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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

F 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.
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
But we do not have to accept such low standards of exchange. somewhat; however, the level of concern among scientists, re-
Sound bites and pithy rhetoric may have their place in the search institutions, animal-rights groups and those who reg-
fight for the public’s ear, but there is always room for dispas- ulate animal use remains high.
sionate analysis and solid scholarship. There is also much room to chal-
When it comes to animal research, there is plenty of reason lenge the benefits of animal research
for legitimate dispute. First, one has to determine what val- and much room to defend such re-
ues are being brought to the table. If one believes animals search. In the next few pages,
should not be used simply as means to ends, that assumption you will find a debate between
greatly restricts what animal research one is willing to accept. opponents and supporters of
Most people, though, believe some form of cost-benefit anal- animal research. It is followed
CHRISTOPHER BURKE/QB

ysis should be performed to determine whether the use of an- by an article that sets out the
imals is acceptable. The costs consist mainly of animal pain, historical, philosophical and
distress and death, whereas the benefits include the acquisi- social context of the animal-
tion of new knowledge and the development of new medical research controversy. We leave
therapies for humans. it to you to judge the case.
There is considerable disagreement among scientists in
judging how much pain and suffering occur in the ANDREW N. ROWAN is
housing and use of research animals. More atten- director of the Tufts Uni-
tion is at last being given to assessing these versity Center for Animals
questions and to finding ways of minimizing and Public Policy.

Forum: The Benefits and Ethics of Animal Research


Copyright 1997 Scientific American, Inc. Scientific American February 1997 79
Animal Research Is During the 1920s and 1930s, studies
on monkeys led to gross misconcep-
tions that delayed the fight against po-

Wasteful and Misleading liomyelitis. These experiments indicat-


ed that the poliovirus infects mainly the
nervous system; scientists later learned
this was because the viral strains they
by Neal D. Barnard and Stephen R. Kaufman had administered through the nose had
artificially developed an affinity for brain
tissue. The erroneous conclusion, which
contradicted previous human studies

T 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-
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-
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
ly seductive, they are poorly suited to diovascular and nervous systems, for cultures in 1949 first showed that the
addressing the urgent health problems example—that have complex interac- virus could be cultivated on nonneural
of our era, such as heart disease, cancer, tions with one another. A stimulus ap- tissues taken from the intestine and
stroke, AIDS and birth defects. Even plied to one particular organ system limbs. Yet in the early 1950s, cell cul-
worse, animal experiments can mislead perturbs the animal’s overall physiolog- tures from monkeys rather than humans
researchers or even contribute to illness- ical functioning in myriad ways that of- were used for vaccine production; as a

DIGITAL COLLAGE BY JENNIFER C. CHRISTIANSEN; NEW YORK ACADEMY OF MEDICINE (left); NATIONAL LIBRARY OF MEDICINE (center); PETA (right)
es or deaths by failing to predict the tox- ten cannot be predicted or fully under- result, millions of people were exposed
ic effects of drugs. Fortunately, other, stood. Such uncertainty severely under- to potentially harmful monkey viruses.
more reliable methods that represent a mines the extrapolation of animal data In a striking illustration of the inade-
far better investment of research funds to other species, including humans. quacy of animal research, scientists in
can be employed. the 1960s deduced from numerous ani-
The process of scientific discovery of- Animal Tests Are Inapplicable mal experiments that inhaled tobacco
ten begins with unexpected observations smoke did not cause lung cancer (tar
that force researchers to reconsider ex-
isting theories and to conceive hypothe-
ses that better explain their findings.
I mportant medical advances have been
delayed because of misleading results
derived from animal experiments. David
from the smoke painted on the skin of
rodents did cause tumors to develop,
but these results were deemed less rele-
Many of the apparent anomalies seen Wiebers and his colleagues at the Mayo vant than the inhalation studies). For
in animal experiments, however, merely Clinic, writing in the journal Stroke in many years afterward, the tobacco lob-
reflect the unique biology of the species 1990, described a study showing that by was able to use these studies to delay
being studied, the unnatural means by of the 25 compounds that reduced dam- government warnings and to discour-
which the disease was induced or the age from ischemic stroke (caused by lack age physicians from intervening in their
stressful environment of the laboratory. of blood flow to the brain) in rodents, patients’ smoking habits.
Such irregularities are irrelevant to hu- cats and other animals, none proved ef- Of course, human population studies
man pathology, and testing hypotheses ficacious in human trials. The research- provided inescapable evidence of the
derived from these observations wastes ers attributed the disappointing results tobacco-cancer connection, and recent
considerable time and money. to disparities between how strokes nat- human DNA studies have identified to-
The majority of animals in laborato- urally occur in humans and how they bacco’s “smoking gun,” showing how
ries are used as so-called animal mod- were experimentally triggered in the an- a derivative of the carcinogen benzo(a)-
els: through genetic manipulation, sur- imals. For instance, a healthy animal pyrene targets human genes, causing
gical intervention or injection of foreign that experiences a sudden stroke does cancer. (It turns out that cancer research
substances, researchers produce ailments not undergo the slowly progressive ar- is especially sensitive to differences in
in these animals that “model” human terial damage that usually plays a cru- physiology between humans and other
conditions. This research paradigm is cial role in human strokes. animals. Many animals, particularly rats

80 Scientific American February 1997 Copyright 1997 Scientific American, Inc. Debate: Animal Research Is Wasteful and Misleading
and mice, synthesize within their bodies humans taking the drug (five of these pa- identifying the causes of human disease.
approximately 100 times the recom- tients died as a result of the medication, Consider the success of research on
mended daily allowance for humans of and the other two received liver trans- atherosclerotic heart disease. Initial epi-
vitamin C, which is believed to help the plants). The commonly used painkiller demiological investigations in humans—
body ward off cancer.) zomepirac sodium was popular in the notably the Framingham Heart Study,
The stress of handling, confinement early 1980s, but after it was implicated started in 1948—revealed the risk factors
and isolation alters an animal’s physiol- in 14 deaths and hundreds of life-threat- for heart disease, including high choles-
ogy and introduces yet another experi- ening allergic reactions, it was with- terol levels, smoking and high blood
mental variable that makes extrapolat- drawn from the market. The antidepres- pressure. Researchers then altered these
ing results to humans even more diffi- sant nomifensine, which had minimal factors in controlled human trials, such
cult. Stress on animals in laboratories toxicity in rats, rabbits, dogs and mon- as the multicenter Lipid Research Clin-
can increase susceptibility to infectious keys, caused liver toxicity and anemia ics Trial, carried out in the 1970s and
disease and certain tumors as well as in humans—rare yet severe, and some- 1980s. These studies illustrated, among
influence levels of hormones and anti- times fatal, effects that forced the manu- many other things, that every 1 percent
bodies, which in turn can alter the func- facturer to withdraw the product a few drop in serum cholesterol levels led to at
tioning of various organs. months after its introduction in 1985. least a 2 percent drop in risk for heart
In addition to medical research, ani- These frightening mistakes are not disease. Autopsy results and chemical
mals are also used in the laboratory to mere anecdotes. The U.S. General Ac- studies added further links between risk
test the safety of drugs and other chem- counting Office reviewed 198 of the 209 factors and disease, indicating that peo-
icals; again, these studies are confound- new drugs marketed between 1976 and ple consuming high-fat diets acquire ar-
ed by the fact that tests on different spe- 1985 and found that 52 percent had terial changes early in life. And studies
cies often provide conflicting results. For “serious postapproval risks” not pre- of heart disease patients indicated that
instance, in 1988 Lester Lave of Carne- dicted by animal tests or limited human eating a low-fat vegetarian diet, getting
gie Mellon University reported in the trials. These risks were defined as ad- regular mild exercise, quitting smoking
journal Nature that dual experiments verse reactions that could lead to hospi- and managing stress can reverse athero-
to test the carcinogenicity of 214 com- talization, disability or death. As a re- sclerotic blockages.
pounds on both rats and mice agreed sult, these drugs had to be relabeled with Similarly, human population studies
with each other only 70 percent of the new warnings or withdrawn from the of HIV infection elucidated how the
time. The correlation between rodents market. And of course, it is impossible virus was transmitted and guided inter-
and humans could only be lower. David to estimate how many potentially useful vention programs. In vitro studies using
Salsburg of Pfizer Central Research has drugs may have been needlessly aban- human cells and serum allowed re-
noted that of 19 chemicals known to doned because animal tests falsely sug- searchers to identify the AIDS virus and
cause cancer in humans when ingested, gested inefficacy or toxicity. determine how it causes disease. Inves-
only seven caused cancer in mice and tigators also used in vitro studies to as-
rats using the standards set by the Na- Better Methods sess the efficacy and safety of important
tional Cancer Institute. new AIDS drugs such as AZT, 3TC and
PETA (left); BRIAN GUNN IAAPEA (center); CHRISTOPHER BURKE/QB (right)

Indeed, many substances that ap-


peared safe in animal studies and re-
ceived approval from the U.S. Food and
R esearchers have better methods at
their disposal. These techniques in-
clude epidemiological studies, clinical
protease inhibitors. New leads, such as
possible genetic and environmental fac-
tors that contribute to the disease or
Drug Administration for use in humans intervention trials, astute clinical obser- provide resistance to it, are also emerg-
later proved dangerous to people. The vation aided by laboratory testing, hu- ing from human studies.
drug milrinone, which raises cardiac man tissue and cell cultures, autopsy Many animals have certainly been
output, increased survival of rats with studies, endoscopic examination and bi- used in AIDS research, but without
artificially induced heart failure; hu- opsy, as well as new imaging methods. much in the way of tangible results. For
mans with severe chronic heart failure And the emerging science of molecular instance, the widely reported monkey
taking this drug had a 30 percent in- epidemiology, which relates genetic, studies using the simian immunodefi-
crease in mortality. The antiviral drug metabolic and biochemical factors with ciency virus (SIV) under unnatural con-
fialuridine seemed safe in animal trials epidemiological data on disease inci- ditions suggested that oral sex present-
yet caused liver failure in seven of 15 dence, offers significant promise for ed a transmission risk. Yet this study

Debate: Animal Research Is Wasteful and Misleading Copyright 1997 Scientific American, Inc. Scientific American February 1997 81
did not help elucidate whether oral sex eries is not relevant to what is necessary tions are easily skewed. For example,
transmitted HIV in humans or not. In now for research and safety testing. Be- proponents of animal use often point to
other cases, data from animal studies fore scientists developed the cell and tis- the significance of animals to diabetes
have merely repeated information al- sue cultures common today, animals research. But human studies by Thomas
ready established by other experiments. were routinely used to harbor infectious Cawley, Richard Bright and Appolli-
In 1993 and 1994 Gerard J. Nuovo and organisms. But there are few diseases naire Bouchardat in the 18th and 19th
his colleagues at the State University of for which this is still the case—modern centuries first revealed the importance
New York at Stony Brook determined methods for vaccine production are saf- of pancreatic damage in diabetes. In ad-
the route of HIV into the female body er and more efficient. Animal toxicity dition, human studies by Paul Langer-
(the virus passes through cells in the cer- tests to determine the potency of drugs hans in 1869 led to the discovery of in-
vix and then to nearby lymph nodes) us- such as digitalis and insulin have largely sulin-producing islet cells. And although
ing studies of human cervical and lymph been replaced with sophisticated labo- cows and pigs were once the primary
node samples. Later, experimenters at ratory tests that do not involve animals. sources for insulin to treat diabetes, hu-
New York University placed SIV into the man insulin is now the standard thera-
vaginas of rhesus monkeys, then killed A Rhetorical Device py, revolutionizing how patients man-
the animals and dissected the organs; age the disease.
their paper, published in 1996, arrived
at essentially the same conclusion about
the virus’s path as did the previous hu-
A nimal “models” are, at best, analo-
gous to human conditions, but no
theory can be proved or refuted by anal-
Animal experimenters have also as-
serted that animal tests could have pre-
dicted the birth defects caused by the
man studies. ogy. Thus, it makes no logical sense to drug thalidomide. Yet most animal spe-
Research into the causes of birth de- test a theory about humans using ani- cies used in laboratories do not develop
fects has relied heavily on animal exper- mals. Nevertheless, when scientists de- the kind of limb defects seen in humans
iments, but these have typically proved bate the validity of competing theories after thalidomide exposure; only rab-
to be embarrassingly poor predictors of in medicine and biology, they often cite bits and some primates do. In nearly all

left to right: SPL/PHOTO RESEARCHERS, INC.; CHARLES GUPTON UNIPHOTO; DOE/SPL/PHOTO RESEARCHERS, INC.; JIM OLIVE UNIPHOTO
what can happen in humans. The rates animal studies as evidence. In this con- animal birth-defect tests, scientists are
for most birth defects are rising steadily. text, animal experiments serve primari- left scratching their heads as to whether
Epidemiological studies are needed to ly as rhetorical devices. And by using humans are more like the animals who
trace possible genetic and environmen- different kinds of animals in different develop birth defects or like those who
tal factors associated with birth defects, protocols, experimenters can find evi- do not.
just as population studies linked lung dence in support of virtually any theo- In this discussion, we have not
cancer to smoking and heart disease to ry. For instance, researchers have used broached the ethical objections to ani-
cholesterol. Such surveys have already animal experiments to show that ciga- mal experimentation. These are critical-
provided some vital information—the rettes both do and do not cause cancer. ly important issues. In the past few de-
connection between neural tube defects Harry Harlow’s famous monkey ex- cades, scientists have come to a new ap-
and folate deficiency and the identifica- periments, conducted in the 1960s at preciation of the tremendous complexity
tion of fetal alcohol syndrome are no- the University of Wisconsin, involved of animals’ lives, including their ability
table findings—but much more human separating infant monkeys from their to communicate, their social structures
population research is needed. mothers and keeping some of them in and emotional repertoires. But prag-
Observations of humans have proved total isolation for a year. The experi- matic issues alone should encourage sci-
to be invaluable in cancer research as ments, which left the animals severely entists and governments to put research
well. Several studies have shown that damaged emotionally, served primarily money elsewhere. SA

cancer patients who follow diets low in as graphic illustrations of the need for
fat and rich in vegetables and fruit live maternal contact—a fact already well NEAL D. BARNARD and STEPH-
longer and have a lower risk of recur- established from observations of hu- EN R. KAUFMAN are both practicing
rence. We now need intervention trials man infants. physicians. Barnard conducts nutrition
to test which specific diets help with var- Animal experimenters often defend research and is president of the Physi-
ious types of cancers. their work with brief historical accounts cians Committee for Responsible Medi-
The issue of what role, if any, animal of the supposedly pivotal role of animal cine. Kaufman is co-chair of the Medical
experimentation played in past discov- data in past advances. Such interpreta- Research Modernization Committee.

82 Scientific American February 1997 Copyright 1997 Scientific American, Inc. Debate: Animal Research Is Wasteful and Misleading
Animal Research Is views of the prominent British surgeon
Joseph Lister, who pioneered the use of
carbolic acid to sterilize surgical instru-

Vital to Medicine ments, sutures and wound dressings,


thereby preventing infection of wounds.
In 1875 Queen Victoria asked Lister to
address the Royal Commission inquiry
by Jack H. Botting and Adrian R. Morrison 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

E 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-
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
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
ate existing ailments and respond to the culture given to healthy chickens and been essential to his own work on asep-
emergence of new disease. As any med- rabbits produced cholera, thus proving sis and that to restrict research with an-
ical scientist will readily state, research that Pasteur had correctly identified the imals would prevent discoveries that
with animals is but one of several com- offending organism. By chance, he no- would benefit humankind.
plementary approaches. Some questions, ticed that after a time, cultures of the
however, can be answered only by ani- microorganisms lost their ability to in- Dozens of Vaccines and Antibiotics
mal research. We intend to show exact- fect. But birds given the ineffective cul-
ly where we regard animal research to
have been essential in the past and to
point to where we think it will be vital
tures became resistant to fresh batches
that were otherwise lethal to untreated
birds. Physicians had previously ob-
F ollowing the work of Pasteur and
others, scientists have established
causes of and vaccines for dozens of in-
in the future. To detail all the progress served that among people who survived fectious diseases, including diphtheria,
that relied on animal experimentation a severe attack of certain diseases, recur- tetanus, rabies, whooping cough, tuber-
CHRISTOPHER BURKE/QB (left); CORBIS-BETTMANN (center); GEOFF TOMPKINSON SPL/Photo Researchers, Inc. (right)

would require many times the amount rence of the disease was rare; Pasteur culosis, poliomyelitis, measles, mumps
of space allotted to us. Indeed, we can- had found a means of producing this and rubella. The investigation of these
not think of an area of medical research resistance without risk of disease. This ailments indisputably relied heavily on
that does not owe many of its most im- experience suggested to him that with animal experimentation: in most cases,
portant advances to animal experiments. the administration of a weakened cul- researchers identified candidate micro-
In the mid-19th century, most debili- ture of the disease-causing bacteria, doc- organisms and then administered the
tating diseases resulted from bacterial tors might be able to induce in their pa- microbes to animals to see if they con-
or viral infections, but at the time, most tients immunity to infectious diseases. tracted the illness in question.
physicians considered these ailments to In similar studies on rabbits and gui- Similar work continues to this day.
be caused by internal derangements of nea pigs, Pasteur isolated the microbe Just recently, scientists developed a vac-
the body. The proof that such diseases that causes anthrax and then developed cine against Hemophilus influenzae
did in fact derive from external micro- a vaccine against the deadly disease. type B (Hib), a major cause of meningi-
organisms originated with work done by With the information from animal ex- tis, which before 1993 resulted in death
the French chemist Louis Pasteur and periments—obviously of an extent that or severe brain damage in more than
his contemporaries, who studied infec- could never have been carried out on 800 children each year in the U.S. Early
tious diseases in domestic animals. Be- humans—he proved not only that infec- versions of a vaccine produced only
cause of his knowledge of how contam- tious diseases could be produced by mi- poor, short-lived immunity. But a new
inants caused wine and beer to spoil, croorganisms but also that immuniza- vaccine, prepared and tested in rabbits
Pasteur became convinced that microor- tion could protect against these diseases. and mice, proved to be powerfully im-
ganisms were also responsible for diseas- Pasteur’s findings had a widespread munogenic and is now in routine use.
es such as chicken cholera and anthrax. effect. For example, they influenced the Within two months of the vaccine’s in-

Debate: Animal Research Is Vital to Medicine Copyright 1997 Scientific American, Inc. Scientific American February 1997 83
troduction in the U.S. and the U.K., Hib icillin: Alexander Fleming, working in cations; animal research has been in-
infections fell by 70 percent. 1929, did not use mice to examine the strumental in generating solutions to
Animal research not only produced efficacy of his cultures containing crude these problems. Experiments on cats
new vaccines for the treatment of infec- penicillin (although he did show the cul- helped develop techniques for suturing
tious disease, it also led to the develop- tures had no toxic effects on mice and blood vessels from the host to the do-
ment of antibacterial and antibiotic rabbits). In 1940, however, Howard W. nor organ so that the vessels would be
drugs. In 1935, despite aseptic precau- Florey, Ernst B. Chain and others at the strong enough to withstand arterial pres-
tions, trivial wounds could lead to seri- University of Oxford finally showed pen- sure. Investigators working with rab-
ous infections that resulted in amputa- icillin to be dramatically effective as an bits, rodents, dogs and monkeys have
tion or death. At the same time, in both antibiotic via the mouse protection test. also determined ways to suppress the
Europe and the U.S., death from puer- Despite the success of vaccines and immune system to avoid rejection of the
peral sepsis (a disease that mothers can antibacterial therapy, infectious disease donor organ.
contract after childbirth, usually as a remains the greatest threat to human life The list continues. Before the intro-
result of infection by hemolytic strepto- worldwide. There is no effective vaccine duction of insulin, patients with diabe-
cocci) occurred in 200 of every 100,000 against malaria or AIDS; physicians in- tes typically died from the disease. For
births. In addition, 60 of every 100,000 creasingly face strains of bacteria resis- more than 50 years, the lifesaving hor-
men aged 45 to 64 died from lobar pneu- tant to current antibacterial drugs; new mone had to be extracted from the pan-
monia. When sulfonamide drugs became infectious diseases continue to emerge. creas of cattle or pigs; these batches of
available, these figures fell dramatically: It is hard to envisage how new and bet- insulin also had to be tested for safety
by 1960 only five out of every 100,000 ter vaccines and medicines against in- and efficacy on rabbits or mice.
mothers contracted puerperal sepsis, and fectious disease can be developed with- When we started our scientific ca-
only six of every 100,000 middle-aged out experiments involving animals. reers, the diagnosis of malignant hyper-
men succumbed to lobar pneumonia. A Research on animals has been vital to tension carried with it a prognosis of
range of other infections could also be numerous other areas in medicine. Open- death within a year, often preceded by
treated with these drugs. heart surgery—which saves the lives of devastating headaches and blindness.
The story behind the introduction of an estimated 440,000 people every year Research on anesthetized cats in the
sulfonamide drugs is instructive. The in the U.S. alone—is now routine, thanks 1950s heralded an array of progressive-
team investigating these compounds— to 20 years of animal research by scien- ly improved antihypertensive medicines,
Gerhard Domagk’s group at Bayer Lab- tists such as John Gibbon of Jefferson so that today treatment of hypertension
oratories in Wuppertal-Elberfeld, Ger- Medical College in Philadelphia. Re- is effective and relatively benign. Simi-
many—insisted that all candidate com- placement heart valves also emerged larly, gastric ulcers often necessitated
pounds be screened in infected mice from years of animal experimentation. surgery with a marked risk of morbid-
(using the so-called mouse protection The development of treatments for ity afterward. Now antiulcer drugs, de-
test) rather than against bacteria grown kidney failure has relied on step-by-step veloped from tests in rats and dogs, can
on agar plates. Domagk’s perspicacity improvement of techniques through an- control the condition and may effect a
was fortunate: the compound pronto- imal experiments. Today kidney dialy- cure if administered with antibiotics to
sil, for instance, proved to be extremely sis and even kidney transplants can save eliminate Helicobacter pylori infection.
potent in mice, but it had no effect on the lives of patients suffering from renal

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


bacteria in vitro—the active antibacter- failure as a result of a variety of ailments, Common Misconceptions
ial substance, sulfanilamide, was formed including poisoning, severe hemorrhage,
from prontosil within the body. Scien-
tists synthesized other, even more pow-
erful sulfonamide drugs and used them
hypertension or diabetes. Roughly
200,000 people require dialysis every
year in the U.S.; some 11,000 receive a
M uch is made in animal-rights pro-
paganda of alleged differences be-
tween species in their physiology or re-
successfully against many infections. For new kidney. Notably, a drug essential sponses to drugs that supposedly render
his work on antibacterial drugs, Do- for dialysis—heparin—must be extract- animal experiments redundant or mis-
magk won the Nobel Prize in 1939. ed from animal tissues and tested for leading. These claims can usually be re-
A lack of proper animal experimenta- safety on anesthetized animals. futed by proper examination of the lit-
tion unfortunately delayed for a decade Transplantation of a kidney or any erature. For instance, opponents of ani-
the use of the remarkable antibiotic pen- major organ presents a host of compli- mal research frequently cite the drug

84 Scientific American February 1997 Copyright 1997 Scientific American, Inc. Debate: Animal Research Is Vital to Medicine
thalidomide as an example of a medi- tion of a vegan diet that avoids all ani- insufficiency, caused by a defect in the
cine that was thoroughly tested on ani- mal products. Whereas we support the heart’s mitral valve. The production of
mals and showed its teratogenic effect promulgation of healthy practices, we prosthetic heart valves stemmed from
only in humans. But this is not so. Sci- do not consider that our examples could years of development and testing for ef-
entists never tested thalidomide in preg- be prevented by such measures. ficacy in dogs and calves. The artificial
nant animals until after fetal deformities valve can be inserted only into a quies-
were observed in humans. Once they ran A Black Hole cent heart that has been bypassed by a
these tests, researchers recognized that heart-lung machine—an instrument that
the drug did in fact cause fetal abnor-
malities in rabbits, mice, rats, hamsters
and several species of monkey. Similar-
O ur opponents in this debate claim
that even if animal experiments
have played a part in the development
itself has been perfected after 20 years’
experimentation in dogs. If, despite the
benefit of 35 years of hindsight, critics
ly, some people have claimed that peni- of medical advances, this does not mean of animal research cannot present a con-
cillin would not have been used in pa- that they were essential. Had such tech- vincing scenario to show how effective
tients had it first been administered to niques been outlawed, the argument treatment of mitral valve insufficiency
guinea pigs, because it is inordinately goes, researchers would have been forced could have developed any other way,
toxic to this species. Guinea pigs, how- to be more creative and thus would have their credibility is suspect.
ever, respond to penicillin in exactly the invented superior technologies. Others Will animal experiments continue to
same way as do the many patients who have suggested that there would not be be necessary to resolve extant medical
contract antibiotic-induced colitis when a gaping black hole in place of animal problems? Transgenic animals with a
placed on long-term penicillin therapy. research but instead more careful and single mutant gene have already provid-
In both guinea pigs and humans, the respected clinical and cellular research. ed a wealth of new information on the
cause of the colitis is infection with the In fact, there was a gaping black hole. functions of proteins and their roles in
bacterium Clostridium difficile. No outstanding progress in the treat- disease; no doubt they will continue to
In truth, there are no basic differences ment of disease occurred until biomedi- do so. We also anticipate major progress
between the physiology of laboratory cal science was placed on a sound, em- in the treatment of traumatic injury to
animals and humans. Both control their pirical basis through experiments on the central nervous system. The dogma
internal biochemistry by releasing endo- animals. Early researchers, such as Pas- that it is impossible to restore function
crine hormones that are all essentially teur and the 17th-century scientist Wil- to damaged nerve cells in the mamma-
the same; both humans and laboratory liam Harvey, who studied blood circu- lian spinal cord has to be reassessed in
animals send out similar chemical trans- lation in animals, were not drawn to the light of recent animal research indi-
mitters from nerve cells in the central animal experiments as an easy option. cating that nerve regeneration is indeed
and peripheral nervous systems, and Indeed, they drew on all the techniques possible. It is only a matter of time be-
both react in the same way to infection available at the time to answer their fore treatments begin to work. We find
or tissue injury. questions: sometimes dissection of a ca- it difficult to envision how progress in
Animal models of disease are unjustly daver, sometimes observations of a pa- this field—and so many others in bio-
criticized by assertions that they are not tient, sometimes examination of bacte- logical and medical science—can be
identical to the conditions studied in hu- ria in culture. At other times, though, achieved in the future without animal
mans. But they are not designed to be so; they considered experimentation on an- experiments. SA

instead such models provide a means to imals to be necessary.


study a particular procedure. Thus, cys- We would like to suggest an interest- JACK H. BOTTING and ADRIAN
tic fibrosis in mice may not exactly mim- ing exercise for those who hold the view R. MORRISON have been active in
ic the human condition (which varies that animal experiments, because of their the defense of animal research since the
considerably among patients anyway), irrelevance, have retarded progress: take 1980s. Botting, a retired university lec-
but it does provide a way to establish an example of an advance dependent on turer, is the former scientific adviser to
the optimal method of administering animal experiments and detail how an the Research Defense Society in Lon-
LLEWELLYN UNIPHOTO

gene therapy to cure the disease. Oppo- alternative procedure could have pro- don. Morrison is director of the Labo-
nents of animal experiments also allege vided the same material benefit. A suit- ratory for Study of the Brain in Sleep at
that most illness can be avoided by a able example would be treatment of the the University of Pennsylvania School
change of lifestyle; for example, adop- cardiac condition known as mitral valve of Veterinary Medicine.

Debate: Animal Research Is Vital to Medicine Copyright 1997 Scientific American, Inc. Scientific American February 1997 85
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

T 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
jealousy and deceit among primates. Al-
though not so popular with scientists,
such anthropomorphic views of animals
fueled the passage of laws regulating
experimentation.
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
countries, the total has fallen by half And the scientists have changed. Those envisage a hierarchy of organisms rath-
since the 1970s. In Canada, mammals entering the biomedical profession in re- er than a sharp division, their influence
have largely been replaced by fish. The cent decades have imbibed at least some on the animal-rights movement is limit-
figures for the U.S. are unclear. The U.S. of the concerns of the movement, if not ed to vague inspiration and vegetarian
uses between 18 and 22 million animals its ideals; many are willing to acknowl- recipes. The real roots lie in secular phi-
a year, but exact numbers are unknown edge the moral dilemmas of their craft. losophy. In 1780 the English barrister
for roughly 85 percent of these—rats, Some experiments that were applauded Jeremy Bentham asked what “insupera-
mice and birds. Primate use has stayed in the 1950s would not be done today, ble line” prevented humans from ex-
constant, whereas the use of dogs and because they would be deemed to cause tending moral regard to animals: “The
cats is down by half since the 1970s. too much suffering. Oftentimes biotech- question is not, Can they reason? nor,
No one reason accounts for the de- nology is allowing test tubes to be sub- Can they talk? but, Can they suffer?”
cline, but several factors are obvious. In stituted for animals. And a few research- The question became more poignant
1975 the animal-rights movement ex- ers, cognizant that only their expertise in 1859 with the advent of Charles Dar-
ploded onto the scene with the publica- can help reduce the need for animals, win’s theory of evolution. The theory
tion of Animal Liberation by the Aus- are avidly seeking alternatives. All these provided a scientific rationale for using
tralian philosopher Peter Singer. The efforts are bearing fruit. animals to learn about humans, and
book’s depiction of research, and a se- Darwin endorsed such use. But he also
ries of exposés by suddenly vigilant ac- The Philosophers believed in an emotional continuum be-
tivists, threw a harsh spotlight on scien- tween humans and animals and was
tists. In the following years, public per-
ceptions of animals became increasingly
sympathetic. Dian Fossey, Jane Goodall
T he underlying force behind these
changes appears to be society’s
evolving views of animals. These per-
troubled by the suffering that experi-
mentation could cause. This dichotomy
inspired clashes between animal lovers
and other ethologists related to an en- ceptions owe a great deal to philosophy and experimenters in 19th-century Eng-
thralled audience tales of love, sorrow, and to science—and very little to reli- land, culminating in the 1876 British

The Evolution of Animal 1866


Use in Research Henry
Bergh
1822 British anticruelty act introduced founds
by Richard ASPCA
1859 in U.S.
Martin
(holding Charles
donkey). He Darwin
later founded publishes
the RSPCA the theory
of evolution

ROYAL SOCIETY FOR THE PREVENTION OF CRUELTY TO ANIMALS CORBIS–BETTMANN CORBIS–BETTMANN

86 Scientific American February 1997 Copyright 1997 Scientific American, Inc. Trends in Animal Research
Cruelty to Animals Act regulating ani- they are not merely means to an end. to use other creatures. This argument,
mal experimentation. But the phenom- Many other philosophers have lent which some say elevates “survival of the
enal success of medicine in the next cen- their voices to the animals, but few have fittest” to a moral philosophy, falls prey
tury made the animal-protection move- come to the aid of researchers. One who to a proposition called the naturalistic
ment recede into the background. did so, Michael A. Fox, author of The fallacy. To paraphrase the 18th-century
It rebounded in the 1970s, with Sing- Case for Animal Experimentation (Uni- philosopher David Hume, what “is”
er’s attack. A philosopher in the utilitar- versity of California Press, 1986), later cannot dictate what “ought to be.” So
ian tradition of Bentham, Singer holds declared himself convinced by his crit- natural history may well illuminate why
that in all decisions the total amount of ics and became an advocate for animals. human morals evolved into their pres-
good that results—human and animal— Attempts to refute Singer and Regan ent form, but humans can transcend
should be weighed against the suffer- usually involve pointing to morally rele- their nature. One animal advocate de-
ing—human and animal—caused in the vant criteria that separate humans from clares: “Killing and eating [meat] is an
process. Not that to him the interests of animals. Raymond G. Frey of Bowling integral part of the evolution of human
humans and animals have equal weight: Green State University has written that beings. Not killing and not eating [meat]
life is of far greater value to a human animals cannot have interests, because is the next step in our evolution.”
than, for example, to a creature with no they cannot have desires, because they Many philosophers fall into the trou-
self-awareness. But if there is something cannot have beliefs, because they do not bled middle, arguing for interests or
one would not do to, say, a severely in- have language. Regan counters that a rights to be ordered in a hierarchy that
capacitated child, then neither should dog may well believe “that bone is tas- allows some uses of animals but bars
one do it to an animal that would suffer ty” without being able to formulate the others. Such distillations of animal-lib-
as much. Ignoring the interests of an an- phrase and that a human infant would eration ideas have been finding their
imal just because it is not human is, to never learn to speak unless it could ac- way into legislation. The U.K., Austra-
Singer, “speciesism,” a sin akin to rac- quire preverbal concepts to which it lia, Germany and several other nations
ism. Invoking the connections between could later assign words, such as “ball.” require a utilitarian cost-benefit analy-
humans and the great apes, Singer, Another supporter of research, Carl sis to be performed before an animal ex-
Goodall and others have issued a call Cohen of the University of Michigan, periment can proceed. And in Novem-
for these creatures, at least, to be freed has argued that rights are not inherent: ber 1996 the Netherlands passed into
from experimentation. they arise from implicit contracts among law the statement that animals have “in-
Although Singer started the modern members of society, and they imply du- trinsic value”: they are sentient beings,
animal-rights movement, it takes its ties. Because animals cannot recipro- entitled to the moral concern of humans.
name and its most uncompromising cate such duties, they cannot have rights.
ideas from Tom Regan’s The Case for This argument meets with the retort The Public
Animal Rights (University of California that infants and the mentally ill cannot
Press, 1983). Regan believes that all hu-
mans and most animals have inherent
rights, which he describes as invisible
fulfill such obligations either but are
not left out of the realm of rights: Why
omit animals? (One response is that hu-
N ot that, of course, all the Dutch are
vegetarians. Rational argumenta-
tion may have influenced public opin-
“no trespassing” signs hung around man rights are based on characteristics ion, but as Harold A. Herzog, Jr., a psy-

ILLUSTRATION OF SCROLL BY LAURIE GRACE


their necks. They state that our bodies of “typical” humans, not on borderline chologist at Western Carolina Universi-
may not be transgressed, no matter how cases, prompting animal advocates to ty, remarks, the average person’s stance
much good might thereby result. Regan ask what these special qualities are—and on animal issues remains wildly incon-
does not equate humans with animals— so on and on.) sistent. In one survey, questions phrased
to save survivors in a lifeboat, a dog Some research proponents also note in terms of rats yielded a far more pro-
could be thrown overboard before a hu- that nature is cruel: lions kill zebras, cats vivisection outcome than those mention-
man would—yet he states that animals play with mice. Evolution has placed hu- ing dogs. Jesse L. Owens, a neuroscien-
cannot be experimented on, because mans on top, so it is only natural for us tist at the University of Alaska, protests

1891
1885 Diphtheria antitoxin produced
(serum is being drawn from a horse)
1876
British Cruelty
to Animals Act
regulates
animal
experimentation

Louis Pasteur (at patient’s


right) develops rabies vaccine Tetanus antitoxin found

SCIENTIFIC AMERICAN SCIENTIFIC AMERICAN OLIVER MECKES Photo Researchers, Inc.

Trends in Animal Research Copyright 1997 Scientific American, Inc. Scientific American February 1997 87
that medical research is “the only use of ence sentiments, aggravated by poor ing animals and were moved enough by
animals that is essential” and like other public knowledge of science. But accord- it to seek substitutes. Scientists choose
researchers is bewildered by people who ing to a 1994 survey led by Linda Pifer to use animals because they feel it is the
eat meat and in the same gulp condemn of the Chicago Academy of Sciences, only way to help humans. Donald Sil-
experimentation. negative attitudes toward animal exper- ver, who did cancer studies on mice at
Not surprisingly, the animal-libera- imentation in the U.S. correlate only Sloan-Kettering Hospital in the 1970s,
tion movement has coincided with soci- weakly with lack of knowledge about recounts that whenever he had doubts
ety’s becoming increasingly distant from science. And in Belgium, France and about his work, he had only to think
farms—and shielded from the reality Italy, for instance, greater scientific lit- about the terminally ill patients in the
behind dinner. Those who grew up on eracy is connected with an increased re- children’s ward.
farms often see animals as objects to be jection of animal experimentation.
used, whereas those who had pets tend Sociologists agree that opposition to The Scientists
to express more sympathy. One line vivisection derives primarily from sym-
along which attitudes divide is gender.
In all countries surveyed, women are
more pro-animal and antivivisectionist
pathy for animals. Almost all animal
rightists are vegetarians; many are “veg-
ans,” eschewing milk, eggs, leather and
O f course, scientists’ perceptions of
animals have evolved as well. In
the early 20th century Darwinian wor-
than men, and three quarters of Ameri- other animal products. “My philosophy ries about emotions were dispelled by
can animal-rights activists are women. of living as softly on the earth as I can is the rise of behaviorism. Because thoughts
Also noticeable is a generation gap. Sur- my life,” one activist told Herzog. In cannot be measured, but behavior can,
veys by Stephen R. Kellert of Yale Uni- striving to cause the least suffering pos- practitioners such as C. Lloyd Morgan
versity find that those who are older or sible, these individuals labor under a and, later, B. F. Skinner sought to de-
less educated are more likely to see ani- heavy moral burden that sits lightly on scribe animals purely in terms of their
mals as resources, whereas those who the rest of us. Some activists have in- responses to stimuli. Bernard Rollin, au-
are younger or more educated tend to dulged in threatening researchers, break- thor of The Unheeded Cry (Oxford Uni-
view animals with compassion. ing into laboratories or even arson. But versity Press, 1989), argues that at some
Public support of animal experimen- the number of such illegal acts, listed by point, the animal psyche went from be-
tation, though higher in the U.S. than in the U.S. Department of Justice, dropped ing impossible to measure to being non-
Europe, has been slowly declining. In from about 50 a year in 1987 to 11 in existent. The test of a good theory,
1985, 63 percent of American respon- 1992. (More recent figures are unavail- “Morgan’s canon,” required all actions
dents agreed that “scientists should be able but are believed to be small.) to be interpreted in terms of the lowest
allowed to do research that causes pain Many animal experimenters are also psychological faculties possible. In prac-
and injury to animals like dogs and chim- animal lovers. Surveys by Harold Ta- tice, this meant that a rat would not be
panzees if it produces new information kooshian, a sociologist at Fordham Uni- feeling pain even if its “writhes per min-
about human health problems”; in 1995, versity, reveal that biomedical research- ute” were being used to test the efficacy
53 percent agreed. Even in disciplines ers have the same mixed feelings about of an analgesic. Its neurochemistry was
that have traditionally used animals, the animals and animal research as does the merely inducing a physiological reflex.
trend is unmistakable. A survey by Scott general public. (The groups that gave “We were taught as undergraduates
Plous of Wesleyan University finds that animals the lowest rating and vivisec- not to think of animals as other than
psychologists with Ph.D.’s earned in the tion the highest were farmers, hunters stimulus-response bundles,” asserts Mel-
1990s are half as likely to express strong and the clergy.) Thomas M. Donnelly, a anie Stiassney, an ichthyologist at the
support for animal research as those veterinarian at the Rockefeller Universi- American Museum of Natural History.
with Ph.D.’s from before 1970. (Part of ty’s animal center, also runs a shelter to “The dogma is you can’t credit them
this result comes from the increased pres- which he takes cats that are no longer with feelings.” In turn, it is often thought
ence of women, but there is a significant needed for research. Almost all the tox- undesirable for a researcher to have feel-
drop among men as well.) icologists and pharmacologists at a 1996 ings about the animal under study: emo-
Opposition to animal experimenta- meeting on alternatives to animal ex- tions can impair professional judgment
tion is often said to derive from antisci- perimentation had experience with us- and also make it hard to perform cer-

1952 1954
1951
Jonas Salk Humane Society
Christine Stevens develops of the U.S.
founds Animal killed-virus founded
Welfare Institute polio vaccine
in U.S. 1953
Albert Sabin
develops live,
attenuated polio
vaccine

UPI/CORBIS-BETTMANN UPI/CORBIS-BETTMANN

88 Scientific American February 1997 Copyright 1997 Scientific American, Inc. Trends in Animal Research
tain procedures. Arnold Arluke, a soci- in which the animal dies of the disease (Methuen, London, 1959), in which they
ologist at Northeastern University who or procedure being studied. Instead the put forth the “three Rs.” This principle
studied animal laboratories from 1985 committee works with the researcher to sets out three goals for the conscientious
to 1993, reports that some technicians define a stage at which the creature can researcher: replacement of animals by in
were deeply disturbed when a playful be put out of its misery. vitro, or test-tube, methods; reduction
dog or a roomful of mice had to be put One area of concern to American vet- of their numbers by means of statistical
down. Such distress was officially dis- erinarians involves paralytic drugs. These techniques; and refinement of the ex-
couraged and therefore kept secret. But agents immobilize an animal for surgery, periment so as to cause less suffering.
after being “burned” by the death of a for six or more hours at a time; anesthe- Although they took some decades to
favorite animal, laboratory workers sia, however, may wear off in an hour or catch on, the three Rs define the mod-
learned to avoid emotional connections two. A few researchers are reportedly ern search for alternatives.
with the creatures. reluctant to administer additional anes- Starting in the 1960s, humane orga-
The resulting dissociation, which is of- thetics for fear that an overdose could nizations and governments began to
ten likened to that of a surgeon from a kill the animal before the experiment is fund studies in alternative methods. Eu-
patient, allows a researcher to function over, leading to a loss of data. But with- ropean governments, especially, have
with a minimum of stress. But given the out such “topping up,” the animal may invested considerable resources. For the
emotional separation, a scientist may become conscious during the operation past 15 years, Germany has been giving
not realize when an animal is in pain— and not be able to convey, by twitch or out about $6 million a year in research
especially if the very existence of pain is cry, that it is in agony. And some scien- grants alone; the Netherlands spends
in doubt. Nowadays, many researchers tists object to using painkillers because $2 million a year (including overheads
are aware of dissociation and seek objec- they do not want to introduce a new for its alternatives center). The Euro-
tive ways to detect distress. And animal variable into the experiment. pean Center for the Validation of Alter-
pain has come into its own. At a 1996 Compassionate feelings for animals native Methods, a body set up in 1992
meeting on the Guide to the Care and also influence studies, although research- by the European Commission, requires
Use of Laboratory Animals—a collection ers rarely admit to such unscientific, if another $9 million annually. In the U.S.,
of guidelines that all researchers funded creditable, motivations. When asked governmental interest has been com-
by the National Institutes of Health have about their choice of species subjects, for paratively low; the National Institute of
to follow—veterinarian Gerald F. Geb- example, three neuroscientists—working Environmental Health Sciences (NIEHS)
hart of the University of Iowa stated that on monkeys, rats and frogs, respective- is now offering $1.5 million worth of
the pain-sensing apparatus is the same ly—replied unhesitatingly that it was de- grants a year, for three years. And indus-
throughout the vertebrate kingdom and termined by the scientific question at try provides the $1 million a year that
offered this rule of thumb: “If it hurts hand. But later in the conversation, the the Center for Alternatives to Animal
you, it probably hurts the animal.” frog experimenter confided that he, per- Testing (CAAT) at Johns Hopkins Uni-
Increasingly, animal experimenters try sonally, could not work on “a furry an- versity disburses in grants. (Although
to balance scientific imperatives with imal,” and the rat experimenter said he 15 federal agencies have recently formed
humaneness. Keith A. Reimann, a vet- would not work with a cat or even with the Interagency Coordinating Commit-
erinarian at Harvard University’s ani- a rat in a more painful protocol. tee for Validation of Alternative Meth-
mal facility, does AIDS-related research ods, this venture is as yet unfunded.)
in monkeys. He insists that a macaque The Three Rs All this effort has yielded a variety of
be euthanized as soon as it becomes sick, means for reducing animal use. Statisti-
even if additional information might be
gained by following the course of the
illness. Franz P. Gruber of the Universi-
S cientists’ concern for animals first
became visible professionally in the
1950s, when the behavioristic paradigm
cal sophistry, for example, is allowing
the classical LD50 (or lethal dose 50
percent) test for acute toxicity to be elim-
ty of Konstanz in Germany, who serves came under attack. British zoologist Wil- inated. This test requires up to 200 rats,
on a board overseeing animal experi- liam M. S. Russell and microbiologist dogs or other animals to be force-fed
mentation, says his committee does not Rex L. Burch published The Principles different amounts of a substance, to de-
allow “death as an end point”—studies of Humane Experimental Technique termine the dose that will kill half a

1959
William M. S. Russell 1975
and Rex L. Burch state
three Rs of animal 1966 1970
experimentation
Amendments
Animal Welfare Act to AWA
(AWA) passed cover warm-
in the U.S. blooded animals
1969 and require
pain relief
Dorothy Hegarty founds Fund
for the Replacement of Animals in Peter Singer publishes
Medical Experiments in U.K. animal-liberation philosophy

COURTESY OF NEW YORK REVIEW OF BOOKS

Trends in Animal Research Copyright 1997 Scientific American, Inc. Scientific American February 1997 89
group. Although in vitro alternatives are standard ways. “It was so senseless,” later assist experienced surgeons in ac-
still far away—because the mechanisms Cussler shakes his head. tual operations. In the U.S., more than
underlying toxicity are poorly under- In 1989, after observing that produc- 40 of the 126 medical schools do not
stood—protocols currently accepted tion of monoclonal antibodies in mice use animals in their regular curricula.
worldwide call for a tenth the number of with tumors causes much suffering, The most significant change has been
animals. The Organization for Econom- ZEBET funded industry research into in mind-set. Since 1985 in the Nether-
ic Cooperation and Development, for ex- test-tube alternatives. Consequently, the lands, every scientist starting research
ample, asks for between three and 18 an- antibodies, used in cancer therapy, are on animals has been required to take a
imals to be used: if the substance kills the now rarely manufactured in mice in three-week course. They learn hands-
first three, it need be tested no further. Europe (although mice remain the norm on procedures, proper anesthesia, spec-
Another unpleasant procedure is the in the U.S.). Production of polio vaccines ifications of inbred strains and so on—
LD80 test for vaccines. Experimental is another success story. In the 1970s the as well as the three Rs. First the students
animals are vaccinated against a dis- Netherlands used 5,000 monkeys a year; design an animal experiment; then they
ease; they and a control group are then now kidney cell cultures from just 10 are asked to find ways of answering the
exposed to it. The vaccine passes only if monkeys provide enough vaccine for ev- same question without animals. The re-
at least 80 percent of the experimental eryone. Hormones or vaccines manufac- sulting discussion and hunt for infor-
group remains healthy and if 80 percent tured in cell cultures are also purer than mation induces a new way of thinking.
of the control group dies. Again using those made in vivo (that is, in the ani- “It gives them time for reflection,” says
statistics, Coenraad Hendriksen of the mals themselves), so each batch need not Bert F. M. van Zutphen of Utrecht Uni-
National Institute of Public Health and be tested as before for safety and efficacy. versity, who pioneered the course. “It’s
the Environment in the Netherlands In 1993 the Department of Transpor- of utmost importance. To know how far
found a way of testing diphtheria and tation became the first U.S. agency to I can go for my own conscience.”
tetanus vaccines that requires simply accept in vitro tests, for skin corrosivity.
checking the level of antibodies. Apart The traditional test requires placing a The Laws
from greatly reducing the suffering, it substance on a rabbit’s shaved back to
uses half the number of animals.
“Data mining”—the sifting of moun-
tains of information for relevant new
see how far it eats in. The test’s replace-
ment uses reconstructed human skin or
a biomembrane such as Corrositex—
A nother source of change in scientists’
attitudes has been legislation. In
the U.S., laws tend to derive from iso-
findings—has also proved astonishingly testimony to the role played by venture lated incidents. The Animal Welfare Act
helpful. Horst Spielmann of ZEBET, capital in finding alternatives. Several of 1966—the federal law regulating an-
the German center for alternatives to an- cosmetics manufacturers have entirely imal use—came into being because of
imal testing, surveyed decades of indus- eliminated animal testing: they rely on Pepper, a Dalmatian believed by its own-
try data on pesticides and concluded in-house substitutes or use ingredients ers to have been stolen and sold to a
that if mice and rats prove sensitive to a that have been tested in the past. lab, and a Life magazine article depict-
chemical, it does not have to be tested As yet, most researchers in the basic ing starving dogs in dealers’ pens. Per-
on dogs. Spielmann anticipates that 70 sciences see little hope of replacing ani- haps the most significant change came
percent of the dog tests can be dispensed mals. They stick to reduction or refine- in 1985, in the wake of two exposés in-
with. Klaus Cussler of the Paul Ehrlich ment, such as using an animal lower on volving primates. In Silver Spring, Md.,
Institute in Langen, Germany, reviewed the phylogenetic tree. The next spate of macaques belonging to Edward Taub
data on the “abnormal safety test” for cuts in animal use, Spielmann predicts, of the Institute for Behavioral Research
vaccines (called the “mouse and guinea will come in the field of medical educa- were found to be chewing on their limbs,
pig safety test” in the U.S.), which in- tion, for which alternative teaching tools to which the nerves had been cut. And in
volves vaccinating mice and guinea pigs have been devised. British surgeons, in 1984 videotapes from the University of
and watching for untoward reactions. fact, have not trained on animals since Pennsylvania Medical Center displayed
Their findings led to the test being the 1876 act banned such use; instead laboratory personnel mocking baboons
dropped for vaccines checked in other they practice on human cadavers and whose heads had been smashed in dur-

1981 1985 1992


Amendments to AWA European Center
result from for the Validation
Silver Spring, of Alternative
Md., and Penn- Methods
sylvania pri- founded
mate exposés 1996
1993 Second World
First World Congress Congress
on Alternatives on Alternatives
held in the U.S. held in the
Center for Alternatives to Animal Netherlands
Testing founded in U.S.
JOHNS HOPKINS SCHOOL OF PUBLIC HEALTH COURTESY OF NATIONAL PRESS BOOKS

90 Scientific American February 1997 Copyright 1997 Scientific American, Inc. Trends in Animal Research
The Numbers of Research Animals
c USE OF DOGS, CATS AND NONHUMAN PRIMATES IN U.S.

THOUSANDS OF ANIMALS
U 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,
250
200
DOGS CATS PRIMATES

150
hamsters and others but exclude rats, mice and birds—an
estimated 17 million additional animals per year. Primate 100
BRYAN CHRISTIE; SOURCES: USDA (a–c); NATIONAL CENTER FOR RESEARCH RESOURCES, NIH (d); CANADIAN COUNCIL ON ANIMAL CARE (e)

use is roughly constant, although the numbers of cats and 50


dogs (c) is declining. (In many instances, dogs are being re- 0
placed by pigs, calves and other farm animals. These have 1973 ’75 ’77 ’79 ’81 ’83 ’85 ’87 ’89 ’91 ’93 ’95
been counted since 1990 but are not included in the
d DISTRIBUTION OF FUNDS IN NIH EXTRAMURAL RESEARCH

DOLLARS AWARDED
chart.) The National Institutes of Health supports research 2.0
into invertebrate models (d); however, funding has been INVERTEBRATES HUMANS

(BILLIONS)
1.5 NONHUMAN VERTEBRATES
increasing more steeply for vertebrate (and human) stud-
ies. In Canada, animal numbers (e) have hovered at around 1.0
two million a year, but fish have replaced mammals in 0.5
many areas, especially toxicology.
0
1983 1984 1985 1986 1987 1988 1989
a USE OF ANIMALS IN U.K. AND THE NETHERLANDS
6 U.K. THE NETHERLANDS e USE OF ANIMALS IN CANADA
5
OF ANIMALS

MICE
1.4
MILLIONS

4
3 1975 1992
2 1.2
1
MILLIONS OF ANIMALS
0 1.0
1973 ’75 ’77 ’79 ’81 ’83 ’85 ’87 ’89 ’91 ’93 ’95

RATS
0.8
b USE OF ANIMALS IN U.S. (EXCLUDES RATS, MICE AND BIRDS)
2.5
2.0 0.6
OF ANIMALS

FARM ANIMALS
FOWL
MILLIONS

GUINEA PIGS
1.5
0.4
1.0

RABBITS

MONKEYS

OTHER
FISH

DOGS
0.5 0.2

CATS
0
1973 ’75 ’77 ’79 ’81 ’83 ’85 ’87 ’89 ’91 ’93 ’95 0

ing experiments on head trauma. The The laws have generally had the ef- Another controversy has to do with
outcry following these revelations al- fect of driving up the costs of animal re- so-called performance standards. When
lowed Senator Robert Dole of Kansas search. Animal protectionists complain, writing regulations for the 1985 amend-
to bring an amendment to the act. It es- however, that the Animal Welfare Act ments, the USDA refrained, for example,
tablished institutional animal care and and its amendments invariably get di- from stating how many times a week the
use committees (IACUCs) at each fa- luted at the implementation stage. The dogs had to be walked. Such specifics
cility using regulated animals and re- act, for instance, refers to warm-blood- are referred to as engineering standards.
quired laboratories to exercise dogs and ed animals, but the regulations written Instead the agency allowed each facility
to ensure the psychological well-being by the USDA exclude rats, mice and to come up with its own plans for dog
of primates. birds. The agency says it does not have and primate well-being, the “perfor-
The “well-being” clause can be con- funds for inspecting the laboratories mance” of which was to be evaluated.
sidered an instance of the public’s im- that use these creatures, which is true; (Because these plans are kept in-house,
posing a scientific paradigm on scientists. animal welfarists, however, say the and not with the USDA, the public can-
An inspector from the U.S. Department omission originally came from lobbying not obtain them through the Freedom
of Agriculture, which administers the by the biomedical community. In 1990 of Information Act.)
Animal Welfare Act, sought expert ad- humane organizations sued to have Researchers are enthusiastic about the
vice at that time on primate psychology. these animals included. Although they flexibility of performance standards,
There was no such thing, he was told. initially won, the suit was thrown out whereas Martin L. Stephens of the Hu-
Now, just 10 years later, primates have on appeal, on the grounds that animal mane Society of the U.S. calls them “eu-
emotions. At the 1996 NIH meeting, protectionists have no legal standing: phemisms for no standards.” USDA in-
Gebhart listed fear, anxiety, boredom, only those who are injured—that is, the spectors are divided. Some argue that
separation and isolation as conditions rats, mice and birds—can bring a civil the standards are vague and unenforce-
to which experimenters should attend suit. Dale Schwindaman of the USDA able. Among others, Harvey McKelvey
in their subjects. And a few labs are even has promised, however, to include these of the USDA’s northwestern region says
trying to enrich the lives of their rabbits. animals within the next five years. they let him use his judgment: “If I see

Trends in Animal Research Copyright 1997 Scientific American, Inc. Scientific American February 1997 91
present to the USDA or the NIH. A pain scale would make it easier for
Or it might be a researcher or IACUCs to rate the suffering involved
technician. in different schemes for doing an exper-
Still, the USDA can offer few iment. At present, the committees are
reassurances to informants. A required to certify that the animal re-
former member of the animal searcher has looked for alternatives and
care committee at New York that the number of animals used is rea-
University Medical Center claims sonable. Alan M. Goldberg of CAAT
to have been fired in August wishes that they would also evaluate the
1995 for protesting irregulari- experimental design. “Right now, using
ties in N.Y.U.’s labs and cooper- method A, they check: Is it the right
ating with the USDA’s investiga- number of animals? They don’t look at
tions. The university states that method B or C”—which could involve
his position became redundant. in vitro techniques. Nor—unlike com-
But the scientist, along with an mittees in Germany, Australia and else-
administrator who was also dis- where—are they required to weigh the
missed, is suing N.Y.U., as well benefits of research against the suffer-
as the USDA—which, he says, ing or to include representatives of ani-
failed to provide whistle-blower mal-welfare organizations in the review
protection. (The agency did fine process. (The IACUCs do have to in-
N.Y.U. $450,000 for assorted clude someone unaffiliated with the in-
violations of the Animal Wel- stitution, but who fills that position is
fare Act.) Several USDA inspec- again a source of controversy.)
PETA

tors express frustration with


their agency’s provisions on in- The Propaganda
ANTIVIVISECTION POSTER attacks the ratio-
formants. “We can’t protect a
nales behind animal research.
whistle-blower,” McKelvey says.
“The regulation is weak.” Un-
an animal is bored with its toy, I can like civil-discrimination suits, which re-
C hange in the U.S. has been slow
and painful. Notwithstanding some
evolution of practices, the ferocity of the
write that it needs a new one. I couldn’t quire only a concatenation of circum- attacks by the most fervent animal right-
do that with engineering standards.” stances, the USDA needs to prove that ists has led to a sense of moral outrage
The new NIH guide also embraces per- the person was fired because of having and an unwillingness to compromise—
formance standards. blown the whistle. on both sides. Almost all activists insist
The animal care committees have em- Also controversial are the statistics that animal research is unnecessary; to
powered those scientists who wish to on pain and distress provided by the them, investigators using animals are
cut down on wastage and improve con- IACUCs to the USDA. They indicate that cruel and corrupt, consumed by a desire
ditions for animals. “If you have an in- in 1995, 54 percent of the regulated an- for ever more papers and grants. One
stitution with conscientious people, the imals had no pain or distress, 37 per- antivivisection tract is entitled Slaughter
IACUC system works fairly well,” says cent had distress alleviated by painkill- of the Innocent, and the cover of an-
Ralph A. Meyer of Carolinas Medical ers, and only 8.8 percent suffered unal- other features splashes of blood. To an-
Center. Cathy Liss of the Animal Welfare leviated pain or distress. The data have imal liberators, the killing of more than
Institute in Washington, D.C., agrees that been widely criticized for being unreli- six billion animals a year, mostly for
some committees do far better than the able, because the USDA does not specify food, represents a holocaust, and Adolf
law. But there is concern about the re- how to classify pain. Andrew N. Ro- Hitler’s doctors are proof that experi-
mainder. In 1992 an audit of the USDA’s wan of the Tufts University Center for menters can be inhumane.
enforcement activities by the Office of Animals and Public Policy has noted that Many animal researchers, in turn,
the Inspector General revealed that out some rather painful procedures, such as think of animal rightists as being brain-
of 26 institutions selected at random, toxicity testing or antibody production, less “bunny huggers” at best and dan-
12 “were not adequately fulfilling their are commonly placed in the nonpainful gerous fanatics at worst. Leaflets pub-
responsibilities under the act.” Everyone category. Although the USDA proposed lished by the American Medical Associ-
agrees that enforcement is inadequate: a pain scale in 1987, it was withdrawn ation represent the animal-rights position
at present, there are only 69 inspectors, after objections by researchers. as equating humans with animals; a
who may not be able to visit each of the There are difficulties with assessing quote from Ingrid Newkirk of PETA,
1,300 regulated laboratories (and also animal distress. Nevertheless, many Eu- “A rat is a pig is a dog is a boy,” is of-
animal dealers, transporters and exhibi- ropean nations, as well as Canada, Aus- fered as evidence. (Newkirk claims her
tors) every year. tralia and New Zealand, have developed statement was “When it comes to feel-
As a result, the inspectors rely on whis- pain scales in which each procedure is ing pain, a rat is a pig is a dog is a boy.”)
tle-blowers. “We need eyes out there,” assigned a grade. As a result, their re- In an essay entitled “We Can’t Sacri-
McKelvey explains. It might be an ani- ports are more informative. The Neth- fice People for the Sake of Animal Life,”
mal-rights activist who has infiltrated a erlands listed in 1995 that 54 percent of Frederick K. Goodwin, former head of
laboratory: groups such as People for animals had minor discomfort, 26 per- the National Institute of Mental Health,
the Ethical Treatment of Animals (PETA) cent had moderate discomfort, and 20 has argued that the issue of animal rights
prepare detailed case histories that they percent suffered severe discomfort. threatens public health. In this vein, re-

92 Scientific American February 1997 Copyright 1997 Scientific American, Inc. Trends in Animal Research
search advocates sometimes portray pro- rective by Congress, the NIH
posals to control animal research as be- awarded about $2.5 million in
ing attacks on human life. For instance, earmarked grants between 1987
one organization advises this response and 1989. But F. Barbara Or-
to a query about experimentation on lans of the Kennedy Institute of
pound animals: “How would you feel Ethics at Georgetown Universi-
if the one research project that may ty charges that the money did
save your child’s life was priced out of not constitute a special alloca-
existence because pound animals were tion for alternatives: 16 of the
banned?” Some writers invoke Hitler as 17 grants went to studies that
proof that animal advocates are antihu- had traditionally been funded.
man: he was an animal lover who passed (Like other public health agen-
anticruelty laws in 1930s Germany. cies worldwide the NIH supports
Finding itself under moral—and some- research into invertebrate, in
times physical—siege, the research com- vitro and computer models that
munity has often retreated behind elec- are not billed as alternatives.)

FOUNDATION FOR BIOMEDICAL RESEARCH


tronic surveillance systems—and an eth- In 1993 Congress directed the
ical code that frequently denounces NIH to come up with a plan for
internal dissent as treason, “giving am- implementing the three Rs. The
munition to the enemy.” One scientist resulting document, entitled
interviewed for this article said that if “Plan for the Use of Animals in
his criticisms became known, he would Research,” is an overview of
be fired. In 1991 two animal researchers, biomedical models, with some
John P. Gluck and Steven R. Kubacki of emphasis on nonmammalian
the University of New Mexico, wrote a systems. “The central message of
MEDICAL NECESSITY of animal experiments
treatise deploring the lack of ethical in- the plan,” explains Louis Sibal
is emphasized in a pro-research poster.
trospection in their field. Gluck testifies of the NIH, “is that scientists
that the article quickly changed his sta- have to decide for themselves
tus from an insider to a distrusted out- what the best method of solving their “It is possible to be both pro research
sider. Arluke’s studies revealed an ab- problem is.” Whereas the European and pro reform,” Orlans says. She and
sence of discussion about ethics: in 33 Union plans to cut animal use in half by others in the troubled middle have a
of 35 laboratories, moral positions were the year 2000, a 1989 NIH report stated simple message: the impasse must end.
defined institutionally. Newcomers were that animal use is not likely to decrease. Animal liberators need to accept that
given to understand that senior scien- One arena in which the propaganda animal research is beneficial to humans.
tists had answered all the difficult ques- battles have been especially fierce is the And animal researchers need to admit
tions, leaving them little to worry about. classroom: both sides see dissection as that if animals are close enough to hu-
The insulation has made it difficult the key to the next generation’s sympa- mans that their bodies, brains and even
for changes in other branches of the life thies. Animal advocates say dissection psyches are good models for the human
sciences—or from across the Atlantic— in schools is unnecessary and brutaliz- condition, then ethical dilemmas surely
to filter in. Primatologists, for instance, ing and that the 5.7 million vertebrates arise in using them. But the moral bur-
have been discussing complex emotions (mostly wild frogs, but also cats, fetal den is not for scientists alone to bear.
in their subjects for decades. But many pigs, pigeons and perch) used every year All of us who use modern medicine and
American experimenters still refuse to are procured in inhumane ways. Re- modern consumer products need to ac-
use the word “suffering,” because it sug- search advocates fear that without dis- knowledge the debt we owe to our fel-
gests an animal has awareness. Even the section, instruction will be inadequate, low creatures and support science in its
word “alternatives” is suspect; instead and fewer students will be attracted to quest to do better by the animals. SA

the NIH describes these as “adjuncts” or or equipped for the life sciences.
“complements” to animal research. In 1989, when the National Associa-
Some researchers seem to regard the tion of Biology Teachers (NABT) an- Further Reading
three Rs as an animal-rights conspiracy. nounced a new policy encouraging al-
Robert Burke of the NIH has stated: “To ternatives, it provoked a violent reaction. In the Name of Science: Issues in Re-
argue that we must refine our methods Barbara Bentley of the State University sponsible Animal Experimentation.
suggests that they are currently inade- of New York at Stony Brook, for in- F. Barbara Orlans. Oxford University Press,
1993.
quate or unethical... . In my view, it is stance, denounced the monograph on
The Monkey Wars. Deborah Blum. Ox-
intellectually dishonest and hypocritical implementing the policy as “an insidi- ford University Press, 1994.
to continue to advocate the original three ously evil publication—evil because it is The Animal Research Controversy:
Rs as a goal for science policy. It is also, a barely disguised tract produced by Protest, Process and Public Policy.
without question, dangerous to give our animal rightists.” An intense campaign Andrew N. Rowan and Franklin M.
enemies such useful tools with which to followed, and in 1993 the NABT issued Loew, with Joan C. Weer. Center for Ani-
pervert the scientific enterprise.” a new policy statement, warning teach- mals and Public Policy, Tufts University
School of Veterinary Medicine, 1995.
Of the 17 institutes included in the ers to “be aware of the limitations of al- More coverage of the animal-rights debate is
NIH, only the NIEHS has been active in ternatives.” There is no high school dis- available on-line at http://www.sciam.com
researching alternatives. Following a di- section in most European countries.

Trends in Animal Research Copyright 1997 Scientific American, Inc. Scientific American February 1997 93