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A CRITICAL LOOK

AT ANIMAL

EXPERIMENTATION

Christopher Anderegg, M.D., Ph.D.

Kathy Archibald, B.Sc.

Jarrod Bailey, Ph.D.

Murry J. Cohen, M.D.

Stephen R. Kaufman, M.D.

John J. Pippin, M.D., F.A.C.C.

The Medical Research Modernization Committee (MRMC) is a non-profit

health advocacy organization composed of medical professionals and scientists

who identify and promote efficient, reliable and cost-effective research

methods. The MRMC focuses exclusively on the scientific merits

of different research approaches, even though some undoubtedly raise

serious and important ethical concerns. MRMC-sponsored activities include

research, publishing and student education.

To order additional copies of this booklet free of charge, for regular

Email reports and/or for more information about animal experiments,

contact:

• In the United States: Medical Research Modernization Committee,

P.O. Box 201791, Cleveland, Ohio 44120, U.S.A., Tel./Fax 216-283-6702,

Email: stkaufman@mindspring.com, www.mrmcmed.org

• In the United Kingdom: Europeans for Medical Progress, P.O. Box 38604,

London W13 0YR, U.K., Tel./Fax 020 8997 1265, Email: info@curedisease.

net,

www.curedisease.net

• In Switzerland: Association for the Abolition of Animal Experiments, Ostbuhlstrasse

32, CH-8038 Zurich, Switzerland, Tel./Fax +41 (0)44 482 73 52,

Email: ch.anderegg@freesurf.ch, www.animalexperiments.ch

Proponents of animal experimentation (tests, experiments and

«educational» exercises involving harm to animals) claim that

However, several medical historians argue that key discoveries in

such areas as heart disease, cancer, immunology, anesthesia and

psychiatry were in fact achieved through clinical research, observation

Human data has historically been interpreted in light of laboratory

data derived from nonhuman animals. This has resulted

in unfortunate medical consequences. For instance, by 1963 prospective

and retrospective studies of human patients had already

shown a strong correlation between cigarette smoking and lung

lung cancer in animals had failed. As a result, Clarence Little, a

leading cancer animal experimenter, wrote: «The failure of many

investigators to induce experimental cancers, except in a handful

of cases, during fifty years of trying, casts serious doubt on the validity

animal data failed to agree, this researcher and others distrusted

the more reliable human data. As a result, health warnings were

delayed for years, while thousands of people died of lung cancer.

By the early 1940s, human clinical investigation strongly indicated

that asbestos causes cancer. However, animal studies repeatedly

failed to demonstrate this, and proper workplace precautions

population studies have shown a clear risk from exposure to

low-level ionizing radiation from diagnostic X-rays and nuclear

1

studies have stalled proper

Likewise, while the connection

between alcohol consumption

and cirrhosis is indisputable

in humans, repeated efforts to

produce cirrhosis by excessive

alcohol ingestion have failed in

all nonhuman animals except

baboons, and even the baboon

Many other important medical

advances have been delayed

because of misleading information

derived from animal «models

». The animal model of polio,

for example, resulted in a

misunderstanding of the mechanism

of infection. Studies on

monkeys falsely indicated that the polio virus was transmitted via

resulted in misdirected preventive measures and delayed

the development of tissue culture methodologies critical to the

used for vaccine production, it was research with human cell cultures

which first showed that the polio virus could be cultivated

clogged arteries with the patient’s own veins was impeded

by dog experiments which falsely indicated that veins could not

We now know that kidney failure suppresses the immune system,

which increases tolerance of foreign tissues.

Nevertheless, society continues to support animal experimentation,

primarily because many people believe that it has been vital for

has been necessary or even beneficial to medical progress.

In 1971 the National Cancer Act initiated a «War on Cancer»

that many sponsors predicted would cure cancer by 1976. Instead,

this multibillion dollar research program has proven to be a failure.

The age-adjusted total cancer mortality rate climbed steadily

In order to encourage continued support for cancer research

– now exceeding two billion dollars annually in the U.S. alone

– researchers and administrators have misled the public. In 1987

the U.S. General Accounting Office (GAO) found that the statistics

of the National Cancer Institute (NCI) «artificially inflate

the amount of ‹true› progress», concluding that even simple fiveyear

termed five-year survival a «cure» even if the patient died of the

cancer after the five-year period. Also, by ignoring well known

statistical biases, the NCI falsely suggested advances had been

Commenting on the research program’s discouraging results

after 15 years, epidemiologist and program administrator John C.

Bailar III stated in 1986: «[We] are losing the war against cancer.

A shift in research emphasis, from research on treatment to

research on prevention, seems necessary if substantial progress

more than a decade later, Bailar reiterated in 1997: «The

Why hasn’t progress against cancer been commensurate with

the effort (and money) invested? One explanation is the unwarranted

humans and other animals have prevented animal models from

serving as effective means by which to seek a cancer cure. Mice

Weinberg has commented: «The preclinical [animal] models of

human cancer, in large part, stink… Hundreds of millions of dollars

are being wasted every year by drug companies using these

«If you want to understand where the War on Cancer has gone

Despite their extensive use since the early 1980s, animal models

have not contributed significantly to AIDS research. While

mice, rabbits and monkeys born with severe combined immunodeficiency

can be infected with the AIDS Virus (HIV), none develops

infected with HIV since 1984, only one allegedly developed symptoms

that chimpanzees, as members of an endangered species

who rarely develop an AIDS-like syndrome, are unlikely to

prove useful as animal models for understanding the mechanism

Other virus-induced immunodeficiency syndromes in nonhuman

animals have been touted as valuable models of AIDS, but

they differ markedly from AIDS in viral structure, disease symptoms

discussing anti-AIDS therapy, has acknowledged: «Candidate antivirals

have been screened using in vitro systems and those with

acceptable safety profiles have gone directly into humans with

little supportive efficacy data in any in vivo [animal] system. The

reasons for this are complex but certainly include … the persistent

view held by many that there is no predictive animal model

AIDS researcher Margaret Johnston has concurred: «HIV/

AIDS [animal] models have not yielded a clear correlate of immunity

nor given consistent results on the potential efficacy of

clinical trial in humans in 1987, more than 100 clinical trials

have been funded by the U.S. National Institute of Allergy

and Infectious Diseases through mid-2006. Yet every one of the

more than 50 preventive vaccines and more than 30 therapeutic

vaccines that were successful against HIV/AIDS in primate

studies

Human clinical investigation has isolated HIV, defined the

disease’s

tissue culture) research using human white blood cells has identified

both the efficacy and toxicity of anti-AIDS medicines, including

mandates misleading and unreliable animal toxicity testing.

Animal «models» in experimental psychology, which researchers

traditionally subject to painful stimuli in order to study their behavior,

have been strongly criticized in part because human psychological

problems reflect familial, social and cultural factors

disapprove of psychological animal experiments which

Harry Harlow’s «maternal deprivation» experiments in the

1950s and 1960s involved separating infant monkeys from their

mothers at birth and rearing them in total isolation or with «surrogate

» mothers made of wire and cloth. Their terror and subsequent

psychopathology, Harlow claimed, demonstrated the importance

of maternal contact. However, this had been shown

Despite their conceptual shallowness, numerous maternal deprivation

studies continue, claiming relevance to human developmental

psychology, psychopathology and even immune and

Experimental psychology continues to rely on painful research

on animals, despite clinical psychologists’ disregard for animal research

literature. A review of two clinical psychology journals revealed

that only 33 out of 4,425 citations (0.75 %) referred to animal-

Animal models of alcohol and other drug addictions are similarly

ill-conceived, failing to reflect crucial social, hereditary and

mental factors. Pharmacologist Vincent Dole has acknowledged:

damental insights into the causes of this self-destructive behavior

Scientists have located the genetic defects of many inherited diseases,

including cystic fibrosis and familial breast cancer. Trying

to «model» these diseases in animals, researchers widely use animals

– mostly mice – with spontaneous or laboratory-induced genetic

defects. However, genetic diseases reflect interactions between

the defective gene and other genes and the environment.

Consequently, nearly all such models have failed to reproduce the

transgenic mice carrying the same defective gene as people

with cystic fibrosis do not show the pancreatic blockages or lung

Numerous standard animal toxicity tests have been widely criticized

test – which determines how much of a drug, chemical or household

product is needed to kill

50 % of a group of test animals

– requires 60 to 100 animals

(usually rats and mice), most

of whom endure great suffering.

Because of difficulties extrapolating

the results to humans,

Also, since such variables as an

animal’s age, sex, weight and

strain can have a substantial

effect on the results, laboratories

often obtain widely disparate

data with the same test substances.

been validated to replace the

from the test guidelines of the Organisation for Economic

The Draize eye irritancy test, in which unanesthetized rabbits

have irritant substances applied to their eyes, yields results that

and rabbits differ in the structure of their eyelids and corneas, as

well as in their ability to produce tears. Indeed, when comparing

rabbit to human data on duration of eye inflammation after exposure

to 14 household products, they differed by a factor of 18

Animal tests for cancer-causing substances, generally involving

rodents, are also notoriously unreliable. When applied to human

cancer causation, Lester Lave et al. found the false positive

«Tests for human carcinogens using lifetime rodent bioassays are

expensive, time-consuming and give uncertain results.» The tremendous

economic costs of such research have recently been reported

in a study which examined over 500 rodent carcinogenicity

studies and concluded that rodent cancer assays are scientifically

A combination of in vitro tests provides data that compares favorably

with existing carcinogenicity databases and costs far less

Institute (NCI) developed a panel of 59 human cancer cell lines

to screen compounds for anti-cancer activity, due to its «dissatisfaction

with the performance of prior in vivo primary screens

the NCI in 1990, by which time the agency had also adopted a

panel of about 100 human cell lines to screen compounds for

Animal tests for teratogens (drugs and chemicals that cause

birth defects) are equally misleading and unreliable. Jarrod Bailey

et al. conducted a comprehensive review of animal tests of 1,396

different substances and found that of those substances known to

cause birth defects in humans, animal tests indicated that almost

half were safe. Conversely, of those substances known to be safe

ous. And almost one-third of all substances tested yielded varying

differences in the physiological structure, function and biochemistry

of the placenta aggravate the usual differences in the absorption,

distribution, metabolism and excretion of drugs and chemicals

that exist between species, thus making reliable predictions

In vitro tests, such as the embryonic stem-cell test, the whole

embryo culture, and the micromass test, provide data that are considerably

more reliable and predictive and far less costly than animal

teratogenicity tests. While such in vitro tests currently utilize

cells and embryos derived from animals (thus rendering their

extrapolation to humans difficult), advances in human cell culture

technology should, in the future, permit a much closer in vitro

Animal laboratories are not necessary for teaching biological and

medical principles and skills to medical students, and 85 % of U.S.

and Canadian medical schools have eliminated animal labs from

include lectures and written course materials, videos and interactive

virtual reality programs, mentored patient care encounters

and surgery participation, and lifelike programmable interactive

patient simulators. Comparative studies of simulation technologies

for many aspects of medical education (e.g. anatomy, physiology,

pharmacology, surgical skills, trauma management and invasive

procedures) have repeatedly demonstrated superior training outcomes,

fewer patient complications, greater trainee acceptance,

Further evidence of the emerging primacy of simulation-based

medical education is the American College of Surgeons’ (ACS)

to replace the use of animals and human cadavers for its Advanced

Trauma Life Support (ATLS) program. Furthermore, in 2006 the

ACS implemented a sweeping educational reform that incorporated

a wide variety of simulators to eliminate animal use in its

own conferences and educational programs, in addition to establishing

the Accredited Education Institutes program to achieve

Animal studies can neither confirm nor refute hypotheses about

human physiology or pathology; human clinical investigation is

the only way such hypotheses can be tested. At best, animal experiments

can suggest new hypotheses that might be relevant to

How valuable is animal experimentation? The Medical Research

Modernization Committee’s review of ten randomly chosen animal

models of human diseases did not reveal any important contributions

conditions in animals were given names analogous to the human

diseases they were intended to simulate, they differed substantially

from their human «counterparts» in both cause and clinical course.

Also, the study found that treatments effective in animals tended

Indeed, when MRMC physicians evaluate specific animal-research

projects, they consistently find them to be of little, if any, relevance

MRMC’s reviews have revealed that, because animal models

differ from human diseases, researchers tend to investigate those

aspects of the animal’s condition that resemble features of the human

disease, generally ignoring or discounting fundamental anatomical,

physiological and pathological differences. Because most

disease processes have system-wide effects and involve many interacting

factors, focusing on only one aspect of a disease belies

the actual complexity of biological organisms.

In contrast to human clinical investigation, animal experimentation

involves manipulations of artificially induced conditions.

Furthermore, the highly unnatural laboratory environment

invariably stresses the animals, and stress affects the entire organism

by altering pulse, blood pressure, hormone levels, immunological

activities

For example, artifact from unnaturally induced strokes in animals

on over 4,000 studies demonstrating efficacy for more than

tested in human clinical trials failed to show any benefit.

PA) administered within three hours of stroke onset has proven

beneficial in reducing symptoms, but it was associated with ten

times as many intracerebral hemorrhages and did not increase

the answers to many of our questions regarding the underlying

pathophysiology and treatment of stroke do not lie with continued

attempts to model the human situation more perfectly in animals,

but rather with the development of techniques to enable

the study of more basic metabolism, pathophysiology and anatomical

Since 1990, several hundred gene therapies that were successful

in animal studies have been tested on thousands of patients

worldwide. Yet only one gene therapy, for children with the severe

immune system disorder X-SCID, appears to have succeeded. Of

the ten successfully treated children, however, three developed

leukemia and one of them died of it – a side effect that animal experiments

failed to predict and that prompted the U.S. Food and

Drug Administration (FDA) to halt several gene therapy trials in

of hemophilia was discontinued in 2004 due to «safety problems

… in the human trial that weren’t predicted in animal studies»,

survival of rats with artificially induced heart failure, but humans

Fialuridine appeared safe in animal tests, but it caused liver failure

in 7 out of 15 humans taking the drug, five of whom died and two

to predict the dangerous heart valve abnormalities in humans

Hormone replacement therapy increased women’s risk of heart

disease, breast cancer and stroke, but experiments with mice, rabbits,

widely prescribed arthritis painkiller Vioxx appeared safe and even

beneficial to the heart in animal tests, but was withdrawn from the

global market in 2004 after causing an estimated 320,000 heart

attacks, strokes and cases of heart failure worldwide – 140,000 of

and Medicine in the Office of Drug Safety at the FDA, described

Vioxx as the «single greatest drug safety catastrophe in the history

failed to predict the cases of partial or total blindness suffered by

mandatory, extensive animal testing, adverse drug reactions remain

the fifth leading cause of mortality in the United States, accounting

In London in March 2006, a new anti-inflammatory drug

called TGN1412 caused devastating reactions including multiple

organ failure in all six volunteers in phase 1 clinical trials, despite

«proof of safety» established by tests on monkeys who were

given 500 times the human dose. Many commentators noted that

the animal tests provided a false sense of security. The incident

prompted calls for an overhaul of drug safety testing requirements

In animal tests to evaluate the carcinogenicity of the artificial

sweetener saccharin, the weight-adjusted daily saccharin dose given

to rats was equivalent to a human consuming about 1,100 cans of

soda containing saccharin. Such massive dosing alone can result in

cancers, regardless of a compound’s actual carcinogenicity at typical

is further complicated by the observation that saccharin-induced

bladder cancers occurred only in male rats. It was later found that

male rats possess a protein in greater quantity than female rats

(and lacking in humans) that interacted with saccharin to form

irritating crystals in the male rats’ bladders, causing cancer. The

fact that some rats developed cancers did not (and cannot) clarify

Similarly, despite almost 40 years of human consumption, its

use in more than 9,000 food and beverage products worldwide, and

aspartame is still being tested on animals, and regulatory authorities

continue to evaluate the results of such studies. Most recently,

an Italian study carried out in 2005 on 1,800 rats demonstrated

an increased risk for lymphomas and leukemias in rats fed aspartame

study involving 340,045 men and 226,945 women and reported

on at the 2006 meeting of the American Association for Cancer

bladder cancers from saccharin and female rats getting lymphomas

and leukemias from aspartame, no cancer risk from either

sweetener has been found for humans of either sex.

Scientists recognize that, even between humans, gender, ethnicity,

Perhaps the most striking example of the specificity of drug effects

comes from the demonstration that even human monozygotic

twins display different drug responses and that these become

between species is much more hazardous than within a species.

Indeed, according to the FDA, a staggering 92 % of all drugs found

safe and therapeutically effective in animal tests fail during human

clinical trials due to their toxicity and/or inefficacy, and are

8 % of drugs which do gain FDA approval must later be withdrawn

In addition to squandering scarce resources and providing misleading

results, animal experimentation poses real risks to humans.

The mind-set that scientific knowle