Science January 2023

Teaming up to keep tabs on Young scientists’ Thousand Talents program a massive Amazon dam p. 18 favorite failures p. 24 nurtures Chinese scientists p. 62 $15 6 JANUARY 2023 science.org MELTING AWAY Glacial mass loss scales linearly with air temperature increase pp. 29 & 78

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CONTENTS 6 JANUARY 2023 • VOLUME 379 ISSUE 6627 18 16 Virus hunters test new INSIGHTS PHOTOS: (TOP TO BOTTOM DADO GALDIERI/HILAEA MEDIA; SILVIO AVILA/AFP/GETTY IMAGES surveillance tools Cleysson Juruna helps Ropes, drones, insects, and dust cloths LETTERS keep watch on how a giant could make monitoring faster, safer, and hydroelectric project is cheaper By J. Cohen 24 NextGen Voices: The fruits of failure affecting Brazil’s Xingu River. F E AT U R E S PERSPECTIVES NEWS 18 A river’s pulse 26 Wastewater surveillance for IN BRIEF In the Brazilian Amazon, Indigenous public health people and researchers join hands to monitor Wastewater contains information on 8 Areas to watch: What to expect the impacts of a controversial dam pathogen spread, evolution, and outbreak in research and policy risk By J. I. Levy et al. By S. Moutinho and D. Galdieri IN DEPTH PODCAST 11 China is flying blind as the pandemic rages 32 Official death tolls are impossibly low, and some worry new variants may escape science.org SCIENCE detection By D. Normile 12 Did ancient tentacled microbes kick-start complex life? New studies suggest early Asgards evolved into eukaryotes By E. Pennisi 13 Once banned, spending earmarks see resurgence Lawmakers can’t resist steering cash to universities and research projects back home By J. Mervis 15 Ancient points suggest Asian roots for early American tools Finds may support coastal route hypothesis for first settlers By M. Price 4 6 JANUARY 2023 • VOL 379 ISSUE 6627

28 Obesity confers macrophage memory 84 Epigenetic programming of myeloid cells in obesity contributes to macular degeneration In vivo imaging reveals a fourth meningeal layer in the brain. CREDIT: K. MØLLGÅRD ET AL. By K. D. Mangum and K. A. Gallagher 62 Expatriate scholars 100 Mpox Has China’s Young Thousand Talents Structure of monkeypox virus DNA RESEARCH ARTICLE p. 45 program been successful in recruiting polymerase holoenzyme Q. Peng et al. and nurturing top-caliber scientists? 29 Acting now will reduce glacier loss D. Shi et al. D E PA R T M E N T S Many of the world’s glaciers will disappear, but quick action will make a difference Development 7 Editorial 66 Immotile cilia mechanically sense the Energy in 2023 By G. Aðalgeirsdóttir and T. D. James direction of fluid flow for left-right By J. S. Yeston et al. RESEARCH ARTICLE p. 78 determination T. A. Katoh et al. 110 Working Life 30 Toward ultrathin optics 71 Cilia function as calcium-mediated Tired of persevering Function determines the minimum thickness mechanosensors that instruct left-right of an optical system By F. Monticone asymmetry L. Djenoune et al. By K. Hardeman RESEARCH ARTICLE p. 41 78 Glaciers ON THE COVER Global glacier change in the 21st century: Meltwater from Nepal’s Khumbu Glacier drains POLICY FORUM Every increase in temperature matters through an ice cave. By the end of the 21st D. R. Rounce et al. century, 49 to 83% of the world’s glaciers are 32 Soil biodiversity needs policy projected to disappear, depending on future without borders PERSPECTIVE p. 29 greenhouse gas emissions. Given that mass loss Soil health laws should account for global is directly related to temperature changes, every soil connections By W. H. van der Putten et al. 84 Brain anatomy A mesothelium divides the subarachnoid increase in temperature BOOKS ET AL. space into functional compartments matters. As glaciers K. Møllgård et al. respond to climate change, 35 The right to strive in a changing world societies must adapt to A philosopher prioritizes agency and 89 Metallurgy changes in water availabil- Anthropocene concerns in a theory of animal Machine learning–aided real-time detection ity, natural hazards, and justice By D. Jamieson of keyhole pore generation in laser powder sea level. See pages 29 and bed fusion Z. Ren et al. 78. Photo: Jason Gulley/ 36 Materialism meets transcendence American Reportage A new documentary series follows a 94 Plant science physicist’s pursuit of the profound Maize resistance to witchweed through Science Staff ..................................................6 changes in strigolactone biosynthesis New Products.............................................106 By R. S. Krauss C. Li et al. Science Careers ......................................... 107 RESEARCH IN BRIEF 37 From Science and other journals REVIEW 40 Optics Lithium niobate photonics: Unlocking the electromagnetic spectrum A. Boes et al. REVIEW SUMMARY; FOR FULL TEXT: DOI.ORG/10.1126/SCIENCE.ABJ4396 RESEARCH ARTICLES 41 Optics Why optics needs thickness D. A. B. Miller PERSPECTIVE p. 30 45 Immunology Past history of obesity triggers persistent epigenetic changes in innate immunity and exacerbates neuroinflammation M. Hata et al. PERSPECTIVE p. 28 SCIENCE (ISSN 0036-8075) is published weekly on Friday, except last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue, NW, Washington, DC 20005. Periodicals mail postage (publication No. 484460) paid at Washington, DC, and additional mailing offices. Copyright © 2023 by the American Association for the Advancement of Science. The title SCIENCE is a registered trademark of the AAAS. Domestic individual membership, including subscription (12 months): $165 ($74 allocated to subscription). Domestic institutional subscription (51 issues): $2411; Foreign postage extra: Air assist delivery: $107. First class, airmail, student, and emeritus rates on request. Canadian rates with GST available upon request, GST #125488122. Publications Mail Agreement Number 1069624. Printed in the U.S.A. Change of address: Allow 4 weeks, giving old and new addresses and 8-digit account number. Postmaster: Send change of address to AAAS, P.O. Box 96178, Washington, DC 20090–6178. Single-copy sales: $15 each plus shipping and handling available from backissues.science.org; bulk rate on request. Authorization to reproduce material for internal or personal use under circumstances not falling within the fair use provisions of the Copyright Act can be obtained through the Copyright Clearance Center (CCC), www.copyright.com. The identification code for Science is 0036-8075. Science is indexed in the Reader’s Guide to Periodical Literature and in several specialized indexes. SCIENCE science.org 6 JANUARY 2023 • VOL 379 ISSUE 6627 5

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EDITORIAL Energy in 2023 T he new year 2023 arrives with promising de- mat still requires the focused writing that enhances the Jake S. Yeston velopments in fusion research. In December, clarity of the published papers, but without compromis- Editor of Research, scientists at the US National Ignition Facility ing transparent reporting on the work. Supplementary Science. jyeston@ (NIF) focused 2.05 megajoules of laser light Materials will continue to be published online, with the aaas.org onto a capsule of fusion fuel and produced accompanying data, curated at repositories such as Ze- 3.15 megajoules of energy. This was the first nodo and Dryad, expected to grow. We will continue to Valda Vinson Executive Editor, laser-driven fusion demonstration in which allow some longer Research Articles to appear online Science. vvinson@ aaas.org the reaction produced more energy than the laser and with a one-page summary in the print magazine. H. Holden Thorp light used to start it—a goal set for NIF at its found- Up until now, two criteria for retractions have been ex- Editor-in-Chief, Science journals. ing. Massachusetts Institute of Technology physicist plained in the Editorial Policies. One applies to instances [email protected]; @hholdenthorp Anne White, who was not involved in the work, de- when misconduct is clearly demonstrated, and the other scribed it to Science as “a major breakthrough.” Af- concerns errors that undermine the core conclusions of ter a year of ups and downs in science policy and a paper. All other errors were often accommodated by research, this was the kind of exciting event needed Science’s publication of an Erratum or a Corrections to propel scientists into the notice. We are now adding a promises of 2023. third criterion for when a pa- As always, with these kinds of “We are making a per has received enough cor- advances, scientists and the fed- rections or contains enough eral government must be careful number of important errors to cause the editors to not to exaggerate the practical lose confidence in it. Although implications. The achievement changes to Science has always had the lati- was announced at a high-profile our Information tude to retract a paper for rea- press conference hosted by the sons deemed sufficient to the US Secretary of Energy. But as for Authors editors, we are now stating this Science’s Daniel Clery wrote, and Editorial Policies.” additional criterion explicitly. “fusion power stations are still a distant dream.” The NIF re- The analysis of published sult is a glimmer of promise, images in research papers has but many technical challenges become more prominent and cataloged on sites like Pub- still lie ahead. Scientific results Peer, and image sleuths like announced by press conference Elisabeth Bik have brought prior to the publication of a peer-reviewed paper do not more energy to the careful maintenance of the sci- always hold up well, so we will have to wait to see the entific record. Scientists are human, and mistakes— data, hopefully this year. whether intentional or inadvertent—are inevitable Similarly, 2023 brings new energy to Science. We are by both authors and journals. Fortunately, science is making a number of important changes to our Informa- a self-correcting process that ultimately leads to the tion for Authors and Editorial Policies. These include right answer. Unfortunately, when we contact authors updating the types of research papers that we publish about concerns that have been raised about their Sci- and adding a new category for retractions. ence papers, we are often met with defensiveness and Over the history of the magazine, research papers denial. That needs to change. A quick correction or have gotten longer and longer with more data and fig- retraction builds confidence that we all are commit- ures. These developments are good for open science, ted to an accurate scientific record. The community as the experimental methods and results must be re- needs to work to reduce the stigma of correcting the ported in sufficient detail to allow reproducibility. As a record so that—in this time of extraordinary scrutiny result, Science is ending the category of Reports, which and waning confidence—we can show the world that were shorter than Research Articles. Now there will be self-correction provides a basis for trust. We hope that one category of research paper—the Research Article— this new criterion for retractions will contribute to en- which will be around five pages in the printed journal. hancing that trust. This will typically include 2000 to 3000 words of text, Here’s to an energetic 2023—for fusion and more. three to five figures, and 50 references. The majority of Science’s papers already fit into this category. This for- –Jake S. Yeston, Valda Vinson, H. Holden Thorp 10.1126/science.adg4111 SCIENCE science.org 6 JANUARY 2023 • VOL 379 ISSUE 6627 7

NEWS IN BRIEF Edited by Jeffrey Brainard AREAS TO WATCH: WHAT TO EXPECT IN RESEARCH AND POLICY Science strives to keep up with an evolving coronavirus A s the COVID-19 pandemic enters its fourth year body’s mucosal linings; compared with shots in the arm, PHOTO: JULIAN RETTIG/PICTURE ALLIANCE/DPA/AP IMAGES as a global health emergency, researchers will these should elicit a stronger, quicker defense against continue pushing to help make the disease man- initial infection. But public health specialists worry ageable and ordinary. They will track hundreds widespread vaccine hesitancy may persist, with long- of subvariants of Omicron, the highly transmis- lasting consequences for battles against both COVID-19 sible but seemingly less lethal strain of SARS- and other diseases. The search for effective treatments CoV-2 that dominated in 2022. Virologists will watch for COVID-19 will reboot because the evolution of the vi- the virus’ evolution this year to see whether it has fi- rus has made several existing antibody-based drugs in- nally slowed or a more dangerous variant pops up, evad- effective. Randomized trials of potential drugs to treat ing much of the immunity that humanity has Long Covid may yield their first results, bene- built up to previous ones. Vaccine researchers A crowd boards a fiting millions of people suffering from fatigue hope to develop new shots that provide broad bus in Germany, where and other debilitating symptoms. protection against a variety of coronaviruses. some states have In the rest of this section, Science’s News staff Another priority is to introduce nasal vaccines that prompt immune responses within the eased masking rules forecasts other areas of research and policy for passengers on likely to make headlines in the coming year. local public transit. 8 6 JANUARY 2023 • VOL 379 ISSUE 6627 science.org SCIENCE

Nations mull climate-losses pact which they remove a patient’s blood stem threatened or endangered. Scientists cells, use the CRISPR gene-editing tool to expect the new data will boost comparative C L I M AT E P O L I CY | This year, diplomats switch on a healthy gene for fetal hemo- genomics studies and provide insights into from two dozen countries will debate the globin, which cells shut off after birth, and evolution and life history. terms of an agreement requiring wealthy reinfuse the modified cells. The one-time nations, responsible for most historical treatment has ended most patients’ severe A bid to end mpox greenhouse gas emissions, to help pay for pain episodes and the need for blood damages caused by climate change. The transfusions. The companies are seeking PU B L I C H E A LT H | Health authorities will commitment was the only substantive new approval from U.S. and European regula- strive this year to eliminate human-to- policy to emerge from the U.N. climate tors, and a decision on at least one side of human transmission of mpox (previously summit in Egypt in November 2022. A new the Atlantic could come by year’s end. The known as monkeypox), which in 2022 fund would pay for economic losses and next concern will be cost. Gene therapy, exploded across the globe for the first time. property damage linked to heat, flooding, an older approach that treats genetic More than 80,000 people were sickened, and other effects of climate change. But disorders by adding rather than modify- prompting the World Health Organization signatories put off details, such as which ing genes, has come with price tags from to declare a Public Health Emergency of countries should pay, which should benefit, $850,000 to $3.5 million. International Concern. As the year ended, and how the money should be spent. Those the number of new cases had declined details could come into focus at this year’s Animal genomes proliferate steeply, but hundreds of cases were still U.N. climate summit in the United Arab reported every week. Experts hope to better Emirates. Observers are skeptical about GENOMICS | Scientists have sequenced and understand how much of the decline stems the deal’s prospects, noting that wealthy studied thousands of human and microbial from immunity built up through infections nations have failed to honor past promises genomes, but the complete deciphering and immunizations and how much can to provide such financial support. of the DNA of other multicellular organisms be explained by behavior change in the has lagged. A new chapter will begin this most affected group: gay men and their Big funders to get new leaders year, when a surge of nonhuman genome sexual networks. Studies underway could sequences will be unveiled, the fruits of reveal how well the one vaccine, a repur- B I O M E D I C I N E | Two of the world’s larg- cheaper, more precise technologies. The posed smallpox shot, protects against the est biomedical research sponsors—the Earth BioGenome Project, an umbrella effort disease and compare different doses and U.S. National Institutes of Health (NIH) that encompasses more than 50 sequencing ways to administer the shots. Whether the and the Wellcome Trust—will likely get efforts covering a broad range of organisms, vaccine will be available in African countries new directors this year. Researchers have expects to see 2000 sequences released this that have long experienced mpox outbreaks grown impatient waiting for the White year. Many groups under that umbrella have will be a crucial test of global health policy. House to nominate a successor to Francis focused on particular types of animals: For Collins, who stepped down as director of instance, the Wellcome Sanger Institute’s China to launch space telescope the $47.5-billion-a-year NIH in December Darwin Tree of Life Project has been study- 2021. The agency’s next leader, who will ing insects and other invertebrates, and the ASTRONOMY | China’s space science efforts require Senate confirmation, will over- Zoonomia Project has scrutinized mammals. will continue to mature with the launch see NIH’s efforts to boost diversity in the Two other consortia will release sequences of three missions this year, including the research workforce and likely face a grilling of more than 200 nonhuman primates, Chinese Survey Space Telescope, also by Republican lawmakers over the agency’s many of which have been designated called Xuntian (“sky survey”). The 2-meter response to the COVID-19 pandemic. Also PHOTO: MARCELO ISMAR SANTANA/UNIVERSITY OF BRAZIL awaiting a permanent director is NIH’s $6.6 billion National Institute of Allergy and Infectious Diseases, which Anthony Fauci led for 38 years before he stepped down last month. In addition, Wellcome, a nonprofit organization that provides more than £1 billion annually for research, will seek a replacement for Director Jeremy Farrar, who announced he will leave early this year after a decade in that role to become chief scientist of the World Health Organization. Human gene editing nears OK The Vieira’s titi monkey (Plecturocebus vieirai) in Brazil is among many endangered species of primates whose genomes will be published, in one of several projects that have been sequencing the DNA of animal species. BIOMEDICINE | The new year could bring a milestone for medicine: the first approved medical treatment based on gene editing. People with sickle cell disease and beta-thalassemia carry defects in the gene for hemoglobin, the oxygen-carrying protein in blood. The biotech companies Vertex Pharmaceuticals and CRISPR Therapeutics have run clinical trials in SCIENCE science.org 6 JANUARY 2023 • VOL 379 ISSUE 6627 9

NEWS | IN BRIEF telescope, China’s first space-based optical 12 candidate sites around the world that scientists want to see more data about probe, is not quite as big as the 2.4-meter contain lake muds, ice cores, or other Qdenga’s safety. Their wariness comes from Hubble Space Telescope, but it will have features that clearly document the shift in experience with Dengvaxia: Children who a field of view 350 times larger, benefiting emissions and could be used to formally had never been infected by the virus and astronomical surveys. It will study exo- define the new epoch. After the working received the vaccine had a higher risk planets, star formation, and galaxy evolu- group announces its choice, three more of severe symptoms. This problem—which tion, as well as dark matter and dark energy, committees will have to approve it. Should may be linked to an unusual phenom- mysterious phenomena that control the the definition be voted down, it cannot be enon in which antibodies to one group of expansion of the universe. The telescope will reconsidered for 10 years. Passage is far dengue viruses “enhance” the ability of a fly in the same orbit as China’s Tiangong-3 from guaranteed. Many geologists acknowl- distinct second group to infect cells—has space station and be able to dock for main- edge the unprecedented changes wrought not occurred in Qdenga trials. tenance. Xuntian is scheduled to launch in by human activity but question the need to December and start observations in 2024. change a system that describes millions of Amazon conservation reboots The Chinese Academy of Sciences’s National years of geologic time to mark shorter lived Astronomical Observatories has promised to events driven by humanity. LEADERSHIP | Brazil’s new left-wing presi- share the data. China’s other two missions dent, Luiz Inácio “Lula” da Silva, is expected are x-ray observatories—the Space Variable Dengue vaccine nears debut this year to renew efforts to protect the Objects Monitor, a joint project with France, Amazon and fight climate change—a rever- and the Einstein Probe, in cooperation with I N F ECT I O US D I S E AS ES | A new vaccine sal from the pro-development agenda of the European Space Agency. against dengue won approval in Europe his far-right predecessor, Jair Bolsonaro, last month and may soon become widely who presided over record deforestation. Anthropocene may get a marker available in Indonesia, protecting far more Lula, who was also president from 2003 to people than a product currently on the 2010, has promised to end illegal deforesta- GEOLOGY | Researchers will soon market. Only people previously infected tion. He may start by revoking hundreds announce their choice of a site to serve as by the virus can safely take a dengue vac- of laws and decrees issued by Bolsonaro the “golden spike” for the Anthropocene cine marketed since 2015, Sanofi Pasteur’s that weakened policing of illegal logging epoch, a controversial proposal to designate Dengvaxia. Now, the pharmaceutical com- and mining. Enforcement may be limited an official geological span of time marked pany Takeda has shown in multicountry by other demands on Brazil’s budget, by humanity’s indelible effects on the studies of more than 28,000 people that its however, such as fighting rising poverty. planet. The Anthropocene Working Group, vaccine, Qdenga, can safely protect people But other countries might help by reinstat- assembled by the International Commission never infected by dengue. The virus causes ing subsidies to support conservation that on Stratigraphy, already picked the 1950s, fever and other debilitating symptoms were suspended during Bolsonaro’s term. an era of surging fossil fuel use, as the start in an estimated 100 million people a year, Norway and Germany both resumed such of the epoch. And the group has reviewed and, in rare cases, can be fatal. Some contributions days after Lula’s election in October 2022. Researchers remove a sediment core at Crawford Lake in Canada, a site under consideration to mark South Africa tells Homo’s story humanity’s geological footprint. H U M A N O R I G I N S | New analyses this year could lend support to the idea that key PHOTO: BRENNA BARTLEY/CONSERVATION HALTON events in the evolution of our genus, Homo, happened in South Africa. Researchers working in Kromdraai Cave say they plan to publish descriptions of newly unearthed fossils of Homo that may date to earlier than 2 million years ago—soon after the date of the earliest Homo fossils, 2.7 million years ago in east Africa. Distinctive fea- tures of the Kromdraai fossils, including rarely found lower limbs, could bolster a controversial hypothesis that fossils discov- ered last year at nearby Drimolen quarry belonged to H. erectus, a direct human ancestor—which might indicate that the species first appeared in South Africa rather than in east Africa or Asia, as many have thought. Analyses of other new South African fossils, including forerunners of Homo, could also help untangle the histo- ries and relationships of hominin species that lived in the area. SCIENCE.ORG/NEWS Read more news from Science online. 10 6 JANUARY 2023 • VOL 379 ISSUE 6627 science.org SCIENCE

IN DEPTH Tongren Hospital in Shanghai was overflowing with patients on 3 January. Even basic epidemiological data about China’s COVID-19 wave are lacking. COVID-19 China is flying blind as the pandemic rages Official death tolls are impossibly low, and some worry new variants may escape detection PHOTO: HECTOR RETAMAL/AFP/GETTY IMAGES By Dennis Normile scientists worry a genomic monitoring plan long been inconsistent, Huang says, with unveiled last month doesn’t have the power some regions reporting all fatalities in which M ost scientists believe China’s deci- to detect new SARS-CoV-2 variants arising SARS-CoV-2 was a factor, as most countries sion to end its zero-COVID policy as the virus works its way through one-fifth do, and others excluding people who died was long overdue. But now they of the world population. from other conditions, such as heart attacks, have a new worry: that the country even if they had COVID-19. In early Decem- is collecting and sharing far too lit- Earlier in the pandemic China’s daily ber, China’s government decided the nar- tle data about the rough transition counts of COVID-19 cases and deaths, based rower definition should be used nationwide. to a new coexistence with the virus. partly on its exhaustive testing programs, were generally believed to be accurate. Now, Even then, the official count is astonish- China abruptly dropped virtually all con- they are anyone’s guess. Patients with mild ingly low: just eight deaths for the entire last trols a month ago, after protests, a sagging symptoms are not encouraged to get tested, week of December, which is “not matching economy, and the extreme transmissibility let alone those who are asymptomatic. Peo- media reports and what is being seen on of the virus’ latest variants made clinging to ple testing positive at home are not asked to social media,” says Louise Blair, who tracks zero COVID untenable. Now, “SARS-CoV-2 report their results. China’s COVID-19 outbreak for Airfinity, a has an open goal in front of it: a population London-based health analytics firm that with very low levels of standing immunity,” The China Center for Disease Control and estimates about 9000 people were dying of says evolutionary biologist Edward Holmes Prevention (China CDC) put the number of COVID-19–related causes every day in late of the University of Sydney. But how the epi- confirmed cases the last week of Decem- December. Also missing are data on case fa- demic is unfolding is a mystery because the ber 2022 at more than 35,000—a fraction tality rates, the average number of new infec- country has practically stopped collecting of the official number in the United States. tions stemming from each case, and hospital basic epidemiological data. But leaked notes from an internal meeting and intensive care admissions. “These are suggest a very different reality: The agency critical data” that would help health authori- Models that predicted a massive wave was told that almost 250 million people in ties get a handle on the surge and further the of infection and death if China ended China—roughly 18% of the population— world’s understanding of the pandemic, says zero COVID appear to have been correct. may have caught COVID-19 in the first Xi Chen, a public health scientist at the Yale Press reports and social media posts have 20 days of December. Some experts said School of Public Health. shown intensive care units stretched be- the number is implausibly large, but yond capacity, with crowds of patients in Yanzhong Huang, a global health specialist A major worry is that the wave will breed wheelchairs and on gurneys in hallways. at the Council on Foreign Relations, a U.S. a new and even more troublesome SARS- Doctors and nurses are reportedly working think tank, says it’s “not unreasonable,” CoV-2 variant. “It’s possible that something while sick. Crematoriums are overwhelmed. given credible reports that 80% of Beijing might be emerging, because there is such a But China’s official COVID-19 death toll is residents have been infected by now. big population in China,” says George Gao, widely considered laughably low. And some who in July 2022 stepped down as head of As to the death toll, China’s reporting had SCIENCE science.org 6 JANUARY 2023 • VOL 379 ISSUE 6627 11

NEWS | IN DEPTH China CDC but is now helping track circu- Images of Lokiarchaeum lating variants. But, he told Science, “There ossiferum (left) suggest its are no novel mutants—yet.” At a 20 Decem- ber press briefing, Xu Wenbo, head of the ancient relatives were National Institute for Viral Disease Control precursors to the complex and Prevention, explained that the BA.5.2 cells of plants and animals. and BF.7 Omicron subvariants, which are now causing most infections globally, are EVOLUTION also dominant in China. BQ.1 and XBB, which have recently been spreading in Eu- Did ancient tentacled microbes rope and North America, have turned up in kick-start complex life? limited numbers in several provinces. New studies suggest early Asgards evolved into eukaryotes Experts are split on whether China is look- ing closely enough. Three designated sentinel By Elizabeth Pennisi and eukaryotes, the evolutionary branch that PHOTO: THIAGO RODRIGUES-OLIVEIRA/UNIVERSITY OF VIENNA hospitals in different cities in each of China’s encompasses everything from microbes such 31 provinces, municipalities, and regions are W hat may be the earliest ancestors as yeast to humans. Still, archaea and bacte- supposed to sequence and analyze samples of humans, plants, and all other ria have key similarities: Both generally lack from 15 outpatients, 10 severe cases, and all complex life are coming out of the core eukaryotic features such as mitochon- deaths every week. “I’m afraid [that] sample shadows. The unusual tentacled dria, cells’ internal powerhouses, or DNA size is too small,” Chen says. A stronger plan microbes called Asgards were ini- encased inside a nucleus. Many researchers would consider province size and popula- tially known just from DNA ex- think early eukaryotic cells arose some 2 bil- tion density, instead of picking three cities in tracted from marine sediments. Then, one lion years ago when an archaeon engulfed each, and adopt other sampling approaches, was grown a few years ago in the lab—but in bacteria, which eventually became the mito- says Elizaveta Semenova, an epidemiologist such low numbers that only its genome could chondria. But they have struggled to explain at the University of Oxford. Semenova is a be studied in detail. Now, recent studies are how other features of eukaryotes evolved, co-author of a study of how well 189 coun- painting a clearer portrait of these organisms such as their many internal structures. “Un- tries have detected new variants, published and strengthening the case that the complex til recently, life’s journey towards complexity in November 2022. It concluded that effec- cells making up all multicellular life—and was a blur,” says Masaru Nobu, a microbio- tive surveillance requires sequencing about some single-cell organisms—are descendants logist at Japan’s National Institute of Ad- 0.5% of cases, with a turnaround time of less of ancient Asgard-like microbes. vanced Industrial Science and Technology. than 21 days. China’s plan is unlikely to come close to that percentage. Some recent work has shown that As- The idea that Asgard-like archaea might gards, which belong to a group of rudimen- be the ancestors of eukaryotes emerged in But Gao and others say the program will tary life forms known as archaea, have genes 2015. Thijs Ettema, an environmental micro- pick up new variants in a timely way. If the once thought to exist only in more complex biologist at Wageningen University, discov- surveillance plan gets up to speed, it will organisms. And in the most striking study, ered eukaryotelike genes in archaeal genetic sequence 2000 to 3000 genomes per week, published last month in Nature, research- material from sediment samples collected by a level that “should be able to detect [new ers cultured a second Asgard, found in mud Christa Schleper, now a microbiologist at the variants] and their transmission trends,” from an estuary in Slovenia. They managed University of Vienna, and her student, Steffen says Leo Poon, a virologist at the University to grow enough for individual microbes to be Jørgensen. By 2017, Ettema had found simi- of Hong Kong who has helped track variants imaged with electron microscopy, revealing lar genes in several more groups of archaea, there. Poon notes that China is sharing data complex internal structures suggestive of which he collectively called the Asgards, after from the outbreak on GISAID, the world’s those in our own cells, such as the complex the home of the Norse gods. largest database of SARS-CoV-2 sequences. cytoskeleton made of the protein actin. At the time, however, Ettema knew the As- In addition to China CDC, research groups “This paper is beautiful,” says Buzz gards only from roughly assembled genomes at more than 30 hospitals and universities Baum, an evolutionary cell biologist at the cobbled together from environmental DNA are also tracking SARS-CoV-2 variants, says Medical Research Council’s Laboratory of (eDNA)—the jumble of genetic material a Chinese epidemiologist who asked not to Molecular Biology in London. “The images from many organisms in a soil or water sam- be identified. These groups “will report im- are stunning.” ple. Skeptics argued he couldn’t be sure the mediately if a dangerous variant emerges,” eukaryotelike genes really belonged to ar- the source says. Considered a third domain of life by most chaea. But in 2019, Nobu, with microbio- scientists, archaea are distinct from bacteria Still, the lack of reliable data is already undermining faith in China’s handling of the outbreak. A dozen countries, includ- ing the United States and France, have an- nounced they will require pre- or postflight tests on air travelers from China. Huang says that is unlikely to keep new variants out. The goal should be to convince the Chi- nese to be more forthcoming about what’s happening on the ground—and for that, “quiet diplomacy may work better than travel restrictions,” he says. j With reporting by Bian Huihui. 12 6 JANUARY 2023 • VOL 379 ISSUE 6627 science.org SCIENCE

logist Hiroyuki Imachi of the Japan Agency microbes and their complex innards. U.S. BUDGET for Marine-Earth Science and Technology The new Asgard, which is different enough Once banned, spending and colleagues, cultured the first Asgard mi- from those studied before to deserve its own earmarks see resurgence crobe, isolated from ocean mud off Japan, genus with the tentative name Lokiarchaeum Lawmakers can’t resist and reported that its genome also had eu- ossiferum, has thickenings and small bubbles steering cash to universities and research projects karyotic genes. along the tentacles. Its cell wall, too, is com- back home Additional evidence came earlier this year plex, with tiny lollipop structures sticking By Jeffrey Mervis when Victoria Orphan, a geobiologist at the out, as if to sample the environment. “Over- T he $1.7 trillion spending package that President Joe Biden signed into law California Institute of Technology, and her all, the cellular structures of [these cells] last week does more than fund the entire U.S. government for the first colleagues isolated enough of two other As- look like they come from another planet,” 9 months of this year. Senators and members of the House of Repre- gard species—this time from a hydrothermal Ettema says. sentatives from both parties also used it to funnel $15 billion to 7200 projects in vent in the Gulf of California—to sequence Its genome is larger and richer in eukary- their districts that federal funding agen- cies never requested. The projects include their complete genomes. Their genes also otic genes than that of the other cultured new research facilities and academic programs at hundreds of public colleges suggested a kinship with eukaryotes, Orphan Asgard, and it includes four genes for the and universities. and her colleagues reported on 13 January protein actin, a key component of a eukary- That spending signals the robust re- surgence of earmarks, the sometimes 2022 in Nature Microbiology. otic cell’s internal skeleton, Schleper’s team controversial—and until recently banned— practice in which legislators reward Researchers including Ettema, Baum, and reports. That skeleton extends throughout constituents using their constitutional au- thority over federal spending. The dollar Mohan Balasubramanian, a cellular micro- the cell and into the tentacles, and it var- amount and number of earmarks rose by half over last year, according to one count biologist at the University of Warwick, re- ies from cell to cell, suggesting it’s capable by The New York Times. The new total also tops levels seen before Congress banned cently pinpointed a more specific link. They of being rearranged. “We show that the ‘eu- the practice in 2010 after some notorious earmarks drew widespread ridicule—and scanned the Asgard genomes sequenced so karyotic’ cytoskeleton—which is crucial for figured in the conviction of one lawmaker for accepting bribes. far for genes encoding the protein complexes eukaryotes—was an invention within ar- However, in early 2021 Congress re- that eukaryotic cells use to shape and stitch chaea,” Schleper says. moved the ban starting with the 2022 fis- cal year. Proponents argued successfully together membranes to form internal com- “This study further strengthens [the that such directed funding addresses lo- cal and state needs, increases support for partments. Known archaea lack idea] that our ancestor is ar- must-pass spending bills, and serves as a counterweight to the spending priorities of those same compartments and chaea,” Imachi agrees. He and the executive branch. others now believe the most “Until recently,were believed to have no more Most earmarks do not relate to sci- ence; they typically fund transportation than two of the protein com- life’s journey likely scenario for the emer- upgrades, new housing, or other forms plexes. But Asgard genomes con- towards gence of eukaryotes is that of regional economic development. Still, tain instructions for making four an Asgard-like microbe en- research-related earmarks make many sci- entists uncomfortable. One complaint is of them, the team reported on complexity veloped other bacteria to cre- 13 June 2022 in Nature Commu- ate the complex eukaryotic nications, just one short of five was a blur.” cell, with its many organelles complexes in eukaryotic cells. and compartments. In the lab, the Asgard proteins Masaru Nobu, Others, however, aren’t per- appeared to work similarly to National Institute of suaded by this scenario. Sven the eukaryotic versions. To the Advanced Industrial Gould, an evolutionary cell bio- scientists, that suggests the mem- Science and Technology logist at Heinrich Heine Uni- brane-manipulating machinery versity Düsseldorf, calcu- predates the evolution of eukaryotes. lated from genomic data that Asgard Firming up the links between eukaryotes archaea contributed very little to the first and Asgards would require more lab studies, eukaryotes—as little as 0.3% of their pre- and an example that grew more readily than dicted protein families. In a 10 November the Japanese find. It took 12 years of trial and 2022 paper in eLife, he and his colleagues error to culture that first Asgard, and the sec- propose that complex features of the eu- ond one from Slovenia wasn’t much easier. “I karyotic cell came not from an Asgard, didn’t know how difficult it would be,” says but from the effects of stress on a much Schleper, who led the 7-year project. simpler ancestor after it absorbed bacteria. With their long tentacles, the Asgard cells In this view, the stresses spurred the evo- are fragile, a barrier to concentrating and lution of eukaryotic features such as the growing them. Schleper’s postdoc Thiago nucleus, the network of membranes and Rodrigues-Oliveira figured out culturing internal compartments called the Golgi tricks that helped keep cells intact and tried apparatus, and even sexual reproduction. different combinations of nourishment— Ettema agrees that the full story has yet including milk powder—until he hit a sim- to unfold. He notes that based on eDNA ple formula that encouraged growth. The sampling by his group and others, the two resulting high concentrations enabled the cultured Asgards represent just a small team to create samples for cryo–electron to- subset of the group’s diversity, and the true mography, a technique in which fast-frozen ancestor of eukaryotes may still be at large. specimens are viewed at many angles by an So, he and others are trying to culture and electron microscope to develop a composite characterize other Asgards. image. After solving a further challenge— “It will be exciting to see what other picking out Asgard cells from other cells in Asgard-like archaea are discovered and what the images—the team had a clear view of the they look like,” Baum says. j SCIENCE science.org 6 JANUARY 2023 • VOL 379 ISSUE 6627 13

NEWS | IN DEPTH that those earmarks don’t go through the from the National Science Foundation— they requested, and they couldn’t fund merit-based competition used to allocate but has loftier ambitions. And when MSU for-profit entities or projects that would most federal research dollars. Science ad- needed a new science building, Smart benefit them directly. A few legislators vocates also worry the growth in earmarks turned to the state’s senior U.S. sena- opted for even greater transparency, get- might shrink the pot available for competi- tor, Republican Roy Blunt, who delivered ting input from community leaders on tively awarded grants. $85 million in earmarks. what earmarks they should request. House members were also limited to 10 requests, Legislators acknowledge that the ear- “Our science classrooms and labs are in although last year the cap was raised to 15. marking process can appear arbitrary. But buildings that are 50, 70, and 90 years old even those who favor more funding for and that require more than $100 million to Only a tiny fraction of the thousands competitive research also seek earmarks, bring them up to today’s standards,” Smart of accounts that fund government ac- seeing them as another way to increase says. “We would not have been able to do tivities are designated for earmarks. But federal support for research. that without the directed spending that their presence is significant at one science Senator Blunt championed for us.” agency, the National Institute of Standards “If there were a perfect science of how and Technology (NIST). This year, ear- to go about [funding research], we would Blunt, whose long tenure on the Senate marks comprise more than half of the ad- probably embrace that,” says just-retired appropriations committee has given him ditional $103 million the agency received Representative Eddie Bernice Johnson (D– considerable influence, inserted earmarks for its in-house research account and nearly one-quarter of NIST’s overall bud- Senator Roy Blunt (R–MO, center) toured Missouri State University’s aging science building with MSU President get of $1.6 billion. Clif Smart (right) before earmarking $85 million to renovate it. Blunt and several other prolific ear- TX), outgoing chair of the House science worth more than $300 million into each of markers who didn’t run for reelection in PHOTO: KEVIN WHITE/MISSOURI STATE UNIVERSITY committee. “But there is not. And so we try the last two federal spending bills. Those November 2022 went out with a bang. to use every opportunity to make sure that totals make him one of the top five ear- The reigning king, Senator Richard Shelby the importance of research is recognized.” markers in Congress. (R–AL), routed $762 million to his home Johnson’s earmarks in this year’s appro- state in the new spending bill. Shelby also priations bill include $2 million for Texas If each of the 535 members of Congress pioneered the concept of federally funded Tech University’s Health Sciences Center secured as many earmarks as Blunt, this endowments to hire and support faculty, in her Dallas district. year’s tally would have topped $160 bil- sending a total of $100 million to the Uni- lion. That’s twice what nondefense agen- versity of Alabama, Tuscaloosa, over the There’s little research on how the out- cies now spend annually on science. But past 2 years. Another departing champion, comes of science-related earmarks com- Smart says the re-emergence of earmarks Senator Patrick Leahy (D–VT), steered $212 pare with those produced by competitive is not his concern. million to his state, including a $30 million awards. But a recent study of projects that faculty endowment for the Honors College legislators inserted into one Department “There probably should be some limits at the University of Vermont. of Energy program to fund hydrogen re- or constraints,” he says. “But I’ll let people search found they generated as many pub- smarter than me worry about what the Blunt’s total includes $61 million for lications and patents as projects chosen caps ought to be. We’ve got 24,000 students research facilities at the state’s flagship via merit review. [at MSU], 2500 of whom are majoring in University of Missouri, Columbia, and science and another 8000 of whom take $20 million for an innovation center at Clif Smart, president of Missouri State [science] classes. … My responsibility is its Rolla campus. He has also funneled University (MSU), is one academic who making sure they have adequate facilities.” $6 million to MSU for an endowment to doesn’t see any downside to earmarks. The attract and retain science faculty. former teachers’ college has a minuscule In reinstating earmarks, the Democrats research portfolio—it ranked 321st among who controlled Congress adopted rules MSU will miss Blunt’s presence in Wash- U.S. universities in 2021, according to data designed to prevent the worst abuses. ington, D.C., Smart says. “My guess is that we Members had to disclose every earmark will get substantially fewer directed expen- ditures,” he predicts, noting that Missouri’s two senators, including Blunt’s successor, oppose the practice on the grounds that it wastes precious government resources. But relatively few members of Congress have taken such a stance. House Repub- licans recently rejected by a three-to-one margin a proposal to reinstate the earmark ban after they assume control this week. In Missouri, meanwhile, Blunt’s gener- osity to MSU won’t be forgotten. The cur- rent science building is named for Allen Temple, a pioneer in communications technology who chaired the school’s sci- ence department for 40 years in the early 20th century. But last month the school’s trustees renamed the new facility Roy Blunt Hall, and relegated recognition of Temple’s long service to the university to a plaque in the atrium. j 14 6 JANUARY 2023 • VOL 379 ISSUE 6627 science.org SCIENCE

Found on the banks of an Idaho river, these ancient points resemble even older ones from Japan. ARCHAEOLOGY making it one of the earliest known human- occupied sites on the continent. Ancient points suggest Asian roots for early American tools For the new work, Davis’s team—including interns from the Nez Perce Tribe—went Finds may support coastal route hypothesis for first settlers 25 meters upriver from previous digs and unearthed three cylindrical pits that con- PHOTO: LOREN DAVIS By Michael Price in an ice-free corridor. At the time, an over- tained the spear points and hundreds of bits land route into the North American conti- of bone, likely from animals, that an outside T hirteen razor-sharp projectile points nent from the Bering Strait would have been lab radiocarbon dated to between about found along a river in southwestern blocked by massive ice sheets. But some re- 16,000 and 15,600 years ago, firming up the Idaho appear to represent the oldest searchers have proposed that the earliest mi- dates reported in the earlier study. evidence so far of toolmaking in the grants from Siberia boated along the shore of Americas—and may bolster the idea an ice-covered Bering Strait. “If you’re com- Smith says the new analysis brings that the first people to reach the re- ing south along the Pacific coastline entering “needed rigor” to the previous Cooper’s Ferry gion migrated from Asia in boats along the North America … the first major left-hand dates. But Ben Potter, an archaeologist at the coast of the Pacific Ocean. turn south of the ice is the Columbia River, University of Alaska, Fairbanks, remains un- and if you head upstream, you can get to convinced, arguing the artifacts from the pits Likely deposited into pits by a group of Cooper’s Ferry,” says Loren Davis, an Oregon are too jumbled to conclusively link them to hunter-gatherers, the points were recently State University, Corvallis, archaeologist who any of the animal bone dates. “Their precise dated to between 16,000 and 15,600 years led the new study. age remains unclear, in my opinion.” ago, according to a study in Science Ad- vances last month. The tips are examples of Devastating floods and avalanches de- Although no genetic evidence connects “stemmed point technology,” which allowed stroyed or buried nearby valleys, but Coo- the ancient toolmakers to modern Nez Perce ancient people to fashion weapons from per’s Ferry was relatively unscathed, he says. people, Williamson-Cloud says he believes a wide range of available stone. Based on “As far as we can tell, people early on decided “these are truly our ancestors. … It’s a place the objects’ similarities to even older points this was a really great place to live, and they where our lineage came from—people who found in East Asia, the blueprint for mak- kept coming back over and over and over are alive today.” ing the Idaho points may have come with again.” That tracks with Nez Perce history, the Americas’ original settlers, the study au- says Nakia Williamson-Cloud, cultural re- Davis and the study’s other authors, who thors propose. sources program director for the tribe, on include Japanese and Chinese archaeo- whose lands the artifact-filled site sits. Sto- logists, think there’s a good case to be made A lot more work will need to be done to ries passed down over thousands of years tell that the first migrants from Asia brought prove that, says Heather Smith, an archaeo- of a young couple founding the village after with them the rough-and-ready stemmed logist at Texas State University, but “it looks a catastrophic flood destroyed their previous point technology, with fluted ends that were like a really interesting agenda to pursue.” home across the river. wedged into spear tips. The points at Coo- per’s Ferry, they say, most closely resemble The site where the points were unearthed Davis began working at Cooper’s Ferry in projectile points made by people who lived a few years ago is on the banks of Idaho’s 1997 as a graduate student and never left. In near modern-day Hokkaido, Japan, some Salmon River. The Nez Perce people, who 2019, he and colleagues published a paper in 20,000 years ago. have inhabited the region for thousands of Science that included tentative radiocarbon years, refer to it as Nipéhe, for an ancient dates of between 16,560 and 15,280 years for Genetic studies show these people were village there. In English, it became known bits of animal bone and charcoal excavated not ancestors of modern Native Americans, as Cooper’s Ferry. in collaboration with the Nez Perce Tribe, but Davis believes they may have passed technological traditions on to other Asian Sixteen thousand years ago, the river sat groups that did migrate through northeast- ern Siberia and into the Americas. “[Those travelers] didn’t invent this stuff when they got to the Americas,” he says. “When they left northeast Asia, they had a whole set of tech- nological ideas in their minds.” Davis’s scenario makes sense to Matthew Des Lauriers, an archaeologist at Califor- nia State University, San Bernardino, who studies stone tool technologies. David Meltzer, an archaeologist at South- ern Methodist University, remains skepti- cal. He says the similarities between the two regions’ stemmed points appear ge- neric. Finding more evidence of human artifacts at sites in between Japan and the U.S. Pacific Northwest would help make the authors’ case, Meltzer adds, but “de- tecting actual links between populations so distant in space and time can only be done reliably with ancient genomics.” j SCIENCE science.org 6 JANUARY 2023 • VOL 379 ISSUE 6627 15

A handheld air sampler keeps watch for airborne viruses at a Cambodian market. The device can also be loaded onto a drone or toy car to reach inaccessible spots. INFECTIOUS DISEASES Virus hunters test new surveillance tools Ropes, drones, insects, and dust cloths could make monitoring faster, safer, and cheaper By Jon Cohen, in Phnom Penh, Cambodia that could cause the next pandemic. If the only one element,” she says. “Does the virus PHOTO: J. COHEN/SCIENCE AeroCollect works well, he won’t need to have the ability to spill over from animals O n a Friday morning in September don masks and gloves and get permission into humans? And if so, what does that last year, Erik Karlsson visited the to draw chickens’ blood and swab their be- cause? Is it a dead end or does it have an sprawling Orussey market here, hinds. Karlsson also plans to test flying the epidemic outbreak risk?” Just such a criti- where vendors hawked pots and device on a drone into bat caves—which are cism has dogged the Global Virome Proj- pans, phone cords and radios, hats known viral hotbeds—so researchers don’t ect, an ambitious scheme that promises to and dresses—and myriad types of have to enter them. find the vast majority of pathogens that Southeast Asian food. Dozens of orange- threaten humans but has struggled for colored, whole roasted pigs hung on hooks, Other scientists are tapping advances in many years to find the funding to launch crabs the size of two fists filled buckets, nanotechnology, sequencing devices, artifi- (Science, 23 February 2018, p. 872). and stacked fruit and dried fish formed cial intelligence, and robotics to improve vi- mountains on tables. rus hunting and provide a more timely, deeper To properly gauge the risk of outbreaks, understanding of potential threats. Programs researchers have to conduct repeated sur- Karlsson had come for the live poultry, to monitor SARS-CoV-2’s spread and evolu- veillance for viruses in spillover hot spots but not because he was planning a dinner. tion using wastewater (Science, 11 March such as live-animal markets, farms, and As an epidemiologist at Cambodia’s Pasteur 2022, p. 1100) have shown how new methods bat caves, and at the clinics near them, Institute, he was hunting for potentially can help. says epidemiologist Christine Johnson, dangerous pathogens, both known and who directs the EpiCenter for Disease Dy- unknown. He had nothing with him but a Many of the projects, including namics at the University of California (UC), cellphone in one hand and, in the other, a Karlsson’s, are at the proof-of-concept Davis. “I don’t think we just want to do a device that resembles a portable credit card stage, but Maria Van Kerkhove, who heads snapshot in time,” she says. “It has to be reader, which he held close to men who the emerging diseases and zoonoses unit at fundamentally more of a long-term, watch- were slaughtering, boiling, and defeather- the World Health Organization, welcomes ing things evolve to really gain any true ing chickens. The AeroCollect, as it’s called, them. “I’m really excited about the stuff insight or understanding.” has a chip that uses an electric field to suck Erik is doing,” says Van Kerkhove, who in and trap air in microscopic chambers. sampled birds at Orussey market herself Still, most virus hunters agree a bit of Later, back at his lab, Karlsson flushed each more than a decade ago as part of a Ph.D. ingenuity and creativity can make identify- chamber’s content with a water rinse and project on bird flu. “Air sampling is leap- ing threats a lot easier. Here are some of ran a polymerase chain reaction (PCR) to frogging in technology.” the avenues they are exploring. amplify any viral RNA in the air. But new surveillance technologies must JOHNSON’S TEAM is giving wild monkeys Karlsson is one of many researchers look- not lead to what Van Kerkhove calls “a something to chew on—literally. It is explor- ing for simpler, faster, cheaper, and safer stamp collecting exercise”: simply identify- ing whether scientists can sample the ani- ways to find viruses—including the ones ing the hundreds of thousands of viruses mals’ saliva by giving them treats on ropes. in wild and captive animals. “Detection is 16 6 JANUARY 2023 • VOL 379 ISSUE 6627 science.org SCIENCE

NEWS | IN DEPTH PHOTO: TIERRA SMILEY EVANS The project grew out of the U.S. gov- IN THE NETHERLANDS, veterinarian Marion out of dense forests that researchers can- ernment’s PREDICT, a 30-country effort Koopmans and colleagues have been plac- not easily enter. A team led by plant viro- launched in 2009—and run by UC Davis— ing electrostatic cloths in chicken barns logist Philippe Roumagnac at the University to identify viral threats. Sampling wild to collect dust that can be analyzed for of Montpellier wondered whether the ants primates traditionally requires trapping viruses. “There’s remarkably little high- pick up the pathogens infecting their meals and anesthetizing the animals. That raises quality information on viromes of farmed along the way. In Gabon, Roumagnac and ethical and practical issues, however, so animals,” she says. “We’re exploring ways his colleagues captured 209 army ants from some scientists have simply collected fe- to make surveillance more accessible.” 29 different colonies of the genus Dorylus, ces or urine instead. But those approaches ground them up, and conducted a metage- have drawbacks as well: They often re- There are 22 billion chickens in the nomic survey of the DNA inside them. Se- quire direct observation or accessing the world, according to a 2017 estimate, and quences from 157 different viral genera animals’ nests in trees, and neither is ideal they harbor dangerous viruses—H5N1 in- popped up, the group reveals in a preprint for viruses that primarily shed through the fluenza is the most famous one—that oc- posted last month on bioRxiv. Metagenomic mouth and nose. casionally spill over into humans and analyses can also reveal what species the ants might cause the next pandemic. Earlier ate, helping tie specific viruses in a sample These limits led Johnson and veteri- this year, Koopmans and colleagues re- to what they may have infected. Using ants narian Tierra Smiley Evans to test ropes peatedly visited three farms and compared avoids focusing on animals that humans laced with treats such as strawberry jam dust snagged by the cloths with chicken think pose the greatest risks, Roumagnac or banana baby food that monkeys chew feces scooped up by hand, the usual way says: “They have no sampling bias.” on, leaving behind gobs of saliva. In to look for avian viruses. They didn’t sim- proof-of-principle studies in Uganda and ply test the samples for known viruses, To validate the method, the team plans to Nepal, they found simian foamy virus, para- sample bat guano in Gabon for viruses and influenza 3, enteroviruses, and herpes- Scientists analyzed viruses left on this rope compare them with what they find in army viruses. The group has also collected plants after a monkey ate an attached treat. ants feeding on the same guano. Roumagnac chewed and discarded by Uganda’s endan- is optimistic: “Army ants could be one of gered mountain gorillas, most recently to but used metagenomics to sequence any the key players that could give clues about assess whether people were infecting them genetic material in the sample. Samples the bigger picture of the ecology and evolu- with human herpesvirus-1 (HSV-1), which from both sources yielded similar results— tion of viruses in a single ecosystem.” has sickened and killed captive lowland go- viruses from four families—confirming the rillas. There were no signs of HSV-1 in the “electrostatic dustfall collectors” are a good KARLSSON’S PHNOM PENH OFFICE is filled plant discards from 294 gorillas, the team alternative to sampling poop, the group re- with what he calls “toys” that might ex- reported in October 2022 in the American ported in Scientific Reports last year. pand the AeroCollect’s surveillance pow- Journal of Primatology, but they did con- ers. A drone could be used to sample bat tain gorilla-specific herpesviruses. Koopmans hopes the technique can help caves—even ones that only rock climbers scientists forecast where trouble is brewing. can now reach. Karlsson recently purchased UC Davis has more futuristic projects “Right now, the way our surveillance works a remote-controlled, pint-size car that can in the works. A team is exploring whether is really very reactive,” she says. “How can hold the device—he plans to drive it around a sandwich-size air sampler can identify we move surveillance forward so we pick up farms to collect samples from a distance. active viral infections in humans from things before you see human disease?” Battery-powered, downsized PCR devices patterns of volatile organic compounds and portable sequencing machines will ac- (VOCs) in their breath. Several respira- SOME VIRUS HUNTERS want to send in an celerate the analysis. “We want to bring the tory diseases, including influenza, tuber- army—of ants. Voracious army ants prey on lab to the field,” Karlsson says. “If we’re at culosis, and COVID-19, come with specific many insect and vertebrate species and can an outbreak, we can get ahead of it faster.” molecular breath signatures, researchers travel about 1 kilometer a day, often in and have found. In a December 2022 paper The Pasteur team that Karlsson joined in Communications Medicine, a UC Da- 5 years ago has a long history of working to vis team led by Mitchell McCartney and improve viral surveillance in Cambodia, fo- Cristina Davis even reported distinctive cusing on how bird flu evolves and spreads breath markers during the spread of the to humans. The team also understands the Delta and Omicron variants. The group challenge of translating its findings into has also tested the air sampler’s ability to actions that protect people—a challenge detect disease signatures while attached to underscored by PREDICT, which, despite a person’s hip or flown on a drone. an investment of more than $200 million, did not identify the threat of SARS-CoV-2. The “breath biopsy” field is still in its Veasna Duong, who heads the Pasteur In- infancy, despite a surge of interest during stitute’s virology division, adds that pre- the pandemic in room air samplers and ventive measures require political will and breathalyzerlike devices. (The Netherlands acceptance by local people who often don’t used SARS-CoV-2 breathalyzers for wide- accurately perceive the risk. spread COVID-19 testing, but officials soon deemed them unreliable.) In their attempt That’s no reason not to try, Karlsson to make “breath the new blood” for diag- says. “Can we prevent pandemics?” he noses, Davis and an international group of asks. “I think we can be better prepared for colleagues last year launched the Human the next one, that’s for sure.” j Breath Atlas, an effort to conduct large- scale investigations into the rare VOCs peo- Reporting for this story was supported by a grant ple exhale when sick. from the Alfred P. Sloan Foundation. SCIENCE science.org 6 JANUARY 2023 • VOL 379 ISSUE 6627 17

NEWS FEATURES A RIVER’S PULSE In the Brazilian Amazon, Indigenous people and researchers join hands to monitor the impacts of a controversial dam By Sofia Moutinho; Photography by Dado Galdieri S oon after sunrise one warm day He pulls a disk-shaped fish with bright ber 2014, the best fishing months of that in September 2022, 26-year-old gray scales and a yellowish belly from year, fishermen in Muratu caught a total Josiel Pereira Juruna boards a the net and hands it to Josiel, who hangs of 770 kilograms of pacu. Over the same small motorboat and sets out it from a portable scale. “One hundred months in 2021, that number dropped to on the emerald-green waters of and fifty grams,” he declares, then presses 175 kilograms. the Xingu River in the Brazilian a ruler against the animal, known as a Amazon. Accompanying him are big-eyed pacu. “Fifteen centimeters,” he “Now we only catch very skinny and biologist Cristiane Carneiro and says, as Carneiro takes notes. small pacu, almost without fat,” Josiel says Pedrinho Viana, a fellow fisher- with disappointment as he gestures to the man from their village of Muratu in the It’s a ritual of weighing and measur- specimen in his hand. Paquiçamba Indigenous Reserve in north- ing that Josiel has performed nearly daily ern Brazil’s Pará state. After a short ride, for the past 3 years to monitor the river’s The likely cause lies 30 kilometers up- Viana hauls in a gillnet set out in a creek fish stocks. Of all fish in this stretch of the stream of Muratu: the largest hydroelectric the night before. Xingu, the seven species of pacu are the project in the Amazon basin, a complex of most important for his community, the dams, reservoirs, and power stations known This story was produced with support from Juruna, who rely on fishing for food and as Belo Monte. The project was originally the Rainforest Journalism Fund in partnership income. Known as vegetarian piranhas, slated for construction in 1975, but years with the Pulitzer Center. pacu can reach up to 1 meter long. But they of protests from Indigenous communities are dwindling. In November and Decem- and a lack of investment stalled it. In the 2000s, after major electricity blackouts in 18 6 JANUARY 2023 • VOL 379 ISSUE 6627 science.org SCIENCE

Fishermen from the Indigenous village of Muratu catch a pacu, a fish that provides sustenance and income along the Xingu River in Brazil. Indigenous researchers are tracking pacu numbers and size (left) to monitor the effects of a giant dam just upstream. PHOTO: DADO GALDIERI/HILAEA MEDIA the country, President Luiz Inácio “Lula” The impacts were evident right away, Environmental Institute, the Juruna estab- da Silva (recently reelected) pushed for the when an abrupt release of water from the lished a partnership with an informal net- project, despite international opposition dam killed 16.2 tons of fish. The Brazil- work of scientists from public universities from environmentalists and scientists, and ian Institute of Environment and Renew- across Brazil. Among them was Carneiro, it began operating in 2016. able Natural Resources (IBAMA) imposed who was doing a Ph.D. in ecology at the a fine of 35.3 million reais ($6.6 million) local Federal University of Pará (UFPA), The main dam, called Pimental, had a on Norte Energia, the company that runs Belém. Together, the Juruna and the sci- dramatic impact on the river, creating a the hydroelectric project. Josiel and other entists have been recording change in the 359-square-kilometer reservoir and divert- people from the Paquiçamba reserve were abundance, habits, and size of the fish and ing much of the Xingu’s flow northeast not surprised at the havoc. “The elderly in turtles living in the changed river. through a 17-kilometer canal to a secondary our villages knew we would have this kind reservoir and hydroelectric station. Down- of problem with the dam,” Josiel says. “We For Philip Fearnside, a biologist at the stream, along the 130-kilometer river stretch knew the fish would suffer with a river flow National Institute of Amazonian Research called the Big Bend of the Xingu, the diver- that is no longer natural.” (INPA), the collaboration “is essential to sion reduced the river’s flow by up to 80%. show the huge impact instead of simply It also interrupted the river’s annual cycle They had already asked researchers to accepting it.” Fearnside, who isn’t involved of flooding, crucial to its rich biodiversity. help them document the changes. In 2013, in the collaboration but has been studying The Juruna call 2016, the year the main with the support of a local nongovern- dams in the Amazon for more than 30 years, dam was completed, “the end of the world.” mental organization known as the Socio- says partnerships between Indigenous peo- SCIENCE science.org 6 JANUARY 2023 • VOL 379 ISSUE 6627 19

The Belo Monte hydroelectric project is the Amazon basin’s largest. The main dam (above), called Pimental, diverts much of the Xingu River into a secondary reservoir, where it drives turbines. A woman from the Juruna community applies ceremonial paint to biologist Janice Muriel Cunha (right) ple and researchers are critical in Brazil, PHOTOS: DADO GALDIERI/HILAEA MEDIA during a September 2022 meeting to discuss research ties between Indigenous people and scientists. where government approvals to build and operate dams are often “a token gesture,” 20 6 JANUARY 2023 • VOL 379 ISSUE 6627 and companies “can go ahead and build the dam anyway,” regardless of impact. In a statement sent to Science, Norte En- ergia said changes in Xingu fish populations are within the range of what was predicted in the environmental impact studies con- ducted before the dam’s construction. But the full scope of those impacts is emerging in the data the Juruna and their scientist collaborators have collected. Their findings have been published in peer-reviewed jour- nals and used to fight for reparations and for the dam’s operators to restore some of the river’s natural flow. Now that Lula is once again president, after campaigning on promises of a strong environmental agenda and plans to cre- ate an Indigenous Ministry, the Indigenous people and their scientist allies hope their findings will lead to permanent changes at Belo Monte—and in the hundreds of other dams being planned or built in the Amazon. “I think things will get better for Indigenous peoples during this government and maybe more water will be released to the Big Bend,” Josiel says. “That is what I hope for.” science.org SCIENCE

NEWS | FEATURES Threatened fish nurseries The Juruna mapped more than 30 fish breeding sites in flooded forests and islands along the Big Bend of the Xingu, a 130-kilometer river stretch with unique biodiversity and surrounded by Indigenous villages. These seasonally flooded areas hosted multiple species of fish and turtles but have been mostly dry since the construction of the Pimental Dam. Fish breeding sites Belo Monte hydropower dam Altamira Bypass canal Xingu River Muratu Indigenous Indigenous reserve village Paquiçamba Pimental Dam, Belo Monte BRAZIL 0 10 Indigenous reserve km Arara da Volta Grande do Xingu GRAPHIC: K. FRANKLIN/SCIENCE BEFORE THE DAM, the Juruna—and the fish— work. Every day since the project began in fish to feed and spawn. Now, even in March, could count on the river’s seasonal rhythm. 2013, one of them is tasked with recording Josiel can stand on the island’s leaf-littered During the rainy Amazonian winter, from the weight and length of individual fish, as ground. The instruments have never mea- December to May, as much as 20,000 cubic well as the total amount of fish caught in sured more than 2 meters of water. meters per second of water surged down the reserve. the river, overflowing its several channels Up to 70% of the Big Bend’s seasonally and spilling onto islands and adjacent for- More recently, the Juruna also started to flooded forests no longer flood under the ests. In the summer the flow falls as low as investigate how the change in the river flow current water regime, according to data 2000 cubic meters per second. Over millen- has affected fish breeding sites in the igapós from Norte Energia. Other Amazon dams nia, this flood pattern has shaped the river’s (from the Guarani language for “root for- likely have similar impacts. Although Bra- landscape and species. ests”), the seasonally flooded forests on the zil requires environmental assessments river margins and islands. For multiple spe- for dam projects, the laws don’t specifi- Now, the dam has cut the winter flow by cies of fish and turtles, these forests are vital cally mention flooded habitats such as the more than half. Worse is to come: a new habitats. Pacu, matrinxã, curimatá, and other igapós. “Our legislation has not kept pace flow regime that in alternate years will re- local fish feast on ripe fruit that falls into the with the scientific knowledge,” says Andre duce the maximum winter flow by another water from the trees, a bounty that includes Sawakuchi, a geologist at the University of 50%, to one-fifth the natural level. (IBAMA the tiny red cherrylike sarão (Myrciaria du- São Paulo’s main campus who is involved had approved the plan, but until recently bia), the yellow plum-shaped cajá (Spondias in the effort with the Juruna. “Igapós are courts had blocked it.) Because of the water mombin), and the round seringa, the fruit of forests inside the river. If you lose them, diversion, “The cycle of the flood pulse, the the rubber tree (Hevea brasiliensis). you cannot just replant. You cannot replant most basic characteristic of that ecosystem, a river.” was completely altered,” says Camila Ribas, In 2019, Josiel and a team of research- an INPA biologist who collaborates with the ers from UFPA installed flood gauges on Without a place to spawn, fish have been Indigenous peoples. “If you change this, you Zé Maria, a forested island 4 kilometers found with dry eggs inside their bodies “like change all the relationships within this sys- from Muratu village. Every November be- dead babies inside a woman’s belly,” Josiel tem and may permanently destroy it.” fore the dam was built, the rain-swollen says. The fish have also lost an important Xingu would slowly advance over the is- source of food. “The fruits now fall onto dry The Juruna and their scientist partners land’s sandy beaches, reaching the top of ground, and the fish cannot eat,” Josiel ex- have been monitoring the consequences. its trees in April. The island remained sub- plains. “It is very sad.” Outside researchers trained 12 people from merged in up to 30 meters of water for the the Juruna community to conduct the next 6 months, bringing an abundance of The resulting decline of the Big Bend fisheries has hit the Juruna hard. “Before SCIENCE science.org 6 JANUARY 2023 • VOL 379 ISSUE 6627 21

NEWS | FEATURES A weakened pulse trade had already depleted it, and in 2022 the International Union for Conservation In natural conditions, the Xingu River has a high volume during the Amazonian “winter” (December of Nature declared it critically endangered to May) and a low volume in the summer. But the construction of the Pimental Dam drastically reduced because of the dam. the water flow. (Hydrograms A and B represent alternating flow regimes.) In 2019, the government temporarily forced the dam to release more water. Now, scientists and the Juruna community have THE COLLABORATION’S FINDINGS are already proposed increasing the flow to minimize environmental damage in the river. having an impact. The data are often sent to IBAMA—and the Brazilian Federal Pub- Average annual river flow (1971–2014) lic Prosecutor’s Office, which has filed sev- eral lawsuits against Norte Energia. Some Adjusted flow: Temporary hydrogram Proposed hydrogram accuse the company of “ethnocide,” the Actual flow: crime of destroying Indigenous cultures, Hydrogram A Hydrogram B because of the severe impacts of the dam on their lives. 20,000 In its statement to Science, Norte Ener- 16,000 gia said it has compensated the commu- nities. New fish farming tanks installed Flow rate (m3/s)12,000 in Indigenous villages have provided 660,000 reais ($124,000) in income to local 8000 CREDITS: (GRAPHIC K. FRANKLIN/SCIENCE; (DATA BRAZILIAN NATIONAL AGENCY OF WATERS, ANALYZED BY ANDREfamilies since 2019, the company says. In No- SAWAKUCHI/FEDERAL UNIVERSITY OF SÃO PAULO; (PHOTO DADO GALDIERI/HILAEA MEDIA vember 2022, the company also agreed to pay 4000 an undisclosed sum in reparations to about 2000 local fishermen. IBAMA had ordered 0 this compensation as a condition for renew- Nov. Dec. Jan. Feb. Mar. Apr. May Jun. Jul. Aug. Sep. Oct. ing the dam’s operating license. In winter, the swollen Xingu River normally floods Zé Maria island to a depth of tens of meters. A flood For the Juruna, no money or mitigation gauge placed by Indigenous researchers recorded last winter’s much-reduced flood. project can substitute for the altered pulse of the river and their own lives. “Belo Monte [the dam], we could fill three coolers of search, partially funded by Norte Energia took our river, and it was like draining our 160 liters with fish in a week,” remembers and conducted with data the company was blood out,” says Giliarde Juruna, Muratu’s Maria das Graças, a Juruna fisherwoman required to collect, found a 29% decline in chief. “Today, we are adapting to this new and Viana’s wife. She and her husband the number of species and a 9% drop in the reality of drought. But we don’t know how raised their three children on fish from the abundance of all fish in the Big Bend. The our future will be without the river.” Xingu. What the family didn’t consume, decline was sharpest for pacu. The results they used to sell. “Now, we go out fishing are just the beginning of a “tragedy” that will The collaboration hopes its data can be for 10 days and can barely fill two coolers.” worsen, says Kirk Winemiller, an ichthyo- used to push for more water to be released logist at Texas A&M University, College Sta- from the dam. In 2019, based on the Juru- The data collected by the Juruna have tion, and an author of the study, because na’s data, IBAMA deemed the dam’s water quantified the change. Sent to researchers “we are only looking at the very early signs” flow insufficient and forced Norte Energia at UFPA for further analysis, the findings of the dam’s impact. to temporarily increase it, reducing the have led to academic papers on Xingu eco- amount of water delivered to the power systems and changes in Indigenous ways Winemiller thinks some species may face turbines. IBAMA also asked the company of life, and have gone into monthly reports extinction. The catfish acari-zebra (Hy- to conduct further impact studies. In 2021, presented in open meetings in the villages. pancistrus zebra), a match-size fish with however, then-President Jair Bolsonaro’s black and white stripes only found within administration reversed the ruling and al- A separate study published in Science of the Xingu’s Big Bend, is one of his biggest lowed Norte Energia to reinstate the origi- the Total Environment in September 2022 worries. Illegal fishing for the aquarium nal, reduced water flux. The agency did confirms the Juruna’s observations. The re- require the company to invest 157 million reais ($29 million) in environmental and social mitigation actions, such as replant- ing trees. In August 2022, the Juruna and their sci- entist partners sent IBAMA another pro- posed water regime that would increase the volume released from the dam by up to 68%. The increased flow would restore flooding to 32 mapped piracemas, or fish breeding sites, like those on the island of Zé Maria. The plan would also do away with the abrupt daily changes in flow that the river experiences now, like the one for which Norte Energia was fined in 2016. “The water needs to go up and down grad- ually to guarantee that the fish juveniles can develop,” says Janice Muriel Cunha, an 22 6 JANUARY 2023 • VOL 379 ISSUE 6627 science.org SCIENCE

The acari-zebra, unique to the Big Bend of the Xingu River, already faced pressure from collectors supplying the aquarium trade. The dam and its impact on the river could push the fish toward extinction. PHOTO: DADO GALDIERI/HILAEA MEDIA ichthyologist at UFPA. “They need at least THE JURUNA HOPE things will take a better the new government. But he remains con- 3 months to grow in the calm waters of the turn with Lula. It’s unclear how the politi- cerned about the future, and not just for his flooded forests, and then go back to the cian, who said in a recent interview that people. There are about 150 other dams in main stream.” he would approve the construction of Belo the Amazon basin already, and 350 more Monte again, will follow through on his are planned—including another on the IBAMA is now evaluating the suggestion campaign promises on the environment. Xingu, upstream from Belo Monte. and should answer soon. But approval is Biviany Rojas, who coordinates the pro- unlikely, the researchers admit. More wa- gram that supports the Juruna’s monitoring Although he only has a high school degree ter down the river means less flowing to project at the Socio-Environmental Insti- so far, Josiel has been thinking about becom- the turbines, and less electricity produced tute, expects that under the new govern- ing a biologist. The challenges to achieving by a complex that is already falling short of ment, IBAMA will recover the autonomy it that goal are multiple, but he thinks science expectations. Because of drought and poor had lost during Bolsonaro’s administration can give a voice and memory to the knowl- planning, Belo Monte only generates on av- to make decisions based on technical in- edge of his people, passed down from genera- erage 4571 megawatts of power, less than formation rather than on politics. “This is tion to generation, including what he learned half its installed capacity. “Based on the an opportunity for Lula to redeem himself from his grandfather about the river and how history so far, it is difficult to believe that with the Xingu people,” she says. to live from it. “It is a way to show future gen- Norte Energia would reduce energy produc- erations of our community how the river was tion to increase the water volume in the Big For his part, Josiel is confident there will before, how abundant the fish was,” he says. Bend,” Sawakuchi says. be more dialogue between his people and “And how it will never be again.” j SCIENCE science.org 6 JANUARY 2023 • VOL 379 ISSUE 6627 23

INSIGHTS LETTERS NEXTGEN VOICES The fruits of failure We asked young scientists: Are you grateful for a setback that you experienced? What mistake did you make, and what good came from it? In the responses below, they share the discoveries and revelations that made their would-be regrets worthwhile. Follow NextGen Voices on Twitter with hashtag #NextGenSci. —Jennifer Sills Interdisciplinary collaboration Two years ago, I was trying to construct prioritize my physical and mental health. I ILLUSTRATION: ROBERT NEUBECKER mathematical models for predicting the worried that the delay would mean missed After many unsuccessful attempts to pro- risk of maternal inheritance of pathogenic opportunities, but I now have more time duce diffraction-quality protein crystals, I mtDNA mutations. As a medical student, I to participate in scientific events, develop finally asked others for help. By doing so, seldom receive mathematics training. After friendships, and stand out in classes. When I I changed my routine from solo lab work struggling for a month, I turned to a friend found out that I was accepted to an exciting to collaboration, which gave me a broader studying information science for help. He writing internship, I realized that saying no understanding of the challenges faced solved the functions easily, making me to certain options is saying yes to others. I by experts, peers, and junior scientists. realize the importance of interdisciplinary may not graduate in the expected time for Viewing mentorship and science fund- collaboration. Last year, we established an most people, but I’m graduating in the right ing from the lens of a struggling scientist organization dedicated to promoting the time for me, while doing something I love: led me to a new career. I became a grants integration of medicine and other disci- communicating science in an accessible, manager at a funding body, where I was plines, including bioengineering, computer entertaining, and useful way. responsible for science communication, technology, and artificial intelligence. grant writing workshops, collaboration, Ning Zhang Camila Fonseca Amorim da Silva and networking events for scientists. As a Olá, Ciência!, University of São Paulo, São Paulo science administrator, I could enhance the First School of Clinical Medicine, Anhui Medical 03828-000, Brazil. quality of science through funding, build- University, Hefei, Anhui 230032, China. Email: [email protected] ing capacity for addressing the “behind the Email: [email protected] scenes” matters of research. If I had not I signed up for a course at a local museum, faced failure working in silos in a lab, Writing opportunities hoping for a research experience. On my I would never have discovered my passion. first day, however, I realized that I had acci- I’m currently taking 2 extra years of college dentally signed up for an intensive writing Garima Singh because I wanted to keep up an adequate seminar. Little did I know that the course Mott MacDonald, Noida, Uttar Pradesh 201301, academic performance in classes and would expose me to an area of science India. Email: [email protected] extracurricular research projects as well as that would prove invaluable in my career. 24 6 JANUARY 2023 • VOL 379 ISSUE 6627 science.org SCIENCE

The seminar taught me how storytelling Ashley Barbara Heim focus. This serendipitous finding led me to is central to sharing scientific discoveries. Department of Ecology and Evolutionary Biology, pursue a full-time PhD course to explore a Were it not for that seminar, I would never Cornell University, Ithaca, NY 14853, USA. new avenue of research. have undertaken journalism internships, Email: [email protected] developed a passion for science writing, or Bryce W. Q. Tan become as thoughtful a scientist. I planned to major in chemistry and then Department of Medicine, National University Divyansh Agarwal work in the lab of some industry or research Hospital, Singapore 119228, Singapore. facility. However, after failing to receive Email: [email protected] Massachusetts General Hospital, Harvard Medical a scholarship I applied for, I had to find School, Boston, MA 02108, USA. another source of income. I had never After a tough semester in my undergradu- Twitter: @divyansh_aga thought of myself as a teacher before, but I ate physics education, I had not completed took a job preparing students for their final enough courses to be eligible to continue Reaffirmed values exams. Suddenly, I realized that teaching with the mandatory undergraduate thesis was my vocation and quickly updated my project the same year. I was devastated. Several years after publishing our research academic plan. Now an assistant professor Soon afterward, I discovered a new field findings, we realized that we had made at the university level, I aim to help stu- of research that sparked my interest. The some errors. We promptly contacted the dents follow this path, one I may never have field—biophysics—was outside the tradi- journal, which decided to retract the manu- found if I had secured that scholarship. tional topics offered at my institution, but script. Because we had been transparent, I found a research group and convinced we were allowed to submit a corrected ver- Wagner Eduardo Richter the institution to let me do a biophysics sion, which was later accepted. Although Department of Chemistry, Federal University of project. Had I not failed and postponed my retractions are often seen as academic fail- Technology–Paraná, Ponta Grossa, Paraná, Brazil. thesis, I would probably not be working in ures, going through the process reminded Email: [email protected] biophysics today. me that integrity and honesty are the cor- nerstones of our research and made me feel Improved procedures Cathrine Bergh more committed to our values as scientists. KTH Royal Institute of Technology, 11423 After my manuscript was published, I Stockholm, Sweden. Email: [email protected] Salam Salloum-Asfar realized, to my horror, that we had used Qatar Biomedical Research Institute, Hamad Bin identical reference protein images in two Supportive relationships Khalifa University, Qatar. separate results. I checked my original data Twitter: @Dr_SalamSalloum archives and discovered how difficult it was Because I initially overlooked the accep- to find the raw images. After providing the tance email for a summer program, I With only a bachelor’s degree in physics and right pictures to the journal, I immediately missed the window to submit my prefer- chemistry and a sense of purpose, I tried to asked a computer expert to help me develop ences. I was auto-matched to a venom create a hydroponic system that would lower a better data storage system. Now I upload lab, where I learned to my consternation the price margins in my country and provide my raw data daily, all processed data is that I would be hand collecting spiders fresh, organic, and affordable vegetables. organized and saved, and all files are backed at midnight from a forest. However, this The journey was rough, and the start-up up weekly. Publishing a mistake taught me unexpected topic came with enthusiastic suffered heavy financial losses. However, my the importance of proper data management. mentors. No snake, turtle, or scorpion efforts led to more fresh organic produce went without a photo, and the group took in Trinidad’s supermarkets, an award for Yongsheng Ji lengthy detours just to appreciate the ingenuity, and two publications. Those suc- Division of Life Sciences and Medicine, University scenery. I was new to research, and good cesses inspired me to venture into medical of Science and Technology of China, Hefei, Anhui mentorship and memorable experiences research, where I found opportunities that 230026, China. Email: [email protected] outweighed all else. The experience fueled brought me closer to my ultimate goal of my interest in pursuing science as a career. contributing meaningfully to humanity. Once, after a chemistry experiment, I poured liquid waste containing ammonia directly Jackson Ross Powell Stephanie Mohammed into the toilet. The strong odor it produced Vagelos Molecular Life Sciences Program, Department of Physics, Faculty of Science and did not go unnoticed by my supervisor. University of Pennsylvania, Philadelphia, PA 19104, Technology, The University of the West Indies, Remembering the smell and the subsequent USA. Email: [email protected] St. Augustine Campus, Trinidad, St. Augustine, criticism I received has motivated me to take Trinidad and Tobago. extreme care when conducting and cleaning In high school, I found a welcoming men- Email: [email protected] up experiments ever since, possibly saving tor who catalyzed my love for research. I me from accidents and injuries. asked him if I could work in his lab during Passion for teaching the summer, and he jumped through hoops Yuan Zhi to include me. When I told him later that I As a first-generation undergraduate, I was School of Economics, Guizhou University, Guiyang, had applied to other programs as well and excited to be accepted by a PhD program Guizhou 550025, China. Email: [email protected] had accepted another offer, he was under- in zoology immediately after I graduated. standably livid. By taking him for granted However, I didn’t take the time to consider New research avenues and failing to understand the logistics of my career goals, and after a year of frus- lab staffing, I ruined my relationship with tration, I began to doubt whether I was One night during medical school, my last him. Today, remembering my mistake cut out for grad school. Because my solace task was to take out two western blots for constantly reminds me to appreciate and from research struggles was instructing two different experiments and place them communicate with my mentors. undergraduate biology, a mentor recom- in antibodies specific against different pro- mended looking into discipline-based teins. The next day, I realized that in my ex- Sai Sarnala education research programs. Only after haustion I had swapped the blots. Because Department of Chemistry, University of I was accepted into a doctoral program of this silly mistake, I stumbled upon a Pennsylvania, Philadelphia, PA 19104, USA. in biological education did I realize how novel modification of my protein of interest! Email: [email protected] wonderful research could be. The solution to a 2-year mystery came into 10.1126/science.adg1443 SCIENCE science.org 6 JANUARY 2023 • VOL 379 ISSUE 6627 25

PERSPECTIVES A University of California San Diego researcher collects wastewater on campus for SARS-CoV-2 analysis and sequencing. EPIDEMIOLOGY sensitive concentration measurements of specific pathogens can be obtained affordably Wastewater surveillance and in only a few hours. Pathogen concentra- for public health tions accurately estimate prevalence (the number of current infections in the popula- Wastewater contains information on pathogen spread, tion), and given that wastewater trends often evolution, and outbreak risk precede corresponding clinical detections, they may allow for early detection (8). By Joshua I. Levy1, Kristian G. Andersen1, ratory and analytical advances to identify the PHOTO: ERIK JEPSEN/UC SANDIEGO Rob Knight2,3,4, Smruthi Karthikeyan2 diverse pathogens present in sewage will be Wastewater can be used to track infectious essential to ongoing efforts to understand disease dynamics from the community level D ating back to the origins of modern disease risks and will transform infectious to building level, and from sources rang- epidemiology, wastewater surveil- disease surveillance. ing from sewers and wastewater treatment lance has predominantly been used to plants (WWTPs) to surface waters and point track pathogens spread by fecal-oral Pathogen surveillance typically involves sources (e.g., natural pooling sites) (9). At transmission such as those that cause sampling of infected individuals, requir- large WWTPs and other sites of converging cholera and polio. However, more ing extensive specimen acquisition, clinical wastewater flows, a single sample can cap- than just these “enteric” pathogens are shed testing, and sequencing coordinated across ture the community-wide pathogen land- via the gut, as highlighted by the success of different sites and laboratories. This type scape, even for cities with millions of inhabit- severe acute respiratory syndrome coronavi- of clinical surveillance is expensive, time- ants (10). Such approaches are cost-effective rus 2 (SARS-CoV-2) wastewater surveillance consuming, and subject to bias owing to dis- and time-efficient and maximize the number (1, 2), recent work on tracking influenza virus parities in public participation and frequency of individuals covered by surveillance. In (3) and monkeypox virus (4), and observa- of testing and sequencing, which may limit many countries, WWTPs already collect com- tions of extensive pathogen diversity in stool outbreak preparedness and response by pub- posite wastewater samples (taken regularly (5, 6). Wastewater is now a core component lic health organizations, especially in under- throughout the day) that can be analyzed to of infectious disease monitoring, providing served communities (7). Although clinical yield essential information on local pathogen a variant-specific, community-representative surveillance will remain fundamental to in- prevalence, which enables timely mobiliza- picture of public health trends that captures fectious disease response, wastewater-based tion of public health interventions. In areas previously undetected spread and pathogen approaches enable fast and cost-effective sur- lacking centralized sewer infrastructure, transmission links. Building on recent labo- veillance, even in current blind spots. similar methods can be used to study sam- ples from surface waters and point sources, 1Department of Immunology and Microbiology, The Scripps Wastewater monitoring enables rapid although additional considerations of topog- Research Institute, La Jolla, CA, USA. 2Department of pathogen detection and community preva- raphy, water pooling, and flow are needed to Pediatrics, University of California San Diego, La Jolla, CA, lence quantification. At sites where wastewa- maximize catchment size (11). USA. 3Department of Computer Science and Engineering, ter from the population collects and mixes, so University of California San Diego, La Jolla, CA, USA. too do a diverse array of microbes shed from At a focused spatial scale, wastewater 4Department of Bioengineering, University of California individuals. The resulting mixture is repre- can be used for monitoring at the level of San Diego, La Jolla, CA, USA. Email: [email protected]; sentative of local infections, and with now- individual or small clusters of buildings to [email protected] standard laboratory processing and quan- enable reliable detection of even a single titative polymerase chain reaction (qPCR), infected person (10, 12). Such monitoring is of particular importance to vulnerable com- munities and high–population density sites, such as health care (e.g., nursing homes) or educational facilities (12), as well as airports, where detection can be acted on to contain pathogen spread. Understanding the determinants of patho- gen incidence, however, including mutational changes, variant introductions, or emerging pathogens, requires genomic sequencing. Unlike qPCR, sequencing is effective regard- less of pathogen variant and identifies muta- tion frequencies across the entire genome, even for mutations that exist at low levels in the population. During the COVID-19 pan- demic, wastewater sequencing–based analy- ses have enabled early detection of emerging SARS-CoV-2 variants, estimation of variant prevalence (10, 13), identification of the im- pact of specific mutations on pathogen fit- ness, and characterization of the mutational processes that lead to variants of concern 26 6 JANUARY 2023 • VOL 379 ISSUE 6627 science.org SCIENCE

INSIGHTS (14). Sequencing of building-level wastewater tion infrastructure (liquid-handling robots), public health, and wastewater as one of our samples has enabled extraction of single ge- and labor-intensive processing, with ~2- to nomes that have been used to identify new 4-week turnaround times. However, because most powerful assets. National and regional mutations and variants; reveal cryptic, or un- wastewater collections capture community- detected, spread (especially at sites that are wide trends, samples can be prioritized for wastewater surveillance programs are rap- not well covered by clinical surveillance); and low-throughput, fast-turnaround sequenc- elucidate local transmission networks (10). ing at higher cost per sample for real-time idly being established across the globe, al- The ease of sharing sequencing data enables tracking of pathogen dynamics. For example, collaborative analyses of pathogen trends highly automated fast-turnaround sequenc- lowing for continued analysis of SARS-CoV-2 around the world, enhancing preparedness ers enable automation of the entire process and informing public health guidance. from library preparation to analysis, require variant dynamics despite limited clinical minimal technical expertise, and permit 24- For sequencing of a specific pathogen, tar- hour sample receipt to data turnaround, but monitoring. Expansion of multipathogen and geted amplicon-based approaches are needed lead to a 10-fold increase in per-sample cost. to selectively amplify and sequence patho- metagenomic wastewater sequencing efforts gens of interest from wastewater. Although For deployment in low-resource settings, this approach presents technical challenges sequencing workflows need to be reconfig- is enabling broad pathogen detection and and requires ongoing development, amplicon ured in accordance with available instru- sequencing can provide similar sensitivity to ments, reagents, funding, and facilities. genomic characterization, including envi- qPCR, excellent sequencing coverage and Portable low-throughput sequencers can depth, and effectiveness regardless of patho- provide results much faster, are low cost, do ronmental contamination by Vibrio cholerae gen variant. As a result, almost all clinical not require automation infrastructure, and and wastewater sequencing of SARS-CoV-2 can be deployed almost anywhere. However, (which causes cholera) in sites without effec- has used this targeted approach. Initiating they generally have higher sequencing error the collection of high-quality pathogen- rates and require additional laboratory and tive sewage treatment, human and livestock- specific sequencing data requires only mini- bioinformatics training. In low- and middle- mal training, aided by community efforts income countries, where reagents generally borne rotavirus (which causes gastroenteritis such as ARTIC that provide open-source am- need to be imported from abroad, transport plicon scheme designs and protocols. is often slow and expensive, and reagents in children), and vaccine-derived polioviruses requiring refrigeration can degrade dur- Although targeted approaches are excel- ing shipping or at facilities with unstable recently observed in London and New York. lent for monitoring known pathogens of electricity supply. Progressing toward more concern, they examine only a tiny fraction equitable and sustainable surveillance Beyond infectious pathogens, wastewater of microbes in wastewater. For a broad sur- will require continued development of lo- vey of pathogens, untargeted metagenomic cal, self-sustaining scientific ecosystems also has the potential to reveal changes in and metatranscriptomic shotgun sequenc- through laboratory and computational ing approaches can be used to identify any methods development and training, capac- the human gut microbiome, which have been circulating microbial DNA or RNA. A single ity building efforts, and financial support of sample can indicate the presence of viruses domestic scientific enterprise. correlated with a wide range of health condi- including monkeypox and influenza, identify pathogenic and antibiotic-resistant strains of Ongoing method development is key to tions and disease risks. bacteria (15), detect protist parasites includ- further expanding the capabilities of waste- ing Plasmodium falciparum (which causes water surveillance. At present, untargeted There is now an opportunity to build upon malaria), and search for new pathogens, al- metagenomic and metatranscriptomic meth- though standard approaches may not provide ods suffer from bias toward a limited number existing momentum to form the backbone sufficient sensitivity to detect rare pathogens. of dominant bacterial species in wastewater Unlike amplicon-based surveillance, which and will require new laboratory techniques of future surveillance capacity and scientific can identify pathogen variants shed by a to ensure reliable detection of pathogens at handful of individuals within a population of low concentration. The latest enrichment ecosystems across the world. Doing so will re- millions (10, 14), untargeted methods require methods for semi-targeted sequencing of greater prevalence for reliable detection, al- pathogens from wastewater are specific to quire global surveillance networks to encour- though increasing sequencing depth can help viruses and will need to be redesigned and improve the likelihood of pathogen detection. tested for other types of pathogens. Current age equitable technology distribution, data For more detailed profiling of a specific class computational methods are still unable to of pathogens (e.g., viruses), probe-based en- identify new variants from community-wide sharing, and collective exploration of micro- richment methods can be used prior to shot- mixtures and are just beginning to produce gun sequencing for “semi-targeted” study of a wider range of informative readouts, in- bial diversity, both human and zoonotic, to the group of interest and may be necessary to cluding growth rates, which are essential to detect rare pathogens. evaluate the potential size and speed of an help pinpoint possible outbreaks and spill- emerging outbreak. As these methods evolve, Designing an effective wastewater se- there will also be a need for new standard- over risks. Close integration with local and quencing strategy gives rise to a fundamental ized protocols and computational workflows trade-off between speed, cost-effectiveness, that are open source and easily reproducible international public health organizations and local deployability. To keep costs down, anywhere in the world. most current sequencing is performed with will be essential to ensure timely, transpar- hundreds to thousands of samples in paral- The COVID-19 pandemic has laid bare lel, requiring expensive machinery, automa- the importance of pathogen surveillance to ent, and effective intervention. Wastewater provides the means to identify, prepare for, and respond to future pandemic threats— what remains is to expand capacity to ensure readiness for the next potential outbreak. j REFERENCES AND NOTES 1. A.E.Kirby et al.,MMWR Morb.Mortal.Wkly.Rep.70,1242 (2021). 2. F.Amman et al.,Nat.Biotechnol.10.1038/s41587-022- 01387-y (2022). 3. M.K.Wolfe et al.,Environ.Sci.Technol.Lett.9,687 (2022). 4. S.Wurtzer et al.,bioRxiv 10.1101/2022.08.18.22278938 (2022). 5. L.Ma et al.,Environ.Sci.Technol.50,420 (2016). 6. S.R.Finkbeiner et al.,PLOS Pathog.4,e1000011 (2008). 7. A.F.Brito et al.,medRxiv 10.1101/2021.08.21.21262393 (2021). 8. S.Karthikeyan et al.,mSystems 6,e00045-21 (2021). 9. S.Lamba et al.,medRxiv 10.1101/2022.07.14.22277616 (2022). 10. S.Karthikeyan et al.,Nature 609,101 (2022). 11. C.B.Uzzell et al.,medRxiv 10.1101/2021.05.21.21257547 (2021). 12. R.K.Fielding-Miller et al.,medRxiv 10.1101/2021.10.19.21265226 (2021) . 13. K.Jahn et al.,Nat.Microbiol.7,1151 (2022). 14. D.A.Gregory et al.,medRxiv 10.1101/2022.06.03.22275961 (2022). 15. A.Harrington et al.,Sci.Total Environ.853,158577 (2022). ACKNOWLEDGMENTS The authors are supported by National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases U01AI151812 (K.G.A), National Center for Advancing Translational Sciences UL1TR002550 (K.G.A), Centers for Disease Control and Prevention contracts 75D301- 20-C-09795 (K.G.A., R.K.) and 75D301-22-R-72097 (K.G.A, R.K.), and NIH 5T32AI007244-38 (J.I.L.). 10.1126/science.ade2503 SCIENCE science.org 6 JANUARY 2023 • VOL 379 ISSUE 6627 27

INSIGHTS | PERSPECTIVES AGING Obesity confers macrophage memory Epigenetic programming of myeloid cells in obesity contributes to macular degeneration By Kevin D. Mangum and span. Hata et al. demonstrate that deple- case, fatty acids, and transduces them into Katherine A. Gallagher tion of both local and distal myeloid popu- downstream cellular signaling cascades lations in mice that were once obese nor- that induce inflammatory gene expression O besity is an important and often malizes retinal dysfunction and limits the and a metabolic shift that poises immune modifiable risk factor that induces development of AMD, indicating that both cells toward an inflammatory response to systemic inflammation through local retinal and systemic ARMs contribute further stimulus. Oxidized low-density lipo- reprogramming of hematopoietic to AMD. protein (LDL) particles, which occur at high cells. Evidence suggests that envi- concentrations in the circulation of people The concept of epigenetic memory, in ronmental factors such as free fatty which cells stably retain the ability to trans- with obesity, induce an innate immune re- acids, which are present in high amounts mit specific gene expression patterns to cell sponse and confer epigenetic memory in in obesity, train innate immune cells such progeny, has been increasingly observed in monocytes and myeloid precursors in bone as monocytes and macrophages to an in- several disease states, such as cancer and marrow and spleen that influences inflam- flammatory phenotype (1–3). However, the cardiovascular disease (5–8). The exact mation and disease (1). In this manner, my- mechanisms that alter immune cells in molecular mechanisms that result in epi- eloid cells from mice that are fed a high-fat this setting are unclear. On page 45 of this genetic memory are unclear. Studies have diet, even when switched to a normal diet, issue, Hata et al. (4) report that free fatty linked myeloid cell–mediated inflamma- exhibit augmented TLR responses. acids associated with obesity epigenet- tion to the Toll-like receptor (TLR) family, In a metabolic disease state, such as ically alter adipose-resident macrophages which “senses” danger signals, or, in this diabetes, myeloid cells are epigenetically (ARMs) toward a proinflamma- reprogrammed distally in bone tory phenotype, which is retained marrow and the spleen, and then, through “epigenetic memory” dur- Epigenetic reprogramming of macrophages through chemokines released in ing the aging process in mice. These the local tissue environment, these patterned macrophages then travel Fatty acids, such as stearic acid, present in the adipose tissue of cells traffic to their respective sites to the eye, where they initiate an in- obese mice confer epigenetic alterations in adipose-resident (e.g., wounds, kidneys, heart) with flammatory program that promotes macrophages through Toll-like receptor 4 (TLR4)–mediated chromatin an altered phenotype, where they opening that recruits activator protein-1 (AP-1) transcription factors. age-related macular degeneration These epigenetically reprogrammed macrophages traffic to the regulate disease (6, 9, 10). In the (AMD). eye, where they promote pathological inflammation and age-related example of cutaneous tissue injury, Hata et al. found that ARMs from macular degeneration, even after mice return to normal weight. peripheral monocytes are recruited mice fed a high-fat diet exhibit in- to the wound, where they first dif- creased expression of inflammatory Adipose tissue ferentiate into proinflammatory genes, including tumor necrosis fac- Stearic acid O macrophages—which secrete in- tor (Tnf), interleukin-1b (Il1b), and OH flammatory cytokines such as IL-1b, Il6, which persists after mice re- AP-1 TNF, and IL-6—and then transition turn to normal weight. The authors TLR4 transcription to an anti-inflammatory phenotype factors show that this lasting proinflam- that promotes tissue repair (11). matory state is mediated by epigen- However, in diabetes, macrophages etic changes that occurred in ARMs Promoter are epigenetically altered at dis- during the obese state. These epi- Proin ammatory genes tal sites, and once recruited to the genetic alterations facilitate open tissue, they exhibit a sustained in- chromatin at binding sites for the Adipose-resident flammatory response that interferes activator protein-1 (AP-1) family of macrophage with wound repair and prevents transcription factors, which allows them from transitioning to an anti- expression of inflammatory genes, inflammatory macrophage pheno- thereby promoting pathologic in- type (12). Consistently, Hata et al. flammation (see the figure). Using show that resident inflammatory a laser-induced model of AMD, the Mouse eye cells in adipose tissue can be epige- authors find that previously obese Adipose-resident netically reprogrammed and later mice exhibited increased choroi- macrophage traffic to distant sites (the eye) and dal neovascularization, a feature enters circulation locally regulate disease severity. of AMD, compared with mice that The study of Hata et al. raises GRAPHIC: A. FISHER/SCIENCE were never obese and maintained a important questions about the up- normal weight throughout their life stream pathways that are respon- sible for epigenetic reprogramming Departments of Surgery and Microbiology and Reprogrammed In ammation Age-related macular in macrophages and whether tar- Immunology, University of Michigan, Ann Arbor, MI, macrophages Neovascularization degeneration geting these pathways can reverse USA. Email: [email protected] promote: Angiogenesis epigenetic changes. Although the 28 6 JANUARY 2023 • VOL 379 ISSUE 6627 science.org SCIENCE

authors selectively depleted ARMs in mice C L I M AT E to inhibit their functional effect on AMD, the therapeutic potential of this strategy Acting now will reduce is limited by off-target effects, because glacier loss macrophages in adipose tissue are likely important for maintaining adipose tissue Many of the world’s glaciers will disappear, homeostasis and performing compensa- but quick action will make a difference tory functions elsewhere. Accordingly, as intricacies of these epigenetic-based By Guðfinna Aðalgeirsdóttir1 and a better understanding of both. mechanisms are further uncovered, it will Timothy D. James2 Global models projecting glacier response be necessary to address how to design ef- fective, cell-specific treatments. Likely A s global mean temperature rises in to climate are fairly recent, evolving strategies involve cell-specific targeting of pace with increasing greenhouse gas from relatively simple volume-change epigenetic enzymes themselves, interac- emissions, the future of the world’s projections; to more complex models with tions between transcription factors (e.g., glaciers looks bleak. Rates of glacier different approaches for representing melt, AP-1 family) and epigenetic enzymes (e.g., mass loss have increased over the accumulation, frontal ablation, and geometric histone acetyltransferases), or upstream past two decades (1), a trend that changes; to the ambitious ensemble projects, signaling cascades that regulate epigenetic will continue even if emissions are capped such as the Glacier Model Intercomparison alterations. Other possible targets include (2–4). Despite their small size relative to the Project (Glacier-MIP) (4, 9). Most models the transcriptional regulators identified by Greenland and Antarctic ice sheets, these have represented glacier dynamics—the studies of epigenetic patterning induced in dwindling ice stores are important. They important component of glacier mass myeloid cells by a high-fat diet, such as the currently contribute as much to sea level as balance involving ice flow and iceberg signal transducers and activators of tran- the ice sheets (3), their disappearance means calving—using basic assumptions about mass scription (STAT) family, nuclear factor- water insecurity for millions, and their redistribution or the relationship between kB (NF-kB), interferon regulatory factor retreat increases glacier hazard frequency, glacier volume and area. Until now, only one (IRF), and JUN (1). such as glacier outburst floods and landslides of these global models (10) has simulated (2). Although most countries have agreed glacier dynamics using a flowline model, Elucidating the specific upstream to pursue temperature limits within 1.5°C which is a more realistic way to model glacier mechanism(s) that promote the open chro- above preindustrial levels (5), these targets changes, where each glacier is represented matin conformation also warrants further are unmet (6). On page 78 of this issue, by a centerline along its length. Despite investigation. Moreover, interrogation of Rounce et al. (7) present a model of the fate recent unprecedented efforts in global glacier TLR signaling may help uncover how al- of all 215,547 glaciers under different climate projections, several key physical processes terations in this pathway affect cellular scenarios. Their findings emphasize the need that control glacier mass loss remain absent. and metabolic shifts in ARMs that are re- to act now to prevent substantial glacier loss. sponsible for their dysregulated function The study by Rounce et al. is a substantial in disease. For example, does activation The path to a global projection model for step forward in predictive modeling. They of TLR signaling alone confer epigenetic individual glaciers has been long. Historically, provide a set of predictions for every glacier memory in macrophages? And if so, what glacier measurements were made directly, on Earth, covering 2015 to 2100. These are is the overlap between TLR-induced re- on the surface, and later from aircraft using based on reference future greenhouse gas gions of open chromatin and those found aerial photography. Both methods are labor emission (representative concentration in ARMs from obese mice? According to intensive and costly, and, therefore, they can pathways) (11) and socioeconomic (shared the study of Hata et al., substantial overlap only be undertaken consistently and over socioeconomic pathways) (12) scenarios, between these regions might be expected; long time periods for a handful of accessible taking advantage of new datasets of global however, nonoverlapping regions might be glaciers (8). Nonetheless, these records glacier mass balance (1) and near-global used to identify alternate upstream regu- provided important early evidence of the frontal ablation (13). Their model represents lators of myeloid patterning. Additionally, sensitivity of glaciers to changes in climate glacier dynamics with a flowline model and the specific contribution of tissue-resident and of their dynamic nature. Since then, includes important physical processes, such macrophages versus bone marrow–derived satellite data provide records of the number as the effect of surface debris on melt and myeloid cells to inflammatory diseases and area of glaciers, elevation changes, their frontal ablation. Although there is room for should be dissected further to guide more velocity, and measurements of mass changes improvement, with more-accurate glacier effective and targeted therapeutics. j for essentially every glacier on Earth. thickness estimates and higher-resolution Although these records are insufficient for climate condition forecasts, this model is the REFERENCES AND NOTES understanding either the effects of climate most comprehensive so far. changes from the more distant past or 1. A. Christ et al., Cell 172, 162 (2018). how glaciers will change in the future, By providing model results in the context 2. K. Ganeshan, A. Chawla, Annu. Rev. Immunol. 32, 609 they have provided key calibration data for of policy-relevant end-of-century mean global glacier models that can help provide global temperature increases, the authors (2014). directly attribute regional mass loss, sea 3. M. G. Netea et al., Science 352, aaf1098 (2016). 1Institute of Earth Sciences, University of Iceland, level contributions, and the number of lost 4. M. Hata et al., Science 379, 45 (2023). Reykjavík, Iceland. 2Department of Geography and glaciers to the consequences of meeting 5. L. J. Gaydos, W. Wang, S. Strome, Science 345, 1515 Planning, Queen’s University, Kingston, ONT, Canada. and failing to meet the Paris Agreement’s Email: [email protected]; [email protected] 1.5° to 2°C temperature limit, and they tell (2014). a tragic tale. Even in the optimistic best-case 6. G. J. Koelwyn et al., Nat. Med. 26, 1452 (2020). 7. A. S. Kimball et al., Immunity 51, 258 (2019). 8. F. M. Davis et al., J. Exp. Med. 218, e20201839 (2021). 9. M. Tomczyk et al., Basic Res. Cardiol. 112, 39 (2017). 10. T. Tran et al., Nat. Commun. 14, 13 (2022). 11. T. A. Wynn, K. M. Vannella, Immunity 44, 450 (2016). 12. J. Yan et al., Nat. Commun. 9, 33 (2018). 10.1126/science.adf6582 SCIENCE science.org 6 JANUARY 2023 • VOL 379 ISSUE 6627 29

INSIGHTS | PERSPECTIVES Iceland Historical changes at Iceland’s Sólheimajökull OPTICS 05 Since the 1890s, the Sólheimajökull glacier has retreated nearly 2 km Toward km (data are from https://islenskirjoklar.is). The model results reported ultrathin optics by Rounce et al. suggest that glaciers such as Sólheimajökull will retreat Mýrdalsjökull another ~8 km in just 80 years by the end of 2100. Function determines the minimum thickness of an optical system By Francesco Monticone Glacier outlines Sólheimajökull O ptical systems are ubiquitous in GRAPHIC: V. ALTOUNIAN/SCIENCE 2021 today’s world, from smartphone 1945 02 cameras to microscopes and tele- 1890 scopes, all capturing ever-increas- km ing amounts of data and augment- scenario, where global mean temperature is ing our visual perception. Making kept within 1.5°C of preindustrial levels, the support for climate policies than focusing lenses and other optical components thin- results of Rounce et al. suggest that nearly on urgency and consequences (15). Rounce et ner has been an important goal in the field 60% of the world’s glaciers will be lost by al., while issuing a stark warning about the of optics in recent years. Creating thin and 2100 (see the figure). Within 2°C, the agreed consequences of insufficient action, achieve lightweight virtual and augmented reality warming limit of the Paris Agreement, ~70% this framing with an important message: headsets or night-vision goggles, for ex- of glaciers <1 km2 and nearly 20% of glaciers Although it is too late to avoid losing many ample, would be a game changer for con- between 1 and 10 km2 will be lost. However, glaciers, any effort to limit global mean sumer and military applications. The push estimates from COP26 predict that global temperature rise will have a direct effect toward miniaturization requires better mean temperature increase is headed toward on reducing how many glaciers will be lost. theoretical understanding of how thin an ~2.7°C by 2100 (6). At these temperatures Although projections provide important optical system can be. On page 41 of this and higher, rates of mass loss will increase insight into the magnitude, patterns, and issue, Miller (1) derives quantitative limits even for the large glaciers in the polar regions timing of changes that are key for adaptation on the minimum possible thickness of an that remain largely insensitive to increases and mitigation, when presented in a way that optical system, based only on the function below 2°C. Importantly, even if temperature translates any climate action into observable that the optics is to perform. This find- is stabilized at any level, the glaciers that outcomes, these projections can provide a ing and other recent results (2–9) address remain will continue losing mass beyond the key motivational message that is needed in foundational questions regarding why op- model’s 2100 end point. Taken together with this critical decade for climate action. j tical systems require certain thicknesses. forecasts predicting the loss of summer Arctic sea ice, increasing melt from Greenland REFERENCES AND NOTES Any optical system, such as a virtual real- and Antarctica, rising sea levels (3), and an 1. R.Hugonnet et al.,Nature 592,726 (2021). ity headset or a smartphone camera, is com- alarming decline of biodiversity (14), the 2. The Intergovernmental Panel on Climate Change (IPCC), posed of a combination of optical elements “climate emergency” has never been clearer. “IPCC Special Report on the Ocean and Cryosphere in a (usually lenses), optoelectronic devices Changing Climate,”H.-O.Pörtner et al.,Eds.(Cambridge (such as an imaging sensor or a display), Despite this urgency, national climate Univ. Press, 2019). and empty spaces between them. In a sim- action plans to cut emissions and adapt to 3. IPCC,“Climate Change 2021:The Physical Science Basis. ple imaging system, such as the human eye climate impacts (submitted ahead of COP26) Contribution ofWorking Group I to the SixthAssessment or a camera, a lens bends light rays, which continue to be insufficient to achieve the Report of the Intergovernmental Panel on Climate then converge in the space behind the lens, temperature goal of the Paris Agreement Change”(Cambridge Univ.Press,2021). focusing onto the electronic sensor, film, (6). Disappointingly, substantial attempts 4. B.Marzeion et al.,Earth’s Future 8,e2019EF001470 or retina where the image is formed. The were made at COP27 to weaken ambitions (2020). optical behavior of such a system, and its to quickly cut greenhouse gas emissions, 5. United Nations (UN)/Framework Convention on physical limits, may be better described and the negotiations ended without a Climate Change,“Adoption of the ParisAgreement,21st by considering the wave nature of light. commitment to phase out fossil fuels. We Conference of the Parties”(UN,2015). The physics of waves explains the natural seem to be stuck. Although the causes of 6. UN Environment Programme (UNEP),“Emissions Gap tendency of light to spread out, especially these failures are complex, maybe scientists Report 2021:The Heat Is On –AWorld of Climate Promises around obstacles and through apertures—a could help by doing a better job with NotYet Delivered”(UN,2021). phenomenon known as diffraction, which messaging. Recent studies have revealed that 7. D.R.Rounce et al.,Science 379,78 (2023). was first systematically observed and docu- positive opportunistic framing of climate 8. M.Zemp et al.,Nature 568,382 (2019). mented by the Italian physicist Francesco change is more effective at inciting public 9. R.Hock et al.,J.Glaciol.65,453 (2019). Maria Grimaldi in the 17th century. For a focusing lens, the wavefront emerging from 10. F.Maussion et al.,Geosci.Model Dev.12,909 (2019). 11. D.P.vanVuuren et al.,Clim.Change 109,5 (2011). School of Electrical and Computer Engineering, 12. B.C.O’Neill et al.,Clim.Change 122,387 (2014). Cornell University, Ithaca, NY 14853, USA. 13. W.Kochtitzky et al.,Nat.Commun.13,5835 (2022). Email: [email protected] 14. WorldWildlife Fund (WWF),“Living Planet Report 2022: Building a Nature-Positive Society”(WWF,2022). 15. N.Dasandi et al.,Commun.Earth Environ.3,239 (2022). 10.1126/science.ade2355 30 6 JANUARY 2023 • VOL 379 ISSUE 6627 science.org SCIENCE

the lens, which may be interpreted as the rials. This last step is related to light dif- light effectively experiences more space superposition of secondary spherical waves, fraction because the natural spreading of than what actually exists. The combination converges at a certain distance where a spot waves makes it difficult to confine light in of metalenses (replacing standard lenses) of concentrated light is formed. Because of channels with a small cross section relative and spaceplates (compressing space for diffraction through the finite lens aperture, to the wavelength. This implies that the light propagation) may lead to substantial the width of this focal spot, which deter- size of the transverse aperture, and there- miniaturization of any optical system. This mines the resolution of the imaging system, fore the thickness of the optical system, could enable, for example, a paper-thin depends on the area of the lens and the fi- must grow in proportion to the number of camera with large optical magnification nite wavelength of light. The wave nature channels it needs to accommodate and to despite its small thickness. In these future of light therefore explains the fundamental the finite wavelength of light. Thus, wave systems, the optics may be implemented as need for area in optics to achieve a certain physics explains not only the fundamental a planar ultrathin structure integrated di- imaging resolution. need for a minimum area but also the need rectly on top of an electronic sensor. for a minimum thickness, determined by The reason why optics may also require the function of the optical system and not Miller’s study provides a general ap- a nonzero thickness is more involved. This by its specific implementation details. proach to understanding how thin these can be explained by first recognizing that, systems can ultimately become. For exam- in most optical systems, such as a cam- Interest in the ultimate thickness limits ple, Miller directly applied his analysis to era, the output of the system at a certain of optics is motivated by recent advances spaceplates, showing that the derived lim- point (e.g., the light intensity on a sensor in the quest to miniaturize optical systems. its are obeyed and approached by existing pixel) depends on the input not just at a Engineered nanostructured films known as designs (15). The same approach was also single point but over an extended region metasurfaces or metalenses, for instance, used to determine the minimum required (e.g., the light on the entire lens surface). have the potential to replace conventional thickness for imaging systems as well as This type of input-output relationship is refractive lenses and enable much greater for metasurfaces that perform analog com- known as nonlocal and implies that the design flexibility (10). However, even after putations and image processing operations optical system may need to route waves replacing all optical elements with ultra- (11). Based on different methods, other re- cent studies have addressed the question How thin can an optical system get? of minimum required thickness for other classes of devices that fall beyond the pur- In a lens-sensor imaging system (left), a certain area and a certain distance between the focusing lens and view of Miller’s study, including light ab- the sensor are needed. A combination of new optical elements (right) allows a reduction in thickness. This may sorbers (3, 4), metasurface reflectors (4, 9), lead to the miniaturization of a wide range of optical systems, approaching their ultimate thickness limits. and full-color metalenses (6, 7). Thickness Reduced thickness As the race toward creating ultrathin optical systems is expected to accelerate in Lens aperture Flat nano- the coming years, new concepts and cut- structured lens ting-edge technologies, such as metasur- Incident (metalens) faces and spaceplates, and new approaches light to understanding their fundamental lim- its will play increasingly important roles. Transverse These advances may pave the way for a aperture new generation of optical systems, finally approaching—after nearly four centuries Wavefronts since the first systematic observations of light diffraction—the ultimate thickness Focal spot limits allowed by wave physics. j Wavelength Lens Sensor with N pixels Space com- REFERENCES AND NOTES pression device (spaceplate) 1. D.A. B. Miller, Science 379, 41 (2023). 2. D.A. B. Miller, J. Opt. Soc.Am. B 24,A1 (2007). GRAPHIC: A. MASTIN/SCIENCE sideways from a portion of the input sur- thin metasurfaces, a typical optical system 3. Z. Kuang, L.Zhang, O. D. Miller, Optica 7, 1746 (2020). face to a point on the output surface, cross- would still require large empty spaces to 4. M. Gustafsson, K. Schab, L.Jelinek, M. Capek, New J. ing a transverse aperture (see the figure). let light propagate—converging or diverg- Mathematically, this can be interpreted ing according to the desired functionality. Phys. 22, 073013 (2020). as a communication problem between Miniaturization of these spaces has been a 5. P. Chao, B. Strekha, R. Kuate Defo, S. Molesky, the two surfaces, where a certain number focus within the emerging field of nonlo- of channels are needed for such commu- cal flat optics, which seeks to enhance the A.W. Rodriguez, Nat. Rev. Phys. 4, 543 (2022). nication. Following these considerations, nonlocal response inherent in wave-based 6. F. Presutti, F. Monticone, Optica 7, 624 (2020). Miller showed that solely on the basis of systems (11, 12). Nonlocal effects are engi- 7. J. Engelberg, U. Levy, Optica 8, 834 (2021). the function that the optical system is to neered to create planar optical systems that 8. K. Shastri, O. Reshef, R.W. Boyd,J. S. Lundeen, perform (e.g., imaging), one can calculate are substantially thinner or are endowed the number of independent channels that with new functionalities. Notably, these F. Monticone, Optica 9, 738 (2022). must cross the transverse aperture and ideas are the basis of new optical elements 9. M. I.Abdelrahman, F. Monticone, Adv. Optical Mater. then determine the size of the aperture known as spaceplates (8, 11, 13–15), which needed to accommodate the number of are designed to mimic the way that light 10.1002/adom.202201782 (2022). channels, assuming that the system only propagates and spreads in empty space but 10. P. Lalanne, P. Chavel, Laser Photonics Rev. 11, 1600295 contains transparent, nonabsorbing mate- over a shorter distance. With a spaceplate, (2017). 11. K. Shastri, F. Monticone, Nat. Photon. 10.1038/s41566- 022-01098-5 (2022). 12. A. Overvig,A.Alù, Laser Photonics Rev. 16, 2100633 (2022). 13. C. Guo, H.Wang, S. Fan, Optica 7, 1133 (2020). 14. O. Reshef et al., Nat. Commun. 12, 3512 (2021). 15. A. Chen, F. Monticone, ACS Photonics 8, 1439 (2021). 10.1126/science.adf2197 SCIENCE science.org 6 JANUARY 2023 • VOL 379 ISSUE 6627 31

Soybean is harvested in Brazil for animal feed in Europe and China, where nitrogen and other nutrients accumulate. This is an example of worldwide connections of soils and soil health. POLICY FORUM of processes that are involved in land deg- radation, but most existing soil laws that SOIL HEALTH should protect soils now focus on single is- sues, such as desertification or soil contam- Soil biodiversity needs policy ination. Moreover, soil protection laws are without borders mostly national (3), although soil protec- tion does not stop at national frontiers. For Soil health laws should account for global soil connections instance, current climate change caused by poor land use and industrialization outside By Wim H. van der Putten1,2, understanding the distribution and func- sub-Arctic regions causes melting of the PHOTO: SILVIO AVILA/AFP/GETTY IMAGES Richard D. Bardgett3, Monica Farfan4,5, tional roles of soil biodiversity in develop- permafrost, which in turn exacerbates cli- Luca Montanarella6, Johan Six7, ing policy on restoring and protecting soil mate change through the release of carbon Diana H. Wall4,5 health across borders. Thus, policy should dioxide and methane to the atmosphere. focus not only on soils within a nation or S oil biodiversity is crucial for healthy union of nations but also on preventing Although it is widely acknowledged that soils, on which we all depend for negative footprints on each other’s soils. plants, birds, butterflies, and many other food, human health, aboveground animal species need to be protected, little biodiversity, and climate control. It is Numerous factors—such as urbanization, explicit attention exists for protecting soil well known that land use intensifica- automation, disease outbreaks, natural di- biodiversity (4). The European Union (EU) tion, climate change, environmental sasters, and even wars—influence how land Soil Strategy for 2030 (5) has been set up to pollution, and mining activities degrade is used, which affects the capacity of soils combat declining soil health in Europe and soil biodiversity. However, most current to perform multiple functions, also called beyond. The ambition is to have healthy and intended policies on soil protection not soil health (1). Searching for sustainable soils in the entirety of Europe by 2050. An only lack a holistic view on how biological, land use while providing food and feed for important aspect of this ambition is that physical, and chemical components of soil a more demanding population and dealing the EU is planning to propose a binding health are integrated but also overlook how with growing demands on land for multiple European Soil Health Law in 2023. To the soils across national borders and continents other functions requires insights into the best of our knowledge, this is the first and are connected by human activities. The many factors that influence land use. Often, most inclusive soil health protection law challenge is to use recent advancements in land use options are considered trade-offs, that recognizes the ecosystem services pro- and the challenge is to search for win-win vided by healthy soils and the need to pro- 1Netherlands Institute of Ecology, Wageningen, options, for example, climate change miti- tect those services for future generations. Netherlands. 2Department of Nematology, Wageningen gation by biodiversity restoration. A trans- Proposing a soil health law is an important University, Wageningen, Netherlands. 3Department of Earth disciplinary approach may help to under- step toward a sustainable society; however, and Environmental Sciences, The University of Manchester, stand possibilities and trade-offs to achieve the real challenge is to make it work. Manchester, UK. 4School of Global Environmental a more sustainable society (2). Although an Sustainability, Colorado State University, Ft. Collins, CO, awareness that healthy soils are the basis of To make the EU’s Soil Health Law opera- USA. 5Department of Biology, Colorado State University, Ft. a healthy society is growing, anchoring this tional, soil health needs to be measurable. Collins, CO, USA. 6European Commission, Joint Research view into policy is still a challenge. Different from soil quality, which is largely Centre, Ispra, VA, Italy. 7Department of Environmental chemical in focus and mostly used to char- Systems Science, ETH Zürich, Zürich, Switzerland. Soil protection requires an integrated acterize the status of soil to sustain crop Email: [email protected] legal framework to address the multitude productivity, soil health is a more holistic concept (6). It is based on the recognition of the ecosystem services that soils provide. As defined in the EU soil strategy, soils are healthy when they are in good chemical, biological, and physical condition and are able to continuously provide as many of the ecosystem services as possible. Soil health addresses the sustainability goals set by the United Nations (UN), which have been adopted by many countries. However, find- ing effective, easy-to-measure indicators for soil health is challenging, because there is no one-size-fits-all indicator for all circum- stances, just as in the case of soil quality (7). STRUGGLE FOR INDICATORS Measuring soil health requires information on biological, chemical, and physical prop- erties of soil, the obtainment of which is a substantial effort that will be too costly for 32 6 JANUARY 2023 • VOL 379 ISSUE 6627 science.org SCIENCE

INSIGHTS individual landowners. For example, soils chemical crop protection, crop rotation, Molecular identification, through DNA or contain an immense amount of biodiver- or intercropping. However, excessive use RNA barcoding, is widely used to character- sity. One handful of soil might contain more of chemical fertilizer and soil tillage, as ize the diversity and community composi- than 5000 taxa, including species of viruses, well as narrow crop rotation, enhance the tion of microbes, protists, nematodes, and bacteria, archaea, fungi, protists, nema- abundance of crop growth–reducing plant- other taxonomic groups of soil organisms. todes, earthworms, and other small inver- parasitic nematodes but reduce the abun- The use of metagenomics and metatran- tebrates. These organisms feed on live plant dance of most beneficial soil fungi (8). This scriptomics can assist in assessing soil mi- material, organic debris, and on each other makes intensive agriculture vulnerable to crobial communities and their functional as part of an intricate belowground food extreme drought and rainfall events, which potential. However, challenges remain in web. Analyzing the full soil biodiversity of increases the need for irrigation and drain- developing uniformly standardized meth- every piece of land at time intervals that are age of soils. Meanwhile, fertilizers, biocides, ods to conduct sample collection and analy- realistic for soil biota is costly. Therefore, and mechanical soil tillage are increasingly ses (10). This standardization is needed the EU Soil Strategy has proposed an EU- needed to grow high-yielding crop varieties. because expressions of units of species and wide scheme to enable landowners to per- Implementation of a soil health law requires individuals vary from numbers per weight form soil analysis with the “test your soil for assessments that inform on the complexity or volume of soil to numbers per square free” initiative. and functioning of the entire soil food web. meter(s), which makes comparisons across The question remains whether there are studies and taxonomic groups challenging These free tests are a great preliminary simple indicators for such complexity. (11). The use of environmental DNA (eDNA) step, but the numerous tests that are avail- might provide more uniformity and practi- able are not all equally well calibrated. It will also be challenging to find natu- cality for biodiversity assessments, provided Because soil biota perform many different ral soils that can act as a reference for that they are well calibrated (12). functions, there is no species that can repre- healthy agricultural soils. In natural eco- sent all. Some species provide soil structure systems, burrowing soil organisms such Using new molecular identification tech- by converting plant litter into plant-accessi- as earthworms promote soil structure and niques may help to determine which soil ble nutrients and others determine whether water infiltration, decomposing bacteria species can be found where and whether soils produce or consume greenhouse gases, and fungi recycle organic and mineral nu- they are threatened or not. The current whereas certain soil biota provide plants with trients by breaking down plant litter and lack of knowledge hampers policy on soil protection against natural enemies, both be- root excretion products, and symbiotic and biodiversity protection. It is unknown low and above the ground (6). In addition, mutualistic microbes, as well as soilborne whether certain soil organisms should be mutualistic symbionts, such as mycorrhizal pathogens, may have a positive role in sup- placed on a “red list” of species that are fungi and nitrogen-fixing bacteria, play an pressing dominant plant species, thereby threatened by extinction (1). There are important role in enhancing soil fertility, and promoting the coexistence of multiple several examples of highly sensitive eco- they may protect plants against soilborne species in natural grasslands, forests, and systems in which single soilborne species pathogens and root-feeding herbivores. other ecosystems. Moreover, belowground perform essential functions, such as the biota are indirectly involved in the control southernmost bacteria-eating nematode Likewise, although soil types have been of aboveground enemies, including patho- Scottnema lindsayae, which lives in the relatively well described at a regional scale, genic bacteria and fungi and shoot-feeding dry valleys of Antarctica and is threatened local soil conditions can be highly variable. insects. In densely populated industrialized by climate warming. This nematode plays For example, soils are made up of different parts of the world, it is likely that most, if a crucial role in nutrient cycling. layers, or horizons, with contrasting physi- not all, soil is affected by human activities. cal, chemical, and biological characteristics. The challenge for soil laws will be how to There are also examples of invasive Proper quantification of biological, physi- develop gold standards for healthy soils. soil organisms, such as the oomycete cal, and chemical soil properties at realistic Phytophthora cinnamomi, which destroys spatial and temporal scales requires inten- ASSESSING SOIL BIODIVERSITY forest vegetation in Australia, and invasive sive soil sampling and laboratory analyses. The Convention on Biological Diversity earthworms that change nutrient cycles in Implementation of this information in a soil defines biodiversity as the variation in life North American forests. The EU soil strat- health law requires indicator values that are from genes to ecosystems and landscapes. egy makes explicit reference to the need as simple as possible and can be used to pro- This confronts comprehensive soil biodi- to assess the risk of alien flatworm species pose measures to be implemented locally. versity monitoring with several challenges. for their potential inclusion in the list of For instance, the proposed establishment of At the genetic level, the species concept is “invasive alien species of Union concern,” EU-wide Soil Health Districts will enable a less clear for microbes than for plants or in line with the EU Invasive Alien Species locally adapted approach. The first precur- animals, so that microbes are identified as Regulation. Nevertheless, the concepts of sors of these districts are the 100 Living Labs operational taxonomic units (9). These ap- rarity and invasiveness, which are well ac- and Lighthouses to be established within the proaches are often used for analyzing com- cepted for plants and aboveground animals, research mission of the EU named “A Soil munity composition, both of microbes and remain largely unused for soil biodiversity Deal for Europe.” This regionalized consider- small invertebrate fauna that occur in soil. protection across the globe. ation of soils mirrors a similar successful ap- Detailed studies of soilborne pathogens, proach in the United States that established root parasites, and model organisms have When considering the substantial efforts operational Soil Conservation Districts, revealed a high level of genetic diversity in that will be required to design and under- which have been the key to the success of individual species. Examples include the ge- take representative soil sampling, key ques- the US Soil Conservation Act of 1935. This netic population structure of soilborne pest tions arise: What sort of data are needed act reversed the “dust-bowl syndrome” that and pathogen species, such as that of fungi and for what purpose, and how can this caused displacement and hunger for mil- that cause plant wilting. However, these information be collected and made avail- lions of Americans. analyses may be too detailed for general soil able to all? It is likely not necessary to first health assessments. identify and describe all species of soil biota Farmers are strongly focused on con- before using the presently available infor- trolling pathogens and root feeders using mation for biodiversity protection. An alter- SCIENCE science.org 6 JANUARY 2023 • VOL 379 ISSUE 6627 33

INSIGHTS | POLICY FORUM native to species identification is to qualify trialized countries requires additional feed co-create knowledge that leads to sustainable soil biota according to traits, such as nitrite from other locations. The resulting flow of development (15). At the core of such global oxidizers or cellulose degraders. This func- resources (e.g., nitrogen, phosphorus, potas- approaches is the agreement between science tional approach has also been used to de- sium) may degrade soil biodiversity and soil and society on common definitions and gold velop food web models to analyze carbon health in both feed-production and feed- standards of soil health. and nitrogen flows through soils. consumption locations. At feed-production locations, soil biodiversity may decline as a PRESERVE WHAT IS HERE ENHANCING SOIL LITERACY result of lowered soil organic matter content It is essential that what is already here is Despite the challenges of analyzing soil bio- and export of nutrients, whereas in feed- protected and preserved. Draining carbon- diversity, progress has been made in bring- consumption locations, excessive availability rich soils, harvesting carbon from the re- ing soil biodiversity to a wider audience. For of manure results in nutrient enrichment of maining peatlands, or destroying pristine example, the publication of global maps of soil, shifts to bacteria-based soil food webs, soil biodiversity to convert land for yield diversity within taxonomic groups—bacte- and increased abundance of soil parasites maximization of single crop species might ria, (mycorrhizal) fungi, nematodes, micro- and pathogens. generate short-term profit for some but arthropods, and earthworms—has raised are self-destructive for society as a whole some awareness of the enormous diversity The global transport of nutrients has ma- in the long term. Moreover, climate change of life in soil and how it is distributed, as jor consequences for adaptation and mitiga- mitigation activities need to acknowledge has the recent production of the Global Soil tion under climate change. For instance, both the roles of soils in global biogeochemical Biodiversity Atlas (13) and the first Global the loss of soil organic matter in feed-produc- cycles. Planting trees in natural grasslands Soil Biodiversity Assessment (1). These tion regions and the shift to bacteria-based and peatlands, for instance, can have un- publications provide the most up-to-date soil food webs in feed-consumption regions desirable consequences for biodiversity syntheses of the current status of soil bio- result in lowered soil stability (14). As a re- and the huge amounts of carbon in their diversity and have stimulated the initia- sult, soils in both feed-production and feed- soils. Real action is urgently needed to pre- tion of the International Network on Soil consumption locations will be more sensitive vent vast amounts of fertile topsoil from Biodiversity (NETSOB), which aims to be- to climate change–induced extreme weather being washed away in waterways and onto come a network of Global Soil Biodiversity events. Restoring circularity by bringing ocean floors. It takes only a few years to Observatories (GLOSOBs). back manure to feed-production areas is destroy what nature has built over centu- one option for addressing these imbalances, ries. Therefore, the protection of soils, soil How soil observatories will work and but that would increase global transport. biodiversity, and soil health should be high what will be measured is still under devel- Another possibility is to reduce the distance on the policy list of all nations and regions, opment. Ideally these will be sites where between feed production and consumption because dead soil does not provide a sus- soil biodiversity is monitored over longer and close cycles within regions. Restoring cir- tainable business model anywhere. j periods with standardized protocols to cular food systems and therefore soil health quantify consequences of global changes will be a major challenge for enhancing sus- REFERENCES AND NOTES in climate, land use, invasive species, ero- tainable food production and will require sion, and other changes that require de- transdisciplinary research approaches that 1. Food andAgriculture Organization of the United Nations tailed and long-term monitoring efforts. involve not only socioecology, economics, (FAO),et al.,“State of knowledge of soil biodiversity— These observatories will complement and other relevant disciplines but also a wide Status,challenges and potentialities: Report 2020”(FAO, the global Soil Biodiversity Observation variety of stakeholders, practitioners, and 2020); http://www.fao.org/documents/card/en/c/ Network (SoilBON) and EU Land Use and policy-makers. CB1928EN. Coverage Area frame Survey (LUCAS) pro- gram, which have started to collect soil bio- The decisions of farmers are influenced 2. C.Folke et al.,Ambio 50,834 (2021). diversity information from numerous sam- by numerous external factors, such as the 3. O.C.Ruppel,Soil Secur 6,100056 (2022). pling sites across Europe. These large-scale price of land and the price of fertilizers, crop 4. EuropeanAcademies ScienceAdvisory Council, monitoring programs may also be linked to protection chemicals, and agricultural prod- evaluations of the EU’s Soil Health Law and ucts on the world market. As a result, local “Opportunities for soil sustainability in Europe”(EASAC national surveys and to citizen science ac- soil conditions, including soil biodiversity Policy Report 36,German NationalAcademy of Sciences tivities on soils and soil biodiversity, such as and health, are influenced by national and Leopoldina, 2018), p. 48. the Dutch Soil Animal Days project. Public global decisions, such as on trade and envi- 5. European Commission,“Communication from the availability of data from such surveys will ronmental protection. Soil health policy will Commission to the European Parliament,the Council, facilitate further use. also influence human decisions; for example, the European Economic and Social Committee and the farmers may decide to move industrialized Committee of the Regions.EU Soil Strategy for 2030: WORLDWIDE SOIL CONNECTIONS agricultural practices to less-industrialized Reaping the benefits of healthy soils for people,food, Restoring soil health in one region also re- countries. Thus, wherever enacted, soil health nature and climate”(COM/2021/699 final European quires attention to its consequences in other laws will need to account for these side ef- Commission,2021); https://ec.europa.eu/environment/ regions of the globe. Worldwide, soils and fects to prevent soil health gain in one region publications/eu-soil-strategy-2030_en. soil biodiversity are connected through in- from resulting in soil health loss elsewhere. 6. J.Lehmann et al.,Nat.Rev.Earth Environ.1,544 (2020). ternational trade, climate change, invasive Therefore, global networks of soil observa- 7. E.K.Bünemann et al.,Soil Biol.Biochem.120,105 (2018). exotic species, tourism, atmospheric compo- tories—such as those initiated by SoilBON, 8. M.A.Tsiafouli et al.,Glob.Change Biol.21,973 (2015). sition, pollutants, and other environmental LUCAS, and the Food and Agriculture 9. N.-P.Nguyen et al.,NPJ Biofilms Microbiomes 2,16004 changes. Improving soil health in the EU may Organization of the United Nations’ (2016). have planned or unplanned side effects else- International Network on Soil Biodiversity— 10. C.A.Guerra et al.,Nat.Commun.11,3870 (2020). where on the globe. Those side effects need need to be embedded into “living labs” that 11. R.D.Bardgett,W.H.van der Putten,Nature 515,505 to be monitored for policy improvement. For test experimental approaches under real-life (2014). example, intensive animal farming in indus- conditions. In these living labs, researchers 12. J.Fediajevaite et al.,Ecol.Evol.11,4803 (2021). need to collaborate with all stakeholders to 13. A.Orgiazzi et al.,Global Soil BiodiversityAtlas (European Commission,Publications Office of the European Union,2016); https://www.globalsoilbiodiversity.org/ atlas-introduction. 14. F.T.deVries et al.,Proc.Natl.Acad.Sci.U.S.A.110,14296 (2013). 15. C.A.Guerra et al.,Science 371,239 (2021). ACKNOWLEDGMENTS All coauthors contributed equally to this work. 10.1126/science.abn7248 34 6 JANUARY 2023 • VOL 379 ISSUE 6627 science.org SCIENCE

Some actions, such as mitigating environmental pollution, will improve the lives of many animals. Another strength of this book is Nussbaum’s full-on embrace of the Anthropocene. She acknowledges that directly or indirectly, through action or omission, humans affect virtually every living thing on the planet, thus giving rise to broad and deep obliga- tions. This is in welcome contrast to views that tend to cordon off “nature” and relieve humans of responsibility for what happens there. There are also valuable discussions of such topics as why death can be a harm and how extinction hurts individual animals, as well as interesting historical asides. Nussbaum envisions a “multispecies BOOKS et al. world in which all have opportunities for flourishing.” Although she acknowledges con- flicts and challenges, there is an overall sense of unworldly optimism in this book. She un- ANIMAL STUDIES derstands how important human population The right to strive in a control is to realizing her vision, for example, but seems to think that educating women is enough to put this concern to rest. She also changing world discusses various problems that arise from keeping companion animals, but there is little mention of, for example, the toll that A philosopher prioritizes agency and Anthropocene domestic cats take on songbirds. Nor does she really address the discomfort that many concerns in a theory of animal justice people will feel about establishing a govern- ment office of “domestic animal welfare” or allowing animals to sue their guardians. By Dale Jamieson either through negligent or deliberate action. Nussbaum tends to be too categorical in at- Nussbaum argues for the superiority of her tributing commonsense psychological states S ince the publication of Peter Singer’s theory over those of others and goes on to to animals, and some of her most controver- Animal Liberation in 1975, attitudes discuss the harm of death, tragic conflicts, sial claims (e.g., that fish can be painlessly toward nonhuman animals have our responsibilities to animals in a variety of killed) are not well anchored in the literature changed drastically (1). Singer’s book settings, the possibility of human friendship she cites. There is little acknowledgment of was followed by papers and mono- with animals, conflicts of duty, and the role of the constancy of change in nature and the graphs by other philosophers, and a law in achieving justice for animals. disruption that it entails. Whether new field of animal studies emerged in its Nussbaum’s writing is ener- in the Anthropocene or some other wake. Justice for Animals, by the eminent getic and direct, full of stories and epoch, natural selection will drive philosopher and law professor Martha Nuss- anecdotes. The book is pleasingly speciation and extinction, and nu- baum, is a welcome addition to this literature. constructive rather than deaden- trients in any form, whether bacte- According to Nussbaum, all sentient ingly polemical. Its major accom- rial or mammalian, are seldom left animals have “imperfect rights”—rights not plishments, in my view, are the fol- on the table. The multispecies world against any particular person but against lowing: First, by showing how the will never be a peaceable kingdom. “humanity imagined as capable of collective Capabilities Approach can support Justice for In a book of such sweep and action.” These rights, she argues, should be a theory of justice for animals, it Animals: ambition, marked by the clarity recognized as actionable legal rights. strengthens the argument that our Our Collective and boldness of its claims, there is The “Capabilities Approach,” a theory of systematic treatment of nonhuman Responsibility bound to be a lot with which one well-being that Nussbaum worked out in animals is morally indefensible from Martha C. Nussbaum can take issue. Indeed, it is a virtue its original form with Nobel Prize winner almost any normative perspective. Simon & Schuster, of this book that the mind of the au- Amartya Sen, provides the foundation for a thor is so clearly on display. Even if The Capabilities Approach also 2023. 400 pp. substantive account of what it is for a crea- puts respect for agency at the center of in the end they are not fully convinced by PHOTO: ZANSKAR/ISTOCK PHOTO ture to flourish and thus what opportunities what we owe animals. Previous work has Nussbaum’s arguments, a confirmed species- rights should protect. The core idea is that an tended to neglect agency and focused in- ist or a Benthamite utilitarian can read this injustice occurs when an animal’s “significant stead on animal suffering (2). This is un- book with pleasure and profit. j striving” is inhibited by “wrongful thwarting” derstandable given the sheer scale of suf- REFERENCES AND NOTES fering entailed by practices such as the 1. P. Singer, Animal Liberation (HarperCollins, 1975). The reviewer is at the Center for Environmental and Animal mass production of meat. Yet the neglect of 2. D.Jamieson, Harv. Rev. Philos. 25, 111 (2018). Protection, New York University, New York, NY 10003, USA. agency can obscure the full range of ways Email: [email protected] in which we encounter animals. 10.1126/science.adf6029 SCIENCE science.org 6 JANUARY 2023 • VOL 379 ISSUE 6627 35

INSIGHTS | BOOKS SCIENCE AND SOCIETY Materialism meets transcendence A new documentary series follows a physicist’s pursuit of the profound By Robert S. Krauss laureate Jack Szostak and the Dalai Lama ner world of perception, consciousness, as proponents of these two camps, respec- and self-awareness. He meets Erik Sorto, S ome years ago on a summer night, tively. Although the Dalai Lama expresses who lost all movement from the neck Massachusetts Institute of Technology enthusiasm for scientific investigation, most down after being shot in the back. With physicist, philosopher, and novelist scientists will likely resonate with Szostak’s electrodes implanted into his posterior pa- Alan Lightman lay down in a boat off declaration that “It’s not just atoms and mol- rietal cortex and 2 years of training, Sorto a remote coast of Maine, stared up at ecules, it’s the organization…it’s no less won- learned to control the movement of a ro- the stars, and experienced a transcen- derful or beautiful because we understand botic arm by thought. This is an extraor- dental feeling of deep connection to nature that there is a natural origin for [life].” dinary achievement, and Lightman posits and the cosmos. What had happened in that Part 2, “The Big & The Small,” begins that it is an example of the beginning of moment? he later wondered. This question with the familiar “powers of 10” view of the our transition from Homo sapiens into sent Lightman on a personal journey in Universe, moving from the subatomic to Homo techno, part-human, part-machine which he attempted to reconcile his physi- the galactic. Lightman then queries what entities that reflect the modification of cist’s materialism with his profound experi- such explorations have to do with con- human evolution by technological means. ence in that boat. Lightman now shares his sciousness, conversing with BINA48, an ex- From an actual evolutionary biology stand- point, this is nonsensical, and it is unclear that Lightman even means to propose such an idea, but this section’s loose language will rankle some viewers. At another point in the series’ final epi- sode, Lightman finds himself dizzy from talk of neurons and galaxies and takes refuge in closely examining a single square inch of earth. His biophilia is obviously meaningful to him, and it would have been stimulating had the episode included interviews with an evolutionary biologist or naturalist, who might have helped to better articulate this facet of the human experience. The series closes, appropriately, with philosophical musings about the need for each of us to find meaning for ourselves. A small problem at the outset is the in- herent impossibility of conveying transcen- Alan Lightman’s efforts to answer life’s biggest questions reveal the joy of scientific searching. dence through description—the degree to which viewers relate to Lightman’s moment journey in Searching: Our Quest for Meaning traordinary humanoid robot programmed of enlightenment will depend on their own in the Age of Science. by artificial intelligence with >100 hours experiences and inclinations. Additionally, In part 1, “The Stars & The Osprey,” of a real woman’s memories. Here, he Lightman’s screen persona leaves something Lightman undergoes functional magnetic speculates that BINAs of the future may to be desired. There are, however, few people resonance imaging and interviews neuro- achieve consciousness. He then probes better qualified to explore these issues, and PHOTO: SEARCHING: OUR QUEST FOR MEANING IN THE AGE OF SCIENCE scientist Robert Desimone about how much this issue over Zoom with the Dalai Lama, as the series progresses, his humanity shines neuroimaging can tell us about Lightman’s whom viewers observe watching a movie through, bringing a welcome lightness to transcendental experience. He ultimately of BINA48 conversing with the woman some potentially ponderous material. finds this approach unsatisfying and intro- from whom BINA48 was programmed; Despite its focus on phenomena cur- duces viewers to the debate between mecha- this multilayered interaction is simulta- rently unexplainable by science, Searching nists, who believe that the laws of physics, neously disconcerting, comical, is full of the joy and passion that chemistry, and biology are sufficient to ex- and wondrous. After additional Searching: can be found in the doing of sci- plain life, and vitalists, who believe that liv- interviews with a bioethicist, a Our Quest for ence and succeeds in conveying ing creatures are imbued with an additional rabbi, and others, Lightman ul- Meaning in the Age how deeply meaningful science spiritual quality not explainable by science. timately concludes that we may is to its practitioners. It is well be just atoms and molecules, but, of Science worth your time and is espe- Here, he interviews biologist and Nobel in the words of Emily Dickinson, Geoffrey Haines-Stiles, cially recommended to families “The brain is wider than the sky.” with kids curious about life and The reviewer is at the Department of Cell, director our world. j Developmental, and Regenerative Biology, Icahn School In part 3, “Homo Techno,” Premieres 7 January of Medicine at Mount Sinai, New York, NY 10029, USA. Lightman contemplates our in- 10.1126/science.adf7352 Email: [email protected] 2023 on PBS.org and on public television stations; check local listings. 36 6 JANUARY 2023 • VOL 379 ISSUE 6627 science.org SCIENCE

RESEARCH an innate immune niche ide- ally positioned to surveil the IN SCIENCE JOURNALS cerebrospinal fluid. —SMH Edited by Michael Funk Science, adc8810, this issue p. 84 MPOX The mpox virus DNA- synthesizing machine Mpox (formerly called monkeypox) is an active public health emergency that requires more effective means of treatment and pre- vention. Peng et al. focused on a complex that plays a key role in the genome replication process of the mpox virus. They used cryo–electron microscopy to determine a structure of the DNA poly- merase F8, which catalyzes the synthesis of viral DNA, in complex with the processivity factor consisting of A22 and E4 and the DNA substrate. The mode of operation of the processivity factor shown by the structure differs from existing ideas and may pro- vide a basis for antiviral drug design. —DJ Science, ade6360, this issue p. 100 PHOTO: ETHAN BASS, CREATIVE COMMONS SHARE ALIKE 4.0 PLANT SCIENCE EXPATRIATE SCHOLARS Diversity reveals infection resistance Measuring returning scientists’ success P arasitic witchweed (Striga) reduces the yield of maize grown in infected fields. Strigolactones from maize roots encourage Striga germination. Li et al. analyzed the China is a top sender of natural variation in types of strigolactones exuded from maize roots. Maize geno- students overseas, and the types that produced mainly zealactol suffered less Striga infection than those that Chinese government launched produced mainly zealactone. A single cytochrome P450 catalyzes several of the the Young Thousand Talents oxidative steps in strigolactone biosynthesis, including conversion of precursors to either program to recruit and nurture zealactol or zealactone. —PJH Science, abq4775, this issue p. 94 high-caliber, early-career expatriate scientists who A flowering Striga plant overwhelming a susceptible maize host return to China after they receive doctorates abroad. Shi BRAIN ANATOMY a fourth meningeal layer called kilodaltons, effectively subdivid- et al. examined how effective the subarachnoid lymphatic-like ing the subarachnoid space into the program has been in sup- An extra layer lines membrane (SLYM). SLYM is two different compartments. porting the young scholars’ the brain immunophenotypically distinct SLYM is the host for a large productivity when they return from the other meningeal layers population of myeloid cells, the to China compared with their The traditional view is that the in the human and mouse brain number of which increases in peers that remained overseas. brain is surrounded by three and represents a tight bar- response to inflammation and They found that the scholars layers, the dura, arachnoid, and rier for solutes of more than 3 aging, so this layer represents were high (but not top) caliber pia mater. Møllgård et al. found and outperformed overseas peers in last-authored pub- lications because of greater access to larger research teams and better research funding in China. —EEU Science, abq1218, this issue p. 62 SCIENCE science.org 6 JANUARY 2023 • VOL 379 ISSUE 6627 37

RESEARCH | IN SCIENCE JOURNALS INNATE IMMUNITY but how this flow is sensed IN OTHER JOURNALS and transduced into later Keeping flagellin molecular and anatomical Edited by Caroline Ash silent left-right asymmetry has been and Jesse Smith unclear. Working with mouse Flagellin is a protein in the embryos, Katoh et al. found VACCINES CANCER PHOTO: PATRICK AVENTURIER/GETTY IMAGES bacterial flagellum that can that immotile cilia sense the stimulate Toll-like receptor 5 mechanical force generated Mapping vaccine-induced Make your own (TLR5)–mediated immune by the flow and suggest a bio- immune signatures neoantigens responses; however, some physical mechanism by which commensal bacteria manage to the direction of the flow is Most studies examining vaccine- Immunotherapies activate avoid triggering immune acti- sensed. Independently, work- induced immune responses the body’s own immune vation. By screening publicly ing in zebrafish, Djenoune have largely focused on one vac- system to fight cancer, but available gut metagenomes, et al. used optical tweezers cine at a time, which provides their effectiveness is limited Clasen et al. identified a class and live imaging to show that a limited understanding of the by their ability to distinguish of “silent” flagellins that bind immotile cilia in the organizer advantages and disadvantages cancer cells from healthy to TLR5 but only induce weak function as mechanosensors of various formulations. Looking cells. Chemical inhibitors are activation. The activity of TLR5 that translate extracel- for a more systemic overview, a mainstay of cancer therapy, is controlled by a domain that lular fluid flow into calcium Hagan et al. analyzed the human but they too have limitations is absent in these silent flagel- signals. When motile cilia transcriptional responses to 13 because cancer cells fre- lins. Such proteins were found were paralyzed and normal vaccines against various patho- quently become resistant to in human organoids, mice, flow stopped, mechanical gens from previously published drug treatment. Putting the and human stool and were manipulation of the cilia could datasets. Many of these vac- two together, Hattori et al. produced by Lachnospiraceae rescue, or even reverse, left- cines triggered expression from developed an approach that gut bacteria. —DAE right patterning. Thus, ciliary some common gene signatures draws on the strengths of both force sensing is necessary, linked to the induction of innate drug therapy and immuno- Sci. Immunol. 8, eabq7001 (2023). sufficient, and instructive for immunity and plasmablasts, therapy. The authors first embryonic laterality. —SMH although the effect of each treated lung cancer with the M E TA L LU R GY vaccine was different. Once drug sotorasib, which targets Science, abq8148, abq7317, the authors controlled for the KRAS, a mutant gene involved Tracking down the pores this issue p. 66, p. 71 magnitude and kinetics of each in cell signaling pathways vaccine’s distinct immune that control cell growth, cell Laser fusion techniques build CORONAVIRUS response, they were able to use maturation, and cell death. metal parts through a high- machine learning to develop a Engineered antibodies were energy melting process that Protection spanning common time-adjusted signa- then administered that specifi- too often creates structural viral variants ture that could predict antibody cally recognize neoantigens defects in the form of pores. responses to the vaccines. created by mutant KRAS Ren et al. used x-rays to track Despite the success of the —STS protein bound to sotorasib. the formation of these pores early generations of severe The antibodies killed even while also making observations acute respiratory syndrome Nat. Immunol. 23, 1788 (2022). with a thermal imaging system. coronavirus 2 (SARS-CoV-2) This setup allowed the authors vaccines, viral evolution and to develop a high-accuracy immune evasion have made method for detecting pore the development of next- formation from that thermal generation broadly protective signature with the help of a vaccines essential. Zhao et al. machine learning method. used the evolutionary history Implementing this sort of of the SARS-CoV-2 S protein tracking of pore formation to develop Span, a vaccine would help avoid building parts antigen that carries amino with high porosity that are acid residues that are con- more likely to fail. —BG sistent across SARS-CoV-2 strains. When administered Science, add4667, this issue p. 89 to mice, Span elicited a more broadly neutralizing antibody DEVELOPMENT response than a wild-type S protein vaccine. Span also Going with the flow conferred substantial protec- tion against challenge with In most vertebrates, left-right the Beta, Delta, and Omicron differences are specified dur- variants despite Delta and ing early embryogenesis by a Omicron arising after Span was small cluster of cells called the designed. —CSM left-right organizer. Within this organizer, motile cilia move Sci. Transl. Med. 15, rapidly to create a leftward eabo3332 (2023). directional flow of extracel- lular fluid that is the first sign of a left-right difference, 38 6 JANUARY 2023 • VOL 379 ISSUE 6627 science.org SCIENCE

V I T I C U LT U R E later in life among the children before they gave birth to the Climate change shifts grandchildren. —BW wine country Am. Econ. Rev. 10.1257/ A mong other threats to biodiversity and live- aer.20210937 (2022). lihoods, climate change is predicted to have major effects on European wine production. THERMOELECTICS Sgubin et al. modeled changes to pheno- logical phases, including flowering and fruit Tuning the transport maturity, for early- to late-ripening grape varieties under two global warming scenarios. With increas- Thermoelectric materials can ing temperatures, potential wine-producing areas convert heat into electricity, and are expected to expand north across Europe. many of these materials are Swaths of traditional wine-producing areas will becoming increasingly com- likely become unsuitable for grapevines by 2100. petitive with bismuth telluride Predicted losses will occur at much higher rates for commercial applications. if warming exceeds 2°C, with limited ability to Improving thermoelectric compensate by switching wine varietals. Extreme efficiency usually requires decou- heating or cooling events may alter predictions, pling the electrical and thermal but maintaining future warming below 2°C could transport properties. Yu et al. help to ensure the future production of high- discovered that planar defects quality wine. —BEL called quantum gaps manage this decoupling in germanium Glob. Chang. Biol. 10.1111/gcb.16493 (2022). telluride. The presence of these defects results in a material with Climate change is threatening traditional wine production improved thermoelectric proper- areas such as this drought-stricken site in southern France. ties. Engineering quantum gaps into other thermoelectric materi- als should help to improve their efficiencies. —BG Nat. Commun. 13, 5612 (2022). sotorasib-resistant cancer cells that demonstrate operating of their newborn children, but CELL BIOLOGY but spared normal cells that do temperatures suitable for prac- also contributed, years later, to not have mutant KRAS. —YN tical applications, with energy improved health of their newborn Fixing leaky lysosomes densities surpassing the US grandchildren. Analyzing records Cancer Discov. 10.1158/ Department of Energy’s techni- on all US births from 1975 to Lysosomes are a key degrada- 2159-8290.CD-22-1074 (2022). cal target for TES. —YS 2017 to study expansion of the tive compartment within cells, Medicaid program in the 1980s, so their integrity is essential. ENERGY STORAGE J. Am. Chem. Soc. 144, 21617 (2022). East et al. suggest that impacts A membrane repair process on the grandchildren of improved involving the so-called ESCRT Thermal energy storage HEALTH ECONOMICS in utero care for the children machinery is known to help in salt hydrates were not driven by changes in maintain lysosomal integrity by Health care benefits fertility behavior or selection into pinching out damaged regions Most of the energy produced span generations pregnancy as the children grew of membrane. Radulovic et al. in the United States ends up up. Instead, expanded prenatal describe an additional repair wasted as heat, one of the Expanded access to health care care likely contributed to better mechanism that involves major challenges for our sus- for low-income pregnant women health and economic conditions recruitment of the endoplasmic tainable future. Thermal energy not only improved the health reticulum (ER) and cholesterol storage (TES) technologies transfer. Lipidomic analyses of PHOTO: DSZC/GETTY IMAGES aim to minimize these losses. Expanded health care for low-income pregnant women resulted years later in the isolated lysosomes after mem- Among various TES systems, improved health of their newborn grandchildren. brane damage showed increased those based on thermochemical lysosomal phosphatidylserine, materials (TMs) demonstrate cholesterol, and phosphorylated the highest energy densities, phosphatidylinositol species. but they have not been actively The ER proteins VAPA and VAPB studied so far. Using density and the cholesterol-binding functional theory and machine protein ORP1L were recruited learning models, Kiyabu et al. to damaged lysosomes and developed an efficient approach thereby provided a source of to search for new TMs among membrane for successful repair. salt hydrates, a promising class Interference with this process of TMs, and to establish design resulted in cell death after guidelines for maximizing their lysosomal membrane damage. energy density. The authors —SMH identified a series of hydrates EMBO J. 41, e112677 (2022). SCIENCE science.org 6 JANUARY 2023 • VOL 379 ISSUE 6627 39

RESEARCH ALSO IN SCIENCE JOURNALS Edited by Michael Funk EPIDEMIOLOGY BIOCHEMISTRY has largely been limited by the optical materials available. Enabling wastewater Mutant misbehavior at Recent developments in fabrica- surveillance the membrane tion and optical component design now widen what can The COVID-19 pandemic has Dynamic remodeling of the be achieved. In particular, flat highlighted the importance and neuronal plasma membrane is optics or metasurfaces can be effectiveness of analyzing waste- critical for neuronal develop- designed with the functional- water to understand disease ment. Beeman et al. investigated ity of bulk optical components spread, prevalence, and evolu- why mutations in the kinase but with their thickness shrunk tion. In a Perspective, Levy et al. TAOK1 are associated with to just several hundred nano- discuss different approaches to neurodevelopmental disor- meters. Miller now presents a wastewater surveillance that can ders. TAOK1 bound to plasma theoretical study to determine enable pathogen detection at membrane phospholipids what the minimum thickness the community level, as well as through a helical region, and can be for a specific optical at the level of individual build- binding was inhibited by phos- function (see the Perspective ings. Additionally, wastewater phorylation of that region by the by Monticone). The approach analyses can elucidate the kinase domain. Kinase domain is general and should provide emergence and prevalence of mutations associated with bounds on the minimum size new variants, which can inform neurodevelopmental disorders of other wave systems, includ- public health services. There are abrogated catalytic activity, ing radio and acoustic systems. also untargeted approaches to locking TAOK1 into a mem- —ISO monitor known pathogens and brane-bound state that caused inform outbreak risk. Although abnormal protrusions and Science, ade3395, this issue p. 41; further technical advances are growth and maturation defects see also adf2197, p. 30 needed to improve the deploy- in dendrites of mouse hippocam- ment and uptake of wastewater pal neurons. —LKF IMMUNOLOGY surveillance across the globe, wastewater is an important Sci. Signal. 16, eadd3269 (2023). Lingering immune resource that has much to offer changes after obesity public health monitoring. —GKA GLACIERS A past period of obesity caused Science, ade2503, this issue p. 26 Melting away by a high-fat diet in mice produces persistent changes OPTICS Mountain glaciers, perennial ice in innate immunity even after masses excluding the Greenland weight loss and normaliza- Lithium niobate and Antarctic ice sheets, are a tion of metabolism. Hata et al. photonics critical water resource for nearly found that such diet-induced two billion people and are threat- obesity in mice, even after it The optoelectronic and nonlin- ened by global warming. Rounce was resolved, led to persistent ear optical properties of lithium et al. projected how those epigenetic changes in chromatin niobate make it a workhorse glaciers will be affected under in macrophages associated with material for applications in global temperature increases increased expression of genes optics and communication of 1.5º to 4ºC, finding losses of that function in inflammatory technology. Boes et al. reviewed one quarter to nearly one half responses (see the Perspective the science and technology of of their mass by 2100 (see the by Mangum and Gallagher). lithium niobate and its role in Perspective by Aðalgeirsdóttir Experiments with transplants of various aspects of photonic and James). Their calculations adipose tissue or bone marrow technology. They surveyed the suggest that glaciers will lose implicated alterations of myeloid evolution from bulk lithium nio- substantially more mass and cells in exacerbating inflamma- bate through weakly confining contribute more to sea level rise tory responses to experimentally waveguides to the recent devel- than current estimates indicate. induced injury in the eye. If similar opments with thin-film lithium —HJS processes occur in humans, niobate. The ability to span the then the authors propose that entire spectral range from radio Science, abo1324, this issue p. 78; such changes could contribute to optical wavelengths illustrates see also ade2355, p. 29 to predisposition to age-related the versatility of lithium niobate macular degeneration associated as a platform material in inte- OPTICS with obesity. —LBR grated photonics. —ISO Determining limits on Science, abj8894, this issue p. 45; Science, abj4396, this issue p. 40 optical thickness see also adf6582, p. 28 The functionality and perfor- mance of optical components 39-B 6 JANUARY 2023 • VOL 379 ISSUE 6627 science.org SCIENCE

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RESEARCH ◥ efficiency, miniaturization, and production scale and cost and has been widely imple- REVIEW SUMMARY mented for diverse applications. OPTICS ADVANCES: Lithium niobate, a crystal that was first grown in 1949, is a particularly attractive Lithium niobate photonics: Unlocking the photonic material for frequency mixing because electromagnetic spectrum of its favorable material properties. Bulk lithium niobate crystals and weakly confining wave- Andreas Boes*†, Lin Chang*†, Carsten Langrock, Mengjie Yu, Mian Zhang, Qiang Lin, Marko Loncˇar, guides have been used for decades for access- Martin Fejer, John Bowers, Arnan Mitchell ing different parts of the EM spectrum, from gigahertz to petahertz frequencies. Now, this BACKGROUND: Electromagnetic (EM) waves diodes enable the generation of millimeter material is experiencing renewed interest owing underpin modern society in profound ways. (mm) and terahertz (THz) waves, which span to the commercial availability of thin-film lith- They are used to carry information, enabling from tens of gigahertz to a few terahertz. At ium niobate (TFLN). This integrated photonic broadcast radio and television, mobile tele- even higher frequencies, up to the petahertz material platform enables tight mode confine- communications, and ubiquitous access to level, which are usually defined as optical fre- ment, which results in frequency-mixing effi- data networks through Wi-Fi and form the quencies, coherent waves can be generated ciency improvements by orders of magnitude backbone of our modern broadband internet by solid-state and gas lasers. However, these while at the same time offering additional de- through optical fibers. In fundamental physics, approaches often suffer from narrow spectral grees of freedom for engineering the optical EM waves serve as an invaluable tool to probe bandwidths, because they usually rely on well- properties by using approaches such as dis- objects from cosmic to atomic scales. For ex- defined energy states of specific materials, which persion engineering. Importantly, the large ample, the Laser Interferometer Gravitational- results in a rather limited spectral coverage. refractive index contrast of TFLN enables, Wave Observatory and atomic clocks, which for the first time, the realization of lithium are some of the most precise human-made To overcome this limitation, nonlinear niobate–based photonic integrated circuits on instruments in the world, rely on EM waves frequency-mixing strategies have been devel- a wafer scale. to reach unprecedented accuracies. oped. These approaches shift the complexity from the EM source to nonresonant-based ma- OUTLOOK: The broad spectral coverage, ultra- This has motivated decades of research to terial effects. Particularly in the optical regime, low power requirements, and flexibilities of develop coherent EM sources over broad spec- a wealth of materials exist that support effects lithium niobate photonics in EM wave gen- tral ranges with impressive results: Frequencies that are suitable for frequency mixing. Over eration provides a large toolset to explore in the range of tens of gigahertz (radio and the past two decades, the idea of manipulat- new device functionalities. Furthermore, the microwave regimes) can readily be generated ing these materials to form guiding structures adoption of lithium niobate–integrated pho- by electronic oscillators. Resonant tunneling (waveguides) has provided improvements in tonics in foundries is a promising approach to miniaturize essential bench-top optical systems 10 THz Mid-IR 150 THz Near-IR 400 THz using wafer scale production. Heterogeneous HHG Vis integration of active materials with lithium THz OFC OFC 800 THz niobate has the potential to create integrated OPO ible photonic circuits with rich functionalities. EOM Applications such as high-speed communica- 0.3 THz tions, scalable quantum computing, artificial OR SCG SHG intelligence and neuromorphic computing, and compact optical clocks for satellites and Radio AOM UV-A precision sensing are expected to particu- larly benefit from these advances and provide χ(2) LN EO AO a wealth of opportunities for commercial ex- χ(3) ploration. Also, bulk crystals and weakly con- fining waveguides in lithium niobate are expected to keep playing a crucial role in the near future because of their advantages in high-power and loss-sensitive quantum optics applications. As such, lithium niobate pho- tonics holds great promise for unlocking the ▪EM spectrum and reshaping information tech- nologies for our society in the future. Bulk LN Weakly confining LN Tightly confining LN The list of author affiliations is available in the full article online. *Corresponding author. Email: [email protected] Lithium niobate spectral coverage. The EM spectral range and processes for generating EM frequencies (A.B.); [email protected] (L.C.) when using lithium niobate (LN) for frequency mixing. AO, acousto-optic; AOM, acousto-optic modulation; These authors contributed equally to this work. c(2), second-order nonlinearity; c(3), third-order nonlinearity; EO, electro-optic; EOM, electro-optic modulation; Cite this article as A. Boes et al., Science 379, eabj4396 HHG, high-harmonic generation; IR, infrared; OFC, optical frequency comb; OPO, optical paramedic oscillator; (2023). DOI: 10.1126/science.abj4396 OR, optical rectification; SCG, supercontinuum generation; SHG, second-harmonic generation; UV, ultraviolet. READ THE FULL ARTICLE AT https://doi.org/10.1126/science.abj4396 40 6 JANUARY 2023 • VOL 379 ISSUE 6627 science.org SCIENCE

RESEARCH ◥ the “the silicon of photonics” (11), turns out to be particularly suitable for the generation and REVIEW manipulation of EM frequencies because it offers a rare combination of advantageous OPTICS properties: (i) large electro-optic, piezoelectric, and nonlinear-optic material coefficients; (ii) Lithium niobate photonics: Unlocking the engineerability of velocity matching through electromagnetic spectrum quasi–phase matching (QPM) and waveguide dispersion; (iii) broad transparency (400 nm to Andreas Boes1,2,3*†, Lin Chang4,5*†, Carsten Langrock6‡, Mengjie Yu7,8, Mian Zhang9, Qiang Lin10, 5 mm); (iv) long-term stability; and (v) wide- Marko Loncˇar7, Martin Fejer6, John Bowers11, Arnan Mitchell1 spread commercial availability of large, low- cost, optical-quality wafers. This makes LN Lithium niobate (LN), first synthesized 70 years ago, has been widely used in diverse applications one of the key photonic materials that has the ranging from communications to quantum optics. These high-volume commercial applications have potential to expand access to an ultrawide part provided the economic means to establish a mature manufacturing and processing industry for of the EM spectrum and support the next gen- high-quality LN crystals and wafers. Breakthrough science demonstrations to commercial products have eration of scientific breakthroughs and com- been achieved owing to the ability of LN to generate and manipulate electromagnetic waves across a mercial products. broad spectrum, from microwave to ultraviolet frequencies. Here, we provide a high-level Review of the history of LN as an optical material, its different photonic platforms, engineering concepts, spectral LN platforms coverage, and essential applications before providing an outlook for the future of LN. LN is a ferroelectric crystal and was first syn- T he technological development of our then manipulated through conventional com- thesized in 1949 (12) in its polycrystalline form. modern society is closely linked to our plementary metal-oxide-semiconductor (CMOS) From this discovery, it took 15 years until further electronics. Signals with frequency greater studies identified the material’s characteristic ability to make use of electromagnetic than 100 GHz (typically referred to as milli- electro-optical (13) and second-order nonlinear- meter waves) up to a few THz can be generated, optical (14) properties. The growth of single- (EM) waves. The wide EM spectrum, for example, by resonant tunneling diodes and crystalline LN using the Czochralski technique processed by high-speed electronics that use (15, 16) represented a breakthrough; this tech- spanning from radiowaves and micro- silicon or III-V semiconductors. For higher fre- nique is still in use today and is able to produce quencies (10 THz to 1 PHz) in the optical regime, optical-quality wafers up to a diameter of 150 mm waves through infrared radiation, visible light, the most common methods for EM wave gen- (6 inches), and several crystal compositions— eration use solid-state, fiber, gas, and semicon- such as congruent, near-stoichiometric, or doped and ultraviolet (UV) radiation up to high- ductor lasers. Although these strategies have with alkaline or transition metals—are avail- successfully enabled many applications, each able commercially. Over the decades, three main energy x- and γ-rays, has transformed the platform individually can only offer a limited LN photonic platforms have emerged, namely way we record images, carry information, and spectral coverage because of the specific plat- bulk crystals, weakly confining waveguides, and form’s dependence dependence on well-defined tightly confining waveguides, whose evolution transmit energy. Driven by the sophisticated energy bands or levels of solid-state materials, can be found in Fig. 1. atoms, and molecules. control of EM waves, the past few decades Bulk LN crystals To overcome this limitation, another impor- have witnessed notable breakthroughs in a tant strategy, parametric nonlinear frequency Bulk LN crystals have found wide adoption mixing, was introduced. Starting from optical for generation and manipulation of EM waves wide range of areas such as high-speed com- frequencies (hundreds of THz), this process owing to their compatibility with free-space leverages broadband parametric nonlinear optical setups, ability to handle high optical munication (1, 2), ultraprecision time-frequency effects for multiwave mixing to unlock previ- power, ease of fabrication, and low cost. Such metrology (3–5), bioimaging (6–8) and quantum- ously inaccessible EM frequencies on demand. crystals are typically millimeter- to centimeter- information science (9, 10). This approach shifts the complexity from a scale blocks of LN with optical-grade polished custom EM wave source to nonresonant ma- facets (see right side of Fig. 1). The generation and manipulation of EM terial effects, which can be engineered with additional degrees of freedom, allowing access Early demonstrations in bulk LN crystals in- waves lies at the heart of all scientific and to a much broader part of the EM spectrum clude electro-optic modulation (13) and second- (THz to PHz) with unprecedented control and harmonic generation (SHG) (14). A breakthrough technological explorations. Depending on the performance. In addition to nonlinear fre- discovery occurred when it was observed that quency mixing, the GHz to THz part of the EM the spontaneous polarization of LN crystals frequencies, there are several main strategies spectrum can be bridged through microwave- could be inverted locally by applying a high to-optical conversion, enabling the efficient pro- electric field at room temperature (17). This for generation and processing: Radio fre- cessing of EM waves through well-established process, referred to as “electric-field poling,” CMOS electronics. opened a reliable path for engineering the quency (RF) (<~100 GHz) signals can readily phase-velocity matching (i.e., momentum con- These prospects spurred the development of servation) between different waves and made be produced by microwave oscillators and a wide range of nonlinear and electro-optic previously explored domain-inversion methods material platforms over the past few decades. that relied on high-temperature ionic diffusion 1Integrated Photonics and Applications Centre (InPAC), School Among these platforms, lithium niobate processes (18) obsolete. Photorefraction was of Engineering, RMIT University, Melbourne, VIC 3000, (LiNbO3, or LN), which has been described as first discovered when investigating LN for non- Australia. 2Institute for Photonics and Advanced Sensing linear devices (19), which later provided the (IPAS), University of Adelaide, Adelaide, SA 5005, Australia. means for high-density data storage in LN (20). 3School of Electrical and Electronic Engineering, University of Adelaide, Adelaide, SA 5005, Australia. 4State Key Laboratory of Advanced Optical Communications System and Networks, School of Electronics, Peking University, Beijing 100871, China. 5Frontiers Science Center for Nano-optoelectronics, Peking University, Beijing 100871, China. 6Edward L. Ginzton Laboratory, Stanford University, Stanford, CA 94305, USA. 7John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. 8Ming Hsieh Department of Electrical and Computer Engineering, University of Southern California, Los Angeles, CA 90089, USA. 9HyperLight, Cambridge, MA 02139, USA. 10Department of Electrical and Computer Engineering, University of Rochester, Rochester, NY 14627, USA. 11Department of Electrical and Computer Engineering, University of California, Santa Barbara, CA 93106, USA. *Corresponding author. Email: [email protected] (A.B.); [email protected] (L.C.) †These authors contributed equally to this work. ‡Present address: Keysight Laboratories, Santa Clara, CA 95952, USA. Boes et al., Science 379, eabj4396 (2023) 6 January 2023 1 of 12

RESEARCH | REVIEW 2ω LiNbO3 discovery SHG Photorefraction Ti diffused wg. Proton exchange wg. LN Bulk 1949 1974 1982 LN 1965 1966 1950 1960 1980 1970 EO modulator +f Single crystal Ti EO modulator 1964 1966 1975 WGMR Optical rectification EFP High-density lon diffused 2004 2000 1993 Holography Weakly 1991 confining LN LN 2000 EO Mod. PPLN OPO Er3+ laser 1990 long haul 1995 1991 TFLN 1998 Nonlinear QPM 2004 1989 Non-resonant, Entangled photon CMOS voltages Heterogeneous LN cw squeezing generation & control for EO modulator laser on LN SiO2 2014 2018 2021 2007 2010 2020 Tightly confining LN Ar milling f 2009 Pockels laser PPTFLN dB/m 3D PPLN Resonant Comb 2022 wg. 2017 2019 2016 2018 SHG 2018 Fig. 1. Timeline of LN as a photonic material. LN has been developed into three major platforms: bulk crystals, weakly confining waveguides, and tightly confining waveguides (indicated by blue, pink, and purple, respectively). Milestone demonstrations are highlighted. cw, continuous-wave; EO, electro-optic; wg., waveguide; EFP, electric-field poling; WGMR, whispering gallery resonator; PPTFLN, periodically poled thin film LN. Bulk crystals have also been formed in the magnitude when compared with bulk crystals. electro-optic modulators, such waveguides shape of discs or ring cavities, by careful This relaxes the optical power requirements were a key component for long-haul commu- polishing of their facets (21–23). Such discs can and enables efficient EM wave generation at nication systems (38). This platform has been form so-called whispering gallery resonators moderate optical powers in the range of milli- explored for low-loss quantum-optical appli- (24), with quality factors reaching hundreds watts (continuous-wave) or few nanojoules cations, for example, up-conversion to near- of millions (25), making them attractive for (pulsed). visible wavelengths for single-photon detection highly coherent optical wave or microwave (39) and on-chip entangled photon-pair gen- sources and nonlinear-optical applications. Weakly confining LN waveguides can be eration by spontaneous parametric down- Recently, it was shown that ferroelectric do- formed by slightly altering the material com- conversion and control of the generated photons main engineering can also be achieved in position or structure to locally increase the (40). A large body of work in this field is re- three dimensions by using femtosecond laser refractive index to form the guiding core. The viewed in Gil-Lopez et al. (41). pulses that are focused into the crystal (26). first weakly confining waveguides were dem- This demonstration opens opportunities for a onstrated by lithium out-diffusion (29), which Weakly confining waveguides are attrac- new class of wave-mixing devices that were not was followed shortly thereafter by titanium tive because their mode volume is naturally previously feasible, such as three-dimensional in-diffusion (30) and later proton exchange close to that of standard optical fibers, which nonlinear photonic crystals. (31) and femtosecond laser writing (32). Ti- enables low interface losses (<0.5 dB at near- tanium in-diffusion and proton exchange re- infrared wavelengths) between waveguide Bulk crystals are particularly attractive in main common fabrication methods and require and fiber. Thus, a wide range of optical equip- optical cavity configurations such as parame- increased temperatures to drive the diffusion ment that has been developed for high-speed tric oscillators (27, 28) (see Fig. 2) to enhance processes (~1100°C for titanium in-diffusion optical communication can readily be con- the nonlinear interaction. They are also at- and ~200°C for proton exchange), which in- nected to these waveguides, providing a large tractive for high-power applications, for use crease the extraordinary refractive index of range of linear and nonlinear optical signal inside laser cavities (Q-switch, intracavity LN by a few times 10−3 (33) and ~0.1 (34), processing functionalities (42). These wave- SHG), or when using ultrashort, high–peak respectively. To form low-loss, nonlinear-active guides can be inexpensively produced on a power laser pulses. waveguides through proton exchange, an an- wafer scale and only require standard litho- nealing step at ~300°C is used, which reduces graphic tools with readily available micro- Weakly confining LN waveguides the index contrast to ~0.02. Such waveguides meter resolution. have been used for a number of frequency- Weakly confining LN waveguides maintain mixing demonstrations such as the first im- Tightly confining LN waveguides interacting fields over centimeter-length dis- plementation of QPM (see Fig. 3) for SHG in tances in small-mode volumes at high inten- LN (35, 36) and integrated erbium lasers (37). Tightly confining LN waveguides are a relatively sities (Fig. 1), thereby increasing nonlinear Importantly, when used as low-loss, high-speed new class of LN structures with even smaller mixing efficiencies by two to three orders of mode volumes that reach subwavelength mode Boes et al., Science 379, eabj4396 (2023) 6 January 2023 2 of 12

RESEARCH | REVIEW A Optical nonlinearities (2) B (3) Process SHG kFH kSHG SFG kFH1 kSFG DFG kPump kSignal FWM kPump1 kSignal FWM kPump kSignal kDFG kIdler kIdler kPump2 kPump kFH kFH2 difference-frequency non-degenerate degenerate second-harmonic sum-frequency generation four wave mixing four wave mixing generation generation Example ω LN 2ω ω1 ω1 + ω2 ωs ωi ω2 LN ωp LN frequency-doubled sodium-yellow optical parametric optical parametric Kerr resonator solid-state laser guide star oscillator amplifier Spectrum octave + _ _ ω 2ω ω1 ω2 ω1 + ω2 ωi ωs ωp ωi ωp1 ωp2 ωs ωi ωp ωs Frequency Frequency Frequency Frequency Frequency C Electro-optic effect D Photo-elastic & Piezo-electric effect n Electro-optic single / dual sidebands photo-elastic piezo-electric Acousto-optic Modulator GHz n E modulator E index change polarization, phase and ω ε ε amplitude modulation, due to electric field amplitude modulation index change beam deflection & wideband EO-combs due to strain electric field frequency shifting LN G due to strain S single sideband Process G LN LN MHz Example ω piezo ω Spectrum Process Example Spectrum Fig. 2. LN material properties used for generating and manipulating EM waves. (A to D) Illustration of the (A) second-order and (B) third-order nonlinear- optic, (C) electro-optic, and (D) photo-elastic and piezo-electric material properties of LN that are used for efficient generation and manipulation of EM frequencies on demand. diameters. This results in frequency mixing frequency doublers (45, 47, 48), electro-optic bulk materials such potassium titanyl phos- efficiencies that are nearly two orders of mag- modulators (49, 50), optical frequency comb phate (KTP) and b-BaB2O4 (BBO) are frequently nitude higher than those of weakly confining (OFC) generators (51Ð53), and lasers and am- used. However, one advantage of thin-film plat- waveguides, in addition to offering broad inte- plifiers based on Er doping (54, 55). forms, such as TFLN, over bulk solutions is the gration and dispersion-engineering opportunities. flexibility of engineering the waveguide geom- The thin-film LN (TFLN) platform enables etry, and hence dispersion, which results in Such strongly confining waveguides (43) photonic integration at a scale and density ap- greater flexibility of phase and group velocity use a thin film of LN on a lower-index cladding proaching that available on semiconductor matching, enabling tailoring of components layer, akin to the silicon-on-insulator platform, platforms (56). This is a highly attractive pro- within integrated systems to access previously which can be manufactured at scale with good position because the material properties of LN unachievable operating regimes. film uniformity and quality. Optical wave- allow for the homogeneous integration of im- guides are typically made by dry etching (44) portant active and passive photonic functions, Material properties and engineering concepts the LN film to form ridge waveguides or by often eliminating the need for additional ma- for bridging the EM spectrum strip-loading with a material that has a refrac- terials. To incorporate lasers and detectors on tive index that is higher than that of the top TFLN, building blocks based on III-V semi- LN is one of several materials that has many cladding (45); however, methods such as laser conductor materials still require heterogeneous attractive properties for generating and ma- ablation and diamond-blade scoring have also integration (57), which may be accomplished nipulating EM waves, including large non- been explored. The optical modes in such wave- using techniques developed for other popular linear-optic, electro-optic, and piezo-electric guides are tightly confined because of the integrated-photonic platforms such as silicon coefficients, as illustrated in Fig. 2. LN can also subwavelength waveguide dimensions and and silicon nitride (58). support various engineering concepts to fur- the high refractive index contrast between the ther enhance these effects, as shown in Fig. 3. guiding core and cladding, which enables Because TFLN combines high confinement dense integration using low-loss small-radius and high nonlinearity, it is particularly suit- Nonlinear-optical effects bends (46). This high index contrast has led to able for low-power continuous-wave and low- highly efficient and compact frequency-mixing energy pulsed applications (59). For high-power Nonlinear-optical effects can be used to gener- and frequency-generating components such as or high-energy pulsed excitation, confinement ate new EM waves through second-order [c(2)] or nonlinearity are less critical, and many other and third-order [c(3)] nonlinear-optical processes. Boes et al., Science 379, eabj4396 (2023) 6 January 2023 3 of 12

RESEARCH | REVIEW A Velocity matching B Dispersion engineering C Quasi–phase matching Process Process Process coherence length LC ω RF vp(ωRF) ω1 ω vp(ω) in phase ωOpt ω2 = ω3 ≠ vg(ω) nonlinear polarization ωN vp(2ω) 2ω in phase 180°out of phase Strategy gelectrode Strategy Strategy telectrode LN welectrode wLN dLN LN phase mismatch SiO2 Substrate SiO2 2.0 Substrate 2.0 1 μm tLN LN Δk = k2-ω 2kω = K KQPM 1 μm SiO2 Substrate QPM kω k2ω 1.9 Substrate Group vel. mismatch RF effective index (fs/mm) 20 300 nm 40 300 nm pQePriMod Λ 0 1.8 1.8 0 -40 crystal length L 4 μm telectrode periodic domain inversion QPM 4 μm telectrode dLN 400 nm -80 400 nm dLN kω 1.7 -20 Effect 4 6 8 10 12 conservation of 5 10 15 20 25 Electrode gap (μm) 2000 2100 2000 2100 momentum Electrode width (μm) Fundamental wavelength (nm) Effect Effect Modulator response (dB) 0 1.2 1.0 -2 Δn=0.0 Transfer function QPM Period 0.8 SH power (a.u.) Theory tched 0.6 matche -4 Δn=0.1 Λ = 2LC= 2π/Δk d 0.4 GraKtQinPMg=k-2vπe/cΛtorpqhausaemsia–phas e -6 Δn=0.2 0.2 conventional Δn=0.3 0.0 phase mismatched -8 2000 2050 2100 2150 2200 2250 0 50 100 150 200 Fundamental wavelength (nm) 01 2 3 4 Frequency (GHz) Propagation distance (LC) 100 μm Ground D G RF in Signal H Ground Microwave z 500 μm Ground(G) E 40 μm Signal(S) y Ground(G) F 2 μm Fig. 3. Engineering concepts used in LN technology to enable efficient efficient nonlinear optical interaction by inverting LNÕs spontaneous polarization coupling for a wide spectral range. (A to C) Some of the most commonly used periodically. a.u., arbitrary units. (D) EO comb generators that leverage velocity concepts in LN technology include the following: (i) Velocity matching (A) for matching and dispersion engineering. [Reprinted by permission from Springer broadband electro-optic interaction. Broadband electro-optic modulators can be Nature Customer Service Centre GmbH: Springer Nature (53), 2019]. (E) High- realized by engineering the electrode dimensions to achieve velocity matching speed EO modulators that leverage velocity matching. [Reprinted by permission between the phase velocity of a single-frequency RF signal and the group velocity from Springer Nature Customer Service Centre GmbH: Springer Nature (49), of the optical wave. (ii) Dispersion engineering (B) for broadband nonlinear 2019]. (F) A Kerr microcomb generator that leverages dispersion engineering. optic interaction. Broadband nonlinear optical interaction can be realized by [Reprinted with permission from (52) © The Optical Society]. (G) SHG engineering the waveguide dimension to achieve low group velocity (vel.) waveguides that leverage dispersion engineering and QPM. [Reprinted with mismatch. (iii) QPM (C) for efficient second-order nonlinear interaction. Phase permission from (59) © The Optical Society]. (H) An SHG waveguide that mismatch between the interaction waves can be compensated to achieve leverages QPM. [Reprinted with permission from (144) © The Optical Society]. Below the Curie temperature of LN (1150°C), tensor. For LN the strongest component is optical processes in LN use its nonlinear re- its crystal structure is noncentrosymmetric, where both EM waves are polarized along the fractive index (n2) of 1.8 × 10−19 m2/W (60), giving rise to a large second-order nonlinearity. axis of crystal asymmetry(termed d33) and is which is similar in strength to that of Si3N4 Meaning that an EM wave polarized along one 27 pm/V at 1064 nm. Common second-order (2.5×10−19 m2/W at 1.55 mm), enabling efficient crystal axis can cause a phase shift in another nonlinear processes include SHG, sum-frequency four-wave mixing processes that are suitable EM field with a certain polarization. The full generation (SFG), and difference-frequency gen- set of such interactions is called the nonlinear eration (DFG) (Fig. 2A). Third-order nonlinear for applications such as optical frequency comb (Fig. 2B). Boes et al., Science 379, eabj4396 (2023) 6 January 2023 4 of 12

RESEARCH | REVIEW Linear electro-optic effect achieved by engineering waveguide and elec- LN photonics for unlocking the EM spectrum The linear electro-optic effect (or Pockels effect) trode dimensions as well as material disper- LN’s combination of material properties and changes the refractive index of LN proportional sion. In the weakly confined LN waveguide engineerability provides the means to generate to an applied electric field, which can be used platform, the relatively high dielectric constant EM frequencies over a range that covers nearly to modulate EM waves that pass through the (x11,22 = 44, x33 = 27.9) of LN at microwave five orders of magnitude (53, 74–77), span- crystal, generating new frequencies around the frequencies results in a velocity mismatch, which ning from UV light to microwaves. Figure 4 injected wave spaced by a single or multiple can be addressed by using thick electrodes (a illustrates the breadth of frequencies that have of the electrical modulation frequency (Fig. few micrometers) to increase the phase velocity been experimentally generated and manip- 2C). LN’s largest electro-optic coefficient is of the RF wave. The lower dielectric constant of ulated using LN as a linear and nonlinear crystal-axis dependent (closely related to the SiO2, which is a common buffer layer for tightly frequency-mixing platform. nonlinear tensor) with the largest component confining waveguides, increases the phase ve- being on the order of 30 pm/V and typically locity of the RF wave, overcoming the need for Visible and UV light requires interaction lengths of several milli- thick electrodes for velocity matching. meters up to a few centimeters to achieve the Visible and UV light (400 to 900 THz) expe- desired phase shifts with reasonably low volt- Dispersion engineering riences very low material losses in LN owing ages. The effect has been used to modulate and to the 3.93-eV-wide bandgap (~950 THz) (78) manipulate EM waves with electrical signals Dispersion engineering uses the material of LN. Light in this spectral range is required from static or very low frequency to hundreds stack and waveguide dimensions as degrees for applications such as virtual reality (79) and of gigahertz. A key advantage of LN is that the of freedom to engineer the modal dispersion. probing atomic transitions for optical clocks electro-optic effect only changes the phase of Waveguide dispersion is determined by the or magnetic field sensors (80), as well as for light with no change to absorption. This is in wavelength-dependent field distribution in molecules and cells for bioimaging (6). Visible contrast to silicon and other semiconductors the core and cladding of the waveguide (Fig. frequencies can be generated in LN by making where it is difficult to achieve independent 3B). This waveguide (or geometric) dispersion use of the material’s second- and third-order phase and amplitude control. can become an important factor in the overall optical nonlinearities in combination with well- dispersion, otherwise solely determined by developed near-infrared light sources. For ex- Photo-elastic effect the material properties, by providing control ample, the second-order optical nonlinearity over the group-velocity mismatch and group- has enabled the generation of blue (17, 81–83), The photo-elastic effect changes the refractive velocity dispersion (59, 66). Within the LN plat- green (82, 84), yellow (82), orange (82, 85), and index of LN as a function of strain, which can forms mentioned above, meaningful dispersion red (82) frequencies by using either SHG, which be used for modulating and frequency-shifting engineering is usually only available in TFLN increases the EM frequency by one octave; SFG; EM waves by interacting with periodically because of the large index contrast between or a combination thereof. The highest EM fre- sheared or compressed LN caused by the ex- core and cladding. quencies that can be generated by such non- citation of acoustic waves via the piezoelectric linear optical processes are only limited by the effect (Fig. 2D). Typically, operation frequen- QPM UV absorption edge of LN (~950 THz, or 315 nm) cies of acousto-optical devices in LN are in and can reach up to 800 to 900 THz (77, 82) in the megahertz to single-digit gigahertz range, QPM is a technique that compensates for the the near UV spectral range. mainly because of practical considerations phase-velocity (i.e., momentum) mismatch of such as the size of the crystal and manufactur- different waves. This can be achieved by either Supercontinuum generation (SCG) provides ability of the electrodes. periodically inverting the spontaneous polar- another means to generate visible light in LN ization of the crystal when the phase mismatch by generating EM frequencies over a very broad Advantages of LN reaches 180° [after a distance called the coher- spectral bandwidth that possibly covers the ence length LC (17)] (Fig. 3C) or, in guided-wave entire visible spectrum and can reach all the A more detailed description of these effects and platforms, by periodically perturbing the mag- way to 850 THz (59, 76, 86). SCG typically uses their use in LN can be found in several other nitude of the nonlinear coupling through mod- the third-order nonlinearity in dispersion- review papers (60–65). Important to note is ifications of the waveguide dimensions (67). In engineered waveguides. However, in LN, the that LN does not necessarily exhibit the stron- the small signal conversion regime, this results second-order optical nonlinearity can further gest material effects when compared with other in a unidirectional energy flow over the entire help to push the generated spectrum toward materials. Indeed, there are many other ma- propagation length. The periodic reversal of shorter wavelengths through SHG and SFG terials such as KTP, BBO, GaAs, and InP that the spontaneous polarization can be achieved (76). Furthermore, the cascading of two second- have attractive material properties. However, by using well-developed optical, thermal, and order processes can result in a large effective LN distinguishes itself by its maturity, stability, electrical domain-engineering methods (68), third-order nonlinearity, which exceeds the commercial availability, wide transparency range, among which the electric-field poling method material’s third-order nonlinearity and whose and engineerability with respect to the cou- is the most widely adopted one and has been sign can be controlled through the choice of pling between EM frequencies within a wide applied to all three LN platforms to generate the sign of the phase mismatch. (87, 88). spectral range, making their generation more periodically and aperiodically poled LN crys- efficient and tailorable. tals with periods reaching submicron dimen- Near-infrared frequencies sions (69). Because of the Fourier-transform Velocity matching relationship between the QPM grating and Near-infrared frequencies (150 to 400 THz) the device’s transfer function (70–72), a non- are of particular interest because they are low Velocity matching is used for one of the most trivial frequency response can also be readily enough for Rayleigh scattering to be minimal common optical components in LN, namely engineered (73). It is important to note that but high enough such that molecular absorp- broadband electro-optic traveling-wave modu- electric-field poling and QPM engineerability tion can be avoided in specific windows, which lators (Fig. 3A). For efficient electro-optic in- are not available in most other optical material enables low loss transmission through optical teraction of the RF wave with the optical wave, platforms, which is one of the main reasons for fibers and on photonic integrated circuits the phase velocity of the single-frequency RF the wide adoption of LN for nonlinear optical (PICs). This makes them particularly attractive wave and the group velocity of the optical applications. for applications such as optical communications wave should ideally be identical. This can be (1, 2), microwave photonics (89), and quantum Boes et al., Science 379, eabj4396 (2023) 6 January 2023 5 of 12

RESEARCH | REVIEW Spectral brightness (a.u.)101 Idler Pump Mid-IR 150THz Near-IR Power (dBm) II I 0 II 1 10-1 10THz 400THz -20 5ω 6ω 7ω 8ω V 4ω 500 10-2 600 700 800 9ω 80 100 120 140 160 180 200 0.3THz I 800THz -40 Frequency (THz) 900 1000 Frequency (THz) THz isible 400 (110) IV (84) III (81) Radio quenc UV-A (104) V Mid IR (122) (49) Fre ies Higher Harmonics THz pulse EO comb Supercontinuum Normalized Power (a.u.) III Generated THz radiation 0 IV 0V 1.0 -20 -20 Power (dBm) -40 Power (dBm) -40 0.5 Pump -60 -60 -80 -80 0 -100 -100 0 1 2 3 4 5 360 380 400 183 184 185 186 187 188 189 190 191 192 200 300 400 500 600 700 800 Frequency (THz) Frequency (THz) Frequency (THz) Fig. 4. LN spectral coverage. The semicircle illustrates the EM spectrum range examples]. The circled dots in the spectrum indicate the pump frequency. and examples of generated EM frequencies when using LN for frequency mixing, with The illustrations and the detailed spectra surrounding the semicircle (from left I to V representing OPO midÐinfrared (IR) (I), higher harmonic (II), THz (III), to right, top to bottom) provide examples for (IR) (I) (74), (II) (77), (III) (75), EO comb (IV), and supercontinuum (V) generation [see (49, 81, 84, 104, 110, 122) for (IV) (53), and (V) (76). optics (9, 10), as well as for free-space applica- at near-infrared wavelengths using high–Q- by using bulk periodically poled LN (PPLN) tions that operate outside the visible spectrum, factor, dispersion-engineered Kerr micro reso- crystals. Use of this process has enabled the such as light detection and ranging (LiDAR) nators in TFLN (51, 52, 96), which use the generation of EM waves from near-infrared fre- and deep-space communication (90). Depend- third-order optical nonlinearity of LN or cas- quencies down to 56 THz in the mid-infrared ing on the application, near-infrared frequencies caded second-order optical nonlinearities (97). region (104–106), which is at the edge of the can be generated in LN through a wide range of Optical pump frequencies in the center of the transparency window of LN. More recently, mid- approaches, including Raman lasing and DFG, C-band (~192 THz) are often used because of infrared frequencies generated by DFG have which are processes that generate one or two the availability of inexpensive light sources, been demonstrated in weakly confining (107, 108) new EM frequencies, as well as Kerr micro- such as narrow-linewidth and mode-locked as well as TFLN waveguides, with continuous combs, SCG, and electro-optic combs, which can lasers and high-power fiber amplifiers. An wave conversion efficiencies improving by one generate tens to hundreds of new EM frequen- alternative way to generate near-infrared wave- to two orders of magnitude. TFLN waveguides cies in the form of OFCs. For example, the lengths is to use SCG (similar to the process can also be used to efficiently translate near- generation of photons at 185 THz was demon- outlined for visible-frequency generation), infrared frequency combs to the mid-infrared strated using Raman lasing in a high–Q-factor which has been used for generating OFCs that region owing to the large conversion band- TFLN resonator (91) pumped at 192 THz. A pop- cover the full near-infrared frequency range width afforded by dispersion engineering (109). ular approach for the generation of widely tun- and even reach into the visible (600 THz) able EM frequencies is the use of an optical and mid-infrared (100 THz) regions (59, 98). Kerr microcombs (110) and SCG (98, 111) have parametric oscillator (OPO). Here, two EM Electro-optic combs provide another power- both been used to generate OFCs in the mid- waves are generated, the signal and idler, which ful tool to generate OFCs—hundreds of comb infrared region, with the former relying on can be tuned by adjusting the phase-matching lines from 183 to 192 THz spaced by 25 GHz high–Q-factor TFLN ring resonators to generate condition to enable the generation of frequen- have been demonstrated (53, 99–101). an OFC from 139 to 162 THz (96). The frequen- cies between 200 and 268 THz (signal) and 110 cy combs generated by SCG have a wider spec- and 178 THz (idler) (92). Such OPOs, operating Mid-infrared frequencies tral width and can reach all the way to 60 THz with either continuous-wave or pulses of light, (111), a value limited by the phonon absorption are commercially available and offer wide spec- Mid-infrared frequencies (10 to 150 THz) expe- of LN. In the TFLN platform, the material tral tunability, which is difficult to achieve by rience low losses in LN for frequencies above absorption of the silica cladding layer under- other means. Squeezed light sources have also ~55 THz, when the phonon absorption starts to neath the LN thin film can also limit the gen- been demonstrated in the near-infrared spec- take place (102). Mid-infrared frequencies are erated frequencies, which has recently been tral range as fundamental building blocks for attractive because they can be used to excite overcome by using sapphire as a low-index quantum sensing and computing using degen- vibrational states of molecules (103) and hence cladding material (109) or by undercutting the erate parametric down conversion (93–95). are useful sources for spectroscopic sensors in waveguide region (112). applications such as air-quality monitoring in Applications that require the generation of cities or for process monitoring of chemical THz frequencies many closely spaced EM frequencies can use plants and emissions from pipelines. Such fre- OFCs. These combs have been demonstrated quencies have historically been generated in OPOs THz radiation (0.3 to 10 THz) can penetrate paper, plastics, and fabric and is therefore Boes et al., Science 379, eabj4396 (2023) 6 January 2023 6 of 12

RESEARCH | REVIEW attractive for standoff sensing and security (38), and strongly confining TFLN waveguides strations, for example, as part of self-referencing imaging, such as at airports. LN crystals are (49), with the latter being particularly attractive systems for optical clocks, in which the LN com- attractive for the generation of narrow-band, because of the attainable high modulation ponents can be connected to other sophisticated high-intensity THz frequencies by optical rec- speeds and low drive voltages. The bandwidth photonic infrastructure. Furthermore, the low- tification, which is a second-order nonlinear- of these electro-optic modulators can reach loss interfacing of weakly confined waveguides optic process and can also be described by over 100 GHz (49, 64, 120, 121) and even ap- is important for quantum optics applications, intrapulse DFG. In this process, the spectral proach THz levels (122). Acousto-optic devices for example, for the generation of photon pairs frequency components of ultrashort optical have also been demonstrated in bulk crystals, by spontaneous parametric down-conversion as pump pulses interact with each other and weakly confining waveguides (123) and strong- well as for frequency translation between quan- generate new EM-frequency components. This ly confining TFLN waveguides (124, 125), with tum nodes and long-haul fiber networks, in process can generate frequencies up to the interaction frequencies typically ranging from addition to heterogeneous intranode conver- difference between the blue and red edges of MHz to GHz levels. Such acousto-optic devices sion. Although LN is a well-studied material, the pulse spectrum, so that a 10-fs pulse cen- are traditionally used to induce small frequency more work is needed to investigate the opti- tered at 800 nm, for example, could generate shifts, as beam deflectors, as well as moderate- mization of light-induced absorption changes frequencies up to ~44 THz (6.8 mm). ly fast switches and power regulators (123–126). (photochromic effect), particularly for opera- More recently, they have enabled quantum trans- tions at short wavelengths (128). The pump pulses that have been used for duction for superconducting qubits (119, 127), optical rectification in bulk LN crystals are in which is attributable to the small acoustic mode The wider adoption of tightly confining LN the near-infrared region owing to the avail- volume in nanophotonic resonators fabricated waveguides is, at present, mainly hampered ability of high-power, ultrashort optical light in TFLN. by two shortfalls: (i) the poorly understood sources, which commonly generate pulsed THz uniformity, repeatability, and reliability of radiation with frequencies ranging from 0.2 to Future of LN technology the commercially available starting material 4 THz (75, 113–116), although higher frequency and (ii) the lack of low-loss interfaces to stan- generation is possible, as indicated above. Pulse LN, in all three modalities (bulk LN crystals, dard optical fibers. Although there has been energies up to 1.4 mJ at 0.4 THz have been weakly confining, and strongly confining LN some progress in solving the interface problem demonstrated by operating bulk PPLN crystals waveguides), is widely used for nonlinear optic, for submicron waveguides in LN (129, 130), at cryogenic temperatures and using chirped acoustic, and electro-optic processes to gen- they still require specialized fibers and high- laser pulses (75), with conversion efficiencies erate and manipulate EM frequencies over precision multistep e-beam lithography and reaching up to 0.9% (117). The generation a wide spectral range. Since LN’s inception, etching, which may not be practical or econom- of continuous-wave THz radiation, tunable the material and manufacturing processes have ical for large-scale, fully packaged solutions. from 1.34 to 1.70 THz and 3.06 to 3.59 THz, matured, resulting in mostly discrete compo- has also been demonstrated using cascaded nents that perform well-defined functions. In A high-volume application, such as optical optical parametric processes in a singly reso- the future, bulk LN crystal components will short-distance data communication, will pro- nant OPO using a bulk PPLN crystal for phase remain important for EM-frequency generation vide the commercial means to address both matching (104). across the spectrum, particularly for applica- the shortfalls and maturation of TFLN tech- tions that require high optical powers, such nologies. It will also drive the reduction of Microwave frequencies as in high-power OPOs, free-space acousto- TFLN wafer and manufacturing costs as well optic and electro-optic modulators, and Q- as increase diversity in TFLN suppliers. This Microwave frequencies (0.3 to 300 GHz) are switches in laser cavities. However, for the LN high-volume communication application is used in applications such as 5G and 6G com- waveguide platforms, we foresee a rapid accel- motivated by the ever-increasing need for munication, radar, and radio astronomy. In eration of developments across two dimensions: data center and cloud infrastructure, which recent years, “RF photonics” has become a (i) complexity and (ii) spectral breadth (Fig. 5). requires increased speed, reduced power con- widely used term to describe applications such Complexity will transition from millimeter- sumption, and lower cost for next-generation as the generation of ultrastable microwave scale single components on chip to micrometer- communication systems. Indeed, TFLN is an sources or the low-loss remoting of source and scale nanophotonic circuits followed by complex ideal candidate because of its low drive volt- transmitter, which uses light to carry modu- multilayer networks in which diverse materials age, compatibility with CMOS electronics (49), lated signals to an antenna and subsequent are heterogeneously integrated with LN and co- and high bandwidth. Long-haul telecom appli- conversion to microwaves. In the nonlinear packaged with electronic circuits. The spectral cations may also become commercial drivers optic context, such microwave frequencies can breadth of these devices will transition from to mature the TFLN platform because the be generated directly through a DFG process operating primarily at near-infrared frequen- major challenge for this application is per- in a whispering gallery mode resonator for cies to generating and manipulating EM fre- formance, where TFLN’s demonstrated data the optical and microwave mode (118) or by quencies from visible to microwave frequencies (symbol) rate of 120 gigabaud and beyond is using TFLN-superconductor hybrid electro- on demand. highly attractive (49). These devices can be optic systems (119). drop-in replacements for existing guided-wave Near-term LN electro-optic modulators, allowing for low However, in most RF photonics applications, threshold commercial adoption while offering LN is used to translate microwave frequencies In the near-term (next 5 years), bulk crystals performance advantages. For LiDAR appli- onto an optical carrier, which can then be trans- and weakly confining waveguides will remain cations, the recent breakthrough of Pockels mitted and manipulated in the optical do- essential platforms for the generation of EM cavity lasers (131) by integrating III-V semi- main and subsequently generate microwave frequencies, particularly in the near-infrared conductor gain sections with TFLN-based frequencies using a photodetector with an and visible frequency region because they offer external cavities offers unrivaled frequency appropriate bandwidth. The main mecha- mature fabrication and packaging processes. modulation speed and reconfigurability to nisms of conversion from microwave to optical The high-power handling capability and the low integrated lasers; injection locking of a laser frequency rely on the electro-optic and acousto- interface loss of such commercially available diode into an external LN ring modulator can optic effect in LN (see Fig. 2, B and C). Electro- products make them particularly attractive for also achieve fast frequency modulation while optic modulators have been demonstrated serving as individual devices in system demon- the wavelength tuning range is limited (132). in bulk crystals weakly confining waveguides Boes et al., Science 379, eabj4396 (2023) 6 January 2023 7 of 12

RESEARCH | REVIEW 15 YEARSTime Quantum computing Waveguide loss: <0.1 dB/m Atomic manipulation Superconductor On-chip photodetector Efficient optical-RF transduction Optical frequency division Atomic clock Self-referenced comb 3D packaging Atomic manipulation AR/VR Efficient visible generation Large scale PICs: >105 components 10 YEARS Frequency Precision broadband optical metrology Self-referenced comb synthesizing AI accelerator Large scale PICs: Bias monitoring >105 components 3D packaging Linear chirping Large scale PICs: >103 3D packaging LiDAR Fast reconfigurable laser Efficient THz generation Power handling: Watts level THz sensing/communications Efficient microwave/mm-wave Power handling: generation 6G Watts level 5 YEARS Optical to RF spectrum translation Mid-IR comb CO2 Gas sensing Optical to RF spectrum translation Broad spectrum comb Medical/Bio-sensing < 1V Vπ , up to 500 GHz bandwidth Radio over fiber Power handling: Optical communication Watts level CMOS-driven modulator 100 GHz BW Waveguide loss: <0.3 dB/cm DC RF mmWave THz MIR NIR Vis Frequency UV Fig. 5. Outlook of LN photonics and its applications. The applications are devices and systems, both of which jointly enable new applications. illustrated by the symbols in the center, which require the functionalities Emerging applications stimulate the improvement of material processing on either end of the spectrum. The continued development of quality and high-volume device production. DC, direct current; MIR, mid-infrared; engineering and production scalability drives the performance of photonic NIR, near-infrared; Vis, visible. An alternative approach is the adiabatic fre- scale becomes large. We anticipate that in the gains that reach an octave using microwatt av- quency conversion using LN-based resonators next 5 years, substantial investments will be erage powers or femtojoule-level pump ener- (133). These approaches can potentially provide made in this space, which will build the foun- gies (66, 134). The same approach can be used a chip-based, low-cost solution to frequency- dation of the wide-scale adoption of tightly to develop widely tunable, on-chip oscilla- modulated continuous-wave LiDAR. Fur- confining LN waveguide circuits as commer- tors for challenging spectral regimes, such as thermore, phase modulation with minimal cial devices. the visible and mid-infrared spectral ranges intensity modulation in LN can be used to for addressing atomic and molecular systems tune the emission angle of the light beam, At the same time, we foresee rapid progress used for metrology and spectroscopy, or ef- without sensitivity degradation during the in the development of TFLN at the device level ficient mm-wave and THz generation for wire- scanning. Addressing these near-term indus- for high-efficiency frequency mixing applica- less communication and sensing. Along this trial applications with relatively simple, high- tions, such as miniaturized OPOs and optical track of integrated OPOs and OPAs, squeezed- yield designs will help to mature the platform phase arrays (OPAs) using integrated PPLN- state generation for continuous-variable quan- and achieve the statistical understanding of based waveguides or microcavities, where earlier tum computing, quantum random number issues such as device yield, uniformity, repeat- commercial adoption is feasible. For these ap- generation, and quadratic dissipative soliton ability, and reliability. They will also provide a plications, several devices can be manufactured formation operating in a strongly nonlinear better understanding of photorefractive and on the same chip with parameter sweeps to ac- regime can be implemented. charging effects (e.g., bias drift in electro- count for uniformity and fabrication-tolerance optical modulators) in TFLN, which can have issues, such that the best devices can be isolated One essential trend we expect to happen in detrimental impacts on the performance and and packaged (i.e., “hand-picked”). These de- the next 5 years is the development of het- stability of LN PICs, particularly when their vices will be of high value because they can erogeneous integration on the TFLN platform. provide ultrabroadband, ultrahigh parametric Based on wafer-bonding, LN waveguides will Boes et al., Science 379, eabj4396 (2023) 6 January 2023 8 of 12