National Anti-Vivisection Society – Written evidence (LSI0044)

(1) Summary

• Animal models are poor scientific models and are costly in terms of expense and time, while non-animal technologies (NATs) can be faster, more reliable and cheaper.
• Non-animal methods have been identified as disruptive technologies with beneficial commercial impact. The scientific community needs to be incentivised to reduce barriers in adopting NATs.
• International regulatory agencies, governments and funding bodies are encouraging a shift away from animal testing. The UK is at risk of falling behind in the development and uptake of animal-free methods.
• Investment is essential in order to keep pace with international developments and facilitate the adoption of methods to benefit academia, industry and public health.
• Despite the significant potential of NATs to reduce development time and costs, and increase throughput compared with animal models, the 2011 strategy for UK life sciences placed minimal emphasis on progress within animal-free science and the 2017 life sciences industrial strategy does not specifically target the field of animal research.
• In order for the UK to become a world leader in the development and adoption of NATs, the appropriate infrastructure must be put in place to support, educate and train, create new jobs, and foster collaboration between academia and industry.
• When the UK leaves the EU there is a risk it will fall further behind Europe in the advancement and promotion of advanced and cutting edge disruptive technologies. Through investing in NATs, identified as an area which can drive economic growth, Brexit provides a unique opportunity to take the lead in the life sciences, enhancing the quality of science and industry in the UK.

Science and innovation

How can investors be encouraged to invest in turning basic life science research into new innovations in treatments?

(2) Investors must be made aware of the issues surrounding the use of animal models in advancing human health and drug development. The scientific limitations of animal research are becoming increasingly acknowledged; animal models, known to be costly in terms of time and expense, have low predictive value for humans[1],[2]. Translation of animal models to human research can hinder progress in drug development[3], with resource-intense animal models failing to predict severe side effects in humans, resulting in drug disasters[4], adverse drug reactions (ADRs) and withdrawn medicines[5]. Animal research has poor scientific validity, putting patient safety at risk; 95% of drugs that have proved promising in animal trials fail in human trials[6] resulting in huge economic and scientific costs. For drugs which make it to market, the European Commission (2008) estimates that ADRs are one of the leading causes of death, killing 197,000 people in the EU each year and costing €79bn[7]. In the UK it is estimated that hospital admissions related to ADRs cost the NHS in excess of £637 million annually[8]. In the US and Canada, over a 20 year period up to 2011, 52% of drugs were either withdrawn due to safety reasons or had serious safety warnings[9]. Globally, standard animal test results are to establish substance safety and guide first in human and further clinical trials[10]. Ultimately animal models are a poor model in terms of science and, consequently, economics; the quality of scientific output suffers and resources are wasted when animals are used as models for humans.

(3) Conversely, non-animal technologies (NATs) can be faster, more reliable and cheaper[11], as well as having advantages for human health, business and the economy; they have even been identified as disruptive technologies which have the potential to drive economic growth[12]. They attract business investment, fuelling the shift away from a reliance on animal research in the scientific sector. Institutionalised animal use,  the “gold standard” against which all new technologies are compared, threatens to impede NATs from being validated and adopted[13], another reason to incentivise a shift away from animal test reliance. It is worth noting that in vitro methods developed the principles of validation[14], a process which animal research models have not undergone.

Why has the UK underperformed in turning basic research in the life sciences into intellectual property? What needs to be done to address this historic weakness in the UK and grow new companies to commercialise new research and related technologies in the life sciences? 

(4) The recent Green Paper “Building our Industrial Strategy”, published by the Department of Business, Energy and Industrial Strategy”, [15]  identifies that “Innovation is not just about a few people in labs making breakthroughs, but about adopting new and more productive ways of working”. Adapting to change, therefore, such as that brought about by disruptive technologies like NATs, is a key component to driving innovation. Potential for commercial uptake should be a key motivation for research and development into NATs.  Innovate UK has identified NATs as an emerging sector with “great commercial impact”[16]; unfortunately the UK has historically been weak at commercialising innovation generally, as identified in the recent Green Paper[17].

(5) Changing perceptions and building confidence in animal-free methods in some sectors of the scientific community is needed. Innovate UK recognise that overcoming scepticism in the scientific community, about the ability of NATs to model biological processes, will help to close  a major barrier to the uptake of technologically advanced animal-free methods. Inertia by those who continue to use animal 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 NATs”[18]. Similarly, it is possible that entrenchment may extend to regulators and funders, therefore it is essential that the appropriate incentives are put into place to encourage engagement with NATs.

(6) Investors can provide incentive by specifically funding basic research with a realistic potential to become the new innovations which replace unreliable, slow and costly animal tests. Much work has been done in animal-free toxicology since the National Research Council in the US published “Toxicity Testing in the 21st Century: A Vision and Strategy” in 2007 but more progress needs to be made, particularly to bridge the gap between regulatory acceptance and innovative animal-free research. It is essential that non-scientific considerations (including political, institutional, social, trade, policy and legal) do not impede regulatory progress and the development of a scientific framework for implementing advanced human-relevant (non-animal) methods[19].

How does the UK compare to other countries in this sector?

(7) Innovate UK published “A Non-Animal Technologies Roadmap for the UK”, supported by British scientific industry organisations including NC3Rs, BBSRC, DSTL, EPSRC and the MRC. This economic based report “identified non-animal technologies as one of a series of emerging technologies with the potential to drive future UK economic growth”. 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 NATs and position the UK as the “global powerhouse in this area”[20].

(8) In order to remain in competition with the global race to create the most innovative and efficient technologies for investigating disease and developing drugs, it is essential that the UK invests in NATs as a substantial part of its strategy for the development of the life sciences industry.  “It has been estimated that the global market just for cell based assays in drug discovery, safety, and toxicology will reach $21.6 billion by 2018. The estimated global market for induced pluripotent stem cells is expected to reach $2.9 billion in 2018, and the 3D cell culture market is expected to grow to about $2.2 billion in 2019”[21].

(9) On an international level, regulatory agencies, governments and funding bodies are encouraging a shift away from animal testing, including:

• In 2016 the Netherlands National Committee for the protection of animals used for scientific purposes (NCad) proposed a timetable to phase out animal procedures and encourage innovation without animal methods, with the view to the Netherlands becoming a world leader in laboratory animal-free innovations by 2025[22].
• Horizon 2020 in the EU funds “EU-ToxRisk” which focuses on human cell responses in toxicity testing in order to drive a paradigm shift away from animal tests[23].
• Directive 2010/63/EU Recital (10)which states that the final goal is “full replacement of procedures on live animals for scientific and educational purposes as soon as it is scientifically possible to do so” (Recital 10)[24];
• In order to modernise their regulations, China’s Food and Drug Administration (CFDA) has signed a “Memorandum of Understanding” to bring non-animal test methods to China for the regulation of cosmetics and their ingredients[25].
• In the US NICEATM (National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods) has moved away from investing in refinements to working “almost entirely on replacing animal tests with other methods”[26];
• The US National Research Council “Toxicity Testing in the 21st Century: A Vision and a Strategy” which focuses on new tests based on human cells and cell components[27].
• The “Frank R. Lautenberg Chemical Safety for the 21st Century Act” in the US, which amended the country’s primary chemicals testing law, promotes the use of non-animal alternative testing methodologies[28];
• The ICCVAM (Interagency Coordinating Committee on the Validation of Alternative Methods) proposes that “In order to realize the full potential for improving and protecting human health offered by advances in science and technology, the U.S. must develop a strategy for the safe, effective, and timely implementation of human-based predictive approaches for toxicity testing”[29];
• With a significant move in recognition of the need to develop drug evaluation, over $200 million was offered over six months in three funding opportunities in the US, with the goal of advancing the Human on a Chip concept. A group of US agencies (National Institutes of Health, Food and Drug Administration, and the Department of Defense) collaborated to produce three-dimensional human organ equivalents based on stem cell and chip technology[30].
• Dr Francis Collins, Director of the USA National Institutes for Health, recently stated that within 10 years, animal safety tests will be largely replaced by human tissue chips and iPS cells “giving results that are more accurate, at lower cost and with higher throughput”[31].

(10) The UK has also fallen behind in the adoption of simulation technology in medical and military training. Medical schools in the USA and Canada no longer use live animals for medical training purposes[32]; India has exclusively adopted animal-free methods for undergraduate and postgraduate education for ethical reasons and because simulation technology is available[33],[34] ; 19 countries in the EU use simulation technology over animal methods for military training, including the NATO Centre of Excellence for Military Medicine based in Hungary which does not use any animal models, alive or dead for medical military training[35].

(11) Important developments in animal free research are being made around the world:

• France, US - Bioprinting of 3D models of human organs and tissues, created by printing replica living human tissue, to test whether potential drugs are toxic[36],[37],[38].
• Singapore - Human iPSC technology, where cells are capable of turning into any type of human cell, so that different chemicals can be added to observe their toxicity[39].
• US, The Netherlands, Luxembourg - Organoid technology which can create mini-organs from patient stem cells specific to the disease they are suffering[40],[41].
• US, Germany - fMRI and other neuroimaging techniques have improved dramatically more recently, with improved power and resolution; ultra-high field MRI is currently five times more powerful than mainstream systems[42],[43].

(12) It is clear that there is much international competition in driving forward animal-free methods in the life sciences. The lack of recognition of non-animal research in the 2011 strategy for UK life sciences  adds to the risk of the UK falling behind on global developments in this field and missing opportunities for growth of an innovative industry. For the benefit of UK science, business and the economy it is essential that the UK invests in animal-free science in order to keep pace with international developments and adoption of methods that can benefit academia, industry and public health.

Industrial strategy

What can be learnt from the impact of the 2011 UK life sciences strategy?

(13) In the 2011 strategy for UK life sciences there was minimal emphasis on progress within animal research in general, and specifically the field of animal-free science (p. 27). Generally it was stated that the reduction and improvement of animal research was an aim[44]. The reduction and refinement of animal research continues to invest in and rely on models that are not validated or reliable for humans, and these efforts do not aid the development of innovation or technological advancement. Investment into NATs by contrast can cut development time and costs, increase throughput and provide mechanistic insights that are not possible with animal models[45].

(14) Worldwide, in the past six years NATs have progressed exponentially, with advancements being made in the fields of in vitro and in silico science, as well as using weight of evidence and read-across methods to promote animal-free research. Outside of the UK, there has been huge international progress made toward animal-free science. For example, the US has made significant advancements within the field of NATs, with the Wyss Institute now a global leader in Organ-on-a-Chip technology which is fast becoming a disruptive technology within cell culture science across the world[46]. The US is also leading the way in animal-free medical training[47] and trauma training[48] with the adoption of simulation technologies.

(15) It is vital that the UK builds support for growth within NATs into a strong industrial strategy, so that it does not fall behind internationally in this sector.

Does the strategy contain the right recommendations? What should it contain/what is missing?

(16) The 2017 life sciences industrial strategy does not specifically target the field of animal research[49], hugely disappointing for the future of advancements in replacement technologies. The vision for the UK to be the “home of clinical research and medical innovation” requires a solid foundation of preclinical research comprising validated models that are human-relevant and incorporating the latest innovations in NATs.

(17) The 2017 strategy wants to “support a 50% increase in the number of clinical trials over the next 5 years...with novel methodology”. In order to achieve this, there needs to be greater focus on NATs at the preclinical stage of development – the scientific concerns surrounding the validity of animal models in preclinical research is not acknowledged within the 2017 strategy. Ultimately investment in NATs has the potential to bring effective treatments to the market more quickly and at a lower cost than current animal research is doing[50] resulting in “more rapid discovery and development of medicines, agrichemicals, chemicals and consumer products”[51].

Responsibility and accountability

Who should take responsibility for the implementation of the Life Sciences Industrial Strategy and to whom should they be accountable?

(18) A central public body is needed that is dedicated to funding, research and development, and fostering collaboration between research and different sectors. The body should be solely focused on encouraging more efficient and human-focused animal-free science. Continuing to invest in reduction and refinement of animal research does very little to drive innovation, as is evident from progress made in NATs outside of the UK since the 2011 industrial strategy.

What should the role of the academic, charitable and business sectors be?

(19) In terms of developing animal-free methods of research, the key roles of academia should be to conduct basic research into innovative replacement technologies and support the lifelong education and training of existing and new scientists in this area, including established scientists who want to train in other areas of research, helping promote more multidisciplinary innovation.

(20) It is important that the charity sector is given the opportunity to be involved. NGOs may have access to a wide network of people who can help foster collaboration or access to, and uptake of, existing technologies. Such organisations may be able to carry out thorough searches in technological advances, to be used as a resource for finding relevant scientists, working in specific fields of research, who use non-animal methods. Charitable funding can also be used to attract scientists and business from outside the UK[52].

(21) The pharmaceutical industry will be responsible for taking up new technologies in order to bring innovative and human-focused treatments to market.

What is the role of companies within the sector, particularly the large pharmaceutical companies, in the implementation of the strategy? How are they accountable for its success?

(22) Companies in the sector can play a number of roles in implementing a strategy to increase the uptake of NATs.

(23) Building networks of collaborators across different disciplines and sectors. Encouraging cooperation between industry (“big pharma” and SMEs) and academia is essential to allow for greater investment, development opportunities and commercialisation of research[53]. These can all play a major role in creating new jobs.

(24) Early regulatory engagement is important for the fast uptake and regulatory acceptance of NATs, as this is currently a considerable challenge for those developing animal-free methods. Pharmaceutical companies can work with regulators to ensure that animal-free methods are driving the industry. The UK is home to two of the largest pharmaceutical companies in the world (AstraZeneca and GlaxoSmithKline) as well as hundreds more companies working in the pharmaceutical sector – these available resources can be effectively utilised. 

(25) Promote the UK NATs industry globally and draw together relevant industries and expertise to revolutionise toxicity and efficacy testing in the UK[54].

Does the Government have the right structures in place to support the life science sector? Is the Office of the Life Sciences effective?

(26) In order for the UK to become a world leader in the development and adoption of NATs, the appropriate infrastructure should be put in place to support, educate and train, create new jobs, and foster collaboration between academia and industry. The Innovate UK report[55]  outlines a number of strategies to achieve this:

• Supporting skills which allow the development of NATs, such as the ability to integrate different disciplines as well as skills training regulators who need to move away from traditional animal pathologies.
• Investment in technology development and breaking down barriers among scientists about moving away from animal use. Basic research should be a key focus for funding, particularly within academia; there is opportunity for the UK to become a major leader in animal-free methods.
• Investment in commercially successful and marketable products give the greatest opportunity for economic impacts, if particular attention is paid to the deficiencies in the current safety testing process. These include routine use of human tissue, complex 3D cell culture models, data sharing and preclinical models more relevant to human biology. The recent Green Paper[56] has identified that the UK is not performing as well  as other countries in terms of commercialising innovation.

(27) Investment in NATs needs to draw on the pillars identified by the Green Paper[57] in order to have wide-ranging effects across the economy, including:

• Investment in science, research and innovation: investment needs to occur at academic and industry level to drive commercialisation of NATs. Research and development funding needs to extend beyond the “golden triangle” of Oxford, Cambridge and London. 
• Developing skills: established and emerging scientists, as well as regulators and funders, will require skills support in NATs.
• Supporting businesses to start and grow: businesses must be encouraged and supported to be able to grow within the sector of NATs.
• Improving procurement: with international growth in NATs, the UK needs to have the capacity to support a growing industry from within the UK.
• Encouraging trade and inward investment: bringing “new ways of doing things to the UK” (ie NATs) will increase competition, productivity and growth across our economy
• Cultivating world leading sectors: for the UK to become a strong competitor or even a world leader in NATs we need to help new sectors to flourish, which can involve “challenging existing institutions and incumbents”.
• Driving growth across the whole country: the framework needs to encourage collaboration in order to draw strengths from different sectors (eg animal researchers and those working in animal-free science) and provide infrastructure that will have wide-reaching benefits (particularly in terms of marketable treatments for patients). 
• Creating the right institutions to bring together sectors and places: the Government needs to provide support to strengthen existing work into NATs, and also create new institutions to provide support for the funding, innovation, development and uptake of NATs. 

Should the Government appoint a dedicated Life Sciences Minister?

(28) A dedicated Minister should be appointed for the Life Sciences in order to create the infrastructure needed for the UK to become a global leader in the development and commercialisation of NATs. As a vast and constantly changing area, it will be vital that the Minister keeps pace with technologies being developed in NATs internationally. The UK needs a team exclusively working on the development of NATs, dedicated funds available to NATs in academia and industry, training and re-training of scientists in new and collaborative projects, and support to bring NATs to market.

Brexit

What impact will Brexit have on the Life Sciences sector? Will the strategy help the sector to mitigate the risks and take advantage of the opportunities of Brexit?

(29) “The UK’s decision to withdraw from the EU entails uncertainty and potential risks for many areas of UK research and innovation concerning future access to EU programmes and funding”[58]. When the UK leaves the EU there is a risk it will fall behind Europe in the advancement and promotion of advanced and cutting edge disruptive technologies which have the potential to replace animals.  The UK industry receives a substantial amount of EU funding for research and innovation and were the largest recipient, receiving 85% of the fund[59],  of Horizon 2020 – the biggest EU funding programme of research and innovation - with some of this funding open to research in NATs. Prioritisation of research and development into innovative animal-free science will be necessary for the UK to continue competing with the progress seen in the EU and rest of the world.

(30) As the recent Green Paper[60] notes about innovation into potential disruptive technologies, “ultimately we must 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”.

(31) Grant money is not the only motivator for participating in EU initiatives. A recent report commissioned by the UK National Academies and generated from targeted interviews stated that “For industry stakeholders...access to networks and strategic initiatives were among recurring concerns and several also emphasised the role of EU funding in supporting broader ‘ecosystems’ within which they operate”[61].

(32) It is especially important that funding for the life sciences go towards validating animal-free methods, considering that the UK may no longer be able to access the European Union Reference Laboratory for Alternatives to Animal Testing, who are responsible for validating NATs, after the UK leaves the EU,. It will be essential to have a UK validation body dedicated to animal replacement in order for academia and industry to continue to collaborate with the EU.

(33) With the support of the Government, Brexit provides a unique opportunity for the UK to take the lead in the life sciences, enhancing the quality of science and industry in the UK. Importantly, investment and development of NATs have been identified as having the potential to drive economic growth in the UK[62]. Increased funding in NATs would positively impact business and scientific progress, reducing development time and costs and thus increasing efficiency and human-focussed treatments. There is an opportunity to move towards greater reliability in predicting human safety and help prevent wasted costs in drug attrition.  With its world-leading universities and home to some of the largest pharmaceutical companies in the world[63], the UK is in a strong position to build a strong economy that can compete with global innovation. Increased investment and research in animal–free science is an essential part of achieving this.

15 September 2017