Category Archives: Alternatives to animal testing and research

Will you support us?

Are you already a member of Humane Research Australia (HRA)? If so, I invite you to renew your membership. It’s only $30 pa. If you are not a member, would you consider becoming one?

I started this blog 3 ½ years ago. I’m the president of HRA, and while I’ve mentioned HRA in some of my blog posts, I haven’t dedicated a whole post to HRA. So this is what we do and what we want to achieve:

Here in Australia, the use of animals in research is very high for such a small country. Only the USA, Japan and China use more animals. We want to see animal experimentation phased out and replaced by humane and human-relevant methods.

Why do we want this? We can’t be sure that insights gained from experiments with animals will be applicable in humans. Animals are not reliable models for human disease. For example, cancer was cured in mice decades ago, but the results didn’t translate to humans. Sadly, scientists know more about mice than humans. Animal research involves many procedures that would be regarded as animal abuse if carried out on our pets. Even when no painful procedures are carried out, the animals are usually kept captive in artificial environments that do not allow for species-specific behaviours. It is a sad situation, both for the lab animals who suffer stress and pain, and for people who miss out on treatments and cures because the research is not relevant to humans.

Many people still think animal experimentation is a necessary evil. But research articles pointing to the many shortcomings of animal research are accumulating*.

So what does HRA do? Below are some of the activities and achievements over the last 12 months.

Campaigns

The Ban Primate Experiments campaign has highlighted the use of non-human primates in invasive, cruel experiments. The macaques, marmosets and baboons involved in these experiments are bred in three government-funded facilities in Australia. While these sentient animals are genetically and cognitively similar to us, they are sufficiently different for primate experiments to result in research findings of little value to humans.

I and another member of HRA’s committee of management (Dr Eleonora Gullone) were signatories to an open letter asking to stop neuroscience research involving non-human primates. It was signed by 22 scientists, primatologists and animal welfare experts, among them Sir David Attenborough and Dr Jane Goodall.

Following a campaign by People for the Ethical Treatment of Animals (PETA) and HRA, the Royal Australasian College of Surgeons (RACS) announced earlier this year that it will phase out the use of live animals for its Early Management of Severe Trauma (EMST) program by 2018. EMST trains physicians and Australian Defence Force (ADF) medical officers on treating traumatic injuries. To date, the training involves cutting holes into the throats, chests, and limbs of live animals including dogs and pigs. This will be replaced by human-simulation technology.

Earlier this month the Australian Government introduced a bill to ban animal testing of cosmetic products. This is a result of campaigning by animal welfare groups around the country, and including HRA and Humane Society International’s Be Cruelty Free Campaign.

Case studies

It is difficult for the public to find out exactly what experiments are conducted on animals. Universities and other research institutions are reluctant to provide detail. Not all animal research is published in professional journals. When it is published, the articles are often behind a pay wall and written in a way that does not make much sense to the lay person. HRA has summarised some of these studies in plain English.

These scenarios are not only highly unethical; they are unscientific. Data cannot be extrapolated from one species to another with certainty of success.

We need to challenge the researchers and the funding bodies and encourage them to embrace new technologies – non-animal methodologies that are both more humane and scientifically-valid as they relate specifically to human conditions. This is the critical role of HRA. It’s imperative that the community and HRA supporters particularly, are aware of what is happening and what they can do to help stop it.

Over the last year, the Australian media have reported on cruel experiments. Some of these reports have been re-published in other countries. For example, the Sydney Morning Herald reported about cruel greyhound experiments at Monash University and the Alfred Hospital in Melbourne, where the dogs were suffocated and had their hearts removed. Those hearts were then transplanted into other greyhounds who were killed after the procedure.

Animal use statistics

Unlike many other countries, Australia does not have a national collection of animal use data. HRA attempts to make up for this absence of data. The states and territories collect these data, but not all states make them available. HRA collects the available data, publishes them on its website, and provides an estimate of the total number of animals used for research and teaching in Australia. For 2015 this number was close to 10 million animals (this also includes environmental studies where animals were observed rather than experimented on).

Submissions

HRA writes submissions to government bodies, encourages its members and the public to write submissions, and provides background information to assist with submission writing. At present, the proposed Code of Practice for the Keeping of Racing Greyhounds (in Victoria) is open for public comment until 14 August 2017.

This is not all we do. For example, we also lobby the federal government and funding agencies to redirect funding away from animal experimentation and instead provide financial incentives to researchers to develop alternatives to animals. This lobbying takes considerable time and resources. We need your financial support to continue this work, and your assistance to help us to do this is greatly appreciated.

Follow us on Facebook or Twitter , or subscribe to our e-news to learn more about our work.

Here is a video of me (and my best mate Sheba) asking you to support us in the important work we do to end cruel and unnecessary animal experiments. If you have a look at the video, you’ll see that we don’t waste money on media production. It was done in-house, in the HRA office, with our multi-talented CEO Helen Marston directing, filming and editing.

Unlike many other charities, HRA does not have DGR (Deductible Gift Recipient) status – because our work is not classified as public benevolent, and does not involve “hands on” care of animals. This means that we do not qualify for many philanthropic grants that are available and which many charities depend on for their continued work. It also means that we are unable to take advantage of various other schemes such as workplace giving as these also require DGR status.

Furthermore, we do not receive ANY government funding. We are therefore solely reliant on memberships and donations to fund the important work that we undertake towards ending cruel and unnecessary animal experiments.

Thank you for reading this, and I’m more than happy to respond to any questions and/or suggestions.

* On the HRA website, we have dedicated a page to links to academic papers, conference proceedings and government reports that show animals as bad models for human medicines and treatments. Search for “bias” (without the quotation marks) on this web page.

 

Advertisements

Australia’s new cosmetics testing bill – a welcome move

830637807_a37e6cdd9c_o

Source: Flickr/ Lynette Olanos

During the 2016 election campaign, the Australian Government committed to introduce a ban on animal testing of cosmetic products. The Industrial Chemicals Bill 2017 has been introduced in the House of Representatives on 1 June 2017 to implement this commitment. The following sections of the bill refer to animal testing:

103 Ban on animal test data for determining category for cosmetics

(1) Without limiting paragraph 102(1)(b), if an industrial chemical is to be introduced     for an end use solely in cosmetics, rules made for the purposes of that paragraph may include the requirement mentioned in subsection (2).

(2) The requirement is that, when determining the category of introduction for such an industrial chemical, a person must not use animal test data obtained from tests conducted on or after 1 July 2018 in circumstances prescribed by the rules.

168   Ban on animal test data for applications for cosmetics

(1) Without limiting subsection 167(1), if an industrial chemical is to be introduced for an end use solely in cosmetics, an application under this Act relating to the introduction must meet the requirement in subsection (2).

(2) The requirement is that the application must not include animal test data obtained from tests conducted on or after 1 July 2018 in circumstances prescribed by the rules for the purposes of this subsection.

Government legislation to support the end of cosmetic animal testing and trade in Australia is very welcome. However, the draft legislation offers a loophole which would allow newly animal tested cosmetic ingredients to be introduced to the Australian market after the bill becomes law. This would fail to meet the Coalition’s election promise and the expectations of the Australian public to fully end cosmetics testing in Australia.

The loophole rests on the word solely. Only new animal test data used in introductions which are solely for cosmetics use would be prohibited. If the new chemical ingredient would also be used for other purposes, for example in cleaning products, animal testing would still be allowed.

A joint statement by #BeCrueltyFree Australia and Humane Research Australia observes:

This is very welcome progress; however, as not all substances are used exclusively as cosmetic ingredients, some cosmetic ingredients will still be able to be newly animal tested and introduced into Australia under the current proposed language. This is an important departure from existing bans in the European Union, Norway, Switzerland, Israel, and India, which have all banned the use of newly animal-tested ingredients when introducing or marketing cosmetics.

How many of the new chemicals might be used for multiple purposes? A 2013 report by the European Commission stated that:

… large cosmetics manufacturers estimated that, on average, around 10% or less of the new ingredients used by large cosmetics manufacturers were new to market (i.e. have not previously been used in other product sectors).

Dropping the word solely from the bill might fix this loophole. It would ensure that the ban applies to all cosmetics ingredients, and the use of chemicals for non-cosmetic purposes would not be impacted by the ban.

What would happen if a chemical not previously used in cosmetics has been tested in animals and a human health risk has been assumed? Obviously, such a chemical would not be introduced for use in cosmetics, irrespective of the ban (this case would represent disqualifying a chemical for use in cosmetics, rather than introducing one).

On the whole, while this bill does not change much for companies that manufacture cosmetics, it sends a message that Australia does not support cruel and unnecessary testing on animals – if for cosmetics only.

The bill will not have much impact on the number of animals used in animal experiments in Australia, as – to my knowledge – no cosmetics testing on animals has taken place here for some time. But is it a first step towards phasing out animal experimentation for other purposes, too?

4554133914_0a7869981c_o

Source: Flickr/ Melody

 

Other countries have made much more progress in this regard. For example, the Parliament of the Netherlands in 2016 passed a motion to phase out all research on non-human primates, and by 2025 the Netherlands aims to become a world leader in animal-free science. The Netherlands National Committee for the Protection of Animals Used for Scientific Purposes (NCad) has provided a schedule for phasing out animal procedures.

In the EU, the Directive 2010/63/EU on the protection of animals used for scientific purposes requires national governments to assist in the advancement of alternative methods to animal testing and to promote the use of non-animal methods.

Unlike Australia, the European Union keeps track of progress made in developing and using alternatives to animal testing. The European Chemicals Agency has just published its third report on “The use of alternatives to testing on animals for the REACH Regulation”. It looks promising:

Registrants use existing information and alternatives to animal testing. Altogether, 6290 substances were analysed for the report. Out of these, 89 % have at least one data endpoint where an alternative was used instead of a study on animals.

The most common alternative method was using information on similar substances (read-across), used in 63 % of the analysed substances, followed by combining information from different sources (weight of evidence, 43 %) and computer modelling (QSAR prediction, 34 %).

In the US, the Federal Accountability in Chemical Testing (FACT) Act was introduced in Congress earlier this year:

The FACT Act would improve reporting by EPA, FDA, NIH, USDA and other government agencies about their efforts to replace inefficient, multi-million-dollar animal tests with faster, less costly and more effective alternative methods for assessing the safety of chemicals, drugs, foods, cosmetics and other substances.

6118102919_83e77057cd_o

Source: Flickr/ pumpkincat210

 

However, it’s anyone’s guess if or when this bill might become law, given that the U.S. Department of Agriculture has removed public access to tens of thousands of reports relevant to animal welfare.

Banning cosmetics testing on animals in Australia has been long overdue and is a welcome contribution towards the global move away from animal experimentation more broadly.

 

 

PS – On 6/06/2017 the Humane Cosmetics Act was introduced in the U.S. House of Representatives. See this press release.

The organs-on-chips market

After looking at the animal model market, I wondered about industry predictions for new developments in biomedical research that are human-relevant. Perhaps the field known as organs-on-chips holds the greatest promise for physiologically relevant, precisely controlled, and scalable engineered systems for use in the drug development process.

According to the Wyss Institute for Biologically Inspired Engineering at Harvard University, human organs-on-chips are microchips lined by living human cells that can be used in drug development, disease modelling and personalised medicine.

This is what they look like:

The development and testing of new drugs takes many years and is expensive. Very expensive. The cost of developing a new prescription drug is now around $2.6 billion. Traditionally, animals such as mice and dogs have been used in the development of  drugs. But around 90% of new drugs that have been found to be safe and effective in animals fail in clinical trials with humans.

To understand this high attrition rate between drug development and approvals, it is imperative to consider the drawbacks of the current methods of preclinical testing. Traditional 2D cellculture models can be effective in providing a broad indication of
compound efficacy and toxicity; however, they fail to represent cell function and physiology accurately because these cultures are monolayers as opposed to the 3D structures found in an intact organ and hence important tissue–tissue interactions are absent. Furthermore, upon the ingestion of a drug, it undergoes important transformations that allow it to be absorbed, distributed, metabolized and excreted (ADME). Examining these processes provides important information on the pharmacokinetics (PK) of the drug including dose, concentration and toxicity profiles. These parameters are traditionally tested in animals such as rodents and dogs along with a determination of safety and efficacy. However, a simple extrapolation of the PK and toxicity profiles from animals to humans is inaccurate owing to the vast differences in the genomes between the two species, as in the case of TGN1412. The development of assays that can better predict the safety, pharmacology and toxicity of a drug in humans is of paramount importance. Organs-on-chips is one such system that has the potential to reduce the dependence on animal testing and provide a more accurate readout of the safety and efficacy profile of a drug compared with conventional methods.
Source: Balijepalli, A., & Sivaramakrishan, V. (2017). Organs-on-chips: research and commercial perspectives. Drug Discovery Today, 22(2), 397-403.

In 2010, Donald Ingber at the Wyss Institute developed the first organ-on-a-chip, a lung-on-a-chip. Since then, academic institutions and private companies – sometimes working in partnership – have added miniature models of, for example, the liver, kidney, heart, bone marrow, cornea, brain, spleen and the human gut.

A multidisciplinary team at the Wyss Institute have also developed a chip that smokes cigarettes like a human. So there is no excuse to force mice to inhale cigarette smoke, as researchers at the Hunter Medical Research Institute and The University of Newcastle have done.

An organ-on-a-chip is about the size of a human thumb and “made from a flexible, translucent polymer. Microfluidic tubes, each less than a millimeter in diameter and lined with human cells taken from the organ of interest, run in complex patterns within the chip. When nutrients, blood and test-compounds such as experimental drugs are pumped through the tubes, the cells replicate some of the key functions of a living organ“.

Organs-on-chips can be used to study many biomedical phenomena. Apart from drug development and toxicity testing, other possible uses include, for example, personalised medicine (where stems cells derived from individual patients could be used to identify which therapies might be likely to succeed) or testing responses to biological and chemical  weapons.

As an alternative to conventional cell culture and animal models, human organs-on-chips could transform many areas of basic research and drug development. They could be applied to research on molecular mechanisms of organ development and disease, on organ-organ coupling and on the interactions of the body with stimuli such as drugs, environmental agents, consumer products and medical devices. Fundamental questions that might be addressed include how microenvironmental cues regulate cell differentiation, tissue development and disease progression; how tissues heal and regenerate (e.g., mechanisms of control of angiogenic sprouting and epithelial sheet migration); and how different types of immune cells and cytokines contribute to toxicity, inflammation, infection and multi-organ failure. When combined with patient-specific primary or iPS cells, or with gene editing technologies (e.g., CRISPR) to introduce disease-causing mutations, this technology could be used to develop personalized models of health and disease.
Source: Bhatia, S. N., & Ingber, D. E. (2014). Microfluidic organs-on-chips. Nature Biotechnology, 32(8), 760-772.

A recent article in the journal Drug Discovery Today provided the following examples of investment in organ-on-chip developments:

These are only a few examples of work on organs-on-chips. Worldwide, it is considered a multi-million, or even billion dollar market. For example, Yole Développement estimates that “the market could grow at a compound annual growth rate from 2017-2022 of 38-57% to reach $60M-$117M in 2022.” Another company, Accuracy Research, expects the organs-on-chips market to grow around 69.4% over the next decade to reach approximately $6.13 billion by 2025.

Large pharmaceutical and cosmetics companies are expected to start using organs-on-chips. Some companies have already partnerships with organs-on-chips developers, such as L’Oréal, Pfizer, AstraZeneca, Roche and Sanofi.

Ethical concerns are also at the heart of this new market: more than one hundred million animals are used in laboratory experiments worldwide every year, and could be replaced by pieces of microfluidic technology. Source: Yole Développement

Where does Australia sit in this market?

Some projects at the Australian Institute for Bioengineering and Nanotechnology, University of Queensland involve “the development of tumour-on-a-chip, organs-on-a-chip for rapid preclinical evaluation of potential nanomaterials for targeted therapeutics”. At the International Conference on Biomedical Engineering in December 2016, Professor Justin Cooper-White from this institute presented a keynote address on “Human kidney organogenesis from pluripotent stem cells on a chip”. There were other presentation on organs-on-chips, but none from Australia.

Two PhD Scholarships Bioengineering 3D in vitro model systems were recently advertised by Swinburne University of Technology.

A few academics with affiliations to Australian universities have published articles on organs-on-chips. However, it is unclear whether they are involved in the development of this technology. I could locate three articles in peer-reviewed journals on the topic:

  1. Nauman Khalid, a Postdoctoral Research Fellow at Deakin University has co-authored two articles, titled “Recent lab-on-chip developments for novel drug discovery” and “Industrial lab-on-a-chip: design, applications and scale-up for drug discovery and delivery“. I could not locate any information on the Deakin University website that links him to current work on organs-on-chips.
  2. One of the 14 authors of “Screening out irrelevant cell-based models of disease” lists Queensland University of Technology as an affiliation. In the article, the authors discuss new opportunities for exploiting the latest advances in cell-based assay technologies, of which organs-on-chips are one.
  3. Researchers from RMIT had a review of “Successes and future outlook for microfluidics-based cardiovascular drug discovery” published.

 

Where is the investment in organs-on-chips?

The published outcomes of the 2016 NHMRC Grant Application Round include two projects that involve work on organs-on-chips. The project descriptions are as follows:

Neurodegenerative diseases such as dementia and motor neuron disease are a major health burden for Australia and new approaches to treatment are urgently required. Essential trace elements such as copper, zinc and iron show major changes in neurodegneration, however, we do not understand how this drives disease processes. This proposal will develop an innovative 3D ‘brain on a chip’ cell model to probe the role of trace elements in brain pathology and identify exciting new treatments options.

and

New human cell culture models of Alzheimer’s disease are urgently needed to help translate drugs into successful patient outcomes. In this proposal we will develop an Alzheimer’s disease brain-on-a-chip that contains the major human brain cell types and neuropathological features of the Alzheimer’s. We will demonstrate the applicability of the model for identifying new Alzheimer’s disease drugs and diagnostics and show that the model can be readily adopted by Australian Alzheimer’s researchers.

Total grant funding for all 1,056 funded projects adds up to $828 million. The extent of the funding for the two organs-on-chips projects is not obvious from the published data, nor at which university, research institute or hospital the work will be undertaken.

I could not find information about investment on this technology by private companies.

body-on-a-chip Khalid et al 2017

Body-on-a-chip. Source: Khalid, Kobayashi & Nakajima, 2017.

Perhaps there is more work on organs-on-chips occurring in Australia, but I couldn’t find relevant information (I searched Google and PubMed). By and large, in Australia researchers continue to use archaic methods that hurt animals, are costly and ineffective. Despite the development of more human-relevant methods, the use of animals for research and education purposes is not decreasing in Australia.

The latest available statistics have just been published by Humane Research Australia. They “show that approximately 10.27 million animals were used in research and teaching in Australia in 2015, although this high number is largely due to NSW counting 4,123,049 native animals in environmental studies which involved observation only.” This compares to approximately 7 million animals in 2014.

Here we have a potentially multi-billion dollar market, and Australia is fiddling at the edges.

 

 

The Netherlands – Not just a pretty country

In December 2016, the Netherlands National Committee for the Protection of Animals Used for Scientific Purposes (NCad) provided an advisory report to the Dutch Minister of Agriculture Martijn van Dam after the Minister had requested a schedule for phasing out animal procedures. The report is titled “Transition to non-animal research – About the possibilities for phasing out animal procedures and stimulating innovation without laboratory animals”.

Earlier in 2016, the Dutch Parliament had already passed a motion to phase out all research on non-human primates. The Government aims now at phasing out animal research methods by 2025 and becoming a world leader in animal-free science.

So what is the NCad’s advice?

Overall, the NCad observes that it is time for a paradigm shift. While the animal model has become the “golden standard” in a number of research areas, it inflicts pain and suffering on animals and is perpetuated, for example, “because the current scientific quality assessment system is generally based on bibliometric criteria”, because journals impose animal data requirements on authors, and because the use of animal procedures is stipulated in many guidelines and laws.

Conversely, alternative approaches are becoming more common and “will increase in number and importance”. But the provision of funding for alternatives and innovation is not enough for a paradigm shift to occur. The parties involved in the field will also need to no longer regard animal research as the golden standard, or animal research is “no longer delivering the necessary results”.

In regard to the latter, I would argue that for some decades animal research has not delivered the necessary results for governments and citizens, although it has delivered profits and careers for the industry.

The report argues for strong government leadership to enable a paradigm shift to animal-free science.

The NCad believes that it is only with a broad-ranging and coordinated effort by the ministries involved and other stakeholders that significant progress can be made in reducing the use of animals in research. The choice of a clear direction, clear objectives and concrete steps is essential in this context, but emotions, social structures and other factors over which less influence can be wielded inevitably play a role, given the nature of transitions.

According to the report, regulatory research and testing can and should be phased out by 2025:

The use of laboratory animals in regulatory safety testing of chemicals, food ingredients, pesticides and (veterinary) medicines can be phased out by 2025, whilst maintaining the existing safety level. The same applies to the use of laboratory animals for the release of biological products, such as vaccines.

This should occur together with an international review of the regulatory risk assessment process.

However, the NCad suggests that regulatory pre-clinical research “cannot be phased out at the same pace”.

In regulatory clinical research, medicines that were successful in animal procedures often fail in clinical trials. For these instances, so-called backward validation studies can be used to investigate or determine the predictive value of pre-clinical animal tests and innovative methods for clinical research on human subjects. On the basis of the insights obtained, pre-clinical research models can be improved. The NCad recommends for the Minister for Agriculture to make funds available for this.

For fundamental scientific research, the NCad recommends the development of a 10-year plan for the different areas of basic research in consultation with the public and the scientific community.

In regard to applied and translational research, the NCad observes that “more rapid progress can be made than is being made at the present time. There is a great deal of innovative potential that could be better exploited.”

For education and training,

NCad recognises that the use of laboratory animals in training professionals involved in the field will continue to be necessary to a certain extent, but believes that, here too, cultivating a mindset that does not rely on laboratory animals will help keep the number of animal procedures to a minimum.

The NCad encourages the Netherlands Government to take leadership at the international level. For example:

Urge the European Commission to define a European strategy that takes an ambitious and integrated approach to non-animal research, one that includes animal welfare and the 3Rs in impact assessments and the development of new legislation and regulations. Also, call for existing legislation and regulations to be critically reviewed in this respect, and for it to be mandatory for accepted alternatives to be included, for funds to be made available for the further development of innovations without laboratory animals and for EU standards to be observed in commercial treaties.

…consider collaborating with the US organisations EPA (for the risk assessment of substances and pesticides) and FDA (for the risk assessment of medicines and food additives), as part of a European alliance or otherwise, on the theme of New Risk Management in approval of substances.

… In collaboration with the ministries of Health, Welfare and Sport and Infrastructure and the Environment, the RIVM and relevant international organisations, endeavour to obtain European agreements that make it easier to depart from regulatory animal procedures where possible through the use of validated alternative methods. Also, aim for transparent communication regarding situations where alternatives to the regulatory animal procedures have been used.

Overall, this is a great initiative towards phasing out animal experiments. It shows that it can be done given the political will. Congratulations to Minister van Dam and his government. Congratulations also to the citizens of the Netherlands who have advocated for this change. I hope that other countries will follow your example.

Where is Australia at the 3R Olympics?

Source: Flickr/ Romano Guidotti

Source: Flickr/ Romano Guidotti

Right now Australia is doing well at the Olympics in Rio. We are a sporting nation, and the sports competition between countries captures our attention. I don’t care much about competitive sports. But imagine countries competed to eliminate animal experimentation and develop more human-relevant research methods!

While Australia can compete with the rest of the world in sport, when it comes to animal experimentation we have some catching up to do.

How many animals are used for scientific research and teaching?

Unlike countries such as Canada, Great Britain, Germany or New Zealand, Australia does not keep a central collection of animal use data. Instead, some states collect data, while others don’t. Collection methods vary, and it can take up to five years until data are made available.

Humane Research Australia (HRA) collects annual statistics from the states/territories and publishes them on its website. The latest available statistics are from 2014 and only available from four of the eight states/ territories (Victoria, New South Wales, Tasmania, Western Australia).

According to these stats, the approximate total number of animals used in Australia was 6.99 million in 2014 (figures for Queensland, South Australia, the Australian Capital Territory and the Northern Territory were estimated on the basis of figures provided for previous years). Let’s compare this with some other countries:

Germany (2014) – 2 million animals

Canada (2014) – 3.75 million animals

Great Britain (2015) – 4 million animals

Australia (2014) – 6.99 million

European Union (27 member states, 2011 or 2010) – 11.5 million

(These stats do not include the number of animals killed for research and teaching without prior experimentation. For example, in Germany just under 800,000 animals were used in this way in 2014.)

Number of animals used in research and teaching; Germany, Canada, Great Britain, Australia

Australia has a much smaller population than Germany, Canada or Great Britain. Per head of population, Australia uses 8.4 times as many animals as Germany, 4.6 times as many animals as Great Britain, and 2.8 times as many animals as Canada.

pop x no of animals used.png

Using so many animals in Australian labs, shouldn’t we be ahead of other countries in regard to new drug discoveries, new treatments, new insights into human biology? Sadly, that’s not how it works. With new discoveries and insights gained from animals we can’t be sure that they will be applicable in humans. They rarely are.

What efforts are made to develop and validate non-animal methods in research and teaching?

I’ve written about Government support for the development and validation of non-animal research methods in a previous blog. Not much has changed since then (January 2015).

Perhaps a legislative change in the US is noteworthy. In June this year, President Obama signed into law the Frank R. Lautenberg Chemical Safety for the 21st Century Act. The Physicians Committee for Responsible Medicine describes the improvement:

The bill requires alternatives to animal tests be considered and used, and places restrictions on animal testing–which are stronger than current law–that will over time facilitate the development and adoption of human-relevant, nonanimal methods. Because information obtained on chemicals will be human-relevant, products Americans use will be safer.

Principles to replace and reduce animal-based test methods and to increase the use of information from human-based and mechanistic tools are integrated into the heart of the legislation.

Countries like Australia, the USA, the UK, Germany (and the rest of the European Union) all subscribe to the 3Rs in animal research: replacement (not using animals where possible), reduction (reducing the number of animals used) and refinement (minimising impact).

Sadly, there is no competition to achieve these goals. But many countries are doing much better than Australia. For example, in the USA federal agencies are required to support the development of alternative test methods.

Here, our major funder of research, the National Health and Medical Research Council (NHMRC), does NOT offer incentives or specific grants to encourage the development of more human-relevant methods, there are NO government prizes for such research, and there appears NO interest in documenting progress made towards the 3Rs. Further, there is no dedicated centre for development and/or validation of alternative methods (government-sponsored centres exist in the USA, Europe, Brazil, Japan, Canada and Korea; in Germany some federal states fund academic positions to progress animal-free research).

At the 3R Olympics, Australia is somewhere right at the back.

 

 

World’s largest funder of medical research and the limitations of animal experimentation

Neural pathways in the brain. Source: Flickr/ NICHD

Neural pathways in the brain. Source: Flickr/ NICHD

In December 2015, the National Institutes of Health (NIH) released the NIH-Wide Strategic Plan, Fiscal Years 2016–2020: Turning Discovery Into Health. NIH is the world’s largest source of medical research funding. It consists of 27 institutes and centres (ICs), along with program offices, which collectively are referred to as ICOs. The Strategic Plan had been requested by Congress.

The NIH receives nearly thirty billion dollars a year from the US Government, and the total number of active grants in 2014 was more than 47,000.

Because a broad research portfolio is critical for carrying out NIH’s mission, the agency’s portfolio of grants and contracts covers the full range of biomedical, behavioral, and social sciences research, from basic to applied. (p. 5)

While NIH institutes and centres have their own strategic plans, the document is meant to lay out a common approach for priority setting across all NIH’s components.

The plan has four objectives:

  1. advance opportunities in biomedical research in fundamental science, treatment and cures, and health promotion and disease prevention;
  2. foster innovation by setting NIH priorities to enhance nimbleness, consider burden of disease and value of permanently eradicating a disease, and advance research opportunities presented by rare diseases;
  3. enhance scientific stewardship by recruiting and retaining an outstanding biomedical research workforce, enhancing workforce diversity and impact through partnerships, ensuring rigor and reproducibility, optimizing approaches to inform funding decisions, encouraging innovation, and engaging in proactive risk management practices; and
  4. excel as a federal science agency by managing for results by developing the “science of science,” balancing outputs with outcomes, conducting workforce analyses, continually reviewing peer review, evaluating steps to enhance rigor and reproducibility, reducing administrative burden, and tracking effectiveness of risk management in decision making.

What about animal experimentation?

In the following, I will focus on the part that animal research plays in this Strategic Plan.

Like Australia’s largest funding body of biomedical research, the National Health and Medical Research Council (NHMRC), the NIH funds experimentation on animals. Unlike the NHMRC, the NIH is explicit in acknowledging the limitations of such research AND dedicates significant funding to the development of more human-relevant research.

Discovery of potential therapeutic targets and candidate therapies are essential first steps in the development of new treatments and cures, but they are far from the only steps. The transition of scientific discoveries to human clinical trials has become increasingly costly and time consuming, with a great number of candidate therapies failing to cross what has been dubbed the “Valley of Death.” NIH-funded research will play an increasingly important role in identifying hurdles in this process, as well as generating approaches for accelerating the development and testing of potential treatments and cures. … Development of a new therapeutic is a long, costly, and risky endeavor. Currently, a novel drug, device, or other medical intervention takes about 14 years and $2 billion to develop, with a failure rate exceeding 95%. (p. 19)

So what are the human-relevant methods that are mentioned in the document and supported by grants?

Organs-on-chips and Tissue Chip for Drug Screening

Tissue Chips. Petri dish and animal models often fail to provide good ways to mimic disease or predict how drugs will work in humans, resulting in much wasted time and money while patients wait for therapies. To address that challenge, NIH, DARPA, and FDA are collaborating to develop 3D platforms engineered to support living human tissues and cells, called tissue chips or organs-on-chips. An integrated body-on-a-chip is the ultimate goal. (p. 38)

… the development of innovative ’tissue- and organ-on-a-chip’ systems is helping to bridge the gap between fundamental and translational science, providing new models of complex pathology for understanding basic mechanisms of disease. (p. 15)

Toxicology in the 21st Century (Tox21)

Tox21 researchers aim to develop better toxicity assessment methods to quickly and efficiently test whether certain chemical compounds have the potential to disrupt processes in the human body that may lead to negative health effects.

The “better” in the above quote surely refers to the unpredictability of animal testing.

New innovations such as molecule cross-coupling methods and human 3D organoid technologies

Despite the many exciting scientific opportunities for speeding the development of treatments and cures, significant challenges remain. Over the next 5 years, NIH will support research aimed at addressing a wide range of obstacles that lie at various points throughout the therapeutic development process. … To improve the efficiency, relevance, and accuracy of preclinical research, NIH will catalyze powerful innovations, including molecule cross-coupling methods that will open a vast new frontier of “chemical space” and human 3D organoid technologies that will be better than animal models. (p. 22)

Like the mouse running around and around in the wheel, animal experimentation is getting nowhere. Medical science has moved on, and it’s time to move away from outdated methods.

Despite acknowledging the proven usefulness and further potential of non-animal methods, the NIH continues to fund animal experimentation. But it’s a step in the right direction. It will waste fewer resources on unreliable methods using animals, and continue and strengthen investment in more reliable, often cheaper and faster, human-relevant research methods.

Last thoughts for 2015

Source: Flickr/ Marji Beach

Source: Flickr/ Marji Beach

It’s the time of year for reviews and setting new goals. I don’t do New Year’s resolutions. For this blog I did not set specific goals for 2015. But in January 2015 I wrote of my intention

to monitor publicly available sources for information on the development and validation of animal free research methods.

I did write about this topic (here, here, here, here). Other topics included, for example, companies’ animal welfare supply chain policies, the shortcomings and futility of animal research, and ethical consumption.

On average, I posted twice per month. The two most viewed posts during the year were “Vegan now mainstream? – Yes, but elsewhere” and “Has my dinner been tested on animals?

During 2015, I contacted 30 Australian food companies, asking them whether their company conducts or commissions animal research. Nine of these responded, telling me that they do not use animal testing. But I do not know whether any Australian companies do use animals to test their products (some overseas companies still do so).

(The results from my 2014 survey of 117 ASX listed companies in the industry sectors Pharmaceuticals, Biotechnology & Life Sciences, Health Care Equipment & Services, and Household & Personal Products are still here.)

Also, I emailed four Australian supermarket chains, asking them questions about their vegetarian and vegan products. The responses did not tell me much.

I hope you found the 2015 ozsheba blog posts interesting and useful. There were a few likes throughout the year, but no comments (why were there no comments?).

So what is ahead for 2016? More of the same. That is, posts of interest to investors and consumers about the treatment of animals in research and the production of food, and related topics. Perhaps readers could send a few comments and let me know which topics are of particular interest.

Source: Flickr/ Chi King

Source: Flickr/ Chi King

In the meantime, I wish you good health, joy and peace in the new year. And I wish us all a more compassionate world for the animals.