FRAME News 67

FRAME News Fund for the Replacement of Animals in Medical Experiments

Editor: Anne Jeffery

No. 67 October 2011

The Continuing Campaign During FRAME’s 40th anniversary year, the question was asked whether FRAME had served its purpose and was no longer needed.

The organisation had already achieved a great deal: the introduction of the Animals (Scientific Procedures) Act 1986; development of validated toxicity tests; promotion of the Three Rs in the UK; and much more.

Even though there was apparent progress it was generally agreed that FRAME still had a role to play. Today, with many changes taking place in research and legislation, it seems that FRAME is needed just as much as ever.

Despite years of campaigning, the number of procedures carried out on animals in UK

laboratories is increasing every year. Home Office statistics for 2010 show a steep rise. (see pages 6 and 7) New rules being introduced by the European Union aim to improve welfare and care for laboratory animals and level out disparities between Member States but some parts of the new legislation fall short of existing UK standards. (Page 10) A long-awaited review of the use of nonhuman primates in UK laboratories revealed that 9% of projects involving them between 1997 and 2007 brought no significant scientific or medical benefits. (Page 8) So FRAME is continuing its vital work in promoting the Three Rs, involving politicians (Page 10) and educating new researchers about the importance of Replacement, Reduction and Refinement. (Page 11) The FRAME Alternatives Laboratory (FAL) is continuing to develop new ways to investigate diseases and potential treatments without the need for animals. (Page 2)

FRAME Research

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News from the FAL

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The World Congress in Canada

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Trustee changes

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Animal testing on household products

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The Dorothy Hegarty 5 Award 2010 Latest Home Office statistics

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Primate News

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FRAME Staff continue to take part in conferences and scientific meetings to spread the Three Rs message. (Page 3)

FRAME Annual Lecture

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The scientific journal ATLA continues to build on its international reputation for publishing key research into alternative methods and to attract new readers. (Pages 5 and 12)

FRAME and Parliament

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Training schools update

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Botulinum toxin testing

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ATLA’s role in promoting the Three Rs

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As long as animal experimentation goes on FRAME will continue its campaign.

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INSIDE...

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FRAME Research The FRAME Alternatives Laboratory (FAL) By Rita Seabra Since its foundation in 1982, the FRAME Alternatives Laboratory (FAL) has been at the forefront of the search for alternatives to animal experiments. Under its current Director, Dr Andrew Bennett, the FAL is continuing a programme of high quality research.

Pain and inflammation Many different health conditions, such as liver disease and osteoarthritis, are made more complex because they have an inflammatory component. The FAL is currently working on a project to investigate inflammatory pain and the way it is signalled in the body.

Researchers are working with human blood cells donated by volunteer patients at the Queen’s Medical Centre in Nottingham to investigate one of the mechanisms of pain signalling and whether it would be a suitable target for analgesia.

role of a specific pain receptor, called the transient receptor potential vanilloid channel 1, or TRPV1, which is known to play a central role in transferring painful stimuli.

Currently available pain-killers, such as non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, can have a wide range of side-effects, including gastrointestinal problems and effects on mood. For that reason they are not ideal as a long-term treatment.

By understanding the mechanisms behind pain and inflammation, it might be possible to identify therapies with fewer side effects that could be used to treat chronic conditions.

The FAL has already identified one inhibitor, which blocks the pathway involving TRPV1. The lab has recently recruited two new PhD students, who will investigate possible drug treatments based on the findings.

Obesity One of the most serious diseases in the developed world is obesity. Being overweight is a precursor to a whole range of health problems, including diabetes, cardiovascular problems and mobility difficulties.

Through its links with the School of Biomedical Sciences at the University of Nottingham, the FAL is investigating how weight gain happens and why some people find it easier to control their body mass.

Several rodent models are in use for obesity research, but none of them fully represents the problem in humans.

It is not possible to replicate human variability in laboratory animals. Also, since obesity is linked to chronic longterm diseases, it is difficult to study in relatively short-lived animals.

By means of a range of techniques including indirect calorimetry, insulin clamps, blood chemistry analysis, DNA microarray, and real-time PCR, the FAL project uses data from human studies to investigate potential treatments.

Although a number of animal pain models are available, using human cells makes results more directly relevant to patients.

Dr Bennett said: “The relevance of animal models is always limited, because their tissues and responses are not the same as those of humans. The results may not apply directly to humans. By doing the research with human cells, that uncertainty does not apply to our data.�

The aim is to conduct fundamental medical research to identify and understand the

Dogs Project Dr Jarrod Bailey works as a consultant for a number of animal protection organisations in Europe and the USA. He is currently working with the BUAV and FRAME to assess the use of dogs in research, testing and education in the UK, with a view to conducting a truly critical evaluation of their use

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as research subjects. Information on numbers of dogs, uses, purposes and procedures will be documented, together with recommendations for positive progress based on the Three Rs. Dr Bailey will also critically evaluate the scientific validity and justification of dog use, in order to encourage informed debate on this area of acute public concern.

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FRAME News

8th World Congress on Alternatives & Animal Use in the Life Sciences The 8th World Congress on Alternatives and Animal Use in the Life Sciences has taken place in Montréal Canada.

WC8 provided a forum to support both the ethical use of animals and quality science. In Canada, scientific animal use policy is developed with input from scientists, regulators and the public. This tradition of consensus-building inspired this year’s Congress motto “The Three Rs – Together it’s Possible”.

As usual, FRAME took an active part in the World Congress programme by presenting scientific posters, leading and participating in discussions, delivering lectures, and offering practical training sessions.

of her PhD project into the use of non-human primates in laboratories. (see page 9) Michelle also cochaired a session, with Marlies Leenaars of the Radboud University Nijmegen Medical Centre, The Netherlands, on Not all hard work: there were plenty of social activities that gave systematic review of an opportunity to meet new animal experiments. people and network.

The Congress had a number of themes: Safety and Efficacy Testing of Chemicals, Pharmaceuticals and Biologicals; Policy and Law on Animal Use, Public Engagement and Montréal — Ethics Review; The conference venue by night Incorporation of the Three Rs in Education and Training; Animal Welfare for Refinement and High Quality Science; and Replacement and Reduction in Basic Research.

FRAME Scientific Programme Manager Michelle Hudson presented details

Within the field of animal experimentation it is not yet common practice to perform systematic reviews, even though it has gained full acceptance as necessary for evidence-based medicine. The session considered why systematic reviews are needed and some of the hurdles to overcome in introducing them.

Delegates discussed the Montréal Declaration on Systematic Reviews of Animal Studies, which was adopted with a number of changes, including its title, at the end of the Congress.

The Montréal Declaration During the Congress delegates adopted a declaration that calls for a change in the culture of planning, executing, reporting, reviewing and translating animal research.

It says that there is universal agreement that animals should only be used for scientific purposes when no Replacement alternative is available and only when scientifically and ethically justified.

This is necessary to implement the principles of humane science. Where animals continue to be used, it is both a scientific and ethical imperative to ensure that animal studies are of the highest relevance and quality.

An important step prior to experiments should be a thorough check of previously performed studies relevant to the research question, in order to prevent unnecessary duplication of research. In the case of animal experiments this would also avoid needless suffering and wasting of animal lives.

Widespread use of this practice should: identify areas where additional animal studies may not be warranted; improve the scientific quality of animal studies; better inform the ethical review of animal studies; help to achieve the Three Rs; improve scientific reporting; and improve the value of animal research models.

A follow-up meeting will be held to establish an international working group with the aim of furthering this initiative.

Herman Koëter led the final discussions on the Declaration.

(see right) Part of the poster exhibition

Director of the FRAME Alternatives Laboratory Dr Andrew Bennett co-chaired a session, with Michel Tremblay of the Goodman Cancer Research Centre in Montréal, on animal reduction through better use of mechanistically-based translational animal disease models.

The session examined refinements that enhance the quality of life of laboratory animals, including positive welfare, and looked at their impact on the validity of scientific outcomes.

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FRAME Trustees Dr Andrew Bennett, Director of the FRAME Alternatives Laboratory (FAL), has been appointed a FRAME Trustee.

Dr Bennett graduated from the University of Nottingham in 1987 with a BSc in biochemistry and genetics, and went on to complete a biotechnology PhD at Cranfield University in 1991.

In 1992 he began a MAFF-funded study of the effects of dietary fat and carbohydrate on metabolic gene expression in rodent models. In 1996 he was appointed lecturer in biochemistry at the University of Nottingham, and became associate professor in 2003.

His continuing work led him to realise the pressing need for the use of human subjects and human-derived cell cultures because of the very different ways in which rodent and human metabolic gene expression is regulated.

As a result of his interest in finding human-based alternative models, he was appointed Director of the FAL in 2006, where he and colleagues continue to work on primary human cell culture.

Chairman of the FRAME Trustees Professor Michael Balls said: “We are all very pleased that Andrew has accepted our invitation to become a Trustee.”

David Morton Professor David Morton has retired as a FRAME Trustee after 18 years. Professor Balls said: “David’s expertise in assessment of animals’ pain and distress during their use in research has been invaluable to FRAME. We all wish him well in his retirement.”

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Training Schools on Show in Canada FRAME’s highly successful training schools in the design and analysis of animal experiments were demonstrated at the World Congress in Montréal.

FRAME Scientific Programme Manager Michelle Hudson assisted Dr Derek Fry in running a shortened training session. Dr Fry is a medical academic, who was Chief Inspector in the UK Animal Scientific Procedures Inspectorate until his retirement in 2008. He has been a regular lecturer at the FRAME schools. The session was attended by 60 international participants.

protocols and projects, and monitoring.

Michelle said: “The schools have proved very popular in the UK and Europe. The session at the World Congress was a wonderful opportunity to spread the message about the importance of experimental design to a wider audience on the North American continent.”

“We hope to persuade some of the universities in the USA and Canada to adopt similar courses as part of their training for students in biological sciences.”

A series of short lectures was interspersed with group tasks, and the participants said they gained a great deal from the experience.

The session covered features of good design, staging experimental sequences,

Animal Tests on Household Products The UK Government recently announced that it plans to introduce a ban on testing household products on animals. Animal protection groups have campaigned for years for such a ban.

FRAME welcomes the change, both as an ethical statement about what is unacceptable in terms of animal testing and ‘convenience’ products, and for its significance in the political agenda of replacing animal procedures.

However, its impact on animal welfare and numbers of animals used in testing is likely to be negligible, given the numerous other factors threatening to increase animal-based scientific procedures. No details have yet been issued, but, even though completed products will not be tested, it is highly likely that ingredients used in them will have had to undergo testing under other rules, such as the EU REACH legislation.

have fluctuated, but there has been a general downward trend, ranging from 9,309 procedures in 1986 to none in 2006 and in 2009. In the past, species used in tests in this category included dogs, fish, guinea-pigs, mice, rabbits, rats, and a few (non-human) primates, but dogs and primates have not been used in recent years.

These tests account for less than 0.1% of the total number of procedures carried out on animals in UK laboratories. Although relatively few animals are involved, a ban on testing household products is welcome, because it could lead to further consideration of other areas of animal use.

Home Office statistics include the number of procedures conducted for household products, but do not distinguish between ingredients and finished items. Numbers

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Dorothy Hegarty Award 2010 A team from the Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken in Germany has won the Dorothy Hegarty Award 2010. It was presented to authors Stephanie Hein, Michael Bur, Tobias Kolb, Bernhard Muellinger, Ulrich F. Schaefer and Claus-Michael Lehr for their paper in FRAME’s scientific journal ATLA (Alternatives to Laboratory Animals).

The award is presented annually to the authors of the paper published in the previous year’s issues of ATLA which, in the opinion of the Editorial Board, is likely to make the most significant contribution to the reduction, refinement and replacement of animal experimentation.

Each Board member can nominate up to five papers, and this year’s winners were chosen from a very varied selection, which reflects the range of work covered in the journal.

The winning paper described the PADDOCC system (Pharmaceutical Aerosol Deposition Device On Cell

Cultures), which can mimic the process of aerosol drug delivery (for example in the treatment of asthma). It also recreates aerosol generation, deposition of a substance onto cells in the lung and the subsequent absorption into the body.

Ulrich F. Schaefer

Early work concentrated on dry powder formulations, but the team is now modifying the system for the application of drug solutions and suspensions. It will therefore be applicable to testing new liquid drugs in their early stages.

The award is named after Mrs Dorothy Hegarty who co-founded FRAME in 1969, with biologist Dr Charles Foister. The charity was established to support research to find alternative methods to replace the use of animals in laboratories. In its very earliest days FRAME was run from Mrs Hegarty’s home.

Stephanie Hein

Michael Bur

ABSTRACT Stephanie Hein, Michael Bur, Tobias Kolb, Bernhard Muellinger, Ulrich F. Schaefer and Claus-Michael Lehr. The Pharmaceutical Aerosol Deposition Device On Cell Cultures (PADDOCC) In Vitro System: Design and Experimental Protocol. ATLA 38(4).

The development of aerosol medicines typically involves numerous tests on animals, due to the lack of adequate in vitro models. A new in vitro method for testing pharmaceutical aerosol formulations on cell cultures was developed, consisting of an aerosolisation unit fitting a commercial dry powder inhaler (HandiHaler®, Boehringer Ingelheim, Germany), an air-flow control unit (Akita®, Activaero, Germany) and a custom-made sedimentation chamber. This chamber holds three Snapwell® inserts with monolayers of pulmonary epithelial cells. The whole set-up, referred to as the Pharmaceutical Aerosol Deposition Device On Cell Cultures (PADDOCC) system,

aims to mimic the complete process of aerosol drug delivery, encompassing aerosol generation, aerosol deposition onto pulmonary epithelial cells and subsequent drug transport across this biological barrier, to facilitate the investigation of new aerosol formulations in the early stages of development. The development of the design and the protocol for this device are described. By testing aerosol formulations of budesonide and salbutamol sulphate, respectively, reproducible deposition of aerosol particles on, and the integrity of, the pulmonary cell monolayer could be demonstrated.

Tobias Kolb

Bernhard Muellinger Claus-Michael Lehr

Little Progress Shown in Home Office Statistics Primates The latest figures from the Home Office have shown that the number of animals involved in experiments in the UK has gone up again. The 2010 Statistics of Scientific Procedures on Living Animals revealed a total of just over 3.7 million. The rise is almost entirely due to the continued increase in the breeding and use of genetically altered animals.

The 3% increase on 2009 brings the number to the highest level since the Animals (Scientific Procedures) Act 1986 (ASPA) came into force.

There had been a slow decline since the Act was introduced, but the last decade saw a new trend as genetically altered (GA) animals became more significant in research. The 2010 total is more than a million higher than the lowest record in 2001.

Types of animals used in 2010 The main types of animals used are mice, fish and rats, which together make up 93% of all procedures. The largest increases in procedures in 2010 involved fish (up 23% to 490,944), birds (up

Animal type

No. of proceddures 2010

Mouse

2,670,067

+2

305,139

–9

13,660

–29

6,247

–5

14,833

–10

Cat

187

–32

Dog

5,782

–2

Ferret

792

–11

Other carnivore

771

–23

3,175

–15

Sheep

37,795

–1

Cattle

3,585

–18

Other ungulate

8,457

–6

Primate

4,688

+10

Other mammal

1,214

–8

142,034

+12

15,356

–27

490,944

+23

3,724,726

+3

Rat Guinea-pig Other rodent Rabbit

Pig

Bird Reptile/amphibian Fish Total

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Change from 2009 (%)

12% to 142,034), and primates (up 10% to 4,688). The largest decreases were in procedures involving cats (down 32% to 187), guinea-pigs (down 29% to 13,660), and reptiles and amphibians (down 27.5% to 15,356).

These figures represent the number of procedures carried out, not the number of animals involved. Full details can be seen in the table.

Purposes of the research The majority of procedures were conducted for breeding GA animals (44%), an increase of 6%. The second highest increase was in fundamental biological research (35%), which has risen by 10% since 2009. This section includes studies on cancer, genetics, immunology and physiology and reflects a continued rise in the animal experimentation conducted in universities.

Work in universities first overtook the number of procedures in the commercial sector in 2002. Since then the trend has continued. The commercial decline is driven by a reduction in the number of toxicology procedures being undertaken, which went down by 11 per cent in 2010.

The remaining tests were mainly for pharmaceutical compounds and to meet a combination of legislative requirements.

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It is extremely disappointing that the UK continues to use primates in laboratories, and that more procedures on them are conducted here than in all the other EU Member States.

Their high level of sentience means that primates can anticipate and remember events that cause them distress, so they have the potential to suffer greatly in experimental procedures. It is also very difficult to provide for their sophisticated behavioural and social needs in the laboratory setting.

The 2010 UK statistics show that the number of procedures conducted on primates rose by 10% to 4688, although the actual number of animals decreased slightly. Just over 2000 procedures involved the re-use of animals. Each re-use must be specially authorised by the Home Office, and is generally conditional upon the animal having suffered no significant adverse effects as a consequence of the first use. However, given the capacity for primates to understand what happens to them in terms of whether it will cause them pain and distress, there must be concern that the cumulative effects of re-use, even when only mild procedures are involved, may significantly compromise their welfare.

The recently-published Bateson Review of Research Using Non-Human Primates found that one in ten of the primate research programmes reviewed had led to no clear scientific, medical or social benefit (see page 8). It is hoped that reviews of this nature will continue to be conducted to ensure that work such as this is identified and prevented from being repeated.

Further resources, collaboration and dissemination must be initiated to work towards replacement of the need for primate models altogether.

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Fish Fish are now the second mostfrequently used animals in scientific research and testing in the UK. While there was a dip in 2009, the number of procedures

involving fish increased again in 2010, in what seems to be an overall upward trend.

The statistics do not provide information on which species of fish were used, but it is known that the zebrafish (Danio rerio) is becoming increasingly popular as a laboratory animal.

The species is being exploited as a model system for vertebrate development, disease processes, specific human diseases, and drug discovery. It is regarded by some as an alternative organism for disease modelling to replace some use of mammalian models.

However, it should be remembered that zebrafish are vertebrate animals, and that they have evolved highly sophisticated sensory organs. There is some evidence to support the assumption that some fish species have brain structures which make them potentially capable of experiencing pain and fear.

There has been little research into the zebrafish’s ability to experience pain, but given their increasing use, it would be reasonable to give them the benefit of the doubt. It would also be helpful to have the figures broken down by species and for specific studies to be carried out to gauge each type’s potential for suffering.

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Genetically altered animals

Percentage of all procedures involving that animal

Change in number of procedures from 2009 (%)

The main reason for the Number of Animal type procedures ongoing increase in the total number is use of genetically Mouse 1,826,307 68 +5 altered (GA) animals. The Fish 155,914 32 +19 GA total includes two types: genetically modified animals Rat 17,379 6 –16 (GM), which have had their Amphibian 1,754 12 +76 genomes directly manipulated, by using Domestic fowl 834 0.6 +70 modern DNA technology; Rabbit 31 0.2 +100 and animals produced by Sheep 28 0.1 –35 selective breeding, which have natural or induced mutations Pig 0 0 –100 in their DNA. GM animals make up the majority of GA animals involved in use of the mouse genome, the GA trend the UK (80%). is likely to continue for some time.

For the first time in 2009, procedures involving FRAME is particularly concerned about all GA animals overtook those involving normal of this for a number of reasons. The animals, and this trend continued in 2010. processes used to generate GA animals Breeding and use of GA animals now accounts are inefficient and can lead to harmful for more than half (54%) of all the procedures. abnormalities that are not always easily The number of procedures using non-GA recognised. That means potentially severe animals has stayed relatively stable over the last animal welfare costs that are difficult to decade, at around 1.7 million. predict. There is also a great deal of Most genetic manipulation takes place using animal ‘wastage’ when the desired genetic mice, closely followed by fish, then rats. Given status is not achieved. Further studies the level of work being carried out on GA mice need to be conducted to evaluate whether and the existence of collaborative projects that the benefits of such procedures truly are currently taking place to increase potential outweigh the costs.

Disappointment FRAME is extremely disappointed that the number of animal procedures continues to increase despite the claim that the UK has the strictest rules about animal experimentation.

With the possibility that the new EU Directive (see page 10) could weaken those rules it is of great concern that animal-based studies and tests continue to rise unabated and could even reach the high numbers from before the current Act was put in place. The UK’s reputation for high standards of animal welfare and scientific quality must not be compromised.

There needs to be the political and scientific will to reduce numbers in the future. It remains to be seen how strong the Coalition Government’s commitment is and what real impact it will have on actual numbers.

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Primary purpose of experimental procedures on animals in 2010 Other 1%

Breeding 44%

Fundamental biological research 35%

Human medicine or dentistry 14%

Veterinary medicine 4%

Protection of man, animals or the environment 2%

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Primates Poster FRAME Scientific Programme Manager Michelle Hudson took part in a post-graduate poster competition at the University of Nottingham.

Her entry was connected with her PhD project investigating ways to replace primates in laboratory experiments.

Monkeys are still used in many areas of scientific research and her project concentrates on two diseases: schistosomiasis and Parkinson’s disease.

Her study investigates how scientists justify their selection of experimental model and choice of area of research. The findings will be used to identify barriers and drivers that affect the research, to develop strategies that can effectively bring about the replacement of primates in studies looking at these two diseases.

She hopes that this will ultimately lead to wider changes in primate use practice and policy.

The competition was held to mark the launch of new priority groups at the University of Nottingham.

Science, Technology and Society (STS) is one of a number of new areas of research that have been prioritised by the university. It has established a number of Research Priority Groups, or key areas of research focus, to support the delivery of research excellence.

The priority groups aim to improve the university’s range of research and knowledge transfer, which addresses global issues and challenges, and is designed to attract significant external funding.

The poster can be seen on the opposite page

The Bateson Review of Primate Research Almost a tenth of projects showed no significant benefits.

FRAME is deeply concerned about the use of non-human primates (NHPs) in research, because their sentience and social nature mean that the costs to them of experimentation and captivity are very high.

The use of primates in laboratories is a much debated topic, but the different views tend to be highly polarised, with little common ground.

A systematic review was recommended five years ago by a Working Group led by Sir David Weatherall.

A panel of scientists chaired by Professor Sir Patrick Bateson looked at projects that used non-human primates between 1997 and 2007, and has published a number of recommendations based on the findings.

The recommendations include: O subjecting all applications for funding to use NHPs to rigorous review O examining the justification for choosing primates as the test species and whether human subjects could be used as an alternative O investigating the potential use of in vitro and in silico approaches as alternatives Each piece of research was judged according to its scientific quality and importance, the probability of medical and public benefit, and the likelihood of animal suffering. The availability of alternatives was also taken into account.

Concerns over 9% The panel concluded that in many cases the use of NHPs was justifiable even in the

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context of current understanding of animal welfare. However, it was concerned about a proportion (approximately 9%) that appeared to produce no significant scientific, medical or social benefit.

The panel stressed the ethical imperative that maximum benefit should be derived from experiments using primates and that all data should be shared. Members said that researchers using NHPs have a moral obligation to publish their results, even if they are negative, to prevent unnecessary duplication of work.

Funding bodies should take care to support only those projects that are likely to produce scientific, medical or social benefits and they should encourage the use of less invasive techniques such as neuroimaging and transcranial magnetic stimulation whenever possible.

Further reviews The panel also said that further reviews should be carried out periodically to assess the impact of NHP research.

The Bateson Review was commissioned and funded by the Biotechnology and Biological Sciences Research Council (BBSRC), the Medical Research Council (MRC) and the Wellcome Trust.

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FRAME Annual Lecture FRAME and Parliament

New Parliamentary group FRAME is providing the secretariat for a new parliamentary group.

Every year FRAME holds its annual lecture, featuring the latest developments in the field of the Three Rs. Speakers are gathered from leading institutions and organisations concerned with the implementation of Replacement, Reduction and Refinement.

The inaugural lecture was given in 1999

by Bill Russell, one of the authors of the work that introduced the Three Rs principles to research.

Since then there have been talks by many key figures and the lecture is always well received by its invited audience.

One of the speakers, Jon Richmond, former Chief Home Office Inspector, described it as ‘The most prestigious annual UK lecture on the Three Rs’.

Other speakers have included: Horst Spielmann of the Freie Universität Berlin, Ian Kimber of the University of Manchester, Rodger Curren of the Institute for In Vitro Sciences, Alan Goldberg of CAAT at Johns Hopkins University, Julia Fentem of Unilever, Vicky Robinson of the NC3Rs, and Kelly BéruBé of Cardiff University School of Biosciences.

In 2009, FRAME’s 40th anniversary year, Trustees Michael Balls and David Morton looked back at the charity’s record and considered the future of the Three Rs. In 2005 the lecture was renamed to commemorate the life of Bill Annett,

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who served as a FRAME consultant for many years and died, aged 92, while still supporting the charity. He had been awarded an OBE in the 1998 New Year Honours, with the citation, “for services to animal welfare, especially FRAME”.

Since then the lecture has carried both titles. This year will be the thirteenth FRAME Annual Lecture/the seventh Bill Annett lecture.

2011 Speaker This year’s speaker is Kevin Park, Professor of Pharmacology and Head of the School of Biomedical Sciences at the University of Liverpool. He is also Director of the MRC Centre for Drug Safety Sciences. The over-riding theme of his work is bridging “molecule-to-man” and back again, that is, enabling the prediction of adverse drug reactions based on the chemical structure of the drug and the identification of susceptible human individuals.

This work has been expanded by using pharmacogenomics and toxicogenomics to link findings in patients to the chemical structure of the drug.

His lecture is entitled: “Mechanisms of adverse drug reactions: from man to molecule and back again”.

Professor Park has received a number of honours and distinctions which include the BPS Sandoz Prize for Pharmacology, the Pfizer Medal for Innovative Science, The SmithKline and Beecham Prize for Clinical Pharmacology, The Vane Prize for Drug Metabolism, and The Werner Kalow Lectureship (Canada).

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The All-Party Parliamentary Group for the Replacement of Animals in Medical Experimentation held its inaugural meeting in July and was entered in the register of all-party groups. It replaces the All-Party Parliamentary FRAME Group, which had been in almost continuous existence since 1981.

The Group includes members of all parties, and both Houses of Parliament, who are concerned about laboratory animal use and its Chair is Nic Dakin MP. Its function will be to monitor and advise on future legislation concerning the use of animals in laboratories in the UK, and to promote the Three Rs and the use of non-animal alternative procedures.

There is still much work to be done to ensure that new laws preserve the UK’s existing high standards of welfare and scientific validity and continue to improve on them.

EU Directive negotiations FRAME is among a group of animal welfare and alternatives organisations who have met with Home Office officials to discuss the implications of the new EU Directive on the protection of animals used for scientific and other experimental purposes.

There are concerns that the Directive does not go far enough in promoting the Three Rs and that some of the measures could actually lead to a reduction in existing standards of care. It removes the special protection currently offered to dogs, cats and equids and would allow the use of great apes in certain restricted circumstances.

FRAME has submitted detailed recommendations in response to Home Office consultation on the Directive, which is due to become part of UK law in January 2013.

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Botulinum Test News An alternative method has been approved for testing products containing botulinum toxin. The new procedure will replace the very controversial LD50 animal test.

Botulinum toxin can be used for a range of therapeutic purposes, but its commonest use is in anti-wrinkle treatments. The increased use of products such as Botox® has sparked criticism because of the need to assess each batch for potency using the mouse LD50 test. LD50 uses death by paralysis and suffocation as its endpoint and about 100,000 animals are used each year for it.

Since FRAME highlighted the situation in 2003, various other organisations,

including the Humane Society of the United States (HSUS), have joined in efforts to apply the Three Rs to LD50 testing of botulinum-based products.

Now Botox manufacturer Allergan has announced that it has developed a cellbased alternative potency test, which has received regulatory approval by the US Food and Drug Administration (FDA).

The company has spent $65 million and more than 10 years on research to develop the new procedure, and expects that within three years their animal use for Botox testing will be reduced by 95%. Dr Martin Stephens, vice-president for animal research issues for the HSUS, has urged Allergan “to

work with companies that manufacture products with active ingredients similar to that used in Botox, to see if the new method can be tailored to those products, thereby sparing additional animals”.

FRAME Chairman of Trustees Professor Michael Balls said: “Having spent such a large amount on the development of the new procedure, Allergan not only has a commercial advantage, it can claim to occupy the moral high ground. Will the company allow its competitors to use the highly sensitive cell line it has developed inhouse, and if so, on what conditions and at what price?”

Training Schools Success FRAME has held two more of its highly successful training schools in Experimental Design and Statistical Analysis of Biomedical Experiments, the first time that two have been held in one year.

Places are limited to 50 each time, to ensure that trainees receive the best instruction and have the opportunity to talk over specific challenges in their research.

However, the schools are extremely popular and are always over-subscribed.

High demand In response, FRAME decided to arrange an extra school this year to cater for demand but both schools were still fully booked.

Plans are already in place to hold another school in UK next year and possibly others in Europe and further afield.

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delegates to discuss their research problems and experiences with each other and the expert tutors.

Attendees are given instruction in how to design effective experiments in order to maximise the data collected from the minimum number of animals. Many of the delegates are responsible for training other researchers, as well as carrying out their own work, so the schools help to reduce the number of animals that will be used in laboratories in the future.

The programme takes place over several days and includes focused workshops, group exercises and an opportunity for

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Both schools attracted delegates from all over the UK as well as from Europe, Scandinavia and the Far East. The first was held at the University of Edinburgh and was extremely popular with Scottish researchers.

The second school was held in Porto, Portugal. Some of the attendees from Europe said it was much more convenient for them and they would support future schools on the European mainland.

FRAME is grateful for generous sponsorship from the European Partnership for Alternative Approaches to Animal Testing (EPAA) and Laboratory Animals Ltd, and also to the lecturers who gave their time free of charge.

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ATLA’s role in Promoting the Three Rs ATLA is FRAME’s scientific journal. It promotes the reduction, replacement and refinement of animals in medical and scientific research, education, and safety testing in a number of ways: by raising awareness of the issues

ATLA’s Editorial and the Comment articles highlight potential problems and suggest ways of overcoming them. FRAME’s response to the EU Commission’s Draft Report on Alternative (Non-animal) Methods for Cosmetics Testing: Current Status and Future Prospects — 2010 was put forward as a Comment. Its relevance to the necessary testing of cosmetics for reproductive toxicity was featured in an Editorial. by publishing results of fundamental research and development of alternative methods Eventual implementation of alternative methods begins in the laboratory, where they are developed and performance-tested.

ATLA recently featured an article on development of a model based on in vitro use of pig nasal tissue to test metal surgical implants. Another report described the design of an apparatus to mimic how aerosol-based medicines are deposited on airway cells. This apparatus will be useful in developing and testing improved drugs of this type. by reporting outcomes and recommendations from Workshops and Expert Meetings In these collaborative meetings, a range of experts from different fields, as well as product manufacturers, safety regulators etc., identify relevant issues and problems — and then collate a list of recommendations for the way forward.

ATLA published the two reports of the European Centre for the Validation of Alternative Methods Skin Irritation Task Force, in 1998 and 2002. This Task Force organised the validation of alternative methods for acute skin irritation testing. by supporting validation studies to allow alternative methods to be used in testing for regulatory purposes Alternative methods cannot be used to

replace animals in regulatory testing without being validated. A number of studies must be perfomed under strictly controlled conditions, to confirm that the method will give correct and consistent results within the same laboratory and in other laboratories. In 2005 and 2007, ATLA helped publish validation results of a successful non-animal alternative to the 4hour rabbit skin-patch test, which involves substances being left in contact with the rabbit’s shaved skin. The non-animal alternative is an artificial skin model, which was validated in the EU in 2007. by providing examples of successful use of existing alternative methods Methods can be used in research or for educational purposes. ATLA recently showed how use of a cheap and simple model to teach vein cannulation to veterinary students greatly increased their success rate in mastering the technique.

This model reduces the need to practise the procedure on anaesthetised, living animals.

A recent review paper described how in vitro methods can be used to investigate how cancer develops, as well as to test substances for their carcinogenic potential. by publicising national and international conferences, training courses and workshops

ATLA features a regular Conference Diary, as well as News and Views from the Institute for In Vitro Sciences (IIVS, in the USA), the European Centre for the Validation of Alternative Methods (ECVAM, in Italy), and the European arm of the Johns Hopkins University Center for Alternatives to Animal Testing (CAAT). by informing the international scientific community about the use of Three Rs (reduction, refinement and replacement) alternatives in other countries Through ATLA, international authors can inform the rest of the world about current legislation and ways in which Three Rs principles are promoted (or rejected) by scientists in their country. Chinese, Brazilian, Russian and Korean authors, among others, have made use of this information channel.

FRAME’s ultimate aim is the elimination of the need to use laboratory animals in any kind of medical or scientific procedure.

FRAME is dedicated to the development of new and valid methods that will replace the need for laboratory animals in medical and scientific research, education, and testing.

Where the use of animals is currently necessary, FRAME supports the reduction of numbers involved to an unavoidable minimum and refinement of the experimental procedures to minimise any suffering caused.

FRAME relies entirely on grants and donations to carry out its vital work promoting the development of new and valid methods that will replace the need for laboratory animals in medical and scientific research, education, and testing.

It receives no financial support from local or central government so any gifts from supporters, either individuals or companies, are always gladly received.

As an independent charity, FRAME welcomes any donation, however small, either from individuals or companies.

Published by FRAME Russell and Burch House, 96–98 North Sherwood Street, Nottingham NG1 4EE Phone: 0115 958 4740 www.frame.org.uk

by valuing research into alternatives

ATLA presents the Dorothy Hegarty Award each year. (see page 5)

E-mail: frame@frame.org.uk Registered Charity No. 259464