Orphan diseases, affect not more than 5 in 10000 people, With some 29 million sufferers in the EU;

The EU offers the pharmaceutical industry some incentives to investigate rare illnesses. According to the General Director of LEEM, Philippe Lamoureux, European-backed research into drugs for the treatment of orphan diseases has led to 68 new medicines approved between 2000 and 2011. But there are between 6,000 and 7000 different rare diseases, so these drugs help just a fraction of sufferers.

Where does animal testing fit into the orphan drug equation? It is present in preclinical trials – as is the case with all drugs – but would it be right to ban the use of animals in research when patients have so few treatments to choose from in the first place? The Journal of Animal Ethics proposes that doctors tell patients, or their carers, the role that animals played in the development of their medicines. If sufferers of rare illnesses had access to this information, would they refuse treatment?

Stopping experimentation on animals in the EU probably wouldn’t stop European patients using drugs that have been tested on animals. The problem would simply be relocated, with testing taking place further away, in countries with less stringent regulations. Banning animal testing could also lead to a slowdown in research, as scientists consider alternative means of testing. The question remains: would sufferers of rare diseases be able to wait?

Some believe that not enough is being done to develop orphan drugs. According to work published by three Italian pharmaceutical researchers, a lack of testing on recommended animal species may have affected the investigations of 24 molecules, candidates for treatment of rare diseases. So when it comes to orphan drugs, should there be more, rather than less, research?

Sufferers of orphan diseases already face limited treatment options. Take animal experimentation out of the equation, and drug development options shrink even further.

Given my interest in issues around animal testing, these timely reminders of the burden of disease got me thinking about the contribution that research has made to human health.

Survival rates from breast cancer have been improving for 30 years due in no small part to basic research using animals. Cancer is still to be dreaded however outcomes are much more promising than in the past and anti-cancer treatments are becoming more targeted (and so have fewer side effects).

These days it’s not uncommon to find cancer patients who want to be enrolled in phase III clinical trials so they have a chance of benefitting from the latest innovation medical science has to offer.

They believe new anti-cancer treatments, like chemotherapy, are safe – because they’ve been tested on animals – and they hope the drug will help prolong their lives.

What about non-fatal diseases?

Okay, so cancer is often put forward as a case where the deaths of animals in the lab ultimately helped prevent the deaths of people on oncology wards, albeit not in equal number.

But what about diseases like rheumatoid arthritis (RA)? This is a disease which too often strikes women in their prime. Statistics of woman effected vary slightly but stand at about 75%, compared to 25% of men. Unlike cancer, diagnosis of RA is not received as a death sentence – but it is a prescription for misery, pain, and a dramatic decline in quality of life.

Here we’re talking about a disease which is not immediately life threatening but which can prevent a young mother from playing with her children or heap severe strain on entire families.

Less than a decade ago, a new class of so-called ‘biologic’ drugs – monoclonal antibodies – arrived in doctors’ arsenals. Early work in this field was done using antibodies from mice and rats, and even now some of the human antibodies used in these therapies are produced using transgenic mice.

These drugs changed people’s lives almost overnight. Men and women with RA who could barely move – who couldn’t make a fist let alone drive to work – were given back a large portion of their independence.

‘Something must be done’

When we hear patient stories during awareness days/weeks/months, the visceral reaction is often to say “something should be done about this”.

Indeed it should. But what do we mean when we demand action? That science should find a cure or a treatment to end the suffering? Do we presume that this will involve animal research and, if so, are we okay with that?

So, dear reader, the question to you is:

How do we weigh animal suffering against the burden of human disease?

Is it okay to sacrifice animals to cure cancer? What about arthritis? Or depression? Or restless leg syndrome?

There’s no easy answers – but what’s yours?

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's in a name? Animal research vs testing vs experimentation
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

In online searches, animal testing is the most commonly used term and is used to represent any use of animals by scientists. However animal testing actually refers to the use of animals to test a substance – a drug, cream or chemical – that will be released into the environment. The substance is tested to see if it works, how it distributes in the body and whether it is toxic. Fewer than 20 per cent of lab animals are used for this purpose and it is a legal obligation demanded by various authorities before performing human testing (clinical trials).

‘Testing’ is done by the chemical industry, the pharmaceutical industry and academics. I was surprised to learn that the pharmaceutical industry is keen to stop animal testing and is actively looking for reliable replacements that will not compromise patient safety.

Animal experimentation is a general term to describe both testing and research and has a negative connotation. The term vivisection, is also negative and mainly used in the UK. It is associated to any type of animal-related testing and research. However vivisection actually refers to the dissection of living animals; the definition includes human surgery. In previous times this was done without anesthesia.

While the proportion of animals used for testing is declining, the proportion of animals used in ‘research’ is growing.

Animal research is carried out by the biomedical community – the pharmaceutical industry and academia. In terms of research, scientists are not obliged to do studies with animals, they use animals as models to better understand diseases and find ways to influence the cause of them. Essentially they look for an animal that has a disease similar to man, either naturally occurring or one that they can recreate through genetic modification. This is not testing, where an animal is exposed to compounds, this is research and accounts for 60 – 80% of the animals are used.

We regularly hear about medical advancement for diseases like cancer, which are reported in the press –“research with mice has uncovered a cure for x disease”. Yet do we, the general public, consciously make this connection between medical breakthroughs and the use of animals?

Some argue that it doesn’t matter what you call it, as animals are still suffering for the protection of man. However I think it’s important that we understand the terminology and use it properly to ensure we know what we fighting for, or against, and how this might impact our own lives.

Also read:

Finding the right balance between animal welfare & human welfare

What’s driving the increase in animal research?

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