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Research Roundup: Death of a pioneer, 2017 Brain Prize, and unsubstantiated claims by PETA

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Welcome to the first in a series of weekly Research Roundups. These aim to inform our readers about the many stories that relate to animal research each week.

Do you have an animal research story we should include in next week’s roundup? You can send it to us via our Facebook page or through the contact form on the website.

  • Thomas Starzl the father of organ transplantation has died. Beginning with his work on liver transplantation in dogs in the 1950s, and subsequent refinement of the procedure using livers from pigs and primates, today “more than half of the liver-transplant patients who underwent surgery in 1998 were alive ten years later, and in 2009, almost 50,000 Americans carried a transplanted liver” (Lasker Foundation).” Read more about this here and here.

The father of organ transplantation, Thomas Starzl.

  • 2017 Brain Prize announced – Peter Dayan, Ray Dolan and Wolfram Schultz. Collectively, their work examines the ability of humans and animals to link rewards to events and actions. This research, involving non-human primates, provides valuable insights into motivation to perform both positive and negative behaviour, how those behaviours regulate emotions such as happiness and how dysregulation may affect addictive/compulsive behaviours such as gambling. Read more about this here.

  • An unannounced four-day inspection of the animal research facilities at the University of Pittsburgh found no wrongdoing. The inspection was triggered by unspecified allegations by the animal rights group PETA, though USDA officials could not find evidence corroborating the claims by PETA. This is not the first time we have noted that animal rights groups claims against labs which cannot be substantiated by inspectors. More here.
  • Tasmanian devil cancer is a major threat Tasmanian devils with more than 80% of the population being wiped out since it emerged 20 years ago. Fighting cancer with cancer, and in a culmination of 6 years of research, scientists have managed to achieve a 60% survival rate (3 out of 5). The application of animal research takes all forms, and this is a good example of techniques being developed in the lab on nonhuman animals being used to save other nonhuman animals. More here and here.

Tasmanian devils under threat

  • Ethical deliberation of the killing of wild animals humanely for conservation is considered here. The killing of animals by humans warrants moral and ethical consideration. Animal research can be used to inform such decisions so that they are grounded in sound scientific evidence.
  • In a concerning move, advisors to President Trump suggested removing regulations requiring pharmaceutical companies to perform pre-clinical trials which ensure human safety before bringing them to the market. You can read more about the value of animal research in pre-clinical trials here.
  • The NC3Rs has awarded the 2016 3Rs prize to Daniel Weary who investigated possible refinements to the legislative requirements for rats housed in the laboratory for research. Read more here and here. This prize and this research highlights governing bodies’ and researchers’ dedication to the health and well-being of the animals under their care. Well done, Daniel!

Check back next Friday for another weekly roundup.

Jeremy Bailoo and Justin Varholick


Filed under: News, Research Roundup Tagged: animal research, animal testing, Research Roundup, Starzl

Research Roundup: March for Science, promising headway in stem cell treatments, new treatment for cystic fibrosis and more!

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Welcome to this week’s Research Roundup. These Friday posts aim to inform our readers about the many stories that relate to animal research each week. Do you have an animal research story we should include in next week’s Research Roundup? You can send it to us via our Facebook page or through the contact form on the website.

  • On Saturday April 22nd, hundreds of thousands of people are expected to march in defense of science in cities around the world, including Washington DC, London, Paris. Toronto, Berlin and more. Speaking of Research has a history of holding rallies in defense of science, and we wish those who are attending events on Saturday the very best of luck. With science funding in many countries under threat, it is important that we all stand up and be counted.

SR-March

 “The March for Science champions robustly funded and publicly communicated science as a pillar of human freedom and prosperity. We unite as a diverse, nonpartisan group to call for science that upholds the common good and for political leaders and policy makers to enact evidence based policies in the public interest.”
https://www.marchforscience.com/
#MarchforScience

  • Stem cell treatment and transplant shows vision and promise. Using induced pluripotent stem cells, a Japanese man is the first human to receive reprogrammed stem cells from another human being as a means of treating macular degeneration — a form of blindness that affects 1% of all humans over the age of 50. Before this procedure made its way to humans, safety and efficacy trials in mice (.e.g., 1,2,3) and non-human primates were undertaken (e.g., 1,2,3) — although it is worth emphasizing that some have raised concerns about the stringency of Japanese preclinical regulatory process. Takahashi, the lead scientist behind this trial, stated that the surgery has gone well, but that success cannot be declared without further monitoring the fate of the transplanted cells.

    SR-StemCells

    Somatic stem cells exist naturally in the body. They are important for growth, healing, and replacing cells that are lost daily through wear and tear.  Source: University of Utah

  • A new study finds that exposure to low doses of antibiotics early in life can have long term consequences on behaviour in mice. Adding to a growing body of literature, this study found that low but clinically relevant doses of penicillin administered prenatally in mice can lead to lasting effects in both sexes on gut microbiota, immune functioning, and alters anxiety-like, social and aggressive behaviour. Concurrent supplementation with Lactobacillus rhamnosus JB-1 via drinking water prevented some of these alterations — potentially via alterations to the vagus nerve. Subsequent replication and extension of these findings needs to be undertaken, particularly in regards to the length of exposure and when exposure occurs (early or later in gestation or even postnatally). The authors of this study concluded that “these results warrant further studies on the potential role of early-life antibiotic use in the development of neuropsychiatric disorders, and the possible attenuation of these by beneficial bacteria.” This study was published in Nature Communications.
    SR-miceantibiotics
  • Humane endpoints for zebrafish released on the Humane Endpoint website at Utrecht University in English, Dutch and German. “A humane endpoint is the earliest indicator in an animal experiment of pain or distress in the animal. Researchers can use these indicators to avoid or limit pain and distress in laboratory animals.” Zebrafish are a commonly used as laboratory species and, for example, in the Netherlands, an average of 5000 experiments are performed on zebrafish each year. Consistent with the 3Rs, these guidelines contribute the refinement aspect of the 3Rs “since it teaches scientists, animal technicians and animal caretakers how to prevent unnecessary pain and distress in laboratory animals.” Access to this website is free and for further details on who can and how to access all content can be found here.

    Zebrafish_Sanger

    Zebrafish: Wellcome Trust Sanger Institute

  • Vaccination of prairie dogs planned in an effort to save the black footed ferret. Black footed ferrets are members of the weasel family and were brought to the brink of extinction in the 1960s due to habitat destruction. By the 1980s it was estimated that only 18 remained. Due to conservation efforts, there are now approximately 300 of these ferrets in the wild and a further 300 in captive breeding facilities. Approximately 90% of the diet of these ferrets are comprised of prairie dogs. However, because of the Sylvatic plague, prairie dogs living in the habitats of the black footed ferret are now in danger of being decimated and spreading this disease to the ferrets that eat them. To combat this problem, wildlife conservationists such as the USGS National Wildlife Center are planning to a vaccination campaign in specific habitats of the black footed ferret. This is a great example of the reach of biomedical research with vaccinations developed in animals being used to save other animals.
  • Potential new treatment for cystic fibrosis found. Cystic fibrosis is a progressive genetic disease that leads to persistent lung infections and limits the ability to breathe. In particular, it affects the Cystic fibrosis transmembrane conductance regulator (CFTR) gene. In addition, it can prevent the pancreas from releasing digestive enzymes due to the buildup of mucus. It affects approximately 70,000 people worldwide. These researchers investigated whether thymosin alpha 1 (Ta1) — a naturally occurring protein with an excellent safety profile in the clinic — can rectify some of the multiple tissue defects associated with cystic fibrosis. Using inbred mice, they found that this protein leads to reduced inflammation and increased CFTR maturation, stability, and activity — indicating that Ta1 has a strong potential to be a single-molecule therapeutic agent to treat and stop the progression of cystic fibrosis. This study was published in Nature Medicine.
SR-CF

Image courtesy of National Library of Medicne


Filed under: News, Research Roundup Tagged: animal testing, mice, Research Roundup, zebrafish

Animal Testing and Human Trials: Alternatives or Complements?

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The Animal Justice Project, a British-based animal rights group, is no stranger to misinformation. Previously we have debunked their factual errors regarding malaria studies in Sweden and eye injury studies. There was also the time they produced a press release which suggested 52oC (125oF) was the same as boiling water (which admittedly might be true if you tried to make a cup of tea in the lower stratosphere).

Recently on their website, a blog by Judith Snaith has been put up. The blog is a mash up of animal rights myths and misinformation, but one line was of particular interest.

More than 100,000 humans are killed yearly by prescription drugs that passed animal testing. Animal research is not the final phase, 90 per cent of drugs that pass the animal tests fail in human trials. So if we have to test on humans to be accurate, can we not skip out the middle monkey?

Let’s break this down bit by bit. The figure of 100,000 is an American one (Lazarou et al, 1998) with the figures for the UK approximated at around 10,000 (Pirmohamed et al, 2000) using a similar methodology. We have mentioned the flaws in these figures in our “Animal Rights Pseudoscience” page:

The statistic of 100,000 deaths in a year is taken from a 1998 meta-analysis by Lazarou and colleagues that examined rates of adverse drug reactions (ADRs) observed in 39 studies undertaken between 1966 and 1996 (Lazarou et al, 1998). The methods used in this meta-analysis were subsequently criticised for failing to adequately take into account differences between the 39 studies examined, a failing which may have lead to an over estimation of the number of deaths due to ADRs (Kvasz et al, 2000).

Between 2001 and 2002 Pirmohamed and colleagues analysed admissions to two hospitals in Merseyside, in order to determine if the cause of admission was an adverse drug reaction (Pirmohamed et al, 2000). Their results indicated that ADRs accounted for 6.5% of hospital admissions, and that ADRs may be responsible for up to 10,000 deaths a year in the United Kingdom. The study also found that:

  • 95% of ADRs were predictable from the known pharmacology of the drugs (i.e. from animal testing and human clinical data).

  • A large majority of ADRs were caused by older drugs.

  • About 70% of ADRs were either possibly or definitely avoidable.

So a large amount of these deaths come down to human error as the adverse drug reactions were both predictable and avoidable.

Judith mentions that these 100,000 deaths came from drugs which had passed animal tests. What she chooses not to mention is that these 100,000 deaths came from drugs which had also passed clinical trials in humans. There is no logical reason to put these deaths at the feet of animal tests – particularly as the animal tests do not check for the common causes of drug deaths – accidental overdose, negative drug-drug interactions from secondary medications, incorrectly prescribed medication etc.

Judith then goes on to mention that 90% of drugs that pass animal tests go on to fail in humans:

Animal research is not the final phase, 90 per cent of drugs that pass the animal tests fail in human trials

We’ve definitely seen and debunked this statistic before. The inference is that animal tests are not effective as many drugs fail later on. Prof Lovell-Badge explains some of the many flaws in this argument. Firstly, there is a similarly high failure rate in the human trials:

Consider that of all the drugs which pass Phase 1 clinical trials in humans, 86% will fail in later stage human trials. Yet, we do not hear activists suggesting that humans are an entirely inappropriate model for drug development (though we should note that one human is not a perfect model for another).

Furthermore, this whole argument is premised on a misunderstanding of the different role of animal and human trials:

The role of preclinical animal tests is to check if the drug offers any potential therapeutic value and, importantly, if it is safe enough to move to Phase 1 trials in humans. This does not even mean free of all side effects, but to learn whether a drug can safely be given to humans and at what approximate dosage.

Put another way, every stage of drug testing acts as a safety barrier for dangerous drugs being sold. Pre-clinical in vitro tests, pre-clinical animal tests, Phase I clinical trials, and Phase II-III clinical trials all work successively to remove potentially dangerous compounds from reaching the market. These are not their only functions, animal tests may help assess appropriate therapeutic doses, which can be later refined during clinical trials. These tests (animals and humans) may also help discover potential side effects (this does not mean the drug will be rejected – it depends on the seriousness of the condition it is intended to treat).

Judith Snaith goes on to combine her two assertions to claim that we don’t need to do the animal tests – we can just move straight to humans.

So if we have to test on humans to be accurate, can we not skip out the middle monkey?

This ignores the huge number of dangerous compounds which are removed from the drug development process because they show toxic effects in animals. To skip this step would be to allow these compounds to be trialled in humans. Furthermore, when one safety check doesn’t guarantee safety, that doesn’t mean removing the check makes anyone safer.

Animal testing is not an alternative to human trials, it complements it. Medieval castles had high walls and soldiers in them – both protect the defenceless people in the keep. Sometimes high walls and soldiers were not sufficient, and the castle was sacked, but no one would conclude that high walls were pointless and that everyone would be safer if there were just the soldiers. In reality, doing away with the castle would mean more soldiers would die, just as doing away with animal tests would likely lead to more deaths in Phase I and II clinical trials; the consequence of this would be that fewer people would volunteer for clinical trials (just as fewer soldiers would wish to defend a low-walled castle).

We use a variety of methods in biomedical science – computer simulations, tissue studies, animal models, clinical trials, epidemiology etc. Different methods can teach us different things and the results are often used in combination to build our knowledge and understanding of physiology and disease. The same is true in safety testing – all methods of screening drugs have advantages and drawbacks, but if we use them effectively, in combination, we can see that safe and effective drugs make it to market.

Would the French soldiers have taunted King Arthur if they didn’t have high walls? (Monty Python’s Holy Grail)

Speaking of Research


Filed under: #ARnonsense, Animal Rights News, News Tagged: 90%, alternatives, Animal Justice Project, animal testing, clinical trials

The Fact Check: PETA vs. Christine Lattin

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A systematic evaluation of PETA’s claims about Dr. Christine Lattin’s research highlights a lack of context, misrepresentation of her work, and – in some cases – statements that are just not factually accurate. Again, PETA demonstrates to the world why we should not take such claims at face value.

PETA’s campaign against Dr. Christine Lattin, an early career researcher at Yale University, began in May 2017. At first blush, this seemed like the usual nonsense that PETA often gets up to: sensational claims and some selective reporting about the issue at hand – usually in an effort to get the maximum emotive response regardless of the truth or of the consequences (see for e.g., here, here, here, here).

A quick search (see Dr. Lattin’s website and Twitter) reveals a researcher that is open and transparent about her research, critical about the limits of interpreting her research, and one willing to stand up to these allegations without fear – a sign of true conviction about one’s work. Recently, PETA upped the ante and posted a long diatribe claiming that Dr. Lattin, who was defending herself and her research via Twitter, was presenting an alternate version of the facts.

We decided to evaluate PETA’s claims against Dr. Lattin in order to provide a public view of the facts and context that are relevant to considering PETA’s statements. We are not claiming an absence of potential bias, nor should others. PETA also has a particular interest in the topic, as they clearly state their view opposing all use of animals by humans (for research, but also food, clothing, and entertainment). As well, many of us that are affiliated with Speaking of Research study animals in our own research, and therefore have a vested interest in this topic. With these starting assumptions in mind let’s jump in.

Sub-topics:

VALUE OF THE WORK IN TERMS OF APPLICABILITY TO OTHER SPECIES?

Lattin claim (paraphrased by PETA): “[I]f my research wasn’t [sic] applicable to humans or any other species, it wouldn’t get approved, funded or published.” (Twitter, August 3, 2017)

PETA response: Applicability to humans or other species is not a condition for approval, funding, or publication of research. Indeed, the results of many of the most abusive experiments using animals are not relevant to humans and are driven only by curiosity. For instance, the National Institutes of Health (NIH) funded a series of infamous stress experiments [by Harry Harlow, emphasis added] in which infant monkeys were stuffed into tiny cages and then terrorized with loud noises. A horrific variation on this involved drugging mother monkeys, taping over their nipples, and then observing how their frightened babies frantically tried to wake them up. The experimenter responsible for this cruelty admitted publicly that his results were not relevant to human mental illness. Yet NIH saw fit to fund these experiments for more than 30 years with a total of more than $35 million.

Applicability to humans or other species is not a condition for approval, funding, or publication of research. That is a strength of science – a feature, not a bug, because the foundation of scientific discoveries and advances depend on basic research. It would be disingenuous to stop there though. Where research can potentially cause harm or distress there generally needs to be a clear justification of applicability, for example, either to the species being studied or to other animals, in order for such work to be conducted. Some of Dr. Lattin’s research involves a degree of stress, and will therefore have been subject to an analysis that weighs risks to the animals with consideration of scientific objectives and potential benefits from the research.

Indeed, if one were to read Dr. Lattin’s publications, which are posted freely on her website, one would see that her research is not driven by simple curiosity but clearly states the applicability of her research to other species of passerine birds. And, as an example of selective reporting, PETA fails to post/address the very next comment that Dr. Lattin’s posts on her Twitter feed where she provides an example of the applicability of her work to other species.

We have previously addressed the one sided argument against the NIH funded research of Harry Harlow. We also note that Harlow died over 35 years ago. Harlow’s work, and that of his contemporary colleagues, is one used in arguments by those opposed to animal research.  As we state in a previous article:

“Contrary to prevailing views in the 1950s and before, the Harlows’ studies of infant monkeys definitively demonstrated that mother-infant bonds and physical contact—not just provision of food—are fundamentally important to normal behavioral and biological development. Those studies provided an enduring empirical foundation for decades of subsequent work that shed new light on the interplay between childhood experiences, genes, and biology in shaping vulnerability, resilience, and recovery in lifespan health.”

We, and others – including NIH and leading scientific organizations have addressed and supported the contemporary research to which PETA refers (e.g., NIH statement, APA statement, ASP statement).

IS RESEARCH WITH WILD BIRDS REGULATED IN THE USA? YES.

Lattin claim (paraphrased by PETA): “Also: there is a TON of oversight on all animal research (mine included). It’s not illicit or secret.” (Twitter, August 3, 2017)

PETA response: Lots of paperwork does not equal protection for animals. The systems of oversight in laboratories are weighted in favor of the experimenters and often fail the animals they are designed to protect. The only law that offers any sort of protection for animals in laboratories deals primarily with housekeeping issues and excludes birds, mice, rats, reptiles, amphibians, and animals used in agricultural experiments. No experiment is illegal.

Experimenters can deliberately inflict psychological suffering and pain with the flimsiest of justifications and still receive approval by oversight committees. As a result, many experiments that are wasteful and irrelevant and cause significant suffering are approved. Just two of many recent examples include experiments on dogs with canine muscular dystrophy that have failed to lead to any effective treatments and others in which hamsters were given cocaine and forced to fight.

PETA lumps a lot of little things together (a gish gallop tactic), perhaps in the hope that by doing so, the perception of similarity/applicability is achieved. The first criticism states that the Animal Welfare Act in the USA does not cover rats, mice, and non-mammalian vertebrates. However, this does not mean that these animals are not without protection or consideration, as we have previously explained. In fact, these animals receive oversight in numerous ways. Among them, federal law mandates compliance with standards, provides external oversight and mechanisms for public transparency of federally-funded research with rats, mice, and birds.  Further, accreditation by AAALAC requires compliance with standards. Finally, the research is subject to IACUC approval and oversight.

Moreover, the wild birds that Lattin studies are covered under the Animal Welfare Act, as explained by Ellen Paul, executive director of the Ornithological Council. Additionally, some of Dr. Lattin’s work actually informs standards for the keeping of wild birds in captivity and for example, include the consequences of captivity across time on the behavior and physiology of wild birds.

“The Animal Welfare Act covers all warm-blooded animals. In the past, the regulations excluded rats, mice, and birds. After litigation, the USDA agreed to include these taxa but a Farm Bill amendment excluded “purpose-bred” rats, mice, and birds.”

As Dr. Lattin’s birds are wild caught, and not purpose bred, they remain covered by the Animal Welfare Act.

The second criticism – that research can involve significant suffering and pain on a whim is not supported by the available evidence. Only approximately 3% of all approved experiments are rated as severe, and cause significant suffering (inferred from the severity ratings of countries that provide them and categorized in the USA as “E”). Moreover, and as mentioned previously, the risk benefit analysis in the USA, and the Harm-Benefit analysis in Europe and Switzerland, all require that any harms experienced by the animals are weighed with respect to the scientific objectives, the potential benefit of performing the experiment, or both. So, once again, PETA’s statements are demonstrably false.

Dr. Christine Lattin checks the tag on a bird to be released as part of her research.

WHAT DOES THE FACT-CHECK OF PETA’S SELECTIVE EVALUATION OF DR. LATTIN’S RESEARCH REVEAL?

PETA continues: Like these, Lattin’s studies have not led to any useful real-world applications, hinge on the deliberate infliction of pain and suffering, and require the death of the birds used. Here’s a sampling of what birds have endured in her experiments with “oversight”:

  1. Experimenters subjected birds to terrifying stressors, including rattling their cages, rolling them on a cart so that they could not perch, and physically restraining them, for 30 minutes four times per day at random intervals.[1]

What are these procedures that PETA calls “terrifying stressors?” They are part of a well-established approach to studying stress, called chronic mild stress, in biomedical research. Paul Willner, was the first to describe and subsequently validate this approach, and in a recent open access methodological review highlights the translational value of this model.

“Now 30 years old, the chronic mild stress (CMS) model of depression has been used in >1300 published studies, with a year-on-year increase rising to >200 papers in 2015. Data from a survey of users show that while a variety of names are in use (chronic mild/unpredictable/varied stress), these describe essentially the same procedure. This paper provides an update on the validity and reliability of the CMS model, and reviews recent data on the neurobiological basis of CMS effects and the mechanisms of antidepressant action: the volume of this research may be unique in providing a comprehensive account of antidepressant action within a single model. Also discussed is the use of CMS in drug discovery, with particular reference to hippocampal and extra-hippocampal targets. The high translational potential of the CMS model means that the neurobiological mechanisms described may be of particular relevance to human depression and mechanisms of clinical antidepressant action.

Dr. Lattin also addresses this in her paper but this rationale, justification, and context are not fully evident in PETA’s consideration. For example, in the paper that PETA references, Dr. Lattin first points out why studying chronic stress is important, and in particular, relevant to our understanding of the bird itself.

“…diagnosing chronic stress is not simple – the effects of presumed cases of chronic stress vary by species, stress paradigm, life history stage and other factors…”

“…knowing whether animals are successfully coping with stressors or suffering deleterious effects from an overactive HPA axis can be crucial for diagnosing the health of an individual animal.”

Dr. Lattin then highlights why she used these particular mild stressors.

The stressors usedhave all been shown individually to significantly increase CORT titers…” [note CORT refers to the stress hormone cortisol]

Yet, none of these considerations are highlighted by PETA, even though they are clearly and logically presented in Dr. Lattin’s publication.

  1. PETA: “One bird died during the administration of anesthesia prior to euthanasia.[2]

This is factually incorrect: “One male from the chronic stress recovery group died prematurely under anesthesia during perfusions” NOT during anesthesia – meaning that the animal was successfully rendered unconscious. Because Dr. Lattin’s wild caught birds are a heterogeneous population, i.e., they may vary in age, body status, immune composition etc., there will be individual differences in the way they respond to the anesthetic and sometimes, may do so in an unpredictable way — even when the recommended dosing is followed. Moreover it highlights why we need more research on wild caught birds – so that we may better understand why these individual differences exist and to accommodate such predictions into existing anesthesia protocols. Finally, because this bird was rendered unconscious at the time of death – it experienced no pain at its time of death.

  1. PETA: “Twenty-six feathers at a time were plucked from birds without pain management.[3] Plucking large numbers of feathers can cause bleeding, skin irritation, discomfort, and difficulty with thermoregulation.

In this paper, Dr. Lattin plucks feather from these birds to induce molting. Here, she was interested in validating a less invasive and integrated measure of a birds’ stress response. Note that this is first line of text in the paper.

“The newly described technique of extracting corticosterone (CORT) from bird feathers may serve as a less invasive, more integrated measure of a bird’s stress response.”

In the paper, Dr. Lattin states that she followed the method of Strochlic and colleagues. Of relevance here is that this procedure is performed under anesthesia – meaning that the animal was unconscious during the procedure.

“Starlings were briefly anesthetized with halothane, an inhalable anesthetic, administered in a nose cone and feathers were plucked by hand…”

It is not standard veterinary practice to administer analgesics following this procedure as it is not considered to be painful after the initial plucking; again note that this procedure was performed under general anesthesia. It is unlikely that this procedure causes bleeding, or the administration of analgesia, topical or otherwise would have been prescribed. Moreover, it is standard procedure to maintain birds at temperatures that may cause thermoregulatory distress.

These arguments presented by PETA therefore seem to be strawmen, meant to evoke an emotive response but once again are not supported by the available facts.

  1. PETA: “Capsules were surgically implanted under birds’ skin to administer drugs and then removed without pain medication.[4]

In the paper, Dr. Lattin again states that she followed the method of Strochlic and colleagues. Of relevance here is that this procedure is, again, performed under anesthesia – meaning that the animal was unconscious during the procedure. Please see the preceding the point for further discussion about the necessity of analgesia.

“All birds were anesthetized with metafane and implants were inserted subcutaneously between the shoulder blades. Silk sutures closed the incisions.”

  1. PETA: “Birds were used for multiple experiments and in some cases kept in captivity for several months before being killed.[5], [6], [7]

The same animals were studied as part of a single research program that addresses multiple questions. Studying the fewest animals possible often means the same animals are used within multiple studies. Re-using animals for experiments is consistent with the 3R principle of reduction, and minimizes the overall stress experienced by removing the need to capture more wild birds. Again, Dr. Lattin is transparent about this in her publication.

“As part of another study published previously (Lattin et al., 2014), we took body mass measurements and blood samples from all birds immediately before the onset of feeding and 2 and 4 weeks into the feeding experiment. The results of this sampling have been described in detail elsewhere (Lattin et al., 2014).”

  1. PETA: “Two birds died of “unknown causes” after two weeks of captivity.[8]

This is transparently stated in the paper. One should not confuse the use of the term “unknown causes” with the implication of wrongdoing.

  1. PETA: “Birds lost 8 percent of their bodyweight and heart mass, and their muscle density decreased during the stress of captivity and repeated experimentation.[9]

This is precisely some of the information Dr. Lattin seeks to discover. In this research, Dr. Lattin investigates the long-term effects of captivity on wild birds by measuring behavior and physiology. From this research she determines, “From a conservation perspective, this study … suggests that time in captivity should be minimized when birds will be reintroduced back to the wild.” Therefore, the loss of 8 percent bodyweight etc., is evidence for future researchers to reduce the time birds spend in captivity before being reintroduced back into the wild. It is not evidence to justify not doing the research in the first place; it is evidence that such research needs to be refined – which is exactly how refinements in animal care progresses and is reflected in the 3R perspective of refinement.

  1. PETA: “Birds exhibited behavior that indicated stress and anxiety, such as beak wiping and feather ruffling.[10]

Another glaring example of where context matters. Dr. Lattin investigates in this paper whether “experimentally reducing stress-induced corticosterone [i.e., stress hormones, emphasis added] may mitigate some captivity-induced behavioral changes”. And, indeed, she does find a decrease in beak wiping but not feather ruffling in animals treated with a drug to reduce stress. So contrary to PETA’s claims, Dr. Lattin shows that one of the detrimental consequences of captivity, increased beak-wiping, can be reduced in birds brought to the laboratory for various purposes, including conservation – a further case of refinement.

  1. PETA: “Wounds were inflicted on birds’ legs without pain medication.[11]

In Dr. Lattin’s paper it clearly states, “Prior to wounding we anesthetized birds using isoflurane.” What that means is that the birds are unconscious during the procedure and therefore were not able to perceive pain. The Ornithological Council’s guide states:

“An anesthetic is an agent that produces analgesia (loss of pain sensation) and, in the case of general anesthetics, immobilization and loss of consciousness so that the individual is unresponsive to stimulation. Anesthesia ideally minimizes stress and eliminates pain during a research procedure.”

  1. PETA: “Some birds were so distressed that they lost 11 percent of their bodyweight within five days of capture.[12]

Dr. Lattin has previously shown that decreased body weight is a consequence of captivity and in the present paper she uses captivity as a model for chronic mild stress (see point 1 and 7). She also notes in her paper, “After 5 days of captivity, house sparrows lost 11% of initial body mass, although birds lost more weight during molt and early winter”. This indicates, that the weight loss is within the normal range for these animals; although she also finds “the simultaneous demands of molting and chronic stress resulting from captivity may be part of the reason that molting birds lost significantly more weight than sparrows at other times of year.” Now the question can be asked, why did Dr. Lattin do this and what are the implications of her work? She is quite open about this, and together with her work which shows changes in behavior and body weight as a consequence of captivity, it also highlights for the benefit for future birds, “…it may be desirable to avoid bringing birds into captivity during particularly vulnerable stages (such as during molt in birds) for purposes such as translocation

DOES UNDERSTANDING OF BIRDS HAVE IMPLICATIONS FOR HUMANS?

Lattin claim (paraphrased by PETA): “Because the hormone and neurotransmitter systems I study are very similar across vertebrates, my work also has important implications for human health.” (www.christinelattin.com)

PETA response: Lattin’s experiments lack applicability to humans. Her studies of chronic stress focus on the effects of the hypothalamic-pituitary-adrenal (HPA) system, or axis, but there are significant anatomical and physiological differences between human and birds. The HPA axis regulates the secretion and release of steroid hormones and plays an important role in stress responses for both humans and animals. Birds’ adrenal glands produce steroid hormones that are different from those produced by human adrenal glands—the main adrenal hormone produced in birds is corticosterone, while in humans and other mammals it is cortisol. Unlike humans, most birds produce very low levels of aldosterone,[13] and their adrenal glands lack the distinct outer cortex and inner medulla that is characteristic of human adrenal glands. Some male birds possess an appendix epididymis that extends into the adrenal gland, while others have adrenal tissue in the epididymis, a feature that does not exist in human males.[14] With such anatomical and functional differences, the physiological response to chronic stress in birds cannot be extrapolated with any reliability to other species, including humans.

Here PETA throws up a superficial argument at best. The argument may be read as a lack of awareness, or even a deliberate ignorance about whether and how the comparative study of similarities and differences between species such as human and other non-human animals have led to major advances in our understanding of behavior, physiology, and the treatments of disease. We have covered this issue in many posts previously, including here. But even without acknowledging the benefit of the comparative approach to humans, PETA appears to be very selectively reporting. Dr. Lattin also states on her website “One of the major areas of my research is the stress response…..understanding stress in wild animal populations is important because stressors like habitat destruction, climate change, and species invasions now affect most, if not all, animal species…stress is also a major risk factor for depression, heart disease, drug abuse, and suicide in humans. Understanding more about the physiology of stress could help lead to the development of new medicines and procedures to reduce stress in humans and animals.

IS REMOVAL OF INVASIVE SPECIES FROM AN ECOLOGICAL NICHE BENEFICIAL?

Lattin claim (paraphrased by PETA): “[B]ecause they are an invasive species in North America that competes directly with native bird species for nest sites and other resources, there is no negative [conservation] impact, and potentially, even a mild beneficial impact, of removing them from the wild.”[15]

PETA response: Even if some groups designate certain species as “invasive,” this does not justify capturing, confining, and tormenting them. Lattin isn’t killing these birds in the interests of conservation—she’s holding them captive and deliberately inflicting frightening and painful procedures on them for weeks and sometimes months before finally ending their lives. This has nothing to do with conservation or protecting native species.

Again, it appears that PETA has selectively reported and paraphrased Dr. Lattin’s paper. Dr. Lattin provides four reasons for the use of this species of bird; yet PETA presents none of these other explanations. Dr. Lattin justifies quite comprehensively why she studied what she studied, and in what species; but you can decide.

House sparrows are excellent subjects for these kinds of toxicological studies for several reasons. First, they are easy to catch and do well in captivity, unlike many avian taxa, such as shorebirds. Second, because they are an invasive species in North America that competes directly with native bird species for nest sites and other resources, there is no negative impact, and potentially, even a mild beneficial impact, of removing them from the wild. Third, as a passerine species, they are taxonomically similar to many birds living in coastal and riparian areas contaminated by oil, such as seaside sparrows (Ammodramus maritimus) and tree swallows (Tachycineta bicolor). Finally, the extensive validation data necessary for receptor binding studies are missing for most avian species, but are available for house sparrows.”

DOES SYSTEMATIC DOSING ALLOW US TO DRAW GENERAL CONCLUSIONS ABOUT CONSUMPTION IN THE WILD?

Lattin claim (paraphrased by PETA):  [regarding experiments in which she fed crude oil to sparrows]: “Doing this research in a lab environment allowed me to control a lot of things that might vary in the wild and make it hard to draw clear conclusions about cause and effect. What I found was that oil specifically impacted birds’ adrenal glands, preventing them from secreting normal amounts of stress hormones.” She cites this as being among “some important discoveries.” (www.christinelattin.com)

PETA response: In these experiments, Lattin fed a uniform dose of crude oil to birds until it achieved her desired effect and she was able to see measurable results, failing to take into account the wide variability in the level of exposure that would occur in a natural setting. When she compared two groups of birds, one of which was fed oil, both groups were under so much stress that they experienced the same rate of weight loss, and one bird died of undisclosed causes.[16] Additionally, there is little correlation between sparrows and aquatic birds, the species generally affected by oil spills. Studies of penguins and ducks, some of which were conducted decades ago, have produced widely varying results, including, respectively, an increase in corticosterone caused by oil exposure, a decrease, and no difference at all.[17], [18], [19] Not only are oil-feeding studies in sparrows irrelevant—as the sparrow is a nonaquatic species and therefore unlikely to be exposed to oil spills—they also fail to yield any results that can be extrapolated to other species of birds. They cannot mimic realistic situations and, as such, lack real-world applicability to conservation problems.

Dr. Lattin’s justification for her work was covered in the preceding point evaluation; however Dr. Lattin has also discussed this quite clearly in her paper. Additionally, and in response to PETA’s claim about a lack of applicability, this research is already being used by other researchers to show health problems and deaths observed in wild dolphins and sea turtles after Deepwater Horizon were due to oil exposure.

DOES UNDERSTANDING STRESS IN BIRDS HELP US TO UNDERSTAND RESPONSE TO ENVIRONMENTAL CHALLENGE?

Lattin claim (paraphrased by PETA): “Understanding how hormones and the brain affect stress resilience will allow us to predict what kinds of individuals will be the winners and losers in the face of current and future environmental challenges.” (www.christinelattin.com)

PETA response: It stretches credulity to equate the extreme stress of capture and the subsequent terror that Lattin deliberately inflicts on birds to the pressures brought on by, for example, climate change. In its 2015 “Audubon’s Birds and Climate Change Report,”[20] the National Audubon Society stated, “The persistence of many North American birds will depend on their ability to colonize climatically suitable areas outside of current ranges and management actions that target climate change adaptation.” So for instance, a species’ chance of surviving a warming world increases if nearby higher elevations offer a more suitable habitat and the birds are not blocked from moving into those areas. Nowhere does the report mention that the ability to withstand being rattled in a cage, rolled on a cart, and physically restrained is indicative of a bird’s resilience in the face of climate change.

It is quite likely that PETA finds incredulous Dr. Lattin’s statement that understanding how hormones and the brain affect stress resilience is highly applicable to the survival of different species in response to environmental challenge. It is possible that this is simply be because PETA and its representatives do not understand how science works (at best, e.g., here). Or perhaps it is a case of deliberate ignorance (at worst). But one does not need to look far to understand the relationship between Dr. Lattin’s work and the environmental challenges that are well appreciated and of deep concern. In PETA’s own paraphrasing of Dr. Lattin, it is first obvious that she does not talk about climate change, but environmental challenges. This may include climate change, but could also include factors such as food scarcity and increased predation. Here, PETA uses the buzz word, climate change, perhaps because it is easily relatable, but it is used out of context to Dr. Lattin’s own statement.

IS SYSTEMATIC LAB BASED RESEARCH RELEVANT TO WILD ANIMALS?

Lattin claim (paraphrased by PETA): “My current research focuses on one type of stressor that has direct implications for the conservation of endangered and threatened species—bringing birds into captivity. The transition from the wild to captivity is a strong psychological stressor, even if birds have unlimited food and water and large clean cages.” (www.christinelattin.com)

PETA response: Here, Lattin claims that her experiments will somehow provide insight into the best way to mitigate the effects of captivity on endangered birds taken from their natural habitats. In a 2017 paper,[21] she purports that in order to do so, it is important to know whether these effects are caused by the release of the hormone corticosterone or other physiological effects. To test this theory, she treated one group of birds with mitotane, a drug that limits the production of corticosterone by the adrenal glands.

Both the mitotane and non-mitotane groups experienced an increase in beak wiping—a sign of distress—the longer they were kept in captivity. While the mitotane-treated group experienced a smaller increase in this behavior, the effect was slight. Moreover, this group still lost the same amount of weight and demonstrated other stress-related types of behavior, such as increased feeding and feather ruffling, to the same degree as the control group.

Despite this underwhelming result, Lattin draws the sweeping conclusion that “experimentally reducing stress-induced corticosterone may mitigate some captivity-induced behavioral changes.” She seems to be making the absurd suggestion that captive birds should be subjected to the stress of an injection every other day in order to very slightly reduce one stress-related form of behavior.

When researchers or wildlife officials take the extreme step of capturing endangered birds to treat injuries, translocate them, or include them in breeding programs, they aim to lessen the stress experienced during capture and captivity. The birds might initially be hooded, kept in a quiet room, and provided with appropriate perching material. If Lattin truly wanted to design an experiment that aimed to explore what these unfortunate captives experience, she would have tried to reduce their stress instead of cruelly compounding it.

PETA again appears to be deliberately disingenuous here, selectively reporting. The first issue worth pointing out is that Dr. Lattin does not make a sweeping conclusion, but clearly states,

Lattin: “…our data suggest that experimentally reducing stress-induced corticosterone may mitigate some captivity-induced behavioral changes.”

We might ask whether PETA understands the distinction between conditional statements and sweeping conclusions (may mitigate versus will mitigate). PETA also fails to acknowledge the great lengths that Dr. Lattin went to avoid pain and unnecessary distress in the administration of the drug mitotane:

We also wished to avoid muscle damage that can be caused by intramuscular administration. Therefore, we injected mitotane subcutaneously over the breast muscle every other day, which can reduce circulating CORT in house sparrows to the low physiological range …”

Finally, it is now unsurprising given all of the misrepresentation of facts that no consideration beyond PETA’s own agenda is given to Dr. Lattin’s clear statement of applicability in this paper:

“Broadly, our results emphasize that researchers should take behavioral and physiological differences between free-living animals and captives into consideration when designing studies and interpreting results. Further, time in captivity should be minimized when birds will be reintroduced back to the wild.

SUMMARY

What can conclude from this (very lengthy) analysis?  In part, that simple lies are easier to convey than are complicated truths. Readers here already know that and have seen any number of similar campaigns in which research is misrepresented. Campaigns against animal research continue despite the fact that the facts, context, and accurate information about the rationale, conduct, and care for animals appears in scientific papers, in scientists’ public presentations, in a range of venues, websites, books, and papers.

It is also true though that it takes a great deal of time to address each of the claims so easily made and publicized by groups like PETA.  And so often, the claims remain unaddressed. Groups like PETA may well bank on the fact that most scientists and institutions do not have – or will not take – the time to rebut claims. And they would be correct, as we’ve often seen.

In this case though, Dr. Lattin has engaged in rebuttal. It falls to the rest of the scientific community to join her. Not only in defense of her work, but in defense of public interests in making informed decisions on the basis of facts, context, and serious consideration.

CONTRIBUTIONS OF DR. LATTIN’S WORK TO SCIENCE, BASIC RESEARCH, CONSERVATION AND THE 3RS

  • Her research has been cited hundreds of times by other scientists doing research on stress, conservation, and health, including scientists working on many other bird species (including endangered species like the Florida Scrub Jay and Egyptian vultures), and dozens of other species of animals, including fish, newts, frogs, snakes, sea turtles, lizards, dolphins, whales, mice, rats, voles, ground squirrels, hamsters, cheetahs, tigers, and monkeys.
  • She has pioneered new techniques in house sparrows that allow for less invasive ways of studying stress – for example, her work validating the technique of extracting hormones from feathers, and her current research using PET and CT imaging techniques to study the brain and body.
  • Her studies on sparrows have clear and direct conservation applications. For example, her research showing that birds caught right before and during molt dramatically altered their normal physiology in response to captivity stress suggests that conservation efforts using translocation and reintroductions of birds should avoid capturing birds at these times.
  • Her research showing rapid changes in body composition in captive wild birds demonstrates that the amount of time in captivity should be minimized for wild birds that need to be released.
  • Her research showing that oil-exposed animals cannot mount a normal hormonal response to an injection of adrenocorticotropin hormone (a minimally invasive technique that does not require euthanizing animals) shows that this technique could be used to compare animals in a population where oil effects are suspected to animals in a reference, unimpacted population.
  • Many of her studies also make major contributions to understanding fundamental biological processes that are similar across all groups of vertebrate animals. For example, her research demonstrates that animals are capable of regulating hormone levels somewhat independently from receptor levels in different tissues, and that gene expression and protein expression appear to be regulated separately for stress hormone receptors in the brain. This work helps us understand how the body regulates and responds to hormonal signals.

Speaking of Research


Filed under: #ARnonsense, Animal Rights News, News Tagged: #ARnonsense, animal rights, animal testing, bird, lattin, peta, research, sparrow

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