Since the 1960s, when thousands of babies with malformed limbs and other birth
defects were born to women taking the sedative and anti-nausea medication
thalidomide, all drugs and other chemicals have increasingly been
subject to safety testing in animals.
Our survey exposes a testing system
that performs so poorly that one could almost obtain a similarly
successful predictive rate by flipping a coin. |
Researchers have tested chemicals on a wide variety of pregnant
animals in hopes of determining how “safe” the substances
may be for humans. The object has been to identify any “teratogens,”
substances that cause birth defects. Over the decades, they’ve
compiled vast amounts of data on substances ranging from pharmaceuticals
to pesticides and plastics. And tens of millions of rodents, monkeys,
dogs, cats, pigs, cows, sheep, and ferrets—to name but a few
of the species—have inhaled, or been force-fed or injected
with, thousands of such chemicals in order to assess their effects
on the development of the animals’ unborn offspring.
These tests rely, of course, on the basic assumption that their
results are applicable to pregnant human beings. A comparison of
animal test data with what is known about human birth defects reveals
how flawed this assumption is. My colleagues and I recently conducted
a comprehensive review of animal experiments used to test 1,396
different substances. Our findings showed:
- Almost half of all animal experiments involving substances
known to cause human birth defects indicate that they are “safe.”
- Almost half of all animal experiments using substances known
to be safe in humans indicate that they are dangerous.
- Finally, almost one-third of all substances tested yielded
varying results, depending on the species.
No Better Than a Coin Toss
Our survey exposes a testing system that performs so poorly that
one could almost obtain a similarly successful predictive rate by
flipping a coin. Indeed, virtually every human teratogen was initially
identified as a result of epidemiology and clinical case studies—that
is to say, despite, rather than because of, animal testing.
In the case of thalidomide, it wasn’t until 12,000 babies
were born with missing and deformed limbs and other birth defects
that the drug was pulled from the market. Animal testing prior to
its release had revealed a very low level of toxicity, and subsequent
“retrospective” experiments using pregnant animals were
largely negative and eventually showed characteristic limb defects
in only a few specific breeds of rabbits and monkeys. Where teratogenesis
did occur, the effects were highly variable, inconsistent, and often
of low incidence and only when extremely high doses had been administered.
Far from serving to protect millions of human children from premature
death or a life of suffering and disability, animal testing may
actually be one of the major causes of such tragedies. The consequences
are many: Harmful drugs and chemicals are reaching the marketplace
because of erroneous suggestions of safety in animals. Conversely,
potentially beneficial drugs may well be discarded before they can
be used. And many substances remain without a firm classification
of risk, due to the disarray in animal test results; after all,
how does one conclude that a substance does or does not pose a risk
to humans when the animal results are a mix of positives and negatives?
The problem stems from fundamental biology: There are simply too
many differences in physiology and biochemistry for animals to be
good predictors of what will cause birth defects in humans. No nonhuman
animal species absorbs, metabolizes, or eliminates test substances
like a human.
Long History of Failure
Notable examples of the discordance found in teratology include:
- Cortisone, a prescribed steroid, that is harmless in humans
but teratogenic in every animal species tested.
- Diazepam (Valium), the ubiquitous tranquilizer that can cause
human birth defects when taken by women early in a pregnancy.
Birth defects are seen in the offspring of mice and hamsters,
but only at doses of dozens to hundreds of times greater than
the human dose. Similarly large doses have no teratogenic effect
on rats or rabbits.
- Aspirin, a classic teratogen in numerous species (mice, rats,
rabbits, cats, and dogs), which is not classed as a teratogen
in humans.
Better Tests Are Available
Better test methods exist. The best of them, the Embryonic Stem
Cell Test (EST), utilizes cells that can be grown indefinitely in
the laboratory. In official validation tests conducted by the European
Centre for the Validation of Alternative Methods, this test was
found to have an accuracy of 78 percent—a significant improvement
on the animal-based equivalent. In addition, it is much cheaper,
easier and quicker to perform, and more repeatable and reliable.
The advent of the EST appears to be timely: 400 new drugs and between
50,000 and 70,000 new chemicals are introduced to the market each
year. Even if animal tests were predictive, they would have a tough
time keeping pace with these numbers. Clearly, it’s time to
embrace safer new technologies to minimize risk and make sure another
thalidomide crisis never occurs.
 The
findings summarized in this article are to be published in a full
and extensive review in the European scientific journal Biogenic
Amines in May 2005. An abstract can be read on the journal's Web site.
Jarrod Bailey, Ph.D., is a project development coordinator
in the School of Population and Health Sciences at the University
of Newcastle Upon Tyne in England and a PCRM consultant.
Media
Center | Health | Research
| About PCRM | Catalog
| Join Us | Search
| Site Index | Home
The site does
not provide medical or legal advice. This Web site is for information purposes
only.
Full Disclaimer | Privacy Policy
|
