Experts: prioritise advanced, non-animal COVID-19 research methods

Source: Flickr/ Prachatai

Animal Defenders International (ADI) have fronted an open letter, urging the World Health Organization, national governments, funding bodies, regulators and the scientific community to speed up the development of effective vaccines and treatments for COVID-19 by giving priority to advanced non-animal research methods and technologies. The letter has been signed by close to 100 experts, academics and other concerned parties.

Advanced techniques include mathematical modelling of transmission and size of the epidemic; the use of patient lung fluid cultures to study the virus genome; patient biopsy samples to investigate lung tissue damage; artificial intelligence models to predict which drugs could treat COVID-19; using antibodies from COVID-19 survivors to treat patients; human organ-on-a-chip technology emulating human lung infection for drug discovery; organoids to investigate how the disease infects human tissue; and in vitro3D human airway cell models for evaluating drugs.

Last year, I wrote a report that summarises new and not so new human-relevant research and testing methods that do not use animals: “Better ways to do research: An overview of methods and technologies that can replace animals in biomedical research and testing”. The report is free to download and read, and written in plain English, but referenced like an academic paper. It also includes examples of how these methods have been applied and been of benefit to humans.

Currently, researchers working on COVID-19 vaccines and treatments are using already some of these advanced methods. However, too much effort is still wasted on finding the ideal animal model, and animal research is underway using mice, ferrets, primates, guinea pigs, pigs and cats.

The World Health Organization-China Joint Mission has advised that the “ideal animal model for studying routes of virus transmission, pathogenesis, antiviral therapy, vaccine and immune responses has yet to be found”, and yet significant funding and precious time is being spent on animal research. This is despite the known species differences which make the results from such data unreliable when translated to humans.

In the race to find vaccines and cures for COVID-19, animal models also slow down the research effort. Many non-animal methods are also cheaper.

The undersigned scientists, academics, organizations and concerned parties urge the World Health Organization, national governments, funding bodies, regulators, and the scientific community as a whole to prioritize funding and resources for advanced non-animal scientific methods to accelerate the path to finding effective vaccines and treatments for SARS-COV-2 and, going forward, for other human diseases.

I am one of the nearly 100 experts and academics who signed the open letter. But there is also a petition which, at the time of writing, had already more than 53,000 signatures. Animal Defenders aim for 55,000 signatures. I urge you to sign.

 

Talking about non-animal research and testing methods

My presentation at the Animal Activists Forum on 19 October 2019 in Melbourne, Australia:

AAF2019_monikamerkes

US advances paradigm shift towards humane science

Source: Wikimedia.

The US has recently joined the Netherlands in setting end dates for certain types of animal research and testing.

In 2016, the government of the Netherlands decided to phase out the use of animals in regulatory research and testing by 2025. This is part of a paradigm shift to animal-free science, with end dates for animal-free basic research and applied and translational research yet to be determined.

Earlier this month, the US Environmental Protection Agency (EPA) made a commitment to reduce animal testing and announced US $4.25 million in funding to five universities for the development of alternative test methods and strategies that reduce, refine, and/or replace vertebrate animal testing. By 2025, all requests for research involving live mammals and funding for such research will be reduced by 30%. All mammal study requests and funding will stop by 2035. In addition, from this year the EPA will hold an annual conference on new non-animal methods (NAMs).

While an end to all animal research and testing can’t come soon enough, this is good news.

New NAMs are available and being used. For example, the European Chemicals Agency noted in a 2017 report that out of the 6,290 substances analysed for the report 89% had at least one data endpoint where an alternative was used instead of a study on animals, and 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%).

Australia too has taken a first step towards phasing out animal research – at least that’s how I’d like to see it. So far, it is only a symbolic step. From 1 July 2020, new animal test data for substances solely used in cosmetic products will no longer be acceptable to the regulator (for details see a previous blog post). However, the vast majority of chemical substances used in cosmetics are also used in other products, such as household products, and thus are not affected by this ban. Also, to my knowledge, no cosmetics testing on animals has taken place in Australia for many years.

In contrast, implementation of the recent EPA announcement will see a large reduction in the number of animals currently suffering in labs. The United States Department of Agriculture’s Animal Welfare Act does not cover all mammals. Mice and rats are exempt, and there is no requirement to keep data on the number of rodents used in research and testing. It is estimated that 95% of all animals used in US laboratories are mice and rats, and estimates for annual use vary between 10 million and 100 million. Of these, around 9% are used for toxicity testing.

Nude mouse with a tumor, grown from implanted LNCaP prostate tumor cell lines. Source: Wikimedia

“I think it’s a big day for the field of alternatives to animal testing,” said Dr. Thomas Hartung, director of the Center for Alternatives to Animal Testing at Johns Hopkins University. “Officials have long mostly given lip service to the idea of finding substitutes”, he said. This might finally change.

Better ways to do research

 

Humane Research Australia has just published an overview of methods and technologies that can replace animals in biomedical research, testing, education and training. “Better ways to do research: An overview of methods and technologies that can replace animals in biomedical research and testing” is available as a pdf document, free to read and download.

I am the author of the 74-page overview in plain English that outlines diverse methods and technologies, provides examples for their use, and suggests in what areas of research, testing and education they can replace animals. My sources are mostly scientific publications in peer-reviewed journals and government reports, and I provided references so that the interested reader may find out more from the original article or report.

Each year, millions of non-human animals  worldwide are harmed by animal experimentation. An estimated more than 115 million animals are used each year to supply the biomedical industry. The countries that use the most animals include China, the US, Japan and Australia. About half these animals are used in fundamental or basic research. This is curiosity driven, exploratory research that aims to increase and advance scientific knowledge. Applied research aims to solve specific practical problems, such as using animals as a model to seek a cure for a human disease or condition. Animals are also used in (regulatory) testing and in education and training. Current laws in many countries make it difficult to avoid using animals for regulatory testing, but there is no legal requirement for other types of animal research.

For a long time, many people have considered the use of animals in research, testing, training and education a necessary evil. But more and more, people question the ethics of this approach. At the same time, the animal research community increasingly recognises the problems with animal research: it is costly, lengthy and not very effective. Also, it may have held back the discovery of treatments and cures for humans because they did not work well in animals.

For example, aspirin was patented in 1900. It is considered safe for human beings, but it would not have been possible to market aspirin with current methods and criteria for safety because it was found to cause birth defects in mice, rats, guinea pigs, rabbits, cats, dogs, sheep and monkeys.

The use of animals in science is outdated and unnecessary. Human-relevant methods that offer a more effective and ethical approach to science are available. Broadly, these include: In-vitro methods (performed with microorganisms, tissues, whole cells or parts of cells in test tubes, Petri dishes etc.), in-silico (computer-based) methods, studies with human volunteers, and simulators.

I will only highlight two of these methods here: organs-on-chips and read-across. Organs-on-chips are bio-engineered devices that mimic key aspects of the physiology and function of human organs. Scientists have used microchip manufacturing methods to engineer culture devices that contain tiny chambers and tunnels through which fluids flow in a controlled manner. Organs-on-chips enable the study of biological processes, the modelling of diseases and investigation of the effects of drugs. They can also be used in personalised medicine, where, for example, tissue samples of a patient can be grown on a chip and tested with different drugs to determine which drug is most likely to be most effective as a treatment for that patient.

For example, researchers have dosed a brain-on-a-chip with the street drug crystal methamphetamine (also called “ice”). Crystal meth is a stimulant drug that speeds up the messages moving between the brain and the rest of the body. After connecting three chips with different types of brain cells to model the blood-brain barrier and adding crystal meth, the researchers could  observe how the drug affects the brain. They were able to observe previously unknown interactions between blood vessels and neurons in the brain.

Chemical and biological substances, such as newly developed drugs, need to be tested to determine whether they are harmful to humans, animals or plants. Currently, over 100,000 chemicals available on the market lack toxicity information. Safety testing reportedly costs US$10 – 20 million per product and takes several years. It is also difficult to obtain toxicological data for the 1,000 new chemicals created every year. Computer programs and large data bases can make testing of substances much faster and cheaper – and without using animals (although data obtained in the past from animals may be used).

For example, the read-across method uses data from a substance for which toxicity information is available, to make predictions for a similar substance about which not much is known. The software builds a map where similar chemicals are placed close to each other. Then, it places new chemicals on the map, based on their structural similarity with chemicals already on the map. The next step is to assess what is known about the new chemical’s neighbours, and from that information predict potential harmful health and environmental effects.

Human-relevant research and testing methods/technologies and their application

Governments, the scientific community, industry and other stakeholders, in particular in the EU and the US, have started to make efforts to pool knowledge and resources to replace animal experimentation with more humane, more human-relevant, and often cheaper and faster methods.

We need urgent change. From an animal rights perspective, it was never acceptable to inflict pain and suffering on animals for the real or perceived benefit of humans. For proponents of animal welfare, the use of animals is justified as long as harm is minimised. With awareness of the many shortcomings of animal research and testing and increasing availability of better ways, animal research is no longer justified.

We need to advocate for greater investment in innovative and promising non-animal methods, firm policy initiatives and robust collaborations of all interested parties, so that better treatments and cures for human diseases can be developed. This will also end the suffering of millions of animals.

Let the Australian Government know that you want a full ban of cosmetics testing on animals

Source: Flickr/ Otwarte Klatki

In March this year, Australia passed the Industrial Chemicals Act 2019. It is part of a package of Acts and establishes a legislative framework for the Australian Industrial Chemicals Introduction Scheme (AICIS). From 1 July 2020, AICIS will regulate the introduction (importation and manufacture) of industrial chemicals. This will ensure that chemicals used in consumer products such as cosmetics are safe for consumers and the environment.

The new legislation introduces a de facto ban on new animal testing for ingredients solely used in cosmetics from 1 July 2020. The ban does not apply to animal testing as such, but to the use of data from animal testing to prove that chemicals manufactured in or imported to Australia are safe to humans and the environment. Under the new legislation, industrial chemicals for sole use in cosmetics can be imported or manufactured only if they provide safety data that do not rely on animal testing conducted after 1 July 2020. This provides a disincentive for companies to conduct safety (toxicity) testing on animals, because such data will not be acceptable under the new legislation. Technically this is not a ban on animal testing, but it is as good as a ban – but a ban that applies only to single use cosmetics ingredients. Most cosmetics ingredients are used for other purposes as well.

For more detail see my previous post.

The Industrial Chemicals Act gives power to the Minister to make rules that guide the implementation of the Act. While the Act provides an overarching framework, the Ministerial Rules will add detail about the operation of the scheme. The Australian Government is now seeking feedback on draft Rules:

We are seeking your feedback on changes we are proposing to the draft General Rules for the new scheme. … After we consider your feedback, we will finalise the General Rules for the Minister to make. These Rules will then be tabled in Parliament.

The consultation period ends on 17 May 2019, a day before the federal election. Feedback can be provided via an online form or email to nicnas.reforms@nicnas.gov.au.

I encourage you to add your voice and let the government know that we want a complete ban on cosmetics animal testing, and that such a ban should be the start of phasing out animal testing more broadly. In the following, I offer the points I will be making in my submission. You are welcome to make use of these in your submission.

Source: Flickr/ Otwarte Klatki

The following comments refer to section 4 of the consultation document – “Proposed changes related to the use of new animal test data”, pp. 6-7.

Multi-purpose chemicals

The consultation document notes the following:

We are proposing that the General Rules restrict the use of new animal test data for these introductions where the chemical has multiple end uses, including in cosmetics, unless certain exceptions apply to maintain human health and environment protection

I support the intention of extending the ban on new animal test data to include multi-purpose chemicals used in cosmetic products. However, exceptions – if they are permitted at all – should only be acceptable for a short period and a date for their end should be set. This will give industry an incentive to develop human-relevant non-animal test methods, or use those non-animal methods that are already available. The ban of cosmetics testing in the European Union – at a time before validated non-animal testing methods were available for all toxicity endpoints – has shown that legislation can speed up the development of non-animal tests. For example, the European Commission made the point that:

Past experience demonstrates clearly that animal testing provisions in the cosmetics legislation have been a key accelerator in relation to the development of alternative methods and have sent a strong signal far beyond the cosmetics sector and far beyond Europe.

In response to exceptions that are proposed to apply when “there are no validated alternative tests to determine this characteristic other than animal tests”, I make the following observation: Chemical safety testing has historically been based on animal testing, although animal tests have not undergone the same type of validation which has been developed and/or is required for non-animal tests. Indeed, animal tests are mostly not predictive of human response to drugs and disease.

Non-animal test methods

The consultation paper refers to read-across information*. I suggest that the office of the Executive Director of the new Australian Industrial Chemicals Introduction Scheme include staff with expertise in new human-relevant non-animal testing methods and technologies. Further, I recommend

• that AICIS staff inform and educate industry on relevant non-animal methods and facilitate their uptake, and
• that AICIS collaborate with the NHMRC to make a portion of funding for biomedical research available to support the development and uptake of new animal-free testing methods that will be acceptable under the new legislation.

Transparency

I suggest that the office of the Executive Director of AICIS publish annual statistics on the use of animal test data. The public is interested in such data.

Phasing out of animal toxicity testing

I propose that AICIS, in collaboration with relevant stakeholders (which should, among others, include representatives from animal advocacy groups such as Humane Research Australia), develop a plan to phase out animal toxicity testing for all industrial chemicals. The government of the Netherlands has such a plan: it will phase out animal procedures in regulatory safety research (such as testing of chemical substances, food ingredients, pesticides, medicines and vaccines) by 2025, and transition to animal-free methods in fundamental scientific research and applied and translational research at a later time. In other countries, collaborations on the development and uptake of non-animal testing and research methods are already in progress, such as Toxicology in the 21st Century (US) and the European Partnership for Alternative Approaches to Animal Testing.

In conclusion, the Australian Government is to be commended for its intention to broaden the ban on the use of new animal test data for ingredients that are solely used in cosmetics. A ban on animal test data for ALL chemicals used in cosmetic products would be welcome. Most Australians are opposed to animal testing of cosmetics and want this cruel and unnecessary practice to stop. While the new legislation and the proposed Ministerial Rules are a step in the right direction, too many loopholes are of concern.

 

* Read-across is a computer-based method that uses data from a substance for which safety (toxicity) information is available, to make predictions for a structurally similar substance about which not much is known.

 

Transparency of animal experimentation – An Australian perspective

“Animal experimentation: Working towards a paradigm change“ was published on 25 March 2019 by Brill as part of the Human-Animal Studies series. The book is edited by Kathrin Herrmann and Kimberley Jayne. In 28 chapters, 51 authors from the US, UK, Brazil, Germany and Australia critically examine animal use in science and suggest ways towards human-based, animal-free research, testing and education. After a foreword by Peter Singer, the chapters focus on why and how to shift the paradigm, politics and legislation of animal experimentation, openness in animal experimentation, the ethics and philosophy of animal experimentation, effectiveness of the animal model, animal-free education and training, and advanced animal-free approaches. John P. Gluck, a former animal researcher, wrote the afterword.

The electronic versions of the book (pdf and e-book) are free to read and download.

My contribution to the book, together with Rob Buttrose, is chapter 9: “Increasing the transparency of animal experimentation: An Australian perspective”.

Below is a summary of the chapter:

Transparency in Australia

Many people are not aware that live animals are used in experimental research in Australia, and most people don’t know much detail about the numbers and species of animals used, the types of procedures they endure, or the pain and suffering involved. But the public is interested in these facts.

Researchers collect data about animal experimentation, but regulators and research institutes are very selective in what they allow to be publicly available.

…the public debate on animal experimentation is constrained by selective openness and by the motivation to enlighten an uninformed public, hoping to gain public acceptance.

Animal research in Australia is guided by the NHMRC’s Australian Code for the Care and Use of Animals for Scientific Purposes:

The purpose of the Code is to promote the ethical, humane and responsible care and use of animals for scientific purposes. The Code provides an ethical framework and governing principles to guide decisions and actions of all those involved in the care and use of animals for scientific purposes. The Code details the responsibilities of investigators, animal carers, institutions and animal ethics committees (AECs), and all people involved in the care and use of animals, and describes processes for accountability.

Under the Australian federal system, the states have responsibility for animal welfare, and all states and territories have incorporated the Code into state legislation. Statutory provisions relating to animals used in research vary between jurisdictions. For example, some states and territories do not make animal use data publicly available. There is no central registry for such data. The only national statistics in Australia are those collated and published by Humane Research Australia (HRA). The latest statistics available are from 2016, and HRA estimated that 9 million animals were used in research and teaching during that year.

HRA asks for information about incidents in laboratories and other facilities that come to its attention, such as details on the unexpected deaths of two non-human primates at a breeding colony in New South Wales in 2015. Requests are made directly to the research institutes, and often followed up by Freedom of Information (FOI) requests. Many requests for information are refused.

Under the Code, all research  and educational projects using animals need approval from an AEC. AECs collect and keep information about projects in various reports, records and databases. However, this information is not publicly available.

Universities and other bodies that undertake animal research must have a license to do so. These licences are issued by state government departments, often the department of agriculture. Some states make the names of institutions that hold a license publicly available, others do not. For example, HRA tried unsuccessfully – via a FOI request – to obtain a list of licensed institutions in Victoria. The FOI was refused because providing this information might “endanger the lives or physical safety of persons … who have provided confidential information in relation to the enforcement or administration of the law”.

In its submission to the FOI Commissioner, the department’s evidence that revealing license holders would endanger individuals, consisted solely of the claim that, in a previous FOI request, two license holders had concerns about being identified, as they had been the target of threats, disruptive action, and property damage from protesters in the past.

Transparency in the European Union

The Concordat on Openness on Animal Research is a UK initiative that aims to make animal research more transparent. To date, it has been signed by 121 universities, charities, commercial companies and others who have made a commitment to:

• Being clear about when, how, and why they use animals in research
• Enhancing communications with the media and the public about their research using animals
• Being proactive in providing opportunities for the public to find out about research using animals
• Reporting on progress annually and sharing their experiences.

However, the efforts towards more transparency are variable.

Signatories to the Concordat tend to stress the benefits of animal research, generally, and the importance and necessity of their own researchers’ work in particular; while downplaying the pain and suffering caused to animals and the number of animal deaths. Unsuccessful research and negative findings are not reported.

In EU countries, non-technical summaries (NTS) of animal research projects are mandated by the EU Directive 2010/63/EU. A directive is a legal act of the European Union which requires member states to achieve a particular result without prescribing how to achieve that result.

NTS provide information on the objectives of a project; predicted harm and benefits and the number and types of animals to be used; and a demonstration of compliance with the requirement of replacement, reduction, and refinement. NTS are anonymous and do not contain the names and addresses of the user and its personnel. EU Member States are required to publish the summaries, including any updates.

Detail and quality of the published information vary.

Applicants often comment that achievement of the aims of the research limits the minimization of suffering possible.

Beyond selective openness

We proposed the following steps to reform the current Australian system:

• A register of all publicly funded animal research projects
• A cost-benefit analysis
• Ethical reproducibility (reporting the concrete features of study design that deal with the specific ethical challenges of a research study)
• Development of non-animal methods and training
• As a first step, already existing information should be made publicly available (such as records of AEC meetings, AEC annual reports to their institutions, licensed institutions’ reports to their state/territory government, institutions’ reports of AEC external reviews)
• The National Health and Medical Research Council (NHMRC), the largest funder of biomedical research in Australia, should make details of funded animal research publicly available
• Non-technical, plain language summaries to be published online and accessible to the public (similar to the NTS in the EU)
• A national statistics compilation that clearly describes what happens to animals undergoing procedures in a way that the public can understand.

At Humane Research Australia, we are convinced that when this kind of information is revealed, public opinion will swing against animal experimentation.

 

 

 

Australia has new legislation on cosmetics testing, and it’s good news

Source: Flickr/ Marco Verch

From 1 July 2020, Australia will have a de facto ban on new animal testing for chemicals solely used in cosmetics.

Whilst the ban does not actually apply to animal testing as such, it targets the use of data from animal testing to prove that chemicals manufactured in or imported to Australia are safe to humans and the environment and is therefore, for all intents and purposes, a ban. Under the new legislation, industrial chemicals for sole use in cosmetics can be imported or manufactured only if they provide safety data that do not rely on new animal testing. This provides a disincentive for companies to conduct toxicity (safety) testing on animals, because such data will not be acceptable under the new legislation.

The new legislation

The Industrial Chemicals Act 2019 became legislation on 12 March 2019. It is part of a package of Acts and establishes a legislative framework for the Australian Industrial Chemicals Introduction Scheme (AICIS). It replaces the previous scheme, the Australian Government’s National Industrial Chemicals Notification and Assessment Scheme (NICNAS). From 1 July 2020, AICIS will regulate the introduction (importation and manufacture) of industrial chemicals. This will ensure that chemicals used in consumer products are safe for consumers and the environment.

Under the new Act, industrial chemicals do not include chemicals used for agricultural, veterinary or therapeutic purposes, or in food or feed. These are regulated by other legislation. Cosmetic products are considered industrial chemicals, and they will be regulated under AICIS.

The new legislation does not apply to historical animal test data. The restrictions only apply to data obtained by a test on animals conducted after 1 July 2020.

Ministerial Rules

The Act gives power to the Minister to make rules that guide the implementation of the Act. The Act provides an overarching framework, and Ministerial Rules will add much of the detail of how the scheme will operate. This is where Minister McKenzie’s 11 commitments made to Humane Society International (HSI) and the #BeCrueltyFree Australia Campaign will come into play.

The Minister’s commitments

Despite the fact that most ingredients for cosmetics have multiple end uses, we are encouraged that the Government has promised to look at the possibility of extending the ban to include multi-use cosmetics ingredients.

This promise is one of Minister McKenzie’s 11 commitments to HSI, which had lobbied for additional measures to strengthen the ban.

The 11 commitments, if adopted as Ministerial Rules, will reduce animal testing of cosmetics ingredients further, and will perhaps signpost the way towards a broader ban on animal testing of chemicals and drugs.

Animal testing can and must be banned when better, cruelty-free methods are available. Such  human-relevant, non-animal test methods are already available and are being used in other countries, for example in the European Union. But we need more of these methods, and government support is essential for further progress in this area.

So it is reassuring that Minister McKenzie has made a commitment to explore whether it is possible to make a portion of existing funding available to support the development and uptake of new animal-free testing methods that will be acceptable under the new legislation.

Other Ministerial commitments refer to encouraging the cosmetics industry not to use animal test data even if the legislation allows them to do so, to publish statistics on the use of animal test data, and generally consult with all stakeholders. For example, she committed to “Include representatives from HSI and other relevant stakeholders, in a governance arrangement to guide the implementation of its policy to ban cosmetic testing on animals”.

The new legislation is indeed good news. Although no animal testing of cosmetics has occurred in Australia for years, the new Act will ensure that we don’t slip backwards. The Minister has acknowledged the “general international trend away from reliance on the use of animals to determine the hazards and risks associated with the use of industrial chemicals”. Together with the Minister’s  11 commitments, this gives us hope for further progress on the slow road towards phasing out all animal research and testing, which will be replaced with better methods that are relevant to humans.

Our colleagues at HSI have worked tirelessly to negotiate and achieve commitments in addition to the Act, and we commend them on their hard work.

 

This article was first published on the website of Humane Research Australia on 16 March 2019.

Ethical investing and animal welfare

Source: Flickr/ chenjack

Today, I received an email from Bank Australia announcing its clean money campaign. Bank Australia informed me that it does not invest in fossil fuels, live animal exports, weapons, tobacco and gambling. Instead, “to help create positive impact for people, their communities and the planet”, the bank lends money to individual customers, housing for people with disability, affordable housing, renewable energy projects and not-for-profit organisations.

For those of us who want to invest our money ethically, it’s great to have such a bank in Australia. But “ethical investing” doesn’t mean the same to everybody. Most ethical investment considers environmental and social factors in addition to financial return. Consideration for the welfare of non-human animals is rare. So it’s wonderful that Bank Australia doesn’t do business with companies involved in live animal export.

Cruelty Free Super goes further. This superannuation fund screens out investment in companies that engage in animal cruelty, such as animal testing, fish farming, animal racing or breeding, the production of fur and animal skins, food retailers and processors who use or sell animal-based foods, and companies who produce equipment for fishing and hunting.

Australian Ethical is another company that applies ethical screening in regard to animal welfare. For example, it does not invest in companies which raise animals for live export for food. While its website declares that “We avoid investments that harm: People, animals, society, environment”, the harm done in animal experimentation is not recognised. Australian Ethical’s Ethical Charter acknowledges “the dignity and well being of non-human animals”, but that does not appear to include laboratory animals. Companies that are known to conduct or commission animal testing are included in its list of investments (for example, Ansell Limited, Cochlear Limited, Fisher & Paykel Healthcare Corporation Limited).

For my self-managed superfund, I have been looking for managed funds that screen out animal testing. I have not been able to find such a fund in Australia, but have noticed one in the UK: Kames Capital’s ethical investment screening excludes companies based on the following criteria: animal welfare, the military, nuclear power, the environment, political donations, genetic engineering, gambling, alcohol, tobacco, pornography, banks with exposure to large corporate or Third World debt, and oppressive regimes. What a collection of unethical business pursuits!

Kames’ animal welfare exclusion criteria apply to companies that

• Provide animal testing services or manufacture or sell animal-tested cosmetics, household products or pharmaceuticals
• Have any involvement in intensive farming
• Operate abattoirs or slaughterhouse facilities
• Are producers or retailers of meat, poultry, fish or dairy products or slaughterhouse bi-products

Both Kames and Australian Ethical are included as case studies in a recent report by FAIRR (Farm Animal Investment Risk & Return): FAIRR in action: How leading global investors are factoring intensive farming issues into their investment processes.

Source: Flickr/ peapod labs

As it’s the end of the year: Thank you for reading my blogs throughout 2018. I wish you joyful, safe and cruelty-free holidays!

The new NHMRC Corporate Plan – a missed opportunity

Source: Flickr/ Igor Spasic

As more and more researchers point to the inadequacy of using animal models to study human conditions, Australia’s National Health and Medical Research Council (NHMRC) – the major funder of biomedical research – still does not seem to make any moves towards encouraging more human-relevant research.

The NHMRC’s Corporate Plan 2018-2019 has just been published. From the NHMRC website:

The NHMRC Corporate Plan 2018–2019 covers the period 2018–19 to 2021–22. It identifies the major health issues for this period, how we will deal with these issues and a strategy for medical research and public health research, in line with the requirements of the NHMRC Act. It also describes NHMRC’s purposes, planned activities and performance measures for the period and addresses our capability, environment and risk oversight and management.

The Plan does not touch on the transition from outdated animal research to human-relevant research. While “advances in technology” and “engagement with industry and support of innovation” are mentioned in the section on “NHMRC’s environment”, the strategy to dealing with this “risk” is limited to “timely and effective leveraging of advanced technology to reduce the burden on applicants and assessors and enable reporting on the return on investment in health and medical research.”

Animal studies do not predict adequately what will happen in humans. Many research “breakthroughs” observed in animals do not translate to clinical trials with humans and into medical practice. However, this is not acknowledged in the Plan, which includes a section on research translation. (The NHMRC does fund several research and translation centres)

Source: Flickr/ National Center for Advancing Translational Sciences. Neurovascular Unit-on-a-chip

The value of animal experiments for predicting the effectiveness of treatment strategies in clinical trials has remained controversial, mainly because of a recurrent failure of interventions apparently promising in animal models to translate to the clinic. (van der Worp et al., 2010)

Source: National Center for Advancing Translational Sciences. Lung-on-a-chip.

Following target discovery, as much as 90% of novel medications fail to make their way through the different phases of clinical trial to approval. The majority fail to pass at phase II – the transition through proof of concept to large scale trial at Phase III (Cook et al., 2014; Perrin, 2014; DiMasi et al., 2016). Many critics attribute this high rate of attrition to the models on which the targets are discovered – usually laboratory rodents; the argument being that the differences between animal models and human disease are too great to be able to draw valid conclusions between them. In other words, targets derived from animal models are not suitable for use in clinical populations, and hence fail at trial. (Perry & Lawrence 2017)

The lack of leadership is disappointing. Other countries’ government agencies are more proactive. For example:

• A review of the implementation of the European Union Directive 2010/63/EU on the protection of animals used for scientific purposes noted that “many 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”. (more here)
• The Brussels-Capital Region in Belgium recently announced a ban on experiments on dogs, cats and non-human primates. (more here)
• The Netherlands’ National Committee for the Protection of Animals Used for Scientific Purposes (NCad) has provided a schedule for the phasing out of animal procedures for research on the safety of chemicals by 2025. (more here)
• The National Institutes of Health in the U.S. have a “Roadmap to guide progress toward replacing animal use in toxicity testing” that encourages the use of new non-animal methods and technologies such as high-throughput screening, tissue chips and computational models. (more here)
• Last month, the United States Environmental Protection Agency announced funding of $4.25 million for “Advancing actionable alternatives to vertebrate animal testing for chemical safety assessment”.
• In 2012, the U.S. federal Defense Advanced Research Projects Agency (DARPA), the National Institutes of Health and the FDA provided a grant of $37 million towards creating 10 different human organs-on-chips.
• In 2016, the U.S. National Center for Advancing Translational Sciences announced $13.5 million in grants to create models of human disease using tissue chip technology for testing the effectiveness of new drugs.
• The European Commission is contributing to a range of projects that aim to replace the use of animals in research, for example Building a 3D innervated and irrigated muscle on a chip (EUR 1.26 million), 3D bioprinting of pancreatic tissue for biomedical research (EUR 788,865), Chromatin organization PROfiling with high-throughput super-resolution microscopy on a CHIP (EUR 601,250), Genetically engineered human pluripotent stem cells, functionalized silk-fibroin platforms and bio-inks: a novel solution for large-scale ex-vivo platelet production, transfusion and drug research (EUR 738,327).

Source: Flickr/ National Center for Advancing Translational Sciences. Growing mini-brains in a dish.

Indeed, in the past few years, a substantial number of research grants have been invested in organ-on-a-chip projects from the National Institute of Health (NIH), the Food and Drug Administration (FDA), and the Defense Advanced Research Projects Agency (DARPA) in the USA, from Framework Program 7 (FP7) in the EU, and from Japan Agency for Medical Research and Development (AMED) in Japan. This investment also shows the magnitude of expectations for research related to organ-on-a-chip technology. (Kimura, 2018)

Source: Flickr/ National Center for Advancing Translational Sciences. This illustration highlights some of the tissue and organ systems that scientists in NCATS’ Tissue Chip for Drug Screening program are working on.

It’s disappointing that we are not pulling our weight in contributing to innovative biomedical research, that Australia is lagging behind comparable countries. It’s disappointing that a good proportion of public funds are wasted on ineffective research. It’s disappointing that, as a consequence, patients are not seeing the treatments and cures that are missed because our scientists study the wrong species. Actually, the latter is more than disappointing. It’s infuriating.

Good news from Brussels for cats, dogs and primates of all kinds

Source: Flickr/Jeheme

The Netherlands were first with their plan for a transition to non- animal research. Now the Brussels-Capital Region, one of three regions in Belgium, has announced a ban on experiments on dogs, cats and non-human primates:

From 1st January 2020, experiments involving dogs, cats and primates will be forbidden in the Brussels-Capital Region. Not only will tests on dogs, cats and primates no longer be allowed, from 1st January 2025 animal experiments will also be prohibited in education and in safety tests except in cases where no alternatives are available and the tests are deemed absolutely necessary.

This is great news, and it shows it’s possible to phase out animal research. Of course, animal testing on cosmetics has already been banned in the 28 European Union countries, as well as in Norway, India and Israel. Several other countries are considering a ban.

Phasing out animal experimentation is not only possible, it is also necessary because the results vary for different species, strains and sexes. Transferability from animal to human studies can’t be assumed.

A recent news item illustrates this: 11 babies died after their mothers were given a Viagra-like drug during pregnancy. The women were part of a drug trial in the Netherlands that tested whether the drug sildenafil citrate could help boost the growth of the baby. Sildenafil had been tested on several animal species, including mice, rats, rabbits and dogs, and the authors of a systematic review concluded that:

… no teratogenic or fetotoxic effects of sildenafil have been reported in experimental animal models at dose levels much higher than those used in humans.

The review also included reports about a small number of pregnant women who were treated with sildenafil as a treatment for premature delivery. The efficacy of sildenafil was reported as “limited” and “conflicting”.

Meanwhile, a Queensland study using sildenafil on pregnant women has been temporarily halted. The Queensland study is different to the study in the Netherlands, and so far has no negative outcomes.

Leo, a former “tool for research”. Source: Humane Research Australia

But back to the “good” news. Phasing out animal research depends on the availability of non-animal, human-relevant methods and technologies.

This month, researchers from the Johns Hopkins University demonstrated that artificial intelligence is more accurate than animal testing in spotting toxic chemicals. Professor Thomas Hartung, one the researchers, wrote:

… we have now developed a computer method of testing chemicals that could save more than a US$1 billion annually and more than 2 million animals. Especially in times where the government is rolling back regulations on the chemical industry, new methods to identify dangerous substances are critical for human and environmental health.

Hartung’s research group found that chemicals that are known to be toxic in humans are only proven so in about 70 % of repeated animal tests. The new computer software, however, identified toxic substances in 89% of 48,000 (toxic) chemicals that were tested.

Another area where fast progress is being made is organs-on-chips. The organs-on-chips market is expected to grow rapidly: from US $9.6 million in 2017 to US $45.6 million by 2022. (see also previous blog post from 25/04/2017)

Animal research is an inaccurate “science”, and better, human-relevant methods and technologies have been and are being developed. Which country or jurisdiction will be next to start phasing out animal research?