Animal testing:

2015 annual report

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Animal testing: 2015 annual report

The University of Groningen and the UMCG conduct animal experiments. In 2015, 26,086 animal experiments were conducted, of which 47% at the Faculty of Mathematics and Natural Sciences and 53% at the UMCG. Mice were the most commonly used laboratory animal (13,035), followed by rats (4280) and birds (6671, excluding chickens and quails).

The University and the UMCG want their fundamental and applied research programmes to compete with the best in the world. Healthy Ageing and a Sustainable Society are policy spearheads of the University of Groningen and the UMCG with the aim of facilitating a healthy society and a population that can continue to participate actively into old age. Many of our research programmes focus on themes such as Alzheimer’s disease, diabetes and Parkinson’s disease, and sometimes this research requires animal testing. Experiments involving animals are also required to solve ecological puzzles, such as the migratory behaviour of birds.

Animal testing at the University and the UMCG is organized so as to ensure optimum animal welfare. The University of Groningen has an impartial Animal Experiments Committee (DEC) that advises the national Central Animal Experiments Committee (CCD) on project applications submitted by both the University and the UMCG. The DEC assesses new research proposals against the existing legislation and regulations. It also weighs the benefits of an animal experiment against the suffering caused to the laboratory animals. The IvD then supports the researchers in the planning and execution of the animal experiment. Laboratory animal experts monitor the welfare of the animals, ascertain that the staff are complying with the legislation and regulations and provide education and training.

The University and the UMCG apply the 3R principle to research and teaching involving laboratory animals: Replacement and Reduction of laboratory animals and Refinement of the animal experiments. In concrete terms, this entails using as few laboratory animals as possible and causing as little suffering as possible to those animals that we do use. The University and the UMCG wish to reduce the number of surplus animals. To this end we are developing the technique of cryopreservation of breeding lines and we use surplus animals wherever possible for teaching and training.

Download 2015 annual repportClose summary

The University of Groningen and the University Medical Center Groningen (UMCG) conduct tests on animals for research and educational purposes, because some important and relevant questions cannot be answered without the use of laboratory animals.

We have a transparent animal testing policy and we openly describe how our animal experiments are carried out and how we justify these on our website. We want to contribute to the public debate on animal testing so that everyone will be able to form a well-considered opinion on this subject.

Animal research legislation: the revised law

The protection of laboratory animal welfare is effectively organized in Dutch law. The Animal Experiments Act came into effect in 1977. The Act imposes strict requirements on animal experiments based on the ‘No, unless’ principle: animal experiments are only allowed if there are no alternatives. There has been a strong reduction in the number of animal experiments since the introduction of this Act. The original Animal Experiments Act was revised on 18 December 2014. The revised act has consequences for the way animal experiments are organized and assessed and upholds the requirement that animal experiments may only be conducted if there are no other options.

Why has the Animal Experiments Act been revised?

There were major differences between the animal research regulations of the various members of the European Union. Not all member states maintained the same, high standards applied in countries like the Netherlands. The European Commission drafted a directive to rectify this situation. All member states are required to harmonize their existing animal research legislation with this directive. The Netherlands has accordingly revised the Animal Experiments Act to this end.

What has changed in practice?

The revised Act entails a number of organizational changes. ‘There is a stronger distinction between implementation and assessment in the new situation,’ explains the head of the Central Animal Facility (CDP), Flip Klatter. Under the old legislation, an Animal Experiments Committee (DEC) assessed the animal research licenses for the organization. In the revised Act, only a national body, the Central Animal Experiments Committee (CCD), may assess these licenses. The local DEC does retain an advisory role. Both the DEC and the CCD assess the ethical aspects of the license applications. All institutions are required to establish an Animal Welfare Committee (IvD) to ensure that experiments are carried out correctly. The IvD will be peopled by experts who will cooperate with the researcher to ensure that the animal experiment is conducted with the least possible suffering for the animal. Alongside the organizational changes, the definition of an animal experiment has also been changed.

2015: transition year

‘Although the revised Animal Experiments Act only came into force in late 2015, the University of Groningen and the UMCG implemented much of the new legislation earlier,’ explains laboratory animal expert Catriene Thuring. For example, the IvDs were established in 2013 in anticipation of the legislation. But Flip Klatter says that 2015 is still a real transition year. ‘The license applications and the way they are assessed is changing and we all need to get used to the new system. In 2016 we will find out what effects these changes will have in practice. I believe the procedures will be more efficient and possibly also faster than with the old legislation.’

Animal testing in figures

In 2015 the University of Groningen and the UMCG performed 20,932 animal experiments, an decrease of 5,154 experiments in relation to 2014. The number of animal experiments fluctuates annually based on the available budgets and research capacity. The most used animals were mice, rats and birds. In these figures, an animal experiment is the sum of the procedures conducted on a single animal. An animal experiment is only included in this overview after it has been completed.

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  • 11644
  • 3932
  • 122
  • 157
  • 498
  • 00
  • 00
  • 00
  • 00
  • 00
  • 00
  • 00
  • 104
  • 00
  • 4377
  • 00
  • 98
  • 00
Total:
  • 13035
  • 4280
  • 84
  • 209
  • 907
  • 3
  • 00
  • 10
  • 00
  • 00
  • 2
  • 00
  • 18
  • 00
  • 6671
  • 00
  • 865
  • 2
Total:
  • 11894
  • 5264
  • 42
  • 119
  • 49
  • 8
  • 00
  • 00
  • 00
  • 00
  • 3
  • 00
  • 84
  • 00
  • 5387
  • 00
  • 951
  • 00
Total:
  • 13211
  • 8475
  • 70
  • 204
  • 223
  • 7
  • 00
  • 00
  • 00
  • 16
  • 2
  • 00
  • 190
  • 00
  • 6401
  • 00
  • 1733
  • 00
Total:
mouse-now

Why do we use animals in experiments?

Healthy ageing and a sustainable society are policy spearheads of the University of Groningen and the UMCG. Many of our research programmes focus on themes such as Alzheimer’s disease, diabetes and Parkinson’s disease, and sometimes this research requires animal testing. But experiments involving animals are also required to solve ecological puzzles, such as the migratory behaviour of birds.

The University of Groningen and the UMCG want their fundamental and applied research programmes to compete with the best in the world. Where these programmes require animal testing, we want this to be done as ethically and effectively as possible: this entails providing maximum care for and guarantees of the welfare of the laboratory animals and optimum facilities for the animal experimenters.

Of the animal experiments we conduct, 61% are conducted at the UMCG and 39% at the University’s Faculty of Mathematics and Natural Sciences (FMNS). These organizations accommodate a number of research institutes where most of the animal experiments are carried out:

 

  • Behavioural and Cognitive Neurosciences (CBN/BCN-BRAIN)

Fundamental and applied research on the functioning of the brain, central nervous system abnormalities in patients with neurological and psychological disorders, and the mechanisms that determine behaviour.

  • Centre for Ecological and Evolutionary Studies (CEES)

Fundamental research on areas including animal behaviour and ecophysiology.

  • Groningen Research Institute of Pharmacy (GRIP)

Fundamental and applied research on drugs.

  • Groningen University Institute for Drug Exploration (GUIDE)

Lead development and the development of new drugs.

  • Health Research and Epidemiology (SHARE)

Fundamental and applied research into the factors that enable healthy ageing.

  • European Research Insitute for the biology of ageing (ERIBA)

Fundamental research on the factors that cause ageing.

  • Biomaterials (W.J.Kolff Institute)

Applied research on biomaterials and implants.

  • Fundamental, Clinical and Translational Cancer Research (Cancer Research Center Groningen)

Fundamental and applied research on oncology and tumour development.

The research examples in this annual report are illustrative of the research conducted at the University of Groningen and the UMCG. The University website contains an overview of the departments where animal experiments are conducted.

The University and the UMCG confer with various stakeholders to discuss the theme of animal testing. For example, they are participating in the working group on Transparency and Accountability together with Stichting Proefdiervrij (an anti-animal testing lobby), Wageningen University and Research Centre, Radboud University Medical Center, Utrecht University and University Medical Center Utrecht. This working group aims to establish a transparent and uniform annual reporting system. University animal testing experts and the head of CDP are also participating in talks at the Ministry of Economic Affairs, which is responsible for the animal testing portfolio, on the introduction of the new Experiments on Animals Act (WOD).

    Prof. Rob Coppes, Radiotherapy

    Growing salivary glands from stem cells

    ‘After radiotherapy, many patients suffer from damaged salivary glands, resulting in a dry mouth. This may sound like a harmless side effect, but in fact it is not. These patients are more subject to tooth decay, they have difficulty speaking and swallowing and their sense of taste is impaired. I am studying how tissues react to radiation and how radiation damage can be limited. We are also growing salivary glands from stem cells in our laboratory.’

    ‘Salivary glands are sensitive to radiation. Many patients who have had radiotherapy in the head and neck region suffer from damaged salivary glands. They suffer from a dry mouth, a side effect with a major impact on their quality of life. Saliva has an important protective function. A lack of saliva leads to more mouth infections, tooth decay and speech and swallowing problems. Food is not mixed properly in the mouth, which inhibits the ability to taste. Patients with this problem will avoid social situations where food is involved.

    Other tissues are also extremely sensitive to radiation. For example, lung tissue is an ultra-thin membrane made up of a single layer of cells. Even a small dose of radiation will destroy this tissue, resulting in lung infection and the development of scar tissue, while the tumour itself remains unaffected. Research on how tissues react to radiation can help limit the damage and improve the treatment. Such research and improved radiation techniques have led to many improvements in recent decades. For example, radiation is now applied to the head from all sides, so that salivary glands are exposed to a lower dose and are more likely to retain their function. But still, forty per cent of patients suffer complaints due to damaged salivary glands.

    Much of my current research focusses on a promising technique: stem cell therapy. Stem cells can develop into any type of tissue cell and the idea is to use them to grow small organs, known as organoids. In the ideal scenario, the patient will give stem cells from the salivary gland before radiotherapy and these will be multiplied as organoids in vitro. After radiotherapy the new stem cells produced from the patient’s own tissue will be transplanted.

    However, it is not easy to make stem cells form a particular type of tissue. Their growth depends on the environment, the substances in the growth medium and many other factors. We researchers are working hard to develop this technique further. In our laboratory, we are currently growing salivary glands of about 1mm in size from stem cells.

    We are using mice to test whether the stem cells we grow still function after transplantation. We first tested this from mouse to mouse and we are now testing a human to mouse transplantation (i.e. we have introduced human salivary gland cells into a mouse). The next step is to inject salivary gland stem cells into people.

    The mouse is a suitable model for research like this because most organisms suffer similar effects from radiation damage to DNA. Because the mouse is the most-used laboratory animal for such experiments, this also makes it easier to share knowledge on this research. In time, the production of stem cells and organoids in the laboratory will probably result in a reduction in the number of laboratory animals needed. Thanks to all the knowledge we are currently gaining on organoids, in the future it is likely that we will be able to carry out much more of our research on organs grown from stem cells and so we will require fewer laboratory animals.’

    Dr Floris Foijer, group leader Genomic instability

    Researching genetic instability in cancer cells

    A lot of cancer cells have more or fewer chromosomes than normal cells. In healthy cells, abnormal numbers of chromosomes result in a slowdown in growth or the death of the cell. The result in cancer cells, however, is exactly the opposite: it speeds up the growth of the tumour. I want to find out exactly what goes wrong at that point, and am trying to identify the specific genes that trigger the process. This fundamental knowledge about tumour growth is ultimately needed to develop new drugs and to improve and refine existing therapies.

    ‘DNA, neatly rolled up in chromosomes, is present in every cell in our body. A normal cell contains forty-six pairs of chromosomes. But if something goes wrong during cell division, cells can develop with too many or too few chromosomes. This is called aneuploidy. My group is studying this abnormal amount of DNA in cells. It is essential that we understand aneuploidy, as it plays an important role in many forms of cancer.

    Two-thirds of cancers are aneuploid, which is in itself a remarkable statistic. Aneuploidy harms normal cells, causing them to grow more slowly or stop growing altogether. But for some reason, cancer cells are able to turn this abnormality into an advantage and their growth rate increases rapidly. To find out how cancer cells do this, and what the precise effect of chromosome numbers is, we are reproducing aneuploidy in mice. We activate and deactivate random genes to find out which combinations of genes and aneuploidy develop into cancerous cells.

    Our search has identified many of the genes that are needed to turn an aneuploid cell into a cancer cell. Some of them were already known to be important factors in tumour growth, but we have also discovered new genes. These genes may prove to be suitable, specific leads for devising therapies to combat cancer: aneuploidy is, after all, most common in tumours. The present generation of drugs not only targets cancer cells, but also healthy cells, which is why patients suffer such serious adverse effects.

    We also made a striking discovery when we implanted tissue from human tumours into mice. The chromosome composition of the tumours appeared to change continuously under the influence of its surroundings. This would seem to indicate that tumours are very flexible, despite our previous assumption that tumour cells do not change once they have transformed into cancer cells. Laboratory findings like this have a direct impact on our efforts to improve and refine existing clinical therapies. This particular discovery also means that this kind of rearrangement of genetic material can also take place in patients under the pressure of treatment. In other words, the genetics of tumours can change during treatment. This is something that doctors should take into account when treating patients.

    I am currently writing a new, proposal for a major research project using mouse models. I want to find out how and why aneuploidy develops. We know that something goes wrong during cell division, but we do not know exactly what. So we want to reproduce the process in mice. Since the revised Experiments on Animals Act came into effect, applying for a project has become a lengthy business, which can take several years. This makes things more difficult and forces you to think very carefully. On the other hand, I am pleased that a major application like this is dealt with in a practice-based process with the Animal Experiments Body (IvD). We are not simply issued with unilateral policy, but we work together towards a joint goal: to find the best way to organize the research so that the animals suffer as little as possible.’

    Prof. Simon Verhulst, Behavioural Biology

    Research on ageing mechanisms in jackdaws

    ‘Why does one jackdaw fledgling leave the nest in good health while the other does not? What is the influence of nesting conditions on their chances of survival? And how does this influence their life expectancy? What is it that determines whether a jackdaw will live a long or a short life? I am trying to answer these questions by manipulating jackdaw brood sizes. This research reveals how the ageing process in jackdaws works and at the same time it is a useful model for studying ageing mechanisms in humans.’

    ‘We have been studying the survival rates and ageing processes of wild jackdaws in the Groningen region since 1996. Jackdaws live in colonies and brood in nest boxes, which makes it easier to study these birds. We manipulate the brood size in order to improve or worsen the conditions for the young. We make half of the broods a bit larger and half a bit smaller, resulting in two populations that are easy to compare.

    Brood size proves to have a major impact on cellular aging. Jackdaws that raise many chicks age three times faster than jackdaws with small broods. The chicks from the enlarged nests also did less well than their fellow chicks from smaller broods. We can follow the development of the fledglings by taking blood samples. This is a relatively minor intervention: birds have veins just below the skin under their wings, so a pin prick is sufficient to collect the required drops of blood.

    We measure the length of the telomeres in the blood. Telomeres are protective caps on the ends of chromosomes, rather like the caps on the ends of shoelaces. Chromosomes become slightly shorter after every cell division because the ends fray and this process is accelerated in stressful situations. The length of these telomeres proves to be a predictor of life expectancy.

    We have discovered that the telomeres of jackdaw chicks from large broods become shorter faster than those of jackdaw young in smaller broods. They age faster and so their chances of survival are smaller too. But why do these telomeres get shorter? What factors are behind this? We don’t know yet. Nor do we know what the consequences of the shorter telomeres are in the long term. Does it also have a detrimental effect on their young? These are all questions we hope to answer in the next few years.

    As a behavioural biologist, these answers can help me to understand more about maturing and ageing processes in birds. The research is also beneficial to studies of human ageing, because the fundamental mechanisms mostly work in the same way. For example, short telomeres also result in a shorter life expectancy in humans. Due to the long life span of humans and the limitations in the types of experiments that are possible, research on humans is always restricted and descriptive rather than quantitative. In relative terms, the process of telomere shortening is more than one hundred times faster in jackdaws than in humans. This means that you can test hypotheses on basic ageing mechanisms in jackdaws in a relatively short period of time.’

    Prof. Geny Groothuis, Drug Metabolism and Toxicology

    The search for alternatives to animal testing in pharmaceutical research

    ‘Much pharmaceutical research is performed using laboratory animals, but it is becoming increasingly clear that there are important differences in the way drugs work in animals and people. My research focuses on finding ways to test drugs without the need for laboratory animals. Non-animal research has two important advantages: it means less animal testing while at the same time it helps us to improve our predictions of the efficacy and toxicity of drugs.’

    ‘An important step in the development of a new drug is the toxicological research: is the drug poisonous and are there any side effects? Some of this research is performed on laboratory animals; however, the animal testing model is far from ideal because drugs often work differently on animals than on people. Pharmaceutical companies regularly have to remove a drug from the market that passed all the experiments and tests on animals because it proves to have unexpected side effects on humans. Vice versa, some drugs are bound to be kept from the market because they failed the animal experiments, while they may actually be effective on humans, which is of course extremely unfortunate.

    Alternative methods that work with human data, and hence have a greater predictive value, are desperately needed. For example, in our lab we are developing techniques for testing drugs on ultra-thin slices of liver obtained from humans. These pieces of liver are leftovers from surgery and we keep the cells alive for our research. This is hard work: material like this is an unexpected by-product of surgery or it becomes available at unexpected times, which means in our lab we have to keep abnormal working hours.

    The material we obtain in this manner contains a wealth of information, because the liver is an important organ for toxicological research due to the fact that it is where various substances are metabolized. The by-products can be harmful, the best known example of which is probably paracetamol. The liver can metabolize harmless paracetamol into a toxic by-product that can actually be fatal. Various metabolic processes also take place in the intestine and the kidney, which is why we are also trying to culture thin slices of these organs.

    The beauty of these techniques is that they allow us to accurately and realistically predict what drugs will do in a human body. Using tissue cultures and computer programs we can also make more realistic calculations of the effects of varying doses than with animal experiments. A factor that has both advantages and disadvantages is that we use liver cultures obtained from various people. This means that human variability is automatically built in to our results, while the variation between laboratory rats is much smaller. However, this variation also makes it more difficult to publish conclusive results and increase support for this alternative technique.

    But getting rules changed is a very slow process anyway. Animal experiments are currently a compulsory part of getting a drug to market, but it is only a question of time before alternatives will be accepted for at least some of the tests. The complete replacement of animal testing with non-animal alternatives is not yet in sight. It is also a matter of priorities. Over the past twenty years we have made a lot of progress in the dissemination and implementation of non-animal alternatives. This all could have gone much faster if more money had been available for research into alternatives. Much brainwork and research is required before a full transition to non-animal alternatives can become reality.’

    Legislation and regulations

    Animal testing is bound by strict legislation and regulations. The welfare of experimental animals in the Netherlands has been protected in the WOD since 1977. In addition to this Act, the Experiments on Animals Decree came into force in 1985. The starting point of the Act is the ‘No, unless’ principle: animal testing is prohibited, unless there are no alternatives. If, for example, the research can also be conducted with a computer model or cadavers, then animal testing is prohibited. In 2014, a revised WOD came into force.

    An animal experiment is defined as the sum of procedures performed on a live vertebrate whereby the animal suffers or there is a risk of the animal suffering. Experiments on invertebrates such as worms, snails and insects are not considered animal experiments. The WOD was drawn up to protect laboratory animals in the Netherlands. The WOD stipulates that only qualified persons may use laboratory animals and only within institutes that are licensed to conduct experiments on animals.

    Codes of Practice

    The legislation and regulations provide frameworks, but not details, so there is sometimes uncertainty about the exact interpretation. Laboratory animal experts have established Codes of Practice on a number of themes, namely animal testing in cancer research (1999), immunization of laboratory animals (2000) and welfare monitoring of laboratory animals (2001). All persons working with laboratory animals must comply with these codes.

    In addition, the Animal Experiments Committee (DEC) of the University has drafted three documents with internal guidelines to facilitate standardization. The documents present the committee’s position on the codes of discomfort, the choice of animal species and ethical considerations.

    Revised Animal Experiments Act

    On 18 December 2014, the Animal Experiments Act was revised to comply with the new European directive. An important change is that institutions now combine their knowledge of animal welfare in an Animal Welfare Committee (IvD). The IvD assesses the animal welfare aspects of a research project after it has been approved by the DEC and CCD. The IvD also advises the researcher on animal welfare issues and the application of the 3R principle. The IvD members are a laboratory animal expert, the animal facility Location Supervisor, a scientist and if necessary an external expert such as a radiation expert or biological safety officer. Alongside the organizational changes, the definition of an animal experiment has also been changed.

    New role for the DEC

    The changes to the Animal Experiments Act also entail changes for the role of the DEC. The DEC is no longer authorized to grant or extend licenses for animal experiments. This committee will now focus on assessing applications and advising the CCD on these. This national committee makes the definitive decision to grant or reject the project license for the experiment. The CCD publishes non-technical summaries of the licenses it has granted on its website.

    Another national committee has been established called the National Advisory Committee for Animal Research Policy (NCad). NCad’s role is to bring about improvements in the application of the 3R principle (Replace, Reduce and Refine) and the ethical assessment thereof in scientific and applied research and education in order to minimize the use of laboratory animals both nationally and internationally.

      Animal experiment expert, Dr Catriene Thuring, and the heads of the animal facilities, Flip Klatter and Dr Martijn Salomons

      The revised Experiments on Animals Act (WOD): stronger distinction between implementation and assessment

      The revised Experiments on Animals Act (WOD) came into force in the Netherlands on 18 December 2014. Although the revised Act upholds the strict standards for animal testing that already applied in the Netherlands, it also has consequences for the way animal experiments are organized and assessed. The introduction of local Animal Welfare Bodies and a national Central Animal Experiments Committee has created a stronger distinction between implementing and assessing experiments on animals. The University of Groningen and University Medical Center Groningen incorporated most of the terms of the new legislation into their practices in 2014.

      ‘There are huge differences in the way that European countries allow experiments on animals’, says Flip Klatter. ‘Some countries, including the Netherlands, are highly professional, whereas others still leave a lot to be desired. The European Directive approved in 2010 was designed to bring all European countries up to the same high standard.’ The Netherlands incorporated the Directive into national legislation on 18 December 2014, hence the revised Experiments on Animals Act.

      Although under the old legislation the Netherlands was already operating at the level of the new Directive, the revised Act has introduced a few changes. ‘It has had particular consequences for the way animal experiments are organized and monitored’, says Klatter: ‘There is now a stronger distinction between implementing and assessing experiments on animals.’

      Two of the most important changes involve the introduction of Animal Welfare Bodies (IvDs) in every organization that conducts research using animals, and a national Central Animal Experiments Committee (CCD).

      Assessing and implementing
      The CCD is responsible for granting licences for animal experiments. The ethical assessment is carried out locally by the Animal Experiments Committee (DEC) and nationally by the CCD. Klatter: ‘More emphasis has been put on the ethical assessments, which are now carried out by committees set up specifically for this task. I think this is a good thing. Ethical assessments are extremely difficult, with aspects such as culture, faith and history all playing a role. It is a highly complex business. The changes make these assessments less speculative. In addition, a national body can look further than the boundaries of the individual organization. It has an overview of experiments being conducting elsewhere and can therefore prevent animal experiments being repeated unnecessarily.’ However, there is also a pitfall, warns Martijn Salomons: ‘It is important to reproduce certain experiments. You have to find the right balance.’

      After granting a licence, the IvDs ensure that animal experiments are optimally prepared and conducted. Catriene Thuring: ‘The IvD is right there on the work floor. Experts consult with researchers about the best way to conduct an experiment. The animal experiment experts are also members of the IvD, which has altered my position within the organization. I now have more contact with the work floor, making it easier to offer my specialist knowledge on animal welfare.’ Klatter continues: ‘The monitoring task has become a consultation task: almost everyone involved sits around the table together. We all benefit if an experiment is conducted as efficiently as possible.’

      ‘The fact that the IvDs have close contact with the work floor means that every IvD is slightly different, according to the organization and the type of research being carried out’, says Thuring. ‘In Groningen, the two IvDs comprise an animal experiment expert, the location manager of the animal experiment facility, a bio-technician and the researcher.’ A conscious decision was made to give the researcher a full seat on the Animal Welfare Body. Salomons: ‘We want to deal with the questions that arise during discussions as honestly as possible, so it is better if the researcher is there in person rather than having to rely on an intermediary.’

      Transitional year
      ‘Revising the legislation has been a lengthy process. Here in Groningen, we didn’t wait until the revised Experiments on Animals Act actually came into force’, explains Thuring. ‘We gave it a trial run in 2014; that was our transitional year. It gave everyone the chance to get used to the new structures.’

      It is always difficult to change embedded structures, says Klatter: ‘We expect our researchers to conduct research; if not, they are called to account. Changes to procedures take time and effort, which distracts from the research itself. And there is still uncertainty about the speed of granting licences under the new system. In 2015, we will find out more about the impact of these changes on our practices. I believe that the procedures will be more efficient and possibly also faster than under the old legislation.’

      Salomons: ‘Applying to the CCD for licences is one of the things that researchers are still struggling with. The application must contain enough detail for an ethical assessment, but researchers need to be flexible and are not keen to restrict themselves by laying down all the details of a long-term experiment in advance. We don’t have any good examples of applications like this yet, but I’m sure we will soon sort it out.’ Klatter: ‘Everyone has to get used to the new situation: the researchers, as well as the members of the IvDs, the DEC and the CCD. All will become clear in the next few years.’

      Dr Jocelien Olivier, Assistant Professor in behavioural physiology

      Research into the effects of antidepressants during pregnancy

      ‘Many women who use antidepressants stop taking them during or just before pregnancy. However, many of these women fall back into depression. Will the child benefit from stopping the medication? Or is it preferable for the mother to continue using antidepressants so that she is less depressed? This is what I want to discover with my research.’

      ‘Some one million people in the Netherlands take antidepressants. Many women who use antidepressants stop taking them during or just before pregnancy. They are worried about how the chemicals will affect the pregnancy. A quarter of women do continue to take the medication during the entire pregnancy. Of those who stop, some seventy per cent relapse into depression.

      So the question is whether stopping is a good idea for pregnant women. People take antidepressants because they make them feel better, so the baby may well be better off if the mother continues the medication and so feels less depressed. After all, we know that depression during pregnancy can have a negative impact on the mother’s offspring. For example, they have a higher risk of suffering from autism, aggressive behaviour, depressions and anxiety disorders. I want to try to answer this question in the coming years during my research here in Groningen.

      I am using a rat model for depression to investigate the effect of antidepressant use during pregnancy on children. People are not all equally susceptible to depression. Genes and environmental factors play an important role. For example, stressful events such as divorcing, losing a job or moving home can induce depression in some people while others are unsusceptible in these situations. The rats I use in my research are also more sensitive to stressful events, making them ideal models for depression.

      I am primarily interested in what happens to the offspring. I want to know if there is a difference between the offspring of depressed rats that have been administered antidepressants and those that have not. To find this out, I am subjecting the baby rats to various tests. One of these is the ‘three room test’ to determine how social the rats are. The rat is placed in a cage with an empty cage on one side and a cage containing another rat on the other. A social animal is more likely to move towards the other rat while a more antisocial rat will choose the side on which the empty cage is placed.

      Alongside behavioural research, I also want to analyse the brains of the rats to find out whether genetic or epigenetic changes have taken place. This research cannot be performed without laboratory animals.

      Before I joined the University of Groningen, I worked on the same research in Nijmegen in the Netherlands and Stockholm and Uppsala in Sweden. I have maintained strong relationships with these universities; we are all studying the same thing, but we each have our own niche and so we share information. For example, my animal experiments here may shed new light on the clinical work they do in Uppsala. It is these different perspectives that will help us to understand the complicated interaction between antidepressant use and pregnancy.’

      Prof. Theunis Piersma, Migratory Bird Ecology, winner of the Spinoza Prize 2014

      Tracks migratory birds all over the world

      ‘Migratory birds such as godwits literally go on a round-the-world journey every breeding season. Some fly eleven thousand kilometres in only ten days. I follow their lives by attaching transmitters to them:  where do they go, when do they die, and why? These are interesting questions for an ecologist, but migratory birds can also tell us a lot about our world and they link us to each other. They can also reveal our weaknesses, such as how our western agricultural methods are harming farmers in Africa, for example, or how disastrous the reclamation project in the Yellow Sea is turning out.’

      ‘Migratory birds are under enormous pressure everywhere in the world. I am trying to figure out what exactly is going wrong. My research group is following migratory birds in the field. We are focussing on godwits, but we also track ruffs, spoonbills and knots. There is always a degree of suspense involved in field research like this, because the birds have to be caught and tagged first. Upon capture, we try to collect as much data as possible on the bird: we identify the sex, check for parasites, take blood samples for DNA testing and we fit some birds with a transmitter. We are currently tracking more than ten thousand individuals.

      Attaching transmitters to birds is a very tricky business. You need a lot of skill and experience to do it without influencing the birds’ behaviour. We have to make hundreds of decisions: what weight, what type of transmitter, how to attach it… and everything has to be just right. It’s very precise work. We try to practice as much as possible on birds in captivity.

      Over the past years we have refined two different attachment methods: little backpacks attached to the backs of knots and hip bags for godwits. It took us more than two years to work out how to precisely attach backpack satellite transmitters made elsewhere to the backs of the birds. These transmitters are a wonder of science: they only weigh a few grams and are powered by micro solar panels. The birds are able to fly all the way from Australia to China with them on – some six thousand kilometres – and do not appear to be hindered very much by them.

      The data we collect is extremely valuable. For example, in previous research we demonstrated that bar-tailed godwits can fly eleven thousand kilometres without stopping. The birds travelled across the Pacific from Alaska to New Zealand non-stop during a flight of ten to eleven days. This was thought to be impossible; researchers thought that five thousand kilometres was about the limit for migratory birds.

      Being able to track the movements of migratory birds is also important for nature conservation. At the moment, the Chinese and Koreans are rapidly reclaiming land around the edges of the Yellow Sea. The tidal flats there are quickly disappearing. It is not hard to imagine that this will harm migratory birds, but how can you prove it? Most conservation research is based on observations, for example that a population is declining. By the time you have empirically proven the cause you are already too late. Thanks to our research using birds fitted with tags and transmitters, we can now catch the offenders red-handed, as it were. We are able to pinpoint exactly where and when a population collapsed. Happily, although governments are not particularly pleased to be confronted with such hard data, they do take it seriously.

      So in the case of the reclamation of the Yellow Sea, the effects are apparent in the form of declining bird populations thousands of kilometres away. But intensive agriculture here in the Netherlands also has effects elsewhere in the world. The godwit departs from this country earlier every year to return to Senegal and Guinea-Bissau in West Africa. They now arrive there some six weeks earlier than they used to. This has consequences for the West African farmers: the godwits turn up precisely when the Balanta women are sowing their rice. The godwits eat the germinating rice seed and so ruin the freshly sown crop. The farmers have been forced to use a more labour-intensive method whereby they first propagate the rice plants. And so the godwit is a link between the agriculture of the two countries. Migratory birds thus allow us to view the world from a holistic perspective. This perspective can help us to prevent things from getting even worse.’

      Ethical assessment

      Animal testing leads to an ethical dilemma: does the research or educational benefit justify the suffering of the laboratory animals? An impartial Animal Experiments Committee (DEC) assesses research proposals against the legislation and regulations and weighs the benefits of the animal experiment against the suffering that this causes the animals. The starting point here is that every animal has an intrinsic value. The DEC also takes into account the psychological complexity of laboratory animals and the emotional worth and status accorded to the various species by society.

      The DEC is an impartial committee that assesses animal testing by the University and the UMCG. The members of the DEC are experts in the fields of laboratory animals and their protection, animal testing, alternatives to animal testing and ethical assessments.

      The DEC assesses each new research proposal against the existing legislation and regulations. It also weighs the benefits of an animal experiment against the suffering caused to the laboratory animals. The DEC also sets down requirements for the preparation of research and the expertise and training of the researchers.

      The intrinsic value of every animal forms the starting point for the decision-making on whether or not an animal experiment is ethically acceptable, although other considerations also play a role, such as the psychological complexity of an animal (e.g. apes), or the social status accorded an animal on the basis of factors such as emotional relationships (dogs and cats), historic values (farm animals) or social relationships (seals).

      The University and the UMCG do not have facilities for testing apes and the University has drafted a separate position on these mammals.

       

      New role for the DEC

      The changes to the Animal Experiments Act also entail changes for the role of the DEC. The DEC is no longer authorized to grant or extend licenses for animal experiments. This committee will now focus on assessing applications and advising the CCD on these. This national committee makes the definitive decision to grant or reject the project license for the experiment. The CCD publishes non-technical summaries of the licenses it has granted on its website.

      Another national committee has been established called the National Advisory Committee for Animal Research Policy (NCad). NCad’s role is to bring about improvements in the application of the 3R principle (Replace, Reduce and Refine) and the ethical assessment thereof in scientific and applied research and education in order to minimize the use of laboratory animals both nationally and internationally.

      Dierproeven doelen

      Veruit de meeste dierproeven hebben onderzoekers uitgevoerd om een wetenschappelijke vraag te beantwoorden. De figuur hiernaast geeft aan waarover deze vragen gingen. Naast het beantwoorden van wetenschappelijke vragen, zijn ook dierproeven gedaan voor onderwijs en training, bijvoorbeeld om studenten en biotechnici op te leiden.

      Animal suffering

      Laboratory animals always suffer a certain degree of discomfort. The Dutch government describes four categories of animal suffering. Suffering does not necessarily entail pain: stress and anxiety are also forms of suffering. The figure displays the degree of suffering caused by animal tests in 2014. In 18% of the animal experiments the laboratory animal was euthanized without any prior procedures being performed on them. These animals fall under the the lowest category of suffering.

      48%

      Gering ongerief

      21%

      Gering tot matig ongerief

      24%

      Matig ongerief

      6%

      Matig tot ernstig ongerief

      1%

      Ernstig ongerief

      0%

      Zeer ernstig ongerief

      Animal testing objectives

      The vast majority of animal experiments are conducted in order to answer a scientific question. The figure on the right provides an overview of the scientific research that involved animal testing. Alongside scientific questions, animal experiments were also conducted for educational and training purposes, for example in order to train students and biotechnicians.

      Wild cats on Schiermonnikoog

      The University of Groningen has not conducted experiments on cats for a long time, but in 2015 they studied ten wild cats on the island of Schiermonnikoog. Wild cats cause problems for the local populations of breeding birds on the Wadden islands because these islands have no natural ground-dwelling predators.

      In the research on Schiermonnikoog, scientists studied the effect these cats have on bird populations by establishing the cats’ activity patterns using GPS collars. The cats were caught with cage traps and sedated for a brief period so that the transmitters could be fitted. After biometric data had been collected and the sedative had completely worn off, the cats were released in the same place where they had been caught. The cats were recaptured at the end of the observation period to remove the collar. The suffering of the ten cats was assessed as moderate.

      Breeding efficiency

      The University and the UMCG breed animals, in particular transgenic and normal mice and rats. Not all animals produced by the breeding programme are used in experiments: a large number are euthanized prematurely, for example because they lack the right characteristics or are only required for breeding. In 2015, 51,993 animals were bred, of which 36,632, some 70%, were not used in experiments. These animals are called ‘surplus animals’ or ‘breeding surplus’. Institutes and governments in the Netherlands and abroad recognize that the large numbers of surplus animals are a cause for concern. The University and the UMCG are at the forefront of efforts to increase breeding efficiency by means of improving communication between researchers and animal carers (supply and demand) and by reducing the breeding surplus by developing the technique of cryopreservation.

      Unfortunately, some degree of breeding surplus will always be unavoidable. Animals used in experiments typically have to be as identical as possible in order to produce reliable research results. For example, they will need to be the same age and sex or have been born under identical conditions. Some animals will not have the required genetic characteristics. In one experiment for example, some 170 mice needed to be bred in order to obtain a population of 60 identical transgenic animals: you can read more about this experiment on the website of Stichting Informatie Dierproeven (a Dutch language website with information about animal testing). A significant proportion of the breeding programme is required in order to maintain unique or valuable breeding lines.

      However, it is unacceptable to breed large amounts of animals that are subsequently not used for either research or educational purposes. The University and the UMCG therefore strive to increase breeding efficiency. We constantly and critically monitor animal numbers, strive to breed as efficiently as possible and use surplus animals for educational purposes whenever possible. We also see cryopreservation as an important technique for reducing the breeding surplus.

       

      Cryopreservation

      If a breeding line is not needed for a long period of time, then the technique of cryopreservation can be used to freeze the egg cells or sperm, rather than maintaining the line by means of live animals. If the breeding line is needed again, a fertilized egg cell is introduced into a pseudopregnant female. This means that no animals are required to maintain the line in the interim period.

      However, freezing egg cells or sperm is a complicated technique. For example, many frozen embryos do not remain viable. The University of Groningen and the UMCG consider cryopreservation to be an important technique for reducing the breeding surplus and so they have been working to master this technique since 2011. The cryopreservation team followed training in the ‘cryopreservation of sperm’ in late 2015. This is a highly efficient method for freezing a breeding line that requires only two male mice. Not all breeding lines are suitable for cryopreservation in this manner, but it will result in a reduction in laboratory animal numbers nevertheless. Some breeding lines have also been cryopreserved by external companies. Nineteen breeding lines were frozen in 2015.

      The last step of the experiment

      Killing animals is part of animal testing, but this is not a step that animal carers and researchers enjoy carrying out.

      Most laboratory animals are killed because the research has been competed or because the animal is surplus. The euthanasia procedure is designed to prevent animal suffering. The animals are placed in a container with a mixture of oxygen (O2) and carbon dioxide (CO2), in which the CO2 concentration is gradually increased. The animals first lose consciousness and then quietly pass away.

      In a limited number of cases, the animals experience complications during an experiment and may suffer more than was expected. In these cases, the researchers apply the ‘humane endpoint’. They remove the animal from the experiment at the point at which the animal’s suffering is deemed unacceptable. The animal is then euthanized to prevent further suffering.

      3R principle

      The University and the UMCG apply the ‘3R principle’ to research and education involving laboratory animals: Replacement and Reduction of laboratory animals and Refinement of the animal experiments. In concrete terms, this entails using as few laboratory animals as possible and completely avoiding animal testing whenever possible. Where testing is necessary, we try to limit the animals’ suffering as much as possible. The University’s Animal Welfare Authority (IvD) helps the researchers put the 3R principle into practice.

      Replacement

      A researcher may only conduct an animal experiment if no other option is available. Whenever possible, we conduct our research and education activities with alternatives to laboratory animals such as invertebrates, cells, tissue, computer simulations, video training or material from the meat processing industry.

      Reduction

      If animal testing is necessary, we try to reduce the number of animals required by conducting experiments with the lowest possible number of laboratory animals that will still produce reliable results. This can be achieved by breeding standard lines so that the research results are more comparable or by having the researchers conduct pilots first.

      In some cases, laboratory animals will be able to be used for other experiments or educational purposes following the original experiment. In 2013, 3% of laboratory animals were used for a second experiment.

      Refinement

      The researchers, animal carers, biotechnicians and laboratory animal experts continually work on refining their methods. Optimum housing arrangements and careful application of experimental techniques and anaesthesia limit the suffering of the laboratory animals. For example, social animals such as rats are housed in groups, which limits stress.

      By refining animal experiments, the welfare of the animals is improved. This is better for the animals and better for the quality of the research.

      Organization and facilities

      Animal testing at the University and the UMCG is organized so as to ensure optimum animal welfare. Before a researcher can actually conduct an animal experiment, the research proposal must first be approved by an impartial Animal Experiments Committee (DEC).

      The Animal Welfare Authority (IvD) can then help the researcher to prepare for the animal experiment as efficiently as possible. This involves discussing animal welfare issues and the application of the 3R principle. The University also employs two specialized veterinarians (laboratory animal experts). The laboratory animal experts monitor the welfare of the laboratory animals and sit on the IvD.

      Two modern laboratory animal facilities have been established in order to guarantee optimum care of the animals and effective research using them: the Central Animal Facility (CDP) in the UMCG and the Faculty Department of Animal Care (FDD) in the Linnaeusborg.

      An institute may only conduct animal experiments if it is licensed to do so by the government. The Board of the University (CvB) is the legal licensee for research and education involving laboratory animals at the University of Groningen and the UMCG. The Netherlands Food and Consumer Product Safety Authority (NVWA) monitors the licensee’s compliance with the WOD.

       

      Animal Experiments Committee

      The University has an impartial Animal Experiments Committee (DEC) that assesses animal testing by the University and the UMCG. The members of the DEC are experts in the fields of laboratory animals and their protection, animal testing, alternatives to animal testing and ethical assessments. The DEC reports to the licensee and the NVWA annually.

      The committee is impartial: the chair and at least two of the members of this committee may not be employees of the University. At least five of the members have no involvement in animal testing. The DEC is advised by the University’s laboratory animal experts.

       

      Animal Welfare Authority

      The expertise on animal welfare is combined in the Animal Welfare authority (IvD). After the DEC has given its approval, the IvD helps the researcher to prepare properly for the animal experiments. They discuss animal welfare issues and the application of the 3R principle with the researcher. The IvD members are a laboratory animal expert, the animal facility Location Supervisor, a scientist and if necessary an external expert such as a radiation expert or microbiologist.

      Laboratory animal experts

      The laboratory animal experts are specialized in analysing and assessing the welfare of laboratory animals. They monitor the welfare of the animals. The laboratory animal experts advise researchers on the design of their animal experiments and how they can limit the suffering of the animals.

      The laboratory animal experts consult with their local and international colleagues so that they can assess whether the research proposals submitted to them are feasible and whether they can learn from other institutes when new research techniques are to be introduced.

      The laboratory animal experts also advise the DEC on how to reduce laboratory animal suffering, provide training for researchers, animal carers and biotechnicians and help form policy on laboratory animal facilities. Finally, they register all animal experiments, the numbers of laboratory animals used, the degree of suffering involved and the numbers of new animals bred. The laboratory animal experts report their findings to the licensee and the NVWA annually.

       

      Housing

      The animal experiments carried out by the University and the UMCG are conducted in the field or in laboratories with special laboratory animal facilities. We give the utmost attention to providing optimum housing for the laboratory animals, as these are the areas where the animals will spend most of their lives. This involves more than just complying with the legal requirements. The CDP and the FDD were completely renovated in 2009 and 2011 respectively and are among the most advanced facilities in Europe. The temperature, light and humidity in the animal housings can be exactly regulated. Journalists of the University newspaper reported on a visit to the CDP in 2013.

      Stichting Proefdiervrij has its say

      You can’t polish a gem without friction

       

      ‘The University of Groningen and Proefdiervrij (an anti-animal testing lobby) have been debating the use of animal testing and how to replace this practice for many years. A dialogue of this kind cannot be conducted without transparency, […] as this dialogue is not confined to the University of Groningen and Proefdiervrij, but must reach as many people as possible with an opinion on animal testing.’

      The University of Groningen and Proefdiervrij (an anti-animal testing lobby) have been debating the use of animal testing and how to replace the practice of experimenting on animals for many years. A dialogue of this kind cannot be conducted without transparency. Annuals report are a good instrument for ensuring transparency, as they force organizations to give a yearly account of all their activities. Proefdiervrij considers transparency and accountability to be an important element of the social dialogue on animal testing. This dialogue is not confined to the University of Groningen and Proefdiervrij, but must reach as many people as possible with an opinion on animal testing.

      An annual report is a reasonably static document. It gives an account of the past year, and is in fact virtually a chronicle. Events taking place here, now and in the future are actually much more interesting and probably more in keeping with the things that Proefdiervrij and animal-lovers in general would like to know. So in addition to an annual report, Proefdiervrij would like to generate some kind of ongoing involvement. Tell us about the projects currently being implemented or projects that are about to start, and explain what is happening. Or is that a frightening prospect? It might take some getting used to. After all, if you tell people what you are doing and why, they will probably respond and tell you what they think. Sometimes you will disagree, but this isn’t necessarily a bad thing because you will have achieved an open and honest discussion or debate. In fact, a serious disagreement can sometimes help – you can’t polish a gem without friction!

      At the end of the day, nobody wants to experiment on animals. I think this is something we all agree on; it’s what unites us. Looking for a way towards animal-free testing and working out how long it will take are the main subjects of our ongoing discussions with the University of Groningen. And we will find a way to stop animal testing; this is not only my dream, but also my conviction. To do this, we must work alongside researchers at the University of Groningen and other establishments that conduct tests on animals. They rely on us to ask questions and make comments from an entirely new perspective, so that they can find a way to make animal testing a thing of the past.
      This is why Proefdiervrij is committed to transparency, accountability and dialogue.
      With kind regards,
      Marja Zuidgeest
      Managing Director of Proefdiervrij

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