Author Archives: Blue Sky Science

Stop vivisection Initiative fails to impress at EU hearing

In March we discussed a new attempt by animal rights supporters to ban animal research in Europe, The Stop Vivisection European Citizens’ Initiative, which was signed by  1.2 million people (half of them in Italy). The initiative calls for “the European Commission to abrogate directive 2010/63/EU on the protection of animals used for scientific purposes and to present a new proposal that does away with animal experimentation”. On Monday 11th May the organizers of the initiative had an opportunity to present it to a joint session of  several European Parliament committees, in a hearing that was also addressed by scientists who spoke in favor of keeping directive 2010/63/EU.

So how did it go?

Well, an editorial in last week’s edition of Nature gave a fair assessment of it when they described the session as “a pretty grey affair” in which the duo who presented the initiative – Gianni Tamino and Claude Reiss – “spoke calmly but unconvincingly” to a half-filled auditorium. A transcript and summary of the key points made by the European Animal Research Association and put together the key points that were said during the meeting (download here) indicates that the initiative is almost certain to fail in its objective of  persuading the EU Commission to repeal Directive 2010/63/EU.

European-Parliament

A look through the EARA report  shows why. Any MEPs (Members of the European Parliament) hoping to hear new evidence from Dr Ray Greek and Dr Andre Menache, the scientific advisors who the Stop Vivisection Initiative organizers had brought along, were in for a  disappointment, as instead they presented a veritable greatest hits of anti-vivisection claims. Their testimony included Dr Ray Greek’s trademark  misrepresentation of what “prediction” means in biomedical research, while Dr Menache reheated the old 0.0004% myth. Surprisingly, these were far from being the worst claims made by supporters of the Stop vivisection initiative. Particularly low points came when MEP, and initiative supporter,  Anja Hazekamp stated that there has been massive increase in animal testing (The EU’s own statistics show the opposite) and when Claude Reiss, one of the organizers of the Stop Vivisection petition, ventured deep into conspiracy theory territory with a claim that there is a patent on HIV treatment that completely cleans the virus from the body, but has not been developed because it is not profitable.

In contrast the voice of science was very ably represented. Professor Francoise Barré – Sinoussi, 2008 Nobel Laureate in Physiology or Medicine for her role proving that HIV causes AIDS, put forward a very strong case for the importance of animal research in advancing medicine, and repeatedly demolished false claims made by anti-vivisectionists, particularly claims that animal research had not made a useful contribution to HIV research and the development of a vaccine against HIV infection. On this she is on safe ground as there is no doubt that animal research has made very important contributions to HIV research and development of therapies (for examples see here, here and here), and while development of an effective vaccine has been slow – because it’s very, very difficult – there has been real progress in recent years, and most HIV experts is that studies in  non-human primate models of the infection have a critical role to play in evaluating potential vaccination strategies.

Francoise Barré - Sinoussi, undoubted star of the EU parliament hearing.

Francoise Barré – Sinoussi, undoubted star of the EU parliament hearing.

Throughout the hearing one very important voice was conspicuous by its absence, that of the patients who rely on medical research. MEP Françoise Grossetête, who spoke in favor of retaining Directive 2010/63/EU, noted in particular that EURORDIS, the organization that represents rare disease patients in Europe, had not been invited to present evidence at the hearing. We hope that the EU commission will now actively seek the advice of EURORDIS and other European patient organizations before making their final decision.

What happens now?

At the hearing the Vice-President of the European Commission confirmed that the Commission will provide a formal response to the initiative by 3 June 2015. On the basis of what we saw at the hearing, and the fact that the majority of MEPS present were in favor of retaining Directive 2010/63/EU, it is a near certainty that the EU commission will reject the Stop Vivisection initiative and retain the Directive.

In 2017 the Directive will undergo it’s first 5 year review, which is likely to focus on its implementation across the EU, but the commission have also promised to organize a scientific conference that year to discuss the validity of animal research. With that in mind it’s good to see that last week’s Nature editorial noted that scientists across the EU are becoming increasingly – and refreshingly – vocal on the need to support animal research as a pillar of scientific and medical progress. In recent weeks we’ve seen thousands of scientists sign a motion of solidarity with a neuroscientist targeted by animal rights extremists in Germany, more than 140 research organizations, patient organizations, medical research funders and scientific associations sign up to a statement in support of Directive 2010/63/EU, Sixteen European Nobel laureates publish an open letter in UK and German newspapers to rebut the Stop Vivisection campaign. We’ve also seen several excellent letters appear in the national press, including a letter in the Times by Steve Ford, Chief executive of Parkinson’s UK, on the importance of animal research, and articles such as that written by Oxford University Duchenne muscular dystrophy researcher Professor Kay Davies.

The Stop Vivisection Initiative may have almost run its course, but the threat to the future of biomedical science in the EU is sadly never very far away. We hope that the current re-invigoration of the European scientific community continues, and that scientists strengthen and expand their engagement with politicians, journalists and citizens in the run-up to 2017 and beyond.

Speaking of Research

Zebrafish: the rising star of animal models

Today we have a guest article by Jan Botthof, a PhD Student at the Cambridge University Department of Haematology and the world renowned Wellcome Trust Sanger Institute. Together with the EMBL-European Bioinformatics Institute – with which it shares the Genome Campus a few miles south of Cambridge – the Sanger Institutes is one of the World’s top centres of expertise for genome research. As EMBL-EBI’s associate director Ewan Birney highlighted in a recent article for the MRC Insight blog, by studying the biology of a wide variety of model organisms – including humans and zebrafish among many others – the more than one thousand scientists working on the Genome Campus a gaining critical insights into biology that are advancing 21st century medical science.

When most people think of animal research, they imagine mice, rats or maybe fruit flies. However, other models are increasingly being used in addition to the more traditional organisms. The number of zebrafish (Danio rerio) in particular is steadily increasing in biomedical research each year. You might be wondering why scientists are using fish instead of animals more closely related to humans for their studies. Let’s have a look at some of the advantages of the zebrafish to explain this matter. This list is obviously not going to be comprehensive, because many advantages are field-specific and quite technical, but it should give you an idea why researchers might want to choose fish over other animals.

The zebrafish, a rising star star of medical research.

The zebrafish, a rising star star of medical research.

First of all is something that makes zebrafish more attractive to scientists who pressed for time, such as PhD students wanting to graduate punctually (like me!): zebrafish reproduce at a rapid rate. Each female can lay several hundred eggs each week, which will develop into mature adults in about three months. This is especially useful if you need to breed a large number of animals very quickly, or when you want to cross several lines with modified genes. Rapid breeding also greatly reduces the time it takes to introduce novel genetic modifications into the animals, as several generations are required before a stable modification of the gene in question is achieved. This makes zebrafish a very efficient species for research.

4-day old zebrafish embryo.

4-day old zebrafish embryo.

Another really useful trait of zebrafish is that their embryos are relatively large and initially transparent. This makes it easy to manipulate the embryo, which is very helpful if you are injecting various substances to modify their properties. In my case, I’m using a technique called CRISPR-Cas9 to very precisely switch off certain genes, but there are many other applications.  An added advantage is that you can treat these embryos chemically to stop pigmentation from forming, making it very easy to study early embryonic development (Figure 1). Moreover, the embryos are permeable to many chemicals and drugs – making them ideal for screening large numbers of toxicology samples or drug candidates.

The zebrafish genome has been fully sequenced, which is a must-have for model organisms nowadays.  This effort showed that their genome is remarkably similar to the human one, with at least 70% of human genes having a zebrafish equivalent – a figure that is even higher when only disease-causing genes are considered. There are also efforts underway (by the same group that sequenced the zebrafish genome, which coincidentally happens to be right next to my research group) to mutate every single gene in the zebrafish genome. This can be very helpful if you study a certain gene and wonder what happens to the whole organism when it is lost – and having such large scale resources can save the wider research community huge amounts of time and effort.

Apart from fish with mutations in specific genes, there are also numerous lines containing genes from other organisms (transgenic lines). Usually the proteins encoded by these genes are fluorescent and are used to mark specific cells, as we can control (at least partially) in which tissue a protein is made. One of these is called green fluorescent protein or GFP (originally from a jellyfish). Using techniques such as GFP it is possible to visualize changes in specific cell populations in real time in living animals. Just to give you a personal example: I study blood development, so naturally I want to look at the different types of blood cells. Depending on what cell type I want to look at, I can select an appropriate zebra fish line, where this type is labelled. For an example, have a look at Figure 2, which shows early blood cells during embryonic development labelled with GFP. As these fluorescent proteins come in different colours, it’s possible to look at two or more different cell types at the same time.

A recent advance is the generation of fully transparent adult zebrafish, aptly named “Casper” after the popular cartoon ghost. You can look up the freely available original paper here if you want to see what these fish look like. Of course, scientists are not making transparent fish just because they look cool, but they are very useful tools for research. One application is the easy study of tumour metastases, as the cancer cells are just much easier to spot in transparent fish. Adding fluorescent labelling as described above can make this technique even more powerful.

Usually when we use zebrafish, we take advantage of the fact that many fundamental processes have been evolutionary conserved between fish and humans. Because of these similarities, we can use zebrafish as a model for what happens in humans. Sometimes differences between animals and humans can be more telling though. For example, many animals can regenerate much more efficiently than humans (you might have heard about the ability of salamanders to regrow lost limbs or tails) and this is also true to some extent for zebrafish. One very well studied research area is heart regeneration. Humans are unable to regenerate heart muscle tissue, which is of course problematic when parts of it die off during a heart attack or following injury. In contrast, zebrafish can use stem cells to regenerate the lost tissue – if we could induce a similar process in humans, it might help treating people recovering from cardiac injury. The British Heart Foundation is funding important research in this particular field through its “Mending Broken Hearts” campaign. In the even longer term, it might be possible to adapt similar principles to other tissues and thereby help in treating a variety of injuries.

The regenerative capacity of zebrafish isn’t only interesting for medical research, but it has a very practical advantage: you can cut a tiny part of the tail fin off and use it to extract DNA from the tissue. Then, the mutation status of a specific gene can be determined, which is essential when you want to know whether an animal is a carrier for the mutation you are interested in. The fin then grows back within two weeks, so the animal is not harmed.

Lastly, I just want to mention some financial considerations. Animal research in general is really expensive, which is one of the reasons why alternatives are used whenever possible. These costs are largely determined by how much effort and space is required to house, feed and care for the animals. Of course, this makes large or exotic species especially expensive, so they are used less often. However, even rodent colonies can cost quite a lot of money to maintain. Zebrafish require much less space per individual, are relatively inexpensive to feed , and it’s also relatively straightforward to ship animals (usually as embryos) between labs. This facilitates collaborative research and reduces the number that need to be used, since they don’t have to recreate the same genetically modified line all over again.

In conclusion, zebrafish have a lot of useful characteristics that make them very practical and useful model organisms, which explains their rising  popularity among researchers.

In the next article of this series, I’m going to have a closer look at zebrafish care, as well as daily work in a fish facility and some of the rules and regulations surrounding fish welfare.

Jan Botthof

Max Planck neuroscientist abandons primate research due to animal rights lies and harassment

To show your solidarity with Professor Nikos Logothetis please sign this open letter published by neuroscientists at the University of Tubingen.

http://www.cin.uni-tuebingen.de/sign-open-letter.php

Last week by Professor Nikos Logothetis of the Max Planck Institute for Biological Cybernetics in Tubingen, Germany, announced in an email to colleagues that he will no longer use non-human primates in his research into the physiology of cognitive processes, and that the work of his team will in future focus on rodent studies. This announcement is a major blow to neuroscience research in Germany, and indeed in the EU as a whole. His decision also raises serious question as to what more the Max Planck Society, and indeed Nikos Logothetis’ fellow scientists in Tubingen and further afield could and should have done to publicly support him and his colleagues over the last few months.

Nikos Logothetis

Nikos Logothetis has long been recognized as one of Europe’s top neuroscientists, with a particularly strong track record in improving MRI techniques and technology (see also this Nature review), and  has also been one of the few neuroscientists and primate researchers in Germany to regularly engage with the media, and to explain to the public the importance of work being done in the institute and how they ensure the welfare of the research animals.

On 12 September 2014 German animal group Soko Tierschutz, in collaboration with the British Union for the Abolition of Vivisection (BUAV), published video footage taken by an infiltrator purporting to show mistreatment of monkeys at the Max Planck Institute for Biological Cybernetics.  The allegations were investigated by the Max Planck Society and animal protection authorities in the state of Baden-Württemberg, who cleared the institute of any major animal welfare infringements (the MPS decided afterwards to provide additional funding to the institute for minor improvements to one area of animal care provision), while a third investigation by local Tübingen authorities is still ongoing. That the allegations made in the SOKO/BUAV video appear to have been highly misleading should come as no surprise, we have seen only a few weeks ago in Cambridge how BUAV laboratory infiltrators manipulate and distort the facts, and even stage footage of distressed animals, to further their agenda.

Nikos Logothetis has issued a full and detailed rebuttal of the allegations made by the BUAV, which you can download here, pointing out where they had misrepresented veterinary and post operative care. He also discusses how the infiltrator produced footage of monkeys exhibiting stereotypical movement patterns:

Lastly, in their effort to “disclose” the animal suffering in our institute, BUAV/SOKO presented a couple of animals with unusual stereotypical movement patterns, such as animals continuously turning in circles. Such behavior patterns are often observed in animals living in small single-animal cages. Our monkeys are held in a natural group setting with an enriched, stimulating environment. Small cages are only used for short times, i.e. if there is some need to separate an animal from the group, e.g. for medical treatment Such stereotypical movements have not been witnessed in our facilities for over 16 years. They can, however, be induced by any person standing too close to the cages, in particular when the animal is in a small cage and becomes nervous. In the filmed case, such stereotypical movements were almost certainly induced intentionally by the caregiver.

Deliberately inducing distress in lab animals and subsequently using the footage thus obtained in propaganda is of course a familiar animal rights tactic.

surgical-suite-of-prof-logothetis

The surgical suite at the Max Planck Institute for Biological Cybernetics

Unfortunately, the Max Planck Society (MPS) took almost a week to issue a statement in support of Nikos Logothetis in response to the SOKO/BUAV allegations, too little and far too late to influence most of the media coverage. Likewise the Society for Neuroscience and Federation of European Neuroscience Societies issued a statement of support, but again far too late to impact on the initial coverage. While some news reports  in the intervening days were factual and balanced, many were not, and the result is that Nikos Logothetis and his colleagues have been subjected to months of character assassination, hate mail and harassment. Some politicians have since spoken up in support of Nikos Logothetis, but  the response of the other Max Planck Institutes in Tubingen left a lot to be desired, with one simply issuing a statement saying they didn’t conduct primate research, and there’s no doubt that this and similar dishonorable behavior by others in the research community contributed to Nikos Logothetis feeling that he and his colleagues had been badly let down.

The MPS has now responded to news of Nikos Logothetis decision to cease primate research with a statement condemning the threats and abuse that Nikos Logothetis and his colleagues received and reiterating their strong support for non-human primate research (in Tubingen and elsewhere).

The Society will continue to conduct research involving nonhuman primates, as it believes that this is still the only way to develop therapeutic approaches for neurological brain disorders such as Alzheimer’s or Parkinson’s disease, and psychiatric disorders as schizophrenia. The Max Planck Society will also promote innovative approaches to research in the field of primate research in the future.

This commitment from the MPS is very welcome, and we hope it is a sign that they are moving towards take a much stronger public position on the importance of animal research, and will in future make greater efforts to engage with the media and the public on this important issue. In the past the MPS has been somewhat lukewarm when it comes to public outreach on potentially controversial topics in research; if nothing else the Tubingen debacle shows that such hesitancy is ultimately counter-productive.

We have written many times on this blog on the need for scientists and supporters of biomedical research –  as individuals and as societies and institutions – to speak up for science and animal research, and we stand ready to help and advise those who agree that remaining silent is no longer an option.

We would like to take this opportunity to express our solidarity with Nikos Logothetis and his colleagues at the Max Planck Institute for Biological Cybernetics in Tubingen. Lets now make sure now that no scientist in Europe ever has to go through what they experienced again!

Speaking of Research

Animal research openness in action – from Cambridge to Florida

Last week we published an article calling on all involved in animal research to speak up for science as animal rights activists held their annual World Week for Animals in Laboratories (WWAIL), writing:

This year, if your university or facility is among those that attract attention during WWAIL, we ask that you join in the conversation by providing protestors, public, and media your own voice.  Whether it is via banners, websites, or talking with reporters– speak up for science and for public interests in advancing scientific understanding and medical progress. Although it may not matter to those committed to an absolutist agenda, it can matter to those who are interested in building a dialogue based in fact and serious consideration of the complex issues that surround public interests in the future of science, health, and medicine.”

The past few days have seen several great examples of just the sort of engagement with the public that we had in mind, including videos form two top universities in the UK that take viewers inside their animal research facilities.

The first comes from the University of Cambridge, who have published a video entitled “Fighting cancer: Animal research at Cambridge”, which focuses on how animals used in research are cared for and how the University implements the principles of the 3Rs. It includes interviews with Professor Gerard Evans of the Department of Biochemistry, who uses mice in studies of lung and pancreatic cancers, and Dr Meritxell Hutch of the Gurdon Institute, who has developed 3D liver cell culture models that she uses to reduce the number of mice required for her studies of tissue repair and regeneration, as well as with members of staff as they care for the animals.

The second example is another video, this time from Imperial College London, which also show how research staff care for the animals used in research, and features an interview with Professor of Rheumatology Matthew Pickering, who studies the role of complement proteins in liver damage in mice.

For the third example we cross the Atlantic to South Florida, where animal rights activists are trying to close down several facilities in Hendry County  that are breeding monkeys for medical research, a service that is hugely important to biomedical research. One of the companies being targeted by the animal rights campaigns is Primate Products, so we were delighted to see Dr. Jeff Rowell, a veterinarian and President of Primate Products, speak up about the vital work they do in an interview with journalist Amy Williams of local news outlet News-Press.com.

Primate products

During the interview Dr. Rowell discusses how the work of Primate Products is misrepresented by dishonest animal rights campaigns, including the inaccurate and malicious allegations made by the group Stop Animal Exploitation Now (SAEN) in 2010. As we discussed in a post at the time, these allegations were based on the deliberate misrepresentation of photos taken during veterinary care of injuries several macaques received in fighting with other macaques when housed in social groups (a normal though infrequent behaviour in the species in the wild and in captivity).

The News-Press.com article also shows that there is still a lot of work to be done to improve openness in animal research, as the three other companies that are breeding monkeys for research in Hendry County refused to speak with the Amy Williams, a shame considering that it was their decision to base themselves in the county that triggered the current animal rights campaign. While they are justifiably nervous of speaking with the press (some journalists and publications are arguably beyond redemption) the truth is that the “No comment” approach works for no-one apart from those who oppose animal research. In speaking at length with Amy Williams, Jeff Rowell has provided an excellent example that his colleagues in Hendry County would do well to follow.

The initiatives we have seen from the University of Cambridge, Imperial College London, and Primate Products over the past few days are extremely welcome, and we applaud them for their efforts. Nonetheless, we acknowledge that the future of medical science will never really be secure until they are the norm rather than the exception.

Before we conclude, it’s worth noting that it’s not just in the US and UK that researchers are beginning to realise the importance of openness in animal research to counter misleading antivivisectionist propaganda. In Italy Prof. Roberto Caminiti, a leading neurophysiologist at the University La Sapienza in Rome whose work is currently being targeted by animal rights activists, was interviewed recently for an excellent video produced by Pro-Test Italia, in which he discusses his primate research and how it is regulated.

Speaking of Research

Animal Research and the 2015 UK General Election

On May 7th 2015 the British voters will flood to the polls to determine the next Government (which for the second time in a row is likely to be a coalition). The political landscape has changed a lot since the 2010 election resulted in a Conservative-Liberal Democrat Coalition, with the rise of several smaller parties including the United Kingdom Independence Party (UKIP) and the Scottish National Party (SNP). The negotiation process of forming a coalition will mean that smaller parties can make demands on the largest parties (Conservatives and Labour) to secure a coalition agreement.

In the last week the parties have released their manifestos, outlining what they promise to do over the next five years if they are elected into Government. Many of the manifestos have specific pledges relating to the use of animals in medical and scientific research (which is supported by around two-thirds of the British population).

Nature and the Guardian have analysis of what the parties and their  manifestos say about science in general, so this article will concentrate on policies specific to regulation of animal research.

UK General Election 2015

The Conservatives Conservative animal research

The Conservatives (or “Tories”) are the larger of the two parties in the 2010-15 ruling Coalition. Their manifesto’s only mention of animal research says:

“We will encourage other countries to follow the EU’s lead in banning animal testing for cosmetics and work to accelerate the global development and take-up of alternatives to animal testing where appropriate.”

This fits the business-focused Conservative messages. The Coalition Government’s 2014 Delivery Plan on “Working to reduce the use of animals in scientific research“, which called for the UK to “develop an international strategy towards the eventual eradication of unnecessary animal testing of cosmetics products, adopting a science-led approach” (2.2.3).

The Labour Party Labour animal testing

Labour is the second largest party in British politics, currently neck and neck with the Conservatives. Their manifesto mentions hunting, protecting dogs and cats, and defending the UK ban on hunting with dogs, but does not mention animal research explicitly anywhere. Separately, Labour released a manifesto called “Protecting Animals“, signed by the Labour leader which expands on the main manifesto, but similarly lacks any specifics on animal research.

During their previous term in government, which ended in 2010, Labour established the National Centre for the 3Rs, and implemented legislation to stop campaigns of harassment and intimidation against scientists by animal rights extremists.

The Liberal DemocratsLiberal Democrats animal experiments

Traditionally third party in British politics, the Liberal Democrats (or “Lib Dems”) were in Coalition with the Conservatives during 2010-15. The last two Home Office ministers in charge of animal research – Lynne Featherstone and Norman Baker, have both been from the party. Their manifesto states (p82):

“Liberal Democrats believe in the highest standards of animal welfare. We will review the rules surrounding the sale of pets to ensure they promote responsible breeding and sales and minimise the use of animals in scientific experimentation, including by funding research into alternatives. We remain committed to the three Rs of humane animal research: Replace, Reduce, Refine.”

Under the 2010-15 Coalition, funding for the National Centre for the 3Rs rose from £5.3 million to over £8 million. The manifesto also uses the word “minimise” rather than “reduce”, so as not to focus on baseline figures, but on the 3Rs – preventing a repeat of confusion over terminology surrounding early Coalition pledges.

The Scottish National PartySNP animal studies

Buoyed by the Scottish Independence Referendum, the Scottish National Party (SNP) look to be mopping up almost all the Scottish seats in (the Westminster) Parliament, and will likely become the third largest party. Their manifesto promises “further animal welfare measures” but does not specifically mention animal research. They separately promise to increase funding for Motor Neurone Disease, which would likely involve animal studies.

While no other party is likely to reach over 10 seats in parliament (of 650 seats), the following parties are still worth mentioning (of these, only the Democratic Unionist Party (in Northern Ireland) is likely to get over 5 seats).

United Kingdom Independence PartyUKIP animal testing cosmetics

UKIP are a relatively new party at the far right of the British political spectrum. While their polling suggests them getting around 10-15% of the vote, they are unlikely to get more than 3 seats in parliament. Their anti-EU platform means they believe that the UK “can only regain control of animal health and welfare by leaving the EU”. Their manifesto calls for:

  • “Keep the ban on animal testing for cosmetics;
  • Challenge companies using animals for testing drugs or other medical treatments on the necessity for this form of testing, as opposed to the use of alternative technology;
  • Tightly regulate animal testing.”

It would appear that UKIP are trying to put in place the existing UK regulatory system. As Chris Magee, from Understanding Animal Research, says:

“these aren’t bad policies – but we know this because they have been working effectively for at least the last 29 years.”

The Green PartyGreen party ban animal experiments

The Green Party have recently surged in British politics, but are unlikely to make gains beyond the single seat they currently hold.

Their manifesto reads like it was written by the animal rights group, the BUAV:

  • “Stop non-medical experiments, experiments using primates, cats and dogs. End the use of live animals in military training.
  • Stop the breeding and use of genetically altered animals.
  • End government funding of animal experimentation, including any that is outsourced to other countries.
  • Provide greater funding for non-animal research methods and link funding to a target for developing of humane alternatives to animal experiments.
  • Increase transparency and ensure publication of all findings of animal research, including negative findings.
  • Introduce a comprehensive system for reviewing animal experiments and initiate a comparison of currently required animal tests with a set of human-biology based tests.”

Four of these pledges have analogues among the BUAV pledges, and it would similarly result in the end of over 80% of animal experiments in the UK. Quite simply, this policy is a disaster for human and animal health. Interestingly, both the leader of the Green Party (Natalie Bennett), and their only MP (Caroline Lucas), have both signed the BUAV’s pledges.

Plaid Cymru 

This party will be contesting all forty parliamentary seats in Wales. They are likely to come out with up to five of them (they currently have three). Their manifesto pledges:

“[T]he introduction of a European-level Animal Welfare Commissioner and adoption at all government levels of the new and comprehensive Animal Welfare law to end animal cruelty.”

The Democratic Unionist Party

Contesting seats in Northern Ireland, and likely to win 5 – 10 seats (currently holding 8), their manifesto does not mention animal research but says:

“[We want] a UK wide charter for animal protection.”

Some predictions (from April 22nd) on the number of seats parties will win. 326 seats are needed for a majority

Some predictions (from April 22nd) on the number of seats parties will win. 326 seats are needed for a majority

Animal Rights Election Activism

There are also various animal activist groups which are working to convince parliamentary candidates (PPCs) to put in place new regulations for conducting animal studies. Those that have contacted candidates include:

The National Anti-Vivisection Society (NAVS) are focusing on household product animal tests (which will be banned from October 2015), and reforming Section 24 (which is already underway).

The British Union for the Abolition of Vivisection (BUAV) are running their “Vote Cruelty Free” campaign, which asks candidates to make six pledges which would effectively destroy British medical and veterinary research. These include bans on GM animals, on “non-medical research” and on the use of cats an dogs.

Animal Aid are calling for an end to all taxpayer money used to fund research involving animals – thereby denying the National Health Service of many future treatments.

Speaking of Research

Pioneering non-beating heart transplant success – thanks to animal research!

Yesterday a team led by Consultant Surgeon Stephen Large at Papworth Hospital near Cambridge in the UK announced the successful transplant of a non-beating donor heart to heart failure patient Huseyin Ulucan, the first time such an operation has been performed in Europe.

Current practice is for donor hearts are obtained when the donor has been declared brain dead, but their heart is still beating, and the heart is then cooled and transferred to the recipient.  The technique used in Mr Ulucan’s operation involves re-starting the heart in the donor five minutes after death and perfusing it and other vital organs with blood and nutrients at body temperature using the Transmedics Organ Care System (OCS). In this case the donor heart was kept nourished and beating for three hours before being transplanted into Mr Ulucan. The main importance of the technique it that it has the potential to substantially increase the  number of donor hearts available for transplant, though it also enables the surgical team to assess the health of the donor heart more thoroughly.

Transmedics_OCS

The Transmedics Organ Care System.

 

The technique they used was developed by Cardiothoracic Transplant Registrar Simon Messer, who developed it with Consultant Surgeon Ayyaz Ali, and commented:

Using techniques developed to recover the abdominal organs in non-heart beating donors, we wanted to apply similar techniques to hearts from these donors.

“Until this point we were only able to transplant organs from DBD (Donation After Brain-stem Death) donors. However, research conducted at Papworth allowed us to develop a new technique not used anywhere else in the world to ensure the best possible outcome for our patients using hearts from non-heart beating donors.”

This approach, known as normothermic donor heart perfusion, is an example of a technique that is showing great promise in surgery, in 2013 we discussed how the normothermic transplantation technique using the OrganOx system – developed through research in pigs – had been used successfully in a liver transplant operation, and large scale clinical trials are now underway.

In a review entitled “Normothermic donor heart perfusion: current clinical experience and the future” published in 2014 (1) Simon Messer and colleagues highlights the role of research in animals including dogs, pigs and monkeys in demonstrating that Donation After Cardiac Death (DCD) heart transplantation is possible, and that normothermic donor heart perfusion improves the success rate.

DCD heart transplantation has been shown to be possible in animal models [32-34] and in humans [35, 36] provided that the warm ischaemic time could be kept below 30 min. However, we suspect that the only safe way to adopt DCD heart transplantation into routine clinical practice is by ex vivo functional and metabolic assessment following appropriate reconditioning. Normothermic blood perfusion has been shown to be superior to cold storage in preserving DCD hearts in dogs [37]. In the pig, reconditioned DCD hearts were shown to have comparable function to BSD donor hearts [38]. In an asphyxiation pig model, DCD hearts exposed to 30 min of warm ischaemia were evaluated on the OCS using lactate assessment. Four of seven transplanted DCD hearts were subsequently weaned off cardiopulmonary bypass on low dose inotrope [39].”

In a key paper published in 2013 (2) – reference 38 above – an Australian team assessed whether the Transmedics OCS system could be used to successfully transplant non-beating hearts in pigs, concluding that:

The Transmedics OCS provides an excellent platform to assess DCD heart recovery following warm ischemia. Using a clinically applicable model, we have shown that DCD hearts with WIT ≤30 mins appear to be a viable source of additional organs in cardiac transplantation and warrant human studies.”

Pigs are a excellent species for many transplant research studies. Image courtesy of Understanding Animal Research.

Pigs are a excellent species for many transplant research studies. Image courtesy of Understanding Animal Research.

Results such as this led to Simon Messer and colleagues concluding in their 2014 review (1) that:

It is estimated that use of DCD hearts may increase the number of heart transplants by 11–15% [40]. We believe that functional assessment during ex situ normothermic donor heart perfusion must be made prior to transplantation in this setting. In Papworth Hospital, we are currently investigating whether DCD human hearts can be assessed on the OCS using pressure volume loop measurements.

In conclusion, cold ischaemic preservation for the donor heart has been universally adopted into clinical practice over the last 45 years. However, the diminishing pool of ideal donors coupled with the drive to further improve heart transplant outcomes mandate a rethink in this area. Normothermic donor heart perfusion is the logical next step and from the clinical experience to date, appears to hold promise.”

We congratulate Stephen Large, Simon Messer, Ayyaz Ali and colleagues at Papworth Hospital for taking this next important step successfully, and we wish Huseyin Ulucan a full recovery and long life.

Yesterday’s announcement was a reminder that more than 50 years after Norman Shumway’s pioneering heart transplants studies in dogs, animal research remains crucial to progress in this important field of medicine.

Paul Browne

1) Messer S1, Ardehali A, Tsui S.”Normothermic donor heart perfusion: current clinical experience and the future.” Transpl Int. 2014 May 23. doi: 10.1111/tri.12361. PubMed:24853906

2) Ali AA, White P, Xiang B, et al. “Hearts from DCD donors display acceptable biventricular function after heart transplantation in pigs.” Am J Transplant 2011; 11: 1621. Link

 

Animal research successes spur growth in science…but PeTA can only complain

What do multiple myeloma, influenza, advanced breast cancer, atrial fibrillation, thyroid cancer, ear infection, advanced ovarian cancer and obesity all have in common? One commonality is obvious – they cause suffering, sickness and sometimes death in people around the world. Another commonality is less obvious – these are each conditions that are now being treated with new drugs just approved by the U.S. Food and Drug Administration (FDA) in the past three months alone. That’s right… in the period from Thanksgiving 2014 until now, new drugs that treat each of these conditions have become available, and these agents will be used to treat the illnesses that may affect millions of Americans. Eventually, they will likely have enormous worldwide impacts on these diseases. That’s something to be thankful for.

While some are thankful that the scientific progress is successfully tackling human suffering and disease, others cast doubt on the way that progress is achieved. In a newly published analysis entitled “Trends in animal use at US research facilities” [1], employees of People for the Ethical Treatment of Animals (PeTA) – a self-avowed animal rights organization – report that, amongst the largest research universities in the United States, the number of animals involved in research has grown by over 70% during the past 15 years. In their publication, the authors express alarm over the growing use of animals not covered by the Animal Welfare Act (AWA), mostly mice and fish, in biomedical research, without making any mention of the impact of this research growth.

This growth in animal research in the US is directly linked to an accelerating pace of scientific study and its benefits. A brief visit to the FDA’s “New Drugs at FDA page” makes it quickly apparent that the rate of approval of new medications is astounding. Where is this progress coming from? At least in part, it’s coming from the scientific discoveries that are pouring out of the research laboratories located in colleges and universities, institutes and pharmaceutical and biotechnology companies around the globe. A good example is the innovative BiTE antibody Blincyto (blinatumomab) which was approved for use in treating B-cell acute lymphoblastic leukemia in December 2014 (clinical evaluation against other cancers is ongoing); as we discussed in a blog post in 2008, animal research – particularly studies in mice – played a key role in its development and early evaluation.

Thanks to the researchers that occupy laboratories around the world, scientific discoveries are coming faster than ever, and all of us benefit. It’s not just that there is more research being done – it’s that the impact of the science is better than ever thanks to more advanced technologies, accumulating knowledge of how the body works and more advanced animals models, including ones that mimic human disease processes in increasingly sophisticated ways that promote new discoveries and new opportunities to develop novel drugs.

Why is the scale of animal research growing in the US? The answer is clear: scientific progress is cumulative. One discovery often enables multiple other lines of work. The discovery of the structure of DNA, for example, enabled thousands of efforts to find the genetic causes of disease. Because of this, successes build on successes and research grows.

What is the consequence of the growth in animal research? The answer is: new treatments, new cures, less sickness and longer, healthier lives.

In their paper, the PeTA employees fail to mention any of the following accomplishments, allow of which resulted from the growing scientific research efforts around the world:

But this isn’t the end. To these existing accomplishments, add the work that was started in the past 15 years and will yet unfold in the forthcoming decade AND the overwhelming progress in basic/fundamental research that will lead to new treatments and cures throughout the first half of the 21st century, and you have the recipe for a growing animal research infrastructure in this country.

As recent statistics from the UK indicate, the increase in the use of mice and fish in research is driven almost entirely by the increasing number of studies that involve the use of genetically-modified (GM) animals. In other words, the increase is driven by scientific and technological advances that had a profound impact on biomedical research over the past 15 years, rather than any desire to avoid using species regulated by the AWA (while mice and fish studied in Universities are not covered by the AWA, research involving them is regulated in multiple ways, including through the federal Office of Laboratory Animal Welfare which issues the PHS Guide for the Care and Use of Laboratory Animals).

“Recent statistics from the UK indicate, the increase in the use of mice and fish in research is driven almost entirely by the increasing number of studies that involve the use of genetically-modified (GM) animals.”

Growing study of GM animals has occurred because these models are enormously useful. To take just one example, the National Institute of Child Health and Development recently published an online article entitled “It’s in the DNA: Animal Models Offer Clues to Human Development”, discussing the role of animal models in helping to understand human development and developmental disorders. But this is far from the only example, studies in GM mice are key to many of the state-of-the-art emerging fields in biomedical research. These range from the very new areas of optogenetics – which uses light to control activation of individual cells – and gene editing techniques such as CRISPR that have the potential to cure genetic disorders, to new therapies such as cancer immunotherapy and treatments for rare genetic disorders such as progeria and Pompe disease which are being used to successfully treat patients for whom effective therapies were previously unavailable.

The rise in the numbers of zebra fish is also driven by their value as research models. As vertebrates they share over 84% of the genes that cause disease when defective in humans, while their rapid reproduction and transparent eggs make them ideal subjects for genetic and developmental studies. It’s not surprising that they are both an increasingly popular species in basic biomedical research, and in the preclinical evaluation of potential new therapies and of the environmental safety of chemicals.

In recent years zebra fish have become an increasingly popular species in biomedical research.

What the statistics presented by PeTA in their article don’t tell you is that, while the number of experiments and studies have increased, animal research increasingly involves Refined techniques that produce minimized harm to the subjects and Reduced numbers of animals per study. And of course, animal research directly led to the ability to Replace animals in some types of studies, altogether. The efficacy and efficiency of animal research is advancing, and individual discoveries are, on average, being made with fewer animals. That is a fact missed entirely by the PeTA article.

Furthermore, within the concept of refinement is the idea that researchers should use animals that will suffer less in a laboratory setting wherever possible [2]. So replacing a small number of “higher” mammals with a high number of “lower” animals is consistent with the 3Rs principles of animal welfare. PeTA neglect to mention that USDA statistics show a 40% fall in the use of AWA-covered species over the last 15 years, and it is likely that a small proportion of the rise in use of non-AWA covered species is due to technological advances that have allowed non-AWA species (e.g. GM mice) to replace AWA species (e.g. monkeys) in some studies, for example to develop new treatments for HIV/AIDS, in line with the principle of Refinement we have outlined.

Number of animals used annually for research in the US

“PeTA neglect to mention that USDA statistics show a 40% fall in the use of AWA-covered species over the last 15 years”

Through the implementation of these 3Rs, scientists ensure that they engage in socially-responsible and ethical work. What the authors of the PeTA study should do is to explain how achieving their end goal of a virtual end to animal research, which will reverse the trend of accelerating discovery and medical progress upon which it depends, is ethical or defensible.

  1. Goodman, J., Chandna A., and Roe K. 2015. Trends in animal use at US research facilities in: J Med Ethics. 0:1-3
  2. Richmond, J., 2014. Refinement Alternatives: Minimizing Pain and Distress in Allen, D. and Waters M. ed. In Vivo Toxicity Testing” in: Reducing, Refining and Replacing the Use of Animals in Toxicity Testing. Cambridge: RSC. pp. 133

David Jentsch