about 2.5 times the annual ing for certain properties.
PLOS Biol. 18, e3000742 (2020). PAC spending and one-third Szyniszewski et al. created a
new material, called Proteus,
that is highly deformable yet

of the total federal lobbying resistant to cutting. Proteus

spending—and it is tax exempt consists of ceramic spheres

and thus subsidized by taxpay- embedded in aluminum foam to

of autoreactive T cells. This work reactions involving electrolyte ers. —BW accomplish this unique property

therefore cautions that LXR- and cathode. Using Pd/CNT Am. Econ. Rev. 110, 2065 (2020). pairing. The authors show

focused thymic regeneration as cathode that effectively that this multiscale material is

therapies may need to be cell catalyzes Li2CO3 decomposi- NEURODEVELOPMENT resistant to the extreme loads
specific to prevent unwanted tion, the authors developed a of angle grinders, power drills,
autoimmunity. —STS Early vision matures and even water jet cutters. The
rechargeable Li-O2/CO2 battery underlying design principles
J. Exp. Med. 217, e20200318 (2020). with high energy capacity and Prior to eye opening, neurons

long storage life. —YS in the visual cortex of certain should be useful for developing

ENERGY STORAGE Angew. Chem. Int. Ed. 10.1002/ mammals respond to orienta- other architected materials for a
anie.202006303 (2020). tion of a visual stimulus but range of applications. —BG
Advancing Li-air batteries cannot parse its direction of
Sci. Rep. 10, 11539 (2020).

Lithium (Li)–air batteries

demonstrate ultrahigh theoreti-

cal energy densities, but their

practical realization is subject

to various technical limitations

because of the poor chemical

stability of their components

under exposure to air. Chen et

PHOTO: WESTEND61 GMBH/ALAMY STOCK PHOTO al. showed that CO2, which is
traditionally considered one of

the chemical mediators that

facilitate parasitic chemical

reactions, could in fact improve

battery stability. When intro-

duced into the feeding gas, CO2
facilitates the formation of a

passivated, protective Li2CO3
film on the Li anode and cap-

tures O2–, thus suppressing side Newborn ferret pups’ eyes can discern light despite being closed, but they cannot follow its direction of motion until they open.

SCIENCE 14 AUGUST 2020 • VOL 369 ISSUE 6505 785

Published by AAAS


Edited by Michael Funk


Making chemistry Prototype DNA vaccines Nuclear transport Heterogeneity
less precious for SARS-CoV-2 controls chronic pain and herd immunity

Much of modern chemistry relies The development of a vaccine Chronic neuropathic pain is In response to severe acute
on catalysis by precious metals to protect against severe acute debilitating and difficult to treat. respiratory syndrome corona-
such as platinum, palladium, respiratory syndrome coro- Marvaldi et al. now show that virus 2 (SARS-CoV-2), some
and rhodium. By contrast, more navirus 2 (SARS-CoV-2) is an chronic pain is regulated by a politicians have been keen to
abundant metals such as iron urgent biomedical need. Yu et al. specific nuclear import factor in exploit the idea of achieving herd
and copper suffice in biochem- designed a series of prototype peripheral sensory neurons (see immunity. Countering this possi-
istry. Bullock et al. review the DNA vaccines against the SARS- the Perspective by Yousuf and bility are estimates derived from
opportunities presented from CoV-2 spike protein, which is Price). Importin a3 is required work on historical vaccination
the study of enzymes to shift the used by the virus to bind and for nuclear import of the tran- studies, which suggest that herd
balance in synthetic catalysts invade human cells. Analysis of scription factor c-Fos in sensory immunity may only be achieved
further toward the use of these the vaccine candidates in rhesus neurons, and perturbation of at an unacceptable cost of lives.
abundant metals. Whether by macaques showed that animals this pathway ameliorates sus- Because human populations are
modifying the enzymes them- developed protective humoral tained neuropathic pain in mice. far from homogeneous, Britton
selves or by designing ligand and cellular immune responses Candidate drugs were identified et al. show that by introducing
and support architectures that when challenged with the virus. that mimic this pathway and age and activity heterogene-
take advantage of the cheaper Neutralizing antibody titers were alleviate neuropathic pain in ities into population models for
metals’ characteristic electron also observed at levels similar to mouse models. Identification of SARS-CoV-2, herd immunity
transfer properties, recent work those seen in humans who have a nuclear transport factor that can be achieved at a population-
points toward substantial prog- recovered from SARS-CoV-2 regulates pain mechanisms wide infection rate of ~40%,
ress. —JSY infection. —PNK offers opportunities for future considerably lower than previous
analgesic development. —SMH estimates. This shift is because
Science, this issue p. 786 Science, this issue p. 806 transmission and immunity are
Science, this issue p. 842; concentrated among the most
NEURODEVELOPMENT CORONAVIRUS see also p. 774 active members of a population,
who are often younger and less
Neural progenitors Immunity from ELECTROCHEMISTRY vulnerable. If nonpharmaceutical
disrupted reinfection interventions are very strict, no
Delivering protons herd immunity is achieved, and
Symptoms of Huntington's dis- One of the many open questions with electrons infections will then resurge if
ease (HD) manifest in adulthood about severe acute respira- they are eased too quickly. —CA
despite the aberrant protein tory syndrome coronavirus Many chemical reactions involve
being present much earlier in 2 (SARS-CoV-2) infection is concurrent transfer of a proton Science, this issue p. 846
persons carrying the disease- whether an individual who has and an electron. In electrochemi-
causing mutation. Barnat et al. cleared the virus can be infected cal synthesis, this mechanism SUPERCONDUCTIVITY
studied the cellular effects of a second time and get sick. could prove useful in lower-
the HD mutation on human and Chandrashekar et al. and Deng ing the energy necessary for An elusive pocket
mouse fetal brain development et al. generated rhesus macaque cathodic electron transfer alone,
(see the Perspective by DiFiglia). models of SARS-CoV-2 infec- but it is hindered by competing Superconductivity in copper
The authors found that neural tion and tested whether natural direct coupling of the protons oxide materials emerges by
progenitor cells at the brain’s SARS-CoV-2 infection could and electrons to make hydro- doping a special kind of cor-
ventricular zone reach out to result in immunity to viral rechal- gen instead. Chalkley et al. now related state called the Mott
both the apical and basal sur- lenge. They found that animals report a molecular mediator insulator. However, studying
faces of the neuroepithelial wall, indeed developed immune consisting of a dimethylaniline what happens when a small
and their cellular nuclei shuttle responses that protected against base tethered to a cobaltoce- concentration of charge car-
back and forth as the cell cycle a second infection. Although nium electron acceptor. This riers—holes or electrons—is
progresses. With the aberrant there are differences between construct can deliver both a added to a Mott insulator is
protein, these epithelial junc- SARS-CoV-2 infection in proton and an electron to a experimentally challenging. It
tions are disrupted, epithelial macaques and in humans, these substrate from an acid and a has been predicted that the
polarity is disturbed, and the cell findings have key implications cathode while skirting the hydro- so-called “Fermi pockets” should
cycle favors premature neuronal for public health and economic gen pathway. —JSY become visible during experi-
differentiation. —PJH initiatives if validated in human mentation, but such pockets
studies. —PNK Science, this issue p. 850 have not been unambiguously
Science, this issue p. 787; observed. Kunisada et al.
see also p. 771 Science, this issue p. 812, p. 818 studied the unusual cuprate
Ba2Ca4Cu5O10(F,O)2, which
has five copper oxide planes
in a unit cell, whereas most
cuprates have one or two (see

785-B 14 AUGUST 2020 • VOL 369 ISSUE 6505 SCIENCE

Published by AAAS

the Perspective by Vishik). They to warming. Warmed systems approach reduced neuronal
observed two Fermi pockets experienced a reorganiza- loss and increased survival in a
in both photoemission and quan- tion of trophic structure that mouse model of prion disease
tum oscillations data, with the was not rescued by functional without the pancreatic damage
innermost copper oxide planes redundancy or other stabilizing seen with catalytic inhibitors of
playing a crucial role. —JS responses. Such inflexibility may PERK. —LKF
be a precursor of ecosystem col-
Science, this issue p. 833; lapse. —SNV Sci. Signal. 13, eabb4749 (2020).
see also p. 775
Science, this issue p. 829; AUTOIMMUNITY
Autoimmunity promotor
Social contact and PA L E OA N T H R O P O L O GY
reconciliation Tissue-resident memory T
Bedding of grass (Trm) cells are involved in
It has been theorized that and ashes peripheral immunity against
positive intergroup relations can reinfection, but their role in
reduce prejudice and facilitate The Border Cave site in the autoimmunity is unclear. Krebs
peace. However, supporting KwaZulu-Natal region of South et al. examined the contribu-
empirical evidence is weak, Africa has been a rich source of tion of Trm cells in patients with
particularly in the context of archaeological knowledge about antineutrophil cytoplasmic
real-world conflict. Mousa ran- Stone Age humans because of antibody–dependent glomeru-
domized Christian Iraqi refugees its well-preserved stratigraphic lonephritis (ANCA-GN). They
to soccer teams that were record. Wadley et al. now report identified multiple T cell subsets
composed of either all Christian the discovery of grass bed- in healthy kidney tissue biopsies,
players or a mixture of Christian ding in Border Cave, dated to but a marked increase in CD4+
and Muslim players (see the approximately 200,000 years Trm cells was seen in kidney
Perspective by Paluck and ago. The bedding, identified biopsies from patients with
Clark). Playing on the same team with a range of microscopic and ANCA-GN. They infected mice
as Muslims had positive effects spectroscopic techniques, was with Staphylococcus aureus,
on Christian players’ attitudes mingled with layers of ash. It also which induced renal T helper 17
and behaviors toward Muslims incorporated debris from lith- cells with a Trm cell phenotype
within the context of soccer, but ics, burned bone, and rounded and persisted in kidney tissue. In
these effects did not generalize ochre grains, all of which were a mouse model of this disease,
to non-soccer contexts. These of clear anthropogenic origin. S. aureus infection aggravated
findings have implications for The authors speculate that the kidney pathology and appeared
the potential benefits and limits ash may have been deliberately to drive localized renal autoim-
of positive intergroup contact used in bedding to inhibit the mune responses. These findings
for achieving peace between movement of ticks and other provide critical insight into the
groups. —TSR arthropod irritants. These role of CD4+ Trm cells in contrib-
discoveries extend the record of uting to autoimmune disease.
Science, this issue p. 866; deliberate construction of plant —CNF
see also p. 769 bedding by at least 100,000
years. —AMS Sci. Immunol. 5, eaba4163 (202=0).
Science, this issue p. 863
Inflexible webs
It is clear that human activities
are negatively affecting current PERKing up neurons
ecosystems. Predicting how without toxicity
our activities will affect future
systems is more challenging Chronic activity of the unfolded
because it involves estimat- protein response in some
ing the unknown. Nagelkerken neurodegenerative diseases
et al. overcame some of these suppresses the protein synthesis
unknowns by constructing that is necessary for neuronal
small versions, or mesocosms, function and survival and for
of a marine ecosystem that cognition. Hughes et al. found
included species represent- that the phosphorylation of a
ing all trophic levels (see the threonine residue in the stress
Perspective by Chown). They response kinase PERK reduced
then exposed these systems to its interaction with the transla-
predicted future levels of carbon tion initiation factor eIF2a but
dioxide and acidification. The left the kinase activity of PERK
trophic structure was relatively intact. This partial inhibition
resistant to acidification but not

SCIENCE 14 AUGUST 2020 • VOL 369 ISSUE 6505 785-C

Published by AAAS


◥ conditions, using only EAMs, highlights com-
pelling opportunities for the discovery of new
REVIEW SUMMARY catalysis. Although enzymes are versatile plat-
forms for harnessing the properties of EAMs,
C ATA LYS I S they are insufficiently robust under the harsh
pH, temperature, pressure, and solvent condi-
Using nature’s blueprint to expand catalysis tions required for some industrial catalytic pro-
with Earth-abundant metals cesses. Thus, systematic strategies are needed
for directed evolution to extend the reactivity
R. Morris Bullock*, Jingguang G. Chen*, Laura Gagliardi*, Paul J. Chirik, Omar K. Farha, and persistence of engineered enzymes. For
Christopher H. Hendon, Christopher W. Jones, John A. Keith, Jerzy Klosin, Shelley D. Minteer, molecular catalysts, the tunability of the ligands
Robert H. Morris, Alexander T. Radosevich, Thomas B. Rauchfuss, Neil A. Strotman, provides opportunities for systematically vary-
Aleksandra Vojvodic, Thomas R. Ward, Jenny Y. Yang, Yogesh Surendranath* ing the activities of EAMs. Key challenges
include enhancing metal-ligand cooperativ-
BACKGROUND: Catalysis has had a transform- is achieved in enzymatic catalysis by directed ity, controlling transport to EAM active sites,
ative impact on society, playing a crucial role evolution of the amino acid environment, and mastering the interactions of EAM centers
in the production of modern materials, med- resulting in engineered enzymes with extra- with both metal-based and organic-based redox-
icines, fuels, and chemicals. Precious metals ordinary catalytic performance. Similarly in active ligands. In heterogeneous catalysis, tuning
have been the cornerstone of many industrial molecular catalysis, modifying the steric and the lattice environment of EAMs offers new
catalytic processes for decades, providing high electronic properties of ligands can lead to opportunities for catalyst discovery, but for
activity, stability, and tolerance to poisons. In some EAM catalysts with performance supe- practical applications EAM catalysts should
stark contrast, redox catalysis essential to life rior to that obtained from precious metal exhibit long-term stability and high active-
is carried out by metalloenzymes that feature catalysts. In addition, for heterogeneous cat- site density. Thus, advances are needed in
exclusively Earth-abundant metals (EAMs). alysts, the local environment and electronic the synthesis of materials with tunable phase
The terrestrial abundance of some EAMs is structure of active sites can be modified by and nanostructure, as well as insights into how
104 times that of precious metals, and thus bonding to other metals or main-group ele- EAM catalysts undergo electronic and struc-
their increased use would lead to reduced cost ments, facilitating reaction pathways distinct tural changes under sustained catalytic turn-
and environmental footprint. In addition to from those involving precious metals. Innova- over. Strategies for controlling EAM reactivity
these practical considerations, EAMs display tions in the design of EAM catalysts demon- patterns, coupled with advances in synthetic
distinct reactivity profiles that originate from strate their potential to catalyze many of the methods and spectroscopic and computational
their characteristic electronic structure, thermo- reactions that traditionally relied on precious techniques, are critical for the systematic use of
chemistry, and kinetics. The behavior of EAMs metals, although further improvements are
provides compelling scientific opportunities for needed in activity, selectivity, lifetime, or energy ▪EAMs in sustainable catalysis.
catalyst design. We assert that nature’s blueprint efficiency. The characteristics of EAMs point to
provides essential principles for vastly expand- an overarching need for improved theories and The list of author affiliations is available in the full article online.
ing the use of EAMs in sustainable catalysis. computational methods that accurately treat *Corresponding author. Email: [email protected]
their multiconfigurational electronic structure. (R.M.B.); [email protected] (J.G.C.); [email protected]
ADVANCES: Exquisite tuning of the local envi- (L.G.); [email protected] (Y.S.)
ronment around EAM active sites is key to OUTLOOK: The remarkable ability of enzymes Cite this article as R. M. Bullock et al., Science 369, eabc3183
enabling their use in catalysis. Such control to catalyze a variety of reactions under mild (2020). DOI: 10.1126/science.abc3183


Catalysis by Earth-abundant
metals. Nature’s blueprint provides
the fundamental principles for
expanding the use of abundant
metals in catalysis by controlling
the local environment and
electronic structure of metal
centers. Examples include
nitrogenase-based enzymatic
catalysts for N2 reduction,
metalloporphyrin-based molecular
catalysts for reduction of oxygen
and carbon dioxide, and metal
chalcogenides in heterogeneous
catalysis for hydrodesulfurization
and hydrogen evolution reactions.

Bullock et al., Science 369, 786 (2020) 14 August 2020 1 of 1


◥ stone of many industrial catalytic reactions for
decades, owing to their high catalytic activity,
REVIEW thermal stability, and tolerance to chemical
poisons. Pd-catalyzed cross-coupling reactions
C ATA LYS I S that form C-C bonds (10) have broad utility
and tremendous versatility in pharmaceutical,
Using nature’s blueprint to expand catalysis electronic, and materials applications. A sec-
with Earth-abundant metals ond wave of Pd-catalyzed cross-coupling chem-
istry has given rise to powerful methods for C-N,
R. Morris Bullock1*, Jingguang G. Chen2,3*, Laura Gagliardi4*, Paul J. Chirik5, Omar K. Farha6, C-S, and C-O bond-forming reactions that are
Christopher H. Hendon7, Christopher W. Jones8, John A. Keith9, Jerzy Klosin10, Shelley D. Minteer11, widely used (11). Rh-based complexes catalyze
Robert H. Morris12, Alexander T. Radosevich13, Thomas B. Rauchfuss14, Neil A. Strotman15, the CO insertion reaction, hydroformylation
Aleksandra Vojvodic16, Thomas R. Ward17, Jenny Y. Yang18, Yogesh Surendranath13* (12) (Fig. 2, top right). Pt is the prototypical
catalyst for hydrogen production (13) and oxi-
Numerous redox transformations that are essential to life are catalyzed by metalloenzymes that dation (Fig. 2, middle right). Ir oxide catalyzes
feature Earth-abundant metals. In contrast, platinum-group metals have been the cornerstone of many the oxidation of water to O2 (14) in polymer elec-
industrial catalytic reactions for decades, providing high activity, thermal stability, and tolerance to trolyte membrane (PEM) electrolyzers (Fig. 2,
chemical poisons. We assert that nature’s blueprint provides the fundamental principles for vastly bottom right). C-H oxidation and functionaliza-
expanding the use of abundant metals in catalysis. We highlight the key physical properties of abundant tion reactions have been extensively developed
metals that distinguish them from precious metals, and we look to nature to understand how the using Pd catalysts (15). Selective hydrogena-
inherent attributes of abundant metals can be embraced to produce highly efficient catalysts for tion reactions required in oil refining and fine
reactions crucial to the sustainable production and transformation of fuels and chemicals. chemical synthesis routinely use PGM catalysts.
The three-way catalyst in catalytic converters
C atalysis has had a transformative impact that constitute the mid- to late portion of the used daily in hundreds of millions of cars re-
on society, playing a decisive role in the second and third rows have substantially lower quires Pt, Rh, and Pd.
crustal abundance (Fig. 1) (1). Here, we high-
production of modern materials we use light frontier opportunities for designing and EAM catalysts are attractive for many rea-
enabling new catalysts based on Earth-abundant sons. The “terawatt challenge” (16) for global
daily, medicines to keep us healthy, and metals (EAMs), with an emphasis on redox re- energy demand highlights the need to con-
actions crucial to the sustainable production sider the scalability of catalytic materials for
fuels for transportation. Most of the key and transformation of fuels and chemicals. sustainable energy conversions. The crustal
abundance of EAMs exceeds that of PGMs by a
chemical reactions essential to our contempo- Many redox transformations (2) that are es- factor of 104 or greater (Fig. 1), leading to costs
sential to life are catalyzed by EAMs in nature. that differ by similar ratios. Costs are influ-
rary lifestyle are catalyzed by transition metals Because biological organisms must accumu- enced both by abundance and production rate
late metals from their surroundings, evolu- (17). The price of a mole of Rh reached >$15,000
(TMs). The terrestrial abundance of TMs varies tion selected the EAMs exclusively in biological (USD) as of November 2019, whereas the cost of
catalysis. Indeed, there are no known native most EAMs is typically <$2 per mole (although
over a remarkable range. The first-row (3d) biological catalysts that use a PGM. Conse- for many catalytic reactions, the metal cost
quently, metalloenzymes provide an expansive constitutes only a small fraction of the overall
metals of the transition series in the periodic existence proof that EAMs catalyze complex process cost; in the synthesis of pharmaceuti-
redox transformations. A tri-Cu active site in the cal products, the cost of chiral ligands can
table, as well as the early second-row (4d) and laccase enzyme (3, 4) reduces O2 to H2O, a key substantially exceed that of the metal). Prices
cathodic reaction in fuel cells. A cluster con- of PGMs are much more volatile than those of
third-row (5d) metals, are relatively abundant, taining Fe and Mo reduces N2 to NH3 in nitro- EAMs. Moreover, EAMs generally have lower
genase (5). A dinuclear Ni active site catalyzes biological toxicity (18), permitting higher lev-
whereas the platinum group metals (PGMs) the CO insertion reaction in acetyl–coenzyme A els of residual EAMs than of PGMs in phar-
(CoA) synthase (Fig. 2, top left). Enzymes con- maceutical products (19). Lastly, the high
1Center for Molecular Electrocatalysis, Pacific Northwest taining Ni-Fe organometallic complexes carry abundance of EAMs generally leads to a lower
National Laboratory, Richland, WA 99352, USA. 2Department out the reversible interconversion of H2 and environmental footprint associated with their
of Chemical Engineering, Columbia University, New York, NY H+ in hydrogenase (6) (Fig. 2, middle left). A mining and purification relative to PGMs. For
10027, USA. 3Chemistry Division, Brookhaven National Mn-Ca cluster catalyzes the oxidation of water example, the production of 1 kg of Rh generates
Laboratory, Upton, NY 11973, USA. 4Department of to O2 in photosystem II (7) (Fig. 2, bottom left). >35,000 kg of CO2 equivalent, whereas 1 kg
Chemistry, Minnesota Supercomputing Institute, and The selective oxidation of methane to methanol of Ni produces only 6.5 kg of CO2 equivalent
Chemical Theory Center, University of Minnesota, occurs at the dinuclear Fe active site in meth- (Fig. 1, black bars) (20).
Minneapolis, MN 55455, USA. 5Department of Chemistry, ane monooxygenase (8). Diverse C-H function-
Princeton University, Princeton, NJ 08544, USA. alization reactions are catalyzed by Fe-S cluster Given the appealing attributes of EAMs
6Department of Chemistry and Chemical and Biological active sites in radical S-adenosylmethionine noted above, one can ask why PGMs continue
Engineering, Northwestern University, Evanston, IL 60208, (SAM) enzymes (9). All of these transforma- to be so prevalent in many industrial catalytic
USA. 7Department of Chemistry and Biochemistry, University tions involve multielectron redox reactions, and processes. The specific reasons vary according
of Oregon, Eugene, OR 97403, USA. 8School of Chemical and most require precise control of the delivery or to catalytic application. In general, the require-
Biomolecular Engineering, Georgia Institute of Technology, removal of protons. ment for effective integration of a catalyst into
Atlanta, GA 30332, USA. 9Department of Chemical and an overall process often places stringent con-
Petroleum Engineering, University of Pittsburgh, Pittsburgh, In contrast to the extensive use of EAMs in straints on the choice of catalyst. For example,
PA 15261, USA. 10Core R&D, Dow Chemical Co., Midland, nature, PGMs have historically been the corner- in a fuel cell, the use of fast ion conductivity
MI 48674, USA. 11Department of Chemistry, University of in Nafion (separating charge transfer between
Utah, Salt Lake City, UT 84112, USA. 12Department of
Chemistry, University of Toronto, Toronto, Ontario M5S 3H6,
Canada. 13Department of Chemistry, Massachusetts Institute
of Technology, Cambridge, MA 02139, USA. 14School of
Chemical Sciences, University of Illinois, Urbana, IL 61801,
USA. 15Process Research and Development, Merck & Co.
Inc., Rahway, NJ 07065, USA. 16Department of Chemical and
Biomolecular Engineering, University of Pennsylvania,
Philadelphia, PA 19104, USA. 17Department of Chemistry,
University of Basel, CH-4058 Basel, Switzerland.
18Department of Chemistry, University of California, Irvine,
CA 92697, USA.
*Corresponding author. Email: [email protected]
(R.M.B.); [email protected] (J.G.C.); [email protected]
(L.G.); [email protected] (Y.S.)

Bullock et al., Science 369, eabc3183 (2020) 14 August 2020 1 of 10


Fig. 1. Definition of different groups of transition metals. Platinum group metals (PGMs) include Ru, Rh, Pd, Os, Ir, and Pt. The broader term, precious
metals, includes PGMs along with Re, Au, and Ag. Earth-abundant metals (EAMs), sometimes referred to as base metals, include all other transition metals.
(Tc is shown but is radioactive and unstable.) The height of the pillar for each metal indicates its crustal abundance on a log scale; the values range from 5.6% (Fe)
to ~0.001 ppm (Rh, Ir). The black bar on each metal shows (also on a log scale) the relative amount of CO2 produced through mining and purification for each
metal (20), which is markedly larger for PGMs than for EAMs.

Fig. 2. Many of the transformations carried out by enzymatic EAM catalysts are replicated in the anodes and cathodes) requires an acidic pH,
chemical industry by means of PGM catalysts. thereby constraining the choice of catalysts
to corrosion-resistant PGMs. Likewise, the
requirement for high-temperature operations
in catalytic converters places stringent re-
quirements on durability, constraining viable
replacement of PGMs. In addition, the high
capital and energy cost of complex downstream
separations imposes a constraint on the mini-
mum selectivity of catalytic processes, and this
consideration may dominate relative to the
cost and environmental footprint of the metal
catalyst itself. These factors motivate the em-
phasis on the development of EAM catalysts
in tandem with new processes that can cir-
cumvent the constraints of current catalytic

EAM catalysts are currently successfully
used in several major industrial processes.
The Haber-Bosch reaction, which converts
N2 to ammonia, uses an Fe-based catalyst,
despite the higher performance of a Ru-based
analog (21). Hydrogenation of CO to methanol
is carried out using a Cu/Zn-based catalyst.
Hydrogen is produced from water in commer-
cial electrolyzers under basic conditions using
Ni/Fe-based catalysts. Olefin oligomerization
and polymerizations are carried out worldwide
on a tremendous scale using EAMs, dominated
by Ti, Zr, and Cr catalysts. Terephthalic acid
is produced on a large scale through oxidation
of p-xylene using Co and Mn catalysts. Some
industrial processes are catalyzed by both PGMs
and EAMs. For example, hydroformylation is
conducted using either Co- or Rh-based catalysts

Bullock et al., Science 369, eabc3183 (2020) 14 August 2020 2 of 10


(12), and propane dehydrogenation is carried for the increased use of EAMs in enzymatic, TM complexes, the overlap deficit leads to more
out on either Pt- or Cr-based catalysts (22). molecular, and heterogeneous catalysis. ionic character in metal-ligand bonds and a
Despite these examples, it remains clear that small frontier d-orbital splitting (Fig. 3, top),
the scope of EAM catalysis is limited relative The origins of divergent reactivity between stabilizing high-spin electronic configurations.
to the remarkable diversity of transformations EAMs and PGMs High spin configurations are extremely rare
catalyzed by EAMs in nature. Electronic structure (29, 30) among 4d and 5d TM complexes owing
to their much higher frontier orbital splitting
Whereas biology provides an invaluable The distinctive reactivity profiles of EAMs energies (Fig. 3, top). Similar phenomena are
(although sometimes inscrutable) guide to relative to PGMs originate from fundamental observed for extended solids: Attenuated orbital
the broadened implementation of EAMs, indus- differences arising from periodic trends of the overlap between 3d metal atoms leads to a
trial catalysis often requires substrates, reac- elements (27). In particular, 3d orbitals extend diminished spread in the d-band energies and
tions, and reaction conditions quite different to a lesser extent beyond the 3s and 3p orbitals a corresponding increase in the d-band center
from those in biology; PGM catalysts prolif- (28), leading to attenuated orbital overlap with of 3d metals relative to the 4d and 5d counter-
erate in this arena. For example, alkenes, which bonding partners, relative to the corresponding parts (Fig. 3, top). The prevalence of high-spin
are derived from petroleum, are processed 4d and 5d counterparts. This overlap deficit has electronic configurations among 3d TMs
quite differently by enzymes than by industrial a considerable impact on the electronic struc- has important implications for reactivity (31).
catalysts. With the notable exception of Cu- ture of 3d metal-based catalysts. For molecular
based ethylene-sensor proteins (23), metal-alkene
complexes are unknown in nature, although Fig. 3. Physical properties of EAMs versus PGMs, illustrating substantial differences that lead to
transfer hydrogenations of C=C bonds are divergent reactivity that can be exploited in catalysis. Data are from (1, 38, 124).
catalyzed by a family of biocatalysts, ene re-
ductases (24). In stark contrast, industrial
catalytic transformations of alkenes include
polymerization, carbonylation, and metathesis;
analogs of these processes are absent from
the biocatalysis repertoire. Instead, alkenes are
often processed in natural systems by attacking
weakened allylic C-H bonds using iron-oxo-
based radicals (25).

Considering the diversity of catalysis per-
formed by biological systems, a central challenge
revolves around coaxing biological macromole-
cules into displaying entirely abiotic reactivity/
selectivity/stability characteristics that have
traditionally been the domain of PGM-based
catalysts. A daunting challenge in designing
bio-inspired catalysts is to identify and replicate
only the parts of the metalloenzyme structure
(first, second, or outer coordination sphere)
that are thought to be required for catalytic
activity, recognizing that while biological re-
action networks must maintain life, their
catalytic functionality may be accessible from
synthetically simpler structures. Replicating the
active site is necessary but not sufficient for
achieving catalysis comparable to that found
in enzymes, as dynamics and conformational
changes often exert a large influence on enzy-
matic catalysis (26).

The considerations discussed above have
fueled burgeoning interest in developing new
EAM-based catalysts. We assert that this en-
deavor is best advanced by establishing the
fundamental science of EAMs that embraces
their particular physical properties and result-
ant catalytic activities. Herein, we put forward
the premise that nature’s blueprint provides
the fundamental principles for vastly expand-
ing the use of EAMs in catalysis. We highlight
the key physical properties of EAMs that dis-
tinguish their reactivity from those of PGMs,
and then seek to understand how the inherent
attributes of EAMs can be embraced, leading
to highly efficient catalysis. Building on that
foundation, we identify compelling opportunities

Bullock et al., Science 369, eabc3183 (2020) 14 August 2020 3 of 10


Fig. 4. The utility of enzymatic catal-
ysis can be enhanced by expanding
active-site reactivity to abiotic sub-
strates, minimizing the enzymatic
scaffolding, and enabling operation
in nonphysiological reaction envi-
ronments. Images were obtained from
PDB code 1W0E, cytochrome P450.

Homogeneous PGM catalysts typically cycle than 1 V. Likewise, Pt (111) and Pd (111) surfaces change on the 3d TMs offers the opportu-
through two-electron processes, including famil- have an O-atom affinity of ~0.5 eV (12 kcal/mol), nity for rapid catalysis. Two key properties
iar examples of oxidative addition/reductive whereas Ni (111) surfaces have an O-atom af- sought are kinetic stability of the metal-
elimination of RhI/RhIII and Pd0/PdII. In con- finity of ~4 eV (92 kcal/mol) (Fig. 3). Because supporting ligand ensemble and labile coor-
trast, 3d TM complexes more readily engage these baseline reduction potentials correspond dination sites with appropriate affinities for
in single-electron bond activation reactions, to interconversion of the metallic solid and substrates. The challenge arises from the fact
including M-X bond homolysis. Additionally, aquated metal ions, they are influenced by that lability of EAMs can also lead to the
the availability of multiple spin states among the coordination, electrostatic, and hydrogen- rapid exchange of supporting ligands that tune
EAMs can lead to multistate acceleration of bonding environment of the metal center (35). the local electronic structure and reaction en-
certain reactions. Because of these effects, the active-site EAMs vironment of the metal center. To circumvent
in metalloenzymes span a wide range of po- problems with lability in molecular complexes,
Thermochemistry tentials (2) that differ substantially from their polydentate ligands are often used to strongly
baseline values. Similar potential ranges can sequester the metal ion while preserving one
The differences in the electronic structures be accessible through changes in the coordi- or more coordination sites for catalysis. Con-
of EAMs and PGMs are manifested in the nation environment of synthetic coordination sequently, tridentate or tetradentate ligands
thermochemistry of interactions of metals compounds (36). are ubiquitous in catalysis by synthetic 3d TMs
with ligands, reactants, products, and inter- relative to PGMs, so as to overcome the in-
mediates. The classical Sabatier principle states The differences in reduction potential be- herent differences in lability relative to PGMs.
that an optimal catalyst should bind inter- tween EAMs and PGMs are of central impor- The premier examples of multidentate lig-
mediates neither too strongly nor too weakly, tance in electrocatalysis, where electron flow ands in biocatalysis are porphyrins, where
essentially a “Goldilocks” effect (21). In general, drives the conversion of reactants to products. four metal-nitrogen bonds confer substan-
bonding to 3d TMs in molecular complexes is For example, the very positive potential for tial kinetic inertness.
weaker relative to 4d/5d TM centers with the oxidizing Pt allows it to avoid corrosion at the
same ancillary ligand environment. For exam- oxidizing potentials of the O2/H2O couple in In extended solids, the kinetics of substitu-
ple, the bond dissociation energies of the M-H fuel cells, making it the only currently viable tion at EAMs also play a central role in the
bond in MH(h5-C5H5)(CO)2 are 68 kcal/mol corrosion-resistant cathode catalyst for PEM longevity of catalysts. The weaker M-lattice
(32), 77 kcal/mol (32), and ≥82 kcal/mol (33) fuel cells. To achieve similar feats, enzymes bonding in mid- to late 3d metal and metal
for Fe, Ru, and Os, respectively; for MH(CO)5, such as multi-copper oxidases, laccases (3, 4), oxide materials contributes to their high pro-
the values are 68 kcal/mol and 75 kcal/mol for and cytochrome c oxidase (37) use an ensemble pensity to sinter, restructure, become amor-
Mn and Re, respectively (34). Additionally, of metal centers organized within the protein phous, and corrode under catalytic conditions,
the greater extension of the d-orbitals of the environment that markedly alters their redox relative to 4d and 5d analogs. A richer under-
second and third TMs also provides for stronger properties and oxophilicities. standing of how to control metal lability in
back-bonding interactions with p-accepting extended solids is essential for creating robust
ligands, such as CO and olefins, increasing Kinetics EAM catalysts, particularly for harsh reaction
their binding strength. Intermediates bear- environments.
ing such ligands are critical in a number of Owing to their weaker metal-ligand bonds,
industrially important processes such as complexes of the 3d metals are much more Computational insights
hydroformylation. labile than their 4d and 5d counterparts (Fig. 3,
bottom). The rate accelerations can be extra- Much of our physical understanding of EAMs
The differences in metal bonding thermo- ordinary: Exchange of a water ligand on a high- has been enhanced through consistent bench-
chemistry are also mirrored in changes in the spin Fe(III) center is faster than on Ru(III) marking between experiment and theory. A
reduction potentials of metal ions. PGMs are by a factor of 108 (38). We emphasize that comprehensive understanding of EAM reac-
commonly referred to as noble because of their lability is a kinetic phenomenon; many labile tivity will require a refined understanding of
resistance to oxidation, a reflection of their complexes are thermodynamically stable. Al- electronic structure, thermochemistry, and
much higher reduction potentials and of the though typically viewed as an impediment to kinetics. Yet current theoretical tools that
lower O-atom affinities of 4d and 5d metals understanding catalytic reactivity, the higher are effective at modeling multiconfigurational
(Fig. 3, middle, black) relative to 3d TMs (Fig. lability of EAMs can, in principle, be beneficial electronic structure commonplace among EAMs
3, middle, blue). For example, whereas the PtII/0 for catalysis. Turnover frequencies are often are often ineffective for predicting thermochem-
and PdII/0 reduction potentials are 1.18 and strongly influenced by the rates of association ical and kinetic properties (39). This impasse
0.951 V, respectively, versus the standard hydro- and dissociation of reactants and products, results from the enormous computational
gen electrode (SHE), the corresponding NiII/0 a manifestation of the Sabatier principle (21). expense required to calculate the properties
reduction potential, –0.26 V, is lower by more Thus, the inherently higher rate of ligand ex- of EAMs that reside in shallow potential

Bullock et al., Science 369, eabc3183 (2020) 14 August 2020 4 of 10


Fig. 5. EAM enzymes provide the blueprint for molecular EAM catalyst design. The example shown is provides a diversity of reactivity for the dis-
covery of abiotic enzymatic catalysis. There
[Fe-Fe]-hydrogenase (center; PDB code 5LA3). (A) Proton relays positioned proximate to EAM active has been increasing recognition that biological
cofactors featuring EAMs are active, albeit at a
sites (blue highlight) are deployed in molecular catalysts for hydrogen production (125). (B) Multimetallic low level, for a wide array of abiotic trans-
formations that are commonly carried out by
cluster active sites catalyze energy conversion reactions (95). (C) Transport to active sites via enzyme synthetic PGM-based catalysts. For example,
carbene insertion reactions, which enable the
channels can be mimicked in porous molecular materials (126). (D) The density of available electronic states rapid elaboration of simple organic feedstocks
is increased through redox-active ligands that can steer reactivity in synthetic systems (90). Me, methyl; tBu, into fine and pharmaceutical chemicals, are
tert-butyl; iPr, isopropyl; Ph, phenyl. catalyzed efficiently by synthetic Rh-based
catalysts (48). Remarkably, many native hemo-
energy wells with a diversity of available spin tary to ML approaches, theoretical schemes proteins also display low-level activity for these
configurations. such as alchemical perturbation DFT allow same reactions, and directed evolution of these
rapid screening of adsorbate binding energies enzymes has led to a family of biocatalysts
The widely used density functional theory (45) with minimal precalculated reference data (49) with excellent activity and selectivity for
(DFT) has strengths and weaknesses, and both and low computational cost. carbene insertion into C-H, N-H, and Si-H
are highlighted in modeling catalysis by EAMs. bonds. The activity and selectivity of these
In some cases, trends can be identified readily Emerging opportunities for catalytic reactivity evolved metalloproteins now rival and even
using simple basis sets and commonly used of EAMs exceed those of Rh-based catalysts. One recent
functionals. Often complementing experimen- study (50) showed that hemoproteins can be
tal results, theoretical studies can identify rate- Recent progress in the design of EAM catalysts repurposed to catalyze carbon-carbon bond for-
determining steps, assign vibrational bands, demonstrates their potential in many reac- mation by insertion of a carbene, rather than
and determine redox potentials. Useful ther- tions that traditionally use PGMs, although oxygen, into a C-H bond—a reaction tradition-
mochemical predictions of energies can often they often fall short of the performance of ally dominated by PGMs (51). Implementing the
be obtained, even if specific spin states may PGM catalysts on one or more benchmarks blueprint from nature requires precise control
not be easily determined reliably. Spin transi- (46): activity, selectivity, lifetime, or energy of the local environment by modifying the
tions and d-orbital splitting of EAMs are difficult efficiency. Yet EAM-based enzymes have evolved active site to bind an abiotic reactant, such as a
to treat because states that are very similar in in nature to facilitate an impressively diverse carbene, while minimizing the binding of the
energy occur frequently with EAMs. array of reactions. We assert that nature’s native substrate (i.e., O2) with exquisite selec-
blueprint provides invaluable guidance for tivity (52). The fundamental workflow of protein
Machine learning (ML)–based methods have frontier areas of exploration in EAM catalysis engineering—identifying promiscuous reactiv-
generated enormous recent interest in the com- that takes advantage of the inherent electronic ity for abiotic substrates, then using protein-
putational analysis of catalysis (40). In a typical structure, thermodynamic, and kinetic charac- engineering tools to maximize performance—
application of ML, large datasets (often result- teristics of EAMs. We discuss below how to serves as a valuable blueprint for further
ing from thousands of DFT calculations) are use biologically inspired approaches to design advances in catalysis of abiotic reactions.
used for statistical regression analyses with ML EAM catalysts with enhanced performance Continued progress to expand the palette of
methods to identify the most accurately pa- in the context of enzymatic, molecular, and enzymatic catalysis will benefit from the devel-
rametrized model for the dataset. A well-trained heterogeneous reactivity. opment of new methods for identifying enzyme
ML model should successfully interpolate within candidates and strategies for accelerating directed
the chemical/materials space of the training Enzymatic catalysis evolution and selection of high-performance
data and be useful for screening molecular/ mutant enzymes.
material properties for hypothetical homoge- Biological catalysts with TM active sites feature
neous (41, 42) and/or heterogeneous (43, 44) exclusively EAMs; a central challenge revolves The macromolecular scaffolds that house
catalyst active sites across larger regions of around modifying enzymes to display abiotic EAM active sites in enzymes are critical to their
chemical and materials space than are acces- functions (Fig. 4). Many metalloenzymes display function but invariably afford high–molecular
sible with DFT calculations alone. Complemen- promiscuous activities (47), a feature that weight catalysts. For commodity-scale catalysis,
the density of active sites is a critical determi-
nant of space-time yield, imposing constraints
on overall performance. In some cases, sub-
units of enzymes can be discarded without
greatly lowering catalytic efficiency; this sug-
gests that there is ample opportunity for en-
hancing active-site density without necessarily
decreasing the turnover frequency or selectivity
of each site. In other cases, mutation of a sin-
gle amino acid remote from the active site can
appreciably alter catalytic performance (53).
Reliable methods for discriminating the por-
tions of the enzyme scaffold that are essential
for catalysis from those that are not necessary
will facilitate the wider use of enzymatic EAM
catalysis for large-scale industrial processes.

Many abiotic reactions of critical impor-
tance are ideally performed under conditions

Bullock et al., Science 369, eabc3183 (2020) 14 August 2020 5 of 10


(temperature, pressure, pH) that are far re- In addition to modifications of the ligands reactant and product molecule in different
moved from the mild conditions of biology. For bound directly to the metal (primary coordina- directions, with the EAM active sites precisely
example, catalysts in fuel cells and electrolyzers tion sphere), the environment of molecular positioned at the junction of these conduits.
often operate at the extremes of pH to facilitate catalysts can be tuned by positioning secondary Similar precision has been difficult to achieve
ion conduction, and many heterogeneous cata- coordination sphere substituents, such as Lewis in synthetic systems, and efforts toward con-
lysts operate at elevated temperatures to enhance acids (59), positively charged groups (60–62), structing molecular materials with active sites
the reaction rate and facilitate heat integra- hydrogen bond donors (63), and pendant amines at the intersection of multiple transport con-
tion. Biological systems offer opportunities for functioning as proton relays (64–68) (Fig. 5A) duits could substantially advance selectivity in
adapting enzyme catalysis to extreme reaction proximal to the EAM center. These strategies EAM catalysis.
conditions. In particular, thermophilic archaea have enhanced the rates of molecular EAM
sustain life processes at temperatures exceed- catalysis of electrochemical H2 evolution (64–66), Because of their low field strengths, EAM
ing 100°C and at extremes of pH (54). It has H2 oxidation (65, 66, 68), CO2 reduction (60), and complexes have a propensity to undergo single-
long been recognized that some enzymes display O2 reduction (69). Because the redox reactivity electron transfer pathways (82). The control
enhanced catalytic activity in organic solvents involves coupling of electron flow and bond levers noted above are particularly important
(55), yet there remains limited fundamental rearrangement, the secondary coordination for embracing and controlling radical reactiv-
understanding of the characteristics of enzymes sphere substituents must be precisely positioned ity. Because of their smaller d-orbital splitting
that engender persistent activity under these to foster optimal cooperativity. For example, the and weaker spin-pairing energy, EAMs tend to
conditions. Additionally, whereas abiotic reac- rates of proton-coupled electron transfer (70, 71) react in enzymes through radical intermedi-
tivity modes can be screened using abiotic can be sensitive to sub–angstrom-level changes ates. Controlled radical reactions are central to
reagents, screening for enzymatic performance in the distance between proton donor and biological detoxification by heme centers in
under abiotic reaction conditions is more dif- acceptor (72). Cooperativity between the primary cytochrome P450 enzymes, the synthesis of
ficult because the biological replication machinery and secondary coordination spheres in enzymes DNA precursors mediated by ribonucleotide
operates within a narrow domain of conditions. is achieved through the dynamic flexibility reductase, and many other critical transfor-
Strategies for driving directed evolution within of the protein scaffold (26), a property that is mations mediated by cobalamins and radical
extremophile hosts, and a deeper understand- difficult to recreate systematically in synthetic SAM enzymes (9). By controlling the reactivity of
ing of the factors that contribute to protein EAM catalysts. Strong electric fields can in- Co(III) carbon-centered radicals generated from
stability, provide plentiful opportunities for fluence enzyme catalysis (73) by manipulating Co(II) porphyrin complexes, eight-membered
extending the rich EAM catalytic reactivity of the energies of intermediates or transition rings have been produced from ring-closing
enzymes toward the harsher conditions often re- states, thereby changing the rates and selec- reactions; this strategy provides attractive syn-
quired for thermal and electrochemical catalysis. tivity. Computations offer the opportunity to thetic methods for reactions that traditionally
prescreen the impact of positioning of the required precious metal catalysts (83). Coop-
Molecular catalysis secondary coordination sphere moieties; such erative catalysis using EAM complexes of two
studies could motivate synthetic efforts toward metals, Ti and Cr, has provided a highly selective
The modern molecular synthetic toolkit affords optimized secondary coordination sphere con- route to anti-Markovnikov alcohols through
virtually unlimited scope for tailoring the pri- trol in EAM catalysis. ring-opening of epoxides (84). This hydrogen-
mary, secondary, and outer coordination spheres ation of epoxides is unusual because at dif-
around a molecular EAM active site. Several Controlling transport to EAM active sites is ferent steps of the mechanism, a chromium
areas of exploration leverage this synthetic difficult to achieve with freely diffusing small complex transfers an electron, a hydrogen atom,
capability to embrace the distinctive physical molecules, but improved transport environ- and a proton.
properties of EAMs (Fig. 5). ments can be created by anchoring molecular
EAM active sites on the surfaces of, or within Aerobic oxidation of primary alcohols to
EAM active sites in nature are subject to the pores of, extended solid host materials aldehydes and H2O2 is catalyzed in natural
exquisite tuning by the arrangement of prox- including, for example, graphitic carbon, micro- systems by galactose oxidase, a copper-containing
imal amino acid residues and cofactors, as porous silica, and metal-organic frameworks enzyme. A bio-inspired synthetic binuclear cop-
well as by the enzyme channels that gate the (MOFs) (74). Solid-supported site-isolated EAMs per complex exhibiting metal-ligand cooperative
transport of reactants and products in and have been used to catalyze a wide array of reactivity catalyzes the oxidation of primary
out. Similarly, achieving precise control over reactions; they benefit from structural con- alcohols using O2 from air (85). Similar to the
the local environment and transport in syn- straints that prevent inhibitory bimolecular accepted mechanism for galactose oxidase, the
thetic molecular EAM catalysts is critical for reactivity between metal centers while facili- rate-determining step of the synthetic system
realizing their full potential. The ability to syn- tating catalyst separation and recycling. For is proposed to involve hydrogen atom transfer
thesize increasingly sophisticated ligands pro- these molecular materials, the extended lattice from a C-H bond of the alcohol to the oxygen-
vides control of steric and electronic attributes, can serve as scaffolding to incorporate secondary centered radical bound to Cu.
as demonstrated by remarkable progress in coordination sphere elements proximate to the
asymmetric hydrogenations, which are used embedded active site, and the pore structure Many of the EAM active sites that occur
extensively to achieve the enantioselectivity and dimensions can be used to gate the trans- naturally, particularly those carrying out multi-
required in the preparation of pharmaceut- port of reactants and products to and from electron redox transformations, feature multiple
icals and agrochemicals. This field has been the active site. MOFs with EAM active sites metal centers linked to each other in cluster
dominated by Rh- and Ru-based catalysts with have been deployed to carry out, for example, active sites or metal centers coupled to redox-
chiral diphosphines (56), but recent examples photocatalytic CO2 reduction (75), ethylene active cofactor ligands. The presence of these
show that EAM catalysts can offer outstanding hydrogenation (76), oxidation of alcohols additional metals and redox-active ligands ex-
selectivity. For example, an Fe complex cata- (77), olefin cyclopropanation (78), arene C-H pands the number of available redox states ac-
lyzes the asymmetric transfer hydrogenation borylation (79), tandem oxidation and function- cessible over a range of potentials. This increased
of ketones with performance superior to that alization of styrene (80), and selective oxidation density of electron states serves to buffer redox
of Ru catalysts (57), and a Co complex catalyzes of methane to methanol (81). Enzymes often changes at the metal center that binds and
the asymmetric hydrogenation of the C=C feature disparate channels that transport each activates the reactant, thereby lowering the
bond of enamides (58). energy barrier to multielectron transforma-
tions. Harnessing the full power of EAMs

Bullock et al., Science 369, eabc3183 (2020) 14 August 2020 6 of 10

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