Author Archives: ozsheba

Change, slow but steady

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How can we tell whether public opinions are changing? How can we tell whether views on particular issues have changed compared to some time ago? As animal advocates, our aim is to achieve change to policies, regulation and legislation that improves the lives of animals. Changing public opinion alone can make a difference to the lives of animals – when, for example, consumers stop buying the eggs of caged hens -, and it is essential to achieve regulatory and legal change.

Surveys and polls are a common way of gauging public views on political and social issues. They are important tools to monitor and evaluate animal advocacy, and provide direction for future strategies.

So what do we know about awareness of and views on animal experimentation, and whether they are changing?

Overseas surveys tell us that the public’s views on animal experimentation are changing:

  • a Pew Research Center survey from 2015 in the U.S. informed us that approximately equal numbers of people favour and oppose the use of animals in scientific research (47% vs 50% respectively), while the vast majority of scientists (89%) favour animal research, a difference of 42 percentage points.
  • a Gallup poll in 2015 found that a third of Americans want animals to have same rights as people (compared to 25% in 2008), while 62% said animals deserve some protection but can still be used for the benefit of humans.
  • A 2017 Gallup poll in the U.S. found a 51% acceptance of medical testing on animals, a decreased acceptance rate compared to polls in previous years.
  • In an Ipsos MORI 2016 poll in the UK, 65% (compared to 68% in 2014) of people said they could accept the use of animals in research as long as it is for medical purposes, and there is no alternative.
  • In Germany in 2017, a Forsa poll found 71% of respondents in favour of a ban on painful animal experiments, while 23% did not consider such a ban necessary.

In Australia, the results from a survey commissioned by Humane Research Australia (HRA) have just come in: Nexus Research surveyed 1,006 people in April 2018. The sample was quota controlled by age and gender, and selected in proportion to the population aged 16+ years in each State/Territory. A survey of this size is considered sufficient as a representative sample of the Australian population, with an error margin of around ±3%. More information about the survey can be found on the HRA website.

Taking small samples from large populations is a valid statistical technique for getting accurate information about the wider population, for a fraction of the time and cost.

HRA commissioned similar surveys in 2008 and 2013. Below are some of the findings, comparing how people’s awareness and views changed over the 10 years since the first survey.

Awareness

Awareness of animal research has changed over the years. While in 2013 only 57% of people were aware of animals being used in research, this increased to 71% in 2018. In the latest survey, people under the age of 30 and those with an income between $80,000-$120,000 had the highest awareness of animal research (both 79%).

awareness of AR.jpg

In 2013 and 2018, people were asked whether they were aware that monkeys and other non-human primates are used in medical research in Australia. The vast majority of respondents were not aware of this (91% in 2013, 82% in 2018). On the other hand, over the last five years the number of people who know that non-human primates are used in laboratories has doubled from 9% to 18%.

In the last survey, a new question was added: ‘Do you consider that our governments provide sufficient information to understand the extent of animal experimentation in Australia?’ About the same proportion as those who were not aware of primate research answered this question with ‘no’ (81%).

Positions against animal experimentation are typically based on two arguments: ethical considerations that deem inflicting suffering on sentient beings as morally wrong, and/or scepticism about the scientific validity of animal experimentation. Both were explored in the surveys.

Ethical concerns

Do humans have the moral right to experiment on animals? In all three surveys, more than half of the respondents did not believe this, and a significant proportion was unsure. More men than women (31% vs 15%) and more people aged 70+ than people under 30 years (34% vs 21%) believed that humans have the right to experiment on animals. People living in households with pets expressed a much stronger view against animal experiments than those who did not live with pets (64% vs 53%), while the latter expressed greater indecision (13% vs 22%).

moral right to exp

To gain more nuanced views, questions were asked about the purpose of research and the species of animals used. About three in four people opposed the use of animals for developing household products and cosmetics testing in all three surveys. Interestingly, this proportion decreased slightly over the 10-year period, while the proportion of those opposed to basic/scientific research, teaching/educational purposes and developing pharmaceuticals for people (medicines/tablets) rose slightly. A question about environmental research was only asked in 2018.

oppose use for of AR

People do not feel as strongly for rodents (mice and rats) and rabbits as they do for dogs and non-human primates. While concern for all four species increased slightly over the years, half as many people opposed research on rodents compared to dogs.

oppose by species

The level of discomfort and pain inflicted on animals also influenced people’s views: the more painful the procedures, the greater the opposition to animal research (2018: from 33% to 72%).

oppose by level of pain

Overall, more women than men expressed ethical concerns, as did younger people (<30) compared to older people (>70), and people who live in households with pets compared to those who do not.

Transferability

All three surveys asked respondents about their views on the transferability of results from animals to humans. However, the wording of the question changed in the 2018 survey:

‘Do you believe or not believe that it is always safe to transfer results from animal research (e.g. from rabbits, mice, rats and dogs) to apply to humans?’ (2008 and 2013)

‘Do you believe that it is safe to transfer results from animal research (e.g. from rabbits, mice, rats and dogs) to apply to humans?’ (2018)

The change in wording might explain the significant increase in the number of people who believed that results from animals apply to humans (2008: 14%, 2013: 13%, 2018: 35%). About a third of respondents were unsure. In 2018, significantly more men than women (42% vs 29%) and older people aged 70+ compared to those aged under 30 years (50% vs 31%) believed that it is safe to transfer results from animal research to apply to humans.

transferability

Alternatives

In 2018, people were asked whether they were ‘aware of any current alternatives instead of using animals in research for human medicines. Only 20% responded that they were aware of such alternatives.

It is no surprise then, that the vast majority of respondents favoured ‘allocating a proportion of medical research grants to finding scientific alternatives to animal experiments’, although this support decreased over the years from 79% to 67%. I have no explanation for this trend.

Change, more change

To my knowledge, this Nexus survey is the only of its kind in Australia. How sure can we be that it describes accurately Australians’ opinions about animal experimentation? Nexus Research recruited survey participants from a panel. While there have been concerns expressed about this type of recruitment, ‘the quality of the answers obtained from online panels does not seem to be worse than that from more traditional methods of data collection and, in some cases, may be better.’ So, for the time being, this is the best we have.

As the president of Humane Research Australia I’d like to think that our work has contributed to greater awareness of animal research and increasing compassion with the animals used in laboratories. It is clear that the public wants accurate and comprehensive information about animal research. It is also clear that the public needs to be better informed about alternatives to animal research. Without such knowledge, how can people develop informed views and considered moral judgment about animal research?

 

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World Week for Animals in Labs

This week is World Week for Animals in Laboratories when we commemorate the suffering of millions of animals in laboratories around the world and raise awareness of better, human-relevant research methods that do not involve inflicting pain on animals.

Animal research is still a mostly secret industry. Although research institutions are required to collect data about animal research, this information is not made publicly available in full. Here in Australia, Humane Research Australia (HRA) collects available data and makes them available on its website. The latest available statistics  indicate that during 2015 approximately 9.9 million animals were used in Australia (although this includes studies that involve observation only). HRA also publishes case studies of horrific procedures that are being carried out on animals in this country.

Over the last decades, increasingly evidence has come to light showing the pitfalls of animal research. For example, scientist have been able to cure different types of cancer in mice, but a cure in humans is still elusive.

The development of penicillin was delayed because the researcher Dr. Alexander Fleming thought it was ineffective in a rabbit model of systemic infection. In fact, Fleming later stated “How fortunate we didn’t have these animal tests in the 1940s, for penicillin would probably never have been granted a license, and possibly the whole field of antibiotics might never have been realised. (Kramer & Greek 2018)

While animals have been used in experiments for decades, animal models have not been validated; they have not been tested to see whether they are fit for purpose. And yet, most regulatory testing still requires that new drugs and treatments be tested on animals before they are evaluated for safety and efficacy in clinical trials with humans. On the other hand, any new testing method that does not involve animals has to go through a rigorous validation process.

The vast resources dedicated to animal experimentation have an opportunity cost for humans: new drugs that fail in animals but would benefit humans do not become available. We know that one in ten new drugs that are safe and effective in animals fail in humans. We do not know how many new drugs that would be safe and effective in humans never made it to drug trials in humans. And we do not know how many patients have suffered or died prematurely due to this opportunity cost.

 Even for two individuals within the same species, small differences in DNA can mean the difference between life and death. A tiny difference of one amino acid within the human chromosome is all that separates a patient with life‐threatening sickle cell anemia from those of us who do not suffer from that condition. Dramatic differences can exist across species even without changes in amino acid sequences. Genes are regulated—turned on and off—by other genes. For example, mice and humans share the gene that allows mice to grow a tail. The reasons humans do not normally grow a tail during development is that the gene is never turned on (i.e., expressed). Differences in gene regulation and expression vary within and between species and account for differences in response to drugs and disease. (Kramer & Greek 2018)

Even supporters of the practice point to numerous flaws in animal research. The National Health and Medical Research Council (NHMRC) is the major funder of biomedical research in Australia. In 2017, it published a report  with the title Best practice methodology in the use of animals for scientific purposes. This report includes a long list of flaws in animal research: flaws in the quality of experimental design, flaws in the quality of experimental statistics, flaws in the quality of techniques and procedures, and flaws in reporting (pp. 10-13).

Animal experimentation is cruel, ineffective and a waste of our taxes. It supports an industry that is outdated and needs to change. This change has started, but it is very slow. I have written about this in previous posts, for example here. Unfortunately, Australia is not at the forefront of innovation.

So what can we do to get a move on the end of animal experimentation and replace the use of animals with advanced science? Some ideas: Share your views on outdated animal research with friends and family, politicians and on social media. Make a donation to a charity that works towards ending animal experimentation. Organise a fund-raising event. Don’t buy cosmetics and household products that have been tested on animals.

Thoughts and prayers on World Day for Laboratory Animals on 24 April and during the week are not enough.

Toxicity testing without animals

When I mention that I am against animal experimentation, the reaction is often: “Would you prefer these tests were done on humans?” In the discussion that follows it turns out that most people don’t know that there are better and less cruel ways of doing biomedical research. Some people suggest that these alternatives, such as computer-based methods, can never be as adequate as a living animal.

However, over the last decade science has made much progress in developing non-animal methods and tools to use in basic and applied research, and for regulatory testing such as the testing of new drugs and chemicals. Governments are now encouraging and mandating researchers to use these new methods instead of live animals. For example, earlier this year 16 federal agencies in the US developed a Roadmap to guide progress toward replacing animal use in toxicity testing.

The roadmap was developed to guide the application of new technologies, such as high-throughput screening, tissue chips, and computational models, to toxicity testing of chemicals and medical products.

What exactly are these new technologies? An open access article published last year by Mary T. McBride – Future platforms for toxicity testing – provides a good summary of current and future methods for toxicity testing without animals:

  • In vitro model systems, using cells and cell cultures, such as stem cells, tissue engineering and organs-on-chips, with a human-on-a-chip being under development.

 

  • In vitro pathway-based assays and quantitative high-throughput screening (HTS). The latter employs liquid robotics handling systems and computerised data processing, to screen a single compound against a large number of assays to identify toxicity pathways or to test a large number of compounds using a single assay.

 

  • Cell-based imaging technologies and high-content screening, using imaging tools such as innovative microscopy methods, ultrasound, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Positron Emission Tomography (PET).

 

  • Omics approaches, such as genomics, transcriptomics (a microarray technology to establish human genome-wide gene expression profiles by measuring all of the approximately 100,000 mRNA molecules or ‘transcripts’ produced in a cell or a population of cells), proteomics (the comprehensive study of the entire complement of proteins and their modifications of an organism to understand cellular processes) and metabolomics (the study of metabolites, such as lipids and proteins, and used to identify all of the metabolites present in a given cell or organism at a specific time).

 

  • Data integration analysis and interpretation: bioinformatics and visualisation tools. This involves combining data from different platforms and assays across multiple experiments.

 

  • Computational toxicology, which includes the integration of mathematical and computer models to map, model and understand the biological circuitry of toxicity pathways to predict the toxicity of environmental chemicals and pharmaceuticals and their dose-response relationships.

 

Tissue engineering has made tremendous advancement in the field of tissue-engineered preclinical models. Such models now exist for many whole tissues including skin, muscle, cartilage, blood vessels, bone, bladder, liver, cornea, reproductive tissues, adipose, small intestine, neural tissues, kidney and cardiopulmonary systems.

McBride suggested that “the new approach may significantly reduce costs and time required to conduct chemical safety assessments and could markedly diminish and potentially eliminate animal testing.” She pointed out that this is not an exhaustive list, and that rapid advances in biology and biotechnology are continuously emerging.

Various databases listing resources for non-animal research are available to researchers and the general public, for example ALTBIB (Resources for Alternatives to the Use of Live Vertebrates in Biomedical Research and Testing) and EURL ECVAM (European Union Reference Laboratory for alternatives to animal testing).

So no, the often cruel and painful experiments currently conducted on live animals don’t need to be done on humans. Nor do they need to be done on animals.

 

 

UK biotech companies call for more human-relevant research methods to meet patient needs and increase profits

 

Industry leaders say that the key issue is the low predictive power of existing pre-clinical models, with academic research supporting this hypothesis. We will address this by bringing more patient-derived approaches into the mainstream. These include advances in patient derived targets and biomarkers, and more complex models, such as organoids, for discovery and pre-clinical research. These technologies need to be woven throughout the discovery process to place the patient at the heart of the research process.

A new report from the UK has pointed to a productivity crisis in pharmaceutical research: new drugs have a high failure rate, the number of drugs launched per $1bn of research and development spending has fallen nearly thirty-fold over the last 40 years, leaving the pharmaceutical industry return on capital now at only 3.2%.

Let me briefly recap the phases of development that a new drug undergoes. Preclinical research is the stage of research that occurs before the drug is tested on humans. It usually involves in vitro and in vivo tests. In vitro (Latin: in glass) tests are sometimes called test-tube experiments, for example microorganisms in Petri dishes. More recently developed in vitro methods involve omics, such as genomics, proteomics or metabolomics.  In vivo (Latin: within the living) tests are conducted on living organisms or cells. In biomedical research, in vivo methods generally involve animal experiments.

Preclinical research is followed by three stages of clinical trials on humans. Phase I is usually conducted for safety testing. If the drug is found to be safe, it is tested in Phase II to see whether it works as intended. Phases I and II involve small numbers of humans. If the drug is found to be safe and effective, it proceeds to Phase III, where it is tested on a larger number of people and compared to placebo or other treatments for the condition under study. Sometimes there is a fourth phase: after the drug has been marketed, further information is collected on effectiveness of the drug and side effects, or to investigate the effectiveness of the drug for a different condition or in combination with other drugs.

Three pharmaceutical industry groups collected data on clinical development success rates from 2006-2015 and found the following average rates:

probability of success

NDA – New Drug Application to the FDA (US Food and Drug Administration)
BLA – Biologic License Application to the FDA

After in vitro and/or in vivo testing, on average only 9.6% of new drugs achieved approval from the FDA. Cancer drugs had the lowest approval rate (5.1%), haematology drugs the highest (26.1%). A dismal – and very expensive – failure rate.

Back to the UK report. Based on over 100 in-depth interviews with senior executives of UK drug discovery companies and electronic surveys of 250 experts, the authors summarised the problems as follows:

  • Global R&D productivity is under unprecedented pressure
  • The model of medicines R&D must be radically reshaped to meet patient needs
  • A key problem is reliance on using inadequate models for human diseases
  • Commercialising emerging technology will require new models of collaboration
  • Data science is now indispensable to medicines R&D: research data is now generated in such high volumes that the ability to harness it has become a critical factor in developing new medicines
  • It is imperative for the UK to provide industry with straightforward, well-governed access to consented patient data and human tissue samples – this is an acute problem for SMEs*
*SMEs – small and medium-sized enterprises

The authors of the report observed that too much of the preclinical research is patient-free and relies on animal models of disease and toxicology that are a poor approximation of humans. They wrote that drug discovery must be ‘humanised’:

Our interviews and surveys identified many emerging technologies that can ‘humanise’ the drug discovery process. These technologies make the early stages of research more predictive of how a drug will work in real life. They can generate a wealth of humanised in-vitro data, resulting in better drug candidates entering human trials. The benefit is lower attrition and therefore improved research productivity for industry.

… and pointed to new and emerging technologies that don’t involve animal research:

There are many emerging technologies that can make pre-clinical drug development more humanised. Most are derived from human stem cells and the resultant technologies that allow us to create and sustain human tissue in the laboratory. Just 20 years ago, keeping such tissue alive in the lab was a challenge. Now, thanks to pluripotent stem cells, advanced culture methods, microfluidics and precision gene editing we can manipulate the way such tissue grows and differentiates, even down to the substructures of cells and the stratum of the disease which the model reflects. When linked to large human cohorts, we can develop libraries of disease models that reflect the molecular spectrum of human disease, just as the Sanger Centre has done with their library of cancer cell lines. These complex predictive models, when used appropriately, have the potential to be much more discriminating in their ability to weed out the false positives in drug discovery i.e. those compounds that are too toxic, or insufficiently disease modifying.

The report also called for better collaboration between all stakeholders, the sharing of data and better access to consented patient data and human tissue samples.

Data from failed trials and failed pre-clinical projects could be transformative in reducing rework.

Further, a lack of validation efforts was noted. The experts that were interviewed said that ‘many potentially powerful human in vitro models remain in academia. There they have no obvious commercialisation path in the UK, given they often lack IP and so are hard to spin-out.’ Several people pointed out that validation is not a good fit for grant funding.

Many reasons tied up with their careers hold researchers in academic institutions back from leaving animal experiments behind:

It is important to recognise that researchers can be reluctant to invest time and money in implementing a new technique, or to replace an animal model that has served as the basis of their research for many years. … There may be concerns about a lack of historic data comparability, or invalidating past results. Setting up a new model can require additional technical expertise or development of new infrastructure. Referees are familiar with data from the ‘gold standard’ animal models, and may request additional in vivo data to be generated to support in vitro findings. These factors can delay publication in a highly competitive research environment and result in a lack of motivation to change models. (Jackson and Thomas 2017)

Researchers in the pharmaceutical industry are free of some of these constraints. The animal model research paradigm is truly outdated and better, human-relevant methods and technologies are available and are being further developed. This report by Medicines Discovery Catapult and the UK BioIndustry Association is a welcome guide to a future of biomedical research that serves patients, leaves behind cruel and unnecessary animal experiments, and promises a better return on investment for biomedical companies.

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Many thanks to Andrew Tilsley for his permission to use an image of his artwork ‘Cures for Diseases’.

Animal agriculture – a taxing problem

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Source: Flickr / Brian Hart

The Guardian today published an article about a “green taxation shift” in Norway. Via taxation and other incentives, the Norwegian government encourages its citizens to switch to electric cars. Electric cars do not attract import tax and VAT, are subject to a reduced road tax (which will go down to zero next year), and owners of electric cars do not have to pay road tolls, ferry fees and city emission charges. They don’t pay for parking and can bypass traffic by driving in some bus lanes. To top it off, running costs are lower because in Norway electricity is cheaper than petrol and diesel.

These incentives have resulted in nearly a third of new cars being electric cars, and this proportion is expected to rise to 40% next year. What a great set of policies to nudge people towards more sustainable driving, and for the government to meet its greenhouse gas emissions targets.

But what about the foregone revenue? A politician commented:

Of course the government needs its revenue. But this is part of what we call a green tax shift. You have to tax what you want less of, and promote what you want more of.

Exactly. That’s what I would expect a rational government to do.

With animal agriculture accounting for more greenhouse gas emissions than the global transport sector – including ALL modes of transport, such as cars, motorcycles, trucks, trains, ships, aircraft – wouldn’t it be a rational move to tax meat and other animal products to reduce their vast contribution to climate change?

Research by Chatham House found that it will not be possible to limit temperature rises to below the “danger level” of 2°C if “livestock” production and consumption are not reduced.

 … adopting global dietary guidelines with lower meat consumption would cut food-related emissions by 29%, vegetarian diets by 63%, and vegan diets by 70%

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Source: Flickr / Like_the_Grand_Canyon

Governments in Denmark, Germany, China and Sweden have reportedly discussed creating animal product related taxes in the past two years. An added benefit of a reduced consumption of these products would be the health benefits and cost savings from diets based on plants. Still, increasing taxes for meat and other animal products is not popular with producers and most consumers.

A recent University of Oxford study suggests that if unaddressed, the public health and environmental expenses associated with the increased demand for animal products could be up to $1.6 trillion globally by 2050.

In Australia, 40% of cancer deaths are preventable, claims a recent study. One of the eight lifestyle factors that contribute to these deaths includes a low intake of fruit and vegetables and high intake of red and processed meat. But no, the Australian government does not intend to address its people’s high consumption of animal products. On the contrary, it has been claimed that

The Australian government has a vested interest in ensuring the country’s consumption of meat remains the highest in the world, even to the detriment of the population

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Source: Flickr / theunquietlibrarian

So what are we to do? With our government dragging its feet, it’s up to us to think about the future and make our lifestyle choices more sustainable. A toast to plant-based diets and good health in 2018. Let’s be gentle with our planet and compassionate towards all life that it sustains.

Replacing live animals in research and teaching – Progress in the EU

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Source: Flickr/ Alpha Bravo Foxtrot

Earlier this month (8 November 2017), the European Commission published a review of the implementation of the Directive 2010/63/EU on the protection of animals used for scientific purposes (the Directive). All use of live animals in the European Union for research, education or drug testing must comply with the Directive, and it requires member states to assist in the advancement of alternative methods to animal testing and to promote the use of non-animal methods.

While the Directive took effect on 1 January 2013, it took until 2015 for all member states to adopt relevant national legislation. The common standards for animal accommodation and care only entered into force in January 2017. This is the first review of the implementation of the Directive, and it is noted that the “report can only give preliminary indications of progress, problem areas and good practice”.

I was most interested in the section of the report that deals with the uptake of alternatives. In the context of the Directive, “alternative” means any tools or strategies implementing the 3Rs* which:

  • Obtain the required information without the use of live animals.
  • Use fewer animals whilst obtaining the same level of information.
  • Improve the way procedures are carried out so as to cause less pain, distress or suffering, or improve welfare.
* 3Rs: Replace, Reduce and Refine the use and care of animals used for scientific purposes

Unfortunately, the report states that “[a]t this stage of the Directive’s implementation, it is too early to assess its impact on the promotion and uptake of alternatives.” However, four areas hindering a more rapid uptake of alternatives were identified: lack of knowledge; insufficient communication/ spreading of information; acceptability, and cost.

Many stakeholders felt, however, that there is significant scope for the replacement of animals used for educational purposes where many alternatives are already available, but not always taken up.

On a positive note, “[m]any Member States have increased their activities in promoting alternatives, e.g., increasing research funding, voluntary development of Three Rs centres, supporting educational events and other information dissemination efforts. Half of the Member States have submitted voluntary reports detailing the actions taken towards the development, validation and promotion of alternative methods”. I had a look at these reports and compiled the summary below:

Government projects/initiatives to develop and/or validate non-animal methods (does not include projects funded or undertaken by animal charities or the private sector; does not include funding for promoting non-animal methods, training or resource development)

United Kingdom 

  • NC3Rs-funded projects – € 10 million annually
  • Non-animal alternative test for botulinum toxin testing; development and validation – Approx. € 8 million
  • Innovation in developing 3Rs technologies – € 5 million in 2014-15

Germany

  • Foundation for the Promotion of Alternate and Complementary Methods to Reduce Animal Testing – Approx. € 500,000 annually
  • Research/ welfare prizes – € 55,000 annually, € 65,000 every 2 years, € 25,000-100,000 every 2-3 years, € 15,000 every 5 years

Finland

  • Ministry’s (MAF) programme to promote the development and use of alternative methods established in 2013 – MAF funding €100,000 annually 2013-2015 and € 200,000 in 2016.
  • Finnish Centre for Alternative Methods (FICAM) – € 250,000 annually, € 350,000 in 2014-2015
  • MAF research grants – €15,000-€30,000 per year 2010-2016
  • Adipose in vitro model development for diabetes II – Approx. € 100,000 in 2014-15

Belgium

  • Development of alternative toxicity tests – Approx. € 1 million
  • Development of an alternative model for hepatotoxicity testing – € 60,000

Denmark

  • Establishing a Danish 3R-Centre – € 190,000
  • Support for the development of new 3R methods and models – € 200,000
  • 3R prize – € 1,500 in 2014

Italy

  • Development of in vitro alternative approaches – € 552,500

Sweden

  • Swedish Research Council grants – Approx. € 1,380,000 annually
  • Swedish Fund for Research Without Animal Experiments grants – € 100,000-200,000 annually
  • Contribution to participation of Swedish laboratories in validation studies at EU level – Approx. €212,000 annually

Several countries listed their activities, but did not include monetary values.

Welfare organisations expressed frustration at the slow progress towards validation and acceptance of new alternative methods. Validation and regulatory acceptance processes vary between different regulatory areas, which are not directly regulated by this Directive. Nevertheless, there is evidence of investment and activity advancing this field. The Directive contributes towards these objectives through obligations on Member States and the European Commission.

In addition to government funding, funding is also available from industry and charitable organisations. For example, in the UK the Dr Hadwen Trust (now Animal Free Research UK) provided approx. € 1,8 million to develop new research models and methods to replace the use of animals in medical research. The EU also provides funding. A recent example is the ORgan-on-Chip In Development (ORCHID) project with € 520,477.

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Zebrafish in the lab. Source: Flickr/ detroitstylz

While countries in the EU are slowly moving towards a future where fewer and fewer live animals are used in biomedical research, testing and training, the Australian Government does not have any policies similar to the Directive, nor does the Government’s main funding body, the NHMRC, provide grants specifically to reduce and/or replace animal experiments.

The 2017 Tenth World Congress on Alternatives and Animal Use in the Life Sciences – 3Rs in Action conference in Seattle featured close to 700 oral and poster presentations. Only one Australian researcher is listed among the presenters, and her presentation did not focus on the development of non-animal research methods. This speaks for itself.

 

References

European Commission. (2017). Report from the Commission to the European Parliament, the Council, the European Economic and Social Committee and the Committee of the Regions in accordance with article 58 of Directive 2010/63/EU on the protection of animals used for scientific purposes. Brussels: European Commission. Available at http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:52017DC0631&from=EN

European Commission. (2017). Commission Staff Working Document. Accompanying the document Report from the Commission oo the European Parliament, the Council, the European Economic and Social Committee and the Committee of the Regions. In accordance with Article 58 of Directive 2010/63/EU on the protection of animals used for scientific purposes. Brussels: European Commission. Available at http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:52017SC0353

Faustman, E., Zurlo, J., & Kavlock, R. (2017). ALTEX proceedings. Abstracts of the 10th World Congress, Seattle, 2017. Alternatives and animal use in the life sciences 2017: 3Rs in action. Seattle: ALTEX. Available at http://www.altex.ch/resources/WC10_entire_issue1.pdf

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.