Tag Archives: animal 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.

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

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

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

Transmedics_OCS

The Transmedics Organ Care System.

 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Paul Browne

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

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

 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Number of animals used annually for research in the US

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

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

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

David Jentsch

Implementing the 3Rs at the University of Oxford

This Guest Post is by Stuart Peirson, Associate Professor in the Nuffield Laboratory of Ophthalmology and chair of the 3Rs sub-committee at The University of Oxford. This article was originally posted on the website of the National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs) and is reprinted with full permission. This article explains how Oxford is supporting the 3Rs, please read out page on UK research regulations and the 3Rs for more information.

Oxford imageThe University of Oxford is one of the world’s leading centres for biomedical research, with outstanding strengths in both basic science and its clinical application. The University’s Policy on the Use of Animals in Scientific Research outlines the University’s commitment to ensuring that all those involved in animal-based research are proactive in pursuing the 3Rs, engage fully in the ethical review process, and fulfil their moral and legal responsibilities for the care and welfare of animals.

Ethical review

Reflecting the enormous breadth of research across Oxford, the University currently holds over a hundred different project licences, with over a thousand personal licence holders. This poses a number of challenges for the coordination of ethical review as well as the dissemination of best-practice and advances in the 3Rs.

The critical element in this process is the Animal Welfare and Ethical Review Board (AWERB). All applications for project licences require the ethical approval of the University before they are passed to the Home Office. At Oxford, this involves a rigorous and objective process of ethical review that challenges scientists to justify their use of animals, and that requires them, where the use of animals is unavoidable, to minimise animal numbers and maximise animal welfare.

At Oxford the AWERB process consists of two principal elements. Firstly, a central Committee on Animal Care and Ethical Review (ACER) is responsible for setting policy, as well as reviewing applications involving the use of non-human primates, severe protocols or novel techniques. Secondly, Oxford also relies upon a network of Local Ethical Review Panels (LERPs), which consider all other project licence applications. All project licences are required to provide a written retrospective review for their LERP at two years and four years, providing a critical opportunity for the LERP to assess how project licences have applied the 3Rs in their research.

The 3Rs sub-committee

In addition to the ethical review process, the University also has a 3Rs sub-committee reporting directly to ACER, which receives copies of all retrospective reviews to identify key developments in the 3Rs across the University. These developments are combined to form a termly 3Rs newsletter, which also contains information on relevant workshops, lectures and courses, such as NC3Rs notifications.

In addition, the committee also recognises the achievements of particular groups in the application of the 3Rs, providing letters of commendation to those project licence holders who show particular commitment and dedication to the 3Rs.

Since the introduction of the University’s Policy on the Use of Animals in Scientific Research, all departments involved in such research are also required to have termly Departmental Animal Welfare meetings. These are attended by project and personal licence holders, vets, Named Animal Care and Welfare Officers (NACWOs) and animal care staff, and provide a valuable forum for discussion of advances in the 3Rs.

The relationships within the network of animal committees at the University of Oxford

Summary of the role of the 3Rs sub-committee within the ethical review process

The 3Rs sub-committee also arranges lectures and workshops in areas it has identified as being important. For example, in 2013 we held a workshop on ‘Developments in Transgenic Mouse Models’, involving speakers from both Oxford and MRC Harwell, covering subjects ranging from colony management and background strains to existing transgenic resources and developing new transgenic models.

Working together

Biomedical Services (BMS) is an independent University Department of the Medical Sciences Division. BMS provides world class animal facilities that provide accommodation and care for its animals, delivered by professionally trained staff. A central principle of the University’s policy is the commitment to a culture of care, encouraging a team approach to animal work that fosters good communication and collaboration between all those working with animals in scientific research.

To facilitate this, in addition to their role on AWERBs, BMS staff, (including vets and NACWOs), routinely attend Departmental Welfare meetings, providing an informal opportunity for project and personal licence holders to discuss their work. The regular interaction has encouraged BMS staff and academic scientists to work together to achieve both high quality research and animal welfare.

Finally, BMS also provides key central services, such as the University’s new online training and competency records and colony management systems. Furthermore, practical veterinary assistance is also provided, such as a recent series of workshops on aseptic technique.

The future

Whilst Oxford has made great progress in implementation of the 3Rs throughout its scientific research programme, more can still be done. For example, we are currently building a ‘3Rs Knowledge Bank’ containing key and up-to-date references and protocols relating to best practice in the 3Rs.

We are also currently working on a University Strategy for the 3Rs, based upon the NC3Rs publication ‘Implementing an Institutional Framework for the 3Rs’. This will ensure that the 3Rs are thoroughly embedded in the research activities of the University, and that when animal research is necessary, it is conducted to the very highest of standards.

Professor Stuart Peirson

Chimpanzee Retirement: Facts, Myths, and Motivation

How often have you heard the claim that chimpanzees who have moved to a sanctuary have felt “dirt and grass under their feet, sunshine on their faces” for the first time in their entire lives because they have come from laboratories where they have only known barren, concrete environments?

Yerkes chimpanzees

Chimpanzees at the Yerkes National Primate Research Center.

You may hear it pretty often if you follow the fundraising and publicity campaigns that are aimed at raising money to support facilities that care for animals retired from research.  Among many examples, are recent comments by Cathy Willis Spraetz, president and CEO of Chimp Haven. Chimp Haven is the US chimpanzee sanctuary supported and administered primarily by the National Institutes of Health (NIH) through public, federal funds that assure lifetime retirement care of research chimpanzees. Chimp Haven was founded in 1995 by behavioral scientist Dr. Linda Brent and a group of primatologists and business professionals.

In a recent presentation, Chimp Haven’s current CEO Spraetz said:

“Many of these chimpanzees have spent literally decades in laboratories. And so their experience has been concrete and mesh, not grass, not dirt. And so after decades of being there, coming to Chimp Haven is a novel experience and a very scary one. Many of them do not want to put their feet down on grass or dirt. …  We try to accommodate the chimpanzees and meet them where they are. The good news is that many of them, after a couple of years, actually can transition. But in the meantime, we give them a lot of different spaces so they can feel comfortable where they are.” [Emphasis added.]

Similarly, in a CNN story this weekend“Retired means to sanctuary. Labs are lots of things, but they are certainly not sanctuaries, and so it’s important that the chimps come here,” Spraetz said. She noted that some lab chimps have lived in cages for so long, they’re afraid of grass when they arrive at Chimp Haven. Gradually, they become accustomed to living in a more natural setting.”

The image and language resonate. They evoke emotional responses in compassionate people who care about animal welfare. But are they claims that are representative of the actual situation?

In many cases, they are not at all. For example, the picture below shows chimpanzees in four settings. In each, it is easy to see that the chimpanzees have dirt under their feet and sunshine on their faces.  Where are they?  Two are current research facilities, one is an NIH-funded sanctuary, and one is a publicly-funded zoo.

chimp housing [Autosaved]

Clockwise: Top – Yerkes National Primate Research Center, Atlanta, GA (Note: Yerkes’ chimpanzees are not NIH-owned or supported); Lincoln Park Zoo, Chicago, IL;  MD Anderson Keeling Center for Comparative Medicine, Bastrop, TX; Chimp Haven, Keithsville, LA.

In fact, the majority of research chimpanzees in the US live in settings that provide outdoor housing, including dirt and sunlight. They also provide extensive and complex climbing structures, opportunities for foraging and tool-use, toys, fresh produce and treats, bedding, interaction with expert and compassionate caregivers, and state-of-the-art medical care and facilities.

Are all the facilities equal in all aspects? No. But neither are the sanctuaries, zoos, and other settings that house chimpanzees in the US– more chimpanzees, in fact, than are housed in research facilities (Chimp Care).*  Furthermore, those research facilities are subject to more extensive standards, greater public oversight, and more public transparency than the zoos, sanctuaries, entertainment, and private homes that house chimpanzees.

Misrepresenting chimpanzees’ current housing and care is a problem.

There are a few explanations for why anyone would make the claim, or use partial truths, to encourage others to believe that most research chimpanzees live in barren concrete environments. One is simple lack of knowledge and experience. Another is a deliberate misrepresentation. Neither serves the animals or partnership with others in order to thoughtfully provide for the chimpanzees’ best long-term care. Nor does it serve the public.

It is likely that many members of the public may not be familiar with accurate representation of the conditions and housing of chimpanzees in NIH-funded primate centers.  That is not the case, however, for many involved in sanctuary efforts and who have first-hand knowledge of the dirt, sunshine, and enriched care that chimpanzees receive in many– if not all– research facilities.

Chimpanzees 2

Chimpanzees at the Yerkes National Primate Research Center.

The question isn’t whether there is room for continuing improvement in captive chimpanzee care and housing. No one would claim any captive setting is the same as the wild, or that any sanctuary, zoo, or research facility is beyond improvement. (The same is true for the wild, where chimpanzees are subject to many negative outcomes due to human influence and vital conservation efforts require more support.) But in reality, there is often more similarity than difference in chimpanzees’ actual care and housing between many of the best sanctuaries, zoos and research facilities in the US and in other countries. The question is how to identify best practices that balance animal welfare and the facilities’ purposes and then find workable solutions and funds to make them common practices.

Furthermore, a closer comparison of the actual conditions at the federal sanctuary facility and those at the facilities in which the animals currently live is also key to serious, fact-informed evaluation of statements made about the NIH’s progress and eventual decisions about moving chimpanzees from their current homes to Chimp Haven.  In this weekend’s CNN story, the director of Chimp Haven makes a number of arguments in favor of increased funding and speeding the movement of chimpanzees to the Louisiana facility.  Many of those arguments revolve around whether, and how much of a difference there is between the different settings, and whether there is a difference to the animals’ well-being.

The quality of all of those evaluations depends on factual and specific comparison, as well as evidence for meaningful difference in the animals’ well-being.  The balance of benefit and harm includes the known stress to the animals that is caused by moving across country, into new situations, and into new social groups. Although movement to sanctuary may have benefits, it also has costs to the animals. For example, beyond relocation to unfamiliar housing, care practices and caregivers, the animals also face potential disruption of their social groups, introduction to new groups and upheaval in dominance hierarchies. The adverse impact of these stressors is of particular concern for elderly animals and for others who may be especially vulnerable to negative health effects of stress. Thus, consideration of those balances and comparison of different facilities must be taken together to inform decisions about investments that best suit the animals’ needs.

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Chimpanzees at MD Anderson Keeling Center for Comparative Medicine, Bastrop, TX.

Federal public funding for retired chimpanzees
Over the past 15 years the US public, through federal legislation with overwhelming bipartisan support, has committed to an estimated $86 million to support the lifetime care, housing, and enrichment of retired research chimpanzees. In 2000, federal legislation (Chimpanzees Health Improvement, Maintenance, and Protection; CHIMP Act) established the first national chimpanzee sanctuary and committed life-time funding for retired NIH chimpanzees. As a result, in 2002, a $30 million public investment was made to build and fund Chimp Haven. Chimp Haven is the only federally-funded– though not the largest– US chimpanzee sanctuary.  (For more history and information see here: http://dpcpsi.nih.gov/orip/cm/chimpanzee_management_program)

By 2013, following NIH’s decision to retire the majority of its chimpanzees, additional funds were required for Chimp Haven’s ongoing support. Thus, the CHIMP Act Amendments of 2013 were passed by the US House, Senate, and President. Under new legislation, NIH may

“use already-appropriated funds to pay for care of chimpanzees housed in federal sanctuaries if doing so would be more efficient and economical for the NIH.”

An analysis by the Congressional Budget Office (CBO) in 2012 estimated an additional $56M cost to retire and maintain federally funded chimpanzees for a 5 year period (not the animals’ lifespan). The cost to support the entirety of the NIH’s ~500 chimpanzees may be roughly $8M each year; although the cost will likely vary significantly with increasing medical and care needs as the population ages. The CBO analysis also determined that there was no cost savings to moving federally-owned chimpanzees to sanctuary instead of research facilities.

US federal funds provide the majority of revenue for Chimp Haven and support the majority (~75%) of the cost of each NIH chimpanzee retired at Chimp Haven. Chimp Haven was built and funded primarily for retirement of publicly-owned research chimpanzees. However, it is also used for retirement of privately owned animals who are not supported directly via federal funds. In October of 2014, NIH reported an annual expenditure of $4.44M to Chimp Haven for the care of 191 NIH-owned chimpanzees and an average care cost of $63 per day per chimpanzee. The same report includes a range of $32-60 daily care cost for chimpanzees in other NIH facilities that house NIH-owned chimpanzees.

Chimp Haven photo from NAPSA

Chimp Haven, US federal chimpanzee retirement facility. http://www.primatesanctuaries.org/sanctuaries/chimp-haven-inc/

Federal support for chimpanzees goes beyond direct care of research animals. For example, NIH and NSF supported scientific research has produced new knowledge that continues to benefit chimpanzees in the wild and in captivity. Furthermore, federal investment in the nation’s primate research centers from the 1960s on supported continuing advances in chimpanzee housing, care, and enrichment that now drive best practices and chimpanzee health care in zoos, sanctuaries, and research facilities.

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Chimp Haven, US federal chimpanzee retirement facility. http://www.primatesanctuaries.org/sanctuaries/chimp-haven-inc/

Is misrepresenting research facilities necessary?

It is unfortunate that some of those leading sanctuary publicity and fundraising efforts continue to base their appeals in claims that generally have little basis in current fact. It is also unfortunate that the many campaigns for fundraising for the federal sanctuary fail to let the public know that the NIH and US have, in fact, pledged lifetime support for federally-owned chimpanzees. This level of public support has not always occurred in those countries that have dismantled their chimpanzee research facilities.

Some of the current campaigns centered on US chimpanzees give the impression that NIH ended research and put the chimpanzees out on the street without a dime, leaving others to provide for their “rescue.” That is far from the truth.

Fundraising is required to meet roughly one-quarter of the cost for NIH-owned chimpanzees at Chimp Haven and the full cost for chimpanzees at other sanctuaries.  But for those that care about supporting the animals and decisions in the animals’ best interests, that fundraising should not require a storyline based in half-truth or deliberate misrepresentation of the conditions in other facilities or the efforts of others who care for chimpanzees.

Allyson J. Bennett


* An estimated 1,822 chimpanzees live in the US. The care for roughly half of the chimpanzees in the US, including most of the 206 chimpanzees retired to the federal sanctuary (Chimp Haven), is provided in large measure by federal public funds. According to Chimp Care, a census project from Lincoln Park Zoo, US research facilities house 625 chimpanzees, while a research reserve houses 172.  Private sanctuaries house roughly one fifth of US chimpanzees (N=318). Nearly one-quarter of the chimpanzees in the US live in zoos, both those accredited by a non-public agency, the American Zoological Association, (262) and facilities designated as unaccredited in Chimp Care’s data (174). Chimpanzees in the US are also kept in entertainment venues (14) or by private breeders and private owners who regard them as pets (51). Such private ownership of primates is opposed by leading scientific organizations including the American Society of Primatologists.

Students in Rome to rally for Prof Caminiti and future of science in Italy

Tomorrow students at the Sapienza University of Rome – Italy’s largest University – will join their Professors and members of the campaign group Pro-Test Italia outside the Department of Physiology and Pharmacology to show solidarity with Professor Roberto Caminiti, a leading neurophysiologist whose work is being attacked by animal rights extremists.

Tomorrow Pro-Test Italia will return to the streets of Rome, joining students and scientists in support of crucial research.

Tomorrow Pro-Test Italia will return to the streets of Rome, joining students and scientists in support of crucial research.

As with many recent instances of anti-scientific populism in Italy, the campaign against Prof. Caminiti began in earnest with a dishonest broadcast on the Italian tabloid TV news programme Striscia la Notizia which misrepresented the work being done by Pr0f. Caminiti and his colleagues. Prof. Caminiti responded to these false allegations in a video which you can watch here (in Italian with English subtitles)

Following the broadcast the European Animal rights Party (PAE) announced that they would be holding a demonstration Sapienza University of Rome, on February 5 2015, with the declared will to “free” the monkeys that are used by Pr0f. Caminiti and his colleagues. This has sparked concerns that the PAE – and the more extreme animal rights groups who will no doubt accompany them – will attempt to repeat the events of 20th April 2013, when five animal rights activists forced entry into the Pharmacology Department of the University of Milan, stealing hundreds of mice and destroying years of research.

There is, however, a major difference between 2013 and today; today scientists and students are ready to stand up and  defend their research. A group of neurobiology students at the Sapienza University of Rome have organized a counter-demonstration (see this Facebook event for details) tomorrow morning – February 5 – to show support for Prof Caminiti, defend their department, and speak up for the future of scientific research in Italy.

On Monday their stand received a boost when Professor Vincenzo Vullo, Head of the Faculty of Pharmacy and Medicine at Sapienza University of Rome, circulated an email to all scientists, staff and students to express support for Prof. Caminiti, and called on them to join him in defense of the research being undertaken at the Department of Physiology and Pharmacology:

Dear colleagues, dear students,

I transmit an open letter by Prof. Roberto Caminiti in defense of the unacceptable smear campaign underway against the scientific activity of the Laboratory of Behavioral Neurophysiology, Department of Physiology and Pharmacology of our University.

In this regard, I wish to emphasize the scientific value of Prof. Caminiti, an internationally acclaimed researcher whose research has made a significant contribution to the knowledge of the central nervous mechanisms of motor control. I also want to remember especially his human qualities, demonstrated in the constant respect and care with which he always treated animals necessary for his studies.

In expressing my personal solidarity with Prof. Caminiti, I ask for the support of all members of the faculty in defense of the scientific research conducted at the Laboratory of Behavioral Neurophysiology of our university.

Vincenzo Vullo”

The email also included a letter addressed to all staff and students from Prof. Caminiti:

Dear Colleagues, dear Students,
On December 18 2014 the TV show “Striscia la Notizia”, using images illegally shot in our animal facilities, broadcast a report with the aim of stirring in the public opinion a campaign condemning the scientific activity of the Neurophysiology of Behaviour Laboratory, in the Department of Physiology and Pharmacology of our Atenaeum, where other professors and I carry out our scientific activity, which started in the year1985.
To reply to the accusation of animal cruelty, as an act of absolute transparency of research towards the public, I posted online a reasoned reply, in which it is showed and commented on everything that is performed in our laboratories, thanks to several projects financed by MIUR (Italian Government research funder- Speaking of Research) and the EU, and according to experimental protocols regularly authorized by the Ministry of Health.
On January 23 2015, once again “Striscia la Notizia” returned to the topic, using the images we put online, to claim, with the help of a “flora and fauna” specialist (!) that our studies were useless and cruel, where it is unanimously recognized in the scientific community that our research, together with other work carried out in a select group of international laboratories, lead to the development of brain-computer interface in humans and to the cerebral control of artificial prostetics in patients with paralysis due to neurodegenerative or neurovascular diseases, just like similar researches lead to the development of deep brain stimulation in the treatment of Parkinson’s disease.
Exploiting the footage broadcasted by “Striscia la Notizia”, the European Animal rights Party (PAE) launched a national demonstration, set to take place on February 5 2015, in front of our Department, with the declared will to “free” the animals that we are working with, and together with the Antivivisection League (LAV) stated that they have submitted a complaint to the Prosecutor’s Office in Rome, to open an investigation aimed to the confiscation of the animals, and to open a criminal case against me for animal cruelty.
I call on you, confident that you believe in a country guided by reason, commitment and study, and not driven by obscurantism, just like the “Stamina” case, that you all well know (for more on the Stamina scandal see this recent report -Speaking of Research) . And I ask yo to defend, with the appropriate instruments, the scientific activity and the dignity of a Department of our Atenaeum.
On the morning of February 5, wearing a white lab coat and flower in the buttonhole, I will be in front of my Department to defend and reaffirm that ideal that drove us all to become MDs and researchers.
With best regards,
Roberto Caminiti

We congratulate both faculty and students at Sapienza University of Rome for taking this action in support of science, and wish them, Pro-Test Italia, and all friends of medical progress every success as they stand together in this noble cause.

Speaking of Research