Tag Archives: regulation

The ethics and value of responsible animal research

This post, signed by over 90 scientists, is in response to an article published 09/04/16 in the New York Times titled: “Second thoughts of an animal researcher.” 

The ethics and value of responsible animal research

Last week we learned that in the first decade since its introduction the HPV (human papilloma virus) vaccine has cut the rate of cervical cancer by half. Experts estimate that the vaccine could eradicate cancer caused by the virus within the next 40 years. This is indeed good news, as today cervical cancer kills about 250,000 women every year.

Such breakthroughs are the result of decades of research that typically begin with the study of basic mechanisms of cancer in-vitro, the development of disease models and therapies in animals, and their translation to humans. In the particular case of the HPV vaccine rabbits, mice, cattle and human volunteers were used in the research dating back to the 1930s, when Richard Shope first isolated viral particles from wart-like tumors in the Eastern cottontail rabbit.

Medical history is replete with such stories and their contribution to human health is undeniable. A couple of generations ago a visit to a physician might have resulted in a recommendation to induce vomiting, diarrhea or, more commonly, bleeding. Diphtheria, mumps, measles and polio were common and untreatable. Treatment for mental health disorders included malarial shock therapy, lobotomy, lifelong institutionalization, and worse. Life expectancy in the U.S. was less than 50 years; it is now close to 80 years.

Animal research was instrumental in most of these past achievements, and the overwhelming majority of scientists agree that the use of animals in research is critical to make progress in many areas of biomedical and behavioral research. However, some members of the public and a few scientists express doubt about the moral justification for the work.

Such is the case with Professor John Gluck, a former primate researcher who conducted lab research decades ago, in the 1960s-1980s, during a time with different standards and regulations compared to contemporary practice. Gluck writes about his own ethical unease which eventually led him to abandon his work with animals and to argue that the existing system for reviewing and conducting animal research should be revised. Gluck appears to think that if others have not arrived at his same conclusion it must be because of their failure to engage in moral reasoning.

Studies in rhesus macaques first indicated that Tenofovir could block HIV infection. Photo: Understanding Animal Research

Studies in rhesus macaques first indicated that Tenofovir could block HIV infection. Photo: Understanding Animal Research

The fact is that most scientists and the public have wrestled with moral questions about the use of animals in research for over 100 years. The results of this ongoing, thoughtful reflection are personal and professional codes of ethics, laws and regulations in the US and other countries, and widespread societal changes in our views and treatment of other animals. Society as a whole considers as morally permissible the regulated and justified use of animals to advance medical knowledge, to improve the well-being of human and nonhuman animals alike, and to understand the health of the environment.

Had animal research leading to the HPV vaccine been banned, cervical cancer today would continue to kill women at a constant rate. Many of us believe that there is a moral imperative to use scientific knowledge and research skills to improve the lives of these women by means of well-regulated, responsible animal research. Opponents may argue that such research should be banned because all nonhuman animals deserve equal moral concern to what we offer human beings.

Image of mice courtesy of Understanding Animal Research

Image of mice courtesy of Understanding Animal Research

As a society we must grapple with and debate these questions and arrive at a democratic decision to such moral disputes. It is unfortunate that meaningful debate is impeded when critics attack the work by falsely claiming that animal research has no value for human health. They incorrectly assert that scientists can do as they please in their laboratories or, worse, that scientists, veterinarians and technicians do not truly care about the well-being of their animal subjects. And they mislead the public by claiming that alternatives exist (such as computer simulations, cell culture, human testing) that can fully substitute the goals of animal research. Indeed, Professor Gluck attempted to reinforce such falsehoods about animal research and animal researchers in his op-ed piece.

The truth is that the care and treatment of animal subjects is protected not only by carefully specified standards, but also by a well-developed federal oversight system that is transparent to the public. Alternatives are used when they exist and when it is possible. Scientists themselves have worked effectively to produce many of the alternative methods and to continue to refine practices to improve animal welfare. The weighing of scientific objectives with consideration of animal welfare is required by law before the approval of any experimental protocol.

Gluck argues that the US government should convene a national commission to consider the ethical treatment of nonhuman animals in medical research. However, he must recognize that animals in research studies are just a small fraction of all animals used by humans for a wide range of purposes that include food, entertainment, labor, clothing, and companionship.

The comparison is particularly true with respect to the number of chickens, turkeys, cows, pigs, and fish that are eaten. But even restricting the discussion to nonhuman primates (the topic of Gluck’s essay) it is also the case that nonhuman primates are a small, but important, fraction- generally less than 1%- of captive animals involved in research. Furthermore, in the US, there are just over 1,000 facilities that house nonhuman primates and that are licensed or registered with the USDA. Of those, fewer than 20% are research-registered facilities. The gross majority are licensed zoos, or various entertainment venues for the public.

Rhesus monkeys at the California National Primate Research Center. Photo credit: Kathy West

Rhesus monkeys at the California National Primate Research Center. Photo credit: Kathy West

Dr. Gluck and others have called on NIH to review its ethical practices when, in fact, following their logic, they should be asking the FDA for a moral justification for the production and consumption of filet mignon. Eating a steak has never saved a life; vaccines and therapies developed with the use of animals in research do so every single day. When such inversion of priorities is made evident, one must conclude that it is not those seeking to advance knowledge and human health via carefully regulated work who are at fault in their moral reasoning.

Moral decisions about the use of animals in research require consideration of the fact that science does not provide a recipe that will lead us directly to a cure for an illness. Instead, it provides a recipe to understand incrementally the physical and biological processes in nature, which we can then apply to make this a better world by reducing suffering for humans and for other animals.

Scientists, students, veterinarians, and staff who engage in biomedical and behavioral research with animals do it not because they have failed to consider the moral issues. They do it precisely because they have thought about them carefully and arrived at the conclusion that failing to do the research would prevent us from developing new cures, such as the HPV vaccine that now stands to eradicate cervical cancer, or being prepared to face new threats, such as confronting the Zika virus.

As the National Institutes of Health convenes this week to examine the science and ethics of research with nonhuman primates, one must remember the important contributions the work has made to the study of child health and development, diabetes and obesity, mental health, transplant tolerance, vaccines, HIV/AIDS, deep brain stimulation (DBS) and the development of brain-machine interfaces, among many other areas. Evidence for the contributions of animal research to such advances is widely available, including most recently, in a white paper. It is this evidence that provides the foundation for why animal research — occurring within an ethical and regulatory framework that requires consideration of both scientific objectives and animal welfare — is endorsed by a wide range of scientific and medical organizations.

Dario L. Ringach, PhD, Departments of Neurobiology & Psychology, University of California Los Angeles

Allyson J. Bennett, PhD, Department of Psychology, University of Wisconsin-Madison

Megan R. Gunnar, PhD, Institute of Child Development, University of Minnesota

Mark A. Krause, PhD, Department of Psychology, Southern Oregon University

Mary Dozier, PhD, Department of Psychology, University of Delaware

Aaron Batista, PhD, Department of Bioengineering, University of Pittsburgh

Bijan Pesaran, PhD, Center for Neural Science, New York University

Brittany R. Howell, PhD, Institute of Child Development, University of Minnesota

Greg Horwitz, PhD, Department of Physiology and Biophysics, University of Washington

John P. Capitanio, PhD, Department of Psychology, University of California-Davis

Jose Carmena, PhD, Helen Wills Neuroscience Institute, University of California, Berkeley

Robert A. Shapiro PhD, Department of Neuroscience, University of Wisconsin-Madison

Koen Van Rompay, DVM, PhD, California National Primate Research Center

David Jentsch, PhD, Department of Psychology, Binghamton University

George F. Michel, PhD, Department of Psychology, University of North Carolina-Greensboro

Chana Akins, PhD, Department of Psychology, University of Kentucky

Ian Nauhaus, PhD, Center for Perceptual Systems, University of Texas at Austin

Kimberley A. Phillips, PhD, Department of Psychology and Neuroscience Program, Trinity University

Drake Morgan, PhD, Department of Psychiatry, University of Florida

Michael Shadlen, MD/PhD, The Kavli Institute for Neuroscience, Columbia University

Ed Callaway, PhD,  The Salk Institute for Biological Sciences

Eliza Bliss-Moreau, PhD, Department of Psychology, University of California-Davis

Mehrdad Jazayeri, PhD, McGovern Institute for Brain Research, MIT

Wayne E. Pratt, PhD, Department of Psychology, Wake Forest University

Ken Miller, PhD, Center for Theoretical Neuroscience, Columbia University

Kristina Nielsen, PhD, The Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University

Mary E. Cain, PhD, Department of Psychological Sciences, Kansas State University

Mar Sanchez, PhD, Department of Psychiatry & Behavioral Sciences, Emory University

Anthony Movshon, PhD, Center for Neural Science, New York University

Michael E. Goldberg, MD, Departments of Neuroscience and Psychiatry, Columbia University

Michele Basso, PhD, Brain Research Institute, University of California Los Angeles

Andreas Tolias, PhD, Baylor College of Medicine

Margaret Livingstone, PhD, Harvard Medical School

Doris Tsao, PhD, Department of Biology and Biological Engineering, California Institute of Technology

Dora Angelaki, PhD, Baylor College of Medicine

Jeff Weiner, PhD, Department of Physiology and Pharmacology, Wake Forest School of Medicine

Elizabeth Simpson, PhD, Department of Psychology, University of Miami

Robert Wurtz. PhD, Scientist Emeritus, NIH

Christian R. Abee, DVM, DACLAM, University of Texas MD Anderson Cancer Center

Jon Levine, PhD, Wisconsin National Primate Research Center, University of Wisconsin-Madison

John H. Morrison, PhD, California National Primate Research Center, University of California Davis

Paul Johnson, MD,  Yerkes National Primate Research Center, Emory University

Nancy L Haigwood, PhD, Oregon National Primate Research Center, Oregon Health & Science University

Michael Mustari, PhD, Washington National Primate Research Center, University of Washington

Andrew A. Lackner, DVM, PhD, Dipl. ACVP, Tulane National Primate Research Center, Tulane University Health Sciences Center

Alessandra Angelucci, PhD, Department of Ophthalmology and Visual Sciences, University of Utah

Brenda McCowan, PhD, Population Health & Reproduction School of Veterinary Medicine, UC-Davis

Alan Brady DVM, ACLAM, Michale E. Keeling Center for Comparative Medicine and Research, University of Texas MD Anderson Cancer Center

Lisa Savage, PhD, Department of Psychology, Binghamton University

Steven J. Schapiro, PhD, Department of Veterinary Sciences, University of Texas MD Anderson Cancer Center

Nicolle Matthews-Carr, PhD, BCBA-D

Stephen I Helms Tillery, PhD, School of Biological & Health Systems Engineering, Arizona State University

Regina Gazes, PhD, Department of Psychology, Bucknell University

Nim Tottenham, PhD, Department of Psychology, Columbia University

Michael J. Beran, PhD, Department of Psychology, Georgia State University

Doug Wallace, PhD, Psychology Department, Northern Illinois University

Gary Greenberg PhD, Professor Emeritus, Psychology, Wichita State University

Richard Born, MD, Harvard Medical School

Lee E. Miller, PhD, Departments of Physiology & Biomedical Engineering, Northwestern University

Paul M Plotsky, PhD, Professor Emeritus, Department of Psychiatry & Behavioral Sciences, Emory University

John J. Sakon, PhD, Center for Neural Science, New York University

Rick A. Finch, PhD, Department of Veterinary Sciences, University of Texas MD Anderson Cancer Center

Charles R. Menzel, PhD, Language Research Center, Georgia State University

Farran Briggs, PhD, Department of Physiology and Neurobiology, Dartmouth University

Alan M. Daniel, PhD, Department of Social Science, Glenville State College

Corrina Ross, PhD, Department of Biology, Texas A&M University

Cynthia Anne Crawford, PhD, Department of Psychology, California State University

William D. Hopkins, PhD, Neuroscience Institute, Georgia State University

Klaus A. Miczek, PhD, Department of Psychology, Sackler School of Biomedical Sciences, Tufts University

Jeffrey Schall, PhD, Psychological Sciences, Vanderbilt University

David A. Washburn, PhD, Department of Psychology, Georgia State University

Gene P. Sackett, PhD, Professor Emeritus, Department of Psychology and National Primate Research Center, University of Washington

Jerrold S. Meyer, PhD, Department of Psychology, University of Massachusetts

Lynn Fairbanks, PhD, Professor Emeritus, Department of Psychiatry and Biobehavioral Sciences, UCLA

Moshe Syzf, PhD, Department of Pharmacology and Therapeutics, McGill University

Mark Seagraves, PhD, Department of Neurobiology, Northwestern University

Thomas Albright, PhD, Salk Institute for Biological Studies

Peter J. Pierre, PhD, Wisconsin National Primate Research Center, UW-Madison

Jack Bergman, PhD, Department of Behavioral Biology, McLean Hospital, Harvard Medical School

Michael A. Taffe, PhD, The Scripps Research Institute

Kim Wallen, PhD, Department of Psychology and Yerkes National Primate Research Center, Emory University

John A. Vanchiere, MD, PhD, Department of Pediatrics, LSU Health Sciences Center – Shreveport

Anita A Disney, PhD, Department of Psychology, Vanderbilt University

Limin Chen, MD, PhD, Department of Radiology & Radiological Sciences, Vanderbilt University

Stanton B. Gray, DVM, PhD, DACLAM, Department of Veterinary Sciences, University of Texas MD Anderson Cancer Center

David Abbott, PhD, Department of Obstetrics and Gynecology, University of Wisconsin-Madison

Ramnarayan Ramachandran, PhD, Department of Hearing and Speech Sciences, Vanderbilt University Medical Center

Dorothy M. Fragaszy, PhD, Behavioral and Brain Sciences Program, Psychology Department, University of Georgia

Joe H. Simmons, DVM, PhD, DACLAM, University of Texas MD Anderson Cancer Center

Kathleen A. Grant, PhD, Department of Behavioral Neuroscience, Oregon Health Sciences University

Gary Dunbar, PhD, Department of Psychology, Central Michigan University

Paul Glimcher, PhD, Professor of Neural Science, Psychology and Economics, New York University

Larry Williams, PhD, Department of Veterinary Sciences, UT MD Anderson Cancer Center

Julie M. Worlein, PhD, Department of Psychology, University of Washington

Nathan Fox, PhD, Department of Human Development and Quantitative Methodology, University of Maryland

Mary Dallman, PhD, Emerita, Department of
Physiology, University of California, San Francisco

W. Thomas Boyce, MD, Departments of Pediatrics and Psychiatry, University of California, San Francisco

Philip H. Knight Chair, PhD, PSI Center for Translational Neuroscience,  University of Oregon

The signatories here are expressing their personal views which do not necessarily reflect those of their institutions.

Opinions, evidence, and anti-research agendas: A recap of a session at the American Society of Primatologists/International Primatological Society Meeting 2016

Research with nonhuman primates in laboratory settings is a tiny fraction of both laboratory research and nonhuman primate research. The topic is of disproportionate interest, however, for many reasons, and is reflected by a recent symposium at the joint meeting of The American Society of Primatologists and International Primatological Society. The session was titled “Use and care of captive non-human primates: Evaluating and improving ethical requirements.”  The session was notable for a number of reasons.

  • Despite its inclusion in the scientific program of scientific societies, the session presented little evidence and little balance.
  • The panelists were tied to organizations and/or campaigns opposed to laboratory research with nonhuman primates, yet did not disclose these ties upfront and failed to provide their basic starting assumptions or to acknowledge their positions.
  • The fact-less rhetoric did not provide a basis for productive discussion about captive primate care or changes to existing regulations, as would have been provided with evidence-based presentations.
Rhesus monkeys at the California National Primate Research Center. Photo credit: Kathy West

Rhesus monkeys at the California National Primate Research Center. Photo credit: Kathy West

Starting assumptions

We wrote yesterday about why providing basic starting assumptions is key when entering any dialogue, particularly when that dialogue involves conversations about the ethical and moral considerations related to the use of animals in biomedical research. If basic starting assumptions are not put forth at the start of a dialogue, then potential areas for agreement cannot be identified – if they in fact exist at all.

Unfortunately, this tenet was not practiced during the symposium. The organizers, anthropologists Drs. Barbara J. King and Marni M. LaFleur, wrote that the symposium was intended to“invite IPS and ASP members to come together and discuss how we may best manage the care and oversight of captive-living nonhuman primates.” At face value, this invitation seemed like a safe haven for “discussion and collaboration amongst researchers, veterinarians, technicians, and caregivers.” (In fact, data-driven sessions like these occur regularly at ASP meetings amongst the experts who care for and study captive primates.) However, the organizers and panelists failed to disclose their basic assumptions upfront, namely that they oppose the use of nonhuman primates in biomedical research.

Several speakers in the symposium have affiliated with campaigns by PETA, an organization that very clearly offers an absolutist position stating that animals should never be experimented on. The Vice President of Animal Research Issues at the Humane Society of the United States (HSUS), Kathleen Conlee, was also featured. HSUS’ position is less clear, though one of Conlee’s slides stated that the organization’s aim is to “Promote 3R’s but push for replacement of invasive research as quickly as possible.”

Macaques. Kathy West. CNPRC. 17

Macaques. Photo credit: Kathy West

As many attendees of the session attested after it concluded, the panelists’ failure to establish positions upfront resulted in a session with a very narrow focus that did not actually result in constructive discussion. Although the speakers’ stances on biomedical research were not stated upfront, they became readily apparent in each presentation.

The symposium followed a roundtable format, with the 6 speakers each presenting for about 5 minutes and a Q&A session for about an hour and a half afterward. Notably, the speakers did not include information on the well-established regulations and processes that are in place to balance research objectives, animal welfare, and public interests in scientific advances. (In 2015, ASP held a roundtable that thoroughly addressed these topics with evidence-based material.) Some presenters did show historical timelines of a few pieces of legislation enacted to address and ensure animal welfare (e.g., the passage of and amendments to the Animal Welfare Act), though nearly all presentations were lacking in evidence-based arguments. Instead, they often relied on outdated and out-of-context photographs (some from undercover investigations, which Conlee proudly acknowledged to the audience that HSUS had undertaken). Granted, the 5-minute time-slot for each speaker precluded the ability to delve into details, but one has to wonder if this format was a means to deliberately exclude the evidence-based regulations and processes that exist for laboratory animals.

Macaque. Kathy West. CNPRC.

Macaque. Kathy West. CNPRC.

Who should evaluate primate research?

The first speaker, LaFleur, wrote in the abstract of her presentation: “Ethical standards and cost-benefit analyses of non-human primates in research must continually be evaluated and reevaluated, by a diverse range of experts (including those without vested interests).” By “vested interests,” LaFleur presumably meant those working in primate research. What wasn’t clear is whether the panelists believe that they themselves and organizations such as PETA and HSUS also have clearly vested interests. For example, PETA has an extremely vested interests in this issue, yet nowhere during the session was it disclosed that panelist King has worked actively on campaigns organized by PETA (for other panelists’ ties to PETA; see below).

Most important though, from the perspective of beginning with fact:  The analyses of non-human primates in research to which LaFleur refers already routinely occurs by experts in the field: the trained scientists, veterinarians, and colony managers, including many members of ASP, who work with primates in captive settings on a daily basis and dedicate much of their research programs toward understanding and improving their welfare (see, for one recent example, this special issue of the American Journal of Primatology, dedicated solely to the well-being of laboratory nonhuman primates).

LaFleur also wrote in her abstract, “I argue that experimental procedures which cause permanent and irreversible harm on individual non-human primates should not be deemed ethically permissible.”

Macaques. Kathy West. CNPRC. 19

Photo credit: Kathy West

Yet, LaFleur failed to make a clear case for exactly why her position is justified in a way that is more appropriate than the position held by others who were part of the multi-level review that weighs scientific objectives and animal welfare and grants approval for research projects.

Furthermore, the slides that LaFleur presented at the conference showed data-free descriptions not of experimental procedures broadly, but of a single research topic. Her focus was on studies of infant development in monkeys (work she termed “maternal deprivation”) at the NIH and the criticism that she, King, and others leveled at ASP in regards to the society’s open support for research at the NIH. For example, in one of her slides, LaFleur stated that 54 members of ASP had signed a letter she co-authored to ASP asking for a reconsideration of their support letter for an NIH research project. In fact, in reading through the list of signatories, it is not at all clear to long-time members of ASP whether many of the signatories had ever been members of the society. One must question why this misinformation was presented at such a large meeting and also why this single research topic was the focus.

Another slide asked the question, “Can we not have differing opinions from our friends and colleagues?” Of course differing opinions may exist. What we strive for, however, are regulations and policies that are based in scientific evidence in order to provide for animal health and well-being. In the context of dialogue and the supposed focus on the symposium, the larger question is whether focusing on differing opinions about one research project and one area of study is a good substitute for serious and thoughtful consideration to identify core principles that can guide continuing changes in practice and policy.

Dr. Stacy Lopresti-Goodman came closest to laying out her basic assumptions upfront in her abstract, in which she wrote, “the primate research community should consider whether retirement of all NHP from biomedical research to sanctuary is warranted.” Lopresti-Goodman provided a few slides that cited research studies to back her written statement that “many individuals who experience…adverse conditions exhibit abnormal and/or stereotypic behaviors, and develop symptoms of psychological distress that mirror those of psychopathology in humans,” though it is notable that she did not disclose at any time during the session that she has co-authored articles with PETA employees and others staunchly opposed to animal research.

Zebrafish: Wellcome Trust Sanger Institute

Zebrafish: Wellcome Trust Sanger Institute

Moreover, several in the audience questioned her direct knowledge, experience, and expertise on the topic given her training and publication record in human perception and cognition.

 

Evaluating a claim from HSUS:  What is the evidence on environmental enrichment for nonhuman primates in captive settings?

In the US, all facilities registered or licensed to house nonhuman primates by the federal agency charged with oversight and enforcement of the Animal Welfare Act (AWA) are required to have a plan for environmental enrichment for those animals. Evidence-based evaluation of practices aimed at meeting the goal of maintaining animals’ health and well-being, in balance with scientific objectives, is the subject of research by many ASP members and those scientific results are on display at most ASP meetings.  The findings inform practices across the range of settings in which nonhuman primates live in captivity.

Conlee’s symposium presentation took a very narrow view, focusing on an analysis that her organization (HSUS) completed of enrichment plans from 38 universities and 18 federal facilities. Those plans were obtained, in part, via use of open records laws. The analysis was aimed at evaluating whether the plans were compliant with federal law. The abstract made a startling claim:  “Plans were scored according to compliance with the minimum Animal Welfare Act standards … The analysis revealed a majority of plans (44) were not adequate.”  To be clear, what that claim suggests is that 44% of the facilities — facilities that are regularly inspected by a federal agency, the USDA– are failing to comply with federal law.

Marmosets. Kathy West. CNPRC.

Titi monkeys. Photo credit: Kathy West

Serious claim – can it be evaluated?  Unfortunately, not well.  The analysis is unpublished and unavailable for public view or critique. Conlee provided no details about the methodology, including critical definitions of coding schemes for “plans [that] were scored according to compliance with the minimum Animal Welfare Act standards” and the subsequent data analysis.

The results Conlee presented were confined to bullet points on one slide rather than actual data with accompanying statistical analysis. Collectively, the “study” did not meet ASP’s (and other societies’) criteria for scientific presentations, but was nonetheless was presented as though it were an empirical study. While that is disappointing enough, the fact that the presentation and abstract made serious claims potentially misrepresenting a large number of dedicated research centers is even more reason to hold presenters to a standard of evidence.

Finally, Conlee presented a slide stating, “USDA requirements for all regulated facilities: no change in 30 years.” However, this statement is misleading. As Justin McNulty, IACUC & IBC Manager at The University of Texas at Austin, pointed out in the discussion following the presentations, “The Guide for the Care and Use of Laboratory Animals was just revised in 2011 and was reviewed by some of the people in this room. The recommendations contained in the Guide were based on published data, scientific principles, and expert opinion.” As described in the preface to the 8th Edition of The Guide, “The Guide is intended to assist investigators in fulfilling their obligation to plan and conduct animal experiments in accord with the highest scientific, humane, and ethical principle.”

Lack of evidence for the benefit-risk ratio in laboratory primate research?

LaFleur also gave King’s presentation in her absence. In her written abstract, King wrote, “I will discuss case studies that are lab-based and involve maternal-deprivation and other invasive experiments on cercopithecines; peer-reviewed scientific material from both the cercopithecine and also the comparative chimpanzee literature will provide context for discussing the benefit-harm ratio of such research on monkeys.” However, this presentation also lacked evidence-based claims and relied on references from the news media, as in one slide that touted the primate facilities that closed, or are in the process of phasing out, in 2015. In giving the presentation, LaFleur incorrectly stated that, with respect to the phasing out of the NICHD’s primate research, “those 300 monkeys [were] from the maternal deprivation work.”  This is false: only a small percentage of the colony at this facility each year has undergone nursery-rearing. Furthermore, as noted above, the actual process in place for evaluating balance of potential benefit and scientific objectives with animal welfare was not well addressed by the panelists.

Summary

Collectively, the session left much to be desired for those seeking data-driven suggestions for improving the captive care of non-human primates. As Dr. Karen Hambright, Professor of Psychology at the College of Coastal Georgia and long-time ASP member, stated during the discussion period, “As an educator who has worked with and is familiar with the conditions of animals in both zoos and labs, it my job to teach people to think critically and to base their views on evidence and not on emotional responses to polarizing rhetoric.”

King and LaFleur’s symposium abstract ended with the question, “How specifically can productive discussion about ethics be furthered among primatologists who work primarily on lab science and primatologists who work primarily on animal welfare, always acknowledging that these two groups may overlap?” A good start would be to enact practices that are foundational to any honest dialogue: namely, spelling out basic positions upfront and disclosing any potential conflicts of interest. Productive discussion could then ensue with evidence-based comments and suggestions.

Amanda Dettmer

Amanda M. Dettmer, PhD, is a Postdoctoral Fellow at the Eunice Kennedy Shriver National Institute of Child Health & Human Development. Her writing does not reflect the opinions of the NICHD or the NIH.

 

Confusing public agendas: Is it animal welfare? Or an absolutist campaign disguised as a call for “dialogue”?

A recent symposium at the joint meeting of The American Society of Primatologists and International Society of Primatologists focused on questions about the oversight and regulation of the housing, care, and treatment of nonhuman primates in research. Presentations of scientific research that primatologists conduct in order to inform animal care practices are a regular occurrence at ASP. This session, however, was billed as a call for dialogue. The organizers and participants included affiliates of groups and campaigns, including HSUS and PETA, that are often opposed to many types of primate research. ASP and ISP members conduct primate research in field, laboratory, zoo, and other settings across the world. The focus of this conference session appeared to be largely on laboratory  research, and particularly, that work funded by the US federal agency—the National Institutes of Health—that is charged with scientific research relevant to advancing public health.

Macaque. Photo credit: Kathy West. CNPRC.

Macaque. Photo credit: Kathy West. CNPRC.

Such research is a popular target for PETA and other groups opposed to the use of nonhuman animals in research, yet it remains a fact that the great majority of US facilities that house nonhuman primates are not dedicated research facilities (see graphic; summary illustration of data from USDA). As shown here, of the just over 1,000 US facilities that are either USDA-registered for research or USDA-licensed to house nonhuman primates for other purposes,  roughly 1/5th hold research registration. The majority are exhibitors. That includes zoos and other facilities that display animals to the public or engage in public interaction with the animals. In the US, the number of primates housed within each facility is reported annually for research institutions and is published by the USDA (for example, see here); however, the number of primates housed in licensed facilities is not easily accessible. This is similar to other countries.

Number of facilities by type of USDA-registration or license. Exhibitors include zoos and other facilities with public interaction.

Number of facilities by type of USDA-registration or license. Exhibitors include zoos and other facilities with public interaction. (Note: Although not necessarily required by federal law, sanctuaries may choose to be licensed as exhibitors because there is no separate category for sanctuaries.)

We’ve written previously about the standards of care, external oversight, and public transparency of federally-funded research within dedicated research facilities in comparison to zoos, sanctuaries, breeders, dealers, and private owners of nonhuman primates (Bennett & Panicker, 2016). In fact, some of these comparisons are central to discussions in recent months about decisions to ensure the best outcomes and long-term care of retired chimpanzees (1, 2, 3, 4, 5).

The limited focus of the recent ASP/ISP conference session to nonhuman primates used in research in the US (18% of facilities) could have many explanations. We will return to consideration of these points, and to a fuller discussion of the session, in subsequent posts. To begin, however, we return to excerpts from a post we made in 2013, with points that are foundational and key to a fair dialogue.

*****

Macaque. Kathy West. CNPRC.

Macaque. Kathy West. CNPRC.

Fair partners in dialogue: Starting assumptions matter and they should be spelled out

The importance and need for civil, open dialogue about the complex set of issues involved in use of animals is among the points of agreement between members of the scientific community, the public, animal rights activists, and others. Speaking of Research, along with others, has consistently advocated for and engaged in such dialogue via a number of venues, including our blog, public events, conference presentations, and articles.

One of the important purposes of dialogue is to communicate diverse viewpoints and values on animal research and one key to understanding those viewpoints and values is consideration of the basic starting assumptions, or positions, from which they arise. However, such dialogue often takes place without clear specification of the starting positions held by the people engaged in the conversation. Speaking of Research has previously highlighted the problem with this approach– for example, see Prof. Dario Ringach’s posts on a series of public forums on ethics and animal research (here, here, here).

Image of mice courtesy of Understanding Animal Research

Image of mice courtesy of Understanding Animal Research

The basic position of those engaged in animal research is obvious in part by the nature of their work. Furthermore, the very structure of the current regulations and practices reflect– both implicitly and explicitly – a set of positions on the ethical and moral considerations relevant to the use of animals in research (*see below).

What are the positions of those who oppose laboratory animal research?

In some cases, these are clearly stated. In the case of absolutists, the position is that no matter what potential benefit the work may result in, no use of animals is morally justified. This extends across all animals – from fruit-fly to primate. Furthermore, all uses of animals, regardless of whether there are alternatives and regardless of the need, are treated identically. In other words, the use of a mouse in research aimed at new discoveries to treat childhood disease is considered morally equivalent to the use of a cow to produce hamburger, the use of an elephant in a circus, or a mink for a fur coat.

In this framework, the focus often excludes consideration of the harms that would accrue as a consequence of enacting the animal rights agenda. For example, the harm to both humans and other animals of foregoing research or intervening on behalf of animals. As a result, while the absolutist position is often represented as one that involves only benefits and no harms, this is a false representation. While some animal rights groups are clear about their absolutist position, others—to our knowledge—are not.

On the other hand are those who avoid identifying directly with an absolutist position, but instead focus on the need for development of alternatives to use of animals in invasive research. This is a goal that may be widely desired and shared. It does not, however, address the question of what should be done in absence of alternatives and in light of current needs that can only be addressed by animal studies. In turn then, this position is silent with respect to moral and ethical consideration of a broad swath of research and fails to offer a framework to guide current actions.

Pigtail macaques at the Washington National Primate Research Center

Pigtail macaques at the Washington National Primate Research Center

We believe that the goal of promoting better dialogue would be assisted by making these positions clear and we provide a starting place below. We welcome additions by individuals and groups, as well as clarification or correction if any are unintentionally misrepresented. (For additional groups see original post).

People for the Ethical Treatment of Animals: Offers clear statement of absolutist position. “PETA has always been known for uncompromising, unwavering views on animal rights. PETA was founded in 1980 and is dedicated to establishing and defending the rights of all animals. PETA operates under the simple principle that animals are not ours to eat, wear, experiment on, or use for entertainment.”

New England Anti-Vivisection Society: Offers clear statement of absolutist position. “Is NEAVS against all animal experiments? Yes. For ethical, economic and scientific reasons, NEAVS is unequivocally opposed to all experiments on animals and works to replace them with humane and scientifically superior alternatives that are more relevant and predictive for humans.”

Humane Society of the United States (HSUS): Does not, to our knowledge, offer a clear position on whether it is morally acceptable to use animals in research when there is no alternative. What they do say: “As do most scientists, The HSUS advocates an end to the use of animals in research and testing that is harmful to the animals. Accordingly, we strive to decrease and eventually eliminate harm to animals used for these purposes.”

Physicians Committee for Responsible Medicine (PCRM/Physicians Committee): Does not, to our knowledge, offer a clear position on whether it is morally acceptable to use animals in research when there is no alternative. What they do say: “We promote alternatives to animal research and animal testing.”

How is this relevant to building productive dialogue?

For those engaged in dialogue about the ethical and moral considerations related to the use of non-human animals in research, even this brief list makes clear that it is important to ask participants to begin by putting their basic starting assumption forward. Why? For one reason, because those assumptions are key to identifying whether there are potential areas of agreement or none at all.

For example, discussing refinement of laboratory animal care with an absolutist—someone fundamentally opposed to animals in laboratories—misses the point. No amount of refinement would make the work acceptable to them. In this case, the more critical questions for discussion would include consideration of the relative risks and potential benefits of failing to perform research for which there are currently no alternatives to animal-based studies. Consideration of species’ capacities and criteria for differential status– if any– would also be a useful starting point.

white-mouse-pair-in-cage-with-cardboard-tubeWhat about dialogue with those individuals and groups who do not provide a clear position? Does it matter?

Some would argue that it does not because the dialogue is only concerned with animal welfare and with reducing harm to nonhuman animals, or with pushing forward to develop non-animal alternatives for some types of research. In fact, framed in this way, most scientists are not only in the same camp, but are also the people who work actively to produce evidence-based improvements in welfare and development of successful alternatives.

The problem, however, is that real-time, critical decision-making about human use of other animals in research is not simple. It does require serious, fact-based consideration of the full range of risks and potential benefits, including consideration of the health and well-being of both human and nonhuman animals. It also requires clarity about alternatives, where they exist and where they do not. And it requires some understanding of the time-scales in which knowledge unfolds – often decades – and a basic appreciation for the scientific process.

It is easy to argue that developing non-animal alternatives for invasive research should be prioritized. But this argument does little to address the question of what to do now, what we do in absence of these alternatives, and what choices we should make as a society. Those questions are at the center of dialogue and the core issues with which the scientific community and others wrestle. To address them productively, and in a way that considers the public interest in both the harms and benefits of research, requires articulation of starting assumptions and foundational views.

Allyson J. Bennett

Excerpted from previous post “Fair partners in dialogue: Starting assumptions matter and they should be spelled out” 6/12/13

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*For example, in the U.S., the laws and regulations that govern animal research mandate that proposals for use of vertebrate animals (including rats, mice, birds) provide, among other things: 1) a justification of the potential benefits of the work; 2) an identification of potential harms and means to reduce them; 3) evidence that alternatives to using animals are unavailable; 4) the use of the least “complex” species necessary to answer that question; and 5) much detail about the animals’ care and treatment, including the qualifications and training of the personnel involved. Consideration of these issues occurs not only at the stage of IACUC evaluation, but throughout the scientists’ selection of questions and studies to pursue, peer review and selection of projects for funding (more here). Furthermore, the entirety of the project must proceed in compliance with a thorough set of regulations designed on the basis of the 3Rs – reduce, replace, and refine (for more about regulation see here, more about 3Rs, here).

In other words, while there is always room for continued improvement, the structure is designed to require that the major ethical and moral considerations relevant to animal research be addressed by those involved in performing and overseeing the work. This structure also incorporates explicit consideration of changes that arise from new knowledge. That includes evolving knowledge about different species’ capacities and needs, as well as the development of alternatives to animal-based studies for particular uses. It also includes advances in our scientific understanding that demonstrate the greater need for basic research that requires use of animals to address key questions.

When are rats, mice, birds and fish protected by US federal laws?

There is sometimes confusion about how US law protects rats, mice and non-mammalian vertebrates such as birds and fish. Much of this confusion is rooted in the fact that the US Animal Welfare Act (AWA) explicitly excludes purpose-bred rodents (rats of the genus Rattus rattus, mice of the genus Mus mus), as well as birds that were specifically bred for research. Research with these purpose-bred rats and mice likely comprises the overwhelming majority of vertebrate animals in research in the US, but it is not overseen by the United States Department of Agriculture (USDA).

Sometimes this fact is used mistakenly (or perhaps purposely?) to suggest that all species not covered by the Animal Welfare Act are not protected by any federal laws.

Claims that research with non-AWA-covered species is not subject to care standards, external oversight, and public transparency are demonstrably untrue.

This post aims to address these misconceptions by looking at when and how rats, mice, and birds in research are covered by federal laws.

Mouse Science

Image from Understanding Animal Research

In the US, both the USDA, through the Animal and Plant Health Inspection Service (APHIS), and the Department of Health and Human Services (DHHS), through the Public Health Service (PHS) and National Institutes of Health (NIH) Office of Laboratory Animal Welfare (OLAW), are responsible for the oversight animal research. The table below provides a broad overview of the federal regulation and oversight agencies for different species and types of research.

Covered species are defined as: "with certain exceptions, any live or dead dog, cat, monkey (nonhuman primate mammal), guinea pig, hamster, rabbit, or such other warm-blooded animal, as the Secretary [of Agriculture] may determine is being used, or is intended for use for research”

Overview of animal research regulation in the US. The Animal Welfare Act (AWA) states that covered species are defined as: “with certain exceptions, any live or dead dog, cat, monkey (nonhuman primate mammal), guinea pig, hamster, rabbit, or such other warm-blooded animal, as the Secretary [of Agriculture] may determine is being used, or is intended for use for research” (7 U.S.C. 2132(g) The 2002 Farm Bill amended this definition to exclude purpose-bred rats, mice, and birds from the provisions of the AWA. Note that certain types of research with animals and most animal testing are also subject to regulation and oversight by the US Food and Drug Administration (FDA).

Animal Welfare Act (AWA) and USDA. The USDA is charged with enforcement of the AWA. The AWA applies to research with a range of species that includes: “with certain exceptions, any live or dead dog, cat, monkey (nonhuman primate mammal), guinea pig, hamster, rabbit, or such other warm-blooded animal, as the Secretary [of Agriculture] may determine is being used, or is intended for use for research” (7 U.S.C. 2132(g), referred to here as “USDA-covered species.” Institutions that engage in research with covered species must be registered with the USDA.  The AWA also applies to zoos, entertainment facilities, breeders, and other facilities that engage covered species in activities that involve public contact. All such facilities must be licensed by the USDA and research may also be conducted in facilities licensed for non-research purposes.

An amendment to the 2002 Farm Bill  specifically excluded from AWA oversight rats of the genus Rattus rattus, mice of the genus Mus mus, and birds specifically bred for research. Thus, research with these rats, mice, and birds, which likely comprises the overwhelming majority of vertebrate animals in research in the US, is not overseen by the USDA.

Does that mean rats, mice, and birds are not covered by federal animal welfare laws?

It depends on the funding! In fact, many rats, mice, and birds bred for research are covered by federal law.

Why?  Because, for federally-funded research, another federal regulation specifies the conditions for animal care, animal research, external oversight, and associated public transparency via a second federal agency. This includes, for example, university research funded by the National Institutes of Health, the National Science Foundation, or other federal agencies.

PHS and OLAW. The Health Research Extension Act (HREA; 1985) provides the statutory authority for the PHS Policy on Humane Care and Use of Laboratory Animals (PHS Policy), which applies to all PHS-funded research with live vertebrate animals.  In brief, such research must follow the National Research Council’s Guide for the Care and Use of Animals in Research (The Guide) (NRC, 2011).  Each institution receiving PHS funding for research with vertebrate animals is required to have an Assurance of Compliance (Assurance) with OLAW. The Assurance describes policies and procedures adopted by the institution in order to comply with PHS Policy.

The NIH website provides extensive information about PHS policy and OLAW.

http://grants.nih.gov/grants/olaw/faqs.htm

Guide for the Care and Use of Laboratory Animals

Guide for the Care and Use of Laboratory Animals

Food and Drug Administration (FDA). Certain types of research with animals and most animal testing are also subject to oversight and regulation by the US FDA.

Part of the federal regulation governing animal research also requires that each institution engaged in research has a mechanism for ethical consideration, approval, oversight and monitoring of animal care and research. Thus, there are also oversight bodies at each institution that are charged with the approval, monitoring, and reporting of activities with animals.

Institutional Animal Care and Use Committees (IACUC). Animal research oversight at the institutional level is entrusted to an Institutional Animal Care and Use Committee or “IACUC.” The responsibilities of the IACUC are spelled out in the AWA regulations and the PHS policy. Read more about IACUC here: http://grants.nih.gov/grants/olaw/tutorial/iacuc.htm

What about rats, mice, and birds that are not in federally-funded research?

While privately-funded research is not subject to the AWA or PHS Policy, there are other mechanisms that are used to ensure standards of animal care and research review, such as voluntary accreditation of the institutions’ animal care program. Such research may also fall under FDA oversight and, as such, be required to follow PHS Policy.

Private accreditation.  An institution may choose to seek and maintain voluntary accreditation by a private agency, AAALAC, International (AAALAC). In the US, AAALAC accreditation depends on demonstrating compliance with the The Guide; thus, institutions that are not overseen by APHIS or OLAW may choose to be accredited and adopt the same standards for the care and treatment of research animals. Private accreditation for the care of captive animals is common across different kinds of facilities that house nonhuman animals, including those in research, but also in zoos and sanctuaries, who have their own accreditation organizations (e.g., American Zoological Association, AZA; Global Federation of Animal Sanctuaries, GFAS). Importantly, however, unlike oversight by a federal entity, voluntary accreditation does not provide a venue for public oversight and enforcement, nor does it allow for public transparency. For example, both USDA’s APHIS and PHS’s OLAW are responsive to public requests for investigation of facilities and records relating to oversight of those facilities. Private accreditation agencies do not provide public transparency of the accreditation process and/or inspection reports.

In Conclusion:

There are many sources of federal and local protection of animals in laboratories. Any research on AWA-covered species OR research that receives federal funding will be covered by federal laws aimed at ensuring laboratory animal welfare. Those laws provide for external oversight and for public transparency of records including, for example, inspection and investigation reports.

Most research is also covered by the IACUC system, which provides for oversight and, for many public institutions, another route of public transparency via state open records. Finally, many facilities– both public and private– maintain voluntary accreditation, which also should have a positive impact on animal welfare.

Speaking of Research

For more information about regulation, also see:

Update 5/24/16:  “New MOU Among NIH, USDA, and FDA.  NIH, USDA, and FDA have participated under a Memorandum of Understanding (MOU) Concerning Laboratory Animal Welfare for over 30 years. Each agency, operating under its own authority, has specific responsibilities for fostering proper animal care and welfare. This agreement sets forth a framework for reciprocal cooperation intended to enhance agency effectiveness while avoiding duplication of efforts in achieving required standards for the care and use of laboratory animals. The new MOU is available at: http://grants.nih.gov/grants/olaw/references/finalmou.htm.”

 

Nobel Prizewinner John O’Keefe warns of threat to science from overly restrictive animal research and immigration rules

In an interview with the BBC yesterday 2014 Nobel laureate  John O Keefe has warned of the dangers posed by regulations that restrict animal research and the free movement of scientists across borders.

“It is an incontrovertible fact that if we want to make progress in basic areas of medicine and biology we are going to have to use animals.

“There is a worry that the whole regulatory system might begin to be too difficult, it might be constrictive.”

Professof John O'Keefe, 2014 Nobel Laureate in Medicine or Physiology. Image: David Bishop, UCL.

Professof John O’Keefe, 2014 Nobel Laureate in Medicine or Physiology. Image: David Bishop, UCL.

His concerns are well founded. Our post yesterday discussed the key role of recordings of single neuron activity in rats to the discoveries made by John O’Keefe, May-Britt Moser and Edvard Moser. The post also discusses two other advances made through basic research in animals whose impact in medicine has been recognized by awards, deep brain stimulation in Parkinson’s disease, and infant massage in preterm babies. Nevertheless in many countries around the world there is increasing pressure from animal rights groups on politicians to restrict, and even ban, animal research. Scientists have a key role to play in ensuring that important basic and translational research, and we welcome John O’Keefe’s statement,  it’s an example that scientists around the world should follow.

The issue of immigration is another important one for science, and John O’Keefe knows this better than most. Born in New York, he completed his PhD at the University on Montreal under the supervision of renowned Psychologist Ronald Melzack, before moving to the UK to undertake a postdoctoral fellowship, and credits the research environment in the UK and at UCL for giving him the opportunity to make his discoveries, and later May-Britt and Edvard Moser spent time as postdoctoral researchers at his laboratory.  For science to flourish scientists must be free to travel to centres of excellence in other countries, to learn skills and establish collaborations that are key to success in many fields of research in the 21st century. This freedom is under threat from narrow-minded isolationism in many countries, for example earlier this year Switzerland found its position as a leading scientific nation undermined by a new immigration law that threatens its ability to recruit talented scientists from abroad, and has disrupted its participation in a key EU research programmes.

John O’Keefe’s warning is a reminder that the threats to scientific research can come from many directions, and of the need for supporters of science to be ready to take action to defend the freedoms on which science is built.

Speaking of Research

UK Regulations: How do you get a licence to carry out animal research?

There are three levels of licensing required before a procedure can take place in the UK. The project, the individual and the institution must all have licenses from the Home Office. This post aims to discuss the process of getting a personal licence in the UK and is written by Peter Wright a PhD student at the National Heart and Lung Institute, Imperial College London (He is also the founder of KeepResearchAfloat).

In the UK the ability to perform animal experiments is regulated by the Animals in Scientific  Procedures Act 1986 (ASPA 1986) (1). ASPA has recently been revised to transpose European Directive 2010/63/EU (2) on the protection of animals used for scientific purposes into UK law. The revised legislation came into force on 1 January 2013. The basic relationship between these two pieces of legislation is that ASPA 1986 defines the regulations and 2013/63 provides harmonisation with other EU member states. The reality was that 2010/63 makes little noticeable difference to individual UK researchers save for tightening controls on aspects such as record keeping in areas like training and numbers of animals used. It is with no small amount of pride that I can point out that this means the UK was working under the modern standards of regulation for at least a quarter of a century. ASPA 1986 is enforced by the UK Home Office and the Secretary of State rather than the Department of Business, Innovation and Skills.

Who can do research using animals in the UK?

      ‘No person shall apply a regulated procedure to an animal unless…

a)      He holds a personal licence qualifying him to apply a regulated procedure of that description to an animal of that description
b)       the procedure is applied as part of a programme of work specified in a project licence authorising the application, as part of that programme, of a regulated procedure of that description to an animal of that description and
c)       the place where the procedure is carried out is a place specified in the personal licence and the project licence.

So to do research using animals one must have; a personal licence (PIL:regulating the person) that can be used in conjunction with a project licence (PPL:regulating the experiment) at licenced establishment (regulating the place). Hierarchically then, the personal licence is subordinate to the project licence which in turn is subordinate to the licencing of premises. No procedure can be performed without any part of this chain missing.

The process of acquiring PPL (3) and establishment licences is outside of the scope of this piece. But briefly a PPL application will require the researcher to define the question of interest, provide evidence of scientific and ethical necessity for this research (in answering unanswered questions pertaining to human or animal health). They will then list the experiments required, the techniques and species that will be used and the reasons for this including whether they are the species of lowest neurophysiological sensitivity suitable for the experiment. Importantly the worker will then define how severe the procedures are going to be in terms of invasiveness and or pain with predefined limits as to when the experiment must be abandoned and the animal humanely euthanized. This entire application will then be assessed by a panel of scientific experts, veterinarians, animal care staff and lay people (often clergy interestingly?!).

So how does one obtain a PIL? (4) Usually, the candidate will be either working or undertaking studies at a licenced establishment. It is unusual for researchers of less than graduate level to be in possession of a PIL. Prospective PIL holders need to undertake a mandatory Home Office accredited PIL course. Given the symbiotic nature of the three licence types most institutions will provide their own programme. Training before application for a PIL is split into modules focusing on different elements essential to being a PIL holder. A PIL can be obtained after completing Modules 1-3 but this will inhibit the scope of what experiments can be done (i.e. this will not permit the PIL to perform recovery surgical procedures). The training process will usually require between 30- 40 hours of study including lectures, practical training and written examinations.  The syllabus for candidates is loosely defined by the ‘Guidance on operation of ASPA 1986’ (5, 6- Table 1). All institutions will have slightly different focuses but the general frame work will be as follows.

Table 1: Modules required for PIL

Table 1: Modules required for PIL

This course will usually involve participation and lecturing by the institutions ‘named veterinary surgeon’ (NVS) and ‘named animal care and welfare officer’ (NACWO). Institutions are legally obliged to have a staff of fully licenced vets who are wholly detached and disinterested in the research program. The NVS is usually the chief vet and the NACWO a very senior animal technician, in most large institutions there will be staff of animal technicians (AT). The basic function of an AT is to care for the animals. Animal technicians assist with the monitoring of the maintenance of the facilities (e.g. strict environmental parameters) and surveillance of the animals and importantly the compliance of researchers.

Module 1 introduces how legislation came to be as it is and the place of animals in research. This includes the ethics of animal research and in my experience was quite in depth, exploring ideas of animal rights in culturally Christian societies, through Benthamite/Enlightenment thought and finally the arguments of Peter Singer. The law is then illustrated in depth as new PIL holders must accept the very strict regulations on what they will be doing. Consequently, there is a necessity for them to be able to define what is and isn’t allowed by law given their personal PPL/PIL situation.

It is instilled in tutees that if the animals are not treated well, they are stressed; treated carelessly or diseased the resulting physiologic alterations will obviate the collection of meaningful data.

Module 2 covers state of the art methods of interpreting pain in other species. History has meant that many of the animals we use for research are prey species. These species unlike modern humans do not modify their behaviour in extreme ways unless they are severely ill. To ensure that humane endpoints described in PPL’s are not being exceeded PIL holders must be able to interpret animal behaviour. There are practical sessions on animal handling which are not trivial as most rodent species are handled as little as possible in the research environment. This lack of intervention ensures that they are subjected to the least amount of stress. But this means that they will be keen to escape and so are aggressive in the case of mice and may even injure themselves in the case of rabbits. Quick and humane euthanasia is also demonstrated and practice may be done on cadavers if available. Physical and pharmacologic methods are used and many facilities will require people to demonstrate they can do this effectively on live animals, once they are PIL holders. Local procedures for ensuring good health and safety, housekeeping, infection control and security will be described to the candidates at this point to ensure the efficient running of the premises.

Module 3 is the most scientifically and technically challenging of the course as it requires people from disparate fields such as engineering and neuroscience to be brought to the same level. The biology and husbandry of animals teaches many aspects of caring for common research model species. Some of which is surprising, for example, did you know the average rectal temperature of a rabbit is a degree higher than that of a rat? There is also a great focus on environmental enrichment for different species, this is quite simple with small rodent species but obviously requires great deal more thought for larger mammals. Previous work on pain recognition is built on in tutorials on diseases, their prevention and detection. Animal facilities utilize sentinel animals and regularly send off biological samples to test for common pathogens. Most of these common diseases are not life threatening and will not cause obvious symptoms but will severely hamper research. For this reason many facilities will have rooms of differing health and hygiene statuses and these procedures are carefully outlined to tutees. As a PIL holder it is therefore your responsibility to obey local rules to protect the work of others as well as your own. Module Four represents a continuation of Module Three and as such builds upon skills and knowledge in areas of surgery, analgesia and anaesthesia. Module Four is very much more practically focused than the other modules. Finally, some basic anaesthetic techniques and some surgery and suturing on cadavers will be demonstrated and a hands on practical given

White Rabbit involved in animal experiment

Did you know the average rectal temperature of a rabbit is a degree higher than that of a rat? If you had a PIL licence you would.

After the final assessment is completed and marked, as per the accredited training bodies requirements, notification of successful completion will be issued and a formal certificate of modular training issued. The opinion of the NVS, NACWO, animal technicians and other parties who have assisted in the course may also be sought on whether or not a candidate has satisfactorily demonstrated the appropriate attitude towards animal welfare and the use of animals for in vivo research during the course. If they have, an application is sent to the home office and a civil servant acting on behalf of the secretary of state will issue a defined PIL.

In much the same way as you only truly learn to drive after passing your driving test you only truly learn to do animal research after completing this course. ASPA 1986 does not permit using animals to teach techniques after all it is not morally acceptable, scientifically relevant or sadly as in many matters cost effective to treat one animal as the practice and another as the real. If we do a procedure on an animal it has to be as part of a scientific study. The process of training in animal research then becomes ‘on the job’ more often than not procedures will be demonstrated and supervised by more experienced PIL holders or PPL Holders as part of a team. In turn this is always with the support and supervision of NVS and animal facility staff. An obvious learning curve is therefore present and data from very preliminary studies by newer staff will therefore be treated with some scepticism initially. But with adequate supervision and controls this data should always be scientifically relevant.

Peter Wright
National Heart and Lung Institute
Imperial College London

(1)    http://www.legislation.gov.uk/ukpga/1986/14/pdfs/ukpga_19860014_en.pdf
(2)    http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2010:276:0033:0079:en:PDF
(3)    http://www.homeoffice.gov.uk/science-research/animal-research/project/
(4)    http://www.homeoffice.gov.uk/science-research/animal-research/personal-apps/
(5)    http://www.official-documents.gov.uk/document/hc9900/hc03/0321/0321.pdf
(6)    http://www.homeoffice.gov.uk/publications/science-research-statistics/animals/transposition_of_eudirective/aspa-draft-guidance?view=Binary
(7)    http://tna.europarchive.org/20100413151426/http://scienceandresearch.homeoffice.gov.uk/animal-research/index.html

YES to Animal Welfare and NO to a Ban on Animal Research

The following is a guest piece by Prof. Michael Hengartner of the Basel Declaration. An organization founded in Germany to promote well-regulated humane research using animals.

The Goals of the Basel Declaration and the Basel Declaration Society

Animal welfare and scientific and medical progress are not contradictory. More than 800 international researchers have already shown their commitment to accepting greater responsibility in animal experiments by signing the Basel Declaration and supporting the corresponding organization. The Basel Declaration Society aims for a more impartial approach to scientific issues by the general public, and more trusting and reliable cooperation with national and international decision makers.

In November 2010, life science researchers from Switzerland, Germany, Sweden, France and the UK addressed the challenges of animal research and adopted the “Basel Declaration”. This document marks an unprecedented effort by the scientific community to achieve more trust, transparency and communication around animal research. The event was echoed in international media, among them the Scientific American, the Medical Tribune and nature.

“The high quality of medical care today would not have been achieved without research in animal experiments. It is important to inform society about the major significance of research using animal experiments for the health of humans and animals,”

– Prof. Dr. Burkhard Ludewig, Director of the Medical Research Center, Institute of Immunobiology, Kantonsspital St. Gallen, Switzerland.

Signatories to the Basel Declaration commit to accepting greater responsibility in animal experiments. They also sign up to intensive, unprejudiced dialogue with the general public. This dialogue is factual, and focuses on achieving concrete goals. The signatories additionally demand that animal experiments needed to obtain research results remain permitted, now and in the future.

“The Basel Declaration came about not in response to any specific occasion, but as a spontaneous voluntary commit­ment by the scientific community to the best-possible approach to indispensable animal experiments. We present a picture of our modern animal experiment-based science, the deliberation process, the basic conditions and our approach to the issue of animal experiments and show openly what we do and why,”

– Prof. Dr. Stefan Treue, Director, German Primate Center, Göttingen, Germany.

The goal is to make the Basel Declaration the worldwide ethical guideline on animal research, comparable to the Helsinki Declaration which defines ethical guidance on research into humans.

“Basically we have long regarded the principles behind the Basel Declaration as a matter of course, because no researcher performs animal experiments unnecessarily. The Basel Declaration establishes a platform for us on which we can network internationally in order to demonstrate this to the public more clearly still. The message is evidently getting across: For the first time we are now engaged in sustained dialogue with representatives of critical organizations in a spirit of genuine partnership that bring all sides together more than any extremist slogans do,”

– Prof. Dr. Rolf Zeller, Department of Biomedicine at the University of Basel, Switzerland and first President of the Basel Declaration Society, which was founded in September 2011.

The Basel Declaration Society celebrates its first birthday

Sign the Basel Declaration!

“The aim is for as many researchers as possible to learn of our initiative and affiliate themselves with it. We invite all colleagues and the general public to accept this offer of a genuine dialogue and to really live this Basel Declaration,”

– Prof. Dr. Michael Hengartner, Dean of the Faculty of Mathematics and Natural Sciences, Institute of Molecular Biology, University of Zurich, Switzerland.

Everybody involved in animal research or animal care around the world is asked to sign the Basel Declaration, and to become a member of the Basel Declaration Society. Doing so marks a commitment to strengthen public awareness of the importance of animal models in experimental biomedical research, to foster communication between researchers and the public, and to enhance acceptance of the Basel Declaration.

Animal research is under ever-increasing public and governmental scrutiny, even though its importance for biomedical innovation and the necessity of animal experiments to further knowledge in basic research are beyond controversy.

Scientists and technical staff conducting animal experiments face increasing public distrust, and often even aggressive rejection. Media covering the topic frequently lack objectiveness.

This is why already more than 800 international leading scientists have signed the Basel Declaration, to show their conviction that responsible animal research and the sustainable advancement of science and medical progress are compatible.

We hope you will join them with your signature.

Better education

“Animal experiments will remain necessary in biomedical research for the foreseeable future, but we are constantly working to refine the methods with animal welfare in mind,”

– Prof. Dr. Michael Hengartner, Dean of the Faculty of Mathematics and Natural Sciences, Institute of Molecular Biology, University of Zurich, Switzerland.

Advancing the knowledge, implementation and use of 3R principles to reduce, replace and refine animal experiments plays an important role in embedding the Basel Declaration in daily practice. All stakeholders, i.e. everyone engaged in experimental research, the general public and authorities/decision takers, must be made more aware of 3R principles and their current implementation. Moreover, 3R-related issues must be an integral part of scientific publications, and peer reviewers must be better informed about the use, dissemination and quality control of 3R methods. More research is required that captures results in a comprehensive and validated database related to 3R technology and methods.

The 3R principle (replace, reduce, refine) has its origins with William M. S. Russell & Rex L. Burch, who published their “Principles of Humane Experimental Technique” in 1959. These principles are regarded internationally as the guideline for avoiding or reducing animal experiments and the suffering of laboratory animals:

  • Replacement: replacement of animal experiments by methods that do not involve animals
  • Reduction: reduction in the number of animals in unavoidable animal experiments
  • Refinement: improvement in experimental procedures, so that unavoidable animal experiments

More than a piece of paper

On October 16-18, 2011, more than 80 international life sciences researchers and signatories to the Basel Declaration met in Berlin. Their aim was to continue making a constructive and active contribution to the debate taking place in society. They request that the incorporation of the new EU Directive on the protection of animals used for scientific purposes into national law by January 2013 happens consistently in all European countries, and to the highest standards – like those in Switzerland.

Animal Welfare is a high priority for scientists

The Swiss severity classification system helps to identify the impact of scientific procedures on the health and well-being of experimental animals. A thorough severity degree classification is essential for improvement in line with the 3R principles. It helps to define humane endpoints in advance, and to assess progress in refinement, project by project. Participants in the Berlin conference recommend the implementation of severity classification systems, and voluntary use of such systems by the scientific community in countries where these are not yet mandatory.

Obligation to the public

Berlin conference delegates unanimously agreed that science must not only take a clear stand on the responsible handling of laboratory animals, but also has to show greater transparency towards the general public. To make their motivation and methods more comprehensible to the public and decision makers, the researchers committed to cooperate more closely with politicians, the media and schools, and to give greater importance to the communication of science. As a first step they presented position papers, developed in working groups, to representatives of the European Parliament, the EU Commission and the Federal Swiss Veterinary Office FVO.

The Basel Declaration signatories acknowledge the need for greater discussion of animal experiment issues and also of the risks of research approaches and possible misuse of new technological developments. In addition, they declare their intention to communicate not only results und scientific controversies, but also processes and approval procedures, in order to foster a deeper understanding of research.

“We realize that society funds our research and has a lot of justified questions on the subject of animal experiments and on research in the life sciences. Our aim is to engage in an in-depth, sustained and transparent dialogue. This reduces anxieties and promotes acceptance of views – on both sides,”

– Prof. Dr. Michael Hengartner, Dean of the Faculty of Mathematics and Natural Sciences, Institute of Molecular Biology, University of Zurich, Switzerland.