Written Evidence Submitted by Lord Dowding Fund for Humane Research

(RFA0016)

About LDF

The Lord Dowding Fund for Humane Research (LDF) supports and funds advanced methods of scientific and medical research and training, which replace the use of animals or lead to the adoption of non-animal research methodologies. The LDF present evidence to demonstrate why the new UK research funding agency must prioritise the funding of New Approach Methodologies (NAMs), which will have benefits for science, public health and the economy. 

Summary points

• The primary gap in the current UK research and development system, is the strategic funding and building of a supportive infrastructure, to support the development and uptake of new approach methodologies (NAMs) in biomedical research and testing. Agencies across the world are prioritizing the growth of NAMs, which have the potential to revolutionise disease research and drug development, bringing safer and more effective treatments to the market, more quickly and at a lower cost, compared to traditional animal methods. To remain a world leader in research and innovation, it is essential that the UK keeps pace with the international developments in this field.
• The new funding agency should act as an example for existing funding bodies, prioritising NAMs that could reap the greatest public health and economic benefits for the UK. Actions should be coordinated in order to avoid duplication.
• Protecting and enhancing current, and future, public health must be a key research funding priority, particularly with the current health crisis. The focus should be on NAMs, where these can lead to significant economic gains, and attract international investment into UK science.
• It is important for research and development funding to extend beyond the “golden triangle” of London, Oxford and Cambridge. To drive forward innovation, it is important to provide opportunities to other institutions, which are progressive and enterprising in their research ambitions, and unlock the potential of new and emerging scientists. Multidisciplinary collaboration is vital and should be incentivised. Collaboration between academia and industry would enable partnerships to capitalise on the commercialisation potential of NAMs.

What gaps in the current UK research and development system might be addressed by an ARPA style approach?

1. It is highly encouraging to note UK efforts, in the creation of the new UK research funding agency, to take an approach similar to that of the Advanced Research Projects Agency (ARPA, now the Defence Advanced Research Projects Agency, DARPA), one which seeks transformational, rather than incremental, changes and taking advantage of technology opportunities, to increase research output.[1],[2] The primary gap in the current UK research and development system, which could be addressed by an ARPA style approach, is the strategic funding of, and building of a supportive infrastructure, to support the development and uptake of advanced and innovative technologies in biomedical research and pharmaceutical and chemicals testing. Such methods are promised to deliver “improved decision-making tools that result in more rapid discovery and development of medicines, agrichemicals, chemicals and consumer products”.[3]

2. For the UK to remain a world leader in research and innovation, it is vital that these efforts are strategic and aligned with international research priorities. Protecting and enhancing current, and future, public health must be a key research funding priority, particularly with the current health crisis. As well as emerging diseases, such as COVID-19, many major existing diseases remain poorly understood and lack adequate treatments.[4] The lack of available treatments places substantial economic burden on healthcare systems, which face increasing pressure from a growing population that is living longer. Of the treatments that are available, effectiveness is suboptimal, with many causing adverse outcomes or even serious illness, further burdening our healthcare system.[5], [6], [7] For example, hospital admissions caused by adverse drug reactions account for 4% of bed capacity,[8] and in England alone, cost the NHS up to £1.6 billion per year.[9] This is despite huge investment in traditional research methods within the biomedical sciences.[10]

3. To address this ongoing global healthcare crisis, agencies across the world are prioritizing the growth of new approach methodologies (NAMs) in biomedical research and testing. NAMs are defined as “new scientific approaches that focus on human biological processes to investigate disease and potential treatments, using human cells, tissues, organs and existing data”.[11] NAMs have been identified as disruptive technologies,[12] which have the potential to revolutionise disease research and drug development, bringing safer and more effective treatments to the market, more quickly and at a lower cost, compared to traditional animal methods.[13], [14], [15], [16] LDF calls for the new UK research funding agency to prioritise the funding of NAMs.

4. In the past several years, NAMs have progressed exponentially across the world, with significant advancements being made in the fields of in vitro and in silico science. For example, the Wyss Institute in the US is now a global leader in Organ-on-a-Chip, which is fast becoming a disruptive technology within cell culture science across the world.[17] Given that data obtained  by Organ-on-a-Chip are more accurate, can be achieved at a lower cost and with higher throughput than compared to traditional animal based methods, in 2016, the Director of the US National Institutes of Health predicted that within 10 years this method will mostly replace traditional methods of testing drug toxicity.[18] The predicted business opportunities for NAMs are substantial: Organ-on-a-Chip technologies could save up to a quarter (~$700 million) of total drug development costs,[19] and they are expected to be worth between $60-117 million by 2022;[20] cell-based assays are expected to reach $18.9 billion by 2024;[21] stem cell technologies to reach $28 billion by 2029;[22] and in vitro toxicity testing expected to reach $14.4 billion by 2025.[23]

5. In order to advance predictive biology in the UK, a 2015 collaborative report was published by Innovate UK, NC3Rs, BBSRC, DSTL, EPSRC and the MRC. This economics-based report identified NAMs as disruptive technologies with “the potential to drive future UK economic growth” and attract investment into UK industries. The report outlines how UK strengths in the pharmaceutical sector, consumer goods and personal care companies, contract research organisations and academic researchers have the ability to deploy NAMs and position the UK as the “global powerhouse in this area”.[24] Following this, in 2018 and 2019 the Medicines BioIndustry Discovery Catapult and BioIndustry Association (funded by Innovate UK) published the reports “State of the Discovery Nation”, with recommendations to develop technologies to humanise drug discovery through NAMs in order to improve research productivity for industry.[25] Unfortunately, no specific actions have been taken by the Government on these reports towards advancing NAMs and human-focused biomedical research methods.[26]

6. On an international level, for over a decade, regulatory agencies, governments and funding bodies have been encouraging a shift towards NAMs, with many producing roadmaps, consisting of targets, deadlines and actions to progress their development and uptake. Some of these include:

• United States National Research Council (2007): Toxicity Testing in the 21st Century: A Vision and a Strategy.[27]
• Transatlantic Think Tank for Toxicology (2012): Roadmap for the Development of Alternative (Non-Animal) Methods for Systemic Toxicity Testing.[28]
• Netherlands National Committee for the protection of animals used for scientific purposes (2016): Transition to Non-Animal Research.[29]
• United States Environmental Protection Agency (2016; 2019): Strategic Plan.[30]
• United States Food and Drug Administration (2017): Predictive Toxicology Roadmap.[31]
• The Interagency Coordinating Committee on the Validation of Alternative Methods (2018): Strategic Roadmap for Establishing New Approaches to Evaluate the Safety of Chemicals and Medical Products in the US.[32]

7. With the international competition in driving forward NAMs in the biomedical sciences, the UK is at risk of falling behind on global developments in this field and missing opportunities for growth of an innovative industry that can also benefit public health and the economy. After the UK’s decision to leave the EU, the Department of Business, Energy and Industrial Strategy published a Green Paper, “Building our Industrial Strategy” [33]. With uncertainties around access to EU funds and data/knowledge sharing, the Green Paper reports that it is vital that we “embrace innovation to keep ahead of the competition, create more good jobs, and make sure jobs in the UK are secure”, particularly at a time when “the pace of scientific discovery and innovation is quickening across the world”. The UK needs to keep “at the cutting edge of new technologies and developing solutions to global challenges”.[34]

8. Protection of public health should be the fundamental motivator for the new research funding agency. To be a strong competitor in the global race to create the most innovative and efficient technologies for investigating disease and developing drugs, it is essential that the UK prioritises its investment in NAMs as disruptive technologies, through dedicated funding. With Governmental support, we now have the unique opportunity for the UK to take the lead in biomedical sciences, enhancing the quality of science and industry in the UK. With its world-leading universities and home to some of the largest pharmaceutical companies in the world, the UK is in a strong position to build an economy that can compete with global innovation, reaping rewards for public health. Increased investment in, and prioritising of, NAMs through the new UK research funding agency is an essential part of achieving such “high reward science”, positively impacting public health and the economy.

What are the implications of the new funding agency for existing funding bodies and their approach?

The new UK research funding agency can stimulate interest, investment and funding across the board, which will benefit other funding bodies. It should lead by example, prioritising NAMs that could reap the greatest public health and economic benefits for the UK. The actions of this new agency should help to inform the priorities of existing UK funding bodies by highlighting where the greatest research output can be achieved. Prioritisation of NAMs funded by the new UK research funding agency should also be coordinated with existing agencies in order to avoid duplication.

What should be the focus be of the new research funding agency and how should it be structured?

9. The focus of the new research funding agency should be on the protection of public health, with a specific focus on NAMs, where these can lead to significant economic gains, and attract international investment into UK science.

10. For the UK to compete internationally in creating the most innovative and efficient technologies for investigating disease and developing drugs it is vital that this is built on a strong foundation of preclinical research comprising validated in vitro and in silico models that incorporate human tissue and data. Greater focus on NAMs at the preclinical stage of development has the potential to bring effective treatments to the market more quickly and at a lower cost than current methods[35] resulting in “more rapid discovery and development of medicines, agrichemicals, chemicals and consumer products”.[36]

11. Particular focus should be on NAMs in biomedical research where existing models contribute little to understanding of disease or effective and efficient drug development. Diseases such as stroke, cancer, heart disease, Alzheimer’s disease and other dementias all remain poorly understood and lack adequate treatment, despite substantial research investment over many decades.[37], [38], [39], [40], [41], [42] For example, Alzheimer’s disease models have been criticised because of the lack of translation into human health benefits: “This is almost certainly due to the imperfect replication of human [Alzheimer’s disease] in any other animal species, as well as species-specific functions of structurally identical genes and responses to targeted therapies. To date, no single animal model has exhibited both neuropathological and behavioural symptoms characterizing human [Alzheimer’s disease]”.[43]

12. In terms of the structure of the new research funding agency, the UK is particularly lacking in investment to build the appropriate infrastructures for the UK to become a world leader in the development and adoption of NAMs and mobilise their full benefits. The 2015 report from Innovate UK, and supporting organisations, outlines the appropriate infrastructure that should be put in place to support, educate and train, create new jobs, and foster collaboration between academia and industry.[44] Further considerations should include:

• Investment in technology. Basic research should be a key focus for funding, particularly within academia [Ref Innovate]. Infrastructure including scientific equipment, resources such as archives or scientific data (including ‘big data’), e-infrastructures, and particularly multidisciplinary communication networks, should be targeted to incentivize researchers to develop innovative and commercially viable NAMs. Capital funding is also needed to invest in research centres dedicated to developing NAMs which could yield significant public health and economic benefits.
• Investment in commercially successful and marketable products. Support for NAMs with the potential for commercial uptake should be a key consideration in providing infrastructure, which also increases the potential to attract business investment and international collaboration.[45] NAMs have been identified as an emerging sector with “great commercial impact” for the UK[46] but unfortunately the UK has historically been weak at commercialising innovation generally.[47] A strong infrastructure and target funding opportunities would further the development, validation and commercialisation opportunities of NAMs. Particular attention should be paid to the deficiencies in the current safety testing process, prioritising disruptive technologies that include routine use of human tissue, complex 3D cell culture models, data sharing and preclinical models relevant to human biology.
• Supporting skills. Dedicated funding is essential for training new and established scientists, encouraging collaboration, and integrating different disciplines to work together to advance the development of NAMs. Young researchers need to be incentivized to adopt careers in the UK biosciences and biotechnology industry through offering world class facilities and access to resources to carry out innovative research. Investment in skills needs to occur for the public, private, third and research sectors to drive the innovation and commercialisation of NAMs. The funders themselves may also require further training in order to identify the most aspiring and promising NAMs that have high commercial potential. Early engagement with regulators and end users is also important to ensure efficient adaption to these new and emerging technologies.[48]
• Breaking down barriers. To ensure a strategic approach to providing supportive infrastructures for bioscience research and innovation, it important to recognise barriers that can exist in adopting new technologies. Changing perceptions and building confidence in NAMs in some sectors of the scientific community is needed. If the infrastructure was in place for new and established researchers to have greater engagement with NAMs, this could help to break down some of these barriers, particularly for those who have limited opportunities to access these advanced technologies. Overcoming scepticism in the scientific community about the ability of NAMs to model biological processes will help to close a major barrier to their uptake. Inertia by those who continue to use traditional models could be overcome by encouraging scientists “to think beyond their immediate research areas to how their skills, technology and “know-how” can be leveraged and exploited to accelerate the development and adoption of [NAMs]”.[49]

13. Following the report from Innovate UK and others, LDF co-authored a white paper as part of the Alliance for Human Relevant Science, alongside NAM experts and businesses which further outlined actions required by the UK to capitalise on the health and economic benefits of NAMs, including:

• supportive infrastructure to enable strategic coordination of the development and uptake of NAMs, and to provide access to resources and communication networks
• strategic funding to incentivise full engagement with NAMs, particularly those with market potential that might attract business investment
• improved education on the benefits of NAMs, alongside skills training for new and established scientists
• multidisciplinary collaboration and forging of new partnerships between basic and applied researchers, industry and end-users
• engagement with regulators to promote the adoption of data generated from NAMs into regulatory guidelines. [50]

14. Investment in infrastructure that supports the development and uptake of NAMs should be the focus of the new research funding agency, facilitating the UK becoming a world leader in high impact, innovative biomedical research.

What benefits might be gained from basing UK ARPA outside of the ‘Golden Triangle’ (London, Oxford and Cambridge)?

15. It is important for research and development funding to extend beyond the “golden triangle” of London, Oxford and Cambridge, where research is already established as centres of excellence, and for which large funds are readily available. To drive forward innovation, particularly in the area of NAMs, it is important to provide opportunities to other institutions, which are progressive and enterprising in their research ambitions, and unlock the potential of new and emerging scientists.

16. Multidisciplinary collaboration is vital and should be incentivised. Researchers using traditional biomedical research methods should be encouraged to forge collaborations with researchers across other disciplines to establish new and innovative ways of asking research questions and the methods used for answering them. As well as collaboration across disciplines, collaboration also needs to be encouraged across industries. There is currently a gap between academia and industry, which limits opportunities for commercialising NAMs or the strategic development of NAMs that have the best commercial potential. Collaboration between academia and industry would enable partnerships to ensure that basic research is being driven by industry need and demand. Funding infrastructure which supports such networks would facilitate knowledge transfer and sharing or resources across disciplines and industries.

17. The UK’s new research funding agency should not be limited to academia. The key roles of academia should be to conduct basic research into innovative technologies that can advance public health and benefit the economy, and to support the lifelong education and training of existing and new scientists in this area, including established scientists who want to retrain in other areas of research. Networks of collaborative research activities also need to be built across different disciplines and sectors. Encouraging cooperation between industry (e.g., “big pharma” and small-to-medium enterprises) and academia is essential to allow for greater investment, development opportunities and commercialisation of research. These can all play a major role in bringing together the best minds to drive forward innovation of NAMs in the UK.

18. NAMs have been identified as an emerging sector with “great commercial impact”,[51] unfortunately the UK has historically been weak at commercialising innovation generally.[52] But “Innovation is not just about a few people in labs making breakthroughs, but about adopting new and more productive ways of working”.[53] Adapting to change, such as that brought about by disruptive technologies like NAMs, is a key component to driving innovation. Potential for commercial uptake should be a key motivation for funding research and development into NAMs. 

19. It is essential that collaborations and partnerships are encouraged for the UK to keep pace with international research priorities and to be a strong global partner and competitor. For the benefit of UK science and business, the UK’s new research funding agency should invest in NAMs in order to keep pace with international developments and adoption of methods that can benefit all areas of research and development from academia to industry, as well as bringing about significant economic and public health benefits.