Category Archives: PiLAS

The 9th World Congress on Alternatives and Animal Use in the Life Sciences

The 9th in this series of congresses which began in 1993, was held at the Hilton Prague Hotel, Czech Republic, on 24–28 August 2014. Its organisation was co-chaired by Dagmar Jirová (Prague) and Horst Spielmann (Berlin), on behalf of the Alternatives Congress Trust, with the administrative support of Guarant International.

The Congress was attended by about 1,100 participants, and the programme consisted of seven plenary lectures, more than 450 oral presentations, and about 500 posters. In addition, there was an exhibition with 60 booths, plus a number of satellite meetings and workshops, and many private discussion sessions.

The overall focus of the Congress was Humane Science in the 21st Century, as represented by nine main themes: new technologies; predictive toxicology; the Three Rs in academia and education; communication, dissemination and data sharing; efficacy and safety testing of drugs and biologicals; human relevance; ethics; refinement and welfare; and global co-operation, regulatory acceptance and standardisation.

The congress facilities provided by the hotel were superb, which helped to make this a particularly friendly congress. Many of the participants in the 1993 Congress were present, but it was also good to see a great number of younger scientists, 41 of whom had been specifically invited due to generous sponsorship.

It would be impossible to say much in detail about the Congress, given the enormous variety of topics covered. However, it is worth noting that two of the plenary lecturers gave contrasting insights into the state of humane science and the Three Rs as it is today.

Uwe Marx (Berlin) described the breathtaking progress being made toward developing a “human-on-a-chip”, as means of providing information of direct relevance to humans, replacing the need to resort to laboratory animal models. Early organ-on-a-chip versions — comprising artificial lungs, liver, kidneys, heart and gut — are already in use.

By contrast, Roman Kolar (Neubiberg) warned that many apparent commitments to the Three Rs have proved to be no more than lip-service, and political initiatives to avoid or replace animal experimentation have either failed dramatically, or have been watered down in the political decision-making process.

Of the Three Rs, it appeared that Reduction was rarely mentioned in Prague, and Refinement, however welcome, pales into insignificance in the face of the huge ethical and logistical dilemmas involved in maintaining animals under laboratory conditions. Replacement took the centre stage in most of the sessions, but, given the year-on-year increase in the production and use of, in particular, genetically-modified animals, there is a lot more to be done before humane science becomes more than just a dream. The 10th Congress will be held in Seattle in 2017 — it is to be hoped that much more progress will have been made by then.

Animal Experimentation in the UK: Probing Beyond the Rhetoric

The amended Animals (Scientific Procedures) Act 1986 (ASPA) came into force on 1 January 2013, in compliance with the requirements of Directive 2010/63/EU on the protection of animals used for scientific purposes, amid a flood of rhetoric about the uniquely high standards of laboratory animal care and use in the UK.

A few weeks later, the British Union for the Abolition of Vivisection (BUAV) sent Imperial College London a dossier containing allegations about what were claimed to be a wide range of infringements of the ASPA at the College. The Home Office, which is the government department responsible for the administration of the ASPA, immediately began an enquiry, and Imperial College, to its great credit, set up its own enquiry, by an independent committee, under the chairmanship of Professor Steve Brown, Director of the Medical Research Council’s Mammalian Genetics Unit at Harwell.

The remit of the committee was “not to investigate the specific allegations made by the BUAV”, but “to undertake a broad and detailed examination of all aspects of animal experimentation at the College facilities”. The committee interviewed a wide range of personnel, obtained a large number of documents, and visited the facility that was the focus of the BUAV’s allegations, and concentrated its deliberations on four areas: a) the Animal Welfare and Ethical Review Body (AWERB) process; b) the operations of the Central Biomedical Services (CBS); c) training and competency assessment; and d)culture, leadership and management.

On 10 December 2013, the committee produced a severely critical 38-page report,1 in which it concluded that the College’s animal research facilities are understaffed, under-resourced, and operating without adequate systems for training, supervision, management and ethical review.

The AWERB process was considered to be “not fit for purpose” and in need of “wholesale reform”, and required “a new senior administrative appointment … to manage the process”. The committee found the facilities to be “well equipped”, with “a high quality of animal husbandry”, but there was room for considerable improvement “in terms of operational structures and standards, communication and working practices, as well as the mechanisms for reporting animal welfare concerns”, which would “have a substantive impact upon animal welfare and the Three Rs”. However, “the provision for training, supervision and competency assessment” was “ad hoc”, with “little evidence of effective mechanisms for sharing information and best practice”. They found “a strong emphasis on process and procedural issues to the detriment of focus on improvements in the Three Rs”, with “relatively limited opportunities for interactions that bring together and promote ideas and developments for the Three Rs between diverse groups”, and that, “overall, a culture of whole teams working together was lacking”.

The committee made 33 recommendations, and emphasised the need for “a clear restatement of the key role of the Named Veterinary Surgeon (NVS) and the Named Animal Care and Welfare Officer in animal welfare and the Three Rs, along with a clear route for escalation of concerns to the AWERB”. Again to its credit, the College “accepted all the recommendations”, admitted that there was “significant scope for improvement”, and said that it “will now move quickly to implement the recommendations”.2 The need for this investigation leads to two important questions. First, why was such a situation allowed to develop at Imperial College, one of the world’s most prestigious universities? Why were the Certificate Holder, the senior academics, the project and personal licence holders, the NVS, the Home Office Inspector and others, not performing their duties up to even the minimal standards required of them?

The second question, is that: if this situation could be allowed to develop at Imperial College, in what other institutions do similar problems exist and are similarly low standards considered acceptable? Professor Paul Flecknell, a member of the committee and director of the research animal facilities at Newcastle University, said that, while the report was specific to Imperial College, “every institution will pick up something we’ve said and think, ‘we should take more note of that’ ”.3 The Home Office, and the equivalent authorities in other countries, should insist that they do just that.

 

References

1 Anon. (2013). Independent Investigation into Animal Research at Imperial College London, 38pp. London, UK: Imperial College. Available at: http://brownreportinfo/wp-content/uploads/2013/12/Brown-Report-Final-EMBARGOED-0001GMT-10-12-132.pdf.

2 Jones, J-P. (2013). Imperial responds to animal research investigation report. London, UK: Imperial College. Available at: http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_9-12-2013-18-21-18.

3 Cressey, D. (2013). Report slams university’s animal research. Nature News, 10 December 2013. Available at: http://www.nature.com/news/report-slams-universitys-animal-research-1.14329.

Time for Reconsideration

Laboratory animals have long been used as surrogates for human beings, because it has been considered acceptable to expose them to conditions and procedures which would not be considered ethical, if applied to ourselves. Initially, the focus was mainly on gaining a better understanding of how the body’s cells, organs and systems function and are controlled, and how failures of one kind or another can lead to pathological conditions. Then, from about the middle of the last century, animals came to be used more and more in tests to determine the effects of exposure to chemicals and chemical products — in attempts to determine information of direct relevance concerning the efficacy of drugs and vaccines and/or the adverse effects of chemicals and various kinds of chemical products, in the hope of predicting likely effects in humans, as a basis for appropriate action.

However, attitudes toward the reliance on this approach are now changing, with the increasing recognition that the knowledge gained from animal studies cannot be expected to have direct relevance to humans, which has uncertain, and even dangerous, consequences. This problem is particularly acute for the pharmaceutical industry, which is in a state of crisis, because of the late withdrawal of new drugs as a result of lack of efficacy or unacceptable side-effects not detected during preclinical testing, despite the application of highly expensive and seemingly sophisticated testing in animals. There are two main reasons for these difficulties. Firstly, functions and controls in animals and humans tend to be very different in detail, however similar they may appear to be on the surface. Animals are highly adapted to their individual and specific lifestyles and environments.

During evolution, species separate and diverge from common ancestors, based on these adaptations, which tend not to involve the emergence of something totally new, but which rely instead on modifications of what was already there. This has profound implications for attempts to model human diseases in animals, especially since, in view of the absence of sufficient knowledge about what is being modelled, it is impossible to judge whether or not the model has any value. One response to this unsolvable problem of species differences is the attempt to humanise animals by transferring human genes into their genomes, in the hope of simulating effects and responses in humans. However, that can be considered naïve, since the manipulation of complex networks of interacting controls, which are not well understood and which will inevitably differ considerably in animals and humans, is likely to produce information which cannot be interpreted with confidence, and which may be dangerously misleading. Perhaps introducing human genes in animals will have an outcome analogous to the unforeseen and unwanted effects of introducing rabbits into Australia!

The second insuperable problem is that the ‘human’ being to be modelled in animals doesn’t actually exist. Human polymorphism leads to infinite variety, and there are many, many sub-populations within the overall human population, which will differ in their susceptibilities to disease and in their responses to chemicals and chemical products, including drugs. One resultof this is that a drug which is highly effective in one patient can be lethal to another. Similarly, a chemical which has no effect in some individuals, could result in a highly allergic response in others. The only way forward is to recognise that the modern, but still developing, techniques of cell biology and molecular biology, combined intelligently with the vast information storage and computational systems which are now available, should be applied directly to human material in vitro and ex vivo, and, with strict ethical controls, to human volunteers.

Carefully planned and executed, this approach could take account of human polymorphism, past or concurrent diseases or therapies, and the differential effects of age, occupation, geographical location, lifestyle and exposure to medicines and other chemicals. In the pharmaceutical industry, for example, the ‘one drug suits all’ concept has been overthrown, and therapies in the future will involve personalised medication, where the treatment will be designed specifically for the individual patient. A contribution to this development could be the Personal Genome Project, which began at Harvard University in 2005. The aim is to recruit people willing to freely donate their individual genome sequences and associated medical and other biologically-relevant data, for use for research purposes.

The data are to be placed within the public domain and made freely available to researchers, so that they can test their hypotheses about the relationships between genotype, phenotype and environment — as well as susceptibility to disease and responses to therapies. A related initiative was launched in the UK on 7 November 2013, with the hope of persuading 100,000 individuals to agree to take part. While this kind of initiative may appear to offer the solution to some problems, it also opens up new ones, including quality control of the data (which will come from diverse sources of uneven quality), protection of the privacy of the data donors, and management of the commercial exploitation of what is donated.

Responsibility for Animal Experiments: Where the Buck Stops

bunny and arm

Sadly, just after the Animals (Scientific Procedures) Act 1986 had been amended1 to bring into force in the UK the new European Directive 2010/63/EU on the protection of animals used for scientific purposes,2 allegations were made about the abuse of laboratory animals at one of the country’s leading academic research establishments.3 Nothing more must be said about that, pending the outcome of various investigations. However, it raises the question of who is responsible for ensuring that animals are used properly, and who is culpable, when things go wrong.

In the UK, we have long experience of the clearly-defined responsibilities of the Home Office ministers and officials, including the Animals in Science Regulation Unit (ASRU) Inspectorate, and various named persons in the breeding or user establishment, including the certificate holder, the day-today care person, the veterinary surgeon, the project licensees and the personal licensees. The former EU Directive, Directive 86/609/EEC, said relatively little about specific responsibilities, but the new Directive says far more in several of its articles, as follows:

Article 23 requires Member States to ensure the competence of all staff, by seeing that all staff are adequately educated and trained before they perform any of their functions.

Article 24 spells out the specific requirements for personnel to be responsible for overseeing the welfare and care of the animals in the establishment, ensuring that the staff dealing with animals have access to information specific to the species housed in the establishment, and ensuring that the staff are adequately educated, competent and continuously trained, and supervised until they have demonstrated the requisite competence, whilst also ensuring that projects are carried out in accordance with the project authorisation.

Article 25 requires Member States to ensure that each establishment has a designated veterinarian with expertise in laboratory animal medicine, charged with advisory duties in relation to the well-being and treatment of the animals.

Article 26 lays down the requirement for an animal welfare body, while Article 27 outlines its tasks in relation to the welfare of the animals, the application of the Three Rs, the internal establishment and review of operating procedures with regard to monitoring, reporting and follow-up, including the development and outcomes of projects and their further contributions to the Three Rs.
Article 30 requires the Member States to ensure that all establishments keep records of the number and species of animals involved, their origins, their use and their death or re-homing.

Article 34 specifies that the competent authorities of the Member States must carry out regular inspections, to verify compliance with the requirements of the Directive, taking into account the number and species of animals involved, the record of the establishment in complying with the requirements of this Directive, the number and types of projects carried out, and any information that might indicate noncompliance.

Article 35 states that, when there is due reason for concern, the Commission shall undertake controls of the infrastructure and operation of national inspections in Member States, and the competent authority of the Member State concerned shall undertake measures to take account of the results of the control.

There are, of course, other individuals and organisations with responsibilities. These include the research funding bodies and the peer reviewers who assess research grant proposals, as discussed in a useful booklet, Responsibility in the use of animals in bioscience research,4 published by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). Also of importance are the editors and editorial boards of the journals which publish articles which involve the use of laboratory animals, as was considered in a thoughtful article by Helen Galley.5

Given the clarity of the legislation and the specified responsibilities of so many different kinds of people, how can things go so wrong, as happens, as far as we know, on relatively rare occasions? First of all, human beings are involved, and whether those involved are doctors, lawyers, airline pilots, other professionals or even parents, we are a fallible
species and sometimes do wrong things, accidentally or deliberately. We need rules within which to work, and people in place to try to ensure that we do so, but they can’t watch all of us all of the time. In the end, it all depends on personal integrity, and, in the case of performing potentially-harmful experimental procedures on living vertebrates, the ultimate and inescapable responsibility must rest with those who actually perform the procedures. That is where the buck stops.

References
1 Anon. (2012). The Animals (Scientific Procedures) Act 1986 Amendment Regulations 2012. Statutory Instrument No. 3039, 57pp. London, UK: The National Archive. Available at: http://www.legislation.gov.uk/uksi/2012/3039/contents/made (Accessed 23.05.13).
2 Anon. (2010). Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Official Journal of the European Union L276, 20.10.2010, 33–79.
3 Woolf, M. & Jacobson, S. (2013). Inquiry into ‘abuse’ of lab rats at college. The Sunday Times, 14 April 2013, p. 8.
4 Anon. (2013). Responsibility in the use of animals in bioscience research, 24pp. London, UK: NC3Rs. Available at: http://www.nc3rs.org.uk/downloaddoc.asp? id =719 (Accessed 23.05.13).
5Galley, H.F. (2010). Mice, men and medicine. British Journal of Anaesthesia 105, 396–400.

Words of Support for PiLAS

Jane Goodall
Dr Jane Goodall. (Photo Stuart Clarke)

Jane Goodall, PhD, DBE
Founder of the Jane Goodall Institute; UN Messenger of Peace

I am very pleased that PiLAS is being launched by FRAME because, unfortunately, many of the issues raised by those concerned about the use of animals in laboratory experimentation have not been adequately addressed. Although I am not qualified to speak in depth about the need for the use of animals as models for human beings, I have discussed this with many people who are, and I have read extensively about the subject. And it seems conclusive that animals can never be really good models for human beings since they are anatomically, physiologically and behaviourally adapted to ways of life very different from our own. In short, experiments on animals lead to too much pain for too little gain. As technical advances provide for new ways of gaining knowledge, the use of animals is becoming increasingly unnecessary. And as we learn more about animals’ capacity to suffer — physically and psychologically — increasingly unethical. Almost never can the basic needs of laboratory animals be adequately addressed. In the 21st century, it is imperative that we move away from the use and abuse of animals for this purpose.

Professor David Greenaway
Vice Chancellor, University of Nottingham
FRAME Patron

The issues raised by animal experimentation are complex and emotive, yet it is crucial to consider and debate these, if we are to find alternative methods and reduce the need for laboratory animal procedures. PiLAS will provide an excellent platform to facilitate high quality unbiased and informed discussion, and build on the outstanding work of the Alternatives to Laboratory Animals journal over the past 30 years. I welcome the new supplement and look forward to reading about the important topics it deals with.

Nic Dakin MP
House of Commons

As Chair of the All-Party Group on Replacement of Animals in Experimentation, I am delighted to welcome the launch of PiLAS. This will create a significant new forum for professionals from all disciplines to share their expertise and ideas about how to further improve the quality of experiments to the benefit of both animals and humans. I anticipate that the quality of discussion it generates will be very high indeed. It is likely to make an exciting contribution to a subject of great interest to the general public, as well as to the scientific community.

Cleo Paskal
Literary Executor of Bill and Claire Russell

Bill Russell was extremely gratified when Michael Balls, among others, rediscovered The Principles of Humane Experimental Technique, decades after it was published, not for reasons of personal vanity, but because it gave him hope that the rigorous science that it contained might yet be fully integrated into laboratory science, resulting in more-humane, and better, research. PiLAS is a further, and much needed step along that road. Bill would be pleased.

A pdf of these comments is available by CLICKING HERE