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
Neurological diseases/ conditions
2009
In brain
tumour research it is clear that the development of three-dimensional tissue
culture models, which utilise both cells and serum of human origin, offer a real
alternative to some of the established laboratory animal models which have been
found to be wanting when clinical translation to the disease in man is
considered. Geoffrey J Pilkington BSc PhD CBiol
FIBiol FRCPath, Professor of Cellular & Molecular Neuro-oncology, School of
Pharmacy & Biomedical Sciences at University of Portsmouth http://www.politics.co.uk/opinion-formers/press-releases/animal-welfare/adi-meps-buckle-under-vivisection-industry-pressure-$1293593$464772.htm
2008
The following quotes are all taken from: Jim Schnabel,
Standard Model: Questions raised about the use of
‘ALS mice’ are prompting a broad reappraisal of the way that drugs are tested
in animalmodels of neurodegenerative disease. Nature, Vol 454,682-685.
- The results of drug tests in mice have
never translated perfectly to tests in humans. But in recent years, and
especially for neurodegenerative diseases, mouse model results have seemed
nearly useless.
- In the past year, for example, three
major Alzheimer’s drug candidates, Alzhemed (3-amino-1-propanesulphonic acid),
Flurizan (tarenflurbil) and bapineuzumab, all of which had seemed powerfully
effective in mouse models, have performed weakly or not at all in clinical
trials involving thousands of human Alzheimer’s patients.
- In the case of ALS [amyotrophic lateral
sclerosis, a progressive, usually fatal disease of the nerves], close to a
dozen different drugs have been reported to prolong lifespan in the SOD1 mouse,
yet have subsequently failed to show benefit in ALS patients. In the most
recent and spectacular of these failures, the antibiotic minocycline, which had
seemed modestly effective in four separate ALS mouse studies since 2002, was
found last year to have worsened symptoms in a clinical trial of more than 400
patients.
- The wrong model?
Perhaps
the biggest issue facing the field is whether the mouse models faithfully
reproduce the biology of the human disease. Alzheimer’s mouse models
typically develop amyloid ‘plaques’ in their brains, but they do not develop
an Alzheimer’s-like dementia and anti-amyloid strategies have repeatedly
failed to slow the disease in clinical trials.
- Parkinson’s researchers have never had
a good mouse model for the full disease process, and even the mouse model for
Huntington’s disease — a relatively simple genetic disease— does
not fully reproduce the clinical signs seen in humans with the disorder.
- The debate over [the ALS mouse model's]
relevance to the majority of human ALS cases feeds a broader worry, namely that
it may be unrealistic to think of modelling the ful complexity of
ageing-related human brain disorders in mice whose disease course is usually
accelerated by a single, crude genetic modification.
- ...Mouse models could therefore end up
being not only more difficult and expensive to use with acceptable rigour, but
at the same time more narrowly predictive of the human condition.
- But whether preclinical researchers
will accept such a radical change remains to be seen.
“I
think there’s a sense of desperation that we need a convenient model for bringing
drugs to clinical trial,” says Benatar. “And I do sort of hear that concern.”
But desperation, he adds, is an inadequate justification for the continued
use of a poor model. “It’s a bit like the proverbial drunk who keeps looking
for his lost keys under the lamp post, simply because the light’s better there.”
2007
Testing drugs
against AD on animals is not easy because animals don’t develop the disease.
When using mice, scientists need to artificially induce one or several
mutations in the mice and check whether they develop symptoms of the disease
that are similar to the human ones. We showed that some of the mice currently
bred to develop the disease don’t get better when they receive previously
tested drugs. Professor Sascha Weggen,
Heinrich-Heine-University, Germany, quoted on the American Society for
Biochemistry and Molecular Biology website (16th August), referring to his
article published in the Journal of Biological Chemistry, 282: 24504 - 24513.
In my
research, animal models don't represent human patients sufficiently well, and that's a problem that extends across pain research as
a whole. New and highly sophisticated brain-imaging
technology is providing vital insights that animal research has failed to
produce. I would like to see far greater uptake of these and other
human-relevant approaches to pain research. Professor Qasim Aziz, the Barts and the London School of
Medicine and Dentistry, speaking at the Pain workshop organised by Focus on
Alternatives, April.
Our study
shows that these mouse breeds may not reflect what may really happen in the
brains of Alzheimer’s patients if they were treated with such compounds in
future clinical studies. These compounds may seem to be ineffective on these
mice, while it’s actually the mouse breed that is to blame. Professor Sascha
Weggen. Professor Sascha Weggen, Heinrich-Heine-University,
Germany, quoted on the American Society for Biochemistry and Molecular Biology
website (16th August), referring to his article published in the Journal of
Biological Chemistry, 282: 24504 -
24513.
The following
quotes are taken from: Andrea Gawrylewski, The Scientist, The Trouble with Animal Models, Volume 21, Issue 7,
Page 44.
- "There's no doubt about the absence of an effect [of
NYX-059], and that called into question the many other studies in stroke, and
how good are the animal models?" says Gilman. “So many agents appeared to
be effective in the animal model and failed in human trials.” (Sid Gilman,
Director of the Michigan Alzheimer's Disease Research Center in the Department
of Neurology at the University of Michigan). Because of these failures,
hundreds of millions of dollars, and a potential approach to stroke treatment,
have disappeared down the drain. The failure of NXY-059 may have stalled the
quest for a neuroprotective agent, at least for some time. "This trial has
poisoned stroke studies," says Gilman. "I'm doubtful that investors
will want to invest in clinical stroke trial[s] for a while." The fault,
it appears, may rest in the slipshod use of animal models.
- To the dismay of clinicians and researchers of acute stroke, the
compound showed limited efficacy in neuroprotection versus the placebo.
Instead, NXY-059 joined the family of more than a dozen failed neuroprotective
agents... All had reached Phase III clinical trials and failed miserably at
doing what their animal model tests had suggested they would: stop the cascade
of necrosis in the event of stroke, and protect the remaining viable brain
cells.
- That NXY-059 had fallen victim to the same fate was particularly
disheartening to a stroke roundtable group that had, in 1999, directly
addressed the disconnection between animal models for stroke and their
counterpart human trials. The group had devised a set of guidelines whose aim
was to standardize the path to stroke therapeutics. During its development,
NXY-059 had been its poster child. "This drug was being hailed as the
first one to follow the standards," says Sean Savitz, assistant professor
of neurology at Harvard Medical School. "But it didn't do that."
- The difficulties associated with using animal models for human
disease result from the metabolic, anatomic, and cellular differences between
humans and other creatures, but the problems go even deeper than that. One of
the major criticisms of the NXY-059 testing was the lack of correlation between
how the effects of the drug were monitored in animals versus in humans… Indeed, some consider the two phases of testing, from
animal to human, completely out of whack, and that only by statistical fluke
was SAINT I, the first clinical trial, deemed a success.
- Nonetheless, even genetically manipulated mice have their
problems. The current knockout mouse model for amyotrophic lateral sclerosis
(ALS) may be completely wrong, according to John Trojanowski at the University
of Pennsylvania School of Medicine…Until now, research has focused primarily on
SOD-1 knockout mice, with virtually no success in human trials. The new
findings relating to the TDP-43 protein suggest that the SOD-1 knockout model
for ALS could be wrong. "There was this nagging doubt" about the
validity of the current models, Trojanowski says.
- A recent study at the Massachusetts Institute of Technology shows
distinct differences between gene regulation in humans and mouse liver… they
found that transcription factor binding sites differed between the species in
41% to 89% of the cases.
- Many of the underlying limitations associated with mice models
involve the inherent nature of animal testing. The laboratory environment can
have a significant effect on test results, as stress is a common factor in
caged life.
- Richard N. Sifers, Associate Professor, Departments of
Pathology and Molecular and Cellular Biology, University of Oklahoma Health
Sciences Center, Baylor College of Medicine commented on the above article:
“We, as
scientists, must admit that models are simply models! Although statistical
robustness is certainly needed in animal studies, it must be accepted that
models do not, and often cannot, recapitulate sophisticated human physiology.
Similarities exist between apples and oranges (both are round and contain
seeds), but one had better focus on an apple tree if interested in
understanding the intimate details of its fruit. In a similar manner, only in
very limited ways will any non-primate model recapitulate human physiology.
However, these vast differences are not identified until one examines systems
at a biochemical level, and this has become a very rare event. For too long, we
have studied evolution in terms of investigating similarities between different
species. These examples gave us clues as to the existence of evolution.
However, the evolutionary process, by definition, actually refers to the vast
differences that exist between species, and even between cells within a given
species. Although many of the genes are shared, the regulation of their
products can differ considerably!
I suspect that even if all the animal models faithfully mimicked the actual
primary defects found in human diseases that they would still fall short of
mimicking the human situation. Finally, model systems are certainly appropriate
for some endeavors, but they will likely fall short (more times than not) when
trying to identify drugs that will correct human diseases. For this reason, I
sometimes wonder to what extent science actually advanced (in terms of
understanding human disease) during the genomics era?”
All the following quotes are from: Faden &
colleagues, Archives of Neurology. 2007;64:794-800.
- The ability of pharmacological agents to limit secondary
biochemical damage and cell death has been well established in numerous animal
models of stroke, head injury, and spinal cord injury, yet the results of such
neuroprotective treatment strategies in human injury have been disappointing.
- However, after numerous failed clinical trials of drugs showing
preclinical promise, questions have been raised about the relevance of current
experimental models for human brain or spinal cord injury.
- Critical preclinical issues include the clinical predictiveness/
relevance of animal models, the adequacy of pharmacological methodology, and
outcome measures used.
- Numerous methodological problems have been raised with regard to
development of animal models that have meaningful clinical relevance. One area
of concern relates to the choice of species, strain, or sex of the animal. For
example, how well do models of brain trauma or ischemia in rodents reflect
injury in higher species? Moreover, even within a given species, the same model
can produce vastly different injury levels and outcomes across various strains.
This issue is critical both for evaluating drug targets and regarding the
choice of outcomes.
- Lastly, most animal models are highly constrained. To increase
consistency, genetically identical animals are used under highly controlled
experimental conditions.
- Such studies highlight the important caveat that even strong
experimental data in lower species may not predict therapeutic effectiveness in
human injury.
The field of
Parkinson's Disease (PD) research was greatly stimulated by the therapeutic
attempts of neurosurgeons using dopaminergic brain transplantation in animals
and humans which came to the fore in the 1980s and have since largely receded.
There have been too many false positives to record here. Many possible false
negatives may also have been ignored as part of widely documented publication
bias. The most common non-human primate model of PD results from monkeys being
poisoned with the neurotoxin MPTP. It is widely acknowledged that profound
disparities (anatomical, physiological, neurochemical, pathological, and temporal)
exist between the MPTP non-human primate model and humans with idiopathic PD.
Despite these paramount concerns of human reproducibility, hundreds of studies
involving thousands of animals have followed with conflicting and
non-predictive results. There is no evidence to suggest that their overall
predictive concordance with human PD treatment, if subjected to the meticulous
quantitative analysis of Perel and co-workers (BMJ 2007;334:197-200), would
exceed the best case 50:50 coin toss probability established. Dr Marius Maxwell, Oxford, Cambridge &
Harvard-trained neurosurgeon.
2006
We have to
remember that what works in mice does not unfortunately always work in men. Dr Lee Dunster, head of research and information at
the Multiple Sclerosis Society, quoted in http://news.bbc.co.uk/1/hi/health/5245048.stm 6th August 2006.
Experimental allergic
encephalomyelitis is not a suitable animal model for testing treatments
for multiple sclerosis and it is time to explore alternative experimental and
therapeutic approaches. Abhijit
Chaudhuri, consultant neurologist, British Medical
Journal, 2006;332:416-419.
Researchers
have long sought a neuroprotectant drug that could salvage some of the brain tissues
starved of oxygen after a stroke. But of more than 100 drugs that have entered
major clinical trials over the past couple of decades after strong results in
animals, none has proven effective in patients. That's probably because the
artery-clogging clots in the human brain are caused by a diverse collection of
underlying diseases that are not reflected in animal models. Pearson, Nature 444, 532 - 533.
Compounds to
treat cancer and central nervous system disorders, including stroke, have
particularly high failure rates - partly because animal models are such a poor
mimic of the way these diseases affect humans. Pearson, Nature 444, 532 - 533.
Translation
of positive results obtained in the laboratory into the clinic has been
exceptionally elusive, and the stroke [research] community needs to think long
and hard about whether these animal models are financially and ethically
viable. The Lancet, 368:1548.
2005
For stroke, the [animal] models
and the clinical condition are extremely different, which is reflected
in the failure of molecules in the human condition. Carney, Drug Discovery Today, 10, 1025–1029.
Already then (1980) I had a few reservations about such experimental models...I pointed out
my doubts and asked whether the
treatment would have an equal efficacy in humans
as it had in rats. There was no good answer. Twenty-four years later and having been a principal investigator and a
steering committee member in many
acute stroke trials, I still have my doubts. Kaste, Use of animal models has not contributed
to development of acute stroke therapies: Pro, Stroke 36, 2323–2324.
Since the early days of neuroprotecting agents in
treatment of acute stroke, more than
700 drugs have been studied and more than
4000 papers describing their neuroprotective efficacy have been published, and yet none of those
drugs has been accepted by regulatory
authorities to be used for treatment of patients with acute stroke in the United States or the European Union. Kaste, Use of animal models has not contributed to
development of acute stroke therapies: Pro, Stroke 36, 2323–2324.
Animal models have helped us better understand the
pathophysiology of ischemic brain damage, but have they otherwise contributed
much to clinical practice so far? I cannot say that they have, whereas
randomized, clinical trials (RCTs) have had a major impact. The need of
discipline, an essential part of any RCT, has influenced ordinary patient care
in many positive ways. I do not expect either that more developed animal models
could contribute to emergency stroke care so that a neuroprotective agent would
be able to reduce the volume of an infarct in patients with stroke by 50% as
they do in rats, at least if the therapy is not combined with thrombolysis or
other neuroprotective therapies. Kaste, Use of
animal models has not contributed to development of acute stroke therapies:
Pro, Stroke 36, 2323–2324.
It must be recognized that no animal stroke model
will precisely mimic human acute
ischemic stroke, a condition that is quite heterogeneous. Recognizing the inherent limitations of animal stroke
modeling should provide important
lessons for both basic and clinical stroke researchers. Fisher and Tatlisumak, Use of animal models has not
contributed to development of acute stroke therapies: Con, Stroke 36, 2324–2325.
Many stroke clinicians have been perplexed by the
failure of other compounds trialed
over the past 2 decades, despite strong evidence
for efficacy in animal models. Donnan and Davis, Stroke 36, 2326.
One striking exception to the conventional pathway
of drug development has been the
positive results using recombinant factor VIIa to attenuate hematoma growth in patients with primary intracerebral hemorrhage. The biologic plausibility of
this approach was based on clinical
studies of the dynamics of hematoma growth documented
by repeated computed tomography scans rather than animal models. The compound was already in clinical use as a hemostatic agent for another indication.
This illustrates our view that
although the majority of candidate stroke compounds need to be evaluated in preclinical animal models, there is always a place for astute clinicians to
recognize the potential of compounds
already in use for another clinical indication. Donnan
and Davis, Stroke 36, 2326.
2004
The
following quotes are all taken from: Stephen H. Curry, Trials and Tribulations
in the Search for Stroke Drugs, Preclinica, Vol. 2, No. 6, November/December,
p378-381.
- Side effects in patients are often very
difficult to predict from animal safety studies or even from healthy human
volunteers.
- Animal studies can be and often are
conducted with a variety of treatment delays, in order to determine the window
of opportunity in the species concerned, but there is little basis for
extrapolation of that information to humans.
- Central to this entire problem is the
extreme difficulty of extrapolation from animals to humans.
- Some remarkable efficacies have been
demonstrated in laboratory animals. Logical attempts have been made to relate
the doses used and the drug concentrations in the blood supply to the brain in
the various species, so that the human exposure is similar to that shown to be
efficacious in animals. Yet, with remarkable and alarming repeatability, the
promise of the animal results has not been borne out in the clinic, raising
important questions concerning whether the entire process is flawed. It may be
that experimental strokes in animals differ fundamentally from spontaneous
stroke in humans or that the models are not being used properly.
- It may be impossible to produce a model
of human stroke in the laboratory.
- In the most exhaustive analysis of the
relevance of animal models to date, Green et al. first documented the most
recent failures (in the 3 years up to and including 2003), bringing the score
card to greater than 37 potential neuroprotective agents in more than 114
clinical trials, with no clinically efficacious agent identified or in use in
the Western world.
- A further challenge with NMDA
antagonists is a relative lack of subcortical protection, and attention has
also been drawn to the fact that rat brains contain relatively little white
matter, which is a major area of damage in humans.
- Humans tend to have longer
pharmacokinetic half-life values than do rats, but not in proportion to body
weight.
- Thus, in the human, the rise in
glutamate after initiation of a stroke is slower than in the rat, the maximum
concentration reached is lower, but the glutamate half-life is many times that
of the rat.
2003
Any suggestion about which is the ‘best’ rodent
model to test putative neuroprotective agents is likely to prove contentious.
Most investigators have personal variants of the major published models and all
claim that their model has particular relevance, even though the predictive
value cannot be demonstrated in the absence of a clinically efficacious drug. Green & colleagues, Animal models of stroke: do
they have value for discovering neuroprotective agents? Trends in
Pharmacological Sciences, Vol.24
No.8, p402-408.
It was proposed recently that animal models should
be modified to reflect more accurately the complexity of human stroke. This is
a near impossible goal, particularly for the purposes of drug screening. Green & colleagues, Animal models of stroke: do
they have value for discovering neuroprotective agents? Trends in
Pharmacological Sciences, Vol.24
No.8, p402-408.
Although it was suggested .10 years ago that animal
models were flawed and would not produce a reliable prediction of clinical
efficacy, they have continued to play a key role in the evaluation of putative
neuroprotectants. Green & colleagues, Animal
models of stroke: do they have value for discovering neuroprotective agents? Trends
in Pharmacological Sciences, Vol.24
No.8, p402-408.
2002
Alzheimer's,
Parkinson's and other neurodegenerative diseases occur in humans and it is in
human tissue that we will find the answers to these diseases. Dr. John Xuereb, Director of the Cambridge Brain Bank
and Wolfson Brain Imaging Centre, BBC Radio Cambridge 7th February.
Discovery of drugs that
act on the human central nervous system, are best studied in human-cell based
systems. Drs Palfreyman,
Charles and Blander, The importance of using human-based models in gene and
drug discovery, Drug Discovery World, Fall 2002, p33-40.
The following quotes are from: Behan
PO, Chaudhuri A, Roep BO. The pathogenesis of multiple sclerosis revisited. Journal Royal College
Physicians Edinburgh, 32:244-265.
- Experimental allergic encephalomyelitis (EAE: the animal
“model” used for MS) is totally different clinically, immunologically and
histologically from MS although it does have similarities with other human
demyelinating diseases.
- Experimental allergic encephalomyelitis has been used as
a model for MS and it is the best studied organ-specific autoimmune disease: it
is not acceptable as a model for MS for many reasons, some of which have
already been alluded to...Treatment protocols in EAE are many but those used in
humans, based on the findings in animal EAE, have singularly failed in alleviating
the symptoms and signs of MS. Our contention is that it is inaccurate to
extrapolate the findings in this putative animal model to the pathogenesis of
human MS.
- Suffice it to say that the immunological reactions
involved in EAE, whilst of clear importance in their own right in elucidating
pathogenesis, have not been shown to occur in humans. Thus therapeutic
strategies based on findings in EAE have failed to succeed in humans.
- A large number of potential MS therapies have been
envisaged from experiments in animals with EAE...The list is far from complete
but it should be stressed that the application of these potential therapeutic
techniques to humans has been consumately associated with failure.
- Attempts at therapy based on experiments in rodents with
EAE have so far failed.
- It is difficult, if not impossible, to induce EAE in
neonatal animals;108 immunisation is only successful after a certain age. This
is very important since the age at which animals become susceptible to
developing EAE corresponds in humans to about the age of two years...If
sensitised lymphocytes invading the brain are thought to be involved in the
pathogenesis of MS, one might therefore not expect to find MS occurring below
the age of two. However, there have been several reports of MS occurring in
infants.
- The acceptance of EAE as a model for MS is an unfortunate
error that has its basis on faith rather than science. Whilst EAE is a good
example of an experimental organ-specific autoimmune disorder in animals, it
cannot be accepted as a model for MS for a wide variety of reasons. This is
particularly important in relation to the development of MS pharmacotherapy.
The following
quotes are from: Gladstone &
colleagues. Toward wisdom from failure: lessons from
neuroprotective stroke trials and new therapeutic directions. Stroke 33:2123-2136.
- Neuroprotective
drugs for acute stroke have appeared
to work in animals, only to fail when tested in humans.
- Of >49 neuroprotective agents studied in >114 stroke trials, none has
proven successful clinically.
Similarly, neuroprotective therapy has been unsuccessful in clinical trials of head trauma. With the failure of so many trials, some clinicians may
ask, "Is neuroprotective stroke
therapy just a fantasy invented by basic scientists?" Will it ever play a clinical role? The
answer is unclear. Gladstone &
colleagues. Toward wisdom from failure: lessons from
neuroprotective stroke trials and new therapeutic directions.
- Reasons for the failure of so many
neuroprotective agents in clinical
trials, despite their apparent benefit in animal (mostly rodent) models, have been the subject of intense discussion recently. In addition, despite significant similarities between
the rodent and human genomes, the
differences that do exist are sufficient to remind us that conclusions reached regarding genomic and proteomic characteristics in rodent studies may not
apply to human stroke.
- Neuroanatomical, pathophysiological,
pharmacokinetic, and genetic differences
between rodents and humans notwithstanding, there has been a fundamental "disconnect" in the way that
the efficacy of putative
neuroprotective agents has been assessed in animal studies compared with clinical trials.
- Experimental stroke models are
homogeneous, whereas human stroke is heterogeneous.
1999
The following quotes are from:
Recommendations for Standards Regarding Preclinical Neuroprotective and
Restorative Drug Development, Stroke, 30:2752.
- Despite
much animal research concerning the pathophysiology of focal ischemic brain injury,
little of this work has translated into effective treatment modalities for
stroke in humans.
- What
remains curious is that although many of these agents appear quite effective in
preclinical studies with small-animal models of ischemia (rats, mice, or
gerbils), none of these have been conclusively effective in humans.
- A
drug dose effective in the mouse or rat may or may not be effective in large
animals &/ humans. It may not be sufficient or correct to merely scale up
the dose of a drug in milligrams per kilogram from the mouse to larger animals
& humans. Pharmacokinetics & pharmacodynamics may vary considerably
among species.
- Another
aspect to consider is that neuroprotective drug dose ranges & toxicities in
animals may not overlap with those tolerated in humans.
- Gerbil
models should be avoided because many pharmacological agents act as protectants
in gerbils but not in other species.
- No
animal model can exactly mimic stroke in humans.
- It
is uncertain if benefit in young, healthy animals can be extrapolated to
elderly, sick humans.
- There are a number of dissimilarities
between the rodent brain & that of humans & nonhuman primates that may
lead to differences in response to an identical ischemic insult. Therefore it
is difficult to know how to scale up dosing regimens from rodents to humans...
As noted above, recovery in rodent models occurs rapidly over the 1st few weeks after stroke. Recovery in humans with stroke may occur over a longer
time, up to several months after stroke. Thus timing & duration of drug
administration for humans is not easily extrapolated from rat models. A similar
concern applies to drug dosage.
1993
For cortical
regions, such as the language areas, we cannot use the macaque brain even as a
rough guide as it probably lacks comparable regions." Crick and Jones, Nature, 361: 109-110.
1990
Ultimately,
the answers to many of our questions regarding the underlying pathophysiology
and treatment of stroke do not lie with continued attempts to model the human
situation more perfectly in animals, but rather with the development of
techniques to enable the study of more basic metabolism, pathophysiology and
anatomical imaging detail in living humans. Professor
David Wiebers, Mayo Clinic, Stroke, 21: 1-3.
Over-reliance
upon such animal models may impede rather than advance scientific progress in
the treatment of this disease. Professor David
Wiebers, Mayo Clinic, Stroke, 21:
1-3.
1989
The repeated
failures of laboratory proven stroke therapies in humans can be due only to the
inapplicability of animal models to human cerebral
vascular
disease." Neff, Stroke, 20:699-700.
1987
It is clearly
not easy to establish a reliable indicator of the relative toxicities of the
various anti-depressants, although some form of comparison is necessary. The
'natural experiment' of cases of self-poisoning has to be taken as the starting
point as the results of experiments in animals cannot reliably be extrapolated
to man and the induction of even mild toxicity in man, besides being unethical,
may in any case not correspond to the drug's lethal toxicity. Drs Cassidy and Henry, British Medical Journal, vol 295, p 1021-1024. |
