Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 1
1
Introduction and Overview1
Animals are widely used in neuroscience research to explore normal
and abnormal biological mechanisms of nervous system function, to iden-
tify the genetic basis of disease states, and to provide models of human
disorders and diseases for the development of new treatments. Numerous
laws, policies, and regulations are in place governing the use of animals in
research. These measures are intended to ensure the humane care and use of
animals, including the implementation of practical steps to use the smallest
number of animals necessary to achieve significant results while minimiz-
ing pain and distress. Many animal care and use issues are generic to all
types of biomedical research; however, animal regulations have implications
specific to neuroscience research.
To consider these issues from a global perspective, the Institute of
Medicine Forum on Neuroscience and Nervous System Disorders, in col-
laboration with the National Research Council Committee on Science,
Technology, and Law and the Institute for Laboratory Animal Research,
1 This workshop was organized by an independent planning committee whose role was
limited to identification of topics and speakers. This workshop summary was prepared by
the rapporteurs as a factual summary of the presentations and discussions that took place at
the workshop. Statements, recommendations, and opinions expressed are those of individual
presenters and participants, and are not necessarily endorsed or verified by the Forums or the
National Academies, and they should not be construed as reflecting any group consensus.
Furthermore, although the current affiliations of speakers and participants are noted in the
report, many qualified their comments as being based on personal experience over the course
of a career and are not being presented formally on behalf of their organizations (unless
specifically noted).
1
OCR for page 2
2 INTERNATIONAL ANIMAL RESEARCH REGULATIONS
convened the workshop “U.S. and European Animal Research Regula-
tions: Impact on Neuroscience Research.” Held at the Kavli Royal Society
International Centre in Buckinghamshire, UK, on July 26-27, 2011, the
workshop brought together neuroscientists, legal scholars, administrators,
and other key stakeholders to discuss current and emerging trends in animal
regulations as they apply to the neurosciences. As outlined by co-chairs
Colin Blakemore, professor of neuroscience at the University of Oxford,
and Arthur Sussman, of the University of Chicago Law School, the work-
shop was designed to
• identify and discuss current international animal use regulations;
• examine the implications of current policies on the research enter-
prise, including the impact of disparate policies;
• discuss developments in law school curriculums, animal law prac-
tice, and activity in the courts that may affect the use of animals
in research;
• explore the reasons for the establishment of specific regulations; and
• discuss opportunities for harmonization of regulations and/or the
development of global core principles.
ANIMAL RESEARCH IN THE NEUROSCIENCES:
INTRODUCTION BY COLIN BLAKEMORE
As background for the workshop discussions, Blakemore highlighted
some of the current issues surrounding the use of animals in neuroscience
research. In research involving animals, he acknowledged a necessary ten-
sion between the desire to benefit from the advances in knowledge that
accrue from studies in animals and the desire to avoid deliberate harm to
the animals. Opinions on the use of animals in research are polarized. Re-
searchers, clinicians, and institutions that support animal research, along
with a portion of the general public, accept its importance for progress in
medicine. The principal argument for using animals in biomedical research
states that it is ethically more acceptable than neglecting the suffering of
the sick (human or animal, as animal research also benefits animals). Some
individuals and organizations, however, oppose animal research on ethical
grounds; they contend that humans should not benefit from animal suf-
fering (a deontological argument: actions are either intrinsically right or
wrong, regardless of the consequences). Some challenge the validity of ani-
mal models and the unreliability of treatments developed through the study
of non-human species (a utilitarian argument: the correct action is the one
that maximizes the overall good, specifically considering the consequences).
Others claim that alternative methods to animal use are already available
or could be available with increased efforts to develop them.
OCR for page 3
3
INTRODUCTION AND OVERVIEW
BOX 1-1
Particular Issues Surrounding Animal Use in Neuroscience
• odels of nervous system disease may include behavioral and cognitive phe-
M
notypes that have the potential to result in suffering:
o esearch on conditions such as addiction, depression, anxiety, and fear
R
may be problematic.
• ain, which is normally avoided in the design of experiments, is an important
P
topic of study.
• odification of sensory experience may be considered a form of suffering.
M
• on-human primate use raises concerns due to costs and public perception.
N
• esearch may involve invasive methodology, restriction or control of food or
R
water intake, and/or prolonged or repetitive procedures.
SOURCE: Blakemore presentation.
Animal Use Issues Specific to Neuroscience
Blakemore highlighted several issues associated with the use of animals
that are specific to neuroscience research, such as the use of non-human
primates, pain as a topic of study, and the use of invasive methodologies
(Box 1-1). Non-human primates, due to their close phylogenetic relatedness
to humans, make them the preferred species to study issues such as fine
motor control, high-level cognitive functions, and decision making. This
close evolutionary proximity to humans increases scrutiny of the use of
non-human primates and raises special concerns, including public attitude
about their use, supply issues, and costs. The 2006 Weatherall Report2
concluded that there is scientific justification for the carefully regulated
use of non-human primates when there is no other way to address clearly
defined questions, including those raised by certain neuroscience studies
(MRC, 2006).
Another issue is the use of genetically modified animals. Modification
of genes that regulate the nervous system and neurologic development can
produce a particular phenotype with behavioral and cognitive consequences.
The impact of the phenotype itself, in terms of suffering, must be taken into
account even before considering the impact of procedures to be carried out
on genetically modified animals. The introduction of human genetic mate-
2 Note that a comprehensive 5-year follow-up review of the quality and impact of primate
research has been published. Review of Research Using Non-Human Primates: Report of a
Panel Chaired by Professor Sir Patrick Bateson FRS is available at http://www.mrc.ac.uk/
Utilities/Documentrecord/index.htm?d=MRC008083.
OCR for page 4
4 INTERNATIONAL ANIMAL RESEARCH REGULATIONS
rial into animals is another topic of much discussion. For example, a variety
of mouse models for Huntington’s disease, a neurodegenerative disorder,
incorporate a portion of the human Huntington gene. Blakemore referred
participants to an Academy of Medical Sciences (UK) report on the use of
animals containing human genetic material that was released the same week
as the workshop (AMS, 2011).
Neuroimaging is increasingly being used in animal studies. While im-
aging is noninvasive, such studies are generally longitudinal, involving
repetitive procedures. It is not always clear, Blakemore noted, that imaging
is preferable to invasive methodologies.
A Framework for Research on Animals
Blakemore suggested there is a strong need for a regulatory framework
that is ethically secure, consistent, legally strong, and defensible but not so
overly burdensome that it impedes scientific progress. Such a framework
might include strict requirements for and a commitment to high-quality
welfare and good husbandry; good recordkeeping; transparency and ac-
countability; provisions for public engagement; certification of researchers
so that their skills are documented and controlled; and a system for ap-
proval of individual projects based on cost-benefit analysis.
Cost-benefit analysis, while theoretically straightforward, is challenging
to apply to animal research. By definition, research involves the unknown,
and potential future benefits cannot definitively be known in advance. In
contrast, the immediate costs relative to the suffering of animals can be
determined before and during animal experiments. Therefore, individuals
continually weigh potential benefits against definite costs, Blakemore said.
A 1999 poll published in the New Scientist found that 83 percent of
those surveyed would support research on mice to study childhood leuke-
mia if there were no pain involved (Aldhous et al., 1999). If pain or death
was involved, 63 and 69 percent respectively still supported the research.
In a 2000 poll by the UK-based Ipsos Market and Opinion Research Inter-
national (Ipsos MORI) firm, only 32 percent of those surveyed supported
research on animals in general if there were no alternatives, but when the
same group was asked whether they would accept the use of animals for
medical research if there was no unnecessary suffering, 84 percent agreed
(Ipsos MORI, 2000). This, Blakemore said, shows that people are perform-
ing quite complex personal calculations and shifting their views depending
on the perceived costs and benefits.
Opinion has changed dramatically and progressively over the past
10 years in the United Kingdom, Blakemore noted. The greatest change in
opinion was between 1999 and 2004. Since 2004, polls conducted by Ipsos
MORI have consistently shown that 87 percent of the public conditionally
OCR for page 5
5
INTRODUCTION AND OVERVIEW
accepts the use of animals in research for medical benefit, if suffering is
minimized and/or there is no alternative to the use of animals (Ipsos MORI,
2010).
A key component of the shifting views toward animal research in the
United Kingdom has been due to increased openness and public engage-
ment. It is important, Blakemore stressed, that scientists themselves speak
out to win the trust of the public, politicians, and the media. Ipsos MORI
polls show that the majority of the public trusts scientists to tell them the
truth, yet scientists do not normally engage with the public to provide in-
formation about their research (Ipsos MORI, 2008). Blakemore noted that
in recent years, against the backdrop of political support, including new
legislation to prevent violence, there has been an increase in the willing-
ness of researchers to talk openly about their work. In addition, there was
growing public support of animal research with groups such as Pro-Test3
holding rallies in support of animal testing in medical research. In reports of
advances resulting from research, more institutions are openly identifying
the animal species used in the research, which, Blakemore noted, has had
a positive impact on public opinion.
ORGANIZATION OF THE WORKSHOP AND REPORT
Following the overview of issues presented by Blakemore, the work-
shop considered current and emerging international regulations governing
animal research and the impact of legal trends, including animal rights laws,
Freedom of Information requests, and state “sunshine laws,” on the use of
animals in research (Chapters 2 and 3). The next session of the workshop
focused on the implications of these laws, regulations, and policies for
neuroscience research, and considered case studies applying the “3Rs” (re-
placement, refinement, and reduction) to neuroscience research (Chapters 4
and 5). The final portion of the workshop focused on engaging the public,
politicians, and the media in animal research issues, and developing core
principles for regulating the use of animals in research (Chapters 6 and 7).
In the closing session, session chairs identified what they viewed as the key
points that emerged (Chapter 8 and summarized below).
Highlights of Workshop Sessions
Session chairs noted key points that emerged during workshop presen-
tations and discussions:
3 In February 2011, 5 years after it formed, Pro-Test wound up its UK operations because
it had successfully met its goals. See http://www.pro-test.org.uk/.
OCR for page 6
6 INTERNATIONAL ANIMAL RESEARCH REGULATIONS
• Regulatory Harmonization (Session I): Animal research regulations
in the United States and the European Union are more similar than
different. International collaborations are helping to influence new
regulations, raise standards in emerging regions (e.g., Asia, South
America), and contribute to global harmonization.
• Administrative Burden (Sessions I and III): Regulatory systems have
a variety of costs, including financial costs, the costs of increased
oversight for regulators, and the costs of lost research time for
scientists. Appropriate measures of the success of animal welfare
regulations can be useful because it is unclear whether increased
costs and burdens result in improved animal welfare.
• Legal Trends (Session II): The effect of increased attention on ani-
mal rights laws is unclear. Freedom of Information requests and
state sunshine laws are used in the United States to allow the public
to access detailed information about the use of animals in research.
The effect of these laws on animal research is not yet known.
• Non-Human Primates in Neuroscience (Session III): Non-human
primates continue to be used in biomedical research, including
neuroscience research. Such studies complement in vitro studies, in
silico modeling, human brain imaging, and parallel investigations
in rodents and other species.
• Data Sharing (Session IV): Systematic reviews of preclinical data
could potentially support the 3Rs (replacement, refinement, and
reduction), improve the quality and value of animal studies,
and better inform clinical trials. Research might benefit if pre-
clinical animal data are more accessible, including negative data,
primary data, and precompetitive data.
• Engaging the Public (Session V): Communication between the sci-
entific community and the public, the media, and policy makers
about the role and welfare of animals in neuroscience research is
critical. In some countries, public engagement and education can
impact the public view of the use of animals in research.
• Aligning Core Principles to Achieve Consistent Animal Care and
Use Outcomes (Sessions I and VI): Animal research regulations
might benefit from a careful balance of quality science, animal
welfare, and public confidence. Animal welfare can be considered
together with scientific goals and the larger needs of society. Align-
ment of animal research principles can be achieved independent
of differing policies or practices. Core principles governing how
animal studies might be conducted are the same for any discipline,
including neuroscience.
