Impact case study database

Antibody-based drugs are a major growth area for pharmaceutical companies. The freely accessible abYsis software, developed at UCL, is a web-based analytical tool that has helped accelerate drug development. [ S1]. Over 40 biotech companies have used the software in their drug design work and since 2013, more than 200 patents applications have cited abYsis. In addition, patent lawyers, courts and the WHO are using the evidence and analysis provided by the software and presented by Professor Martin, to resolve patent disputes and standardise naming of antibody-based drugs.

Use of abYsis by biotech companies to accelerate drug development and patent lawyers to resolve patent disputes

AbYsis allows users to compare their antibody sequence data with sequences stored in databases such as Genbank or trEMBL, together with structural data from the Protein Data Bank. Comparing sequences allows researchers to identify unique or unusual features of their antibody sequences. The abYsis web site ( www.abysis.org) also allows users to determine how human-like the antibodies appear.

Since 2013 approximately 40 new companies have used the freely available software [ S2] and patent lawyers are also making significant use of the web site, including Fenwick, Morrison & Foerster, and Sheridan Ross.

Although abYsis is freely accessible online, commercial users can purchase a licence that allows them to store and analyse proprietary sequence and 3D structure data locally. Since 2013, seven major pharma (Lundbeck, Johnson and Johnson, Pfizer, Bayer, Teva, Boehringer Ingelheim and UCB) have bought commercial licences for the software together with more than 20 smaller biotechnology companies including AbCellera, Alexion Celldex, CytomX, Dragonfly, Eisai/KAN, Gilead, IBio Solutions, Imclone, Incyte Lake Pharma Harpoon, Ohana, Molecular Templates, Shionogi, StemCentrx, Surrozen-Arcus Biosciences, SutroBio, Tizona, Twist Bioscience, Versau. Revenue generated in 2019/20 financial year was over GBP 325,000, with a gross total since 2013 of GBP 534,000. It is the largest grossing software sold by UCL Business [ S3].

The software has helped accelerate drug design by enabling companies to identify unusual features in their sequences and to improve strategies for humanisation [ S4-S7].For example, [TEXT REMOVED FOR PUBLICATION] state [ S4] that their “entire antibody engineering team uses this software for multiple applications”, that it has “facilitated many programs and is […] an in-expendable tool” reducing the time for these efforts “by at least 25%”. They have “successfully enhanced or humanized antibody leads that have or are currently entering the clinic”. Twist Bioscience state [ S5] that they “have used abYsis in the design of antibody libraries for in-house use [for development of drug leads] and for sale to customers”. They estimate the use of the software to result in a “50% saving in time”. They state that they have “employed >10 highly skilled staff to develop antibodies and libraries that all rely on using abYsis.” SutroBio have said that it is “a central tool […] for internal synthetic library designs” used by their “entire Protein Engineering team”. They estimate that they can do their analyses “3-4x faster than using alternative solutions” [ S6]. UCB have said that abYsis “continues to be an integral component […] to support the antibody design and development activities”. As a result it has “supported, in part, hundreds of Antibody design campaigns.” [ S7]

AbYsis software cited in patents underpinning drug development

The research underpinning the abYsis software has been cited in over 300 patent documents since 2013 [ S8] and ‘abYsis’ itself has been cited by more than 200 organisations making patent applications. Companies include Novartis, Immunogen, Kite Pharma Inc, Gilead Sciences Inc, Janssen Biotech Inc, Leucid Bio Ltd, MAB Immune diagnostics, Millenium Pharm Inc, Bristol Myers Squibb, Pfizer and Biogen as well commercial applications by KCL, Harvard College and Massachusetts Institute of Technology [ S8].

Providing expertise to the World Health Organization International Nonproprietary Names committee

In 2016, Professor Martin was invited to be an expert advisor to the WHO International Nonproprietery Names (INN) Committee, providing expertise on nonproprietary names for biologic drugs and antibodies in particular. As stated by the WHO, his “long career in research on antibodies and [his] expertise in the field enabled [him] to research and develop an annotation scheme that is computer-readable”. In 2018 Martin “performed some research on computational linguistics and developed a program that allows a rapid comparison of potential new antibody names against a database of existing names” and that “[t]his has been invaluable during INN Consultations to allow rapid comparisons as new names are discussed” [ S9] (manuscript in preparation).

Acting as an expert witness in court cases relating to patent disputes

The UCL team’s research and resources, including the abYsis tool have been used to provide expert testimony in patent disputes relating to equivalence and obviousness. Professor Martin has acted as an expert witness to provide evidence in written reports in at least 6 court cases. For example, between August 2013 and November 2014, Martin provided written evidence and attended the European Patent Commission for [TEXT REMOVED FOR PUBLICATION] in a dispute with [TEXT REMOVED FOR PUBLICATION] in an opposition to patent EP1725261 (Avidity IP) [ S10]. Between September 2017 and August 2018 Martin wrote a report for Genentech to demonstrate infringement of their patent in Brazil by Pró Genericós. This patent relates to Genentech’s blockbuster drug Avastin and resulted in the Brazilian court issuing an injunction against Pró Genericós to stop them producing these drugs. (Williams & Connolly) [ S11].

In a related dispute with Amgen in the US, Williams & Connolly stated that Martin “prepared reports related to infringement and patent validity” and “[h]ad it gone to trial, Dr. Martin would have been the primary witness to explain antibody humanization technology to an American jury” [ S11]. In a related dispute in Ireland, William Fry state that Martin’s “expertise in this highly complex area and [his] ability to clearly explain the technical issues involved meant that our team was confident [his] affidavit would assist the Court in understanding the background to and the subject matter of the proceedings”. [ S12]

In another case (May 2018–Jan 2019) Martin acted as an expert witness in the High Court for Genentech in their dispute with Lilly who were trying to have Genentech’s patent EP1641822B1 declared invalid. Marks & Clark [ S13] state that “based on Professor Martin’s evidence, Genentech was successful in overcoming a number of Lilly’s pleaded attacks on the validity of the patent and also in establishing that Lilly’s product fell within the scope of its claims” The judge wholly accepted Prof Martin’s evidence on this issue, the analysis for which was performed using the UCL team’s open source software. The statement also says: “some measure of the importance of [Martin’s] evidence may be gleaned from the deductions from Lilly’s recoverable costs that were ordered by the judge”. The costs payable by Genetech to Lilly were reduced by 11.5% as a result and amounted to GBP690,000.

In 2018, abYsis was selected as an Impact case by the BBSRC [ S14].

Impacts on international policy-making

Establishing international biodiversity baselines and metrics: The indicators that we developed at UCL and IOZ have been instrumental in establishing baseline measures that underpin key international treaties and targets on biodiversity, which must be met if we are to mitigate the ongoing catastrophic decline in the planet’s biodiversity. The indices have been used to track progress towards these critical targets, making signatory countries and other political and economic actors accountable for progress towards these goals and indicating priority areas for action.

Our research has underpinned the frameworks for measuring biodiversity of several international treaty organisations and conservation observatories. The LPI and SRLI have both been used to track progress towards meeting the UN Convention on Biological Diversity (CBD) targets in 2014 and 2020. They are quoted by the UN Global Biodiversity Outlook report as authoritative measures of the speed of biodiversity decline, for example in the report’s section on progress towards the goals of the Strategic Plan and the Aichi Biodiversity Targets (goal C, improving biodiversity status): “Two indicators of the state of biodiversity within this goal, the Living Planet Index and the Red List Index, show current declines and an extrapolation of continuing decline to 2020 based on current drivers.” [S1] . The two indices have also been highlighted as indicators for the post-2020 global target framework [S1]. The Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) has also used the LPI, RLI and BII to quantify trends in biodiversity in its Global Assessment report on Biodiversity and Ecosystem Services [S2]. The SRLI has, for the first time, enabled the IPBES to quantify the threat to particular species and families and to communicate these figures in ways that make clear to laypeople the urgency and scale of threat to particular types of plants and animals. For example, the SRLI revealed that 18.99% of Reptiles are threatened with extinction and 40.55% of conifer trees and their relatives are threatened [S2, page 53]. Evidence from these indices have underpinned the IPBES’ grave warning that “around a million animal and plant species are currently threatened” [S2, page 6].

Additionally the International Union for the Conservation of Nature (IUCN), the global authority on the status of the natural world and the measures needed to safeguard it, states that the IoZ/UCL work on the Red List and biodiversity indices “has had, and continues to have, significant impact on [their] understanding of extinction risk and global biodiversity” [S3].

Monitoring and conservation impact: As well as influencing global biodiversity monitoring and targets, IoZ/UCL research has led to new species-level IUCN monitoring and conservation efforts. As the global authority on the status of the natural world and conservation with over 1,400 member organisations and signatory governments, the IUCN maintains the Red List, the world’s most comprehensive index on the extinction risk of animal, fungus and plant species. Revisions and refinements to the Sampled Red List by the our researchers has been used to determine the extinction risk of groups such as reptiles, which were not previously represented. This led to the assessment of 1,500 species and their subsequent listing on the IUCN Red List. New IUCN guidelines drawing on this research have also been established for assessing species vulnerability to climate change (section 12.1 of the IUCN Guidelines for Using the Red List Categories and Criteria) and this led to the creation of the IUCN climate change impacts modelling group, chaired by UCL researcher Pearson. For example the IUCN listed Coffee arabica, which is a highly valuable crop, as endangered in 2018 following review of climate change impact models by the group [S3].

All three metrics (LPI, BII, RLI) underpinned the WWF’s flagship biennial report, the ‘Living Planet Report’ in 2016 and 2018 [S4]. This report has a global reach: it is published in 110 countries and in more than 20 languages, and it is estimated that the press coverage reach was over 100 million people [S4]. In the UK, biodiversity loss figures from our indicators found in this report were cited as the impetus for an Early Day Motion on Global Biodiversity in the House of Commons on 31 October 2016: “The catalyst for this debate was the Living Planet Report, prepared by the World Wildlife Fund and the Zoological Society of London, that shows that the global wildlife population fell by more than half between 1970 and 2012.” [S5] As a result of this debate, 41 MPs signed a motion urging the UK government to tackle the effects of climate change, habitat loss and degradation, species over-exploitation, pollution and animal diseases [S5].

The indicators developed at both UCL and IoZ (BII and LPI indices) informed the UN Environment Programme’s assessment of the state of the environment, ‘Global Environment Outlook 6’ (2019) which explained the indices’ ability to create a more nuanced and accurate picture of biodiversity and species loss than previous measures:

“...these indicators provide finer spatial and temporal resolution. Trends in global vertebrate species population abundances as measured by the Living Planet Index show an average decline of 60 per cent between 1970 and 2014 … Globally, average local abundance of terrestrial species is estimated to have fallen to 85 per cent of modelled abundances in the absence of anthropogenic land-use change (Newbold et al. 2016)” [S6, page 156].

Research on these indices has thus led to a step-change in international environmental policy, whereby measures of biodiversity loss can be presented with confidence, informed and binding targets can be set and progress towards recovery can be accurately assessed.

Influencing regional and national policy-making

As a result of the widespread adoption of the tools developed at IoZ/UCL by major international and intergovernmental organisations, our researchers have undertaken commissioned assessments of biodiversity for a range of thematic groups across the world, including in:

The Arctic: The Arctic Species Trend Index [S7] was commissioned by the Arctic Council and the Conservation of Arctic Flora and Fauna (CAFF), based upon the methodology and dataset developed for the LPI. CAFF have described this as “a new method and the first species indicator to understand and monitor the biodiversity of the Arctic” [S12].

European wetlands: The LPI methodology and open-source tools were also used to produce the Wetland Extent Index [S8].

Rewilding Europe: Further adaptation of these tools underpinned a Rewilding Europe project on extinction risk and abundance, and was presented in the ‘Wildlife Comeback in Europe’ report in 2013 [S9]. This report celebrated successful conservation efforts in 18 mammal and 19 bird species across the continent of Europe, and our indicators were used to assess the impact of these interventions and the lessons that could be learned from them for future projects and policy makers.

Canada: IoZ researchers also developed a series of regional assessments of biodiversity, again building upon the methodology and data developed for the global LPI. The Sustainability Directorate, Environment and Climate Change Canada and IoZ researchers collaborated to adapt the LPI methodology to establish the Canadian Species Index. This filled a gap in intelligence on vertebrate population changes across Canada and enabling the measurement of progress towards the Canadian Environmental Sustainability Indicators and the 2020 Biodiversity Goals and Targets for Canada [S10], now used by the Canadian Government to monitor national biodiversity trends [S10].

Australia: In Australia, IoZ researchers collaborated with the nation’s Threatened Species Recovery Hub and the University of Queensland to help develop the Australian Threatened Species Index (TSX) to track wildlife abundance of threatened species there.

UK: The Biodiversity Intactness Index of the UK, developed by UCL researchers, was featured in the UK’s ‘State of Nature Report’ (2016), an annual snapshot of the state of the UK’s biodiversity assembled from data from over 50 organisations [S11].

The CATH classification, made available on a UCL-hosted website maintained by the Orengo group, is an internationally renowned resource and one of the world’s leading protein structure classifications in this field [S1]. There are more than 22,500 unique web visits to CATH per month and 2,000,000 pages are accessed per month [S1]. Two-thirds of these web visits are from industry-based sites [S1]. CATH has been made an ELIXIR Europe-wide Core Data Resource (CDR) [S2], one of only three European national resources to be endorsed as meeting the highest standards in data quality and data access established by the ELIXIR (European Strategy Forum on Research and Innovation), - excellent science, community served, high quality of service and impact - and, notably, the only CDR to be endorsed in the UK . [TEXT REMOVED FOR PUBLICATION].

CATH data is further disseminated through the InterPro web server, at the European Bioinformatics Institute (EBI). Outside academia, InterPro is one of the most widely used web portals by biologists in industry, with over 723,000 unique visitors per year. It combines protein family data from multiple resources to assign greater confidence. CATH data is also disseminated via the web portal of the international protein structure resource, the Protein Databank (PDB), with over 4,411,871 unique users/year, and UniProt, a major source of protein functional data with over 10,800,000 unique users/year (2,220,00 of which are from industry). Further links to CATH are provided by many international web-based computational biology resources, for example Pfam, BRENDA [S1]).

CATH was one of four major resources used to establish the UCL spinout company Inpharmatica. It was also used by Inpharmatica to provide data and services for predicting protein structures and functions for large pharmaceutical companies including Pfizer, AstraZeneca, Merck and Glaxo-Wellcome [S3]. [TEXT REMOVED FOR PUBLICATION] Inpharmatica has since been acquired by biotechnology company Galapagos. Since 2013, Galapagos has attracted over GBP11,000,000 in investment [S4].

The structure comparison algorithms underpinning CATH (CATHEDRAL) have been distributed directly to pharmaceutical companies, including UCB Celltech and Cubist Pharmaceuticals, generating GBP34,931 in licence income to UCL within the census period [S5]. Papers published by Orengo have been cited across eight patent documents, demonstrating the commercial relevance of the work.

Users in industry exploit the CATH prediction methods, domain assignments and methods (e.g. CATHEDRAL) for analysing their structures. For example, R&D staff in DSM Chemical Technology R&D BV used CATHEDRAL to search CATH for structural homologues of a protein they were solving; a biocatalyst valuable for the pharmaceutical industry because of its ability to synthesis various beta-hydroxy amino acids - compounds widely used in food processing and drug development [S6].

Specific applications to problems in the pharmaceutical industry

Identifying disease drug targets: CATH is routinely used by the pharmaceutical industry to identify the structures of proteins implicated in disease. Predicted functional site data is used to assess the effects of disease-associated residue mutations and to identify putative ligand (i.e. drug) binding sites and variation in drug-binding modes across families. CATH has been used, for example, by:

• Gene Tools LL and BrainMicro LLC, to identify domain boundaries in enzymes being structurally characterised as potential therapeutic targets for toxoplasmosis and other parasitic infections [S7];

• Phylogica Ltd to search fold space in the characterisation of a peptide library used for target discovery, and for identifying new cell-penetrating peptides [S8];

• Acpharis, to identify the domains of kinases - a major drug target family for pharmaceutical companies [S9]; and

• AstraZeneca, for structural analyses that identified pharmacophore binding motifs for NAD (Nicotinamide adenine dinucleotide– an critical component in metabolism) and its analogues across different protein families [S10].

Biologic drug design: CATH data is also being used for biologics in large pharma companies. [TEXT REMOVED FOR PUBLICATION].

Pathogen protein structure-based drug design: CATH FunFam technology was exploited by NIH-funded, international, structural genomics initiatives (between 2013 and 2017) to select proteins from pathogenic organisms for structure determination to aid drug design. More than 2,400 protein structures were deposited into the Protein Databank from all sources, worldwide, during this period. These structures have shed light on how structure is linked to function and provided important details of binding sites in proteins implicated in cancer and pathogen associated diseases.

Covid-19: More recently, CATH FunFam analyses of binding sites involved in SARS-CoV-2 infection of animal hosts was used by the WHO and a UN Food and Agriculture Organisation policy unit [S11] in strategy discussions on animals at risk from infection, or which are likely to become reservoirs for the virus. These sites constitute major mechanisms of infection which are targetable by drugs. The work was also reported in several newspapers globally.

Orengo has given talks on CATH in Europe, the United States, Singapore, China, Malaysia, Africa and India, including the EBI Industry program and to computational biologists at several pharmaceutical companies.

Training and capacity-building in amphibian disease detection and treatment:

Since 2013, IoZ researchers and technical staff have trained over 40 amphibian disease researchers from across Europe, Africa, Latin America, the Caribbean, North America and Asia in methods for detecting infections and for isolating fungal and ranaviral isolates [E1]. They have also trained researchers in experimental procedures used for examining disease dynamics in amphibians [E2]. Trainees have applied what they learned to develop their careers at the PhD, post-doctoral and faculty levels. Former trainee Dr Xavier Harrison says “ the research arising from my fellowship at the IoZ was critical in allowing me to secure a permanent academic position at the University of Exeter”. Another, Dr. David Daversa says “ training was critical to my success as a PhD student and Postdoc” and Dr Vojtech Baláž says thanks to the gained skills and knowledge, I have got involved in multiple pathogen related research projects”. Several have established their own national pathogen surveillance programmes, including Professor Jacob Hoglund, who says: “ Without this assistance the first country-wide survey of [Batrachochytrium dendrobatidis] in Sweden….could not have been undertaken”. Trainees have established their own experimental facilities, diagnostic and detection facilities and NGOs, and in several cases acquired funding for their own research programmes in collaboration with IoZ scientists and as independent researchers [E2]. Dr Claudio Soto says he has been “ *awarded seven amphibian conservation project grants for work in Chile…..for USD540,000, including two consecutive Chilean Science and Technology Fund (the most prestigious scientific funding in Chile)*”.

In April 2019 IoZ scientists held a workshop on rapid decision making when disease outbreaks are identified. Contributors from across North America and Europe participated in the simulated emergency meeting and provided inputs that were i) used to manage the site the workshop was based on; ii) used in the management advice for the province in the Netherlands responsible for the management, as well as in the national action plan for B. salamandrivorans, written for the Dutch Ministry of Agriculture, Nature and Food Quality; and; iii) co-developed and shared with the United States Department of Interior inter-agency advisory task force on B. salamandrivorans “for uptake in subsequent management recommendations” [E3].

Meeting UK responsibilities for amphibian disease surveillance and reporting:

Chytridiomycete fungi and ranaviruses are the only OIE-listed pathogens that affect amphibians, and as an OIE member the UK is mandated to report cases of infection with either pathogen. The IoZ has been a partner of the government’s GB Wildlife Disease Surveillance Partnership (GBWDSP) since its inception in 2011 and is contracted to carry out national disease surveillance of amphibians. IoZ scientists accomplish this through the IoZ’s Garden Wildlife Health project, in which members of the public, ecological consultants and herpetologists are encouraged to submit observations of amphibian morbidity or mortality online. Where possible, the IoZ researchers obtain specimens for post-mortem examination to establish cause of death. Samples are collected as a routine to screen for chytridiomycete fungi and ranaviruses and results are included in the UK’s annual submission to the OIE. Novel findings on amphibian disease are communicated to the government’s Veterinary Risk Group and reported in quarterly open access GBWDSP reports [E4].

Raising awareness of best practice to safeguard wild amphibian health:

Incorporating the IoZ-founded Frog Mortality Project, the Garden Wildlife Health (GWH) project was launched in 2013: since this time citizen scientists have submitted approximately 2,000 amphibian disease incidents, and IoZ veterinarians have carried out approximately 600 amphibian post-mortem examinations. Running for 30 years, this is the longest-running citizen science amphibian health project globally. IoZ has converted surveillance findings and peer-reviewed studies to a library of 10 amphibian disease factsheets targeted at the public and fieldworkers, available via the GWH website. These provide science-based guidance for habitat management for amphibian disease prevention and control. This includes 2017’s Amphibian and Reptile Groups of the UK (ARG UK; 72 regional groups across the UK) and IoZ’s ‘Amphibian disease precautions: a guide for UK fieldworkers who are working with amphibians’ [E4]. In addition, in collaboration with a network of ten zoological organisations, NGOs, industry and government, IoZ researchers created the Amphibian Disease Alert to highlight the risk of B. salamandrivorans incursion to the wild in GB, and the biosecurity measures that can be taken by herpetologists with captive collections to mitigate this threat [E4]. Over the last 12 months, the GWH website received >58,000 user sessions by >48,000 users, who viewed>93,000 pages.

Controlling flow of amphibian infections through amphibian trade:

Cunningham’s membership on the OIE’s Ad Hoc Group for Amphibian Diseases was a direct outcome of the science he produced investigating the infectious disease causes of amphibian declines [E5]. This work led to amphibian chytridiomycosis and ranavirosis and their causative agents being included in the Aquatic Animal Health Code and directly contributed to the addition of B. salamandrivorans to the code in 2018 [E5]. Collaborative work by IoZ researchers involved screening more than 5,000 amphibians across four continents and combined experimental assessment of pathogenicity with phylogenetic methods to estimate the threat that the infection poses to amphibian diversity. This work also provided the scientific evidence that B. salamandrivorans is a recently emerged amphibian pathogen that arrived in Europe via the transport of Asian amphibians in the pet trade [R3], [E5]. This evidence was used to enact international restrictions on the importation of caudate amphibians into the U.S.A. (U.S. Fish and Wildlife Service listing 201 salamander species as potentially injurious wildlife species through carrying B. salamandrivorans) and Canada (adding all salamanders to Schedule II of the Wild Animal and Plant Trade Regulation) and into and between EU member states (European Commission implementation OJ L 062 5.3.2018, page 18) [E5], [E6].

Impacts on the environment and Conservation Action Plans:

IoZ scientists have identified several possible strategies for preventing disease in wild amphibians against both species of fungus that cause chytridiomycosis. Applications of some of these have achieved both short- and long-term reductions and even eliminations of infections, which has directly benefited on-the-ground conservation efforts in the Caribbean and Europe [R9]. More than 2,000 Mallorcan midwife tadpoles were collected from the two drainage basins affected by chytridiomycosis and treated for infections, and the same was done for 220 frogs on Montserrat. Treatment on Mallorca likely saved one region from species extirpation, and lessons learned on Mallorca are being applied more broadly in the Iberian peninsula [E7]. On Montserrat, treatment of dozens of adult frogs provided short-term benefits and further research is now guiding the design of habitat refuges to prevent severe manifestations of disease [E7]. IoZ researchers helped establish captive management and disease diagnostic facilities on Dominica that continue to inform amphibian conservation activities on the island and helped establish a new NGO responding to the additional impacts of habitat loss attributable to Hurricane Maria [E8]. In addition, research, position statements on mitigating disease and field trials have all contributed to national and global action plans for the conservation of species at risk of extinction through to setting priorities for the global conservation of amphibians. As examples, IoZ research has helped develop the conservation actions plans for the Mountain Chicken Frog on Dominica and for Darwin’s frogs (two species) in Chile, and setting priorities of the Infectious Diseases Thematic Working Group of the IUCN’s Amphibian Conservation Action Plan [E9].

Between 2012 and 2018 Mace, as an influential member of the UK Government’s Natural Capital Committee, has worked closely with colleagues on the committee to provide independent advice to the government on the sustainable use of natural capital. Most of the work described in this case study was done in collaboration with Professor Ian Bateman, an environmental economist at the University of Exeter and member of the Natural Capital Committee, as well as the economists Julian Harlow (Department for Environment, Food and Rural Affairs - Defra) and Russell Elliot (Natural Resources Wales). Mace led the ecological aspects of the work.

Developing and applying a comprehensive approach to the valuation of UK ecosystem services

Market-based decisions inevitably favour monetizable and tradeable services such as food and fuel, but the social value of non-market services such as carbon storage, recreation or urban green space is hundreds of times greater than than the value of marketed food and other produce. The first part of the work, as presented in [R1], was influential in stimulating activities such as:

1. the funding of a ‘Valuing Nature Network’ (VNN, a five-year, GBP6.5m programme with over 2,000 members) by NERC to grow research capability. As part of the Natural Capital Coalition (NCC) management team, Mace utilised [R1] as a framework to ensure a direct flow of evidence from the VNN to government, resulting in policy changes (e.g. the UK Peatland Code) via the project’s policy briefings and engagement network. [E1]

2. the Defra ‘Ecosystem Markets Task Force,’ which reported to Defra, DECC (Department of Energy and Climate Change) and BEIS (Department for Business, Energy and Industrial Strategy) and advised on opportunities for UK business from expanding green goods, services, products, investment vehicles and markets which value and protect ecosystem services. Working with Mace, Bateman briefed the Ecosystem Markets Task force in its early days on the UK National Ecosystem Assessment and its implications for business opportunities [E2].

3. the cross-sector NCC that was founded in the UK and is now developing globally. The NCC has become the global leader in mainstreaming natural capital approaches in the private sector, with over 370 leading orgnizations engaged. [R1] was cited directly in both the NCC’s biodiversity protocol and the UK Ecosystem Assessment [E3].

Development of natural capital approaches and their implementation in policy.

Natural capital is recognised by economists as one of the four major types of capital that underpin human welfare (along with human capital, financial capital and produced capital). Ecosystem services are the flows of benefits to society that are delivered by well-maintained natural capital assets. In [R2], Mace and her colleagues proposed a framework for the classification of natural assets and investigated the ecosystem service benefits that were degrading or at risk in the UK (the natural capital ‘risk register’), and [R3] was influential in translating ecological concepts for application by economists. This work led to specific recommendations to the government by the Natural Capital Committee, concerning the ecosystem service benefits at highest risk (e.g., clean water, wildlife conservation, climate regulation) and the ecosystem restoration projects that could secure them for the future (e.g. restoring and conserving woodlands, maintaining wetlands and coastal marshes, restoring peatland) [E4].

Advising on the UK Government’s 25 year Environment Plan and the 2020 Environment Act

In 2017, a new Defra Secretary of State (Michael Gove) revitalised the research to meet the 2012 policy commitment ‘to be the first generation to leave the natural environment in a better state than it inherited’. The Natural Capital Committee recommended that this generation-scale commitment needed a long-term plan. The work described in [R1], [R2] and [R3] directly informed work in Defra to develop a 25 Year Environment Plan for England. This plan, launched by the Prime Minister in January 2018, highlighted six target outcomes for society which directly trace back to the risk register work [R2], as well as work contributed by Mace and colleagues to the Natural Capital Committee’s third report [E5]. Julian Barlow, deputy head of land-use policy at DEFRA, has commented that “At the heart of this 25 YEP [Year Environment Plan] is the natural capital conceptual framework and metrics developed by Professor Mace.” [E6]

A significant consequence of the UK’s decision to leave the EU was the need to establish a system to replace the Common Agricultural Policy (CAP), to support food production but also to secure the wider benefits from the natural environment. Two new Government bills were developed in Defra: the Agriculture Bill and the Environment Bill.

The Agriculture Act (2020) adopts a novel objective that public money should support public goods, emphasising that land owners need to be incentivised to secure the non-market goods of high public value that were highlighted in [R1], rather than private goods of limited public value.

The Environment Bill deals more centrally with environmental outcomes identified in the 25 Year Environment Plan. Legislation is pending (the bill has reached the Report Stage and was debated by MPs on 26 January 2021), but its framing and draft indicator set published by Defra in May 2019 is founded on the NCC framework (described in section 2) and the targets and indicators identified in [R2]. Defra’s Julian Barlow has written that “ The Government is currently in the process of legislating for future Environmental Improvement Plans and a suit of environmental targets, all of which flow directly from the NCC’s [Natural Capital Committee’s] work – specifically the contributions of Prof Mace which wholly underpins the approach.” [E6]

IoZ works to promote best practice conservation translocations, with impact falling into three main areas: the recovery of endangered focal species (animal species that provide an essential ecological function); capacity building through IUCN training; and influencing the adoption of IUCN guidelines into policy.

Focal species recovery

IoZ research has led to population recovery of multiple endangered species globally:

Hihi (stitchbird): IOZ played a critical role in the recovery of NZ’s endemic hihi alongside collaborators at Massey University. Hihi had become restricted to a single small offshore island for more than a century before early success in reintroduction to Kapiti Island in 1991 [R2]. Based on the findings that population vital rates can be improved via supplementary feeding [R2] all reintroduction sites are fed but closely monitored to refine feeding management decisions [S1]. IoZ research set methods for assessing monitoring data for making decisions on releasing birds [R3)]. These approaches were used to establish three new populations between August 2013 and December 2020, growing the number of populations to seven and spreading hihi into two new mainland regions within their historic range after an absence of more than a century. IoZ research has been used to define national management protocols requested by the NZ government [S1]. Ewen et al.’s methods of modelling projections of both source and destination populations [R3] have been used to give permission for or against translocation [S2], as evidenced by communication from NZ Department of Conservation’s Director General: “ *We are so impressed with the work you do and the increasing recovery of these remarkable birds.*” [S3]. Alienor Chauvenet, the IoZ PhD student who carried out the research [R2] was awarded a RSPB Conservation Science Award 2014 for outstanding PhD thesis in conservation science, with the RSPB judges commenting: “Alienor’s thesis was chosen because it has already had a tangible impact on the conservation of a threatened species, and will contribute to the conservation of many others in future.” [S3].

Mauritius parakeet: Once the world’s rarest parrot, with 8 to 12 individuals in 1987, the Mauritius parakeet now numbers about 400-450 mature individuals. The work of IoZ researchers, alongside collaborators at the University of Kent, showing that chemical treatment of nest boxes reduced breeding success [R4], resulted in the Mauritius Wildlife Foundation (MWF, an in-country NGO) discontinuing chemical treatment of nest boxes in 2017, a process that had been in place for over a decade. This improved parakeet breeding success by 5% [R4], as well as removing a resource intensive component of population management [S4]. Similarly, IoZ work done with MWF predicting cheaper management with equal population growth in the critically endangered Mauritius olive white-eye (the rarest bird species in Mauritius; 191 to 327 mature individuals) [R5] resulted in the MWF reducing management effort involving supplementary feeding in 2015. MWF’s Conservation Director stated that “ this research gave us the evidence needed to change from twice daily feeding with expensive imported nutritional supplements to single daily feeds with a much cheaper and locally produced food, cutting our costs by more than half” [S4]. In both cases there has been a substantial ease in the workload and no compromise on the recovery of either species.

Regent honeyeater: In Australia, IoZ and Monash University research on the critically endangered Regent honeyeater (350 to 400 mature individuals remaining) quantified the predicted outcome of alternative nest protection actions [R6]. This research was used by the species recovery team to select and apply new nest protection measures using tree collars in 2019. Birdlife Australia’s National Regent Honeyeater Recovery Coordinator stated: “ Gemma and the IoZ team helped us work through a complicated choice to find the best balance for action and risk for us”) [S5].

Capacity building through IUCN training

Capacity building can allow faster uptake of best practice. In 2016, the Chair of the IUCN Conservation Translocation Specialist Group (CTSG) engaged IoZ to lead on developing an IUCN CTSG practitioner training course [S6], which features worked examples including [R1], [R2], [R3], [R4], [R6]. This four-day course has been running annually since 2016 and has trained 110 practitioners from 27 countries to date (including 26 practitioners from developing countries). Feedback from the course has been excellent, for example, one participant from Natural England said: “I really enjoyed the course and sat through most of it thinking my job would be so much easier if people applied the methods discussed at least to some extent.” Another from The Nature Conservancy stated: “I am so grateful to have had the opportunity to participate in that training. It was one of the best investments of time in that kind of thing I’ve made in memory. It was really, really good.” [S6].

Ongoing contact with course alumni has also demonstrated the enduring impact of the training. For example, in release planning of the extinct-in-the-wild Guam kingfisher (sihek). The Coordinator of Bird Programmes at Guam’s Department of Agriculture notes that “ *It is amazing to say that sihek releases will take place within the next one to two years. Had I not attended the training in 2016, there is no doubt this project would still be stuck.*” (Course alumni Hawaii 2016; [S7]). Also, for the recovery planning of NZ’s rarest breeding bird, the tara-iti, a technical advisor from NZ’s Department of Conservation states: “ We are now able to move forward with a robust recovery strategy for tara iti, due to Dr Ewen’s work, the approach promoted by the IUCN training course and work showcased from the group at the Institute of Zoology” (course alumni Chicago 2018; [S8]). Both projects follow methodologies taught in the course materials including direct comparison of alternatives as stated in [R1] and decision support methods as detailed in [R3] and [R6].

Influencing the adoption of IUCN guidelines into policy

Success stories from IoZ research in [R2], [R3], [R4] and [R5] attracted wider sector interest from NGOs and policymakers via their exposure in IUCN training. This led Ewen to be invited to the British and Irish Association of Zoos and Aquariums (BIAZA) Reintroduction Advisory Group, where he drafted the BIAZA Policy on Conservation Translocations. This policy was signed off by the BIAZA council in March 2019, providing best practice of translocation to all BIAZA zoos and aquariums in Britain and Ireland [S9]. In addition, Ewen was invited as a sounding board member for Natural England’s ‘Code and Good Practice Guidance for Reintroductions and Conservation Translocations’ , where the Principal Specialist for Species Protection at Natural England noted: “ his key recommendation has been to encourage conservation translocation decisions based on an iterative approach judging alternatives against clearly defined objectives” as outlined in [R1] [S10] .

Research from UCL/Birkbeck has transformed the way museums, archives and cultural heritage sites conserve their collections by raising awareness of the dangers of volatile organic pollutants and providing simple and economic ways to protect collections. They have also promoted and demonstrated the effectiveness of sustainable materials for conservation treatments. Through wide-ranging collaborations, workshops and international presentations, the methods and tools devised at UCL/Birkbeck are now embedded in best practice guidelines and applied to collections around the world, from national museums to small private collections. Since 2013, more than 120 conservators at cultural heritage sites and in museums in at least 14 countries have used these new conservation methods, better protecting thousands of priceless objects.

Implementation of L-PQC to detect volatile organic pollutants in museums across Europe

Traditionally, the presence of VOCs, such as acetic and formic acids have been detected in museums using lead coupons (shiny lead strips of known mass) or expensive passive diffusive samplers. The L-PQC dosimeters developed at UCL/Birkbeck provide conservators with an effective and inexpensive alternative. The metal-coated piezoelectric quartz crystals (PQC) detect and evaluate levels of corrosivity more quickly, more accurately and also remotely. Thousands of artifacts are now being protected following evaluations using L-PQC in the UK and Europe ( S1). The head conservator at Spain’s SIT Madrid said: ‘ Since August 2013 until 2020, … L-PQC (lead coated piezoelectric quartz) …were used to test air quality in showcases and microclimate frames in public museums and private art collections in Spain.… As part of our projects for 2020, we are offering the air quality measure service to private art collectors in EU’ ( S2).

Remote monitoring using PQC arrays with additional metal coatings (Fe,Cu,Ni and Sn) for detection of corrosivity from inorganic pollutant gases O₃, NO₂ and SO₂, have been used within the Royal Palaces of Abomey in Benin (UNESCO World Heritage site) and Apsley House (English Heritage) and differences due to geographical location recorded ( S1).

Best practice guidance and decision support model for preservation of organic-based heritage objects worldwide

The UCL/Birkbeck team’s research and unique database including a combination of model samples subjected to accelerated ageing and a range of historical samples, has directly informed a decision support model published by English heritage ( S3, S4).

Objects and samples from collections from around the world are tested periodically. The decision support model acts as an early warning system (based on traffic lights code) where red alerts conservators to the need for intervention.

It provides guidelines for optimal display and storage conditions to preserve organic-based heritage objects. The guidelines are used by more than 120 heritage institutions worldwide to ensure best practice in conservation and preservation. The Senior Conservation Scientist at English Heritage said: “ *Dr Odlyha’s work has been of immense benefit to managing the national collection of over 1 million objects in English Heritage’s care. …The research was critical to the MEMORI decision support model.*“

The decision support model has been shared with over 300 professional and student participants in 14 international workshops and is currently used in major international museums in more than 15 major cities from Paris to Uzbekistan ( S1). English Heritage is using the model to check all its 1000 showcases and painting frames. As part of the programme it has to-date, refurbished over 90 showcases and 32 painting frames across 19 sites, better preserving more than 3000 precious objects as a direct result of its findings ( S1).

Advancing detection of damage to collagen-based materials using Atomic Force Microscopy in the UK

Atomic Force Microscopy (AFM) for application to collagen-based materials can detect damage at the collagen fibril level and also reveals presence of localised gelatinised areas. These areas are prone to cracking and can lead to loss of script. Since 2013, a database of AFM images has been established which has facilitated damage assessment on fibres from documents and from leather book-bindings e.g. Charles Darwin notebooks in English Heritage collections, Down House ( S1). The protocol was used in the MEMORI project to evaluate effect of exposure of parchment and leather to volatile organic acids and the resulting damage categories included in the decision support model which is currently widely used by English Heritage. The possibility of in situ imaging with portable AFM has allowed conservators to assess damage non-invasively on the object, including an historical 18^th century parchment manuscript at The National Archives (London, UK), a historic violin, and surfaces of paintings at the Tate during treatment ( S5).

Application of novel nano materials for sustainable conservation of cellulose based artifacts worldwide

In paintings conservation, Dr Odlyha introduced the damage assessment protocol involving mechanical analysis to evaluate effects of alkaline-based nanoparticles applied to cellulose containing materials (paper and painting canvases) to negate acidic conditions which develop as these materials age and eventually lose their strength. These results and evaluations of these products has assisted the Centre for Colloid and Surface Science, Florence (CSGI) in marketing these preparations. The products have now been sold in 18 countries across Asia, Europe and North and South America in sufficient quantities to protect more than 100,000 cellulose containing objects including painting canvases ( S6). In addition, nanocellulose-based products which were introduced to consolidate the canvases in the NANORESTART project were tested using this protocol and further developments were made ( S7). Odlyha has collaborated with Lacerta Technology (UK) to test and develop the approach using programmed RH cycles with mechanical testing together with dielectric analysis ( S8). The positive evaluation of these conservation treatments has led to their use by practising paintings conservators across Europe, including via an ERASMUS programme collaboration between UCL/Birkbeck and the School of Conservation in Copenhagen ; in art conservation studios in Paris (Aurelia Chevalier, working with the Louvre); Centre for Colloid and Surface Science (CSGI), Florence; ZFB, Leipzig, Germany; and the Department of Arts and Conservation, University of Barcelona where paintings conservators are trained ( S9, R8).

Head conservator at the School of Conservation, Denmark said: “Dr.Odlyha has been a prominent researcher with her work forming part of the group of researchers that laid the basis for an entirely new way of understanding the behaviour and deterioration of canvas paintings in art museums….“ Participants at the sector’s leading conference held at Yale University in 2019 to review conservation research hailed Odlyha’s research as “ one of the most prominent and wide-ranging new treatment options announced at the conference”. ( S10) .

Improving conservation of earthen architecture in Brazil

The methods developed at UCL /Birkbeck have also been used to test the effect of using termite mounds in restoration of earthen architecture. Previously, synthetic materials had been used for restoration, but these have different moisture absorption properties to the original materials, affecting stability. The results of tests carried out by UCL/Birkbeck on two large manor houses in Brazil, built using earthen architecture, have led to changes in their practice ( S11).

‘Museums on Prescription’ (MoP)

MoP, led by Chatterjee, was not only the first study to assess the role of social prescribing in museums, but also directly benefitted the wellbeing of those adults who participated. Health, social care and third sector partners including Age UK, Camden Carers and Kent County Council identified local socially isolated, vulnerable and lonely older adults and referred them to participate in the programme at seven partner museums across London and Kent (The British Museum; The British Postal Museum and Archive; Canterbury Museums and Galleries: The Beaney; Central Saint Martins Museum and Study Collection; Maidstone Museum & Bentlif Art Gallery; Tunbridge Wells Museums & Art Gallery; and UCL Museums). Older adult participants in the project reported an increased sense of belonging, improved quality of life, renewed interest in learning, increased social activity and continued visits to museum, and there was a statistically significant improvement across all measures of wellbeing and loneliness reduction. Testimonials from participants attest to the programme’s positive impact, with one noting: “It made me feel less lonely. And coming out into places where there are quite a few other people, makes a place like a museum feel more familiar.” Another confirmed how the activity eased their loneliness: “This sort of thing, it helps lonely people, helps with confidence as well and I think that’s the other thing with being lonely or on your own…you haven’t got the confidence to go in on your own.” One participant said that the activity had changed their perspective: “ I’ve learnt so much from it. It’s expanded my thinking, it’s keeping my brain going because it’s given me a different way of looking at things.” [S1].

Not only did the programme benefit older adult participants, but also the project partners. For example, the Head of the Evidence Unit in the Personalised Care Group, NHS England and NHS Improvement said: “Helen [Chatterjee]'s work (such as Museums on Prescription and the Community COVID research) is helping to raise awareness of the benefits of arts-based activities for health and wellbeing, as well as getting a better understanding of what works” [S2]. Through offering novel community-based programmes for their service users, and helping to reach previously untapped audiences, the project has also benefitted referrers. The Assistant Curator, Community Programs at the Art Gallery of Ontario, Canada has said that Chatterjee’s research “provides me with the ability to justify, propose, develop and implement programming which has a fundamental impact on wellbeing” [S3].

A key impact of MoP was a best practice resource ‘Museums on Prescription: A guide to working with older people’, which was co-produced by the whole project team, including several older adult participants. Lessons learned from the development of novel MoP schemes are now changing and influencing other museums’ practices through the creation of this resource. Chatterjee has received scores of requests for further information about the project, over 20 invitations to give talks about the project including keynotes in the UK and overseas, such as the Alberta Museums Association (September 2019), Group for Education in Museums (September 2015) and the International Culture, Health and Wellbeing Conference, Bristol (June 2017).The project has also received the following awards:

• 2018: National Museums and Heritage Awards: Best Educational Initiative

• 2017: Royal Society for Public Health (RSPH): Special Commendation from Public Health England for Sustainable Development

• 2017: RSPH: Arts and Health Award.

‘Not So Grim Up North’

The ‘Not So Grim Up North’ project directly contributed to the wellbeing of people with dementia, mental illness, stroke survivors and those in addiction recovery through creative activities run by The Whitworth, Manchester Museum and Tyne & Wear Archives & Museums. These museums have developed long-term relationships with local healthcare services (e.g. Trafford Hospital) and local third sector charities, and engaged with the project because they were interested in developing a better evidence base around the impact of their work.

After engaging with the programme, participants reported (in a series of interviews carried out by the project team) that their mood had improved, that they were reconnecting with other people, and getting involved in volunteering. One participant in The Whitworth’s GROW Programme, Manchester, said: “I did feel a lot happier, every time I finished the session. I felt a sense of achievement very much so, self-esteem… a sense of belonging as well and doing something that refers to myself and especially with other people. It just made me feel not only more solid within my beliefs in myself and what I can do but a lot more connected, because it was done in a group session as opposed to a one-to-one.” Another felt that the programme created a sense of community through activities with people who shared the experience of mental health difficulties: “It was very important to relate to people, that we had a common ground factor and that was our mental health experiences. Any other art group that wasn’t focused around mental health, I would never be able to have the same chats and the same connection and the same understanding and empathy” [S4].

Museum staff also reported benefits, as described by the Assistant Outreach Officer from Manchester Museums, who said: “Participant X was quite agitated at first (shouting), however, as time went on he completely engaged – talking about the objects and asking about what was happening next week. He told me he was looking forward to seeing me next week!” [S4]. Participating museums also noted how the project had improved their outreach practice. The Head of Outreach at Tyne and Wear Archives and Museums said that “being involved in this research has positively impacted how we design, develop and deliver our outreach services and programmes, which in turn leads to wellbeing improvements for our audiences” [S5].

‘Arts and Forced Displacement’

The GCRF-funded ‘Arts and Forced Displacement’ project showed that creative activities offered opportunities for displaced people to be seen as something other than a refugee or asylum seeker; in addition, participants enjoyed acquiring language skills and gained a chance to explore difficult issues associated with displacement in a safe space outside the clinical setting. One client in the midst of seeking asylum described the “ sense of community” that the project offered: “with that opportunity of people meeting up in the groups where there is a therapeutic activity going on, again it’s a distraction from immigration and we know we are all going through it […]. And learning new things like polishing our existing skills, it’s just amazing.” [S6]. Another participant point out the programme’s ability to create long-lasting social connections: “If you’re in a situation where you’ve been completely isolated from people for a while and you just don’t know who to trust, or to be around people, it’s one of those spaces where you can get to meet people, socialise, and actually make friends. […] And these friendships do last” [R5].*

‘National Alliance for Museums, Health and Wellbeing’

Chatterjee’s research into heritage and wellbeing led her to become Chair and Co-Founder of the National Alliance for Museums, Health and Wellbeing (from 2014 to 2018, funded by Arts Council England), which established a national sector support organisation providing training, conferences and a free online course. In 2018 the Alliance merged to form the Culture, Health and Wellbeing Alliance, which Chatterjee helped to set up. CHWA has over 5,000 members and provides the secretariat to the All-Party Parliamentary Group (APPG) on Arts, Health and Wellbeing, on which Chatterjee advises. The APPG’s Inquiry Report ‘Creative Health: The Arts for Health and Wellbeing’ includes a special section on Chatterjee’s Museums on Prescription project, and Lord Darzi, (Professor of Surgery, Imperial College London) has said that the report “[laid] out a compelling case for our healthcare systems to better utilise the creative arts in supporting health and wellbeing outcomes, building on a growing body of evidence in mental health, end-of-life care and in supporting those living with long-term conditions” [S7].

The impact of Chatterjee’s work in relation to wider sector support and on policy can be seen through her role as an Advisor for the APPG on Arts, Health and Wellbeing and the Culture, Health and Wellbeing Alliance (CHWA) where she chairs the Strategic Alliance Partners Committee including senior reps from the NHS, Public Health England, Local Governments Association and Arts Council England. Lord Howarth (Co-Chair of the APPG) described Chatterjee’s presence on the APPG as “an invaluable source of ideas to all involved,” in part due to her “ability to communicate technical matters intelligibly to those without her specialised expertise” [S8]. The Policy Project Manager for the Heritage Fund said that “Professor Chatterjee’s expertise within the All-Party Parliamentary Group on Arts, Health and Wellbeing has led directly to a long-term improvement in the profile and social impact of UK cultural participation, including resource allocation” [S9].

The influence of this work on wider heritage policy can be seen in its frequent citation in recent reports from key stakeholders in the heritage sector. For instance, The Heritage Alliance 2020 report, ‘Heritage, Health, and Wellbeing,’ featured a section on heritage wellbeing, saying that “Heritage can provide healing spaces and activities for people living with particular conditions, such as dementia and post-traumatic stress disorder (PTSD). This work has been spearheaded by Professor Helen Chatterjee and her colleagues at University College London” [S10]. The World Health Organisation cited [R2], [R3], and [R5] in its 2019 evidence report, ‘What is the evidence on the role of the arts in improving health and well-being?’ and a recent report commissioned by the Department for Culture, Media, and Sport cited [R5] to argue that “the evidence base on arts and social cohesion is strong and can be trusted to guide policy development” [S10].

The research finding that cheetahs and wild dogs require conservation across geographic scales seldom considered in terrestrial ecosystems inspired Durant and Woodroffe to address this challenge by establishing, in 2006, the Range Wide Conservation Programme for Cheetahs and African Wild Dogs (RWCP). This programme works with national governments, non-governmental organisations, and other partners to support and encourage conservation of the two species on the vast geographical scales needed, across protected and unprotected lands, within and across national borders [S1, S2]. Informed by Durant and Woodroffe’s research, between 2013 and 2020 the RWCP:

• Developed national conservation action plans for cheetahs and wild dogs in partnership with seven range state governments (Algeria, Angola, Benin, Chad, Namibia, Niger, and Tanzania) and local non-governmental organisations, together covering 1.6 million km² of known cheetah range and over 500,000 km² of known wild dog range [S1], [S2], [S3], [S4]. In developing and implementing these plans, national wildlife authorities have learned to address the unique conservation challenges posed by these very wide-ranging predator species [S1], [S3], [S4].

• Reviewed and updated the International Union for Conservation of Nature/Species Survival Commission’s IUCN/SSC regional strategic plan for the conservation of cheetahs and African wild dogs in southern Africa, and reviewed and updated three national conservation action plans for cheetahs and wild dogs in partnership with three range state governments (Botswana, Zimbabwe and Zambia) [S1], [S2]. This process allowed national wildlife authorities to take stock of progress to date, to incorporate new research, and to revise and update their plans in line with progress and current scientific research [S1], [S2].

• Developed national capacity for cheetah and wild dog conservation by training, mentoring and supporting National Coordinators in 14 range states, to oversee the implementation of new and existing National Action Plans [S1], [S2], [S3], [S4], [S5], [S6]. Each of these Coordinators is embedded within their national wildlife authority, and their training has included sustainable ways to protect these species while also benefiting local people, allowing cheetahs and wild dogs to survive in human-dominated landscapes [S6].

• Supported the Convention on Migratory Species (CMS) to establish a new policy initiative (the African Carnivores Initiative) in partnership with the Convention on International Trade in Endangered Species (CITES) [S1], [S7]. This joint Initiative, which started work in 2018, provides an international framework to promote cheetah and wild dog conservation on the huge geographic scales needed, including a recommendation to “ establish a national coordination structure based on the Range Wide Conservation Programme for Cheetah and Wild Dog to provide technical support, training and mentoring to coordinators and a platform for regular meetings” [S7].

• In partnership with national governments and local experts, facilitated developing the first conservation plans for the species in two Trans-Frontier Conservation Areas (TFCAs); the Kavango-Zambezi TFCA in Botswana/Namibia/Angola/Zambia/ Zimbabwe (>500,000km²), and the W-Arly-Pendjari-Oti-Mandouri TFCA in Benin/Burkina Faso/Niger/Togo (23,000km²), promoting cheetah and wild dog conservation across international borders [S2], [S4].

• Established a new conservation initiative in the W-Arly-Pendjari-Oti-Mandouri TFCA (23,000km²) to secure habitat and prey for the last cheetah population in West Africa [S2], [S4].

• Developed a carnivore management plan for the Tsavo ecosystem in Kenya/Tanzania (24,421km², in partnership with Kenya Wildlife Service, Kenyan NGO Osilalei, and local stakeholders) [S2], [S5], and a management plan for Luando National Park in Angola (8,737km², in partnership with the Angola Ministry of Environment) [S2].

• Discovered two previously unknown populations of African wild dogs covering 13,000km² in the course of surveying protected areas across Angola, a country recovering from decades of conflict [S8].

• Initiated a new on-the-ground project in Zambia, to help local communities to coexist with wild dogs, cheetahs, and other wildlife, hence securing a vital but unprotected wildlife corridor which connects wild dog and cheetah range in Kafue National Park (30,680km²), to range in the Kavango-Zambezi TFCA (558,189km²) [S1], [S2].

In addition, demographic evidence that the illegal pet trade poses a serious extinction risk for cheetahs prompted RWCP to:

• Work through CITES to raise awareness of the illegal trade in cheetahs among range states, transit, and destination countries. This resulted in a formal assessment of the impact of trade on cheetah populations (which lists RWCP as one of the organisations contributing information), and establishment of a cheetah working group within CITES, with Durant as a member [S1].

• Provide the first CITES Illegal Trade Resource Kit, to be used by customs and other enforcement officials across the world to address illegal trade in cheetahs, including identifying cheetahs and cheetah products, and ensuring that any confiscated cheetahs are managed appropriately [S1], [S2].

Moreover, Woodroffe’s evidence that rabies caught from domestic dogs can kill whole packs and devastate wild dog populations prompted her Kenyan PhD student, Dedan Ngatia, to establish the Laikipia Rabies Vaccination Campaign (LRVC), which aims to protect both people and wild dogs by vaccinating domestic dogs [S10]. Although the World Health Organisation aims to eradicate human rabies by 2030, most efforts have targeted urban areas. Drawing tangible links between human and wildlife health has encouraged donors to support rural rabies control [S1], and the LRVC, which is conducted in partnership with Kenya’s national and county governments, and local communities, is estimated have prevented approximately 75 human rabies deaths since its establishment in 2015 [S5]. Under the auspices of the RWCP, Woodroffe’s team is now using evidence from their own research, and the experience of the LRVC, to develop disease management plans for wild dogs in Kenya, which are expected to provide a model for other wild dog conservation projects throughout Africa [S1], [S5].

In a recent independent review after 13 years of operation using the Conservation Excellence Model (CEM), the Range Wide Conservation Programme for Cheetah and African Wild Dogs was assigned a score of greater than 500. The assessors noted, that: “ *For comparison, amongst programmes previously assessed against CEM, only two other programmes achieved assessment scores in excess of 500 points, both of which have been established more than 20 years)*” [S2].

Lane’s pioneering reconception of the evolution of life in energetic terms has had global reach and influence through his 2015 book The Vital Question. This book synthesised his research on energy flows and the origin of life, the evolution of complex cells, and the adaptation of complex traits into an accessible exploration of life, reproduction, ageing, and death. By translating his research into this popularly written form, Lane’s research has had four main areas of impact: It has reshaped public perception of evolution; reached millions through extensive media impact; inspired students and the public to engage with and study science; and generated funding and enthusiasm for space missions.

Reshaping media and public perception of evolution

The Vital Question, has sold more than 100,000 copies globally and been translated into 14 languages [S1]. Describing it as “ one of the deepest, most illuminating books about the history of life to have been published in recent years”, The Economist selected it as a book of the year, as did Nature, New Scientist, The Times, FT, Independent, Sunday Times, Telegraph and the Wall Street Journal [S1]. Reviews highlight how Lane’s view of energy has transformed our understanding of life as a cosmic process by challenging the long-established gene-centric mind set. Peter Forbes wrote in the Guardian that “Lane’s theories are ingenious, breathtaking in scope and challenging in every sense… intellectually what Lane is proposing, if correct, will be as important as the Copernican revolution.” This challenge to conventional scientific thinking was echoed by Peter Requarth in the New York Times, who wrote that “Dr Lane’s broad perspective, which attempts to address the origins of life, sex and death, is seductive and often convincing… Dr Lane’s many predictions, however incredible they seem, are testable and could keep scientists busy for years.” Likewise, the geneticist Ravinder Kanda was challenged, writing in the Times Literary Supplement that Lane “approaches the question of the origin of life from a very different perspective: energy…. He certainly made me think about the question from a standpoint that is very different from the one I’m used to as a geneticist.”

The impact of The Vital Question was recognised by the Royal Society Michael Faraday Prize, the UK’s premier award for excellence in science communication. Lane’s prize lecture has been viewed more than 50,000 times on YouTube. The Chair of the Royal Society public engagement committee in 2016 commented that the book “inspired individuals to embrace science and engineering as a career choice and motivated non-scientists to use evidence-based approaches to address current and key scientific issues affecting humanity” [S2].

These reviews brought The Vital Question to the attention of Bill Gates, who addressed the role of energy in human health on his GatesNotes blog, Facebook and Twitter, with a review and video feature viewed more than 300,000 times on Facebook, with 25,000 shares, 11,000 loves and 1,200 comments [S3]. Gates called attention to Lane’s “attempt to right a scientific wrong by getting people to fully appreciate the role that energy plays in all living things… Lane’s focus on energy will be seen as an important contribution to our understanding of where we came from, and where we are going.” Gates was inspired by the practical applications of Lane’s work: “Our foundation’s global health team is talking to Nick about potential implications for the fight against malnutrition” [S3]. Lane has been regularly consulted by the President of Global Health at the Gates Foundation, who states in an email that he met with “Bill Gates and select scientific leaders” to give one of “a small number of updates on key scientific policy issues”. Lane led a discussion on the applications of his research as a springboard “for a candid conversation about the future of R&D and how emerging scientific innovations can support efforts to tackle the world’s greatest health challenges” [S3].

Generating excitement around, and funding for, space missions

The Vital Question has generated excitement and funding for NASA space missions. A former NASA Associate Administrator for Science wrote that “ I found the book inspirational in presenting a likely pathway to the origins of life on Earth, and on ice-covered ocean worlds such as the moon of Jupiter, Europa, and of Saturn, Enceladus. Working with NASA, the Administration (Office of the President), and Congress, I helped to create an Icy Worlds Research program, and initiated the Europa Clipper Mission, led by the NASA Jet Propulsion Laboratory. The Vital Question provided me a sound scientific basis (I’m an astrophysicist) for my support for those planetary science programs” [S4]. The funding committed to the Europa Clipper Mission alone totals USD4bn. This former NASA Associate Administrator and the Director of NASA’s Space Telescope program commissioned Lane to feature in a film, ‘The Hunt for Planet B’, which was designed to generate excitement around the launch of the USD10bn James Webb space telescope in October 2021. With “ unprecedented access to NASA’s high-stakes James Webb Space Telescope”, the film is being launched at the influential SXSW Film Festival in March 2021, and will be placed on one of the major streaming TV outlets (Netflix, Amazon, HBO, Discovery, CNN) [S5]. The Producer of ‘The Hunt for Planet B’ wrote that Lane is “ essential to the film,” as he “ made us understand what life is and what we might find in the universe” [S5].

Lane helped raise awareness and generate excitement for Breakthrough Initiatives’ mission to Saturn’s moon, Enceladus. He was interviewed as one of four prominent astrobiologists for a short film designed to raise awareness of the big questions around life in the universe among prominent technology and internet entrepreneurs around the world, with a view to raising funding for potential small-scale space missions to explore some of these questions. The film was shown at five private events between 2017 and 2018, in London, Berlin, Bangalore, Beijing and San Francisco, where it was viewed by leading figures from the tech engineering and investment sectors of those countries [S5]. The Creative Director of Breakthrough Initiatives wrote that Lane “ offered crucial insights into the origin of life on Earth and the chemistry of primaeval deep-sea hydrothermal vents…both his expertise and his infectious excitement about the science played a big part in the excellent response to the film at all the events" [S5]. The film assisted Breakthrough Initiatives to sign a contract with NASA in 2018 to create the concept for a flyby mission to probe the plumes of Enceladus, the first privately funded deep-space mission.

Conveying the excitement of astrobiology to millions through media impact

In part because Bill Gates thrust the book into the spotlight, The Vital Question inspired widespread interest across the media. As a result, Lane has engaged with millions through broadcast media on the question of planetary life. He appeared as an expert on Horizon ‘Oceans of the Solar System’ (BBC2, 2016; [TEXT REMOVED FOR PUBLICATION])), ‘It’s Not Rocket Science’ (ITV, 2016; [TEXT REMOVED FOR PUBLICATION]) and ‘Secrets of the Solar System’ (CuriosityStream/ Yesterday, 2020). Lane has advised on the making of other programmes, including ‘One Strange Rock’ (National Geographic, 2018, with over 100 million viewers worldwide [S6] and ‘Forces of Nature’ (BBC with Brian Cox, 2016; 2 million viewers worldwide). He was scientific consultant and featured as an on-screen expert on the US/international version of episode two, ‘Mars and Earth’ for Brian Cox’s ‘The Planets’, made by the BBC and screened by NOVA in the US ([TEXT REMOVED FOR PUBLICATION]). On national radio, Lane has been interviewed on BBC Radio 4’s ‘The Life Scientific’ (2016), ‘In Our Time’ (2018, 2015, each listened to approximately 3 million times), ‘Infinite Monkey Cage’ (2016), ‘Inside Science’ (2018, 2017), ‘Today Programme’ (2015) and ‘Start the Week’ (2015). A book celebrating 20 years of ‘In Our Time’ shows how much Lane’s ideas have engaged the public. The book features 50 programmes (of which 10 are on science) from over 900 recorded. The Producer of ‘In Our Time’ wrote: “[We] have been looking at the programmes that listeners say they’ve enjoyed the most and, while it’s a very long list, we’ve chosen ‘Photosynthesis’ [featuring Lane] as one of those for the Science section. It has proved a very popular edition since it was broadcast” [S6]. Online platforms featuring Lane’s work include Aeon, Nautilus, Buzzfeed and Radiolab (with 12 million listeners to the podcast and radio show) [S6]. The inspirational impact of Lane’s engagement is captured in an email from Scientific Director of the University of California Berkley Innovative Genomics Institute, who wrote: “I loved the recent episode of Radiolab… I have assigned the Radiolab episode featuring yourself to my students this semester in Genetics and Society, and will do so next semester in Biology for Voters” [S6].

Inspiring students and the public to engage with and study science

The Vital Question is now widely recommended on reading lists at universities including Oxford and Cambridge (e.g. ‘So You Want to Go to Oxbridge? Tell me about a Banana’) and in online student forums e.g. the Student Room. Since 2015 Lane has given more than 20 talks in schools. Lane’s writing has inspired pupils who would not have considered STEM to take a biology degree; UCL admissions records show that 50% of students cite Lane’s book on their UCAS form as an inspiration for applying to study biology. A teacher at Colchester Royal Grammar wrote: “I wanted to let you know the lasting impact your lecture had for my students. Many are now in year 13 and have been busily writing their personal statements for UCAS this term. Quite a few of them mention your talk, and the additional reading that this then led them to undertake. One student in particular wrote extensively about his learning from your books and is today being interviewed at Oxford for Biological Sciences!” [S7]. Lane spoke at two Molecular Frontiers events for schools at the Swedish Royal Academy of Sciences (in 2019 and 2017), and featured in an inspirational short video for students [S8]. He has given over 30 public talks at science and literary festivals since 2015. Reaching more than 15,000 people directly, many of these talks were recorded and are available on YouTube, where they have had more than 300,000 views [S1]. The reach of Lane’s ideas is illustrated by a transmission on the South American YouTube channel Migala, viewed live by over 30,000 people, despite being in English. The host Pepe wrote that the transmission was so inspirational that “people in the chat started to translate the conversation for those who couldn’t understand. Also, a couple volunteers started working on the Spanish subtitles already, so a lot more people are going to listen to it” [S9].

Eric Idle, of Monty Python fame, attended one of Lane’s public lectures in 2016 and was inspired to write a musical on the subject of death—one of the key topics explored in The Vital Question. He emailed to say: “As I have only a bare pass in O level Physics with Chemistry and that’s my only science it is a compliment to you to say how much fun I find [your writing]… I think laymen are intrigued by things that really exist in the Universe. We can’t help it. You do a great job of explaining. I’ve been working on a new musical which deals with the subject of death and I would like to fact check it. It’s for ‘Death the Musical’… My play seeks to cheer people up in the face of their own mortality. Bright Side and all that...” [S10].

The impact of research from UCL and IoZ falls into three main areas: informing zoonotic disease research funding; influencing international policy priorities and public health responses to disease outbreaks; and improving public understanding of links between environmental change and zoonotic disease spill-over risk. As evidenced by communication from the Wellcome’s Director: “ This research has had a global impact over many years, events of the last twelve months have underlined just how critical it is to all our health here in the UK, in so many countries around the world and to global health security” [S1].

Informing research funding priorities for zoonotic diseases

UCL and IoZ research has informed funding priorities both internationally and nationally. Some key examples include:

Emerging disease hotspots information: [R2] was used as the basis for the geographical targeting of the US Government’s international aid to countries at high risk of emerging diseases. From 2008 to 2019, approximately USD1.5 billion was spent through USAID’s Emerging Pandemic Threats program, including the PREPARE, IDENTIFY, PREDICT, RESPOND, and One Health Workforce programmes. As evidenced by the Director of EcoHealth Alliance, a key partner in PREDICT: “ The maps from this paper …remain a central core of the geographic targeting for all USAID pandemic prevention work to date” [S2].

Key evidence from [R2] also contributed to the DFID (now Foreign and Commonwealth Development Office) scoping report in 2012 on the links between zoonotic disease emergence and livestock systems. This resulted in the establishment of the Zoonoses and Emerging Livestock Systems (ZELS) research programme, which allocated millions of pounds of funding to 17 projects. Updates planned on these scoping reports will inform new research programming over the next few years [S3].

Evidence from [R1], [R2] and [R3] has furthermore contributed to the 2020 IPBES report on Biodiversity & Pandemics, has influenced the establishment of the EU’s PREZODE initiative to develop fundamental and operational research to prevent and manage future zoonotic disease outbreaks [S2] and [S4].

Key evidence on zoonotic spill-over [R2], [R3], has informed the 2020 Trinity Challenge (a coalition aiming to improve the world’s protection against health emergencies, using data-driven research and analytics) representing millions of pounds of investment. Trinity Challenge Board Chair and former UK Chief Medical Officer Dame Professor said: “ Your work on identifying global hotspots and EID risk has informed a lot of our early thinking in our “Identify” category of The Trinity Challenge” [S5].

Policy and public health responses: Research conducted by UCL and IOZ researchers is among key evidence linking emerging zoonotic diseases with land use and climate change. As a result, it has informed international and national policy priorities and public health responses to disease outbreaks [S1]. Some key policy impact examples include:

• Providing a scientific rationale and synthesis of research [R1] for ‘One Health’ multi-sector approach to improving public health outcomes which is now a major component of pandemic prevention policy around the world [S2];

• Evidence [R1], [R2] and [R3] used for the United Nations Environment Programme (UNEP)’s rapid assessment report (2020) ‘Preventing the next Pandemic’ led to UNEP joining an alliance with the World Organisation for Animal Health (OIE), Food and Agriculture Organisation (FAO), and World Health Organisation (WHO), recognising that there was a need to strengthen the environmental dimension of One Health global efforts [S6].

• Underpinning evidence [R1], [R2], [R3] provided to the WWF ‘Beyond Boundaries’ 2020 report contributed directly to WWF’s ongoing work to influence policy and practice in a range of areas on linkages between environmental degradation, emerging infectious disease risk and human health. One example is the organisation’s work around mitigating the risk posed by the wildlife trade, particularly in East and South East Asia [S7].

• Evidence on the impact of ecosystem degradation on zoonotic risk [R2] was provided by in 2020 for The Dasgupta Review commissioned by the UK’s HM Treasury setting out how nature should be accounted for in economics and decision making. This will inform policy discussions at the Convention on Biological Diversity (CBD) COP 15, United Nations Framework Convention on Climate Change (UNFCCC) COP 26, and the G7 meeting in 2021 [S8]. In 2019, as evidenced by communication with the Chief Scientific Officer at FCDO: “ The Ebola risk map from Redding et al. provided important contextual information to inform discussions with ministers in our short and medium term thinking on our response to Ebola” [R6].

• Finally, evidence on zoonotic disease emergence [R1], [R2], [R3] is informing current discussions within UK government and the G7 to develop a more strategic approach to understanding emerging zoonotic and biodiversity threats [S9].

3. Increasing public understanding of zoonotic disease risk

The research in understanding zoonotic disease spill-over processes [R1], [R2], [R3], [R4], [R5], [R6] has been communicated extensively through the international broadcast news and print media over the assessment period, thereby improving public understanding of zoonotic disease risks. Clear scientific communication has been particularly relevant during the global COVID-19 pandemic and the research team have appeared in over 150 national, specialist, and international media outlets in 2020, sharing the research with an estimated audience of over 300 million people [S11]. Highlights have included contributions to BBC Radio 4’s flagship news show the ‘Today Programme’ and its ‘Inside Science’ programme, as well as the BBC World Service. Additionally, Professor Jones gave a cross-departmental talk within the UK Government on predicting pandemics [S9] and co-wrote, with Dr Redding, a special briefing to UK Government’s Cabinet Office [S10]. This informed several of the UK prime minister’s speeches for example, to the UN Summit on Biodiversity and to the UN General Assembly in 2020 [S9], [S10]. The research also helped to provide evidence on the environmental links to the emergence of zoonotic diseases for the UK Environmental Audit Committee [S11] in 2020. Jones acted as a scientific consultant on the BBC’s Horizon programme and its ‘Extinction: the Facts’ documentary presented by David Attenborough, which covered the links between deforestation and pandemic risk.