[back] Animal Experiments
‘There is no way in the world to extrapolate animals to human circumstance. Animal research is cruel to the animal, dangerous to the public and misleading to the scientist.’ – Dr G Dettman
“The idea, as I understand it, is that fundamental truths are revealed in laboratory experimentation on lower animals and are then applied to the problems of the sick patient. Having been myself trained as a physiologist, I feel in a way competent to assess such a claim. It is plain nonsense.” - Sir George Pickering, Regius Professor of Medicine at the University of Oxford, BMJ, Dec 26, 1964.
"Animal research was NOT responsible for the development of
coronary bypass surgery. In 1961 in France, Kunlin first used a portion of a
person's own vein to replace obstructed arterial segments. This gave birth to
arterial bypass surgery for different parts of the body, the heart included. By
contrast, Beck of Ohio and Vineburg of Canada took their theories to the animal
laboratory in search of surgical answer to the complications of coronary artery
disease. Each devised more than one procedure, envisioning success from their
findings in animals. Not long after, their recommended operations were
performed on thousands of human patients. What were the results? To say the
least, unworthy. To put it bluntly; a fiasco, a total failure. I am witness to
this event and the least I can do is speak out. Animal experimentation
inevitably leads to human experimentation. That is the final verdict, sad as it
is. And the toll mounts on both sides."
"Dogs have been extensively used in heart research, but their coronary arteries differ from those of humans - they have smaller connections with one another and the left coronary artery dominates, while in humans the right does so. In addition, the conduction system has a different pattern of blood supply, and consequently, researchers have had difficulty in producing ischemic heart blocks in dogs, which occurs frequently in humans. The blood coagulation mechanism is unlike ours, therefore using dogs to test prosthetic devices and valves is unreliable. A dog's reaction to shock is also very different to that of humans.
After massive blood loss a dog's intestines are congested, while in humans we see pallor and ischemia. No wonder conclusions from dog experiments extrapolated to human beings frequently brings about catastrophic results and regrettable failures, which occurred with the earlier models of heart valves and in the first several years of using the heart-lung machine. For the benefit of medical science vivisection should be stopped. We must put an end to the medical fraud of vivisection."------Dr Moneim A. Fadali, for 25 years one of America's leading cardiovascular surgeons. This highly respected doctor is also: Diplomate to the American Board of Surgery; Diplomate to the American Board of Thoracic Surgery; Certified with the Canadian Board of Surgeons; Certified with the Royal College of Surgeons, Canada; twenty-five years on the clinical staff of the University of California where he currently practises. The statements of Dr Fadali, are confirmed and supported by doctors equally impressive and prestigious in many fields of medicine who are vociferous in their agreement that abolitionists are correct in their claim that vivisection is fraudulent and that those engaged in it are scoundrels and charlatans who should be imprisoned.
Dr Fadali's evidence is borne out by medical historian who writes:
"As for bypass surgery, animal research actually retarded this therapy for humans. Because a dog's clotting characteristics and coronary valves are so different from ours, the initial human patients died. The first success was Dr Kunlin's work in France. Dr Kunlin's work was clinical and had nothing to do with animal research."------Dr M. Beddow Bayly in Clinical Medical Discoveries
Ironically, in 1933, the Nazi's passed a law for the protection of animals. The law cited the prevention of cruelty and indifference to animals as one of the highest moral values of a people, animal experimentation was unthinkable, but human experimentations were acceptable. The victims of the crime of these doctors numbered into the thousands. Mind Control By Harry V. Martin and David Caul
"Animal studies are done for legal reasons and not for scientific reasons. the predictive value of such studies is meaningless--which means our research may be meaningless."--Dr JD Gallagher, Director of Medical Research, Lederle Laboritories, 1964
“The history of the publication of this book (Slaughter of the Innocent) provides some valuable and frightening insight into the methods and power wielded by vivisectionists and their allies; how they were able to squelch a book already printed and make it disappear — at least for a time……Rizzoli, Italy's largest publisher, had been forced to suppress the book shortly after its publication in 1976.......Bantam did not reply to charges that they were deliberately suppressing the book---until 3 years later, when an executive stated that it had been allowed to go out of print "because it wasn't selling". Yet Bantam's Fall 1978 catalogue listed Slaughter among their bestsellers. How could a publisher of such prominence to so pressured?.....So in Western democracies, no book burnings are necessary; there are subtler and more effective ways to stifle information unfavourable to the industrial powers-that-be.” Hans Ruesch
"A drug is a substance that, when injected into a rat, produces a scientific paper."------Dr. Toni Jefferys PhD
"Vivisection is a social evil because if it advances human knowledge, it does so at the expense of human character."-----George Bernard Shaw (1856-1950)
"The prescription drugs you take are being tested on you".--Melinda Kalaya
"Animal studies can neither prove or guarantee the safety of any drug. They are not a substitute for testing in humans".--J Jennings, Vice President Science & Technology of Pharmaceutical Manufacturers Association.
"A medical myth is an aggressive defensive device used by orthodox medicine to retain the status quo and impede progress in the introduction of new and valuable therapies. ....The myth originates in some inadequate sloppy in vitro or animal experimental work from which unwarranted broad conclusions are drawn as to possible effects on man. There is never any hard human evidence involved, just pure speculation. The second step is that the news media pick it up and being more interested in sensationalism than in facts, magnify these speculations and terrify a gullible public. Further repetition of these unwarranted conclusions by the medical press gives them the status of medical dogma to be quoted and requoted."----Irwin Stone and A. Hoffer, M.D.
Dr Irwin Bross in 1986 he was quoted in Cancer Research on Animals as saying: "They [scientists] may claim to love truth; but when it is a matter of truth versus dollars, they love the dollars more."
Dr Werner Hartinger, a German surgeon, surmised in 1989: "There are, in fact, only two categories of doctors and scientists who are not opposed to vivisection: those who don't know enough about it, and those who make money from it."
According to Dr Ray Greek: "Most pharmaceutical firms do more testing than the government requires, so they can say in court that they saw no effects like the one that killed the plaintiff's wife. Officials will tell you off the record that they rely on animal testing and think that it is a big factor in protection from lawsuits." Or, the companies can turn around and dismiss the animal tests as being unreliable in humans. Either way, it is extremely hard for victims to take legal action against them. The Human Cost of Animal Experiments by Katrina Fox
Contrary to the propaganda put forward by the medical establishment to justify its work, animal experimentation does not save human lives. As the industry's own evidence proves, it does just the opposite.The Human Cost of Animal Experiments by Katrina Fox
Vivisection: The Psychopathic Aspect. Sadism is a very ugly word, which serves to define a very ugly psychopathy - a mental disease. Vivisectors have been known to accept with equanimity the allegation of being money grubbers - of doing cruel experiments only to gain money or a professorship. But we have never known a vivisector who bore with equanimity the allegation of being a sadist. They always reacted to all such allegations with frothing, like other psychopaths when they are confronted with the nature of their disorder. If it is a mistake to believe that all vivisectors are sadists, it would be another mistake to believe that sadism is not rampant in the animal laboratories. It is. In fact, for men and women (more men, as a rule) who are affected by this grave psychopathy (mental malady), and on top of it are animal haters, what kind of remunerated occupation could be more gratifying than a job in a viviection laboratory? Preface by Hans Ruesch to 1000 Doctors (and many more) Against Vivisection"The vaccination causes, furthermore an explosion of leukaemia."---(Dr B. Duperrat, Presse Medicale, March 12 1955.)
"No amount of testing can make a drug safe because humans react differently from animals."----(Lord Platt, President of the Royal College of Physicians, 1957-1962.)
"Immunization with an attenuated virus cannot prevent distemper. The author has treated many dogs, which have developed distemper despite two or three injections of the preventative agent. He is of the opinion that fits, chorea, hysteria, etc, in dogs have become more frequent since the use of distemper vaccine. Successful prevention will never be achieved by inoculation."---Dr J.E.R. McDonagh, F.R.C.S., bacteriologist, wrote in The Nature of Disease, Vol. 1, pages 75-76:"If we halted research using animals today the result would be immediate and beneficial."----(The late Dr Robert S. Mendelsohn, Confessions of a Medical Heretic.)
"Information from one animal species cannot be taken as valid for any other. It is not a matter of balancing the cruelty of suffering animals against the gain of humanity spared from suffering, because that is not the choice. Animals die to enable hundreds of new drugs to be marketed annually, but the gain is to industry, not to mankind."---The 1963 Report of the British Pharmaceutical Industry's Expert Committee on Drug Toxicity
"During the past fifty years scientists experimenting with thousands of animals have found 700 ways of causing cancer. But they had not discovered one way of curing the disease."---(Dr J. F. Brailsford, M.D., Ph.D., Birmingham Evening Dispatch, January 10 1956.)"It is time to end cancer research on animals because it is not related to humans."----(Dr A. Sabin.)
DAVID KORN Chairman of the National Cancer Institute's (sometimes known as the National Mouse Institute) Advisory Board says:
"For 35 years U.S. scientists labouring in the National Cancer Institute's screening programme have injected more than 400,000 chemicals into leukemic mice, hoping to find chemotherapies that would help solve the riddles of cancer... We've been using the wrong system as the screening device."
"The new system which is being employed at the Development Therapeutics
Programme in Frederick, Maryland, uses an arsenal of automated devices and
computers to test potential cancer-fighting drugs on real human cancer
cells grown in laboratories rather than on mice. This enables scientists to
test more than 300 chemicals a week. Many of these drugs had failed in the
past when tested on mice."
("Giving up on the Mice. Scientists Searching for Cancer-cures Try a New Tactic", Time Magazine, September 17 1990.)
"From a comparison of the results of the present study with those of other studies, one can draw the following conclusions: compounds that cause hepatomas (liver cancers) in mice, may not always be carcinogenic in rats, or if carcinogenic in both species, the compounds may have different primary target sites. The extrapolation of such results to define any risk to humans remains a troublesome problem."----(Journal of the National Cancer Institute, Vol. 67.)
"The ultimate dilemma with any animal model of human disease is that it can never reflect the human situation with complete accuracy."---(D.J. Galloway, Animal Researcher, Glasgow's Western Infirmary, Cancer Surveys, Vol. 8, 1989, pages 169-188.)
"Experimentation on animals undermines the very foundations of practical medicine."---(Dr J. Burton, Medical World, May 18 1945.)
"Leukemia has been dramatically increasing, especially among
children, ever since the various modern 'therapies' have been inflicted upon
a frightened, artfully misinformed public. Urethane has sometimes an
inhibitory effect on human leukemia in contrast to what animal experiments
"The characteristic effects in leukemia were detected solely as a result of clinical observation. The various leukemias in the mouse and rat were relatively refractory to the influence of urethane, and the remarkable effect in the human might have eluded discovery if attention had been directed to the animal alone. That illustrates the hazards of such work."
(Prof. Alexander Haddow, British Medical Journal, December 2 1950, page 1272.)
"The argument from man is so much more convincing than the argument
from mice - which indeed, may be completely misleading, as in the case of
urethane, which has some inhibitory action on human tumours, but a marked,
though temporary one on chronic human leukemias."
(Dr C.G. Learoyd, Surgeon, Medical World, August 1954, page 172.)
"The drugs Prednisone and Vincristine are often hailed as 'curing'
childhood leukemia. Both drugs were rejected by the US National Cancer Institute as
'useless' on the basis of animal tests. Prednisone was developed as a
result of clinical observation of the effects of adrenal extract.
Vincristine is an alkaloid of 'Vincra Rosea', a type of periwinkle plant,
and extracts of periwinkle were used in the Roman Empire to 'dry tumours'
(Pliny). They were eventually brought to clinical trials. The children
cured of leukemia owe their lives to clinical observations and trials - and
not to the animal 'model'."
(Brandon Reines, Cancer Research on Animals: Impact and Alternatives.)
Robert Matthews, technical correspondent of The Times, told Jon Rappoport of the New York Native, June 29 1987:
"The World Health Organisation which had been running their 13-year smallpox eradication programme in the third world until 1980 wondered if the vaccinations were connected to the AIDS pandemic. They hired an outside consultant to do a study on it. He did and said... 'Yes your suspicion is correct.' But the report was buried by the WHO and so the consultant came to us... His credentials can not be dismissed... We are not giving his name, but the WHO know he is our source."
"You and I are being lied to by the animal research establishment when they tell us all this cruelty is "necessary" for scientific research. We are being fed this lie by people who make a living of their practices behind closed doors at universities and scientific institutes: by people who are deeply interested in keeping things in this six-billion-a-year business just the way they are."---Dr Elliott Katz, Veterinarian (U.S.) in CIVIS Foundation Report, Nr. 2, Summer 1998:"I am fully in agreement with the bills against vivisection, for the abolition of vivisection can only be seen as an advance in public education"
"Orthodox medicine condones ill-conduct and seeks to restore health without
rectifying it. True health cannot be attained in this manner. Vivisection has
no philosophy, no ethics, and no width of vision. It will, therefore, disappear
in the course of time."
(Bertrand P. Allinson, M.R.C.S., L.R.C.P., in Hans Ruesch's One Thousand Doctors (and many more) Against Vivisection.)
"Modern medicine is a negation of health. It isn't organised to serve human
health, but only to serve itself as an institution. It makes more people sick
than it heals."
(Ivan Illich, Medical Nemesis.)
"Since the introduction
of diabetes drugs in the 1950s the international death rate for diabetics in the
past twenty years have risen in England, Wales, Germany, Japan, and Israel,
probably because of the use of insulin."
(R. Warner, Public Citizens Health Research Group, Washington D.C., U.S.A.)
"Within ten years, the Italian Ministry of Health has withdrawn from the
market 22,621 drugs because of toxic side-effects."
(A Parliamentary Bulletin of August 8 1983.)
"Formerly it was the lie under the guise of religion that deceived mankind;
now it is the same lie under the guise of science that is deceiving the whole
world, and there is no weapon against it other than reason. Reason teaches us
that the true healing of diseases and the maintenance of health consists in
freeing the body of impurities and keeping it clean."
(Dr med. Franz Hartmann, Hallein in Tirol: (Lotusblueten, 1895) From Hans Ruesch's One Thousand Doctors (and many more) Against Vivisection.)
Forty thousand children starve to death each day in the Third World. One
fifth of the children in the poorer countries die of malnutrition and lack of
clean water and basic medical care before their fifth birthday. Two hundred and
fifty million children worldwide are going blind through lack of vitamin A in
(UNICEF report, New Scientist, September 16 1983.)
"Animal studies are done for legal reasons and not for scientific
reasons. The predictive value of such studies for man is meaningless."
- Dr James D. Gallagher, Director of Medical Research, Lederle Laboratories, Journal of the American Medical Association, March 14 1964.
The following quotes came from Safer Medicines Campaign
We have learned well how to treat cancer in mice and rats but we still can’t cure people. Professor Colin Garner, quoted in Accelerator MS Is a Powerful New Tool, Genetic Engineering & Biotechnology News, Vol. 27, No. 15.
We do trials in people because animal models do not predict what will happen in humans. Dr Sally Burtles, Cancer Research UK, Report of the Expert Scientific Group on phase one clinical trials, following the TGN1412 clinical trial disaster.
You really have to design the medicine for the species of interest…You'll find it very rare to find a medicine that will work in both…Patrick M. O'Connor, head of oncology research for Pfizer, quoted in The New York Times, 24 November.
In summary, mouse xenograft models should not be viewed as ideal models for cancer drug development. Altered, nonhuman host stroma, poor predictive value when applied in an empirical sense, and questionable relation to the naturally occurring human disease are but a few features, which temper enthusiasm for their use. Sausville & Burger, Cancer Research, 66, 3351-3354, April 1.
Even when drugs with evidence of anticancer activity in preclinical in vivo models are given at their maximum tolerated doses, they frequently fail to produce useful activity in humans. Sausville & Burger, Cancer Research, 66, 3351-3354, April 1.
In the U.S. NCI retrospective (2001), activity in at least 33% of models of a variety of histologies predicted for clinical activity in some disease. In the NCI of Canada retrospective (2003), generally similar conclusions were reached. It should be cautioned, however, that the drugs used in these studies were for the most part "classic" cytotoxics. Whether "targeted" therapeutics, such as signal transduction inhibitors, antiangiogenic, or stroma-modifying agents, would perform better or worse remains to be defined. Sausville & Burger, Cancer Research, 66, 3351-3354, April 1.
Change is needed. Thirty years of experience with subcutaneous xenografts, human tumors implanted under the skin of the mouse, have satisfied few because so many drugs that cure cancer in these mice fail to help humans. A 2004 analysis in the Journal of the American Medical Association showed that only 3.8% of patients in phase I cancer drug trials between 1991 and 2002 achieved an objective clinical response — and the response rate is declining. Almost all drugs tried in humans work against subcutaneous xenografts in mice. “How many more negative data do you want? It’s very depressing.” said Isaiah Fidler , Ph.D., of the University of Texas M. D. Anderson Cancer Research Center in Houston. Ken Garber, Journal of the National Cancer Institute, Vol. 98, No. 17, September 6.
Given that many of these investigational anticancer drugs eventually fail, the animal models on which clinical trials are predicated must at best be limited in power, and at worst wildly inaccurate. Dr Alexander Kamb, Global Head of the Oncology Disease Area at the Novartis Institutes for Biomedical Research, Nature Reviews Drug Discovery, 4, 161 - 165.
The problem with animal carcinogenicity tests is not their lack of sensitivity for human carcinogens, but rather their lack of human specificity. A positive result has poor predictive value for humans. Knight, Bailey & Balcombe, British Medical Journal USA, Vol. 5, p477.
It’s been well known for maybe two decades that many of these preclinical human cancer models have very little predictive power in terms of how actual human beings – actual human tumours inside patients – will respond…Preclinical models of human cancer, in large part, stink…Hundreds of millions of dollars are being wasted every year by drug companies using these [animal] models…Prof. Robert Weinberg, Massachusetts Institute of Technology, Fortune, 9th March.
[mouse models are] woefully inadequate…if you look at the millions and millions and millions of mice that have been cured, and you compare that to the relative success, or lack thereof, that we've achieved in the treatment of metastatic disease clinically, you realize that there just has to be something wrong with those models. Homer Pearce, research fellow at Eli Lilly. Fortune, 9th March.
In Tamoxifen’s case, a drug first developed as a potential contraceptive languished for many years before its present application was found. Furthermore, its propensity to cause liver tumours in rats, a toxicity problem that thankfully does not carry over into humans, was not detected until after the drug had been on the market for many years. If it had been found in preclinical testing, the drug would almost certainly have been withdrawn from the pipeline.Nature Reviews Drug Discovery 2003; 2:167.
The in vitro cell line model was predictive for non-small cell lung cancer under the disease-oriented approach, for breast and ovarian cancers under the compound-oriented approach, and for all four tumor types together. The mouse allograft model was not predictive. The human xenograft model was not predictive for breast or colon cancers, but was predictive for non-small cell lung and ovarian cancers when panels of xenografts were used. Voskoglou et al. Clinical Cancer Research Vol. 9, 4227-4239.
…some findings in colon cancer mice, which were very good models, actually led to clinical trials in humans which resulted in an increase in cancer. Dr Jeffrey E. Green of the National Cancer Institute’s Laboratory of Cell Regulation and Carcinogenesis. Journal of the National Cancer Institute, 93:976.
For 39 agents with both xenograft data and Phase II clinical trials results available, in vivo activity in a particular histology in a tumour model did not closely correlate with activity in the same human cancer histology, casting doubt on the correspondence of the pre-clinical models to clinical results. Johnson and colleagues, British Journal of Cancer, 84(10):1289-90.
People are very complacent with their animal models. But this begs the question of whether there exists a good model of cancer. Dr Andy Maniotis, The American Journal of Pathology, 155: 739.
My own medical perspective is that animal cancer research should be regarded as the scientific equivalent of gossip – with about the same chance of turning out to be true, i.e. truly effective in humans. Some gossip turns out to be true, but most of it does not…and gossip can cause great anguish for those affected, in this case millions of desperate cancer patients worldwide. G. Timothy Johnson MD, Boston Globe, May 22.
The history of cancer research has been a history of curing cancer in the mouse. We have cured mice of cancer for decades, and it simply didn’t work in humans. Dr Richard Klausner, Director, National Cancer Institute, LA Times, May 6.
God knows we’ve cured mice of all sorts of tumours. But that isn’t medical research. Thomas E Wagner, senior scientist at Ohio University’s Edison Biotechnology Institute, the Columbus Dispatch, March 20.
The fundamental problem in drug discovery for cancer is that the model systems are not predictive at all," says Alan Oliff, executive director for cancer research at Merck Research Laboratories in West Point, Pennsylvania…Researchers blamed the failures on the fact that the drugs were being tested against mouse, not human, tumors… the xenograft tumors don't behave like naturally occurring tumors in humans – they don't spread to other tissues, for example. Thus, drugs tested in the xenografts appeared effective but worked poorly in humans. "We had basically discovered compounds that were good mouse drugs rather than good human drugs," says Sausville (associate director of the division of cancer treatment and diagnosis, NCI). Science, 278; 1041-1042.
One might expect that these animals would mimic human symptoms, not just the genetic mutations. In fact, that is usually the exception, not the rule. Dr Tyler Jacks, regarding genetically modified mice in cancer research. Science, 287: 1041.
Since its inception 25 years ago, EPA [the US Environmental Protection Agency] has applied the same logic to hundreds of other substances, extrapolating from high levels in animal studies to arrive at acceptable levels for humans. But that approach, say scientists both inside and outside the federal government, may no longer be the best way to safeguard public health...EPA's new emphasis on molecular data is based on a growing body of evidence that extrapolations from megadoses can provide a misleading picture of the effects of low-level exposure. Chloroform is a good example. EPA's current strict standards were derived from a study in which mice developed liver tumors after exposure to massive daily doses of chloroform pumped into their stomachs over several months. However, those findings may not be relevant to human exposures, according to a paper picked by the Society of Toxicology as the best published last year in its journal. Richard Stone, Science, vol 268, p 356-357.
1-3 Butadiene, an important industrial chemical and a common environmental air pollutant, has been shown to be a weak carcinogen in the rat, but a potent carcinogen in the B6C3F1 mouse. This species difference makes risk extrapolation to humans difficult, and the underlying mechanism must be clarified before meaningful risk extrapolation to humans can be made. Dr Gunnar Johanson, of the National Institute of Occupational health, Sweden, Alternatives to Laboratory Animals, vol 21, p 173180.
Why the dog was ever considered as an appropriate animal for carcinogenicity testing is also not entirely clear... Despite the obvious problems of study design and interpretation, carcinogenicity tests in the dog, lasting 7 years, were requested by regulatory authorities from the late 1960s...One of the best known examples of the inappropriate use of the dog was the carcinogenicity testing of hormonal contraceptives. It is now understood that mammogenesis in the dog is very different from that in primates; quantitative and qualitative differences exist in the feedback control mechanisms, receptor content and behaviour, and target sensitivity and responsivity. As a result of this biological difference there was a high incidence of mammary tumours in long-term studies in dogs treated with progestagens/contraceptive steroids such as lynestrol. Ultimately pressure from the scientific community led, relatively recently, to the requirement for carcinogenicity studies in dogs being dropped. Parkinson and Grasso, Human and Experimental Toxicology, vol 12, p 99-109.
In the course of tumour progression, it has been known for many years that mice and men are totally different. Nature, Nov 26.
The following quotes are all from Philip H Abelson, Science, vol 255, p 141.
[Regarding tamoxifen, an anti-cancer drug] "Experimentally, tamoxifen has carcinogenic potential. In some strains of rat, but not mouse or hamster, tamoxifen can cause liver cancers at doses as low as 5mg/kg per day... However, there are doubts about the correlation of [the results] with the risk of malignant disease even in rats, let alone in other rodents, mammals, or human beings. There are many uncertainties in extrapolating these experimental data from rats to women. The effect depends on bioavailability, hepatic [liver] blood flow, and hepatic [liver] metabolism to active genotoxic carcinogens, all of which differ enormously between rat and man. Dr Trevor Powles, The Lancet, vol 340, p 1145-1147.
For example, the control incidence of mouse liver tumour varies between 0 and 58% in 41 NTP [National Toxicology Program] bioassays where these tumours are induced by a test chemical. Ashby and Morrod, Nature, vol 352, p 185-186.
Yes, I think it is very clear to all of us who are engaged in the business of assessing toxicity data that, when volumes of data are proudly presented to us after a carcinogenicity study, showing that there was a tumour in this organ or that, we look at it and we scratch our heads, and we wonder what on earth we can make of it. This is especially true when huge doses are given, with nothing to suggest what would be expected at low doses. I think very often the carcinogenicity studies are a waste of everybody's time and a fearful waste of animals. They are conducted partly because we are not sure what to do instead, and partly because they are a political gesture and a very miserable one at that. Professor Andre McLean, speaking at a conference reported in Animals and Alternatives in Toxicology, p86, ed. Balls, Bridges and Southee (publ. Macmillan).
The [pharmaceutical] industry is left with an expensive and time consuming test which uses large numbers of animals and whose very basis is questioned by scientists. Professor D Davies, quoted in the pharmaceutical magazine Scrip, 2nd October, p 23.
[Animal carcinogenicity tests on new drugs are] inaccurate, often insensitive and generally misleading. Dr John Griffin, Director of the Association of British Pharmaceutical Industry, quoted in the pharmaceutical magazine Scrip, 2nd October, p 23.
It seems sometimes that almost everything we eat, drink or take can cause cancer in rats. That does not necessarily relate to tumours in humans. Tony Watson, President of the British Association of Plastic Surgeons, quoted in The Times, 9th May.
Our risk models are based on at least 50 assumptions, none of which has been scientifically demonstrated. For example, we assume that there is no difference between continuous (as in animal tests) or intermittent (as in human experience) dosages. But that ignores our growing knowledge of the way in which DNA repairs the human system . . .We feed rodents `all-you-can-eat' buffets every day, yet we know that caloric intake is the single greatest contributing cause of cancer [in rodents]. In fact, we found you can modify the cancer causing impact of one of the most potent carcinogens from 90% down to less than 3%, just by cutting caloric intake 20%. Dr. Ronald Hart, Director of the Center for Toxicological Research in Arkansas, quoted in Business Review Weekly, 27th April.
… Predictions of carcinogenicity from laboratory animals are without meaning for there is no evidence that the studies were conducted in a way that took into consideration the pharmacodynamics in the species investigated, or with any appreciation of end organ sensitivity (with respect to contraceptive steroids). Ralph Heywood, Chapter 7: Clinical Toxicity- could it have been predicted? Post-marketing experience, Animal Toxicity Studies: Their Relevance for Man (publ. Quay).
Risk assessment policy that relies solely on screening bio-assay results from the most sensitive species is not based on scientific principles. Neither is it credible or reliable. Dr Vernon Houk, director of environmental health at the American Center for Diseases Control, addressing a conference in the USA, 1989, and quoted in Business Review Weekly, 27th April.
The principal method of determining potential carcinogenicity of substances is based on studies of daily administration of huge doses of chemicals to inbred rodents for a lifetime. Then by questionable models, which include large safety factors, the results are extrapolated to effects of minuscule doses in humans... The rodent MTD test that labels plant chemicals as cancer-causing in humans is misleading. The test is likewise of limited value for synthetic chemicals. The standard carcinogen tests that use rodents are an obsolescent relic of the ignorance of past decades. Philip H Abelson, Science, vol 249, p 1357.
... numerous chemicals have been found to have potential toxicity/carcinogenicity in rat or mouse, which, we are reasonably certain, have little or no potential hazard in man. The reason for this is again species differences, for the biological defence mechanism which protects against toxic chemicals is most highly evolved in man, who therefore generally has a higher resistance to chemical toxicity and carcinogenicity than have rodents and other species… Parke, Ioannides and Lewis, Alternatives To Laboratory Animals, vol 18, p 91-102.
Elsewhere, I have pointed out that overfeeding of rats profoundly influences the incidence particularly of endocrine tumours. Furthermore, endocrine tumours and tumours of tissues, such as the breast and uterus, which are very directly under sex-hormone control, constitute a very high proportion of the tumours observed in most carcinogenicity studies in rats. [Comparing] the incidences of tumours in these categories in men and women with those in male and female rats... [shows] the differences between the two species are sufficiently striking to make one wonder how appropriate the laboratory rat is as a model for man in terms of the spectra of tumours to which they are prone. Dr Francis Roe, Advances in Applied Toxicology, p 10, ed. A D Dayan & A J Paine (publ. Taylor & Francis).
There are marked differences in carcinogenicity across sexes, strains and species. Often, the-same chemical will cause one kind of cancer in one experiment and another kind in another experiment Indeed, the most hard-bitten advocates of animal experiments do not claim to be able to predict which organ will be affected in humans by a chemical that is carcinogenic in animals. Freedman and Zeisel, Statistical Science, vol 3, p 3-28.
[Regarding animal carcinogenicity tests on saccharin] Published risk estimates, starting from the same animal data but using various [statistical] models, differ by factors of over 5,000,000. Freedman and Zeisel, Statistical Science, vol 3, p 3-28.
[Regarding the difficulties of applying animal results to humans] "There turn out to be many different ways to measure this difference [in size]. For example, a man weighs 2800 times as much as a mouse, eats 300 times as much per day and lives 40 times as long. Which factor should be used to rescale the dose? Freedman and Zeisel, Statistical Science, vol 3, p 3-28.
There are many unresolved problems in the standard bio-assay, including... how to account for inter-species and intra-species differences in metabolism and pharmacokinetics. Omenn & Lave, Mutation Research, vol 205, p 41.
Data from dose-response relationships are sometimes employed to estimate the expected tumour incidence at dose levels very much lower than those which could possibly be employed in conventional [animal] experiments. A number of mathematical models have been employed in such estimates and the results obtained vary considerably. Despite these uncertainties - and the possibly greater ones in extrapolating from animals to man - such models are often employed in some quarters to estimate the likely risk to man. Dr Paul Grasso, Perspectives in Basic and Applied Toxicology, p268-284, ed. Ballantyne (publ. Butterworth).
Extrapolating from one species to another is fraught with uncertainty... For almost all of- the chemicals tested to date, rodent bio-assays have not been cost-effective. They give limited and uncertain information on carcinogenicity, generally give no indication of mechanism of action, and require years to complete." [They are] "rarely the best approach for deciding whether to classify a chemical as a human carcinogen. Lave, Ennever, Rosenkrantz and Omenn, Nature, vol 336, p 631.
...of the 20 probable human non-carcinogens with conclusive animal bioassay results, only one, methotrexate, is negative, and the other 19 are positive... Thus, the standard interpretation of animal bioassay results provides essentially no differentiation between definite human carcinogens and probable human non-carcinogens. Drs Ennever, Noonan and Herbert, Mutagenesis, vol 2, p 73-78.
The standard carcinogenicity bioassay, which involves treating two rodent species for a minimum of 2 years, at a range of doses, is acknowledged to be an insensitive tool because of the background `noise' of spontaneous disease. Most strains of rat used in such studies have high incidence of pituitary and mammary tumours; some inbred rat strains frequently develop leukaemia or testicular tumours; mice strains show high incidence of malignant lymphomas and liver tumours. Dr Mary Tucker, Human Toxicology, vol 6, p107-109.
If we wish to understand human cancer, the [research] effort should be made in humans because the genetic control seems to be different in different species. Renato Dulbecco (Nobel Laureate). Science, 231: 1055-1056.
Let us look at some animal carcinogens – gold, DDT, clofibrate and bromocriptine. There is no doubt that all of these can rightly be regarded as carcinogenic for rodents, and yet there is really quite good evidence that they are not carcinogenic to man. Prof Andre McLean, Long Term Animal Studies-Their Predictive Value for Man (publ. MTP Press).
During a chronic study the problem may be complicated by the presence of concomitant diseases; it is in fact known that acute inflammation or the presence of a tumor may affect the kinetics of chemical, thus altering their potential toxicity. Silvio Garattini, Toxic Effects of Chemicals: Difficulties in extrapolating data from animals to man; Critical Reviews in Toxicology, vol 16, issue 1, p1-29.
It is painfully clear that carcinogenesis in the mouse cannot now be predicted from positive data obtained from the rat and vice versa. Dr F J Di Carlo, Drug Metabolism Reviews, vol 15, p 409-413.
The major problems of animal studies are the validity of cross-species comparisons and relevance to human disease. Johanna Dwyer, Fundamental & Applied Toxicology 3: 63-67.
The lifetime feeding study of mice and rats appears to have less than a 50% probability of finding known human carcinogens. On the basis of probability theory, we would have been better off to toss a coin...The `definitive bioassay for carcinogenesis' as now designed has never been subjected to proper validation as an assay for human carcinogens. At attempt made in this paper to examine the literature suggests that it may have an unacceptably high false negative rate and that it produces so many contradictory answers as to suggest a very poor specificity. Dr. David Salsburg, Fundamental and Applied Toxicology, vol, 3, pp. 63-67.
Animal model systems in cancer research have been a total failure…not a single essential drug for the treatment of human cancer was first picked up by an animal model system. All of the drugs in wide current clinical use were only put into animal model systems after finding clinical clues to their therapeutic possibility. The money was spent…for two main reasons. First, it was a highly profitable undertaking for certain medical schools and research institutions that were incapable of doing any genuine cancer research. Second, it was sustained by a superstitious belief in a grossly unscientific notion: mice are miniature men…in sum, from the standpoint of current scientific theory of cancer, the whole mystique of the animal model systems is hardly more than superstitious nonsense…the moral is that animal model systems not only kill animals, they also kill humans. There is no good factual evidence to show the use of animals in cancer research has led to the prevention or cure of a single human cancer. Dr Irwin Bross, Dr Irwin Bross (formerly Director of the Roswell Park Memorial Institute for Cancer Research) November issue, Fundamental and Applied Toxicology.
The rodent’s 6 pairs of mammary glands suggest an increased likelihood for tumor development compared to the human. Bernard L. Oser, Journal of Toxicology & Environmental Health; vol. 8, p521-642.
The discovery of chemotherapeutic agents for the treatment of human cancer is widely heralded as a triumph due to the use of animal models… However, there is little, if any, factual evidence that would support these claims… Indeed, while conflicting animal results have often delayed and hampered advances in the war on cancer, they have never produced a single substantial advance in either the prevention or treatment of human cancer. Dr Irwin Bross (formerly Director of the Roswell Park Memorial Institute for Cancer Research) testifying to US Congress.
Even when there are common target sites for a given carcinogen, there are usually important differences, between man and animals, and between different species and strains of animals. These 'spontaneous' tumours in rats and mice... [vary] widely according to sex, strain, diet, conditions of maintenance, hormonal status, immunological status and latent virus infections. Dr R L Carter, British Journal of Cancer, vol 41, p 494.
…one of the great fallacies in this calculation is that they are assuming that the mouse or rat or the hamster predicts for man, and we have no basis for this prediction…So it’s again a half-baked guess… Does the animal model have any relevance to human disease? If not we’re wasting a lot of time, a lot of money, a lot of good scientists, and a lot of good space at NIH… I completely agree with Dr. Clayton that extrapolation is unscientific… the chief objective here is to keep us all employed and to make sure we do interesting experiments so we can keep coming back to nice places like this. Coulston and Shubick (Eds) Human Epidemiology and Animal Laboratory Correlations in Chemical Carcinogenesis, p391-3 and p309 (publ. Ablex).
It is in fact hard to find a single, common solid neoplasm [cancer] where management and expectation of cure has been markedly affected by animal research. Most human cancers differ from the artificially produced animal model… Harrison, Clinical Oncology, 15: 1-2.
We have a discrepancy between animal data and human data…clearly, right now our animal models are totally and absolutely inadequate to answer all the obvious questions before us. Human Epidemiology and Animal Laboratory Correlations in Chemical Carcinogenesis, Coulston and Shubick (Eds), p13 (Ablex Publ.).
As a cancer specialist engaged in clinical practice, I can’t agree with the researchers who believe that results obtained with laboratory animals are applicable to human beings. Dr Heinz Oeser, Quick, 15th March.
Unfortunately, extrapolations from animal results to man remains largely problematic and no amount of mathematical sophistication can render such extrapolation more certain. Higginson and Muir, Cancer Detection and Prevention, 1(1) p79-105.
Warning is given not to carry over, without reservation, to man, the conclusions based on animal experiments. In monkeys none of the powerful carcinogens [of man] has been shown to produce cancers. The Lancet (1952) Aug 9, p 274.
The characteristic effects in leukaemia were detected solely as a result of clinical observation. The various leukaemias in the mouse and rat were relatively refractory to the influence of urethane, and the remarkable effect in the human might have eluded discovery if attention had been directed to the animal alone. That illustrates the hazards of such work. Dr Alexander Haddow, British Medical Journal, Dec 2, p1272.