The Continuing Campaign

FRAME News Fund for the Replacement of Animals in Medical Experiments Editor: Anne Jeffery No. 67 October 2011

FRAME News http://www.frame.org.uk

INSIDE...FRAME Research 2

News from the FAL 2

The World Congress 3in Canada

Trustee changes 4

Animal testing onhousehold products 4

The Dorothy Hegarty 5Award 2010

Latest Home Office 6statistics

Primate News 8

FRAME Annual 10Lecture

FRAME and 10Parliament

Training schools 11update

Botulinum toxin 11testing

ATLA’s role in 12promoting the Three Rs

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

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

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

During FRAME’s 40thanniversary year, thequestion was askedwhether FRAME hadserved its purpose andwas no longer needed.

As long as animalexperimentationgoes on FRAME willcontinue itscampaign.

laboratories is increasing every year. HomeOffice statistics for 2010 show a steep rise.(see pages 6 and 7)

New rules being introduced by the EuropeanUnion aim to improve welfare and care forlaboratory animals and level out disparitiesbetween Member States but some parts of thenew legislation fall short of existing UKstandards. (Page 10)

A long-awaited review of the use of non-human primates in UK laboratories revealedthat 9% of projects involving them between1997 and 2007 brought no significantscientific or medical benefits. (Page 8)

So FRAME is continuing its vital work inpromoting the Three Rs, involving politicians(Page 10) and educating new researchersabout the importance of Replacement,Reduction and Refinement. (Page 11)

The FRAME Alternatives Laboratory (FAL) iscontinuing to develop new ways to investigate

diseases and potential treatments withoutthe need for animals. (Page 2)

FRAME Staff continue to take part inconferences and scientific meetings tospread the Three Rs message. (Page 3)

The scientific journal ATLA continues tobuild on its international reputation forpublishing key research into alternativemethods and to attract new readers. (Pages5 and 12)

2 http://www.frame.org.uk FRAME News

Since its foundation in 1982, the FRAMEAlternatives Laboratory (FAL) has been atthe forefront of the search for alternativesto animal experiments. Under its currentDirector, Dr Andrew Bennett, the FAL iscontinuing a programme of high qualityresearch.

Pain and inflammation

Many different health conditions, such asliver disease and osteoarthritis, are mademore complex because they have aninflammatory component. The FAL iscurrently working on a project toinvestigate inflammatory pain and the wayit is signalled in the body.

Researchers are working with human bloodcells donated by volunteer patients at theQueen’s Medical Centre in Nottingham toinvestigate one of the mechanisms of painsignalling and whether it would be asuitable target for analgesia.

Although a number of animal pain modelsare available, using human cells makesresults more directly relevant to patients.Dr Bennett said: “The relevance of animalmodels is always limited, because theirtissues and responses are not the same asthose of humans. The results may notapply directly to humans. By doing theresearch with human cells, that uncertaintydoes not apply to our data.”

The aim is to conduct fundamental medicalresearch to identify and understand the

role of a specific pain receptor, called thetransient receptor potential vanilloidchannel 1, or TRPV1, which is known toplay a central role in transferring painfulstimuli.

Currently available pain-killers, such asnon-steroidal anti-inflammatory drugs(NSAIDs) and opioids, can have a widerange of side-effects, includinggastrointestinal problems and effects onmood. For that reason they are not idealas a long-term treatment.

By understanding the mechanisms behindpain and inflammation, it might bepossible to identify therapies with fewerside effects that could be used to treatchronic conditions.

Dogs Project

Dr Jarrod Bailey works as aconsultant for a number of animalprotection organisations in Europeand the USA. He is currentlyworking with the BUAV and FRAMEto assess the use of dogs inresearch, testing and education inthe UK, with a view to conducting atruly critical evaluation of their use

The FRAME AlternativesLaboratory (FAL) By Rita Seabra

FRAME Research The FAL has already identified oneinhibitor, which blocks the pathwayinvolving TRPV1. The lab has recentlyrecruited two new PhD students, who willinvestigate possible drug treatments basedon the findings.

Obesity

One of the most serious diseases in thedeveloped world is obesity. Beingoverweight is a precursor to a whole rangeof health problems, including diabetes,cardiovascular problems and mobilitydifficulties.

Through its links with the School ofBiomedical Sciences at the University ofNottingham, the FAL is investigating howweight gain happens and why somepeople find it easier to control theirbody mass.

Several rodent models are in use forobesity research, but none of them fullyrepresents the problem in humans.

It is not possible to replicate humanvariability in laboratory animals. Also,since obesity is linked to chronic long-term diseases, it is difficult to study inrelatively short-lived animals.

By means of a range of techniquesincluding indirect calorimetry, insulinclamps, blood chemistry analysis, DNAmicroarray, and real-time PCR, the FALproject uses data from human studies toinvestigate potential treatments.

as research subjects. Information on numbers ofdogs, uses, purposes and procedures will bedocumented, together with recommendationsfor 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.

FRAME News http://www.frame.org.uk 3

As usual, FRAME took anactive part in the WorldCongress programme bypresenting scientific posters,leading and participating indiscussions, deliveringlectures, and offering practicaltraining sessions.

The Congress had a numberof themes: Safety and EfficacyTesting of Chemicals,Pharmaceuticals andBiologicals; Policy and Law onAnimal Use, PublicEngagement andEthics Review;Incorporation ofthe Three Rs inEducation andTraining; AnimalWelfare forRefinement andHigh QualityScience; andReplacement andReduction inBasic Research.

FRAME Scientific Programme Manager Michelle Hudson presented details

of her PhD project intothe use of non-humanprimates inlaboratories. (see page9)

Michelle also co-chaired a session, withMarlies Leenaars ofthe RadboudUniversity NijmegenMedical Centre, TheNetherlands, onsystematic review ofanimal experiments.

Within the field of animalexperimentation it is not yetcommon practice to performsystematic reviews, even though ithas gained full acceptance asnecessary for evidence-basedmedicine. The session consideredwhy systematic reviews are neededand some of the hurdles toovercome in introducing them.

Delegates discussed the MontréalDeclaration on Systematic Reviews ofAnimal Studies, which was adopted

with a number of changes, including itstitle, at the end of the Congress.

(see right)

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

WC8 provided a forum to support both the ethical use of animals andquality science. In Canada, scientific animal use policy is developedwith input from scientists, regulators and the public. This tradition ofconsensus-building inspired this year’s Congress motto

“The Three Rs – Together it’s Possible”.

Part of the poster exhibition

Not all hard work: there wereplenty of social activities that gavean opportunity to meet newpeople and network.

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 animalreduction 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.

The MontréalDeclarationDuring the Congress delegates adopted adeclaration that calls for a change in theculture of planning, executing, reporting,reviewing and translating animal research.

It says that there is universal agreement thatanimals should only be used for scientificpurposes when no Replacement alternativeis available and only when scientifically andethically justified.

This is necessary to implement theprinciples of humane science. Whereanimals continue to be used, it is both ascientific and ethical imperative to ensurethat animal studies are of the highestrelevance and quality.

An important step prior to experimentsshould be a thorough check of previouslyperformed studies relevant to the researchquestion, in order to prevent unnecessaryduplication of research. In the case ofanimal experiments this would also avoidneedless suffering and wasting of animallives.

Widespread use of this practice should:identify areas where additional animalstudies may not be warranted; improve thescientific quality of animal studies; betterinform the ethical review of animal studies;help to achieve the Three Rs; improvescientific reporting; and improve the valueof animal research models.

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

Montréal —The conference venue by night

Herman Koëter led the final discussions on the Declaration.

FRAMETrustees

Dr Andrew Bennett, Director of the

FRAME Alternatives

Laboratory (FAL), has beenappointed a

FRAME Trustee.

Dr Bennett graduated from the

University of Nottingham in 1987

with a BSc in bio-chemistry and genetics, and

went on to complete a biotechnology PhD at Cranfield University in 1991.

In 1992 he began a MAFF-funded studyof the effects of dietary fat andcarbohydrate on metabolic geneexpression in rodent models. In 1996 hewas appointed lecturer in biochemistry atthe University of Nottingham, and becameassociate professor in 2003.

His continuing work led him to realise thepressing need for the use of humansubjects and human-derived cell culturesbecause of the very different ways in whichrodent and human metabolic geneexpression is regulated.

As a result of his interest in findinghuman-based alternative models, he wasappointed Director of the FAL in 2006,where he and colleagues continue to workon primary human cell culture.

Chairman of the FRAME TrusteesProfessor Michael Balls said: “We are allvery pleased that Andrew has acceptedour invitation to become a Trustee.”

David Morton

Professor David Morton has retired as aFRAME Trustee after 18 years. ProfessorBalls said: “David’s expertise inassessment of animals’ pain and distressduring their use in research has beeninvaluable to FRAME. We all wish him wellin his retirement.”

FRAME’s highly successful training schoolsin the design and analysis of animalexperiments were demonstrated at theWorld Congress in Montréal.

FRAME Scientific Programme ManagerMichelle Hudson assisted Dr Derek Fry inrunning a shortened training session. Dr Fryis a medical academic, who was ChiefInspector in the UK Animal ScientificProcedures Inspectorate until his retirementin 2008. He has been a regular lecturer atthe FRAME schools. The session wasattended by 60 international participants.

A series of short lectures was interspersedwith group tasks, and the participants saidthey gained a great deal from theexperience.

The session covered features of gooddesign, staging experimental sequences,

protocols and projects, and monitoring.

Michelle said: “The schools have provedvery popular in the UK and Europe. Thesession at the World Congress was awonderful opportunity to spread themessage about the importance ofexperimental design to a wider audience onthe North American continent.”

“We hope to persuade some of theuniversities in the USA and Canada toadopt similar courses as part of theirtraining for students in biological sciences.”

The UK Government recently announcedthat it plans to introduce a ban on testinghousehold products on animals. Animalprotection groups have campaigned foryears for such a ban.

FRAME welcomes the change, both as anethical statement about what is unacceptablein terms of animal testing and ‘convenience’products, and for its significance in thepolitical agenda of replacing animalprocedures.

However, its impact on animal welfare andnumbers of animals used in testing is likelyto be negligible, given the numerous otherfactors threatening to increase animal-basedscientific procedures. No details have yetbeen issued, but, even though completedproducts will not be tested, it is highly likelythat ingredients used in them will have hadto undergo testing under other rules, suchas the EU REACH legislation.

Home Office statistics include the numberof procedures conducted for householdproducts, but do not distinguish betweeningredients and finished items. Numbers

Animal Tests onHousehold Products

have fluctuated, but there has been ageneral downward trend, ranging from9,309 procedures in 1986 to none in2006 and in 2009. In the past, speciesused in tests in this category included dogs,fish, guinea-pigs, mice, rabbits, rats, and afew (non-human) primates, but dogs andprimates have not been used in recentyears.

These tests account for less than 0.1% ofthe total number of procedures carried outon animals in UK laboratories. Althoughrelatively few animals are involved, a ban ontesting household products is welcome, because it could lead tofurther consideration of other areas of animal use.

4 http://www.frame.org.uk FRAME News

Training Schools onShow in Canada

Cultures), which can mimic the process of aerosol drugdelivery (for example in the treatment of asthma). Italso recreates aerosol generation, deposition of asubstance onto cells in the lung and the subsequentabsorption into the body.

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

A team from the Department of Biopharmaceutics andPharmaceutical Technology, Saarland University,Saarbrücken in Germany has won the Dorothy HegartyAward 2010. It was presented to authors StephanieHein, Michael Bur, Tobias Kolb, Bernhard Muellinger,Ulrich F. Schaefer and Claus-Michael Lehr for theirpaper in FRAME’s scientific journal ATLA (Alternativesto Laboratory Animals).

The award is presented annually to the authors of thepaper published in the previous year’s issues of ATLAwhich, in the opinion of the Editorial Board, is likely tomake the most significant contribution to thereduction, refinement and replacement of animalexperimentation.

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

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

Dorothy HegartyAward 2010

The award is named after Mrs DorothyHegarty who co-founded FRAME in1969, with biologist Dr CharlesFoister. The charity was established tosupport research to find alternativemethods to replace the use of animalsin laboratories. In its very earliestdays FRAME was run from MrsHegarty’s home.

The development of aerosol medicinestypically involves numerous tests onanimals, due to the lack of adequate invitro models. A new in vitro method fortesting pharmaceutical aerosolformulations on cell cultures wasdeveloped, consisting of an aerosolisationunit fitting a commercial dry powderinhaler (HandiHaler®, BoehringerIngelheim, Germany), an air-flow controlunit (Akita®, Activaero, Germany) and acustom-made sedimentation chamber. Thischamber holds three Snapwell® insertswith monolayers of pulmonary epithelialcells. The whole set-up, referred to as thePharmaceutical Aerosol Deposition DeviceOn Cell Cultures (PADDOCC) system,

aims to mimic the complete process ofaerosol drug delivery, encompassingaerosol generation, aerosol depositiononto pulmonary epithelial cells andsubsequent drug transport across thisbiological barrier, to facilitate theinvestigation of new aerosol formulationsin the early stages of development. Thedevelopment of the design and theprotocol for this device are described. Bytesting aerosol formulations of budesonideand salbutamol sulphate, respectively,reproducible deposition of aerosolparticles on, and the integrity of, thepulmonary cell monolayer could bedemonstrated.

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

Tobias Kolb

BernhardMuellinger

Ulrich F. Schaefer

Claus-Michael Lehr

Michael Bur

Stephanie Hein

Types of animals used in 2010

The main types of animals used are mice,fish and rats, which together make up93% of all procedures. The largestincreases in procedures in 2010 involvedfish (up 23% to 490,944), birds (up

12% to 142,034), and primates (up 10%to 4,688). The largest decreases were inprocedures involving cats (down 32% to187), guinea-pigs (down 29% to13,660), and reptiles and amphibians(down 27.5% to 15,356).

These figures represent the number ofprocedures carried out, not the number ofanimals involved. Full details can be seenin the table.

Purposes of the research

The majority of procedures wereconducted for breeding GA animals(44%), an increase of 6%. The secondhighest increase was in fundamentalbiological research (35%), which has risenby 10% since 2009. This section includesstudies on cancer, genetics, immunologyand physiology and reflects a continuedrise in the animal experimentationconducted in universities.

Work in universities first overtook thenumber of procedures in the commercialsector in 2002. Since then the trend hascontinued. The commercial decline isdriven by a reduction in the number oftoxicology procedures being undertaken,which went down by 11 per cent in 2010.The remaining tests were mainly forpharmaceutical compounds and to meet acombination of legislative requirements.

6 http://www.frame.org.uk FRAME News

Little Progress Shown in Home Office Statistics

No. of Changeproced- from

Animal dures 2009type 2010 (%)

Mouse 2,670,067 +2

Rat 305,139 –9

Guinea-pig 13,660 –29

Other rodent 6,247 –5

Rabbit 14,833 –10

Cat 187 –32

Dog 5,782 –2

Ferret 792 –11

Other carnivore 771 –23

Pig 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

Bird 142,034 +12

Reptile/amphibian 15,356 –27

Fish 490,944 +23

Total 3,724,726 +3

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

The 3% increase on 2009 brings the number to the highest level sincethe Animals (Scientific Procedures) Act 1986 (ASPA) came into force.There had been a slow decline since the Act was introduced, but the lastdecade saw a new trend as genetically altered (GA) animals became moresignificant in research. The 2010 total is more than a million higher thanthe lowest record in 2001.

Primates

It is extremely disappointing that the UKcontinues to use primates in laboratories,and that more procedures on them areconducted here than in all the other EUMember States.

Their high level of sentience means thatprimates can anticipate and rememberevents that cause them distress, so theyhave the potential to suffer greatly inexperimental procedures. It is also verydifficult to provide for their sophisticatedbehavioural and social needs in thelaboratory setting.

The 2010 UK statistics show that thenumber of procedures conducted onprimates rose by 10% to 4688, althoughthe actual number of animals decreasedslightly. Just over 2000 proceduresinvolved the re-use of animals. Each re-usemust be specially authorised by the HomeOffice, and is generally conditional uponthe animal having suffered no significantadverse effects as a consequence of thefirst use. However, given the capacity forprimates to understand what happens tothem in terms of whether it will cause thempain and distress, there must be concernthat the cumulative effects of re-use, evenwhen only mild procedures are involved,may significantly compromise their welfare.

The recently-published Bateson Review ofResearch Using Non-Human Primates foundthat one in ten of the primate researchprogrammes reviewed had led to no clearscientific, medical or social benefit (seepage 8). It is hoped that reviews of thisnature will continueto 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 replace-ment of the need for primate modelsaltogether.

FRAME News http://www.frame.org.uk 7

Genetically alteredanimals

The main reason for theongoing increase in the totalnumber is use of geneticallyaltered (GA) animals. TheGA total includes two types:genetically modified animals(GM), which have had theirgenomes directlymanipulated, by usingmodern DNA technology;and animals produced byselective breeding, which havenatural or induced mutationsin their DNA. GM animalsmake up the majority of GA animals involved inthe UK (80%).

For the first time in 2009, procedures involvingGA animals overtook those involving normalanimals, and this trend continued in 2010.Breeding and use of GA animals now accountsfor more than half (54%) of all the procedures.The number of procedures using non-GAanimals has stayed relatively stable over the lastdecade, at around 1.7 million.

Most genetic manipulation takes place usingmice, closely followed by fish, then rats. Giventhe level of work being carried out on GA miceand the existence of collaborative projects thatare currently taking place to increase potential

use of the mouse genome, the GA trendis likely to continue for some time.

FRAME is particularly concerned about allof this for a number of reasons. Theprocesses used to generate GA animalsare inefficient and can lead to harmfulabnormalities that are not always easilyrecognised. That means potentially severeanimal welfare costs that are difficult topredict. There is also a great deal ofanimal ‘wastage’ when the desired geneticstatus is not achieved. Further studiesneed to be conducted to evaluate whetherthe benefits of such procedures trulyoutweigh the costs.

Fundamentalbiologicalresearch

35%

Breeding44%

Humanmedicine or

dentistry14%

Other 1%

Veterinarymedicine

4%

Protection of man,animals or the

environment 2%

Disappointment

FRAME is extremely disappointed that thenumber of animal procedures continues toincrease despite the claim that the UK hasthe strictest rules about animalexperimentation.

With the possibility that the new EUDirective (see page 10) could weaken thoserules it is of great concern that animal-basedstudies and tests continue to rise unabatedand could even reach the high numbers frombefore the current Act was put in place. TheUK’s reputation for high standards of animalwelfare and scientific quality must not becompromised.

There needs to be the political and scientificwill to reduce numbers in the future. Itremains to be seen how strong the CoalitionGovernment’s commitment is and what realimpact it will have on actual numbers.

Primary purpose ofexperimental

procedures onanimals in 2010

Fish

Fish are now the second most-frequently used animals inscientific research and testing inthe UK. While there was a dip in2009, the number of procedures

involving fish increased again in2010, in what seems to be anoverall upward trend.

The statistics do not provideinformation on which species offish were used, but it is knownthat the zebrafish (Danio rerio) isbecoming increasingly popular as alaboratory animal.

The species is being exploited as amodel system for vertebratedevelopment, disease processes,specific human diseases, and drugdiscovery. It is regarded by someas an alternative organism fordisease modelling to replace someuse of mammalian models.

However, it should be rememberedthat zebrafish are vertebrateanimals, and that they haveevolved highly sophisticatedsensory organs. There is someevidence to support theassumption that some fish specieshave brain structures which makethem potentially capable ofexperiencing pain and fear.

There has been little researchinto the zebrafish’s ability toexperience pain, but given theirincreasing use, it would bereasonable to give them thebenefit of the doubt. It wouldalso be helpful to have the figuresbroken down by species and forspecific studies to be carried outto gauge each type’s potential forsuffering.

Percentage Change inof all number of

procedures proceduresNumber of involving from 2009

Animal type procedures that animal (%)

Mouse 1,826,307 68 +5

Fish 155,914 32 +19

Rat 17,379 6 –16

Amphibian 1,754 12 +76

Domestic fowl 834 0.6 +70

Rabbit 31 0.2 +100

Sheep 28 0.1 –35

Pig 0 0 –100

Her entry was connected with her PhDproject investigating ways to replaceprimates in laboratory experiments.

Monkeys are still used in many areas ofscientific research and her projectconcentrates on two diseases:schistosomiasis and Parkinson’s disease.

8 http://www.frame.org.uk FRAME News

Her study investigates how scientistsjustify their selection of experimentalmodel and choice of area of research. Thefindings will be used to identify barriersand drivers that affect the research, todevelop strategies that can effectively bringabout the replacement of primates instudies looking at these two diseases.

She hopes that this will ultimately lead towider changes in primate use practice andpolicy.

The competition was held to mark thelaunch of new priority groups at theUniversity of Nottingham.

Science, Technology and Society (STS) isone of a number of new areas of researchthat have been prioritised by theuniversity. It has established a number ofResearch Priority Groups, or key areas ofresearch focus, to support the delivery ofresearch excellence.

The priority groups aim to improve theuniversity’s range of research andknowledge transfer, which addressesglobal issues and challenges, and isdesigned to attract significant externalfunding.

context of current understanding of animalwelfare. However, it was concerned about aproportion (approximately 9%) thatappeared to produce no significantscientific, medical or social benefit.

The panel stressed the ethical imperativethat maximum benefit should be derivedfrom experiments using primates and thatall data should be shared. Members saidthat researchers using NHPs have a moralobligation to publish their results, even ifthey are negative, to prevent unnecessaryduplication of work.

Funding bodies should take care to supportonly those projects that are likely toproduce scientific, medical or socialbenefits and they should encourage the useof less invasive techniques such asneuroimaging and transcranial magneticstimulation whenever possible.

Further reviews

The panel also said that further reviewsshould be carried out periodically to assessthe impact of NHP research.

The Bateson Review was commissioned andfunded by the Biotechnology and BiologicalSciences Research Council (BBSRC), theMedical Research Council (MRC) and theWellcome Trust.

The Bateson Review of Primate Research

Primates PosterFRAME Scientific ProgrammeManager Michelle Hudsontook part in a post-graduateposter competition at theUniversity of Nottingham.

The poster can be seenon the opposite page

A systematic review was recommendedfive years ago by a Working Group led bySir David Weatherall.

A panel of scientists chaired byProfessor Sir Patrick Bateson looked atprojects that used non-human primatesbetween 1997 and 2007, and haspublished a number of recommendationsbased on the findings.

The recommendations include:

� subjecting all applications for fundingto use NHPs to rigorous review

� examining the justification forchoosing primates as the test speciesand whether human subjects could beused as an alternative

� investigating the potential use of invitro and in silico approaches asalternatives

Each piece of research was judgedaccording to its scientific quality andimportance, the probability of medicaland public benefit, and the likelihood ofanimal suffering. The availability ofalternatives was also taken into account.

Concerns over 9%

The panel concluded that in many casesthe use of NHPs was justifiable even in the

Almost a tenth of projects showed nosignificant benefits.

FRAME is deeply concerned about the useof non-human primates (NHPs) in research,because their sentience and social naturemean that the costs to them ofexperimentation 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.

FRAME News http://www.frame.org.uk 9

10 http://www.frame.org.uk FRAME News

FRAME Annual Lecture

Every year FRAME holds its annuallecture, featuring the latest develop -ments in the field of the Three Rs.

Speakers are gathered from leadinginstitutions and organisationsconcerned with the implementation ofReplacement, Reduction andRefinement.

The inaugural lecture was given in 1999by Bill Russell, one of the authors ofthe work that introduced the Three Rsprinciples to research.

Since then there have been talks bymany key figures and the lecture isalways well received by its invitedaudience.

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

Other speakers have included:

Horst Spielmann of the Freie UniversitätBerlin, Ian Kimber of the University ofManchester, Rodger Curren of theInstitute for In Vitro Sciences, AlanGoldberg of CAAT at Johns HopkinsUniversity, Julia Fentem of Unilever,Vicky Robinson of the NC3Rs, andKelly BéruBé of Cardiff UniversitySchool of Biosciences.

In 2009, FRAME’s 40th anniversaryyear, Trustees Michael Balls and DavidMorton looked back at the charity’srecord and considered the future of theThree Rs.

In 2005 the lecture was renamed tocommemorate the life of Bill Annett,

who served as a FRAME consultant formany years and died, aged 92, while stillsupporting the charity. He had beenawarded an OBE in the 1998 New YearHonours, with the citation, “for servicesto animal welfare, especially FRAME”.

Since then the lecture has carried bothtitles. This year will be the thirteenthFRAME Annual Lecture/the seventh BillAnnett lecture.

2011 Speaker

This year’s speaker is Kevin Park,Professor of Pharmacology and Head ofthe School of Biomedical Sciences at theUniversity of Liverpool. He is alsoDirector of the MRC Centre for DrugSafety Sciences. The over-riding theme ofhis work is bridging “molecule-to-man”and back again, that is, enabling theprediction of adverse drug reactions basedon the chemical structure of the drug andthe identification of susceptible humanindividuals.

This work has been expanded by usingpharmacogenomics and toxicogenomics tolink findings in patients to the chemicalstructure of the drug.

His lecture is entitled: “Mechanisms ofadverse drug reactions: from man tomolecule and back again”.

Professor Park has received a number ofhonours and distinctions which include theBPS Sandoz Prize for Pharmacology, thePfizer Medal for Innovative Science, TheSmithKline and Beecham Prize for ClinicalPharmacology, The Vane Prize for DrugMetabolism, and The Werner KalowLectureship (Canada).

FRAME andParliamentNew Parliamentary group

FRAME is providing the secretariat for a newparliamentary group.

The All-Party Parliamentary Group for theReplacement of Animals in MedicalExperimentation held its inaugural meeting inJuly and was entered in the register of all-partygroups. It replaces the All-Party ParliamentaryFRAME Group, which had been in almostcontinuous existence since 1981.

The Group includes members of all parties, andboth Houses of Parliament, who are concernedabout laboratory animal use and its Chair is NicDakin MP.

Its function will be to monitor and advise onfuture legislation concerning the use of animalsin laboratories in the UK, and to promote theThree Rs and the use of non-animal alternativeprocedures.

There is still much work to be done to ensurethat new laws preserve the UK’s existing highstandards of welfare and scientific validity andcontinue to improve on them.

EU Directive negotiations

FRAME is among a group of animal welfare andalternatives organisations who have met withHome Office officials to discuss the implicationsof the new EU Directive on the protection ofanimals used for scientific and otherexperimental purposes.

There are concerns that the Directive does notgo far enough in promoting the Three Rs andthat some of the measures could actually lead toa reduction in existing standards of care. Itremoves the special protection currently offeredto dogs, cats and equids and would allow theuse of great apes in certain restrictedcircumstances.

FRAME has submitted detailedrecommendations in response to Home Officeconsultation on the Directive, which is due tobecome part of UK law in January 2013.

FRAME News http://www.frame.org.uk 11

FRAME has held two more of its highlysuccessful training schools in ExperimentalDesign and Statistical Analysis of BiomedicalExperiments, the first time that two havebeen held in one year.

Places are limited to 50 each time, toensure that trainees receive the bestinstruction and have the opportunity to talkover specific challenges in their research.However, the schools are extremely popularand are always over-subscribed.

High demand

In response, FRAME decided to arrange anextra school this year to cater for demandbut both schools were still fully booked.Plans are already in place to hold anotherschool in UK next year and possibly othersin Europe and further afield.

Attendees are given instruction in how todesign effective experiments in order tomaximise the data collected from theminimum number of animals. Many of thedelegates are responsible for training otherresearchers, as well as carrying out theirown work, so the schools help to reducethe number of animals that will be used inlaboratories in the future.

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

delegates to discuss their research problemsand experiences with each other and theexpert tutors.

Both schools attracted delegates from allover the UK as well as from Europe,Scandinavia and the Far East. The first washeld at the University of Edinburgh and wasextremely popular with Scottish researchers.

The second school was held in Porto,Portugal. Some of the attendees fromEurope said it was much more convenientfor them and they would support futureschools on the European mainland.

FRAME is grateful for generoussponsorship from the European Partnershipfor Alternative Approaches to AnimalTesting (EPAA) and Laboratory AnimalsLtd, and also to the lecturers who gave theirtime free of charge.

An alternative method has been approvedfor testing products containing botulinumtoxin. The new procedure will replace thevery controversial LD50 animal test.Botulinum toxin can be used for a range oftherapeutic purposes, but its commonestuse is in anti-wrinkle treatments. Theincreased use of products such as Botox®

has sparked criticism because of the need toassess each batch for potency using themouse LD50 test. LD50 uses death byparalysis and suffocation as its endpointand about 100,000 animals are used eachyear for it.

Since FRAME highlighted the situation in2003, various other organisations,

including the Humane Society of the UnitedStates (HSUS), have joined in efforts toapply the Three Rs to LD50 testing ofbotulinum-based products.

Now Botox manufacturer Allergan hasannounced that it has developed a cell-based alternative potency test, which hasreceived regulatory approval by the USFood and Drug Administration (FDA).

The company has spent $65 million andmore than 10 years on research to developthe new procedure, and expects that withinthree years their animal use for Botoxtesting will be reduced by 95%. Dr MartinStephens, vice-president for animal researchissues for the HSUS, has urged Allergan “to

Training Schools Success

Botulinum Test Newswork with companies that

manufacture products with activeingredients similar to that used in Botox, tosee if the new method can be tailored tothose products, thereby sparing additionalanimals”.

FRAME Chairman of Trustees ProfessorMichael Balls said: “Having spent such alarge amount on the development of thenew procedure, Allergan not only has acommercial advantage, it can claim tooccupy the moral high ground. Will thecompany allow its competitors to use thehighly sensitive cell line it has developed in-house, and if so, on what conditions and atwhat price?”

ATLA’s role in Promoting the Three Rs

Published by FRAME Russell and Burch House, 96–98 North Sherwood Street,Nottingham NG1 4EE

Phone: 0115 958 4740

www.frame.org.uk

E-mail: frame@frame.org.uk

Registered Charity No. 259464

ATLA is FRAME’s scientific journal. Itpromotes the reduction, replacement andrefinement of animals in medical andscientific research, education, and safetytesting in a number of ways:

by raising awareness of the issues

ATLA’s Editorial and the Comment articleshighlight potential problems and suggestways of overcoming them. FRAME’sresponse to the EU Commission’s DraftReport on Alternative (Non-animal)Methods for Cosmetics Testing: CurrentStatus and Future Prospects — 2010 wasput forward as a Comment. Its relevance tothe necessary testing of cosmetics forreproductive toxicity was featured in anEditorial.

by publishing results of fundamentalresearch and development of alternativemethods

Eventual implementation of alternativemethods begins in the laboratory, wherethey are developed and performance-tested.ATLA recently featured an article ondevelopment of a model based on in vitrouse of pig nasal tissue to test metal surgicalimplants. Another report described thedesign of an apparatus to mimic howaerosol-based medicines are deposited onairway cells. This apparatus will be useful indeveloping and testing improved drugs ofthis type.

by reporting outcomes andrecommendations from Workshops andExpert Meetings

In these collaborative meetings, a range ofexperts from different fields, as well asproduct manufacturers, safety regulatorsetc., identify relevant issues and problems— and then collate a list ofrecommendations for the way forward.ATLA published the two reports of theEuropean Centre for the Validation ofAlternative Methods Skin Irritation TaskForce, in 1998 and2002. This TaskForce organised thevalidation ofalternative methodsfor acute skinirritation testing.

by supportingvalidation studiesto allow alternative methods to be used intesting for regulatory purposes

Alternative methods cannot be used to

replace animals in regulatory testing withoutbeing validated. A number of studies mustbe perfomed under strictly controlledconditions, to confirm that the method willgive correct and consistent results withinthe same laboratory and in otherlaboratories. In 2005 and 2007, ATLAhelped publish validation results of asuccessful non-animal alternative to the 4-hour rabbit skin-patch test, which involvessubstances being left in contact with therabbit’s shaved skin. The non-animalalternative is an artificial skin model, whichwas validated in the EU in 2007.

by providing examples of successful use ofexisting alternative methods

Methods can be used in research or foreducational purposes. ATLA recentlyshowed how use of a cheap and simplemodel to teach vein cannulation toveterinary students greatly increased theirsuccess rate in mastering the technique.This model reduces the need to practise theprocedure on anaesthetised, living animals.A recent review paper described how invitro methods can be used to investigatehow cancer develops, as well as to testsubstances for their carcinogenic potential.

by publicising national and internationalconferences, training courses andworkshops

ATLA features a regular Conference Diary,as well as News and Views from theInstitute for In Vitro Sciences (IIVS, in theUSA), the European Centre for theValidation of Alternative Methods(ECVAM, in Italy), and the European armof the Johns Hopkins University Center forAlternatives to Animal Testing (CAAT).

by informing the international scientificcommunity about the use of Three Rs(reduction, refinement and replacement)alternatives in other countries

Through ATLA, international authors caninform the rest of the worldabout current legislation andways in which Three Rsprinciples are promoted (orrejected) by scientists in theircountry. Chinese, Brazilian,Russian and Korean authors,among others, have made useof this information channel.

by valuing research into alternatives

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

FRAME is dedicated to thedevelopment of new and validmethods that will replace the needfor laboratory animals in medical andscientific research, education, andtesting.

Where the use of animals is currentlynecessary, FRAME supports thereduction of numbers involved to anunavoidable minimum and refinementof the experimental procedures tominimise any suffering caused.

FRAME relies entirely on grants anddonations to carry out its vital workpromoting the development of newand valid methods that will replacethe need for laboratory animals inmedical and scientific research,education, and testing.

It receives no financial support fromlocal or central government so anygifts from supporters, eitherindividuals or companies, are alwaysgladly received.

As an independent charity, FRAMEwelcomes any donation, howeversmall, either from individuals orcompanies.

FRAME’s ultimate aim is theelimination of the need to uselaboratory animals in any kindof medical or scientificprocedure.