An Ethical Framework for Thinking about Canine Research — and Animal Research More Generally DAVID DEGRAZIA, PH.D. SENIOR RESEARCH FELLOW, DEPARTMENT OF BIOETHICS, NIH ELTON PROFESSOR OF PHILOSOPHY, GWU
Disclaimer & Disclosure I speak today for myself, not for NIH or any other part of the U.S. federal government I have no conflicts of interest
Plan Background for the ethical framework Principles of Social Benefit Principles of Animal Welfare A word about the 3 Rs A decision tree for evaluating canine studies Final thoughts
Background PART 1
Our project Beauchamp & DeGrazia, Principles of Animal Research Ethics (Oxford UP, in production) About my coauthor: coauthor of Principles of Biomedical Ethics Commentaries by ◦ Larry Carbone ◦ Frans de Waal ◦ Rebecca Dresser ◦ Joseph Garner ◦ Brian Hare ◦ Margaret Landi ◦ Julian Savulescu
But why now? Growing public concerns about animals Advances in scientific study of animal cognition & consciousness Growth of animal ethics as a discipline Increasing concerns among scientists about translation Advances in science of alternatives
Purpose Present a framework of general principles for (laboratory) animal research Should be ◦ responsive to these recent developments ◦ ethically defensible ◦ politically reasonable ◦ useful to those engaged in review or conduct of animal research
Challenge Differences about animals’ moral status & value of animal research ◦ Biomedical research community ◦ Animal-protection community
Strategy: work from points of convergence Claims that open-minded members of both communities can accept: ◦ 1. Sentient animals have moral status ◦ 2. Any justification for harming (nonconsenting) beings w/moral status must appeal to substantial social benefits ◦ 3. Any permissible harming of animal subjects is limited by considerations of animal welfare
Sentience Sentience = capacity to have (un)pleasant experiences Which animals? Working assumption: vertebrates & cephalopods Includes dogs Works well with current US and EU policy
Other points of convergence Any justification of animal research must appeal to: ◦ Prospect of substantial social benefits ◦ Adequate protection of animal subjects’ welfare Core values: social benefit & animal welfare Already accepted Yet support principles of a new framework
Structure of framework Social Benefit Animal Welfare No Unnecessary Harm No Alternative Method Basic Needs Expected Net Benefit Upper Limits to Harm Sufficient Value to Justify Harm
Principles of Social Benefit PART 2
1. No Alternative Method The knowledge sought must not be realistically obtainable from alternatives I dea: Beings w/moral status shouldn’t be harmed if benefits are obtainable w/out harming them If principle is met, animal study offers prospect of unique benefit
What about alternatives? Where alternatives are adequate, animal studies don’t offer unique benefits The scientific issues are highly complex But alternatives are making progress
For toxicity testing A. Rowan : EPA’s ToxCast program is comparably accurate to the best animal tests of chemicals — and much faster & cheaper (“ Ending the use of animals in toxicity testing and risk evaluation ,” CQHE 24 [2015]: 448-58) Some scientists are impressed by potential of microdosing (R. D. Combes et al., “Early microdose drug studies in human volunteers can minimise animal testing,” European Journal of Pharmaceutical Sciences 19 [2003]: 1-11)
Beyond toxicity Growing interest in naturally occurring diseases in animals, including dogs, as a model (J. Rowell, “Dog models of naturally occurring cancer,” Trends in Molecular Medicine [17] [2011]: 380-88; G. Ranieri et al., “A Model of Study for Human Cancer: Spontaneous occurring tumors in dogs,” Critical Reviews in Oncology/Hematology 88 [2013]: 187-197) FDA Commissioner S. Gottlieb about the possibility of eliminating use of dogs in animal drug development : “In our study, no dogs would be euthanized. …[R] esearchers will draw a small amount of blood … at specified intervals…. [W]e expect to be able to use these data to develop informatics tools that can model the absorption of drugs in the future, rather than requiring the drugs to be tested on live dogs” (FDA Statement, November 16, 2018; available at www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm626060.htm)
More on alternatives Isn’t No Alternative Method equivalent to “Replacement” ? Different force ◦ “Methods such as mathematical models, computer simulation, and in vitro biological systems should be considered ” (U.S. Government Principles) ◦ Present principle states a requirement
2. Expected Net Benefit Some animal studies offer unique benefits All animal research has costs This principle focuses on costs & benefits to humans Requires that prospect of benefit exceed anticipated costs
Complexity of expected benefit Expected benefit = (1) amount of benefit (if achieved) x (2) likelihood of achieving it So hoped-for benefit must be multiplied by x < 1 While logically obvious, the probability factor is often overlooked
RE Benefits: Concerns about translation Attrition rate from successful animal studies may be 80 or 90% (I. Kola & J. Landis, “Can the pharmaceutical industry reduce attrition rates?” Nature Reviews 3 [2004]: 711-715; H. B. van der Worp et al., “Can animal models of disease reliably inform human studies?” PLOS Medicine 7 [3] [2010 ]; S. Perrin, “Make mouse studies work,” Nature 507 [2014]: 423-425); J. Garner, “The significance of meaning: Why do over 90% of behavioral neuroscience results fail to translate to humans, and what can we do to fix i t?” ILAR Journal 55 [2014]: 438-456) A systematic review: Among highly cited animal studies, about 1/3 translated (D. G. Hackman and D. A. Redelmeier , “Translation of research evidence from animals to humans,” JAMA 296 [2006]: 1731-1732) Don’t have data for canine studies in particular
Costs to consider Relevant costs in Expected Net Benefit are costs to humans Include financial costs, opportunity costs & risks associated w/imperfect models The less adequate an animal model (for testing), the greater the risk of ◦ False toxicity negatives ◦ False toxicity positives ◦ False efficacy negatives ◦ False efficacy positives
Expected Net Benefit is required for justification even from a human-centered standpoint As a necessary condition, seems self-evident Yet it sets a rigorous standard
3. Sufficient Value to Justify Harm Suppose 1 st two principles are met: an animal study (1) offers a unique benefit and (2) prospect of benefit exceeds projected costs (to humans) Doesn’t follow that it’s ethical Q: Is the prospect of benefit important enough to justify anticipated harms to canine (or other animal) subjects? Note: We cannot expect full agreement on the answer
Together, principles of social benefit require prospect of unique, net benefit sufficient to justify anticipated harms to animals Both champions of animal research & animal protectionists can accept this demand Will sometimes disagree on which studies satisfy it
Principles of Animal Welfare PART 3
1. No Unnecessary Harm Grounded in nonmaleficence States that animal subjects must never be harmed (1) through negligence or (2) intentionally unless such harm is unavoidable given scientific objectives that satisfy principles of social benefit
Relevant harms not limited to procedures Include conditions of housing, handling, transport, accidental spread of disease, etc.
2. Basic Needs Requires meeting animals’ basic needs unless incompatible with scientific objectives Basic needs = what’s ordinarily required for a decent life
Why do research animals deserve such benefits? Principle justified via special relationship between human personnel & animal subjects Idea: In relationships where some are made totally dependent on others’ continued care, failure to meet basic needs = harm
List of basic needs Nutritious food & clean water Appropriate shelter Adequate stimulation, exercise, opportunities for canine- typical functioning Sufficient rest for health Veterinary care
(cont.) Access to compatible dogs or social group members Freedom from significant experiential harm Freedom from disease, injury, disability Freedom of movement w/adequate space
A possible addition to list Avoidance of premature death? Left open …
3. Upper Limits to Harm Principles so far permit harm when necessary for justified scientific objectives Set no limit on permissible harm None exists in U.S. policy Permitted ◦ Induced terminal heart attacks in dogs (C. Khalid et al., “Reversal of global apoptosis and regional stress kinase activation by cardiac r esynchronization,” Circulation 117 [2008]: 1369-77) ◦ Induced 3 rd -degree burns & severe lung injury in conscious sheep (J. Zwischenberger et al., “The paracorporeal artificial lung improves 5-Day outcomes from lethal smoke/burn- induced acute respiratory distress s yndrome in sheep,” Annals of Thoracic Surgery 74 [2002]: 1011-18)
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