May
1995
Drug
Testing on Trial
By Robert Wilbur
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I had two encounters with a drug called phenylbutazone
(Butazoladin), one in a human being and one in a dog. The human being
was my father, who nearly died of heart failure caused by phenylbutazone,
a powerful non-steroidal anti-inflammatory agent that had been mindlessly
prescribed for a trivial muscular ache. Some time later, my then-sixteen
year old pit bull, Suzy, became increasingly crippled by arthritis of
the spine. Her vet, Dr. Paul Cavanagh of the Westside Veterinary Hospital
in New York City, wanted to prescribe phenylbutazone. I was taken aback
by the suggestion, but Paul assured me that phenylbutazone can be given
safely to dogs. And in fact, Suzy tolerated phenylbutazone without any
problems.
This is just one example of a drug whose toxicity differs in human and
non-human animals. The scientific literature is replete with similar
examples, leading to the conclusion that drugs differ in their effectiveness,
rate of metabolism, and toxicity in different species. Some side effects
can’t even be measured in animal experiments. Thus, in one comparative
survey of six different drugs given to rats, dogs, and humans, 89 different
toxic reactions were observed. Of these reactions, 33 (37%) fell into
the category of headache, depression, ringing of the ears, foul taste
in the mouth, etc., none of which could be measured in rats and dogs.1
The foregoing conclusions have important implications for the present-day
practice of using animals to test chemicals for safety and effectiveness
as drugs in humans. Most of the drugs that reach the market every year
are “me too” drugs, namely compounds that differ in minor
ways from a prototype drug. This should not come as a surprise, since
the animal “models” that are used to screen chemicals are
models that responded favorably to the prototype. If Drug X and Drug
Y differ only by a minor chemical modification, then they’re likely
to have similar biological effects. Not surprisingly, the Food and Drug
Administration estimates that only about 3% of the drugs that reach
the market are significant medical advances.2
Nobel Prize winner Sir James Black, the pharmacologist who discovered
propranolol (Inderal) for treating high blood pressure and cimetidine
(Tagamet) for treating ulcers, is a harsh critic of animal models because
of species differences.3 Black, who now heads his own research institute
in England, believes that drug scientists must work from conceptual
models of receptors — the chemical entities to which drugs
bind in cells — in order to design fundamentally new drugs.
Certainly the outcome of animal experimentation has been pretty pathetic.
Notwithstanding all the pain that has been inflicted on millions of
cats, dogs, mice, rats, primates, and other species, the World Health
Organization concludes that a mere 200 drugs are medically essential.4
What’s more, animal experimentation has failed to come up with
medically essential drugs for major killers like AIDS, cancer, multiple
sclerosis and hundreds of other medical horrors.
Pressure from the animal rights movement, coupled with purely pragmatic
considerations like those expressed by Black, has led to some changes
in drug development. The usual lag time from the test tube to the pharmacist’s
shelf used to be about ten years, but the FDA has slashed this to two
years for AIDS drugs, mainly by drastically reducing the amount of animal
experimentation and getting drugs into clinical (e.g. human) testing
much more rapidly. Animal activists have to keep up the pressure for
prompt clinical testing of all drugs. Second, we must demand alternatives
to preclinical studies using nonhuman animals. Such alternatives are
already in use, and include computer simulation and studies of drug-receptor
interactions derived from tissue cultures. If we are to have credibility
we must demand that experiments be productive and humane; we must demand
an end to the old way of screening drugs because it is inefficient and
hurtful.
1. Litchfield J.T., Jr: "Evaluation of the safety of new drugs
in animals." Clin Pharmacol Ther 3: 665 (1962)
2. PETA Factsheet: "Drug testing: pain, not gain." People
for the Ethical Treatment of Animals: Washington, DC (1995), p. 2
3. Bernard L: "Drug design helped little by animal models."
Cornell Chronicle, April 23, 1992, p. 3
4. PETA Factsheet, ibid. p. 2
Robert Wilbur is a scientist and researcher. He
is also president of the Carriage Horse Strike Force. He lives in New
York City.
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