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The coronavirus disease 2019 (COVID-19) has had a profound impact on the academic research enterprise. Over the span of just a few weeks in March 2020, most large U.S. research institutions closed the majority of their laboratories, studios, and offices, suspended travel and fieldwork, and paused the majority of human research, resulting in the halt of more than 80% of all on-site research activity (1). After months of limited operations, laboratory- and field-based research in the basic and natural sciences were among the first activities to resume. These activities presented relatively low risk for transmission with implementation of proper control measures such as face coverings, health screens, and social distancing. Performing human research during a global pandemic raises new ethical and practical challenges on a scale never before seen. To safely and ethically restart more of the human research portfolio, institutions must develop guiding principles and an explicit plan for managing human research during the pandemic. Image credit: Carey Lumeng (University of Michigan, Ann Arbor, MI). Performing human research during a global pandemic, however, raises new ethical and practical challenges on a scale never before seen. Across the clinical, social, and behavioral sciences, human research can require close contact between researchers and participants, over variable observational periods, and across a variety of locations (e.g., clinics, schools, prisons). Therefore, research with human participants has been slower to resume given the risks associated with potential direct and/or airborne transmission between and among researchers and participants. Indeed, early evidence suggests that research disciplines that rely on face-to-face human contact are among the disciplines that have seen the steepest drop in productivity during the pandemic (2), despite the fact that human research constitutes a significant fraction of the research enterprise. Not all human research paused as stay-at-home orders were implemented across the United States. … [↵][1]1To whom correspondence may be addressed. Email: stroh{at}med.umich.edu or nwigg{at}umich.edu. [1]: #xref-corresp-1-1

A gradual, stepwise approach to reopening, informed by public health expertise, will be essential

Many companies have proprietary resources and/or data that are indispensable for research, and academics provide the creative fuel for much early-stage research that leads to industrial innovation. It is essential to the health of the research enterprise that collaborations between industrial and university researchers flourish. This system of collaboration is under strain. Financial motivations driving product development have led to concerns that industry-sponsored research comes at the expense of transparency ( 1 ). Yet many industry researchers distrust quality control in academia ( 2 ) and question whether academics value reproducibility as much as rapid publication. Cultural differences between industry and academia can create or increase difficulties in reproducing research findings. We discuss key aspects of this problem that industry-academia collaborations must address and for which other stakeholders, from funding agencies to journals, can provide leadership and support.

Microbial Physiology Methane associated with coal beds is an important global resource of natural gas. Much of the methane in coal comes from microbial methanogenesis. Mayumi et al. characterized a strain of Methermicoccus shengliensis that, unexpectedly, is capable of making methane from the dozens of methoxylated aromatic compounds found in a variety of coal types (see the Perspective by Welte). Isotope tracer experiments showed that this organism could also incorporate carbon dioxide into methane. Science , this issue p. [222][1]; see also p. [184][2] [1]: /lookup/doi/10.1126/science.aaf8821 [2]: /lookup/doi/10.1126/science.aai8101

Bioinspired Materials Many of the materials that animals use to make shells and skeletons are built with brittle or soft molecules. They owe their amazing mechanical properties to their layered construction, which is a challenge for synthetic fabrication. Pearly nacre, for example, has proved challenging to make owing to its complex structure of aragonite crystals in an organic matrix. Using an assembly-and-mineralization approach, Mao et al. have managed to fabricate nacre in the laboratory (see the Perspective by Barthelat). First, a layered, three-dimensional chitosan matrix is made, within which aragonite nanocrystals are precipitated from a solution containing calcium bicarbonate. Science , this issue p. [107][1]; see also p. [32][2] [1]: /lookup/doi/10.1126/science.aaf8991 [2]: /lookup/doi/10.1126/science.aah6507

Photosynthesis Some cyanobacteria are able to use the far-red end of the light spectrum by synthesizing chlorophyll f pigments. Introducing the protein responsible for chlorophyll f synthesis into crop plants could potentially expand the range of wavelengths that such plants use during photosynthesis and thereby increase their growth efficiency. Ho et al. identified chlorophyll f synthase (ChlF) in two cyanobacteria that are acclimatized to grow using far-red light. Introducing the ChlF-encoding gene into a model cyanobacterium allowed the organism to synthesize chlorophyll f. Similarities between ChlF and a core protein of photosystem II suggest that they have a close evolutionary relationship, and ChlF may even represent a more primitive photochemical reaction center. Science , this issue p. [886][1] [1]: http://www.sciencemag.org/content/353/6302/886.full

Enzyme Mechanisms Microorganisms are the main drivers of Earth's methane cycle. The enzyme ultimately responsible for biological methane production has an ambiguous mechanism because it involves difficult-to-isolate reaction intermediates. Wongnate et al. used stopped-flow and rapid freeze-quench experiments to trap a methyl radical in the active site of methyl-coenzyme M reductase (see the Perspective by Lawton and Rosenzweig). Spectroscopy demonstrated that cofactor F430 contained Ni(II), consistent with computational results. The final step of methanogenesis thus proceeds through Ni(II)-thiolate and methyl radical intermediates rather than an organometallic methyl-Ni(III) mechanism. Science , this issue p. [953][1];, see also p. [892][2] [1]: /lookup/doi/10.1126/science.aaf0616 [2]: /lookup/doi/10.1126/science.aaf7700

Metalloproteins Many enzymes catalyze reactions through the production of radical intermediates. Radical SAM enzymes, the largest superfamily of enzymes in nature, do this by using an iron-sulfur cluster to cleave S-adenosylmethionine and produce a radical intermediate. Using freeze quenching, Horitani et al. were able to trap a previously unseen radical intermediate from bacterial pyruvate formate-lyase activating enzyme. Spectroscopy revealed that the intermediate consists of a short-lived covalent bond between the terminal carbon of 5′-deoxyadenosyl and the single iron atom of the iron-sulfur cluster. Not only does the observation of this radical expand our mechanistic understanding of radical SAM enzymes, but it expands the range of enzyme active sites or cofactors that function through an organometallic center. Science , this issue p. [822][1] [1]: /lookup/doi/10.1126/science.aaf5327

Geobiology Microorganisms have shaped Earth's oceans and atmosphere over billions of years. Ancient microbes left very little direct morphological evidence of their existence in the rock record, thereby requiring geochemical clues for evidence of their activity. Amor et al. show that magnetotactic

Microbial Physiology Methane-munching archaea in marine sediments live closely coupled to sulfate-reducing bacteria in a syntrophic relationship. Surprisingly, however, these archaea do not necessarily need their bacterial partners to survive or grow. Scheller et al. performed stable isotope

Earth History Humans are undoubtedly altering many geological processes on Earth—and have been for some time. But what is the stratigraphic evidence for officially distinguishing this new human-dominated time period, termed the “Anthropocene,” from the preceding Holocene epoch? Waters et al. review climatic, biological, and geochemical signatures of human activity in sediments and ice cores. Combined with deposits of new materials and radionuclides, as well as human-caused modification of sedimentary processes, the Anthropocene stands alone stratigraphically as a new epoch beginning sometime in the mid–20th century. Science , this issue p. [10.1126/science.aad2622][1] [1]: /lookup/doi/10.1126/science.aad2622

Microbial Metabolism Microorganisms can respire sulfur compounds in the absence of oxygen, eventually leading to the production of hydrogen sulfide. This ancient metabolism is common in modern anoxic environments, but the enzymatic pathways aren't yet fully resolved. Through in vivo and in vitro experiments, Santos et al. clarify the enzymology of the sulfate reduction pathway in both bacteria and archaea (see the Perspective by Fritz and Kroneck). Reduction of the sulfite intermediate results in the linkage of two cysteine residues to a third sulfur atom from sulfite, forming a trisulfide product. Because the reduction of sulfite conveys a strong isotopic signature on sulfur in the environment, isotope fractionation models should account for this additional step. Science , this issue p. [1541][1]; see also p. [1476][2] [1]: /lookup/doi/10.1126/science.aad3558 [2]: /lookup/doi/10.1126/science.aad8139

How traceability, measurement, and standardization might tame an unwieldy web

Mineral Surfaces Carbonate minerals are important for Earth's carbon cycle. They precipitate directly from solution into diverse materials, depending on their physical or biological source. Whether carbonate minerals grow or dissolve is controlled by the thermodynamic drivers of the mineral/water

Inorganic Chemistry Making a synthetic analog of plant photosynthesis is a key goal for exploiting solar energy and replacing fossil fuels. Zhang et al. synthesized a manganese-calcium cluster that looks and acts like the oxygen evolution center in photosystem II (see the Perspective by Sun). The mimic structurally resembles the biological complex, with the notable exception of bridging protein ligands and water-binding sites on a dangling Mn atom. Functionally, however, the cluster's metal center readily undergoes four redox transitions, which contribute to splitting water into oxygen. This and other synthetic mimics will pave the way for developing more efficient catalysts for artificial photosynthesis. Science , this issue p. [690][1]; see also p. [635][2] [1]: /lookup/doi/10.1126/science.aaa6550 [2]: /lookup/doi/10.1126/science.aaa9094

Soil Science The future of humanity is intertwined with the future of Earth's soil resources. Soil provides for agriculture, improves water quality, and buffers greenhouse gases in the atmosphere. Yet human activities, including agricultural soil erosion, are rapidly degrading soil faster than it is naturally replenished. At this rate, human security over the next century will be severely threatened by unsustainable soil management practices. Amundson et al. review recent advances in understanding global soil resources, including how carbon stored in soil responds to anthropogenic warming. Translating this knowledge into practice is the biggest challenge remaining. Science , this issue [10.1126/science.1261071][1] [1]: /lookup/doi/10.1126/science.1261071

Earth History The largest mass extinction in Earth's history occurred at the Permian-Triassic boundary 252 million years ago. Several ideas have been proposed for what devastated marine life, but scant direct evidence exists. Clarkson et al. measured boron isotopes across this period as a highly

Structural Biology Both bacteria and mitochrondria produce NADPH for amino acid biosynthesis and to remove reactive oxygen species. The enzyme that makes NADPH must translocate a proton across the membrane and transfer a hydride from NADH to NADP+—processes that happen some 40 A apart. To

Biocatalysis Organic compounds containing silicon are important for a number of applications, from polymers to semiconductors. The catalysts used for creating carbon-silicon bonds, however, often require expensive trace metals or have limited lifetimes. Borrowing from the ability of some metallo

Synthetic Biology Biological carbon fixation requires several enzymes to turn CO2 into biomass. Although this pathway evolved in plants, algae, and microorganisms over billions of years, many reactions and enzymes could aid in the production of desired chemical products instead of biomass. Schwander