Public dialogue about US research chimpanzee retirement: Unanswered questions

Growing concerns about NIH’s plan for retired research chimpanzees summarized in a WIRED article last week continue to provoke more questions than answers. These questions fall into three general areas discussed below. In many cases, they are questions that could stem simply from a lack of transparent, public information. One example of this is found in the reported deaths of nine chimpanzees within 18-months of transfer to the federal sanctuary, Chimp Haven. Whether the number of deaths is higher than expected given the age, health, and average mortality rates for chimpanzees is unclear and has not been addressed with public, factual information about what happened to those nine animals.

Similarly missing is information needed for serious consideration and public dialogue about the plan for relocating chimpanzees; continuing research with retired chimpanzees; and the processes and standards in place for chimpanzee care, external oversight, and public transparency across different types of facilities. Rather than addressing these questions, some have instead simply dismissed “the lab community” as unfair critics of the federal sanctuary (for example, Chimp Haven’s CEO).  That response fails to answer what should be common concerns not only across the many communities that care about chimpanzees, but also more broadly to the public that ultimately provides support for the animals, the research, and the policies that set the framework for decisions that govern chimpanzee care across the many facilities in which they live.

Three sets of questions—largely unanswered—that are integral to informed, serious, public consideration of the future of US chimpanzees are summarized below. They are:

Photo credit: Kathy West

Photo credit: Kathy West

  • Chimpanzee health and well-being: Is everything that can be done to ensure the best care, health, and well-being of the chimpanzees being done?
  • Research:  Should federally-supported retired research chimpanzees within sanctuaries be involved in research?
  • Decisions and evidence: What is the process for decision-making?  How are conflicts of interests handled?  What kind of evidence supports the decisions about chimpanzee health and well-being?

1)  Chimpanzee health and well-being: Is everything that can be done to ensure the best care, health, and well-being of the chimpanzees being done?

First and foremost are questions about the animals’ health and well-being.  The primary question here is whether relocation is the best option for all of the chimpanzees. A number of posts here have provided detail about the issue. The main consideration is whether decisions about the transfer of chimpanzees from their current homes to a new home are adequately informed to ensure the best outcome for each animal. Of particular concern is whether there is a process for examining previous outcomes in order to identify whether changes are needed.

The latter is exactly why the deaths of 9 of 13 chimpanzees transferred from the National Center for Chimpanzee Care (Bastrop) to the federally-supported sanctuary, Chimp Haven, continue to raise questions.  The questions are not—as has been repeatedly emphasized—about the quality of care at Chimp Haven. Nor are they about population-level mortality analysis as was conducted and reported in a yet-to-be-reviewed manuscript posted by a scientist at NIH (see below for further discussion). Rather, as would be the case in most facilities that operate under federal license or registration with the USDA,  the question is whether the circumstances surrounding those deaths has been reviewed carefully and thoughtfully in order to inform future practices and decisions in a way that minimizes future risk and ensures the best outcomes for the chimpanzees. For example, it would be logical to ask whether the circumstances surrounding the deaths were examined by the USDA, or whether NIH commissioned, or requested, any evaluation of the deaths. This would be common procedure in any facility subject to USDA oversight.

Chimpanzees in research, zoo, and sanctuary facilities

Chimpanzees in research, zoo, and sanctuary facilities

Consideration of decisions about relocation goes far beyond these nine deaths, however. There are a number of factors that inform concerns about the plan to transfer chimpanzees from their current homes. Among them: 1) the animals’ age and health; 2) the consequences of relocation, including disruption of existing social groups and separation from long-time environments and caregivers, introduction into novel environments, with novel caregivers, and chimpanzees; 3) the time-span over which the transfers will occur.

All of these factors underlie questions about the end result of the recently announced plan to move all NIH-owned and supported chimpanzees to Chimp Haven over the next 10 years. As summarized by a commenter on our previous post:

“I have read with bewilderment the recent NIH announcement about their plan to retire the remaining chimpanzees housed at Alamogordo, Bastrop and Southwest Foundation and the press release from HSUS applauding the plan and their appreciation of all the effort by Dr. Collins and NIH have made to implement the plan. Why should anyone be excited about this plan? From what I read, their plan is attrition. For presumably the next 10 years, NIH is going to watch and monitor the chimpanzee mortality rate at Chimp Haven and fill the vacancies with chimpanzees currently residing at APF, Bastrop and then Southwest (the NIH preferred order). How can attrition and replacement be considered a reasonable and humane retirement plan by either the research community or animal welfare advocates?”

2) Research: Should federally-supported retired research chimpanzees within sanctuaries be involved in research? 

The announcement of a partnership with the Lincoln Park Zoo, funded by a private agency (Arcus Foundation), apparently part of broader effort to promote research with chimpanzees at the federally-funded retirement facility raised a host of questions. On the one hand is the obvious question about why chimpanzees retired from research should be the source of fundraising in order to conduct research (see here). The very definition of sanctuary and what differentiates a sanctuary from a zoo or a research facility was also raised by the announcement (see here).

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Photo credit: Kathy West

There are many who do support ongoing behavioral, psychological, cognitive, genomic, neural and other noninvasive research. This is the very same conclusion that was reached by the Institute of Medicine committee that reviewed the necessity of chimpanzee research (see report here). But the announcement of a research program at Chimp Haven raised many questions about how the research conducted there now, and in the future, will be overseen. For example, in contrast to well-established and transparent practices for decisions about NIH, NSF, or other federally-funded research, there appears to be little public information about the process for research approval and conduct of research at Chimp Haven.

The broad questions surrounding research at Chimp Haven are whether information about the review, oversight, and transparency of research projects is available and where it can be found. Moreover, the announcement that the sanctuary intends to recruit scientists and more research raises questions about whether there should be further consideration and open dialogue about whether the processes put into place by the private facility are appropriate for research conducted with animals who receive 75% of their support from federal sources.

Questions include: What is the process for deciding whether, and which, research projects are conducted with federally-supported chimpanzees within the sanctuary? What are the mechanisms for external oversight, transparency, and ethics review of the research proposals? How are perceived and actual conflicts of interests handled? The answer to these questions at present appears to be that Chimp Haven has a review board that operates as an Institutional Animal Care and Use Committee (IACUC) for the facility. In general though, there is not enough information about process to inform serious and thoughtful consideration. For example, among other questions, it is not clear that the facility has a scientific merit review or a mechanism to guard against conflicts of interests or to promote equitable access.

3)  Decisions and evidence: What is the process for decision-making?  How are conflicts of interests handled?  What kind of evidence supports the decisions about chimpanzee health and well-being?

A third set of questions that have become of increasing concern as events, decisions, and announcements about chimpanzee retirement unfold surround processes for decision-making. Again, the issue here is about unanswered questions in response to community concern and public interest. The two previous points highlight a number of questions rooted in “process.” Most recently, the issue of what kinds of evidence should be used to inform decision-making was put into sharp relief by the appearance of an analysis of chimpanzee mortality across dedicated research centers and the federal sanctuary. That report was posted online, ahead of peer-review or publication in a scientific journal, and the day before NIH’s announcement that all NIH-owned chimpanzees would move to Chimp Haven over a 10-year period.

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Photo credit: Kathy West

While it may not be entirely clear to those outside the scientific community, the online article had not been subjected to review – either via comments online, in an open-access venue, or by expert peer-review. Peer-review  is normally conducted by scientific journals and is part of online publication as well.  Peer review is an important part of the scientific process. In brief, the purpose of such review is to identify potential flaws in the study design, analysis, or interpretation of the data. The process of review then requires the author to address criticisms. In some cases, the criticisms are rebutted and the paper improved by clarifications. In other cases, the criticisms cannot be rebutted because the study, analysis, or interpretation is flawed.

What is important to remember is simple. Confidence in the conclusions of a study, particularly one for which criticisms have been raised and not yet addressed, should be measured accordingly. Yet, already the conclusions of this article have been cited as “proof” for a position about relocating chimpanzees. For example, in a posting from the Jane Goodall Institute:

“As animal transfers are sometimes considered potentially harmful, it is satisfying to note it was found that there is no proven link between relocation and premature death of captive chimpanzees.

In fact, the article cited does not substantively address the claim. Rather, as chimpanzee research expert, Professor William Hopkins, points out, “the analyses performed in the study are not designed to test for a “link” between relocation and premature death. As others have noted, this would require an analysis of the mortality rate of chimpanzees transferred to Chimp Haven be compared with age-sex matched apes that are not transferred. These kinds of comparisons that are necessary to make these inferences are absent in the paper as it is currently written.”

Thus, not only do a number of questions and criticisms of the article remain unanswered, but it is also true that the mortality analysis does not address the fundamental point for which it is being cited as supporting. What the analysis does appear to show is that many – perhaps most—of the retired chimpanzees are likely to die before they are transferred. From data presented in Figure 4 of the paper, it appears that roughly 20% of the chimpanzee population would be predicted to die within 3 years and that less than 40% will be alive in 9 years. By extension, of the animals who are now slated to move within the 10 year period announced by NIH, it could be the case that only 30% will be alive at that point. Again, however, conclusions based on this analysis should be viewed with caution. Nonetheless, if this interpretation were true then it would seem that the majority of chimpanzees will, in fact, remain in their current homes for a substantial amount of time. In turn, several considerations and new discussions of alternatives might be raised– as they were in comments that we will return to in a subsequent post.

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Chimpanzees at NCCC. Photo credit: Kathy West.

Furthermore, the NIH plan and discussion surrounding it has yet to reveal how the mortality analysis will inform decisions at the level of the individual chimpanzee. Given that age is nearly certain to be the biggest mortality predictor, the question is whether the oldest animals will be the least or the most likely to move first? In the NIH plan, age is ranked ahead of existing social group as a consideration for priority in relocation to sanctuary. The question there is – given social groups are generally comprised of animals of mixed ages—will groups be prioritized for movement based on the age and health of the oldest members?

Decisions about the priority order for moving chimpanzees are undoubtedly incredibly difficult and must account for complicated sets of factors. Whether there should be transparency in those decisions, at the level of the individual animals, is one of the main questions that arose in discussion of the deaths of 9 NCCC chimpanzees transferred to the federally-funded sanctuary. It arose for the simple reason that Chimp Haven’s CEO, in defending her facility, raised pointed questions about the decision to transfer particular animals. She claimed:

“…the selection of the individuals to be transferred was not made by Chimp Haven, or even The National Institutes of Health, but by the laboratory itself.  In fact, Chimp Haven has never had a say in selecting any individuals for retirement despite the fact that we have advocated for such a role to ensure that these retirement transfers were best planned and operated. So one might reasonably question why several of the transferred chimpanzees were placed on “quality of life” watch prior to transfer. Or why most of the transferred chimpanzees were well beyond the median life expectancy for the species.”

Whether this is true or not cannot be easily – if at all– discerned by the public. Why? Because the process of decision-making is mostly not transparent in public view. As a result, competing claims cannot be fully evaluated with any serious, thoughtful consideration by members of the public, nor by the media, policy-makers, or members of the research, sanctuary, and zoo communities. Nor does it appear that there is any mechanism for unanswered questions to be addressed. There are many things that are troubling about the situation. From the perspective of dialogue and community efforts to guide decisions in the best interests of the animals’ health and well-being, research, and public support, the continuing lack of response to questions or perceived criticism is among the largest of the obstacles to progress and understanding.

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Photo credit: Kathy West

Summary.  One of the goals of Speaking of Research is to provide a place for public dialogue about ongoing events, perspectives, and consideration of animal research. We hope that the questions posed above might help move the dialogue forward with answers to questions that remain unaddressed and information that can fill gaps in public knowledge. In turn, the answers may help provide a better understanding of the situation and a more thoughtful, broad public consideration of the future for retired chimpanzees and for chimpanzee research.

Speaking of Research

Hungary publishes 2015 animal research statistics

Hungary has published its annual statistics showing the number of procedures carried out on animals for scientific purposes in 2015. This post has translated much of the statistics into English and aims to interpret the data as a whole. In 2015, Hungary conducted 184,648 animal procedures on animals – all regulated under EU Directive 2010/63. This figure is 8% lower than in 2014.

Procedures on animals in Hungary for research in 2015. Click to Enlarge

Procedures on animals in Hungary for research in 2015. Click to Enlarge

Overall, 87.7% of procedures were done on mice, birds and rats. This figure rises to 93.8% when cold-blooded animal reptiles, amphibians and fish are included. Dogs, cats and primates together accounted for less than 0.15% of the total.

Trend over time in animal experiments in Hungary. Click to Enlarge.

Trend over time in animal experiments in Hungary. Click to Enlarge.

Using the trend graph we can see how – bar an anomalous year in 2013 – there has been a steady downward trend in animal procedures in Hungary from over 300,000 in 2007, to less than 200,000 in 2015. Perhaps coincidentally the 2013 high point coincides with the implementation of the EU Directive (and its rules around counting procedures), meaning it is possible that this figure is a statistical error caused by incorrect data from the first year under a new counting regime.

Animal Research by Species in  Hungary Pie Chart 2015

Other things to note in the Hungarian statistics:

  • Only 3.8% of animal procedures were on genetically altered animal – a much lower proportion than, say, the UK, where almost half of procedures were the breeding of a genetically altered animal.
  • 40% of procedures were for regulatory purposes, 34% were for translational or applied research, 21% was for basic research, and the remainder was for other purposes. It is common in smaller European countries for a larger proportion of animal studies to be for regulatory purposes.
  • Hungary also provided retrospective severity data for animal procedures. 71% of procedures were classified as mild, 15% as moderate, 6% as severe, and 8% as non-recovery (where the animal is not woken up after being anaesthetised for surgery).

Speaking of Research seek to be the best source of information on the internet on animal research and testing statistics. Unfortunately language barriers mean that we often find it hard to get statistics from non-English speaking countries. If you speak multiple languages and are able to help us out finding the statistics from other countries we would be very grateful. See more about how to help here.

Find more on the Hungarian stats here: https://www.nebih.gov.hu/data/cms/176/152/Allatkiserleti_jelentes_2015.pdf

Speaking of Research

Research using sheep leads to a new device to record and stimulate the brain

A group of Australian and American researchers have used sheep to develop and test a new device (original paper) – the stentrode – for recording electrical signals from inside the brain. The research was published in Nature Biotechnology. This new technology removes one of the main obstacles to developing efficient brain-computer interfaces: the need for invasive surgery.

The “stentrode” is a group of small (750 µm) recording electrodes attached to an intracranial endovascular stent, which allows implantation of the electrodes inside the brain without invasive surgery. This allows high quality recording or stimulation of specific areas of the brain, without many of the risks associated with invasive brain surgery.

Image courtesy of the University of Melbourne

Image courtesy of the University of Melbourne

A stent is a tube-shaped device whose walls are made from a metallic mesh, designed to navigate inside brain’s system of blood vessels, until a desired position is reached. Once in place the mesh is expanded, securing it against the blood vessel walls. Importantly, stents are designed to be implanted by inserting them through a large blood vessel, like the jugular vein, and gradually “pushing” them into the desired position, by twisting and turning at critical juncture points where veins branch. During this implantation procedure the surgeons observe the stent’s location using a non-invasive imaging technique named cerebral angiography.

Recording the electrical activity of brain cells with high fidelity is the basis of new technologies to restore quality of life to many people with neurological diseases. For example, through brain-computer interfaces that interpret neural signals, people paralysed by damage of the spinal cord have been made able to control external devices, such as wheelchairs, robotic arms, and exoskeletons. Much of this work was initially done in monkeys– getting them to also control wheelchairs and robotic arms. Moreover, brain recording devices can be used to detect the timing and location of seizures with great precision, which helps minimise damage to healthy parts of the brain when treatment involving surgery is necessary.

One obvious problem with the current technologies is that there is a clear trade-off between the quality of recordings obtained, and degree of invasiveness. To explain this, let’s look at two extremes of techniques for recording brain activity – electroencephalogram (EEG) and microelectrode arrays.

EEG, recording from the scalp, is by far the least invasive technology: electrical activity of the brain can be recorded through a cap dotted with electrodes, and no surgery is required. However, because the signals being measured are so weak (due to the distance between brain cells and the recording electrodes), this technique can only detect the combined activity of millions of brain cells, when they work at the same moment (signals from small groups of cells tend to average out, not producing an electrical “spike” large enough to be detected far away). Thus, devices controlled by brain-computer interfaces based on EEG tend to be difficult to control, and have few “degrees of freedom” (how many different actions can be specified by the user). Moreover, it is difficult to determine exactly where the signals of interest are coming from, and electrical activity from regions well inside the brain is much harder to detect.

EGG. Image courtesy of Saint Luke’s Health System

EGG. Image courtesy of Saint Luke’s Health System

At the other end of the continuum are recordings using microelectrode arrays- small devices that are implanted directly in the brain, which contain many small metallic probes each capable of “listening” to the electrical activity of a single neurone, or a small groups of neurones. This technique, developed over many years of studies in rats, cats and monkeys, has been used recently to demonstrate the ability of a tetraplegic patient to control its own muscles again, using a brain-computer interface which included a microelectrode array to record the signals that encoded the participant’s intention to move, coupled to stimulation devices attached to different arm muscles.  Much more refined control can be achieved with this method, as one can potentially record individual signals from thousands of neurones, across many brain areas. The disadvantage, however, is clear: these devices have to be implanted directly in the brain, requiring complex neurosurgical procedures. Moreover, the insertion of the electrode arrays in the brain causes local damage, which triggers inflammatory tissue responses that, over time, can reduce the quality of recordings. Although this damage can be minimised by using larger electrodes that lie on the surface of the brain, instead of penetrating it (electrocorticography, ECoG), the need for invasive surgery remains.

Microelectrode array. CC Image by Richard A Normann. Tbe actual size of this array is 4 x 4 mm

Microelectrode array. CC Image by Richard A Normann. Tbe actual size of this array is 4 x 4 mm

As we can see, the stentrode has the potential to be the best of both worlds – offering the accuracy of microelectrode arrays and the benefits of avoiding non-invasive surgery usually associated with technologies like EEG.

Part of the problem solved by the stentrode developers was to find an adequate animal model, which would yield information valid to the situation of the human brain. Sheep were chosen due to the similar topology of the brain’s venous system, and the similar diameter of the critical blood vessels. The stentrodes were implanted inside a large vein that lines the somatosensory cortex – the part of the brain that encodes sensory information about touch, as well as muscle contraction and position of the body’s joints. Importantly, once implanted, they stayed in place without damaging the brain or blood vessels, and allowed stable neural recordings for over 6 months – while the sheep were freely moving around.

Stock image of sheep in research (in the UK) by Understanding Animal Research.

Stock image of sheep in research (in the UK) by Understanding Animal Research.

Currently envisaged applications of this new technique include “reading” signals for control of artificial limbs and seizure prediction in epilepsy. With some modifications, the same technique can be used for localised electrical stimulation of the brain, which may allow new treatments for Parkinson’s disease, and obsessive-compulsive disorder. Deep Brain Stimulation, a currently used treatment to treat the tremors associated with Parkinson’s, requires invasive brain surgery to implant electrodes – this process could be made easier and safer using stentrodes. Besides being good news for people who may one day benefit from an easier way to have electrodes inserted in the brain for treatment of diseases, this story also illustrates two important points. First is the usefulness of animal models to develop treatments that directly benefit people. The sheep brain is not identical to the human brain, but can be judiciously used to model a critical feature of the latter, in a manner that is directly relevant for testing a device intended for human use. Second, that results take time to translate from basic research in animals to human use. The current generation of brain-computer interfaces would never have been developed were it not for decades of research on seemingly “basic” topics, such as how to best record different types of electrical signals from the brain, how and where the brains of various animals encode information for sensation and movement, and how blood vessels are organised and function. This is however just the beginning, and a lot more needs to be done on the way to useful and safe devices.

Marcello Rosa and Tom Holder

Original Paper: Oxley, Thomas J., 2016, Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recording of cortical neural activity, Nature Biotechnology34, 320-327. Doi:10.1038/nbt.3428

Switzerland’s animal research in numbers for 2015

The statistics for animal research conducted in Switzerland in 2015 were released last week. We have translated these tables to English and these data are summarized below.

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Animal Research in 2015 in Switzerland. Click to Enlarge

Number of animals used in research in Switzerland in 2015. We have added a column titled "Total 2014" to aid comparison. Click to Enlarge

Number of animals used in research in Switzerland in 2015 in greater detailClick to Enlarge

Overall, there were 682,333 animals (not including invertebrates except Cephalopoda and lobsters) used in research and animal testing in Switzerland in 2015. Most of these animals were involved in basic research (66.1%), with “discovery, development and quality control” being the next most common (19.2%). The remainder were used for other reasons including disease diagnosis, education and training and protecting the environment. Mice were again the most prevalently used species (60.4%).

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Click to Enlarge

92.2% of the animals used in research and testing were conducted on mice, rats, fish and birds, similar to other European countries. Monkeys (198), cats (621) and dogs (2,518) together accounted for 0.6% of all research animals, with an overall decrease of 547 animals from 2014 for these species.

Animal Research in Switzerland

Animals used in research in Switzerland in 2015. Click to Enlarge

Pain, suffering and harm, were also measured and classified under four grades of severity; 0, 1, 2 and 3. In 2015, 42.9% of experiments were Grade 0, 34% were Grade 1, 21% were Grade 2 and 2.1% were Grade 3. These are defined as follows:

The following four categories are used for constraints on animals resulting from procedures or measures in the context for animal experiments:

  • Severity grade 0 – no constraint: Procedures and actions performed on animals for experimental purposes that do not inflict pain, suffering or harm on the animals, engender fear or impair their general well-being;
  • Severity grade 1 – mild constraint: Procedures and actions performed on animals for experimental purposes that cause short-term mild pain or harm or a mild impairment of general well-being;
  • Severity grade 2 – moderate constraint: Procedures and actions performed on animals for experimental purposes that cause short-term moderate or medium to long-term mild pain, suffering or harm, short term moderate fear or short to medium-term severe impairment of general well-being;
  • Severity grade 3 – severe constraint: Procedures and actions performed on animals for experimental purposes that cause medium to long-term moderate pain or severe pain, medium to long-term moderate harm or severe harm, long-term severe fear or a severe impairment of general well-being.
Severity Data in Switzerland since 1997. Click to Enlarge

Severity Data in Switzerland since 1997. Click to Enlarge

These numbers are relatively consistent across time, with on average 78% of all animals being exposed to no or minor short-lasting pain and distress.

Trend over time in animal experiments in the Switzerland. Click to Enlarge.

Trend over time in animal experiments in the Switzerland. Click to Enlarge.

Overall there has been a steady downward trend in the number of animals used in research in Switzerland over the last 30 years, despite the observed increase in the number of animals used between 2014 and 2015. According to SwissInfo, Switzerland’s federal veterinary office said in a statement that “the increase in animal experiments was linked to studies involving large herds of animals and to species conservation projects”.

See details of Switzerland’s 2014 statistics

Speaking of Research

A New Culture of Openness in Animal Research

Animal research has been credited with improving human health and leading to many medical breakthroughs. However, animal research still remains a controversial topic, with many animal rights groups believing that animal research is wasteful and pointless. One way to improve the public opinion of animal research is through education and openness. Openness can be achieved by showing the public what an animal research facility looks like and what research takes place there, in addition to discussing how that research affects human health.

In order to address the goal of transparency and openness in animal research, 72 organizations involved with bioscience in the United Kingdom (UK) launched the Concordat on Openness in Animal Research. Currently, over 100 UK organizations have signed the Concordat and pledged to “be clear about when, how and why [they] use animals in research”, “enhance [their] communications with the media and the public about [their] research using animals”, “be proactive in providing opportunities for the public to find out about research using animals”, and “report on progress annually and share [their] experiences”. The Concordat, and the new environment of openness it seeks to encourage, has led many institutions to become more open to the media.

Last week, The Sun published an article about animal research at the University of Leicester in the UK. The University had opened its animal research facility to a journalist and a photographer who had an opportunity to witness the research first hand as well as talk to the researchers and staff at the facility. The article is a great example of not only openness in animal research but in research in general.

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Click to Enlarge

Andrew Fry, Director of Research in the College said:

“At Leicester we’re very keen to make sure that we are completely open about the animal research that we undertake and that it fully adheres to all national guidelines. Our research on animals is entirely aimed at improving human health and includes important studies on some of the most common and devastating illnesses, from cancer and heart diseases to diabetes and obesity. Many important breakthroughs have been made as a result of our animal research and it’s vital that we explain this clearly to the public.”

The article provides an accurate and unbiased view of animal research. The author describes the research on the animals truthfully and details the care and dedication the researchers have for the animals they work with. Also provided within the article are pictures from inside the lab documenting the living conditions of the research animals involved in the studies. While media visits inside labs are becoming more commonplace in the UK, it is still amazing to see that journalists were allowed to watch and capture images of research procedures – such as the injection of a gel into the brain of a rat, followed by suturing of the incision.

Rat in Surgery

Overall, The Sun piece has been met with optimism from the animal research community.

Wendy Jarrett, Chief Executive of Understanding Animal Research who supported the University throughout the project, said: “Many congratulations – I know its nail-biting stuff doing visits like this, but pitch-perfect coverage like this shows that it is so worth persevering.”

Openness from researchers in animal research has not always been easy. Efforts to open up have often met resistance from those with memories of the “bad old days”, when acts of animal rights extremism were still the norm. These tactics were used by a small minority of animal rights activists in an attempt to force the end of animal research. Although extremism is not gone, it is at an all-time low in most countries – including the UK. Furthermore, animal rights extremism can be countered by scientists speaking openly about their research and trying to inform public opinion by providing facts about animal research.

Although this article is a step in the right direction for a new culture of openness in animal research, as several of the commenters suggest, there is still more work that can be done to continue to educate the public of the importance of animal research. However, continuing openness by animal researchers, not only in the UK but around the world, can help the public better appreciate the importance of animal research.

Sarah Elkin

What is science?

We learned today from an NIH announcement about a new plan by the federal agency to relocate and transfer all of the NIH-owned chimpanzees to the federally-funded sanctuary, Chimp Haven, by 2021 or later. The announcement was quickly the subject of announcements and proclamations of victory by PETA, HSUS, and some associated with Chimp Haven.

For others, in light of the concerns raised about the death of 9 of 13 chimpanzees transferred to Chimp Haven recently and subsequent calls for a thoughtful examination of these cases—at least a review of what might be done to minimize future risk—the announcement was troubling.

PETA on nih chimp announce 08.11.16It does appear that NIH either shared, or was at least responsive to the need to address, the concerns that were expressed about the consequences of relocation on the chimpanzees’ health and welfare. That is evidenced by the fact that NIH did undertake an analysis of mortality rates at Chimp Haven and the research centers that house NIH chimpanzees.  That is as it should be – scientists use data to inform decisions.  No problem there. NIH conducted the analysis on the basis of data requested from each of the centers. It also appears that they referenced the findings of the analysis in their decision.  So what’s the problem?

It appears that the only evidence of the mortality analysis is a non- reviewed paper that was posted just yesterday to a website (Biorxiv) by the study author, NIH’s Dr. Michael Lauer. tweet bioRxiv 08.11.16That paper may be viewed here. After even a cursory review and analysis of the Lauer paper, many questions are raised about both the methods and the conclusions drawn from the results.  Just a few of the issues or potential problems that an academic reviewer might raise are listed below. Others may read the paper and have different impressions or questions.The data includes 764 chimpanzees; 314 died during the 7 year median follow-up. The author states that: “The analyses were conducted to inform NIH’s plans to retire its surviving chimpanzees.”

To see NIH use data from an unpublished, non-peer reviewed manuscript as a basis for their decisions is incredibly disheartening. It defies the very premise and basis on which the scientific process works. Science doesn’t accept as fact those data and findings that are presented on the internet and that have not been properly vetted through the peer review process.  Image Biorxiv 08.10.16 LauerBut before turning to questions about the paper, let’s be clear on a critical point:  The questions and critiques raised here would be raised regardless of the conclusions of the paper and regardless of the direction of NIH’s decision. The questions raised here are at the heart of how science is used to inform decisions and judgments.  

In other words, what would we conclude if NIH had used a non-reviewed paper to suggest that relocation was a threat to chimpanzee well-being and that the chimpanzees should be retired in place?  The same criticism would hold.  The issue is about the conduct of science and how it should be shared and viewed in decision-making. In this case, it is particularly important because of the close relationship between the findings and decisions that have immediate and real impact. Furthermore, in a time where scientific rigor and reproducibility are the subject of a great deal of concern and discussion, it is even more troubling to see that the results of an unreviewed paper posted only yesterday in public  view are the basis for an announcement made today.

That means that there was no opportunity for a broader public consideration, for thoughtful analysis, for viewing the data, for asking questions about the approach, methods, analysis, interpretation of results, and conclusions.  Thus, we post here some initial questions and comments about the unpublished and unreviewed paper from several scientific reviewers. We hope others read the paper (here) and offer their comments, or offer additional insight into the approach, analysis, and conclusions.

To be clear, these comments are not designed to advocate for or against the transfer of chimpanzees to Chimp Haven. Nor are they designed to judge the quality of care the animals receive after arriving there. Rather, they are designed to illustrate the fact that decisions about the welfare of captive chimpanzees that are being made by NIH appear to be based on data and analyses that are arguably flawed, at least as presented in the current draft of the Lauer paper.  Dr. Lauer might have excellent responses and answers to these critiques, which may then validate the claims in the current paper.

And, that is the point: the data will then have been subjected to critical peer review, the bedrock of the scientific method. It is disappointing, and frankly, stunning, that NIH appears to have accepted these results without proper peer review. Making captive chimpanzee retirement and movement decisions based on these findings seems premature and foolish.  Sadly, that may lead to unnecessary deaths of chimpanzees. NIH is clearly committed to sending their chimpanzees to Chimp Haven; if that is the mandate, then why try to justify the decision based on methods and analyses that have not been subjected to the normal scientific peer review process?  That ultimately raises more questions than answers and stands to further confuse the public view of how science works and how claims should be evaluated.

Finally, we would also note that the data does not appear to be publicly available. In other words, while the un-reviewed article is in public view and its conclusions appear to have informed the decisions the data is not in view and cannot be evaluated or analyzed by scientists or others who are independent of the decisions and the centers involved.

Below are just a few issues, or potential problems, that any reviewer might point out.

  • The first part of the study was aimed at addressing mortality rates in chimpanzees housed at Chimp Haven compared to other facilities (Bastrop, Southwest Foundation and Alamogordo Primate facility). The author reported that age and sex had strong effect on mortality rates whereas location had only moderate effects. In point of fact, the influence of location was not a trivial effect based on the results presented in Table 2 but rather a statistically significant one.  The author seems to want to minimize the significance of the location effect because the overall p-value (p=.0173) was close to the significance level adopted in their analysis.  The effect for Chimp Haven was far below that, at p=.005. The problem, however, is that the argument for adjusting alpha as reported by the author was because they had 6 predictor variables, they therefore they increased alpha to control for possible Type I error. There are a number of issues here. First, it is not clear how the authors dummy coded the location variable. Second, even if there were 6 predictor variables, there were also more than 700 subjects in the study and thus whether the author had adequate power to guard against Type I error (and thus needed to adjust alpha below the traditional < .05) is not entirely clear without presentation of effect size or further rationale. In turn, to state that sex and age had strong effects and location had a moderate effect on mortality is simply not supported by any statistics other than the p-levels.
    Maynard at MD Anderson.

    Maynard at MD Anderson.

    The paper reports: “The strongest predictor, by far, of mortality was
    age (as calculated to be on January 1, 2005), followed by male sex and location. Older age predicted higher mortality (adjusted hazard ratio comparing animals 30 years versus 17 years 2.23, 95% CI 1.91 to 2.61); males also had higher mortality (adjusted hazard ratio 1.50, 95% CI 1.20 to 1.88). Location was only marginally associated with mortality (Wald c2=10, df=3, P=0.017). Compared to Chimp Haven, mortality was lower at APF (adjusted hazard ratio 0.65, 95% CI 0.48 to 0.88), while it was similar at Bastrop (adjusted hazard ratio 0.84, 95% CI 0.60 to 1.16) and almost identical at SNPC (adjusted hazard ratio 1.00, 95% CI 0.71 to 1.39).”

  • The second part of the paper was designed to examine the influence of relocation/transfer on mortality rates in the different chimpanzee populations. This aspect of the study is likely in response to recent reports of higher-than-normal rates of mortality in chimpanzees transferred to Chimp Haven but sadly neither the design nor data analysis allow for any meaningful conclusions to be drawn.  Specifically, there is no control or comparison group. According to the author, at Chimp Haven (CH), chimpanzees die as they get older and this isn’t due to factors such as when they arrived at Chimp Haven, the season of year, etc….but these analyses are irrelevant. What one would want to know is what the mortality rate is for chimpanzees that get transferred to CH compared to either: 1) chimpanzees that stay at their original facility and don’t transfer; or 2) mortality in chimpanzees that transfer INTO CH from a lab compared to mortality rates of chimpanzees that are transferred FROM CH to another facility or 3) mortality rates of chimpanzees that have been transferred INTO another sanctuary (e.g., Save the Chimps).  The second situation does not occur; however, the 3rd situation could be analyzed. Furthermore, there is a 4) mortality rates of chimpanzees that transferred FROM other facilities and INTO Bastrop.  None of these comparisons were made in the paper though they are necessary to make inferences about the effect of transfers on the quality of care and mortality. Thus, this entire part of the paper addressing the effects of transfer on mortality is fundamentally flawed. Of course, it is also recognized that in addition to the analyses, appropriate balancing of covariates that relate to the mortality for each of these four comparisons may be difficult, post hoc; however, the alternatives and limitations should be a feature of a carefully considered conclusion and discussion.
  • For the Chimp Haven sample, why were non NIH-owned chimpanzees excluded from the mortality analyses? Chimp Haven has taken chimpanzees from other facilities such as Ohio State, Yerkes and New Iberia. If the question is not about mortality rates at a given facility, but rather the effect of transferring individuals from established housing conditions, why exclude any individuals? Further, were the non NIH-owned chimpanzees included in the sample size census within Chimp Haven? In other words, in Table 1, it indicates that the Chimp Haven had 273 chimpanzees. Is that all the chimpanzees at CH, or only those that are NIH-owned? A reviewer might guess is that these numbers are based on the entire sample of chimpanzees at Chimp Haven but it is far less clear on the mortality numbers (107). Moreover, peer review would surely point out that the methods are not sufficient for reproducibility.
  • In Table 2, the most relevant comparison (at least in relation to the current issue, the transfer of NIH chimpanzees to CH) is starkly missing. Specifically, for location, Chimp Haven needs to be the reference group, so that comparisons of transfer from all other sites can be made. This is particularly strange as the text lists Chimp Haven as the reference group and interprets the data in this regard. If the point of this analysis is to inform the decision to transfer the animals to CH, vs retire-in-place, then the comparisons should be made with CH as the reference group so that we can see how it truly stacks up against leaving the animals where they are.

 

 

 

 

Heat or light? An Analysis of Chimp Haven’s Message

Earlier this week the president of Chimp Haven, Cathy Willis Spraetz, issued a rebuttal to “a number of articles and blog posts focusing on the retirement of federally-owned chimpanzees to Chimp Haven.” She identifies the goal of the open message as a response to address the “concerns and resistance from some in the laboratory community,” whom she described as increasingly direct and vocal.

Spraetz is correct that there are increasingly direct and vocal questions about the retirement of federally-owned chimpanzees. But rather than focusing on the serious and challenging questions that have been raised, or on the repeated calls for the communities involved to have a more thoughtful, fact-informed consideration of the topic, she instead frames the issue as a polarized situation in which the “laboratory community” is unjustifiably criticizing Chimp Haven. To do so, she provided a series of misinterpretations and inaccuracies of the articles and blog posts. We respond to some of those below, but also encourage people to read her letter in its entirety and to read recent posts and articles in order to evaluate the claims Spraetz makes. More importantly, we continue to urge people to step back from polarization and instead identify what information is needed and what considerations and actions should be taken in order to make the best decisions that balance the chimpanzees’ health and wellbeing.

The first issue the letter poses is that the Chimp Haven CEO, Spraetz, failed to include links to the original articles she aims to rebuke. That is problematic because the omission of the original sources prevents readers from reading what she interprets as “accusations” (Spraetz’s term) and forming their own opinions. Whether accidental or deliberate, such omission is irresponsible and should be corrected in the posting on the Chimp Haven site.

The omissions, in addition to the framing and language in the letter, do nothing to further thoughtful dialogue on the topic at hand – the welfare of retired research chimpanzees. What it does is distract from serious consideration with a fueling of the “Us vs. Them” rhetoric. In this case, the “Them” is the “laboratory community,” one that Spraetz seems to cast as unconcerned about chimpanzees’ health and welfare. Unfortunately many may buy into this message. Why? Because rather than taking a thoughtful look at the animals’ care, conditions, and actual outcomes, it is easier to simply argue that “labs” are bad and “sanctuaries” are good.

I encourage interested readers to take the time to thoroughly read the Spraetz piece and the sources that inspired her message. Here, I address Spraetz’s message piece by piece (as I did on Twitter) and clarify the ways in which it distorts quotes and makes inferences that simply are not true. By reading the original sources that Spraetz described, it is clear that blaming Chimp Haven – or the excellent behavioral and care staff – for the deaths of the chimpanzees that were relocated there several months ago is not the focus. Rather, the focus in on better understanding and consideration of what happened to recently relocated animals – a consideration that should inform future decisions.

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In fact, Dr. Buckmaster did not write that the chimps “’suffered and died’ because of their transfer to Chimp Haven.” This claim distorts the “suffered and died” quote by taking it out of context. Rather, Buckmaster wrote:

“In a blog posted in 2013, the CEO of the Humane Society of the United States congratulated his followers for their hard work, reinforcing their effort by stating that criteria put forth by a NIH working group made it clear that “not one laboratory could be considered ethologically appropriate” for chimpanzees. This is not true. In fact, many of our chimps would fare better if they were allowed to retire in place. And several of these precious creatures have already suffered and died because the NIH would not allow them to do so.” (emphasis added; Lab Animal, Vol. 45, No. 7, p. 271).

Buckmaster made an argument for retirement-in-place; she did not claim that Chimp Haven was responsible for the chimps’ deaths.

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There are several inaccuracies here. The first inaccurate statement, “invasive research with this species,” implies that until NIH’s November 2015 decision to “retire all federally owned chimpanzees,” all research was invasive in nature. In fact, since 2012, the facility from which these particular chimps retired conducted no biomedical research but only conducted observational studies.

Ironically, recently Chimp Haven proudly announced that it has entered into a partnership with Lincoln Park Zoo that will enable similar observational research, and that may also include biomedical research.

Another inaccuracy is the accusation, “…we cannot allow this community to disparage the quality of care we provide…or to question our organization’s dedication to our mission…”

This is followed shortly by the statement that Buckmaster “is able to so clearly judge the quality of Chimp Haven.” In reading and re-reading the articles that Spraetz refers to, one sees that there is not a single instance of any article or post author questioning the quality of care at Chimp Haven or Chimp Haven’s dedication. The sole instance is a commenter on the blog. In fact, the word “quality” does not appear once in Buckmaster’s article, and appears only once in Speaking of Research’s article on the partnership in the concluding sentence:

“Conducting research is compatible with both high quality care and with truly valuing what the animal contributes to new knowledge that benefits individuals, the species, and the future.”

Likewise, the word “dedication” does not appear either in Buckmaster’s article or in Speaking of Research’s article on the partnership.

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First, Buckmaster does not quote Dr. Abee at all in her article. Rather, Abee was quoted in this article from December 2015 in which, again, the focus is on making the argument for retirement-in-place. Further, Spraetz’s quote of Abee is taken out of context. Abee’s entire quote reads:

“I don’t mean this as a criticism of Chimp Haven, but we uprooted them, took them from their family groups, we moved them cross country, we put them in unfamiliar settings with caregivers who didn’t know them, and four died,” Abee said. “We would not have anticipated those four to die if they had stayed here.”

So Abee made a point not to criticize Chimp Haven and to make it abundantly clear that he had issue with the transfer itself.

Second, underscoring the statement, “the labs themselves made such decisions when they selected which chimpanzees to send” suggests that if the labs had “chosen” these particular chimps to leave at a later time, their outcomes may have differed. In fact, most of the chimps that died were very old. Research shows that involuntary relocation in old age is stressful (and a new paper shows that relocation of lab chimps to a sanctuary resulted in chronic stress and behavioral changes). Thus, it is possible that it would not have mattered when these chimps moved; their fates may have been the same. But that is unknown right now and is a question that can only be answered by examining what happened to the animals that have transferred, including those 9 of 13 who died. It is exactly this kind of review—based in facts, actual records, and expertise—that is called for in order to inform future decisions. An unwillingness to do so – and to share these with the public and others who have interest – undermines confidence that everything that can be done is being done to protect the animals.

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The statement, “The anonymous blog author questioned the partnership…” is another misrepresentation. Any reader can see that Speaking of Research actually clearly explained why such research would be warranted. In fact, Spraetz’s explanation for the research sounds a lot like Speaking of Research’s:

“It may seem odd that a sanctuary—a place whose justification and primary goal is to provide chimpanzees with care—has a need to evaluate the effect of visitors on the animals’ welfare. However, although the sanctuary is not open to all members of the public on a daily basis, it does appear to have extensive public visitation and education programs that presumably results in a need to evaluate the effect of visitors on the animals.”

Moreover, the blog author goes on to state, “the sanctuary offers a resource that zoos cannot for studies that are adequately powered to test scientific hypotheses.”

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This statement as a whole is not supported by any of the articles to which Spraetz refers. No author has made a accusations toward Chimp Haven’s care, and certainly no attacks on it have been made in these articles. The conversations have been focused on the issue of transferring the chimps versus allowing them to retire-in-place, on the bigger questions about what defines sanctuary and research,  and what is needed for a serious, thoughtful, and balanced consideration to inform decisions going forward.

Spraetz’s comment is precisely the kind of statement that leads to inflammatory reactions and further divides the people who have the same goal: the optimal conditions and highest quality of life for the chimpanzees.

Spraetz did have it right in one part of her message: the relationship between the lab and sanctuary communities has dissolved. But for her to distort the conversation by making claims that the laboratory community disparages the quality of care at Chimp Haven and attacks Chimp Haven’s operations in a public message is irresponsible. It actually exemplifies her quote from earlier in the message: “It’s an unfortunate characterization of our organization, which is based less on facts and more on rhetoric and mischaracterizations.”

CH message image 9By not providing the original references, which clearly show that the laboratory community is focused on the issue of transferring the animals, not the quality of care at Chimp Haven, Spraetz permits most readers to take her statements at face value. This then leads to unproductive and at times hostile dialogue in forums like Facebook, which do nothing to promote chimpanzee welfare.

Furthermore, for Chimp Haven to do nothing to counter the hostile and false statements made by its supporters – and for Chimp Haven to even go so far as to “Like” comments on Facebook that falsely describe laboratory researchers as “torturing animals” and calls them “A-holes” – seems completely incompatible with the goal of public education. It is this behavior that raises additional questions. That includes questioning why, given their public education goals, Chimp Haven does not take the responsibility to provide accurate counter to wrong statements and accurate information to support education and dialogue.

CH response tweet imageAmanda M. Dettmer