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Within national and international innovation systems a pandemic calls for large-scale action by many actors across sectors, to mobilise resources, developing and manufacturing Crisis-Critical Products (CC-Products) efficiently and in the huge quantities needed. Nowadays, this also includes digital innovations from complex epidemiological models, AI, to open data platforms for prevention, diagnostic and treatment. Amongst the many challenges during a pandemic, innovation and manufacturing stakeholders find themselves engaged in new relationships, and are likely to face intellectual property (IP) related challenges. This paper adopts an IP perspective on the COVID-19 pandemic to identify pandemic related IP considerations and IP challenges. The focus is on challenges related to research, development and urgent upscaling of capacity to manufacture CC-Products in the huge volumes suddenly in demand. Its purpose is to provide a structure for steering clear of IP challenges to avoid delays in fighting a pandemic. We identify 4 stakeholder groups concerned with IP challenges: (i) governments, (ii) organisations owning existing Crisis-Critical IP, described as incumbents in Crisis-Critical Sectors (CC-Sectors), (iii) manufacturing firms from other sectors normally not producing CC-Products suddenly rushing into CC-Sectors to support the manufacturing of CC-Products (new entrants), and (iv) voluntary grassroot initiatives that are formed during a pandemic. This paper discusses IP challenges related to the development and manufacturing of technologies and products for (i) prevention (of spread), (ii) diagnosis of infected patients and (iii) the development of treatments. We offer an initial discussion of potential response measures to reduce IP associated risks among industrial stakeholders during a pandemic., Comment: 18 pages, 4 figures, 3 tables

This protocol documents the production of BenBio 1X PCR Master Mix "Wet" and "Dry" formulations including the different colors of the Wet formulations (Rubis or oink and Saphir or blue). This method uses OpenVent cellular reagents. The PCR master mixes are then stored for subsequent PCR reactions. Cellular reagents are defined as common molecular biology enzymes expressed in E.coli but not subsequently purified before use i.e. dried E.coli cells are used as the reagent (Bhadra et al (2018)).

Kanamycin is an aminoglycoside antibiotic which binds the 30S ribosomal subunit; causes mis-translation. It is used for the selection of cells containing Kanamycin-resistant plasmids on plates and on liquid media at a working concentration of 50-100 µg/mL. It is most often prepared as a 1000x working stock of 50 -100 mg/mL that is stored at -20 ºC. The kanamycin solution is measured and then mixed into a container of liquid or plate media before it has solidified. Cells are then streaked onto the plates or grown in the liquid media. Only cells containing the plasmids resistant to kanamycin will grow.

COVID-19 differs from other recent public health crises with respect to its sudden onset, its rapid spread, the lack of any known vaccine or cure and resulting shortages of critical medical equipment. The convergence of these factors has prompted both governments and IPR holders around the world to seek ways to increase the availability of IPR necessary to combat the pandemic. Governmental compulsory licensing, IPR pools and voluntary IPR pledges have all been used in the past, though in situations that differ in important respects from the COVID-19 pandemic. Each is designed to result, to a greater or lesser degree, in a publicly-accessible “commons” of rights and technologies that are broadly available for use to support an important public health goals. Here, we compare and contrast these differing approaches to IPR commons formation and assess their suitability to address the COVID-19 crisis.

Cell-free systems for gene expression have gained attention as platforms for the facile study of genetic circuits and as highly effective tools for teaching. Despite recent progress, the technology remains inaccessible for many in low- and middle-income countries due to the expensive reagents required for its manufacturing, as well as specialized equipment required for distribution and storage. To address these challenges, we deconstructed processes required for cell-free mixture preparation and developed a set of alternative low-cost strategies for easy production and sharing of extracts. First, we explored the stability of cell-free reactions dried through a low-cost device based on silica beads, as an alternative to commercial automated freeze dryers. Second, we report the positive effect of lactose as an additive for increasing protein synthesis in maltodextrin-based cell-free reactions using either circular or linear DNA templates. The modifications were used to produce active amounts of two high-value reagents: the isothermal polymerase Bst and the restriction enzyme BsaI. Third, we demonstrated the endogenous regeneration of nucleoside triphosphates and synthesis of pyruvate in cell-free systems (CFSs) based on phosphoenol pyruvate (PEP) and maltodextrin (MDX). We exploited this novel finding to demonstrate the use of a cell-free mixture completely free of any exogenous nucleotide triphosphates (NTPs) to generate high yields of sfGFP expression. Together, these modifications can produce desiccated extracts that are 203-424-fold cheaper than commercial versions. These improvements will facilitate wider use of CFS for research and education purposes.

Molecular biologists often use tris-based conduction buffers like TBE or TAE in running DNA gels. These buffers are known to overheat at high voltages, causing problems with gel integrity, sample denaturation and more. The voltage thus needs to be limited to a maximum of 5-10 volts/cm (e.g 100 volts for a 10 cm gel) leading to extended running time, sometimes to hours. With 10mM Sodium Tetraborate (CAS#: 1330-43-4, Na2B4O7, Borax), the voltage can be increased to 35 volts/cm without any problem, reducing the time taken to run gels by up to 7 times for standard applications (e.g. separation of DNA fragments from 100 bp - 5 kbp). Our lab’s standard DNA gel buffer has become 20 g of Borax into 1 l of water which gives a 20x stock solution. Small gels run in 10-15 minutes at 200V. SCOPE: Preparation of gel electrophoresis buffer for separation of DNA fragments from 100 bp - 5 kbp

Protein reagents are indispensable for most molecular and synthetic biology procedures. Most conventional protocols rely on highly purified protein reagents that require considerable expertise, time, and infrastructure to produce. In consequence, most proteins are acquired from commercial sources, reagent expense is often high, and accessibility may be hampered by shipping delays, customs barriers, geopolitical constraints, and the need for a constant cold chain. Such limitations to the widespread availability of protein reagents, in turn, limit the expansion and adoption of molecular biology methods in research, education, and technology development and application. Here, we describe protocols for producing a low-resource and locally sustainable reagent delivery system, termed "cellular reagents," in which bacteria engineered to overexpress proteins of interest are dried and can then be used directly as reagent packets in numerous molecular biology reactions, without the need for protein purification or a constant cold chain. As an example of their application, we describe the execution of polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) using cellular reagents, detailing how to replace pure protein reagents with optimal amounts of rehydrated cellular reagents. We additionally describe a do-it-yourself fluorescence visualization device for using these cellular reagents in common molecular biology applications. The methods presented in this article can be used for low-cost, on-site production of commonly used molecular biology reagents (including DNA and RNA polymerases, reverse transcriptases, and ligases) with minimal instrumentation and expertise, and without the need for protein purification. Consequently, these methods should generally make molecular biology reagents more affordable and accessible. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Preparation of cellular reagents Alternate Protocol 1: Preparation of lyophilized cellular reagents Alternate Protocol 2: Evaluation of bacterial culture growth via comparison to McFarland turbidity standards Support Protocol 1: SDS-PAGE for protein expression analysis of cellular reagents Basic Protocol 2: Using Taq DNA polymerase cellular reagents for PCR Basic Protocol 3: Using Br512 DNA polymerase cellular reagents for loop-mediated isothermal amplification (LAMP) Support Protocol 2: Building a fluorescence visualization device.

TBE and TAE buffers are often used in procedures involving nucleic acids, the most common being electrophoresis. Tris-acid solutions are effective buffers for slightly basic conditions, which keep DNA deprotonated and soluble in water. EDTA is a chelator of divalent cations, particularly of magnesium (Mg2+). As these ions are necessary cofactors for many enzymes, including contaminant nucleases, the role of the EDTA is to protect the nucleic acids against enzymatic degradation. But since Mg2+ is also a cofactor for many useful DNA-modifying enzymes such as restriction enzymes and DNA polymerases, its concentration in TBE or TAE buffers is generally kept low (typically at around 1 mM). TBE buffer is used to prepare agarose gels and as running buffer in agarose gel electrophoresis to separate and identify and analyse nucleic acids. SCOPE: This protocol covers the steps involved in making 1L of 10x TBE buffer from Tris, Borate and EDTA powders DEFINITIONS: TBE: Tris Borate EDTA

As the second year of the COVID-19 pandemic begins, it remains clear that a massive increase in the ability to test for SARS-CoV-2 infections in a myriad of settings is critical to controlling the pandemic and to preparing for future outbreaks. The current gold standard for molecular diagnostics is the polymerase chain reaction (PCR), but the extraordinary and unmet demand for testing in a variety of environments means that both complementary and supplementary testing solutions are still needed. This review highlights the role that loop-mediated isothermal amplification (LAMP) has had in filling this global testing need, providing a faster and easier means of testing, and what it can do for future applications, pathogens, and the preparation for future outbreaks. This review describes the current state of the art for research of LAMP-based SARS-CoV-2 testing, as well as its implications for other pathogens and testing. The authors represent the global LAMP (gLAMP) Consortium, an international research collective, which has regularly met to share their experiences on LAMP deployment and best practices; sections are devoted to all aspects of LAMP testing, including preanalytic sample processing, target amplification, and amplicon detection, then the hardware and software required for deployment are discussed, and finally, a summary of the current regulatory landscape is provided. Included as well are a series of first-person accounts of LAMP method development and deployment. The final discussion section provides the reader with a distillation of the most validated testing methods and their paths to implementation. This review also aims to provide practical information and insight for a range of audiences: for a research audience, to help accelerate research through sharing of best practices; for an implementation audience, to help get testing up and running quickly; and for a public health, clinical, and policy audience, to help convey the breadth of the effect that LAMP methods have to offer.

This protocol is a low-cost approach for preparing competent cells using 0.1M CaCl2 solution which is useful in cases where commercial competent cells are unaffordable, it is challenging to receive products on dry ice or you do not have an ultra low temperature freezer.

RT-LAMP (reverse transcription - Loop-mediated isothermal amplification) has gained popularity for the detection of SARS-CoV-2. The high specificity, sensitivity, simple protocols and potential to deliver results without the use of expensive equipment has made it an attractive alternative to RT-PCR. However, the high cost per reaction, the centralized manufacturing of required reagents and their distribution under cold chain shipping limits RT-LAMP’s applicability in low-income settings. The preparation of assays using homebrew enzymes and buffers has emerged worldwide as a response to these limitations and potential shortages. Here, we describe the production of Moloney murine leukemia virus (M-MLV) Reverse Transcriptase and BstLF DNA polymerase for the local implementation of RT-LAMP reactions at low cost. These reagents compared favorably to commercial kits and optimum concentrations were defined in order to reduce time to threshold, increase ON/OFF range and minimize enzyme quantities per reaction. As a validation, we tested the performance of these reagents in the detection of SARS-CoV-2 from RNA extracted from clinical nasopharyngeal samples, obtaining high agreement between RT-LAMP and RT-PCR clinical results. The in-house preparation of these reactions results in an order of magnitude reduction in costs, and thus we provide protocols and DNA to enable the replication of these tests at other locations. These results contribute to the global effort of developing open and low cost diagnostics that enable technological autonomy and distributed capacities in viral surveillance.

Nature Biotechnology asks a selection of faculty about the most exciting frontier in their field and the most needed technologies for advancing knowledge and applications. What will be the most important areas of research in biotech over the coming years? Which technologies will be most important to advance knowledge and applications in these areas? Nature Biotechnology reached out to a set of faculty doing outstanding work in research areas representative of the journal’s remit and asked them to contribute their vision of where their fields are going.

Standardisation is an important component in the maturation of any field of technology. It contributes to the formation of a recognisable identity and enables interactions with a wider community. This article reviews past and current standardisation initiatives in the field of Open Source Hardware (OSH). While early initiatives focused on aspects such as licencing, intellectual property and documentation formats, recent efforts extend to ways for users to exercise their rights under open licences and to keep OSH projects discoverable and accessible online. We specifically introduce two standards that are currently being released and call for early users and contributors, the DIN SPEC 3105 and the Open Know How Manifest Specification. Finally, we reflect on challenges around standardisation in the community and relevant areas for future development such as an open tool chain, modularity and hardware specific interface standards., Comment: 9 Pages without abstract and references (else 13), no figures

The concept of Intellectual Property (IP) strategies has a growing importance for technology-based firms in recent years, which includes open IP strategies such as permissive licensing making IP free for others to use or choosing not to protect IP at all. At the same time, the question of how IP should be used as an asset to promote innovation and protect the economic return for firms has been debated across various emerging industries. This study aims to understand the current IP strategies of synthetic biology start-ups and their willingness to open up IP in the future. A conceptual framework of ranking different IP strategies and the concept of Willingness to Open are first proposed. Then, qualitative data is collected from eight synthetic biology case studies in the UK. The companies’ IP strategies are divided into in-bound and outbound, and ranked within the conceptual framework. The motivations and impacts of these IP strategies are analysed and discussed. Finally, each company’s willingness to open up their IP in the future is ranked from high to low, alongside their reasonings. These analyses have proven the value of this exploratory work, however more studies are required to clarify the current findings and broaden the research.

Funder: Shuttleworth Foundation, Funder: Mozilla Foundation; funder-id: http://dx.doi.org/10.13039/501100012642, We recently developed ‘cellular’ reagents–lyophilized bacteria overexpressing proteins of interest–that can replace commercial pure enzymes in typical diagnostic and molecular biology reactions. To make cellular reagent technology widely accessible and amenable to local production with minimal instrumentation, we now report a significantly simplified method for preparing cellular reagents that requires only a common bacterial incubator to grow and subsequently dry enzyme-expressing bacteria at 37°C with the aid of inexpensive chemical desiccants. We demonstrate application of such dried cellular reagents in common molecular and synthetic biology processes, such as PCR, qPCR, reverse transcription, isothermal amplification, and Golden Gate DNA assembly, in building easy-to-use testing kits, and in rapid reagent production for meeting extraordinary diagnostic demands such as those being faced in the ongoing SARS-CoV-2 pandemic. Furthermore, we demonstrate feasibility of local production by successfully implementing this minimized procedure and preparing cellular reagents in several countries, including the United Kingdom, Cameroon, and Ghana. Our results demonstrate possibilities for readily scalable local and distributed reagent production, and further instantiate the opportunities available via synthetic biology in general.

This article reports on a conference workshop conducted at CYTO 2018. During the workshop a new Open Science forum "CYTO Lab Hacks" has been launched within the International Society for the Advancement of Cytometry (ISAC). Its goal is to serve as an open, transparent, sustainable and accessible forum for innovation-exchange in cytometry. Here we report the captured status quo, the perceived requirements of the members in relation to open innovation sharing and dissemination and publicize the format of "CYTO Lab Hacks".

Without hardware, there is no science. Instruments, reagents, computers, and other equipment are essential for producing systematic knowledge. Yet, current supply chains limit access and impede creativity and customization through high mark-ups and proprietary designs, compounded by proprietary hardware licenses and patents. Open Science Hardware (OSH) addresses part of this problem by sharing designs, instructions for building, and protocols. Expanding the reach of OSH within academic research, NGO initiatives, citizen science, and education has potential to increase access to experimental tools and facilitate their customization and reuse. We organized with others the “Gathering for Open Science Hardware” (GOSH) in 2016 to address what we see as the primary barrier to OSH: early adopters are disparate and separated by geographical and disciplinary borders which limit interaction, exchange and community building. This inaugural gathering brought together 50 of the most active developers, users, and thinkers in the OSH movement, complemented by expertise from diverse backgrounds, to seed a global community. This article provides a review of the activities and debates we conducted at GOSH 2016.

It’s tough for Peter getting out of bed today – yesterday he travelled to Brussels and back, fighting for ‘The Right to Read is the Right to Mine’ (R2RR2M). Content mining – also known as text and data mining (TDM) – is a hot topic in Europe. It’s got huge promise, with two million scholarly publications a year and so much data that we can’t take it all in – 5,000 papers a day (and grey literature, and theses, and…). So we must have machines to help.

ContentMine/Hypothes.is Proposal

The prospect of widespread content mining of the scholarly literature is emerging, driven by the promise of increased permissions due to copyright reform in countries such as the UK and the support of some publishers, particularly those that publish open access-journals. In parallel, the growing software tool set for mining, and the availability of ontologies such as DBPedia mean that many scientists can start to mine the literature with relatively few technical barriers. We believe that content mining can be carried out in a responsible, legal manner causing no technical issues for any parties. In addition, ethical concerns including the need for formal accreditation and citation can be addressed, with the further possibility of machine-supported metrics. This chapter sets out some approaches to act as guidelines for those starting mining activities.

Summary - Looking at Open Science and Open Data from a broad perspective. This is the idea behind “Scientific data sharing: an interdisciplinary workshop”, an initiative designed to foster dialogue between scholars from different scientific domains which was organized by the Istituto Italiano di Antropologia in Anagni, Italy, 2-4 September 2013.We here report summaries of the presentations and discussions at the meeting. They deal with four sets of issues: (i) setting a common framework, a general discussion of open data principles, values and opportunities; (ii) insights into scientific practices, a view of the way in which the open data movement is developing in a variety of scientific domains (biology, psychology, epidemiology and archaeology); (iii) a case study of human genomics, which was a trail-blazer in data sharing, and which encapsulates the tension that can occur between large-scale data sharing and one of the boundaries of openness, the protection of individual data; (iv) open science and the public, based on a round table discussion about the public communication of science and the societal implications of open science. There were three proposals for the planning of further interdisciplinary initiatives on open science. Firstly, there is a need to integrate top-down initiatives by governments, institutions and journals with bottom-up approaches from the scientific community. Secondly, more should be done to popularize the societal benefits of open science, not only in providing the evidence needed by citizens to draw their own conclusions on scientific issues that are of concern to them, but also explaining the direct benefits of data sharing in areas such as the control of infectious disease. Finally, introducing arguments from social sciences and humanities in the educational dissemination of open data may help students become more profoundly engaged with Open Science and look at science from a broader perspective

Data provides the evidence for the published body of scientific knowledge, which is the foundation for all scientific progress. The more data is made openly available in a useful manner, the greater the level of transparency and reproducibility and hence the more efficient the scientific process becomes, to the benefit of society. This viewpoint is becoming mainstream among many funders, publishers, scientists, and other stakeholders in research, but barriers to achieving widespread publication of open data remain. The Open Data in Science working group at the Open Knowledge Foundation is a community that works to develop tools, applications, datasets, and guidelines to promote the open sharing of scientific data. This article focuses on the Open Knowledge Definition and the Panton Principles for Open Data in Science. We also discuss some of the tools the group has developed to facilitate the generation and use of open data and the potential uses that we hope will encourage further movement towards an open scientific knowledge commons.

[perspective] Lorsque certains blocages techniques et juridiques auront ete surmontes, le text mining ou exploration automatique des contenus ouvrira d’immenses perspectives pour la litterature grise, comme le demontre le retour d’experiences de certains champs scientifiques qui y recourent deja.

One of the foundations of the scientific method is to be able to reproduce experiments and corroborate the results of research that has been done before. However, with the increasing complexities of new technologies and techniques, coupled with the specialisation of experiments, reproducing research findings has become a growing challenge. Clearly, scientific methods must be conveyed succinctly, and with clarity and rigour, in order for research to be reproducible. Here, we propose steps to help increase the transparency of the scientific method and the reproducibility of research results: specifically, we introduce a peer-review oath and accompanying manifesto. These have been designed to offer guidelines to enable reviewers (with the minimum friction or bias) to follow and apply open science principles, and support the ideas of transparency, reproducibility and ultimately greater societal impact. Introducing the oath and manifesto at the stage of peer review will help to check that the research being published includes everything that other researchers would need to successfully repeat the work. Peer review is the lynchpin of the publishing system: encouraging the community to consciously (and conscientiously) uphold these principles should help to improve published papers, increase confidence in the reproducibility of the work and, ultimately, provide strategic benefits to authors and their institutions. Future incarnations of the various national Research Excellence Frameworks (REFs) will evolve away from simple citations towards measurable societal value and impact. The proposed manifesto aspires to facilitate this goal by making transparency, reproducibility and citizen-scientist engagement (with the knowledge-creation and dissemination processes) the default parameters for performing sound research.

The effects of both intravenous administration of recombinant human erythropoietin (rhEPO) and blood withdrawal, either individually or in combination, on the frequency of micronucleated immature erythrocytes (MIE) in the bone marrow were investigated in 10-week old male Han Wistar rats. Clear increases in MIE frequency and evidence of erythroid hyperplasia were seen in the bone marrow after 1350 IU kg−1 rhEPO but only marginal increases in MIE were seen at the lower dose of 135 IU kg−1. At the lower dose, blood levels of rhEPO were found to be approximately 120 pg mL−1 within one hour of dosing. Withdrawal of 5 blood samples of 0.45 mL on each occasion during 24 hours, the maximum allowed by the Home Office licence, did not increase MIE frequency but did result in levels of endogenous EPO of 15–19 pg mL−1 24 to 72 hours after the start of treatment, with some evidence of increased erythropoiesis. Although the increased plasma amounts of EPO, resulting from blood withdrawal, were lower than the blood levels achieved by the administration of exogenous rhEPO that were required to give increases in micronucleus frequency, the possibility that blood withdrawal might influence the MIE response to genotoxins cannot be totally excluded without further investigation.