50 Disasters of Animal Testing
1. Benzene was not withdrawn from use as an industrial chemical despite
clinical and epidemological evidence that exposure caused leukemia in humans,
because manufacturer-supported tests failed to reproduce leukemia in mice.[1]
Benzene is carcinogenic in both mice and rats.
http://ntp-server.niehs.nih.gov/htdocs/LT-studies/tr289.html
And it causes leukemia in mice,
Cronkite, E.P., Bullis, J.E., Inoue, T. & Drew, R.T. (1984) Benzene inhalation produces leukemia in mice. Toxicol. appl. Pharmacol., 75, 358-361
2. Smoking was thought to be non-carcinogenic because smoking-related
cancer is difficult to reproduce in lab animals. Consequently many continued
to smoke and to die from cancer.[2]
As early as 1954, there was solid evidence from laboratory animals (mice) that smoking was linked to cancer (work done by Ernest Wynder and Evarts Graham). These studies were dismissed by manufacturers, ironically, based on *exactly* the same logic that ARAs now dismiss animal research — the tobacco companies said that just because it killed mice and rats did not mean it was harmful to human beings. The tobacco companies pioneered the sort of nonsense the ARAs spout.
3. Animal experiments on rats, hamsters, guinea pigs, mice, monkeys,
and baboons revealed no link between glass fibers and cancer. Not until 1991,
due to human studies, did OSHA label it carcinogenic.[3][4][5]
4. Though arsenic was a known human carcinogen for decades, scientists
still found little evidence in animals to support the conclusion as late
as 1977.[6] This was the accepted view until it was eventually possible to
produce in animals.[7][8][9]
Both sentences are, on the whole false.
The carcinogenicity of arsenic was actually first noticed in 1887, but no one really paid much attention until 1965 when Tseng et al. published a study showing that workers in Taiwan who were chronically exposed to arsenic had high rates of skin cancer.
Animal toxicology clearly mislead researchers in the intervening century, largely because the rate of cancer is relatively low and most of the human clinical studies of arsenic that were done tended to be small studies with methodological problems — until Tseng came along (that research had problems too, but the effect was clear).
Note, too, that one reason this took so long to come out was that most developed countries had by the early 1920s set acceptable levels of arsenic to relatively low levels, meaning the number of extra cases of cancer would have been very small and hence difficult to pick up on.
5. Many humans continued to be exposed to asbestos and die because
scientists could not reproduce the cancer in laboratory animals.
Asbestos causes cancer in mice, rats, hamsters and rabbits. In fact, studies done on rats in 1911(!) showed that asbestos appeared to harm the animals (see Merewether, E. R. A. and Price, C. W., 1930, Report on effects of asbestos dust on the lungs and dust suppression in the asbestos industry. London.)
6. Pacemakers and heart valves were delayed in development because
of physiological differences between animals on which they were designed and
humans for whom they were intended.
7. Animal models of heart disease failed to show that a high cholesterol/high
fat diet increases the risk of coronary artery disease. Instead of changing
their eating habits to prevent the disease, people continued their lifestyles
with a false sense of security.
8. Patients received medications that were harmful and/or ineffective
due to animal models of stroke.
9. Animal studies predicted that beta-blockers would not lower blood
pressure. This withheld their development.[10][11][12] Even animal experimenters
admitted the failure of animal models of hypertension in this regard, but
in the meantime, there were thousands more stroke victims.
10. Surgeons thought they had perfected radial keratotomy, surgery
performed to enable better vision without glasses, on rabbits, but the procedure
blinded the first human patients (The rabbit cornea is able to regenerate
on the underside, whereas the human cornea can only regenerate on the surface).
Surgery is now performed only on the surface.
Hmmm… no footnote on this one. I wonder why. Pretty much a lie. RK was invented by a Russian scientist in the early 1970s and then brought to the United States in the late 1970s. It was widely used in this country even though no systematic testing of the procedure was performed until the 1980s.
11. Combined heart lung transplants were supposedly ‘perfected’ on
animals, but the first 3 human patients all died within 23 days.[13] Of the
28 patients operated on between 1981 and 1985, 8 died peri-operatively, and
10 developed obliterative bronchiolitis, a lung complication that the dogs
on whom experiments had been conducted did not develop. Of those 10 humans
who developed obliterative bronchiolitis, 4 died and 3 never breathed again
without the aid of a respirator. Obliterative bronchiolitis turned out to
be the most important risk of the operation.[14]
12. Cyclosporin A inhibits organ rejection, and its development was
a watershed in the success of transplant operations. Had human evidence not
overwhelmed unpromising evidence from animals, it would never have been released.[15]
Not according to: http://www.smw.ch/pdf200x/2001/21/smw-09702.pdf
13. Animal experiments failed to predict the kidney toxicity of the
general anesthetic methoxyflurane. Many people lost all kidney function.
14. Animal experiments delayed the use of muscle relaxants during general
anesthesia.
15. Research on animals failed to reveal bacteria as a cause of ulcers
and delayed treating ulcers with antibiotics.
16. More than half of the 198 new medications released between 1976
and 1985 were either withdrawn or relabeled secondary to severe unpredicted
side effects.[16] These side effects included complications such as lethal
dysrhythmias, heart attacks, kidney failure, seizures, respiratory arrest,
liver failure, and stroke, among others.
17. Flosint, an arthritis medication, was tested on rats, monkeys and
dogs; all tolerated the medication well. However, in humans it caused deaths.
“MYTH Animal tests fail to predict the effects of drugs with tragic consequences….Flosint, another anti-inflammatory – Committee on Safety of Medicines had received reports of 217 adverse effects, including 7 deaths. Bitter Pills, NAVS Leaflet
FACT Indoprofen was widely studied in normal volunteers and patients before being put on sale in this country. In an early study indoprofen was shown to cause much less intestinal bleeding than aspirin as judged by the excretion in the faeces of 51Cr labelled red cells1. Similarly, in a large study (6764 osteoarthritic patients) carried out in South America, Italy and Greece, only 0.2% of patients had any gastrointestinal bleeding although 10% reported abdominal pain2. Nevertheless when indoprofen was used in the UK there were frequent reports of gastrointestinal bleeding, and its licence for sale was suspended.
The reason for this toxicity emerging despite apparently careful testing in volunteers and patients maybe that the toxicity appears after prolonged use (the large clinical study2 lasted only one month).”
18. Zelmid, an antidepressant, was tested on rats and dogs without
incident, but it caused severe neurological problems in humans.
19. Nomifensine, another antidepressant, was linked to kidney and liver
failure, anemia, and death in humans. And yet animal testing had indicated
that it could be used without side-effects occurring.
A toxicity index of 2.5 per 1,000,000 prescriptions. Not bad I’d say and neither do a ton of doctors.
20. Amrinone, a medication used for heart failure, was tested on numerous
animals and was released without any trepidation. But humans developed thrombocytopenia,
a lack of the type of blood cells that are needed for clotting.
21. Fialuridine, an antiviral medication, caused liver damage in 7
out of 15 people. 5 eventually died and 2 more needed liver transplants.[17]
And yet it had worked well in woodchucks.[18][19]
MYTH “Fialuridine (FIAU) was an experimental drug for hepatitis B infection. In June 1993, during Phase II trials 5 out of 15 patients died, whilst two others survived with emergency liver transplants, as a result of the drug’s side effects which included liver and kidney failure….. it is known that FIAU was extensively studied in 4 non-human species, all of which did not show this acute liver toxicity. This drug was spotted by human safety tests, before it reached the market. This surely prevented a major tragedy caused, partly at least, by over-reliance on misleading animal tests.” BUAV Factsheet M11. January 1995
FACT Fialuridine had shown a remarkable effectiveness in the treatment of hepatitis B infection in two short trials. As a result, NIH was planning a 6-month trial. Before this started problems began to emerge.
Four months after the end of the second trial a patient died of liver failure. In all, 5 patients subsequently died, showing an unusual sort of long-delayed toxicity. It has been proposed that the toxicity is due to damage to mitochondrial DNA.
Until now it has not been the practice to look for such a delayed toxic effect in animal studies. A Subcommittee of the Advisory Committee to the Director of the NIH was set up to investigate the trial. It concluded: “There is no villain other than the emergence and identification of a new and unique form of delayed drug toxicity. Only in retrospect are there clues.”
They recommended that: “preclinical animal tests should mimic the proposed protocol for human studies. Delays between studies should be longer and patients should be followed for up to nine months if delayed toxicity is suspected”1.
A further review of the trial, by the Institute of Medicine, has now been published2. The report recommended that patients be monitored for six months to detect side effects of drugs that modify DNA. In addition, animal testing should occur to learn more about FIAU and related drugs.
It is clear that the animal studies were not responsible for the deaths that occurred in this trial. Animal studies have not, up to now, been designed to detect a toxic effect that emerges months after the drug is stopped. As suggested above, presumably now experimental studies will be extended to include such a test, just as teratogenic studies were instituted after the thalidomide tragedy.
22. Clioquinol, an antidiarrheal, passed tests in rats, cats, dogs
and rabbits. But it had to be withdrawn all over the world in 1982 after
it was found to cause blindness and paralysis in humans.
23. Eraldin, a medication for heart disease, caused deaths and blindness
in humans despite the fact that no untoward effects could be shown in animals.
When introduced, scientists said it noted for the thoroughness of the toxicity
studies on animals. Afterwards, scientists were unable to reproduce these
results in animals.[20]
Picking what should be the worst example – eraldin (number 23 on the list)- is interesting. This should show animal tested drugs in their worst light as eraldin (or practolol to give it its proper name, eraldin is a trade name)was actually withdrawn. The real story is more complex..and just to show how often the 50 claims are made, here is a standard eraldin “debunk” I’ve lifted from the RDS UK website:
“Practolol [eraldin] The beta adrenoceptor blocking drug practolol was studied in the clinic from 1967 and came on the market in 1970. Due to its cardioselectivity it was found to be good for patients who manifested bronchospasm to propranolol. Early clinical studies did not reveal any serious toxicity – in one study in 2,100 patients the most serious toxic effect noted was constipation in 44 patients (1).
By 1974 experience with practolol amounted to 250,000 patient years. It was only at this time that it was noted that that a few patients treated with practolol developed some serious symptoms including rashes, changes in eyes and ears and retroperitoneal fibrosis(2).
This effect of practolol is a rare occurence, producing unacceptable ill-effects in a small minority of patients. Neither animal tests nor clinical trials restricted to 5,000- 10,000 patients would uncover such a toxicity. Practolol is still available for intravenous administration to treat certain cardiac arrhythmias. Shanks (3) states “many doctors obtained confidence in beta adrenergic blockade by using practolol and although it had to be withdrawn it had served a most useful purpose”.
References (1) R. Wiseman (1971) Postgrad med J 47, (suppl) 68 – 74. (2) P. D Arcy (1986) in Iatrogenic Diseases, 3rd ed. (ed. D Arcy and Griffin) Oxford Medical Publications. (3) R. Shanks (1984) The discovery of beta adrenoceptor blocking drugs, in Discoveries in Pharmacology (ed. Parnham and Bruinvels) Elsevier”.
24. Opren, an arthritis medication, killed 61 people. Over 3500 cases
of severe reactions have been documented. Opren had been tested on monkeys
and other animals without problems.
25. Zomax, another arthritis drug, was responsible for the death of
14 people and causing suffering to many more.
26. The dose of isoproterenol, a medication used to treat asthma,
was calculated in animals. Unfortunately, it was much too toxic for humans.
3500 asthmatics died in Great Britain alone due to overdose. It is still
difficult to reproduce these results in animals.[21][22][23][24][25][26]
27. Methysergide, a medication used to treat headaches, led to retroperitoneal
fibrosis, or severe scarring of the heart, kidneys, and blood vessels in
the abdomen.[27] Scientists have been unable to reproduce this in animals.[28]
28. Suprofen, an arthritis drug, was withdrawn from the market when
patients suffered kidney toxicity. Prior to its release researchers had this
to say about the animal tests: ‘…excellent safety profile. No…cardiac,
renal, or CNS [central nervous system] effects in any species’.[29][30]
29. Surgam, another arthritis drug, was designed to have a stomach
protection factor that would prevent stomach ulcers, a common side effect
of many arthritis drugs. Although promising in lab animal tests, ulcers occurred
in human trials.[31][32]
30. Selacryn, a diuretic, was thoroughly tested on animals, but it
was withdrawn in 1979 after 24 people died from drug induced liver failure.[33][34]
31. Perhexiline, a heart medication, was withdrawn when it produced
liver failure which had not been predicted by animal testing. Even when the
particular type of liver failure was known, it could not be induced in animals.[35]
32. Domperidone, designed as a treatment for nausea and vomiting, made human
hearts beat irregularly and had to be withdrawn. Scientists were unable to
reproduce this in dogs even with 70 times the normal dose.[36][37]
33. Mitoxantrone, a treatment for cancer produced heart failure in
humans. It was extensively tested on dogs, which did not manifest this effect.[38][39]
34. Carbenoxalone was supposed to prevent formation of gastric ulcers
but caused people to retain water to the point of heart failure. After vivisectors
knew what it did to humans they tested it on rats, mice, monkeys, rabbits,
but could not reproducing this effect.[40][41]
35. Clindamycin, an antibiotic, causes a bowel condition called pseudomenbraneous
colitis. And yet it was tested in rats and dogs every day for a year; moreover,
they were able to tolerate doses ten times greater than humans are able to.[42][43][44]
36. Animal experiments did not support the efficacy of valium-type
drugs during development or subsequently.[45][46]
37. The pharmaceutical companies Pharmacia and Upjohn discontinued
clinical tests of its Linomide (roquinimex) tablets for the treatment of
multiple sclerosis after several patients suffered heart attacks. Of 1,200
patients, 8 suffered heart attacks as a result of taking the medication.
Animal experiments had not predicted this.
38. Cylert (pemoline), a medication used to treat Attention Deficit
Hyperactive Disorder, caused liver failure in 13 children. Eleven either
died or required a liver transplant.
39. Eldepryl (selegiline), a medication used to treat Parkinson’s
disease, was found to induce very high blood pressure. This side effect has
not been seen in animals.
40. The diet drug combination of fenfluramine and dexfenfluramine was
linked to heart valve abnormalities and withdrawn although animal studies
had never revealed heart abnormalities.[47]
41. The diabetes medication troglitazone, better known as Rezulin,
was tested on animals without significant problems, but caused liver damage
in humans. The manufacturer admitted that at least one patient had died and
another had to undergo a liver transplant as a result.[48]
42. The plant digitalis has been used for centuries to treat heart
disorders. However, clinical trials of the digitalis-derived drug were delayed
because it caused high blood pressure in animals. Fortunately, human evidence
overrode and as a result, digoxin, an analogue of digitalis, has saved countless
lives. Many more people could have survived had the animal testing been ignored
and digitalis been released earlier.[49][50][51][52]
43. FK 506, now called Tacrolimus, is an anti-rejection agent that
was almost abandoned before proceeding to clinical trials due to severe toxicity
in animals.[53][54] Animal studies suggested that the combination of FK 506
with cyclosporin might prove more useful.[55] In fact, just the opposite
proved true in humans.[56]
44. Animal experiments suggested that corticosteroids would help septic
shock, a severe bacterial infection of the blood.[57][58] However, humans
reacted differently. This treatment increased the death rate in cases of
septic shock.[59]
45. Despite the ineffectiveness of penicillin in rabbits, Alexander
Fleming used the antibiotic on a very sick patient since he had nothing else
to try. Fortunately, Fleming’s initial tests were not on guinea pigs or hamsters
because it kills them. Howard Florey, the Nobel Prize winner credited with
co-discovering and manufacturing penicillin, stated: ‘How fortunate we didn’t
have these animal tests in the 1940s, for penicillin would probably never
been granted a license, and possibly the whole field of antibiotics might
never have been realized’.
46. Fluoride, a cavity preventative, was initially withheld because
it caused cancer in rats.[60][61][62]
47. The notoriously dangerous drugs thalidomide and DES were tested
in animals and released for human usage. Tens of thousands suffered and/or
died as a result.
48. Animal experiments misinformed researchers about how rapidly HIV
replicates. Based on this false information, patients did not receive prompt
therapies and their lives were shortened.
49. Animal-based research delayed the development of the polio vaccine,
according to Dr. Albert Sabin, its inventor. The first rabies and polio vaccines
worked well on animals but crippled or killed the people who tried them.
50. Researchers who work with animals have succumbed to illness and
death due to exposure to diseases that while harmless to the animal host
(such as Hepatitis B) are potentially or actually deadly for humans.
Endnote.
Time, money, and resources devoted to these experiments could have gone
to human-based research. Clinical studies, in vitro research, autopsies,
post-marketing drug surveillance, computer modeling, epidemiology, and genetic
research pose no hazard to humans and provide accurate results.
Importantly, animal experiments have exhausted resources that could have
been dedicated to educating the public about health hazards and health maintenance,
therein diminishing the incidence of disease that require treatment.
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