Tag Archives: NHMRC

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.

 

 

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What’s new in the new guidelines for primate research?

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Baboons. Source: Flickr/  Derek Keats

Scientific purposes: all activities conducted with the aim of acquiring, developing or demonstrating knowledge or techniques in all areas of science, including teaching, field trials, environmental studies, research (including the creation and breeding of a new animal line where the impact on animal wellbeing is unknown or uncertain), diagnosis, product testing and the production of biological products.

Under the Australian federal system, responsibility for animal welfare rests with the states, and all states and territories have incorporated the Code – not always to its full extent – under their animal welfare or animal research laws. This is acknowledged in the new “Principles and guidelines for the care and use of non-human primates for scientific purposes”:

On some issues, this document represents an aspirational standard which may not currently be supported by state and territory legislation and in which case the state and territory legislation takes precedence.

Positive changes (compared to the previous 2003 policy)

Let’s start with the positives in the new principles and guidelines. By that I mean specifications or requirements that are positive from an animal welfare perspective and that were not included in the previous policy.

Great apes (gorillas, orang-utans, chimpanzees and bonobos) are now afforded greater protection. The document notes that no great apes are held in Australia for scientific purposes.

The only great apes held in Australia are in zoological collections for conservation breeding purposes.

And for entertainment purposes, I would like to add.

Now, the use of great apes for scientific purposes in Australia is permitted only when their use:

i) will not have any appreciable negative impact on the animals involved, e.g. observational studies, activities already being undertaken for management or veterinary purposes

ii) will potentially benefit the individual animal and/or their species.

There hasn’t been any research using great apes for decades in Australia. While this is a positive step, it will not impact any current research. For other primates, hardly anything has changed since the previous policy.

But back to the positives:

Non-human primates that are imported from overseas must be captive bred and must be accompanied by documentation to certify their captive-bred status.

It’s prohibited to tear primates from their wild habitats. Still, young animals are torn from their mothers, and import from breeding facilities overseas involves stress during transport.

Further, the new guidelines specify that retirement at conclusion of the research must be considered. The previous policy noted that the existing breeding facilities “will not generally accept animals that have been used for scientific purposes. In most cases, euthanasia will be the only option.” Does this mean that Australian primate breeding facilities accept now animals after they have been used in research?

Provisions for non-human primates at the conclusion of their use must take into account their long-term welfare. Retirement must be considered as an option if suitable in terms of the health and temperament of the animal, and space and resources are available at a facility that can meet their species-specific physical, social and behavioural needs.

But does the NHMRC anything to ensure rehoming options are available? To my knowledge, the answer is “no”.

According to the new guidelines, breeding facilities are not supposed to breed more animals than are needed for research (Australia has breeding colonies for macaques, marmosets and baboons):

Procedures must be in place at all non-human primate breeding facilities to ensure that the breeding programs are matched to the demand for animals, and to avoid or minimise the production of excess animals. Investigators must discuss their requirements for non-human primates with the management of the supply facility early in the planning stages for the project to assist with management of breeding programs.

The previous policy noted that investigators performing experiments overseas under the auspices of an Australian institution obtain approval from an Australian animal ethics committee, and that this may include the delegation of authority to inspect sites and monitor projects at remote sites. The new guidelines state explicitly that undertaking the experiments overseas must not be a way to bypass the Code:

If a project involving the use of non-human primates is to be conducted in another country, Clauses 2.6.9- 2.6.14 of the Code must be upheld. The conduct of a project in another country should not be used as a mechanism for avoiding compliance with Code.

The new guidelines include a section on reward-based training. It is proposed that using positive reinforcement techniques should be considered part of experimental designs for three reasons:

i) assisting in captive management, by seeking the animal’s compliance with routine husbandry and behavioural training

ii) improving the animal’s welfare, by training to facilitate the conduct of routine procedures without the need for chemical restraint

iii) ensuring the quality of the scientific data collected.

The new requirement for “training methods … not be based on approaches that involve punishment such as pain or psychologically distressing stimuli” appears to be primarily motivated by the intent to improve compliance of the captive animal.

Positive changes (compared to the draft guidelines)

The draft guidelines had proposed that the requirement of notifying the NHMRC’s Animal Welfare Committee (AWC) of primate imports be dropped because importing animals is subject to Commonwealth regulation. However, this proposed change did not go ahead:

The institution should ensure that the AWC of NHMRC is notified of the importation of non-human primates after approval from the institutional AEC has been obtained. For NHMRC funded activities, this requirement is mandatory.

In the section concerned with transport of animals, the following sentence was added:

Transport conditions must be designed to minimise stress (see Clauses 3.2.5–3.2.8 of the Code).

But shouldn’t all conditions – in regard to housing, transport and experiments – be designed to minimise stress?

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Macaques. Source: Flickr/ Franx’

Serious problems remain

While non-human primates are our closest relatives and genetically the most similar to us humans, does experimenting on these animals really benefit humans? Aren’t there better, more human-relevant research methods? And more importantly, is it morally defensible to subject these highly sentient and cognitive animals to the stress, pain and often death after experimentation?

Overall, the new guidelines do not represent compelling progress. A few baby steps may lead toward slightly improved animal welfare, but the guidelines are still steeped in an outdated paradigm. Even within this paradigm, we can decry the lack of transparency in animal research, non-existent or insignificant benefits for humans and animals, and the NHMRC and its funded institutions’ lack of taking responsibility for the fate of non-human primates after completion of research projects. The NHMRC funds primate breeding colonies, and funding a sanctuary for “retired” primates should be its responsibility, too.

So, what’s new in the new guidelines for non-human primates? Hardly anything that reduces pain and suffering and improves the lives of our closest relatives who are used for scientific purposes.

The primates used by medical research are sensitive and intelligent beings. We owe them a decent life, not confinement, suffering and untimely death in the lab.

Disclosure

Together with Sir David Attenborough, Dr Jane Goodall and 19 other scientists, primatologists and animal welfare experts I signed an open letter “Testing on non-human primates in neuroscience research is no longer justifiable”, supporting Cruelty Free International in raising concerns about the controversial use of non-human primates in neuroscience research.

 

Further reading  

National Health and Medical Research Council. (2016). Principles and guidelines for the care and use of non-human primates for scientific purposes. Canberra: National Health and Medical Research Council, Australian Government.

Helen Marston, CEO of Humane Research Australia, has commented on the new guidelines on her blog: “New guidelines for primate research will not protect our closest relatives”.

Jeory, T., & Stone, J. (2016, 8 September). David Attenborough calls for end to ‘cruel’ brain tests on primates by neuroscientists. Exclusive: Sir David joins 21 signatories to an open letter published in The Independent. The Independent.

Lidbury, B. A. (2016). Medical science has moved on: it’s time to end primate testing. Australian Doctor(17 March).

Academic articles:

Bailey, J., & Taylor, K. (2009). The SCHER report on non-human primate research – biased and deeply flawed. Alternatives to laboratory animals : ATLA, 37(4), 427-435.

Bailey, J., & Taylor, K. (2016). Non-human primates in neuroscience research: The case against its scientific necessity. Alternatives to Laboratory Animals – ATLA, 44(1).

Bailey, J., Thew, M., & Balls, M. (2015). Predicting human drug toxicity and safety via animal tests: can any one species predict drug toxicity in any other, and do monkeys help? Alternatives to Laboratory Animals, 43(6), 393-403.

Burm, S. M., Prins, J. B., Langermans, J., & Bajramovic, J. J. (2014). Alternative methods for the use of non-human primates in biomedical research. Altex, 31(4), 520-529.

Chandrasekera, P. C., & Pippin, J. J. (2015). The human subject: an integrative animal model for 21st century heart failure research. American Journal of Translational Research, 7(9), 1636-1647.

Gilbert, S., Kaebnick, G. E., & Murray, T. H. (2012). Animal research ethics. Evolving views and practices: The Hastings Center.

Gordon, N., & Langley, G. (2008). Replacing primates in medical research. An expert report by: Dr Hadwen Trust, FRAME, St Andrew Animal Fund.

Greek, R., Hansen, L. A., & Menache, A. (2011). An analysis of the Bateson Review of research using nonhuman primates. Medicolegal and Bioethics, 1, 3-22.

Taylor, K. (2010). Reporting the implementation of the Three Rs in European primate and mouse research papers: are we making progress? Alternatives to laboratory animals : ATLA, 38(6), 495-517.

Wendler, D. (2014). Should protections for research with humans who cannot consent apply to research with nonhuman primates? Theoretical Medicine and Bioethics, 35(2), 157-173.

 

 

Where is Australia at the 3R Olympics?

Source: Flickr/ Romano Guidotti

Source: Flickr/ Romano Guidotti

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

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

How many animals are used for scientific research and teaching?

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

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

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

Germany (2014) – 2 million animals

Canada (2014) – 3.75 million animals

Great Britain (2015) – 4 million animals

Australia (2014) – 6.99 million

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

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

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

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

pop x no of animals used.png

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

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

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

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

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

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

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

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

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

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

 

 

Which bank is taking a stand against experimenting on non-human primates?

Baby macaque. Source: Flickr/ Tambako The Jaguar

Baby macaque. Source: Flickr/ Tambako The Jaguar

It’s ING. This bank is not listed on the ASX; it has its head office in the Netherlands. But ING’s animal welfare policy might give ASX listed banks new ideas.

ING provides financing to the food industry, such as producers, traders, transport companies and companies that handle and process food products. The company has recently announced that it has broadened the range of activities involving animals that it won’t finance.

From clients in the animal husbandry sector, ING expects industry best practices as well as prove that animals are treated in line with the Five Freedoms. ING has also expanded the list of what they won’t finance. Their exclusion list includes now:

  • Animal testing for cosmetic purposes
  • Sponsoring requests for events with animals where the Five Animal Freedoms are not respected
  • Animal trade involving endangered species for commercial purposes
  • Use of endangered species or non-human primates for any testing/ experimental purposes
  • Support of any type of animal fights for entertainment
  • Operating fur farms
  • The trade and manufacturing of fur products
  • The development of genetic engineering or genetic modification on plants or animals for non-medical purposes.

(Source: ESR, page 3)

It’s not unusual for a bank in Europe to speak out against animal testing for cosmetics, which has been banned in the EU for some years. A testing ban on finished cosmetic products applies since 11 September 2004; the testing ban on ingredients or combination of ingredients applies since 11 March 2009.

However, it’s unusual to find a bank that won’t do business with companies or organisations that experiment on non-human primates with the expressed aim of advancing human health (whether this aim is achieved is a different issue). I call this leadership.

I do not know whether Australian banks do business with companies/organisations involved in experimentation on non-human primates. But I will try to find out. (Also, there will be a blog post soon about ASX listed banks and animal welfare policies in general. Stay tuned!)

Marmoset. Source: Flickr/ Frank Kehren

Marmoset. Source: Flickr/ Frank Kehren

As to experiments on non-human primates, they do occur in Australia. The National Health and Medical Research Council (NHMRC) funds three breeding colonies: one in New South Wales for baboons and two in Victoria for macaques and marmosets.

At a recent Senate Environment and Communications Legislation Committee hearing Anne Kelso, Chief Executive Officer of the NHMRC, reported that last year 36 non-human primates were used in research funded by the NHMRC. If additional primate research is undertaken by the pharma or biotech industry, such research would need to be licensed by the state bureaus of animal welfare. Information about these licenses is, depending on the state, difficult or impossible to obtain.

If the NHMRC funded research on non-human primates is the only such research occurring in Australia, a policy by a financial institution to not support such research would be without practical consequences. However, it would still make a statement that experiments on non-human primates are unacceptable.

 

Further reading

ING requests LEI to do research in reaction to the report of the Dutch NGO ‘Wakker Dier’

ING Environmental and Social Risk Framework (or go to this page and click on ESR)

Animal testing has saved tens of millions of lives

Bailey, J., Thew, M., & Balls, M. (2015). Predicting human drug toxicity and safety via animal tests: can any one species predict drug toxicity in any other, and do monkeys help? Alternatives to Laboratory Animals, 43(6), 393-403.

Gordon, N., & Langley, G. (2008). Replacing primates in medical research. An expert report by: Dr Hadwen Trust, FRAME, St Andrew Animal Fund.

 

 

Why so secret?

Source: Flickr/ @Doug88888

Source: Flickr/ @Doug88888

Two days ago the Sydney Morning Herald published an article titled “Baboons used in ‘Frankenstein-like’ medical experiments”. Yesterday it was followed by an editorial – “Medical testing on primates: more openness and transparency needed” – and another article, also on the topic of research on non-human primates, “Thousands sign petition urging an end importing of primates for medical research”. Numerous online media have republished the “Frankenstein” article and people have taken to social media to comment.

During a six-month investigation, journalist Natalie O’Brien uncovered medical experiments on non-human primates, secretly conducted at a number of Sydney hospitals and universities, including a kidney transplant from a pig to a baboon. O’Brien writes that

Millions of dollars of research grants are being used for a variety of experiments but the hospitals involved have refused to release details about how many baboons or other primates have been experimented on, and how many have died or had to be killed.

NSW Health also denied a whole organ transplant had taken place, despite details emerging of Conan, a baboon who had to be killed because of fatal complications arising from the insertion of a pig’s kidney into his body.

In response to a Government Information Public Access (GIPA) request NSW Health had denied that diabetes research involved whole organ transplants, while the NHMRC acknowledged in writing that it has funded research for “whole organ animal to animal xenotransplantation”.

Meanwhile, Greens Senator Lee Rhiannon has introduced a Bill to end the import of primates for medical research. A Senate inquiry into the importation of primates into Australia for use in medical research is due to be published in March. And Humane Research Australia has handed a petition with more than 14,000 signatures calling for a ban on importing primates for medical and scientific research to the Federal Parliament.

The main issues that the articles are concerned with are the secrecy and the ethics of this research. Reliability of the animal model is another concern.

Why have these experiments been conducted secretly, as they are entirely legal? Being legal and being accepted by the public are not the same. Indeed, the law is often lagging behind views that many, if not most citizens have come to regard as acceptable and/or desirable. Examples are marriage equality and voluntary euthanasia.

The procedures performed on animals in biomedical research would anywhere other than in licensed laboratories considered to be animal cruelty, punishable by law.

The RSPCA defines animal cruelty as follows:

Animal cruelty can take many different forms. It includes overt and intentional acts of violence towards animals, but it also includes animal neglect or the failure to provide for the welfare of an animal under one’s control. In addition to this, it is important to remember animal cruelty is not restricted to cases involving physical harm. Causing animals psychological harm in the form of distress, torment or terror may also constitute animal cruelty.

Given that animals share with us the ability to suffer, it is not surprising that many people find animal experiments abhorrent. Researchers tend to keep invasive animal experiments out of public view, usually for fear of negative press or harassment. But every now and then animal advocates and journalists manage to find out about particularly gruesome instances of animal experimentation and make them public. The monkey research reported in the recent articles is such an example, and it has generated condemnation and questions about what else goes on behind closed doors.

But is the secrecy justified? Isn’t it understandable that researchers are fearful of the consequences of being open about the details of animal research? Recent experience from the UK tells us that greater transparency has NOT resulted in negative consequences for researchers and their institutions.

The Concordat on Openness on Animal Research in the UK was launched in May 2014. It is a collaboration of now 98 universities, charities, commercial companies, research councils, umbrella bodies and learned societies with a common aim:

The aim of the Concordat is culture change within the life-science sector, and a resulting shift to greater societal understanding of why and how research organisations use animals in science. The Concordat creates a shared commitment and critical mass to encourage organisations to take strategic and practical steps towards greater openness.

Following a survey of signatory institutions, the first Concordat on Openness Annual Report was published in September 2015. The survey found no reports of any adverse consequences for those organisations that provided the public with more information about their research than they had previously done.

When the Concordat was developed there was considerable concern cited about the risks of openness, and a fear that transparency would bring researchers into physical danger. The information provided by signatory institutions about their communications activities since May 2014 indicates clearly that this has not been the case. The success of many initiatives developed by signatory organisations over the first year including media interviews and documentaries, the development of websites and videos, public engagement events and mention of animals in staff recruitment processes, places this risk into context and paves the way for more activity in the future.

The types of additional information that organisations provided varied. It included, for example, numbers and species of animals used, lay summaries of research projects, images of animals, and images including animal facility staff. Funding bodies revealed the proportion of grants that are used to fund animal research, and one organisation published on their website the minutes of Animal Welfare Ethical Review Board (AWERB) meetings.

Here in Australia, we have no such initiative. While we will see how genuine the Concordat signatories are about real openness, at least it’s a good start. Here, it is extremely difficult to obtain details of animal research. Helen Marston, CEO of Humane Research Australia (HRA), describes the difficulties of obtaining any information on her blog.

A large proportion of medical research grants involve animal experimentation. We don’t know the exact extent of this proportion, but the public has a right to know how these public funds are spent. We need transparency in animal experimentation so that we as a society can have an informed dialogue about the ethics and usefulness of this research.

 

Further reading (and viewing)

Animal experimentation. Animals Australia.

Ban primate experiments. Humane Research Australia.

Knight, A. (2007). Systematic reviews of animal experiments demonstrate poor human clinical and toxicological utility. Alternatives To Laboratory Animals, 35, 641–659.

Knight, A. on animal experimentation. A series of video clips.

Nobis, N. (2011). The harmful, nontherapeutic use of animals in research is morally wrong. American Journal of the Medical Sciences, 342(4), 297-304.

Regan, T. (1985). The case for animal rights. In defense of animals. P. Singer. New York, Basil Blackwell: 13-26.

Tyler, A. (2015). The scientific case against the use of animals in biomedical research. UK, Animal Aid.

 

Australia failing to protect non-human primates in research

A re-post of a piece I wrote for the Conversation:

The NHMRC code on animal use requires researchers to minimise harm, pain and distress but doesn’t provide guidance on how to do it. International Fund for Animal Welfare Animal Rescue Blog/Flickr, CC BY-NC

The NHMRC code on animal use requires researchers to minimise harm, pain and distress but doesn’t provide guidance on how to do it. International Fund for Animal Welfare Animal Rescue Blog/Flickr, CC BY-NC

Monika Merkes, La Trobe University

In late April, a US judge granted lawyers acting for two chimpanzees used in research at the State University of New York at Stony Brook, Hercules and Leo, a hearing about their unlawful imprisonment. The case will test legal personhood for the animals. But in Australia, non-human primates may be about to see their circumstances change for the worse because of an impending research ethics policy change.

Public consultation on the National Health and Medical Research Council’s (NHMRC) draft Principles and guidelines for the care and use of non-human primates for scientific purposes will close tomorrow (Friday May 8). The document, which is an update of a 2003 policy and complements the Australian code for the care and use of animals for scientific purposes, will remove some existing safeguards for ethical use of these animals in research.

In Australia, regulatory responsibility for animal welfare, including the care and use of non‐human primates in research and teaching, rests with state and territory governments. While the NHMRC’s code is not legally binding, it requires researchers it funds to follow its policy on animal welfare.

The new draft guidelines

The code requires researchers to minimise harm, pain and distress to the animals they use. It states all teaching and research activities “must balance whether the potential effects on the wellbeing of the animals involved is justified by the potential benefits”. But it doesn’t provide guidance on how to do this, so it’s up to researchers and local animal ethics committees to determine what procedures are justified.

Great apes (gorilla, orang‐utan, chimpanzee and bonobo) and other non-human primates are treated differently by the new draft. The use of great apes in research is permitted only when it “will not have any appreciable negative impact on the animals involved, e.g. observational studies, activities already being undertaken for management or veterinary purposes” or when it “will potentially benefit the individual animal and/or their species”. The former was not included in previous guidelines, so this is a step forward.

But, to my knowledge, great apes have not been used in Australian research for a long time. While this new clause will protect great apes from being used in NHMRC-funded research, it is unlikely to impact current research practice.

Other non-human primates used for research (macaques, marmosets and baboons) are not so lucky. The NHMRC has already acknowledged that non-human primates have the capacity to suffer more than other research animals because of their higher cognitive abilities and well-developed social structures. In spite of this, many of its purported protections are ambiguous and ultimately meaningless.

Weak protections

The NHMRC wants feedback on proposed changes to requirements
that its animal welfare committee be notified when non-human primates are to be housed for periods longer than six weeks without access to an outside enclosure, or imported.

The reason for the latter is that importing animals is subject to Commonwealth regulation. But since the draft guidelines still require notification of export of non-human primates, there is no good reason why import should not be treated in the same way. The public has an interest to know, and this information would be difficult, if not impossible, to collect from animal ethics committees.

Removing the requirement on housing weakens animal protection because it shifts power from the NHMRC’s animal welfare committee to local animal ethics committees. Not requiring local committees to justify their decisions to an external body could enable conditions that are not in the animals’ interest.

Marmosets and other non-human primates are not as well protected as the great apes, despite also having high cognitive abilities. Tambako The Jaguar/Flickr, CC BY-ND

Central overview checks potential abuse through oversight as well as overcoming lack of knowledge and expertise among small local animal ethics committees. Self-regulation is not sufficient to protect animals who cannot speak for themselves; we need more transparency to ensure this is happening, not less.

Indeed, transparency is an important issue not addressed by the NHMRC code or draft guidelines. In Australia, there is no publicly available information about the use of non-human primates – as well as other animals – in research and teaching. Not only does this mean there is no way of knowing research isn’t duplicated, it also stops the public finding out details of research that is funded through their taxes.

Australia is not unique in this regard but there is a precedent for transparency. A European Union directive effective since 2013 mandates the publication of a non-technical summary of all animal research projects after any trade secrets or information that could identify researchers or institutions is redacted. If European researchers can provide this information, why can’t researchers in Australia?

Some serious problems

There are much bigger problems here, too. The umbrella group for councils that fund research in the United Kingdom recently ended a two-year investigation that found an excess of animal lives were being wasted on poorly designed projects that produced meaningless results. Most likely the situation is similar in Australia but the lack of transparency means we have no way to find this out.

There are still outstanding questions about whether there are actual benefits in using animals for biomedical research. Indeed, the authors of a recent article in the BMJ have suggested that this kind of work may be diverting funds from research that is more relevant.

What’s more, we have valid research methods that replace non-human primates in research of debatable quality.

But all we have in Australia are these new draft guidelines that will more likely than not move us backwards. Apart from the problems already discussed, they lack guidance on the fate of research animals after their use, by leaving these decisions to animal ethics committees.

We don’t know where these animals go after research projects are completed, or whether they’re killed because there is no appropriate place for them to live. Surely, since the NHMRC funds primate breeding facilities, funding a sanctuary for them to spend the rest of their days after they have been used in research for human benefit is its responsibility, too.

While we erode the rights of non-human primates in Australia, Hercules and Leo will have their day in court. Even if they don’t achieve legal personhood, their case will be a step towards ending experimenting on animals that are so much like us.

The Conversation

Monika Merkes is Honorary Associate, Australian Institute for Primary Care & Ageing at La Trobe University.

This article was originally published on The Conversation.
Read the original article.

NHMRC public consultation on the care and use of non-human primates for scientific purposes

Pondering primate. Source: Flickr/ jjjj56cp

Pondering primate. Source: Flickr/ jjjj56cp

The National Health and Medical Research Council (NHMRC) of Australia is consulting the public on new guidelines for the care and use of non-human primates for scientific purposes. The closing date for submissions is Friday, 8 May 2015, 5:00pm.

I have just submitted my comments. Here is my submission:

Re: Public consultation on the draft principles and guidelines for the care and use of non-human primates for scientific purposes

Thank you for the opportunity to comment on the above document.

First of all, I wish to state that I am opposed to the use of animals in teaching and research on ethical and scientific grounds.

However, I wish to make the following comments in response to the draft document:

Pages 2 – 3. The NHMRC is particularly interested in feedback on proposed changes to notification requirements to its Animal Welfare Committee (AWC). The requirements that would be removed are:

  • Exemption from the AWC regarding housing of non‐human primates for periods longer than six weeks without access to an outside enclosure.
  • Notification to the AWC of the importation of non‐human primates which is subject to Commonwealth regulation.
  • Inspection by the AWC of facilities where non‐human primates will be housed and used.

I am against the removal of these requirements, because they weaken the existing protections and extend self-regulation. Self-regulation is not sufficient to protect the animals effectively, and a central overview is important. It is crucial that all use of primates is reported to the NHMRC and that a database is established to monitor all aspects of their use.

In addition, I encourage you to establish a national data base for all animal research to inform the public and to insure research is not duplicated. Such a database is mandated in the European Union. The EU requires the publication of nontechnical summaries of all animal research projects minus any trade secrets or information that could identify researchers or institutions. Researchers in the EU provide this information, and Australia should follow their lead.

The draft document notes that “Great apes must not be imported from overseas”, yet it is proposed to even drop the requirement to notify the AWC of the importation of other non‐human primates. If we have breeding facilities here in Australia, why import non-human primates thereby subjecting them to considerable stress during transport? As stated above, ideally we should ban the use of all non-human primates for scientific purposes, but if this does not occur, then at least stress and suffering should be minimised.

Points 2 and 5

Great apes and other non-human primates are treated differently by the new draft guidelines, suggesting that “the use of great apes (gorilla, orang‐utan, chimpanzee and bonobo) raises even greater ethical concerns than that of other non‐human primates”. The use of great apes for scientific purposes is only permitted when it “will not have any appreciable negative impact on the animals involved” or when it “will potentially benefit the individual animal and/or their species”. This conveys stronger protection than the previous guidelines issued in 2003, and I commend this change.

Considering there is little difference between great apes and other primates in their capacity to suffer, their cognitive abilities and well-developed social structures, the protections granted to great apes should be extended to all other primates.

Many of the purported protections are ambiguous and ultimately meaningless. For example:

  • Point 15. “The capacity for the particular species of non-human primate involved to experience pain and distress must be taken into account when making decisions about the possible impact of procedures or conditions on the wellbeing of an individual non-human primate”. — “Taking into account” is unspecific and can mean anything.
  • Point 16. “When non-human primates are supplied to a project approved by an institutional AEC, the animals must be obtained from an established Australian breeding colony unless another source is approved by the AEC”. — It would be more honest to say that the AEC can approve any type of sourcing of non-human primates.
  • Point 25 (i).“Australian‐bred non‐human primates must not be exported unless … for a specific purpose. Examples of specific purposes would be maintenance of genetic diversity or provision of overseas researchers with a model of a primate disease”. — “A specific purpose” can be found easily.

Point 28. The draft document notes that the 3Rs need to be applied at all stages. In regard to the first R (i.e. Replacement) I’d like to point out that many countries have dedicated research centres for the development and validation of non-animal research methods. These centres receive government support and funding. This is not the case in Australia. It would be appropriate for the NHMRC to demonstrate a similar commitment.

In summary, in the absence of a ban on the use of all non-human primates for scientific purposes, I propose the following:

  • Extend the protections granted to great apes to other non-human primates.
  • Start a national database for all animal research. This could follow the EU example.
  • Many countries have government-supported dedicated research centres for the development and validation of non-animal research methods. Australia needs to catch up and contribute to the development of effective and ethical research methods that do not involve the use of animals. The NHMRC is the appropriate body to advance and support this.
  • At present, Australia does not have a facility for “retired” primates. We need a sanctuary for non-human primates in Australia, and the NHMRC should fund such a sanctuary.


If you feel strongly about the protection of non-human primates used in research and teaching, I encourage you to make a submission. It doesn’t have to be a long document. Feel free to “borrow” from my submission. Further, Humane Research Australia has provided a few pointers that you can use.

Let’s do what we can to improve the lives of animals unfortunate enough to end up in a research institute.