Monthly Archives: June 2017

Research Roundup: Heart regeneration, understanding of organ rejection, the saliva of ticks and more

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

  • An understanding of the genetics that allow sea anemone to regenerate their heart could one day help human patients. Sea anemones are quite unique when compared to typical vertebrates (e.g. humans) — for example, they have genes that can produce heart cells even though they themselves do not have a heart. The also have the capacity to to regenerate where, for example, if an anemone is cut into pieces, each piece will regenerate into a new anemone. When analyzing the relationship between this regeneration capability and the functioning  of the “heart genes” in sea anemones, scientists at the University of Florida discovered that the genes interact with one another differently than human “heart genes”. Heart genes in humans have what are called lockdown loops, which tell the heart genes to turn on and stay on for the entire lifetime of the animal. Sea anemones do not have these lockdown loops, which allows them to turn cells with heart genes into any other kind of cell for regeneration. By further investigating the evolution of lockdown loops for sea anemone to vertebrates, scientists may be able to better understand possibilities for regeneration in vertebrates, who do not currently regenerate tissue — many lizards can regenerate tails, which is another line of research in this field.  This study is a perfect example on how basic research in organisms completely different from humans may one day have large reaching effects on human health. This study was published in the journal Proceedings of the National Academy of Sciences.

Image courtesy of Whitney Lab for Marine Bioscience

  • Earliest molecular events leading to organ rejection identified in mice. Organ rejection remains a problem for transplant recipients — approximately 50% of all transplanted organs are rejected within 10 to 12 years. While methods are available to reduce the risk of organ rejection — such as immunosuppressant drugs — understanding the early molecular steps via which the body identifies cells as “non-self” provides important insight to reduce such risk. Fadi Lakkis, M.D., a senior co-author and scientific director of University of Pittsburgh’s  Thomas E. Starzl Transplantation Institute (STI) says, “For the first time, we have an insight into the earliest steps that start the rejection response.” The team hopes that  manipulating these earliest steps will disrupt the rejection process eliminating or minimizing transplantation failures. The study was a collaborative effort between researchers at the University of Pittsburgh, the Hospital of Sick Kids, the University of Toronto and Kobe University.  Using mice, they identified that a molecule called SIRP-alpha leads to the innate immune system activation and response, and that this molecule differs between non related individuals. In particular, when foreign tissue is transplanted, the SIRP-alpha of this new tissue binds to a receptor called CD47 in the host. This binding is what triggers the activation of the immune system leading to the rejection process. Both humans and mice express SIRP-alpha. Researchers say that sequencing this gene to identify potential donors and recipients may lead to lower organ rejection rates.  They also found that blocking the binding of SIRP-alpha and CD47 prevented the activation which may be used to find new ways to prevent organ rejection for patients that are not an exact match. This research was published in the journal Science Immunology.
knockout mice, animal research, animal rights

Laboratory mice (image courtesy of NIH)

  • Insight into how humans developed their daytime vision comes from research on chick embryos.  Humans — along with other primates, various fish, reptiles, and birds — have a small spot in the center of their retina that allows them to have sharp vision in the daylight. Although, researchers have long acknowledged the existence of this spot, little has been known about the development of this sharp vision spot, known as the fovea, in humans. Researchers at Harvard Medical School recently investigated the development of this sharp vision spot in chickens, and found that growth factors involved in such development are regulated by enzymes that degrade retinoic acid, a derivative of Vitamin A, that plays important roles in embryonic development. Such pioneering work on the development of structures involved in having sharp vision (e.g. fovea) may help scientists to one day combat medical conditions involved with losing sharp vision (e.g. macular degeneration).
  • A protein found in the saliva of ticks could help treat Myocarditis, according to researchers at the University of Oxford. Ticks are often able to feed on their hosts for over a week thanks to proteins in the saliva, called evasins, which prevent inflammation by binding to and neutralizing chemicals called chemokines. These chemokines also cause inflammation in myocarditis, heart attack and stroke. The scientists were able to grow tick saliva in yeast, using synthetic genes, thereby avoiding needing to individually milk ticks for their saliva. This study was published in Scientific Reports and was funded by the British Heart Foundation.

  • Transcranial stimulation and/or physical therapy improves walking speed in Parkinson’s disease. Parkinson’s disease is a debilitating movement related disorder that affects approximately 10 million people worldwide. In America alone, this translates into a combined cost of approximately 25 billion dollars a year. Like many diseases with such a high prevalence, research is focused on two key aspects — understanding the etiology and the development of effective treatments of the disorder. Animal models, in mice, primates and other mammals, are integral in making progress in both aspects. For example, transcranial stimulation as a proof of  principle owes much to animal models – both in terms of its development and in relation to its evaluation of efficacy. Here, we see a good example of how basic research in animal models leads to improved quality of life due to a debilitating disease. In humans, these researchers found that noninvasive brain stimulation and physical therapy — alone or in combination — improve some measures of walking ability in patients with Parkinson’s disease. This study was published in the American Journal of Physical Medicine & Rehabilitation.

Doors Open: Explaining animal research at the University of Ottawa

Every June, the city of Ottawa, Ontario, Canada holds a “Doors Open” event, as part of a larger province-wide initiative to open facilities such as museums, hospitals, and historical sites to the community in ways which aren’t part of their everyday operations. The Brain and Mind Research Institute at the University of Ottawa opened its labs to the public, offering tours and displays describing the work they do, including their animal research. The University’s Animal Care and Veterinary Service (ACVS) and Animal Ethics & Compliance (AEC) office also participated, with family-friendly informational displays and activities.

The director of the University’s Brain and Mind Research Institute, Dr. David Park, hosted the event this year, as the Faculty of Medicine felt it would be a great way to highlight the leading edge research done at the University. Dr. Diane Lagace, a researcher in the department, demonstrated the preclinical work she is involved with in her lab, using rats and mice in stroke research. Dr Lagace also studies how adult-generated stem cells play a part in how we can recover from strokes.

Displays featured information about animal use at the university, and research-related activities for children. Photo credit: Hilalion (San) Ahn

The animal care displays were run by the ACVS and AEC. Their displays included enriched caging for rats, enrichment devices and treats for the research animals, as well as a demo for children on how to use microchips to identify some species. Volunteers provided the public with informational pamphlets and explanations on the university’s animal care and use program, as well as the regulatory framework that protects animals used in research.

Dr. Holly Orlando, University Veterinarian and Director of ACVS, wanted her department to take part because she felt that it is important to be transparent about the work that we do with animals in science. By doing so, her department could help to clarify misconceptions that the public may have about work with animals, as well as helping to develop engagement with the community. Marie Bédard, the AEC Director, agrees and has been developing materials for the public and explaining the regulatory frameworks for animal use in science.

I also took part, as the Registered Veterinary Technician who manages the zebrafish operations at the University. I brought live zebrafish larvae at various points of development for visitors to observe under microscopes. I also brought examples of what we feed the fish, and how we house them.

Zebrafish larvae on display. Photo credit: Hilalion (San) Ahn.

The facility tours were very popular, with guests able to observe the work of the Animal Behaviour Core facility, which utilizes procedures such as a water maze, climbing, treadmill and other exercise tests to study both how brain deficits occur and can be repaired after a stroke, as well as when and what forms of exercise are helpful for stroke recovery. Guests also observed a Parkinson’s Disease model in fruit flies, which helps researchers to better understand the genetics and other causes behind Parkinson’s disease.

Over 250 people registered for the event and went on tours of the facility. Feedback was very positive, and the public had very thoughtful questions about the operations of both the labs and the animal facility. People were overheard stating that they “never would have imagined that this is happening here in Ottawa”, and more than one youngster exclaimed that they wanted to work with us.

The Director of Animal Ethics and Compliance, discusses enriched rat caging. Photo credit: Hilalion (San) Ahn

This one day event was a great step forward in openness with regards to animal research at the University. A great team did a fantastic job organizing and running the day, which seemed to go off without a hitch. I am looking forward to attending again next year, with an even bigger display!

Christine Archer

Asthma and Animal Research: A Public Health Perspective

As a public health researcher with a focus on behavior change and complex interventions, I am more interested in studying how to get children to adhere to their asthma medication regimen rather than the mechanisms of inflammatory asthma. I am currently studying the risk factors associated with asthma attacks in children, which include among others, sub-optimal medication use, poverty, and access to healthcare. The aim of this research is to understand what risk factors for severe exacerbations – such as asthma attacks that send children to the emergency room – exist, thereby enabling healthcare and public health professionals to mitigate the risks of these ‘at-risk’ children.

My interests have nearly always been in applied in nature, however I understand that basic research underpins everything thing that we do in public health. Animal research is foundational to what we do as public health professionals. Without animal research, we would not be able to mitigate the risk factors these children have as we would not have the asthma medications we do today.

It seems that the sphere of public health shies away from discussing and supporting animal research; I’ve had colleagues tell me to be careful of talking too openly about my experiences in animal research outreach, for fear of alienating others – and potentially hindering my career. However, I strongly believe that public health professionals should be more open to discussing and supporting animal research. It is imperative to the continuation of both public health research and its application.

To illustrate this point, let’s use asthma as an example. The most effective medications for managing asthma are aptly named preventer and reliever medications. Preventer medications contain glucocorticosteriods and they work to prevent symptoms by reducing swelling, sensitivity, and inflammation in the airways. On the other hand, Reliever medications, or bronchodilators, work to open the airways and rapidly relieve symptoms.

Animal research has played an important role in the discovery of both glucocorticosteriods and bronchodilators. Glucocorticosteriods were developed using mouse models and the derived biomedical pathways. Bronchodilators were developed the 1960s, as a result of Otto Loewi’s research on adrenaline and other neurotransmitters.  Loewi used two beating frog hearts, aligned near each other, to demonstrated that slowing the pulse of the one heart and then circulating that perfusate through the other heart that it caused the other unaltered heart to also slow. He found that the same was true when he repeated the experiment, this time increasing the heart rate. This discovery proved that nerve cell communication is chemical rather than electrical, which led to the discovery of the neurotransmitter acetylcholine, and provided the foundation for future neurotransmitter research.

Glucocorticosteroids were developed using mouse models.

In relation to asthma, bronchodilators (beta2 agonists in particular) mimic the sympathetic nervous system discovered through Loewi’s famous experiment and allow health professionals to synthetically relieve the symptoms of asthma. Other studies using mice models have also elucidated the biomolecular mechanisms of airway hyperresponsiveness in asthma. Without Loewi’s initial experiment relying animal animal research, we would not be able to treat asthma as well as we do today. Without animal research, asthma management would likely rely on alternative medications that offer little in the way in relief; without effective treatment applied asthma research would focus only on prevention.

One of the reasons I was drawn towards public health and applied research was the focus on environmental, cultural, and large system-level factors that influence health, but this can come at the expense of ignoring the wealth of basic research that allows us to study these upper-level factors. When we forget the foundational work that lets us pursue our passions, everyone suffers. Public health professionals, at the very least, need to acknowledge–if not actively advocate for—the value animal research has in improving the health of the broader public and  should actively advocate for.

In writing this post, I had to research on how asthma medications came into being. Skimming through the biomedical literature was daunting (and confusing at times), but there are great resources already created to help clarify points for the those less familiar with biomedical research, such as myself – Understanding Animal Research, Animal Research.Info, and this website, Speaking of Research are great resources. I encourage public health professionals to educate themselves in how animal research allows them to do the work they do today. Then share that knowledge, – be that over Twitter, a blog, an email to colleagues, the options are endless. Support well-evidenced and humane animal research, because our work depends on it.

Audrey Buelo, M.P.H.

Research Roundup: Cholesterol vaccine in mice, zebrafish & osteoporosis, new cytomegalovirus treatment, and more!

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

  • Human trials of cholesterol-lowering vaccine are underway after success in mice. This vaccination is designed to stop fatty deposits from clogging arteries — reducing the effects of a form of cardiovascular diseases known as atherosclerosis. This vaccination targets a protein called PCSK9 that allows low density lipoprotein (LDL; “bad cholesterol”) to accumulate in the arteries. In mice, this treatment reduced LDL levels up to 50% over 12 months. This vaccination provides promise of a simpler way “to target high cholesterol and ultimately reduce people’s risk of heart disease.” An editorial on this research was published in the European Heart Journal.

Blocked arteries impede blood flow. Source: Getty.

  • Zebrafish, genetics and osteoporosis. The zebrafish’s ability to regenerate body parts, including scales and fins, has led to their involvement in the study of bone physiology and repair, as well as the identification of treatments for human bone diseases. Researchers at the University of Malta are working with zebrafish as a model to investigate osteoporosis, specifically the genetic factors that may contribute to the disease.  Dr Melissa Marie Formosa, a researcher involved in the project ‘Genetics of Osteoporosis’, writes, “The ultimate aim of genetic research remains that of elucidating the best treatment options based on the person’s genetic make-up and predicting disease outcome in susceptible individuals.”

Healthy bone, left, and osteoporosis, right. Source here.

  • An alternative explanation for loss of consciousness during anaesthesia was published this week in PLOS Computational Biology. Scientists typically speculate that when animals and humans are given anaesthesia, communication between brain areas is disrupted thus leading to loss of consciousness. Although such speculations have been previously tested and suggested to be true, the logic behind such speculation is questionable. Specifically, communication only seems to decrease when less information is available to exchange, thus loss of information should “reduce” rather than “disrupt” communication between brain areas. With these thoughts in mind, German neuroscientists measured brain activity in two ferrets over 3 trials of anaesthesia and recovery — increasing the amount of anaesthesia each time. Their measurements suggested that the ferrets’ brain activity was more subdued when anesthetized, but it didn’t seem communication was disrupted. Rather, the brain areas that send communication signals were less active, and the brain areas that receive communication signals were just as active as normal. This brings into question our current understanding of the mechanisms behind anaesthesia, and will be a starting point for future research in this area.

Lab-housed ferrets. Source: NC3Rs.

Image of mice courtesy of Understanding Animal Research

  • Drug used to treat anxiety found to be effective against the effects of cytomegalovirus (human herpes 5), which can cause major birth defects such as microcephaly, seizures, developmental disabilities, and deafness. Approximately 50% of all humans over the age of 40 harbour the cytomegalovirus and approximately four in 1000 babies suffer massive defects as a consequence. Mice treated during the first three weeks of life with valnoctamide — a drug used in the treatment of anxiety — were found to have reduced levels of the virus available for entry to the brain, to have restored timely acquisition of neurological milestones, and to display rescued motor and behavioral outcomes. Given the pervasiveness of this virus and its debilitating effects, and also that there is no vaccine against this virus, this work is extremely timely and promising. This study was published the Journal of Neuroscience.

Cytomegalovirus (CMV) virus. Source: J. Cavallini.

USDA publishes 2016 animal research statistics – 7% rise in animal use

The USDA/APHIS has published the 2016 animal research statistics. Overall, the number of animals (covered by the Animal Welfare Act) used in research in the US rose 6.9% from 767,622 (2015) to 820,812 (2016). This includes both public and private institutions.

These statistics do not include all animals as most mice, rats, and fish are not covered by the Animal Welfare Act – though they are still covered by other regulations that protect animal welfare. We also have not included the 137,444 animals which were kept in research facilities in 2016 but were not involved in any research studies.

CC-BY: speakingofresearch.com

Click to Enlarge

The statistics show that 52% of research is on guinea pigs, hamsters and rabbits, 10% is on farm animal species, while 11% is on dogs or cats and 9% on non-human primates. In the UK, where mice, rats, fish and birds are counted in the annual statistics, over 97% of research is on rodents, birds and fish. Across the EU, which measures animal use slightly differently, 93% of research is on species not counted under the Animal Welfare Act (AWA). If similar proportions were applied the US, the total number of vertebrates used in research in the US would be between 12 and 27 million, however, there are no published statistics to confirm this.

CC-BY: speakingofresearch.com

Comparing the 2015 and 2016 statistics there has been a small rise in the use of most species, apart from dogs (down 0.2%) and cats (down 5.2%). The largest rises were found in non-human primates (up 15%) and sheep (up 14%). Furthermore, it should be noted that this 6.9% rise comes a year after an 8% fall, putting the total number of animals used in 2016 slightly below the levels in 2014.

Animals used in researchand testing in the US 1973 - 2016

Trend in number of animals used in research in the US, 1973 – 2016 – Click to Enlarge

There has been a general downward trend in the number of animals used in the US over the past three decades; the number of animals used has more than halved (from 1.8million in 1986), with the use of dogs and cats down by over 65%. It is likely that a move towards using more genetically altered mice and fish has reduced the numbers of many other AWA-covered animals used. That said, non-human primates are one of the few species to have risen in use, from an average of 54,000 animals per year from 1977-2006, to 67,000 in 2007-2016.

In the UK, where mice, rats, fish and birds are counted in the annual statistics, over 97% of research is on rodents, birds and fish. Across the EU, which measures animal use slightly differently, 93% of research is on species not counted under the Animal Welfare Act. If similar proportions were applied the US, the total number of vertebrates used in research in the US would be between 12 and 27 million.

Rises and falls in the number of animals used reflects many factors including the level of biomedical activity in a country, trending areas of research, changes to legislations at home and abroad, outsourcing research to and from other countries, and new technologies (which may either replace animal studies or create reasons for new animal experiments).

The annual statistics are one example of openness and transparency in animal research, but the last few years have seen a greater number of institutions from all over the world publically acknowledging their animal research in statements on their website. This week, two separate openness initiatives were announced, with Americans for Medical Progress launching their “Come See Our World” website of free-to-use animal research images, and Understanding Animal Research promoting a 3D tour of four animal facilities in the UK.

Using the virtual tour you walk around real research facilities like this one at the University of Oxford.

On the subject of openness, it was disappointing that neither the USDA, nor APHIS decided to press release the figures when they were released on June 7th 2017, or even mention them in the website’s News and Announcements. The US could follow the past example of the UK, where the Home Office, in conjunction with the Science Media Centre, held a press conference each year to announce the annual statistics and to offer experts to explain and discuss the numbers.

Source of US Statistics:

Speaking of Research Coverage:

We will continue to bring you the latest national statistics as and when they are released.

Speaking of Research

Research Roundup: Pig cells for Parkinson’s Patients, Lab grown cartilage and more

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

  • Brain cells from Pigs have been implanted into Parkinson’s patients in hopes to stop the progression of the disease. Parkinson’s is a neurological disease in humans that causes tremors and difficulty moving, which usually worsens over time. Such dysfunction of the motor system is caused by gradual loss of brain cells that make dopamine. Current technologies synthetically replace dopamine in the brain, however, this is not always effective. Now, a new technology, developed by Living Cell Technologies, implants cells from the choroid plexus of pigs into humans with the aim of nourishing the remaining dopamine-producing cells. The approach was first successful in a rat model and non-human primate model of Parkinson’s disease and has now been done in 4 human Parkinson patients with promising results 18 months after implantation.
  • A new study suggests that the liver may grow and shrink by up to 40% every 24 hours in response to ribosomal activity.  Mammals, in general, consume food at certain times throughout the day (breakfast, lunch, and dinner), in a cyclical rhythm. After consuming this food, the liver plays a pivotal role in producing biochemicals necessary for digestion, regulating glycogen storage, and detoxifying byproducts of metabolism. Recent research, published in the journal Cell, investigated how the liver adapts to daily rhythms of eating using mice as a model of mammals. Their research showed that the mass of the liver, hepatocyte size, and protein levels follow a daily rhythm, that depends on feeding-fasting and light-dark cycles. A second experiment showed that daily rhythms of protein levels in the liver are correlated with daily rhythms in ribosome number. This fundamental research has implications for our general understanding of liver function, which may allow for future cures in liver disease and dysfunction.

  • Lab-grown cartilage has similar mechanical and biochemical properties to natural cartilage. Cartilage helps joints to move, but can easily be damaged by trauma, disease, or overuse. Once damaged, cartilage does not regrow and is often difficult to replace. Biomedical engineers have been developing artificial cartilage using human chondrocytes over the past several years to replace damaged cartilage. Now, researchers from the University of California Davis have tried a new method by growing the artificial cartilage under tension, which helped the cartilage grow stronger and now has similar properties of natural cartilage. The researchers then implanted cartilage into mice and found there were no negative interactions between the cartilage and the living mouse. The next step is to try the lab-grown cartilage on a load-bearing joint to see if it remains durable under stress.
  • Social stimuli may be an inadequate replacement for juice rewards for monkeys in behavioural neuroscience research. A study funded by the NC3Rs aimed to find out if images of other monkeys could be used to reward monkeys for participating in research, rather than traditional juice rewards — which often require fluid-restrictions to work. The researchers conducted the study in 4 rhesus macaques, and first confirmed that these monkeys preferred monkey images (a social stimuli) to nonsense control images. They then tested monkeys on a simple cognitive task, offering only juice reward, juice + social stimuli, or only social stimuli. In all monkeys the juice reward improved motivation, and only one monkey did the social stimuli improve motivation. The scientists concluded that this form of social stimuli might be ineffective, suggesting it may be because all monkeys are pair housed in socially stimulating environments. The study was published in PLOSone.

Macaques were used in the study. Image: Understanding Animal Research

 

  • 8 years of research culminate in a vaccination to fight heroin addiction. Approximately 9.2 million people in the world use heroin, some of which results in death due to heroin abuse — approximately 91 Americans die each day from overdosing on opioids. Using mice and rhesus macaque monkeys, researchers at the Scripps Research Institute developed a heroin conjugate vaccine which reduced the potency of heroin by 15 times in mice and 4 times in monkeys. The effects of these vaccinations persisted for over 8 months. This preclinical research brings us closer to an effective heroin vaccination for treating opioid use disorders. This study was published in the Journal of the American Chemical Society.

360 Virtual Lab Tour allows public to look round four British animal laboratories

Understanding Animal Research has worked with four institutions, MRC Harwell, The Pirbright Institute, the University of Bristol and the University of Oxford, to create a virtual ‘street view’ tour of their laboratories. Go to labanimaltour.org to view the tours for yourself.

VIEW THE LAB ANIMAL TOUR

Visitors are provided with maps of the four facilities, with viewable rooms labeled. The University of Bristol’s research facilities allow human and veterinary surgeons to work side by side on medical research that will benefit man and animals. The MRC Harwell Institute has thousands of mice strains to investigate what genes do and the relationship between genes and disease. The University of Oxford’s primate centre conducts research into how our brains work, and The Pirbright Institute creates vaccines that protect livestock from diseases such as foot-and-mouth and swine flu.

Labanimaltour.org allows you to travel around the University of Bristol’s animal facilities

Inside the room, the tour provides videos of researchers and technicians explaining more about how and why animal research is conducted. Viewers can turn and look around, find more information about things that they see, and watch videos which explain more about the research.

Using labanimaltour.org you can look round primate rooms in the University of Oxford. It also includes videos explaining how and why the primates are used in research.

The videos themselves offer a wealth of information about research on mice, cows, pigs and primates. See the video below about how the University of Oxford trains its primates. In total, over thirty scientists and technicians were filmed as part of the project explaining both the research that is done and the animal welfare considerations that are a key component of lab animal science

The Concordat on Openness on Animals Research, signed by all four institutions, was launched in 2014, and this virtual lab tour marks another success on its third anniversary. Other British institutions have also expressed interest in creating their own 360 lab tour. This launch comes days after Americans for Medical Progress launched their own openness initiative, “Come See Our World“, to show the public accurate images from the lab.

MRC Harwell is an International Centre for Mouse Genetics

The last few years have seen a wealth of new ideas on proactively explaining what goes on in animal labs. It is essential such initiatives continue if the research community is to convince the public that such research is done humanely, under strict regulations, for the benefits of society.

Speaking of Research