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The Benefits and Ethics of Animal Research

March 1997
Scientific American 276(2):79

March 1997
276(2):79

DOI:10.1038/scientificamerican0297-79

Source
PubMed

Authors:

Andrew N Rowan

WellBeing International

This is a brief introduction to a collection of three articles addressing the ethics of animal research. The first article is a summary of the issue by a Scientific American reporter and the other two reflect pro and con positions on animal research. The four articles taken together provide a comprehensive overview of the state of the animal research debate in the United States at the end of the 20th century.

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or the past 20 years, we have witnessed an intense but

largely unproductive debate over the propriety and

value of using animals in medical and scientiﬁc re-

search, testing and education. Emotionally evocative images

and simple assertions of opinion and fact are the usual fare.

But we do not have to accept such low standards of exchange.

Sound bites and pithy rhetoric may have their place in the

ﬁght for the public’s ear, but there is always room for dispas-

sionate analysis and solid scholarship.

When it comes to animal research, there is plenty of reason

for legitimate dispute. First, one has to determine what val-

ues are being brought to the table. If one believes animals

should not be used simply as means to ends, that assumption

greatly restricts what animal research one is willing to accept.

Most people, though, believe some form of cost-beneﬁt anal-

ysis should be performed to determine whether the use of an-

imals is acceptable. The costs consist mainly of animal pain,

distress and death, whereas the beneﬁts include the acquisi-

tion of new knowledge and the development of new medical

therapies for humans.

There is considerable disagreement among scientists in

judging how much pain and suffering occur in the

housing and use of research animals. More atten-

tion is at last being given to assessing these

questions and to ﬁnding ways of minimizing

such discomfort. Developing techniques that explicitly ad-

dress and eliminate animal suffering in laboratories will re-

duce both public and scientiﬁc uneasiness about the ways an-

imals are used in science. At present, indications are that

public attention to the animal research issue has declined

somewhat; however, the level of concern among scientists, re-

search institutions, animal-rights groups and those who reg-

ulate animal use remains high.

There is also much room to chal-

lenge the beneﬁts of animal research

and much room to defend such re-

search. In the next few pages,

you will ﬁnd a debate between

opponents and supporters of

animal research. It is followed

by an article that sets out the

historical, philosophical and

social context of the animal-

research controversy. We leave

it to you to judge the case.

ANDREW N. ROWAN is

director of the Tufts Uni-

versity Center for Animals

and Public Policy.

FORUM

The Beneﬁts and Ethics

of Animal Research

Experiments on animals are a mainstay

of modern medical and scientiﬁc research.

But what are the costs and what are the returns?

by Andrew N. Rowan

Scientific American February 1997 79Forum: The Beneﬁts and Ethics of Animal Research

CHRISTOPHER BURKE/QB

he use of animals for research

and testing is only one of many

investigative techniques avail-

able. We believe that although animal

experiments are sometimes intellectual-

ly seductive, they are poorly suited to

addressing the urgent health problems

of our era, such as heart disease, cancer,

stroke, AIDS and birth defects. Even

worse, animal experiments can mislead

researchers or even contribute to illness-

es or deaths by failing to predict the tox-

ic effects of drugs. Fortunately, other,

more reliable methods that represent a

far better investment of research funds

can be employed.

The process of scientiﬁc discovery of-

ten begins with unexpected observations

that force researchers to reconsider ex-

isting theories and to conceive hypothe-

ses that better explain their ﬁndings.

Many of the apparent anomalies seen

in animal experiments, however, merely

reﬂect the unique biology of the species

being studied, the unnatural means by

which the disease was induced or the

stressful environment of the laboratory.

Such irregularities are irrelevant to hu-

man pathology, and testing hypotheses

derived from these observations wastes

considerable time and money.

The majority of animals in laborato-

ries are used as so-called animal mod-

els: through genetic manipulation, sur-

gical intervention or injection of foreign

substances, researchers produce ailments

in these animals that “model” human

conditions. This research paradigm is

fraught with difﬁculties, however. Evo-

lutionary pressures have resulted in in-

numerable subtle, but signiﬁcant, dif-

ferences between species. Each species

has multiple systems of organs

—the car-

diovascular and nervous systems, for

example

—that have complex interac-

tions with one another. A stimulus ap-

plied to one particular organ system

perturbs the animal’s overall physiolog-

ical functioning in myriad ways that of-

ten

cannot be predicted or fully under-

stood.

Such uncertainty severely under-

mines the extrapolation of animal data

to other species, including humans.

Animal Tests Are Inapplicable

mportant medical advances have been

delayed because of misleading results

derived from animal experiments. David

Wiebers and his colleagues at the Mayo

Clinic, writing in the journal

Stroke in

1990, described a study showing that

of the 25 compounds that reduced dam-

age from ischemic stroke (caused by lack

of blood ﬂow to the brain) in rodents,

cats and other animals, none proved ef-

ﬁcacious in human trials. The research-

ers attributed the disappointing results

to disparities between how strokes nat-

urally occur in humans and how they

were experimentally triggered in the an-

imals. For instance, a healthy animal

that experiences a sudden stroke does

not undergo the slowly progressive ar-

terial damage that usually plays a cru-

cial role in human strokes.

During the 1920s and 1930s, studies

on monkeys led to gross misconcep-

tions that delayed the ﬁght against po-

liomyelitis. These experiments indicat-

ed that the poliovirus infects mainly the

nervous system; scientists later learned

this was because the viral strains they

had administered through the nose had

artiﬁcially developed an afﬁnity for brain

tissue. The erroneous conclusion, which

contradicted previous human studies

demonstrating that the gastrointestinal

system was the primary route of infec-

tion, resulted in misdirected preventive

measures and delayed the development

of a vaccine. Research with human cell

cultures in 1949 ﬁrst showed that the

virus could be cultivated on nonneural

tissues taken from the intestine and

limbs. Yet in the early 1950s, cell cul-

tures from monkeys rather than humans

were used for vaccine production; as a

result, millions of people were exposed

to potentially harmful monkey viruses.

In a striking illustration of the inade-

quacy of animal research, scientists in

the 1960s deduced from numerous ani-

mal experiments that inhaled tobacco

smoke did not cause lung cancer (tar

from the smoke painted on the skin of

rodents did cause tumors to develop,

but these results were deemed less rele-

vant than the inhalation studies). For

many years afterward, the tobacco lob-

by was able to use these studies to delay

government warnings and to discour-

age physicians from intervening in their

patients’ smoking habits.

Of course, human population studies

provided inescapable evidence of the

tobacco-cancer connection, and recent

human DNA studies have identiﬁed to-

bacco’s “smoking gun,” showing how

a derivative of the carcinogen benzo(a)-

pyrene targets human genes, causing

cancer. (It turns out that cancer research

is especially sensitive to differences in

physiology between humans and other

animals. Many animals, particularly rats

Animal Research Is

Wasteful and Misleading

by Neal D. Barnard and Stephen R. Kaufman

DIGITAL COLLAGE BY JENNIFER C. CHRISTIANSEN; NEW YORK ACADEMY OF MEDICINE (left); NATIONAL LIBRARY OF MEDICINE (center); PETA (right)

80 Scientific American February 1997 Debate: Animal Research Is Wasteful and Misleading

and mice, synthesize within their bodies

approximately 100 times the recom-

mended daily allowance for humans of

vitamin C, which is believed to help the

body ward off cancer.)

The stress of handling, conﬁnement

and isolation alters an animal’s physiol-

ogy and introduces yet another experi-

mental variable that makes extrapolat-

ing results to humans even more difﬁ-

cult. Stress on animals in laboratories

can increase susceptibility to infectious

disease and certain tumors as well as

inﬂuence levels of hormones and anti-

bodies, which in turn can alter the func-

tioning of various organs.

In addition to medical research, ani-

mals are also used in the laboratory to

test the safety of drugs and other chem-

icals; again, these studies are confound-

ed by the fact that tests on different spe-

cies often provide conﬂicting results. For

instance, in 1988 Lester Lave of Carne-

gie Mellon University reported in the

journal Nature that dual experiments

to test the carcinogenicity of 214 com-

pounds on both rats and mice agreed

with each other only 70 percent of the

time. The correlation between rodents

and humans could only be lower. David

Salsburg of Pﬁzer Central Research has

noted that of 19 chemicals known to

cause cancer in humans when ingested,

only seven caused cancer in mice and

rats using the standards set by the Na-

tional Cancer Institute.

Indeed, many substances that ap-

peared safe in animal studies and re-

ceived approval from the U.S. Food and

Drug Administration for use in humans

later proved dangerous to people. The

drug milrinone, which raises cardiac

output, increased survival of rats with

artiﬁcially induced heart failure; hu-

mans with severe chronic heart failure

taking this drug had a 30 percent in-

crease in mortality. The antiviral drug

ﬁaluridine seemed safe in animal trials

yet caused liver failure in seven of 15

humans taking the drug (ﬁve of these pa-

tients died as a result of the medication,

and the other two received liver trans-

plants). The commonly used painkiller

zomepirac sodium was popular in the

early 1980s, but after it was implicated

in 14 deaths and hundreds of life-threat-

ening allergic reactions, it was with-

drawn from the market. The antidepres-

sant nomifensine, which had minimal

toxicity in rats, rabbits, dogs and mon-

keys, caused liver toxicity and anemia

in humans

—rare yet severe, and some-

times fatal, effects that forced the manu-

facturer to withdraw the product a few

months after its introduction in 1985.

These frightening mistakes are not

mere anecdotes. The U.S. General Ac-

counting Ofﬁce reviewed 198 of the 209

new drugs marketed between 1976 and

1985 and found that 52 percent had

“serious postapproval risks” not pre-

dicted by animal tests or limited human

trials. These risks were deﬁned as ad-

verse reactions that could lead to hospi-

talization, disability or death. As a re-

sult, these drugs had to be relabeled with

new warnings or withdrawn from the

market. And of course, it is impossible

to estimate how many potentially useful

drugs may have been needlessly aban-

doned because animal tests falsely sug-

gested inefﬁcacy or toxicity.

Better Methods

esearchers have better methods at

their disposal. These techniques in-

clude epidemiological studies, clinical

intervention trials, astute clinical obser-

vation aided by laboratory testing, hu-

man tissue and cell cultures, autopsy

studies, endoscopic examination and bi-

opsy, as well as new imaging methods.

And the emerging science of molecular

epidemiology, which relates genetic,

metabolic and biochemical factors with

epidemiological data on disease inci-

dence, offers signiﬁcant promise for

identifying the causes of human disease.

Consider the success of research on

atherosclerotic heart disease. Initial epi-

demiological investigations in humans

—

notably the Framingham Heart Study,

started in 1948

—revealed the risk factors

for heart disease, including high choles-

terol levels, smoking and high blood

pressure. Researchers then altered these

factors in controlled human trials, such

as the multicenter Lipid Research Clin-

ics Trial, carried out in the 1970s and

1980s. These studies illustrated, among

many other things, that every 1 percent

drop in serum cholesterol levels led to at

least a 2 percent drop in risk for heart

disease. Autopsy results and chemical

studies added further links between risk

factors and disease, indicating that peo-

ple consuming high-fat diets acquire ar-

terial changes early in life. And studies

of heart disease patients indicated that

eating a low-fat vegetarian diet, getting

regular mild exercise, quitting smoking

and managing stress can reverse athero-

sclerotic blockages.

Similarly, human population studies

of HIV infection elucidated how the

virus was transmitted and guided inter-

vention programs. In vitro studies using

human cells and serum allowed re-

searchers to identify the AIDS virus and

determine how it causes disease. Inves-

tigators also used in vitro studies to as-

sess the efﬁcacy and safety of important

new AIDS drugs such as AZT, 3TC and

protease inhibitors. New leads, such as

possible genetic and environmental fac-

tors that contribute to the disease or

provide resistance to it, are also emerg-

ing from human studies.

Many animals have certainly been

used in AIDS research, but without

much in the way of tangible results. For

instance, the widely reported monkey

studies using the simian immunodeﬁ-

ciency virus (SIV) under unnatural con-

ditions suggested that oral sex present-

ed a transmission risk. Yet this study

PETA (left); BRIAN GUNN IAAPEA (center); CHRISTOPHER BURKE/QB (right)

Debate: Animal Research Is Wasteful and Misleading Scientific American February 1997 81

did not help elucidate whether oral sex

transmitted HIV in humans or not. In

other cases, data from animal studies

have merely repeated information al-

ready established by other experiments.

In 1993 and 1994 Gerard J. Nuovo and

his colleagues at the State University of

New York at Stony Brook determined

the route of HIV into the female body

(the virus passes through cells in the cer-

vix and then to nearby lymph nodes) us-

ing studies of human cervical and lymph

node samples. Later, experimenters at

New York University placed SIV into the

vaginas of rhesus monkeys, then killed

the animals and dissected the organs;

their paper, published in 1996, arrived

at essentially the same conclusion about

the virus’s path as did the previous hu-

man studies.

Research into the causes of birth de-

fects has relied heavily on animal exper-

iments, but these have typically proved

to be embarrassingly poor predictors of

what can happen in humans. The rates

for most birth defects are rising steadily.

Epidemiological studies are needed to

trace possible genetic and environmen-

tal factors associated with birth defects,

just as population studies linked lung

cancer to smoking and heart disease to

cholesterol. Such surveys have already

provided some vital information

—the

connection between neural tube defects

and folate deﬁciency and the identiﬁca-

tion of fetal alcohol syndrome are no-

table ﬁndings

—but much more human

population research is needed.

Observations of humans have proved

to be invaluable in cancer research as

well. Several studies have shown that

cancer patients who follow diets low in

fat and rich in vegetables and fruit live

longer and have a lower risk of recur-

rence. We now need intervention trials

to test which speciﬁc diets help with var-

ious types of cancers.

The issue of what role, if any, animal

experimentation played in past discov-

eries is not relevant to what is necessary

now for research and safety testing. Be-

fore scientists developed the cell and tis-

sue cultures common today, animals

were routinely used to harbor infectious

organisms. But there are few diseases

for which this is still the case

—modern

methods for vaccine production are saf-

er and more efﬁcient. Animal toxicity

tests to determine the potency of drugs

such as digitalis and insulin have largely

been replaced with sophisticated labo-

ratory tests that do not involve animals.

A Rhetorical Device

nimal “models” are, at best, analo-

gous to human conditions, but no

theory can be proved or refuted by anal-

ogy. Thus, it makes no logical sense to

test a theory about humans using ani-

mals. Nevertheless, when scientists de-

bate the validity of competing theories

in medicine and biology, they often cite

animal studies as evidence. In this con-

text, animal experiments serve primari-

ly as rhetorical devices. And by using

different kinds of animals in different

protocols, experimenters can ﬁnd evi-

dence in support of virtually any theo-

ry. For instance, researchers have used

animal experiments to show that ciga-

rettes both do and do not cause cancer.

Harry Harlow’s famous monkey ex-

periments, conducted in the 1960s at

the University of Wisconsin, involved

separating infant monkeys from their

mothers and keeping some of them in

total isolation for a year. The experi-

ments, which left the animals severely

damaged emotionally, served primarily

as graphic illustrations of the need for

maternal contact

—a fact already well

established from observations of hu-

man infants.

Animal experimenters often defend

their work with brief historical accounts

of the supposedly pivotal role of animal

data in past advances. Such interpreta-

tions are easily skewed. For example,

proponents of animal use often point to

the signiﬁcance of animals to diabetes

research. But human studies by Thomas

Cawley, Richard Bright and Appolli-

naire Bouchardat in the 18th and 19th

centuries ﬁrst revealed the importance

of pancreatic damage in diabetes. In ad-

dition, human studies by Paul Langer-

hans in 1869 led to the discovery of in-

sulin-producing islet cells. And although

cows and pigs were once the primary

sources for insulin to treat diabetes, hu-

man insulin is now the standard thera-

py, revolutionizing how patients man-

age the disease.

Animal experimenters have also as-

serted that animal tests could have pre-

dicted the birth defects caused by the

drug thalidomide. Yet most animal spe-

cies used in laboratories do not develop

the kind of limb defects seen in humans

after thalidomide exposure; only rab-

bits and some primates do. In nearly all

animal birth-defect tests, scientists are

left scratching their heads as to whether

humans are more like the animals who

develop birth defects or like those who

do not.

In this discussion, we have not

broached the ethical objections to ani-

mal experimentation. These are critical-

ly important issues. In the past few de-

cades, scientists have come to a new ap-

preciation of the tremendous complexity

of animals’ lives, including their ability

to communicate, their social structures

and emotional repertoires. But prag-

matic issues alone should encourage sci-

entists and governments to put research

money elsewhere.

NEAL D. BARNARD and STEPH-

EN R. KAUFMAN are both practicing

physicians. Barnard conducts nutrition

research and is president of the Physi-

cians Committee for Responsible Medi-

cine. Kaufman is co-chair of the Medical

Research Modernization Committee.

Debate: Animal Research Is Wasteful and Misleading82 Scientific American February 1997

left to right: SPL/PHOTO RESEARCHERS, INC.; CHARLES GUPTON UNIPHOTO; DOE/SPL/PHOTO RESEARCHERS, INC.; JIM OLIVE UNIPHOTO

xperiments using animals have

played a crucial role in the de-

velopment of modern medical

treatments, and they will continue to be

necessary as researchers seek to allevi-

ate existing ailments and respond to the

emergence of new disease. As any med-

ical scientist will readily state, research

with animals is but one of several com-

plementary approaches. Some questions,

however, can be answered only by ani-

mal research. We intend to show exact-

ly where we regard animal research to

have been essential in the past and to

point to where we think it will be vital

in the future. To detail all the progress

that relied on animal experimentation

would require many times the amount

of space allotted to us. Indeed, we can-

not think of an area of medical research

that does not owe many of its most im-

portant advances to animal experiments.

In the mid-19th century, most debili-

tating diseases resulted from bacterial

or viral infections, but at the time, most

physicians considered these ailments to

be caused by internal derangements of

the body. The proof that such diseases

did in fact derive from external micro-

organisms originated with work done by

the French chemist Louis Pasteur and

his contemporaries, who studied infec-

tious diseases in domestic animals. Be-

cause of his knowledge of how contam-

inants caused wine and beer to spoil,

Pasteur became convinced that microor-

ganisms were also responsible for diseas-

es such as chicken cholera and anthrax.

To test his hypothesis, Pasteur exam-

ined the contents of the guts of chickens

suffering from cholera; he isolated a pos-

sible causative microbe and then grew

the organism in culture. Samples of the

culture given to healthy chickens and

rabbits produced cholera, thus proving

that Pasteur had correctly identiﬁed the

offending organism. By chance, he no-

ticed that after a time, cultures of the

microorganisms lost their ability to in-

fect. But birds given the ineffective cul-

tures became resistant to fresh batches

that were otherwise lethal to untreated

birds. Physicians had previously ob-

served that among people who survived

a severe attack of certain diseases, recur-

rence of the disease was rare; Pasteur

had found a means of producing this

resistance without risk of disease. This

experience suggested to him that with

the administration of a weakened cul-

ture of the disease-causing bacteria, doc-

tors might be able to induce in their pa-

tients immunity to infectious diseases.

In similar studies on rabbits and gui-

nea pigs, Pasteur isolated the microbe

that causes anthrax and then developed

a vaccine against the deadly disease.

With the information from animal ex-

periments

—obviously of an extent that

could never have been carried out on

humans

—he proved not only that infec-

tious diseases could be produced by mi-

croorganisms but also that immuniza-

tion could protect against these diseases.

Pasteur’s ﬁndings had a widespread

effect. For example, they inﬂuenced the

views of the prominent British surgeon

Joseph Lister, who pioneered the use of

carbolic acid to sterilize surgical instru-

ments, sutures and wound dressings,

thereby preventing infection of wounds.

In 1875 Queen Victoria asked Lister to

address the Royal Commission inquiry

into vivisection

—as the queen put it, “to

make some statement in condemnation

of these horrible practices.” As a Quak-

er, Lister had spoken publicly against

many cruelties of Victorian society, but

despite the request of his sovereign, he

was unable to condemn vivisection. His

testimony to the Royal Commission

stated that animal experiments had

been essential to his own work on asep-

sis and that to restrict research with an-

imals would prevent discoveries that

would beneﬁt humankind.

Dozens of Vaccines and Antibiotics

ollowing the work of Pasteur and

others, scientists have established

causes of and vaccines for dozens of in-

fectious diseases, including diphtheria,

tetanus, rabies, whooping cough, tuber-

culosis, poliomyelitis, measles, mumps

and rubella. The investigation of these

ailments indisputably relied heavily on

animal experimentation: in most cases,

researchers identiﬁed candidate micro-

organisms and then administered the

microbes to animals to see if they con-

tracted the illness in question.

Similar work continues to this day.

Just recently, scientists developed a vac-

cine against

Hemophilus inﬂuenzae

type B (Hib), a major cause of meningi-

tis, which before 1993 resulted in death

or severe brain damage in more than

800 children each year in the U.S. Early

versions of a vaccine produced only

poor, short-lived immunity. But a new

vaccine, prepared and tested in rabbits

and mice, proved to be powerfully im-

munogenic and is now in routine use.

Within two months of the vaccine’s in-

Debate: Animal Research Is Vital to Medicine Scientific American February 1997 83

Animal Research Is

Vital to Medicine

by Jack H. Botting and Adrian R. Morrison

CHRISTOPHER BURKE/QB (left); CORBIS-BETTMANN (center); GEOFF TOMPKINSON SPL/Photo Researchers, Inc. (right)

troduction in the U.S. and the U.K., Hib

infections fell by 70 percent.

Animal research not only produced

new vaccines for the treatment of infec-

tious disease, it also led to the develop-

ment of antibacterial and antibiotic

drugs. In 1935, despite aseptic precau-

tions, trivial wounds could lead to seri-

ous infections that resulted in amputa-

tion or death. At the same time, in both

Europe and the U.S., death from puer-

peral sepsis (a disease that mothers can

contract after childbirth, usually as a

result of infection by hemolytic strepto-

cocci) occurred in 200 of every 100,000

births. In addition, 60 of every 100,000

men aged 45 to 64 died from lobar pneu-

monia. When sulfonamide drugs became

available, these ﬁgures fell dramatically:

by 1960 only ﬁve out of every 100,000

mothers contracted puerperal sepsis, and

only six of every 100,000 middle-aged

men succumbed to lobar pneumonia. A

range of other infections could also be

treated with these drugs.

The story behind the introduction of

sulfonamide drugs is instructive. The

team investigating these compounds

—

Gerhard Domagk’s group at Bayer Lab-

oratories in Wuppertal-Elberfeld, Ger-

many

—insisted that all candidate com-

pounds be screened in infected mice

(using the so-called mouse protection

test) rather than against bacteria grown

on agar plates. Domagk’s perspicacity

was fortunate: the compound pronto-

sil, for instance, proved to be extremely

potent in mice, but it had no effect on

bacteria in vitro

—the active antibacter-

ial substance, sulfanilamide, was formed

from prontosil within the body. Scien-

tists synthesized other, even more pow-

erful sulfonamide drugs and used them

successfully against many infections. For

his work on antibacterial drugs, Do-

magk won the Nobel Prize in 1939.

A lack of proper animal experimenta-

tion unfortunately delayed for a decade

the use of the remarkable antibiotic pen-

icillin: Alexander Fleming, working in

1929, did not use mice to examine the

efﬁcacy of his cultures containing crude

penicillin (although he did show the cul-

tures had no toxic effects on mice and

rabbits). In 1940, however, Howard W.

Florey, Ernst B. Chain and others at the

University of Oxford ﬁnally showed pen-

icillin to be dramatically effective as an

antibiotic via the mouse protection test.

Despite the success of vaccines and

antibacterial therapy, infectious disease

remains the greatest threat to human life

worldwide. There is no effective vaccine

against malaria or AIDS; physicians in-

creasingly face strains of bacteria resis-

tant to current antibacterial drugs; new

infectious diseases continue to emerge.

It is hard to envisage how new and bet-

ter vaccines and medicines against in-

fectious disease can be developed with-

out experiments involving animals.

Research on animals has been vital to

numerous other areas in medicine. Open-

heart surgery

—which saves the lives of

an estimated 440,000 people every year

in the U.S. alone

—is now routine, thanks

to 20 years of animal research by scien-

tists such as John Gibbon of Jefferson

Medical College in Philadelphia. Re-

placement heart valves also emerged

from years of animal experimentation.

The development of treatments for

kidney failure has relied on step-by-step

improvement of techniques through an-

imal experiments. Today kidney dialy-

sis and even kidney transplants can save

the lives of patients suffering from renal

failure as a result of a variety of ailments,

including poisoning, severe hemorrhage,

hypertension or diabetes. Roughly

200,000 people require dialysis every

year in the U.S.; some 11,000 receive a

new kidney. Notably, a drug essential

for dialysis

—heparin—must be extract-

ed from animal tissues and tested for

safety on anesthetized animals.

Transplantation of a kidney or any

major organ presents a host of compli-

cations; animal research has been in-

strumental in generating solutions to

these problems. Experiments on cats

helped develop techniques for suturing

blood vessels from the host to the do-

nor organ so that the vessels would be

strong enough to withstand arterial pres-

sure. Investigators working with rab-

bits, rodents, dogs and monkeys have

also determined ways to suppress the

immune system to avoid rejection of the

donor organ.

The list continues. Before the intro-

duction of insulin, patients with diabe-

tes typically died from the disease. For

more than 50 years, the lifesaving hor-

mone had to be extracted from the pan-

creas of cattle or pigs; these batches of

insulin also had to be tested for safety

and efﬁcacy on rabbits or mice.

When we started our scientiﬁc ca-

reers, the diagnosis of malignant hyper-

tension carried with it a prognosis of

death within a year, often preceded by

devastating headaches and blindness.

Research on anesthetized cats in the

1950s heralded an array of progressive-

ly improved antihypertensive medicines,

so that today treatment of hypertension

is effective and relatively benign. Simi-

larly, gastric ulcers often necessitated

surgery with a marked risk of morbid-

ity afterward. Now antiulcer drugs, de-

veloped from tests in rats and dogs, can

control the condition and may effect a

cure if administered with antibiotics to

eliminate Helicobacter pylori infection.

Common Misconceptions

uch is made in animal-rights pro-

paganda of alleged differences be-

tween species in their physiology or re-

sponses to drugs that supposedly render

animal experiments redundant or mis-

leading. These claims can usually be re-

futed by proper examination of the lit-

erature. For instance, opponents of ani-

mal research frequently cite the drug

Debate: Animal Research Is Vital to Medicine84 Scientific American February 1997

LONNY SHAVELSON Impact Visuals (left); UNIPHOTO (right)

thalidomide as an example of a medi-

cine that was thoroughly tested on ani-

mals and showed its teratogenic effect

only in humans. But this is not so. Sci-

entists never tested thalidomide in preg-

nant animals until after fetal deformities

were observed in humans. Once they ran

these tests, researchers recognized that

the drug did in fact cause fetal abnor-

malities in rabbits, mice, rats, hamsters

and several species of monkey. Similar-

ly, some people have claimed that peni-

cillin would not have been used in pa-

tients had it ﬁrst been administered to

guinea pigs, because it is inordinately

toxic to this species. Guinea pigs, how-

ever, respond to penicillin in exactly the

same way as do the many patients who

contract antibiotic-induced colitis when

placed on long-term penicillin therapy.

In both guinea pigs and humans, the

cause of the colitis is infection with the

bacterium Clostridium difﬁcile.

In truth, there are no basic differences

between the physiology of laboratory

animals and humans. Both control their

internal biochemistry by releasing endo-

crine hormones that are all essentially

the same; both humans and laboratory

animals send out similar chemical trans-

mitters from nerve cells in the central

and peripheral nervous systems, and

both react in the same way to infection

or tissue injury.

Animal models of disease are unjustly

criticized by assertions that they are not

identical to the conditions studied in hu-

mans. But they are not designed to be so;

instead such models provide a means to

study a particular procedure. Thus, cys-

tic ﬁbrosis in mice may not exactly mim-

ic the human condition (which varies

considerably among patients anyway),

but it does provide a way to establish

the optimal method of administering

gene therapy to cure the disease. Oppo-

nents of animal experiments also allege

that most illness can be avoided by a

change of lifestyle; for example, adop-

tion of a vegan diet that avoids all ani-

mal products. Whereas we support the

promulgation of healthy practices, we

do not consider that our examples could

be prevented by such measures.

A Black Hole

ur opponents in this debate claim

that even if animal experiments

have played a part in the development

of medical advances, this does not mean

that they were essential. Had such tech-

niques been outlawed, the argument

goes, researchers would have been forced

to be more creative and thus would have

invented superior technologies. Others

have suggested that there would not be

a gaping black hole in place of animal

research but instead more careful and

respected clinical and cellular research.

In fact, there was a gaping black hole.

No outstanding progress in the treat-

ment of disease occurred until biomedi-

cal science was placed on a sound, em-

pirical basis through experiments on

animals. Early researchers, such as Pas-

teur and the 17th-century scientist Wil-

liam Harvey, who studied blood circu-

lation in animals, were not drawn to

animal experiments as an easy option.

Indeed, they drew on all the techniques

available at the time to answer their

questions: sometimes dissection of a ca-

daver, sometimes observations of a pa-

tient, sometimes examination of bacte-

ria in culture. At other times, though,

they considered experimentation on an-

imals to be necessary.

We would like to suggest an interest-

ing exercise for those who hold the view

that animal experiments, because of their

irrelevance, have retarded progress: take

an example of an advance dependent on

animal experiments and detail how an

alternative procedure could have pro-

vided the same material beneﬁt. A suit-

able example would be treatment of the

cardiac condition known as mitral valve

insufﬁciency, caused by a defect in the

heart’s mitral valve. The production of

prosthetic heart valves stemmed from

years of development and testing for ef-

ﬁcacy in dogs and calves. The artiﬁcial

valve can be inserted only into a quies-

cent heart that has been bypassed by a

heart-lung machine

—an instrument that

itself has been perfected after 20 years’

experimentation in dogs. If, despite the

beneﬁt of 35 years of hindsight, critics

of animal research cannot present a con-

vincing scenario to show how effective

treatment of mitral valve insufﬁciency

could have developed any other way,

their credibility is suspect.

Will animal experiments continue to

be necessary to resolve extant medical

problems? Transgenic animals with a

single mutant gene have already provid-

ed a wealth of new information on the

functions of proteins and their roles in

disease; no doubt they will continue to

do so. We also anticipate major progress

in the treatment of traumatic injury to

the central nervous system. The dogma

that it is impossible to restore function

to damaged nerve cells in the mamma-

lian spinal cord has to be reassessed in

the light of recent animal research indi-

cating that nerve regeneration is indeed

possible. It is only a matter of time be-

fore treatments begin to work. We ﬁnd

it difﬁcult to envision how progress in

this ﬁeld

—and so many others in bio-

logical and medical science

—can be

achieved in the future without animal

experiments.

JACK H. BOTTING and ADRIAN

R. MORRISON have been active in

the defense of animal research since the

1980s. Botting, a retired university lec-

turer, is the former scientific adviser to

the Research Defense Society in Lon-

don. Morrison is director of the Labo-

ratory for Study of the Brain in Sleep at

the University of Pennsylvania School

of Veterinary Medicine.

Debate: Animal Research Is Vital to Medicine Scientific American February 1997 85

LLEWELLYN UNIPHOTO

here is no question about it:

the number of animals used in

laboratory experiments is go-

ing down. In the U.K., the Netherlands,

Germany and several other European

countries, the total has fallen by half

since the 1970s. In Canada, mammals

have largely been replaced by ﬁsh. The

ﬁgures for the U.S. are unclear. The U.S.

uses between 18 and 22 million animals

a year, but exact numbers are unknown

for roughly 85 percent of these

—rats,

mice and birds. Primate use has stayed

constant, whereas the use of dogs and

cats is down by half since the 1970s.

No one reason accounts for the de-

cline, but several factors are obvious. In

1975 the animal-rights movement ex-

ploded onto the scene with the publica-

tion of

Animal Liberation by the Aus-

tralian philosopher Peter Singer. The

book’s depiction of research, and a se-

ries of exposés by suddenly vigilant ac-

tivists, threw a harsh spotlight on scien-

tists. In the following years, public per-

ceptions of animals became increasingly

sympathetic. Dian Fossey, Jane Goodall

and other ethologists related to an en-

thralled audience tales of love, sorrow,

jealousy and deceit among primates. Al-

though not so popular with scientists,

such anthropomorphic views of animals

fueled the passage of laws regulating

experimentation.

And the scientists have changed. Those

entering the biomedical

profession in re-

cent decades have imbibed

at least some

of the concerns of the movement, if not

its ideals; many are willing to acknowl-

edge the moral dilemmas of their craft.

Some experiments that were applauded

in the 1950s would not be done today,

because they would be deemed to cause

too much suffering. Oftentimes biotech-

nology is allowing test tubes to be sub-

stituted for animals. And a few research-

ers, cognizant that only their expertise

can help reduce the need for animals,

are avidly seeking alternatives. All these

efforts are bearing fruit.

The Philosophers

he underlying force behind these

changes appears to be society’s

evolving views of animals. These per-

ceptions owe a great deal to philosophy

and to science

—and very little to reli-

gion. The Bible is unequivocal about the

position of animals in the natural order:

God made man in his image and gave

him dominion over all other creatures.

And although Hinduism and Buddhism

envisage a hierarchy of organisms rath-

er than a sharp division, their inﬂuence

on the animal-rights movement is limit-

ed to vague inspiration and vegetarian

recipes. The real roots lie in secular phi-

losophy. In 1780 the English barrister

Jeremy Bentham asked what “insupera-

ble line” prevented humans from ex-

tending moral regard to animals: “The

question is not, Can they reason? nor,

Can they talk? but, Can they suffer?”

The question became more poignant

in 1859 with the advent of Charles Dar-

win’s theory of evolution. The theory

provided a scientiﬁc rationale for using

animals to learn about humans, and

Darwin endorsed such use. But he also

believed in an emotional continuum be-

tween humans and animals and was

troubled by the suffering that experi-

mentation could cause. This dichotomy

inspired clashes between animal lovers

and experimenters in 19th-century Eng-

land, culminating in the 1876 British

Trends in Animal Research

Increased concern for animals, among scientists

as well as the public, is changing the ways in which

animals are used for research and safety testing

by Madhusree Mukerjee, staff writer

The Evolution of Animal

Use in Research

CORBIS–BETTMANN CORBIS–BETTMANN

1822

1866

Henry

Bergh

founds

ASPCA

in U.S.

Charles

Darwin

publishes

the theory

of evolution

1859

86 Scientific American February 1997 Trends in Animal Research

British anticruelty act introduced

by Richard

Martin

(holding

donkey). He

later founded

the RSPCA

ROYAL SOCIETY FOR THE PREVENTION OF CRUELTY TO ANIMALS

Cruelty to Animals Act regulating ani-

mal experimentation. But the phenom-

enal success of medicine in the next cen-

tury made the animal-protection move-

ment recede into the background.

It rebounded in the 1970s, with Sing-

er’s attack. A philosopher in the utilitar-

ian tradition of Bentham, Singer holds

that in all decisions the total amount of

good that results

—human and animal—

should be weighed against the suffer-

ing

—human and animal—caused in the

process. Not that to him the interests of

humans and animals have equal weight:

life is of far greater value to a human

than, for example, to a creature with no

self-awareness. But if there is something

one would not do to, say, a severely in-

capacitated child, then neither should

one do it to an animal that would suffer

as much. Ignoring the interests of an an-

imal just because it is not human is, to

Singer, “speciesism,” a sin akin to rac-

ism. Invoking the connections between

humans and the great apes, Singer,

Goodall and others have issued a call

for these creatures, at least, to be freed

from experimentation.

Although Singer started the modern

animal-rights movement, it takes its

name and its most uncompromising

ideas from Tom Regan’s The Case for

Animal Rights (University of California

Press, 1983). Regan believes that all hu-

mans and most animals have inherent

rights, which he describes as invisible

“no trespassing” signs hung around

their necks. They state that our bodies

may not be transgressed, no matter how

much good might thereby result. Regan

does not equate humans with animals

—

to save survivors in a lifeboat, a dog

could be thrown overboard before a hu-

man would

—yet he states that animals

cannot be experimented on, because

they are not merely means to an end.

Many other philosophers have lent

their voices to the animals, but few have

come to the aid of researchers. One who

did so, Michael A. Fox, author of The

Case for Animal Experimentation (Uni-

versity of California Press, 1986), later

declared himself convinced by his crit-

ics and became an advocate for animals.

Attempts to refute Singer and Regan

usually involve pointing to morally rele-

vant criteria that separate humans from

animals. Raymond G. Frey of Bowling

Green State University has written that

animals cannot have interests, because

they cannot have desires, because they

cannot have beliefs, because they do not

have language. Regan counters that a

dog may well believe “that bone is tas-

ty” without being able to formulate the

phrase and that a human infant would

never learn to speak unless it could ac-

quire preverbal concepts to which it

could later assign words, such as “ball.”

Another supporter of research, Carl

Cohen of the University of Michigan,

has argued that rights are not inherent:

they arise from implicit contracts among

members of society, and they imply du-

ties. Because animals cannot recipro-

cate such duties, they cannot have rights.

This argument meets with the retort

that infants and the mentally ill cannot

fulﬁll such obligations either but are

not left out of the realm of rights: Why

omit animals? (One response is that hu-

man rights are based on characteristics

of “typical” humans, not on borderline

cases, prompting animal advocates to

ask what these special qualities are

—

and

so on and on.)

Some research proponents also note

that nature is cruel: lions kill zebras, cats

play with mice. Evolution has placed hu-

mans on top, so it is only natural for us

to use other creatures. This argument,

which some say elevates “survival of the

ﬁttest” to a moral philosophy, falls prey

to a proposition called the naturalistic

fallacy. To paraphrase the 18th-century

philosopher David Hume, what “is”

cannot dictate what “ought to be.” So

natural history may well illuminate why

human morals evolved into their pres-

ent form, but humans can transcend

their nature. One animal advocate de-

clares: “Killing and eating [meat] is an

integral part of the evolution of human

beings. Not killing and not eating [meat]

is the next step in our evolution.”

Many philosophers fall into the trou-

bled middle, arguing for interests or

rights to be ordered in a hierarchy that

allows some uses of animals but bars

others. Such distillations of animal-lib-

eration ideas have been ﬁnding their

way into legislation. The U.K., Austra-

lia, Germany and several other nations

require a utilitarian cost-beneﬁt analy-

sis to be performed before an animal ex-

periment can proceed. And in Novem-

ber 1996 the Netherlands passed into

law the statement that animals have “in-

trinsic value”: they are sentient beings,

entitled to the moral concern of humans.

The Public

ot that, of course, all the Dutch are

vegetarians. Rational argumenta-

tion may have inﬂuenced public opin-

ion, but as Harold A. Herzog, Jr., a psy-

chologist at Western Carolina Universi-

ty, remarks, the average person’s stance

on animal issues remains wildly incon-

sistent. In one survey, questions phrased

in terms of rats yielded a far more pro-

vivisection outcome than those mention-

ing dogs. Jesse L. Owens, a neuroscien-

tist at the University of Alaska, protests

British Cruelty

to Animals Act

regulates

animal

experimentation

Diphtheria antitoxin produced

(serum is being drawn from a horse)

Tetanus antitoxin found

ILLUSTRATION OF SCROLL BY LAURIE GRACE

SCIENTIFIC AMERICAN SCIENTIFIC AMERICAN OLIVER MECKES Photo Researchers, Inc.

1876

1891

1885

Louis Pasteur (at patient’s

right) develops rabies vaccine

Scientific American February 1997 87

Trends in Animal Research

that medical research is “the only use of

animals that is essential” and like other

researchers is bewildered by people who

eat meat and in the same gulp condemn

experimentation.

Not surprisingly, the animal-libera-

tion movement has coincided with soci-

ety’s becoming increasingly distant from

farms

—and shielded from the reality

behind dinner. Those who grew up on

farms often see animals as objects to be

used, whereas those who had pets tend

to express more sympathy. One line

along which attitudes divide is gender.

In all countries surveyed, women are

more pro-animal and antivivisectionist

than men, and three quarters of Ameri-

can animal-rights activists are women.

Also noticeable is a generation gap. Sur-

veys by Stephen R. Kellert of Yale Uni-

versity ﬁnd that those who are older or

less educated are more likely to see ani-

mals as resources, whereas those who

are younger or more educated tend to

view animals with compassion.

Public support of animal experimen-

tation, though higher in the U.S. than in

Europe, has been slowly declining. In

1985, 63 percent of American respon-

dents agreed that “scientists should be

allowed to do research that causes pain

and injury to animals like dogs and chim-

panzees if it produces new information

about human health problems”; in 1995,

53 percent agreed. Even in disciplines

that have traditionally used animals, the

trend is unmistakable. A survey by Scott

Plous of Wesleyan University ﬁnds that

psychologists with Ph.D.’s earned in the

1990s are half as likely to express strong

support for animal research as those

with Ph.D.’s from before 1970. (Part of

this result comes from the increased pres-

ence of women, but there is a signiﬁcant

drop among men as well.)

Opposition to animal experimenta-

tion is often said to derive from antisci-

ence sentiments, aggravated by poor

public knowledge of science. But accord-

ing to a 1994 survey led by Linda Pifer

of the Chicago Academy of Sciences,

negative attitudes toward animal exper-

imentation in the U.S. correlate only

weakly with lack of knowledge about

science. And in Belgium, France and

Italy, for instance, greater scientiﬁc lit-

eracy is connected with an increased re-

jection of animal experimentation.

Sociologists agree that opposition to

vivisection derives primarily from sym-

pathy for animals. Almost all animal

rightists are vegetarians; many are “veg-

ans,” eschewing milk, eggs, leather and

other animal products. “My philosophy

of living as softly on the earth as I can is

my life,” one activist told Herzog. In

striving to cause the least suffering pos-

sible, these individuals labor under a

heavy moral burden that sits lightly on

the rest of us. Some activists have in-

dulged in threatening researchers, break-

ing into laboratories or even arson. But

the number of such illegal acts, listed by

the U.S. Department of Justice, dropped

from about 50 a year in 1987 to 11 in

1992. (More recent ﬁgures are unavail-

able but are believed to be small.)

Many animal experimenters are also

animal lovers. Surveys by Harold Ta-

kooshi

an, a sociologist at Fordham Uni-

versity, reveal that biomedical research-

ers have the same mixed feelings about

animals and animal research as does the

general public. (The groups that gave

animals the lowest rating and vivisec-

tion the highest were farmers, hunters

and the clergy.) Thomas M. Donnelly, a

veterinarian at the Rockefeller Universi-

ty’s animal center, also runs a shelter to

which he takes cats that are no longer

needed for research. Almost all the tox-

icolo

gists and pharmacologists at a 1996

meeting

on alternatives to animal ex-

perimentation had experience with us-

ing animals and were moved enough by

it to seek substitutes. Scientists choose

to use animals because they feel it is the

only way to help humans. Donald Sil-

ver, who did cancer studies on mice at

Sloan-Kettering Hospital in the 1970s,

recounts that whenever he had doubts

about his work, he had only to think

about the terminally ill patients in the

children’s ward.

The Scientists

f course, scientists’ perceptions of

animals have evolved as well. In

the early 20th century Darwinian wor-

ries about emotions were dispelled by

the rise of behaviorism. Because thoughts

cannot be measured, but behavior can,

practitioners such as C. Lloyd Morgan

and, later, B. F. Skinner sought to de-

scribe animals purely in terms of their

responses to stimuli. Bernard Rollin, au-

thor of The Unheeded Cry (Oxford Uni-

versity Press, 1989), argues that at some

point, the animal psyche went from be-

ing impossible to measure to being non-

existent. The test of a good theory,

“Morgan’s canon,” required all actions

to be interpreted in terms of the lowest

psychological faculties possible. In prac-

tice, this meant that a rat would not be

feeling pain even if its “writhes per min-

ute” were being used to test the efﬁcacy

of an analgesic. Its neurochemistry was

merely inducing a physiological reﬂex.

“We were taught as undergraduates

not to think of animals as other than

stimulus-response bundles,” asserts Mel-

anie Stiassney, an ichthyologist at the

American Museum of Natural History.

“The dogma is you can’t credit them

with feelings.” In turn, it is often thought

undesirable for a researcher to have feel-

ings about the animal under study: emo-

tions can impair professional judgment

and also make it hard to perform cer-

Trends in Animal Research

88 Scientific American February 1997

Humane Society

of the U.S.

founded

1954

Jonas Salk

develops

killed-virus

polio vaccine

1951

Christine Stevens

founds Animal

Welfare Institute

in U.S.

1952

1953

Albert Sabin

develops live,

attenuated polio

vaccine

UPI/CORBIS-BETTMANN UPI/CORBIS-BETTMANN

tain procedures. Arnold Arluke, a soci-

ologist at Northeastern University who

studied animal laboratories from 1985

to 1993, reports that some technicians

were deeply disturbed when a playful

dog or a roomful of mice had to be put

down. Such distress was ofﬁcially dis-

couraged and therefore kept secret. But

after being “burned” by the death of a

favorite animal, laboratory workers

learned to avoid emotional connections

with the creatures.

The resulting dissociation, which is of-

ten likened to that of a surgeon from a

patient, allows a researcher to function

with a minimum of stress. But given the

emotional separation, a scientist may

not realize when an animal is in pain

—

especially if the very existence of pain is

in doubt. Nowadays, many researchers

are aware of dissociation and seek objec-

tive ways to detect distress. And animal

pain has come into its own. At a 1996

meeting on the Guide to the Care and

Use of Laboratory Animals

—a collection

of guidelines that all researchers funded

by the National Institutes of Health have

to follow

—veterinarian Gerald F. Geb-

hart of the University of Iowa stated that

the pain-sensing apparatus is the same

throughout the vertebrate kingdom and

offered this rule of thumb: “If it hurts

you, it probably hurts the animal.”

Increasingly, animal experimenters try

to balance scientiﬁc imperatives with

humaneness. Keith A. Reimann, a vet-

erinarian at Harvard University’s ani-

mal facility, does AIDS-related research

in monkeys. He insists that a macaque

be euthanized as soon as it becomes sick,

even if additional information might be

gained by following the course of the

illness. Franz P. Gruber of the Universi-

ty of Konstanz in Germany, who serves

on a board overseeing animal experi-

mentation, says his committee does not

allow “death as an end point”

—studies

in which the animal dies of the disease

or procedure being studied. Instead the

committee works with the researcher to

deﬁne a stage at which the creature can

be put out of its misery.

One area of concern to American vet-

erinarians involves paralytic drugs. These

agents immobilize an animal for surgery,

for six or more hours at a time; anesthe-

sia, however, may wear off in an hour or

two. A few researchers are reportedly

reluctant to administer additional anes-

thetics for fear that an overdose could

kill the animal before the experiment is

over, leading to a loss of data. But with-

out such “topping up,” the animal may

become conscious during the operation

and not be able to convey, by twitch or

cry, that it is in agony. And some scien-

tists object to using painkillers because

they do not want to introduce a new

variable into the experiment.

Compassionate feelings for animals

also inﬂuence studies, although research-

ers rarely admit to such unscientiﬁc, if

creditable, motivations. When asked

about their choice of species subjects, for

example, three neuroscientists

—working

on monkeys, rats and frogs, respective-

—replied unhesitatingly that it was de-

termined by the scientiﬁc question at

hand. But later in the conversation, the

frog experimenter conﬁded that he, per-

sonally, could not work on “a furry an-

imal,” and the rat experimenter said he

would not work with a cat or even with

a rat in a more painful protocol.

The Three Rs

cientists’ concern for animals ﬁrst

became visible professionally in the

1950s, when the behavioristic paradigm

came under attack. British zoologist Wil-

liam M. S. Russell and microbiologist

Rex L. Burch published The Principles

of Humane Experimental Technique

(Methuen, London, 1959), in which they

put forth the “three Rs.” This principle

sets out three goals for the conscientious

researcher: replacement of animals by in

vitro, or test-tube, methods; reduction

of their numbers by means of statistical

techniques; and reﬁnement of the ex-

periment so as to cause less suffering.

Although they took some decades to

catch on, the three Rs deﬁne the mod-

ern search for alternatives.

Starting in the 1960s, humane orga-

nizations and governments began to

fund studies in alternative methods. Eu-

ropean governments, especially, have

invested considerable resources. For the

past 15 years, Germany has been giving

out about $6 million a year in research

grants alone; the Netherlands spends

$2 million a year (including overheads

for its alternatives center). The Euro-

pean Center for the Validation of Alter-

native Methods, a body set up in 1992

by the European Commission, requires

another $9 million annually. In the U.S.,

governmental interest has been com-

paratively low; the National Institute of

Environmental Health Sciences (

NIEHS)

is now offering $1.5 million worth of

grants a year, for three years. And indus-

try provides the $1 million a year that

the Center for Alternatives to Animal

Testing (CAAT) at Johns Hopkins Uni-

versity disburses in grants. (Although

15 federal agencies have recently formed

the Interagency Coordinating Commit-

tee for Validation of Alternative Meth-

ods, this venture is as yet unfunded.)

All this effort has yielded a variety of

means for reducing animal use. Statisti-

cal sophistry, for example, is allowing

the classical LD50 (or lethal dose 50

percent) test for acute toxicity to be elim-

inated. This test requires up to 200 rats,

dogs or other animals to be force-fed

different amounts of a substance, to de-

termine the dose that will kill half a

Trends in Animal Research

Scientific American February 1997 89

William M. S. Russell

and Rex L. Burch state

three Rs of animal

experimentation

Animal Welfare Act

(AWA) passed

in the U.S.

Dorothy Hegarty founds Fund

for the Replacement of Animals in

Medical Experiments in U.K.

Peter Singer publishes

animal-liberation philosophy

Amendments

to AWA

cover warm-

blooded animals

and require

pain relief

1959

1966

1969

1970

1975

COURTESY OF NEW YORK REVIEW OF BOOKS

group. Although in vitro alternatives are

still far away

—because the mechanisms

underlying toxicity are poorly under-

stood

—protocols currently accepted

worldwide call for a tenth the number of

animals. The Organization for Econom-

ic Cooperation and Development, for ex-

ample, asks for between three and 18 an-

imals to be used: if the substance kills the

ﬁrst three, it need be tested no further.

Another unpleasant procedure is the

LD80 test for vaccines. Experimental

animals are vaccinated against a dis-

ease; they and a control group are then

exposed to it. The vaccine passes only if

at least 80 percent of the experimental

group remains healthy and if 80 percent

of the control group dies. Again using

statistics, Coenraad Hendriksen of the

National Institute of Public Health and

the Environment in the Netherlands

found a way of testing diphtheria and

tetanus vaccines that requires simply

checking the level of antibodies. Apart

from greatly reducing the suffering, it

uses half the number of animals.

“Data mining”

—the sifting of moun-

tains of information for relevant new

ﬁndings

—has also proved astonishingly

helpful. Horst Spielmann of ZEBET,

the German center for alternatives to an-

imal testing, surveyed decades of indus-

try data on pesticides and concluded

that if mice and rats prove sensitive to a

chemical, it does not have to be tested

on dogs. Spielmann anticipates that 70

percent of the dog tests can be dispensed

with. Klaus Cussler of the Paul Ehrlich

Institute in Langen, Germany, reviewed

data on the “abnormal safety test” for

vaccines (called the “mouse and guinea

pig safety test” in the U.S.), which in-

volves vaccinating mice and guinea pigs

and watching for untoward reactions.

Their ﬁndings led to the test being

dropped for vaccines checked in other

standard ways. “It was so senseless,”

Cussler shakes his head.

In 1989, after observing that produc-

tion of monoclonal antibodies in mice

with tumors causes much suffering,

ZEBET funded industry research into

test-tube alternatives. Consequently, the

antibodies, used in cancer therapy, are

now rarely manufactured in mice in

Europe (although mice remain the norm

in the U.S.). Production of polio vaccines

is another success story. In the 1970s the

Netherlands used 5,000 monkeys a year;

now kidney cell cultures from just 10

monkeys provide enough vaccine for ev-

eryone. Hormones or vaccines manufac-

tured in cell cultures are also purer than

those made in vivo (that is, in the ani-

mals themselves), so each batch need not

be tested as before for safety and efﬁcacy.

In 1993 the Department of Transpor-

tation became the ﬁrst U.S. agency to

accept in vitro tests, for skin corrosivity.

The traditional test requires placing a

substance on a rabbit’s shaved back to

see how far it eats in. The test’s replace-

ment uses reconstructed human skin or

a biomembrane such as Corrositex

—

testimony to the role played by venture

capital in ﬁnding alternatives. Several

cosmetics manufacturers have entirely

eliminated animal testing: they rely on

in-house substitutes or use ingredients

that have been tested in the past.

As yet, most researchers in the basic

sciences see little hope of replacing ani-

mals. They stick to reduction or reﬁne-

ment, such as using an animal lower on

the phylogenetic tree. The next spate of

cuts in animal use, Spielmann predicts,

will come in the ﬁeld of medical educa-

tion, for which alternative teaching tools

have been devised. British surgeons, in

fact, have not trained on animals since

the 1876 act banned such use; instead

they practice on human cadavers and

later assist experienced surgeons in ac-

tual operations. In the U.S., more than

40 of the 126 medical schools do not

use animals in their regular curricula.

The most signiﬁcant change has been

in mind-set. Since 1985 in the Nether-

lands, every scientist starting research

on animals has been required to take a

three-week course. They learn hands-

on procedures, proper anesthesia, spec-

iﬁcations of inbred strains and so on

—

as well as the three Rs. First the students

design an animal experiment; then they

are asked to ﬁnd ways of answering the

same question without animals. The re-

sulting discussion and hunt for infor-

mation induces a new way of thinking.

“It gives them time for reﬂection,” says

Bert F. M. van Zutphen of Utrecht Uni-

versity, who pioneered the course. “It’s

of utmost importance. To know how far

I can go for my own conscience.”

The Laws

nother source of change in scientists’

attitudes has been legislation. In

the U.S., laws tend to derive from iso-

lated incidents. The Animal Welfare Act

of 1966

—the federal law regulating an-

imal use

—came into being because of

Pepper, a Dalmatian believed by its own-

ers to have been stolen and sold to a

lab, and a Life magazine article depict-

ing starving dogs in dealers’ pens. Per-

haps the most signiﬁcant change came

in 1985, in the wake of two exposés in-

volving primates. In Silver Spring, Md.,

macaques belonging to Edward Taub

of the Institute for Behavioral Research

were found to be chewing on their limbs,

to which the nerves had been cut. And in

1984 videotapes from the University of

Pennsylvania Medical Center displayed

laboratory personnel mocking baboons

whose heads had been smashed in dur-

1981

1985

1992

1993

1996

Center for Alternatives to Animal

Testing founded in U.S.

European Center

for the Validation

of Alternative

Methods

founded

First World Congress

on Alternatives

held in the U.S.

Second World

Congress

on Alternatives

held in the

Netherlands

Amendments to AWA

result from

Silver Spring,

Md., and Penn-

sylvania pri-

mate exposés

JOHNS HOPKINS SCHOOL OF PUBLIC HEALTH COURTESY OF NATIONAL PRESS BOOKS

Trends in Animal Research90 Scientific American February 1997

ing experiments on head trauma. The

outcry following these revelations al-

lowed Senator Robert Dole of Kansas

to bring an amendment to the act. It es-

tablished institutional animal care and

use committees (IACUCs) at each fa-

cility using regulated animals and re-

quired laboratories to exercise dogs and

to ensure the psychological well-being

of primates.

The “well-being” clause can be con-

sidered an instance of the public’s im-

posing a scientiﬁc paradigm on scientists.

An inspector from the U.S. Department

of Agriculture, which administers the

Animal Welfare Act, sought expert ad-

vice at that time on primate psychology.

There was no such thing, he was told.

Now, just 10 years later, primates have

emotions. At the 1996

NIH meeting,

Gebhart listed fear, anxiety, boredom,

separation and isolation as conditions

to which experimenters should attend

in their subjects. And a few labs are even

trying to enrich the lives of their rabbits.

The laws have generally had the ef-

fect of driving up the costs of animal re-

search. Animal protectionists complain,

however, that the Animal Welfare Act

and its amendments invariably get di-

luted at the implementation stage. The

act, for instance, refers to warm-blood-

ed animals, but the regulations written

by the

USDA exclude rats, mice and

birds. The agency says it does not have

funds for inspecting the laboratories

that use these creatures, which is true;

animal welfarists, however, say the

omission originally came from lobbying

by the biomedical community. In 1990

humane organizations sued to have

these animals included. Although they

initially won, the suit was thrown out

on appeal, on the grounds that animal

protectionists have no legal standing:

only those who are injured

—that is, the

rats, mice and birds

—can bring a civil

suit. Dale Schwindaman of the

USDA

has promised, however, to include these

animals within the next ﬁve years.

Another controversy has to do with

so-called performance standards. When

writing regulations for the 1985 amend-

ments, the

USDA refrained, for example,

from stating how many times a week the

dogs had to be walked. Such speciﬁcs

are referred to as engineering standards.

Instead the agency allowed each facility

to come up with its own plans for dog

and primate well-being, the “perfor-

mance” of which was to be evaluated.

(Because these plans are kept in-house,

and not with the

USDA, the public can-

not obtain them through the Freedom

of Information Act.)

Researchers are enthusiastic about the

ﬂexibility of performance standards,

whereas Martin L. Stephens of the Hu-

mane Society of the U.S. calls them “eu-

phemisms for no standards.”

USDA in-

spectors are divided. Some argue that

the standards are vague and unenforce-

able. Among others, Harvey McKelvey

of the

USDA’s northwestern region says

they let him use his judgment: “If I see

Trends in Animal Research Scientific American February 1997 91

0.2

0.4

0.8

1.0

0.6

1.2

1.4

USE OF ANIMALS IN CANADA

MILLIONS OF ANIMALS

FISH

MICE

RATS

FOWL

FARM ANIMALS

GUINEA PIGS

RABBITS

DOGS

CATS

MONKEYS

OTHER

1975

1992

’95’93’91’89’87’85’83’81’79’77’751973

USE OF ANIMALS IN U.K. AND THE NETHERLANDS

MILLIONS

OF ANIMALS

U.K.

THE NETHERLANDS

1.0

1.5

2.0

2.5

0.5

’95’93’91’89’87’85’83’81’79’77’751973

MILLIONS

OF ANIMALS

USE OF ANIMALS IN U.S.

(EXCLUDES RATS, MICE AND BIRDS)

100

150

200

250

’95’93’91’89’87’85’83’81’79’77’751973

USE OF DOGS, CATS AND NONHUMAN PRIMATES IN U.S.

DOGS CATS PRIMATES

THOUSANDS OF ANIMALS

DOLLARS AWARDED

(BILLIONS)

0.5

1.0

1.5

2.0

1989198819871986198519841983

DISTRIBUTION OF FUNDS IN NIH EXTRAMURAL RESEARCH

INVERTEBRATES HUMANS

NONHUMAN VERTEBRATES

The Numbers of Research Animals

se of animals in European laboratories has been

slowly declining (a). In the U.S., the available statis-

tics (b) include primates, dogs, cats, guinea pigs, rabbits,

hamsters and others but exclude rats, mice and birds

—an

estimated 17 million additional animals per year. Primate

use is roughly constant, although the numbers of cats and

dogs (c) is declining. (In many instances, dogs are being re-

placed by pigs, calves and other farm animals. These have

been counted since 1990 but are not included in the

chart.) The National Institutes of Health supports research

into invertebrate models (d); however, funding has been

increasing more steeply for vertebrate (and human) stud-

ies. In Canada, animal numbers (e) have hovered at around

two million a year, but fish have replaced mammals in

many areas, especially toxicology.

BRYAN CHRISTIE; SOURCES: USDA (a–c); NATIONAL CENTER FOR RESEARCH RESOURCES, NIH (d); CANADIAN COUNCIL ON ANIMAL CARE (e)

an animal is bored with its toy, I can

write that it needs a new one. I couldn’t

do that with engineering standards.”

The new

NIH guide also embraces per-

formance standards.

The animal care committees have em-

powered those scientists who wish to

cut down on wastage and improve con-

ditions for animals. “If you have an in-

stitution with conscientious people, the

IACUC system works fairly well,” says

Ralph A. Meyer of Carolinas Medical

Center. Cathy Liss of the Animal Welfare

Institute in Washington, D.C., agrees that

some committees do far better than the

law. But there is concern about the re-

mainder. In 1992 an audit of the

USDA’s

enforcement activities by the Ofﬁce of

the Inspector General revealed that out

of 26 institutions selected at random,

12 “were not adequately fulﬁlling their

responsibilities under the act.” Everyone

agrees that enforcement is inadequate:

at present, there are only 69 inspectors,

who may not be able to visit each of the

1,300 regulated laboratories (and also

animal dealers, transporters and exhibi-

tors) every year.

As a result, the inspectors rely on whis-

tle-blowers. “We need eyes out there,”

McKelvey explains. It might be an ani-

mal-rights activist who has inﬁltrated a

laboratory: groups such as People for

the Ethical Treatment of Animals (PETA)

prepare detailed case histories that they

present to the

USDA or the NIH.

Or it might be a researcher or

technician.

Still, the

USDA can offer few

reassurances to informants. A

former member of the animal

care committee at New York

University Medical Center claims

to have been ﬁred in August

1995 for protesting irregulari-

ties in N.Y.U.’s labs and cooper-

ating with the

USDA’s investiga-

tions. The university states that

his position became redundant.

But the scientist, along with an

administrator who was also dis-

missed, is suing N.Y.U., as well

as the

USDA—which, he says,

failed to provide whistle-blower

protection. (The agency did ﬁne

N.Y.U. $450,000 for assorted

violations of the Animal Wel-

fare Act.) Several

USDA inspec-

tors express frustration with

their agency’s provisions on in-

formants. “We can’t protect a

whistle-blower,” McKelvey says.

“The regulation is weak.” Un-

like civil-discrimination suits, which re-

quire only a concatenation of circum-

stances, the

USDA needs to prove that

the person was ﬁred because of having

blown the whistle.

Also controversial are the statistics

on pain and distress provided by the

IACUCs to the

USDA. They indicate that

in 1995, 54 percent of the regulated an-

imals had no pain or distress, 37 per-

cent had distress alleviated by painkill-

ers, and only 8.8 percent suffered unal-

leviated pain or distress. The data have

been widely criticized for being unreli-

able, because the

USDA does not specify

how to classify pain. Andrew N. Ro-

wan of the Tufts University Center for

Animals and Public Policy has noted that

some rather painful procedures, such as

toxicity testing or antibody production,

are commonly placed in the nonpainful

category. Although the

USDA proposed

a pain scale in 1987, it was withdrawn

after objections by researchers.

There are difﬁculties with assessing

animal distress. Nevertheless, many Eu-

ropean nations, as well as Canada, Aus-

tralia and New Zealand, have developed

pain scales in which each procedure is

assigned a grade. As a result, their re-

ports are more informative. The Neth-

erlands listed in 1995 that 54 percent of

animals had minor discomfort, 26 per-

cent had moderate discomfort, and 20

percent suffered severe discomfort.

A pain scale would make it easier for

IACUCs to rate the suffering involved

in different schemes for doing an exper-

iment. At present, the committees are

required to certify that the animal re-

searcher has looked for alternatives and

that the number of animals used is rea-

sonable. Alan M. Goldberg of CAAT

wishes that they would also evaluate the

experimental design. “Right now, using

method A, they check: Is it the right

number of animals? They don’t look at

method B or C”

—which could involve

in vitro techniques. Nor

—unlike com-

mittees in Germany, Australia and else-

where

—are they required to weigh the

beneﬁts of research against the suffer-

ing or to include representatives of ani-

mal-welfare organizations in the review

process. (The IACUCs do have to in-

clude someone unafﬁliated with the in-

stitution, but who ﬁlls that position is

again a source of controversy.)

The Propaganda

hange in the U.S. has been slow

and painful. Notwithstanding some

evolution of practices, the ferocity of the

attacks by the most fervent animal right-

ists has led to a sense of moral outrage

and an unwillingness to compromise

—

on both sides. Almost all activists insist

that animal research is unnecessary; to

them, investigators using animals are

cruel and corrupt, consumed by a desire

for ever more papers and grants. One

antivivisection tract is entitled Slaughter

of the Innocent, and the cover of an-

other features splashes of blood. To an-

imal liberators, the killing of more than

six billion animals a year, mostly for

food, represents a holocaust, and Adolf

Hitler’s doctors are proof that experi-

menters can be inhumane.

Many animal researchers, in turn,

think of animal rightists as being brain-

less “bunny huggers” at best and dan-

gerous fanatics at worst. Leaﬂets pub-

lished by the American Medical Associ-

ation represent the animal-rights position

as equating humans with animals; a

quote from Ingrid Newkirk of PETA,

“A rat is a pig is a dog is a boy,” is of-

fered as evidence. (Newkirk claims her

statement was “When it comes to feel-

ing pain, a rat is a pig is a dog is a boy.”)

In an essay entitled “We Can’t Sacri-

ﬁce People for the Sake of Animal Life,”

Frederick K. Goodwin, former head of

the National Institute of Mental Health,

has argued that the issue of animal rights

threatens public health. In this vein, re-

Trends in Animal Research92 Scientific American February 1997

ANTIVIVISECTION POSTER attacks the ratio-

nales behind animal research.

PETA

search advocates sometimes portray pro-

posals to control animal research as be-

ing attacks on human life. For instance,

one organization advises this response

to a query about experimentation on

pound animals: “How would you feel

if the one research project that may

save your child’s life was priced out of

existence because pound animals were

banned?” Some writers invoke Hitler as

proof that animal advocates are antihu-

man: he was an animal lover who passed

anticruelty laws in 1930s Germany.

Finding itself under moral

—and some-

times physical

—siege, the research com-

munity has often retreated behind elec-

tronic surveillance systems

—and an eth-

ical code that frequently denounces

internal dissent as treason, “giving am-

munition to the enemy.” One scientist

interviewed for this article said that if

his criticisms became known, he would

be ﬁred. In 1991 two animal researchers,

John P. Gluck and Steven R. Kubacki of

the University of New Mexico, wrote a

treatise deploring the lack of ethical in-

trospection in their ﬁeld. Gluck testiﬁes

that the article quickly changed his sta-

tus from an insider to a distrusted out-

sider. Arluke’s studies revealed an ab-

sence of discussion about ethics: in 33

of 35 laboratories, moral positions were

deﬁned institutionally. Newcomers were

given to understand that senior scien-

tists had answered all the difﬁcult ques-

tions, leaving them little to worry about.

The insulation has made it difﬁcult

for changes in other branches of the life

sciences

—or from across the Atlantic—

to ﬁlter in. Primatologists, for instance,

have been discussing complex emotions

in their subjects for decades. But many

American experimenters still refuse to

use the word “suffering,” because it sug-

gests an animal has awareness. Even the

word “alternatives” is suspect; instead

the

NIH describes these as “adjuncts” or

“complements” to animal research.

Some researchers seem to regard the

three Rs as an animal-rights conspiracy.

Robert Burke of the

NIH has stated: “To

argue that we must reﬁne our methods

suggests that they are currently inade-

quate or unethical.... In my view, it is

intellectually dishonest and hypocritical

to continue to advocate the original three

Rs as a goal for science policy. It is also,

without question, dangerous to give our

enemies such useful tools with which to

pervert the scientiﬁc enterprise.”

Of the 17 institutes included in the

NIH, only the NIEHS has been active in

researching alternatives. Following a di-

rective by Congress, the

NIH

awarded about $2.5 million in

earmarked grants between 1987

and 1989. But F. Barbara Or-

lans of the Kennedy Institute of

Ethics at Georgetown Universi-

ty charges that the money did

not constitute a special alloca-

tion for alternatives: 16 of the

17 grants went to studies that

had traditionally been funded.

(Like other public health agen-

cies worldwide the

NIH supports

research into invertebrate, in

vitro and computer models that

are not billed as alternatives.)

In 1993 Congress directed the

NIH to come up with a plan for

implementing the three Rs. The

resulting document, entitled

“Plan for the Use of Animals in

Research,” is an overview of

biomedical models, with some

emphasis on nonmammalian

systems. “The central message of

the plan,” explains Louis Sibal

of the

NIH, “is that scientists

have to decide for themselves

what the best method of solving their

problem is.” Whereas the European

Union plans to cut animal use in half by

the year 2000, a 1989

NIH report stated

that animal use is not likely to decrease.

One arena in which the propaganda

battles have been especially ﬁerce is the

classroom: both sides see dissection as

the key to the next generation’s sympa-

thies. Animal advocates say dissection

in schools is unnecessary and brutaliz-

ing and that the 5.7 million vertebrates

(mostly wild frogs, but also cats, fetal

pigs, pigeons and perch) used every year

are procured in inhumane ways. Re-

search advocates fear that without dis-

section, instruction will be inadequate,

and fewer students will be attracted to

or equipped for the life sciences.

In 1989, when the National Associa-

tion of Biology Teachers (NABT) an-

nounced a new policy encouraging al-

ternatives, it provoked a violent reaction.

Barbara Bentley of the State University

of New York at Stony Brook, for in-

stance, denounced the monograph on

implementing the policy as “an insidi-

ously evil publication

—evil because it is

a barely disguised tract produced by

animal rightists.” An intense campaign

followed, and in 1993 the NABT issued

a new policy statement, warning teach-

ers to “be aware of the limitations of al-

ternatives.” There is no high school dis-

section in most European countries.

“It is possible to be both pro research

and pro reform,” Orlans says. She and

others in the troubled middle have a

simple message: the impasse must end.

Animal liberators need to accept that

animal research is beneﬁcial to humans.

And animal researchers need to admit

that if animals are close enough to hu-

mans that their bodies, brains and even

psyches are good models for the human

condition, then ethical dilemmas surely

arise in using them. But the moral bur-

den is not for scientists alone to bear.

All of us who use modern medicine and

modern consumer products need to ac-

knowledge the debt we owe to our fel-

low creatures and support science in its

quest to do better by the animals.

Trends in Animal Research Scientific American February 1997 93

The Benefits and Ethics of Animal Research

Abstract and Figures

Recommended publications

Animal research.

Animals and scientific research: the ethics that guide us

Drug menus in protocol applications. A la carte is OK

Animal rights activism threatens dissection