Before Virus, After Virus: A Reckoning.

The 2020 Lasker Awards, a celebration of one of the most prestigious international prizes given to individuals for extraordinary contributions to Basic and Clinical Medical Research, Pubic Health, and Special Achievement, was cancelled because of the COVID-19 pandemic. Typically, essays on the awardees and their scientific and medical contributions are solicited and published in Cell in collaboration with the Lasker Committee. This year, the Lasker Committee commissioned an essay to reflect on the historic contributions that scientists and physicians have made to our understanding of immunology and virology, and future directions in medical and basic research that have been highlighted by COVID-19 pandemic.

Seurat's Dots: A Shot Heard 'Round the Art World-Fired by an Artist, Inspired by a Scientist.

The iconic phrase "a shot heard 'round the world" signifies an exceptional event. Seurat's masterpiece La Grande Jatte, painted with many thousand dots of color, came as a shot to the art world-a shot fired by the imagination of the artist and inspired by the color theories of a scientist.

GAVI, the Vaccine Alliance.

This year's Lasker-Bloomberg Public Service Award goes to GAVI, the Vaccine Alliance, for providing sustained access to childhood vaccines around the globe, saving millions of lives, and highlighting the power of immunization to prevent disease.

Teaching Old Dyes New Tricks: Biological Probes Built from Fluoresceins and Rhodamines.

Small-molecule fluorophores, such as fluorescein and rhodamine derivatives, are critical tools in modern biochemical and biological research. The field of chemical dyes is old; colored molecules were first discovered in the 1800s, and the fluorescein and rhodamine scaffolds have been known for over a century. Nevertheless, there has been a renaissance in using these dyes to create tools for biochemistry and biology. The application of modern chemistry, biochemistry, molecular genetics, and optical physics to these old structures enables and drives the development of novel, sophisticated fluorescent dyes. This critical review focuses on an important example of chemical biology-the melding of old and new chemical knowledge-leading to useful molecules for advanced biochemical and biological experiments.

Phagocytosis: The Legacy of Metchnikoff.

This year is the centenary of the death of Elie Metchnikoff, the father of innate immunity. His work on phagocytosis has continued to flourish, particularly over the past half century.

You, Me, and We: Biolabs for the 21st Century.

Twenty-first century biomedical research is advantaged by institutional infrastructures that foster a collaborative, multidisciplinary approach. A few critical elements in the design of labs, research buildings, or campus can make interaction easier while preserving privacy and comfort for the individual researcher.

Highest ocean heat in four centuries places Great Barrier Reef in danger.

Mass coral bleaching on the Great Barrier Reef (GBR) in Australia between 2016 and 2024 was driven by high sea surface temperatures (SST)1. The likelihood of temperature-induced bleaching is a key determinant for the future threat status of the GBR2, but the long-term context of recent temperatures in the region is unclear. Here we show that the January-March Coral Sea heat extremes in 2024, 2017 and 2020 (in order of descending mean SST anomalies) were the warmest in 400 years, exceeding the 95th-percentile uncertainty limit of our reconstructed pre-1900 maximum. The 2016, 2004 and 2022 events were the next warmest, exceeding the 90th-percentile limit. Climate model analysis confirms that human influence on the climate system is responsible for the rapid warming in recent decades. This attribution, together with the recent ocean temperature extremes, post-1900 warming trend and observed mass coral bleaching, shows that the existential threat to the GBR ecosystem from anthropogenic climate change is now realized. Without urgent intervention, the iconic GBR is at risk of experiencing temperatures conducive to near-annual coral bleaching3, with negative consequences for biodiversity and ecosystems services. A continuation on the current trajectory would further threaten the ecological function4 and outstanding universal value5 of one of Earth's greatest natural wonders.

Ancient Rapanui genomes reveal resilience and pre-European contact with the Americas.

Rapa Nui (also known as Easter Island) is one of the most isolated inhabited places in the world. It has captured the imagination of many owing to its archaeological record, which includes iconic megalithic statues called moai1. Two prominent contentions have arisen from the extensive study of Rapa Nui. First, the history of the Rapanui has been presented as a warning tale of resource overexploitation that would have culminated in a major population collapse-the 'ecocide' theory2-4. Second, the possibility of trans-Pacific voyages to the Americas pre-dating European contact is still debated5-7. Here, to address these questions, we reconstructed the genomic history of the Rapanui on the basis of 15 ancient Rapanui individuals that we radiocarbon dated (1670-1950 CE) and whole-genome sequenced (0.4-25.6×). We find that these individuals are Polynesian in origin and most closely related to present-day Rapanui, a finding that will contribute to repatriation efforts. Through effective population size reconstructions and extensive population genetics simulations, we reject a scenario involving a severe population bottleneck during the 1600s, as proposed by the ecocide theory. Furthermore, the ancient and present-day Rapanui carry similar proportions of Native American admixture (about 10%). Using a Bayesian approach integrating genetic and radiocarbon dates, we estimate that this admixture event occurred about 1250-1430 CE.

Forced changes in the Pacific Walker circulation over the past millennium.

The Pacific Walker circulation (PWC) has an outsized influence on weather and climate worldwide. Yet the PWC response to external forcings is unclear1,2, with empirical data and model simulations often disagreeing on the magnitude and sign of these responses3. Most climate models predict that the PWC will ultimately weaken in response to global warming4. However, the PWC strengthened from 1992 to 2011, suggesting a significant role for anthropogenic and/or volcanic aerosol forcing5, or internal variability. Here we use a new annually resolved, multi-method, palaeoproxy-derived PWC reconstruction ensemble (1200-2000) to show that the 1992-2011 PWC strengthening is anomalous but not unprecedented in the context of the past 800 years. The 1992-2011 PWC strengthening was unlikely to have been a consequence of volcanic forcing and may therefore have resulted from anthropogenic aerosol forcing or natural variability. We find no significant industrial-era (1850-2000) PWC trend, contrasting the PWC weakening simulated by most climate models3. However, an industrial-era shift to lower-frequency variability suggests a subtle anthropogenic influence. The reconstruction also suggests that volcanic eruptions trigger El Niño-like PWC weakening, similar to the response simulated by climate models.

Extensive global wetland loss over the past three centuries.

Wetlands have long been drained for human use, thereby strongly affecting greenhouse gas fluxes, flood control, nutrient cycling and biodiversity1,2. Nevertheless, the global extent of natural wetland loss remains remarkably uncertain3. Here, we reconstruct the spatial distribution and timing of wetland loss through conversion to seven human land uses between 1700 and 2020, by combining national and subnational records of drainage and conversion with land-use maps and simulated wetland extents. We estimate that 3.4 million km2 (confidence interval 2.9-3.8) of inland wetlands have been lost since 1700, primarily for conversion to croplands. This net loss of 21% (confidence interval 16-23%) of global wetland area is lower than that suggested previously by extrapolations of data disproportionately from high-loss regions. Wetland loss has been concentrated in Europe, the United States and China, and rapidly expanded during the mid-twentieth century. Our reconstruction elucidates the timing and land-use drivers of global wetland losses, providing an improved historical baseline to guide assessment of wetland loss impact on Earth system processes, conservation planning to protect remaining wetlands and prioritization of sites for wetland restoration4.

Genetic continuity and change among the Indigenous peoples of California.

Before the colonial period, California harboured more language variation than all of Europe, and linguistic and archaeological analyses have led to many hypotheses to explain this diversity1. We report genome-wide data from 79 ancient individuals from California and 40 ancient individuals from Northern Mexico dating to 7,400-200 years before present (BP). Our analyses document long-term genetic continuity between people living on the Northern Channel Islands of California and the adjacent Santa Barbara mainland coast from 7,400 years BP to modern Chumash groups represented by individuals who lived around 200 years BP. The distinctive genetic lineages that characterize present-day and ancient people from Northwest Mexico increased in frequency in Southern and Central California by 5,200 years BP, providing evidence for northward migrations that are candidates for spreading Uto-Aztecan languages before the dispersal of maize agriculture from Mexico2-4. Individuals from Baja California share more alleles with the earliest individual from Central California in the dataset than with later individuals from Central California, potentially reflecting an earlier linguistic substrate, whose impact on local ancestry was diluted by later migrations from inland regions1,5. After 1,600 years BP, ancient individuals from the Channel Islands lived in communities with effective sizes similar to those in pre-agricultural Caribbean and Patagonia, and smaller than those on the California mainland and in sampled regions of Mexico.

Brain Lateralization: A Comparative Perspective.

Comparative studies on brain asymmetry date back to the 19th century but then largely disappeared due to the assumption that lateralization is uniquely human. Since the reemergence of this field in the 1970s, we learned that left-right differences of brain and behavior exist throughout the animal kingdom and pay off in terms of sensory, cognitive, and motor efficiency. Ontogenetically, lateralization starts in many species with asymmetrical expression patterns of genes within the Nodal cascade that set up the scene for later complex interactions of genetic, environmental, and epigenetic factors. These take effect during different time points of ontogeny and create asymmetries of neural networks in diverse species. As a result, depending on task demands, left- or right-hemispheric loops of feedforward or feedback projections are then activated and can temporarily dominate a neural process. In addition, asymmetries of commissural transfer can shape lateralized processes in each hemisphere. It is still unclear if interhemispheric interactions depend on an inhibition/excitation dichotomy or instead adjust the contralateral temporal neural structure to delay the other hemisphere or synchronize with it during joint action. As outlined in our review, novel animal models and approaches could be established in the last decades, and they already produced a substantial increase of knowledge. Since there is practically no realm of human perception, cognition, emotion, or action that is not affected by our lateralized neural organization, insights from these comparative studies are crucial to understand the functions and pathologies of our asymmetric brain.

Lineage tracing.

Lineage tracing is the identification of all progeny of a single cell. Although its origins date back to developmental biology of invertebrates in the 19(th) century, lineage tracing is now an essential tool for studying stem cell properties in adult mammalian tissues. Lineage tracing provides a powerful means of understanding tissue development, homeostasis, and disease, especially when it is combined with experimental manipulation of signals regulating cell-fate decisions. Recently, the combination of inducible recombinases, multicolor reporter constructs, and live-cell imaging has provided unprecedented insights into stem cell biology. Here we discuss the different experimental strategies currently available for lineage tracing, their associated caveats, and new opportunities to integrate lineage tracing with the monitoring of intracellular signaling pathways.

Cellular alchemy and the golden age of reprogramming.

The 2012 Nobel Prize in Medicine or Physiology recognizes the architects of two of the great paradigm-shifting discoveries of the last half-century of biology. In experiments performed nearly 50 years apart, Gurdon and Yamanaka made feasible the reawakening of pluripotency inherent in all cells and challenged forever our notions of cellular identity.

Towards a rigorous understanding of societal responses to climate change.

A large scholarship currently holds that before the onset of anthropogenic global warming, natural climatic changes long provoked subsistence crises and, occasionally, civilizational collapses among human societies. This scholarship, which we term the 'history of climate and society' (HCS), is pursued by researchers from a wide range of disciplines, including archaeologists, economists, geneticists, geographers, historians, linguists and palaeoclimatologists. We argue that, despite the wide interest in HCS, the field suffers from numerous biases, and often does not account for the local effects and spatiotemporal heterogeneity of past climate changes or the challenges of interpreting historical sources. Here we propose an interdisciplinary framework for uncovering climate-society interactions that emphasizes the mechanics by which climate change has influenced human history, and the uncertainties inherent in discerning that influence across different spatiotemporal scales. Although we acknowledge that climate change has sometimes had destructive effects on past societies, the application of our framework to numerous case studies uncovers five pathways by which populations survived-and often thrived-in the face of climatic pressures.

The gender agency gap in fiction writing (1850 to 2010).

Works of fiction play a crucial role in the production of cultural stereotypes. Concerning gender, a widely held presumption is that many such works ascribe agency to men and passivity to women. However, large-scale diachronic analyses of this notion have been lacking. This paper provides an assessment of agency attributions in 87,531 fiction works written between 1850 and 2010. It introduces a syntax-based approach for extracting networks of character interactions. Agency is then formalized as a dyadic property: Does a character primarily serve as an agent acting upon the other character or as recipient acted upon by the other character? Findings indicate that female characters are more likely to be passive in cross-gender relationships than their male counterparts. This difference, the gender agency gap, has declined since the 19th century but persists into the 21st. Male authors are especially likely to attribute less agency to female characters. Moreover, certain kinds of actions, especially physical and villainous ones, have more pronounced gender disparities.

Historical trends in teacher personality from human language.

Understanding the historical perception and value of teacher personalities reveals key educational priorities and societal expectations. This study analyzes the evolution of teachers' ascribed Big Five personality traits from 1800 to 2019, drawing on millions of English-language books. Word frequency analysis reveals that conscientiousness is the most frequently discussed trait, followed by agreeableness, openness, extraversion, and neuroticism. This pattern underscores society's focus on whether teachers are responsible. Polarity analysis further indicates a higher prevalence of low neuroticism descriptors (e.g., patient and tolerant) in descriptions of teachers compared to the general population, reinforcing the perception of teachers as stable and dependable. The frequent use of terms like "moral", "enthusiastic", and "practical" in describing teachers highlights the positive portrayal of their personalities. However, since the mid-20th century, there has been a notable rise in negative descriptors related to openness (e.g., traditional and conventional), coupled with a decline in positive openness terms. This shift suggests an evolving view of teachers as less receptive to new ideas. These findings offer valuable insights into the historical portrayal and societal values attributed to teacher personalities.

Transoceanic pathogen transfer in the age of sail and steam.

In the centuries following Christopher Columbus's 1492 voyage to the Americas, transoceanic travel opened unprecedented pathways in global pathogen circulation. Yet no biological transfer is a single, discrete event. We use mathematical modeling to quantify historical risk of shipborne pathogen introduction, exploring the respective contributions of journey time, ship size, population susceptibility, transmission intensity, density dependence, and pathogen biology. We contextualize our results using port arrivals data from San Francisco, 1850 to 1852, and from a selection of historically significant voyages, 1492 to 1918. We offer numerical estimates of introduction risk across historically realistic ranges of journey time and ship population size, and show that both steam travel and shipping regimes that involved frequent, large-scale movement of people substantially increased risk of transoceanic pathogen circulation.

Antarctica's wilderness fails to capture continent's biodiversity.

Recent assessments of Earth's dwindling wilderness have emphasized that Antarctica is a crucial wilderness in need of protection1,2. Yet human impacts on the continent are widespread3-5, the extent of its wilderness unquantified2 and the importance thereof for biodiversity conservation unknown. Here we assemble a comprehensive record of human activity (approximately 2.7 million records, spanning 200 years) and use it to quantify the extent of Antarctica's wilderness and its representation of biodiversity. We show that 99.6% of the continent's area can still be considered wilderness, but this area captures few biodiversity features. Pristine areas, free from human interference, cover a much smaller area (less than 32% of Antarctica) and are declining as human activity escalates6. Urgent expansion of Antarctica's network of specially protected areas7 can both reverse this trend and secure the continent's biodiversity8-10.