Animal Defenders International

 

Animal Defenders International

The Primate Nations: Species differences, page 1

Posted: 1 September 2006

At the beginning of this report we celebrated many of the similarities between ourselves and our fellow primates, but the biological differences are also critical. These differences undermine the precision necessary for good scientific research and product testing that produces results relevant to humans.

The use of primates in research is often justified on the grounds of the animals’ close physiological likeness to human beings. Yet for all that we have in common, at the tissue and organ level humans and other primates are in many ways quite distinct55. It is these crucial differences between the species – especially at the cellular level – that can make such a huge difference when applying results from biomedical research and testing.

The fundamental problem with animal research is that each species responds differently to substances. Furthermore the results of laboratory tests can be affected by an animal’s age, diet and bedding materials as well as the laboratory environment, which can cause biochemical changes in an animal’s body that affects results.

An example of such species differences hit the news in early 2006 when six healthy young volunteers in a trial for the experimental drug TGN1412 at Northwick Park Hospital suffered appalling side effects (one patient was dubbed ‘elephant man’ by the media). The drug had been given to laboratory primates in doses 500 times stronger than that received by the volunteers, without such side effects.

Furthermore the assumption that animals, especially primate, research is somehow vital for human health has never been properly put to the test through systematic scientific reviews(56),(57). Meanwhile, a growing number of reports suggest that, far from being reliable, animal models are untrustworthy and should be replaced, as a matter of urgency, by scientifically advanced alternative techniques(55),(57).

The International Conference on Harmonisation – the global forum for drug regulation – has acknowledged that in terms of the way a drug is handled by the body, primates can differ from humans as much as any other species(108).

Stress can trigger the release of endorphins in the brain, altering hormone levels, appetite and pain perception(109). According to the European Commission’s Scientific Committee on Animal Health and animal Welfare: “The unnatural restrictive environments and husbandry practices in research laboratories have raised concerns about the possible negative welfare aspects, both for reasons of ethics and experimental validity”(58).

This concern about the failure of animal tests to accurately predict whether a drug is going to have a toxic effect and/or how it is going to be absorbed and distributed through a patient’s body, is not new:

The Toxicology Working Group of the House of Lords Select Committee on Animals in Scientific Procedures stated that “the formulaic use of two species in safety testing is not a scientifically justifiable practice, but rather an acknowledgement of the problem of species differences in extrapolating the results of animal tests to predict effects in humans”, and, “the reliability and relevance of all existing animal tests should be reviewed as a matter of urgency”(59).

Drs Palfreyman, Charles and Blander in ‘Drug Discovery World’ observed: “One of the major challenges facing the drug discovery community is the poor predictability of animal-based strategies . . . many drugs have failed in later stages of development because the animal data were poor predictors of efficacy in the human subject . . . . One of the overriding interests of the pharmaceutical and biotechnologies industry is to create alternative development strategies that are less reliant on poor animal predictor models of human disease . . .”(60).

Others have commented that the way drugs break down and are excreted are similar in monkeys and humans, but metabolism rates differ markedly61, and the cynomolgus macaque has been referred to as the most misleading laboratory animal model for the study of toxic effects on the human heart(62).

In their 2005 report the Nuffield Council on Bioethics concluded that “there is a need for continuing review of the scientific case for using animals in research and testing. It is axiomatic that any such use should be accompanied by active and critical reflection on the validity and relevance of the models and research studies”(63).

Primates, despite their evolutionary closeness to us, are distinct from us in the way they express genes in the brain (’expression’ of a gene is the activity or product that the gene causes to occur in the body). There are even big differences in gene expression between humans and chimps, although gene expression between chimps and other primates is similar(64).

Next: Species differences, page 2

References

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