Quotes from Doctors & Researchers:
It is often claimed that scientists and doctors are united in their belief in the value of, and necessity for, animal experiments to protect human health. This stream of quotes from scientists and doctors, stretching from as far back as the early 20th Century right up to today, shows that there has been a long tradition of scepticism about this issue. Many of the quotes are from scientists who support or conduct animal research; far from diminishing the impact of their words, this fact ought to give them extra weight.
Note: FDA stands for Food and Drug Administration, the US drug regulatory body.
Cancer | Neurological diseases/ conditions | Teratogenicity and thalidomide | Immunology & AIDS & TGN1412 | Miscellaneous
Teratogenicity and thalidomide
2007
It appears
that humans & animal (rodent or non-rodent) models have some differences in
the process of implantation, in addition to the well-known variabilities
with regard to the uptake & metabolism of drugs & chemicals. These
data suggest there is a high uncertainty with regard to the validity of a risk
assessment based on reliance only on animal studies. Therefore, new in
vitro models based on human tissues (cell & tissue culture, uterus
perfusion, etc.) can provide mechanistic information to address the problem of
inter-species variation, & such information can facilitate reliable
predictions which are relevant for human hazard identification. Bremer and colleagues, Alternatives to Laboratory
Animals, 35, 421-439.
All the
parties involved, both in testing for reproductive toxicity & in the
regulatory authorities, are aware of problems in assessing the meaning of
results such as teratogenicity in animal tests. An important consideration is
whether any observed malformation in animal embryo studies is relevant for risk
assessment in relation to human embryos. Bremer
and colleagues, Alternatives to Laboratory Animals, 35, 421-439.
2005
Birth defects induced by maternal exposure to exogenous
agents during pregnancy are preventable, if the agents themselves can be
identified and avoided. Billions of dollars and man-hours have been dedicated
to animal-based discovery and characterisation methods over decades. We show
here, via a comprehensive systematic review and analysis of this data, that
these methods constitute questionable science and pose a hazard to humans. Mean
positive and negative predictivities barely exceed 50%; discordance among the
species used is substantial; reliable extrapolation from animal data to humans
is impossible, and virtually all known human teratogens have so far been
identified in spite of, rather than because of, animal-based methods. Bailey and colleagues, Biogenic Amines, vol.19, N° 2, pp 97-146.
2004
Because most
human teratogens have been discovered by alert physicians or epidemiology
studies, not animal studies, animal studies play a minor role in discovering teratogens...
Well-performed epidemiology studies are still the best method for determining
the human risk and the effects of environmental toxicants. Brent, Pediatrics, 113(4 Suppl):984-95.
1997
The following
comments & recommendations of the National Academy of Sciences/ National
Research Council (1997) concerning teratogenicity testing are equally pertinent
to in utero studies of potential
carcinogenicity: “The ideal animal for teratological testing would have the
following characteristics: (1) the ability to absorb, metabolize, &
eliminate the test substance in a manner similar to that of man, (2) the
ability to transmit the substance & its metabolite across the placenta as
does man, and (3) embryos & fetuses that have developmental schedules &
metabolic pathways similar to those in the human conceptus. Existing
comparative data are too limited for a judgement as to which animal is most
like man in any of these regards; but it is already apparent that no presently
used species, including simians, resembles man in all of these respects.
Furthermore, it is evident that the degree of similarity to man exhibited by a
given species varies from 1 test substance to another.
1994
What is
noxious or ineffective in nonhuman species can be innoxious or effective in
humans. For example, penicillin is fatal for guinea pigs but generally well
tolerated by human beings; aspirin is teratogenic in cats, dogs, guinea pigs,
rats, mice, and monkeys but obviously not in pregnant women despite frequent
consumption. Handbook of Laboratory Animal
Science Volume II Animal Models, p4, Svendensen and Hau (Eds.) (CRC Press).
Uncritical
reliance on the results of animal tests can be dangerously misleading and has
cost the health and lives of tens of thousands of humans. Handbook of Laboratory Animal Science Volume II Animal
Models, p4, Svendensen and Hau (Eds) (CRC Press).
1987
Drugs known to
damage the human foetus are found to be safe in 70% of cases when tried on
primates. Developmental Toxicology:
Mechanisms and Risk, p313,
McLachlan, Pratt, and Markert (Eds).
"...there
is no ideal animal model to extrapolate teratogenicity results to human
exposure because of species sensitivity and species difference. Dr Lin, In Vitro Toxicology, vol 1.
More than 800 chemicals have been
defined as teratogens in laboratory animals, but only a few of these,
approximately 20, have been shown to be teratogenic in humans. This discrepancy
can be attributed to differences in metabolism, sensitivity and exposure time. Schmid, Trends in Pharmacological
Sciences, vol 8, p 133.
1985
It is the actual results of
teratogenicity testing in primates which have been most disappointing in
consideration of these animals’ possible use as a predictive model. While some
nine subhuman primates (all but the bushbaby) have demonstrated the
characteristic limb defects observed in humans when administered thalidomide,
the results with 83 other agents with which primates have been tested are less
than perfect. Of the 15 listed putative human teratogens tested in nonhuman
primates, only eight were also teratogenic in one or more of the various
species…. Schardein, Chemically
Induced Birth Defects (publ.
Marcel Decker).
A number of different animal
species have been used in teratological research in an attempt to determine the
most satisfactory model for predicting the hazard to humans…No single species
thus far evaluated, however fulfills all criteria. Schardein, Chemically Induced Birth Defects (publ. Marcel Decker).
1983
The great majority of perinatal
toxicological studies seem to be intended to convey medico-legal protection to
the pharmaceutical houses and political protection to the official regulatory
bodies, rather than produce information that might be of value in human
therapeutics. Prof Hawkins, Drugs
and Pregnancy: Human Teratogenesis and Related Problems, p 41-49 (publ. Churchill Livingstone).
1982
Unfortunately
species variation in the sensitivity to drug teratogenicity is very widespread.
Even within a species considerable variation can be demonstrated between
different animal strains... Faced with such complexity it is not surprising
that teratological testing based on animal tests has a poor predictive power
and is thought to do little more than exclude grossly toxic substances. Dr Lewis, Archives of Toxicology, suppl 5, p 195-196.
What is the value of routine tests
in animals for prediction of chemical teratogens? The correlation between known
effects in laboratory animals and clinical adverse effects is very low. Dr Larsson and colleagues, in a letter to The
Lancet, p 439, 21st August.
1980
There is at
present no hard evidence to show the value of more extensive and more prolonged
laboratory testing as a method of reducing eventual risk in human patients. In
other words the predictive value of studies carried out in animals is
uncertain. The statutory bodies such as the Committee on Safety of Medicines
that require these tests do so largely as an act of faith rather than on hard
scientific grounds. With thalidomide, for example, it is only possible to
produce specific deformities in a very small number of species of animal. In
this particular case, therefore, it is unlikely that specific tests in pregnant
animals would have given the necessary warning: the right species would
probably never have been used. Prof George
Teeling‑Smith, A Question of Balance; the benefits and risks of
pharmaceutical innovation, p 29,
publ. Office of Health Economics.
The extensive animal reproductive
studies to which all new drugs are now subjected are more in ...the nature of a
public relations exercise than a serious contribution to drug safety. Prof R W Smithells, Monitoring for Drug
Safety, ed. Inman, p
306-313.
In the absence
of useful tests for teratogenicity clinicians have to accept responsibility for
drug exposures in early pregnancy... if clinicians were more aware of the
shortcomings of animal teratogenicity testing they might take this
responsibility more seriously. Dr Peter Lewis,
senior lecturer in clinical pharmacology at Hammersmith Hospital, London, Monitoring
for Drug Safety, ed. Inman, 1980.
1978
There is a fundamental lack of
knowledge of pathogenesis of most malformations and, therefore, extrapolation
to man has to be done with reservation and care. Negative results cannot be
used to predict that an agent will lack teratogenic effect in man. Dr
Ralph Heywood, Journal of the Royal Society of Medicine, vol 71, p 686-689, 1978.
1976
In
approximately 10 strains of rats, 15 strains of mice, 11 breeds of rabbits, 2
breeds of dogs, 3 strains of hamsters, 8 species of primates and in other such
varied species as cats, armadillos, guinea pigs, swine and ferrets in which
thalidomide has been tested, teratogenic effects have been induced only
occasionally. Schardein, J.L., Drugs as
Teratogens, 1976 and Schardein, J.L., Chemically Induced Birth Defects,
1985.
1969
Any chemical can cause birth
defects in humans and/or animals if given at the right time in pregnancy and in
the right amount. Common table salt and even water are teratogens in some
species if given at the right time in the right dose. Acta Anat Nippon 1969; 74:121-4 and Teratology 1971; 4:427-32.
1966
Numerous
attempts to reproduce the malformations which occurred in human babies from
Thalidomide-treated mothers have met with only limited success. Although many
representatives of aves [birds] and mammalian experimental species have been
investigated for this purpose, the results fall short of paralleling the effect
of the drug on the human foetus. Hendrickx,
Axelrod, Clayborn, Nature, 210:958-959.
1965
The factors influencing the
response of an embryo to a drug interact in such complicated ways that one
cannot predict whether a drug will be teratogenic in man from results obtained
in animals…The results are interpreted to cast doubt upon the reliability of
the use of the rat as an adequate laboratory test for possible teratogenic
agents in man. McColl, Globus
and Robinson, Effect of some therapeutic agents on the developing rat foetus. Toxicology
and Applied Pharmacology, 7, 409-417.
1963
We chose a
dose of thalidomide close to the estimated amount required to produce human
anomalies. This dose had no detectable toxic effects in the monkey... Science 1963; 139:1294-95.
1962
Grünenthal has
tried to reproduce phocomelia in rats, mice, and rabbits and has failed, In
Keil the drug was fed to hens and the chicks were normal. Taussig, Journal of the American Medical
Association, 180: 1106–14. |
