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FENS discusses why we need to use animals in research

On July 4, 2016, at the 10th meeting of the Federation of European Neuroscience Societies (FENS), a Special Interest event took place focused on the critical need for communicating effectively to the public, to the scientific community, and to institutions about how and why researchers utilize animals in biomedical research. The lunchtime event was well-attended by conference attendees, who actively participated in engaging discussion and provided thoughtful questions throughout the session.

FENS Why do we need to use animals in researchFirst to present was Francois Lachapelle, Chair of the FENS Committee on Animals in Research (CARE), which advises FENS on the responsible use of animals in neuroscience research. Lachapelle described CARE’s activities and goals to the attendees, which include supporting members and partners in emergency situations (such as attacks from animal rights activists), publishing statements on issues regarding critical situations in animal research (including the continued need for primates), and to develop a culture of proactive communication about animal research. CARE accomplishes this last goal through various videos, media statements, and public lectures and events. Lachapelle highlighted CARE’s active involvement in drafting a statement to the European Parliament in response to the European Citizens’ Initiative (ECI) “Stop Vivisection” movement in 2015.

Juan Lerma, Secretary General of FENS and ex-Director of the Instiuto de Neurosciencias CSIC-UMH in Spain, followed with a discussion of “Actions in Spain Supporting Animal Research.” Lerma promoted a message of transparency to improve the public’s awareness of the importance of animals in research, including providing resources in cities’ and countries’ local languages. Lerma discussed various tactics, from Spain’s active campaign against “Stop Vivisection” via the Confederacion de Sociedades Cientificas de Espana’s (COSCE) outreach efforts, to welcoming opportunities to engage with journalists and even children to teach about the value of animals in research.  Activities like Brain Awareness Week, highlighting an organization’s AAALAC accreditation, and organizing tours all go a long way to promoting openness and transparency. “We are proud of conducting animal research,” Lerma said. “Now it is time for transparency.”

An interesting Q & A followed Lerma’s presentation when a member of the audience asked how one can best convey that, while animal research is beneficial, it does not come without risk – in other words, that it sometimes fails? Lerma answered by stating that people with family members that have a particular disease will understand, and that it is important to also share the successes. Ultimately, Lerma acknowledged that it is more difficult to advocate for animal research without a translational component and that scientists and institutions must convince the public that it is useful. Kirk Leech, Executive Director of the European Animal Research Association (EARA), responded that an intellectual and moral argument for basic research for the sake of science itself is necessary. The conversation was also continued on Twitter:

This stimulating debate was a good segue way into the next speaker, Dario Padovan. Padovan is President of Pro-TEST Italia, a non-profit that “aims to promote and disseminate to the public correct knowledge on scientific research.”  His presentation was less about communicating with the public about animal research and more about avoiding and preventing a crisis in the first place. After demonstrating the myriad ways in which scientists can and have been secretly video recorded by animal rights groups, Padovan continued with security tips to scientists such as restricting animal areas, having a no-cell-phone policy, having visitors wear hazmat suits (presumably to cover hidden camera lenses), and to beware creative editing by animal rights groups. Not only was this advice perceived by many to be in stark contrast to Lerma’s preceding presentation about openness in animal research, but also contrasted his presentation at the Society for Neuroscience’s 2015 meeting just 8 months prior when Padovan gave an inspiring presentation on how Pro-TEST Italia increased positive public perception of animal research in Italy. Padovan did end his talk with a few slides that held key guidelines for openness in animal research, which led nicely into the closing presentation, again by Lachapelle, who discussed general rules for talking with the public about animals in research. Of particular importance is the need for scientist to be proactive (rather than defensive) in their communications, to show their passion to the cause of science, and to emphasize the regulations in place that ensure animal welfare and ethical research.

Speaking of Research promotes openness whilst also respecting the importance of a safe working environment. Each institution must develop individualized strategies to accomplish this intersection within their unique environments. A recent successful example was the first national Biomedical Research Awareness Day, which multiple universities participated in this past May.

In all, the event by FENS served to energize scientists – particularly those in the “next generation” (i.e., trainees and young investigators) to be openly passionate and communicative about the important work they do to both save lives and to promote the study of science.

Amanda Dettmer

Animal Research in Israel – 2015 Statistics Released

You may have noticed that Speaking of Research has expanded its list of national animal research statistics to around 30 countries. We would like to thank the RSPCA’s Lab Animal team for supplying us with some of our more recent EU additions. However, our most recent addition is the 2015 statistics for Israel, which showed that the number of animals used in research had declined by 1.6% to 334,767 animals. These numbers can be found on the Israeli Ministry of Health website.

Testing on Animals in Israel for research in 2015. Click to Enlarge

Testing on Animals in Israel for research in 2015. Click to Enlarge

The number of most species declined, except for the use of mice, rabbits and primates. The main fall (49%) was in “Other Animals”, which includes fish, amphibians and reptiles. A 20% fall in the number of rats used, down to under 40,000, also contributed to the overall slight fall in numbers of animals used in research.

Animals used in research in Israel in 2015. Click to Enlarge

Animals used in research in Israel in 2015. Click to Enlarge

Mice are far and away the most commonly used animal in research in Israel (at 76%). Rats, Mice and Birds accounted for around 95% of animals used in research. The 42 primates used accounted for 0.01% of research animals in 2015. Research on animals, particularly primates, has been under pressure in Israel for the past few years. This led to seven Nobel Prize Laureates and the presidents of seven major research universities writing to the Prime Minister, and warning him of the risks to Israeli research posed by the animal rights community there.

Trends in Israeli animal experiments 2004-15. Click to Enlarge.

Trends in Israeli animal experiments 2004-15. Click to Enlarge.

Historical statistics show that the number of animals used each year has been fairly constant over the past 11 years – fluctuating between around 275,000 and 340,000. The slight variations may account for individual projects which used a lot of animals, or from slight changes in science funding over the years.

According to  YNetNews:

45.2% of the experiments were related to advance health and medicine and to prevent suffering. 44.3% were to promote scientific research. 9% were for testing or manufacturing materials or objects, and 1.5% were for education and teaching

The article also provided information on animal suffering, similar to what is included in standard European statistics.

The research procedures were categorized according to a five-level scale determined by the NCAE, which considers the animals’ suffering. According to this scale, 9% of the studies were at the lowest level, 19% were at the second, 30% at the third, 29% at the fourth, and 13% were at the highest level.

We will be keeping an eye on future statistics.

Speaking of Research

Original Data: http://www.health.gov.il/Services/Committee/animax/Documents/multiyearUse_2015.pdf 

Experimental Design Assistant: Improving the Scientific Method

Studies involving animals are a crucial component of medical research, and without them our understanding of disease and suffering would be decades behind where we are now. However, scientists must always reflect on their work and ensure that animal studies are carried out with the best design, compassion and rigour possible, so animals are not involved in experiments needlessly.

Just as our understanding of science has improved over the years, so has our understanding of scientific methods. In an effort to increase the quality and effectiveness of animal research, the NC3Rs – a UK organisation devoted to promoting the Replacement, Refinement and Reduction of animals in research – created the ARRIVE guidelines in 2010. These guidelines provided researchers with a set of rules on how to report animal experiments, ensuring that animals were used effectively and humanely. So far over 600 journals have signed up to the ARRIVE guidelines. Although there are no quantitative analyses of the effectiveness of the ARRIVE guidelines, they have undoubtedly provided an important framework for animal studies that previously didn’t exist, and have made it harder for poor science to go unnoticed.

Following the success of the ARRIVE guidelines, the NC3Rs has continued its efforts to reduce, refine and replace the use of animals in research. Recently, the organisation has released an innovative new piece of software, the Experimental Design Assistant (EDA).

Experimental Design Assistant - EDAThe EDA allows scientists to plan out their experiments thoroughly and visually, mapping out every aspect of the study from the earliest hypothesis to the last statistical analysis. While the user is completing their experimental plan, the EDA will analyse the study and provide feedback. The feedback includes whether the number of animals involved could be reduced, whether experimental groups are correctly distributed, whether statistical analysis is appropriate, and much more. Already the EDA has over 400 registered users. Overall, the EDA will refine animal studies and could potentially reduce the numbers of animals used in research while simultaneously improving the quality of science that results from animal studies.

An example of a typical experiment designed with the help of the EDA

An example of a typical experiment designed with the help of the EDA. Click to Enlarge

Not only does the EDA aim to improve the quality and effectiveness of animal research, it also aims to increase transparency. The EDA could one day allow funding bodies and independent regulators to observe experiments being designed in real-time. Additionally, experimental designs could, perhaps, be made available to the public, alongside the brief descriptions of each research project that are currently in the public domain. This sort of transparency can help to build trust in scientists and animal research.

University of Manchester researcher Briony Labram is a scientist whose work will benefit from the EDA. Here she talks about how this software is important, especially for animal researchers:

I’m investigating how the Aspergillus fumigatus fungus is involved in severe cases of asthma.

My project started using epithelial cell culture, where we exposed these cells to Aspergillus fumigatus spores. This gave us a lot of interesting results but also raised more research questions.  Many of these questions could not be answered using the simple cell culture model. In order to study a chronic condition such as asthma and ask more complex research questions, longer study durations are necessary. Therefore the only way to answer these questions was to use an animal model.

Researchers should be especially diligent when planning studies involving animals, to ensure the maximum gain in terms of meaningful data while using as few animals as possible. The EDA will ensure the numbers of animals used in an experiment is kept to a minimum while still obtaining reliable and reproducible data.

Briony Labram - University of ManchesterBriony is typical of many animal researchers; she is aware of the importance of reducing and refining the use of animals in her studies. By using the EDA, Briony knows her experiments can be improved while minimising the number of animals involved in her study.

The EDA is clearly an important tool for researchers, but is not without limitations. In its current, early stage, the EDA relies heavily on randomisation, paying less attention to counter-balancing (controlling for the order in which treatments are given), and other crucial aspects of thorough experimental design. In a similar vein, the EDA focuses more on reducing the number of animals used, when just as much effort should go into refining the studies in question. Refining the use of animals involved in research will undoubtedly increase the scientific value of such studies, and this should be a focal point of research tools like the EDA.

It is also important for scientists to retain some autonomy in the process of experimental design, and not rely entirely on software to design studies for them. Scientists using the EDA still need to understand their study in sufficient depth for the EDA’s statistical analysis to be effective. Ideally the EDA will be used as a companion to scientific rigour, rather than its replacement.

Research isn’t perfect, and it probably never will be as long as scientists are imperfect. But tools like the EDA will help to ensure that animals involved in research are kept close to a minimum, and that the medical and scientific value we obtain from them will continue to change lives for the better.

Anyone can access the EDA. Follow the simple registration process here to begin designing your experiments.

Patrick

Austria publishes 2015 statistics on animal research

Austria has published its statistics that show the number of animals used for research and testing in 2015. Austria carried out 227,317 procedures on animals in 2015, 8.7% more than in 2014.

Procedures on animals in the Austria for research in 2015. Click to Enlarge

The rise in the number of experiments is mainly due to a 7.1% rise in mice. There was a significant rise in the number of rabbits (+95%) and other rodents (+58%) used. There were also small rises in dogs (up 68% to 111 procedures) and cats (up 5 procedures to 34).

Animal Experiments in Austria in 2015. Click to Enlarge

Animal Experiments in Austria in 2015. Click to Enlarge

Mice continue to be the most commonly used species at 82%. Mice, rats and fish account for 89% of all animal procedures, rising to 96% if you include rabbits. It is interesting that Austria, rabbits are the second most common species, a fact not seen anywhere else in Europe, though neighbouring Germany also has a relatively high number (3.8% of total). The statistics show that most of these rabbits (93%) were involved in pyrogenicity studies (looking at fever response). No primates were used in Austria in 2015 (or 2014) and dogs and cats accounted for less than 0.07% of all animals used despite the rises in number of procedures for these species.

Animals used in research in Austria in 2015. Click to Enlarge

Animals used in research in Austria in 2015. Click to Enlarge

This year was the second year where there was retrospective assessment and reporting of severity (i.e. reporting how much an animal actually suffered rather than how much it was predicted to suffer prior to the study). Reassuringly the proportions in each severity banding was similar to 2014, suggesting the system has been well understood. The report showed that 60% of procedures were classed as mild, 24% as moderate, 12% as severe, and 4% as non-recovery, where an animal is anaesthetised for surgery, and then not woken up afterwards.

From historical statistics we can see that while there has been an overall decline of almost 50% since 1990, the numbers have been edging upwards since their nadir in 1999. These numbers tend to reflect changing science funding environments within the country.

Trends in Austrian animal experiments 1990-15. Click to Enlarge.

Trends in Austrian animal experiments 1990-15. Click to Enlarge.

Some animal rights groups have criticised the rise in numbers, noting that it is the highest number since 1994. This is cherry picking – the numbers have been relatively stable since 1994, and are far lower than the 450,000+ animals being used in 1990 and 1991.

Austria is one of the first countries to publish its 2015 annual statistics, and we will be looking out for the statistics of other European countries. See our summary of statistics to compare countries.

Italy finally publishes 2013 statistics

While we will be posting Austria’s 2015 statistics on Monday, Italian authorities seem a little bit behind the times having only recently published their 2013 statistics for the use of animals in research. Italy carried out 723,739 procedures on animals in 2013, 5.9% less than in 2012.

Procedures on animals in the Italy for research in 2013. Click to Enlarge

The fall in the number of experiments is mainly due to a large (30%) fall in the number of fish, and a moderate drop in rats (9%) and mice (3.5%). There was also a small fall in dogs (down 45% to 300 procedures) and a rise in the number of primates experiments (up 41% to 475).

Animal Experiments in Italy in 2013. Click to Enlarge

Animal Experiments in Italy in 2013. Click to Enlarge

Rodents accounted for over 90% of all animals used in Italy in 2013 (mainly mice at 67.5% of the total). This rises to almost 98% when you include fish and birds. Primates and dogs together accounted for 0.1% of all research animals. No cats were used in 2013 (0r 2012).

Click to Enlarge

Click to Enlarge

Italy’s 2013 statistics do not include measures of animal suffering – though this should come into the 2014 statistics (which most European countries have already published). What we can see (Table 2) is that most of the animal use (54%) was  basic research, followed by applied human studies (17%) and safety testing of human medicine and dentistry products (14%).

From historical statistics we can see a steady decline of over 25% since 2007. These numbers tend to reflect changing science funding environments within the country.

Trends in Italian animal experiments 2007-13. Click to Enlarge.

Trends in Italian animal experiments 2007-13. Click to Enlarge.

On Monday we should be publishing our 2015 Austrian statistics, and we will publish other country data as we get it. See our summary of statistics to compare countries, and please send us any data you find that we are lacking.

Santa Cruz Biotechnology and the USDA

Speaking of Research have been troubled by the events which have unfolded at Santa Cruz Biotechnology (SCBT), including (but not limited to) the recent actions taken against the organization by the USDA. As an organization that strongly supports and advocates for the humane and responsible treatment of laboratory animals, Speaking of Research is critical of any organisation that does not meet its obligation to ensure the welfare of its animals, as well as any efforts to subvert the regulatory process. If the allegations against SCBT are true, their conduct is reprehensible. SR has written about these allegations in the past in the article’s “Santa Cruz Biotechnology: Dealing with Bad Behaviour” and “Caveat Emptor“. The following article is reprinted, with permission, from the American Physiology Society (images are not from the original article).

On May 19, 2016, antibody producer Santa Cruz Biotechnology (SCBT), Inc. reached an agreement with the USDA to resolve allegations of numerous Animal Welfare Act (AWA) violations. Under the terms of this agreement, SCBT neither admitted nor denied wrongdoing. Nevertheless, the company agreed that by May 31, 2016 it would pay a record $3.5 million fine. SCBT also agreed that as of May 31, 2016, it would cease antibody production involving USDA-regulated species and relinquish its registration as a research facility. SCBT also agreed to allow USDA to revoke its license as a dealer as of December 31, 2016, after which it can no longer sell antibodies made from USDA-regulated species.

Photo credit: Dan Coyro -- Santa Cruz Sentinel

Photo credit: Dan Coyro — Santa Cruz Sentinel

USDA filed three formal complaints against SCBT between July 12, 2012 and August 7, 2015 based upon the observations of inspectors from the agency’s Animal and Plant Health Inspection Service (APHIS) during multiple unannounced visits. The USDA complaints alleged that the company repeatedly violated the AWA in its treatment of goats used for antibody production. (For more about the USDA’s case against SCBT, see Caveat Emptor.) The complaints included allegations that SCBT failed to provide appropriate veterinary care to sick and injured animals; that its staff handled animals improperly; and that the company’s institutional animal care and use committee failed to ensure that animals were housed under appropriate conditions and that the animals’ pain and distress were minimized during antibody production. In its third complaint dated August 7, 2015, USDA also alleged that SCBT “demonstrated bad faith by misleading APHIS personnel about the existence of an undisclosed location where respondent housed regulated animals.” This “undisclosed location” was a barn where some 841 goats—including sick ones—were housed.

Top antibody suppliers in the US in 2012. Image from The Scientist

Top antibody suppliers in the US in 2012. Image from The Scientist

SCBT initially contested the USDA’s allegations and sought a hearing before an administrative law judge. After several delays, a hearing where both sides could present evidence case took place August 18–20, 2015 before Administrative Law Judge Janice Bullard. The hearing was suspended on the morning of August 21 with no explanation given. It was later scheduled to resume on April 5, 2016 and then postponed again until August 15, 2016.

The settlement agreement gives SCBT until the end of 2016—when its license will be revoked—to sell antibodies made from blood and serum it collected from regulated animals prior to August 21, 2015. However, SCBT had to stop producing antibodies from this blood and serum by May 31, 2016 when it agreed to cancel its registration as a research facility. Since the AWA does not regulate rodents bred for research, SCBT can continue to sell antibodies produced in mice.

Antibodies play an important role in both clinical medicine and research because they react to the presence of specific proteins. Antibody production starts by injecting an animal with a protein. This activates the immune system, which generates antibodies to identify the invading protein. Some types of antibodies are purified directly from blood collected from animals injected with a protein. Other types can be produced in a laboratory with cell lines created by fusing an initial batch of purified antibodies to harmless cancer cells. Antibodies target either one region of a protein (monoclonal antibodies) or several regions (polyclonal antibodies).

Why did the SCBT case take almost four years to settle? From a legal perspective, APHIS inspections findings represent allegations of AWA violations, and our system guarantees due process: Those accused of violating the law are entitled to their day in court. Kudos should go to USDA for its persistence in marshaling sufficient evidence to convince SCBT to agree to this settlement.

American Physiological Society

Novo Nordisk demonstrate what good openness looks like

Openness has been a buzz word in science policy over the past five years, particularly for animal research. Today, Speaking of Research reached 250 animal research statements on our list of public statements, up from 200 in February (is your institution included?). Much of our focus has been on universities, particularly in the UK and US. In the past we have showcased examples of good openness including the University of Edinburgh, University of Cambridge, Imperial College London and Primate Products Inc.

Today we will focus on a Danish pharmaceutical company – Novo Nordisk – and their excellent efforts at greater openness and transparency around their animal research.

Novonordisk provide a whole section of their website on Animal Ethics. This starts out with a clear statement about the ongoing need for animals to test new pharmaceutical and medical products.

At present, some research using living animals is essential for all pharmaceutical companies in the discovery, development and production of new pharmaceutical and medical products.
[…]
We only use animals in research where no alternative exists. We recognise that not all research using animals can be replaced in the foreseeable future and consider it our responsibility to actively support the principles of the 3Rs.

This front page also talks about the “Responsible use of animals” including the 3Rs, efforts to replace animal tests and the importance of animal welfare. They include a video on the front page, which shows their facilities.

Novo Nordisk website providing videos of its research animals and facilities

Novo Nordisk website providing videos of its research animals and facilities

There’s dedicated subpages on Housing, Ethical Review, their 3Rs Award, Welfare  and External Contractors. They also have a page with nine different videos showing the animal enclosures. This is among the best sets of videos provided by an animal research institution showing its animals.

There is also a page which outlines the number of each species of animal used at Novo Nordisk over the past three years. In 2015, Novo Nordisk used 67,240 animals, of which almost 97% were mice or rats.

Finally, Novo Nordisk have produced a fantastic 24-page brochure titled “Animals in Pharmaceutical Research: A responsible approach” which explains more about their research, with a particular focus towards their 3Rs efforts.  The brochure provides plenty of pictures and information, as well as the principles of animal use which underpin their animal research work. Explaining why animal research is necessary to their work:

Before new pharmaceutical products can be studied in people, they need to be investigated in animals for efficacy, safety and toxicology, as it is not yet possible to examine the complex interactions in a living organism solely by the use of cell cultures and tissues.

Animals are only used in research and development at Novo Nordisk when no alternative exists. The use of animals in the early phases of the company’s drug discovery and development has been reduced by applying tissue cultures, cell-based and other non-animal models.

Click to Enlarge

Click to go to the brochure

Overall, the information provided by Novo Nordisk is fantastic – above and beyond any other pharmaceutical company’s online offering we have seen to date. If there was one possible area for improvement, it would be the provision of some case studies to explain a few examples of exactly how and why animals are used. This would also give them full marks on our animal research statement ratings.

So all that’s left to say is to congratulate Novo Nordisk for its fantastic web resources. Speaking of Research will continue to celebrate good examples of openness and public outreach wherever we can find it.

Has your institution got a statement or set or web pages explaining its animal research for the public? Is it on our list (if not, tell us)? Could it be improved? Speaking of Research has written about what makes a good public-facing webpage on an institution’s animal research.

Speaking of Research

Montage of images from the Novo Nordisk brochure on its animal research. Click to Enlarge

Montage of images from the Novo Nordisk brochure on its animal research. Click to Enlarge