Category Archives: Science News

Of White Papers And Commentators: The Use Of Nonhuman Primates In Research

Two weeks ago, nine scientific societies, including the American Physiological Society, the Society for Neuroscience, and the American Academy for Neurology, published a white paper entitled “The critical role of nonhuman primates in medical research“. The paper, which notes how nonhuman primates are critical to all stages of research, provides a huge number of examples of medical breakthroughs made possible thanks to studies in nonhuman primates. Among the paper’s appendices is a list of over fifty medical advances from the last fifty years alone; these include: treatments for leprosy, HIV and Parkinson’s; vaccines for measles, mumps, rubella and hepatitis B; and surgeries such as heart and lung transplants. This is no small feat considering the group of species accounts for around only 0.1% of animal research in most countries (that provide data).

critical-role-of-non-human-primates-in-medical-research

On September 2nd, 2016, John P. Gluck wrote an op-ed for The New York Times called “Second Thoughts of an Animal Researcher“. Gluck is a Professor Emeritus in the Department of Psychology at the University of New Mexico. However, this Op-Ed has not come out of the blue. Gluck has long worked alongside PETA and other animal rights groups to condemn nonhuman primate studies. This op-ed is timed for just before today’s NIH workshop on “Ensuring continued responsible research with non-human primates” – a workshop that PETA is petitioning congress about. The article explains why Gluck stopped conducting animal research, his ethical stance against it, and concludes by saying:

“The federal government should establish a national commission to develop the principles to guide decisions about the ethics of animal research. We already accept that ethical limits on experiments involving humans are important enough that we are willing to forgo possible breakthroughs. There is no ethical argument that justifies not doing the same for animals.”

This is disingenuous of Gluck. The strict regulatory system that exists in the US, and most other developed nations, is the very embodiment of principles aimed to guide decisions on when and how we should conduct studies on nonhuman primates (as well as other species). Some countries have specific regulations surrounding primate research (e.g. the UK considers them a specially protected species and researchers must explain why no other species can be used instead). In the US, all primate research is governed by the Animal Welfare Act (enforced by the USDA), and any research receiving federal funds will also be subject to the Public Health Service Policy on Humane Care and Use of Animals (PHS policy; enforced by OLAW). The PHS Policy also endorses the US Government Principles for the Utilization and Care of Vertebrate Animals Use in Testing, Research and Training, which forms the foundation for ethical and humane care and use of laboratory animals in the US. Every research protocol must be approved by an Institutional Animal Care and Use Committee – a group made up of including scientists, veterinarians and lay-persons – who review and evaluate the study, recommending ways in which it could be improved (both scientifically and from an animal welfare perspective).

Other commentators have noticed this as well. As Wesley J Smith writes in the National Review:

Gluck would have readers believe there are no strict ethical regulations that govern primate research. Nothing could be further from the truth. The Animal Welfare Act already has many stringent requirements governing research on monkeys-as the law should-including cost-benefit analyses, the requirement that any pain experiments cause be palliated, and the requirement that oversight boards approve the purpose and approach of proposed experiments.

Ultimately, Gluck’s article reads as an ethical objection to animal research with some scientific gloss. The heart of his objections is Singer-esque in nature (he mentions Peter Singer earlier in the article). He almost directly condemns our different treatment of humans and nonhuman primates as speciesist:

The ethical principle that many of us used to justify primate experiments seemed so obvious: If you are ethically prevented from conducting a particular experiment with humans because of the pain and risks involved, the use of animals is warranted. Yet research spanning the spectrum from cognitive ethology to neuroscience has made it clear that we have consistently underestimated animals’ mental complexity and pain sensitivity, and therefore the potential for harm. The obvious question is why the harms experienced by these animals, which will be at least similar to humans, fail to matter? How did being a different member of the primate grouping that includes humans automatically alter the moral universe?

No doubt our understanding of the cognitive abilities of animals has improved, and with it has come a greater appreciation for their capacity to suffer. We are a long way from the 17th century philosophers, like Malebranche, who thought animals could not suffer. Our greater understanding of the capacity of animals to suffer pain or distress informs the way we treat animals in laboratories. For example, it was not until the early 1990s that the USDA adopted regulations requiring group housing of nonhuman primates (DiVincenti and Wyatt, 2011), this was thanks to many years of studies showing that nonhuman primate welfare was best met by keeping primates in social groups. As such, it is wrong for Gluck to claim that harm to animals “fail to matter”. While we may give animals a different consideration compared to humans (it is legal to eat animals and keep them as pets), it would be wrong to say they exist outside our moral sphere. The UK’s House of Lords set up a select committee in 2002 to look at animal studies; when assessing the ethics they concluded (s 2.5):

The unanimous view of the Select Committee is that it is morally acceptable for human beings to use other animals, but that it is morally wrong to cause them unnecessary or avoidable suffering.

This is the heart of sensible moral consideration – that we should minimise the suffering of animals wherever possible while realising that we also have a moral imperative to conduct animal studies to reduce greater suffering among humans and animals.

Image from Californian National Primate Research Center

Photo by Kathy West.

Primates at the Californian National Primate Research Center. Reproduced with permission.

And there is no doubt we have a moral imperative. To return to the recent white paper:

Research with monkeys is critical to increasing our knowledge of how the human brain works and its role in cognitive, motor and mental illnesses such as Alzheimer’s, Parkinson’s and depression. This research is also fundamental to understanding how to prevent and treat emerging infectious diseases like Zika and Ebola. NHP research is uncovering critical information about the most common and costly metabolic disorder in the U.S. – type 2 diabetes – as well as the obesity that leads to most cases.

Without NHP research, we lose our ability to learn better ways to prevent negative pregnancy outcomes, including miscarriage, stillbirth and premature birth. This research is also helping scientists to uncover information that makes human organ transplants easier and more accessible, literally giving new life to those whose kidneys, hearts and lungs are failing.

The eradication of these diseases is not worth giving up on. For some animals such research could be the difference between survival and eradication. Ebola has a 95% mortality rate for gorillas. An outbreak in 1995 reportedly killed more than 90% of the gorillas at a national park in Gabon. Overall it is estimated that one third of all the world’s gorillas have been wiped out by Ebola in the last 20 years. If nonhuman primate research (primarily in monkeys rather than great apes), can come up with a vaccine then it will be both animals and humans who can benefit. Humans are unique in that they are the only species with the cognitive capability of making a decision of this magnitude. In the words of Wesley J Smith:

This is the difficult fact that can’t be avoided: We need primate research if we are going to advance science, relieve human suffering, and bring new treatments into medicine’s armamentarium. At some point, we have to decide whether to help humans or not experiment on monkeys.

Looking forward to today’s NIH workshop (which will be streamed live online), it would seem they have struck the right tone. Reviewing the evidence, reviewing the policies, and looking to see what can be improved – that is the essence of science – while still appreciating that the duty of the NIH is to improve the health of a nation.

[T]he Office of Science Policy is taking the lead in planning a workshop on September 7th, 2016 that will convene experts in science, policy, ethics, and animal welfare. Workshop participants will discuss the oversight framework governing the use of non-human primates in NIH-funded biomedical and behavioral research endeavors. At this workshop, participants will also explore the state of the science involving non-human primates as research models and discuss the ethical principles underlying existing animal welfare regulations and policies. NIH is committed to ensuring that research with non-human primates can continue responsibly as we move forward in advancing our mission to seek fundamental knowledge and enhance health outcomes.

Tom Holder

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.

Public dialogue about US research chimpanzee retirement: Unanswered questions

Growing concerns about NIH’s plan for retired research chimpanzees summarized in a WIRED article last week continue to provoke more questions than answers. These questions fall into three general areas discussed below. In many cases, they are questions that could stem simply from a lack of transparent, public information. One example of this is found in the reported deaths of nine chimpanzees within 18-months of transfer to the federal sanctuary, Chimp Haven. Whether the number of deaths is higher than expected given the age, health, and average mortality rates for chimpanzees is unclear and has not been addressed with public, factual information about what happened to those nine animals.

Similarly missing is information needed for serious consideration and public dialogue about the plan for relocating chimpanzees; continuing research with retired chimpanzees; and the processes and standards in place for chimpanzee care, external oversight, and public transparency across different types of facilities. Rather than addressing these questions, some have instead simply dismissed “the lab community” as unfair critics of the federal sanctuary (for example, Chimp Haven’s CEO).  That response fails to answer what should be common concerns not only across the many communities that care about chimpanzees, but also more broadly to the public that ultimately provides support for the animals, the research, and the policies that set the framework for decisions that govern chimpanzee care across the many facilities in which they live.

Three sets of questions—largely unanswered—that are integral to informed, serious, public consideration of the future of US chimpanzees are summarized below. They are:

Photo credit: Kathy West

Photo credit: Kathy West

  • Chimpanzee health and well-being: Is everything that can be done to ensure the best care, health, and well-being of the chimpanzees being done?
  • Research:  Should federally-supported retired research chimpanzees within sanctuaries be involved in research?
  • Decisions and evidence: What is the process for decision-making?  How are conflicts of interests handled?  What kind of evidence supports the decisions about chimpanzee health and well-being?

1)  Chimpanzee health and well-being: Is everything that can be done to ensure the best care, health, and well-being of the chimpanzees being done?

First and foremost are questions about the animals’ health and well-being.  The primary question here is whether relocation is the best option for all of the chimpanzees. A number of posts here have provided detail about the issue. The main consideration is whether decisions about the transfer of chimpanzees from their current homes to a new home are adequately informed to ensure the best outcome for each animal. Of particular concern is whether there is a process for examining previous outcomes in order to identify whether changes are needed.

The latter is exactly why the deaths of 9 of 13 chimpanzees transferred from the National Center for Chimpanzee Care (Bastrop) to the federally-supported sanctuary, Chimp Haven, continue to raise questions.  The questions are not—as has been repeatedly emphasized—about the quality of care at Chimp Haven. Nor are they about population-level mortality analysis as was conducted and reported in a yet-to-be-reviewed manuscript posted by a scientist at NIH (see below for further discussion). Rather, as would be the case in most facilities that operate under federal license or registration with the USDA,  the question is whether the circumstances surrounding those deaths has been reviewed carefully and thoughtfully in order to inform future practices and decisions in a way that minimizes future risk and ensures the best outcomes for the chimpanzees. For example, it would be logical to ask whether the circumstances surrounding the deaths were examined by the USDA, or whether NIH commissioned, or requested, any evaluation of the deaths. This would be common procedure in any facility subject to USDA oversight.

Chimpanzees in research, zoo, and sanctuary facilities

Chimpanzees in research, zoo, and sanctuary facilities

Consideration of decisions about relocation goes far beyond these nine deaths, however. There are a number of factors that inform concerns about the plan to transfer chimpanzees from their current homes. Among them: 1) the animals’ age and health; 2) the consequences of relocation, including disruption of existing social groups and separation from long-time environments and caregivers, introduction into novel environments, with novel caregivers, and chimpanzees; 3) the time-span over which the transfers will occur.

All of these factors underlie questions about the end result of the recently announced plan to move all NIH-owned and supported chimpanzees to Chimp Haven over the next 10 years. As summarized by a commenter on our previous post:

“I have read with bewilderment the recent NIH announcement about their plan to retire the remaining chimpanzees housed at Alamogordo, Bastrop and Southwest Foundation and the press release from HSUS applauding the plan and their appreciation of all the effort by Dr. Collins and NIH have made to implement the plan. Why should anyone be excited about this plan? From what I read, their plan is attrition. For presumably the next 10 years, NIH is going to watch and monitor the chimpanzee mortality rate at Chimp Haven and fill the vacancies with chimpanzees currently residing at APF, Bastrop and then Southwest (the NIH preferred order). How can attrition and replacement be considered a reasonable and humane retirement plan by either the research community or animal welfare advocates?”

2) Research: Should federally-supported retired research chimpanzees within sanctuaries be involved in research? 

The announcement of a partnership with the Lincoln Park Zoo, funded by a private agency (Arcus Foundation), apparently part of broader effort to promote research with chimpanzees at the federally-funded retirement facility raised a host of questions. On the one hand is the obvious question about why chimpanzees retired from research should be the source of fundraising in order to conduct research (see here). The very definition of sanctuary and what differentiates a sanctuary from a zoo or a research facility was also raised by the announcement (see here).

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Photo credit: Kathy West

There are many who do support ongoing behavioral, psychological, cognitive, genomic, neural and other noninvasive research. This is the very same conclusion that was reached by the Institute of Medicine committee that reviewed the necessity of chimpanzee research (see report here). But the announcement of a research program at Chimp Haven raised many questions about how the research conducted there now, and in the future, will be overseen. For example, in contrast to well-established and transparent practices for decisions about NIH, NSF, or other federally-funded research, there appears to be little public information about the process for research approval and conduct of research at Chimp Haven.

The broad questions surrounding research at Chimp Haven are whether information about the review, oversight, and transparency of research projects is available and where it can be found. Moreover, the announcement that the sanctuary intends to recruit scientists and more research raises questions about whether there should be further consideration and open dialogue about whether the processes put into place by the private facility are appropriate for research conducted with animals who receive 75% of their support from federal sources.

Questions include: What is the process for deciding whether, and which, research projects are conducted with federally-supported chimpanzees within the sanctuary? What are the mechanisms for external oversight, transparency, and ethics review of the research proposals? How are perceived and actual conflicts of interests handled? The answer to these questions at present appears to be that Chimp Haven has a review board that operates as an Institutional Animal Care and Use Committee (IACUC) for the facility. In general though, there is not enough information about process to inform serious and thoughtful consideration. For example, among other questions, it is not clear that the facility has a scientific merit review or a mechanism to guard against conflicts of interests or to promote equitable access.

3)  Decisions and evidence: What is the process for decision-making?  How are conflicts of interests handled?  What kind of evidence supports the decisions about chimpanzee health and well-being?

A third set of questions that have become of increasing concern as events, decisions, and announcements about chimpanzee retirement unfold surround processes for decision-making. Again, the issue here is about unanswered questions in response to community concern and public interest. The two previous points highlight a number of questions rooted in “process.” Most recently, the issue of what kinds of evidence should be used to inform decision-making was put into sharp relief by the appearance of an analysis of chimpanzee mortality across dedicated research centers and the federal sanctuary. That report was posted online, ahead of peer-review or publication in a scientific journal, and the day before NIH’s announcement that all NIH-owned chimpanzees would move to Chimp Haven over a 10-year period.

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Photo credit: Kathy West

While it may not be entirely clear to those outside the scientific community, the online article had not been subjected to review – either via comments online, in an open-access venue, or by expert peer-review. Peer-review  is normally conducted by scientific journals and is part of online publication as well.  Peer review is an important part of the scientific process. In brief, the purpose of such review is to identify potential flaws in the study design, analysis, or interpretation of the data. The process of review then requires the author to address criticisms. In some cases, the criticisms are rebutted and the paper improved by clarifications. In other cases, the criticisms cannot be rebutted because the study, analysis, or interpretation is flawed.

What is important to remember is simple. Confidence in the conclusions of a study, particularly one for which criticisms have been raised and not yet addressed, should be measured accordingly. Yet, already the conclusions of this article have been cited as “proof” for a position about relocating chimpanzees. For example, in a posting from the Jane Goodall Institute:

“As animal transfers are sometimes considered potentially harmful, it is satisfying to note it was found that there is no proven link between relocation and premature death of captive chimpanzees.

In fact, the article cited does not substantively address the claim. Rather, as chimpanzee research expert, Professor William Hopkins, points out, “the analyses performed in the study are not designed to test for a “link” between relocation and premature death. As others have noted, this would require an analysis of the mortality rate of chimpanzees transferred to Chimp Haven be compared with age-sex matched apes that are not transferred. These kinds of comparisons that are necessary to make these inferences are absent in the paper as it is currently written.”

Thus, not only do a number of questions and criticisms of the article remain unanswered, but it is also true that the mortality analysis does not address the fundamental point for which it is being cited as supporting. What the analysis does appear to show is that many – perhaps most—of the retired chimpanzees are likely to die before they are transferred. From data presented in Figure 4 of the paper, it appears that roughly 20% of the chimpanzee population would be predicted to die within 3 years and that less than 40% will be alive in 9 years. By extension, of the animals who are now slated to move within the 10 year period announced by NIH, it could be the case that only 30% will be alive at that point. Again, however, conclusions based on this analysis should be viewed with caution. Nonetheless, if this interpretation were true then it would seem that the majority of chimpanzees will, in fact, remain in their current homes for a substantial amount of time. In turn, several considerations and new discussions of alternatives might be raised– as they were in comments that we will return to in a subsequent post.

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Chimpanzees at NCCC. Photo credit: Kathy West.

Furthermore, the NIH plan and discussion surrounding it has yet to reveal how the mortality analysis will inform decisions at the level of the individual chimpanzee. Given that age is nearly certain to be the biggest mortality predictor, the question is whether the oldest animals will be the least or the most likely to move first? In the NIH plan, age is ranked ahead of existing social group as a consideration for priority in relocation to sanctuary. The question there is – given social groups are generally comprised of animals of mixed ages—will groups be prioritized for movement based on the age and health of the oldest members?

Decisions about the priority order for moving chimpanzees are undoubtedly incredibly difficult and must account for complicated sets of factors. Whether there should be transparency in those decisions, at the level of the individual animals, is one of the main questions that arose in discussion of the deaths of 9 NCCC chimpanzees transferred to the federally-funded sanctuary. It arose for the simple reason that Chimp Haven’s CEO, in defending her facility, raised pointed questions about the decision to transfer particular animals. She claimed:

“…the selection of the individuals to be transferred was not made by Chimp Haven, or even The National Institutes of Health, but by the laboratory itself.  In fact, Chimp Haven has never had a say in selecting any individuals for retirement despite the fact that we have advocated for such a role to ensure that these retirement transfers were best planned and operated. So one might reasonably question why several of the transferred chimpanzees were placed on “quality of life” watch prior to transfer. Or why most of the transferred chimpanzees were well beyond the median life expectancy for the species.”

Whether this is true or not cannot be easily – if at all– discerned by the public. Why? Because the process of decision-making is mostly not transparent in public view. As a result, competing claims cannot be fully evaluated with any serious, thoughtful consideration by members of the public, nor by the media, policy-makers, or members of the research, sanctuary, and zoo communities. Nor does it appear that there is any mechanism for unanswered questions to be addressed. There are many things that are troubling about the situation. From the perspective of dialogue and community efforts to guide decisions in the best interests of the animals’ health and well-being, research, and public support, the continuing lack of response to questions or perceived criticism is among the largest of the obstacles to progress and understanding.

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Photo credit: Kathy West

Summary.  One of the goals of Speaking of Research is to provide a place for public dialogue about ongoing events, perspectives, and consideration of animal research. We hope that the questions posed above might help move the dialogue forward with answers to questions that remain unaddressed and information that can fill gaps in public knowledge. In turn, the answers may help provide a better understanding of the situation and a more thoughtful, broad public consideration of the future for retired chimpanzees and for chimpanzee research.

Speaking of Research

Research using sheep leads to a new device to record and stimulate the brain

A group of Australian and American researchers have used sheep to develop and test a new device (original paper) – the stentrode – for recording electrical signals from inside the brain. The research was published in Nature Biotechnology. This new technology removes one of the main obstacles to developing efficient brain-computer interfaces: the need for invasive surgery.

The “stentrode” is a group of small (750 µm) recording electrodes attached to an intracranial endovascular stent, which allows implantation of the electrodes inside the brain without invasive surgery. This allows high quality recording or stimulation of specific areas of the brain, without many of the risks associated with invasive brain surgery.

Image courtesy of the University of Melbourne

Image courtesy of the University of Melbourne

A stent is a tube-shaped device whose walls are made from a metallic mesh, designed to navigate inside brain’s system of blood vessels, until a desired position is reached. Once in place the mesh is expanded, securing it against the blood vessel walls. Importantly, stents are designed to be implanted by inserting them through a large blood vessel, like the jugular vein, and gradually “pushing” them into the desired position, by twisting and turning at critical juncture points where veins branch. During this implantation procedure the surgeons observe the stent’s location using a non-invasive imaging technique named cerebral angiography.

Recording the electrical activity of brain cells with high fidelity is the basis of new technologies to restore quality of life to many people with neurological diseases. For example, through brain-computer interfaces that interpret neural signals, people paralysed by damage of the spinal cord have been made able to control external devices, such as wheelchairs, robotic arms, and exoskeletons. Much of this work was initially done in monkeys– getting them to also control wheelchairs and robotic arms. Moreover, brain recording devices can be used to detect the timing and location of seizures with great precision, which helps minimise damage to healthy parts of the brain when treatment involving surgery is necessary.

One obvious problem with the current technologies is that there is a clear trade-off between the quality of recordings obtained, and degree of invasiveness. To explain this, let’s look at two extremes of techniques for recording brain activity – electroencephalogram (EEG) and microelectrode arrays.

EEG, recording from the scalp, is by far the least invasive technology: electrical activity of the brain can be recorded through a cap dotted with electrodes, and no surgery is required. However, because the signals being measured are so weak (due to the distance between brain cells and the recording electrodes), this technique can only detect the combined activity of millions of brain cells, when they work at the same moment (signals from small groups of cells tend to average out, not producing an electrical “spike” large enough to be detected far away). Thus, devices controlled by brain-computer interfaces based on EEG tend to be difficult to control, and have few “degrees of freedom” (how many different actions can be specified by the user). Moreover, it is difficult to determine exactly where the signals of interest are coming from, and electrical activity from regions well inside the brain is much harder to detect.

EGG. Image courtesy of Saint Luke’s Health System

EGG. Image courtesy of Saint Luke’s Health System

At the other end of the continuum are recordings using microelectrode arrays- small devices that are implanted directly in the brain, which contain many small metallic probes each capable of “listening” to the electrical activity of a single neurone, or a small groups of neurones. This technique, developed over many years of studies in rats, cats and monkeys, has been used recently to demonstrate the ability of a tetraplegic patient to control its own muscles again, using a brain-computer interface which included a microelectrode array to record the signals that encoded the participant’s intention to move, coupled to stimulation devices attached to different arm muscles.  Much more refined control can be achieved with this method, as one can potentially record individual signals from thousands of neurones, across many brain areas. The disadvantage, however, is clear: these devices have to be implanted directly in the brain, requiring complex neurosurgical procedures. Moreover, the insertion of the electrode arrays in the brain causes local damage, which triggers inflammatory tissue responses that, over time, can reduce the quality of recordings. Although this damage can be minimised by using larger electrodes that lie on the surface of the brain, instead of penetrating it (electrocorticography, ECoG), the need for invasive surgery remains.

Microelectrode array. CC Image by Richard A Normann. Tbe actual size of this array is 4 x 4 mm

Microelectrode array. CC Image by Richard A Normann. Tbe actual size of this array is 4 x 4 mm

As we can see, the stentrode has the potential to be the best of both worlds – offering the accuracy of microelectrode arrays and the benefits of avoiding non-invasive surgery usually associated with technologies like EEG.

Part of the problem solved by the stentrode developers was to find an adequate animal model, which would yield information valid to the situation of the human brain. Sheep were chosen due to the similar topology of the brain’s venous system, and the similar diameter of the critical blood vessels. The stentrodes were implanted inside a large vein that lines the somatosensory cortex – the part of the brain that encodes sensory information about touch, as well as muscle contraction and position of the body’s joints. Importantly, once implanted, they stayed in place without damaging the brain or blood vessels, and allowed stable neural recordings for over 6 months – while the sheep were freely moving around.

Stock image of sheep in research (in the UK) by Understanding Animal Research.

Stock image of sheep in research (in the UK) by Understanding Animal Research.

Currently envisaged applications of this new technique include “reading” signals for control of artificial limbs and seizure prediction in epilepsy. With some modifications, the same technique can be used for localised electrical stimulation of the brain, which may allow new treatments for Parkinson’s disease, and obsessive-compulsive disorder. Deep Brain Stimulation, a currently used treatment to treat the tremors associated with Parkinson’s, requires invasive brain surgery to implant electrodes – this process could be made easier and safer using stentrodes. Besides being good news for people who may one day benefit from an easier way to have electrodes inserted in the brain for treatment of diseases, this story also illustrates two important points. First is the usefulness of animal models to develop treatments that directly benefit people. The sheep brain is not identical to the human brain, but can be judiciously used to model a critical feature of the latter, in a manner that is directly relevant for testing a device intended for human use. Second, that results take time to translate from basic research in animals to human use. The current generation of brain-computer interfaces would never have been developed were it not for decades of research on seemingly “basic” topics, such as how to best record different types of electrical signals from the brain, how and where the brains of various animals encode information for sensation and movement, and how blood vessels are organised and function. This is however just the beginning, and a lot more needs to be done on the way to useful and safe devices.

Marcello Rosa and Tom Holder

Original Paper: Oxley, Thomas J., 2016, Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recording of cortical neural activity, Nature Biotechnology34, 320-327. Doi:10.1038/nbt.3428

What is science?

We learned today from an NIH announcement about a new plan by the federal agency to relocate and transfer all of the NIH-owned chimpanzees to the federally-funded sanctuary, Chimp Haven, by 2021 or later. The announcement was quickly the subject of announcements and proclamations of victory by PETA, HSUS, and some associated with Chimp Haven.

For others, in light of the concerns raised about the death of 9 of 13 chimpanzees transferred to Chimp Haven recently and subsequent calls for a thoughtful examination of these cases—at least a review of what might be done to minimize future risk—the announcement was troubling.

PETA on nih chimp announce 08.11.16It does appear that NIH either shared, or was at least responsive to the need to address, the concerns that were expressed about the consequences of relocation on the chimpanzees’ health and welfare. That is evidenced by the fact that NIH did undertake an analysis of mortality rates at Chimp Haven and the research centers that house NIH chimpanzees.  That is as it should be – scientists use data to inform decisions.  No problem there. NIH conducted the analysis on the basis of data requested from each of the centers. It also appears that they referenced the findings of the analysis in their decision.  So what’s the problem?

It appears that the only evidence of the mortality analysis is a non- reviewed paper that was posted just yesterday to a website (Biorxiv) by the study author, NIH’s Dr. Michael Lauer. tweet bioRxiv 08.11.16That paper may be viewed here. After even a cursory review and analysis of the Lauer paper, many questions are raised about both the methods and the conclusions drawn from the results.  Just a few of the issues or potential problems that an academic reviewer might raise are listed below. Others may read the paper and have different impressions or questions.The data includes 764 chimpanzees; 314 died during the 7 year median follow-up. The author states that: “The analyses were conducted to inform NIH’s plans to retire its surviving chimpanzees.”

To see NIH use data from an unpublished, non-peer reviewed manuscript as a basis for their decisions is incredibly disheartening. It defies the very premise and basis on which the scientific process works. Science doesn’t accept as fact those data and findings that are presented on the internet and that have not been properly vetted through the peer review process.  Image Biorxiv 08.10.16 LauerBut before turning to questions about the paper, let’s be clear on a critical point:  The questions and critiques raised here would be raised regardless of the conclusions of the paper and regardless of the direction of NIH’s decision. The questions raised here are at the heart of how science is used to inform decisions and judgments.  

In other words, what would we conclude if NIH had used a non-reviewed paper to suggest that relocation was a threat to chimpanzee well-being and that the chimpanzees should be retired in place?  The same criticism would hold.  The issue is about the conduct of science and how it should be shared and viewed in decision-making. In this case, it is particularly important because of the close relationship between the findings and decisions that have immediate and real impact. Furthermore, in a time where scientific rigor and reproducibility are the subject of a great deal of concern and discussion, it is even more troubling to see that the results of an unreviewed paper posted only yesterday in public  view are the basis for an announcement made today.

That means that there was no opportunity for a broader public consideration, for thoughtful analysis, for viewing the data, for asking questions about the approach, methods, analysis, interpretation of results, and conclusions.  Thus, we post here some initial questions and comments about the unpublished and unreviewed paper from several scientific reviewers. We hope others read the paper (here) and offer their comments, or offer additional insight into the approach, analysis, and conclusions.

To be clear, these comments are not designed to advocate for or against the transfer of chimpanzees to Chimp Haven. Nor are they designed to judge the quality of care the animals receive after arriving there. Rather, they are designed to illustrate the fact that decisions about the welfare of captive chimpanzees that are being made by NIH appear to be based on data and analyses that are arguably flawed, at least as presented in the current draft of the Lauer paper.  Dr. Lauer might have excellent responses and answers to these critiques, which may then validate the claims in the current paper.

And, that is the point: the data will then have been subjected to critical peer review, the bedrock of the scientific method. It is disappointing, and frankly, stunning, that NIH appears to have accepted these results without proper peer review. Making captive chimpanzee retirement and movement decisions based on these findings seems premature and foolish.  Sadly, that may lead to unnecessary deaths of chimpanzees. NIH is clearly committed to sending their chimpanzees to Chimp Haven; if that is the mandate, then why try to justify the decision based on methods and analyses that have not been subjected to the normal scientific peer review process?  That ultimately raises more questions than answers and stands to further confuse the public view of how science works and how claims should be evaluated.

Finally, we would also note that the data does not appear to be publicly available. In other words, while the un-reviewed article is in public view and its conclusions appear to have informed the decisions the data is not in view and cannot be evaluated or analyzed by scientists or others who are independent of the decisions and the centers involved.

Below are just a few issues, or potential problems, that any reviewer might point out.

  • The first part of the study was aimed at addressing mortality rates in chimpanzees housed at Chimp Haven compared to other facilities (Bastrop, Southwest Foundation and Alamogordo Primate facility). The author reported that age and sex had strong effect on mortality rates whereas location had only moderate effects. In point of fact, the influence of location was not a trivial effect based on the results presented in Table 2 but rather a statistically significant one.  The author seems to want to minimize the significance of the location effect because the overall p-value (p=.0173) was close to the significance level adopted in their analysis.  The effect for Chimp Haven was far below that, at p=.005. The problem, however, is that the argument for adjusting alpha as reported by the author was because they had 6 predictor variables, they therefore they increased alpha to control for possible Type I error. There are a number of issues here. First, it is not clear how the authors dummy coded the location variable. Second, even if there were 6 predictor variables, there were also more than 700 subjects in the study and thus whether the author had adequate power to guard against Type I error (and thus needed to adjust alpha below the traditional < .05) is not entirely clear without presentation of effect size or further rationale. In turn, to state that sex and age had strong effects and location had a moderate effect on mortality is simply not supported by any statistics other than the p-levels.
    Maynard at MD Anderson.

    Maynard at MD Anderson.

    The paper reports: “The strongest predictor, by far, of mortality was
    age (as calculated to be on January 1, 2005), followed by male sex and location. Older age predicted higher mortality (adjusted hazard ratio comparing animals 30 years versus 17 years 2.23, 95% CI 1.91 to 2.61); males also had higher mortality (adjusted hazard ratio 1.50, 95% CI 1.20 to 1.88). Location was only marginally associated with mortality (Wald c2=10, df=3, P=0.017). Compared to Chimp Haven, mortality was lower at APF (adjusted hazard ratio 0.65, 95% CI 0.48 to 0.88), while it was similar at Bastrop (adjusted hazard ratio 0.84, 95% CI 0.60 to 1.16) and almost identical at SNPC (adjusted hazard ratio 1.00, 95% CI 0.71 to 1.39).”

  • The second part of the paper was designed to examine the influence of relocation/transfer on mortality rates in the different chimpanzee populations. This aspect of the study is likely in response to recent reports of higher-than-normal rates of mortality in chimpanzees transferred to Chimp Haven but sadly neither the design nor data analysis allow for any meaningful conclusions to be drawn.  Specifically, there is no control or comparison group. According to the author, at Chimp Haven (CH), chimpanzees die as they get older and this isn’t due to factors such as when they arrived at Chimp Haven, the season of year, etc….but these analyses are irrelevant. What one would want to know is what the mortality rate is for chimpanzees that get transferred to CH compared to either: 1) chimpanzees that stay at their original facility and don’t transfer; or 2) mortality in chimpanzees that transfer INTO CH from a lab compared to mortality rates of chimpanzees that are transferred FROM CH to another facility or 3) mortality rates of chimpanzees that have been transferred INTO another sanctuary (e.g., Save the Chimps).  The second situation does not occur; however, the 3rd situation could be analyzed. Furthermore, there is a 4) mortality rates of chimpanzees that transferred FROM other facilities and INTO Bastrop.  None of these comparisons were made in the paper though they are necessary to make inferences about the effect of transfers on the quality of care and mortality. Thus, this entire part of the paper addressing the effects of transfer on mortality is fundamentally flawed. Of course, it is also recognized that in addition to the analyses, appropriate balancing of covariates that relate to the mortality for each of these four comparisons may be difficult, post hoc; however, the alternatives and limitations should be a feature of a carefully considered conclusion and discussion.
  • For the Chimp Haven sample, why were non NIH-owned chimpanzees excluded from the mortality analyses? Chimp Haven has taken chimpanzees from other facilities such as Ohio State, Yerkes and New Iberia. If the question is not about mortality rates at a given facility, but rather the effect of transferring individuals from established housing conditions, why exclude any individuals? Further, were the non NIH-owned chimpanzees included in the sample size census within Chimp Haven? In other words, in Table 1, it indicates that the Chimp Haven had 273 chimpanzees. Is that all the chimpanzees at CH, or only those that are NIH-owned? A reviewer might guess is that these numbers are based on the entire sample of chimpanzees at Chimp Haven but it is far less clear on the mortality numbers (107). Moreover, peer review would surely point out that the methods are not sufficient for reproducibility.
  • In Table 2, the most relevant comparison (at least in relation to the current issue, the transfer of NIH chimpanzees to CH) is starkly missing. Specifically, for location, Chimp Haven needs to be the reference group, so that comparisons of transfer from all other sites can be made. This is particularly strange as the text lists Chimp Haven as the reference group and interprets the data in this regard. If the point of this analysis is to inform the decision to transfer the animals to CH, vs retire-in-place, then the comparisons should be made with CH as the reference group so that we can see how it truly stacks up against leaving the animals where they are.