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?

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

Science is rarely as certain or a simple as some expect. It is never possible to know for sure how new knowledge will be used.

Nor is it reasonable to promise that a series of experiments will deliver a particular benefit. If the results were known in advance, the experiment would not be needed.
So the idea that the use of animals in research should be limited exclusively to cases where the investigator can say with confidence that the outcome will produce tangible results is to misunderstand scientific endeavour.

It also stifles scientists’ curiosity; curtailing the quest for knowledge that has taken us to where we are today.

Small steps lead to giant leaps
For example, researchers studying octopuses’ nervous systems decades ago hardly realised their work would be critical to understanding multiple sclerosis in humans. The octopus experts were deepening our understanding of how animals work because they were fascinated by the question.

Science is incremental. Breakthroughs often look from afar like giant leaps but they are in fact just the latest in a series of small steps.

The same goes for the people whose work on the brains of song birds gave us much of our current understanding of the pre-frontal cortex – an area associated with personality and behaviour but also with addiction and psychological disorders.

All of that basic science, conducted 30 years ago, was the first step on the long road that gave us medicines for people with schizophrenia and depression.

Those researchers didn’t know precisely how their work would be used, just like the electronics experts and computer scientists who helped us understand sound had no clue that one day someone from another branch of science would use that information to design a cochlear implant for deaf children.

Guaranteed uncertainty
Most of the animals used in labs right now are for basic research. Guaranteeing a direct human benefit in the short term is impossible.

Some experiments, of course, will not yield results even in the long term. That too is part of how science works.

Just as most successful entrepreneurs have failed ventures behind them, there are few scientists who can’t think back to a wasted weekend in the lab where a promising line of inquiry came to naught.

Science is imperfect and unpredictable. Long may it remain so.

It was clear when talking with Neil about his experience during the first reading that it was a challenging time for him. Each person faces their own personal dilemma about animal research and for Neil it was between his natural love of animals, as a farmer and dog owner, with the desire for legislation that allows medical advancement for humans.

Whether you agree with Neil’s view or not, I hope the video gives you a new or better insight into the thinking behind the development of the new European animal research directive 2010/63/EU.

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What do you think?

After six and a half years at UAR, Simon is moving on to a new sector and new job, but before leaving I caught up with him to hear first-hand about some of the key issues that he has been trying to improve.  Poor scientific communication was at the top of his list, which I wasn’t actually expecting from him, being a supporter of science.

Simon gives an open and frank view on where the scientific community went wrong, why this happened and some concrete actions that the scientific community can do to increase their transparency to the general public.

Just as a side note, Simon uses the word anti-vivisectionists, which is often used in the UK to describe animal rights campaigners.

Enjoy the video.

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Neil Parish MP: balancing science and ethics in a political environment

What’s driving the increase in animal research?

Finding the right balance between animal welfare & human welfare

European society wants to take care of family pets, as it does for the rest of the family. Today, it’s normal for household animals to be attended to by specialized doctors, receive treatments, medicines and vaccines. Our pets are undergoing complicated operations and even cancer therapies to improve their quality of life. All this was made possible thanks to years of medical research, with animals.

In The Netherlands, 65% of dog research and 90% of cat research is to advance the health and safety of cats and dogs. 20% of all animal testing is for the development of veterinary drugs and vaccines. Furthermore medicine destined for animals must first be tested on healthy animals before being used in animal patients.

An example of a new treatment that has been made possible through research with dogs is gene therapy for people with impaired vision or who are blind. Briard dogs with Leber’s disease are born blind. Ten years ago research began with naturally blind Braird dogs to see if their vision could be improved. After successful results, gene therapies have also been performed on humans and as well as blind dogs. Watch this video “RPE65 Gene therapy” illustrating the results of gene therapy on a dog after one of its eyes was treated.

Even though the number of cats used for research is a lot less than dogs, there is an ongoing need for more research and better understanding of this species, be it pedigree or house cat, because more are kept as pets. Moreover, cats get their own kinds of illnesses like flu and Distemper.

So if we ban the use of cats and dogs in experiments we run the risk of not being able to protect them with new vaccines and medicines. It could potentially impact the development of some new medicines for humans. For example dogs are mostly used in research for heart and vascular disease in humans. However contentious that maybe, we shouldn’t ignore how veterinary developments are greatly benefiting from medical advances in humans.

Running parallel to this point, as we strive to improve the health of our animal companions, domestic animals are starting to suffer from similar modern illnesses found in humans. It’s not uncommon these days for dogs and cats to develop lifestyle diseases such as diabetes or heart disease, brought on through poor diet and lack of exercise, quite likely reflecting the owners’ own habits. Read the zebra fish post about heart research to learn more about modern diseases.

Now with these extra facts on the table bringing the consequences closer to home, it would be interesting to ask those 57,000 Dutch citizens if they still want to ban animal research.

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Neil Parish MP: balancing science and ethics in a political environment

What’s driving the increase in animal research?

Misconceptions: Animals are kept in appalling living conditions

I don’t know if this kind of awareness and fund raising is ‘a first’, none-the-less it is certainly honest and brave; particularly in a country of animal lovers and a recent history of outspoken animal rights activism.

So what’s behind the fundraising? Researchers have been studying the tiny zebrafish to understand its ability to rebuild its own damaged heart cells. The hope being, if we can understand how they do it, it will lead to finding a way to coax human hearts to repair themselves after injury brought on by a heart attack. Within five years the foundation hopes to see the beginning of early clinical (human) trials and within 10 years, full trials. Within a further decade, people living with heart failure could literally be healing their own hearts.

To learn from the zebrafish, researchers remove about 20% of its heart, and then they monitor the fish over a couple of weeks as the heart regenerates. Apparently the zebrafish struggle to swim for a few days, but within a month appears to be perfectly normal. Traditionally heart disease research was performed on mice and guinea pigs, however the zebrafish and its larvae have helped to minimize their use.

In the UK alone, heart failure affects over 750,000 people a year, with the problem only growing. When you have a heart attack, a part of the heart muscle dies. This irreversible damage can lead to heart failure as the heart is not pumping as efficiently as it should. Common causes are lack of exercise, poor diet, smoking, drinking, high blood pressure and stress.

I am glad to see that part of the British Heart Foundation’s campaign also includes the promotion of a change in lifestyle, which could positively impact the upward trend in heart disease. I’m sure the Zebrafish would appreciate it too.

Visit the British Heart Foundation to learn more about this work.

What is animal research?

Research is the use of animals as a model, to better understand how the body works, how diseases affect it and find ways to influence the cause of the disease. This is essentially different to testing. The biomedical community use more than 80% of the total number of lab animals in this way, even though the overall number of  lab animals used is still much lower than 30 to 40 years ago , the numbers have grown in recent years.

How are researchers using animals to research?

Researchers look for an animal that has a disease similar to man, either naturally occurring, for example blindness in dogs, or which can be introduced by changing the animals’ environment or through genetic modification. For example to understand how anxiety effects health, we induce stress in mice to see how their hearts beat, how it affects their vision and breathing. To understand how cancer works, we alter genes in mice, so they automatically develop cancer after a certain time. Alternatively we use normal mice and transplant a human tumor into them to see how it develops over time.

Why are mice used so often?

They are small, easy to house with a short breeding cycle, which enables researchers to see many generations in a relatively short period of time. Unlikely many other animals, mice are easier to manipulate genetically.

Are mice really that similar to humans?

In terms of testing, a human is not a 60kg mouse. Testing in mice is valid but not the perfect model. However evolution is quite conservative; 90% of the genes of a mouse and the genes of a human are identical making them a very valid model.

It’s hard to believe a zebra fish is a good human model…

Fish are vertebrates too. The more you go into genetics and embryology you can learn a lot from fish to understand when a gene mutates, especially as their embroyos are transparent. If you look at an embryo of a mouse, fish, cow and man on a metabolic level during embryonic development, until the second or third week of pregnancy there isn’t much difference between them. Nature doesn’t reinvent itself; it improves existing ‘material’.

Why are we still using monkeys in research?

Academics and neuroscientists use monkeys in research when they try to understand how the brain is wired. Industry also uses monkeys for testing vaccines and hormones (biologics) as these interfere with the immune system. Unlike genetic studies, the immune system in humans is quite different from that of a dog or a mouse. So vaccines have to be tested in a non-human primate.

What would happen if we simply stopped research with animals?

If we phase out animal research there would be no suitable alternative to understanding disease mechanisms. You can’t mimic this in a computer model, at least not today. Many people have tried without animals, but it doesn’t work. It’s even getting more complex, and the number of animals will rise, because we have many more scientific questions to address.

In former times we only looked at genes, but we have now discovered epigenetics. This looks at how the body turns genes on and off during a lifetime. We have learnt that those ‘switches’ can be inherited. For example fasting periods in early adulthood can have an effect on your grandchildren leading to diabetes. This kind of research can’t be done in humans, for time or ethical reasons.

Why are woman who have children less likely to get breast cancer? We know it but we don’t know why? What is happening to make people with Huntington’s disease gene become sick and die at 45 years old? Or Alzheimer’s, we can see what’s happening to the brain, but we don’t understand the mechanism behind it and unless we understand that we can’t find a cure or prevention.

How can we motivate researchers to look for alternative methods?

Researchers don’t get a budget to do animal studies, they get a budget to develop research as fast as possible, as safely as possible and as predicatively as possible to find a cause of a disease. Researchers choose their method of research selecting the most effective route that is also the quickest and cheapest. By law, they are not allowed to use animals in their research if an alternative method is available. Moreover, if there’s a way to do research outside the animal model they will, because using animals in research is more expensive and takes longer.

Do we need to continue medical research to find cures or preventive therapies for today’s and tomorrow’s illnesses and diseases?

The argument that we should just stop research and die at some age of something naturally…. what is nature? What is a natural life without therapy? Does it start with vaccines? Or when we use antibiotics? Or when we start using chemotherapy against cancer? The general public want to get healthier and grow older healthier, so industry and academia are following a societal mandate.

Women dying of breast cancer today aren’t old they are mothers raising kids. Nor are men with prostate cancer. People of all ages have allergies and asthma, plus with the impact of global warming, diseases like malaria will return to Europe. Advancing medical knowledge and therapy is a civil society choice. This isn’t something that industry can answer, this is something that society needs to answer and civil society is very clear; they want it.

Also read:

Zebrafish at the cutting edge of heart research

How did we arrive at the 3 Rs: Replacement, Reduction, Refinement?

As animal experimentation and dissection continued, opposition to it grew. First recorded in the seventeenth century, those against vivisection argued that an animal’s physiology could be affected by the pain caused during an experiment, therefore rendering the results unreliable. Others saw animals as inferior to humans and so different that results from animals could not be applied to humans.

In 1954, Charles Hume, founder of the Universities Federation for Animal Welfare (UFAW) in the UK made an original proposal to UFAW to take into consideration alternatives for animal testing and change scientific study in laboratory animal experiments.

The microbiologist Burch and the zoologist Russell were chosen to further develop the Hume’s proposal. "The Principles of Humane Experimental Technique" was published in London in 1959, and the book defined animal testing alternatives as “The Three R's: Refinement, Reduction, and Replacement.”

• Replacement refers to the preferred use of non-animal methods over animal methods whenever it is possible to achieve the same scientific aim.
• Reduction refers to methods that enable researchers to obtain comparable levels of information from fewer animals, or to obtain more information from the same number of animals.
• Refinement refers to methods that alleviate or minimize potential pain, suffering or distress, and enhance animal welfare for the animals still used.

Over the past 40 years the 3Rs have become widely accepted ethical principles, and are now embedded in the legislation and conduct of animal-based science.

Before any research can be performed, an independent panel must consider whether animals are required or whether suitable replacement alternatives exist. When animals are used, the investigator must consider how best to decrease the number of animals used to a minimum and/or how to maximize the amount of information obtained per animal (Reduction alternatives), and must identify potential harms and ways to minimize these (Refinement alternatives).

Also read:

Finding the right balance between animal welfare & human welfare

Zebrafish at the cutting edge of heart research