When evidence and vested interests collide

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Source: Flickr/ Etienne

The scientific method is the best approach we have to study and learn about the physical and natural world. When new knowledge is gained and comes to be the best available evidence at the time (until new, more accurate or in some other way better evidence becomes available), one would hope that the new knowledge finds its way quickly into the relevant disciplines, that practitioners take note and incorporate it into their practice, procedures and policies. In the health area, this time lag has been assumed to be 17 years – but we don’t really know, and “further research is needed”, as they often write in research articles.

There are many reasons for the length of the health research translation process. One of these is conflict of interest. A recent article in MJA InSight demonstrates this nicely. The article is titled “Prostate cancer: urologists fight back”.

We have known for some time that – from a population perspective – screening for prostate cancer and the resultant surgical procedures have overall little benefit for men. Two recent studies have now shown that for men with early prostate cancer, prostatectomy (i. e. surgery to remove all or part of the prostate gland) did not result in reduced mortality, but left many with nasty side effects.

Two recent clinical trials, Prostate Testing for Cancer and Treatment (ProtecT) and Prostate Cancer Intervention versus Observation Trial (PIVOT), completely undermine the stratospheric spin associated with prostate cancer being a death sentence. They are unambiguous in their implications.

The bottom line? Men with early stage abnormalities of the prostate who do not undergo surgery or radiation treatment, but whose condition is monitored for any progression of the cancer, live just as long as men who opted for complete removal of the prostate and who now live with its immediate consequences, including incontinence, intimacy issues, bowel problems and intervention regret.

This should be good news for older men. But they may never be told.

The MJA InSight article quotes prominent urologists who appear to have difficulty accepting the new evidence. Instead, they dismiss the two studies as being flawed.

Besides, a radiation oncologist claims that the surgeons are gatekeepers who often don’t refer higher risk patients to radiotherapy, which – she claims – is as effective as surgery:

There’s a massive financial conflict of interest there, because they don’t have a vested interest in referring men on to a radiation oncologist. They lose income if someone chooses a non-invasive intervention. People are reluctant to say it, but that’s the elephant in the room.

But might radiation oncologists have conflicts of interest as well?

Meanwhile, it may be worth pondering the results of a US study, which compared the recommendations of urologists and radiation oncologists for the treatment of localised prostate cancer. Surprise, surprise: for the same cases, the specialists overwhelmingly recommended the treatment that they themselves delivered.

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Source: Flickr/ Patrick Marioné

I argue there are parallels to animal experimentation. Animal researchers have built their careers on experimenting on animals. That’s their area of expertise, that’s the subject of their publications and conference talks, that’s how they make their living. In universities, the pressure to publish or perish is such that researchers rarely have the luxury to take time out for learning new non-animal, human-relevant methods. Operating on mice and using advanced computer-modelling techniques, for example, are quite different skills.

Grants are won on the basis of prior experience, and the peer review system “punishes researchers with innovative projects that may be risky, but could be highly successful”. Doing things differently and taking risks doesn’t pay:

Well established investigators with mature projects produce large amounts of preliminary data for applications. However, younger researchers (who completed their PhD less than 15 years previously) with new research programs or groundbreaking research, struggle to generate similar volumes of data; their teams are smaller and have less funding; they take more risk and this leads to lower success rates in obtaining funding.

Also, it takes a special person to be able to acknowledge after a career in a particular area that much of their work was of limited use. Dr Elias Zerhouni, ex-director of the US National Institutes of Health (NIH) had this to say:

We have moved away from studying human disease in humans,” he lamented. “We all drank the Kool-Aid on that one, me included.” With the ability to knock in or knock out any gene in a mouse—which “can’t sue us,” Zerhouni quipped—researchers have over-relied on animal data. “The problem is that it hasn’t worked, and it’s time we stopped dancing around the problem…We need to refocus and adapt new methodologies for use in humans to understand disease biology in humans.

The pressure to publish for the sake of publishing can lead to dreadful research. Dreadful because of its cruelty in the treatment of animals, and dreadful because it is a great waste of limited resources. This page on the Retraction Watch website critiques one such study.

The evidence for the limited value of animal experimentation is accumulating. Some point the finger at inferior study design in animal research, or more broadly a lack of scientific rigour, compared to studies that involve humans, while others identify species differences as responsible for the poor predictive value of animal models. For further links to studies that highlight why animals are not good models for human medicine, go to this website and search for the keyword “bias” (without the quotation marks).

Why do we let vested interests, financial or otherwise, have such a detrimental influence on the allocation of resources for biomedical research? That might be a topic for another blog post.

 

 

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.

 

Australia’s new cosmetics testing bill – a welcome move

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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?

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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.

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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 Animal Model Market

Animals are used as “models” for studying human biology and diseases, to test drugs and vaccines. Most of these animals are specifically bred for research purposes, although they are also obtained from other sources. For example, in Australia “surplus” dogs from the greyhound racing industry have ended up in research labs.

Although animals have proven poor models for human disease research, and only around 5% of drugs that are safe and effective in animals are suitable for humans, the animal model market is a big industry. Mice and rats (murine models) are the most commonly used animals in research labs. Other animals bred for research purposes include, for example, monkeys, pigs, dogs, cats, and rabbits. The main applications include physiology, toxicology, cancer research, neurological research, biomedical research, genetic research, and xenotransplantation.

The Animal Model Market does not only include the breeding and sale of animals; the animals also need cages, feed, bedding, and other care products.

The end users in this market are pharmaceutical companies, research institutes, contract research organisations, and educational institutes.

Different types of mice and rats are for sale. For example:

  • inbred mice, genetically engineered mice, conditioned/surgically modified mice, hybrid/congenic mice, outbred mice, spontaneous mutant mice
  • knockout, outbred, inbred, hybrid, immunodeficient, conditioned rats.

Adelaide University’s Laboratory Animal Services provide a price list “for inbred, outbred and hybrid rodents for internal clients and external clients”. Prices range from $3.24 for outbred new born mice under 6 days to $80.80 for a time mated Hybrid F1 mouse.

The following is a collection of quotes (grammatical errors included) from websites that provide/sell information about the Animal Model Market.

Animal model market: Market wise overview

Animal models are emerging globally and there is a growing trend in the usage of animal models in drug discovery. Rapid advancement in the novel technology made the animal models constructive and easy. The market witness high competitiveness and high capital investment with animal models. Even though high cost of animal model research it never hampers the growth. The high incidence rate of diseases and adverse effects of the drugs drives the market towards animal models to ensure the safety of the humans. Other factors the contributing the growth of the animal model includes government involvement in research and research institutes for development of standard protocols for animal models.

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Obese diabetic mouse. Source: Flickr/Mycroyance

Mice

Mice Model Market is poised to reach USD 1.59 Billion by 2021 with 7.5% CAGR during the forecast period of 2016-2021.

In 2016, North America is expected to account for the largest share of the market, followed by Europe, Asia-Pacific, and the Rest of the World (RoW). North America’s large share is attributed to the rising demands for monoclonal antibody production, continued and responsible use of animals ensured by animal care organizations, rising preclinical activities by CROs and pharmaceutical companies, growing stem cell research in Canada, and government support for the development of protein drugs in Canada.

CAGR = compound annual growth rate

The mice model market is projected to reach USD 1.59 Billion by 2021 from USD 1.11 Billion in 2016, at a CAGR of 7.5% in the next five years (2016 to 2021). The growth of the market can be attributed to ongoing innovations in mice models, continuous support in the form of investments and grants, and growing demand for humanized mice models. In the coming years, the mice models market is expected to witness the highest growth rate in the Asia-Pacific region. The high growth in the region can be attributed to less stringent regulations on the use of animal models for research in the region, international alliances for R&D activities in China, growth in regenerative medicine, biomedical, and medical research in Japan, growing presence of global players, development of bioclusters to boost the biotechnology industry in India, ongoing biomedical research activities in Australia, and rising pharmaceutical & biotechnology R&D activities.

Mice Model Market Drivers:

  • Ongoing innovations in mice models
  • Mice models for immune diseases
  • Mice models for cancer
  • Mice models for rare diseases
  • Growing consumption of personalized medicine driving the demand for humanized mice models
  • Continuous support in the form of grants and investments
  • Growing number of pharmaceutical R&D activities
  • Increasing focus of associations on the development of embryonic stem cells as well as knockout and mutant mice
  • International Mouse Phenotyping Consortium (IMPC)
  • International Knockout Mouse Consortium (IKMC)

Mice Model Market Restraints:

  • Growing use of rat models
  • Increased benefits from cryopreservation
  • Regulations and laws for ethical use of animals in research
  • The Animal Welfare Act
  • Public Health Service Policy on Humane Care and Use of Laboratory Animals

Mice Model Market Challenge:

  • Development of alternative methods to animal testing
  • Advancements in zebrafish model development
  • Growing need for improved mice models

Stakeholders of the Mice Model Market 

  • Mice models and services companies
  • Mice model and services distributors
  • Animal care products manufacturers and suppliers
  • Out–licensing life sciences companies (Pharmaceutical/Biopharmaceutical/Biotechnology)
  • In–licensing life sciences companies (Pharmaceutical/Biopharmaceutical/Biotechnology)
  • Clinical research organizations (CROs)
  • Academic institutes
  • Government and private research institutes
  • Medical research centers
  • Public and private animal health agencies
  • Animal care associations
  • Business consultancies
  • Venture capitalists

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Rats

The global rat model market size was valued at USD 412.3 million in 2016 and is expected to grow at a CAGR of 8.3% over the forecast period. Growing development of new medical devices and biotechnological products is anticipated to support growth of the market.

The rising incidence of chronic conditions, introduction of new infectious strains, and growing healthcare economic burden over matured regions such as North America are expected to boost the research activities within the area.

On the contrary, possibility of research at reduced cost in countries such as Japan, India, Thailand, and Singapore is anticipated to promote growth of the rat model industry within the Asia Pacific region. The region is expected to hold over 10.0% of the share by 2025.

 

The Animal Model Market is an industry of substantial size with many stakeholders. Continuation and market expansion is in their interest. Can we expect stakeholders in this market to acknowledge the limitations of animal research, phase out animal experiments and use more human-relevant models?

It is difficult to get a man to understand something, when his salary depends upon his not understanding it!

 

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.

Le Parti Animaliste est là!

The Parliament of the Netherlands was the first in the world to have representation of a political party  that puts the interests of non-human animals and the planet at the centre of its policies: on 22 November 2006 the Party for the Animals got two seats. The Partij voor de Dieren has now a total of 50 seats in the Senate, the Lower House, the provinces, water boards, municipal councils, and one seat in the European Parliament.

Since then, similar parties in 17 other countries followed its lead. The latest is the Parti Animaliste in France, which was launched last month (14 November 2016).

As I’ve started to re-acquaint myself with the French language, the first foreign language I learned, I am taking the opportunity of reading about the French Animal Party in French – not much about it is available in English anyway.  (With thanks to Google for help with translating the odd word that I don’t understand)

The party program (not available in English) includes, for example, demands to incorporate animal protection and rights in the constitution, the creation of a ministry for animal protection, no-kill animal shelters, the prohibition of financial profit from the transfer of pets, compulsory health insurance for pets, an end to zoos and keeping dolphins captive, a ban on hunting, and the protection of habitats of wild animals.

In regard to so-called food animals, mutilation practices such as beak trimming and dehorning are to be prohibited, as well as the practice of force-feeding, the grinding of chicks and ducklings, and breeding that results in suffering (such as fast-growing chickens). Prohibition should also apply to the killing of animals with CO2, and live export to non-EU countries. Cameras should be installed in slaughterhouses and controlled by an independent authority. There are also various suggestions for the promotion of a plant-based diet.

While the above is an incomplete list of examples, I will translate the program as it relates to animal experimentation in full below:

Establish a national agency for non-animal methods

The aim of this agency will be to facilitate the transition from experimental animal research to non-animal methods; it will be responsible for coordinating all the devices and methods, ensuring their application and evaluating their results.

  • Support innovation and the development of alternative methods to animal testing, initiating calls for projects – particularly in the orphan areas* – and using European schemes such as “Horizon 2020“.
  • Develop translational research that makes it possible to move from the stage of scientific discovery to the development of a product or a “routine” alternative method.
  • Support research laboratories in their material and methodological transition towards experimental methods that do not use animals.

Develop training in non-animal methods

  • Put in place the conditions for the retraining of researchers through training on non-animal methods (development of training modules with the national research agency, incentives for retraining for public sector researchers, supporting publications, etc.) and to build training modules specifically dedicated to experts participating in national (or European) bodies.
  • Create multidisciplinary degree courses focusing on non-animal methods for research students (biology, medicine, pharmacology-toxicology etc.).
  • Prohibit animal experiments in higher education and replace them with other teaching methods (synthetic mannequins, 3D models, videos, etc.).

Drive evolution at European level

  • Promote at European level a review of the validation procedures for new non-animal methods so that more new methods can be validated within a reasonable time and at a reasonable cost. Further, the creation in the EU of laboratories dedicated to the pre-validation of methods should be promoted.
  • Promote the creation of a European data bank on alternative methods for animal testing.
  • Introduce into REACH Regulation (EC) No 1907/2006 an obligation to use validated non-animal methods for testing chemical substances.

Improve the transposition into French law of Directive 2010/63/EU in order to allow its full implementation

  • Respect the obligation to publish non-technical abstracts and a posteriori** evaluations in order to ensure transparency.
  • Changing the composition of ethics committees in animal experiments, which are responsible for issuing opinions on the appropriateness of experimental procedures (Article R 214-118 of the Rural Code) in order to guarantee the impartiality of decisions and the absence of conflicts of interest.
  • Establish a National Committee for the Protection of Animals used for scientific purposes (provided for in Article 49).

Improve the protection of animals used for research

  • Put in place regular and unannounced checks that result in effective and inhibitive penalties for unlawful experiments (in accordance with Article 60 of the European Directive).
  • Grant unrestricted access rights to breeding and laboratory animal facilities to the animal protection associations referred to in Article 2-13 of the Code of Criminal Procedure.
  • Ban the capture and import of wild animals to laboratories.
  • Establish a moratorium on animal breeding for laboratories (prohibit the installation of new breeding facilities and the extension of existing ones).

 

* orphan areas – not commercially viable areas
** a posteriori – based on reasoning and evidence rather than assumptions or predictions

Further reading

Partij voor de Dieren (2016) Plan B (in Dutch; program for parliamentary elections in 2017).

Dominique Lestel (2016) Prendre le parti des animaux.

Il est là! Le premier parti animaliste français (YouTube video clip from the launch of Parti Animaliste on 14 Nov 2016)