More Evidence Submitted To The House Of Lords Select Committee on Animals In Scientific Procedures

I have long been opposed to the use of the use of live animals in laboratory experiments. I am opposed to this practice for several reasons. I believe that the use of live, sentient creatures in this way is barbaric, unnecessary and immoral. And I believe that it is the reliance of drug companies on animal experiments which is largely responsible for the current epidemic of iatrogenesis - diseases caused, in general, by doctors and, in particular, by prescription drugs. (I have, in the past, proved beyond doubt that animal experiments are utterly unreliable, unpredictable and therefore quite worthless. On every occasion when I have debated this issue with vivisectors I have won.)

I recently appeared before the Animals in Scientific Procedures Committee at the House of Lords. The Committee, the most important official inquiry into the use of animals in experiments for decades, will report its findings direct to the Government.

After my appearance, the Committee wrote asking me to review papers which had been submitted by the Department of Health in an attempt to substantiate their argument that animal testing is both necessary and efficacious.

The report which follows is a precis of the report which I sent to the Committee; a report which clearly shows that none of the DoH papers prove that animal testing is either necessary or efficacious.

Summary of Conclusions by Vernon Coleman
On the basis of this evidence, and assuming that this is the best scientific evidence that the Department of Health can find in support of its argument that toxicological testing on animals is of value, then, assuming that the Committee intends to base its conclusions on sound scientific evidence, the Committee has no choice but to at the very least call for an independent inquiry (for example a Royal Commission) into the relevance of animal experimentation.

These papers do not substantiate the claims made by the Government. Indeed, on the contrary, the evidence available here proves my point: animal experimentation is unpredictable, unreliable and of no value whatsoever to human beings. I would be happy to appear before the Committee again if the Committee has any questions based on my analysis of these papers. I would also be happy to appear before the Committee and debate with any expert witness provided by the Department of Health.

Analysis
In an attempt to prove the validity of animal experimentation the DoH supplied seven scientific papers. I examined each of the papers in turn.

1. Backmann, K et al (1996) `Scaling basic toxicokinetic parameters from rat to man' - Environmental Health Perspectives 104/4 400-407

This paper is barely relevant since it refers only to `values for half life' and does not purport to offer conclusions about the value of animal experimentation in drug testing.

Even so, there are some remarkable statements made. For example, on page 402, the authors claim: `when explicit weights were not provided rat weights were set at 0.25kg and human weights at 70kg.' Are we to assume that in the absence of accurate figures the authors merely adopted average weights? This hardly seems scientific. The authors list eleven other potential sources of error, including, for example, the fact that `there was insufficient technical detail...to determine whether all studies from which kinetic data were gathered were structured appropriately (i.e. the goodness of the underlying data cannot be validated).'

Conclusion: This paper does not support the claim that animal testing is of value to humans.

2. Migaki G and Capen CC (1984) `Animal models in biomedical research' in Laboratory Animal Medicine, edited by Fox, JG et al (Aademic Press Inc)

This paper merely investigates anatomical and disease similarities between animals and humans and makes no attempt to assess the value of vivisection to doctors or patients.

Some of their observations seem to me to be rather bizarre.

For example, in assessing the value of dogs for experiments on atherosclerosis the authors point out: `It appears that the dog requires a high cholesterol diet rich in hydrogenated coconut oil for the lesions of atherosclerosis to develop...The necessity of adding coconut oil to the diet substantiates its atherogenic property. In contrast to those in humans, the lesions in the dog tend to be located in the small arteries...' (Page 674).

My observation here would be that if you feed a dog on high hydrogenated coconut oil you are changing the dog's normal diet considerably.

The obvious question I would like to ask is: `Just how can results from experiments on this artificially devised morbidity be regarded as relevant to humans?'

This is not a question the authors even attempt to answer.

Conclusion: The Department of Health cannot be seriously suggesting that this paper supports the use of animals in experiments allegedly performed to help protect humans.

3. Cronin MTD and Dearden JC (1995) `QSAR in Toxicology. 2. Prediction of Acute Mammalian Toxicity and Interspecies Correlations', Quantitative Structure-Activity Relationships 14/2. 117-120

This paper can best be summarised with a couple of quotes:

1) `QSAR predictions for mammalian toxicity are generally poorly developed...'

(from the Abstract page 117)

2) `In conclusion QSAR analysis can be applied to acute mammalian toxicity data, but more work is required. An investigation of possible modes of toxic action is necessary and also comparison with toxicity data for other species to see whether extrapolation is feasible. Progress will ultimately be hampered by the lack of reliable data, and by the fact that this is undoubtedly an area of toxicology where it would be difficult morally and scientifically to justify further testing simply in order to improve QSAR models.'
(page 118)

Conclusion: This paper does not prove the Department of Health's claim that animal experiments are essential or of value.

4. Gad SC (1990) `Model Selection in Toxicology: Principles and Practice' , Journal of the American College of Toxicology, 9/3, 291-302

Gad claims (on page 292) that `adverse effects found in two separate and diverse model species have a much higher predictive power for the outcome of exposure in humans...'

I would refer the Committee to the following quote from Zbinden's paper (also submitted in the bundle of papers supplied by the DoH):

`One of the principal arguments in favour of using two distinct species in toxicity testing has always been that this measure increases the likelihood of detecting adverse effects that are relevant for man. In this simplistic form, this conclusion is untenable...'

Gad concludes his introduction with this comment: `...there are times when adverse effects have nothing to do with what will happen in humans.'

My point precisely.

And if you don't know when those times are (and we don't) that makes ALL animal experiments pointless. (If you were given several thousand aeroplane take off times, warned that most of the times were wildly inaccurate, but not told which were the inaccurate times, would you take any notice of ANY of the times?)

Gad continues in his paper to explain that `there is no animal species that mimics humans in all respects'.

He makes a list of criteria for selection of ideal test species and then writes: `It is all too easy to suggest that the animal of choice should fit the criteria enumerated above, but in actuality these are empty words. Actual selections are made generally on practical and `political' criteria rather than these logical points.'

Hardly good support for the DoH case.

Gad goes on to explore the ways in which species are selected for experiments.

`First, economic considerations such as ease of commercial production and availability, housing, lifespan, etc have, as was pointed out above, favoured the use of small laboratory animals.'

So, presumably, vivisectors use whatever animals are lying around in cages and can be used cheaply - regardless of whether or not those animals are likely to prove good `models'.

`The second major set of factors can only be classified generally as custom or habit. What the scientists and technicians are used to using, and what the regulators are used to interpreting data from, is generally what we tend to continue doing. The resulting inertia is the greatest impediment not only to proper model selection, but also to adaptation of new or improved study designs and to the development and use of in vitro models.'

And this is supposed to be science?

I would like to thank the DoH for drawing my attention to this remarkable paper.

In a section headed `Limitations of Models' Gad writes: `Despite our best efforts, when human exposures to a chemical entity (such as a drug) occur, the results do not always come near what was expected based on animal studies.'

Exactly my point.

Gad then lists ten reasons `why data obtained in animal studies do not always match human experience'. The first reason on his list is: `The animal species selected differs in response from humans.'

The other nine reasons are also excellent arguments for abandoning animal experimentation.

In Table 3 Gad gives `Reasons why high dose toxicity testing is usually not predictive of human effects.' In relation to this table I would like to draw the Committee's attention to the paper by Morton below. Morton describes an experiment in which: `The doses necessary to cause the hepatic effects in rats were therefore approximately 2000 fold those that produced similar toxicity in human patients.'

On page 296 Gad continues his excellent paper with a section dealing with `Cross Species Extrapolation'. `There are,' he writes, `life span (or temporal) differences that are not adequately considered, nor have they been in the past.' And he continues:

`Another difficulty is that the lifespan of humans is from 4.4 to 66 times that of common test species. Thus, there is generally a much longer time available for many toxicities to be expressed or developed in people than in test animals. These sorts of temporal considerations are of considerable importance, and this area of chronotoxicology has not yet begun to really be explored.'

Quite.

Gan continues with an admission that the `best scaling factor is not generally agreed upon.' (Transforming results from one species to another is called scaling.)

And finally he admits (page 299) that `there are many factors which can alter the physiological state of an individual' and `there are also individual animal-to-animal variations in temperature, health and sensitivity to toxicities which are recognised and expected by experienced animal researchers but are only broadly understood.'

Precisely.

In the introduction to this paper Gad writes: `Although there are differences in the responses of various species (including humans) to carcinogens, the overall predictive value of such results (when tempered by judgement) is clear.' (page 291/292)

Whose judgement? Who does the tempering? Conclusion: This paper does not substantiate the Department of Health's case. Indeed, I am grateful to them for drawing it to my attention.

5. Morton DM (1998). `Importance of Species Selection in Drug Toxicity Testing', Toxicology Letters, 102-103, 545-550

The author of this paper claims (on page 545) that `...only a few new compounds have been terminated during clinical trials due to toxicity'.

This is, presumably, offered as evidence in support of the value of animal experiments.

But the corollary to this is that iatrogenesis (doctor induced disease) is now widely recognised to be a major cause of illness in people. Illnesses caused by prescription drugs are recognised as one of the main causes of morbidity in humans.

If animal testing was of value then toxicity problems would be picked up at an early stage and iatrogenesis would not be such a significant problem.

Morton's paper continues to give support to my argument in other ways:

`Caution is always required in interpreting toxic effects in different species since such effects may have little relevance in humans.' (page 546)

`...adverse effects of drugs in humans, not easily predicted by animal studies, include nausea, headache, dizziness, tinnitus, vision disturbances and hypersensitivity and skin reactions.' (page 546)

On page 547 Morton writes: `One of the more controversial areas of discussion in toxicity study design and choice of test species has been that of carcinogenicity testing. For many years, carcinogenicity studies in rodent species have been required by worldwide regulatory agencies for drugs proposed for chronic administration in humans.'

But, as I have pointed out, when drugs are shown to cause cancer in animals they are still prescribed for people - on the grounds that animal tests are irrelevant. For example, tamoxifen, currently being prescribed for thousands of healthy women, is known to cause cancer of the liver in rats and cancer of the gonads in mice.

Morton also comments that: `It was later established that rats and mice are highly responsive to the induction of hepatocellular neoplasms with peroxisome proliferators but that dogs, monkeys and humans are much less responsive.' (page 548)

and: `The doses necessary to cause the hepatic effects in rats were therefore approximately 2000 fold those that produced similar toxicity in human patients.'
(page 549)

This is significant because other authors have claimed that massive dosages produce irrelevant results.

See, for example, the list entitled `Reasons why high dose toxicity testing is usually not predictive of human effects' in the paper by Gad (listed no 4 above) submitted by the Department of Health.

Morton concludes:

`In summary, toxicity studies in animals often provide value data to predict adverse effects of new drugs in humans.' (page 550)

I could find no evidence to support this summary in this paper. The author might as well have written that: `In summary, Gordon Brown's next budget will be wonderful.'

Conclusion: This paper provides no evidence supporting the Department of Health's claims for the value of animal experiments.

6. Olsen H et al (2000), `Concordance of the Toxicity of Pharmaceuticals in Humans and in Animals', Regulatory Toxicology and Pharmacology 32, 56-67

I do not understand why this paper was submitted. The first two sentences of the discussion are:

`This study did not attempt to assess the predictability of preclinical experimental data to humans. What it evaluated was the concordance between adverse findings in clinical data with data which had been generated in experimental animals (preclinical toxicology).'

Surely it is the very predictability of preclinical experimental data which the Department of health is attempting to prove? Retrospective studies are of no value.

Looking through a pile of animal experiments and searching for ones which match known data in humans is of no value whatsoever - except, perhaps, to the vivisection industry and the authors of scientific papers.

There are, nevertheless, some interesting comments in this paper:

`There are few published analyses of comparative animal-human toxicity data on pharmaceuticals, with progress presumably inhibited by the perceived confidential nature of such data.' (page 57)

`...toxicities that occurred in rats only were rarely observed in humans and those in dogs only occurred slightly more frequently in humans, while those that occurred in both rats and dogs showed about a 70% concordance with humans.'
(page 57)

`Despite its relatively high incidence in all species, hepatobiliary toxicity in humans was surprisingly poorly predicted from animal studies.'
(page 57)

`Two reviews addressed those drug cases where the clinical toxicity was so severe as to lead to withdrawal from marketing in the approximate period 1960-1990....In one report only 4 of 24 cases were predictable from animal data; in the other report, only 6 of 114 clinical toxicities had animal correlates.'
(page 57).

`A knowledge of pharmacology in various species, including humans, tells us that species can differ markedly in their responses to pharmacological agents.'
(page 57)

`In addition to the fundamental differences between species in biological response, Zbinden (1991) cautioned against too great an expectation from animal toxicology studies for a host of reasons inherent in the designs of such studies and of clinical trials.'
(page 57)

Conclusion: This paper does not prove that animal testing is of value to people.

7. Gerberick et al (2001), `Contact Allergenic Potency: Correlation of Human and Lymph Node Assay Data', American Journal of Contact Dermatitis, Vol 12 No 3 September 156-161 I received an incomplete copy of this paper.

The discussion section of this paper begins: `To increase our ability to conduct sound skin sensitization risk assessments, it is imperative that improved methods for quantifying allergen potency and exposure be developed.' (page 159) I would agree with that statement at least.

I am a little bewildered by this paper. I could find no reference to the number of patients or animals involved. I do note that: `Twenty chemicals were assigned to 1 of 5 human potency classes....based soley on the expert clinical judgement of the authors.'

Conclusion: The part of this paper which I received does not prove that animal testing is essential for human safety. I note that this paper came, in part, from the Human and Environmental Safety Division of Procter and Gamble, USA, that the contact address of the author of this paper is The Procter and Gamble Company in the USA and that the research was supported in part by a grant from the United Kingdom Health and Safety Executive. I find it difficult to understand why British taxpayers supported this work.

The DoH also enclosed several other papers which were not on their list. I have also reviewed these papers.

8. Zbinden G, 1993, `The Concept of Multispecies Testing in industrial Toxicology', `Regulatory Toxicology and Pharmacology 17, 85-94

A review of this paper reveals the following quote on page 89:

`One of the principal arguments in favour of using two distinct species in toxicity testing has always been that this measure increases the likelihood of detecting adverse effects that are relevant for man. In this simplistic form, this conclusion is untenable: if the toxicological responses in the rodent and the nonrodent species are different, then the prediction of a toxic effect in man of at least one, and possibly of both, findings is in error. If rodents and nonrodents respond identically, the prediction for man that is based on such findings may be correct or false.'

Zbinden concludes (on page 93): `contrary findings in rodents and nonrodents occur frequently'.

Proponents of animal testing often claim that the weakness of tests on individual species can be overcome by testing on multiple species.

Conclusion: This paper does not substantiate the Department of Health's claim for the value of animal experiments.

9. Tomatis L, et al, 1990. `The contribution of experimental studies to risk assessment of carcinogenic agents in humans', Exp Pathol, 40 251-266

This paper begins with an extraordinary statement: `...aetiological factors have not yet been identified for cancers that occur in some of the most frequent target organs, such as prostate and colon in men, breast and colon in women.' (page 251)

The authors continue (on page 252) with the equally extraordinary statement that: `the list of etiological factors of human cancer ...still reflects the absolute preponderance of environmental chemical agents.'

This is, quite simply, not true. Both the British and American governments have listed the causative factors for cancer, and environmental chemical agents are of relatively minor significance. The National Academy of Sciences in the USA (founded in 1863 by Act of Congress to serve as an official advisor to the US Government in all matters of science and technology), has reported that researchers have estimated that almost 60% of women's cancers and a little more than 40% of men's cancers are related to nutritional factors. In 1982 the National Research Council in the USA published a technical report entitled `Diet, Nutrition and Cancer' which showed that diet was probably the single most important factor in the development of cancer and there was evidence linking cancers of the breast, colon and prostate to particular foods or types of food.

Details of over 20 scientific papers proving the relationship of diet to cancers of the colon, prostate and breast can be found in my book `Food for Thought'. (I will happily supply copies of this book if the Committee would like to see them.)

Tobacco is, apart from food, the other main cause of cancer in humans.

In my view, the authors do, however, do better with their direct comments on the value of animal experiments: `The attitude prevailing today is that only epidemiological studies may provide unequivocal evidence that an exposure is carcinogenic to humans. This has as a consequence that the experimental evidence, in particular that obtained in long-term animal tests, has been often regarded as a sort of second-rate type of evidence: it is claimed that chemicals proven to be carcinogenic in animals cannot be considered human carcinogens until there is epidemiological proof.' (page 252)

On page 257 they continue: `The main objective support for the value of experimental data in predicting a qualitatively similar effect in humans comes from the fact that experimental evidence of carcinogenicity has on several occasions been obtained before the epidemiological evidence.'

The words `on several occasions' are a remarkable admission since many pro vivisectionists claim that animal experiments are crucial for toxicology testing. But if experimental evidence is only rarely valid it must always be ignored. (Would anyone trust a train timetable which contained 1,000 times, knowing that 700 of those times were wrong?)

The fact is that in practice animal tests are so unreliable and unpredictable that tests which show carcinogenicity are ignored unless there is also reliable human epidemiological evidence. If you are going to ignore the animal experiments there is clearly no point whatsoever in doing them in the first place.

I would remind the Committee that the widely prescribed drug tamoxifen, currently being prescribed for thousands of perfectly healthy women because it is believed that it may help prevent breast cancer, is known to cause cancer of the liver when given to rats and cancer of the gonads when given to mice. These results are ignored on the grounds that animals are different to people and that the fact that the drug causes cancer in rats and mice is of no significance to people. (Why do the tests in the first place if you are merely going to ignore them?)

Later in this paper (on page 258) the authors admit that: `The fact that concordance is imperfect between data in humans and results in experimental animals (namely for 11 of the 35 human carcinogens tested in experimental animals the evidence is less than sufficient) is often taken as an argument to downgrade the value of results from experimental animals in predicting similar effects in humans.'

Quite.

At the end of their paper these authors conclude (on page 264): `The role of carcinogenicity tests in the quantitative estimation of risks is still questionable...'

Conclusion: The paper does not prove the Department of Health's case.

Comment
These papers do not prove the value of animal experiments. On the contrary they clearly prove that animal experimentation is so unpredictable and unreliable that it is worthless to human beings.

I can understand why drug companies support vivisection: it is a double edged tool which enables them to sell drugs for a mass market without the danger of performing tests which might prove that a potentially profitable drug causes dangerous side effects and cannot therefore be marketed. If a test on animals shows that a drug causes cancer (as, for example, with the very widely prescribed drug tamoxifen) the test will be ignored on the grounds that animals are different to people. If a test on animals shows that a drug does not cause cancer the results of the test will be used to help substantiate the claim that the drug is safe for humans. Drug companies just cannot lose when performing animal tests. The Committee will be aware that I submitted a list of 50 drugs which are currently prescribed for human beings but which are known to cause cancer or other serious health problems in animals. These adverse results are all ignored on the grounds that animals are different to people - proving quite conclusively that initial toxicology testing on animals is utterly pointless.

I am perfectly happy to accept that animal testing is more expensive than other forms of testing.

But the evidence supports the view that drug companies perform animal tests because, although they may be more expensive than more effective forms of testing, they enable them to mass-market new drugs without the risk of having to withdraw potentially profitable products in the early stages.

The big question is: `Why does the Government continue to support vivisection when the Department of Health cannot provide one jot of evidence in support of its claim that animal experimentation is valid and of value? Indeed, on the contrary, the evidence supplied by the Department of Health proves my argument much more effectively than it proves their argument.'

Surely the Department of Health should devote itself to finding the truth, and protecting the interests of patients, rather than simply attempting (in vain) to protect the commercial interests of the pharmaceutical industry? Assessing animal experimentation alongside non animal experimentation would be a good starting point.

Finally, I would like the Department of Health to explain why it allows doctors to prescribe a huge number of drugs which cause cancer in animals and yet, at the same time, considers animal experiment results essential for the granting of licences to drug companies.

If you are going to demand that drug companies perform animal tests, and then going to ignore the results of those tests when they are inconvenient, why do the tests in the first place?

Four out of ten patients in the UK suffer unpleasant, severe or fatal side effects after taking prescription drugs. The cost of all these side effects puts a great burden on the NHS. If animal tests were abandoned, and drugs were tested more effectively, the nation would be healthier and the demands on the NHS would be much lighter.

Copyright Vernon Coleman 2003


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