̽��ֱ�� of Cambridge - Jenny Molloy

Open-source toolkit helps developing countries meet demand for COVID-19 research and diagnostics

erh68 — Tue, 08 Dec 2020 00:22:13 +0000

High demand for millions of COVID-19 tests per day combined with a disrupted global supply chain has left many countries facing diagnostic shortages. In a recent Nature commentary, John Nkengasong, Director of the Africa Centres for Disease Control and Prevention, said, “the collapse of global cooperation [has] shoved Africa out of the diagnostics market....African countries have funds to pay for reagents but cannot buy them.”

Scientists across the world are therefore developing new tests that are faster, cheaper, adapted to needs of local health systems and easy to manufacture in order to overcome this challenge.

To enable scientists to access the research tools they need for their work, researchers from the Open Bioeconomy Lab at the ̽��ֱ�� of Cambridge, the Lab de Tecnología Libre at iBio/PUC Chile and the FreeGenes Project at Stanford Universit y teamed up with synthetic biology company Ginkgo Bioworks to design an open source toolkit that enables researchers to produce 16 of the most useful enzymes for a number of diagnostic techniques used to detect SARS-CoV-2, the virus which causes COVID-19.

“Designing the collections was a great collaborative effort between researchers with diverse expertise and different local needs for fighting the pandemic,” said Dr Chiara Gandini from Cambridge’s Department of Chemical Engineering and Biotechnology. “We designed it with other biologists in mind, making it as easy as possible for them to reconfigure the toolkit for their requirements.”

̽��ֱ��‘Molecular Diagnostic Toolkit’ comprises ready-to-use DNA to produce enzymes including DNA polymerases and reverse transcriptases – the enzymes used in gold standard RT-qPCR tests. These enzymes are also useful for tests like LAMP, which is faster and simpler than RT-qPCR and is rapidly being adopted by more labs. Control DNA is also included in the toolkit to validate that tests will specifically detect SARS-CoV-2 but not closely related viruses.

̽��ֱ��Molecular Diagnostic Toolkit uses standard laboratory techniques to produce and purify the enzymes, but many researchers in the Global South work under challenging resource constraints and may need to adapt their work to the local availability of materials. They can therefore make use of the ‘E. coli Protein Expression Toolkit’: a collection of over 100 DNA parts that can be assembled in thousands of combinations to tailor the whole production process. For example, modules are included to bind enzymes to cellulose to develop paper-based tests or to activate enzyme production in cells using light from LEDs instead of expensive chemicals.

̽��ֱ��toolkit has been pre-ordered by over 34 labs from 16 countries, including Brazil, Chile, Peru, Colombia, Costa Rica, Mexico, Cameroon, Ethiopia, India and Vietnam.

“Having access to this palette of molecular tools is crucial for our region to fight any reagent supply shortages in the short-term, and to leverage technological autonomy in diagnostics and viral monitoring in the long term,” said Tamara Matute from the Pontificia Universidad Católica de Chile and iBio, who participated in the design of the collection. Matute’s colleague Isaac Núñez added that mechanisms like the open online community, Reclone Network, are also needed to enhance the usefulness of the collection through peer support including fostering “a collaborative community, crowd-sourced protocols and openly-shared resources.”

While the initial focus of the toolkit is to support research and development, the same DNA could be used to manufacture diagnostic kits with the correct processes and regulatory approvals in place. As it is open source, any company or institution is able to produce and commercialise enzymes from the toolkit. For example, LAMP enzymes will be manufactured at the Ethiopian Biotechnology Institute in a collaboration with the ̽��ֱ�� of Cambridge supported by the Cambridge-Africa Alborada Fund.

Dr Brook Esseye of the EBTi LAMP Initiative said, “this initiative will enhance local capacity for bio-manufacturing and strengthen partnerships among researchers in various countries so we can join hands to fight this global pandemic.”

Looking beyond COVID-19, local bio-manufacturing capacity could underpin other advances in biotechnology research, education and innovation.

“A resilient local supply chain for diagnostics is vital to future health security and pandemic preparedness,” said Dr Jenny Molloy, Shuttleworth Fellow at Cambridge’s Department of Chemical Engineering and Biotechnology. “ ̽��ֱ��same enzymes used to detect COVID-19 can also detect malaria, typhoid and many other diseases. They can be applied in lots of other ways to make positive social and economic impact, including research to breed better crops, measuring the effect of conservation initiatives on biodiversity and tracking antibiotic resistance. This flexibility is why it is so important that key tools for biotechnology are accessible, used and useful for all researchers around the world.”

̽��ֱ��toolkit has been made freely available under the Open Material Transfer Agreement (OpenMTA), which gives explicit permission for recipients to distribute to other labs and to use the toolkit for commercial purposes, and can be ordered online via Stanford ̽��ֱ��’s Free Genes project.

Researchers and users of the toolkit are invited to share protocols, resources and advice via the Reclone Forum.

Researchers have developed a free, open-source toolkit that allows laboratories in developing countries to produce their own tools for COVID-19 research and diagnosis, without relying on an increasingly fractured global supply chain.

A resilient local supply chain for diagnostics is vital to future health security and pandemic preparedness

Jenny Molloy

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Novel Coronavirus SARS-CoV-2

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Report highlights opportunities and risks associated with synthetic biology and bioengineering

cjb250 — Tue, 21 Nov 2017 11:50:43 +0000

Rapid developments in the field of synthetic biology and its associated tools and methods, including more widely available gene editing techniques, have substantially increased our capabilities for bioengineering – the application of principles and techniques from engineering to biological systems, often with the goal of addressing 'real-world' problems.

In a feature article published in the open access journal eLife, an international team of experts led by Dr Bonnie Wintle and Dr Christian R. Boehm from the Centre for the Study of Existential Risk at the ̽��ֱ�� of Cambridge, capture perspectives of industry, innovators, scholars, and the security community in the UK and US on what they view as the major emerging issues in the field.

Dr Wintle says: “ ̽��ֱ��growth of the bio-based economy offers the promise of addressing global environmental and societal challenges, but as our paper shows, it can also present new kinds of challenges and risks. ̽��ֱ��sector needs to proceed with caution to ensure we can reap the benefits safely and securely.”

̽��ֱ��report is intended as a summary and launching point for policy makers across a range of sectors to further explore those issues that may be relevant to them.

Among the issues highlighted by the report as being most relevant over the next five years are:

Artificial photosynthesis and carbon capture for producing biofuels

If technical hurdles can be overcome, such developments might contribute to the future adoption of carbon capture systems, and provide sustainable sources of commodity chemicals and fuel.

Enhanced photosynthesis for agricultural productivity

Synthetic biology may hold the key to increasing yields on currently farmed land – and hence helping address food security – by enhancing photosynthesis and reducing pre-harvest losses, as well as reducing post-harvest and post-consumer waste.

Synthetic gene drives

Gene drives promote the inheritance of preferred genetic traits throughout a species, for example to prevent malaria-transmitting mosquitoes from breeding. However, this technology raises questions about whether it may alter ecosystems, potentially even creating niches where a new disease-carrying species or new disease organism may take hold.

Human genome editing

Genome engineering technologies such as CRISPR/Cas9 offer the possibility to improve human lifespans and health. However, their implementation poses major ethical dilemmas. It is feasible that individuals or states with the financial and technological means may elect to provide strategic advantages to future generations.

Defence agency research in biological engineering

̽��ֱ��areas of synthetic biology in which some defence agencies invest raise the risk of ‘dual-use’. For example, one programme intends to use insects to disseminate engineered plant viruses that confer traits to the target plants they feed on, with the aim of protecting crops from potential plant pathogens – but such technologies could plausibly also be used by others to harm targets.

In the next five to ten years, the authors identified areas of interest including:

Regenerative medicine: 3D printing body parts and tissue engineering

While this technology will undoubtedly ease suffering caused by traumatic injuries and a myriad of illnesses, reversing the decay associated with age is still fraught with ethical, social and economic concerns. Healthcare systems would rapidly become overburdened by the cost of replenishing body parts of citizens as they age and could lead new socioeconomic classes, as only those who can pay for such care themselves can extend their healthy years.

Microbiome-based therapies

̽��ֱ��human microbiome is implicated in a large number of human disorders, from Parkinson’s to colon cancer, as well as metabolic conditions such as obesity and type 2 diabetes. Synthetic biology approaches could greatly accelerate the development of more effective microbiota-based therapeutics. However, there is a risk that DNA from genetically engineered microbes may spread to other microbiota in the human microbiome or into the wider environment.

Intersection of information security and bio-automation

Advancements in automation technology combined with faster and more reliable engineering techniques have resulted in the emergence of robotic 'cloud labs' where digital information is transformed into DNA then expressed in some target organisms. This opens the possibility of new kinds of information security threats, which could include tampering with digital DNA sequences leading to the production of harmful organisms, and sabotaging vaccine and drug production through attacks on critical DNA sequence databases or equipment.

Over the longer term, issues identified include:

New makers disrupt pharmaceutical markets

Community bio-labs and entrepreneurial startups are customizing and sharing methods and tools for biological experiments and engineering. Combined with open business models and open source technologies, this could herald opportunities for manufacturing therapies tailored to regional diseases that multinational pharmaceutical companies might not find profitable. But this raises concerns around the potential disruption of existing manufacturing markets and raw material supply chains as well as fears about inadequate regulation, less rigorous product quality control and misuse.

Platform technologies to address emerging disease pandemics

Emerging infectious diseases—such as recent Ebola and Zika virus disease outbreaks—and potential biological weapons attacks require scalable, flexible diagnosis and treatment. New technologies could enable the rapid identification and development of vaccine candidates, and plant-based antibody production systems.

Shifting ownership models in biotechnology

̽��ֱ��rise of off-patent, generic tools and the lowering of technical barriers for engineering biology has the potential to help those in low-resource settings, benefit from developing a sustainable bioeconomy based on local needs and priorities, particularly where new advances are made open for others to build on.

Dr Jenny Molloy comments: “One theme that emerged repeatedly was that of inequality of access to the technology and its benefits. ̽��ֱ��rise of open source, off-patent tools could enable widespread sharing of knowledge within the biological engineering field and increase access to benefits for those in developing countries.”

Professor Johnathan Napier from Rothamsted Research adds: “ ̽��ֱ��challenges embodied in the Sustainable Development Goals will require all manner of ideas and innovations to deliver significant outcomes. In agriculture, we are on the cusp of new paradigms for how and what we grow, and where. Demonstrating the fairness and usefulness of such approaches is crucial to ensure public acceptance and also to delivering impact in a meaningful way.”

Dr Christian R. Boehm concludes: “As these technologies emerge and develop, we must ensure public trust and acceptance. People may be willing to accept some of the benefits, such as the shift in ownership away from big business and towards more open science, and the ability to address problems that disproportionately affect the developing world, such as food security and disease. But proceeding without the appropriate safety precautions and societal consensus—whatever the public health benefits—could damage the field for many years to come.”

̽��ֱ��research was made possible by the Centre for the Study of Existential Risk, the Synthetic Biology Strategic Research Initiative (both at the ̽��ֱ�� of Cambridge), and the Future of Humanity Institute ( ̽��ֱ�� of Oxford). It was based on a workshop co-funded by the Templeton World Charity Foundation and the European Research Council under the European Union’s Horizon 2020 research and innovation programme.

Reference
Wintle, BC, Boehm, CR et al. A transatlantic perspective on 20 emerging issues in biological engineering. eLife; 14 Nov 2017; DOI: 10.7554/eLife.30247

Human genome editing, 3D-printed replacement organs and artificial photosynthesis – the field of bioengineering offers great promise for tackling the major challenges that face our society. But as a new article out today highlights, these developments provide both opportunities and risks in the short and long term.

Susanne Nilsson

Reaching for the Sky

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Opinion: We need to break science out of its ivory tower – here's one way to do this

Anonymous — Wed, 26 Apr 2017 10:52:33 +0000

Without hardware, there is no science. From Hooke’s microscope to the Hubble telescope, instruments are modern science’s platforms for producing knowledge. But limited access to scientific tools impedes the progress and reach of science by restricting the type of people who can participate in research, favouring those who have access to well-resourced laboratories in industrial or academic institutions.

Scientists in developing countries, grassroots community organisations, and citizen scientists can struggle to obtain and maintain the equipment they require to answer their own research questions.

̽��ֱ��result of this exclusion from participation is that scientific research becomes ever more elitist as a small number of people decide what the worthwhile and valid projects are. For example, the relative neglect of many tropical diseases and agricultural research on African subsistence crops demonstrates that local concerns in areas with limited scientific resources are often not sufficiently addressed by global science.

Likewise, public concerns and desire for transparency around technology can also be ignored. Research on fracking has received $137 million from the United States Department of Energy. But despite vocal concerns about water pollution, no affordable technologies have been developed for communities to use to monitor their own air or water, even though access to the relevant data from industry is difficult. Locking science inside ivory and industry towers restricts what it can look like.

Open hardware

̽��ֱ��open science hardware movement challenges these norms with the goal of providing different futures for science, using hardware as a launching point. It argues that plans, protocols and material lists for scientific instruments should be shared, accessible and able to be replicated. ̽��ֱ��fact that a lot of modern scientific equipment is a consumer product that is patented, not supplied with full design information and difficult to repair also blocks creativity and customisation.

For example, open source project Oceanography for Everyone recently crowdfunded an open conductivity, temperature and depth (CTD) instrument out of frustration with the lack of low-cost instrumentation available. CTD instruments are the workhorses of oceanography research, and usually cost thousands of dollars. Oceanography for Everyone’s model achieves comparable data but costs US$300 to build, and the plans are public on GitHub. Think of OpenCTD like a really nice shirt. You could buy one for $40, or if you don’t have enough money but you do have a sewing pattern and some time, you could purchase the fabric for $5 and make it yourself, and even customise it to your needs and tastes.

Lower cost is only one goal of open science hardware. CERN, the European Particle Physics Laboratory in Geneva, pioneered an Open Hardware License to enable large-scale, open collaboration on projects. One of these, White Rabbit, is an electronic controller for precise synchronisation of signals across vast distances. White Rabbit ensures that some of the world’s largest particle accelerators are coordinated. But it’s also freely available to anyone, and has found new uses in designing smart electricity grids.

Members of CLEAR using hand tools to repair an open science hardware trawl (LADI trawl) for monitoring marine plastics. MEOPAR

Equality or equity?

Instruments such as OpenCTD and White Rabbit are built on the premise of equality, the idea that everyone should have access to scientific tools. Yet the ability to access such tools is only half the story: it doesn’t address the acute disparities in who is creating science in the first place. And these are enormous. In 2015, ̽��ֱ��Guardian reported that Africa produces just 1.1% of global scientific knowledge. And recent data from UNESCO indicates that only 28% of researchers globally are women. Women do not represent 50% of scientists in a single country in the world.

Attempting to address this problem, several feminist laboratories create and use open science hardware. For example, the Civic Laboratory for Environmental Action Research (CLEAR) is a feminist marine pollution lab in Newfoundland, Canada. And the GynePunks are a group of bio-hackers at the forefront of DIY gynaecology, based in Barcelona.

These labs are not merely bringing more women and trans scientist-inventors into science-as-usual. They prioritise equity rather than equality, recognising that when people start from fundamentally different social, economic, educational and political positions, treating everyone the same does not overcome those differences. In doing so, they transform science in terms of how research priorities are chosen and articulated, what kinds of knowledge is considered valid, and, of course, how scientific tools are made and distributed.

Equality vs. Equity. Interaction Institute for Social Change. Artist: Angus Maguire. CC BY 2.0

Beyond the lab

Particularly valuable work is being done by groups attempting to move science out of the lab and into places and frameworks where it would not usually occur.

For example, Public Lab is a US-based environmental science community founded by frustrated citizens on the Gulf Coast following the Deepwater Horizon oil disaster in 2010. Getting accurate, timely and public high resolution data about local damage was impossible due to flight restrictions over the spill area and satellites are too far away to provide the same level of detail. So citizen scientists stitched together photos from cheap cameras suspended from helium balloons. ̽��ֱ��tools are open and accessible, and the research is done by and for local people without science degrees.

Public Lab volunteers mapping the Deep Horizon oil spill using a low-cost weather balloon setup that is openly documented on the Public Lab wiki. Jeff Warren/Flickr

Likewise, the work of Lifepatch, an Indonesian citizen initiative in art, science, and technology which uses low-cost methods and open tools such as webcam microscopes, is deeply rooted in Indonesian collective culture. ̽��ֱ��questions of basic, daily life and everyday needs have driven projects with local communities on river water quality, bio-recovery of soils altered by volcanic eruptions and safe fermentation practices in collaboration with local academics.

All of these projects demonstrate the value of science grounded in specific places, complex local traditions, ethics, contexts and research questions, rather than a universal science that works the same everywhere for everyone. We need to push science towards communal, bottom-up, and collaborative practices; away from territorial, proprietary, institutional, Western-dominated and individualistic practices.

This has significant implications for where science happens, who is involved, and as a result, the types of knowledge that can be produced. Open science hardware is about creating new futures for science.

Max Liboiron, Professor of Geography and Environmental Science, Memorial ̽��ֱ�� of Newfoundland and Jenny Molloy, Coordinator, Synthetic Biology Strategic Research Initiative, ̽��ֱ�� of Cambridge

This article was originally published on ̽��ֱ��Conversation. Read the original article.

Science doesn't work the same for everyone everywhere - there are huge disparities in access to scientific hardware, and in gender and minority representation in labs. In this piece from ̽��ֱ��Conversation, Jenny Molloy (Department of Earth Sciences) and Max Liboiron (Memorial ̽��ֱ�� of Newfoundland) look at some of the initiatives around the world which are attempting to level the playing field for scientists.

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Stem Cell Research

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