Category Archives: News

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

World Week to Speak Up About Animal Research

Banner at UW-Madison, April 2015.

Banner at UW-Madison, April 2015.

Each April a group of people committed to ending all use of animals for any purpose, including medical and scientific research, orchestrate events for a week they designate World Week for Animals in Laboratories (WWAIL). Among the primary objectives of WWAIL is to generate media coverage via picketing and protests. The event often culminates in World Day for Animals in Laboratories (WDAIL).

WWAIL events are primarily coordinated by Michael Budkie, leader of Stop Animal Exploitation Now (SAEN). Budkie is also known for previous misrepresentation of animal research and its rebuttal by federal agencies. Budkie’s group is funded primarily by the Mary T. and Frank L. Hoffman Foundation, a “Biblically based organization” that believes “our call to mission is to restore God’s original creation intent of a plant based diet (Genesis 1:29-30).”  The  mission of the Hoffman Foundation  is quite clear: “To promote through education the elimination of the use of animals in biomedical research and testing, their use as food, or their use for any and all commercial purposes…

Sit-in at UW-Madison during WWAIL (April 18, 2015).

Sit-in at UW-Madison during WWAIL (April 18, 2015).

SAEN is like other absolutist groups whose position is that no matter what potential benefit the work may result in, no use of animals is morally justified. This extends across all animals – from fruit-fly to primate. Furthermore, all uses of animals, regardless of whether there are alternatives and regardless of the need, are treated identically. In other words, the use of a mouse in research aimed at new discoveries to treat childhood disease is considered morally equivalent to the use of a cow to produce hamburger, the use of an elephant in a circus, or a mink for a fur coat.

WWAIL protests are focused specifically on research. Thus, the sites for protest tend to be universities and other research institutions where scientists engage in work that produces the new knowledge and discoveries that drive scientific and medical progress to benefit humans, other animals, and the environment. The protests also target individual scientists with the kind of “home demonstrations” we’ve written about before (see more here and here).  In some cases the protests target businesses that support animal research.

Although the WWAIL activities vary some each year, they have a few consistent themes:

  • First, the primary objective appears to be media coverage. In fact, a quick view of the “successes” claimed by the primary organizing group shows that number of news stories is the prize accomplishment.
  • Second, the number of people participating in the activities is typically a few to a dozen.
  • Third, most of the materials used in the protests, social media coverage, and news releases reliably rely on outdated, out-of-context images and little reference to the protestors’ broad agenda and position.

We agree that public consideration of animal research is important. Stimulating serious, thoughtful education efforts and inclusive public dialogue about science, public interests, medical progress, and animal research are critically valuable to public decision-making and, ultimately, to global health. Informed decisions based in accurate information and in an understanding of the complex issues involved in animal research are in the best interest of the public, science, and other animals.

For that reason, many scientists, universities, educators, advocacy groups, and individuals engage in public outreach, education, and dialogue about scientific research with nonhuman animals. Their goal is to provide the public with accurate and thoughtful information about the range of issues that bear on decisions, policies, and practices related to animal research. Among those topics are:  how science works, its process, timescales between discovery and application, why animal research is conducted, in absence of alternatives; who benefits and what would be lost if it did not occur;  how animals in research are cared for, how ethical review occurs, and how regulation and oversight function.

None of these are simple issues, which is why there are many websites, books, articles, and interviews on the topic. WWAIL provides a unique opportunity for the research community to help point people towards these resources for education, dialogue, and serious consideration of animal research.

At the University of Wisconsin-Madison, we have one example of how to do just that.  The website referenced in the banner shown in the photos here (animalresearch.wisc.edu) provides extensive information about animal research.  The site provides facts, interviews, videos, photos, and links for those interested in learning more about why animal studies occur, the role that they play in scientific and medical progress that serve public interests, how research is conducted, its ethical consideration, and the practices, policies, regulation and oversight that govern animal care.

By contrast, we have the signs held by those below participating in a WWAIL sit-in at UW-Madison on Saturday.  Among the signs are photos of animals from other decades and other countries.  For example, note the repetitive use of a picture of Malish, a monkey who was involved in research in Israel in 2001 (not exactly relevant to UW).  We also see quotes by an actor and numbers that do not reflect those from UW-Madison.  None of these are difficult errors or misrepresentations to correct; but they probably won’t be corrected in absence of voices and sources to provide accurate information.

Sit-in at UW-Madison during WWAIL (April 2015).

Sit-in at UW-Madison during WWAIL (April 2015).

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.

Speaking of Research

En Passage, an Approach to the Use and Provenance of Immortalized Cell Lines

This guest post is by Lisa Krugner-Higby, DVM, PhD.  Dr. Krugner-Higby is a scientist and also a research veterinarian within the Research Animal Resource Center at the University of Wisconsin-Madison. Dr. Krugner-Higby’s research is in development of extended-release formulations of analgesic and antimicrobial drugs. She previously worked in anti-HIV drug development.

I am always fascinated by the idea promoted by some animal rights activists – repeated in many versions and for many decades – that all preclinical biomedical research can be conducted using in vitro cell culture. I have never found one of them who has spent much time working with cell culture. On the other hand, I have spent approximately seven years of my life working with cell cultures, looking at the stainless steel back wall of a laminar flow work station day after day. One thing I can say about immortalized cell lines, or cells that reproduce indefinitely, is that they are not alive in the same way that a mouse is alive.

 

Cell culture

Cell culture

The first thing that a graduate student learns when they begin to work with cell culture is how to take cells that have overgrown the sterile plastic flask they inhabit and put them into a fresh flask with fresh growth medium. It’s called ‘splitting’ the number of cells and ‘passaging’ them into a new home. Split and passage, split and passage… I knew that with every passage, the cell line became a little more different than normal cells and even a little more different than the original cell line. The remedy for this type of genetic drift was to freeze low passage cells in liquid nitrogen and re-order the line from the repository when the low passage stocks were depleted. I was careful with my sterile technique, cleaned the laminar flow hood, and used a new sterile pipet every time in order to avoid contamination of my cells. Unfortunately, the day came when I opened the incubator door and the flasks were black and fuzzy with fungus, and all of my carefully tended cells were dead. An anguished conversation with the tissue culture core technician revealed that this happened every Spring in North Carolina when the physical plant turned on the air conditioning for the year, blowing a Winter’s worth of fungal spores out of the ductwork and into the air. She recommended doing other things for about 6 weeks until the spore load had blown out of the ducts. I have had other cell line disasters in my scientific career: the malfunctioning incubator thermostat that turned a colleague’s two months’ worth of cell culture growth into flasks of overheated goo or that generally reputable vendor that sold us a case of tissue culture flasks that were not properly sterilized resulting in clouds of bacteria in the warm, moist, nutrient-rich environment of the incubator.

I never thought to ask, in those early days, if the cells that I fussed, worried, and wept over, were actually the cells that they were supposed to be. Raji Cells, A549s, U937s, I knew them all, worked with them every day, and never doubted that they were the cells that I thought that they were. I knew that some cell lines had been contaminated with the HeLa cell line. HeLa cells are very hardy and could spread quite easily from one flask to another. But I thought that was in the past. It turns out that there was more to the story than I realized. Cell lines have a provenance, like paintings or other works of art. They have an origin, a laboratory where the line was first isolated and propagated. From there, it may have been distributed to other laboratories and to repositories like the American Type Culture Collection or ATCC. Some cell lines are used by only a few laboratories, and some become used very widely and in a large number of biomedical disciplines. Whereas some paintings are intentionally forged, many cell lines have now been shown to be unintentionally forged. A recent article in the journal Science estimated that 20% of all immortalized cell lines are not what they were thought to be1.

Download original file2400 × 1999 px jpg View in browser You can attribute the author Show me how Multiphoton fluorescence image of cultured HeLa cells with a fluorescent protein targeted to the Golgi apparatus (orange), microtubules (green) and counterstained for DNA (cyan). Nikon RTS2000MP custom laser scanning microscope. National Institutes of Health (NIH).


Multiphoton fluorescence image of cultured HeLa cells with a fluorescent protein targeted to the Golgi apparatus (orange), microtubules (green) and counterstained for DNA (cyan). Nikon RTS2000MP custom laser scanning microscope. National Institutes of Health (NIH).

We now have better methods of identifying cell lines by their DNA, called short tandem repeat (STR) profiling, and scientific journals are beginning to require this testing for cell lines prior to publication. Currently, 28 scientific journals require STR profiling to establish cell line provenance prior to publishing a manuscript from a particular laboratory. Some scientists are also beginning to create catalogs of contaminated cell lines in an attempt to quantitate the damage done by some misidentified, but widely studied, cell lines. The same Science article, notes that the International Cell Line Authentication Committee (ICLAC) maintains a database of misidentified cell lines that now numbers 475 different lines. A cell line geneticist, Dr. Christopher Korch, recently estimated that just two of the immortalized cell lines that were found to be misidentified, HEp-2 and INT 407, have generated 5,789 and 1,336 articles in scientific journals, respectively. These studies cost an estimated $713 million dollars and generated an estimated $3.5 billion in subsequent work based on those papers1. This is because the usual trajectory for testing a new therapeutic modality, especially in cancer research, is to test a compound or technique in cell culture. It will then be tested in mice that express a tumor derived from the cultured cancer cells. If those studies are successful, the compound and/or technique undergoes further toxicity testing in other animal models before entering its first Phase I trial in human volunteers.

A lot of compounds that show early promise in cell culture and in cell line-injected mice turn out not to have efficacy in animal models or in human patients. Sometimes this is simply a matter of the compound being too toxic to organs or cell types that are not represented in the initial cell culture. Often, the reason why particular compounds or strategies fail is not known, and most granting agencies are not keen to fund laboratories to find out why things don’t work. I have wondered if the failure of some compounds or techniques is in part due to misidentified cell lines. I have also wondered if it is a reason why testing in animal models, particularly in animal models with spontaneously-occurring tumors, is necessary.

Testing anti-cancer compounds in models of spontaneously-occurring tumors in animals and/or testing in human tumor cells taken directly from patients and injected into mice (the ‘mouse hospital’ approach) is more time and resource intensive than screening in immortalized tumor cell lines. This approach, however, has the advantage of knowing that the investigator is not just treating misidentified HeLa cells in error. It is always necessary to go from in vitro cell culture models to in vivo animal models to confirm the viability of a therapy.

Science makes claim to no enduring wisdom, except of its method. Scientists only strive to be more right about something than we were yesterday, and efforts are underway to weed out misidentified cell lines. But the fundamental issues behind cell line misidentification highlight one of the reasons why we should not rely on immortalized cell lines without animal models, and why granting agencies should fund more studies to try to identify the disconnect between the results of in vitro and in vivo studies when things do not go as planned. That is a part of good science and part of creating better cell culture models to refine, reduce, and sometimes replace the use of animals in biomedical research.

Lisa Krugner-Higby, DVM, PhD

1) Line of Attack. Science. 2015. Vol. 347, pp. 938-940.

Interview with a Primate Researcher

In the last few months, Italian animal rights activists have conducted a campaign against animal research, in particular against primate research. This is despite the important role that primates have played in breakthroughs in stem cell research and neuroprosthetics, among other things. Nonetheless, activists continue to try to claim such research is useless. In particular, they targeted Prof. Roberto Caminiti, a leading neurophysiologist at the University La Sapienza in Rome, and his research team, accusing them of animal mistreatment. Earlier this year students and scientists at the University rallied round Prof. Roberto Caminiti, his team, and his important research.
To answer some of the activists accusations, Pro-Test Italia has produced a video with Prof. Caminiti to illustrate why primate research is so important in the field of neurophysiology and brain-computer interface, and why animal models remain essential for this kind of research. Pro-Test Italia have also made an English version of the video:

It’s important to spread this video outside of Italy to both explain to the public what is going on, and to encourage other primate researchers not to remain hidden but to be clear about the important research that they do. Researchers should be proud of the important work they do in contributing to medical developments for everyone.

Marco

Animal Justice Project: Same nonsense, different name

When I first took up my job explaining animal science to the public, I thought I would spend much of my time talking about ethics.

I was looking forward to it – my academic specialisms within were rights and ethics and I was more than ready to talk about animal rights and the ethics of using animals in science. As a noted animal lover and adopter of the unadoptable of course I’d thought about and researched the area very carefully indeed. I also want to be on the right side of history, not pick a view and set out in search of cherry-picked corroborating evidence.

Except I didn’t end up spending much time talking about ethics and it’s mainly due to the tactics of the animal rights lobby.

There’s a pretty well worn template for animal rights groups, and in recent years, as the tactics of smaller groups have moved away from violence towards pseudoscience, I find myself saying to new members of staff when a new animal rights claim hits the headlines ‘They’re probably lying, and it’s our first  job to find out how.’

It is little surprise, then, that new animal rights group the Animal Justice Project (AJP) is conforming to the familiar template of smaller organisations such as For Life On Earth and the seemingly defunct Anti-Vivisection Coalition.

Animal Justice Project

Typically, it’s a handful of people who (a) register a company and a website, (b) sign up for one of those virtual addresses which people claim are their business address, (c) rent-a-quote veterinarian, Andre Menache, to be their ‘scientific’ advisor and get to work cherry-picking ‘evidence’, misrepresenting research methods and generally making hair-raising claims which collapse upon further scrutiny. I don’t know how they fund the startup – maybe bigger groups help with the costs. Who knows and who cares – what matters is that they conjure enough faux respectability that journalists will listen to them so it’s their claims which become the focus.

In this case, the AJP appears to be Brit-in-LA Julia Orr, her friend Clare in the UK. And Andre Menache (who is also ‘scientific advisor’ for at least five other animal rights groups). On their website, they have a selection of Freedom of Information requests and papers harvested from PubMed which have been chosen for their methodology and applicability to defence operations. Menache rather hubristically critiques some of the experiments despite not be qualified or knowledgeable in the areas under scrutiny. The template remains intact.

They make a lot of claims, but for the sake of space let’s look at a typical example and see if it stands up.

“55 mice were subjected to laser burns to their eyes to simulate battlefield injuries and, as if this wasn’t bad enough, then had liquid injected into their eyes. The mice then had their necks broken up to six weeks after the experiment.

  • No mention of pain relief following this barbaric experiment.
  • Breaking of animals necks, especially without anaesthetic, is brutal and often animals suffer.
  • The researchers admit that making a link between these experiments in rodents and humans is “difficult”. Added to which, at best mice’s normal eyesight is the human equivalent of being registered blind.
  • Laser treatment for humans has existed since the 1980s and, therefore, so has damage to eyes by lasers. Enough human data means these experiments are no more than curiosity driven.
  • There is no conclusion as to whether the injections into the eyes of mice can help or harm either humans or mice.”

The claims concern this paper . Let’s see how the claims stack up.

The first sentence is true, if hyperbolic – the researchers were looking for a triage technique for the battlefield, or in the event of a terrorist attack, which could save the eyesight of people who’d been affected by a retinal laser injury, so the first sentence is true. Then it all falls apart.

It wasn’t part of the experiment to see how living mice fared with broken neck. Cervical dislocation, which is considered the most humane ways to euthanise small rodents since it is quick and painless, is used to separate the brain stem from the brain resulting in an instant, painless death. This would allow researchers to dissect the now-dead animal to see what physical effects could be observed.

No pain relief was mentioned, but that doesn’t mean it wasn’t there. In such a situation, a general anaesthetic would have been employed for ethical, legal and practical reasons. It would be much harder to do it while the animal was awake.

So far, one could chalk this up to a lack of knowledge, but what comes next is a deliberate deception. Researchers mentioned that it can be difficult to extrapolate some result s of animal experiments to humans, but not their experiment. The original paper reads:

“Given the interspecies differences in anatomy, genomes, and response to injury, in certain disease processes it may be difficult to make a direct correlation between the results observed in rodents and humans. However, as we have discussed, in both the rodent and human eye, photoreceptor cell death following laser injury has been shown in previous work, as has the protective effect on photoreceptors with the use of CNTF. Therefore, our study combines the use of these established facts and thus allows the extrapolation of results specific to cone injury.”

There can be no honest reason for leaving out the second part of the last sentence (my emphasis).

Our score for the first three claims is 1. Technically accurate but misleading, 2. Misleading if not outright wrong and 3. Active cherry-picking giving the exact opposite assertion of the researchers.

Next of their claims: “we have relevant treatments for laser eye injuries.”

The simple answer is no we don’t. Not ones which could be stowed in a medic’s triage kit or easily deployed in a crisis. As the paper notes “Retinal laser injury, for which there is currently no satisfactory treatment, represents an infrequent but potentially devastating cause of irreversible sight loss”.

Finally, they claim that no relevant conclusions were drawn. Really? The paper states “By using a multimodal approach consisting of both in vivo imaging and in vitro histological and molecular techniques, we were able to confirm the protective effect of CNTF in our model of laser injury” and “although our research has a military focus with regard to developing a potential treatment for offensive laser weapons on the battlefield, the model we have developed might be relevant to assessing any treatment relevant to cone neuroprotection and diseases of the human fovea“. Right. So, not only did it present a potential treatment, but it indicated it might be useful in treating other eye conditions to the one being studied.

Out of 5 claims, one was true, and that was the one establishing that the experiment had taken place.

In some ways, ignorance and confirmation bias can be viewed as innocent human foibles, although not ones which have any place informing national debates about science policy. But the deliberate cherry-picking of a scientific paper, presenting unrepresentative parts of papers and misrepresenting papers is the preserve of the scoundrel, whether it’s used in climate change denial, arguing for Creationism or indulging the fallacy that animal models do not have relevance to human physiology.

The tactics employed by the AJP are the same as marketers devising a poster for a new movie, compressing a bad review stating “It’s incredible this movie was even made!” to just “…Incredible…!”

It’s lying to the public, and if any of the activists would like me to comment on their right to do so, or its ethics, I am more than ready to oblige.

Chris

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

 

UK Charities Explaining Animal Research

Following from our previous post on US charities explaining their animal research, we will now take a look at UK charities using the same criteria. Of the UK top 200 charities (by income in 2012), only seven conduct animal research.

The first thing to note is that all seven organisations are members of the Association of Medical Research Charities (AMRC) – an umbrella organisation which demands that its members endorse a statement on the role of animals in research, a portion of which can be read below:

The public supports medical research charities to find new treatments and cures for debilitating and life threatening conditions. All AMRC charities have strategies for how they will fund high quality research to better understand disease and so improve health and wellbeing.
[…]
Whilst not all our members are currently funding research using animals as part of their strategy, they all support the principle of using animals in research when it is necessary to advance understanding of serious health conditions to develop better treatments and there is no alternative that can be used to find out the same information without using animals.

Secondly, six of the seven organisations have signed the Concordat on Openness on Animals in Research in the UK which, among other things, demands signatories will:

Commitment 1: We will be clear about when, how and why we use animals in research

Commitment 2: We will enhance our communications with the media and the public about our research using animals

Ratings Criteria:

The ratings criteria are the same as that used to look at the US charities. To me, the most important thing is that information exists if people need it. Preferably people need to be able to find this information online rather than have to call up for it. Each of the following five criteria will give a charity one star.

  • There is a statement available
  • It provides a good overall explanation of why they fund animal research
  • It is available on their website
  • It provides an explanation on how they determine when to fund animal research
  • Does the website make any mention of the use of animals, for example, in the summaries of research they fund

Cancer Research UK

Five out of Five stars 5/5The main policy page on “The use of animals in cancer research” is disappointing, with only a short statement:

A great deal of cancer research is carried out without using animals. In certain areas, however, animal research remains essential if we are to understand, prevent and cure cancer. Cancer Research UK only uses animals when there is no alternative.

Cancer patients and their families are at the heart of everything we do. We believe that all our research is vital if we are to save the lives of more patients in the future.

However, CRUK also have an easily googleable blog post on the issue which they often provide to those wanting more information. This blog post is fantastic, it begins:

More people are surviving cancer than ever before.

Thanks to decades of research, survival from cancer has doubled in the last 40 years, giving thousands of people more time with their loved ones. In fact, more than half of all patients will now survive for at least ten years.

But this progress simply wouldn’t have been possible without animal research.

At Cancer Research UK, research using animals is part of our efforts to beat cancer. This includes discovering the faulty genes and molecules that cause cancer, investigating how the disease grows and spreads, developing and testing new treatment and tests, and exploring how our immune system can help fight tumours.

The 2,500+ word post, written by the Director of Science Funding, explains why animal research is important, its past contributions, and the reasons and conditions under which animal research projects may be funded. The main pity is that this blog post isn’t linked to from the policy statement, or better yet the information from the blog post put onto the policy statement page.

CRUK also mention animals (usually mice) in research news stories, such as a recent piece that found the activity levels of particular genes in breast tumours could identify more aggressive forms of the disease. This story was mainly about clinical studies, but mentioned early findings in mice that led them there.

Cancer Research UK – 5/5 stars

The Wellcome Trust

Five out of Five stars 5/5
The Wellcome Trust provides an easy-to-find, lengthy statement regarding why they both conduct and fund animal research. Here is a portion.

The use of animals in research has enabled major advances in the understanding of biology and led to the development of nearly every type of drug, treatment or surgical procedure in contemporary medical and veterinary practice. Some of the best-known examples include:

  • antibiotics such as penicillin and streptomycin
  • vaccines for polio, meningitis, distemper, foot and mouth
  • treatments for conditions such as cystic fibrosis and asthma
  • drugs to treat mental diseases like depression
  • organ transplants and blood transfusions
  • the use of insulin for diabetes
  • and contraception for use by people and in controlling animal breeding.

The Wellcome Trust is therefore convinced that the use of animals in research remains valid where the potential benefits to be gained by humans and other animals from such research outweighs the use of animals in that research.

The subheadings in the statement show the breadth of the statement:

  • Why animals are used in medical research
  • How many animals are used?
  • Research involving animals is licenced by the Home Office
  • Research must be approved as ethical
  • Wellcome Trust-funded research involving animals
  • The 3Rs – replacement, reduction and refinement
  • Alternatives to animals in medical research

Wellcome news articles and other communications regularly mention the use of animals. For example their recent letter to the UK House of Lords regarding mitochondrial donation mentions the role of mice and monkeys in the development and testing of this new method.

The Wellcome Trust – 5/5 stars

British Heart Foundation

Five out of Five stars 5/5BHF finish the list of British charities in equal form. They provide an extensive statement about their use of animals providing links to other organisations and to their fantastic leaflet on the issue. Here is a portion of the statement:

BHF's leaflet on animal research

BHF’s leaflet on animal research

By studying new medicines and techniques in human cells in the lab first, and carefully trialling the best ones in animals, we’ve done all we can to make sure they’re going to be effective and safe for treating patients.

Researchers are studying how the heart develops in mice and fish to better understand what can go wrong to cause babies to be born with heart defect

Potential new heart medicines that work on human cells in the dish must be assessed in a living system before trials in patients can be carried out

Animal studies can reveal potential problems with new treatments allowing dangerous side effects to be spotted before clinical trials

The research community is constantly developing new techniques to help reduce the number of animals needed or non-animal models. Scientists we fund carry out as much of their research as possible on human volunteers, cells, or computer models for example.

However, completely replacing all animals in research is not yet possible. There is no alternative method that can reproduce the complicated working of our hearts and circulatory systems.

Similarly their news article and other pages on the website will frequently mention the use of animals like rats, mice and zebrafish. British Heart Foundation should also be congratulated for going front and centre with their animal research when they put out a TV advert mentioning their research on zebrafish.

British Heart Foundation – 5/5 stars

Alzheimer’s Society

Five out of Five stars 5/5The Alzheimer’s Society provides a full page of information on its “use of animals in research”. It outlines some of the medical benefits brought about by animal studies, the ethical challenges they face, how and when they do animal research. It suggests around one third of their research funds are spent on animal studies:

Drugs and new treatments that many of us take for granted, from antibiotics to blood transfusions and the current drug treatments for Alzheimer’s disease, would have been impossible to develop without research involving animals.

Many people are concerned about the well-being of animals used in medical research.  Alzheimer’s Society shares those concerns and strives to ensure that alternatives are used wherever possible.

The statement is good, providing a positive explanation as to why animal research is necessary. It is also easy to find through the website or Google. The research news section of the website makes casual mentions of the different animals used, from fruit flies, to mice.

Alzheimer’s Society – 5/5

Arthritis Research UK

Four out of five stars 4/5Arthritis Research UK are signed up to the AMRC statement, and link to it, but also provide their own perspective. Here is an extract:

Medical research using animals has made a vital contribution to advances in medicine and surgery which have brought major improvements to the health of people. Research using animals will continue to be essential to tackle many of the unsolved problems in understanding and treating musculoskeletal conditions.

The UK has one of the most rigorous systems in the world for regulating animal research. The UK requires permissions from both central Government and local ethical reviews to conduct research involving animals. As part of this approval process, each medical research project using animals must be examined and ways to improve adoption of the 3Rs are considered

The whole statement covers regulation and the 3Rs, to explain when animal research can happen, but I’m not convinced they made the strongest case for why animal research is necessary. An example treatment made possible by animal studies would have really strengthened the statement.

Arthritis Research UK regularly mention animal research in their news posts, such as a recent cell-based approach to regenerate bone and cartilage developed in mice.

Arthritis Research UK – 4/5 stars

Parkinson’s UK

Five out of Five stars 5/5Parkinson’s UK provides a long statement online which includes a strong explanation of why animal research is necessary, past medical breakthroughs made possible thanks to animal studies, quote from a patient, examples of grants, an explanation of the Concordat on Openness on Animal Research and more. Here is an extract:

We believe there is an urgent need for ongoing research to advance our understanding of Parkinson’s, improve treatments and ultimately find a cure. We believe theuse of animals, such as fruit flies and fish, is currently an essential tool in this research, but we are committed to the minimum possible use of animals and to ensuring that highest regulatory standards are maintained.
[…]
Since the 1970s, the lives of millions of people with Parkinson’s around the world has been transformed by the drug levodopa, This acts to partially replace the dopamine that is no longer produced in the brain due the eh death of nerve cells. Research involving animals has formed an essential step in the understanding of the effect of this vital drug.

Parkinson’s UK provide a quarterly publication, which is littered with examples and mentions of animal studies. The most recent issue’s first news story mentions rats, as well as having a letter about the use of animals in research. Parkinson’s are also willing to engage in the news, we have in the past mentioned Parkinson’s UK’s strong letter to a local newspaper responding to activist claims

Parkinson’s UK – 5/5 stars

Leukaemia & Lymphoma Research

Five out of Five stars 5/5Leukaemia & Lymphoma Research have a strong statement and an FAQ on the issue of animal research. Both are easily googleable, and includes details of what animal species are used and what proportion of research projects involve animals (29%).

Some of the biggest achievements in treating blood cancer that are now in routine clinical practice, such as stem cell transplantation, have only been made possible through the use of animals in research.

The achievements of understanding blood cancer progression, understanding the basis for chemotherapy, and identifying the principles of bone marrow transplantation are just some of the revolutionary and lifesaving developments in blood cancer treatment that would not have been possible without using animals.

Whilst there is a considerable amount of research that we support that does not require the use of animals, we believe that animal research is still necessary.  Understanding how disease affects systems within the body, as well as possible treatments, requires investigation in whole body systems. Our animal research mostly uses mice, but we also use other animals like fruit flies and zebra fish.

While the LLR website doesn’t put a lot of news in its research section, when it does it includes mention of the animals. A story about studying genes of patients with blood disorders mentions that cells from mice are also used to study how misfiring enzymes can lead to histone changes.

Leukaemia & Lymphoma Research – 5/5 stars

Summary of Results:

UK Charities doing Animal Research and Animal Testing

Fantastic results from the seven biggest UK medical research charities, though they are far from being the only British charities who talk about their funding of animals. You can see some of these and other charities’ statements below:

When comparing the UK and US charities we see some stark differences. All the UK charities we looked at have a statement available on their website (and googleable). All make an effort to explain how and why animals are used in research. In contrast, most of the US charities do not have a statement available online, though many do mention the use of animals in news articles on the website.

So what can the US charities learn from the British cousins? Well many US charities have prepared statements on the use of animals in research; they just need to get them online. If every charity which had a statement put them online they would raise the average score of American charities from 2.4 out of 5, to 3 out of 5. Many of the American charities could also work to improve their statements – there is good practice both sides of the Atlantic, and they could either take examples from other US charities like the American Cancer Society (see previous post) and Alzheimer’s Association, or they could look to their British equivalents.

But why is it important that charities be open about their animal research? As we discussed in more detail in the previous post there are three main reasons:

They are taking public donations, and the public have a right to know how this money is spent. If charities think funding animal research is important they should be able to explain why frankly and openly.

Charities cannot hide their animal research – animal rights groups can find out even if it is not on their website. However, by putting information openly on their website the charity defends itself against activist attempts to “out” them. The public cannot be “shocked” by the “dirty little secret” that a charity funds animal studies if they have that fact stated openly and clearly on their website (with an explanation as to why). It is better for a charity to state it does animal research and explain the reasons why, than it is to let an activist or journalist put their own spin on it.

Finally, we must foster an environment where both the public, and policy makers, understand the importance of animal research. The former demands the laws and regulations, and the latter put them in place. If the scientific community want to make sure their research environment is secure then they must encourage openness on the issue.

For those charities wanting to improve the way they discuss animal research with the public, there is a fantastic booklet jointly produced by the Association of Medical Research Charities and Understanding Animal Research which provides guidance and support. It covers how a charity can be prepared for questions about its animal research, how to answer those questions (be them by phone, social media, or in person), and finally looks into ways in which charities can find opportunities to be more proactive in their explanation of why they fund or conduct animal studies. The introduction states:

This guide is designed to help medical research charities answer questions from the public about the use of animals in research. Charities have contact with their supporters and the public in many different ways. They need to be able to explain how they are investing donations effectively and be equipped to answer any questions

Hopefully next time we conduct this analysis we will see even higher scores for charities across the world.

Speaking of Research