Machine Learning and Gene Editing at the Helm of a Societal Evolution.

The integration of artificial intelligence (AI) and biotechnology, whilst in its infancy, presents significant opportunities and risks, and proactive policy is needed to manage these emerging technologies. Whilst AI continues to have significant and broad impact, its relevance and complexity magnify when integrated with other emerging technologies. The confluence of Machine Learning (ML), a subset of AI, with gene editing (GE) in particular can foster substantial benefits as well as daunting risks that range from ethics to national security. These complex technologies have implications for multiple sectors, ranging from agriculture and medicine to economic competition and national security. Consideration of technology advancements and policies in different geographic regions, and involvement of multiple organisations further confound this complexity. As the impact of ML and GE expands, forward looking policy is needed to mitigate risks and leverage opportunities. Thus, this study explores the technological and policy implications of the intersection of ML and GE, with a focus on the United States (US), the United Kingdom (UK), China, and the European Union (EU). Analysis of technical and policy developments over time and an assessment of their current state have informed policy recommendations that can help manage beneficial use of technology advancements and their convergence, which can be applied to other sectors. This study is intended for policymakers to prompt reflection on how to best approach the convergence of the two technologies. Technical practitioners may also find it valuable as a resource to consider the type of information and policy stakeholders engage with.

Illegal interlocks among life science company boards of directors.

Competition between life science companies is critical to ensure innovative therapies are efficiently developed. Anticompetitive behavior may harm scientific progress and, ultimately, patients. One well-established category of anticompetitive behavior is the 'interlocking directorate'. It is illegal for companies' directors to 'interlock' by also serving on the boards of competitors. We evaluated overlaps in the board membership of 2,241 public life science companies since 2000. We show that a robust network of interlocking companies is present among these firms. At any given time, 10-20 percent of board members are interlocked; the number of interlocks has more than doubled in the last two decades. Over half of these interlocked firms report over $5 million in historical revenue, exceeding a legal threshold that makes an interlocking directorate a violation of antitrust law. Those interlocks are only illegal if the companies compete, even in part. Using the disease categories for which companies have sponsored clinical trials, we discover that a few markets are responsible for a large fraction of interlocks. We show that in dozens of cases, companies share directors with the very firms they identify as their biggest competitive threats. We provide a data-driven roadmap for policymakers, regulators, and companies to further investigate the contribution of anticompetitive behavior to increased healthcare costs and to enforce the law against illegal interlocks between firms.

Haplotype-resolved assembly of diploid and polyploid genomes using quantum computing.

Precision medicine's emphasis on individual genetic variants highlights the importance of haplotype-resolved assembly, a computational challenge in bioinformatics given its combinatorial nature. While classical algorithms have made strides in addressing this issue, the potential of quantum computing remains largely untapped. Here, we present the vehicle routing problem (VRP) assembler: an approach that transforms this task into a vehicle routing problem, an optimization formulation solvable on a quantum computer. We demonstrate its potential and feasibility through a proof of concept on short synthetic diploid and triploid genomes using a D-Wave quantum annealer. To tackle larger-scale assembly problems, we integrate the VRP assembler with Google's OR-Tools, achieving a haplotype-resolved local assembly across the human major histocompatibility complex (MHC) region. Our results show encouraging performance compared to Hifiasm with phasing accuracy approaching the theoretical limit, underscoring the promising future of quantum computing in bioinformatics.

Moving Research-Based Learning in Life Sciences Upstream, and Beyond Borders: An International Group Research Project for High School Youth.

International cooperation beyond borders, institutions, and intergenerationally is an important aspect of science and research-based learning. Timing of learning also matters. Early exposure to group research-based learning can potentially have lasting positive impacts on youth and their careers in life sciences. Here, we report our work on the International Group Project (IGP), which builds on the International Biology Olympiad (IBO) organized in Yerevan, Armenia, in 2022. The IBO is an annual international competition for high school students held since 1990 around the world. We envisioned the IGP as a novel opportunity for life sciences research-based education among youth. We formed diverse IGP research teams 2 months before the IBO, and comprised high school students from 32 countries, communicating in a digital environment via videoconferencing. Each team formulated a research question in an IGP theme from five domains of life sciences: "Biomedicine," "Molecular and cell biology," "Bioinformatics and Artificial Intelligence," "Bionics and Biomimicry," "Across Species." Subsequently, team members collectively solved their research question by applying life sciences methodologies under supervision from a facilitator scientist. Each team created a poster based on their research and presented in-person to the public at a satellite activity at the IBO. A special subcommittee of the IBO International Jury graded posters and allocated prizes based on scientific ingenuity and presentation quality. This experience from the IGP lends evidence to the feasibility of research-based learning in life sciences for high school youth beyond borders. Moving research-based learning upstream and internationally is well poised to advance 21st century life sciences from both interdisciplinary and intergenerational standpoints. The historic impact of the COVID-19 pandemic suggests that youth engagement in research-based learning and innovation in life sciences is timely.

Biotechnology in India: An Analysis of 'Biotechnology Industry Research Assistance Council' (BIRAC)-Supported Projects.

A comprehensive analysis of 2165 projects funded by India's Department of Biotechnology since 2005 through private-public partnerships, and as of 2012 through the 'Biotechnology Industry Research Assistance Council (BIRAC)' until BIRAC's tenth anniversary at the end of March 2022 reveals details of the science and technology underpinning past and current biotechnology research and development projects in the country. They are led by human healthcare projects (74.9 % overall), of which medical technology (58.7 %) and therapeutics (24.5 %) are the main drivers, ahead of vaccines (4.3 %), regenerative medicine (3.9 %), public health (3.5 %) and others (5.1 %). Agricultural projects (15.2 % overall) have mainly been driven by plant breeding and cloning (24.6 %), animal biotechnology (20.4 %), agri-informatics (13.4 %), aquaculture (6.1 %), and (bio)fertilizers (4.3 %). The key components of industrial biotechnology (9.9 % overall) have been fine chemicals (44.7 %), environmental projects (23.3 %), clean energy (18.1 %) and industrial enzymes (12.1 %). Analysis of the projects funded pre- versus post-2017, compared to the distribution of equity funding as of early 2022 identifies trends in terms of growth areas and locations of industrial biotechnology projects and activities in India.

Erosional exhumation of carbonate rock facilitates dispersal-mediated allopatric speciation in freshwater fishes.

A fundamental goal of evolutionary biology is to understand the mechanisms that generate and maintain biodiversity. Discovery and delimitation of species represent essential prerequisites for such investigations. We investigate a freshwater fish species complex comprising Etheostoma bellator and the endangered E. chermocki, which is endemic to the Black Warrior River system in Alabama, USA, a global hotspot of temperate freshwater biodiversity. Phylogenomic analyses delimit five geographically disjunct species masquerading as E. bellator. Three of these new species exhibit microendemic distributions comparable to that of E. chermocki raising the possibility that they also require protection. The species of the complex are found in streams flowing over carbonate rock and they are separated by waterways flowing over siliciclastic rock, a geographic pattern dictated by the underlying stratigraphy and structural geology. Over time, rivers have eroded downward through layers of siliciclastic rocks in the basin, gradually exposing underlying carbonate rock, the substrate of suitable habitat today. Our results suggest that episodic dispersal to patches of suitable habitat set the stage for allopatric speciation in the species complex. Our study suggests that the presence of heterogeneous rock can facilitate dispersal-mediated allopatric speciation in freshwater organisms in the absence of external tectonic or climatic perturbations.

Strategies for Mitigating Commercial Sensor Chip Variability with Experimental Design Controls.

Surface plasmon resonance (SPR) is a popular real-time technique for the measurement of binding affinity and kinetics, and bench-top instruments combine affordability and ease of use with other benefits of the technique. Biomolecular ligands labeled with the 6xHis tag can be immobilized onto sensing surfaces presenting the Ni2+-nitrilotriacetic acid (NTA) functional group. While Ni-NTA immobilization offers many advantages, including the ability to regenerate and reuse the sensors, its use can lead to signal variability between experimental replicates. We report here a study of factors contributing to this variability using the Nicoya OpenSPR as a model system and suggest ways to control for those factors, increasing the reproducibility and rigor of the data. Our model ligand/analyte pairs were two ovarian cancer biomarker proteins (MUC16 and HE4) and their corresponding monoclonal antibodies. We observed a broad range of non-specific binding across multiple NTA chips. Experiments run on the same chips had more consistent results in ligand immobilization and analyte binding than experiments run on different chips. Further assessment showed that different chips demonstrated different maximum immobilizations for the same concentration of injected protein. We also show a variety of relationships between ligand immobilization level and analyte response, which we attribute to steric crowding at high ligand concentrations. Using this calibration to inform experimental design, researchers can choose protein concentrations for immobilization corresponding to the linear range of analyte response. We are the first to demonstrate calibration and normalization as a strategy to increase reproducibility and data quality of these chips. Our study assesses a variety of factors affecting chip variability, addressing a gap in knowledge about commercially available sensor chips. Controlling for these factors in the process of experimental design will minimize variability in analyte signal when using these important sensing platforms.

Circulation as a Visual Practice.

This special issue looks at some of the ways that images are adopted, co-opted, and adapted in the life sciences and beyond. It brings together papers that investigate the role of visualization in scientific knowledge-production with contributions that focus on the distribution and dissemination of knowledge to a broader audience. A commentary provides a critical perspective. In this editorial we introduce circulation as a practice to better understand scientific images. Along two themes, we highlight connections across the papers. First, the social life of scientific representation follows the contexts, settings, and spaces through which images circulate. Second, authorship, expertise, and trust inform the capacity and the failure of images to circulate. Altogether, this volume raises a set of new questions about circulation as practice in the historiography of images in the life sciences.

Gravity's effect on biology.

Gravity is a fundamental interaction that permeates throughout our Universe. On Earth, gravity gives weight to physical objects, and has been a constant presence throughout terrestrial biological evolution. Thus, gravity has shaped all biological functions, some examples include the growth of plants (e.g., gravitropism), the structure and morphology of biological parts in multicellular organisms, to its effects on our physiological function when humans travel into space. Moreover, from an evolutionary perspective, gravity has been a constant force on biology, and life, to our understanding, should have no reason to not experience the effects of gravity. Interestingly, there appear to be specific biological mechanisms that activate in the absence of gravity, with the space environment the only location to study the effects of a lack of gravity on biological systems. Thus, in this perspective piece, biological adaptations from the cellular to the whole organism levels to the presence and absence of gravity will be organized and described, as well as outlining future areas of research for gravitational biological investigations to address. Up to now, we have observed and shown how gravity effects biology at different levels, with a few examples including genetic (e.g., cell cycle, metabolism, signal transduction associated pathways, etc.), biochemically (e.g., cytoskeleton, NADPH oxidase, Yes-associated protein, etc.), and functionally (e.g., astronauts experiencing musculoskeletal and cardiovascular deconditioning, immune dysfunction, etc., when traveling into space). Based from these observations, there appear to be gravity-sensitive and specific pathways across biological organisms, though knowledge gaps of the effects of gravity on biology remain, such as similarities and differences across species, reproduction, development, and evolutionary adaptations, sex-differences, etc. Thus, here an overview of the literature is provided for context of gravitational biology research to-date and consideration for future studies, as we prepare for long-term occupation of low-Earth Orbit and cis-Lunar space, and missions to the Moon and Mars, experiencing the effects of Lunar and Martian gravity on biology, respectively, through our Artemis program.

Application of the Nicoya OpenSPR to Studies of Biomolecular Binding: A Review of the Literature from 2016 to 2022.

The Nicoya OpenSPR is a benchtop surface plasmon resonance (SPR) instrument. As with other optical biosensor instruments, it is suitable for the label-free interaction analysis of a diverse set of biomolecules, including proteins, peptides, antibodies, nucleic acids, lipids, viruses, and hormones/cytokines. Supported assays include affinity/kinetics characterization, concentration analysis, yes/no assessment of binding, competition studies, and epitope mapping. OpenSPR exploits localized SPR detection in a benchtop platform and can be connected with an autosampler (XT) to perform automated analysis over an extended time period. In this review article, we provide a comprehensive survey of the 200 peer-reviewed papers published between 2016 and 2022 that use the OpenSPR platform. We highlight the range of biomolecular analytes and interactions that have been investigated using the platform, provide an overview on the most common applications for the instrument, and point out some representative research that highlights the flexibility and utility of the instrument.

Conceptual modelling for life sciences based on systemist foundations.

BACKGROUND: All aspects of our society, including the life sciences, need a mechanism for people working within them to represent the concepts they employ to carry out their research. For the information systems being designed and developed to support researchers and scientists in conducting their work, conceptual models of the relevant domains are usually designed as both blueprints for a system being developed and as a means of communication between the designer and developer. Most conceptual modelling concepts are generic in the sense that they are applied with the same understanding across many applications. Problems in the life sciences, however, are especially complex and important, because they deal with humans, their well-being, and their interactions with the environment as well as other organisms. RESULTS: This work proposes a "systemist" perspective for creating a conceptual model of a life scientist's problem. We introduce the notion of a system and then show how it can be applied to the development of an information system for handling genomic-related information. We extend our discussion to show how the proposed systemist perspective can support the modelling of precision medicine. CONCLUSION: This research recognizes challenges in life sciences research of how to model problems to better represent the connections between physical and digital worlds. We propose a new notation that explicitly incorporates systemist thinking, as well as the components of systems based on recent ontological foundations. The new notation captures important semantics in the domain of life sciences. It may be used to facilitate understanding, communication and problem-solving more broadly. We also provide a precise, sound, ontologically supported characterization of the term "system," as a basic construct for conceptual modelling in life sciences.

Scientists as spies?: Assessing U.S. claims about the security threat posed by China's Thousand Talents Program for the U.S. life sciences.

In 2008, the Chinese government created the Thousand Talents Program (TTP) to recruit overseas expertise to build up China's science and technology knowledge and innovation base. Ten years later, in 2018, the Federal Bureau of Investigation (FBI) announced a new "China Initiative" that aimed to counter the transfer by U.S.-based scientists involved in the TTP of knowledge and intellectual property that could support China's military and economic might and pose threats to U.S. national security. This initiative launched a number of investigations into major U.S. federal funding agencies and universities and charged several scientists, many of them life scientists, with failing to accurately report their work and affiliations with Chinese entities and illegally transferring scientific information to China. Although the FBI cases demonstrate a clear problem with disclosure of foreign contracts and research integrity among some TTP recipients, they have failed to demonstrate any harm to U.S. national security interests. At the heart of this controversy are core questions that remain unresolved and need more attention: What is required to transfer and develop knowledge to further a country's science and technology ambitions? And can the knowledge acquired by a visiting scientist be easily used to further a country's ambitions? Drawing on literature from the field of science and technology studies, this article discusses the key issues that should be considered in evaluating this question in the Chinese context and the potential scientific, intelligence, and policy implications of knowledge transfer as it relates to the TTP.

Life Sciences undergraduate students' preferences on online learning.

Online learning is implemented in response to emergency remote teaching during global pandemic. We conducted a survey on Life Sciences undergraduate students on their preferences on mode of lesson delivery, mode of learning and learning activities. Students across different study years responded in a similar order ranking blended learning delivery as highly favorable. The survey gathered insightful understandings on Life Sciences undergraduates' learning preferences on online learning which inform future purposeful learning design taking student's preferences into consideration.

Colonial rodent control in Tanganyika and the application of ecological frameworks.

ABSTRACTAt the end of the 1920s, Tanganyika Territory experienced several serious rodent outbreaks that threatened cotton and other grain production. At the same time, regular reports of pneumonic and bubonic plague occurred in the northern areas of Tanganyika. These events led the British colonial administration to dispatch several studies into rodent taxonomy and ecology in 1931 to determine the causes of rodent outbreaks and plague disease, and to control future outbreaks. The application of ecological frameworks to the control of rodent outbreaks and plague disease transmission in colonial Tanganyika Territory gradually moved from a view that prioritised 'ecological interrelations' among rodents, fleas and people to one where those interrelations required studies into population dynamics, endemicity and social organisation in order to mitigate pests and pestilence. This shift in Tanganyika anticipated later population ecology approaches on the African continent. Drawing on sources from the Tanzania National Archives, this article offers an important case study of the application of ecological frameworks in a colonial setting that anticipated later global scientific interest in studies of rodent populations and rodent-borne disease ecologies.

Editorial introduction: Biomedicine and life sciences as a challenge to human temporality.

Bringing together scholars from philosophy, bioethics, law, sociology, and anthropology, this topical collection explores how innovations in the field of biomedicine and the life sciences are challenging and transforming traditional understandings of human temporality and of the temporal duration, extension and structure of human life. The contributions aim to expand the theoretical debate by highlighting the significance of time and human temporality in different discourses and practical contexts, and developing concrete, empirically informed, and culturally sensitive perspectives. The collection is structured around three main foci: the beginning of life, the middle of life, and later life. This structure facilitates an in-depth examination of specific technological and biographical contexts and at the same time allows an overarching comparison of relevant similarities and differences between life phases and fields of application.

Transformer-based deep learning for predicting protein properties in the life sciences.

Recent developments in deep learning, coupled with an increasing number of sequenced proteins, have led to a breakthrough in life science applications, in particular in protein property prediction. There is hope that deep learning can close the gap between the number of sequenced proteins and proteins with known properties based on lab experiments. Language models from the field of natural language processing have gained popularity for protein property predictions and have led to a new computational revolution in biology, where old prediction results are being improved regularly. Such models can learn useful multipurpose representations of proteins from large open repositories of protein sequences and can be used, for instance, to predict protein properties. The field of natural language processing is growing quickly because of developments in a class of models based on a particular model-the Transformer model. We review recent developments and the use of large-scale Transformer models in applications for predicting protein characteristics and how such models can be used to predict, for example, post-translational modifications. We review shortcomings of other deep learning models and explain how the Transformer models have quickly proven to be a very promising way to unravel information hidden in the sequences of amino acids.

Analysis of recurrent research pathways for assessing and improving effectiveness in life sciences laboratories.

Background: Life sciences research often turns out to be ineffective. Our aim was to develop a method for mapping repetitive research processes, detecting practice variations, and exploring inefficiencies. Methods: Three samples of R&I projects were used: companion diagnostics of cancer treatments, identification of COVID-19 variants, and COVID-19 vaccine development. Major steps involved: defined starting points, desired end points; measurement of transition times and success rates; exploration of variations, and recommendations for improved efficiency. Results: Over 50% of CDX developments failed to reach market simultaneously with new drugs. There were significant variations among phases of co-development (Bartlett test P<0.001). Length of time in vaccine development also shows variations (P<0.0001). Similarly, subject participation indicates unexplained variations in trials (Phase I: 489.7 (±461.8); Phase II: 857.3 (±450.1); Phase III: 35402 (±18079). Conclusion: Analysis of repetitive research processes can highlight inefficiencies and show ways to improve quality and productivity in life sciences.

Reflexive expectations in innovation financing: An analysis of venture capital as a mode of valuation.

Social studies of expectations are premised on the notion that the future is brought into the present, and thereby expectations about the future come to shape our actions, decisions, and practices in ways that performatively bring about the imagined future. In this article, I examine how social actors themselves understand, construct, and deploy future expectations in innovation financing, focusing specifically on the venture capital industry financing of the life sciences sector. I do so to analyse how these reflexive efforts configure the valuation and investment decisions of these social actors and others. I build on analytical perspectives in STS and adjacent fields such as organization studies and economic sociology that analyse the role of expectations - manifested as stories, narratives, and accounts - in social action. To do so, I unpack how reflexivity comes to configure valuation and investment decisions, and the goals (e.g. exits) they rationalize.

Pandemic-Era Digital Education: Insights from an Undergraduate Medical Programme.

The undergraduate medical programme at Newcastle University (NU) includes a fundamental 'Essentials of Medical Practice' (EOMP) phase comprising the first 2 years of study. This period is designed to support entrants in their transition from further education into the advanced study and practice of clinical medicine. The anatomical sciences of gross anatomy, histology and embryology, and life sciences including physiology, pharmacology and genetics are key disciplines taught within the integrated case-based EOMP curriculum. Learners apply basic science knowledge to clinical scenarios during training in practical examination, communication and reasoning skills. Within the modern pedagogic landscape, the development and introduction of technology-enhanced learning strategies have enhanced the provision of remote learning resources in pre-clinical education. However, the emergence of COVID-19 has resulted in widespread technological challenges for educators and learners, and has raised pedagogic, logistical and ethical concerns. Nonetheless, the pandemic has produced favourable conditions for the creation of valuable digital visualisation strategies for learning and teaching, and for developing and modernising universal approaches to remote education. Here, we describe our technology-enhanced adaptations to COVID-19 across the domains of teaching, learning and academic support for pre-clinical learners studying basic life sciences and clinical skills. Moreover, we outline research-informed digital visualisation solutions to pandemic-era challenges and reflect upon experiences gained within our own educational context. In doing so, we provide insights into the impacts and successes of our interventions. While providing a record of unprecedented contemporary circumstances, we also aim to utilise our observations and experiences of COVID-19 pedagogy when developing ongoing strategies for delivering curricula and futureproofing educational practice.

How to teach life sciences students about dual-use research-a view from the field.

To reduce biological risks, raising awareness for dual-use issues already at the level of university education is essential. Currently, most life sciences education programs do not incorporate biosecurity and dual-use in their regular curricula. Consequently, the responsibility rests with individual lecturers and depends on their initiative to incorporate dual-use topics into teaching activities. Students interested in biosecurity and dual-use topics often only have the option to educate themselves in external or online courses. Here, we provide practical guidance on how to initiate and integrate a dual-use education program within the curriculum and provide a selection of existing teaching materials. In addition, we suggest key learning objectives to guide the planning of dual-use courses. Different course formats like lectures, seminars, or stand-alone events are discussed regarding their advantages, disadvantages, and suitability for conveying the learning objectives to different educational stages and audiences. As a minimum, we recommend the incorporation of dual-use issues into at least one mandatory course. Ideally, students should additionally participate in in-depth seminars, which can be voluntary and offered in cooperation with external organisations.