The following is my Shuttleworth Foundation Fellowship Reapplication for 2020-21.

Tell us about the world as you see it.

Biology as a technology is a key component of solving global challenges. It can provide better yielding crops to feed more people using less land, low-cost diagnostics to improve access to healthcare and sustainable ways of producing fuels, plastics, chemicals and the materials that drive our economy. Biological organisms are one of the most sustainable and efficient ways at our disposal to produce these essential commodities in sufficient quantities to meet global demand. However, researchers’ access to biotechnology is very unevenly distributed even at a time when its cost is decreasing. There are huge barriers to participation in the bioeconomy including i) patenting and protection of inventions being the default strategy for technology transfer; ii)  inadequate supply chains which generate unaffordable research tools and materials in emerging economies; iii) lack of autonomy for researchers in resource-constrained contexts to set their own research agenda to meet local challenges. This situation must change to enable people around the world to use biotechnology and fully realise its potential for public good.

During the first year of my Fellowship I conducted many interviews with biologists to better understand what needs to change in terms of technology access. During my second year I established research laboratories from the ground up with teams in Ghana and Cameroon to address what they told me: that resource constraints imposed by the existing market for essential biological tools deny them the ability to innovate - to try, fail and try again - even when they have the same funding and abilities as researchers in the global North. In large part this is because vital research tools are more expensive and take months to reach their lab bench. This is true even when those tools are open, through patent expiry or open licensing. In other words, openness is necessary but insufficient to provide a functioning pipeline for the tools that underpin the bioeconomy. The supply chain itself needs to be fixed and the second year of my fellowship has laid the foundations for that work.

The enthusiasm with which collaborators have embraced the mission of the Open Bioeconomy Lab has been in equal parts encouraging and testament to the scale of the challenge we are facing. I now have formal collaborations in place with researchers in Ghana, Cameroon, Ethiopia, Chile, South Africa and grant proposals submitted with or offers of collaboration from India, Pakistan, Colombia, Egypt, Kenya and several additional countries. These collaborators want to understand the spread of malaria, test potatoes for a crop-devastating disease, diagnose typhoid to improve clinical treatment of patients, improve the safe production of dairy products and accelerate many more projects that address local and global development challenges. They also want to answer deep scientific questions about the world and capture the imaginations of their students while preparing them for employment with practical lab skills.

Barriers to accessing biological tools limit all of these aspirations and also the autonomy that researchers have to pursue what they consider the most impactful research. Local manufacturing would provide part of the solution. We have started with enzymes because they are some of the most expensive but essential biological tools required in biotechnology, yet fewer than 10% of researchers I interviewed had manufactured their own and then only the easiest to produce for which the DNA is readily available. They immediately saw the benefits that expanding to more enzymes could bring in terms of increased autonomy over research questions and improved quality of research. The challenges and successes in my project during 2019 have given me optimism that this change is possible.

What change do you want to make in the world?

My vision remains the same as the first two years of my Fellowship: an open, sustainable and equitable bioeconomy where biology is a technology that benefits everyone. I want to make open biological tools that are used and useful by fixing the pipeline for supply of open biological materials and tools. This will provide more people in more places the agency to experiment with and shape biotechnology, particularly solving local problems without reliance on the priorities of others. To do this, I have to focus  on two aspects that have come to the fore in my work during the first two years of the Fellowship: people and sustainability.

Putting people first and addressing technology and cognitive justice

A resounding lesson for me in the first year of my Fellowship was the injustice of researchers in the global South being approached as providers of biological material, such as clinical samples or new microbes from interesting environments found in their country, rather than as equitable partners. A classic case is microbes from Bolivian salt flats that can be sources of salt-tolerant enzymes much valued for industrial processes like making bioplastics, biofuels, manufacturing dyes and cleaning up industrial waste. Very few papers had a Bolivian first author because samples are exported for analysis rather than local capacity being built. This is sometimes justifiable for practical reasons but my team demonstrated in Ghana and Cameroon in 2019 that a functioning laboratory can be built for less than $30k and local capability and research talent can be found and nurtured.

There is no excuse for the exclusion of global South researchers from biotechnological advances and I aspire that whatever work my team does in the future serves to make our support redundant and transfers the tools for research autonomy to those in resource-constrained labs. For example, we are working hard to ensure that where an enzyme is needed in our enzyme manufacturing process, that enzyme is also part of our toolkit. This follows examples in open hardware such as the RepRap 3D printer whose developers aspired for RepRaps to build the parts for more RepRaps. We ultimately want our collaborations with colleagues to be a choice they make through shared scientific curiosity, values and vision in a resource abundant world, not a necessity due to resource constraints.

I also want to double efforts on making a change on building better environments for researchers to develop as scientists and people. I am proud of our team: the Open Bioeconomy Lab now numbers nine core members across three countries with 2-3 interns at any given time. Two additional team members work solely for Beneficial Bio Ltd, a not-for-profit that I established to enable toolkit distribution and business development. We are changing the research environment through investing in the development of educational resources covering cutting edge but low-cost research techniques, offering internship opportunities to Cameroonian Masters students from local universities and supporting a member of the team to undertake graduate studies in Ghana. I want to expand these opportunities so they are accessible for even more researchers who will drive change in their contexts through biotechnology.

Proving that openness combined with environmental and economic sustainability is feasible

Last year I spent a lot of time thinking about the extent to which we could enable a ‘circular economy of science’: designing out waste and pollution from systems, keeping products and materials in use and regenerating natural systems. We are now embedding this in a practical sense through the use of locally sourced materials like sugar as part of our protocols, using glass reusable petri dishes for growing bacteria, removing the need for cold chain through freeze-drying our enzymes and incorporating solar power in the Cameroon laboratory. I still believe that circularity has to be embedded in the systems change I am trying to create and that by sharing the knowledge of “what works” more widely we can accelerate a transition to more sustainable modes of performing research.

However, I’ve realised that the more urgent change we need to make and one that took significant investment of my time in the second year of the Fellowship is to establish a model for economic sustainability of local biomanufacturing. This is critical not only for the future of the project and delivering benefits to researchers and biotechnologists but also for making the narrative shift I want to see in bioeconomy policy towards openness and biotechnology for the public good. As a key part of my work from the start of my Fellowship, I have advocated to many different audiences in multiple countries that openness can be a strategic choice for achieving beneficial impact and the inevitable counter-argument I hear is that there are no functioning business models to support that approach within the biotech industry. We need counter-evidence through a successful model existing in the world. I want to prove a sustainable revenue-generating model in 2020 and beyond through our partnership with the MboaLab Biotech team in Cameroon and through later adoption of our model in other regions.

What are you going to do to get there?

1. Fix the supply chain for enzymes through an open toolkit and local manufacturing

Deploy the toolkit of open biological research tools

Over the past year my team have synthesised an open toolkit of 42 off-patent enzymes that are essential to molecular biology and are now available at no cost from the Free Genes project under the Open Material Transfer Agreement (OpenMTA). This means that for the first time ever they are easily available with no restrictions on commercial use or redistribution and in a fully-documented form that biologists can manipulate to suit their needs. We also have >50 new DNA sequences entering the synthesis pipeline and have opened up enzyme submissions to the global research community via our website. Addgene, the world’s largest plasmid repository, has also agreed to distribute the toolkit under OpenMTA at highly subsidised costs for those outside well-funded institutes and to publicise our efforts to the tens of thousands of researchers that access their blog and protocol resources. We aim for over 200 researchers to have accessed enzymes in the collection by the end of 2020.

Scale up production of enzymes and prove an economic model to support local enterprise

We established two laboratories in Ghana and Cameroon which successfully produced and used DNA polymerase enzymes in 2019, which was a great success for the team. They were both intended to become enzyme production sites. However, based on the strengths and interests of the teams, Ghana is now focused on our education and research programmes while Cameroon is setting up for production. Beneficial Bio Ltd will partner with Thomas Mboa to found MboaLab Biotech, the first independent for-profit biotechnology company in Cameroon and the first facility to be registered for genetic engineering outside of a university. Our goal is to be revenue-generating in Q2 2020 and breaking even on running costs within 12 months. On the UK side, I will restructure Beneficial Bio Ltd into a registered charity and a for-profit company to better leverage funding opportunities and the team will consider the best model for partnerships with groups and organisations who might want to set up productions sites. This echoes the challenges faced by other Fellows like Tarek Loubhani and Andrew Lamb so I am fortunate to have their experience to draw upon in designing and implementing a model and seeking further funding. By the end of the third year we aim to have a packaged and proven model for setting up an enzyme production facility that can be adopted by companies, universities and government facilities.

Build a community of open enzyme users and demonstrate impact from downstream use

Our Ghana team in collaboration with other nodes have designed a 1-2 week modular training course for local manufacturing of enzymes. The open educational resources will be published online by end Feb 2020 and we have confirmed courses in Ghana, Cameroon, Ethiopia, Argentina and Chile during the next year reaching over 60 active researchers, research students and those interested in establishing biotechnology businesses who will find immediate application of the enzymes collections. We will evaluate their experiences and the impact of local manufacturing on their research. Our aim is that this will save many of them both scarce research funding and weeks of valuable time they would otherwise spend waiting for deliveries.

In addition to the time and cost saving, we want to demonstrate direct impact from the use of the toolkit for projects that would otherwise not be feasible. In addition to work with collaborators (Ethiopia: developing a chosen enzyme of economic importance and local production capacity; Chile: developing crop disease and soil nitrate sensors) and members of our own team (Ghana: designing a multiplex diagnostic for sexually transmitted infections; Cameroon: developing a novel typhoid diagnostic) we will therefore support a small number of OBL Fellows through a competitive proposal process This will provide the opportunity to develop impact metrics for the difference our work is making in the world through the work of our partners and beneficiaries. This is vital work as we transition to new funding sources.

2. Lay out the evidence for inequity in the bioeconomy

Throughout my Fellowship I have been gathering data that illustrates the social, legal and economic realities of an open bieconomy. The motivation for this is that there are needs to be a much stronger narrative to counter innovation policies that either ignore open approaches completely or fail to recognise their realities. Timing is an important part of this work: East African countries are currently authoring their own bioeconomy strategy and the upcoming 2020 Global Bioeconomy Summit offers a perfect moment for reflection and intervention with worldwide leaders. I see that the most urgent need to alter the course of the current conversation is for experimentation with open approaches and initiatives based in developing and emerging economies where markets look very different to the current biotechnology powerhouses of North America and Europe. The transition from research to the real world has to circumvent a much deeper valley in those contexts.

The results of our work in Ghana, Cameroon, Ethiopia and elsewhere will provide part of this evidence. Other projects that I have been undertaking since the start of the Fellowship are running behind schedule as focus shifted to the practicalities of setting up my team and infrastructure during my second year but now the team is in place I plan to divert my personal attention back to this work, which I believe I am uniquely placed to address. I have data from interviews with over 60 researchers about access to enzymes and  data from work on the potential for open diagnostics for HIV viral load based on field work in South Africa which will be expanded next year. The Global Bioeconomy Summit in Nov 2020 offers a perfect opportunity to launch the culmination of my Fellowship policy work.

What challenges or uncertainties do you expect to face?

Developing an open reagent supply chain remains an ambitious challenge to implement sustainably. Dealing with implementation has absorbed more of my second year than anticipated but I am now more certain that I have the right team and partners in place to focus and deliver the evidence and impact we are seeking in year three. I still face uncertainty about the model for scaling but some clarity is emerging which will be honed by an advisory board meeting in Feb 2020. I made productive use of the Foundation and Fellows collective wisdom in year two to think carefully about organisational structures, governance and to what extent I want myself to have a fundamental versus supporting role in establishing these; my view is that a central organisation is needed to hold the branding, quality assurance, legal and regulatory functions all of which present challenges to implement internationally. Some challenges have emerged in my second year that involved more uncertainty than I expected, for example regulation around biotechnology. In Cameroon a law on genetic engineering was passed in 2018 but the Science Ministry does not have clear guidelines to implement the regulations so we are in uncharted territory. I co-authored a book on biosafety in community labs and other resource-constrained spaces during 2019 so combined with establishing Biomakespace (Cambridge’s community biology lab) and membership of my department's biosafety committee I feel as prepared as I can be. However, this is still a challenge as it could severely curtail our activities if approvals are not granted.

Working within an institution like the University of Cambridge has continued to be a challenge in terms of agility but the establishment of Beneficial Bio Ltd this year provides more flexibility in terms of hiring freelancers and dealing with operations and logistics. One of my biggest challenges remains gaining traction with policy makers, particularly as less attention was paid to this than anticipated during 2019. The narrative I’m building is completely opposed to the current focus in biotechnology on strong patent protection and private profit maximisation and the questions I get usually concern risk and business models. My proposed third year activities outlined above will provide the analysis and messaging I need to answer those queries and provide a compelling case for open approaches to be considered a legitimate and feasible approach to technology and knowledge transfer.

What part does openness play in your idea?

The part that openness plays has not altered significantly during the two years of my Fellowship. It remains fundamental to my personal philosophy and the idea behind the open bioeconomy. My vision is a response to the current intractability of open research, development and manufacturing models in biology and increasing proprietary ownership and control of biotechnologies. I view openness as a strategy to increase equitable access to biological research and its benefits and particularly when that access is to the foundational tools and technologies that often result from publicly funded research. While a biological tool like an enzyme being open is insufficient to make it accessible, used and useful; therefore we are building open infrastructure and tools around it to overcome that (e.g. bioreactor, protocols, manufacturing information) as well as taking an open approach to knowledge through our open enzyme educational materials and training courses.

I set out during my first two years skeptical of the power and utility of openness in all contexts and having had the opportunity, time and freedom to think deeply about its role I have not changed that view. Openness is a powerful tool to disrupt incumbent systems and accelerate knowledge production and dissemination but the important questions are still ‘open for whom?’ and ‘for whose benefit?’. In my second year the importance of the type of benefit has become more apparent, for example building capacity and jobs is imperative to our partners and openness is embraced if it helps meet those goals.