Ethical and Scientiﬁc Pitfalls Concerning Laboratory
Research with Non-Human Primates, and
Constança Carvalho 1, * , Augusta Gaspar 2, Andrew Knight 3and Luís Vicente 1
1Centre for Philosophy of Science of the University of Lisbon, Department Animal Biology,
Faculty of Sciences, University of Lisbon, Lisbon 1749-016, Portugal; email@example.com
2Catolica Research Center for Psychological, Family and Social Wellbeing (CRC-W), Universidade Católica
Portuguesa, Palma de Cima, Lisboa 1649-023, Portugal; firstname.lastname@example.org
3Centre for Animal Welfare, Faculty of Humanities and Social Sciences, University of Winchester,
Winchester SO22 4NR, UK; Andrew.Knight@winchester.ac.uk
*Correspondence: email@example.com; Tel.: +351-919943195
Received: 21 July 2018; Accepted: 24 December 2018; Published: 29 December 2018
Legislation and guidelines governing biomedical research with humans and
non-human primates (NHPs) rely on different ethical frameworks. In this paper we argue that the
main ethical framework used to assess and justify NHP experimentation is inadequate for its purpose.
We propose a change of framework that we believe would beneﬁt NHPs and improve research quality.
Basic and applied laboratory research, whenever intrusive or invasive, presents substantial
ethical challenges for ethical committees, be it with human beings or with non-human animals.
In this paper we discuss the use of non-human primates (NHPs), mostly as animal models, in
laboratory based research. We examine the two ethical frameworks that support current legislation
and guidelines: deontology and utilitarianism. While human based research is regulated under
deontological principles, guidelines for laboratory animal research rely on utilitarianism. We argue
that the utilitarian framework is inadequate for this purpose: on the one hand, it is almost impossible
to accurately predict the beneﬁts of a study for all potential stakeholders; and on the other hand, harm
inﬂicted on NHPs (and other animals) used in laboratory research is extensive despite the increasing
efforts of ethics committees and the research community to address this. Although deontology and
utilitarianism are both valid ethical frameworks, we advocate that a deontological approach is more
suitable, since we arguably have moral duties to NHPs. We provide suggestions on how to ensure
that research currently conducted in laboratory settings shifts towards approaches that abide by
deontological principles. We assert that this would not impede reasonable scientiﬁc research.
non-human primate research; biomedical research; deontology; utilitarianism; animal
1. Non-Human Primates in Laboratory Research
Since the mid twentieth century, non-human primates (NHPs) have been widely used in laboratory
research, mostly in biomedical research , and mostly in the cognitive sciences .
In recent years, due to public pressure and legislation, the number of NHPs used in biomedical
research has been signiﬁcantly reduced in the European Union and the United States [
], but has
increased dramatically in some other countries, particularly China .
Some researchers claim that the use of NHPs in biomedical research is crucial, due to their
similarities with humans [
], and state that a total ban on such research would compromise medical
Animals 2019,9, 12; doi:10.3390/ani9010012 www.mdpi.com/journal/animals
Animals 2019,9, 12 2 of 17
advances in several ﬁelds, such as those focused on infectious diseases, cardiovascular diseases,
endocrine diseases, reproductive diseases, neurological disorders, ophthalmic diseases [
certain types of cancer [
], transplants [
] and psychiatric disorders [
]. However, for many years
the presumed beneﬁts of NHP research for medical advances were not subjected to rigorous critical
evaluation. In recent years however, evidence-based assessments have been conducted, frequently
demonstrating that NHP models have provided disappointing contributions toward human medical
In the cognition and behaviour domains, studies with captive primates have made relevant
contributions to psychology and neuroscience, as exempliﬁed by Harlow’s experiments on “the nature
of love” [
] or Selemon and Goldman Rakic’s [
] early brain topography studies. In both cases, as in
many others, discoveries were made which incurred high costs to NHP subjects, including suffering
and death. The ecological validity of behavioural and cognitive studies conducted on captive NHPs
has also been questioned .
2. Similarities between Humans and Non-Human Primates
Moral concerns raised by the use of NHPs in intrusive or invasive research result from their
sentience, consciousness and affective states. In those aspects, NHPs are very similar to humans, which
makes it reasonable to give them similar protection to that afforded to human subjects. However, they
are very different in other aspects, so they are not necessarily good models for human biology.
From the mid-twentieth century onwards, it became clear that NHPs and humans shared so many
traits that trying to categorise any trait as wholly human became something of a futile exercise. Below,
we present a few examples of studies that brought a greater awareness of the high similarity (and
evolutionary continuity) between humans and NHPs.
Some of the very ﬁrst “humanlike” capabilities that attracted considerable scientiﬁc interest
were the discoveries that NHPs build and use tools [
], solve new problems, and develop and
pass on cultural behaviour [
]. NHPs of several species have also demonstrated the ability
to recognise themselves in a mirror—an ability that has been largely interpreted as evidence of
]. This was once thought to be a uniquely human ability. All NHPs that have
been studied to date, from rhesus monkeys to chimpanzees and gorillas, have also been shown to have
distinct personalities with complex behavioural patterns, as occurs with humans [
all NHPs establish strong social bonds [
], and most live in complex societies [
]. Like humans,
NHPs experience and display emotions [
], strong mother–infant and other familial bonds [
are capable of experiencing empathy and behaving sympathetically (e.g., [
]). In addition, an
increasing amount of evidence has accumulated that they have notions of justice and unfairness [
NHPs communicate effectively through vocalisations, gestures, and facial expressions [
possess a linguistic and lateralised brain which allows them to learn and use sign language, among
other skills [
]. NHP cognitive abilities have been astounding us for many years. NHPs can
create lasting memories [
], possess mathematical skills [
], and can even outperform university
students in numerical memory [
]. They can solve complex problems that require intelligence [
These skills are not exclusive to NHPs and can be found across a number of other non-human
animal species. However, NHP behaviour and skills are among the most well documented. The fact
that they are our closest living relatives has probably facilitated the recognition and social acceptance
of their cognitive abilities and emotional lives and has probably made them a preferred target for
Collectively, these and many other studies addressing primate cognition, emotion, and social
behaviour have become the scientiﬁc basis for arguing that NHPs should be afforded a signiﬁcant
moral status, for some authors [
]. It has also been pointed out that the similarities between humans
and NHPs are the main ethical obstacle regarding the laboratory conﬁnement and use of NHPs [
This is indeed a controversial issue within the scientiﬁc community, and for the wider public [
but the recognition that there are signiﬁcant ethical concerns to be addressed is nearly universal.
Animals 2019,9, 12 3 of 17
Because of their anatomical and physiological similarity to humans [
], as well as such cognitive,
behavioural, and social similarities, NHPs have been portrayed as ideal animal models for some
biomedical and cognitive research problems.
However, such similarities do not automatically make NHPs ideal models for humans within
biomedical research [
]. For example, major evolutionary jumps have occurred since the last common
ancestor humans shared with chimpanzees, with homologous brain areas being recruited in humans
for new functions, and new structures emerging altogether .
3. The Ethical Frameworks of Deontology and Utilitarianism
Biomedical research, with both humans and non-human animals, presents considerable ethical
challenges, since it is not uncommonly invasive or intrusive, causing pain, stress or discomfort. For
example, xenotransplantation experiments are classiﬁed under the current legislation as “severe”
procedures, since they are likely to compromise the general health of the animal in the case of organ
rejection. However, NHPs are still presently used in this sort of research [52,53].
In modern human societies, laws should express and enforce society’s moral codes [
Legislation and ethical guidelines have arisen to guide scientists through ethical dilemmas and prevent
forms of abuse that were more common in the past. Classical examples include the use of orphans to
carry smallpox live vaccine through arm-to-arm transportation across the Atlantic Ocean during the
19th century—this involves vaccinating a child and then transferring the vaccine to another as soon as
the infectious pustule forms [
]; medical research conducted with prisoners by German doctors; and
the infamous Tuskegee research, in which African-Americans that had syphilis unknowingly were
not given treatment so the doctors could study the natural progress of the disease in rural American
areas between 1932 and 1972 [
]. After World War II and the subsequent Nuremberg trials, rules
and principles to guide research with human beings emerged. The general rules that guide modern
research with human subjects were written by the Council for International Organizations of Medical
Sciences (CIOMS) in collaboration with the World Health Organization (WHO) in 1982 and revised in
1993 and 2002 [
]. The International Ethical Guidelines for Biomedical Research Involving Human
Subjects—which has been transposed into legislation or guidelines in most countries, established four
basic ethical principles: respect for persons, beneﬁcence, non-maleﬁcence and justice.
Respect for persons includes the principle of autonomy (as described by Beauchamp and
]), and the protection of individuals with impaired autonomy [
]. The beneﬁcence
principle refers to the obligation to maximise beneﬁt, whilst the non-maleﬁcence principle refers to
minimising harm [
], in keeping with the utilitarianism view (see section below), except that in
this case the permissible harm must be mild, regardless of expected beneﬁts [
]. The principle
of justice requires the equitable distribution of resources, which in the case of biomedical research
translates to an equal distribution of burdens and beneﬁts amongst research participants [58,60].
The same principles are stated in The Belmont Report, a document created in the USA in 1978 by
the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research.
This is a critical document for those involved in basic and clinical research with human beings .
Regarding clinical research, the regulations and mechanisms mentioned above seem to be effective
in solving most of the ethical challenges [
], but that is not the case with invasive animal experiments,
particularly those using NHPs [
]. The main reason for these inconsistencies seems to be the use of
different frameworks to evaluate and guide research with humans and NHPs [
]. Guidelines and
legislation that regulate human research rely on mostly deontological principles, while those that
regulate animal research rely on utilitarianism.
The use of different ethical frameworks for humans and NHPs may even result in opposing
ethical recommendations: genetic experiments, which are often restricted from an ethical point of view
when it comes to human beings [
], may be encouraged from an ethical point of view when it
comes to NHPs [6,67].
Animals 2019,9, 12 4 of 17
In the next sections, we brieﬂy describe both ethical frameworks and analyse how each applies to
current NHP research.
Deontological ethics is the normative ethical position often associated with the philosopher
Immanuel Kant, which judges the morality of an action based on the action
s adherence to a rule or
]. The underlying assumption is that something is good because it is the right thing to
]. Deontology stands for principles that must be fulﬁlled regardless of their consequences [
and, according to Kant, there are hypothetical imperatives, which apply to someone who wishes to
achieve a certain goal, and categorical imperatives, which are universal, absolute, and unconditional
requirements that must be obeyed in all circumstances. Subsequent deontological philosophers, such
as Ross [
], included the concept of moral relativism in deontology, which states that the morally
right act is relative to the circumstances.
] also postulated seven prima facie duties: (1) duty of beneﬁcence (help other people to
increase their pleasure, improve their character, and so on); (2) duty of non-maleﬁcence (avoid harming
other people); (3) duty of justice (to ensure people get what they deserve); (4) duty of self-improvement
(to improve oneself); (5) duty of reparation (to repay someone for acting wrongly towards them);
(6) duty of gratitude (to beneﬁt people who have beneﬁted oneself); (7) duty of promise-keeping (to
act according to explicit and implicit promises, including the implicit promise to tell the truth). It is
noteworthy that current legislation and guidelines on research with human subjects encompass the
Deontology was established as an anthropocentric and rationalist framework due to the ﬁrm
belief of rationalist philosophers that humankind is separated from the rest of animal kingdom
by an exclusive capacity of reasoning. Since we now know that reasoning is not an exclusively
human capacity, there is no reason why deontology should not be applied to non-human animals,
as proposed by the American philosopher Tom Regan [
]. His theory of animal rights [
that every individual who is the subject of a life has inherent value. Such an animal is worthy of
moral consideration, regardless of his/her species. According to Regan [
], individuals that fulﬁl
the following criteria are “subjects of a life”: those who have beliefs and desires, perception, memory,
and a sense of future, including their own future, an emotional life together with feelings of pleasure
and pain, preference and welfare interests, the ability to initiate an action in pursuit of a goal, a
psychophysical identity over time; and an individual welfare in the sense that their experiential life
fares well or ill for them. According to Regan [
], “subjects of a life” ought to be respected and must
not be treated as means to an end.
Deontology in Contemporary NHP Research
Within biomedical research, NHPs are usually seen as merely means to an end. For example,
xenotransplantation research aims for engineered animals lacking certain antigens so that their organs
can be used for transplantation into human patients, with a reduced chance of immune rejection [
such cases, the animal is being used as a means to an end. Although the same institutions (e.g., CIOMS)
that wrote regulations and legislations to conduct clinical research also did so for animal research [
the deontological principles that guided the former are totally absent in the latter. Nevertheless,
European Directive 2010/63/EU on the protection of animals used for scientiﬁc purposes states that
“the performance of procedures that result in severe pain, suffering or distress, which is likely to be
long-lasting and cannot be ameliorated, should be prohibited” [
]. This incorporates, to some extent,
the non-maleﬁcence principle.
Even though the beneﬁcence and non-maleﬁcence principles can be found—to a certain extent—in
some NHP laboratory research, the principle of justice is totally absent. As for the principle of
autonomy, this can be found occasionally in cognitive research projects, when the test apparatus is
built or presented in a way that animals enrol in the experiment of their own volition .
Animals 2019,9, 12 5 of 17
Several authors have recommended that NHPs (amongst other animals) involved in biomedical
research should receive ethical consideration similar to that granted to humans, as well as analogous
]. Most deontological guidelines require that the participant give informed
consent prior to participation in research [
], but there are humans who cannot give valid informed
consent (e.g., children or mentally incompetent adult patients). In such cases, the same deontological
principles apply to research conducted on them, resorting to legal guardians, and speciﬁc legislation
with greater restrictions. In most countries, humans who cannot consent may only be engaged in
research that beneﬁts them directly [78,79].
According to the legislation in most countries, research protocols for human studies—especially
for humans who cannot provide consent—must be approved by independent experts (e.g.,
paediatricians in the case of children). Similar criteria could be used for NHPs who cannot consent,
but who can effectively communicate their wishes through behavioural traits interpretable by an
experienced primatologist. Additionally, if NHPs who are enrolled in a research experience had legal
guardians, whose consent was mandatory prior to commencing research—as occurs with humans
unable to understand or communicate informed consent [
], and as occurs in studies involving
owners together with their companion animals [
]—then we believe that research involving NHPs
would likely become more transparent and less exploitative than has sometimes reportedly been the
In sum, within research involving human subjects unable to consent, it is usually mandatory
to have consent from (a) a legal guardian and (b) an expert on the condition that makes the human
unable to consent. In NHP research, both conditions are usually absent: Not only there are no legal
guardians whose task is to safeguard each NHP’s individual interests, but independent experts in
primate behaviour do not normally verify protocol suitability for each animal.
It is interesting to note that it is largely amongst primatologists interested in studying NHPs
by themselves, and not as models for humans, that we ﬁnd the use of deontological principles and
guidelines—mostly the beneﬁcence and non-maleﬁcence principles. For example, guidelines on
darting arboreal primates state that darting cannot occur if the animal is facing the shooter, since the
chest, face, neck, shoulder, thorax and lumber region, head or abdomen are unsuitable target sites that
might harm the animals [
]. Similarly, semi-arboreal NHPs can only be darted on the ground [
These might exclude some animals from the sample in the same way some human participants are
excluded from biomedical research, if they are at signiﬁcantly increased risk of being harmed from an
intervention or procedure .
Utilitarianism is a consequentialist ethical position which asserts that the value of an action is
determined by the utility of its consequences, i.e., the morally right act is the one whose consequences
maximise some form of utility (e.g., pleasure, wealth, wellbeing), for the majority [
]. However, the
magnitude of pleasure and pain for all affected should receive equal consideration [
]. For example,
it is morally justiﬁed to donate blood, because even though the number of individuals harmed is
greater than the number of individuals who beneﬁt from this action, it is a small harm, offset by a
The most popular utilitarian views maintain that all sentient beings are moral subjects and their
interests should receive equal consideration when deciding what is the morally right act [
are, beyond doubt, sentient beings. Hence, when using a utilitarian framework to evaluate the ethics
of a biomedical procedure, the interests of NHPs that will be used as research subjects must receive the
same consideration as the interests of those human beings who will beneﬁt from the procedure. As a
consequence, if the procedure is likely to cause serious harm (e.g., the death of NHP subjects) without
bringing a substantial good (e.g., saving a greater number of human lives), it should not be conducted.
Importantly, the ethical rules and laws that guide animal experimentation rely heavily
on utilitarianism [
]. Most legislation on the protection of animals used for scientiﬁc
Animals 2019,9, 12 6 of 17
purposes—including the current European Directive 2010/63/EU [
] states that the potential beneﬁt
of each research project should be balanced against the likely harm inﬂicted on the animals.
In many cases, the funding agencies evaluate potential beneﬁts, while animal care committees
review proposals in terms of animal harms. These committees do not directly interact, arguably
impeding efforts to compare potential harms and beneﬁts.
Even when this is not the case, the weighting scale is often misused either in predicting the
beneﬁts of the experiments, or in calculating expected harms. Below, we provide evidence of this,
as it is virtually impossible to accurately predict the beneﬁts, and in the calculation of harms, many
variables are commonly left aside.
3.2.1. Predicting Beneﬁts from a Utilitarian Standpoint
NHPs are frequently used in drug trials which are often considered very promising [
retrospective examinations have demonstrated that the majority of those promising trials failed to
translate to humans, or to produce the expected beneﬁts [
], usually because of failures of safety or
]. In fact, data from the Food and Drug Administration showed that 92% of drugs that
succeed in preclinical tests fail to achieve their purpose within human clinical trials, and never reach
the market [
]. These data were previously published in 2004, but more recent papers on the subject
have demonstrated that there has not been a signiﬁcant improvement: the success rate reportedly
varies from 0.4% (in Alzheimer’s trials ) to 20% .
One of us (Andrew Knight) has systematically evaluated the contribution of chimpanzee research
to biomedical progress, showing that approximately half of all publications describing chimpanzee
research identiﬁed in a large-scale study were never cited by any subsequent paper, in any ﬁeld, thereby
making little obvious contribution to the ongoing advancement of knowledge. Even those chimpanzee
studies that were cited by subsequent medical literature rarely made signiﬁcant contributions to
the development of therapeutic methods with signiﬁcant potential for aiding human patients [
] also evaluated the role of chimpanzees in AIDS vaccine research, concluding that claims
that chimpanzees have played a critical role in basic understanding of HIV-1  were overstated.
More recently, Bailey and Taylor evaluated the contribution of NHPs to neuroscience research,
demonstrating that there is a lack of robust evidence to support claims that NHPs are relevant and
beneﬁcial to human medical progress. These authors also concluded that human research methods,
like functional magnetic resonance imaging with electrocorticography, are being simultaneously used
in humans and NHPs for the same purpose, which, in their opinion, makes these NHP studies
]. Garner [
], on the other hand, maintains that the reason animal studies produce such
poor results is the way they are performed, instead of the limitations of animal models.
The fact that one can frequently only evaluate the beneﬁts achieved retrospectively markedly
limits the suitability of utilitarianism in assisting an ethics committee to make an informed decision
about whether a procedure should be permitted.
It is also important to mention the use of NHPs in experiments that will never reach human trials,
due to ethical and legal limitations. Such is the case for experiments using NHP embryos or cloning
experiments, which use NHPs due to their similarities with humans, although the use of humans in
such experiments would be strictly forbidden [
]. Hence, potential beneﬁts for human patients are
absent or severely limited.
When predicting the potential beneﬁts of a biomedical research project, all of humanity is usually
considered to be potential beneﬁciaries. However, that is rarely if ever the case. According to the
World Health Organization, approximately one-third of the people living in developing countries are
unable to receive or purchase essential medicines on a regular basis .
Finally, all basic research produces knowledge, which is in itself a beneﬁt to humankind, since
scientiﬁc knowledge has cultural value in itself. Nonetheless, this beneﬁt is hard to quantify, or to
balance against concrete and substantial costs.
Animals 2019,9, 12 7 of 17
3.2.2. Assessing and Predicting Harms from a Utilitarian Standpoint
While addressing the harms inﬂicted on non-human animals, including NHPs, researchers tend
to focus on the severity of the procedures described in the experimental protocols and overlook other
harms. In fact, European Directive 2010/63/UE, with the aim of regulating the level of severity
inﬂicted on laboratory animals, includes an annex on the severity classiﬁcation of procedures [
This may reinforce the propensity to disregard other sources of pain and distress.
Unlike humans, NHPs cannot be informed about their procedures—hence, even a painless
procedure like an MRI can be terrifying for a naïve NHP [
]. To always classify this procedure as
“mild”, in accordance with current European legislation, ignores subjective experiences, such as fear,
that might vary individually.
Wild-caught NHPs also experience anxiety and pain during capture, in holding facilities, and
often lengthy transportation and conﬁnement, whereas laboratory-bred NHPs may undergo suffering
during breeding, and from maternal separation, potentially much earlier than would occur in the
]. It is noteworthy to mention that due to the intense stress caused by wild capture, the UK
banned the wild capture of primates for their use in research in 1996. Similarly, European Directive
2010/63/EU states that only the offspring of wild-caught NHPs can be used in research experiments.
NHPs who live under laboratory conﬁnement conditions may experience pain and distress not
only during procedures, but also during many other situations that are not normally considered when
evaluating the harms and beneﬁts of the research. Self-injurious behaviour is an obvious sign of stress
that has been extensively described in NHPs living in laboratories (for a review, see Reference [
Similarly, ﬂoating limb syndrome, which can be deﬁned as raising the arms or legs without an obvious
function, is a readily identiﬁable stress-related behaviour [
]. Another easily recognisable sign of
stress in NHPs is the freezing response. In both humans and NHPs, this response is a common and
immediate response to threat situations that allows the individual to evaluate the danger and decide
how to deal with it [
]. When there is a dysregulation in fear response (e.g., post-traumatic stress
disorder—PTSD), this behaviour may emerge in non-threatening or mildly threatening situations and
may last for prolonged periods [
]. Hence, inappropriate freezing behaviour is a signal of fear and
anxiety that researchers should not ignore, regardless of the stimulus. Some types of behaviour, such
as a high frequency of self-grooming, are stereotypic abnormal behaviours in some species but not in
]. However, checking species-speciﬁc ethograms and normal activity time budgets could
help to identify such abnormal behaviours.
Species ethograms can also be helpful in identifying the naturally occurring behavioural repertoire.
In laboratory housing, most NHPs face restrictions on performing certain natural behaviour patterns.
This is not usually considered when assessing harms. The same may occur when an NHP witnesses the
harming or killing of peers [
]. Additionally, experiencing stress, especially at an early age, impacts
the NHP immune system and brain structures [
]. These long-term stress-related harms are not
normally considered when assessing animal welfare impacts and might even reduce the suitability of
some NHPs as models for humans .
Facial expressions could be an important tool to understand NHP emotional states, since they
often convey emotion or pain in many different NHP species (for reviews, see
In the case of chimpanzees, for example, the expression of a full closed grin as described by Goodall [
is reliably associated with fear, distress, and painful contexts [
]. Similarly, in rhesus monkeys, a
grin signals fear or submission [
]. In recent years, the facial action coding system (FACS) developed
by Ekman and Friesen [
] has been adapted to several NHP species, like chimpanzees [
rhesus monkeys [
], gibbons [
], and orangutans [
]. This tool could help researchers to
more objectively assess NHP emotions.
With the help of such tools, it would become easier to evaluate which procedures should be
prohibited or modiﬁed in order to spare NHPs from severe pain or stress. Their use has been suggested
for NHPs [46,61], but has not yet been widely implemented .
Animals 2019,9, 12 8 of 17
4. Ethical limitations of 3Rs Principles
Current policies underpinning animal experimentation follow the 3Rs principles, ﬁrst described
by Russell and Burch [
]. These principles assert that whenever possible, animal models should be
replaced with alternative methods; the number of animals used in experiments should be reduced
to a minimum; and their suffering should, whenever possible, be ameliorated, e.g., through humane
endpoints, less invasive procedures, and the use of anaesthesia (reﬁnement).
Replacement is the ﬁrst and, in our view, the most important of the 3Rs. Its achievement in
a particular case makes implementation of additional Rs unnecessary. However, replacement is
often grounded in the unveriﬁed assumption that animals are good models for human diseases—an
assumption that is increasingly challenged by empirical evidence (for a review, see [
]). To gain
regulatory acceptance and/or be funded, alternative methods often need to demonstrate that they can
provide equivalent or superior data to those obtained through animal testing, even when the current
animal model results are variable rather than consistent, and even when these models have often failed
to reliably predict human responses to drugs [
]. This status quo approach delays the development
of promising non-animal methods in toxicity and drug testing and diverts biomedical research away
from non-animal methods.
These 3Rs principles underpin virtually all legislation and guidelines concerning the use
of animals in scientiﬁc procedures. However, they do not offer a philosophically consistent
ethical framework and are insufﬁcient to address ethical concerns regarding NHP use within
The 3R policies comply—to some extent—with utilitarianism, since reduction and reﬁnement
are tools used to try to minimise the total amount of harm inﬂicted. However, they do not provide
tools to predict beneﬁts, or the extent of long-term harm, which makes them insufﬁcient to fulﬁl the
requirements of utilitarian analysis.
Whilst public health advancement might be a justiﬁable goal, from a utilitarian standpoint, the
pursuit of biomedical NHP research (that might provide only modest beneﬁt) might not be justiﬁable.
From a deontological point of view, the 3Rs are largely irrelevant, since they do not prevent the research
subjects from being used as means to an end. Additionally, the 3Rs do not comply with principles of
autonomy or justice, which are crucial within the deontological approach prescribed by Beauchamp
and Childress .
5. Societal Determination of Ethical Frameworks
Whenever animal-based research is the topic of discussion, the balance between competing
perspectives is often decided at the societal level, and the prevailing culture enables or proscribes a
certain type of scientiﬁc activity .
When it comes to science, people tend to support animal experiments according to utilitarian
principles, i.e., people consider the potential beneﬁts for humanity when assessing their level
of support for certain research [
]. However, when it comes to animals that people
consider companions, such as domesticated dogs, the number of people who support their use
in scientiﬁc research decreases dramatically, regardless of the perceived potential beneﬁts for
]. With these animals, people shift their ethical paradigm, applying the beneﬁcence and
The emergence of ethical decisions is inﬂuenced by the feeling of discomfort that most people
experience when confronted with the suffering of others, and their own sense of wellbeing and
fulﬁlment when contributing to the alleviation of pain or the promotion of happiness [
However, these decisions rely on available information about the phenomenological experiences of
others. Closeness, familiarity, and knowledge of animals, including NHPs, have all been variables
linked to increased empathy for animals [
] and less tolerance for animal use in invasive or harmful
scientiﬁc research .
Animals 2019,9, 12 9 of 17
People are more willing to accept research on nonhuman animals, including NHPs, if they believe
animals are comfortable and well cared for, and in the mid-20th century, according to the National
Opinion Research Centre, 75% of the public believed that medical schools treated laboratory animals as
well as individual owners would [
]. Most owners consider their pets as individuals with intrinsic
value, and veterinary clinical research conducted on pet dogs follows deontological principles similar
to the ones used in human clinical research .
The way animal husbandry is portrayed, as well as the level of familiarity people have with
different species, are thus critical features of engaging society with either utilitarian or deontological
ethical frameworks. Accurate portrayal of the actual state of both variables, as well as a realistic
portrayal of human healthcare beneﬁts that arise from animal research, would, in our opinion, lead to
stronger support for application of the deontological framework.
6. Ethical Research with NHPs
There is no robust evidence that we need NHPs to model speciﬁc human diseases [
therefore, there is no overwhelming moral or scientiﬁc reason to conﬁne NHPs within laboratories,
to be invasively used as defective models for human disorders. In fact, Garner and colleagues
suggested that in order for biomedical research using non-human animals to be more
effective, they should be treated as patients. We agree with this view but emphasise that this is not
possible for animals conﬁned in a laboratory.
6.1. Ethical Research with Possible Healthcare Applications
Disorders that affect humans and NHPs should ideally be studied using NHPs who suffer
naturally from the disorder concerned, either in wild populations, or in captive NHPs who
In 1966, Jane Goodall witnessed a polio outbreak in wild chimpanzees living at Gombe Stream
National Park (Tanzania). In some individuals, the subsequent disability was so severe that some
animals were euthanized [
]. Instead of infecting healthy laboratory animals with polio, these wild
chimpanzees who succumbed to polio from natural causes could theoretically have been studied to
understand polio. The knowledge acquired from these studies would have been useful for science in
general, and for infected chimpanzees speciﬁcally—hence upholding the justice principle. It might or
might not have been useful for humans but, given the more natural induction and progression of the
disease, it could have been more useful than similar research performed on laboratory chimpanzees.
Although the laboratory environment allows for the control of possibly confounding variables, and
manipulation of the exact time of infection, this level of control and information is rarely possible
with human patients. Wild animals that naturally acquire a disease occurring in humans and other
species can be a better model than laboratory animals, since—just like human patients—they are living
in a complex environment where social and natural variables can modulate disease progression. In
human patients, it is very hard or even impossible to determine the exact time of infection and what
other variables (e.g., inadvertent exposure to external viruses) could interfere with disease progression
and/or clinical trial results. Even researchers that support the use of animals as models for human
disorders acknowledge that standardisation of too many variables in the laboratory can be a limitation,
rather than a strength .
There are NHPs previously used by industries (e.g., entertainment, biomedical research)
and subsequently suffering from psychological and behavioural disorders, for whom
psychiatric/psychological treatment is not only appropriate, but also a moral imperative [
Using these animals as research patients for PTSD, for example, could beneﬁt both science and these
particular animals. Again, the data obtained might or might not be useful for human healthcare, but
the results obtained from laboratory animals would not necessarily be more useful.
Epidemiological studies with wild populations can also be conducted with minimal disturbance
of the animals [125,126], hence respecting the autonomy principle.
Animals 2019,9, 12 10 of 17
6.2. Basic Ethical Research
Some may argue that NHP research facilities are useful for purposes other than medical research.
This is the case for basic research, which, according to the Frascati Manual [
], is “experimental
or theoretical work undertaken primarily to acquire new knowledge of the underlying foundation
of phenomena and observable facts, without any particular application or use in view” [
majority of such basic research is laboratory-based.
However, a large amount of such research can be conducted in non-invasive ﬁeld studies, using
wild populations—hence respecting the individuals as subjects with inherent value. For example, Kano
and colleagues used a laboratory apparatus to study differences in gaze behaviour in chimpanzees and
bonobos, concluding that bonobos pay more attention to the eyes and face of other individuals [
the other hand, Fröhlich and colleagues reached the exact same conclusion by observing communicative
interactions in mother-infant dyads of wild populations [
]. Similarly, Fujita and colleagues created
an experimental laboratory procedure to study capuchin monkeys’ deceptive behaviours [
] were able to study tactical deception of the same species in the wild, gathering more robust
and reliable data on the subject. Another good example which has been widely studied is chimpanzee
communication: while in captivity, only 31 gestures were described [
], observations in the wild
raised this number to 66 distinct gesture types to communicate at least 19 different messages [
fact, most of what we know about behaviour and the ecology of NHPs has come from long-term ﬁeld
], and recent ﬁeld studies continue to amaze us by revealing new species [
as well as unexpected behaviour from well-known species, such as bonobo hunting [
], and some
behaviours that might be ritual practices amongst wild chimpanzees [137,138].
These studies have been conducted respecting the beneﬁcence and non-maleﬁcence principles,
and even the principle of justice, since the knowledge obtained from those data, some of it also
presented as documentaries and in other forms for widespread media dissemination, raises awareness
of animal emotion and cognition [
], potentially increasing empathy towards these NHPs, and
ultimately increasing the impetus for their conservation.
However, there are research questions, either in safety and efﬁcacy testing or fundamental
research, where it is not possible to obtain knowledge using only observational techniques (e.g.,
genetics, neuroscience). However, there are ways of continuing this research without overlooking
In questionable situations, it is always pertinent to ask whether the knowledge acquired through
the suffering of other animals complies with the bioethical principles described by Beauchamp and
]. In the literature, we can ﬁnd examples of basic research with non-human animals that
fulﬁl these principles. Berns and colleagues [
] used positive reinforcement to train dogs to stay still
within a functional MRI device. The dogs were unrestrained and free to leave the device at all times,
including during training sessions (autonomy principle). Without harm or distress, much fundamental
knowledge on the canine brain was obtained (non-maleﬁcence principle), which may ultimately beneﬁt
the wider canine population (principle of justice). The researchers would gradually play louder sounds
in the surrounding environment so that animals would not get startled by MRI sounds (principle
of non-maleﬁcence). This innovative method has been providing exciting insights into the canine
], and a similar technique could be used to study NHPs living under semi-natural
conditions, replacing neuroscience NHP laboratories where even the least invasive techniques [
require temporarily restraining fearful animals. Some NHPs share habitat with human beings (e.g.,
rhesus monkeys in India or Nepal) and sometimes even enter and explore human homes, which
should make it possible to conduct experiments with these animals similar to those described above
with dogs. Some NHPs species are particularly harmless and cooperative (e.g., marmosets or capuchin
monkeys). Individuals from those species who are held captive for other reasons (e.g., rescued animals
living in sanctuaries) could also be enrolled in experiments similar to the ones conducted by Bern and
colleagues on dogs [
]. Even potentially dangerous NHPs, such as chimpanzees, can participate
in experiments consensually, in the same way human participants do .
Animals 2019,9, 12 11 of 17
In light of the current knowledge, the use of NHPs in basic research warrants something of a
paradigm shift. We propose that basic research with NHPs should continue only if carried out under
the same ethical deontological criteria that guide basic research with human beings.
Whenever non-invasive basic research protocols require the use of NHPs, the participants should
be recruited from sanctuaries or similar facilities. Local legal guardians of NHPs should evaluate the
procedures to verify whether the principles of autonomy, beneﬁcence, non-maleﬁcence and justice, as
deﬁned by Beauchamp and Childress [
], have been fully incorporated. That being the case, the legal
guardian would provide the necessary informed consent.
By complying with such standards, we would not only grant other primates a level of respect
and protection consistent with that we provide to members of our own species, but we would also
be encouraging researchers to develop better research protocols and higher standards for captive
management, which could, in turn, result in improvements in data quality, and in the reliability of
some research results.
All authors contributed to the conceptualization of this paper and agree on its ﬁnal content.
First Author (C.C.) was responsible for most of the writing. C.C., A.G. and A.K., were involved in the original
draft preparation and writing, and further reviewing and editing; A.K. and L.V. were also involved in supervision
and in Funding acquisition.
First author (C.C.) is sponsored by Animalfree Research Foundation (Switzerland) and by Portuguese
National Funds through CFCUL research unit funding UID/FIL/00678/2013. Second author (A.G.) is
sponsored by Catolica Research Centre for Psychological, Family and Social Wellbeing (CRC-W), third author
(A.K.) is sponsored by the Ketty and Leif Hjordt Foundation, and L.V. by CFCUL research unit funding
We wish to express our gratitude to the editor and anonymous referees for their detailed
comments that greatly helped us improve the quality of the manuscript.
Conﬂicts of Interest:
The authors declare no conﬂict of interest. The founding sponsors had no role in the design
of the study; the writing of the manuscript, or the decision to publish the results.
Phillips, K.A.; Bales, K.L.; Capitanio, J.P.; Conley, A.; Czoty, P.W.;
t Hart, B.A.; Hopkins, W.; Hopkins, W.D.;
Hu, S.L.; et al. Why primate models matter. Am. J. Primatol. 2014,76, 801–827. [CrossRef] [PubMed]
Maestripieri, D. The Past, Present, and Future of Primate Psychology. In Primate Psychology; Maestripieri, D.,
Ed.; Harvard University Press: Cambridge, MA, USA, 2003; pp. 1–16.
European Commission. Seventh Report on the Statistics on the Number of Animals used for Experimental
and other Scientiﬁc Purposes in the Member States of the European Union. Available online: http://eur-lex.
europa.eu/legal-content/EN/TXT/?uri=CELEX:52013DC0859 (accessed on 23 March 2017).
Lankau, E.W.; Turner, P.V.; Mullan, R.J.; Galland, G.G. Use of nonhuman primates in research in North
America. J. Am. Assoc. Lab. Anim. Sci. 2014,53, 278–282. [PubMed]
Zhang, X.L.; Pang, W.; Hu, X.T.; Li, J.L.; Yao, Y.G.; Zheng, Y.T. Experimental primates and non-human
primate (NHP) models of human diseases in China: Current status and progress. Zool. Res.
Zhou, Q. Balancing the welfare: The use of non-human primates in research. Trends Gen.
Friedman, H.; Haigwood, N.; Ator, N.; Newsome, W.; Allan, J.S.; Golos, T.G.; Kordower, J.H.; Shade, R.E.;
Goldberg, M.E.; Bailey, M.R.; et al. The Critical Role of Nonhuman Primates in Medical Research-White
Paper. Pathog. Immun. 2017,2, 352–365. [CrossRef] [PubMed]
Sanal, M.G. Future of liver transplantation: Non-human primates for patient-speciﬁc organs from induced
pluripotent stem cells. World J. Gastroenterol 2011,17, 3684–3690. [CrossRef] [PubMed]
Knight, A. The poor contribution of chimpanzee experiments to biomedical progress. J. Appl. Anim. Welf. Sci.
2007,10, 281–308. [CrossRef]
10. Bailey, J. An assessment of the role of chimpanzees in AIDS vaccine research. ATLA 2008,36, 381–428.
Animals 2019,9, 12 12 of 17
11. Thew, M. Primate studies: Trials don’t always translate. Nature 2012,484, 167. [CrossRef]
Bailey, J.; Taylor, K. Non-human primates in neuroscience research: The case against its scientiﬁc necessity.
ATLA 2016,44, 43–69.
13. Harlow, H.F. The nature of love. Am. Psychol. 1958,13, 673–685. [CrossRef]
Selemon, L.D.; Goldman-Rakic, P.S. Longitudinal topography and interdigitation of corticostriatal projections
in the rhesus monkey. J. Neurosci. 1985,5, 776–794. [CrossRef] [PubMed]
Lewontin, R.C. Primate Models of Human Traits. In Aping Science: A Critical Analysis of Research at the
Yerkes Regional Primate Research Center; Committee on Animal Models in Biomedical Research, Ed.; Medical
Research Modernization Committee: New York, NY, USA, 1995; pp. 5–24.
Goodall, J. Tool-using and aimed throwing in a community of free-living chimpanzees. Nature
Liu, Q.; Fragaszy, D.M.; Visalberghi, E. Wild capuchin monkeys spontaneously adjust actions when using
hammer stones of different mass to crack nuts of different resistance. Am. J. Phys. Anthrop.
Kawamura, S. The process of sub-culture propagation among Japanese macaques. Primates
Eshchar, Y.; Izar, P.; Visalberghi, E.; Resende, B.; Fragaszy, D. When and where to practice: Social inﬂuences
on the development of nut-cracking in bearded capuchins (Sapajuslibidinosus). Anim. Cogn.
605–618. [CrossRef] [PubMed]
20. Gallup, G.G., Jr. Chimpanzees: Self-recognition. Science 1970,167, 86–87. [CrossRef]
Toda, K.; Platt, M.L. Animal cognition: Monkeys pass the mirror test. Curr. Biol.
,25, 64–66. [CrossRef]
Freeman, H.D.; Gosling, S.D. Personality in nonhuman primates: A review and evaluation of past research.
Am. J. Primatol. 2010,72, 653–671. [CrossRef]
Cheney, D.; Seyfarth, R.; Smuts, B. Social relationships and social cognition in nonhuman primates. Science
1986,234, 1361–1366. [CrossRef]
Roubová, V.; Koneˇcná, M.; Šmilauer, P.; Wallner, B. Whom to groom and for what? Patterns of grooming in
female Barbary macaques (Macaca sylvanus). PLoS ONE 2015,10, e0117298. [CrossRef] [PubMed]
Smuts, B.B.; Cheney, D.L.; Seyfarth, R.M.; Wrangham, R.W. Primate Societies; University of Chicago Press:
Chicago, IL, USA, 2008.
Sterck, E.H.; Goossens, B.M. The meaning of “macaque” facial expressions. Proc. Natl. Acad. Sci. USA
105, E71. [CrossRef]
Goodall, J. The Chimpanzees of Gombe: Patterns of Behavior; Harvard University Press: Cambridge, MA,
De Waal, F.B. Putting the altruism back into altruism: The evolution of empathy. Ann. Rev. Psychol.
279–300. [CrossRef] [PubMed]
Yang, B.; Anderson, J.R.; Li, B.G. Tending a dying adult in a wild multi-level primate society. Curr. Biol.
26, 403–404. [CrossRef] [PubMed]
30. Brosnan, S.; De Waal, F.B. Monkeys reject unequal pay. Nature 2003,425, 297–299. [CrossRef] [PubMed]
Wheeler, B.C. Monkeys crying wolf? Tufted capuchin monkeys use anti-predator calls to usurp resources
from conspeciﬁcs. Proc. Biol. Sci. 2009,276, 3013–3018. [CrossRef] [PubMed]
Bard, K.A.; Gaspar, A.D.; Vick, S.J. Chimpanzee faces under the magnifying glass: Emerging methods reveal
cross-species similarities and individuality. In Personality and Temperament in Nonhuman Primates; Weiss, A.,
King, J.E., Murray, L., Eds.; Springer: New York, NY, USA, 2011; pp. 193–231.
Hobaiter, C.; Byrne, R.W. The gestural repertoire of the wild chimpanzee. Anim. Cogn.
Gaspar, A.; Esteves, F.; Arriaga, P. On prototypical facial expressions versus variation in facial behavior: What
have we learned on the “visibility” of emotions from measuring facial actions in humans and apes. In The
Evolution of Social Communication in Primates; Pina, M., Gontier, N., Eds.; Springer International Publishing:
Heidelberg, Germany, 2014; pp. 101–126.
Pasquaretta, C.; Levé, M.; Claidière, N.; Van De Waal, F.; Whiten, A.; MacIntosh, A.J.; Pelé, M.;
Bergstrom, M.L.; Borgeaud, C.; Brosnan, S.F.; et al. Social networks in primates: Smart and tolerant
species have more efﬁcient networks. Sci. Rep. 2014,4, 7600. [CrossRef]
Gardner, R.A.; Gardner, B.T. Teaching sign language to a chimpanzee. Science
,165, 664–672. [CrossRef]
Animals 2019,9, 12 13 of 17
Patterson, F.G. The gestures of a gorilla: Language acquisition in another pongid. Brain Lang
Matsuzawa, T.; Hasegawa, Y.; Gotoh, S.; Wada, K. One-trial long-lasting food-aversion learning in wild
Japanese monkeys (Macaca fuscata). Behav. Neural Biol. 1983,39, 155–159. [CrossRef]
Amici, F.; Barney, B.; Johnson, V.E.; Call, J.; Aureli, F. A modular mind? A test using individual data from
seven primate species. PLoS ONE 2012,7, e51918. [CrossRef]
Cantlon, J.F.; Brannon, E.M. Basic math in monkeys and college students. PLoS Biol.
,5, e328. [CrossRef]
Inoue, S.; Matsuzawa, T. Working memory of numerals in chimpanzees. Curr. Biol.
Natale, F.; Antinucci, F.; Spinozzi, G.; Potí, P. Stage 6 object concept in nonhuman primate cognition: A
comparison between gorilla (Gorilla gorilla gorilla) and Japanese macaque (Macaca fuscata). J. Comp. Psychol.
1986,100, 335–339. [CrossRef]
Herrmann, E.; Call, J. Are there geniuses among the apes? Phil. Trans. R. Soc. B.
Drucker, C.B.; Brannon, E.M. Rhesus monkeys (Macaca mulatta) map number onto space. Cognition
57–67. [CrossRef] [PubMed]
Fenton, A. On the need to redress an inadequacy in animal welfare science: Toward an internally coherent
framework. Biol. Phil. 2012,27, 73–93. [CrossRef]
Wendler, D. Should protections for research with humans who cannot consent apply to research with
nonhuman primates? Theor. Med. Bioeth. 2014,35, 157–173. [CrossRef]
Conlee, K.M.; Rowan, A.N. The case for phasing out experiments on primates. Hastings Cent. Rep.
20–26. [CrossRef] [PubMed]
European Commission. Special Eurobarometer: Science and Technology Report. Available online: http:
//ec.europa.eu/commfrontofﬁce/publicopinion/archives/ebs/ebs_340_en.pdf (accessed on 31 March 2017).
Price, N.; Bourne, J.; Rosa, M. Animal research: Australians rush to reject primate bill. Nature
Harding, J.D. Nonhuman Primates and Translational Research: Progress, Opportunities, and Challenges.
ILAR J. 2017,58, 141–150. [CrossRef]
51. Pollard, K.C. What Makes Us Human? Sci. Am. 2009,300, 32–37. [CrossRef]
Jin, H.; Liu, L.; Ding, H.; He, M.; Zhang, C.; Zhong, X. Comparison of femtosecond laser-assisted corneal
intrastromal xenotransplantation and the allotransplantation in rhesus monkeys. BMC Ophthalmol.
202. [CrossRef] [PubMed]
He, M.; Jin, H.; He, H.; Ding, H.; Wang, W.; Liu, L.; Zhang, C.; Zhong, X. Femtosecond Laser-Assisted Small
Incision Endokeratophakia Using a Xenogeneic Lenticule in Rhesus Monkeys. Cornea
Bilz, K.; Nadler, J. Law, psychology, and morality. In Psychology of Learning and Motivation: Moral Judgment
and Decision Making; Medin, D., Skitka, L., Bartels, D., Bauman, C., Eds.; Academic Press: San Diego, CA,
USA, 2009; Volume 50, pp. 101–124.
55. Barnes, E. Diseases and Human Evolution; University of New Mexico Press: Albuquerque, NM, USA, 2007.
56. Mandal, J.; Acharya, S.; Parija, S.C. Ethics in human research. Trop. Parasitol. 2011,1, 2–57. [PubMed]
Council for International Organizations of Medical Sciences. International ethical guidelines for biomedical
research involving human subjects. Bull. Med. Ethics 2002,182, 17–23.
Beauchamp, T.L.; Childress, J.F. Principles of Biomedical Ethics, 4th ed.; Oxford University Press: New York,
NY, USA, 2005.
Canli, T. Neurogenethics: An emerging discipline at the intersection of ethics, neuroscience, and genomics.
Appl. Transl. Genom. 2015,5, 18–22. [CrossRef]
Smith, C.U.C. Confronting ethical permissibility in animal research: Rejecting a common assumption and
extending a principle of justice. Theor. Med. Bioeth. 2014,35, 175–185. [CrossRef]
Miracle, V.A. The Belmont report: The triple crown of research ethics. Dimens. Crit. Care Nurs.
62. Nardini, C. The ethics of clinical trials. Ecancermedicalscience 2014,8, 387. [PubMed]
Animals 2019,9, 12 14 of 17
Gluck, J.P. Moving beyond the welfare standard of psychological well-being for nonhuman primates: The
case of chimpanzees. Theor. Med. Bioeth. 2014,35, 105–116. [CrossRef] [PubMed]
Jones, R.C.; Greek, R. A review of the Institute of Medicine’s analysis of using chimpanzees in biomedical
research. Sci. Eng. Ethics 2014,20, 481–504. [CrossRef] [PubMed]
Thomas, D. Laboratory animals and the art of empathy. J. Med. Ethics
,31, 197–202. [CrossRef] [PubMed]
Lowenstein, P.R. Clinical trials in gene therapy: Ethics of informed consent and the future of experimental
medicine. Curr. Opin. Mol. Ther 2008,10, 428–430.
67. Ollson, I.A.S.; Sandøe, P. “What’s wrong with my monkey?” Ethical perspectives on germline transgenesis
in marmosets. Transgenic Res. 2010,19, 181–186. [CrossRef] [PubMed]
68. Kant, I. Lectures on Ethics (First Published 1775); Hackett Publishing Co.: Indianapolis, IN, USA, 1930.
Kant, I. Groundwork of the Metaphysic of Morals (First Published 1785); Hutchinson University Library:
Hutchinson, KA, USA, 1972.
70. Darwall, S. Deontology; Blackwell Publishing: Oxford, MA, USA, 2002.
Barrow, J.M.; Gossman, W.G. Deontology; StatPearls Publishing: Treasure Island, FL, USA, 2017. Available
online: https://www.ncbi.nlm.nih.gov/books/NBK459296/ (accessed on 11 March 2018).
72. Ross, W.D. The Right and the Good; Clarendon Press: Oxford, NY, USA, 1930.
73. Regan, T. The Case for Animal Rights; University of California Press: Berkeley, CA, USA, 1983.
Council for International Organizations of Medical Sciences. International Guiding Principles for Biomedical
Research Involving Animals. Available online: https://grants.nih.gov/grants/olaw/Guiding_Principles_
2012.pdf (accessed on 23 March 2017).
European Parliament. Directive 2010/63/EU of the European Parliament and of the Council of 22 September
2010 on the Protection of Animals Used for Scientiﬁc purposes Text with EEA Relevance. Available online:
http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:32010L0063 (accessed on 11 March 2018).
Ferdowsian, H. Human and animal research guidelines: Aligning ethical constructs with new scientiﬁc
developments. Bioethics 2011,25, 472–478. [CrossRef]
Ferdowsian, H.; Fuentes, A. Harms and deprivation of beneﬁts for nonhuman primates in research.
Theor. Med. Bioeth. 2014,35, 143–156. [CrossRef] [PubMed]
Lepola, P.; Needham, A.; Mendum, J.; Sallabank, P.; Neubauer, D.; de Wildt, S. Informed consent for
paediatric clinical trials in Europe. Arch. Dis. Child. 2016,101, 1017–1025. [CrossRef] [PubMed]
Kelley, M.C.; Brazg, T.; Wilfond, B.S.; Lengua, L.J.; Rivin, B.E.; Martin-Herz, S.P.; Diekema, D.S. Ethical
challenges in research with orphans and vulnerable children: A qualitative study of researcher experiences.
Int. Health 2016,8, 187–196. [CrossRef]
Lit, L.; Schweitzer, J.B.; Iosif, A.M.; Oberbauer, A.M. Owner reports of attention, activity, and impulsivity in
dogs: A replication study. Behav. Brain Funct. 2010,6, 1. [CrossRef] [PubMed]
Sauer, U.; Phillips, B.; Reid, K.; Schmit, V.; Jennings, M. Ethical review of projects involving non-human
primates funded under the European Union’s 7th Research Framework Programme. ATLA
Glander, K.E.; Fedigan, L.M.; Fedigan, L.; Chapman, C. Field methods for capture and measurement of three
monkey species in Costa Rica. Folia Primatol. 1991,57, 70–82. [CrossRef] [PubMed]
Cunningham, E.P.; Unwin, S.; Setchell, J.M. Darting Primates in the Field: A Review of Reporting Trends and
a Survey of Practices and Their Effect on the Primates Involved. Int. J. Primatol.
,36, 911–932. [CrossRef]
Unwin, S.; Ancrenaz, M.; Mahe, S.; Boardman, W. African primate handling and anaesthesia. In Pan
African Sanctuary Alliance Veterinary Health Manual, 2nd ed.; Unwin, S.M., Cress, D., Colin, C., Bailey, W.,
Boardman, W., Eds.; Pan African Sanctuary Alliance: Portland, OR, USA, 2009; pp. 214–287.
Bentham, J. The Principles of Morals and Legislation (First Published 1789); Prometheus Books: New York, NY,
86. Mill, J.S. Utilitarianism; Parker; Son & Bourn: London, UK, 1863.
87. Singer, P. Practical Ethics; Cambridge University Press: Cambridge, UK, 1979.
Bayne, K.; Morris, T. Laws, regulations and policies relating to the care and use of nonhuman primates
in biomedical research. In Nonhuman Primates in Biomedical Research: Biology and Management; Abee, C.R.,
Mansﬁeld, K., Tardif, S.D., Morris, T., Eds.; Academic Press: Oxford, MA, USA, 2012; pp. 35–56.
Garner, P. The Signiﬁcance of Meaning: Why Do Over 90% of Behavioral Neuroscience Results Fail to
Translate to Humans, and What Can We Do to Fix It? ILAR J. 2014,55, 438–456. [CrossRef] [PubMed]
Animals 2019,9, 12 15 of 17
Food and Drug Administration. Innovation/Stagnation: Challenge and Opportunity on the Critical Path
to New Medical Products. Available online: https://www.who.int/intellectualproperty/documents/en/
FDAproposals.pdf (accessed on 23 March 2017).
91. Cummings, J.L.; Morstorf, T.; Zhong, K. Alzheimer’s disease drug-develop ment pipeline: Few candidates,
frequent failures. Alzheimer’s Res. Ther. 2014,6, 37. [CrossRef]
92. Perrin, S. Preclinical research: Make mouse studies work. Nature 2014,507, 423–425. [CrossRef]
93. VandeBerg, J.L.; Zola, S.M. A unique biomedical resource at risk. Nature 2005,437, 30–32. [CrossRef]
Wolf, D.P. The non-human primate oocyte and embryo as a model for women, or is it vice versa?
Theriogenology 2008,69, 31–36. [CrossRef]
World Health Organization. Access to Medicine Index 2016. Available online: http://accesstomedicineindex.
org/media/atmi/Access-to-Medicine-Index-2016.pdf (accessed on 23 March 2017).
Ferdowsian, H.; Merskin, D. Parallels in sources of trauma, pain, distress, and suffering in humans and
nonhuman animals. J Trauma Dis. 2012,13, 448–468. [CrossRef]
Latham, N.R.; Mason, G.J. Maternal deprivation and the development of stereotypic behaviour. Appl. Anim.
Behav. Sci 2008,110, 84–108. [CrossRef]
Polanco, A. A Tinbergian review of self-injurious behaviors in laboratory rhesus macaques. Appl. Anim.
Behav. Sci. 2016,179, 1–10. [CrossRef]
Bentson, K.L.; Crockett, C.M.; Wahl, K.L.; Runeson, E.P.; Bellanca, R.U.; Lee, G.H.; Thom, J.P.;
Montgomery, H.B.; Yi, M.H.; McComas, J.G.; et al. Floating limb behaviors and self-biting are associated in
laboratory monkeys. Am. J. Prim. 2010,72, 725–733. [CrossRef]
Bethell, E.J.; Holmes, A.; MacLarnon, A.; Semple, S. Emotion, evaluation and response slowing in a
non-human primate: New directions for cognitive bias measures of animal emotion? Behav. Sci.
6, 2. [CrossRef] [PubMed]
Pryce, C.R.; Rüedi-Bettschen, D.; Dettling, A.C.; Feldon, J. Early life stress: Long-term physiological impact
in rodents and primates. News Physiol. Sci. 2002,17, 150–155. [CrossRef] [PubMed]
Spinelli, S.; Chefer, S.; Suomi, S.J.; Higley, J.D.; Barr, C.S.; Stein, E. Early-life stress induces long-term
morphologic changes in primate brain. Arch. Gen. Psychiatry 2009,66, 658–665. [CrossRef] [PubMed]
Burrows, A.M. The facial expression musculature in primates and its evolutionary signiﬁcance. Bioessays
2008,30, 212–225. [CrossRef]
Gaspar, A. Comportamento facial em Pan e Homo. Ph.D. Thesis, Universidade Nova FCSH, Lisboa,
Ekman, P.; Friesen, W.V. Facial Action Coding System: Manual; Consulting Psychologists Press: Palo Alto, CA,
Vick, S.J.; Waller, B.M.; Parr, L.A.; Pasqualini, M.C.S.; Bard, K.A. A cross-species comparison of facial
morphology and movement in humans and chimpanzees using the facial action coding system (FACS).
J. Nonverbal. Behav. 2007,31, 1–20. [CrossRef]
Parr, L.A.; Waller, B.M.; Burrows, A.M.; Gothard, K.M.; Vick, S.J. Brief communication: MaqFACS: A
muscle-based facial movement coding system for the rhesus macaque. Am. J. Phys. Anthrop.
Waller, B.M.; Lembeck, M.; Kuchenbuch, P.; Burrows, A.M.; Liebal, K. GibbonFACS: A muscle-based facial
movement coding system for hylobatids. Int. J. Primat. 2012,33, 809–821. [CrossRef]
Caeiro, C.C.; Waller, B.M.; Zimmermann, E.; Burrows, A.M.; Davila-Ross, M. OrangFACS: A muscle-based
facial movement coding system for orangutans (Pongo spp.). Int. J. Primatol. 2013,34, 115–129. [CrossRef]
Russell, W.; Burch, R. The Principles of Humane Experimental Technique; Methuen & Co. Ltd.: London, UK, 1959.
111. Knight, A. The Costs and Beneﬁts of Animal Experiments; Palgrave Macmillan: Basingstoke, UK, 2011.
Wilson, S.L.; Ahearne, M.; Hopkinson, A. An overview of current techniques for ocular toxicity testing.
Toxicology 2015,327, 32–46. [CrossRef] [PubMed]
Ormandy, E.H.; Schuppli, C.A. Public attitudes toward animal research: A review. Animals
Plous, S. Attitudes toward the use of animals in psychological research and education: Results from a
national survey of psychology majors. Psychol. Sci. 1996,7, 352–358. [CrossRef]
Metzger, M.M. Knowledge of the animal welfare act and animal welfare regulations inﬂuences attitudes
toward animal research. J. Am. Assoc. Lab. Anim. Sci. 2015,54, 70–75. [PubMed]
Animals 2019,9, 12 16 of 17
Batson, C.D.; Duncan, B.D.; Ackerman, P.; Buckley, T.; Birch, K. Is empathic emotion a source of altruistic
motivation? J. Pers. Soc. Psychol. 1981,40, 290–302. [CrossRef]
Singer, P. The Most Good You Can Do: How Effective Altruism is Changing Ideas About Living Ethically; Yale
University Press: New Haven, CT, USA, 2015.
Paul, E.S. Empathy with animals and with humans: Are they linked? Anthrozoös
,13, 194–202. [CrossRef]
Davis, B.W.; Ostrander, E.A. Domestic dogs and cancer research: A breed-based genomics approach. ILAR J.
2014,55, 59–68. [CrossRef]
Garner, J.P.; Gaskill, B.N.; Weber, E.M.; Ahloy-Dallaire, J.; Pritchett-Corning, K.R. Introducing
Therioepistemology: The study of how knowledge is gained from animal research. Lab. Anim.
46, 103–113. [CrossRef]
Peterson, D. Jane Goodall: The Woman who Redeﬁned Man; Houghton Mifﬂin Harcourt: Boston, MA, USA, 2014.
Brüne, M.; Brüne-Cohrs, U.; McGrew, W.C. Psychiatric treatment for great apes? Science
Brüne, M.; Brüne-Cohrs, U.; McGrew, W.C.; Preuschoft, S. Psychopathology in great apes: Concepts,
treatment options and possible homologies to human psychiatric disorders. Neurosci. Biobehav. Rev.
1246–1259. [CrossRef] [PubMed]
Bradshaw, G.A.; Capaldo, T.; Lindner, L.; Grow, G. Building an inner sanctuary: Complex PTSD in
chimpanzees. J. Trauma Dis. 2008,9, 9–34. [CrossRef]
Cibot, M.; Guillot, J.; Lafosse, S.; Bon, C.; Seguya, A.; Krief, S. Nodular worm infections in wild non-human
primates and humans living in the Sebitoli area (Kibale National Park, Uganda): Do high spatial proximity
favor zoonotic transmission? PLoS Negl. Trop. Dis. 2015,9, e0004133. [CrossRef] [PubMed]
Lantz, E.L.; Lonsdorf, E.V.; Heintz, M.R.; Murray, C.M.; Lipende, I.; Travis, D.A.; Santymire, R.M.
Non-invasive quantiﬁcation of immunoglobulin A in chimpanzees (Pan troglodytes schweinfurthii) at
Gombe National Park, Tanzania. Am. J. Primatol. 2016,80, e22558. [CrossRef] [PubMed]
Organisation for Economic Co-Operation and Development. Frascati Manual: Proposed Standard Practice
for Surveys on Research and Experimental Development. Available online: https://www.oecd-ilibrary.org/
science-and-technology/frascati-manual-2002_9789264199040-en (accessed on 23 March 2017).
Kano, F.; Hirata, S.; Call, J. Social attention in the two species of pan: Bonobos make more eye contact than
chimpanzees. PLoS ONE 2015,10, e0129684. [CrossRef] [PubMed]
Fröhlich, M.; Kuchenbuch, P.; Müller, G.; Fruth, B.; Furuichi, T.; Wittig, R.M.; Pika, S. Unpeeling the layers of
language: Bonobos and chimpanzees engage in cooperative turn-taking sequences. Sci. Rep. 2016,6, 25887.
Fujita, K.; Kuroshima, H.; Masuda, T. Do tufted capuchin monkeys (Cebusapella) spontaneously deceive
opponents? A preliminary analysis of an experimental food-competition contest between monkeys.
Anim. Cogn. 2002,5, 19–25. [CrossRef] [PubMed]
Pollick, A.S.; De Waal, F.B. Ape gestures and language evolution. Proc. Natl. Acad. Sci. USA
Fossey, D.; Harcourt, A.H. Feeding ecology of free-ranging mountain gorilla (Gorilla gorilla beringei). In
Primate Ecology: Studies in Feeding and Ranging Behavior in Lemurs, Monkeys and Apes; Clutton-Brock, T.H., Ed.;
Academic Press: New York, NY, USA, 1977; pp. 415–447.
Galdikas, B.M. Orangutan diet, range, and activity at Tanjung Puting, Central Borneo. Int. J. Primatol.
9, 1–35. [CrossRef]
o, T. The Last Ape: Pygmy Chimpanzee Behavior and Ecology; Stanford University Press: Redwood City, CA,
Chi, M.; Zhi-Pang, H.; Xiao-Fei, Z.; Li-Xiang, Z.; Wen-Mo, S.; Scott, M.B.; Xing-Wen, W.; Cui, L.-C.;
Xiao, W. Distribution and conservation status of Rhinopithecusstrykeri in China. Primates
Surbeck, M.; Hohmann, G. Primate hunting by bonobos at LuiKotale, Salonga National Park. Curr. Biol.
2008,18, 906–907. [CrossRef] [PubMed]
Kühl, H.S.; Kalan, A.K.; Arandjelovic, M.; Aubert, F.; D’Auvergne, L.; Goedmakers, A.; Kühl, H.S.;
Kalan, A.K.; Arandjelovic, M.; Aubert, F.; et al. Chimpanzee accumulative stone throwing. Sci. Rep.
2016,6, 22219. [CrossRef] [PubMed]
Animals 2019,9, 12 17 of 17
Van Leeuwen, E.J.; Cronin, K.A.; Haun, D.B. Tool use for corpse cleaning in chimpanzees. Sci. Rep.
44091. [CrossRef] [PubMed]
139. Rocha, S.; Gaspar, A.; Esteves, F. Developing children’s ability to recognize animal emotions—what does it
take? A. study at the Zoo. HAIB 2016,4, 59–79.
Berns, G.S.; Brooks, A.M.; Spivak, M. Functional MRI in awake unrestrained dogs. PLoS ONE
Berns, G.S.; Brooks, A.M.; Spivak, M. Scent of the familiar: An fMRI study of canine brain responses to
familiar and unfamiliar human and dog odors. Behav. Process 2015,110, 37–46. [CrossRef]
Dilks, D.D.; Cook, P.; Weiller, S.K.; Berns, H.P.; Spivak, M.; Berns, G.S. Awake fMRI reveals a specialized
region in dog temporal cortex for face processing. Peer J. 2015,3, e1115. [CrossRef]
Cook, P.F.; Spivak, M.; Berns, G. Neurobehavioral evidence for individual differences in canine cognitive
control: An awake fMRI study. Anim. Cogn. 2016,19, 1–12. [CrossRef]
Slater, H.; Milne, A.E.; Wilson, B.; Muers, R.S.; Balezeau, F.; Hunter, D.; Thiele, A.; Grifﬁths, T.D.; Petkov, C.I.
Individually customisable non-invasive head immobilisation system for non-human primates with an option
for voluntary engagement. J. Neurosci. Meth. 2016,269, 46–60. [CrossRef]
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