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The 12th Annual FRAME Lecture (The Bill Annett Lecture)

& The 2010 Björn Ekwall Memorial Lecture The Kennel Club, Clarges Street, London Thursday, November 4

PROGRAMME Refreshments available in the bar area before the lectures. 4pm

Presentation of the 2010 Björn Ekwall Memorial Award to Dr Richard Clothier, Trustee of FRAME. Boardroom. Followed by the Björn Ekwall Memorial Lecture by Dr Clothier. Title: “Experience in the Development and Evaluation of In Vitro Alternative Assays”.

5pm

Drinks Reception in the bar area

6pm

The 12th Annual FRAME Lecture (The Bill Annett Lecture) Given by Dr Kelly BéruBé, Director of the Lung and Particle Research Group at Cardiff University. Title: "Alternative Experimental Models for Lung Research: between a rat and a hard place".

7pm

Buffet Supper

The Björn Ekwall Memorial Lecture by Dr Richard Clothier. “Experience in the Development and Evaluation of In Vitro

Alternative Assays”. Abstract Over the past 30 years FRAME has, through its Alternatives Laboratory (FAL), developed and participated in the evaluation and validation of alternative in vitro methods. During 20 of those years Dr Richard Clothier was the Director of the FAL, and during this time participated in the development of the criteria and methodology required to validate alternative in vitro methods. It has also become clear that transparency is an important feature of in vitro experimental methods, including data acquisition and analysis. From the outset of participation in inter-laboratory studies it was considered that human cells should be used in vitro to evaluate potential human adverse reactions. FRAME has also been aware of the problems that have been raised in terms of in vitro assays, including a) should animal or human cells be used?, b) should primary cells or cell lines be used?, c) should monolayers of 3D models be employed? and d) how and with what should the in vitro data be compared to achieve the best human prediction of adverse effects? This presentation considers the experiences in the FAL and reflects upon these issues and how FRAME and the FAL have tackled them and learned from them.

Biography Dr Richard Clothier is a FRAME Trustee, and before he retired was Director of the FRAME Alternatives Laboratory (FAL), at the University of Nottingham medical school. He initially worked on tumour induction in amphibians, but they proved very difficult to induce (the South African clawed toad appears highly resistant to cancer). With Prof. L Rubens at Reed College, Portland, Oregon, USA he studied the mechanisms whereby these animals were so resistant to tumours. One aspect of his research was to culture tissues in vitro, initially from amphibian, then later in vitro culture and toxicity testing with mammalian cells, in collaboration with Prof Michael Balls. Dr Clothier took over directorship of the FAL in 1993. During this period the FAL’s research focused on development of in vitro alternative assays for toxicity. It also participated in the evaluation, via national and international blind trials, of the relevance and reliability of the in vitro approach to acute toxicity prediction. The FAL was involved with the FRAME study in 1983-6, the EC/HO and COLIPA on eye irritancy, the MEIC, SDA, ECVAM/ICCVAM, EU/ COLIPA Phototoxicity, and the AcuteTox studies. The FAL has been involved with the development of FRAME Kenacid Blue assay, the Neutral Red Release assay, the Fluorescein Leakage assay, human skin model for Schistosoma infections, innervated corneal epithelial models and bronchial models for prediction of squamous metaplasia. Dr Clothier was an Associate Professor in the School of Biomedical Sciences in the University of Nottingham, where he taught anatomy and histology, and was the departmental safety officer. He retired in 2005.

The 12th Annual FRAME Lecture (The Bill Annett Lecture) by Dr Kelly BéruBé. "Alternative Experimental Models for Lung Research: between a rat and a hard place". Abstract The pharmaceutical industry is under increasing pressure to deliver products that meet prescribed claims, lack side-effects and perform accordingly despite a patient’s genetic background. To discover a new drug, many compounds must be screened and evaluated for efficacy and toxicity, and much of that testing occurs outside the species of interest, in animals or in their tissues. The ensuing extrapolation of results to humans is fraught with difficulty, especially given that individual people can react differently to the same drug. Researchers therefore require adequate systems that allow early elimination of poor drug candidates, permitting focus on more promising ones. The recycling of human tissues from patient donors (live and post mortem) provides this system, without the need for surrogate animal models. In the specific case of respiratory medicine, lung tissues can now be recapitulated as tools for screening assays for inhalation toxicology, to predict efficacy/toxicity following exposure to drugs and pollutants. The development of human cell-based assays is required to investigate drug targeting to the lung to treat pulmonary disease; examine use of the lung as a portal for the systemic delivery of non-pulmonary drugs; and to target, for example, cancer in other organs.

Biography Dr Kelly BéruBé is the Director of the Lung & Particle Research Group at the School of Biosciences, Cardiff University, UK. With a background in electron microscopy and lung toxicology, she has built an international reputation in the field of air pollution and human health and holds numerous appointments in the USA and UK on funding bodies, advisory councils, professional societies and journal editorial boards that focus on environmental health. Her research focuses on the determination of intelligent biomarkers of exposure and harm in the respiratory system, with a particular interest in understanding how pollutants compromise lung biochemistry and alter gene and protein expression to drive disease mechanisms. Dr BéruBé’s research has been recognised with a number of awards, including the Institute for Science & Health (USA) ‘Scientific Merit Award 2006’ for toxicogenomics of inhaled xenobiotics and the honour of being the British Toxicology Society ‘Australasia Visitor 2006’ to conduct a lecture tour on nanotoxicology. Current work on ‘human tissue equivalents of respiratory epithelia’, as viable in vitro alternatives for in vivo inhalation toxicology, was awarded the UK NC3Rs ‘Replacement Prize’ and the ‘Science & Technology Innovation Prize (Cardiff University) in 2007 and 2010. Dr BéruBé’s field of study is of natural interest to the general public, and as such, she is a prolific science writer and popular invited-speaker, and has worked extensively on communicating her research through public engagements of science for primary schools, laymen groups and professional learned societies.

The Björn Ekwall Memorial Award Each year the Scandinavian Society for Cell Toxicology (SSCT) presents the Björn Ekwall Memorial Award for excellence in advancing in vitro toxicology. The Award was founded in 2001 to commemorate the work of Dr Björn Ekwall (1940–2000). He was an outstanding Swedish cell toxicologist who made pioneering contributions to the field of in vitro toxicology. In 1983 he formulated the "basal cytotoxicity concept", which provided a basis for the estimation of acute systemic toxicity of chemicals in humans by the use of in vitro tests. Together with a group of dedicated Scandinavian toxicologists, Dr Ekwall guided the MEIC project (Multicentre Evaluation of In Vitro Cytotoxicity Programme), in which 50 reference chemicals were tested in 100 laboratories worldwide by 61 different in vitro assays. The MEIC project paved the way for current validation projects.

The Bill Annett Lecture The Bill Annett Lecture is named in memory of Bill Annett (1912–2004), a long-time supporter of FRAME and Secretary to the FRAME Trustees. He was involved in public relations throughout his professional life and readily agreed to share his skills for the good of the charity. He was already 65 when he was asked by FRAME co-founder Mrs Dorothy Hegarty to help out at the charity’s headquarters, then based in Wimbledon. He continued to work for FRAME until his death at the age of 92. In 1998 he was awarded an OBE in the New Year Honours, “for services to animal welfare, especially FRAME”. Since 2005 the FRAME Annual Lecture has been known as The Bill Annett Lecture in his honour.


2010 FRAME Annual Lecture