Monthly Archives: March 2017

Research Roundup: Red blood cell production in the lungs, sea urchin spines to fix bones, and trying to reverse aging in mice

Welcome to our fourth weekly roundup (now called “Research Roundup”). These Friday posts aim to inform our readers about the many stories that relate to animal research each week. Do you have an animal research story we should include in next week’s Research Roundup? You can send it to us via  or through the fake id 18 on the website.

  • A  finds that most of our blood cells are made in the lungs, not bone marrow. Using genetically modified mice that expressed a (GFP) and , scientists were able to track blood platelets as they circulated around the body in real time. Surprisingly, they found a large population of , responsible for the production of blood cells, in the lungs. This population of megakaryocytes was found to produce upwards of 10 million platelets per hour — at least half of the body’s total platelet production. Further experiments, found another population of megakaryocytes just outside the lung tissue — about 1 million per lung. Additionally, using mice with no stem cells in the bone marrow (eliminating blood cell production there), they found that cells from the lungs migrated to and facilitated blood cell production in the bone marrow. Because of technological advances in genetic engineering and microscopy, this study challenged a decades-old assumption, central to the field of biology and medicine. This study will of course need to be replicated and assessment performed of whether these findings generalize to humans.

  • Sea urchin spines can be used to fix bones, to the second most performed transplant procedure, after blood. Current procedures involving transplants for bone defects lead to subsequent complications as, for example, when brittle synthetic compounds break, causing further inflammation. This study therefore investigated whether the rigid structure of sea urchin spines represent a superior alternative material to currently used products. Sea urchin spines were first soaked in for 30 min, and then rinsed in deionized water at 200C for 2 days in order to remove organic material, converting the spine to magnesium-substituted tricalcium phosphate (β-TCMP) scaffolds, while maintaining the rigidity of the original open-cell structures. When testing the material on rabbits and beagles, they found that bone cells and nutrients could flow through the pores and promote bone formation. They also found that the scaffold degraded easily as it was replaced by the new growth.

Image Credit:

  • found that a population of in the is implicated in the . Pavlovian conditioning is a cornerstone of Behavioral Psychology; although the implications for subsequent research investigating links to disorders such as addiction, compulsive behavior, and schizophrenia are probably understated. In the present study, researchers exposed mice to an odor — banana or lemon — followed by a reward of condensed milk. By repeatedly pairing the odor with the reward, mice learned that a certain odor predicted a particular reward. Similar to Pavlov’s earlier experiment, the anticipation of the reward upon presentation of odor also occurred — mice licked the air — analogous perhaps to how humans lick their lips in anticipation of, for example, ice-cream. To understand how the brain regulates this response, these researchers focused on the striatum as this area has previously been associated with reward and decision making. Using and , the researchers “turned-off” a tiny group of cells that support the principal neurons in the striatum. Predictably, mice with these cells turned-off only licked the air in anticipation of milk only half as often compared to baseline levels. This difference was most pronounced in mice that were first learning the odour-reward pairing and less pronounced in mice that had learned the pairing — suggesting that these cells are involved in the encoding of the Pavlovian response. This research may have further implications for other disorders as dysfunction of this group of neurons is also implicated in Huntington’s disease, Parkinson’s disease, and Tourette’s syndrome.

  • Researchers target senescent cells, cells involved in aging, to reverse the signs of aging in mice. “This is the first time that somebody has shown that you can get rid of senescent cells without having any obvious side effects.” says cell and molecular biologist Francis Rodier of the University of Montreal in Canada. Dr. Rodier was not connected to the study.  The cells also share some properties with cancer cells.  Researchers hope to explore applications that could lead to treatments for cancer as well as age-related diseases.

The mice needed for the study are genetically predisposed to faster aging allowing researchers to evaluate their new molecule. Here we see old mice which are less active and have hair loss. Humane endpoints are especially important in these types of studies.to ensure animals do not experience unnecessary discomfort. Image Credit:

  • found to alleviate symptoms associated with Type 2 diabetes (insulin resistance) in mice. affects 29.1 million Americans (9.3% of the population) with 1.4 million new diagnoses annually. It is the 7th leading cause of death in the USA and 90% of all cases of diabetes are of the Management of Type 2 diabetes usually involves diet management and exercise, although may be used to bring glucose levels under control. Therefore, treatments that permit an individual to gain control of their life or to limit the symptoms associated with this disease are wanting. In the present study, scientists investigated the role of low-molecular-weight protein tyrosine phosphatase (LMPTP), in vivo for the first time. Using genetically modified mice that lacked LMPTP in the whole body and specifically in the liver, they found that LMPTP is associated with the development of Type 2 diabetes — improved glucose tolerance and reduced fasting insulin levels. They next developed, in vitro, a molecule inhibitor which preferentially binds to the receptor for LMPTP — blocking its action in the body. Testing this molecule, in mice, they again similar results to the experiment where the gene for LMPTP was removed (knocked out) — improved glucose tolerance and decreased fasting insulin levels. This study provided the first evidence of the signaling role of LMPTP in regards to Type 2 diabetes — and with subsequent replication and further testing may signal new hope for the millions of individuals that suffer from Type 2 diabetes.
  • The University of Cambridge has produced a about how its researchers are using animals (and people) to treat OCD – a that can have debilitating effects. The tracks science journalist and OCD-sufferer, David Adam, as he goes into the research labs at Cambridge and speaks to experts working with rats, monkeys and people. The video shows animal experiments being conducted, explaining why they are necessary. This is a great example of openness by the University of Cambridge. See other examples of videos being produced by labs.

Jeremy Bailoo

Cameras in the lab: Animal research visualised

There are many misconceptions about animal research and the welfare standards that exist in labs. Old footage and pictures, or imagery from countries with lower standards of welfare, are spread across the internet, but unless people see a lab for themselves it is hard to dissuade them of these preconceptions.

The best way to show people to the truth is to invite them into the lab and let them see for themselves. are often amazed by the high standards of welfare that exist and even activists can often be persuaded that their perspective may have been misinformed. However, it is not possible to allow everyone to tour round labs – it would be disruptive to both the people and the animals, and science would potentially suffer.

Therefore another way to show people is to film it. A number of UK universities have brought out videos in the last few years (or in several cases the last few months), showing some of the amazing scientific work they are doing and how animals are a part of it. In this post we provide a few examples.

The University of Cambridge – Animal research into OCD

Just this week, Cambridge released  about how they are using rats, marmosets, and people to better understand Obsessive Compulsive Disorder (OCD) – a condition which can be debilitating for those with severe cases. Science journalist and OCD sufferer, David Adam, visits the University and labs to speak to some of the leading scientists about their use of animals.

Queen Mary University of London – Animal research across the university

QMUL shows images across the labs, talking to scientists about both their research and how animal welfare is maintained. There is a full discussion of how QMUL uses the 3Rs to improve both the science and welfare at the university.

Imperial College London – Welfare at their animal facilities

Imperial wanted to introduce the staff who care for the animals and give them a chance to talk about the important job they do to maintain and improve standards of welfare. The video includes rats and rabbits and discusses some of the regulations that exist in the UK.

University of Cambridge – Animal research and cancer

Another video from the University of Cambridge – this time specifically looking at how the university uses animals (and why it needs to) in order to understand and treat cancer. They also look at how the institution is trying to find non-animal methods to do some research.

University of Oxford – Housing and care of animals

The University of Oxford produced a video which shows some of the features of their animal facility. The video includes footage of mice, rats, frogs, ferrets and macaque monkeys.

Research Roundup: Ending the vaccine-autism myth, spider venom for stroke victims, and causes of polycystic ovary syndrome

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

  • Studies on the relation between the are starting to build, ending the vaccine-autism . No vaccination has met the criteria of being a cause of autism – although increase the risk two to four times. Our understanding of many of these risk factors has been greatly increased with the help of animal research. For example, mouse research on the relation between maternal immune activation and autism-like phenotypes was later found to be consistent in human populations. Also, links to prenatal exposure to medications with teratogens were investigated in rats and found to be consistent with humans.
  • Spiders venom saves stroke victims: Funnel-web spiders are among the world’s deadliest spiders, . Since the venom targets the prey’s nervous system, researchers tested whether it could be harnessed to reverse brain damage after a stroke. After traveling to Fraser Island to collect three Darling Downs funnel-web spiders, researchers at University of Queensland and Monash University “milked” the spiders to collect their venom, then isolated a protein called Hi1a — a molecule that closely resembles another known for its protective effect on neurons. The team then synthesized their own version of Hi1a and gave the compound to rats two hours after an induced stroke. Neuron damage was . Eight hours after a stroke, it was still effective in restoring neurological and motor functions by almost 65 percent. The researchers hope to commence human clinical trials in the next few years, pending replication of these initial findings and further research into the molecule.

  • A has found that (PCOS) may start in the brain, not the ovaries, contrary to previous belief. While the cause of PCOS is unknown, one feature of this syndrome is high levels of . Using a high dose of androgens, PCOS was induced in genetically engineered mice which display a receptor for androgens in specific parts of the body (brain, ovaries, nowhere in the body and a normal control group). Mice with androgen receptors in the normal control group developed PCOS as expected, while those without receptors in the brain and in the entire body did not. Interestingly, mice without androgen receptors in the ovaries also developed PCOS albeit at a lower rate than the control group. These data replicate the finding that high levels of androgens are implicated in the development of PCOS. More importantly, they highlight that it may be the interaction of these androgen in the brain rather than the ovaries that lead to the development of PCOS. PCOS and this study, using mice, has provided valuable insight into the onset of this syndrome.

  • in mice that whole body vibration (WBV), a less intensive form of regular exercise, mimics the benefits derived from regular exercise. To investigate the benefits of WBV, scientists exposed normal mice and mice which don’t produce a receptor for (a hormone associated with the feeling of being full after eating) to no exercise, either daily treadmill exercise, or WBV for three months. They found that in the normal mice and the leptin-deficient mice, WBV and exercise, affected mice in a similar way — reduced body weight, enhanced muscle mass, and insulin sensitivity compared to mice that were sedentary (no exercise group). This research, using mice, suggests that WBV may be useful as a supplemental therapy for individuals suffering from or and where regular exercise is not an option.
  • Researchers have created a that was able to fully oxygenate the blood of sheep . , at the University of Pittsburgh, has subsequently said the device has been used successfully on sheep for five days. The device had to combine a pump and gas exchange while remaining small enough to be carried. Even smaller devices have been developed to , using ultrathin tubing, just 20 micrometers in diameter. Such technologies could allow people with lung failure to continue with many of their daily activities, rather than becoming bed-ridden and attached to today’s artificial lung machines.

Image Credit: William Federspiel

  • A funded by the explores how different handling methods affected behavior in cognitive tasks. Tail handling is still one of the more common methods of handling mice in the laboratory that alternative methods such as cupped or tunnel handling may be less stressful for the animal. The researchers compared how mice reacted to new stimuli after being transferred into the testing area via a tunnel or being picked up by the tail. Because being picked up by the tail may be stressful for mice, tests which involve exploration may be affected by tail handling – as one consequence of stress in mice is freezing behavior (staying immobile). They found that the tunnel handling facilitated greater exploratory behavior, indicating that the simple process of tail handling may confound behavioral measures relating to anxiety. like this can help to understand the needs of animals in research labs, with the aim of improving animal welfare and the replicability of experimental results.

Image Credit: Jane Hurst, University of Liverpool.

Speaking of Research

fake id florida law

  • A study funded by the NC3Rs explored how handling methods influenced mice’s behavior during cognitive tasks
  • Mice were either picked up by the tail or guided into a tunnel, then transferred to the testing arena
  • Mice that were transferred in the tunnel were far more exploratory during the cognitive task
  • Acclimation to handling procedures is important

A published today in Scientific Reports shows that the way experimenters pick up mice can affect their behavior during cognitive tasks. The study was funded by the NC3Rs, which is dedicated to replacing, refining, and reducing the use of animals in research and testing. This particular study focused on refinement: identifying optimal handling methods for mice has important implications for both the welfare of the animals and the validity and usability of data that are collected, which could potentially lead to a reduction in the need for animals in future studies.

Image Credit: Jane Hurst, University of Liverpool.

Drs. Kelly Gouveia and Jane Hurst first placed laboratory mice near a new, attractive stimulus – urine from a novel mouse of the opposite sex – that is known to stimulate approach and investigation. The mice were allowed three sessions to grow accustomed to the new scent. Throughout all three sessions, mice were either picked up by the tail (standard laboratory practice, though there is no obvious scientific reasoning for this method) or were guided into a clear tunnel that is both affordable and easily sterilized. (The method is also .) Mice were then carried to the test arena either by the tail or in the tunnel and allowed to explore. Gouveia and Hurst report that mice picked up by the tail showed very little willingness to explore the test arena, and therefore investigate the new stimulus, whereas those transported in the tunnel showed much higher exploration and a strong interest in the new scent.

Importantly, Gouveia and Hurst then tested the mice’s ability to discriminate between the (formerly) new scent and a second, different urine stimulus. They report that since the mice picked up by the tail performed so poorly from the start, they did not discriminate between the two scents. However, those transported in the tunnel showed robust and reliable discrimination. These findings are noteworthy not only with respect to the psychological welfare of the animals, but also for the important effects that handling and habituation have on yielding usable, reliable data. With the potential to reduce the stress associated with handling, the tunnel method could reduce the anxiety that mice display upon tail handling – thereby resulting in more species-typical behaviors, such as exploration of a novel, conspecific scent. It could also reduce the uncontrolled variation that in and could ultimately produce more reliable data. Thus, identifying optimal handling techniques has the potential to reduce the number of animals needed in laboratory studies in addition to refining the techniques used to study them and enhance their welfare.

Image Credit: Jane Hurst, University of Liverpool.

It is worth noting that a by Novak and colleagues (2015) found no difference in cognitive performance between mice that were handled by the tail or by a less invasive method (“cupping” in the experimenter’s hands). Why might no difference have been found in this study? One possibility is that the cognitive task the researchers used was different from the present study (a radial arm maze vs. novel scent), and the arm maze may probe for different behaviors than a novel odor task. Another possibility is that perhaps mice “prefer” the tunnel to both tail handling and cupping, but neither the 2015 nor the present study compared all three methods. Hurst and her colleague Rebecca West did compare all three methods in a , however, and found that mice preferred both the tunnel and cupping method to tail handling (as assessed by voluntary interaction time with the experimenter); although the cupping method produced more variable results depending on strain and sex. However, in the Novak study, mice were handled daily for many weeks, whereas in the Hurst & West study they were handled only for nine days. Of course, the most parsimonious explanation is that in every handling study, experimenter interaction is confounded with handling. That is, are the mice acclimating to the experimenters, to the handling procedures, or both?

These questions underscore the need for replication before firm conclusions about optimal handling techniques can be drawn. Nevertheless, the findings published today in Scientific Reports are an important addition to the field of animal welfare, and they emphasize the importance of constant, rigorous studies surrounding welfare issues.

Amanda Dettmer

References:

Gouveia K, Hurst JL (2017) Optimising reliability of mouse performance in behavioural testing: the major role of non-aversive handling. Scientific Reports 7: 44999. doi: 10.1038/srep44999

Hurst JL, West RS (2010) Taming anxiety in laboratory mice. Nature Methods. Oct;7(10): 825-6

Novak J, Bailoo JD, Melotti L, Rommen J, Würbel H (2015) An Exploration Based Cognitive Bias Test for Mice: Effects of Handling Method and Stereotypic Behaviour. PLoS ONE 10(7): e0130718. doi:10.1371/journal.pone.0130718

Research Roundup: Ebola vaccine hope for apes, gene therapy for dogs, and research into stroke

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

  • The for Ebola developed for the conservation of wild apes, has completed its first and final biomedical research trial for the foreseeable future. The study, , shows that the vaccine was effective and did not induce health complications or lead to signs of stress in the apes. Lead investigator, “In an ideal world, there would be no need for captive chimpanzees. But this is not an ideal world. It is a world where diseases such as Ebola, along with rampant commercial poaching and habitat loss, are major contributors to rapidly declining wild ape populations.Oral vaccines offer a real opportunity to slow this decline. The major ethical debt we owe is not to a few captive animals, but to the survival of an entire species we are destroying in the wild: our closest relatives.

One of the captive chimpanzees in the research trial receiving the oral Ebola vaccination. Credit: Matthias Schnell, Thomas Jefferson University.

  • A new compound, , brain cell death and to promote new cell growth in a rat model-fake id toronto of ischemic stroke. Nearly 87% of all strokes are ischemic strokes.  130,000 Americans yearly, with someone in the USA having a stroke every 40 seconds and with a death occurring every 4 minutes.
  • A new gene therapy, which aims to treat the fatal muscle-wasting disease, myotubular myopathy or MTM, . Like humans, dogs naturally get this disease as a result of a genetic defect which tends to lead to breathing difficulty and early death. One year after a single gene therapy treatment, the dogs with the condition were indistinguishable from the control group. This offers huge promise for future human therapies for MTM. Results were published in .

Image from

  • A have two autoimmune diseases, multiple sclerosis (MS) and type 1 diabetes, in early stage mouse models. Autoimmune diseases affect an estimated 23 million Americans, and this research using mice highlights the importance of animal research in alleviating these debilitating diseases.
  • A new study finds that Lactobacillus, a common bacteria found in yogurt, to alleviate symptoms associated with depression in mice – providing hope for the 7% of the population that experience a major depressive episode at least once in their lifetime. The study was published in .

Image by Understanding Animal Research.

  • Canadian animal rights group, Last Chance for Animals, has alleged mistreatment of animals at the Contract Research Organisation, ITR Laboratories. The footage was included in a . In response to the infiltration video, ITR Labs saying they had parted ways with a number of technicians seen inappropriately handling animals in the footage. The Canadian Council of Animal Care also explaining that an inspection of the ITR facilities was now being organized.

300 Voices Speaking out For Research

Speaking of Research has worked hard at collating the animal research statements of hundreds of institutions – that list has now reached 300 institutions spanning eleven countries.

We still need your help to complete list – please check that your institution is on there. We are looking for a web page which clearly states that the institution conducts animal studies (and preferably explains why this is important). Submit your institution through our web form.

The excellent animal research pages of the pharmaceutical, Bayer.

We urge institutions to ensure they have an update to date statement which includes a strong explanation of how and why they conduct animal research, as well as the steps they take to maintain and improve animal welfare. Such information can be bolstered by case studies, statistics, images and videos. So far, only 23 (of 300) institutions have achieved full marks when we’ve rated the information available. See the full list at the bottom.

One thing that becomes apparent is that those institutions scoring highly have created a visible, and easily accessible, section of their website – usually with an easy-to-find URL such as (for UK institutions “.edu” is replaced with “.ac.uk”).

  • institution.edu/animal-research
  • institution.edu/research/animal-research
  • institution.edu/research/using-animals-in-research
  • animalcare.institution.edu
  • animalresearch.institution.edu

URL’s like these not only allow the link to be found (usually through a couple of clicks) easily from the homepage, but they also help when Googling for such information. Institutions try googling “institution animal research” and see what comes up – if your institution does not provide much information, will animal rights groups fill the vacuum?

An infographic from the University of Gronigen’s (NL) Annual Report on animal research

Speaking of Research do not believe there is any excuse for open communication about animal research online. The UK has been leading the way here (over half of the statements receiving full marks are from the UK), in part due to the Concordat on Openness – which most animal research institutions have signed up to – demanding such a statement to be drawn up.

Speaking of Research are willing to work with any institution that wants to improve its web content. We are happy to make recommendations and review drafts (for free). 

The 23 institutions receiving full marks are:

  •  [International]
  •  [UK]
  • () [Germany]
  •  [UK]
  •  [Germany]
  •  [Germany]
  •  [UK]
  •  [US]
  •  [US]
  • Speaking of Research [International]
  •  [UK]
  •  [UK]
  •  [UK]
  •  [UK]
  •  [UK]
  • [Netherlands]
  •  [UK]
  •  [US]
  •  [UK]
  •  [UK]
  •  [UK]
  • () [Netherlands]
  •  [US]

The University of Sheffield website got a 4/4 rating for its information

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

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

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

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

The father of organ transplantation, Thomas Starzl.

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

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

Tasmanian devils under threat

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

Check back next Friday for another weekly roundup.

Jeremy Bailoo and Justin Varholick