It was only when animal rights groups began to put pressure on airlines and ferry companies to stop transporting laboratory animals that this came to our attention.

Researchers are concerned that research on non-human mammals, as well as studies involving frogs, insects and fish, could be hampered if companies refuse to transport animals which will be used in labs. This, according to scientists, could even disrupt the fruit fly research used to study genetics.

Interestingly, scientists and policymakers in India managed to convince Air India to reverse an earlier decision to stop transporting animals.

From a European perspective, one wonders whether researchers and politicians in India are more willing to publicly support medical research by working with transport companies and animal welfare groups to find solutions.

What do you think?

Now that the issue is on the agenda, it prompts a number of thorny questions. If animals could not be transported to labs, resulting in a decline in medical research, would this be a price we’re willing to pay?

Should animal welfare campaigners focus on the conditions under which animals are transported – and the length of the journeys they take – rather than on banning transport altogether?

Let us know…

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.

After an intense campaign by policymakers and animal rights groups, the Green Hill animal breeding firm closed its doors, having handed more than 2,500 dogs over to animal rights campaigners in line with the court ruling.

Activists – and plenty of ordinary tweeters who just love dogs – celebrated. If you almost never give much thought to animal research, a headline about dogs in Italy being saved rather than sacrificed looks like good news.

But could the Green Hill story prove to be a pyrrhic victory for animal rights campaigners?

A bit of background

The first thing to consider is how many dogs are used in animal research and why scientists have to use dogs at all.

Using dogs for cosmetics is illegal in Europe but limited use for medical purposes is permitted, under strict conditions.

Around 21,000 dogs were used in European research, according to figures from 2008. While rats and mice are the most commonly used animals in laboratories, larger mammals such as dogs are needed for certain kinds of tests. Many of these are required by EU regulations  to ensure that medicines are safe and effective.

In the event that all research on dogs were to end, much of the current work scientists do in search for new cures of heart disease, cancer and dementia would reach a cul-de-sac.

That might be bad news for human and animal health research but what about laboratory animals themselves?

NIMBY

Europe has the strictest animal welfare standards in the world. If European countries were to become openly hostile to this kind of medical research, would it simply move elsewhere?

Is it unfair to suggest that the campaign against Green Hill is a case of ‘Not In My Back Yard’ – or NIMBY as we like to say.

And are European protests simply going to shift research to jurisdictions where standards are less rigorous?

For pragmatic animal welfare advocates – and dog lovers across Europe – the threat to animal research in Europe presents a dilemma: would pushing dog breeding out of Europe do more harm than good?

The people who work with laboratory animals are a compassionate bunch who would gladly use alternative methods if they could deliver the same results.

Like many people who do what I do, I’d quite like to become redundant. That is, I’d be content if my current job were made obsolete by advances in science.

As a vet in charge of laboratory animal science at a large research-based pharmaceutical company, I would be delighted if other mechanisms were available that could answer the questions we need to answer.

Nobody becomes a vet without first having a love for animals. For those of us who work with laboratories, we are the ones who guarantee round-the-clock care for the animals and safeguard their welfare.

Some people wonder how one can describe themselves as an animal lover yet do this kind of work. I give the example of my own wife who is a heart fibrillation survivor. Thankfully she leads a normal life, having taken a drug for 20 years now, and she is in great shape.

However, the reality is that the drug that has helped her stay healthy was developed through research on animals. We love cats in our house and I have to explain to my kids that a lot of the basic research that led to better treatments for their mother’s disease was actually done on cats and dogs.

The promise of unimaginable

As things stand today, it’s hard to imagine a world where animal research has been replaced with alternative methods. To be frank, I don’t foresee this happening any time soon, but such is the beauty of science that it tends to throw up all manner of unforeseen – even unforeseeable – advances.

Using animals is complicated but for much of our research, they are the best we have.

Advances in cell culture have taken us a long way but there are times when we need to see how a potential therapy responds to hormones and biochemicals from several organs of the body. The only option is to test the drug in a whole animal.

Of course, the research methods of the past are not as good as those available today. Perhaps in the future we’ll look back and think today’s methods to be primitive.

As I said in my last post, the beauty of science is its uncertainty.

According to the World Economic Forum/Harvard School of Public Health, the NCDs are responsible for 63% of all deaths and are currently the world’s main killer. Eighty percent of these deaths now occur in low- and middle-income countries. Over the next 20 years, NCDs will cost more than 22.68 trillion EUR, representing 48% of global GDP in 2010. The WHO European action plan 2012 – 2016 and the OECD both stress the importance of gathering research evidence in the battle against NCDs.

As far as cancer is concerned, for example, Cancer Research UK stated, in 2011: “Thanks to decades of research, survival from cancer has doubled in the last 40 years”. But this progress simply wouldn’t have been possible without animal research. At Cancer Research UK, research using animals is an unavoidable part of our efforts to beat cancer. For a start, it’s a legal requirement in this country that all new drugs (not just cancer drugs) are tested in animals before they’re given to patients, to make sure that they’re safe to use. In April 2012 the organisation Animal Aid has called for Cancer Research UK and other medical research charities to stop funding animal research. In a perfect world, animal research wouldn’t be necessary. But cancer kills more than 400 people every day in the UK, and all our work is aimed at reducing this death toll.”

However, in marking World Laboratory Animal Day on 28 April, animal activists in Hyderabad, India, called for an end to using laboratory animals and suggested moving towards computer-based alternatives. Speaking on the occasion, Dr. Anjani Kumar, director of the animal welfare division in the ministry of environment and forests said: “Though it is far-fetched, there is a hope that in the near future super-computers and DNA-based models could replicate the human body’s functions virtually to enable drug trials.”

When asked whether the animal activists will force the government to ban the use of animals in laboratories, Mahesh Agarwal, secretary for a city-based animal rights organization said: “I do not see any new technology replacing the use of animals in the laboratories. So, until such ways emerge, it would seem futile if we press for a ban on the method, which will seriously impact new drug discovery. What we can say is handle animals with care and less cruelty.”

In short, are scientists too concerned about what they can achieve to stop to consider whether perhaps they should? Xenotransplantation, which is the transplantation of living cells, tissues or organs from one species to another, with the cells, tissues and organs in question referred to as xenografts or xenotransplants, is no exception, and is an innovation that is raising many novel medical, legal and ethical issues

While there appear to be few doubts that xenotransplantation could offer huge potential concerning the treatment of end-stage organ failure in humans, which is a significant health problem in many parts of the industrialised world, a major concern is that many of the animals used, including pigs in particular, have much shorter lifespans than humans, which means that their tissues age far more quickly. Given that the treatment is still very much in its infancy, this concern along with disease transmission (xenozoonosis) and even permanent alteration to the genetic code of animals are being cited by opponents as scientists archetypally ‘playing God’. While whole-organ xenografts have thus far been unsuccessful, less radical transplants have demonstrated great success. Hundreds of thousands of patients have received pig-heart valves since 1975, when the procedure first became commercially available. Cow-heart valves have likewise been used in humans since 1981.

Xenografts involving human beings have been a controversial procedure since they were first attempted by Dr. Keith Reemtsma between 1963 and 1964, in which 13 chimpanzee kidneys were transplanted into humans. Twelve of the 13 recipients died within two months, while the thirteenth survived for nine months after the procedure. Animal-rights groups in particular strongly oppose killing animals in order to harvest their organs for human use while certain religious beliefs, such as the Jewish and Muslim prohibition against eating pork, have been similarly problematic, however according to Council of Europe documentation, both religions agree that this rule is overridden by the preservation of human life.

Additional ethical issues include the informed consent complexities for research subjects, as well as the selection of human subjects, rights of patients and medical staff and public education (as companies may proceed with experiments without public awareness).

Obstacles arising from the response of the recipient’s immune system, specifically the rejection of the xenograft, which can in some cases result in the immediate death of the recipient. The types of rejection that xenograft patients face include hyperacute rejection, a rapid and violent type of rejection that occurs within minutes to hours from the time of the transplant, and is caused by the binding of XNAs (xenoreactive natural antibodies) to the donor endothelium, which activates the human complement system resulting in endothelial damage, inflammation, thrombosis and necrosis of the transplant.

On the other hand, a patient who is already very near to death because of a failing liver or heart is very likely to be willing to risk anything to save his or her life – does any animal-rights activist, no matter how sincere or well intentioned, have the right to deny such patients the chance to prolong their lives?

In addition, there is a worldwide shortage of organs for clinical implantation, with around 60% of patients awaiting replacement organs dying on the waiting list. In many cases there is so little chance of a person actually receiving a transplant, doctors do not even add the person to the list – is it not therefore reasonable to consider the engineering of organs from other species to attempt to minimize the risk of serious rejection, be used as an alternative to human tissues and possibly end organ shortages?

There can be no doubt that the issue is vexed. For readers who want to know more, a good, balanced account of the pros and cons is provided by the following lecture on YouTube, while The Future of Healthcare in Europe, a report released as part of the European Commission’s Europe 2020 Strategy, also raises some interesting questions on xenotransplantation.

Clearly Xenotransplantation has a lot of room for improvement, but should we be doing it at all? What’s your view?

At the core of the issue is the increasing refusal, as reported in the Daily Telegraph and elsewhere, of ferry companies and airlines to carry live mice, rats and rabbits intended for scientific research, following pressure from animal-rights campaigners.

UK Science Minister David Willetts has said that “it would be a pity” if the animal-transportation process was forced to be handed over to the military but, with Stena Line reportedly now having followed DFDS Seaways and P&O Ferries in prohibiting the carriage of test animals and thus closing the last available sea route for medical, researchers are despairing of the situation, given that no UK-based airline nor the Channel Tunnel operators will operate such a service.

The proportion of imported animals used in UK research is relatively small, but researchers stress that access to genetically modified strains bred overseas is vital for certain advanced research techniques. According to scientists, as they strive to improve understanding of diseases and to develop new treatments and cures, alternatives to using animals in research are sometimes not available. Moreover while the vast majority of animals used in the UK for research are bred in the UK, modern scientific research is highly collaborative and global. For example in certain research programmes it is essential that scientists share specific genetic strains of animals, which take a long time to breed. If their transport is stopped then researchers will have to recreate them, requiring the unnecessary use of many more animals over successive generations.

Most headlines put it stridently, with ‘not importing animals puts human lives at risk’ being the gist – Willetts, also speaking with BBC Radio 4's Today programme said that it was is “a serious problem that we do need to tackle”. He added that Britain should be proud of the fact that it developed many of the world's top drugs, and that scientists carrying out animal testing needed to be done so in carefully-controlled conditions complying to "high standards of animal welfare", which the UK Home Office is also very keen to stress. The European Commission, citing Regulation 1/2005, is also keen to stress the “effective monitoring tools in place”. So what are the animal rights campaigners trying to stop?

Essentially, research-animal transport supporters are asserting that a moratorium, as has been actively supported by animal rights groups, would in fact not improve animals’ welfare, given that longer routes and organisations with less experience would have to be used.

So which way now? Scientists are adamant that stopping the transport of animals would harm UK medical research but, with an issue that is as emotive as animal testing, and its opponents seemingly not prepared to budge an inch, Britain’s already overstretched armed forces may soon find themselves providing an unusual kind of taxi service.

Is this kind of animal rights activism improving or aggravating the welfare of animals? What’s your view?

Advances in science will present some people with new dilemmas. What if new research methods mean more primate-based studies but using fewer animals overall?

The latest trends in biopharmaceuticals will make it possible to develop fragments of antibodies – some of which can be used as new therapies – without using as many mice or rats as would have been required in the past.

The early stages of research can be done using large volumes of cell samples and with the help of computer modelling, so we essentially skip the animal-intensive phase of early research where large numbers of potential therapies would previously have been tested on rodents.

Now we are moving into an era where we will find ourselves with a smaller number of candidates – let’s call them ‘could be’ therapies – which are ready for the next stage.

However, these antibodies are so highly specific to primates, the group to which we as humans belong, that testing in rodents is less likely to be succesful. Trying out new biological therapies in humans is a non-runner: some will not work; others could have serious side effects. The upshot is more primate research.

If we carry out studies using, for example, dozens more monkeys but it means thousands of fewer mice are needed, will this be more or less controversial?

Refining research methods

All of this brings me to the question of how we define progress in animal testing. In Europe, the focus has been squarely on the 3Rs – reduction, refinement and replacement.

There is, in my view, a particular emphasis on replacement. But rather than look exclusively at the absolute number of animals involved, we should consider the methods being used and the quality of science being produced.

‘Refinement’ is in danger of becoming the forgotten ‘R’. The total number of animals being used in Europe has been more or less constant in recent years but investment in science has increased and the output has also risen.

So research activity has actually increased without a major leap in the use of animals. To me, this is progress, but if you look only at the total number of animals used in research, it looks like we’re going nowhere fast.

Transgenic and humanised animals

Other developments in animal research – like the ability to breed transgenic animals in order to design highly specific experiments – have also had an impact on the quality of science. We have also been able to create mice that accept an exchange of their mouse blood with human blood, thereby creating an animal that is able to be infected with parasites that only infect human beings.

For example, it was once feared that studying how the parasite which causes malaria affects humans would not be possible using animal models. However, humanised mice allow us to do things never thought possible. These mice allow us to test new drugs that are targeted to the very parasite that causes such havoc in humans in many parts of the world.

Good news? For me, the answer is yes as it opens the door to a deeper understanding of malaria.

Others dislike the idea of creating transgenic or mutant animals because they see it as unnatural. Indeed it is. But if it’s natural to die from a mosquito bite then most will agree that ‘unnatural’ interventions are morally acceptable – if not imperative.

A new era

My point is that science is moving towards an era which will force us to confront difficult questions.

• Will we accept more primate research if it reduces the use of large numbers of rodents?
• How should we view the huge growth in transgenic and other modified animals given the potential benefits for animals and humans?

Philosophical debates, like science, often presents us with complex equations; equations which perhaps cannot be solved by reliance on simplistic interpretations of the 3Rs.

We ought to focus on the quality of our animal science rather than zeroing in on the quantity alone.

That’s how Usher Syndrome, a rare untreatable genetic disease leading to deaf blindness, first became a part of our lives. You can imagine the emotional rollercoaster, taking us from feeling a sense of shock and injustice to the struggle of dealing with an ‘unacceptable’ situation.

We felt like we had a mandate to fight for a change on behalf of our sons; to fight for a cure or a therapy. Because Usher is also a family affair we combined our efforts with families who had the same or a similar situation. It was then that we realised that we were not alone. Other people – other families – were facing the same challenges.

It’s been a long and winding road through uncharted and unfamiliar territory. Along the way, we received inspiring support from patient-focused researchers and highly-motivated scientists working on a tissue engineering approach to tackling Usher Syndrome.

Their work involves exploration of techniques such as gene therapy or cell therapy. Unlike amphibians and birds, the regeneration of a missing or dysfunctional cells does not take place in humans. Therefore the molecular genetic approach requires an appropriate animal model to understand the disease biology in humans.

Years ago, we could see from a role model, Lanzelot, a Briard Dog with a natural retinal degenerative disease, that gene replacement therapy using a viral vector does work: Lanzelot was treated and cured with this technique, he could run and play with all the other dogs after his treatment. It was the first time of the proof of a principle we all had dreamed about: It’s ironic that our hope for a cure came from an animal with a disease, Lanzelot – and meanwhile more than 50 dogs were involved in the research which gave us the promise to find a solution for our children.

After initial tests with lower species like zebrafish, the test results with a mouse mutant animal model could not be translated into humans, confirming the skepticism of researchers that “…mice tell lies…”.

Those were difficult days and we had to look for further, properly regulated, animal research as no non-animal alternatives or other second-best options are available.

After having tried out all other options with in vitro experiments on cell tissue, computer-animated models and so on, in the end an appropriate animal model cannot be excluded as a last resort, before you start clinical trials with human patients.

Living with a severe disability in these days of expectation and hope for a cure for an untreatable condition like Usher also sharpens our view and perspective on the animal research debate. First it is worth mentioning, that none of us are in a position to define what’s ethical what’s not. Furthermore, when weighing the merits of animal research, it’s important to take account of its purpose. One has to clearly differentiate between testing new cosmetics and efforts to heal patients suffering from severe disabilities.

I can see a social and emotional tendency to pit “animal welfare” against “human welfare”. An illness with the gravity of Ushers stands for the dark side of life. And, if Paul Ehrlich was right to refer to life as chemical incident, in our case it’s more like a chemical accident.

In line with the WHO, the “Constitution Of The World Health Organisation” health is defined as follows: “Health is the state of complete physical, mental and social wellbeing. The enjoyment of the highest attainable standards of health is one of the fundamental rights of every human being“. Further on, the “Convention On The Rights Of Persons With Disabilities” states that all people “…have equal rights to education, employment and cultural life…”.

While we would all prefer to live with a good genetic passport, some of us are living in the kingdom of the sick. Therefore, and from the above-mentioned social contract, our society owes it to people with disabilities to provide the necessary “facilitators” including research in cases like Usher.

I can see no dilemma between different ethical positions if one can agree to respect the scientific rationale for research in severe diseases, if there are no non-animal alternatives!

I ask for respect within the animal welfare debate for all who take a diverging opinion. Caretakers, research scientists and doctors are fighting for a better future life of our patients to end the drama of Usher. I stand for the mandate of my sons like all the others in the medical arena and believe in the basic ethical fundament of our Christian civilisation – called “humanity”.

In the past, researchers were celebrated as the catalysts of a better future.  Today they are portrayed as cynical sinister characters “from Einstein to Frankenstein”.

In the stem cell debate the rivalry for ethical supremacy has taken an absurd focus: if the desire to cure very sick people is defamed as utilitarian thinking, a fair discussion is no longer possible. It is all a matter of weighing up ethics, humanity and confidence in treating suffering human beings who can only hope for a cure.

PHOTO CREDIT: NIDCD

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.