Category Archives: Science News

Germany’s animal research in numbers for 2015

The statistics for animal research conducted in Germany in 2015 were submitted to the European Commission last week. We have summarised the data below. We compare that to the 2014 statistics also available on their website.

Tierversuche

Animal research in Germany for 2015 by species [Click to Enlarge]

Germany used 2,799,961 animals in 2015, with an overall decrease (15.5%) in animal use when compared to 2014. Similar to other countries, mice remain the most popular species used in animal research, with an increase in use of 5% compared to 2014. Fish, birds, other rodents and other non-mammals saw sizable percentage decreases in their overall use compared to 2014, albeit compared to the total number of animals used, these relative differences are still small. Fish in particular saw a decrease because of differences in reporting between 2014 and 2015. According to the Bundesministerium für Ernährung und Landwirtschaf (BMEL), in 2014, “708,462 “other fish” (including about 563,600 fish larvae) were reported (21.38 percent). By 2015, however, the share of animals in the “other fish” category was only 2.88% (80,777 animals).”

Tierversuche

Mice, rats and fish account for 91% of all animal procedures, rising to 95% if you include rabbits. Similarly to 2014, Germany remains one of the few European countries where rabbits are the fourth most commonly used species in 2015. Dogs, cats and primates accounted for 0.31% of all animals, despite a doubling in the number of animals used for these species.

Tierversuche

Click to Enlarge

This year was the second year where there was retrospective assessment and reporting of severity (i.e. reporting how much an animal actually suffered rather than how much it was predicted to suffer prior to the study). The report showed that 43% of procedures were classed as mild, 17% as moderate, 4% as severe, and 36% as non-recovery, where an animal is anaesthetised for surgery, and then not woken up afterwards. Compared to 2014, there were some noticeable shifts in relation to severity. While the number of procedures which caused animals moderate and severe levels of stress and distress decreased, the numbers of procedures that were terminal increased.

Severity of animal experiments in Germany

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Looking at the historical data, we see that like several other countries, the number of animal experiments increased steadily between 2000-2012. The sharp increase in 2014 followed by a decrease in 2015, reflect in part differences in the accounting procedures used between 2014 and 2015. Thus, it is too early to say whether the fall in 2015 is a one-off or a sign of a future drop-off in animal experiments. It is likely that this drop also partly reflects a decrease in funding to science during the recession and economic turmoil of the past few years. Next year’s data may provide some insight into whether and how this trend will continue.

Trends in German animal experiments 2000-15. Click to Enlarge.

Trends in German animal experiments 2000-15. Click to Enlarge.

Other interesting information provided by the annual statistical release includes:

  • 8% of animals used were bred within the EU [Table 3]
  • The main purpose of research was “Basic Research” (58.7%), followed by “Regulatory use and Routine production” (22.5%), “Maintenance of colonies of established genetically altered animals, not used in other procedures”, “Translational and applied Research” (13.6%), and all other uses (5.2 %) [Table 9]
  • Two-thirds of the total dogs, cats and primates were used for Regulatory testing [Table 9]
  • 40% of animals were genetically altered, compared with 60% which were not. Over 98% of the genetically altered animals were mice or zebrafish [Table 20]

For further information about animal research (Tierversuche) in Germany see our background briefing, available in English and German.

Speaking of Research

2015 Statistics: http://www.bmel.de/SharedDocs/Downloads/Tier/Tierschutz/Versuchstierdaten2015.pdf?__blob=publicationFile

2014 Statistics: http://www.bmel.de/SharedDocs/Downloads/Tier/Tierschutz/Versuchstierdaten2014.pdf?__blob=publicationFile

N.B. Some our more eagle-eyed readers may have noted the 2014 statistics referenced in this article do not correspond to those we published a year ago. This is because the German authorities changed the counting methodologies for 2015 and re-released an altered 2014 statistics so that they could be fairly compared to the 2015 data.

More thoughts on animal suffering

My recent article “Not just intelligence: Why humans deserve to be treated better than animals” elicited many thoughtful comments and plenty of debate, both on this blog and in Reddit. In this new post I have compiled some new thoughts that came up during the debate. To view the full discussion, please follow the hyperlinks.

Do animals have the ability to suffer?

I think that, strictly speaking, most animals species do not have the ability to suffer. These will include animals like corals, jellyfish, starfish, worms, clams, snails and insects that comprise millions of species with nervous systems so small that cannot possibly endow them with enough consciousness to suffer. In comparison, the species of chordates that can be said to suffer are a tiny minority. My work is in pain neuroscience, where we make quite nuanced distinctions between suffering, distress, pain and nociception. We know that many species have nociception, but we cannot infer from that that they feel pain, and even less that they suffer. Other show the same physiological signs of distress that we have (elevated levels of cortisol in the blood), but this doesn’t necessarily mean that they suffer. There are animals that clearly do not have nociception, pain, distress or suffering, like sponges. On the other end of the cognitive scale, it is clear that humans do suffer. At what point in the evolutionary tree the ability to suffer appears is not an easy question to answer.

automaton

Philosophers have been speaking of suffering as an absolute, something that exist in itself. In fact, neuroscience points out that suffering cannot exist without consciousness and is not independent of certain cognitive abilities like emotions and memory. An animal can only be said to be suffering inasmuch as it is conscious of this suffering, which links the problem of suffering with the “hard problem” of consciousness. This is because an unconscious animal would be just an automaton, something that responds to stimuli without having a subjective experience of those stimuli. As long as a being is self-conscious, including having extended consciousness, the life of that being has value of its own. So, like it often happens when we look at the living world, there is a gradient of minds between complete automatons and fully conscious human beings. Consciousness, and its attending capacities to suffer and be happy, develops gradually with evolution. So suffering, like consciousness, had to develop gradually during evolution. I doubt that there is a threshold, a hard line, with suffering on one side and not suffering on the other, so we have to wrap our minds around the fact that some animals have more capacity for suffering than others. Therefore, different species should be treated according to their mental capacities, which is, if you want, a hard form of speciesism. But it is what we do all the time, for example, when we kill the fleas that afflict our dog. Clearly, the dog has more moral standing in our eyes than the fleas.

In addition to consciousness, I think that suffering requires the presence of a self because otherwise the existence of the subjective experience of suffering doesn’t make sense. This is a variant of the problem of consciousness: do non-human animals have a self? That’s doubtful. Maybe apes and dolphins do, rats and mice probably don’t. But, again, that is highly speculative. Hence, there has to be a scale of suffering. In that scale, humans are capable of much deeper suffering (and much deeper happiness) because we can see ourselves as selves with an existence extending in time, so we not only suffer in the present, but we can see that we have suffered in the past and that we will suffer in the future. Without episodic memory and extended consciousness, animals do not have selves with that continuity in time.

An endangered fox in the California Channel Islands

An endangered fox in the California Channel Islands

Questioning the ability of animals to suffer doesn’t mean that scientists are looking for a justification to inflict pain on animals. Rather, here scientists face two different moral imperatives. The first is the fundamental dictate of science of looking for the truth unhindered by cultural and societal biases. This leads us to examine the questions of animal pain and suffering in an objective way. The second moral imperative is not to be cruel to animals that can potentially suffer. It is because of this and the cautionary principle that we treat animals like rats and mice as if they can suffer, even when we don’t know for sure that they can. However, we do know with absolute certitude that humans can suffer, which is an additional argument to put human suffering before putative animal suffering. Therefore, it is morally justifiable to use animals in biomedical research to alleviate human suffering, while at the same time taking all possible measures to minimize the distress of animals involved in research.

We need a definition of suffering for many practical matters and not just for animal research. Of course, we should treat animals, and even plants, with respect and not harm less for frivolous reason. But sometimes it is necessary to harm animals. There are many cases in which is necessary to kill animals to protect the environment – the case of pigs and goats in the California Channel Islands comes to mind. In those cases we need to balance two wrongs against each other: the suffering caused to the animals and the destruction of the environment produced by them, possibly including the extinction of some species. Animal research is another example: we need to use animals to find the cure for human diseases. When we look at the ethics involved in those cases, we need to carefully consider whether the animals involved do suffer or not, and how much weight we put on that suffering.

Feral pigs are an invasive species in the California Channel Islands

Feral pigs are an invasive species in the California Channel Islands

Suffering is not the only relevant issue in the animal research debate

Some animal rights proponents argue that mental abilities are a red herring because the only question that is relevant in the animal rights debate is whether animals can suffer. This is not true for two reasons.

First, this is in direct contradiction to what other animal rights proponents say: that animal rights go beyond the right to life and the right not to suffer, and also include the right to be free, the right not to be used for somebody’s else goals, etc. Then the question of whether animals have the mental capacities that enables them to know whether they are free or to care about whether they are being used are completely relevant.

Second, the way we treat a being is also determined by the intrinsic value we give to that being. For example, a species has an intrinsic value, so when a species goes extinct this means a terrible loss, and a deep moral wrong. Humans deserve respect not just because they suffer, but because of their intrinsic value. And that intrinsic value is based on our rich mental lives, our ability not just to suffer but also to be happy, to enjoy beauty, to find meaning in our lives. Therefore, mental capacities beyond the ability to suffer or to think intelligently are fundamental. It’s not just about humans, the same reasoning is used to give a dog more intrinsic value than the fleas that it carries in its fur.

But even if we accept the narrow framing that suffering is the only relevant question, suffering does not exist in isolation of all other mental functions. In particular, there cannot be suffering without consciousness because if there is no subjective awareness of the suffering, then it is not really taking place. Also, suffering, like happiness, acquires a deeper meaning for beings like us that can put it in a context of a life with a past and a future, in the middle of a society and a culture that creates a much richer context for any of our experiences.

Ultimately, the thing that worries me the most about the whole animal rights movement is how it has come to degrade the idea of what it means to be human by denying our rich mental abilities and making us equals to animals. Instead of elevating animals to human status, it degrades humans to animal status. Therefore, the animal rights movement is really a form of misanthropy, a radical anti-Humanism.

by Juan Carlos Marvizon

Special Issue of Primate Journal Focuses Solely on Non-Human Primate Well-Being

This month, the American Journal of Primatology published a freely-available Special Issue entitled, “Non-Human Primate Well-Being.” The entire issue is dedicated to the physical, psychological and physiological well-being of laboratory-housed non-human primates, and is notable for its cross-facilities studies as well as for the diversity of primate species that are represented, including rhesus and pigtailed macaques (Macaca mulatta and Macaca nemestrina, respectively), vervet monkeys (Chlorocebus aethiops sp.), and owl monkeys (Aotus sp.)

A female (L) and male (R) pigtailed macaque (Macaca nemestrina) housed at the Washington National Primate Research Center in Seattle, WA. Photo: Dennis Raines.

A female (L) and male (R) pigtailed macaque (Macaca nemestrina) housed at the Washington National Primate Research Center in Seattle, WA. Photo: Dennis Raines.

The Special Issue (synopsis provided in the Introduction) is a compilation of review articles and empirical research articles from non-human primate experts that provide evidence-based information pertaining to social housing for laboratory primates and the utility of techniques to indicate chronic stress and related measures of well-being. With increased regulatory, accreditation, research, and public attention focusing on nonhuman primate well-being, the release of this issue is timely. The issue’s target audience includes those who hold scientific and/or management oversight of captive primate behavioral management programs, though it’s freely-available status provides a unique opportunity for the general public to become familiar with the types of research being conducted to improve the well-being of laboratory primates.

“The well-being of non-human primates in captivity is of joint concern to scientists, veterinarians, colony managers, caretakers, and researchers”

– Baker & Dettmer, Am. J. Primatol., 79:e22520, p. 1

The Special Issue is conceptually comprised of two parts: Pair Housing in Laboratory Primates and Indices of Well-Being in Laboratory Primates. The Pair Housing section begins with two extensive review articles analyzing the scientific literature surrounding social housing introductions and maintenance of social housing in macaques, the most commonly-studied genus of captive non-human primate in the U.S. Included in the first of these articles (Truelove et al., 2017) is a set of recommendations from researchers at the Yerkes National Primate Research Center for many key issues involved in the management of macaques, such as partner selection, introduction, and special populations. The second review article by Hannibal et al. (2017) from the California National Primate Research Center “assists with harmonizing social management and research aims” (Baker & Dettmer, 2017) by highlighting the important fact that changes in the social environment can influence the physiological and physical health of captive non-human primates. Importantly, this article also takes into account how the change in social status may influence research goals.

The remaining articles in the first section present empirical research in which controlled experimental manipulations were conducted to identify the ways in which pair introductions are influenced by species, demography, partner selection techniques, and early interactions. Notable experts in primate behavior provide these important contributions, including John Capitanio et al. (2017) from the California National Primate Research Center, Matthew Jorgenson et al. (2017) from Wake Forest University, Larry Williams et al. (2017) from the MD Anderson Cancer Center, and Julie Worlein et al. (2017) from the Washington National Primate Research Center in Seattle.

Vervet monkey (Chlorocebus aethiops sp.). Photo: Kathy West.

Vervet monkey (Chlorocebus aethiops sp.). Photo: Kathy West.

The second part of the Special Issue on Indices of Well-Being in Laboratory Primates presents, for the first time, research on a long-term index of hypothalamic-pituitary-adrenal (HPA) axis activity: hair cortisol. Cortisol is a hormone associated with stress responsivity, and its measurement in hair is an established biomarker of chronic stress. In several empirical research articles in this section, hair cortisol concentrations (HCCs) are related to behavioral indices of well-being including alopecia (hair loss), anxious behavior, and self-injurious behavior (SIB). Importantly, many of the studies in this section rely on collaborations between several primate facilities across the U.S. The first three papers, by recognized experts in non-human primate well-being, describe risk factors and biomarkers for alopecia in rhesus monkeys. Melinda Novak et al. (2017) from the University of Massachusetts Amherst describe how relationships between alopecia and HCCs over an 8-month period are different for monkeys that regained their hair versus those that continued showing hair loss. Notably, these relationships were facility-specific. Related, Rose Kroeker at al. (2017) from the Washington National Primate Research Center describe how prior facility origin influences rates of alopecia in monkeys that are currently housed at the same facility. Of particular note is the fact that prior facility effects were evident 2 years after relocation. Amanda Dettmer et al. (2017) from the National Institutes of Health describe a unique risk factor for alopecia: pregnancy. They relate this particular risk factor to higher HCCs and differential maternal investment in the neonatal period.

The following three articles provide novel information linking HCCs and behavioral indices of well-being across four facilities. Amanda Hamel et al. (2017) from the University of Massachusetts Amherst describe a cross-facility study showing how HCCs relate to responsivity on a well-established, reliable behavioral assay for non-human temperament and behavioral reactivity: the Human Intruder Test (HIT). Kristine Coleman et al. (2017) from the Oregon National Primate Research Center then describe how alopecia and temperament relate in monkeys housed in the same four facilities, importantly relying on a cage-side version of the HIT that minimized potential reactivity that may result from separation from the social partner. Emily Peterson et al. (2017) study the HIT in relation to SIB, providing new information between SIB and anxious temperament.

Rhesus monkey (Macaca mulatta) mother and infant. Photo: Kathy West.

Rhesus monkey (Macaca mulatta) mother and infant. Photo: Kathy West.

The Special Issue closes with a review by Allison Martin et al. (2017) from the Yerkes National Primate Research Center describing the utility of applying a behavioral analytic theoretical framework in studies of non-human primate well-being, with a special focus on the prevention and treatment of abnormal behaviors. This paper is unique in applying human clinical approaches to primatology, which represents a unique reversal of the translation of research methods.

Collectively, this Special Issue represents a comprehensive, evidence-based collection of rigorous research studies and detailed reviews from recognized experts in primate behavior that serves to provide new, timely, and critical information that will ultimately improve the welfare of these valuable research animals. Funding agencies, professionals working with captive non-human primates, and the public alike should familiarize themselves with these studies, as they highlight the dedication of the research community to continually improving the everyday lives of the animals that contribute important advancements to human health and to general scientific knowledge.

Celebrating the life of Oliver Smithies

In 2008 I was honoured to meet Dr Oliver Smithies at the eponymous Smithies -Maeda Laboratories at the University of North Carolina – Chapel Hill. I was invited to speak to him, and members of his laboratory about the importance of outreach on the animal research issue. Despite the prestige of a Nobel Prize (which he won in 2007), he was a down-to-earth, likeable scientist whose passion for genetics had helped him to the ultimate scientific reward. His attitude to his scientific endeavours can best be summed up from his words at a ceremony honouring him at UNC:

“I don’t go to work every day; I go to play every day. And that’s my advice to students here today: find something you love so much that you can say – as I can say – I never did a day’s work in my life.”

Tom Holder meets Nobel Prize Laureate Oliver Smithies

Speaking of Research founder, Tom Holder, meets Dr Oliver Smithies at the Smithies-Maeda Laboratories in 2008

Born in Yorkshire, England and educated at the University of Oxford, where he gained his undergraduate degree and DPhil, Smithies moved to the Canada in 1954 to start his post-doc research before finally moving to the US in 1960 (read his Nobel biography).

His early notable work, while working at the University of Toronto, was to develop a technique of gel electrophoresis using a potato starch matrix. His method, using Danish potato starch, is still used in medical research and forensics today, to help identify certain proteins (read more here).

Image by The Scientist. Click to Enlarge.

Image by The Scientist. Click to Enlarge.

Dr Oliver Smithies won his Nobel Prize in Physiology or Medicine in 2007, shared with Mario Capecchi and Sir Martin Evans, for “their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells”. The relevant research by Smithies was conducted at the University of Wisconsin in the 1980s where he developed a method of gene targeting in mice by replacing single mouse genes using homologous recombination – changing specific regions of genome in cultured mouse cells. He continued to use this method at UNC in order to create genetically modified animal models of human diseases and conditions. Gene editing techniques continue to advance and support medical advances.

Sadly, on the 10th January 2017, Oliver Smithies passed away, aged 91. He leaves behind a scientific legacy that will forever influence the field of genetics. He is survived by his wife, Dr. Nobuyo Maeda, Robert H. Wagner Distinguished Professor of Pathology and Laboratory Medicine in the School of Medicine.

The following video was created by UNC-Chapel Hill, in Memoriam.

Oliver Smithies, 1925-2017

Tom Holder

Why I am proud to be a Registered Veterinary Technician in animal research

Christine Archer is a registered veterinary technician at the University of Ottawa in Ontario, Canada.  She has worked in animal research for over seven years.  She currently works with aquatic animals and reptiles in biological research. In this post, Christine looks at the interests and motivations that led her to become a laboratory animal technician, and her interest and love of aquatic animals. Fish account for 43% of research animals in Canada, with amphibians adding a further 3%. 

christine-archer-with-fish-ottawa

While I can’t say that I was ever a typical kid growing up in rural Canada, my surroundings definitely shaped my interests as I grew. I was always interested in the “gross” animals, from fish to frogs, and throw some snakes in there, too. I’d drive my mother crazy, catching animals in dubiously secure containers and bringing them home, only to have her insist that I take them right back where they came from. Just about the only exception was this big female wolf spider I rescued from a trough that ended up having an egg sac, which eventually resulted in many tiny spiders all over our house. I remember I’d also saved some newts from a tiny marsh that was being bulldozed for a new house. I hand fed them and kept them for years. They even went on vacation with us, in their not so dubiously secure critter keeper. All the while, I was also keeping many, many aquariums in my parents’ house, and breeding all manner of tropical fish. We had tanks in just about every room, even the bathrooms.

After a false start in engineering, I ended up studying biology in university, but I was so enamored with all of the sciences that I couldn’t decide what I really wanted to do with myself. When I was finishing up my undergrad, my cat Monty got very sick. The process of his treatment and recovery got me very interested in veterinary medicine. While I was feeling rather burnt out by my university studies at this point, I looked into taking a college program that would offer me practical hands-on skills in addition to the science of veterinary medicine. I went to college for veterinary technology, eager to consume all of the veterinary medical knowledge I could, especially everything that pertained to those “weird” animals that I loved. In the middle of my program, I took an internship at a large medical research facility. This is where I found what I was meant to do with my life. Marrying my love for science and the scientific method with my newfound love for veterinary medicine. The only thing missing (so far) were the weird animals I am so fond of. I learned about rodents and rabbits and the nuances of their biology. I learned about the 3 Rs and how essential good animal welfare is to doing good science. Throughout my life, I’d always felt like the weird kid who stood up for the weird animals that everyone didn’t like. I was a voice for them. Now, in research, I realized that I can continue to speak for my charges, no matter what species they are.

Racks of zebrafish at the University of Ottawa

Racks of zebrafish at the University of Ottawa

I finished school and became a Registered Veterinary Technician. I worked in cardiovascular research in a number of roles, working with traditional research animals like rodents and rabbits, and the occasional pig. It was great to be surrounded by colleagues who shared my interest in animal welfare and working hard to ensure that our charges’ welfare needs were being met every day. And then, one day, I got a call. The university’s aquatics and reptile facility needed an RVT for the summer, and my supervisor wondered if I would be interested. I couldn’t believe it. The opportunity to take part in veterinary nursing and the husbandry of all of those “weird” animals I’m still totally obsessed with? I’m there. However, I was reminded that it was only for the summer. Still, totally worth it. I said my tearful goodbyes to my colleagues at the rodent facility and started my position working with zebrafish, goldfish, trout, frogs, lizards, and even the occasional snake. That was more than three summers ago. I am still proudly caring for the veterinary and welfare needs of these animals today, as I was made a permanent staff member of the facility. I am so honored to be able to work with the animals I love, surrounded by passionate people working on everything from CRISPR research with zebrafish, to biomechanics work with fish that can walk on land. We still have so much to learn about these animals and their specific welfare needs, and I am thankful every day to be on the ground floor, working with colleagues who want to advance science while ensuring these animals, these weird, wonderful creatures, get the best possible care from the humans that depend on them.

Fish Facility at the University of Ottawa

Frogs (Silurana Tropicalis) at the University of Ottawa

On an average day in my facility, I can be found setting up zebrafish breedings and collecting embryos, or culturing live food like rotifers and brine shrimp for the fish to eat. My job requires me to be adept at multiple skills, from understanding the husbandry and welfare needs for our many diverse animals, to working with our staff veterinarians on developing and improving methods to anesthetize fish and frogs. Animal welfare is very important to me, and I strongly believe that the quality of my work has a direct impact on the quality of life of the animals I care for, which in turn has an impact on the quality of the research that my colleagues can perform. I work every day with multiple researchers to help ensure they are able to do the best work possible thanks to animals which are healthy, happy, and leading enriched lives.

I am proud to be a Registered Veterinary Technician in animal research, because I care very much about animal welfare and having the opportunity to speak for those who can’t speak for themselves is something I will never tire of.

Christine Archer

Nonhuman primate research gives us otherwise impossible treatments

stuart-bakerLast week, Dr. Stuart Baker, a Professor of Movement Neuroscience at Newcastle University, wrote an article in The Conversation detailing not only the lifesaving research that nonhuman primates contribute to, but also the exceptional care they receive while contributing to human health. Stuart last week also published a paper describing his laboratory’s development of a new device that helps stroke patients to recover, a device that was dependent on development first in rhesus monkeys.  In his piece in The Conversation, Baker highlights the following:

  • Why it is important to understand how the brain controls movement
  • Why nonhuman primates are superior to other animal models for this type of research
  • The state-of-the-art care his laboratory primates receive

Why it is important to understand how the brain controls movement

“We typically take the ability to move in a fluid, coordinated way for granted,” Baker writes. Yet many adults “suffer damage to the brain’s pathways for movement, for example after a stroke. Suddenly, everyday tasks become a tiring, frustrating struggle.” Baker studies how the brain controls movement in order to understand the connections between our brains and our limbs. By understanding how brain cells adapt their neuronal activity during movements, how neurons are connected, and how they reconfigure after injury, Baker can then develop devices for therapeutic treatment like the one he published about in The Journal of Neuroscience last week.

Why nonhuman primates are superior to other animal models for this type of research

In his article in The Conversation, Baker emphasized the need for nonhuman primates in movement neuroscience research. In order to understand the deepest inner workings of the brain – those that don’t contribute to scalp recordings, which can be used in humans – one must probe deeper than the surface. Baker uses an analogy of an airport: “When we record from the scalp, we average the signals from many millions of cells. It’s a bit like placing a microphone on the ceiling of an airport departure hall, and measuring the sound levels.” This type of information is useful because it can tell you “what times of the day the airport is busy.” But “some aspects of the airport’s operations – those outside on the tarmac – would be missed.” Similarly, Baker says, some brain centers that control movement are so deep beneath the skull that a deeper exploration beyond scalp recordings is required. Enter monkey models: “Many pathways for movement control are different between primates such as humans and other animals such as rats. Only a primate model can give us information which is relevant to human diseases.

One of Newcastle’s macaque monkeys. Newcastle University, Photo credit: S. Baker

One of Newcastle’s macaque monkeys. Newcastle University, Photo credit: S. Baker

The state-of-the-art care his laboratory primates receive

Stuart is well aware that there are inaccurate and baseless claims that his lab animals suffer. In The Conversation, he describes in detail the care his monkey receive, from positive reinforcement training so that they learn to perform complex tasks with their hands or arm to undergoing surgery “in a fully equipped operating theatre, with sophisticated anaesthetics and painkilling medication borrowed from state-of-the-art human care.” The monkeys are carefully monitored to ensure they are not distressed or in pain.

Baker also emphasizes the “huge effort [that] goes into minimizing suffering every day.” This effort is not optional, but “an integral part of what we do and who we are.”

Baker’s article is a wonderful example of the type of transparency that scientists should engage in more frequently. Without such candor, the public is unaware of the extent to which animal models contribute to lifesaving therapeutics – and also of the excellent care they receive from the people who truly love working with them.

What can you share about your research and the animals you work with?

Device to help stroke patients to recover moves from primates to people

Every year, 15 million people worldwide suffer a stroke, resulting in almost six million deaths and five million people left permanently disabled. It occurs when blood supply to the brain is blocked, or a blood vessel bursts. This prevents oxygen reaching the brain and can cause brain cells to die.

Many people who suffer strokes will subsequently experience spasticity, where the arm and leg muscles cramp or spasm as a result of message between the brain and muscle being blocked. This can cause long periods of contraction in major muscles resulting in bent elbows, pointed feet, arms pressed against the chest, or the distinctive curled hand common to many stroke survivors.

Neuroscientists at Newcastle University have developed a new device which aims to help stroke patients by strengthening a spinal connection known as the reticulospinal tract that can take over some of the function of more major neural pathways connecting the brain to spinal cord when they are damaged following a stroke. This strengthening can alleviate the symptoms of spasticity in the hand and arm of patients, allowing them additional control that can help them regain an important degree of independence in their life.

An article published yesterday in the Journal of Neuroscience (1) reports on the early success of this device, which is about the size of a mobile phone and can deliver an audible click followed by a small electric shock to the arm of patients. Electrical stimulation has previously been used to improve nerve function in other types of injury, but the combination with an auditory signal is new. The study shows that the device is able to strengthen the connections in the reticulospinal tract – the nerve tract in the spine which passes messages from the brain to the limb muscles. After a stroke, the body tends to recover the strength of connections to flexor muscles  (which allow you to close your hand)  more than extensor muscles (which allow you to open your hand). This is why many stroke patients suffer from a curled (semi-closed) hand.

stuart-baker-fits-the-electronic-device-to-a-patient

Stuart Baker attaches the device to a patient

Healthy patients were wired up to receive weak electric shocks to their arm muscle alongside a click sound. The individuals were then sent about their day. By altering the timing of the clicks and shocks they could strengthen or weaken the patients’ reflexes. By wearing the portable electronic device for seven hours, during which time the patients could carry out their daily work, the scientists were able to show that the signal pathways were strengthened in more than half of the patients (15 of 25).

So how did they discover that following a small electric shock with a click could strengthen the nerve pathways between the brain and the arm? Well, it’s a classic case of “Fortune favours the prepared mind”!

Stuart Baker, Professor of Movement Neuroscience at Newcastle University who has led the work said: “We were astonished to find that a small electric shock and the sound of a click had the potential to change the brain’s connections. However, our previous research in primates changed our thinking about how we could activate these pathways, leading to our study in humans.

In 2012 Baker and his colleagues published a paper reporting on their evaluation of a non-invasive transcranial magnetic stimulation (TMS) in stimulating nerve cells in a part of the brainstem called the reticular formation –  where the reticulospinal tract begins – in anaesthetised macaque monkeys, which they undertook as preparation for using TMS in studies in monkeys and human volunteers.   They observed that while the TMS stimulus produced a the expected quick response in the nerve cells, they also produced a puzzling delayed response, which they thought might be triggered not by the changes in the magnetic field but rather to the audible click that the TMS making made when its coil discharged. To test this idea they used a miniature bone vibrator to generate the same kind of click, and found that it stimulated a very similar pattern of nerve activation to that evoked by the sound of the  TMS coil discharge.

At first they viewed this nerve response to the click sound made by the TMS machine as a complication that needed to be accounted for in future studies of the reticular formation, but very quickly realised that the click response could itself be useful as a non-invasive experimental tool, and might even be useful in the clinic.

Baker wanted to know exactly how much the arm-brain connections were controlled by the reticulospinal pathway they were studying, and determine if the timing of a click following the small electric shock made any difference. To assess this, they got primates to do a similar task to that later evaluated in human volunteers. What they found was that by changing the timing between clicks and small electrical shocks, they could change the strength of reflex of the monkeys by as much as 50%. This has given the researchers the confidence to move this into a clinical trial of stroke patients.

primate-in-stroke-research

The macaques monkeys were given food rewards for performing a simple movement based task.

Baker recently published an article on The Conversation entitled “Using monkeys for research is justified – it’s giving us treatments that would be otherwise impossible“. An extract is provided below:

In my own work, we use a small number of macaques to gain this fine-grain understanding. Many pathways for movement control are different between primates such as humans and other animals such as rats. Only a primate model can give us information which is relevant to human diseases.

To learn how these pathways are actually used to control movements, in some studies we first teach the macaque to perform complex tasks with their hands or arm. Getting it right is rewarded with a treat (typically fruit or nuts, but chocolate or strawberry yoghurt also sometimes feature). Once they know what to do, we carry out a surgical implant to allow us to record from the brain using fine electrodes, with tips around the same size as single cells.

All surgery is done in a fully equipped operating theatre, with sophisticated anaesthetics and painkilling medication borrowed from state-of-the-art human care. Once the macaque has recovered, we can record from the brain cells while they do the trained task. An animal that is stressed or in pain would not willingly cooperate with the experiments. The animals seem to enjoy the daily interaction with the lab staff and show no distress.

Our studies are right at the crossroads of basic and clinical sciences. We are trying to understand fundamental brain circuits, and how they change in disease and recovery. Over the past ten years, we’ve shown that a primitive pathway linking brain to spinal cord can carry signals related to hand use. That was a surprise, as until now it was assumed that the primate hand was controlled only by more sophisticated pathways that developed later in evolution.

A clinical trial will now start in Kolkata, India, involving 150 stroke patients. It aims to see whether this new device can improve hand and arm control. The work at Newcastle University has been funded by the Medical Research Council and the Wellcome Trust.

chris-blowerChris Blower, 30, suffered a stroke at the age of seven, which paralysed him down onside, slurred his speech and caused him to lose bowel control and move unaided. Though he recovered from these immediate effects, he still suffers slow, limited and difficult movement in his right arm and leg. Here is an extract from his story:

My situation is not unique and many stroke survivors have similar long-term effects to mine. Professor Baker’s work may be able to help people in my position regain some, if not all, motor control of their arm and hand. His research shows that, in stroke, the brains motor pathway to the spinal cord is damaged and that an evolutionarily older signal pathway could be ‘piggybacked’ and used instead. With electrical stimulation, exercise and an audible cue the brain can be taught to use this older pathway instead.

This gives me a lot of hope for stroke survivors. My wrist and fingers pull in, closing my hand into a fist, but with the device Professor Baker is proposing my brain could be re-taught to use my muscles and pull back, opening my hand out. The options presented to me so far, by doctors, have been Botox injections and surgery; Botox in my arm would weaken the muscles closing my hand and allow my fingers to spread, surgery would do the same thing by moving the tendons in my arm. Professor Baker’s electrical stimulations is certainly a more appealing option, to me, as it seems to be a permanent solution that would not require an operation on my arm.

Keith toured the animal house at Newcastle University. He noted after:

The macaque monkey that I observed was calmly carrying out finger manipulation tests while electrodes monitored the cells of her spinal cord.

Although this procedure requires electrodes to be placed into the brain and spine of the animal, Professor Baker explained how the monkey had been practising and learning this test for two years before the monitoring equipment was attached. In this way the testing has become routine before it had even started and the animal was in no pain or distress, even at the sight of a stranger (me).

The animals’ calm, placid temperaments carry over to their living spaces; with lots of windows, natural light and high up spaces the macaques are able to see all around them and along the corridors.

It is great to see Newcastle University being clear about the contribution of animal studies to clincal work. In their press release they noted that “the research published today is a proof of concept in human subjects and comes directly out of the team’s work on primates”.

Baker notes in his recent article,” In my opinion, we should not condemn large numbers of people to disability and dependence, but need to use all of the tools of modern science to discover and innovate the solutions. I am confident that the next 50 years will see wonderful progress in treatments for these terrible disorders and primate research will be central to this effort.

You can read more about animal research at Newcastle University from their website.

Speaking of Research

REFERENCES

  1. K.M. Riashad Foysal, Felipe de Carvalho, Stuart N. Baker. Spike-timing Dependent Plasticity in the Long Latency Stretch Reflex Following Paired Stimulation from a Wearable Electronic Device.  Journal of Neuroscience,