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Research on chicken that cannot feel pain

Research on chicken that cannot feel pain



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In was having a conversation about the ethics of vegetarianism, and if it is right to cause pain to other animals.

It is then that I stumbled upon the question, that if, just the way chicken and many other animals have currently been cultured or genetically modified (or by any other means) to have certain desirable qualities (from market and demand perspective) such as the fat content, quality of eggs etc., will it be fine to consume chicken if we also, if possible, raise chicken that do not feel any pain at all (if that is defined, or can we define that?).

I realise that this is not philosophy stackexchange, so I would not ask about the ethics of it.

What I want to ask here is this: is such research taking place (anywhere on earth) to develop breeds of chicken that do not feel pain, if yes I would be thankful to know at least the basics, and if not, do you think it is possible in the near future or what possible approach would you contemplate?


The Great Fish Pain Debate

Do fish feel pain? For over 50 years, this question has been the focus of multiple scientific careers and consumed countless hours of research, debate, and reflection. But a different and related question has received far less attention: how and why did fish pain come to be a contentious scientific question in the first place? The experience of feeling pain has an inescapably subjective dimension for all organisms. Such an experience might be correlated with certain neurophysiological phenomena, but it cannot be fully reduced to such phenomena, nor is it possible to access the interior cognitive state of another individual (human or otherwise) to ascertain how the phenomena might be subjectively perceived. Moreover, fish are an extraordinarily broad category shark species today are about as evolutionarily close to halibut as humans are. So we want to ask not just what science is telling us about fish pain, but what is the fish pain debate telling us about science?

To try to answer this question, we have peered into the history of the great fish pain debate and examined who has been involved, the events that spurred their efforts, and the ways that human values and competing interests have shaped the terms of the debate and the lines of research.

Our history begins with anti-angling campaigns in South Africa in the 1960s. It then moves to West Germany, where animal-rights groups won several battles over the legal standing of fish from the 1980s onward, with a focus on catch-and-release fishing. Arguments about fish pain reached the global stage in the 2000s, as a larger community of researchers began to apply a more diverse set of methods and scientific advances to the question of when and how fish feel pain. Yet for those scientists and advocates who argue that fish cannot feel pain, the reasoning has remained the same for decades: fish do not have a neocortex. The neocortex, which is the outer layer of the cerebral cortex in mammalian brains, is thought to be involved in several processes including sensory perception, consciousness, spatial reasoning, language, and motor commands. The significance and particularities of this singular and persistent criterion for pain in fish can be understood only by a return to the origin of the debate and its links to the recreational fishing sector.


It's Time to Stop Pretending Fishes Don't Feel Pain

Oh no, it's those darned sentient fishes once again

"I have argued that there is as much evidence that fish feel pain and suffer as there is for birds and mammals — and more than there is for human neonates and preterm babies." (Victoria Braithwaite, Do Fish Feel Pain?, page 153)

“Those who define ‘us’ by our ability to introspect give a distorted view of what is important to and about human beings and ignore the fact that many creatures are like us in more significant ways in that we all share the vulnerability, the pains, the fears, and the joys that are the life of social animals.” (Lynne Sharpe, Creatures Like Us)

A recent essay by Ferris Jabr called "Fish Feel Pain. Now What?" caught my attention and a few people wrote to me and asked what I thought about it. Mr. Jabr's essay is an easy read and is available online so here are some thoughts on the evolution of sentience and emotions in fishes. For more discussion on this topic please see Dr. Victoria Braithwaite's excellent book called Do Fish Feel Pain? and "Fish Are Sentient and Emotional Beings and Clearly Feel Pain," a summary of the ground-breaking research of Dr. Culum Brown and his review article called "Fish intelligence, sentience and ethics."

Mr. Jabr's piece focuses on Dr. Brown's and others' research that show fishes do feel pain. It's not all that surprising that the skeptics represent such organizations as the Scottish Fishermen’s Federation and people who like to go fishing. In response to those who still doubt what solid science shows about the presence of sentience in fishes, Mr. Jabr writes, "In truth, that level of ambiguity and disagreement no longer exists in the scientific community." Concerning those who claim fishes don't have enough cerebral complexity to feel pain, he notes, "Moreover, the notion that fish do not have the cerebral complexity to feel pain is decidedly antiquated. Scientists agree that most, if not all, vertebrates (as well as some invertebrates) are conscious and that a cerebral cortex as swollen as our own is not a prerequisite for a subjective experience of the world."

"The number of fish killed each year far exceeds the number of people who have ever existed on Earth."

While there is some progressive countrywide legislation that is increasingly protecting fishes, much more is needed. The number of fishes who are killed is unimaginably staggering. Mr. Jabr writes, "Annually, about 70 billion land animals are killed for food around the world. That number includes chickens, other poultry, and all forms of livestock. In contrast, an estimated 10 to 100 billion farmed fish are killed globally every year, and about another one to three trillion fish are caught from the wild. The number of fish killed each year far exceeds the number of people who have ever existed on Earth."

All in all, Mr. Jabr's essay is a very good summary of the state of affairs concerned with sentience in fishes, but I was surprised that there was no mention of Dr. Jonathan Balcombe's excellent summary of research on the cognitive and emotional lives of fishes called What a Fish Knows: The Inner Lives of Our Underwater Cousins. For more discussion on both sides of the question of whether fishes are sentient beings, please click here. In their essays in the journal Animal Sentience, researchers and other scholars predominantly support the idea that fishes do feel pain.

For an essay I wrote for New Scientist magazine called "Animals are conscious and should be treated as such" about The Cambridge Declaration on Consciousness, there is a wonderful cartoon of animals, including a fish, sitting around a table discussing these issues (reprinted here with permission of the artist, Andrezj Krauze). The print copy was called "Welcome to our world" and it's about time we did so with open hearts.

In his response to an essay published in Animal Sentience by Brian Key called "Why fish do not feel pain," Dr. Brown correctly notes that fish pain is an inconvenient truth and writes, "The primary message from these commentaries is that Key’s argument is fundamentally flawed from an evolutionary perspective. He argues (although later denies it) that human brain architecture is required to feel pain." Along these lines, in their essay called "Pain and other feelings in animals," world renowned neuroscientists Antonio Damasio and Hanna Damasio write, "In conclusion, we do not see any evidence in favor of the idea that the engendering of feelings in humans would be confined to the cerebral cortex. On the contrary, based on anatomical and physiological evidence, subcortical structures and even the peripheral and enteric nervous systems appear to make important contributions to the experience of feelings." Others argue about the strong evidence that fish feel pain from ethological, neuroscientific, and philosophical perspectives.

Mr. Jabr ends his thoughtful essay discussing a culinary tradition known as ikizukuri (roughly translated as "prepared alive") in which people eat the raw flesh of living fishes. It's doesn't make for easy reading, so you can stop reading at the end of the penultimate paragraph and realize that the vast majority of researchers and others accept that fishes are sentient beings and we need to stop pretending they're not.

The precautionary principle shows clearly that the important question is why pain in fishes has evolved, not if it has evolved

Anyone who says that life matters less to animals than it does to us has not held in his hands an animal fighting for its life. The whole of the being of the animal is thrown into that fight, without reserve.” (Elisabeth Costello, in J. M. Coetzee’s The Lives of Animals)

An objective reading of essays by people who essentially comprise a who's who of researchers who study fishes and other animals is that there is compelling evidence that fishes do in fact feel pain and we need to ask why pain in fishes has evolved, not if it has evolved. Robert Jones of the Department of Philosophy at California State University, Chico, notes in his essay called "Fish sentience and the precautionary principle," that Dr. Key's argument contains a logical flaw" and "Surely, by any moral calculus, applying the precautionary principle regarding fish welfare is reasonable and prudential, if not obligatory." (For more discussion of the application of the precautionary principle to animal sentience, please see Dr. Jonathan Birch's essay called "Animal sentience and the precautionary principle" and accompanying commentaries.)

I find the evidence for fish sentience to be credible and irrefutable. It borders on the certainty with which an overwhelming number of researchers, citizen scientists, and others argue, for example, that dogs and other animals enjoy playing with their friends, or that laboratory nonhuman primates and rodents don't like being wantonly abused in highly invasive research. These sentient nonhumans are not behaving "as if" they're having fun or in deep pain, for the data strongly support a compelling argument that they are indeed having fun or suffering from deep pain.

As I wrote in an essay called "A Universal Declaration on Animal Sentience: No Pretending," following up on the signing of the Cambridge Declaration on Consciousness, evidence of animal sentience is everywhere. There's no reason to embellish other animals, because science is showing just how fascinating and feeling they truly are.

Available evidence surely mandates that fishes should be included as full members of the nonhuman animal sentience club and deserve significantly more protection than they're currently granted from being harmed and killed "in the name of humans." I shudder when I think of the number of fishes who are killed for unneeded meals and other reasons.

I look forward to more research on the fascinating and rich cognitive and emotional lives of fishes and also studies of fish personalities (for more discussion please see "Fishes Show Individual Personalities in Response to Stress"). We owe it to them and to all other

1) For further discussion of the science of animal well-being and its focus on the lives of individual animals, please see More references


Empathic chickens and cooperative elephants: Emotional intelligence expands its range again

The more we actually study animals the more we learn about their emotional lives and cognitive skills. A few years ago a prestigious research group discovered that mice displayed empathy but caused a good deal of pain to the mice being studied. Now we've just learned that chickens also feel one another's pain. A research group at the University of Bristol, using non-invasive methods, showed for the first time that "domestic hens show a clear physiological and behavioural response when their chicks are mildly distressed." M other hens and their chicks were exposed to puffs of air. "When the air puff was directed at the hens, they reacted with signs of fear, becoming more alert and preening less, and their eye temperature decreased. When their chicks were exposed to the puffs of air, the hens showed all these signs but in addition, their heart rate increased and they made more clucking calls to their chicks - strong signs of their concern." (see also)

Previous research has shown that chickens are very intelligent so this new discovery is not all that surprising. For years, Karen Davis, president of United Poultry Concerns, has been telling us how smart and emotional birds are and that they deserve far better treatment then they receive in food processing facilities, truly torture chambers, a round the world . Accumulating data from research on chickens (and other birds) support her views. Chickens kept in horrific conditions in battery cages on factory farms don't like it and they also feel the pain and suffering of other chickens who are crammed into these incredibly inhumane prisons. If you're eating chickens you're eating pain and misery and it's not a matter of WHAT'S for dinner it's a question of WHO'S for dinner because billions of sentient animals are slaughtered and tortured for unneeded meals.

Elephants also are making news once again. We all know how smart and emotional these amazing beings are and now we've learned that they will cooperate to pull two ends of the same rope to get obtain a reward and also that an elephant will wait for another elephant to come help knowing that there is no point to pulling the rope alone. "These findings suggest that the elephants had not simply learned to pull on the rope after their partner arrived at the apparatus. They seemed to understand that the cooperative task involved both animals pulling on a rope simultaneously. This puts their performance on a par with that of chimps and bonobos."


What makes triathletes so tough?

Triathletes participate in a grueling endurance sport, swimming, bicycling, and running long distances without rest. In training and competitions, they regularly push their bodies beyond the limits most of us can endure. But while there is no doubt that triathletes are tough, very little is known about what gives them their exceptional abilities.

Now researchers at Tel Aviv University have discovered a possible explanation. Prof. Ruth Defrin and her doctoral student Nirit Geva of the Department of Physical Therapy at TAU's Sackler Faculty of Medicine have found that triathletes feel less pain than casual exercisers. Their findings were published in the journal Pain in August.

"In our study, triathletes rated pain lower in intensity, tolerated it longer, and inhibited it better than individuals in a control group," says Prof. Defrin. "We think both physiological and psychological factors underlie these differences and help explain how triathletes are able to perform at such a high level."

Mind over matter

Nineteen triathletes and 17 non-athletes participated in the TAU researchers' study. The triathletes were people who trained for and competed in at least two triathlons per year -- including in some cases the notoriously challenging Ironman Triathlon, which consists of a 2.4-mile swim, a 112-mile bicycle ride, and a 26.2-mile marathon run. The non-athletes were people who did non-competitive exercises, like jogging, swimming, or aerobics classes.

All the participants were put through a battery of psychophysical pain tests, involving the application of a heating device to one arm and the submersion of the other arm in a cold-water bath. They also filled out questionnaires about their attitudes toward pain.

In the tests, the triathletes identified pain just as well as non-athletes, but they perceived it as less intense and were able to withstand it longer. The researchers explain that detecting pain is a relatively straightforward sensory experience, whereas evaluating pain and being willing and able to endure it involves attitude, motivation, and life experience. The triathletes reported fearing and worrying less about pain, which may help explain their higher tolerance, the researchers say.

The triathletes also showed a better ability to inhibit pain than non-athletes, as measured by conditioned pain modulation -- the degree to which the body eases one pain in response to another. The researchers say psychology may be a factor here too. The triathletes with less fear of pain tended to exhibit better pain regulation. Previous studies have similarly found that psychological manipulation can affect pain perception.

The chicken or the egg?

Another explanation for triathletes' lower pain ratings, higher pain tolerance, and better pain regulation is that they have taught their bodies to respond powerfully to painful stimuli through their intense training. The TAU researchers say their study -- along with existing literature -- suggests that psychology and physiology together enable triathletes to do what they do.

"It is very difficult to separate physiology and psychology," says Prof. Defrin. "But in general, experience is the sum of these factors."

The researchers plan to do further research to determine whether triathletes participate in their sport because they feel less pain or feel less pain because they participate in their sport. If it turns out that intense training in fact helps reduce and regulate pain, it could be used to treat people with chronic pain. Like triathletes, chronic pain patients suffer daily, but their pain is out of their control and has the opposite effect, weakening rather than strengthening pain inhibition.


Fish Aren’t Animals: A Seemingly Common Misperception

A friend of mine recently had a discussion with several people who did not believe fish was meat. Some of their reasoning came from the fact that according to Catholic doctrine, they are allowed to eat fish on days where meat is prohibited.

Two weeks after this discussion was related to me, I had my own fishy experience at work. Paul McCartney’s Meatless Monday campaign came up and a co-worker asked me if one could eat fish on meatless days. When I said no, that fish is meat, an animal, I was met with a “No they’re not!” Why? My co-worker raised her hands to the sides of her head, flapping them back and forth like gills. “They just go ‘glub glub glub.’” I explained that fish actually are social and feel pain, and was met with a skeptical look. The existence of a nervous system was also met with less than enthusiasm.

I did not roll my eyes (I’ve discussed why in a previous post), but unfortunately, this is not an uncommon opinion. Earlier this week I read the following comment on a gossip blog discussing Anne Hathaway and her vegan shoes for Les Mis: “I don’t eat meat but I do eat fish and chicken.”So how do we break this misunderstanding? Biologist Jonathan Balcombe currently has a survey on his website , “What do you think of fishes?” that will help with research he’s currently doing for a book on “fish biology and behavior, human attitudes toward fishes, and the diverse and evolving relationships humans have with fishes.” This is obviously a topic that needs discussing!

It seems to be human nature not to be able to relate to things that are different from us. It’s easier for us to see a mammal as “like us” because, we are, after all, mammals. Insects, amphibians, fish, and birds do not have similar qualities – facial expressions, for instance – that make it easy for us to conclude that they are “like us.”

Is this why it’s so easy for people to go fishing and not even think of the pain associated with a fish having a hook through its mouth? Is this why we don’t think twice about burying our pet goldfish “at sea” in the toilet bowl at the end of its life? Is this why the depletion of our oceans isn’t seen for the very real crisis it is by much of the population?

The miscategorization of fish as “not animals” by human animals is just one example of the great disconnect that occurs when it comes to relating to other living beings on this planet.


Some Recent Findings

  • Review - The chickenlimb - embryology, genetics and teratologyΐ] "The chick embryo has a long history in investigations of vertebrate limb development because of the ease with which its limbs can be experimentally manipulated. Early studies elucidated the fundamental embryology of the limb and identified the key signalling regions that govern its development. The chick limb became a leading model for exploring the concept of positional information and understanding how patterns of differentiated cells and tissues develop in vertebrate embryos. When developmentally important molecules began to be identified, experiments in chick limbs were crucial for bridging embryology and molecular biology. The embryological mechanisms and molecular basis of limb development are largely conserved in mammals, including humans, and uncovering these molecular networks provides links to clinical genetics. We emphasise the important contributions of naturally occurring chick mutants to elucidating limb embryology and identifying novel developmentally important genes. In addition, we consider how the chick limb has been used to study mechanisms involved in teratogenesis with a focus on thalidomide. These studies on chick embryos have given insights into how limb defects can be caused by both genetic changes and chemical insults and therefore are of great medical significance." More? limb
  • Divergent axial morphogenesis and early shh expression in vertebrate prospective floor plateΑ] "The notochord has organizer properties and is required for floor plate induction and dorsoventral patterning of the neural tube. This activity has been attributed to sonic hedgehog (shh) signaling, which originates in the notochord, forms a gradient, and autoinduces shh expression in the floor plate. However, reported data are inconsistent and the spatiotemporal development of the relevant shh expression domains has not been studied in detail. We therefore studied the expression dynamics of shh in rabbit, chicken and Xenopus laevis embryos (as well as indian hedgehog and desert hedgehog as possible alternative functional candidates in the chicken). . While shh expression patterns in rabbit and X. laevis embryos are roughly compatible with the classical view of "ventral to dorsal induction" of the floor plate, the early shh expression in the chick floor plate challenges this model. Intriguingly, this alternative sequence of domain induction is related to the asymmetrical morphogenesis of the primitive node and other axial organs in the chick. Our results indicate that the floor plate in X. laevis and chick embryos may be initially induced by planar interaction within the ectoderm or epiblast. Furthermore, we propose that the mode of the floor plate induction adapts to the variant topography of interacting tissues during gastrulation and notochord formation and thereby reveals evolutionary plasticity of early embryonic induction." Sonic hedgehog
  • Skin transcriptome reveals the dynamic changes in the Wnt pathway during integument morphogenesis of chick embryosΒ] "Avian species have a unique integument covered with feathers. Skin morphogenesis is a successive and complex process. To date, most studies have focused on a single developmental point or stage. . Hierarchical clustering showed that E6 to E14 is the critical period of feather follicle morphogenesis. According to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the DEGs, two kinds of Wnt signaling pathways (a canonical pathway and a non-canonical pathway) changed during feather follicle and feather morphogenesis. The gene expression level of inhibitors and ligands related to the Wnt signaling pathway varied significantly during embryonic development. The results revealed a staggered phase relationship between the canonical pathway and the non-canonical pathway from E9 to E14." Integumentary Development

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  • MORN5 Expression during Craniofacial Development and Its Interaction with the BMP and TGFβ PathwaysΓ] "MORN5 (MORN repeat containing 5) is encoded by a locus positioned on chromosome 17 in the chicken genome. The MORN motif is found in multiple copies in several proteins including junctophilins or phosphatidylinositol phosphate kinase family and the MORN proteins themselves are found across the animal and plant kingdoms. MORN5 protein has a characteristic punctate pattern in the cytoplasm in immunofluorescence imaging. Previously, MORN5 was found among differentially expressed genes in a microarray profiling experiment of the chicken embryo head. Here, we provided in situ hybridization to analyse, in detail, the MORN5 expression in chick craniofacial structures. The expression of MORN5 was first observed at stage HH17-18 (E2.5). MORN5 expression gradually appeared on either side of the primitive oral cavity, within the maxillary region. At stage HH20 (E3), prominent expression was localized in the mandibular prominences lateral to the midline. From stage HH20 up to HH29 (E6), there was strong expression in restricted regions of the maxillary and mandibular prominences. The frontonasal mass (in the midline of the face) expressed MORN5, starting at HH27 (E5). The expression was concentrated in the corners or globular processes, which will ultimately fuse with the cranial edges of the maxillary prominences. MORN5 expression was maintained in the fusion zone up to stage HH29. In sections MORN5 expression was localized preferentially in the mesenchyme. Previously, we examined signals that regulate MORN5 expression in the face based on a previous microarray study. Here, we validated the array results with in situ hybridization and QPCR. MORN5 was downregulated 24 h after Noggin and/or RA treatment. We also determined that BMP pathway genes are downstream of MORN5 following siRNA knockdown. Based on these results, we conclude that MORN5 is both regulated by and required for BMP signaling. The restricted expression of MORN5 in the lip fusion zone shown here supports the human genetic data in which MORN5 variants were associated with increased risk of non-syndromic cleft lip with or without cleft palate." DOI: 10.3389/fphys.2016.00378
  • FGF8 coordinates tissue elongation and cell epithelialization during early kidney tubulogenesisΔ] "When a tubular structure forms during early embryogenesis, tubular elongation and lumen formation (epithelialization) proceed simultaneously in a spatiotemporally coordinated manner. We here demonstrate, using the Wolffian duct (WD) of early chicken embryos, that this coordination is regulated by the expression of FGF8, which shifts posteriorly during body axis elongation. FGF8 acts as a chemoattractant on the leader cells of the elongating WD and prevents them from epithelialization, whereas static ('rear') cells that receive progressively less FGF8 undergo epithelialization to form a lumen. Thus, FGF8 acts as a binary switch that distinguishes tubular elongation from lumen formation. The posteriorly shifting FGF8 is also known to regulate somite segmentation, suggesting that multiple types of tissue morphogenesis are coordinately regulated by macroscopic changes in body growth." Fibroblast Growth Factor | Renal System Development
  • 4D fluorescent imaging of embryonic quail developmentΕ] "Traditionally, our understanding of developmental biology has been based on the fixation and study of embryonic samples. Detailed microscopic scrutiny of static specimens at varying ages allowed for anatomical assessment of tissue development. The advent of confocal and two-photon excitation (2PE) microscopy enables researchers to acquire volumetric images in three dimensions (x, y, and z) plus time (t). Here, we present techniques for acquisition and analysis of three-dimensional (3D) time-lapse data. Both confocal microscopy and 2PE microscopy techniques are used. Data processing for tiled image stitching and time-lapse analysis is also discussed. The development of a transgenic Japanese quail system, as discussed here, has provided an embryonic model that is more easily accessible than mammalian models and more efficient to breed than the classic avian model, the chicken."

Study of crabs suggests they are capable of feeling pain

A hermit crab.

(Phys.org)—A pair of researchers with Queen's University in the U.K. has found via testing, that contrary to conventional thinking, crabs appear to be capable of feeling pain. In their paper published in the journal Biology Letters, Robert Elwood and Laura Adams describe how they subjected a group of crabs to jolts of electricity and the ways they tested them to see if the shocks elicited a pain response.

In humans and a host of other vertebrates, demonstrations of pain are obvious, from cries and moans to activities related to escape to avoidance behavior afterwards. But do invertebrates and/or fish feel pain? It is a reasonable question because of the way that some invertebrates are treated by humans—dunking them, while still alive, into a pot of boiling water, for instance. Doing so to a cow, pig or chicken would be unthinkable, yet it is done routinely with crabs and lobsters, which do generally attempt to escape their fate. The conventional view is that such creatures are not able to experience pain, at least in the sense that humans feel it, because they do not have brain parts that would appear to be able to process it. But, that may be oversimplifying things—to better define if a creature experiences pain, scientists have begun to establish rules or guidelines to help, such as noting types or degree of reactionary behavior or changes in hormone levels—if such guidelines are met, the creature can be said to feel pain, in whatever form.

In this new study, Elwood and Adams set out to determine if common crabs experience pain. To find out they obtained 40 specimens and put them in plastic tanks—all had wires attached but only 20 were actually given shocks—for 200-milliseconds every 10 seconds for a two minute period. All of the crabs were watched to observe their behavior, before, during and after the shocks were applied.

The researchers report that the shocked crabs displayed more vigorous behavior than those in the control group, which included walking around, taking a threatened posture or trying to climb out of the tank. Even more tellingly, they noted that the shocked crabs experienced spiked levels of lactic acid in their haemolymph—a fluid in crabs that is analogous to blood in humans.

Taken together the evidence indicates very clearly, the team claims, that crabs do indeed feel pain.

Abstract
Animal pain is defined by a series of expectations or criteria, one of which is that there should be a physiological stress response associated with noxious stimuli. While crustacean stress responses have been demonstrated they are typically preceded by escape behaviour and thus the physiological change might be attributed to the behaviour rather than a pain experience. We found higher levels of stress as measured by lactate in shore crabs exposed to brief electric shock than non-shocked controls. However, shocked crabs showed more vigorous behaviour than controls. We then matched crabs with the same level of behaviour and still found that shocked crabs had stronger stress response compared with controls. The finding of the stress response, coupled with previous findings of long-term motivational change and avoidance learning, fulfils the criteria expected of a pain experience.


Laboratory Invertebrates: Only Spineless, or Spineless and Painless?

All animals are equal, but some animals are more equal than others.

– George Orwell, Animal Farm

The above well-known quotation from Animal Farm in some ways illustrates humans’ ambivalent view of the relative status of invertebrates and vertebrates in a number of settings: in the research laboratory (differing legal protection), in wildlife conservation (e.g., the appeal of beetles vs. giant pandas), in the home (e.g., swatting flies vs. the humane disposal of mammalian vermin), and in cuisine (e.g., methods for cooking crustaceans vs. chicken). Even the terms “spineless” and “lacking a backbone” are used pejoratively.

Invertebrates are clearly considered by many to be at the “lower end” of a scale of creatures that puts humans at the extreme “upper end,” although the units on the y-axis of this graph are a matter for debate. And within the Vertebrate and Invertebrate subphyla, terminology implying some sort of ranking is often used even in academic publications—fish, which account for about half of vertebrate species, are referred to as “lower” vertebrates (e.g., Sneddon 2004) and Octopus vulgaris (a cephalopod) as an “advanced” invertebrate (e.g., Wells 1978). But Packard (1972) makes a compelling case that the “lower” vertebrate and “advanced” invertebrate are more than a match for each other in evolutionary competition.

The demarcation in the way invertebrates are viewed, and as a consequence treated, extends to the laboratory. While this issue of the ILAR Journal is very welcome and may mark a turning point, it is notable that this single issue covers about 95% of animal species (the more than 1 million invertebrate species) whereas previous issues have been devoted to amphibians, fish, and birds (ILAR 2007, 2009, 2010). This reflects the relative paucity of information in the area of invertebrate welfare and the relative youth of this topic as an area for research, with little study in major areas critical for research, such as criteria for general anesthesia.

Legislation also reflects the invertebrate/vertebrate divide. The United Kingdom enacted one of the first pieces of national legislation covering animal experimentation, the Cruelty to Animals Act of 1876 (Tansey 1998). This Act of Parliament permitted “the advancement of new discovery of physiological knowledge by experiments calculated to give pain” but it applied only to nonhuman vertebrates. It is not unreasonable to suggest that the exclusion of invertebrates indicates that, in contrast to vertebrates, they were considered to have a lesser (if any) perception of pain. Smyth (1978) comments that “invertebrates look far less like us,” so humans may find little to recognize in common with “us” in their appearance or behavior and therefore find it harder to empathize or connect at any level.

The 1876 UK legislation also reflects the species that were commonly used in physiological studies at the time (dogs, cats, rabbits, and frogs). In 1986 the legislation was revised and became the Animals (Scientific Procedures) Act that revision did not include invertebrates but an amendment in 1993 gave O. vulgaris the same legal protection as vertebrates with respect to experimental procedures (however, to date there have been no studies on O. vulgaris under the authority of the Act).

In the European Union the October 2010 revised Directive (2010/63/EU) [1] “on the protection of animals used for scientific purposes” covers “live cephalopods” under Article 1, 3b (however, decapod crustacea—e.g., crabs, lobsters—were included in drafts of the new EU legislation but not in the adopted directive). Member states are required to transpose it into national legislation by November 2012 and apply it by January 2013. Some of the challenges that will need to be addressed in the European Union to comply with this directive are considered in the articles in this issue.

Debating and solving the ethical and welfare issues that are often taken for granted when dealing with laboratory vertebrates in general and mammals in particular for “advanced invertebrates” will provide a useful learning process that will inform best practice when considering invertebrates that lack legal protection. The difficulties likely to be encountered should not be underestimated. Even Russell and Burch (1959, 6) in their classic Principles of Humane Experimental Technique avoided the issue: “The higher invertebrates perhaps deserve a review to themselves, but they raise many problems which would gravely complicate an account which can otherwise be quite general and confident.”

The papers in this special issue cover four major aspects of invertebrates in the laboratory: (1) the use of invertebrates in biomedical and related research, (2) the culture and maintenance of invertebrates, (3) evidence for pain and suffering and their alleviation, and (4) attitudes and their influence on regulation and oversight. Each of these will be reviewed briefly before concluding this introductory overview with some comments about future directions.

Use of Invertebrates in Biomedical and Related Research

…[T]he solution of a physiological or pathological problem often depends solely on the appropriate choice of the animal for the experiment so as to make the result clear and searching.

There is little doubt that invertebrate species have made major contributions to biomedical research even if judged only by their contribution to Nobel Prizes in the last 50 years, as illustrated in the following examples [2] :

  • Caenorhabditis elegans: genetic regulation of organ development and programmed cell death (Brenner, Horvitz, and Sulston 2002)
  • sea urchin and clam eggs: key regulators of the cell cycle (Hartwell, Hunt, and Nurse 2001)
  • Aplysia: signal transduction in the nervous system (Carlsson, Greengard, and Kandel 2000)
  • honeybee: organization and elicitation of individual and social behavior patterns (von Frisch, Lorenz, and Tinbergen 1973)
  • squid: ionic mechanism involved in excitation and inhibition in the peripheral and central portions of the nerve cell membrane (Eccles, Hodgkin, and Huxley 1963).

Wilson-Sanders (2011) provides a comprehensive overview of the diverse species of invertebrates used in biomedical and related research, with tables summarizing their utility in studies of developmental biology, genetics, and diseases.

While the emphasis is on Drosophila melanogaster and C. elegans primarily because of their tractability for genetic and molecular studies, it would be unwise to neglect the potential of the diversity of over a million species of invertebrates to contribute to biomedical research as model organisms to reveal fundamental biological processes including those involved in disease. Among the reasons to consider invertebrates for use in research are their

(1) simpler system than that of vertebrates. This is the argument often applied to studying nervous systems (Usherwood and Newth 1975) such as that of Aplysia californica and using species such as the honeybee as behavioral models.

(2) unique or larger structure than that of vertebrates. For example, the squid giant axon (originally mistaken for a blood vessel and rediscovered by Young in 1933) and giant synapse revealed fundamental insights into the operation of neurones (see Bullock and Horridge 1965 for references). The brain-controlled skin chromatophore system of cephalopods provides another example of a unique biological system (Hanlon and Messenger 2008).

(3) properties not readily exhibited by vertebrates. Pupation in insects provided important insights into the Hox (homeotic) family of genes fundamental to the organization of body plans. The striking capacity for tissue regeneration is seen in many invertebrates but particularly in echinoderms, as exemplified by arm regeneration in brittlestars (Amphiura filiformis Bannister et al. 2005) and regeneration of the gut in sea cucumbers (Holothuria glaberrima Mashanov et al. 2010). It is likely that interest in these properties will increase because of the growth of research in tissue engineering for medical applications.

Several drivers are likely to increase the use of invertebrates in research, including the possibility of “replacing” vertebrate models with invertebrates (“relative substitution” Russell and Burch 1959), although this requires an assessment of sentience so that an animal with “higher” sentience is replaced by one with “lower” (e.g., how would an ethical committee approach the replacement of a trout by an octopus to answer the same biomedical problem?) the relatively low cost of some invertebrates and different regulatory and ethical considerations (but see below). However, the overriding justification should be a scientific one based on a “cost-benefit” analysis—that is, an assessment of the “cost” to the animal and the benefit, in the broadest sense, of doing the research.

Culture and Maintenance of Invertebrates

The use of invertebrates in research immediately raises the question of their sourcing and maintenance, as discussed by Smith and colleagues (2011). This is a crucially important aspect of the laboratory use of invertebrates as most research requires a supply of “standardized” animals throughout the year and journals require increasingly detailed information about the animals used in a reported study (see below). Sourcing and maintenance (including the correct environmental conditions to ensure optimal health, welfare, and, if required, reproduction) may be relatively simple for D. melanogaster and C. elegans, but for marine species obtained from the wild they may be more of a challenge. Advances have been made in the culture of many aquatic invertebrates including cuttlefish (Sepia officinalis and S. pharaonis) and squid (Sepioteuthis lessoniana), but laboratory studies on O. vulgaris and Eledone cirrhosa usually involve wild-caught animals (e.g., Malham et al. 2002).

The inclusion of cephalopods in the revised EU legislation (as mentioned above) will necessitate the development of guidelines covering all aspects of their provision, maintenance, and welfare. Furthermore, bearing in mind the differences between the squid, cuttlefish, octopus, and nautilus, it is likely that each species will need its own set of guidelines. It will also be necessary to develop humane methods for handling (e.g., atraumatic weighing of cephalopods to monitor welfare may not be that simple and even in familiar mammalian species such as mice different handling techniques have a major impact on stress and anxiety Hurst and West 2010) and for anesthesia and euthanasia, together with criteria for anesthesia and identification of pain and distress.

Evidence of Pain and Suffering and Methods for Their Alleviation

Elwood (2011), Crook and Walters (2011), and Cooper (2011) review different aspects of these difficult and somewhat controversial topics, an understanding of which is essential for both ensuring animal welfare during experimentation and minimizing suffering. Elwood (2011) and Crook and Walters (2011) draw attention to the difference between nociception and pain perception and the survival advantage of the ability to detect, avoid, and learn from noxious stimuli that have the potential to damage tissue. The general hierarchical organization of the central nervous system is well established in vertebrates, but it is appropriate to exercise caution about applying preconceived notions to invertebrate nervous systems.

Defining Nociception and Pain

Nociceptors can be identified by a growing range of molecular markers (e.g., those in the transient receptor potential cation channel subfamily V member 1 [TRPV1], or capsaicin, receptor family) and more classically by recording from the afferent nerve with careful characterization of stimulus intensity-response relationships. It is worth recalling that the behavioral consequences triggered by nociceptor activation are encoded in the primary afferent signal transmitted from the tissue to the central nervous system. In vertebrates responses to activation of nociceptors range from localized responses (e.g., edema, vasodilatation) in the affected tissue via axon collaterals if present, to reflex responses mediated via the spinal cord (e.g., limb withdrawal reflex, scratch reflex) and brainstem resulting in a coordinated response often involving several body systems. Complex endocrine responses to “stress” mediated via the hypothalamic-pituitary-adrenal axis require the more rostral projection of the information encoded in the nociceptive afferent, and conscious perception (feeling pain and the associated emotional aspects) requires projection to the thalamus and cerebral cortex.

Humans tend to think of the effects of noxious mechanical, thermal (hot and cold), and chemical stimuli (including pH) on the surface epithelium (“skin”), but both eating and breathing (air or water) can expose the “interior” of the animal to noxious stimuli that may evoke reflex response such as vomiting and coughing (both complex reflex motor responses mediated via the brain stem and widely present in vertebrates) to remove the irritant, and, in the case of ingested toxins, the unpleasant sensation of nausea (requiring cerebral cortical processing in humans) that is important in the genesis of learned aversions (Stern et al. 2011). Researchers have reported ejection of ingested toxic food in the sea anemone (Lindquist and Hay 1995) and gastropod Pleurobranchaea (McClellan 1983) and of gastric contents in the squid Sepioteuthis sepioidea (Garcia-Franco 1992). Painful sensations can also arise from noxious stimulation of the viscera (e.g., gut pain) and could be as much a cause of reduced food intake in an invertebrate as in a vertebrate.

Assessing and Treating Pain/Nociception in Invertebrates

How can scientists determine whether invertebrates “feel” pain? In considering the issue of assessing pain in animals, Bateson (1991) wrote, “We may feel confident about a mammal or even a bird. But what about a locust or an octopus?” For vertebrates there is generally good knowledge of comparative brain neuroanatomy, allowing a degree of reverse engineering based on knowledge of human brain pain pathways to determine whether similar pathways exist in other vertebrates. Even among vertebrates, however, conclusions about “higher” brain functions based on comparative neuroanatomy have been challenged when considering whether fish feel pain (Rose 2002). Furthermore, as imaging techniques have improved it is becoming clear that even among mammals there are differences between primates and nonprimates in the brain pathways involved in processing information from nociceptors (e.g., Craig 2002). Thus investigators should not underestimate the difficulty in identifying functionally analogous pathways in invertebrates with fundamentally differently organized central nervous systems. It is worth recalling that until the late 1980s there was a common view that human neonates did not feel pain (Fitzgerald and McIntosh 1989).

Molecular, neurophysiological, and behavioral studies have provided evidence for responses to noxious mechanical stimuli in the hermit anemone (Calliactis parasitica) and the California sea slug and to noxious mechanical, thermal (heat), and chemical stimuli in the medicinal leech (Hirudo medicinalis), D. melanogaster, and C. elegans (St. John Smith and Lewin 2009 for review).

Behavioral studies provide important insights into the question of pain perception, but knowledge of the way information is processed is important and, together with molecular and physiological (biomarkers of stress such as heart rate, endocrine, and metabolic changes) studies, will be key to identifying endogenous pathways capable of modulating nociception, the transmitters of which provide targets for analgesics (e.g., opioids, cannabinoids, steroids).

Anesthetic and analgesic techniques for invertebrates are relatively poorly developed in contrast to those for vertebrates (and especially mammals), although as Cooper (2011) points out there may be more information in the world literature and a systematic approach is needed for collecting, assessing, and applying that information. There is certainly a need for some consensus on criteria for general (surgical) anesthesia in all invertebrates used in the laboratory and for decapod crustacea and molluscs in particular. Anesthesia has been used only for short-duration manipulation or surgical interventions. Techniques for sustained general anesthesia and maintenance of physiological systems would permit in vivo neurophysiological or functional brain imaging studies, and the lack of such methods limits knowledge of the central processing of nociceptive inputs, especially in cephalopods. [3]

Finally, although pain (usually assumed to be cutaneous) is perhaps the most common focus from a welfare perspective, animals are susceptible to numerous other unpleasant experiences such as anxiety, asphyxia, dyspnoea, fear, headache, itching, and photophobia. Researchers, animal care staff, and IACUC members should be mindful of all such stressors in considering the welfare of invertebrates in the laboratory.

Attitudes and Their Influence on Regulation and Oversight

“Slugs Displace Bunnies in the Lab” (Davis 2002). This headline accompanied a news article reporting the possibility of replacing the Draize test using rabbits with an irritancy test measuring defensive secretions from slug skin. Although many would view this as a positive development, a spokesman for the British Union for the Abolition of Vivisection is quoted as calling the use of any animal “morally unacceptable” (Davis 2002). This example illustrates the difficulty not only in making judgments about the use of animal in research but also particularly in determining the “relative positions” of vertebrates and invertebrates. This is a complex area and Mather (2011) tackles it by considering the philosophical basis for attitudes toward invertebrates. She describes the contractarian, utilitarian, and rights-based approaches, using diverse examples ranging from the treatment of invertebrates in the kitchen, commercial fisheries, public aquariums, and the laboratory. She accords decapod crustacea and cephalopods special consideration (as is the case in several other articles in this special issue). Mather (2011) concludes that “as invertebrates are better understood, people—whatever their value system—will come to appreciate and take better care of them.”

It is to be hoped that greater understanding will translate to the laboratory and this is likely to be facilitated by ethical review and regulatory frameworks, which are reviewed in the final article, by Harvey-Clark (2011). He presents two IACUC case studies that clearly reveal the particular challenges of research using invertebrates and then provides a useful resource to engage researchers and regulators in confronting some of the key issues.

Where Next?

Scientific journals have a key role to play in encouraging adoption of best practice in the welfare of animals used in research by ensuring that experiments on invertebrates are properly reported. The recently published “ARRIVE” guidelines for reporting animal research (Animal Research: Reporting In Vivo Experiments Kilkenny et al. 2010, www.nc3rs.org.uk/ARRIVE) provide a clear list of the essential elements that need to be reported for in vivo experiments and, although primarily aimed at studies in vertebrates, can be readily adapted for use in invertebrates (especially decapod crustacea and cephalopods). Comprehensive reporting of methodological aspects is important to enable assessment of welfare and facilitate the systematic gathering of information on ethics, experimental design, housing, husbandry, and adverse events induced by experimental procedures. Many of these aspects are considered in the following articles and especially that by Harvey-Clark (2011).

There seems to be some agreement that in laboratory procedures involving invertebrates in general, and decapod crustacea and cephalopods in particular, the “precautionary principle” should operate at least until there is definitive evidence of their ability to suffer, recognizing that pain may be only one component of suffering. The agreed special position of cephalopods (particularly octopuses and cuttlefish) is already reflected in some national legislation (e.g., Canada). In the European Union it is likely that over the next 2 years such legislation will spur research to address a range of issues—from optimal anesthetic and handling protocols to recognition of signs of pain and distress analogous to those developed for mammals (e.g., Morton and Griffiths 1985)—as cephalopods, at least, will have the same legal protection as is afforded to vertebrates.

Understanding the functioning of phylogenetically ancient brains in highly evolved animals with a fundamentally different organization (at least anatomically) from vertebrates represents a major intellectual challenge and may also prompt reconsideration of some prevailing ideas of consciousness (see Edelman and Seth 2009 for discussion).

[ 1 ]Available online (http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2010:276:0033:0079:EN:PDF) this and other websites cited in this Introduction were accessed between February 22 and April 11, 2011.

[ 2 ]Information about these Nobel Prizes is available online at http://nobelprize.org/nobel_prizes/medicine/laureates.

[ 3 ]In the European Union it is likely that the forthcoming legislation will drive the development of a consensus view on many of these aspects for cephalopods.

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Research redefines proteins' role in the development of spinal sensory cells

IMAGE: Increasing the concentration of a certain type of BMP increases the production of the same categories of sensory interneurons (red and green). Left: no BMP added center: 1x BMP added. view more

Credit: UCLA Broad Stem Cell Research Center/eLife

A recent study led by Samantha Butler at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA has overturned a common belief about how a certain class of proteins in the spinal cord regulate the formation of nervous system cells -- called neurons -- during embryonic development. These findings could one day inform the creation of stem cell-based therapies that restore the sense of touch in paralyzed patients.

The study was published in the journal eLife, which was founded in part by the Howard Hughes Medical Institute.

Bone morphogenetic proteins -- also known as BMPs--play a key role in human development. These proteins, known as growth factors, are signals that stimulate cellular functions such as growth, proliferation, healing and differentiation. In the developing human spinal cord, BMPs are required for the formation of neurons.

Butler's study focused on a class of neurons called sensory interneurons. Sensory interneurons allow a person to react to the environment, such as flinching from pain stimulus, feeling comforted by a reassuring squeeze from a loved one or being able to hold a cup of coffee without thinking about it.

The lack of the sense of touch greatly impacts paralyzed patients. For example, people with paralysis often cannot feel the touch of another person and the inability to feel pain could result in burns from inadvertent contact with a hot surface.

"The understanding of sensory interneuron development has lagged far behind that of another class of neurons--called motor neurons--which control the body's ability to move," said Butler, associate professor of neurobiology, member of the UCLA Broad Stem Cell Research Center and senior author of the study. "This lack in understanding belies the importance of sensation: it is at the core of human experience. Some patients faced with the reality of paralysis place the recovery of the sense of touch above movement."

Previous research had suggested that different concentrations of BMPs correlated with the formation of different categories of sensory interneurons. It was thought that a lower concentration of BMPs would result in one category of sensory interneuron, whereas a higher concentration would result in a different category. Butler's research has found no evidence to support this model.

The research team first manipulated the concentration of BMPs in the spinal cord of a chicken embryo. They found that a specific type of BMP always produces specific categories of sensory interneurons, regardless of the concentration of the BMP. The team found that increasing the concentration of a certain type of BMP will make more of the same kinds of sensory interneuron, but will not create a completely different category of sensory interneuron.

The team then applied these findings to mouse embryonic stem cells in lab dishes. They found that by adding specific types of BMPs, they were able to push the stem cells to create two different categories of spinal sensory interneurons. The types of spinal sensory interneurons created control the sensation of the position of body in space -- called proprioception--as well as body movements that are activated by touch, such as flinching away from a hot surface.

"Central nervous system injuries and diseases are particularly devastating because the brain and spinal cord are unable to regenerate," said Madeline Andrews, a predoctoral student in Butler's lab during the time of this research and first author of the study. "Replacing damaged tissue with sensory interneurons derived from stem cells is a promising therapeutic strategy. Our research, which provides key insights into how sensory interneurons naturally develop, gets us one step closer to that goal."

Butler's team now plans to apply their findings to human stem cells as well as drug testing platforms that target diseased sensory interneurons. They also hope to investigate the feasibility of using sensory interneurons in cellular replacement therapies that may one day restore sensation to paralyzed patients.

The research was supported by a National Institute of Child Health and Human Development T32 training grant (HD060549) in developmental biology, stem cells and regeneration, the California Institute for Regenerative Medicine (RB5-07320) and its Bridges to Research program (TB1-01183), the National Institute of Neurological Disorders and Stroke (NS085097) and a UCLA Broad Stem Cell Research Center-Rose Hills Foundation Training Award.

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