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…

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 18, 2015).

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

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

US Charities Explaining Animal Research

In June 2012 we reviewed five large American health charities which conducted animal research to see how well they communicated this use. The results were not encouraging: three charities got 0/4 stars for their animal research statements, and two charities for 1/4. So has anything changed?

In this post I will look at those charities conducting or funding animal experiments in the US who are on Forbes’ list of top 50 charities (2014). There were nine charities I found that fit the bill:

Ratings Criteria:

I believe the most important thing is that information exists if people need it. It is one reason why we created a searchable list of organisations with a statement on why they conduct or fund animal research. 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

American Cancer Society

Four out of five stars 4/5There is no information available on the website but by using their webchat I was given the following statement:

The American Cancer Society advocates the use of non-animal systems in research whenever possible; however, there are times when scientific research using animals remains essential for developing treatments and cures for people with cancer.  When that is the case, the American Cancer Society insists that such research complies with the highest ethical standards to protect the health and welfare of animal subjects.

After talking a little longer I was also provided with the following:

The American Cancer Society supports animal research when:

  • The use of animals is appropriate, and no non-animal alternatives exist.
  • Animals are only used when the answers to scientific questions cannot be obtained in any other way.
  • Computer models do not adequately present how individual molecules, cells, or tissues of the body work when healthy or when disease strikes.
  • The researchers guarantee the highest ethical and compassionate standards to protect the health and welfare of animal subjects and comply with federal and institutional guidelines.

Animal research is important to the American Cancer Society because:

  • New cancer drugs must be tested on living systems.
  • Proper doses and possible side effects in human bodies must be identified and evaluated.
  • Research with animals has led to significant advances in medicine, including the discovery of insulin injections for treating diabetes.
  • Research with animal models has produced successful cancer treatments for childhood leukemia.
  • Animal research is crucial for understanding many causes of cancer.

For future research, the American Cancer Society believes:

  • Test tube experiments are often effective in early phases of research.
  • The continued use of stem cell and organ tissue cultures offer hope for non-animal research.
  • The continued use of computer models offers hope for future studies.
  • It shall serve both humans and animals in diseases and prevention.
  • The Society will show continued support of stringent guidelines and regulations for the well-being of all animal subjects.

In all truth this is a fairly good response – it explains when and why they conduct animal experiments. If only they put this up on their website *sigh*.  The research news section of the website does mention the animal models used, for example a recent ACS-funded researcher used mice to assess the best timing for taking anti-cancer drugs – which it turns out is immediately after traditional chemotherapy.

American Cancer Society – 4/5 stars

St. Jude Children’s Research Hospital

Three out of five stars 3/5St Jude does not have any position or policy statement on their website. When I phoned them up the operator wasn’t sure if they conducted research on animals. They passed me to someone else who also didn’t know, and then passed to someone who wasn’t there. After emailing them I did receive a reply:

As a research institution, St. Jude has a unique mission to generate the knowledge that will save the lives of children stricken with cancer and other catastrophic diseases. In the course of our research to find cures for these deadly diseases, we do use laboratory animal models, mostly rats and mice bred specifically for that purpose.

There is no substitute for animal testing when evaluating the effects of diseases and proposed treatments to fight those diseases. Most biological systems do not behave in a predictable manner and cannot be replicated by computer simulations. St. Jude is usually legally required, and always ethically obligated, to test treatments on laboratory models to ensure safety and efficacy before those treatments are studied in children. Without this research, St. Jude would not be able to provide hope for cures to our patients and their families.

Please be assured that St. Jude does not conduct useless laboratory research. We are very careful to abide by the laws, statutes, and ethical guidelines for animal research. Our procedures comply with the government’s Animal Welfare Act, and we are accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International to ensure the best care for the animals used in our research. Our labs are inspected regularly by the Department of Agriculture.

So there is a statement that attempts to explain when animals are used. Get it up on the website and relate it to many neonatal and pediatric treatments than exist thanks to animal studies. There are already many mentions of animals used by St. Jude researchers in the medicine and science news section of the website, such as using specially bred mice to identify a potential target for drugs to combat leishmaniasis.

St. Jude Children’s Research Hospital – 3/5 stars

American Heart Association

Two out of five stars 2/5Despite searching their website I was unable to find a position statement (through the menus or the search bar) on their animal research, however after phoning them up I was guided to a page with position statements on animal research, cloning, gene therapy and stem cell research. The statement is good, but could certainly be expanded to provide more information on animal research.

The American Heart Association supports using animals in biomedical research — because it helps us improve heart health and save lives. In fact, the decline in U.S. death rates from heart disease and stroke since the 1960s is due in part to discoveries from research using animals.

So, when animals are needed for experiments we fund, researchers must handle them responsibly and humanely.

  • Before receiving our funding, we require researchers to show that:
  • They have considered alternative methods to using animals.
  • Their research can’t be successfully done without using animals.
  • Their experiments are designed to produce needed results and information.

So there is a statement, thought its explanation for animal research is a little week. It is online, though not that easy to find.

While a search for “mice” does come up with some search results, most link to the names of scientific papers or presentations rather than explaining the use of animal models in research.

American Heart Association – 2/5 stars

Memorial Sloan Kettering Cancer Center

One out of five stars 1/5There was no information available on their website – something which was confirmed over the phone. The operator seemed very nervous about giving me information, asking repeatedly what I wanted the information for.

A second phone call to the public affairs department didn’t get me any closer. Despite repeatedly being put on hold no one seemed to have any idea about their position on animal research. No statement at all!

This is made more frustrating when you know that there are many mentions of animal research in their Recent Discoveries & Advances section, such as developing a rat model to “study the neurological side effects of radiation to the brain”.

Memorial Sloan Ketering Cancer Center – 1/5 stars

Mayo Clinic

One out of five stars 1/5Nothing on the website. After a phone call I received the following by email:

Mayo Clinic believes in the vital role that animals have in advancing medical knowledge and developing new treatment options. Researchers would not have discovered new ways to treat heart disease, found cures for childhood cancers or advanced knowledge in many neurodegenerative diseases such as Parkinson’s without animals as part of the research process. Animals used to help advance science are treated with the utmost respect and care and in accordance with Mayo’s Institutional Animal Care and Use Committee. Mayo Clinic adheres to or exceeds all federal and state laws and regulations regarding animal use in research and makes every effort to ensure the safety and well being of animals. Mayo uses animals in research only when necessary and always with the goal of providing improved treatment or therapies for patients.

A short statement that didn’t quite say enough to gain stars for why and when its research is done. Better than nothing though.

While searches for “mice”, “rat” and “dog” on the Mayo Clinic website did bring up search results, few of them appeared to give pages meant for public consumption.

Mayo Clinic – 1/5 stars

Leukemia and Lymphoma Society

Three out of five stars 3/5Unfortunately the Leukemia and Lymphoma society does not have a statement on their website. After chatting with someone in their communications department I was sent the following statement:

Our work depends on broad and open-ended scientific inquiry. In this context, LLS supports the appropriate use of animals in conducting research to find potential cures for blood cancer patients.

Much of what we know about the diagnosis and treatment of diseases that afflict humans, including cancers and specifically the blood cancers, is the result of scientific studies conducted in animals. Moreover, lymphoma and leukemia are major killers of domestic and companion animals, and so there are potential benefits not only for humans but also for animals when research yields successful new cancer therapies and vaccines.

LLS requires that research using animals must adhere to federal and state laws, and follow the guidelines put forth by the NIH Office of Laboratory Animal Welfare. Research supported at foreign institutions must also abide by NIH’s policy on animal use. All researchers receiving LLS funding work with their institutional animal care and use committee to review and approve any protocol related to animal use. The purpose of these committees is to ensure that research strictly adheres to all federal and state guidelines regarding the care and use of animals.

We recognize the importance of the development and use of non-animal alternatives such as cell lines and cell cultures, computer simulations and mathematical modeling, and encourage their use when scientifically sound; i.e. accurately representing cancers in patients. However, in many instances the humane and appropriate use of living animals is both critical and ethically valid.

The absence of a suitable non-animal alternative and the explicit justification to use a given species and number of animals are required to qualify an applicant for any research support from LLS, as is the explicit documentation of steps taken to eliminate or minimize any potentially painful procedure. These humane considerations must be developed with the assistance and under the supervision of a qualified veterinarian and fully approved by an applicant’s research institution.

This is a strong statement and it is a pity, like many other charities, that they do not choose to put this up on their website for the public or media to find. It explains why they use animals and the conditions under which animal research is done. It also discusses why alternatives cannot replace all animal studies. Good statement, but they need to get it on their website.

There appeared to be no mentions of animal models in the news releases (or anywhere else) on the website.

Leukemia and Lymphoma Society – 3/5 stars

Dana-Farber Cancer Institute

One out of five stars 1/5The DFCI did not have any information on their website. When I phoned up they confirmed that they conducted such research but had no statement available on their website. When I asked where I could get more information they replied that they “try to stay away from making any public statements on the matter”. Concerning.

This “no comment” approach seemed to contradict a more open attitude to mentioning the use of animal models in their research news. When I checked, one of the top stories in their “Featured Research” was an article entitled “Mouse Models Play Pivotal Role in Testing Combination Therapies” – excellent!

Dana-Farb Cancer institute – 1/5 stars

Alzheimer’s Association

Four out of five stars 4/5The Alzheimer’s Association do have a two page document on their website on the “Use of Animals in Research”. It starts by clearly explaining why they feel animal research is necessary:

Currently, the complexity and intricacy of the human brain is beyond the capacity of even the most sophisticated science to simulate in man-made models (for example, with computers) or through the use of cells grown in the laboratory or lower organisms.

The Alzheimer’s Association believes that the use of animals in research is essential to the success of research into the causes, treatment, prevention and cure of Alzheimer’s disease and related disorders.

It is too long to reproduce in full, but it then goes on to explain the conditions under which they will fund animal research and provides information about knowledge gained through animal research.

A quick search of “mice” on the website brought up just shy of 600 results, though most were abstracts from research grants rather than information oriented for public consumption. The most recent blog entry mentioning mice was in 2013, suggesting that mentioning animal research was not common.

Nonetheless, well done to Alzheimer’s Association – this is probably the best statement. I found it without too much issue and it was fairly comprehensive for a policy statement (certainly compared to other charities). Four stars.

Alzheimer’s Association – 4/5 stars

National Multiple Sclerosis Society

Three out of five stars 3/5Having asked the question by email, I received a link to an obscure policy document. A policy statement on “Research involving human subjects or animals” could be found on Page 6.

For research involving animals, written approval from the grantee’s Institutional Animal Use and Care Committee (IACUC) must be received by the Society prior to the release of any funds. This approval must be signed by the Chairperson of the Committee, and a copy of the letter must be received by the Society on an annual basis during the funding term of the research award.

All biomedical research which involves the use of animals must adhere to the following principles:

  1. Animals shall be used in biomedical research only when no other means of obtaining scientifically sound, valid and useful results are available.
  2. The minimum number of appropriate animals required to obtain and validate results shall be used.
  3. The acquisition, care and use of animals must be in accordance with all applicable federal, state and local laws and regulations.
  4. Certifications must be received from research facilities prior to being approved for a research grant that the facility(ies), its researchers and employees adhere to the Animal Welfare Act, National Research Council Guide for the Care and Use of Laboratory Animals, and any appropriate U.S. Department of Agriculture or National Institutes of Health regulations and standards.
  5. In cases requiring the death of an animal, only the most appropriate and humane form of euthanasia shall be used consistent with the purpose of the research

The statement is sound, but doesn’t seem to be written with the public in mind. It would benefit from a simple and open explanation of when and why animal models can play a key role in developing an understanding of MS.

Despite the relatively weak statement, the NMSS was much stronger in mentioning and explaining the use of animal models in their research news. For example, stories like, “Researchers Funded by National MS Society Report Early Success Testing a Novel Strategy for Protecting the Nervous System in Mice with MS-like Disease“.

National Multiple Sclerosis Society – 3/5 stars

Summary of the Scores:
US Charities doing Animal Research and Animal Testing

Well done to the American Cancer Society and the Alzheimer’s Association for coming top of the list of organisations being open and honest about their animal research. The Alzheimer’s Association is particularly strong in its animal research statement.

On the other end of the scale, the Memorial Sloan Kettering Cancer Center, the Mayo Clinic and the Dana-Farber Cancer Institute need to look at ways of being more open on this issue. Most of the cancer treatments we have today have come about thanks to a huge number of studies on animals. Herceptin, a recent drug for breast cancer, is a humanised mouse antibody which could not have been created except for the use of mice in its development and testing.

So why should charities bother to be open about their animal research? I believe there are three reasons.

Firstly, they are taking public donations, and the public have a right to know how this money is spent. If they believe animal research is an important part of what they fund, then they should be prepared to explain this frankly and openly.

Secondly, regardless of whether they put a statement up on their website, animal rights groups will find out. It took me a few days to ascertain which US charities did, or did not, conduct or fund animal research – others could follow the same process. Putting information openly on the website helps create resilience on the issue – members of the public can no longer be “shocked to discover” that a charity they support funds animal experiments, and animal rights groups cannot go to the paper announcing a charity’s “dirty secret they try desperately to hide”. Any member of the public of journalist can be told straight away by the charity that “Yes, we conduct and fund animal research. We say so openly on our website, and you can find out more information on the reasons why there – we have nothing to hide”.

Lastly, it is important that we 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.

In a second post, we will have a look at British charities which conduct animal research

Speaking of Research