Animals in Research 1

Lindsey McNaughton

Professor Excell

English 1020 MW 3:30

May 4, 2015

"...if it comes to a choice between regulated studies on a few animals and a treatment for an
incurable disease... most people reluctantly make the same choice.” -Professor Chris Higgins,
Vice-Chancellor of Durham University from 2007 to 2014
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Animals in Research

Animals have been used throughout history to develop what little understanding of

anatomy and physiology cultures held at the time. Early Greek physician-scientists such as

Aristotle and Erasistratus used living animals in their experiments in this manner. They examined

nerves and tendons to understand their functions, or physiology, while other early physicians

sought to understand basic anatomy. Since anesthetics were not developed until the mid-

nineteenth century, most early experiments were conducted without the comfort of pain

management. These experiments were conducted under public viewing as a learning method.

Andreas Vesalius was known for conducting vivisections, or the practice of performing

operations on live animals for the purpose of experimentation or scientific research1, usually

involving a dog. In these performances, the dog was surgically cut open during consciousness

and organs were systematically viewed allowing students the opportunity to speculate on the

functions. Today, these methods seem unnecessary, cruel and inhumane; however, this was also a

time of violent sport where watching humans get mauled to death was socially and morally

acceptable.

In the United States, the importance of animals in research, especially pharmaceutical

testing, became relevant during the twentieth century when a pharmaceutical company released

Elixir Sulfanilamide to the public. The drug, which was a combination of sulfanilamide,

diethylene glycol (DEG) and raspberry flavoring, was intended for the treatment of streptococcal

infections and administered heavily. The developers of the drug did not know the DEG

1
"Vivisection" as defined by britannica.com
Animals in Research 3

ingredient was poisonous to humans prior to release, and in 1937 more than a hundred lives were

lost due to poisoning. The public outcry from this event and those similar led to the 1938 Federal

Food, Drug and Cosmetic Act which requires safety testing of drugs on animals before they can

be marketed. Later events in history, such as the release of thalidomide in the 1950's, which was

sold as a miracle drug boasting a cure-all for insomnia, coughs, colds, headaches and morning

sickness and was prescribed to pregnant women, further enhanced the need for regulation when

more than 10,000 children in 46 countries were born with malformations and missing limbs

(Kim & Scialli, 2001, pp. 1-6).

Today, many individuals disapprove of the use of animals in biomedical research and

scientific development. It is argued that animals express pain and pleasure the same as humans,

and therefore can be consciously affected by these experimentations. Consequently, the use of

animals in research is considered cruel and inhumane since alternative methods are available and

not all research is beneficial to society. However, without previous use of animals in research,

society would not stand where it is today. The use of animal models in biomedical research is

justified through strict regulations, limitations of alternative methods and benefits to society.

In scientific research, a number of models, or the generation of a physical, conceptual, or

mathematical representation of a real phenomenon that is difficult to observe directly 2, are used

to create and conduct experiments. Researchers prefer to use in vitro methods when conducting

initial research. This method involves cells or substances grown and observed as the Latin

indicates: "in glass," or more commonly, in a petri dish. This method allows researchers the

ability to observe chemical and physical responses to the environment on a cellular level. In

2
"Scientific Modelling" as defined by britannica.com
Animals in Research 4

comparison to the in vitro method is the in vivo method which is "within the living." This

method allows for further observation of results acquired from the latter in vitro experiments on a

full and functioning system. Researchers apply both of these techniques to the experimental

models suitable for the research being conducted. One such model is the animal model which

allows researchers to use living or deceased animals to conduct experiments with drugs,

treatments, education or even cosmetics.

Many believe the use of animal models in research, whether to benefit a company or to

advance current medical practices, is cruel and inhumane, and alternative methods have been

developed to replace the animal model in scientific research since current laws and regulations

are loosely worded allowing the mistreatment of animals.

Animal Research is Cruel and Inhumane

What is cruel and inhumane about the use of animals in experiments? According to the

New England Anti-Vivisection Society of Boston (NEAVS) the misuse of animals in research

"can include protocols that cause severe suffering, such as long-term social isolation, full-body

restraint, electric shocks, withholding of food and water, or repeatedly breeding and separating

infants from mothers" (New England Anti-Vivisection Society [NEAVS], 2015). NEAVS was

founded in 1895, and is a nonprofit organization advocating the replacement of animals in

research, testing and science education through outreach, education, legislation and policy

change (NEAVS, 2015). The foundation has advocated multiple changes in legislation and the

treatment of animals in addition to being involved in five petitions to protect the mistreated

animals; however, the general consensus is there is still much to be accomplished.

Animals in Research 5

In 1966, the Animal Welfare Act (AWA) was signed regulating the minimum standards of

care and treatment to be provided toward animals used in research, sales and agriculture. It is the

only federal law in the United States to regulate this treatment and excludes many animals used

in scientific research such as mice and birds, which constitute a majority of the percentage of

animals used. The AWA does not have the authority to regulate an experimental protocol once it

has been approved by the Animal Use and Care Committee of the lab (Animal Welfare Act

[AWA], 2015).

Animal right's activists believe this allows a discrepancy in the proper use of animals in

research and provides the opportunity for researchers to behave in cruel and inhumane manners.

They believe researchers can subject animals to irritants causing pain or discomfort; they can

administer drugs with detrimental side effects; food and water can be deprived from the animal

for extended periods of time; and in some cases termination can even be acceptable.

Unfortunately, some of these ideas are occasionally accurate; however, researchers will

follow the protocol for the experiment being conducted. Researchers do not cause pain of

animals out of sheer masochism as animal right’s activists would have the public believe.

Researchers tend to only use the animal model once it is absolutely necessary either for proper

observation or in respect of current regulations. In fact, "the 2004 USDA Annual Report reveals

that 57% of all research procedures with animals involved no more than slight or momentary

pain or distress (i.e., an injection). In 34% of research procedures anesthesia and postoperative

painkillers were used. In 9% of the procedures, neither anesthesia nor pain medication could be

used, as they would have interfered with research results" (Centers for Disease Control and

Prevention [CDC], 2006).

Animals in Research 6

Before surgery, humans are asked not to eat or drink prior to a procedure for up to twelve

hours to prevent pulmonary aspiration which is when stomach contents enter the lungs with the

potential to block airflow and cause death. Animals can not make this decision, so being

deprived of food or water prior to an experiment is up to the researcher to ensure the safety of the

animal, not to be unusually cruel. Most experiments conducted are on mice or other small

animals with short life spans and rapid reproduction rates. This is not because researchers hate

mice as much as a 1950's housewife, but because the frequency of reproduction allows an

observance of the genetic effects in a long-term scenario. As seen with thalidomide, a simple

solution that is fast acting can indeed have a long term effect that we are unaware of, which can

be a mortal mistake.

According to the Centers for Disease Control and Prevention (CDC), "the vast majority

of research animals are mice and rats bred for [research]. Dogs, cats and non-human primates

together account for less than one-half of one percent of the total, and this number has declined

for more than 25 years. Since 1979, the number of dogs and cats needed in animal research has

declined by more than 50%. The number of non-human primates needed represents less than .2%

(.18% in 2004) and has remained relatively constant — in the 50,000 per year range — for the

past decade" (CDC, 2006).

Regulations and laws are constantly being created and amended to provide more suitable

solutions to animals in research. In 2000, the Chimpanzee Health Improvement Maintenance and

Protection Act (CHIMP) was enforced to prevent the euthanasia of no longer wanted

chimpanzees in research (AWA, 2015). This act provided that chimpanzees must be retired to

sanctuaries to live their remaining years in a nourishing environment free of unnecessary pain
Animals in Research 7

and suffering. The Animal Welfare Act regulates "standards of care for research animals with

regard to their housing, feeding, cleanliness, ventilation, and medical needs and requires the use

of anesthesia or analgesic drugs for potentially painful procedures and during post-operative

care" (CDC, 2006). The amendments added to this act, which is used as the minimum

requirement in any research, are constantly being updated to protect animals in our developing

culture. In 2008, an amendment was added to clarify the laws and regulations put in place on dog

fighting, a domestic offense towards animals and not a research related infraction.

While the use of animals in research may not always be a sight the public wishes to see,

the current regulations were created because of cruelty in the past. Today, researchers prefer to

use in vitro methods over animal testing; however, it is because of tragedies throughout history

that animal models are required in experimentation. The Animal Welfare Act strives to protect

the well-being of animals bred for research and researchers uphold these requirements.

Alternative Methods and Research

Alternative methods have been created to replace the animal model in biomedical

research; however, the Food and Drug Administration (FDA) has laws in place requiring the

testing of biocompatibility, pharmacology and toxicology on animals for new medical drugs and

devices. The FDA states “Animals are sometimes used in the testing of drugs, vaccines and other

biologics, and medical devices, mainly to determine the safety of the medical product. For drugs

and biologics, the focus of animal testing is on the drug’s nature, chemistry and effects

(pharmacology) and on its potential damage to the body (toxicology)” (U.S. Food and Drug

Administration [FDA], 2015). The FDA lists the effects these tests are used to measure as: how

much is absorbed in the blood, how the product is broken down, what are the chemical
Animals in Research 8

breakdown components, and how long does it take the body to excrete the materials (FDA,

2015).

The FDA aims to eventually remove the need for animal testing, but acknowledges our

current developments do not provide this opportunity. If a material has already passed an animal

test it is not required to pass another, in example: a new medical device created out of the same

material as a different one will not need to be tested on animals prior to release. The use of

independent animal care and use committees (IACUC) is also supported by the FDA to ensure

the safety of these animals used.

The use of in vitro testing can not fully replace the animal model, though it can limit the

need for unnecessary tests. In a recent study at the University of California, San Diego “an in

vitro, live-cell artificial vessel has been created that can be used to study both the application and

effects of devices used to extract life-threatening blood clots in the brain. The artificial vessel

could have significant implications for future development of endovascular technologies,

including reducing the need for animal models to test new devices or approaches” (University of

California, 2015). Researchers used bovine endothelial cells, which form single layer tissue such

as that which lines blood vessels, to create a live-cell platform in a petri dish that “allows direct

visual characterization of effects and injury patterns to [endothelial cells]." (University of

California, 2015). The research involved introducing the clots to the platform and testing various

retrieval devices and effects after removal. The devices each yielded different effects which were

then validated using in vivo methods. In an interview regarding this work, Alexander Khalessi,

MD, Director of Endovascular Neurosurgery and Surgical Director of Neurocritical Care at UC

Animals in Research 9

San Diego Health System states, “Although transparent and thus easier to study, glass and plastic

tubing does not recapitulate blood vessel biology. In vivo animal models are more realistic, but

we cannot directly observe the interaction between devices and ECs. Plus animals are not perfect

models of humans and they are expensive to use” (University of California, 2015).

In an experiment testing human carcinogen effects using the Hupki mouse model,

researchers acknowledged the mouse genes studied were not optimal for comparison to the

human genes of application due to a “15% discrepancy in base sequence in the DNA-binding

domain and amino acid differences between the two species” (“Applications of the human,”

2010, para. 8). Though the results from this research provided the Hupki mouse model to be

beneficial in understanding the etiology of human cancer caused by exposure to carcinogens, it

was also beneficial in expressing the objectiveness with which researchers approach their

methods. In this study, researchers not only acknowledge there is a genetic difference which can

effect the results, but they also state there is need for follow-up experiments and further research.

Animals aren’t perfect models of humans, but we do share up to 99% of our DNA with

animals such as chimpanzees and have about a 98% similarity with mice. These similarities

allow for adequate testing of chemical reactions our bodies will possibly have with drugs or

medical devices. All mammals have descended from a common ancestor and share the same

basic physiology such as heart, lungs, kidney, liver, etc. The similarities of our functional

systems provides researchers the opportunity to observe results from in vivo methods operating

within a full system. The way a drug is carried from our oral cavity to the cells in our body can

be determined using this method while a simple in vitro experiment can only show the
Animals in Research 10

controlled chemical reaction. The common susceptibility to illness such as diabetes, heart disease

or cancer allows researchers the use of animal models to confirm new methods for treatment. As

the FDA does not require animal tests to be performed on a method already approved, researches

can develop new protocol from existing methods with the aim of gradually reducing the need for

the animal model. Unfortunately, science has not developed to this point, and animal models are

still necessary in research development.

There are a number of alternative methods currently in development and in use. Some

current methods include using human volunteers and administering drugs at low doses to reduce

adverse reactions then analyzing blood samples taken from these volunteers. Artificial human

organs, including skin and ears, have been grown in petri dishes from stem cells. The EpiDerm

Skin Irritation Test (EpiDerm SIT) is a tissue of human cells grown in vitro and was created to

test chemical skin irritants from cosmetics or pharmaceuticals. This product can replace the in

vivo rabbit skin irritation test (Kandárová 2009).

Computer models are another form of alternative method and have been created to

simulate the operating system of the human body. These can be accurate to a point, to the extent

of our current knowledge, but can not always determine the effects of a newly developed drug or

method. The simulation will only provide the results it has been programmed to compute.

However, using computers researchers have been able to develop methods to create functioning

tissues and eventually organs using three-dimensional printers. This method is called 3D

Bioprinting and is currently being refined by researchers and mathematicians.

Animals in Research 11

Why aren't alternative methods replacing the use of animals in research? While

alternative methods exist, it is federal law that any treatment intended for human use be tested on

an animal model prior to release to the public, as the main focus of our government is the welfare

of the people they serve. Alternative methods also provide only a cellular approach to studying

organisms that cause disease, and eventually require the complete system to analyze effects and

reactions which could be applied to human models. While alternative methods have been and

continue to be developed, the animal model is not completely replaceable at this time, but

alternative methods are preferred by researchers due to minimal genetic variation and financial

restrictions.

Benefits, Ethics, and Opportunities

A number of developments have provided humans and animals both with beneficial

treatment and prevention of disease. Veterinarians use methods tested on animals to treat their

patients. Dr. Conn, Associate Director of the Oregon National Primate Research Center, states in

his book The Animal Research War, "we are convinced that knowledge gained from animal

research has extended and improved the quality of human and animal lives" (Conn, 2008, p.

156). Benefits coincide with opportunity as there is usually room for improvement on old or

current methods.

It can be argued that cosmetic testing does not benefit our society and is an unnecessary

use of animals in research. Many countries have actually banned the use of animals in cosmetic

testing for this very reason. Bans on cosmetic testing have been put in place in the European
Animals in Research
Union, Norway, India, and Israel with more, including the United States, considering adopting
the practice.
The following timeline was taken from the Centers for Disease Control and Prevention
outlining major accomplishments in research involving animals.
A * denotes a nobel prize awarded (CDC, 2006).

Year Advance (type of animal)
1796 Vaccine for smallpox developed (Cow)
1881 Vaccine for anthrax developed (Sheep)
1885 Vaccine for rabies developed (Dog,
Rabbit)
1902 Malarial life cycle discovered (Pigeon)*
1905 Pathogenesis of tuberculosis discovered
(Cow, Sheep)*
1919 Mechanisms of immunity discovered
(Guinea Pig, Horse, Rabbit)*
1921 Insulin discovered (Dog, Fish)*
1928 Pathogenesis of typhus discovered
(Guinea Pig, Rat, Mouse)*
1929 Vitamins supporting nerve growth
discovered (Chicken)*
1932 Function of neurons discovered (Cat,
Dog)*
1933 Vaccine for tetanus developed (Horse)
1939 Anticoagulants developed (Cat)
1942 The Rh factor discovered (Monkey)
1943 Vitamin K discovered (Rat, Dog, Chick,
Mouse)*
1945 Penicillin tested (Mouse)*
1954 Polio vaccine developed (Mouse,
Monkey)*
1956 Open heart surgery and cardiac
pacemakers developed (Dog)
12
1964 Regulation of cholesterol Discovered
(Rat)*
1968 Rubella vaccine developed (Monkey)
1970 Lithium approved (Rat, Guinea Pig)
1973 Animal social and behavior patterns
discovered (Bee, Fish, Bird)*
1975 Interaction between tumor viruses and
genetic material discovered (Monkey, Horse,
Chicken, Mouse)*
1982 Treatment for leprosy developed
(Armadillo)
1984 Monoclonal antibodies developed
(Mouse)*
1990 Organ transplantation techniques
advanced (Dog, Sheep, Cow, Pig)*
1992 Laproscopic surgical techniques advanced
(Pig)
1995 Gene transfer for cystic fibrosis
developed (Mouse, Non-Human Primate)
1997 Prions discovered and characterized
(Hamster, Mouse)*
1998 Nitric oxide as signaling molecule in
cardiovascular system discovered (Rabbit)*
2000 Brain signal transduction discovered
(Mouse, Rat, Sea Slug)*
2002 Mechanism of cell death discovered
(Worm)*
2003 Non-invasive imaging methods (MRI) for
medical diagnosis developed (Clam, Rat)*

Animals in Research 13

As observed from the above timeline, many applications created are still effective today.

The use of animals in the development of many vaccines builds a foundation for years of

treatment and future advancements.

Another major factor affecting the decision to support or deny animal testing as a valid

option for scientific and biomedical advancement is the level of ethical practice. In his book,

Animal Ethics, Robert Garner, professor of political theory at the University of Leicester, UK,

references Peter Singer suggesting “that a distinguishing feature of ethics is that ethical

judgements are universable, so ethics requires us to go beyond our own personal point of view to

a standpoint like that if the impartial spectator who takes a universal point of view” (Garner,

2005, p 156). Peter Singer is an Australian moral philosopher well-known for his books on

animals in research including Animal Liberation, originally published in 1975, in which he

argues against speciesism, or the discrimination between beings based upon their species. He

also argues sentient beings should be considered morally equal, and the use of animals for food is

unjustifiable (Singer, 1990).

Research ethics involves the planning, conduct, and reporting of research while ensuring

the animals used are looked after properly and used in minimal numbers. The federal regulations

in place provide researchers with the outline needed to make ethical decisions while working in

the lab. Researchers follow the three R’s when conducting research to guide them in their ethical

decisions. According to Understanding Animal Research of the UK (2015), the three R’s can be

defined as follows:
Animals in Research 14

Replace the use of animals with alternative techniques, or avoid the use of

animals altogether.

Reduce the number of animals used to a minimum, to obtain information from

fewer animals or more information from the same number of animals.

Refine the way experiments are carried out, to make sure animals suffer as little

as possible. This includes better housing and improvements to procedures which

minimize pain and suffering and/or improve animal welfare.

Researchers regard human life with a higher value than that of an animal, particularly a

mouse, but they treat the animals used with respect in an ethical manner. This approach may

seem cruel-hearted, but in reality, which is more valuable: the life of a mouse or the life of a

child suffering from illness? This is the heart of the debate: adding value to the lives of animals.

In our culture, we tend to anthropomorphize animals to the point where we consider them to be

human. In an article exploring the applications of anthropomorphism it is stated that “the aim

must never be to forbid a certain kind of symbols when communicating thoughts on animals, but

to describe animals well” (Karlsson, 2012, p. 719). The article continues to discuss the benefits

of attributing human qualities to animals and how this should be applied in research. When

anthropomorphism is avoided we are left with a “mechanomorphism” that reduces the animals

used to mere machines (Karlsson, 2012, p 707).

The culture of the researcher also needs to be considered as many cultures have different

approaches to the ethical treatment of animals. In a personal interview with budding cultural
Animals in Research 15

anthropologist, Lucor Jordan, an exploration of cultures was analyzed. Lucor states "in

considering the relationship that humans have with animals across cultures, we see that animals

that are highly valued and regarded in some areas are viewed quite differently in others." He

spent the summer on the Indian reservation on Ute Mountain in southwest Colorado. Here he

observed dogs being kept as pets which were "often neglected, abused, tortured, and you would

often find living dogs thrown into dump sites. Although they are viewed as pets, the standards of

treatment are much different." He further discussed how the cultural differences and influences

can be applied to the animals we eat or those we use in research. He mentioned the worship of

animals such as cows, rats, or monkeys in some regions (Lucor Jordan, personal communication,

April 23, 2015). His discussion lead to the question, in an area ridden with plague, why would

we support the growth of the animal population fueling it rather than use them to create

treatments to end the disease?

Experiments of the past were not as ethical as we have proven them to be in the present.

The opportunities our developing technologies provide allow for more ethical and humane

practices when it comes to using animals for education, experimentation, or development of

treatments. While we continue to improve the methods we currently use, the use of the animal

model in scientific and biomedical research continues to be justified through the limited use by

researchers, consistent amendments to existing regulations and laws, and the ongoing

contributions to society which we will benefit from for years to come. 


Animals in Research 16

References

Besaratinia, A., & Pfeifer, G. P. (January 01, 2010). Applications of the human p53 knock-in
(Hupki) mouse model for human carcinogen testing. Faseb Journal : Official Publication
of the Federation of American Societies for Experimental Biology, 24, 8, 2612-9.

Centers for disease control and prevention. (2006, November 16). Animals in scientific research.
Retrieved from http://www.cdc.gov/news/2006_11/animal_care/factsheet_ar_general.htm

Conn, M. & Parker, J. (2008). The animal research war. New York, NY: Palgrave Macmillan.

Garner, R. (2005). Animal ethics. Cambridge, UK: Polity Press.

New England Anti-Vivisection Society (2015). Retrieved from legislation and policies: Retrieved
from neavs.org

James H. Kim and Anthony R. Scialli. (2011). Thalidomide: The tragedy of birth defects and the
effective treatment of disease. Toxicol. Sci. (2011) 122 (1): 1-6 first published online
April 19, 2011 doi:10.1093/toxsci/kfr088

Kandárová, H., Hayden, P., Klausner, M., Kubilus, J., & Sheasgreen, J. (2009). An in vitro skin
irritation test (SIT) using the EpiDerm reconstructed human epidermal (RHE) model.
Journal of Visualized Experiments  : JoVE, (29), 1366. doi:10.3791/1366

Karlsson, F. (2012). Critical anthropomorphism and animal ethics. Journal of Agricultural and
Environmental Ethics, 25(5), 707-720. doi:10.1007/s10806-011-9349-8

ProCon.org. (2014, January 29). Should animals be used for scientific or commercial testing
Retrieved from http://animal-testing.procon.org/#background

Singer, P. (1990). Animal liberation. New York, N.Y: New York Review of Books.

United States department of agriculture (April 2015). Animal welfare act. Retrieved from
http://awic.nal.usda.gov/government-and-preofessional-resources/federal-laws/animal
welfare -act

University of California, San Diego Health Sciences. (2015, April 17). Artificial blood vessel lets
researchers better assess clot removal devices. ScienceDaily. Retrieved from
www.sciencedaily.com/releases/2015/04/150417145029.htm

U.S. Food and Drug Administration (April 30, 2015). Why are animals used for testing medical
products? Retrieved from http://www.fda.gov/aboutfda/transparency/basics.ucm194932