Australian Rickettsial Reference Laboratory Foundation v Director General, Department of Trade and Investment, Regional Infrastructure and Services
[2013] NSWADT 226
•14 October 2013
Administrative Decisions Tribunal
New South Wales
Medium Neutral Citation: Australian Rickettsial Reference Laboratory Foundation v Director General, Department of Trade and Investment, Regional Infrastructure and Services [2013] NSWADT 226 Hearing dates: 20, 21 & 22 May 2013 Decision date: 14 October 2013 Jurisdiction: General Division Before: Magistrate N Hennessy, Deputy President Decision: The respondent's decision to refuse the applicant's applications to be accredited as an animal research establishment and for a licence to supply guinea pigs for use in connection with the research is affirmed.
Catchwords: MERITS REVIEW - decision to refuse applicant's applications to be accredited as an animal research establishment and for a licence to supply guinea pigs for use in connection with the research - meaning and applicability of code of practice and guidelines - effect on guinea pigs of housing singly in cages of 900cm2 - scientific value of research Legislation Cited: Administrative Decisions Tribunal Act 1997
Animal Research Act 1985
Animal Research Regulation 2010
Interpretation Act 1987Category: Principal judgment Parties: Australian Rickettsial Reference Laboratory Foundation (Applicant)
Director General, Department of Trade and Investment, Regional Infrastructure and Services (Respondent)Representation: Counsel
Mr C Mobellan (Applicant)
Ms N Sharp (Respondent)
Harris and Company (Applicant)
Department of Trade and Investment, Regional Infrastructure and Services (Respondent)
File Number(s): 123246
reasons for decision
Introduction
The Australian Rickettsial Reference Laboratory Foundation (the applicant) wants to do research using guinea pigs to develop a new vaccine for humans against Query Fever (Q fever). The Director General, Department of Trade and Investment, Regional Infrastructure and Services (the respondent) refused the applicant's applications to be accredited as an animal research establishment and for a licence to supply guinea pigs for use in connection with the research. The applicant has applied to the Tribunal for a review of those decisions. This is the first case under the Animal Research Act 1985 (AR Act) to come before the Tribunal.
Until the end of 2012, the applicant was accredited to conduct scientific research on mice. It applied for a new accreditation and licence for guinea pigs but wished to use the same laboratory that it had been using at John Hunter Hospital in Newcastle. The applicant proposed to house the guinea pigs singly in individually ventilated cages of approximately 900 cm2. The cage would contain 'environmental enrichment' including hay for foraging, tunnelling and chewing and a plastic tube for shelter.
As an alternative to being accredited and licensed unconditionally, the applicant proposed that the Tribunal grant accreditation and a licence for a four week pilot study and that the research be assessed again after that time.
At the hearing, the respondent gave three main reasons for its decisions to refuse to licence or accredit the applicant:
(a) guinea pigs should not be housed singly if that can be avoided because they are social animals;
(b) the cage size is too small even for one guinea pig and, in particular, the floor area of 900 cm2 is about half the recommended area; and
(c) the cage has limited 'environmental enrichment' such as hay and tunnels because of the small cage size.
Dr Graves, the applicant's medical director, acknowledged that there are commercially available individually ventilated cages with a floor area of 2,000cm2 that would be suitable for the research. His main objection to using those cages was that they would not fit into the biosafety cabinet that is in the Physical Containment Level 3 (PC3) laboratory at John Hunter Hospital. He also said that if the bigger cages were used there would not be enough room for two people to conduct the research safely. Dr Graves agreed that the design of the experiment did not prevent guinea pigs being housed together. But he said that the size of the cages means that only one animal can be housed in each cage.
The AR Act, the code of practice made under that Act and the guidelines regulate the housing of animals used in scientific research. One of the principles in the code is "refinement of techniques used to reduce the adverse impact on animals". An aspect of "refinement" is that the design and management of the accommodation must meet the species-specific needs of the animal. If it is necessary for the purpose of the research or if the predicted scientific value of the research justifies it, an applicant may be accredited and/or licensed despite the fact that the species-specific needs of the animal will not be met.
I have concluded that housing guinea pigs singly does not meet their species-specific needs and is not required for the purpose of the research. While I am satisfied that the research, if successful, will have scientific value, that value does not justify departing from the principle that the design and management of the accommodation meets the species-specific needs of the guinea pigs. My view on that issue is not affected by the proposal for conditional accreditation and licensing.
Tribunal's jurisdiction
The Tribunal has jurisdiction to review the respondent's determination: AR Act, s 45, Administrative Decisions Tribunal Act 1997 (ADT Act), s 38. The Tribunal must decide what the correct and preferable decision is in relation to the accreditation and licensing applications having regard to the factual material before it as at the date of the hearing: ADT Act, s 63. The Tribunal stands in the shoes of the Director General and makes a new decision based on that material.
The applicant and the experiment
The Australian Rickettsial Reference Laboratory Foundation is a "not for profit" organisation and does not currently hold any accreditation or licence under the AR Act. Dr Graves is the applicant's medical director and Dr Islam is the principal investigator. The applicant has previously conducted research on mice in a Physical Containment Level 3 (PC3) laboratory at John Hunter Hospital. The applicant has been given access to this laboratory to conduct the proposed research using guinea pigs. According to Dr Graves it is not practicable or convenient to conduct the research in another laboratory outside Newcastle.
There are four phases of the proposed experiment:
(a) phase one involves infecting guinea pigs with different isolates (strains) of the Coxiella burnetii bacteria (which causes Q fever);
(b) phase two involves infecting guinea pigs with different doses of the same isolate (strain) of Coxiella burnetii;
(c) phase three involves administering the guinea pigs with various doses of the vaccine;
(d) phase four involves "challenging" vaccinated guinea pigs with the selected isolate and doses of Coxiella burnetii (the correct isolate and dose having been determined as a result of phases one and two of the experiment).
If the research is successful and a vaccine for Q-fever is patented, any money derived from the patent would go to the applicant. As the director, Dr Graves would be able to use the money for further research.
At the hearing the applicant put forward a more detailed proposal than that initially put to the respondent. It proposed that it would purchase male guinea pigs between 3 to 4 months old to use in its experiments. The guinea pigs would be housed in their cages for four to five days to allow them to settle in to their new environment. The applicant proposed to house and care for the guinea pigs in cages with the following features:
(a) "Greenline IVC Sealsafe plus Rat" and "GR900", as constructed by Tecniplast S.P.A of Italy;
(b) floor area of 904cm 2;
(c) the following dimensions:
(i) width: 395mm
(ii) depth: 346mm
(iii) height: 213mm
(d) the following forms of physical features by way of environmental enrichment:
(i) hay of at least 10 cm in depth, to be replaced or topped up daily to maintain that depth
(ii) shelters in the form of 12 cm PVC tubing (equivalent to one and a half times the length of the guinea pigs) and
(iii) a ceramic bowl for feeding.
While the guinea pigs would be housed in isolation, Dr Graves stated that he would try to ensure visual, auditory and olfactory contact with other guinea pigs and/or humans on a daily basis.
Legislative scheme
Object of Animal Research Act
The use and supply of animals in research is regulated by the AR Act. The long title of the Act is "[a]n Act to protect the welfare of animals used in connection with animal research." There are three separate regulatory schemes under the Act: accreditation as a research establishment; licensing a person as an animal supplier; and authorising individuals to undertake particular research. The applicant applied to be both accredited and licensed, but no individual has yet applied to be authorised to conduct the research.
Accreditation and licensing
The Director General has power to accredit a corporation as a research establishment: AR Act, s 20. A certificate of accreditation must, among other things, designate the land on which it is intended that the business of animal research will be carried out and specify any conditions to which the accreditation is subject: s 20(6). The Director General also has power to licence a person as an animal supplier: s 39. A licence must, among other things, designate the land on which it is intended that the supply of animals will be conducted, describe the kind of animal which the licence authorises the person to supply and specify any conditions to which the licence is subject: 40(1).
It is an offence for a corporation to carry out the business of animal research unless it is an "accredited research establishment": ss 46-48. It is also an offence for a person to supply animals for use in connection with animal research unless the person is the holder of an "animal supplier's licence": s 48(1).
There is no express guidance in the AR Act as to the matters the Director General should take into account when making accreditation and licensing determinations. Both parties referred to Second Reading Speeches to support their submissions as to the way in which the discretion should be exercised.
The applicant submitted that the regulation of animal research and the supply of animals are for the purpose of public accountability. The licensing scheme should be interpreted and applied to the minimum level commensurate with achieving the objectives of the AR Act. It should not be interpreted or applied in a way that prevents or unnecessarily restricts the carrying out of legitimate animal research. The respondent did not agree that the AR Act should be interpreted in that way.
The use of extrinsic material such as Second Reading Speeches to assist in the interpretation of a legislative provision is governed by the Interpretation Act 1987: s 34. That provision states that extrinsic material may be used if it is "capable of assisting in the ascertainment of the meaning of the provision" to confirm the meaning or determine the meaning. Section 20 and s 39 of the AR Act confer a discretion on the Director General. In my view, the Second Reading Speeches do not assist in ascertaining the "meaning" of the Director General's discretions. Consequently I have not taken the extrinsic material into account.
Authorisation
The individual or individuals who conduct the research must have an authority issued either by the Director General or the accredited research establishment: s 25(1). It is an offence for an individual to carry out animal research unless he or she holds an "animal research authority": s 47(1).
Both the Director General and an accredited research establishment can issue an authority to any individual to carry out animal research for the purpose of a particular research project: s 25(1). Neither can do so without a recommendation from the animal care and ethics committee (AEC) for that research establishment: s 25(2) and (3). AECs must have at least four members, one of whom is independent: s 21(1) and Animal Research Regulation 2010 (AR Regulation): cl 21(1). It is also the AECs role to supervise the carrying out of animal research by holders of animal research authorities: s 14(1)(b). In this case the individuals who the applicant proposed would conduct the research pursuant to an authority were Dr Graves and Dr Ismail.
Role of the Panel
When the Director General receives an application for accreditation as a research establishment, or an application for an animal suppliers licence, he or she must refer the application to the Animal Research Review Panel (the Panel) established by the AR Act: s 19 and s 38. The Panel comprises twelve members including medical officers, academics and representatives from animal welfare organisations and industry: s 6. Its functions include investigating applications and making recommendations to the Director General: s 9. Before determining whether to grant or refuse an application for accreditation or for a licence, the Director General must "consider" the Panel's report. Section 20(1) provides that:
(1) After considering the Panel's report on an application, the Director-General shall determine the application:
(a) by accrediting the applicant as a research establishment, either unconditionally or subject to conditions, or
(b) by refusing to accredit the applicant as a research establishment.
Section 39(1), which relates to licences, is in similar terms. Because the Director General is required to consider the Panel's report, the Tribunal is also required to do so. Neither the Director General nor the Tribunal has to agree with the Panel's reasoning or conclusion.
Regulations and code of practice
The AR Act allows regulations to be made which prescribe a code of practice with respect to the conduct of animal research and the supply of animals in connection with animal research: s 4. The code of practice which was prescribed as at the date of hearing was the Australian code of practice for the care and use of animals for scientific purposes, 7th edition, 2004: AR Regulation, cl 3. The purpose of the code "is to ensure the ethical and humane care and use of animals used for scientific purposes."
Animals may only be used in research where it is "essential" for, among other things, "the maintenance and improvement of human . . . health and welfare." The code is underpinned by the requirement that projects using animals are "justified":
Projects using animals may be performed only after a decision has been made that they are justified, weighing the predicted scientific or educational value of the projects against the potential effects on the welfare of the animals.
The code emphasises the need to consider the "3Rs", being:
(1) the Replacement of animals with other methods;
(2) the Reduction in the number of animals used; and
(3) the Refinement of techniques used to reduce the adverse impact on animals.
In relation to "refinement", the code states that:
1.15 The design and management of animal accommodation should meet species-specific needs. Special consideration is required where this is precluded by the requirements of the project.
1.16 Animals should be transported, housed, fed, watered, handled and used under conditions that meet species-specific needs. The welfare of the animals must be a primary consideration in the provision of care, which should be based on behavioural and biological needs
The code acknowledges that there are "difficult ethical judgements to be made regarding the use of animals for scientific purposes."
Applicability of code
An issue in this case is the extent to which the code of practice should apply to accreditation and licensing determinations as distinct from authorisation decisions. An authority to carry out animal research is an authority to carry out that research in accordance with the code: s 26(2)(b). But there is no reference to the code in the AR Act in relation to the determination of applications for accreditation of research establishments. According to the applicant, the main function of the code is to guide accredited research establishments and their AECs when authorising and supervising particular research projects.
The code itself states that it is directed to "investigators, teachers, institutions, animal ethics committees (AECs) and anyone involved in the care and use of animals for scientific purposes." Appendix 1 to the code makes the point that:
The Code embodies a system of self-regulation by which each institution must put in place processes to ensure that the care and use of animals for scientific purposes is undertaken in an ethical and humane manner.
The respondent submitted that as a "prescribed code" the Director-General would act in accordance with it when making accreditation and licensing determinations.
The code is directed, among other things, to the authorisation and complaint handling processes. It is not expressly directed to accreditation or licensing determinations. But there are provisions in the code relating to the housing of animals. An accredited research establishment and a person licensed to supply guinea pigs must house the animals before any research is carried out. Consequently, those parts of the code that relate to housing are relevant. I accept the applicant's submission that because the code is not prescriptive and the Director General's discretion is otherwise unfettered, the Tribunal need not apply the code if there is a good reason not to apply it. I am not satisfied that there is any good reason not to apply the code and I have applied it in this case.
Guidelines
The Panel has developed a Guideline for the Housing of guinea pigs in scientific institutions (Guideline 21, May 2006). Guideline 21 states that it is "based on principles regarding the care and management of guinea pigs taken from scientific literature" and is designed to address the requirements of the code. The primary researcher and author of Guideline 21 was Dr Peter Johnson, a Veterinary Officer employed in the Animal Welfare Unit of the Department of Primary Industries. He conducted a literature review and prepared a draft document. He then sought comments on the initial draft from the Panel, accredited research establishments, licensed animal suppliers in NSW and a number of international representatives. After considering the comments, the Panel approved the final draft.
Guideline 21 contains several recommendations relevant to these proceedings. Recommendation 1.5.2 explains the principle of 'refinement' in the code in more detail:
Recommendation 1.5.2:
"The Code of Practice recognizes that there may be circumstances where the requirements of experimental procedures will preclude meeting some species-specific needs (Clause 4.4.19). Housing in these situations should still meet the physiological and behavioural needs of guinea pigs as closely as possible."
In relation to cage size, Guideline 21 points out that the recommended floor areas for guinea pigs tend to be greater than they have been in the past:
"The suggested minimum floor area for housing guinea pigs varies between authors and differs according to whether or not the animal is part of a breeding group. However, with advanced knowledge of guinea pig behaviour and husbandry, the recommended areas per individual reported in recent literature tend to be greater than those published in earlier papers. It is generally accepted that the provision of sufficient floor space is essential to the well-being of the animals and the careful positioning of appropriate shelters within the enclosure optimises the floor space that is useable by the guinea pigs."
With that in mind, Guideline 21 recommends the minimum cage size for one guinea pig as 1800cm2 plus further space if more than one guinea pig is in the cage.
Recommendation 2.2.2:
"Weaned guinea pigs kept in non-breeding groups require a minimum useable floor area of 1800cm2 for animals weighing 200-450g allowing 200cm2 for each additional animal weighing > 200g-300g and 500cm2 for each additional animal weighing > 300-450g. For guinea pigs weighing >450g, a minimum floor area of 2500cm2 is required allowing 700cm2 for each additional animal weighing >450-700g and 900cm2 for each additional animal weighing >700g."
Guideline 21 recommends against housing guinea pigs singly unless there is compelling scientific evidence for the need to house guinea pigs in that way. Recommendations 3.1.1 and 3.2.1 state that:
Recommendation 3.1.1:
"Guinea pigs are social animals and should be kept either in single sex groups or in stable breeding colonies."
Recommendation 3.2.1:
"Guinea pigs should not be housed individually unless with the express permission of the Animal Ethics Committee of the institution on the basis of compelling scientific evidence for the need to house guinea pigs in this way. In such cases, where feasible under the experimental protocol, guinea pigs should be in visual, auditory and olfactory contact with other guinea pigs."
The applicant's proposed experiment does not comply with the recommendations in Guideline 21 in two main respects. Firstly, it does not comply because the guinea pigs are housed singly. Secondly, it does not comply because the cage size is smaller than the Guideline recommends.
Applicability of recommendations in Guideline 21
The applicant's expert witness, Dr Donnelly, does not agree that the 'single housing' and 'cage size' recommendations in Guideline 21 should be rigidly applied when determining the species-specific needs of guinea pigs.
Dr Donnelly is a qualified veterinarian with dual Australian and United States citizenship. He is an Adjunct Associate Professor of Exotic Pet Services for the Foster Small Animal Hospital of the Cummings School of Veterinary Medicine, Tufts University in Grafton, Massachusetts, USA. He is also a founding member of the Kenneth S Warren Institute.
In his view, the recommendations in Guideline 21 should be weighed equally with equivalent national and international recommendations. The reasons for his view include:
(1) the fact that there is very little scientific evidence about the effects of housing guinea pigs singly or optimum cage sizes so that Guideline 21 is informed, to some extent, by expert opinion which varies;
(2) the fact that Guideline 21 is only one of several internationally recognised guidelines; and
(3) the lack of consultation on the content of Guideline 21.
According to the respondent's expert witness, Professor Rose, the proposed research should comply with Guideline 21 because there are no good reasons justifying a departure from that guideline. She says Guideline 21 was developed by the Panel to identify and comply with the species-specific needs of guinea pigs. It was designed to meet the requirements of the code and it should be applied in New South Wales. Professor Rose gave evidence that because of the lack of specific scientific research in this area, reasonable 'expert' minds may have different opinions. But, according to Professor Rose, that does not mean that all guidelines are equally legitimate.
Professor Rose is the Director of Research Governance for the South Eastern Sydney and Illawarra Shoalhaven Local Health District. She trained as a veterinarian and has worked in animal and human research for many years. She is a member of the committee which is revising the Australian Code and has also developed and delivered courses in animal care and ethics at universities. Professor Rose was the Chair of the Panel until September 2010.
Dr Donnelly distinguished between a performance approach to guidelines, which focuses on outcomes, and an engineering approach which is more prescriptive. Ideally, engineering and performance standards should be balanced to promote flexibility and individual judgment. He says the respondent has taken a prescriptive or "engineering" approach when applying Guideline 21 to the research proposal. From a scientific perspective, this means the standards are so inhibitory that they impede scientific progress.
Because very little scientific research has been conducted on the issue of guinea pig accommodation and Guideline 21 is only one of several internationally recognised guidelines, the Tribunal may have regard to expert opinion. If the weight of expert opinion is not in accordance with a particular recommendation in the Guideline, it should not be applied. The relevant recommendations in Guideline 21 and in other national and international guidelines will be considered in detail below.
The applicant criticises Guideline 21 because the consultation process was unnecessarily selective. Of the nine international reviewers, six were from Europe, one was from Canada, one was from USA and one was from New South Wales. According to Dr Donnelly there should have been a broader range of international reviewers who could have advised adopting more modest guidelines, pending further science-based animal welfare findings. Of the ten papers which were identified in the Guideline as "Recommended Reading", only one author was approached to provide an opinion on the draft guidelines. The failure to circulate the draft guideline to Dr Sachser, the internationally renowned expert in the field, is significant.
It was Dr Rose's opinion that Guideline 21 was developed and refined in consultation with experts. She says that the fact that one known expert, Dr Sachser, was not consulted is unfortunate, but the consultation does not have to be comprehensive for the recommendations to be valid. I agree with that reasoning and conclusion. I am not persuaded that Guideline 21 should be given less weight because of the consultation process.
Issues
In accordance with the AR Act and the code, the following broad issues arise when determining applications for accreditation and licensing:
(1) Is the research essential for the maintenance and improvement of human health and welfare? (If not, the research should not be conducted.)
(2) Can animals be replaced with other methods, or the number of animals be reduced? (If so, those steps should be taken.)
(3) Does the design and management of the animal accommodation meet the species-specific needs of the animal? In particular, does housing the guinea pigs singly in cage sizes of 900cm2 meet their species-specific needs?
(4) If not, do the requirements of the project prevent those needs being met? (If so, housing should still meet the physiological and behavioural needs of guinea pigs as closely as possible.)
(5) When the predicted scientific value of the research is weighed against the potential effects on the welfare of the animals, should the applicant be accredited and/or licensed?
I will firstly consider the Panel's report and then go on to address each of these issues.
Consideration of Panel Report
The Panel was unanimous in its recommendation not to extend the accreditation or the licence. The main reasons for its recommendation can be summarised as follows:
(1) the only reason for the use of small cages was a lack of space in the available PC3 facility;
(2) the numbers of guinea pigs to be used was significant - at around 100 animals;
(3) the proposed research was not short-term but may run for 1-2 years.
According to the applicant, the Panel's reasoning was inflexible and, in part, based on a misunderstanding about important factual matters, including the following:
(a) "If the work was a one-off and short term, it may be possible to recommend approval."
The Department was informed that each experiment would take around 3 weeks (Email, Graves to Chave dated 25 May 2012)
(b) "It is difficult to see how this can be justified - a facility that can handle bigger cages may have to be found"
The Department was informed that larger cages would not be suitable for the Applicant's small Biological Safety Level 3 facility (Email, Graves to Chave dated 25 May 2012). Also, the Department was informed that a problem existed in the removal of the infected guinea pigs from the cages without exposing staff to Q Fever (Email, Graves to Chave dated 25 May 2012) The Panel was informed by Dr Graves that a larger facility existed in Geelong, but because the Applicant's researchers were based in Newcastle, the Applicant could not utilise that facility.
(c) "Philosophically it did not seem right - putting human OH&S before animal welfare"
(d) "Animal welfare is the primary determinant".
The applicant submitted that these statements demonstrate that the Panel failed to have regard to some of the key planks of the Code, including:
(a) whether the use of the animals was justified, particularly having consideration to the scientific benefits of the research;
(b) placing too great an emphasis on the welfare of the animals in circumstances where the Code makes clear that animal welfare is "always considered" but is not necessarily the "primary determinant";
(c) failing to enquire as to the extent to which the guinea pigs would suffer pain or distress;
(d) failing to balance all of the relevant considerations for and against the applicant's applications, noting that the Code pointed out that the use of animals for scientific purposes raises "difficult ethical judgements";
(e) failing to give "special consideration" to the requirements of the project, when the Panel arrived at the conclusion that the species-specific needs of the guinea pigs could not be met by reason of the requirements of the applicant's proposed research.
The Tribunal's role is to decide what the correct and preferable decision is in relation to the accreditation and licensing applications having regard to the evidence and the law as at the date of the hearing. While the Tribunal must consider the Panel's report, it is not bound by its reasoning or conclusion. In my view the correct approach is to address each of the five issues outlined above.
Is the research essential for the maintenance and improvement of human health and welfare? (If not, the research should not be conducted.)
In relation to the first question, I accept Dr Graves' opinion that the proposed research to develop a new vaccine for humans against Q fever is essential for the maintenance and improvement of human health and welfare. It has no other rationale.
Can animals be replaced with other methods, or the number of animals be reduced? (If so, those steps should be taken.)
One of the principles in the code is to give consideration to the "replacement of animals with other methods". I accept Dr Graves' evidence that animal testing is essential in developing any new human vaccine, including a new Q fever vaccine. It is very unlikely that a Human Ethics Committee in Australia would approve the trial use of a new vaccine in humans without prior success on animals. The best animal for testing Q fever in humans is the guinea pig because the febrile response of guinea pigs to bacteria most closely mirrors the febrile response of humans to bacteria. It was not disputed that the applicant's proposal would use the bare minimum number of animals necessary to achieve scientific validity.
Does the design and management of the animal accommodation meet the species-specific needs of guinea pigs?
Introduction
This question addresses one aspect of the "refinement" principle. For the reasons given below, the answer to the question is "No." But that is not fatal to the applicant's application. Refinement is merely a consideration. The Tribunal must go on to address the remaining three issues set out above.
I will firstly address the question of whether housing guinea pigs singly meets the species-specific needs of guinea pigs and then consider that question in relation to cage size and environmental enrichment.
Housing guinea pigs singly
Scientific evidence on effects of housing guinea pigs singly
Both the experts agreed that there has been very little scientific research on guinea pigs compared with other laboratory animals such as rats and mice. I give no weight to Dr Graves' evidence that in an experiment he conducted on guinea pigs almost 15 years ago, he did not notice any outward signs of distress or anxiety from guinea pigs being housed in isolation. He gave no details of how long they were kept in isolation and did not refer to an important indicia of guinea pig well-being, namely weight. Moreover, it is unlikely that after almost 15 years, Dr Graves still has a specific recollection of the welfare of the guinea pigs.
Dr Donnelly agrees that "best practice" is to house guinea pigs with other guinea pigs. But he maintains that the only scientific evidence regarding single housing establishes that post infancy (and prior to re-introduction to a colony) single housing did not lead to increased stress as measured by increased cortisol levels. Dr Donnelly's opinion that a guinea pig's welfare would not suffer adversely from the isolation proposed in the experiment was based on a 1986 study of Dr Sachser and his group at the University of Munster in Germany: Sachser N. The effects of long-term isolation on physiology and behaviour in male guinea pigs Physiol Bahav 1986; 38(1): 31-39.
In Dr Sachser's study, a number of guinea pigs were isolated at two months of age for 18 months and were then returned to a colony. After eight isolated guinea pigs were re-introduced to the colony, three of them died. Dr Sachser attributed their death to a changed psychological state.
Dr Donnelly says that this research supports the proposition that isolated single housing for four weeks will not cause a stress response, that is, it will not lead to an increase in cortisol levels. He maintains that even 17 months of isolated single housing is no more stressful than group housing. Animal welfare only becomes an issue if long-term isolated males are re-introduced into a male-female colony of guinea pigs. That will not be the case in the applicant's proposal as the guinea pigs will be euthanised.
In direct opposition to Dr Donnelly, Professor Rose expressed the view that Dr Sachser's paper confirms the significant negative effects of isolation on the psychological wellbeing of male guinea pigs. The respondent pointed out that Dr Sachser's findings were limited. First, he did not examine the larger question of guinea pig welfare but only the impact of isolation on adrenal functioning in the isolated male guinea pigs. Secondly, the guinea pigs in Dr Sachser's study still had auditory and olfactory contact with other guinea pigs.
Dr Sachser himself has cautioned against generalising. He wrote in the article that, "as duration of and age at differential housing or source of experimental animals can influence results on grouping/isolation comparisons, simple generalizations should not be drawn from a single experiment". In a 2010 paper, Dr Sachser recommended against housing guinea pigs in isolation (UFAW Handbook, 8th ed Hubrecht and Kirkwood, eds at p 385). Dr Sachser and his co-authors Drs Kaiser and Kruger, said that "[s]ince the ancestor of the guinea pig is a socially living wild species, it seems likely that single housing is not appropriate for its domesticated counterpart. Single-housed male guinea pigs cope with stress situations in a less effective way than guinea pigs living in social groups." The authors also stated at p 386 that, "The most important environmental enrichment for the guinea pig is the social group."
Professor Rose concluded that the available scientific evidence "clearly indicates the importance of social structures, relationships and bonding for the welfare of guinea pigs". She also said, "there is substantive scientific evidence documented in Guideline 21 that individual housing of guinea pigs has a significant negative impact on their welfare and ... will impair the ability of the isolated animal to respond to and cope with stressors including novel treatments". Professor Rose says that the "overwhelming evidence from the literature and from guidelines" is that guinea pigs should be housed in social groups. In her opinion, the cumulative impact of isolation on the guinea pigs would be "significant".
According to Dr Donnelly any adverse effect of isolation could be ameliorated by ensuring that the guinea pig can hear and smell other guinea pigs. Guinea pigs have highly developed senses of smell and hearing. Dr Donnelly agreed that in his proposed experiments olfactory contact between guinea pigs would be limited because of the need to use sealed cages which are individually ventilated. But he contended that the daily examination of the guinea pigs by the researchers would permit some auditory and olfactory contact. In cross examination, Professor Rose appeared to accept that this might be the case if the biosafety cabinet was not wiped after the guinea pigs were handled. She did not agree that any such contact would be sufficient for the guinea pigs' welfare.
Guidelines on housing guinea pigs singly
According to Guideline 21, the scientific literature on guinea pigs establishes that "social support between partners significantly reduces endocrine responses to stressful situations." Guideline 21 states that:
"Bonds existing between guinea pigs ... provide security and health-promoting effects that significantly influence the individual's ability to cope with stress and to survive. The severing of these bonds by the isolation of individuals has measurable physiological effects, with potentially deleterious outcomes for the welfare of the guinea pigs. The maintenance of a familiar environment and provision of visual, olfactory and auditory contact with familiar cohorts reduces the stress associated with individual housing, although some physiological effects persist that may be detrimental to the wellbeing of the animals. These effects may also confound experimental outcomes..."
All the guidelines in evidence recommend that, as a general rule, guinea pigs be housed with companions. If solitary housing is necessary because of experimental requirements, some guidelines recommend that the period be kept to a minimum and that visual, auditory, olfactory and/or tactile contact shall be maintained.
(1) The Victorian Code states that "[s]ingle housing will cause social deprivation and impacts on the animal's capacity to thermoregulate";
(2) Directive 2010/63/EU of the European Parliament and Council on the Protection of Animals Used for Scientific Purposes dated 20 October 2010 ("European Directive"), which sets out the requirements for the care and accommodation in Annex III, relevantly provides at cl.3.3:
(3) "(a) Housing
Animals, except those which are naturally solitary, shall be socially housed in stable groups of compatible individuals. In cases where single housing is allowed in accordance with article 3(3) the duration shall be limited to the minimum period necessary and visual, auditory, olfactory and/or tactile contact shall be maintained."
(4) The "Guidelines for Accommodation and Care of Animals" being Appendix A of the European Convention for the Protection of Vertebrate Animals used for Experimentation and Other Scientific Purposes (15 June 2006) ("European Convention Guidelines") state:
"Animals, except those which are naturally solitary, should be socially housed in stable groups of compatible individuals. Single housing should only occur if there is justification on veterinary or welfare grounds. ... In such circumstances, additional resources should be targeted to the welfare and care of these animals. In such cases, the duration should be limited to the minimum period necessary and, where possible, visual, auditory, olfactory and tactile contact should be maintained."
The European Convention Guidelines also contained recommendations specifically tailored to guinea pigs and relevantly said in that context, "gregarious species should be group housed ... Disruption of established stable and harmonious groups should be minimised, as this can be very stressful."
(5) To the same effect is the United States Guide for the Care and Use of Laboratory Animals, 8th ed (2011) ("US Guidelines"), which states at p.64:
"Single housing of social species should be the exception and justified based on experimental requirements or veterinary-related concerns about animal well-being. In these cases, it should be limited to the minimum period necessary, and where possible, visual, auditory, olfactory, and tactile contact with compatible species should be provided."
Conclusion on housing guinea pigs singly
For the reasons she has given, I accept Dr Rose's opinion that single housing of guinea pigs, as proposed in the applicant's research, does not meet the species-specific needs of guinea pigs. The cages are individually ventilated. That will prevent any significant level of odours or sounds from moving between the cages. There will be little or no opportunity for guinea pigs to smell or hear one another while being examined individually in the biosafety cabinet. The potential adverse effects of single housing are not overcome by the negligible auditory and olfactory contact the guinea pigs will have with one another.
The weight of expert opinion is in accordance with the recommendation in Guideline 21 that guinea pigs should be kept either in single sex groups or in stable breeding colonies. In particular, Professor Rose's opinions should be preferred to Dr Donnelly's about the impact of isolation on guinea pigs because:
(1) the scientific literature establishes that guinea pigs are social animals;
(2) Dr Donnelly relied upon an old and qualified study by Dr Sachser to draw generalised conclusions in circumstances where Dr Sachser himself was not prepared to draw that generalised conclusion;
(3) guidelines around the world universally recommend that guinea pigs should not be housed singly.
Cage size and environmental enrichment
Scientific evidence on the effects of cage size
There are no peer-reviewed papers on the cage size that is necessary for the welfare of a single guinea pig. Information on how guinea pigs use cage space is found in only one peer-reviewed paper that shows they are thigmotaxic, that is they prefer to be along the edges of cages rather than in the exposed centre of the cage. (Use of cage space by guinea pigs, WJ White et al, Laboratory Animals (1989) 23, 208-214). According to Dr Donnelly although it was intuitive that the housing environment of laboratory animals somehow affects their performance and well-being, there is not a great deal of information available to support specific recommendations on guinea pigs.
Dr Rose accepts that there is no generally accepted cage size for guinea pigs that has a scientific basis.
Guidelines on cage size and environmental enrichment
Guideline 21 uses the recommendations of the European Union Directive 2010/63/EU as the minimum acceptable standard for housing guinea pigs. The enclosure should have a minimum area of 1800cm2 for guinea pigs weighing up to 450g and 2500cm2 for guinea pigs weighing more than 450g. This EU Directive recommended a larger area for guinea pig cages compared with previous national and international standards. Dr Donnelly criticises the EU Directive because he says it is based on one non-refereed publication - a fact-sheet on the husbandry of guinea pigs published by the German Veterinary Association for Animal Welfare. The expert opinion was that of a behaviourist who used guinea pigs to study stress, evolution and development of social behaviour. Dr Donnelly's view is that one expert opinion is far less persuasive than sound scientific observation and experimentation.
Guideline 21 and its European counterparts may be contrasted with the approach that has been taken in Victoria and the USA. In Victoria, the 2004 Code of Practice for the Housing and Care of Laboratory Mice, Rats, Guinea Pigs and Rabbits ("Victorian Code") applies. That code recommends that a single guinea pig of between 250 - 550g has 900cm2 of space, the same area as the applicant proposes for its experiments. The US Guideline is even lower than that for Victoria. It recommends that guinea pigs up to 350g have a minimum floor space each of 387cm2 and guinea pigs greater than 350g have a minimum of 651.5cm2 each.
The respondent points out that the Victorian Code was published in October 2004 and accordingly is older than Guideline 21. Unlike Guideline 21, it was not based on an exhaustive literature review and extensive research of guinea pig needs. Rather, it was developed in collaboration with laboratory animal veterinarians and technicians, animal house managers, inspectors and animal welfare officers from academic, research and private industry.
In relation to the US Guideline, the respondent notes that those recommendations are made on the basis that the guinea pigs are housed in groups. As such, it is contemplated that the available space for each guinea pig is at least double the recommended area. Further, the US Guidelines are not based on scientific research as to appropriate floor space requirements. Rather, they are "based on professional judgment and experience."
Dr Donnelly concluded that it is inappropriate to prescribe one recommended minimum floor area. Such an 'engineering' standard is too rigid. A range of available floor space or usable area is acceptable for different rodents depending on the type and quality of the space. In particular, enclosure design or complexity (environmental enrichment) in the form of hay and plastic pipes for shelter and tunnelling can affect space requirements.
Expert opinion relating to cage size and environmental enrichment
Floor area is significant because there must be sufficient space for guinea pigs to engage in certain behavioural activities such as foraging, tunnelling, chewing and sheltering. The applicant's proposal in relation to environmental enrichment includes both hay to a minimum depth of 10cms, and a shelter in the form of a 12cm PVC tube which is approximately 1½ times the length of the guinea pig. The respondent's evidence is that the enrichments that the applicant proposes do not adequately compensate for the cumulative effect of housing the guinea pigs singly in a confined space. Professor Rose suggests that the better approach is to determine floor space by considering what is required for environmental enrichment so that guinea pigs can engage in their usual behaviours. She says that approach was taken in relation to Guideline 21 and the European Directive.
According to Dr Rose, the guinea pigs will weigh approximately 400g after four weeks and the proposed floor area will not provide sufficient space for them to express their normal behaviours. Professor Rose says that guinea pigs are active during both the day and night. They use the floor space for a range of activities including tunnelling, foraging and chewing. She says they are not sedentary creatures and it is important to provide them with sufficient area to exercise and rest as well as adequate shelter.
She is doubtful whether there would be sufficient floor area in the proposed cages to include a shelter as well as a sufficient quantity of hay and leave adequate space for the animals to move around. Dr Rose says that the 12cm tube is not long enough for a 350 g guinea pig because it only gives it enough room to sit, not to explore. She is also doubtful that adequate quantities of hay can be provided to enable the animals to forage and shelter without blocking the air delivery system in the ventilated cage. The lack of environmental enrichment will exacerbate the impact of the isolation.
Dr Donnelly disagrees. He says that based on his experience, a cage of this size is likely to be sufficient for a 300-400g guinea pig to express these behaviours normally. Dr Donnelly says it is conjecture on Professor Rose's part to say that floor area significantly reduces environmental enrichment opportunities. In relation to Professor Rose's concern that there might not be sufficient room in the proposed cages for the required level of hay and the need for space around the air vents, a rudimentary examination of the proposed cages with the hay in them clearly shows there is more than enough room around the air vents and that hay to a depth of 10cm will not block the operation of the air vents.
Dr Donnelly adds that because guinea pigs prefer to be along the edges of cages, larger cage space disproportionately increases the unused centre portion of the cage compared with the used perimeters of the cage.
Conclusion on cage size and environmental enrichment
The two experts came to different opinions about the likely impact on guinea pig welfare of the proposed accommodation arrangements. In summary, Professor Rose considers that the small floor space will not be adequate to permit them to engage in their ordinary behaviours. She sees these effects as cumulative. Dr Donnelly disagrees with Professor Rose's views. He says that the size of the cage will not have a detrimental effect on their welfare.
There is no scientific research on this issue and the various national and international guidelines vary significantly. I agree with Dr Donnelly that it is not possible to say with certainty that a particular floor area or particular environmental enrichments will meet the species-specific needs of guinea pigs and other arrangements will not. It is a matter of degree. A bigger cage with more hay and a longer tube may meet the species-specific needs of a guinea pig to a greater extent than the proposed arrangement. But that does not mean that the proposed arrangement does not meet their needs.
Based on all the evidence, I am satisfied that a cage size of 900cm2 containing the environmental enrichments proposed by the applicant would meet the species-specific needs of a single guinea pig. Reviewing the evidence including the cage itself, I do not share Dr Rose's doubt that there will be insufficient room for the hay or the plastic tube or that those enrichments are inadequate.
But, as I have decided that housing guinea pigs singly does not meet their species-specific needs, my conclusion on cage size is largely irrelevant.
If not, do the requirements of the project prevent those needs being met?
Dr Graves agreed that at no stage of the experiment is it scientifically necessary to house the guinea pigs in 900cm2 cages or singly. It is because the laboratory at the John Hunter Hospital cannot accommodate cages larger than 900cm2 that single housing was proposed.
Dr Donnelly submitted that occupational health and safety laws determine the set up of the laboratory. In his opinion, carrying an 1800cm2 cage to the biological safety cabinet would be a hazard for one individual because of the high chance of dropping such a large cage. Dr Donnelly is not an expert in occupational health and safety and I do not accept his opinion on this point.
Even if I was satisfied that it was not safe to conduct the experiment using bigger cages, there is nothing in the legislative scheme to suggest that the configuration of available research facilities is relevant when determining whether to accredit or licence an applicant. I accept that the fact that Dr Graves lives and works in Newcastle means that it is not convenient for him to conduct the research on behalf of the applicant in another location. That is a commercial and/or a practical consideration for him, not a matter that should be taken into account when making an accreditation or licensing decision. Because the size of the available PC3 laboratory is an irrelevant consideration, I make no finding as to whether it is possible for larger cages to be housed in that laboratory.
The requirements of the project do not prevent the species-specific needs of the guinea pigs being met. But that is not the end of the matter. I must still consider whether, despite that fact, the research is 'justified'.
Is the project justified when the predicted scientific value of the research is weighed against the potential effects on the welfare of the animals?
Scientific value of the project
The purpose of the proposed experiments is to develop a new human vaccine against Q fever. Q fever is transmitted from infected animals, mainly cattle, sheep and goats, to humans, by means of aerosol from contaminated animal birth products, urine, faeces and milk. The bacterium is highly infectious for humans. The disease occurs worldwide in two clinical forms, acute Q fever and chronic Q fever.
Dr Graves gave some evidence about the incidence and mortality rate of Q fever. He said that acute Q fever has a mortality rate which is approximately 1%. I understand that to mean that, in a population of 1,000, there are 10 deaths per year, or 1% of the total. He also said that chronic Q fever has a mortality rate which is approximately 30-40%. While no evidence was given to contradict these assertions, they seem unlikely given other parts of his evidence. He said there are approximately 25 known cases of chronic Q fever each year in Australia but there is no official record of the precise number of people who die from Q fever each year. Based on his experience in the field, Dr Graves estimates that there are approximately ten deaths per year in Australia. There is no reference given for this statistic. Based on the mortality rates he has quoted, there would be considerably more than ten deaths per year.
Assuming that I have either misunderstood Dr Graves' figures on mortality rates or those figures are not correct, I nevertheless accept that many people are hospitalised for Q fever in Australia each year and that people have died from the disease. Dr Graves tendered a document titled 'Statistics and Epidemiology' prepared by the US Centre for Disease Control and Prevention, which records that 131 cases of Q fever were reported in the USA in 2010. Of those, 106 were acute Q fever and 25 were chronic Q fever.
Dr Graves says that the current process of vaccination is difficult because it requires two visits to the doctor. In the course of the first visit, there is a skin test and a blood test. He says a new human Q fever vaccine that can be administered to patients without pre-testing and with only one visit would be a significant improvement. While Dr Graves agreed that many other vaccinations require more than one inoculation, a new single visit regime would be easier to administer and require less specialised knowledge on the part of the treating doctor. If such a vaccine were available it would have a worldwide market. Q fever exists in most countries of the world and a vaccine that is quick and easy to use would be beneficial.
There is already an effective vaccine - "QVAX". The respondent submitted that given the extremely low death rate from Q fever, the potential benefits of a new vaccine should not be overstated. The respondent also submitted that there is no certainty that the proposed research will lead to the development of an effective new vaccine. According to Dr Graves, the vaccine "is still in development and has not yet been confirmed as effective."
If the value of scientific research is categorised as high, moderate or low, I am satisfied that the proposed research has a relatively low value. There is an existing vaccine for Q fever and the incidence of the disease is low. The applicant did not assert that the new vaccine, if developed, would be more effective, just that it would be quicker and easier to administer.
Potential effects on the welfare of the animal
The precise effects on the welfare of guinea pigs from being housed singly are not known. The weight of expert opinion is that guinea pigs are social animals and are likely to experience stress if housed alone. I agree with Professor Rose that the available scientific evidence indicates the importance of social structures, relationships and bonding for the welfare of guinea pigs. Individual housing of guinea pigs has a significant negative impact on their welfare and will impair the ability of the isolated animal to respond to and cope with stressors including novel treatments.
Conclusion
The code acknowledges that there are "difficult ethical judgements to be made regarding the use of animals for scientific purposes." In making that judgment, "refinement" is one of the principles that I must consider. In this case refining the experiment so that the guinea pigs are housed together would reduce the adverse impact on their welfare. That refinement is not precluded by the requirements of the project. Given that fact and the fact that the predicted scientific value of the research is relatively low, I am not satisfied that the way in which the applicant intends to house the guinea pigs is justified.
Conditional approval for pilot study?
As an alternative, the applicant proposed that the Tribunal grant accreditation and a licence for a four week pilot study and that the research be assessed again after that time. The applicant noted that the code provides for a pilot study to allow a staged assessment of the impact on animal welfare and how it will be managed. Under the heading, "Planning Projects" the code states:
3.2.1 Before submitting a proposal to the AEC, investigators and teachers need to consider the following questions during the planning stages of a project:
. . .
(xi) If the potential impact on the animal is unknown, is it appropriate to incorporate a pilot study into the project design to allow a staged assessment of the impact on animal welfare and how it will be managed. Pilot studies should be regarded as integral to the overall project and should be assessed by the AEC according to the usual criteria applied to project approval: Code [3.2.1(xi)].
The details of the pilot study were that:
(1) An in-house veterinarian, who is vaccinated against Coxiella burnetii, as agreed between the parties, could observe the guinea pigs on a daily basis in order to ensure their behavioural and physical indicators do not show any abnormal signs of stress and discomfort (other than that induced by the Coxiella burnetii).
(2) An independent veterinarian, as agreed between the parties, will observe the guinea pigs on a weekly basis in order to ensure their behavioural and physical indicators do not show any abnormal signs of stress and discomfort (other than that induced by the Coxiella burnetii).
(3) The independent veterinarian would need to be trained in biosafety and use all appropriate equipment.
(4) The applicant can prepare a separate sheet for each animal, observing and recording the condition of each animal on a daily basis (including weekends and public holidays). A sheet titled "Monitoring of Experimental Laboratory Animal Following Infection" would be completed.
(5) The in-house veterinarian would keep records of the following indicators to determine the guinea pigs' status in their singular housing in cages of 900 cm2 floor space:
(a) body weight;
(b) assessment of eating and drinking, as indicated by scattering of feed in the cage and water levels in water bottles;
(c) the ability or failure to produce faeces;
(d) assessment of grooming and hair coat (piloerection or "scruffy" reflecting reduced grooming);
(e) examination of motor postures (lack of movement, lying on one's side, hunching or cowering in a corner);
(f) increased vocalisation (distress calls);
(g) aggression;
(h) agitation marked by avoidance of handlers and/or rapid running around cages;
(i) any instances of "freezing".
(6) The independent veterinarian will review the monitoring sheet as part of their weekly observations.
(7) At the conclusion of the four week pilot study, both the in-house and the independent veterinarians would prepare a report to be tabled before the ADT which would:
(j) attach the separate sheets as a record; and
(k) based on the findings in the separate sheets, make a finding as to the impact on the welfare of the guinea pigs.
(8) At the conclusion of the pilot study, the report of both veterinarians could then be tabled at a meeting of the applicant's animal care and ethics committee (AEC) and a recommendation could be made by the AEC as to whether the applicant could continue with the experimentation.
(9) In the event that the AEC determines that the Applicant could not continue with the experimentation, the AEC could inform the Respondent and the Applicant's conditional accreditation could be suspended.
This is not a case where the potential impact on the guinea pigs is unknown. The overwhelming weight of expert opinion is against the single housing of guinea pigs because of the adverse effects on their welfare. If the project required single housing, a pilot study of the kind suggested may be appropriate. In circumstances where the project does not require single housing, I decline to approve the pilot study.
Order
The respondent's decision to refuse the applicant's applications to be accredited as an animal research establishment and for a licence to supply guinea pigs for use in connection with the research is affirmed.
Decision last updated: 14 October 2013
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