Kao 1

Stella Kao

Greg McClure

Writing 39 C

9 June 2018

Contemporary Technology Eliminates Ethical Conflicts in Animal Testing

Animal research has made significant contributions to the advancement in biomedical

research throughout history, but the testing method is unsustainable and unethical. According to

The National Center for Biotechnology Information’s studies, roughly 17 to 22 million animals

are used in laboratory experiments annually in the United States. Although animal

experimentation has been conducted by researchers and scientists for multiple centuries, the

ethical dilemma pertained to this testing method remains an issue. The moral question is: Is it

acceptable for humans to override the rights of animals and discriminate them on the sole basis

of their species-membership? (Singer 4) Radical animal rights advocates believe in the complete

replacement of the method, while moderate animal rights protection organizations and animal

research advocates support the reduced usage in animal testing. The Three R’s Principles

proposed by William Russell instruct scientists to replace, reduce, and refine their research

process. However, although these guiding principles are encouraged, they are rarely enforced.

This gives researchers the option to disregard the morality issue pertained to animal testing and

persist in the use of laboratory animals. As a result, there has been little to no progress in

reducing the use of animal testing and it has in fact been on the rise the past few decades (Olsson

et al.,333). The implementation of in-vitro testing and the use of human volunteers can meet each

of the stated principle in the Three R’s and resolve this issue. Animal research advocates have

criticized the ineffectiveness of such testing methods as they are supposedly poor predicts of
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human response, but evidence have proved otherwise and presented themselves as feasible

solutions.

Handbook of Laboratory Animal Science provides a detailed overview on the history of

animal experimentation. In the 18th century, through the use of animal research, effective

vaccines against viruses and toxins were developed. One of the contributors to this notable

advancement was English physician Edward Jenner (1798) who discovered the principles of

vaccination. Jenner extracted liquid from a cowpox blister and applied it onto a boy. He

immediately showed cowpox symptoms but soon recovered. A few months later, Jenner

inoculated the boy with the vaccine again, but the boy had grown immune to it. Edward Jenner’s

success in vaccine development set the groundwork for the World Health Organization which led

to the eradication of smallpox (Baumans, et al.,12). Louis Pasteur (1885) a French biologist

from the 19th century also contributed to the breakthrough in disease prevention. Pasteur

successfully developed the vaccination against rabies by planting the virus in rabbits. Through

inoculation, he comprehended the property of “passive immunization”, which assisted him with

developing vaccines for other diseases such as diphtheria and poliomyelitis (Baumans, et al.,13).

Due to the use of laboratory animals, these diseases have now become obsolete. Jenner and

Pasteur's accomplishment in finding cures for human diseases therefore illustrates the critical

role of animal testing and highlights its contribution to the advancement in medicine (Baumans,

et al.,12).

As animal testing gained popularity, William Russell (1959) a British zoologist and

animal rights advocate established the Three R’s Principles to voice his opinion to promote

animal welfare. Russell proposed to replace, reduce, and refine animal experimentation.

Reduction instructs the reduced usage of animals during experiments while obtaining the same
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level of information. Replacement refers to the complete elimination of laboratory animals or the

usage of less sentient beings such as invertebrates (Russell, “The Sources, Incidence, and

Removal of Inhumanity”). If replacement could not be achieved for any reason, the refinement

stage then takes place. Under his principles, Russell places a strict emphasis on minimizing pain

and suffering inflicted on laboratory animals (Russell, “Refinement”). Not only does this

encourage animal researchers to practice more humane methods, the experimental results tend to

have higher accuracy. Russell asserts that “the imposition of any degree of distress...disturb[s]

the efficiency of the investigation”, which illustrates that the refinement process strongly

correlates to the success of the study (Russell, “The Concept of Inhumanity”).

1. The graph records a laboratory animal’s heart rate as it undergoes different stimuli. The sharp long
spikes in the heart rate indicate its response to pain stimulus while the stagnant spikes represent the
animal’s response to electrical convulsion. Under anaesthesia, the heart rate is stabilized, showing a
much lower cortisol level in the animal. The refinement method is therefore favored as it minimizes
suffering on animals. (Source: Bloomberg School of Public Health)
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Although the Three R’s Principles established the ethical foundation in animal research,

the principles failed to address the ethics involved with animal experimentation. The 3R’s

Principle — Mind the Ethical Gap highlights the conflicting values that lie within the Three R’s.

A challenge researchers face is to choose between reduction and refinement. Do they inflict pain

on fewer animals or less pain on more animals? Nuno Franco (2012), a respectable researcher

from University of Porto found in his studies that roughly 60% of the participants demonstrate a

higher preference for refinement, which depicts the favored principle among current animal

researchers (Olsson et al.,334). Another question that all stakeholders must consider is whether

replacement is realistic. From the animal rights perspective, banning animal testing and

transitioning entirely into the advanced technological options is attainable, but others disagree.

Richard T. Fosse (2010), a leading researcher of the industry contends that “animals are

indispensable as we chart unknown and new scientific waters...there is no replacement for these

animals – we do not yet know what can be replaced” (Fosse, 2010). The complete substitution of

animal experimentation is highly unlikely as it can impede efficiency in animal research,

according to Fosse.

In addition to the Three R’s Principles, other philosophers raised the moral questions that

the Three R’s failed to address. For instance, “To what extent is animal experimentation

acceptable?” Richard Ryder, a contemporary psychologist and animal activist urges that humans

should stop exploiting other species as we are all related. He believes that speciesism is

analogous to slavery since animals can suffer as much pain as humans do with their similar

nervous systems (Ryder, 2012). Philosopher Peter Singer argues that the assignment of value on

the sole basis of species membership is “ no less justifiable than racism or sexism” (Singer 4).

His utilitarian viewpoint advocates personal actions that maximize the happiness of the
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population. As Singer has stated, it is crucial to “put yourself in the position of others” (Singer,

2011). If we put laboratory animals through multiple testing procedures even with refined

procedures, we are inflicting suffering on them as they could still experience stress. The

alternatives to animal experimentation should therefore be prioritized to avoid this dilemma.

However, animal testing should be acceptable if “the same experiments performed on nonhuman

animals would cause less suffering since the animals would not have the anticipatory dread of

being...experimented upon ” (Singer 4). A more concrete example that better illustrates this idea

would be comparing a cancer patient to an animal who carries the same disease. In Singer’s

perspective, the human will endure a greater suffering due to his higher cognitive abilities. For

this reason, “which is not speciesist”, animal testing is morally justified (Singer 5).

Figure 2. Researchers were asked to rank the acceptability to use the 7 listed species in laboratory
experiments. Chimpanzees are viewed as the least acceptable followed by dogs. Drosophila (fruit fly) is
considered the most acceptable among all the laboratory species. This shows that speciesism still poses
a strong influence on researchers’ moral principles. (Source: Scientists and The Three R’s)

As seen from the ethical debate among contemporary philosophers, conditions for the

Three-Rs Principles are ill-defined and therefore subject to problematic interpretation, but in-
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vitro testing is a straightforward and effective solution that eliminates issues with the vague

research guidelines. In-vitro testing is a tissue-engineering method that evaluates biologic

processes through cell and tissue samples. The Wyss Institute from Harvard University has made

a leap in this testing method with their state-of-the-art invention “organ-on-chips” which can

directly replace the use of laboratory animals (Young, 2012). The micro-engineering device

constitutes human cells, allowing the chip to function as a live organ. The “lung-on-a-chip”, for

instance, is lined with human airway cells, capillary cells, and blood channel and expands and

contracts like real lungs (Young, 2012). Its ability to behave as a functioning organ allows it to

“replicate human physiology, diseases, and drug responses” and, most importantly, eliminate

animal use in drug testing and disease research and thus fulfill the Three R’s (PETA). An

immediate implementation of this microchip technology also makes the research process much

more time efficient and cost effective than animal studies. National Research Council reports in

Science, Medicine, and Animals that during the safety testing stage, drug companies conduct

tests on multiple species in order to test for mutagenicity and carcinogenicity, and this procedure

alone takes 4 years on average to complete (National Research Council 25). In addition to the

lengthy procedures, the cost of the microchip technology is estimated to be around $22,000,

which is a lot more economical compared to the $50,000 spent in laboratory animal studies

(“Towards a body-on-a-chip”, The Economist). In addition, a developer of the microdevice Don

Huh contends that “A lot of people can use it without getting trained. Especially, biologists,

clinicians...chemists...who don’t have any engineering background” (Huh, 2011). The user-

friendly feature of the chip will allow companies to save time on training employees to handle

laboratory animals. The chip also addresses the concerns with accuracy. In the past,

pharmaceutical researchers have experienced high failure rates with animal models, but this
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chip’s ability to behave like a functioning organ can predict practical situations that the

laboratory animals cannot (Hamilton, 2011).

A complementary solution to in-vitro testing is using human volunteers as part of the

studies. Microdosing does not involve laboratory animals yet can successfully depict human

response. By definition, the method refers to “less than 1/100th of the dose calculated to yield a

pharmacological effect of the test substance...and at a maximum dose of <100 micrograms”

(Venitz, 22). Because experimental drugs are given to volunteers in ultra low dosages, they do

not induce whole-body effects, but “a minimal toxic effect” that allows scientists to study

cellular response (Venitz, 22). This particular technique is safe as it prescribes the drug in low

dosages but also permits researchers to collect data directly from the human body and studies

how it metabolizes and responds to the drug, “which offers a much more accurate picture than

such studies in animals” (Physicians Committee for Responsible Medicine). In addition,

according to Substitute of Animals in Drug Research, roughly “40% of drugs fail in the Phase 1

clinical trials, which take up to 18 months and cost £3-5 million...Microdosing takes only 4-6

months and costs £0.25 million per drug”, amplifying that microdosing is much more time-

efficient and cost effective the animal testing (Sharma, et al.). Furthermore, the method

eliminates the use of laboratory animals and more accurately predicts human’s drug response.

“Organs-on-chips” technology coupled with microdosing therefore serve as reliable solutions to

animal testing and the flawed Three R’s Principles.

Although in-vitro testing is a viable solution, animal research advocates think otherwise

and harshly criticize its limitations. The author of The Animal Research War, Michael Conn

asserts that viruses “grow differently in test tubes than in humans. Humans have an immune

system: test tubes do not” (Conn, et al.,94). This is where the use of animal models come into
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play due to our biological similarities. For instance, bleach can be used kill the virus in test tubes,

but it cannot be used to treat humans. Conn emphasizes that killing viruses in “a test tube and

killing [them] in a living animal are two very different accomplishments” (94). The in-vitro

method therefore is not a good model for human diseases since “animal models allow closer

approximation to a human response” (94).

Animal testing, in fact, often fails to predict human behavior. Studies have found that “Of

the drugs that enter human trials after passing all of their animal studies, about 90 percent are

demonstrated to be unsafe or ineffective in humans” because scientists cannot accurately predict

how humans will respond solely based on laboratory studies (“Limitations and Dangers”, New

England Anti-Vivisection Society). In particular, the Vioxx Scandal took place in 2004

discredited primate research as it causes over 60,000 deaths in the United States. The

pharmaceutical company Merck conducted more than eight studies on African Green Monkeys

and five other different species, but it failed to confirm human’s response to the pain relief drug,

which was a critical error that resulted in a national catastrophe (Gartner). This shows that

success in animal trials does not guarantee the same results in humans and thus highlights the

limitations of animals studies and the disastrous outcomes they may result in if researchers were

to heavily rely on them for drug developments.

Human and animal’s high biological similarity is a primary reason why the use of animal

models continues. Brett Nash, a HIV vaccine researcher, claims chimpanzees to be “excellent

models for human disease because they exhibit remarkable similarities to humans in virtually

every aspect of their anatomy, physiology and endocrinology” (Nath). This is something that

animal research advocates believe that other methods cannot offer. Organization Speaking of

Research emphasizes the 92% DNA humans share with mice and contends that “of the 108
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Nobel Prizes awarded for Physiology or Medicine, 96 were directly dependent on animal

research”, which suggests the substitution of animal experimentation will impede biomedical

research (Speaking of Research). It views animal testing as an irreplaceable method due to its

ability to predict human responses.

Figure 3

Figure 3 demonstrates the relationship between animal data and human data. In some instances, human
subjects and animals both achieve high bioavailability, but they vary in most cases. The scattered data
points demonstrate no precision or accuracy, showing that there is very little correlation between
animal and human data. The figure illustrates why a heavy reliance on animal data for drug
development is problematic (Source: Philosophy, Ethics, and Humanities in Medicine).

Biovariability: the rate at which drug is absorbed by the body's circulatory system

However, there have been several instances where experimental drugs put humans at

risks due to the unfounded confidence in animal testing. In 2003, Elan Pharmaceuticals was

forced to terminate its investigational vaccine against Alzheimer’s disease due to the unexpected

side effects. The company suspended the experimental drug after “four of 97 patient developed

central nervous system inflammation” (Akhtar). The same symptoms later appeared in 11 more

patients, leading the abandonment of the vaccine trials. The company, however, did not forsee
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the outcome as “no significant adverse effects were detected in mice or non-human primates”

(Akhtar). As the former Director of the National Cancer Institute Stated by Dr. Richard Klausner

has stated “We have cured cancer in mice for decades—and it simply didn’t work in humans”

(“Cancer Drugs Face Long Road From Mice to Men”). This further confirms animal data’s

inability to accurately project human response.

In the past few years, little progress has been made in the reduction of animal use, but

continuing exploring alternative testing methods could advance the efforts of researchers that

support a diversion from traditional animal use. According to the organization Speaking of

Research, there has been a 7% increase in the use of laboratory animals since the year of 2015

(Speaking of Research). This suggests that animal testing continues to be the prefered model of

research regardless of the alternatives being presented. In addition to organs-on-chips and

microdosing, continuing exploring other developing testing methods such as virtual reality,

advanced imaging, and human-patient simulators, could advance the efforts of conscious

scientists that strive to reduce animal testing. Through these methods, reliance on animal usage

can be reduced and perhaps make animal models become obsolete in the future.
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Works Cited

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Quarterly of Healthcare Ethics, vol. 24, no. 04, 2015, pp. 407–419.,

doi:10.1017/s0963180115000079.

“Alternatives to Animal Testing.” PETA,

www.peta.org/issues/animals-used-for-experimentation/alternatives-animal-testing/.

Cimons, Marlene, et al. “Cancer Drugs Face Long Road From Mice to Men.” Los Angeles Times,

Los Angeles Times, 6 May 1998, articles.latimes.com/1998/may/06/news/mn-46795.

Comstock, Gary, and Mylan Engel. The Moral Rights of Animals. Lexington Books, 2016.

Franco, Nh, and Ias Olsson. “Scientists and the 3Rs: Attitudes to Animal Use in Biomedical

Research and the Effect of Mandatory Training in Laboratory Animal Science.”

Laboratory Animals, vol. 48, no. 1, 2013, pp. 50–60., doi:10.1177/0023677213498717.

Franco, Nuno. “Animal Experiments in Biomedical Research: A Historical Perspective.”

Animals, vol. 3, no. 1, 2013, pp. 238–273., doi:10.3390/ani3010238.

Gartner, John. “Vioxx Suit Faults Animal Tests.” Wired, Conde Nast, 4 June 2017,

www.wired.com/2005/07/vioxx-suit-faults-animal-tests/.

Hau, Jann. Handbook of Laboratory Animal Science. CRC, 2011.

Jamieson, Dale. “Rights, Justice, and Duties to Provde Assistance: A Critique of Regan's Theory

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McAnallen, Samuel, director. The Superior Human.

Nath, Brett. “The Chimpanzee and Other Non-Human-Primate Models in HIV-1 Vaccine

Research.”
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