Alzheimer’s Australia’s Of Mice And Brain

Animals have been used in scientific experiments and tests for many years, providing key findings for advancing new formulas and medications, as well as dietary supplements and health regulations – but is this really the best option?

Are we going to find the best results in helping to ease and eradicate conditions such as Alzheimer’s and cancer in humans by using animals as test subjects, or is the whole procedure cruel and unnecessary? With this technologically-savvy world, are there any alternatives that can help push us forward beyond animal testing to help find the end of these conditions? Will the mouse ever have his day?

There are two sides to every story and both pros and cons to the argument around animal testing.

It has always been a hot topic, but it is has also played an important role in finding ways to better human medical conditions and ease pain in chronic conditions. Animal testing has used a number of different species as test subjects and even native Australian mammals (such as platypi, bilbies and echidnas¹) are used in the National Health and Medical Research Council (NHMRC) scientific testing, but mice and rats are one of the key components in the development of health advancements for diseases such as Alzheimer’s and cancer.

Mice and rats are used for several reasons, including convenience of housing and inexpensive maintenance, as well as their fast reproduction cycles and short lifespans mean that several generations can be observed in a short time period. They are generally docile creatures and are easier to handle than some other mammals, and when used in medical trials they are often inbred and are genetically identical, which makes the trials more conclusive and invariable. Mice and rats also have biological genes and characteristics that are very close to that of humans, making human conditions such as symptoms of cancer and Alzheimer’s disease easy to replicate in the test subjects, and changes easier to identify².

The NHMRC acknowledges that using animals in scientific studies raises important ethical questions and the involvement of mice and rats, as well as other types of species of animals, is a conflicting issue³.

On one hand, reading and hearing the personal stories, experiences and issues that many humans face when living with terminal and non-terminal diseases such as Alzheimer’s disease is heartbreaking. There is so much suffering in the world that people do not deserve to deteriorate in such ways, and that it is a basic human desire to help and do whatever we can to find cures and ways to slow down the process and symptoms of diseases that are living with us and our loved ones. However, there is also a basic fundamental morality concerning the distinction between right and wrong, and the ethical view on all forms of life – not just humans – encompasses the view that all living creatures including animals deserve respect and humane treatment.

Mice have been used as animal testing subjects for Alzheimer’s disease since the 1980s and their role in treatment and medical testing were a highlight for discussion at the 9^th Alzheimer’s + Parkinson’s Disease Symposium, which was hosted in 2015 at The Queensland Brain Institute at the University of Queensland. Professor Frank LaFerla, the Director of the Institute for Memory Impairments and Neurological Disorders at the University of California Irvine, highlighted that no new treatments for Alzheimer’s have emerged, despite the consistent use of mice in research. Professor LaFerla, whose presentation was about the challenges of translating results from Alzheimer’s disease mouse studies into human clinical trials, pointed out that the only two currently approved treatments that are used to reduce the severity of Alzheimer’s disease symptoms (the treatments being acetylcholinesterase inhibtors and memantine) were actually not tested on mice counterparts before human clinical trials began⁴.

Mice studies are rarely translated into human trials due to several reasons, including the fact that animal cell structures are simply genetically different to humans. While there are anatomical, immunological, physiological and behavioral differences, mice brains genetically don’t have much cell loss compared to human brains, creating a widespread difference regarding cognitive impairment.

These major differences are not uncommon. The Humane Research Australia 2013 report “Animal Experimentation – a necessary evil?” states that “different species have a different genetic make-up and is on the genetic and molecular level that variances occurs. Results can differ…” The report, which makes the stance of being “strongly opposed to the use of animals in research on both ethical and scientific grounds,” and “maintain that animal experimentation is NOT a ‘necessary evil’, and that instead it is unreliable science,” do agree that humans and mice share 99% of the same genes, but highlight that the common genes are regulated in different ways⁵.

In order to bridge the gap, mice are currently being genetically modified to mimic the full range of symptoms that are usually associated with Alzheimer’s disease, including the cognitive impairments, the presence of neurofibrillary tangles and synapses, and neuro-degeneration. Professor LaFerla reiterated that these genetically modified mice are still being used in hopes to develop the pathology similar to humans in order to assist in the treatment of Alzheimer’s disease.

The mice – both genetically altered or not – all come under the Australian laws and codes of practice to ensure that all animals used in research are treated ethically and humanely – including in any termination of test subjects.

But is this really good enough? Are there any guarantees on the treatment of the animals at a personal level, and if not, is there something we can do to change this?

There have been further advancements within the medical field that could provide alternative views in favour of ethical testing, as suggested under William Russell and Rex Burch’s The Principles of Humane Experimental Technique. These techniques include Replacement (replacing the use of animals where they would have otherwise been used), Reduction (using strategies to result in fewer animals being used to obtain sufficient data to answer research questions) and Refinement (modifying the experimental procedures to minimise any pain or distress and enhancing the welfare of the animal)⁶. It was identified by Humane Research Australia report that Replacement is the optimal technique regarding providing advancements in human clinical treatments as well as providing ethical treatment of animals.

Some suggestions for ethical and non-lethal alternatives that have advanced the need for animal testing can include:

In Vitro testing, which is a series of human cells grown in a technologically advanced system to mimic the structure and function of human organs and human systems. The “organs on chips” developed by the Harvard Wyss Institute for Biologically Inspired Engineering, can be used in place of animal testing and can replicate different reactions and responses more accurately than animal experiments do⁷.

This momentous leap in non-animal testing has also provided a further advancement for synthetic biology that provides complex cellar reactions to occur outside of living cells on something as small as a pocket sized piece of paper. Using colour changing proteins on the sensors of the model, the synthetic biology will be capable of identifying harmful pathogens such as the Ebola virus⁸. While this new scientific testing is still currently unavailable in laboratories, it shows an amazing innovation for advancing beyond animal testing.

In Silico testing, or computer modelling, is a wide range of sophisticated computer models that simulate human biology as part of a series of mathematical equations, and predict the progression of developing diseases. Many studies for In Silico testing accurately predict the way new drugs react to human biology, and can easily replace the use of animals for exploratory research⁹. These forms of computer modelling and technological advancements have also been able to provide human-patient simulators that can breathe, bleed, convulse, talk and can even die. The robotic simulators mimic illnesses and diseases in humans and can provide the appropriate response to medical intervention, including cardiovascular, respiratory and neurological responses¹⁰.

It is with a satisfactory report that 97% of medical schools across the United States of America have completely ceased all clinical animal trials for technological experiments through human-patient simulations, computer modelling techniques and virtual reality systems¹¹.

So, taking into the consideration these advanced and ethical medical research systems that are bridging the limitations that occur in translating mice and other animal studies to human trials, the future ensuring the welfare of humans and animals – while still under development – are looking to be positive. This means that the leap forward using research other than animal testing could be the research we need to see in order to eradicate and ease these chronic conditions.

In the end, our mice friends might just have their best-laid schemes work out after all¹².