Mice held in tubes and forced to inhale cigarette smoke – Australia’s outdated research

Hsu, A C-Y., Starkey, M.R., Hanish, I., Parsons, K., Haw, T.J., Howland, LJ, Barr, I., Mahony, J.B., Foster, P.S., Knight, D.A., Wark, P.A, Hansbro, P.M. Targeting PI3K-p110α Suppresses Influenza Virus Infection in Chronic Obstructive Pulmonary Disease American Journal of Respiratory and Critical Care Medicine V191, No. 9 (2015)

Associated Institutions
Priority Research Centre for Asthma and Respiratory Diseases, Hunter Medical Research Institute and The University of Newcastle, NSW.

Funding

This research, according to the publication, was supported by grants from the National Health and Medical Research Council of Australia (taxpayer funded) and The Rebecca L.Cooper Medical Research Foundation.

During the period from 2008 to 2012 alone the Hansbro group of researchers at the University of Newcastle have received over 2 million dollars for experiments attempting to develop a mouse model of cigarette smoke-induced disease(1)

The Experiment

In tests, that many people don’t realise are still being conducted in this day and age, laboratory mice by the dozens are loaded into tubes and forced to inhale cigarette smoke for up to 12 weeks.

In one experiment alone(2), the researchers at the University of Newcastle in NSW are attempting to use mice as experimental models of cigarette smoke-induced Chronic Obstructive Pulmonary Disease (COPD) which is a group of progressive lung diseases that block airflow and make it difficult to breathe. The diseases include emphysema, chronic bronchitis and non-reversible asthma.  

Noting that human patients with COPD and other chronic respiratory conditions are more susceptible to influenza virus infection, the researchers have not only forced mice to inhale cigarette smoke but have also infected them with the influenza virus.

The method by which mice are forced to inhale cigarette smoke

Dozens of mice in each experiment are loaded into individual tubes which are then lined up on laboratory benches. These once healthy mice are forced to inhale cigarette smoke for up to 45 minutes twice a day for 5 days a week for up to 12 weeks.

This unscientific research does not replicate the human condition of COPD which develops over many years.

Animals held in smoking devices as shown here suffer complications from the disease forced upon them as well as stress in the cramped unnatural conditions.

Custom-designed and purpose-built directed flow inhalation and smoke-exposure system., A mouse in one of the smoking chambers. Photo for educational purposes.

Photo credit: Copyright © 2017 Elsevier Inc. Journal of Allergy and Clinical Immunology 2013 131, 752-762.e7DOI: (10.1016/j.jaci.2012.11.053) http://www.jacionline.org/cms/attachment/2022388171/2042212475/fx1_lrg.jpg

The Code of Practice for Housing and Care of Laboratory Mice, Rats, Guinea Pigs and Rabbits states: "Animals must be able to perform a variety of natural activities consistent with species specific behaviour, including the opportunity for sufficient exercise within their enclosure"

It also states: "The provision of environmental enrichment for mice and rats should mimic natural habitat and behavioural requirements including in particular tunnelling, foraging, climbing, social groupings and nesting." Whilst the mice are held unnaturally in small cylinders for considerable periods of time it is impossible for them to perform natural activities and behavior.

Relevance to Humans

There is no spontaneous model of COPD and models do not mimic the entire COPD.  Different animals have different reactions to toxins and animals in laboratories are not exposed to cigarette smoke in the same manner or time frame as human smokers are.  In fact different species of the mouse react differently to the exposure.

In past publications(3), scientists have stated that neither small airway disease nor COPD exacerbations caused by cigarette smoke can be effectively modelled in animals.

Cost-Benefit Analysis:

Valuable resources such as grants from the National Health and Medical Research Foundation and the Rebecca L. Cooper Medical Research Foundation are wasted on these unreliable animal experiments and it is doubtful whether any outcomes are likely to be clinically applicable to humans.  The university instead relies on old fashioned models of scientific research instead of developing new and reliable non-animal methods.

The researchers state on the first page of their publication that the most significant risk factor to COPD is cigarette smoking. The amount of over 2 million dollars of taxpayer’s money for developing a mouse model could therefore have been better spent on replacement/alternative research or furthering campaigns to end smoking in the community.  Instead, millions have been spent on attempting to produce a mouse model of a cigarette smoker!

Replacements to animals

It has been acknowledged for many years in the scientific community that laboratory animals are poor models for human disease and in particular they are not good models of chronic bronchitis. 

At a recent workshop (August 2016) in the United States, it was recommended that investment be made into human lung models to assess tobaccos effects. Results of the workshop state that “three dimensional reconstructed models of the human lung providing more human relevant results than animal tests need to be developed and funded to assess the effects of tobacco products on COPD”(4)

Indeed public health can be protected by funding the development of in vitro (non- animal) models of human illness such as smoking caused lung diseases. Alternatives include human 3D models in combination with the latest gene expression technologies.  These alternative in vitro models can be used to understand the biological effects on humans rather than on animals.

Given the prevalence of pulmonary disease and influenza infection among human individuals, further epidemiological and/or advanced human biology-based methods of research should be undertaken in order for results to be directly relevant to human health outcomes.

What You Can Do

Write to the federal funding body - National Health and Medical Research Council - online at  complaints@nhmrc.gov.au, requesting that valid non animal research be funded and not wasted on these cruel and unnecessary mice experiments.

Write to the private funding body - Rebecca L. Cooper Medical Research Foundation - requesting that valid non animal research be funded and not wasted on these cruel and unnecessary mice experiments:
Dr Thomas Cromer, Chairman,
Rebecca L Cooper Medical Research Foundation
PO Box 1021
Edgecliffe NSW 2027
Or online form at http://www.cooperfoundation.org.au/contact.html

Write/email the VC, University of Newcastle, requesting that the university no longer approves such animal research, in particular the flawed model of smoking experiments on mice:
Prof Caroline McMillen,
Vice-Chancellor and President
University of Newcastle
University Drive
Callaghan NSW 2308


For further information about the use of mice and rats in research, see Rats and Mice - Maligned and Misunderstood.

References

1. Beckett EL, Stevens RL, Jarnicki AG, Kim RY, Hanish I, Hansbro NG, Deane A, Keely S, Horvat JC, Yang M, Oliver BG, van Rooijen N, Inman MD, Adachi R, Soberman RJ, Hamadi S, Wark PA, Foster PS, Hansbro PM  A new short term mouse model of chronic obstructive pulmonary disease identifies a role for mast cell tryptase in pathogenesis (2013) J Allergy Clin Immunol Vol 131 No. 3 752-762e7

2. Hsu, A C-Y., Starkey, M.R., Hanish, I., Parsons, K., Haw, T.J., Howland, LJ, Barr, I., Mahony, J.B., Foster, P.S., Knight, D.A., Wark, P.A, Hansbro, P.M.  Targeting PI3K-p110α Suppresses Influenza Virus Infection in Chronic Obstructive Pulmonary Disease American Journal of Respiratory and Critical Care Medicine V191, No. 9 (2015)

3. Wright, JL, Chung, A Animal models of cigarette smoke-induced chronic obstructive pulmonary disease Expert Rev Respir Med 2010 Dec 4(6) 723-34

4. Behrsing H, Raabe H, Manuppello J, Bombick B, Curren R, Sullivan K, Sethi S, Phipps R, Tesfaigzi Y, Yan S, D'Ruiz C, Tarran R, Constant S, Phillips G, Gaça M, Hayden P, Cao X, Mathis C, Hoeng J, Braun A, Hill E. Assessment of in vitro COPD models for tobacco regulatory science: Workshop proceedings, conclusions and paths forward for in vitro model use  Altern Lab Anim. 2016 May;44(2):129-66.

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