2015 Prize Winners
In addition to £200,000 being shared by the winners of the lobbying, training, public awareness, science and young researcher awards, this year the judges decided to present our first ever Black Box awards, totalling £250,000, to winners involved in mapping the first ever ‘human toxicity pathway’.
Congratulations to all our award winners, and to the other short-listed nominees.
Black Box Prize
Key breakthroughs in human toxicity pathways research
The Lush Prize judges believe that mapping the ‘human toxicity pathway’ represents a breakthrough moment marking the first step into a future where a superior molecular science replaces the old, imprecise, technology of testing on animals in laboratories. The award recognises the work conducted on the ‘skin sensitisation pathway’ and has been divided between five winners.
£150,000: The OECD’s Adverse Outcome Pathway programme, France
The programme, directed by Bob Diderich, oversees a range of activities including:
- identifying new non-animal test methods that are candidates to become international ‘Test Guidelines’;
- managing an ‘AOP Knowledge Base’ which is a web-based platform to bring together all knowledge on how chemicals can induce adverse effects.
The OECD is a Paris-based organisation which “provides a forum in which governments can work together to share experiences and seek solutions to common problems.”
£25,000: David Basketter, UK
David is a UK-based researcher who has published over 300 papers on skin sensitisation, bridging the gap between industry and academic research.
He has focussed particularly on trying to predict whether chemicals will cause allergy from their molecular structure and has also chaired important European groups focussed on non-animal tests.
£25,000: Frank Gerberick, USA
Dr Gerberick’s primary research focus has been in the field of skin allergy with over 170 publications. He has also co-authored a book ‘Toxicology of Contact Dermatitis’.
His laboratory at Procter & Gamble in the USA has developed one of the first widely-used non-animal test (the DPRA) to predict toxicity at the first stage in the skin sensitisation pathway.
£25,000: Andreas Natsch / Roger Emter, Switzerland
Andreas Natsch and his colleague Roger Emter have led the development of the second non-animal test to reliably predict toxicity within the skin sensitisation pathway.
Their ‘KeratinoSens’ method, developed in the Givaudan laboratories in Switzerland, uses a human cell line in a test tube and looks for a particular type of gene signalling.
£25,000: Terry Schultz, USA
Terry is emeritus professor at the University of Tennessee where he directed the Biological Activity Testing and Modelling Laboratory.
His focus has been the non-animal testing of chemicals for toxicity and building computer databases of results to help predict outcomes.
He played a key role in mapping the whole pathway in the two 2012 OECD research papers ‘The Adverse Outcome Pathway for Skin Sensitisation Initiated by Covalent Binding to Proteins.’
Policy interventions promoting the use of alternatives
Mojo Mathers MP, New Zealand
A Green Party MP, Mojo Mathers has been a leading figure in the political campaign to ban cosmetics testing on animals in NZ.
She has turned down the offer of a cash element to the award, and offered it to other projects on this year’s short list.
In April 2015 the New Zealand government passed a ban on the animal testing of both finished cosmetics and of ingredients exclusively used for cosmetics.
The Government was initially strongly opposed, claiming that there was no need for a legislative ban as cosmetic animal testing was not carried out in NZ. At the last minute it backed down in response to a staunch and sustained public campaign.
The campaign ran for more than a year and Mojo Mathers played a key role throughout – both inside parliament and out. She worked intensively with a sympathetic lawyer, the New Zealand Anti-Vivisection Society (NZAVS) and Humane Society International (HSI) to develop and table an amendment in parliament that banned all cosmetic animal testing.
To build public support for her amendment, Mojo hosted a number of well-attended public workshops in all the main NZ cities. She also ran an online social media campaign encouraging the public to email all the political parties in support. In parliament, Mojo asked questions of the Minister responsible that showed that previous political assurances that the animal ethics committees would not approve unnecessary and archaic animal tests were not reliable.
It culminated in a hand-over at parliament of a petition organised by HSI, NZAVS and others, signed by 92,242 people from around the world and supported by international models. The following week the government capitulated and announced it would be bringing in a ban.
Mojo very kindly declined the financial part of the Lush Prize for Lobbying, allowing the judges to reward that money to an additional Young Researcher to assist their career in science without using animals.
Public Awareness Prize
Policy interventions promoting the use of alternatives
£20,000: SOKO Tierschutz EV, Germany
SOKO Tierschutz’s campaign against primate research at the Max-Planck-Institute for Biological Cybernetics in Tübingen, Germany, was based on a ground-breaking undercover investigation.
An activist worked for 6.5 months at the facility and was able to document – for the first time in Europe – the reality behind invasive experimental brain research on primates.
The story was published in one of the biggest political TV-magazines and received a considerable amount of follow-up reports in all major media. The images caused a public outcry and over a thousand people demonstrated in Tübingen a week after the report; a month later almost 2,000 people gathered in Stuttgart. This constituted the biggest animal rights demonstration in Germany for 20 years.
Additionally, the investigation and subsequent campaign sparked a huge debate on the use of primates in experimental and medical research with political leaders feeling forced to take a stand. The experiments on primates also became a relevant topic in the 2014 elections campaign for the mayor of Tübingen. SOKO Tierschutz gave dozens of interviews and activists successfully took part in TV discussions with representatives of the Institute and recently with a winner of the Nobel Prize in medical research.
After numerous demonstrations, vigils and continuous media reporting, the head of the Department, Prof. Nikos Logothetis, announced in 2015 that due to public pressure he had decided to give up research on primates – a precedent in the history of the struggle against animal research in Germany.
£20,000: Beagle Freedom Project, USA
For its Identity Campaign to highlight the suffering of dogs and cats in taxpayer-funded laboratories in the USA and encourage the public to use freedom of information legislation to advocate on behalf of those animals.
Beagle Freedom Project (BFP)’s Identity Campaign is a first-of-its-kind public awareness effort that allows members of the public to symbolically ‘adopt’ an actual dog or cat still imprisoned in a United States laboratory.
Utilising state open records laws, BFP has built a publicly accessible database containing the federal identification numbers, date of birth, and laboratory location of more than 1,000 dogs or cats who are awaiting the next painful test. After choosing and naming one of these animals, participants receive a welcome kit containing an adoption certificate, a unique stainless steel ‘Identity’ tag, and a fill-in-theblanks records request form to send to the research facility to learn more about what has happened to their ‘adopted’ animal.
BFP launched the Identity Campaign in March 2015, and the response has already been overwhelming. More than 1,000 people have “adopted” animals. BFP has filed legal complaints against five laboratories that have refused to hand over information about their publicly-financed experiments.
Based on Identity Campaign records, BFP also filed a formal complaint against Ohio State University, alleging that the school violated federal grant guidelines by using dogs obtained from a disreputable “random source” dealer.
21st century Toxicology
£25,000: Oncotheis, Switzerland
Oncotheis have engineered an innovative human lung cancer tissue culture model to test in vitro both the effectiveness and the toxicity of investigational therapeutics while sparing the lives of animals.
Lung cancer is the first leading cause of cancer-related deaths with more than 1 million deaths worldwide each year.
However, despite a huge research and development investment during the last decades, there is to date no effective treatment for patients.
Given the failure of animal models, human oriented models are now required to improve pre-clinical predictability. To tackle this challenge we have engineered an innovative lung-cancer model based exclusively on human cells, OncoCilAir™, that mimics in vitro the progression of the disease as it happens in patients.
In this system, bronchial and lung tumour cells obtained from surgical waste were co-cultured in a petri dish to reconstitute a fragment of human lung. After appropriate differentiation, the culture closely reproduces malignant pulmonary nodules invading a small piece of functional airway tissue.
Because it includes both healthy and cancerous tissues, OncoCilAir™ can be used to test tumour-killing action as well as adverse effects of chemotherapy and other anticancer drugs. Moreover, a single culture can be used for up to three months, which allows the study of prolonged effects, including drug resistance and tumour recurrence.
OncoCilAir™ provides an unique opportunity to accelerate anti-cancers development while reducing animal testing.
£25,000: Prof Michael L. Shuler & Team, USA
Professor Michael L. Shuler, Cornell University & Hesperos
Asst. Professor Mandy B. Esch, Syracuse University
Asst. Professor Gretchen J. Mahler, SUNY Binghampton University
Professor Tracy Stokol, Cornell University
Dr James Hickman, University of Central Florida & Hesperos
Body-on-a-Chip systems, operated with tissues derived from human cell sources, are capable of simulating the human metabolism, including toxic side effects.
They can play a significant role in determining the success of new pharmaceuticals without the use of animals.
Animal experiments are the basis for preclinical drug development but such studies poorly predict human response.
Since 1989 they have developed in vitro systems to predict human response to drugs by using physiologically-based pharmacokinetic (PBPK) models to guide the development of experimental systems that mimic human response to drugs.
These systems have been called “Body-on-a-Chip” systems.
These microscale systems, particularly in our pumpless format, make this technology affordable for commercial scale use. Another in vitro pioneer, J. Hickman, has worked closely with Shuler to augment these systems through use of serum-free media, and measurement of electrical and mechanical activity.
Body-on-a-Chip systems replicate the size relationships of organs, blood distribution, and blood flow in accordance with human physiology. When operated with tissues derived from human cell sources, these systems simulate human metabolism, including the conversion of a pro-drug to its effective metabolite, and its subsequent therapeutic actions and toxic side effects.
Since these devices can be operated with human tissue samples or with cells derived from induced pluripotent stem cells (iPS), they can play a significant role in predicting the success of new pharmaceuticals using patient derived cells.
By providing a platform for testing in the context of human diseases the systems have the potential to eliminate the use of animals in preclinical trials and emulate human disease from patient specific cells.
Training researchers in non-animal methods
£25,000: PETA International Science Consortium Ltd., UK
Minimising animal testing under REACH (European chemical testing regulations) through a series of scientific webinars and face-to-face training sessions for regulators, company representatives and contractors.
The PETA International Science Consortium Ltd (PISC) has a multifaceted approach to providing educational outreach through organising webinars, initiating face-to-face training sessions, and developing educational resources to promote the implementation and acceptance of non-animal methods for regulatory purposes.
As one example, PISC developed and organised a free webinar series on incorporating non-animal methods into testing strategies.
The series featured a variety of experts from the European Union Reference Laboratory for alternatives to animal testing, the European Commission, the European Chemicals Agency, and other leading experts from industry and academia.
Chemical Watch co-hosted the series, which reached thousands of scientists, company representatives and regulators live, with many more viewing the presentations online.
Of the participants surveyed, 80% stated that they had gained useful information on incorporating non-testing or non-animal methods into a testing strategy and 50% were more likely to use these methods for REACH, the largest animal testing programme in history.
PISC also spearheaded training sessions on the use of in vitro methods for regulatory agencies and has provided consolidated guidance on ways in which animal testing can be avoided. It does so through the PISC website, published journal articles, and giving presentations at international conferences and workshops.
£25,000: Dmitry Leporsky, Ukraine
Campaigning for replacement alternatives in the Ukraine, Belarus, Russia and Kyrgyzstan.
In the Ukraine and beyond, alternative methods have been implemented and thousands of animals saved through focused activism involving outreach, negotiations with teachers, formal agreements for replacement, and provision of alternatives.
With support from international organisations, over 85% of university departments that use animals in the Ukraine have now signed agreements to end animal experiments and dissections.
For 2008-2015, this has replaced 48,083 animals – the majority being vertebrates. The strategy of using agreements has now been extended to other former Soviet countries. For 2014-2015, agreements with 18 departments have replaced the annual use of 18,212 animals.
Once replacement has been achieved, the animals are also not used for each subsequent year. To date, the cumulative total of animals no longer facing experiments or being killed is 684,047 for the Ukraine alone.
As he works closely with universities, Dmitry also has the opportunity to liaise with young scientists and researchers to show how replacement in education and training can support the growth of humane research and testing.
Young Researcher Prize
Post-doctoral students specialising in alternative research
£10,000: Laura Bray, Leibniz Institute of Polymer Research, Germany
A proposed project to provide three key developments to animal replacement in cancer research and patients: a toolbox for medical researchers to study acute myeloid leukemia in vitro; a method for high throughput drug screening to accelerate clinical trials; a model system to test patient blood samples, for the purpose of individualising their treatment program.
The poor evidence of animal models for clinical efficacy, due to inherent biological differences between animals and humans, limits the predictability power of pre-clinical models. The replacement of animals in research requires models that should mimic the natural microenvironment, including surrounding cells and extracellular matrix (ECM) in a minimalistic but robust manner.
Dr Bray has developed three-dimensional culture models, using a hydrogel platform, to study cancer development and metastasis, perform drug testing and discover novel therapeutic targets. Our breast and prostate cancer models using this hydrogel platform were recently published, and demonstrated outstanding potential for toxicology research. In comparison with previously published in vivo data, our models displayed similar tumour regression at comparative drug concentrations.
We now propose to create a functional gel-based 3D culture platform system for incorporating primary patient tissue, mimicking specific settings of the ECM of cancer microenvironments, and for investigating cancer development in tissue-like structures.
This proposed project aims to provide three key developments to animal replacement in cancer research and patients:
• a toolbox for medical researchers to study cancer in vitro to identify new targets for therapeutic applications,
• a method for high throughput drug screening to accelerate clinical trials, and
• a model system to test patient samples, for the purpose of individualising their treatment program.
£10,000: Jeremy Caplin, Hashemi Labs, Iowa State University, USA
For work on an alternative to animal testing through the design and use of a “placenta-on-a-chip”. This chip is a 3D microfluidic device that serves as an improved method for drug testing and toxicology.
The “placenta-on-a-chip” utilizes microfluidic technology in order to replicate organ functions in the cotyledon section of the placenta. By using a soft lithography method, a silicon wafer master mold is created containing an imprint of the layer design, which consists of microchannels intended to supplement the microenvironment with media.
Sandwiched between these layers is a nanoporous polyethylene terephthalate membrane positioned to allow diffusion from one layer to the other. In this way, we can consider this analogous to the nutrient/waste transport from mother to foetus.
Epithelial and endothelial cell lines pertinent to the placenta are introduced and cultivated within the chip with the intent of providing an environment that facilities the natural properties found in in vivo placentas. Furthermore, various concentrations of ethanol are introduced into the dynamic flow, such that the effects of alcohol on the system can be monitored.
This design is straying away from current organ-on-a-chip methods in that all animal products will be eliminated. In this way we can provide a more human-realistic model while also eliminating any ethical dilemmas brought by animal testing.
£10,000: Elena Kummer, Università degli Studi di Milano, Italy
For work contributing to understanding the extent and quality of allergic sensitization. The goal is to provide a simple assay based on the use of a commercially available cell lines able to provide potency information, which is required for full replacement of animals in the assessment of the allergenic potential of xenobiotic.
Protein Kinase C (PKC) activation is central to DCs activation. Only PKCβII has beens hown to be consistently activated during DCs differentiation-inducing stimuli in normal and leukemic progenitors.
In particular, PKCβII activation by cytokines in DCs was demonstrated to be associated with upregulation of DCs surface markers (MHC I, MHC II, CD11c, CD40, CD80, CD83 and CD86), with the induction of expression of the NF-κB family member c-Rel, and the ability to stimulate allogeneic T cell proliferation. The aim of this project is to correlate allergen potency with the vigour of PKC activation, co-stimulatory molecules and cytokine production, and longevity in DCs.
DCs activation and maturation will be assessed by measuring up-regulation of co-stimulatory molecules (HLA-DR, CD80 and CD86) and production of cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12p40). These co-stimulatory molecules and cytokines will be related to chemical allergen induced PKC activation.
The effective contribution of PKCβ in chemical allergen induced DCs activation will be assessed using specific PKCβ inhibitors. Dose- and time-related experiments will be conducted on THP-1 cell line to assess the effects of contact allergen-induced on the selected markers to understand the quality and longevity of DCs activation in relation to the potency of allergens.
£10,000: Bianca Marigliani, The Federal University of São Paulo, Brazil
For research to replace the use of fetal bovine serum (FBS), obtained from bovine fetuses during slaughter of pregnant cows. FBS is the most common animal-derivative used as a medium supplement but has both ethical and technical problems.
In vitro methods are among the most favoured alternatives to replace animal tests for safety assessment of cosmetic ingredients. However, current in vitro methods for skin sensitization use animal-derived products.
The most common is foetal bovine serum (FBS), which is inhumanely obtained from bovine foetuses’ clotted blood harvested by cardiac puncture without anaesthesia.
Besides ethical concerns, there are technical scientific problems regarding the use of FBS, especially in sensitization hazard assessment.
As the covalent binding of chemicals to skin proteins is an important first step in allergic contact dermatitis, the presence of foreign proteins and peptides (provided by FBS) in culture medium can lead to misleading results.
EURL ECVAM has recently evaluated the human Cell Line Activation Test (h-CLAT). This alternative method is based on the induction of protein markers in THP-1 cells, a human cell line that may be cultured in serum-free media.
Therefore, this project aims to analyse if serum-free adapted THP-1 cells exposed to reference chemicals show similar results in h-CLAT. The replacement of FBS and other animal derived products in alternative in vitro methods is a step further towards a real animal-free future in hazard assessment.
£10,000: Ilka Maschmeyer, TissUse, Germany
Working on the long-term systemic interconnection of different organs with each other, focusing on the skin tissue, providing the dermal application route for cosmetics and drugs, replacing animal tests.
Drug discovery and safety assessment of cosmetic compounds and drug substances rely historically on the use of animal models.
However, the phylogenetic distance between animals and humans significantly reduces the predictive value of such models. Microphysiological “Human-on-a-Chip” systems may provide a superior alternative for predicting toxicity and efficacy of compounds compared to current cell culture and animal models.
In order to emulate the physiologically relevant in vivo crosstalk with the ability to perform systemic preclinical substance testing, TissUse has developed universal 2 and 4-Organ-Chips for long-term culture of human organ equivalents interconnected within a common capillary microfluidic network.
Both chips have the size of a standard microscopic slide format and an on-chip micro-pump ensures stable long-term circulation of media at variable flow rates for up to 28 days. Our chips are capable of maintaining and connecting tissues derived from cell lines, primary cells or biopsies of various human organs like skin, liver, intestine, hair follicle, kidney and more.
For substance application, oral, dermal and intravenous administration routes are possible. Hence, we provide a Multi-Organ-Chip platform enabling the chronic testing of effects of substances on a set of miniaturized human organs, replacing animal models.
£10,000: Dr Lena Smirnova, Center for Alternatives to Animal Testing, USA
For research on 3D organotypical human in vitro brain model development in combination with multi-omics technologies for (developmental) neurotoxicity testing (DNT). The research goal is to establish a high-throughput testing platform for in vitro chemical testing.
My overall research goal is to develop new, more predictive, and human-relevant in vitro methods in toxicology, which aligns with the concept of “Toxicology for the 21st Century”.
My primary interest is (developmental) neurotoxicity with a focus on molecular mechanisms (especially the role of miRNA) of cellular responses to environmental stress. In my research, I aim to identify
gene-environmental interactions leading to neurological diseases (e.g., autism and Parkinson’s disease) using in vitro human relevant 3D models and pathway of toxicity identification.
During my PhD I focused on the role of miRNA in the Central Nervous System development. I demonstrated cell-type-specific miRNA expression and post-transcriptional regulation of miRNA during neural stem cell differentiation. So far there are only a few other studies addressing the role of miRNA in developmental neurotoxicity (DNT). Therefore, during my PostDoc at ZEBET, I pursued my interest in miRNA and applied them to in vitro toxicology with the goal to establish miRNA profiling as a useful endpoint for in vitro developmental neurotoxicity testing.
A junior faculty position at Johns Hopkins gave me the opportunity to expand my work to contribute to Toxicology for the 21st century, applying organotypic 3D models and combining ~omics approaches to further study (developmental) neurotoxicity.
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