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Use of Animals in Research: A Science - Society Controversy?The American Perspective: Animal Welfare Issues*

Alan M. GoldbergCenter for Alternatives to Animal Testing, Johns Hopkins University, Bloomberg School of Public Health, USA-Baltimore* Presentation at a symposium "Use of animals in research: a science - society controversy?" held by the Doerenkamp-Zbinden-Foundationon March 12 in D-Mainz. This presentation will also be published in an ALTEX-book in print.

SummaryMy paper will focus on those events happening within theUnited States during the last year.The issue of including or excluding rats, birds and mice frominclusion under the Animal Welfare Act has been a difficultbattle for both those that wish to exclude them and those thatwish to include these animals under this legislation. As of thewriting ofthis abstract, the Senate, which originally intended toinclude rats, birds and mice under the Animal Welfare Act, haspassed an amendment which will permanently exclude theirlisting under this Act.During the last several years it has become clear thatrefinement, as one of the 3Rs, has and will become the mostimportant set of activities to add humanness to animal experi-mentation. It is clear that refinement approaches provide theopportunity to possibly eliminate or significantly minimize anypa in or distress in animal protocol. My presentation will focuson CAAT's (http://caat.jhsph.edu) activities in this importantarea.Understanding potential health hazards to environmentalindustrial chemieals has become a major focus of activity bothin the US, Europe and Japan. These programs offer the firstopportunity to provide information, in the public domain, onthese chemicals. One of the consequences, however, is thepotential requirement for large numbers of animals. In thepresentation, I will focus on two approaches to significantlyincluding the 3Rs in these important programs.Although it is common practice in Japan to recognize contribu-tions of laboratory animals through a day of memorialization,this has not been the case in the United States. During the lastyear, several activities have been initiated to begin to institu-tionalize memorial services for animals used in research.As the host institution of Altweb (http://altweb.jhsph.edu), thealternative web site internationally, current statistics andaccomplishments will be provided on its worldwide utilization.

Zusammenfassung: Die Verwendung von Tieren in der For-schung: Kontroverse zwischen Wissenschaft und Gesellschaft?Die amerikanische Perspektive: Fragen des TierschutzesDas Manuskript beschränkt sich auf Ereignisse in den Ver-einigten Staaten im vergangenen Jahr.Die Frage, ob Ratten, Vögel und Mäuse von der Tierschutzge-setzgebung ein- oder ausgeschlossen sein sollen, war einschwieriges Thema für beide Seiten: sowohl für diejenigen,welche den Ausschluss verlangten als auch für diejenigen, dieeine Erfassung durch das Tierschutzgesetz wünschten. Währendich diese Zusammenfassung schreibe, hat der Senat, der ur-sprünglich dazu tendierte, Ratten, Vögel und Mäuse in die Tier-schutzgesetzgebung aufzunehmen, einen Artikel verabschiedet,der die Aufiistung dieser Tiere für immer ausschliesst.Während der letzten paar Jahre wurde es immer klarer, dass mitdem Refinement, einem der 3Rs, die wichtigsten Anstrengungenunternommen wurden und werden, um mehr Humanität in denTierversuch zu bringen. Es wird klar, dass sich mit Refinement-Massnahmen die Möglichkeit ergibt, Schmerzen und Leiden imTierversuch signifikant zu minimieren oder möglicherweiseganz auszuschliessen. Auf die Aktivitäten des CAAT soll hier indiesem Zusammenhang besonders eingegangen werden(http://caat.jhsph.edu).Sowohl in den Vereinigten Staaten und Europa als auch in Japanwird nunmehr das Hauptaugenmerk auf die Kenntnis vonmöglichen Gesundheitsrisiken durch Industriechemikalien in derUmwelt gerichtet. Entsprechende Programme bieten erstmals dieGelegenheit, der Öffentlichkeit Informationen über dieseChemikalien zu geben. Eine der Konsequenzen daraus ist aller-dings der mögliche Bedarf an grossen Tierzahlen. Ich will hierauf zwei Versuche hinweisen, mit denen es gelingen sollte, 3R-Methoden ganz wesentlich in diese Programme zu integrieren.In Japan ist es ein guter Brauch, den von Versuchstieren geleis-teten Beitrag durch einen Gedenktag anzuerkennen, in denVereinigten Staaten ist dies nicht der Fall. Im letzten Jahr wur-den einige Initiativen in die Wege geleitet, um der Versuchstierein der Forschung zu gedenken.Als Gastgeber von Altweb (http://altweb.jhsph.edu), der inter-nationalen Website für Alternativmethoden, werde ichschliesslich noch neueste Statistiken und Angaben zu ihremweltweiten Gebrauch präsentieren.

Keywords: animal welfare act, refinement, toxic ignorance, memorial services, altweb

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1 Introduction

I am very pleased to have the opportunityto share with you an American perspec-tive on the animal research controversy.To have a controversy, one needs at leasttwo different opinions. In this case, theviewpoint of the public, inc1uding boththe lay public and the animal protectionmovement, stands in contrast - thoughnot necessarily in conftict - with that ofthe scientific community.

For the general public, the key issue isthe pain and distress that researchanimals may experience. Animal protec-tionist may be more concerned withe1iminating of the use of animals inresearch, and with the accountability forthose animals that are used. For seien-tists, the animal issue produces a moraldilemma. They know that an im als are,unfortunately, essential to biomedicalresearch; at the same time, many wouldprefer not to use animals.

In poll after poll, if one asks the public,"do you support the use of animals inbiomedical research?" somewherebetween 75 and 80% of the populationanswers in the affirmative. However, ifyou change the question to, "do yousupport the use of animals in biomedicalresearch, even though the animal willexperience pain and/or distress?" thenthe number that supports this researchdrops below 50%.

Thus, the public cares about animalsbut recognizes that their use is necessary.Ethicist Strahan Donnelly has referred tothis group as "the troubled middle."Scientists also want to see the practice ofresearch under the most humane condi-tions, but they tend to remain silent onthis issue. I refer to this group as "thesilent middle." But note the conftuencebetween the public and the scientist -both are concerned with the practice ofhumane science.

2 Rats, mice and birds

In the United States, animal use isgoverned by two sets of laws, the AnimalWelfare Act, administered through theDepartment of Agriculture, and thePublic Health Service laws administeredby the Department of Health and Human

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Services. Although there are c1ear simi-larities between these laws, there are alsosome significant differences. The AnimalWelfare Act, which inc1udes, amongother things, unannounced inspections,has exc1uded from this regulation rats,mice and birds, even though theseanimals make up at least 85-90% of allanimals used in biomedical research (seeTab. 1).

The issue of inc1uding or exc1udingrats, mice and birds from coverage underthe Animal Welfare Act has been a longbattle between the animal protectionmovement and representatives ofthe scientific community (the researchdefense lobby).

A 1970 amendment to the AnimalWelfare Act (originally passed in 1966)gave a defining list of animals to becovered by the act; rats, mice, and birdswould be inc1uded among the "otherwarm-blooded animat(s)." When the lawwas implemented, however, the Depart-ment of Agriculture indicated it did nothave the resources to inc1ude all species,and thus rats, mice and birds wereexcJuded from the list of animals protect-ed by the AWA.

The animal protection world hasattempted through various means to haverats, mice and birds inc1uded, and onegroup reached an out of court settlementwith the U.S. Department of Agriculturethat would have started the process.However, in 2002, U.S. Senator JesseHelms attached a rider to a farm bill thatwould permanently excJude rats, miceand birds from coverage under the Ani-mal Welfare Act. At the time of this sym-posium, the bill had passed the Senateand was to be voted on in the House.Thus, at the writing of this manuscript,

Tab. 1: Rats, Birds and Mice

• Senator Bob Dole indicates AWA wasto include rats, birds and mice

• NAS - holds meeting - Europeansshocked at American scientific position

• Netherlands points out animals haveintrinsic value

• CAAT letter - re: Rats, Mice & Birds

• USDA - can discuss rulemaking, butcannot finalize

• Helms amendment

rats, mice and birds are not consideredanimals under the law. The battle willcontinue.

3 Refinement

Until recently, refinement often seemedthe forgotten alternative among the 3Rs.Over the past several years, however,refinement has become increasinglyimportant as a way of making animalexperimentation more humane. Refine-ment approaches provide a c1earopportunity to eliminate, or at least tominimize, any pain or distress in animalexperimental protocols.

Refinement can take many shapes, fromanimal welfare issues, such asenvironmental enrichment, to non-inva-sive methcidologies for the study of ani-mal biology. Non-invasive technologiesoffer great possibilities for developingmore humane research protocols, andsuch techniques warrant further explo-ration. Refinement approaches can helpform a common ground uniting the laypublic, animal welfare (not animal rights)advocates, and the scientific community.

This year we initiated 4 grants, as asingle project, dedicated to refinement.Details can be found on the CAAT's webpages (http://caat.jhsph.edu). As far aswe know, this is the only group of refine-ment projects coordinated as a singleprogram (see Tab. 2).

4 Toxic ignorance

In the middle 1980s, the National Acade-my of Seiences published a study demon-strating a serious lack of public1y avail-able knowledge on ehernieals in theenvironment - public information wasavailable for less than 20% of all chemi-cals. That seemed inconceivable. But inthe late 1990s, a study by the Environ-mental Defense Fund, called "ToxicIgnorance," confirmed this finding. Inde-pendent studies by the EnvironmentalProtection Agency (EPA) and the Ameri-can Chemistry Council (ACC) furtherconfirmed that the available public litera-ture provided adequate knowledge to dohazard evaluation for only 10-20% ofchemieals in the environment.

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Tab. 2: CAAT Refinement ProgramProjectGrantee/Research Topics

• Bert van Zutphen, Utrecht University,The NetherlandsMeasures to Reduce Stress Caused byExperimental Procedures

• Clifford Roberts, University of California,San FranciscoDifferential Effects of EnvironmentalEnrichment for Mice

• Alicia Z. Karas, Tufts UniversityReducing Postoperative Pain andDistress in Mice

• Norman C. Peterson, Johns HopkinsUniversityGenomic Approaches to Defining Painand Distress in Mice

In the United States, the outcome ofthese studies resulted in specific programsknown as the "High Production VolumeChallenge", "Endocrine Disruptors","Child Health Initiative", among others.In Europe, there was a white paper, and the"REACH" program was established.

In both cases, over the next severalyears somewhere between 30,000 chemi-cals (EU) and 80,000 chemieals (USA)are to be evaluated for their human andanimal safety concerns, as weil as forenvironmental effects.

Here again, opinions differ among thevarious interested groups. The animalprotection movement has suggested thatthis information may not actually be neces-sary. If it is necessary, they argue, it shouldbe collected entirely through non-animalmethods. The environmental movement, asweIl as the scientific and regulatory com-munities, on the other hand, all concur thatthe data is both necessary and appropriate.They would like to see as much of it aspossible obtained with in vitro and, whennecessary, the use of non-invasive methodsand other humane protocols.

Again, application of the 3Rs can go along way to address the concerns of thesevarious groups - the lay public, the ani-mal protection movement (or much of it,at least), and the scientific, regulatory andindustrial communities. That is the goalof the TestSmart Program, developed toprovide a humane and efficient approachto gathering regulatory toxicologicaldata. In the case of high production

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volume chemicals, TestSmart helpedbring about an 80% reduction in theestimated number of animals needed fortesting, while still meeting all the require-ments of the OECD test battery.

Proceedings from several TestSmartmeetings (including workshops devotedto endocrine disruptors and to pharma-ceuticals, as well as to high productionvolume chemicals) are available on theCAAT web site.

5 Memorial services: A functionof animal care committees?

Ethical committees (EU) and institutionalanimal care and use committees (IACUC,USA) function in strikingly differentways. In the EU, ethical committeesevaluate the harm to the animals againstthe benefits to society. Thus some EUcountries have eliminated the use of greatapes as research subjects, on the groundsthat no experimental protocol is worth theharm to the great apes.

In the US, the IACUCs representsocietal concern for animals. Here thequestion at issue is, are the experimentalprotocols as humane as they can be?The review committee cannot change theexperimental design. IACUC memberscan comment on the humaneness of theapproach and suggest how to make thatapproach as humane as possible.

In Japan, it is a common practice torecognize the contribution of laboratoryanimals through a day associated with amemorial service. Until recently, this hasnot been the case in the United States.Over the past few years, a number of U.S.institutions have initiated memorialservices or recognition programs for theanimals used in research.

The development of memorial servicesdemonstrates the care, the concern, andthe emotional ties that scientists and lab-oratory animal technicians have towardthe animals that are used in biomedicalresearch.

6 Johns Hopkins Center for Alter-natives to Animal Testing (CAAT)

This Center was established over 20 yearsaga to advance humane science. CAAT

has three main programs. Our researchgrants program provides funding in sup-port of the development of cell culturesystems and methods, as well as "pro-gram projects" on corneal wound healingand on refinement.

Through the information program,CAAT communicates with the public andthe scientific community through a varietyof printed publications and 2 major websites, including Altweb (hup://altweb.jhsph.edu), a clearinghouse for resources,information, and news of the 3Rs. CAATmanages Altweb on behalf of an interna-tional, multi-organizational project team.

The outreach program serves to pro-mote the development, validation, anduse of alternative methods throughregular workshops, consortia, and confer-ences - typically between two and threemeetings a year. TestSmart, discussedabove, provides a way for us to focus ourattention on forums and workshops thatare highly targeted on regulatory issueswith an outcome that allows the incorpo-ration of humane science into regulatoryrequirements.

Associated with the Center and in-volved in these programs are facultieswhose full-time appointments are at theJohns Hopkins University (or HowardUniversity, in one case). Their areas ofexpertise include laboratory animalsciences (comparative medicine), law,policy, toxicology, and risk assessment.A list of CAAT faculties and their vitaemay be found on the CAAT web site.

7 ConcIusions

Once we understand that the issue pain anddistress is the central concern for most ofthe lay public AND for the scientific com-munity, we have the opportunity to bringtogether the "troubled middle" and the"silent middle" and truly find a commonground.

Correspondence toProf. Alan M. GoldbergThe Johns Hopkins UniversityBloomberg School of Public HealthUSA -BaltimoreTel.: + 1-410- 223-1692Fax: +1-410-223-1603

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