FRAME News 70

FRAME News Fund for the Replacement of Animals in Medical Experiments Editor: Anne Jeffery No. 70 April 2013

One of the reasons for the increasingnumber of potential drugs that fail humantrials is the inability of animal tests tomake accurate predictions aboutidiosyncratic responses in patients.Professor Michael Balls said “This is partlybecause the animal models used in testingstrategies are not sufficiently closelyrelated to what is being modelled, andtherefore cannot be expected to provide asufficiently relevant or reliable basis formaking important decisions.

Yet many companies still cling to animalmethods as the gold standard. “Parts of theindustry remain intent on defending thecontinued use of animal models at almostany cost, whilst seeming to be reluctant torestrict the use of animal procedures toselected, specifically-justifiable circum -stances and to make a more enthusiasticcommitment to the development, validationand application of replacement alternativetests and strategies of direct relevance tohumans and their diseases.”

Professor Balls praises the role of the IMI(Innovative Medicines Initiative) inspeeding up the development of betterand safer medicines by supportingcollaborative, multi-centre, internationalresearch projects. IMI Executive Director,Professor Michel Goldman, delivered theFRAME Annual Lecture in 2012. Readmore on page 2.

The full ATLA editorial is available on theFRAME website at http://www.frame.org.uk/page.php?pg_id=19

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

FRAME has called on thepharmaceutical industry to placemore emphasis on human-focused drug development andtesting. In an editorial inFRAME’s scientific journal ATLA(Alternatives to LaboratoryAnimals) Professor MichaelBalls, Chairman of the FRAMETrustees, acknowledges thechallenges faced by the industry,but says too many companiesstill rely on animal–basedmethods.

He says: “Unlike most otherchemicals and chemicalproducts, medicines aredesigned to be deliberatelytaken into the body, there toexert powerful effects on cells,organs and systems. Given thecomplexity of the body and itscontrol systems, it is notsurprising that they can alsoinduce adverse and seriousside-effects.”

FRAME and thePharmaceuticalIndustry INSIDE...

FRAME Annual Lecture 2

New FRAME trustee 3

PiLAS success

Consultation on HO guidance 4

Online Veterinary AnatomyMuseum launched

Public attitudes to animal 5research

FRAME speakers at international conference

Free access to early issues 6of ATLA

FRAME publishes keyworkshop proceedings

New text book on implant 7dentistry

FRAME assists with testing protocols

FAL PhD Students 8

More training school success 9

Estimating the impact of 10Three Rs research

How does influenza spread?

NIH retires research chimps 11

Heart disease in captive apes

Cost and benefits of animalexperiments

News in brief 12

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

The 14th Annual Lecture was delivered byProfessor Michel Goldman, ExecutiveDirector of the Innovative MedicinesInitiative (IMI), Brussels, Belgium, and wasentitled “New approaches to assess drugsafety through public–privatepartnerships” (PPPs).

The IMI is Europe’s largest public–privatepartnership. A joint undertaking betweenthe European Union and the EuropeanFederation of Pharmaceutical Industriesand Associations (EFPIA), its mission is toimprove the drug development process bysupporting the more-efficient discoveryand development of better and safermedicines.

Professor Goldman leads his staff inbuilding and promoting networks ofinnovation, in close collaboration withmany stakeholders involved inpharmaceutical research and development,to foster the development of more-effective and safer therapies for patientsacross Europe.

In his speech he explained how animalmodels are still widely used to assess theefficacy or safety of new pharmaceutical

products, in spite of their limitations inpredicting actions of drugs inhumans. He said there is anurgent need to revisit the use ofanimals in pharmaceuticalresearch, and discussed some ofthe projects currently beingoverseen by the IMI.

They include several initiativesdesigned to overcome the failureof testing methods currently usedto predict adverse effects of newdrugs. Such variations can lead toincreased costs, delays in thedevelopment of safe, newpharmaceutical products, andeven to their withdrawal aftertheir acceptance for use inpatients.

He and colleagues have alsocontributed an article toFRAME’s scientific journal ATLA(Alternatives to LaboratoryAnimals) giving details of theprojects currently under waythrough IMI initiatives. It says:“In an era of increasing economicpressure on the healthcare

systems and the pharmaceutical industry,public–private partnerships offer uniqueopportunities to overcome the hurdleswhich prevent efficient and safe medicinesfrom reaching patients suffering fromdebilitating diseases.“With increased attention paid toinvestigations centred on human beings,human materials, or based on in vitro andin silico models, PPPs like the IMIcontribute to rationalising the use ofanimals in biomedical research, byfocusing on validated models directlypertinent to drug action in humanpatients.”

The FRAME Annual Lecture/

The Bill Annett Lecture

Every year FRAME holds its annual lecture, featuring thelatest developments in the field of the Three Rs. Speakers aregathered from leading institutions and organisations

concerned with the implementation of Replacement, Reduction andRefinement. The lecture was introduced to give an opportunity forall parties interested in the Three Rs to hear developments in thealternatives field.

Scientists, business people, government officials and FRAMEsupporters get together annually to share their ideas. The lecture isalways well received by its invited audience. In 2005 the lecturewas renamed to commemorate the life of Bill Annett, who servedas a FRAME consultant for many years and died, aged 92, whilestill working on behalf of the charity. Since then the lecture hascarried both titles. The 2012 lecture was held at the Kennel Clubin London and attended by more than 50 people.

The full text can be found athttp://www.

frame.org.uk/page.php?pg_id=19

Professor

Michel

Goldman

The late BillAnnett

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

She graduated from the University of St Andrews in1987 with a first class BSc in physiology andpharmacology and stayed there to study for a PhD inneuropharmacology.

As a post doctoral researcher she moved toNottingham to work with Professor CharlesMarsden, and FRAME Trustee Professor DavidKendall. She was studying the action of a type ofanti-depressant called SSRI (selective serotoninreuptake inhibitors).

She remained in Nottingham to complete a projectstudying the central cannabinoid receptor, a part ofthe nervous system that controls the body’sreaction to plant substances such as THC, the activeingredient of cannabis.

She now lives in Scotland and is marriedwith two children. While bringing up herfamily she has remained busy with charitywork. She also took an MSc in ForensicScience at the University of Strathclyde in2009–10.

She said: “I am well aware of the limitationsof animal models that are used in scientificresearch and the potential benefits of usingcell culture work, having been involved inboth at Nottingham.

“I thoroughly applaud FRAME’scommitment to its Three Rs policy and amdelighted to become a Trustee for theCharity.”Professor Michael Balls, Chairman of theFRAME Trustees, said: “We are very pleasedto have Anna join us.”

N E W FRAMETrustee

FRAME’s new publication PiLAS(Perspectives in Laboratory AnimalScience) has proved popular with itsreaders. PiLAS appears both as asupplement to the scientific journal ATLA(Alternatives to Laboratory Animals) andas a free access website at

www.atla.org.uk.

Its aim is to offer bio-scientists anopportunity to share their expertise,knowledge and ideas concerning issuesraised by laboratory animal use andthereby improve the quality of discussionabout the topic, and about alternativemethods.

PiLAS articles are currently aimed mainlyat the field of veterinary science, becauseof the key role played by the profession inthe care and use of laboratory animals,although it is also attracting readers fromother areas.

Feedback has been very positive andFRAME has already made someadjustments in response to readers’requests. For example, the website nowhas an RSS feed, so people can find outimmediately when updates are made.

The project has been well received inmany areas and messages of supporthave been sent by several leading figuresincluding FRAME Patron Professor DavidGreenaway of the University of

Nottingham, Nic Dakin MP, Chair of theParliamentary All-Party Group onReplacement of Animals inExperimentation, Cleo Paskal, LiteraryExecutor of Bill and Claire Russell, andDr Jane Goodall, Founder of the JaneGoodall Institute and UN Messenger ofPeace.

The publication has six sections:Opinions, Current Dilemmas, Discussions,The Wisdom of Russell and Burch, Pointsof View, and News. Comments andfeedback are welcomed on any of thearticles, or on the publication as a whole.

PiLAS has been made possible by a grantfrom the Phoebe Wortley Talbot CharitableTrust.

PiLAS Success

Taking Veterinary Anatomy Online

Gemma Gaitskell-Phillips, Nick Short and Bara Stanikova

The Online Veterinary Anatomy Museum (OVAM) website

will help to change anatomy teaching

and the way students learn

DISCUSSIONS

The Online Veterinary Anatomy Museum (OVAM) site1

aims to provide open access to a carefully selected,

comprehensive and pedagogically-structured set of

veterinary anatomical resources, closely linked to the

WikiVet project.2 Funding for the project start-up

during the official time-frame was provided by JISC,3

as part of the Content Programme 2011–2013. The

OVAM site was officially launched on 20 November

2012.The online museum currently involves a consortium

of 20 partners from around the world (including vet-

erinary schools and publishing houses), each contribut-

ing resources that have been aggregated and ordered

into a readily-searchable environment — making them

easily discoverable by different cohorts of learners. A

student e-curator from each partner school was

responsible for a project of his/her choice, working

alongside an academic and cataloguing all the available

resources. The structure of this virtual museum mirrors the con-

ventional model, with a ‘backroom stack’, display

‘cabinets’ and student ‘curators’. The interface design

P24

ATLA 40, P24–P25, 2012

Interactive Real 3D Anatomy: Canine Skeleton (University of Bristol, UK;

http://www.real3danatomy.com/bones/dogskeleton3d.html)

FRAME hasappointed a newTrustee.

Dr Anna Cadoganis a specialist inneuropharmacology.

The Home Office has produced aGuidance document for researchers tohelp them with the changes, and has askedinterested bodies such as FRAME for theirviews.

The Guidance follows on from a ‘quickstart’ guide issued last December, andgoes into more detail about how ASPAwas affected when the Directive wastransposed into UK law in January.

It offers advice on what the revised ASPAcovers, and provides guidance on severity

classification, humane killing and theaccommodation and care of animals. It isaimed at holders of establishment licences,project licences and personal licences, andnew licence applicants.

Responses to the consultation wererequested by mid-March and a reviseddraft, based on those comments, will besent to the new Animal Science Commitee,then on to Parliament for approval. Oncepassed, the regulations will immediatelybecome effective.


FRAME has welcomed some changes to

the Guidance. There has been an

improvement on how the document is

laid out and worded. FRAME’s Scientific

Programme Manager Michelle Hudson-

Shore said: “It is much clearer and the

structure is better. It should make it

much easier for researchers to

understand and implement the

regulations.”

The new law requires re-authorisation for

some activities and use of some types of

animal, and the transitional guide sets out

details of those amendments. For example,

all cephalopods (octopus, squid, cuttlefish

and nautilus) are now protected. Under

the old regulations only Octopus vulgariswas included.

The new rules also increase control over

breeding of some frog species and zebra

fish. Increased use of fish in regulatory

testing accounted for a significant rise in

the number of animals used for

toxicology (safety testing) in the last

Home Office statistics on the use of

animals in laboratories in the UK.

Consultation onHO Guidance

An Online Veterinary Anatomy Museum(OVAM) has been launched in a bid toshare resources and provide a centralpoint for information searching.

It aims to offer open access to a compre -hensive collection of data from universitiesand veterinary schools worldwide.

The site says: “The teaching of anatomy inveterinary schools around the worldshares many commonapproaches.

“Whilst textbooks are stillwidely used, there is a move tocreating online teachingresources which can often bemore visually effective andengaging. As a result manyschools are creating their ownmaterials, often duplicating

things that colleagues in other locationsare also producing.”

The online museum currently involves aconsortium of 20 partners from aroundthe world, including veterinary schoolsand publishing houses. Each partner hascontributed resources that have been

aggregated and ordered, making themeasily discoverable by learners.

The collection is organised into categoriesaccording to the species, system andregion covered. The project is a work inprogress and new resources are constantlybeing added.

Online Veterinary AnatomyMuseum Launched

Once again FRAME has responded to consultation by the HomeOffice on new regulations connected with the Animals (ScientificProcedures) Act 1986 (ASPA). An amended version of the Acthas been introduced to align UK legislation with EuropeanDirective 2010/63/EU.

www.onlineveterinaryanatomy.net

Participants were presented with a range ofresearch scenarios related to creation ofanimal models to investigate skin cancer.The variables were species used, methodof inducing genetic modification, and levelof regulation of the research.

The results showed that biomedicalprocedures were acceptable as long asanimal welfare concerns were taken intoconsideration. Methods that wereperceived as painful were equallyunsupported, regardless of species.

The report says: “This result calls intoquestion the assumption that researchdeemed to cause pain will be consideredmore acceptable if performed on ‘lower’

A study of attitudes toward animal use inlaboratories has called for betterinformation to be made available to thepublic in a bid to reduce the gap betweenscientific practice and societal opinions.

Researchers from the Animal WelfareProgram at the University of BritishColumbia in Vancouver, Canada, used anonline survey to establish publicacceptance of the use of mice andzebrafish in experiments. Their findingshave been published in ATLA (Alternativesto Laboratory Animals), FRAME’sscientific journal.

The team found that public attitudes rangefrom a desire for total abolition of animalexperiments to strong support for them.Views were influenced by a number offactors, including age, gender and nationality. They were also affected bythe animal’s characteristics, perception ofsentience, and the level of invasiveness ofthe technique.

Public Attitudes to Animal Research


species such as fish. Greater effort may berequired to inform the public aboutscientific practice and to permit feedbackthrough public engagement, to reduce thegaps between common scientific practiceand societal values.”

The full text can be found in: Elisabeth H.Ormandy, Catherine A. Schuppli & DanielM. Weary. Factors Affecting People’sAcceptance of the Use of Zebrafish andMice in Research. ATLA 40, 321–333,2012.

lectures from ProfessorMarc Bekoff, ProfessorEmeritus of Ecology andEvolutionary Biology atthe University ofColorado, Boulder, USA,and Professor HorstSpielmann, adjunctprofessor at FreieUniversität Berlin, andEuropean Editor ofFRAME’s scientific journalATLA (Alternatives toLaboratory Animals).

Director of the FRAME AlternativesLaboratory (FAL) Dr Andrew Bennett gavea talk on the laboratory’s history andresearch at an international conference.

Dr Bennett was invited to speak at thePortuguese Society for Humane Education(SPEdH) first International Conference ofAlternatives to Animal Experimentation, atRomeu Correia Municipal Forum inAlmada, Portugal.

The conference included 17 internationalspeakers from several different fields ofalternatives to the use of animal methodsin research and education, with keynote

FRAME Speakers at InternationalConference

Andrew

Bennett

Horst Spielmann


past issues, in line with developments inmany fields of science.

The most recent two volumes willstill be subscription-only, buteverything from 2010 and beforecan now be accessed through theFRAME website, free of charge.That is, volume 38 and earlier.

Abstracts from all articles arealready free to view and somecurrent articles are also availableat no charge, such as editorialsand comments, news and views,as well as proceedings ofscientific meetings.

To download past articles, visitwww.frame.org.uk and follow the linksfrom the left-hand column.

You can register to receive email updateswhen a new issue of ATLA becomesavailable. Simply sign up to our electronicnewsletter. Details of how to opt-in can befound on the back page of this copy ofFRAME News.

One of FRAME’s aims is to disseminateinformation about the Three Rs as widelyas possible. As part of that intention itpublishes the scientific journal ATLA(Alternatives to Laboratory Animals).

ATLA is a peer-review scientificpublication, with an international editorialboard, that provides articles on the latestresearch relating to the development,validation, introduction and use ofalternatives to laboratory animals.

It also reports on the latest news andevents, reviews publications and products,and lists a selection of the most significantrecent research papers. Established almost40 years ago, it is published six times ayear and circulated in more than 50countries worldwide.

For some years ATLA has been availableboth as a print publication and as anonline resource with downloadable pdfcopies of articles.

Now it has been decided to give ATLA aneven wider reach by allowing free access to

Free Access to Early Issues of ATLA

FRAME has published the proceedings ofa workshop aimed at developing computermodels to replace animal tests inenvironmental hazard assessment.

The Second CADASTER Workshop (CaseStudies on the Development andApplication of In Silico Techniques forEnvironmental Hazard and RiskAssessment) took place over three days inMunich, Germany.

The event provided information andassistance to those interested indeveloping new models to assessendpoints required in the REACH(Registration, Evaluation, Authorisationand restriction of CHemicals) system,

FRAME Publishes KeyWorkshop Proceedings

which was introduced by the EU toconsolidate and harmonise testingcarried out on new and pre-existingchemicals.

The regulations advocate the use ofnon-animal testing methods, but noguidance is given on how they shouldbe used. CADASTER aims tocontribute to the guidance.

The workshop includedpresentations, lectures and casestudies as well as practical trainingand demonstration of computationaland other models. The proceedingshave been published in FRAME’sscientific journal ATLA (Alternativesto Laboratory Animals) volume 41.

The articles are available to downloadon free access through the FRAMEwebsite at www.frame.org.uk. Published by:

Fund for the Replacement of Animals in Medical ExperimentsRussell & Burch House, 96–98 North Sherwood StreetNottingham NG1 4EE, UK

ATLAAlternatives To Laboratory Animals

Volume 41

Number 1

March 2013

IN THIS ISSUE

EDITORIAL

Computational toxicology is now in-separable from experimental toxicology

CADASTER WORKSHOP PROCEEDINGS

Species sensitivity distributionestimation from uncertain (QSAR-based) effects data

From descriptors to predictedproperties: experimental design byusing applicability domainestimation

Evaluation of CADASTER QSARmodels for the aquatic toxicity of(benzo)triazoles and prioritisationby consensus prediction

Experimental assessment of theenvironmental fate and effects oftriazoles and benzotriazole

Read-across estimates of aquatictoxicity for selected fragrances

Arguments for consideringuncertainty in QSAR predictions inhazard and risk assessments

Uncertainty in QSAR predictions

Prioritisation of polybrominateddiphenyl ethers (PBDEs) by usingthe QSPR-THESAURUS web tool

Principal components of a data set on descriptors (top) andpredicted properties (bottom)

–20

4

2

0

–2

–4

–6

–8

–10

4

2

0

–2

–4

–15 –10 –5 0

DRAGON

dragon

20100–10–20–30 30


FRAME has contributed to a new textbook on major methods andtechniques used in the field of implant dentistry and guided-bone-regeneration research.

The book is aimed at early career students and researchers, and covers avariety of subjects. Chapter topics include basic research approaches, invitro experiments, application of animal models in dental research, imagingtechniques, computer models, biomechanical methods, analytical methodsfor the bone–implant interface, and conducting clinical research.

A chapter on ethics and regulations for the use of laboratory animals, theregulations which govern the manufacture and marketing of chemicals,medicines, medical devices in general, and dental implants in particular, andthe opportunities afforded by new technologies for the replacement ofanimal procedures, has been written by FRAME’s Scientific ProgrammeManager, Michelle Hudson-Shore, and Chairman of the FRAME Trustees,Professor Michael Balls.

Editor Dr Ahmed Ballo is a member of the Department of Biomaterials atSahlgrenska Academy of the Institute of Clinical Science, University ofGothenburg, Sweden. His research interests include applied and clinicalresearch in osseointegration and implant dentistry.

The book came about as the result of a collaboration of internationalclinicians and scientists and is the first of its kind, offering scientific andtechnical information designed to improve the knowledge and technical skillsof professionals in the field of implant dentistry.

FRAME Chapter inNew Text Book onImplant Dentistry

Implant Dentistry Research Guide: Basic, Translationaland Clinical Research is published by Nova SciencePublishers of the United States of America.

The full text of the chapter is available on request [email protected].

Following changes in the official guidelines,FRAME Trustee Dr Richard Clothier ishelping to update in vitro protocols fortoxicity tests that have been validated, andwhich FRAME and the FRAMEAlternatives Laboratory (FAL) wereinvolved with developing.

ECVAM (European Centre for theValidation of Alternative Methods) has adatabase of in vitro tests that have beentested in a number of laboratories or havebeen used in international validation trials.This database was built on the INVITTOXdatabase originally compiled by FRAME,and contains detailed protocols on how toperform and analyse the in vitro non-animal tests, along with a namedexperimenter who can be consulted iffurther guidance is required.

FRAME Assists with Testing ProtocolsECVAM has promoted these tests and a

number of them have been fully

independently reviewed and all the

published data considered such that

internationally acceptable guidelines

could be drawn up.

Dr Clothier is the former Director of

the FAL at the University of

Nottingham. During his tenure, the

FAL helped to develop and modify invitro test models for human eye

irritation based on damage to the

tissue’s barrier function. Due to his

past experience he has been asked to

assist with drawing up the protocols

that are now being accepted by the

Organisation for Economic Co-

operation and Development (OECD).


Richard Maclennan graduated from the University of Sussex witha BSc (Hons) degree in Molecular Medicine. He is currentlyworking for his PhD at the FAL.

His project involves development of a dynamic cell culturesystem that allows cells to retain the characteristics of a humanliver for long periods of time. This could be used in toxicitytesting to identify substances that might cause liver cancer.

Tests currently used to screen for liver tumour development arecarried out on rodents, and often cause pain and stress. Theycan involve dosing the animals with a test compound, or drug,over a period of up to two years, and then examining the liverfor signs of tumour growth.

Richard said: “Results from animal-based tests might nottranslate well to the clinic or the environmental settings in whichsubstances have been shown to perform in completely differentways in rodents and humans.

“The disparity between the data from animal models and humanexposure is a result of fundamental differences in cell signallingand response pathways between rodents and humans. It isimportant to develop human-based systems to tackle humanproblems.”

Louis Brailsford was an undergraduate at the University ofNottingham, where he gained a BSc (Hons) in Biochemistry. Hejoined the FAL in the next academic year, to start a PhDstudying the development of pain associated with osteoarthritis(OA).

OA is a degenerative disease caused by the breakdown of firmflexible cartilage tissue on the surfaces of bones in joints, whichleads to inflammation, pain and bone breakdown. Excess bonereabsorption of the joint surface has been implicated in thedevelopment of OA, and is thought to be a contributing factorto the pain.

Bone breakdown is mediated by a group of cells known asosteoclasts, so lessening their activity could represent anopportunity to treat the causes of OA, and block the source ofpain.

He said: “My research focuses on elucidating the cellularsignalling mechanisms in osteoclast development and activity atthe molecular level, by isolating osteoclast precursors from theblood of human volunteers and culturing these cells in vitro.

“Dissecting the underlying complex signalling networks willallow us to assess the effects of candidate drugs on osteoclastdevelopment and activity. The use of human cells as analternative to animal testing will reduce animal suffering, andbecause the cells are of human origin, will offer the opportunityto develop a much more relevant drug discovery system forosteoarthritic pain in humans.”

FAL PhD Students

The FRAME Alternatives Laboratory (FAL) was founded in 1983 at theUniversity of Nottingham Medical School. It is continuing to discover anddevelop real alternatives to the use of animals in research and testing.

It offers research posts to postgraduate students. Here are details of twowho are currently working there, and their projects.

Louis

Brailsford

Richard

MacLennan


good experimental design and appropriatestatistical analysis. Poorly designed andbadly analysed experiments, which useanimals inefficiently, are unethical and arescientifically unsatisfactory.

Designing experiments to providemaximum information from minimumanimal use needs particular skills, and theFRAME training courses teach researchersthose skills. Attendees are given theopportunity to practise test exercises aswell as ask questions about their ownresearch.

Sessions include discussion of the legaland ethical aspects of implementing theThree Rs and provide practical advice onhow to go about it. There is also trainingin statistical methods and computerprograms that will enable researchers to

handle data more effectively and extract

more information from the data they

gather.

FRAME has held another of itshighly successful trainingschools in experimental design,this time in collaboration withthe University of Nottinghamand NADIR (The Network ofAnimal Disease InfectiologyResearch Facilities).

The four-day event was staged at theUniversity’s Sutton Bonington campus,where the School of Veterinary Medicineand Science is housed. Training sessionswere open to students and researchers atthe vet school as well as participants fromall over Europe and Scandinavia.

The training schools in experimentaldesign and statistics were launched fiveyears ago in order to help scientistscarrying out research on animals toreduce the number they use.

FRAME’s ultimate aim is the elimination ofthe need to use animals in any kind oflaboratory procedures, and it supportsuse of the Three Rs to bring about thatgoal. (See box)

Where replacement is not currentlypossible, it supports reduction of thenumber of animals used. Reduction can beachieved through clearly defined aims,

More Training School Success

Lectures are given by experts in scientificdesign and statistics, who provide theirservices on a voluntary basis. FRAME alsogathers financial support from a numberof sources in a bid to keep the cost todelegates as low as possible and ensurethe maximum number can attend.

Every course also has a social aspect, sodelegates can forge links with scientistsworking in similar fields. Attendees werealso treated to a ghost walk around theold parts of Nottingham city as well asvisiting a historic landmark pub.

The Three RsReplacementReplacement can be defined asmethods or strategies that do notinvolve the use of protected animals inregulated procedures.

Reduction Reduction is the use of appropriateexperimental strategies to ensure theminimum number of animals is used toprovide necessary information of asatisfactory amount and precision, andensuring experiments will not need tobe repeated.

RefinementRefinement means changes in scientificmethods and techniques that minimiseany suffering caused to the animalsinvolved.

The GatewayBuilding

Computertraining

Nottingham’shistoric,landmarkpub

Lectures

Groupdiscussions

A ghost walk inolder parts ofNottingham

A chanceto socialise


organisation so far, and to measure theperformance and efficiency of the fundingprocedure.

It is believed to be the first time that asystematic, quantitative assessment of theimpact of Three Rs project work on thelife sciences has been performed.

Criteria deemed relevant to the surveyincluded reduction in animal numbersused, and reduction in the severity ofprocedures carried out.

The study was carried out by Dr StefanieSchindler, scientific advisor at AnimalfreeResearch (AfR) in Switzerland to mark the25th anniversary of the country’s 3RResearch Foundation (3RRF).

In a report published in 3RRF’s Info-Bulletin she says the Foundation hasinvested 17 million Swiss francs in ThreeRs research projects since 1987.

One of the aims of her study was toexamine the strategy applied by the

Estimating the Impactof Three Rs Research

Between 50–60% of the projects reviewed

included at least some degree of

replacement, but it was very difficult,

particularly with earlier papers, to

establish reliable numbers.

The report says: “It has proved impossible

to gather complete information on a given

project, even though we made use of all

available documentation.”

Even when a project was designed to

provide an immediate replacement from invivo to in vitro methods it was impossible

to establish comparison figures from

before and after the change.

“Since the number of experiments using

the often quicker, easier and cheaper invitro method tends to increase, resulting

numbers of saved animals cannot provide

reliable information.”

very clear — through coughing andsneezing, but it’s what lies beneath thatcough or sneeze which is important. Weneed to know if it’s big particles (largedroplets) or tiny particles (aerosols)which are important in the trans -mission of the virus, as this will affectwhether nursing and medical staffshould wear

Researchers at the University ofNottingham are leading aninvestigation into how the influenzavirus spreads between people.

The Evaluating Modes of InfluenzaTransmission (EMIT) study will administer fluvirus to volunteers in a quarantined setting,enabling scientists to examine in detail how thedisease is transmitted from person to person.

The study is being led by the University’s HealthProtection and Influenza Research Group(HPIRG), which will also coordinate the effortsof the EMIT Consortium, a group of partnersfrom the UK, Australia, Canada and the USA.

The collaborators span multiple disciplinesincluding medicine, epidemiology, infectioncontrol building engineering, aerobiology andmathematical modelling.

HPIRG is led by Professor Jonathan Van-Tam,of the University of Nottingham’s School ofCommunity Health Sciences and the HealthProtection Agency East Midlands.

He said: “People could argue that thetransmission of influenza between humans is

How Does Influenza Spread? A Human Volunteer Study

a simple face mask or a respirator, forinstance, when treating people with thiscondition.

“At first glance, the idea of givingpeople flu sounds unusual, but it’sactually something that has been donefor decades in carefully controlledscientific circumstances using a slightlyweakened virus.

“Scientists regularly give people a well-characterised flu virus to test drugs andvaccines, so we thought why can’t weturn this model on its head and givepeople this flu virus in the same way,but instead of studying treatment, see

how it can be transmitted to other people?”

A review of Three Rs projects has demonstrated howdifficult it is to estimate the number of animal lives savedthrough non-animal research.


BUAV called for the existing ban on theuse of chimpanzees in biomedical researchand testing to be made permanent andlegally binding. There were fears that whenEuropean Directive 2010/63/EU wastransposed into UK law, the ban could berelaxed, as there was a proviso forindividual Member States that they couldbe used in special circumstances.

The UK Government accepted therecommendation, and the use ofchimpanzees is now specifically banned inthe revised Animals (Scientific Procedures)Act.

The American National Institutes ofHealth (NIH) has decided to retiremore than 100 chimpanzees thatwere being held for laboratory useat the New Iberia Research Center.The chimps are to be moved to afederal sanctuary in Louisiana.

Originally, only 10 of the chimps were tobe transferred, but a campaign was carriedout by various animal rights groups in theUSA in a bid to prevent the others beingtransferred to another research facility.

FRAME has a long history of lobbyingagainst the use of great apes for medicalresearch, on both scientific andhumanitarian grounds.

In a joint submission to the CoalitionGovernment last year, FRAME and the

NIH RetiresResearch Chimps

Psychological research has shown thatchimpanzees used in laboratories cansuffer severe and lasting emotional trauma.Even when they are not being subjected toprocedures such as blood testing, biopsyor surgery, they are often kept in crampedconditions, frequently alone, and faceconstant stress from the noise anddisturbance of activities going on aroundthem.

In addition there have been a number ofpublished studies that show chimpanzeestudies have little or no impact on humanhealth or medical advances.

Cost and Benefits of Animal ExperimentsFew ethical issues create as much controversy as invasive experiments on animals and a new book addresses the various opinions.Bioethicist Andrew Knight has set out to provide evidence-based answers to the key question: Is animal experimentation justifiable?

In the book he uses more than a decade of published research, analysis and his experience to tackle the seemingly unbridgeable gulf betweenthose who claim animal experiments are essential for combating human health problems and hazards, and those who say that animal-basedresearch and testing are intrinsically flawed.

The Cost and Benefits of Animal Experiments is published by Palgrave Macmillan, Basingstoke.

A US study has shown that heart disease is asignificant cause of death in many captive apes.

Zoo Atlanta in Georgia, has led the Great Apes Heart Project on behalf ofthe US federal Institute of Museum and Library Services (IMLS). The on-going project aims to identify, diagnose and treat cardiovascular diseases inall four non-human great ape groups: gorillas, orangutans, chimpanzeesand bonobos. More than 50 partners are now involved across the USAand Europe.

The Sunday Times reported that Zoo Atlanta has found that up to 60% ofcaptive apes are likely to develop heart problems. Heart disease was alsosaid to be a significant cause of death in 41% of gorillas, 20% oforangutans, 38% of chimpanzees, and 45% of bonobos. A similar studyon wild apes in Rwanda, Uganda and the Democratic Republic of Congofound only 4% suffered any kind of heart disease.

A recent study by independent pathologists, reported in FRAME’sscientific journal ATLA, found that “the majority of chimpanzees whichdied in laboratories had been suffering from significant chronic or incurabledisease, and most often had multisystem diseases that should have madethem ineligible for future research, on scientific, as well as on ethicalgrounds”.

Heart Disease in Captive Apes

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: [email protected]

Registered Charity No. 259464

FRAME is dedicated to thedevelopment of new and validmethods that will replace the needfor laboratory animals in medicaland scientific research, education,and testing.

Where the use of animals is currentlynecessary, FRAME supports thereduction of numbers involved to anunavoidable minimum andrefinement of the experimentalprocedures to minimise any sufferingcaused.

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.

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.

answers. This is especially serious if animalsare used.

The course is a joint project between theWellcome Trust and the RSPCA and will beheld in May in Cambridge. It aims tointroduce experienced technicians andscientific staff involved with the managementof GM mouse colonies to best practice withrespect to the Three Rs and animal welfare.

Animals in Science Committee

The Home Office is currently recruiting aChair for its new Animals in ScienceCommittee. The new committee has been setup in line with EU Directive 2010/63 andreplaces the former Animal ProceduresCommittee, created in 1987 by the Animals(Scientific Procedures) Act 1986.

Its role is to provide the Home Secretarywith independent advice on issues relating tothe Animals (Scientific Procedures) Act 1986,and changes to it under the new Directive.

Interviews for the position were due to takeplace at the end of March and anannouncement on the appointment isexpected at any time.

New Alternatives Research Centre

A new research centre, the Centre forAlternative Testing and In Vitro Monitoring(CATIM), a European Regional DevelopmentFund Business Technology Centre for theSouth West, has been established at theUniversity of the West of England. CATIM isdedicated to the development of technologiesfor monitoring cells and cell systems. It willoffer state-of-the-art testing facilities andexpertise for businesses, supporting thedevelopment and evaluation of the biocom -patibility and biological potency of newproducts.

New Chair in Animal ReplacementScience

Queen Mary, University of London andthe Dr Hadwen Trust (DHT) for HumaneResearch have announced a joint collabor -ation which will see the world’s first chairdedicated to animal replacement sciencebased within the University’s Blizard Institute.

The DHT funding is made possible by alegacy left to it for this purpose, andrecognises the fact that the Blizard Institutehas been a pioneer in the development of invitro models using human cells and tissues.and in particular, the development of three-dimensional models. Professor Mike Curtis,Director of the Blizard Institute and DeputyVice Principal for Health at Queen Marysaid: “Our aim is to encourage and stimulateresearch and education in animal replacementscience of the highest quality. Areas ofspecial focus will include 3D cell culture, 3Dmodelling and bioinformatics andregenerative medicine with particularemphasis on, but not limited to, diseases ofthe skin and the digestive tract.”

Experimental Design

FRAME will pass on its expertise inexperimental design at a workshop during acourse aimed at researchers who work withlaboratory mice. The workshop will be basedon FRAME’s highly successful trainingschools in experimental design and statistics(see page 9) and will pass on techniques andskills taught there.

The schools are designed to help researchersgain maximum information from theminimum number of animals. When scientistscarry out experiments it is vitally importantthat they are well designed, otherwise theymay waste resources or give the wrong

Join the FRAME emailing listIf you would like to receive regular emails from FRAME simply sign up withMailChimp at http://eepurl.com/hvoVQ . Or visit our website www.frame.org.uk andscroll down the front page to find the link.

All we need is your name and your email address. We promise not to swamp you withmessages and you can opt out at any time. We will only use the information to sendyou news and updates and we will never pass on your details to anyone else.

News in Brief

Documents

FRAME News 70