Canada Releases 2012 Animal Use Statistics

Earlier this month the Canadian Council on Animal Care (CCAC) released its report on the number of animals used in Canada for scientific purposes. The CCAC is an independent oversight body that oversees the ethical use of animals in research. They also develop guidelines and promote training programs to ensure that all individuals involved in animal research or welfare are properly trained before being allowed to work with the animals. The CCAC reports that in 2012, 2,889,009 animals were used for research, teaching and testing in Canada. This is down 444,680 animals, from 3,333,689 animals that were used in 2011. These numbers include all vertebrates and Cephalapods, but do not include invertebrates like fruit flies or nematode worms. Animals can be used in more than one protocol provided these additional protocols do not result in pain.

2012 Canadian Animal research and testing Graph

Mice (43.2%), fish (28.8%), rats (7.8%) and birds (6.6%) were the most common species, together accounting for 86% of animals used. These numbers represent a shift in the type of animal used, as fish have been the animal most frequently used by Canadian institutions for the past three years. The majority of animals (61%) were used in studies of a fundamental nature/basic research, representing 1,815,083 animals. There has been significant changes to the reporting methodology utilized to analyze the current data and the CCAC made the following statement with respect to the 2012, report:

“Due to these differences in data management and reporting, it is not possible to make accurate comparisons with CCAC PAU and CI data from previous years.”

2012 Canadian Research and Testing Table

More information about animal research in Canada can be found within the Speaking of Research Media Briefing Notes for Canada.

Michael

5 Minutes with an Animal Care Facility Coordinator

Richard Marble, an Animal Care Facility Coordinator at Ferris State University, is a dedicated and experienced Animal Technologist who takes his responsibility of caring for the animals in his care seriously.  Following a guest post (It’s All About the Animals) in which Richard wrote giving insight into what is it like being an animal facility manager, he agreed to do an interview with Speaking of Research member, Jazzminn Hembree.

Richard opened up about his responsibilities in caring for animal welfare, and how he oversees all activities taking place within the facility as he seeks to improve animal welfare.  Many improvements have occurred during his time in the field, such as changes in housing and environmental enrichment. Richard explains

Research is like an enigma. Even those of us in the field do not like utilizing animals for research, but until such time as they are no longer necessary- the passionate people in this field are going to go out of their way to give them the best life they can.

Watch the video as he discusses:

  • How he is responsible for Animal Welfare?
  • What improvements he has seen in animal welfare over the past 15 years?
  • How he factors the 3R’s (Reduce, Refine, Replace) into his daily activities?
  • How he thinks animal welfare will improve in the future?

Why People Are Wrong to Oppose the New UK Beagle Breeding Facility

This post was originally posted on Huffington Post UK’s website. It is reprinted with permission from both the author and the Huffington Post. The original hyperlinks which were stripped out of the HP article have been returned.

Where do medicines come from?

It’s not a question most of us bother with when we take advantage of the huge array of medical treatments available to us.

All modern medicine is built on the ‘basic research’ which allows us to understand our physiology, and the diseases we suffer. Much of this research has been done, and continues to be done, in animals. Had Mering and Minkowski not shown the causal link between the pancreas and diabetes in dogs, we might never have discovered insulin (much more work was conducted in dogs by Banting and Best who later won the Nobel Prize for the discovery of insulin). Had Pasteur not shown how dogs could be vaccinated using weakened samples of the virus (made from rabbits), we would not have both the veterinary and human rabies vaccines.

Animals are also used to develop and refine medical techniques. Dogs played a key role in perfecting artery to vein blood transfusions, as well as showing that citrated blood could be safely transplanted (thus preventing the blood from clotting). More recently, 23 pet dogs with paralysing spinal injuries were able to regain some use of their rear legs thanks to a novel stem cell transplant treatment. This research had originally been done in rats, and last year was used to successfully treat a paralysed man in what could prove to be one of the biggest medical advances of the decade.

By law, animals must also be used to test the toxicity and safety of new drug compounds before they can be given to human volunteers. A pharmaceutical company will have used the findings of basic research studies to identify types of drugs which might be effective against certain diseases. They will then use a variety of non-animal tests – computer modelling, cell cultures and more – to identify the most promising drug candidates. Those compounds will then be tested in animals. If they are deemed safe enough, they may then be moved forward to human trials. It is testament to the effectiveness of animal safety tests that nobody has died in Phase I clinical trials in the UK for over 30 years (with only one badly conducted clinical trial causing severe harm in recent times).

Given public misconceptions on the issue, it is worth being clear and saying that in the UK, and across the rest of the EU, it is illegal to use animals to test cosmetic products or their ingredients. The UK ban came into force in 1998, one year after a ban on tobacco research using animals. The Government has also announced a ban on using animals for testing household products.

Graph - Milestones in Animal Research

So what about dogs?

Laboratory DogsDespite the examples used in this article, dogs are not used that much in research in the UK. They account for less than 0.1% of all animals used in the UK each year. This compares to the 98% of procedures which are conducted on mice, rats, fish or birds. In 2013 there were 3,554 dogs used in 4,779 procedures (down 30% from a decade ago). Due to special protections that exist for dogs, cats, primates and horses, researchers must justify to the Home Office why another species, such as a mouse, fish or sheep, cannot be used instead of a dog. The research must be approved by an ethical review board, who will work to ensure the implementation of the 3Rs (Replacement, Refinement and Reduction of animals in research). The researcher, the institution and the individual procedure must each be licensed by the Home Office. The video below, produced by Understanding Animal Research, shows dogs in a typical pharmaceutical laboratory in the UK.

So why a breeding facility?

Currently, around 20% of the dogs used in research in the UK are imported from abroad (those involved in 956 of the 4,779 procedures in 2013). This is because the UK breeding facilities cannot provide all the dogs used in the UK. These dogs have to endure long and potentially stressful flights from other countries. Surely it is better to breed them here in the UK, where we have some of the highest standards of laboratory animal welfare in the world and where our facilities can be easily monitored by the Animals in Science Regulation Unit inspectors? The new breeding facility offers animal welfare standards above and beyond those demanded by the Government. Dogs will be kept in socially housed groups in multi-level pens which can be joined together to create larger runs for the animals. All the animals will have toys and enrichment in their enclosures, and will interact with trained laboratory technicians every day. It is this sort of investment in animal welfare we, as an animal-loving nation, should embrace.

Petitioning the Government to reverse their decision on approving the beagle facility in Hull is misguided. It will not reverse our need to use animals in research, or even change the number of dogs used in the UK. What it will do is force another generation of puppies to take long flights from other countries, having been bred in older breeding facilities away from the UK inspectorate.

Animal research may not be something we want to think about when we take our medicines – but it is something necessary for those medicines to exist. Instead of trying to ban animal research, let’s instead make sure that if we do it, we do it to world-class standards.

Tom Holder

Director of Speaking of Research

Ireland releases 2014 animal research statistics

In our effort to build a comprehensive picture of animal research statistics worldwide, our latest post is on the recently released (permanent link) statistics for Ireland. These are compiled by the Health Products Regulatory Authority of Ireland (HPRA). These statistics are produced in accordance with EU Directive 2010/63 which regulates animal research across EU countries.

The restrictions and standards set by the Directive are expected to enhance animal welfare and ensure that animals are used in studies only when their use is  strongly justified and following independent assessment. The Directive firmly anchors in EU Legislation the 3Rs,  i.e. Replacement, Reduction and Refinement.

The total number of animals used for the first time was 224,249 in 2014,  down almost 20% from 2013. The total number of procedures was slightly higher at 226,684. These numbers include all vertebrates and Cephalapods, but do not include invertebrates like fruit flies or nematode worms.

Unlike countries, like the UK and US, basic research is a much smaller portion of overall research (15%) in Ireland whereas ‘Toxicity and other safety testing’ is larger, accounting for over 61% of all Irish procedures on animals.

Animal Research in Ireland in 2014

95% of animals used in research were rodents (mainly mice). Dogs and cats, combined, accounted for only 0.05% of the total number of animals, and no primates were used at all.

The full Irish statistical document provides information on the source of the animals, the different types of research (broken down in different ways, such as by body system) and the severity – providing a good picture of what research goes on in Ireland.

While the number of animals used is down from the previous year, the HPRA warn about jumping to conclusions on any trend:

The HPRA also advises that in respect of the HPRA’s 2013 data, it would be unsound to directly compare this data as it is only the second year of a new reporting structure to which reporters are getting better acquainted to the changed reporting requirements and provisions required. Extreme caution should be applied therefore in any attempt to draw comparisons to previous years’ figures.

We look forward to seeing another high quality statistical release next year.

Speaking of Research

German Outreach Done Right

The German Primate Center (DPZ) have been producing some excellent resources to show how their primates are housed. This sort of outreach goes a long way to helping understand the lengths that institutions will go to ensure that high standards of animal welfare are maintained for their primates.

The first resource is an interactive tour of the DPZ facility. The website allows users to se pictures of the facility, and discover key information about the site. There are approximately 1300 primates currently kept at the facility, 75% of which are either rhesus macaques or common marmosets – both common research animals.

It isn’t just information about the animals which is provided. The tour explains why staff and visitors must change their shoes as they walk around the facility, and how clothes are decontaminated between areas. While such practices are very normal for researchers and animal care staff, they can seem quite alien, and even intimidating, for those who are less used to the laboratory environment. The tour answers questions about how often cages are cleaned (daily), how sunlight is regulated, what sort of enrichment exists, and much more.

Animal research facility at DPZ

The breakout boxes provide more information about aspects of animal welfare, facility management and the animals themselves.

How does the environment influence animal behaviour

The captive environment should allow and encourage natural behavior as shown by the species in the wild. This can be behaviors and postures like leaping, climbing, hanging upside-down, and running as well as clinging or jumping. The artificial environment should also allow all social behaviors like grooming, playing, huddling or the display of dominance, which is very important to all primate societies.

DPZ have also produced a video (in English) showing the work being done at their Cognitive Neuroscience Laboratory. The video looks at research which aims to understand the filtering process (selective attention) in brain processing – “what are its consequences, what is its neural basis, and what happens if there is a malfunction in that system”. It includes both the human and primate research.

The video is fantastic, showing how the primates are treated in studies at DPZ. This sort of outreach is important to help the public understand what primate research actually looks like.

Speaking of Research congratulate DPZ for these fantastic outreach tools.

USDA publishes 2014 Animal Research Statistics

Congratulations to the USDA/APHIS for getting ahead of the curve and making the US the first country to publish its 2014 animal research statistics. Overall, the number of animals (covered by the Animal Welfare Act) used in research fell 6.4% from 891,161 (2013) to 834,453 (2014).

These statistics do not include all animals as most mice, rats, and fish are not covered by the Animal Welfare Act – though they are still covered by other regulations that protect animal welfare. We also have not included the 166,274 animals which were kept in research facilities in 2014 but were not involved in any research studies.

Types of Animals used in research and testing 2014Statistics from previous years show that most of the “All other animals” species are rodents (but not mice or rats). 53% of research is on guinea pigs, hamsters and rabbits, while 10% is on dogs or cats and 7% on non-human primates. In the UK, where mice, rats, fish and birds are counted in the annual statistics, over 97% of research is on rodents, birds and fish. Across the EU, which measures animal use slightly differently, 93% of research is on species not counted under the Animal Welfare Act. We would expect similar patterns to be true in the US – although there are no statistics to confirm this.

Changes in number of animals used in research from 2013 to 2014 - Click to Enlarge

Changes in number of animals used in research from 2013 to 2014 – Click to Enlarge

If we look at the changes between the 2013 and 2014 statistics we can see a drop in the number of animals of most species , with only the “all other animals” category showing a rise. This is the second year in which the number of many species has fallen. For example, the number of rabbits used in 2014 fell 11.4% from 2013, following a 9.2% fall from 2012.

Most notably the number of non-human primates has fallen by 9.9%, the number of dogs fell 12.4% and the number of cats fell by 13%. This has shown these species taking up a smaller proportion of the research animals used, as can be seen below:

Trend in number of animals used in research 1973 - 2014 - Click to Enlarge

Trend in number of animals used in research 1973 – 2014 – Click to Enlarge

Clearly there has been a downward trend in the number of animals used since the early 1990s with a 61% drop in numbers between 1992 and 2014. It is also likely that, similar to the UK, a move towards using more genetically altered mice and fish has reduced the numbers of other AWA-covered animals used.

Rises and falls in the number of animals used reflects many factors including the level of biomedical activity in a country, trending areas of research, changes to legislations at home and abroad, outsourcing research to and from other countries, and new technologies (which may either replace animal studies or create reasons for new animal experiments).

It is important to note that the number of animals cannot be tallied across years to get an accurate measure of total number of animals. This is because animals in longitudinal studies are counted each year. Thus, if the same 10 animals are in a research facility for 10 years, they would appear in the stats of each year – adding these numbers would incorrectly create the illusion of 100 animals being used.

Speaking of Research welcomes the open publication of these animal research statistics as offering the public a clear idea of what animal research goes on in their country.

Clinical trial success for Cystic Fibrosis gene therapy: built on animal research

This morning the Cystic Fibrosis Gene Therapy Consortium (GTC) announced the results of clinical trial in 140 patients with cystic fibrosis, which demonstrate the potential for gene therapy to slow – and potentially halt – the decline of lung function in people with the disorder. It is a success that is built on 25 years of research, in which studies in animals have played a crucial role.

Cystic fibrosis is one of the most commonly inherited diseases, affecting about one in every four thousand children born in the USA, and is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR gene produces a channel that allows the transport of chloride ions across membranes in the body, and the many mutations identified in cystic fibrosis sufferers either reduce the activity of the channel or eliminate it entirely. This defect in chloride ion transport leads to defects in several major organs including the lungs, digestive system, pancreas, and liver. While the severity of the disease and the number of organs affected varies considerably, cystic fibrosis patients often ultimately require lung transplant s, and too many still die early in their 20’s and 30’s as the disease progresses.

In a paper published in Lancet Respiratory Medicine today (1), the GTG members led by Professor Eric Alton of Imperial College London compared monthly delivery to the airway of a non-viral plasmid vector containing the CFTR gene in the liposome complex pGM160/GL67A using a nebuliser with a placebo group who received saline solution via the nebuliser. They reported stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group after a year. This is the first time that gene therapy has been shown to safely stabilise the disease, and while the difference between the treated and control group was modest, and the therapy is not yet ready to go into clinical use, it provides a sound bases for further development and improvement.

Blausen_0286_CysticFibrosis

The Chief Executive of the Cystic Fibrosis Trust, which is one of the main funders of the GTC, has welcomed the results, saying:

Further clinical studies are needed before we can say that gene therapy is a viable clinical treatment. But this is an encouraging development which demonstrates proof of concept.

“We continue to support the GTC’s ground-breaking work as well as research in other areas of transformational activity as part of our mission to fight for a life unlimited by cystic fibrosis.”

So how did animal research pave the way for this trial?

Following the identification of the CFTR gene in 1989 scientists sought to create animal models of cystic fibrosis with which to study the disease, and since the early 1990’s more than a dozen mouse models of cystic fibrosis have been created. In some of these the CFTR gene has been “knocked out”, in other words completely removed, but in others the mutations found in human cystic fibrosis that result in a defective channel have been introduced. These mouse models show many of the defects seen in human cystic fibrosis patients and over the past few years have yielded important new information about cystic fibrosis, and in 1993 Professor Alton and colleagues demonstrated that it is possible to deliver a working copy of the CFTR gene using liposomes to the lungs of CFTR knockout mice and correct some of the deficiencies observed.

To get a working copy of the CFTR gene to the lungs of cystic fibrosis patients Professor Alton and colleagues needed three things:

• A DNA vector containing the working CFTR gene that is safe and  can express sufficient amounts of the CFTR channel protein in the lungs to correct the disease

• A lipid-like carrier that can form a fatty sphere around the DNA vector to so that it can cross the lipid membrane of cells in the lung, as “naked” DNA will not do this efficiently.

• A nebuliser device that produces an aerosol of the gene transfer agent so that it can be inhaled into the lungs of the patient.

Several early attempts to use gene therapy using viral vectors to deliver the working copy of the CFTR gene to patients failed because the immune response rapidly neutralised the adenoviral vector (see this post for more information on challenges using adenoviral vectors), and while attempts to use non-viral vectors were more promising, it was found that they caused a mild inflammation in most patients, which would make then unsuitable for long term use. As reported in a paper published in 2008 the GTC members developed and assessed in mice a series of non-viral DNA vectors, repeatedly modifying them and testing their ability to both drive CFTR gene expression in the lungs and avoid inducing inflammation. They finally hit on a vector – named pGM169 – which fulfilled both key criteria.

Earlier the consortium had undertaken a study to determine which carrier molecule to use in their non-viral gene transfer agent (GTA). To do this they assessed 3 GTA’s, each consisting of a lipid like molecule that could form a sphere around the non-viral DNA vector; either the 25 kDa-branched polyethyleneimine (PEI), the cationic liposome GL67A, or as a compacted DNA nanoparticle formulated with polyethylene glycol-substituted lysine 30-mer. Because there are significant differences in airway physiology between mouse and human they carried out this study in sheep, whose lung physiology more closely matches that of humans. The study identified the cationic liposome GL67A as the most promising candidate, resulting in robust expression of the CFTR transgene in the sheep lungs.

Studies in sheep play a key role in the development of gene therapy for cystic fibrosis

Studies in sheep play a key role in the development of gene therapy for cystic fibrosis

It now remained to bring the DNA vector and carrier together. In a 2013 publication the consortium reported that repeated aerosol doses of pGM169/GL67A to sheep over a 32 week period were safe and induced expression of the CFTR transgene in the sheep lungs, although the level of expression varied between individuals (this variation was also observed in human CF patients in the clinical trial reported today). A final study, this time in mice, assessed the suitability of the Trudell AeroEclipse II nebuliser as a device to create stable pGM169/GL67A aerosols, finding that it did so in a reproducible fashion. When aerosolized to the mouse lung, the new pGM169/GL67A formulation was capable of directing persistent CFTR transgene expression for at least 2 months, with minimal inflammation. These studies provided the evidence to support the gene delivery system and dosage strategy used in the clinical trial reported today.

The trial results announced today are an important accomplishment, but they mark a beginning rather than the end for Cystic Fibrosis gene therapy. It will be necessary to improve the efficiency of the therapy before it can enter widespread clinical use. Animal research will certainly play an important part in this work, notably the observation that the efficiency of CFTR gene delivery using this strategy was varied between individuals in both sheep and humans indicates that sheep are a good model in which to assess changes to improve the consistency and effectiveness of the gene therapy.

If you would like to know more about this cystic fibrosis gene therapy clinical trial you can watch two videos recorded at a meeting for cystic fibrosis patients at ICL on the  Cystic Fibrosis Trust website.

Paul Browne

1) Alton E.W.F.W. et al. “Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial” Lancet Respiratory Medicine Published online July 3, 2015