The Swiss are somewhat sceptical about animal testing for research purposes. This unsurprising stance was most recently shown in a representative survey of 1000 Swiss voters conducted by gfs.bern on behalf of Interpharma. However, when asked whether animal testing should be banned even where universities and pharmaceutical firms have no other means of advancing research, only 34 per cent of respondents said it should be banned whereas 58 per cent would accept animal testing in such circumstances. There was greater consensus –  70 per cent – regarding approving animal testing for general medical research and research into drugs for the treatment of diseases. There has been barely any change to this critical but approving stance since the last survey in 2009. This is unsurprising considering much medical progress has its roots in animal testing – like the knowledge of the three neuroscientists awarded the Nobel prize in Medicine last week.

It has a lot to do with the conviction of a significant majority of those surveyed – 55 per cent – that Switzerland has a strict animal welfare law. Only 22 per cent of respondents consider animal welfare in Switzerland to be too lax. The remainder do not know or are undecided. They are very capable of deciding however, when it comes to where animal testing should take place. 91 per cent of those surveyed consider it preferable to allow animal testing under strict conditions in Switzerland than for it to be outsourced abroad to where regulations are less strict.

This critical but favourable opinion of animal testing is also the result of efforts by animal welfare organisations, lawmakers and researchers in Switzerland. Instead of the sometimes radical but unsuccessful opposition to animal testing in the 80s and 90s, there is now dialogue. Undeniable progress has been made. The laboratory animal welfare charter, which Interpharma firms adopted in 2010, is not just attracting interest in Switzerland. The industry is recognising that the legitimate interests of animal welfare campaigners should not simply be pushed aside. However, animal welfare organisations and the research-driven pharmaceutical industry continue to evaluate the necessity of animal testing differently. They agree that animal testing should only be carried out when there is no alternative and authorisation has given following careful weighing of the suffering and distress caused to the animal against the expected gain in knowledge.

As such, both sides – the industry and animal welfare organisations – strongly support a national research programme that should increasingly develop alternatives to animal testing following the principles of the 3Rs. These aim to reduce animal testing, replace it as much as possible with alternatives such as computer simulations, testing cells and tissues and refine methods to minimise the stress caused to the animals. This is widely supported in Switzerland: 83 per cent of respondents were in favour of a research programme exploring alternative methods to animal testing. This wish must be taken seriously, particularly given the importance attributed to animal welfare in Switzerland.

About Thomas Cueni

Thomas B. Cueni is Secretary General of Interpharma, the association of the Swiss pharmaceutical research companies. He is a member of the Board and Council of the European Federation of the Pharmaceutical Industries’ Associations (EFPIA) and of the International Federation of Pharmaceutical Manufacturers Associations (IFPMA). Prior to his appointment with Interpharma, Mr. Cueni had a career as an economic and political journalist for two leading Swiss newspapers and spent four years as a London correspondent. After that he joined the Swiss Foreign Service as a career diplomat with postings in Vienna (UNIDO, UN, IAEA) and in Paris where he was a member of the Swiss Delegation to the OECD. Mr. Cueni has a degree in economics (University of Basle) and a Master of Science from the London School of Economics.

Putting animal welfare principles and 3Rs into action

European Pharmaceutical Industry Report 2012 Update

Beyond Compliance:

• How do we ensure that animal welfare standards and practices are put into action throughout the sector both in our industry and among the laboratory and research community more broadly?
• How do we make sure that global regulations reflect 3Rs strategies?
• What internal and external industry initiatives facilitate the implementation of training programmes on animal welfare and care?
• How do scientific advances help progressing 3Rs and Welfare? *New

Leading by Example: 

• How do we share and encourage good practices based on 3R principles across the pharmaceutical industry?
• How do we stimulate putting into practice global animal welfare standards?
• What is being done to rapidly implement and enforce across Europe the revised European Directive 2010/63/EU on the protection of animals used for scientific purposes?
• Are companies independently assessed on how animal welfare standards are applied?

Committing to Open Communication:

• How do we contribute to an open and constructive dialogue on animal welfare?
• How is industry communicating the progress made with animal welfare activities, specifically the 3Rs?​

So why is the Nobel Prize inspiring a blog, here? As with most Nobel Prize research, animal studies were integral to the researchers’ success.  In this case, yeast, cows and genetically modified mice were involved in the research process. Looking back, nearly all Nobel Prizes in Physiology or Medicine have required some form of animal research. According to Americans for Medical Progress, in the past 34 years, all awards but one have been dependent on animal research.

The impact of this year’s prize-winning discovery could be big news for patients suffering from diabetes or brain disorders. The three researchers discovered that vesicles – membranous structures that store and transport cellular products – transport these materials to a precise target, similar to a fleet of ships. This is crucial to many processes – from the release of hormones in the body to brain communication. Defective vesicle transport systems are associated with diabetes and brain disorders – and knowing more about them could help us improve treatment options in these areas.

So congratulations to James Rothman, Randy Schekman and Thomas Sudhof for their Nobel Prize win, and for bringing research a step further.

What are your thoughts on the big Nobel Prize news? Let us know in the comments section below

The reasons for this are many and varied. For one thing, the low-hanging fruit was picked a couple of decades ago so the diseases for which we now need new therapies are the most difficult to treat. This requires a huge investment of time, effort and resources and call for a more collaborative approach to innovation.

For another thing, the cost of conducting research has risen at a time when the rewards are on the wane. A recipe for new drugs it is not.

Yet the world is facing fresh public health challenges due to shifts in demography and lifestyle. Our ageing population means conditions such as Alzheimer’s will become a much greater burden. At the same time diabetes rates are through the roof in develop – and in developing – countries across the world.

What’s this got to do with animal research?

Glad you asked. This slow-motion crisis is paving the way for new approaches to drug development.

One area which shows considerable promise is personalised medicines. The primary goal of research in this field is to develop medicines which are best suited to individual patients or to particular categories of patients. This would mean, for example, that if you had a certain gene, your doctor would choose the medicine most likely to work for people like you.

The push towards deepening our scientific knowledge in this area is changing how research is conducted. In search of more precise and predictive methods of treating people, scientists are developing new models for testing drugs.

Innovation through collaboration

The need for more open collaborative approaches is spawning exciting public private partnerships like the Innovative Medicines Initiative (IMI). NEWMEDS – Novel Methods leading to New Medications in Depression and Schizophrenia – a five-year IMI project funded by the EU and pharmaceutical industry is committed to finding new treatments for psychiatric illnesses.

One of the key elements of the NEWMEDS project will be the search for better animal models. ‘Better’ means more accurate and predictive but using fewer animals.

The investment in better animal models which can more accurately represent human diseases should give scope for using fewer animals in the years ahead. Good news for delivering on scientists’ commitment to pursue the 3Rs of animal research – reduction, refinement and replacement.

Diabetes is a case in point. Around 350 million people worldwide are affected by diabetes and this number is rising steadily. Research using animal models has been central to pretty much all the therapies currently available for managing diabetes but the revolution in personalised medicine might help deliver better medicines using fewer animals. This is addressed by another IMI project, IMIDIA.

So, perhaps the headlines of recent years might be caused for concern given the essential role of the medicines sector in improving public health and generating wealth, but the concerted response for public and private players is cause for hope.

Crises can be catalysts for change. In the future, we could have better medicines developed using fewer animals.

As part of our ‘Shall it stay or shall it go?’ campaign we’ve been asking you about the future of animal research in Europe.

Well it seems that some of the scientists who work in this area have given their verdict: they want it to stay and are more than a little worried about what they see as myths around animal studies.

The folks who run the Understanding Animal Research website have brought together concerned researchers from the UK to create the Science Action Network.

The group wants scientists to enter the debate which it says has been characterised by inaccuracies and confusion, partly because scientists have been reluctant to speak up.

They are asking scientists to give five minutes per week to reply to misinformation on the internet and social media channels. There’s even a dedicated Twitter hashtag – #ARnonsense – which they want scientists to use when debunking myths, and a Facebook page where researchers are encouraged to weigh in on videos and articles about animal science.
 

So, dear reader, the question is: will it work?

Are scientists the right people to discuss the ethics of animal research? Does the campaign target the right people through the right channels? What about the tone? Do you find it abrasive, irreverent – or both?

The goal is to find ways of alleviating the symptoms of these conditions. We look at how trisomy changes neurological mechanisms and how it influences embryonic development, stem cells, and the programming and function of cells. We identify and target these mechanisms and hope to treat them through therapeutic drugs. These mechanisms are often similar to those affecting humans with comparable conditions.

We can hope to heal humans thanks to the mouse model. Ten years ago there were no real prospects for treating Down syndrome. Today, Roche is testing a new drug to reduce its symptoms, including problems with learning, memory and speech. Other drugs are on their way. Ten years of research mean that we now have several promising leads for treating Down syndrome.

The animals we use also allow us to do research on rare and very rare genetic conditions, those affecting as little as 1 in every 10,000 people. These include 17q21.31 and 16p11.2, two syndromes where a part of a chromosome is “deleted,” and ring chromosome 14, which results in difficult-to-treat epilepsy. The rarity of these conditions means that it can be difficult for doctors to know even what the typical symptoms and their intensity are. The animal experiments can help us determine what is representative and how these symptoms can be treated.

The Three R’s

We take very seriously our efforts to reduce as much as possible the degree of suffering and loss of life among our animals. We have mandatory training on animal handling and well-being before being allowed to work with them and this continues with “on the ground” training as we specialise.

In our work we follow the principles of reduction, refinement, and replacement. By reduction we mean that we follow tightly optimised procedures to reduce the number of animals we need to use. For example, we know exactly how many animals we need to detect a 20% difference between a test population and a “normal” reference population.

By refine we mean making the animals’ lives as positive as possible. This means we emphasise non-invasive methods of experimentation and, when needed, we use anaesthetics and analgesics to reduce any pain felt. In terms of mutations, our animals do not undergo anything that doesn’t occur in nature. Human children with these genetic features are born naturally. If ever there are animals with very serious problems we can put them down (which I have not yet had to do).

Finally we try to replace animals where possible with other means, such as growing and experimenting with cells in Petri dishes. However, this is typically not useful for studying mental disabilities due to Down syndrome, such as long-term memorisation, interaction with space and objects, social recognition, thinking, and senses. For this cell cultures are no substitute. But we are “thrifty,” so to speak, in all we do, including our use of animals. We have to be very careful in how we keep and treat them. In Europe, and certainly in France where I work, the use of animals is very well regulated [hyperlink to French regulation].

There are some who say we don’t need animal testing anymore. But for the kind of research we do, there’s very little that can be achieved with cells in Petri dishes. We do it knowing that people will benefit. In the 1920s, research using dogs and bovines led to knowledge of insulin’s role in diabetes and to the creation of medical treatments (including for animals with diabetes). Today there are still countless diseases which we could treat better. We work knowing that in the end our research will help heal people and improve their lives.

Testing chemicals that are used in the pharmaceutical, agrochemical and consumer-products industries to establish the likelihood of their causing cancer (carcinogenicity testing) still requires a great deal of animal experimentation, with up to 800 rodents used for each substance and around 12,500 laboratory animals used annually in the UK.

Finding alternatives to animal tests for assessing cancer risks to humans that are faster, more efficient and which benefit animal welfare is an urgently important issue, as the current carcinogenicity studies are time consuming and expensive and are of limited practical use in large-scale chemical evaluation programmes such as REACH, the European Union regulation concerning the Registration, Evaluation, Authorisation and restriction of Chemicals. In addition, the 3Rs (‘Replacement’, ‘Reduction’ and ‘Refinement’ of animal research) focus on an area of biological research where there is a real need to advance one or more of these legislation criteria concerning animal testing and research. NC3RS are confident that their grants to Professors Newbold and Jenkins will deliver tests that will benefit both animals and the industries in which they are used across the EU and Europe.

In particular, rodent cell-based in vitro tests for detecting a chemical’s potential to damage DNA and/or cause mutations (genotoxicity assays) are already used in regulatory carcinogenicity testing strategies, but are felt to be limited as stand-alone tests, due to their high rate of misleading positives (where chemicals that do not damage DNA in vivo are wrongly classified as potential carcinogens), which then require animal experiments for clarification. For more information concerning the awards, click here.

Professor Claus-Michael Lehr, a drug development scientist at the Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), believes new methods using cell culture instead of rats and mice will help deliver medicines more efficiently.

‘Delivery’ is the watchword. Not only could non-animal methods get some medicines from the lab bench to patients’ bedsides more quickly, they could also be used to target drugs directly to where it’s needed most.

Finding ways to deliver a drug to a particular part of the body can mean more effective therapies with fewer side effects. Think of how the new wave of chemotherapies can target cancerous tumours without killing as many healthy cells as older treatments did.

Cell lines of inquiry
These ideas are what inspired Prof Lehr to explore how cell lines could be used to create models of the gut, skin and lungs. If his team can understand how, for example, the intestine will respond to a potential new medication using cell models it will require fewer rats and mice in the early stages of research.

The German group is also interested in how medicines can be inhaled or given through a patch instead of injected. The potential treatments are themselves promising but it is Prof Lehr’s innovation in the area of non-animal research which had attracted most attention.

His group has created models of healthy and inflamed bowels which could deepen understanding of colitis and inflammatory bowel disease. Through cutting-edge nanotechnology, Prof Lehr is hoping to deliver treatments to the bowel to reduce inflammation without the side effects which are often seen when a drug is taken in tablet form.

Using human cells as part of this research could give a good idea of how effective a treatment will be, he says.

The Saarland group believes that by testing potential medicines and drug delivery systems on real human tissue grown in their lab they can learn more about how healthy and inflamed intestines will respond to the drug.

It will also help figure out whether pharmaceuticals can be transported across the lining of the gut. At present, this kind of work is typically done in live animals but Prof Lehr believes some of these animal testing methods could ultimately be replaced.

Motivation factors
Prof Lehr has won prestigious awards in the German state of Rhineland-Palatine and, recently, a federal research prize for work aimed at “the restriction and replacement of animal experiments”.

So, why did he dedicate himself to non-animal research methods?

“My motivation is truly scientific – it’s not driven by ethical concerns. I want to study how molecules transport across biological barriers like the lungs and the intestine. At present, if scientists want to examine the intestine they use rat and mouse models but these are imperfect. I believe using human tissue can be more efficient. So it’s not just about ethics, it’s about speed and efficiency.”

As a PhD student Prof Lehr’s work included performing surgery on rats and he sees the value of animal research in certain circumstances. “I think animal tests are still necessary in some instances, but in other cases we can get a clearer view if we use in vitro methods.”

Changing environment
Prof Lehr trained as a pharmacist in Germany before completing his PhD in the Netherlands and pursuing post-doctoral research in the US. He has been publishing academic papers for 20 years but has seen non-animal models for drug delivery research moving into the mainstream over time.

Academic interest and funding for the area has increased, slowly but surely, and new regulations have stimulated industry to invest.

“The ban on animal research for new cosmetics had a tremendous impact. It has been a driver for new research to find alternatives to animal testing and to validate them. There are quite a few miles to walk but it’s an expanding area,” he says.
Prof Lehr sees little prospect of a ban on the use of animals in drug development so the impetus will come from scientists and the pharmaceutical industry. “If it is accepted that cell lines can give better and faster results it will be a positive motivator,” he explains.

This may take time but with every research paper – and every prize – the Saarland group edges ever closer to this goal.

Photo credit: SCIEPRO/SCIENCE PHOTO LIBRARY

Nanotechnology is a broad field focused on the study of things of a very small scale, and scientists hope these tiniest of techniques might add to the arsenal of non-animal research methods.

This area has attracted huge interest in recent years and nanotechnologies have already been used in everything from ‘functional foods’ to high-tech sunscreen and odour-free socks (I’m not making this up!).

Sometimes breakthroughs in science come from surprising places: when physicists began probing the miniature world of nanotechnology in the 1980s, the implications for animal research were not on the agenda.

Now, decades later, the potential of nanoscience to deliver new non-animal tests is coming into view.

Gaining momentum
It seems there’s no end to the promise of these tiny technologies and several research groups have been exploring how medical research could benefit.

In recent weeks a couple of headlines have caught our eye which suggests this area could be gaining increased momentum.
Researchers at the Fraunhofer Research Institute in Munich have developed new ‘sensor nanoparticles’ which could be used instead of animal-based methods in some cases.

As this article explains, when scientists need to understand the impact of a particular substance on living cells they typically expose animals to the chemical in question. But Dr Jennifer Schmidt and colleagues believe similar results can be achieved by growing living human tissue in the lab and using this to test new substances.

Here comes the tiny bit: nanosensors are used to detect a molecule called ‘ATP’, which helps scientists decide whether a cell is healthy or not. So if the nanosensor can detect lots of ATP, this suggests that the substance which is being tested hasn’t done much damage to the cells. If ATP levels fall, the cell is no longer healthy.

With new medicines, often the aim is to improve patients’ health without causing any collateral damage to their healthy cells. But sometimes killing cells is the aim of the game: this kind of nanotechnology could be used to test whether new cancer medicines damage or kill tumour cells.

The beauty of nanotechnology is that these tiny particles are not poisonous and can easily pass through cells because they are so small, meaning nanosensors can tell us a lot about how healthy a cell is without causing damage.

Moving to the mainstream
Separately, Prof Claus Lehr’s team at the Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) hopes to use nanotechnology to improve drug delivery.

His work has earned him several awards given their scope for reducing the dependence on laboratory animals in drug development. Prof Lehr is exploring how cell lines could be used to create models of the gut, skin and lungs. In some instances this could mean fewer rodents are needed when researching medicines.

The group has created models of healthy and inflamed bowels which could help doctors to understand diseases like colitis and inflammatory bowel disease. By using nanotechnology to deliver drugs directly, Prof Lehr and his colleagues hope medicines can reduce the inflammation which causes patients discomfort but with fewer side effects than existing treatments.

These are just two examples – feel free to suggest others – but the point is that the use of nanotechnologies in achieving the 3Rs appears to be gaining momentum.

As Prof Lehr told us, when he began looking at this area several years ago there was little academic interest and even less funding available. Now, nanotechnology appears to be taking its place in the mainstream and may be one of several solutions which can be brought together to cut down on the use of laboratory animals.

What do you think? Could small science make a big difference?

Image: Fraunhofer EMFT

What if I told you that these technologies already exist and the trick now is to pull them together, apply them and have them accepted by authorities? Well, it’s true.

Some of these tools can be used by themselves, others can be combined to find innovative approaches to research and testing.

By using so-called Integrated Testing Strategies (ITS), major progress could be made in moving towards the 3Rs.  This approach means using tailor-made combinations of animal and non-animal research methods in developing and testing new medicines, although hurdles remain before Europe makes the leap into this new era.

As we mentioned recently, the European Partnership for Alternative Approaches to Animal Testing (EPAA) – a joint effort by policymakers and industry – devoted its annual conference in Brussels to ITS.

The beauty of so-called Integrated Testing Strategies (ITS) is that it can mean using fewer animals which also generally means lower costs. As Dr Thomas Foerster of Henkel put it, this appeals “not just for ethical reasons but also for budget reasons”.

Ready for total replacement?

So why are some of the non-animal methods which are part of ITS not used universally instead of animals? Why can’t we replace animals altogether? Well, right now, even the best available non-animal methods are imperfect.

In some cases, testing how a group of cells in a dish respond to a new drug can be very useful but scientists also need to know how whole organs interact in the presence of the new substance.

Translation: dropping a new medicine on a few brain cells tells you lots of things about how the brain will respond. Testing this drug on some liver cells also tells you something about how the body will deal with this drug. But it’s not quite the same as seeing how the whole brain, liver, kidneys, heart and so on will respond as a whole.

For now then, it seems ITS can be used to reduce the reliance on animal models, but some animals will still be required.

Show me the data!

More research is certainly needed. The other big hurdle to clear is convincing regulators to accept these new kinds of experiment instead of traditional animal-based testing. According to several speakers at the EPAA event, the industry is reluctant to invest heavily in developing these kinds of non-animal methods unless regulators can guarantee that they will accept them.

For their part, regulators have been slow to make such a commitment until they’ve seen data proving that the new non-animal methods are as good as existing tests.  It’s a classical catch-22. Perhaps the only option is to jump together.

Human nature is also a drag on progress. Scientists working in industry and toxicologists in regulatory bodies are used to current animal-based methods. They understand the techniques; they trust the results.

If ITS are to be embraced, experts who are familiar with them will need to be trained or recruited – which is no easy feat. There is also the global aspect. If new ITS were acceptable in Europe but regulators in the US, China and elsewhere would only accept traditional animal-based testing then new medicines would have to be tested twice – which would increase costs rather than reducing them.

Europe can take the lead in this innovative area but there’s no point running too far ahead of the pack.

The take-home from this year’s EPAA annual event was that ITS offer real promise for reducing the use of animals but making this kind of quantum leap is never easy. It looks like we’re at the beginning of a long but exciting story.