New publication demonstrates the need to replace animal models in medical research

Animals have been used in medical research for centuries. As far back as the 17th century, French philosopher and mathematician Rene Descartes convinced the scientific community that animals are mere automata – reacting like clockwork and having no feelings.

In the mid nineteenth century, French physiologist Claude Bernard, after a temporary trend against the practice, re-instigated animal experiments by convincing the scientific community that if a disease could not be replicated in animals it could not exist. It became understood amongst scientists that animal experimentation could provide both money and reputation.

Bernard is quoted as saying:

The physiologist is not an ordinary man: He is a scientist, possessed and absorbed by the scientific idea that he pursues. He does not hear the cries of animals, he does not see their flowing blood, he sees nothing but his idea, and is aware of nothing but an organism that conceals from him the problem he is seeking to solve.

Bernard did not consider his work to be immoral and was renowned for purloining the family pet. So callous and graphic was his work that his own wife, disturbed by the torturous activities in her own home, founded one of the world’s first anti-vivisection organisations.

In the 1950’s and 1960’s Harry Harlow was renowned for his work on maternal deprivation and social isolation of baby monkeys.

His ‘Pit of Despair’ experiments involved baby monkeys left alone in darkness for up to one year from birth, or repetitively separated from their peers and isolated in a chamber. These procedures quickly and unsurprisingly produced monkeys that were severely psychologically disturbed and served as models for human depression.

Fast forward to today and animals are still used in a wide range of procedures, ranging from observational studies to major physiological challenges and frequently death as an end point. Latest statistics show that around 6-7 million animals are used in Australian research and teaching every year.  Australia is the fourth highest user – behind only China, Japan and the United States and clearly the highest global user per capita. Global estimates suggest the figure for global use is around 50 million animals per year.

However just because animals have been used throughout history in medical experiments does not mean that they are the best mode of research or even necessary at all.

Proponents of using animals point to medical advances that they insist have come about from animal experiments. Opponents point to many examples where reliance on animal experiments has actually delayed medical progress, such as the development of penicillin and blood transfusions, or even shown disastrous results such as the release of Thalidomide.

Regardless of history, today science is studying diseases and drug responses on a very different level than in the 1800s and early 1900s. In the past, science was looking at traits and functions that were largely shared among species thus animals were used as surrogate humans. Science is currently studying disease and drug response at the level where the differences between individual humans are of critical significance.

According to the US Food and Drugs Administration nine out of ten drugs deemed successful through animal tests, fail in human clinical trials. Any other industry that boasts a 90% failure rate would be considered absurd (and more recent reports suggest this has now risen to 95%). Logic suggests that the drugs work in humans not because they were successfully tested on animals but in spite of being tested on animals.  

Further, this not only questions the efficacy and very base argument for using animals, but critically raises the question about the drugs that failed in animals and were discarded: how many might have worked in humans?  How many discarded cures for cancer?  

Let’s consider chimpanzees - the species most closely related to humans. The chimpanzee genome (complete genetic material) is 98.77 percent identical to that of humans, therefore researchers argue that chimpanzees will be the species most likely to replicate human outcomes in scientific (biomedical and toxicity) testing.  However this small genetic variation between human and chimpanzees accounts for very significant differences in the way diseases affect the two species.Chimpanzees are not currently used in Australian research, and those primates that are used have even wider genetic variation to humans, meaning that the differences in results would be greater again.

Despite chimpanzees being the most genetically similar animals to humans, experiments on them have not provided substantial contributions to biomedical research. Therefore, it is logical for us to question, that if the most genetically similar animal to humans is an ineffective model, then how can the use of more genetically distant animals – dogs, mice or fish - assist us?

These concerns are verified in systematic reviews of the literature conducted in the areas of toxicity testing and biomedical research which have shown that scientific alternatives are far more predictive of human outcomes than data obtained from animals.

Such trepidations may well lead to the question; have we been going about medical research all wrong?

A team of international authors expert in innovative toxicology and animal replacement, led by Dr Gill Langley of Humane Society International (HSI), states:

[A] new paradigm is needed for fundamental research into human diseases and for drug discovery. The focus should move decisively away from preclinical animal studies and overly simplistic cell models toward a systems biology framework to integrate new types of scientific data, such as from omics, novel human-specific in vitro models, and clinical studies. Such a framework would help enable a comprehensive and dynamic understanding of disease causation and pathophysiology.

According to Australian co-author and Humane Research Australia scientific advisor, Dr. Brett Lidbury, the article raises the following key issues:

• Closer scrutiny and analyses on the value of pre-clinical animal-models has revealed disappointment in terms of human translation from fundamental research;
• Twenty-first century innovation and technology is now available to provide animal replacement alternatives, particularly through systems approaches (e.g. Integration of external and internal disease-associated processes)
• Fundamental biomedical research can learn much from toxicology and the advances to find alternatives to animal models – a good example is the “adverse outcome pathway” (AOP).

The paper is a welcome development as the current methods of using different species to obtain data for humans is simply not working. We need a different approach – one that focuses on the genetic, anatomic and metabolic intricacies of the species we are trying to study and not erroneous and misleading extrapolations from animal tests.

According to Dr Langley:

It is essential we adopt and utilise human-species specific models in vitro, in vivo (clinical), and in silico (in computer). We need to entirely revise the medical research paradigm, so that novel techniques and their data aren't simply added piecemeal to the existing 'edifice' but are used strategically in a new framework that also eliminates failing animal models.

The article states:

The key driver for a new paradigm in health research is the slow progress scientists have made in understanding human disease. This has resulted in a lack of success in drug discovery and translation of laboratory findings into effective therapies and in the spiraling investment of resources wasted by late-stage drug failures.

Whilst no one wants to harm animals, human medical progress is generally deemed to take priority over animal suffering, and cost/benefit analyses currently allow animal experiments to proceed.  As this recent publication suggests however, it is time we reconsider our approach to medical research and embrace a new paradigm that focuses on the human species and is likely to lead to genuine medical progress.