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The Global Burden of Disease report of 2019 estimated 14 million infection‐related deaths, making it the second leading cause of death after ischaemic heart disease. Bacterial pathogens accounted for 7.7 million deaths and deaths attributable to bacterial antibiotic resistance amounted to 1.3 million, describing a clear demand for novel antibiotics. Antibiotic development had its golden age in 1930–1960. Following failures in the screening of chemical libraries for novel antibiotics at the beginning of this century, the high cost of launching new antibiotics (estimated at US$ 1.4 billion per registered drug) and difficulties in achieving a return of investment for novel antibiotics, pharmaceutical industry has mostly left the field. The current Lilliput review analyses the question whether scientific or economic hurdles prevented the registration of new antibiotics. Scientifically, substantial progress has been achieved over recent years to define the chemical properties needed to overcome the permeation barrier in Gram‐negative pathogens; in extending the chemical space of antibiotic candidates by full modular synthesis of suitable molecules; by extending bioprospecting to previously ‘unculturable’ bacteria or unusual bacteria; by attacking bacterial targets on the outer bacterial membrane; and by looking for support from structural biology, genomics, molecular genetics, phylogenetic analyses and deep machine learning approaches. However, these research activities were mostly conducted by academic researchers and biotech companies with limited financial resources. It thus seems that the development of new antibiotics, frequently described as the drying of the pipeline, is less limited by lack of scientific insight than by lack of the mobilization of the monetary resources needed to bring these discoveries to the market despite recent financial push and pull efforts of the public sector. The current Lilliput review analyses the question whether scientific or economic hurdles prevented the registration of new antibiotics. Scientifically, substantial progress has been achieved over recent years. The lack of profitability for costly novel antibiotic development necessitates push and pull efforts of the public sector to complement what the market forces alone cannot achieve.

Summary Contemporary medical reports from Britain and Germany on patients suffering from a pandemic infection between 1889 and 1891, which was historically referred to as the Russian flu, share a number of characteristics with COVID‐19. Most notable are aspects of multisystem affections comprising respiratory, gastrointestinal and neurological symptoms including loss of taste and smell perception; a protracted recovery resembling long covid and pathology observations of thrombosis in multiple organs, inflammation and rheumatic affections. As in COVID‐19 and unlike in influenza, mortality was seen in elderly subjects while children were only weakly affected. Contemporary reports noted trans‐species infection between pet animals or horses and humans, which would concur with a cross‐infection by a broad host range bovine coronavirus dated by molecular clock arguments to an about 1890 cross‐species infection event. Contemporary clinical reports on patients of the Russian flu pandemic of 1889 to 1891 show striking similarity to COVID‐19 patients, demonstrating *multiorgan affections of the respiratory, intestinal and neural system, *loss of smell and taste, *and long disease symptom duration.

Practical experiments drive important scientific discoveries in biology, but theory‐based research studies also contribute novel—sometimes paradigm‐changing—findings. Here, we appraise the roles of theory‐based approaches focusing on the experiment‐dominated wet‐biology research areas of microbial growth and survival, cell physiology, host–pathogen interactions, and competitive or symbiotic interactions. Additional examples relate to analyses of genome‐sequence data, climate change and planetary health, habitability, and astrobiology. We assess the importance of thought at each step of the research process; the roles of natural philosophy, and inconsistencies in logic and language, as drivers of scientific progress; the value of thought experiments; the use and limitations of artificial intelligence technologies, including their potential for interdisciplinary and transdisciplinary research; and other instances when theory is the most‐direct and most‐scientifically robust route to scientific novelty including the development of techniques for practical experimentation or fieldwork. We highlight the intrinsic need for human engagement in scientific innovation, an issue pertinent to the ongoing controversy over papers authored using/authored by artificial intelligence (such as the large language model/chatbot ChatGPT). Other issues discussed are the way in which aspects of language can bias thinking towards the spatial rather than the temporal (and how this biased thinking can lead to skewed scientific terminology); receptivity to research that is non‐mainstream; and the importance of theory‐based science in education and epistemology. Whereas we briefly highlight classic works (those by Oakes Ames, Francis H.C. Crick and James D. Watson, Charles R. Darwin, Albert Einstein, James E. Lovelock, Lynn Margulis, Gilbert Ryle, Erwin R.J.A. Schrödinger, Alan M. Turing, and others), the focus is on microbiology studies that are more‐recent, discussing these in the context of the scientific process and the types of scientific novelty that they represent. These include several studies carried out during the 2020 to 2022 lockdowns of the COVID‐19 pandemic when access to research laboratories was disallowed (or limited). We interviewed the authors of some of the featured microbiology‐related papers and—although we ourselves are involved in laboratory experiments and practical fieldwork—also drew from our own research experiences showing that such studies can not only produce new scientific findings but can also transcend barriers between disciplines, act counter to scientific reductionism, integrate biological data across different timescales and levels of complexity, and circumvent constraints imposed by practical techniques. In relation to urgent research needs, we believe that climate change and other global challenges may require approaches beyond the experiment. Practical experiments drive important scientific discoveries in biology, but theory‐based research studies also contribute novel—sometimes paradigm‐changing—findings. Here, we appraise the roles of theory‐based approaches focusing on the experiment‐dominated wet‐biology research areas of microbiology. Theory‐based studies can transcend barriers imposed by differences between disciplines, act counter to scientific reductionism, integrate biological data across different timescales and levels of complexity, and circumvent constraints imposed by practical techniques. In relation to urgent research needs, we believe that climate change and other global challenges necessitate approaches beyond the experiment.

Summary The COVID‐19 pandemic is going into its third year with Europe again being the focus of major epidemic activity. The present review tries to answer the question whether one can come to grip with the pandemic by a combination of vaccinations and non‐pharmaceutical interventions (NPIs). Several COVID‐19 vaccines are of remarkable efficacy and achieve high protection rates against symptomatic disease, especially severe disease, but mathematical models suggest that the current vaccination coverage in many countries is insufficient to achieve pandemic control. NPIs are needed as complementary measures because recent research has also revealed the limits of vaccination alone. Here, we review the evidence for efficacy of face mask wearing in various settings. Overall pooled analysis showed significant reduction in COVID‐19 incidence with mask wearing, although heterogeneity between studies was substantial. Controlled trials of mask wearing are difficult to conduct, separating mask wearing effects in population studies from the impact of other NPIs is challenging and the efficacy of masks depend on mask material and mask fit. The combination of vaccination and mask wearing is potentially synergistic since vaccination protects so far well from disease development (the omicron variant is currently an unknown) but immunity from infection wanes over few months after vaccination. In comparison, masks interfere with the virus transmission process at a level of a physical barrier independent of coronavirus variant. Vaccination and masks are much less costly to apply than other NPI measures which are associated with high economic and social costs, but paradoxically both measures are the target of a vocal opposition by a sizable minority of the society. In parallel with biomedical research, we need more social science research into this opposition to guide political decisions on how to end the pandemic. The present review tries to answer the question whether one can control the pandemic by a combination of vaccinations and non‐pharmaceutical interventions. The combination of vaccination and mask wearing is potentially synergistic since vaccination protects so far well from disease while masks interfere with the virus transmission process as a physical barrier against any type of coronavirus variant.

Summary The biotechnological production of succinate bears serious potential to fully replace existing petrochemical approaches in the future. In order to establish an economically viable bioprocess, obtaining high titre, yield and productivity is of central importance. In this study, we present a straightforward engineering approach for anaerobic succinate production with Vibrio natriegens, consisting of essential metabolic engineering and optimization of process conditions. The final producer strain V. natriegens Δlldh Δdldh Δpfl Δald Δdns::pycCg (Succ1) yielded 1.46 mol of succinate per mol of glucose under anaerobic conditions (85% of the theoretical maximum) and revealed a particularly high biomass‐specific succinate production rate of 1.33 gSucc gCDW−1 h−1 compared with well‐established production systems. By applying carbon and redox balancing, we determined the intracellular flux distribution and show that under the tested conditions the reductive TCA as well as the oxidative TCA/glyoxylate pathway contributed to succinate formation. In a zero‐growth bioprocess using minimal medium devoid of complex additives and expensive supplements, we obtained a final titre of 60.4 gSucc l−1 with a maximum productivity of 20.8 gSucc l−1 h−1 and an overall volumetric productivity of 8.6 gSucc l−1 h−1 during the 7 h fermentation. The key performance indicators (titre, yield and productivity) of this first engineering approach in V. natriegens are encouraging and compete with costly tailored microbial production systems. Here we describe the first approach to tailor Vibrio natriegens for the anaerobic succinate production from glucose. By the optimization of production conditions and essential metabolic engineering we increased the succinate yield 10‐fold. Finally, we achieved a maximum productivity of 20.8 g l−1 h−1 in an anaerobic bioprocess with resting cells, highlighting the potential of V. natriegens for succinate production.

Carboxydotrophic metabolism is gaining interest due to its applications in gas fermentation technology, enabling the conversion of carbon monoxide to fuels and commodities. Acetogenic carboxydotrophs play a central role in current gas fermentation processes. In contrast to other energy‐rich microbial substrates, CO is highly toxic, which makes it a challenging substrate to utilize. Instantaneous scavenging of CO upon entering the cell is required to mitigate its toxicity. Experiments conducted with Clostridium autoethanogenum at different biomass‐specific growth rates show that elevated ethanol production occurs at increasing growth rates. The increased allocation of electrons towards ethanol at higher growth rates strongly suggests that C. autoethanogenum employs a form of overflow metabolism to cope with high dissolved CO concentrations. We argue that this overflow branch enables acetogens to efficiently use CO at highly variable substrate influxes by increasing the conversion rate almost instantaneously when required to remove toxic substrate and promote growth. In this perspective, we will address the case study of C. autoethanogenum grown solely on CO and syngas mixtures to assess how it employs acetate reduction to ethanol as a form of overflow metabolism. Microorganisms have a pivotal role in the production of biofuels. Here, we explain how microorganisms that consume (waste) carbon monoxide can be pushed to produce bioethanol.

Summary The Omicron variant rapidly became the dominant SARS‐CoV‐2 strain in South Africa and elsewhere. This review explores whether this rise was due to an increased transmission of the variant or its escape from population immunity by an extensively mutated spike protein. The mutations affected the structure of the spike protein leading to the loss of neutralization by most, but not all, therapeutic monoclonal antibodies. Omicron also shows substantial immune escape from serum antibodies in convalescent patients and vaccinees. A booster immunization increased, however, the titre and breadth of antiviral antibody response. The cellular immune response against Omicron was largely preserved explaining a satisfying protection of boosted vaccinees against severe infections. Clinicians observed less severe infection with Omicron, but other scientists warned that this must not necessarily reflect less intrinsic virulence. However, in animal experiments with mice and hamsters, Omicron infections also displayed a lesser virulence than previous VOCs and lung functions were less compromised. Cell biologists demonstrated that Omicron differs from Delta by preferring the endocytic pathway for cell entry over fusion with the plasma membrane which might explain Omicron’s distinct replication along the respiratory tract compared with Delta. Omicron represents a distinct evolutionary lineage that deviated from the mainstream of evolving SARS‐CoV‐2 already in mid‐2020 raising questions about where it circulated before getting widespread in December 2021. The role of Omicron for the future trajectory of the COVID‐19 pandemic is discussed. The Omicron variant rapidly became the dominant SARS‐CoV‐2 strain in South Africa and elsewhere. This review explores whether this rise was due to an increased transmission of the variant or its escape from population immunity by an extensively mutated spike protein. Clinicians observed less severe infection with Omicron, but other scientists warned that this must not necessarily reflect less intrinsic virulence.

Summary Another animal to human transmission of a coronavirus occurred in December 2019 on a live animal market in the Chinese city of Wuhan causing an epidemic in China, reaching now different continents. This minireview summarizes the research literature on the virological, clinical and epidemiological aspects of this epidemic published until end of February 2020.

The body size of fossil organisms has been an important area of research for paleobiologists for well over a century, because body size can tell us much about widespread trends in the evolution of major groups of living things. However, paleobiologists often study body size by focusing only on size-related information collected from fossils. Without information about a fossil organism's biology and geologic history beyond its size, we cannot understand what is driving body-size change over evolutionary time in a meaningful way. Luckily, the ways evolutionary biologists already think about growth and development (ontogeny) and evolutionary relationships among taxa (phylogeny) can help us resolve this issue. In particular, by looking at how a species' body size, age, and other observable traits (phenotype) change over its growth and development, we can track how a species' body-size changes over the course of its time on Earth. Furthermore, we can compare these patterns between closely related species, and identify the sources of body-size change in deep time. To show how these ideas are a practical solution to problems in the fossil record, we applied them to a common pattern called the “Lilliput effect.” Named after the island of Lilliput and its tiny inhabitants in Gulliver's Travels, this pattern describes a sharp decrease in organism body size during extinctions in Earth history. Despite the Lilliput effect being very common, we understand little about how it occurs. Along with providing a stronger definition for the Lilliput effect, we use our framework to note some likely processes for the Lilliput effect (such as changes to development), and some famous cases where we could easily test these ideas. Body size has a long history of study in paleobiology and underlies many important phenomena in macroevolution. Body-size patterns in the fossil record are often examined by utilizing size data alone, which hinders our ability to describe the biological meaning behind size change on macroevolutionary timescales. Without data reflecting the biological and geologic factors that drive size change, we cannot assess its mechanistic underpinnings. Existing frameworks for studying ontogeny and phylogeny can remedy this problem, par ticularly the classic age–size–“shape” space originally developed for studies of heterochrony When evaluated based on metrics for age, size, and phenotype in populations, propose mechanisms for size change can be outlined theoretically and tested empirically in the record Using this framework, we can compare ontogenetic trajectories within and between specie and determine how changes in size emerge. Here, we outline ontogenetic mechanisms for evo lutionary size change, such as heterochrony, as well as how geologic factors can drive appar ent non-biolo ical size chan e (e ta honomic size sortin) To demonstrate the utility of this framework in actual paleobiological problems, we apply it to the Lilliput effect, a compelling and widely documented pattern of size decrease during extinction events. However, little is known about the mechanisms underlying this pattern. We provide a brief history of the Lilliput effect and refine its definition in a framework that can be mechanistically tested. Processes that likely produce Lilliput effects include allometric and sequence repatterning (including heterochrony) and evolutionary size-selective sorting. We describe these mechanisms and highlight relevant examples of the Lilliput effect for which feasible empirical tests are possible.

West Nile virus (WNV) disease, a mosquito‐transmitted Flavivirus infection, represents a substantial public health research interest. This virus was unknown in the Western hemisphere until it was introduced in 1999 into an immunologically naïve population. WNV caused an epizootic and epidemic in New York City. The infection then swept over North America, causing mass mortality in birds and cumulatively 60,000 human cases, half of whom were hospitalised, mostly with neurological symptoms. The virus closely resembled a goose virus isolated in Israel in 1998. Mosquitoes of the genus Culex were identified as the insect viral vectors. WNV can infect more than 300 bird species, but in the US, the American robin (Turdus migratorius) represented the ecologically most important bird viral reservoir. Mosquito‐to‐mosquito viral transmission might amplify the viral spread, and iatrogenic WNV transmission was also observed, leading to the screening of blood products. Compared with African WNV isolates, the New York WNV isolate NY99 showed a mutation in the nonstructural protein NS3 that increased its virulence in birds and was also observed in WNV outbreaks from Romania in 1996 and from Russia in 1999. During its spread across the US, NY99 acquired a mutation in the envelope gene E that favoured viral infection in the insect vector. Europe reported 1200 annual WNV cases in 2024, with a focus in Mediterranean countries, but a northward spread of the infection to Germany and The Netherlands was also noted. Global warming is likely to affect the geographical distribution of vector‐borne infections such that people living in temperate climate areas might be increasingly exposed to these infections. Therefore, research on temperature effects on WNV transmission by Culex mosquitoes has become a recent focus of research. Pertinent climate aspects of WNV infections are retraced in the present review. The West Nile flavivirus is not only maintained in the USA in a primary infection cycle between the American robin and Culex mosquitoes but also causes incidental infections in horses and humans, causing epizootics and epidemics. The ecological conditions influencing virus transmission in North America and Europe are reviewed.