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

Come See Our World: What Transparency Around Animal Research Looks Like

Yesterday, Americans for Medical Progress (AMP) launched a new outreach initiative aimed at increasing transparency around animal research. “Come See Our World” (CSOW) is a program that relies on the public display and distribution of photographs and videos that accurately reflect animal care and research. “The goal of the program is to replace outdated, inaccurate images of animal research with current, accurate views,” said Paula Clifford, Executive Director for AMP.

Importantly, all collected media will be compiled on a public website allowing them to be shared widely while giving credit to its source. So far, the website contains recent photos of rodents, primates, dogs, cats, farm animals, aquatic animals (fish and frogs), and other animals like rabbits, pigeons, and ferrets in research settings.

CSOW home page. Source: Americans for Medical Progress.

“Come See Our World” succeeds at outreach on multiple levels. There are mechanisms for the website to:

  • Match requests for images and research stories by reporters, researchers, lawmakers, and other non-experts to pictures or videos
  • Receive and share YOUR images, videos, and stories of real, accurate, and groundbreaking research on their “Be an Advocate” page
  • Sign up to receive updates and resources to remain engaged and informed about animals in research

We gave the site a test-run and found it to be extremely easy to navigate, appealing to view, and the information easily digestible by young and old alike. This will be a great resource for educators, scientists, policymakers – anyone, really, who is interested in learning about and promoting the accurate dissemination of animal research-related information. Visit the site now and enjoy the virtual menagerie!

Research Roundup: Monkeys and face recognition, animals advance AI, sugar to treat heart disease, 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.

  • New study challenges our current understanding of how the brain recognizes faces. We can often pick out a face or a person in a crowd (e.g., finding Wally/Waldo), but the cellular mechanism via which this occurs has remained poorly understood. Using rhesus macaques, these researchers investigated which neuronal cells are responsible for facial recognition. By varying aspects of the face systematically (e.g., shape, distance between the eyes) and measuring 205 neurons in 2 animals, researchers found that each neuron responded to a specific combination of facial parameters rather than the face itself, using fMRI. In other words “the neuron is not a face detector, it’s a face analyser”, says Leopold. The brain “is able to realize that there are key dimensions that allow one to say that this is Person A and this is Person B.” Subsequent replication and extension using more subjects is warranted, but these findings provide an exciting new avenue of research with regards to face processing. This research was published in the journal Cell.

    Macaque. Source: Kathy West. CNPRC.

  • Researchers are using animal cognition to make advances in artificial intelligence.  Harvard assistant professor David Cox and his team are studying the rat visual cortex by training rats to play a complex object discrimination video game. While the rats are learning the video game, a 2 photon excitation microscope images neural activity in the visual cortex. These images are then used in conjunction with microscopic images of brain tissue slices to make digital maps of of the visual cortex. The hope is that these neural circuits could become maps for artificial neural networks and next generation artificial intelligence. Check out this video on “How to Digitize a Rat Brain”!
  • Artificial intelligence system detects pain levels in sheep. Researchers at the University of Cambridge have developed an artificial intelligence (AI) system which uses five different facial expressions to recognize whether a sheep is in pain, and to estimate pain severity. Building on earlier work which teaches computers to recognize emotions and expressions in human faces, Dr. Krista McLennan developed the Sheep Pain Facial Expression Scale (SPFES) in 2016, which can recognize pain with high accuracy. In the current study, Dr. Peter Robinson and colleagues developed machine learning techniques to reduce the time required for humans to learn to use SPFES, as well as the confounds of human bias in interpreting facial expressions. Researchers trained the AI model with a small dataset of about 500 photographs of sheep, and early tests showed that the model could estimate pain levels with about 80% degree of accuracy, indicating the system is learning. The next steps for the researchers will be to train the system to detect and recognize sheep faces from moving images, and to train it to work when the sheep are in profile. Ultimately, this research will lead to better pain detection and faster medical attention. The research was presented June 1 at the IEEE International Conference on Automatic Face and Gesture Recognition in Washington, DC.

    Face detection in sheep. Source: Liu et al., 2017, University of Cambridge

  • Lifelong protection from allergies a possibility? When your body comes into contact with a foreign particle, for example, pollen, your immune system kicks into play, producing antibodies (Immunoglobulin E). These antibodies travel to these foreign cells, attempt to “neutralize” them and in this process – triggers an allergic reaction. In order to quickly identify and mount a response to foreign particles that your body has encountered before, the body uses “memory” T cells. However, in some cases, this “memory” may be an “overreaction” of the system and once this “memory” is formed it is virtually impossible to be removed. In the present study using
    mice
    , researchers tackled this issue and were able to desensitize these memory cells which overreact to allergens using therapeutic gene transfer. Approximately 50 million American suffer from some form of allergic disease and this research, which is in pre-clinical trials, provides some hope of treatment. This study was published in the journal JCI Insight.

  • Type of sugar may treat atherosclerosis, mouse study shows. Researchers at the Washington University School of Medicine in St. Louis worked with mice prone to atherosclerosis, clogged arteries due to the buildup of plaque, and found that when injecting trehalose, a natural sugar, the immune system “cleans up” this plaque.  Babak Razani, MD, PhD, an assistant professor of medicine, and his colleagues showed that trehalose activates TFEB, a molecule that then.goes into the nucleus of macrophages and binds to DNA. This turns on specific genes and leads to additional organelles that act as “housekeeping machinery.”  Babak says, “Trehalose is not just enhancing the housekeeping machinery that’s already there,” Razani said. “It’s triggering the cell to make new machinery..”  Trehalose is a mild sweetener and FDA approved for human consumption.  Plaque degradation is not seen when administered orally.  Researchers hope to study trehalose as a potential therapy for atherosclerosis in hopes to find a way to protect its  housekeeping properties when given orally.

    Cross section of mouse aorta with a large plaque. Source: Ismail Sergin

 

 

 

Research Roundup: Risks in gene editing tools, reversing skin ageing, neural code of love, 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.

  • Gene-editing technique that scientists hope will cure cancer and all inherited disease found to have dangerous flaw.  Crispr-Cas9 technology allows editing of a specific section of the genome. This has led scientists to explore its use in curing genetic diseases like muscular dystrophy and blindness and even curing cancer. A team of researchers in the US successfully used this technology to restore sight in mice. They then sequenced the entire genome of two of these animals and found that despite the mice appearing normal, hundreds of areas other than that targeted DNA sections were affected in some mice. Typically a computer algorithm is used to identify areas of the genome that have the potential to be damaged  and then those specific sections are examined. The result of this study shows that when using this technology for live animals, the entire genome needs to be sequenced in order to identify unintended mutations that may have occurred.  One of the researchers, Professor Stephen Tsang, of Columbia University, said: “We hope our findings will encourage others to use whole-genome sequencing as a method to determine all the off-target effects of their Crispr techniques and study different versions for the safest, most accurate editing.”  Researchers are confident that this technology is still medically beneficial but encourage others to be aware of the potential side effects, as with any medical intervention. This study was published in the journal Nature Methods.

  • Research on a specific brain connection brings us closer to understanding the neural code of “love”. Prairie voles are an interesting model species because,like humans, one of their mating/cohabitation styles is that of monogamy. Previous research has identified that brain chemicals such as dopamine and oxytocin, acting on the medial prefrontal cortex and the nucleus accumbens, co-occur with the formation of a monogamous pair bond in this species. In the present study, they found that the prefrontal cortex regulates the rhythmic oscillation of neurons in the nucleus accumbens — and it is this functional connection that leads to the formation of the pairbond. Moreover, using optogenetics, they were able to stimulate this connection during brief cohabitation with a mate — not long enough to facilitate pair bonding — and found that this was sufficient to induce a preference toward this mate. The results of this study lend insight to disorders which are associated with impaired social functioning such as autism. This study was published in Nature.

  • A new tool for genetic modification. Two UC Davis graduates, Arshia Firouzi and Gurkern Sufi, have developed a gene editing tool that they hope will refine animal research. Their start-up company, Ravata Solutions, came about through their combined expertise in electrical engineering (Firouzi) and biotechnology (Sufi), and together these graduates have devised a method to refine genetic engineering in research animals, particularly rodents. Genetically modified mice are widely used in human disease research, and currently these models are developed by “injecting a needle into a cell,” but this invention creates pores in the cells that will allow the insertion of genetic materials “without a trace,” said Sufi.
  • Century old drug, Methylene Blue, shows promise reversing the effects of skin aging in humans. Researchers at the University of Maryland, have recently tested methylene blue on 3D models of human skin, from human donors, and determined that the chemical improves skin viability, increases skin hydration and thickness, promotes skin elastin and collagen synthesis, and protects the skin matrix. Previous research on mice and rats over the past decade, has led to this discovery. A study in 2008 on rat liver cells demonstrated that methylene blue delays cellular aging. Then a study in 2014 suggested that methylene blue extended the lifespan of female mice by 6% when included in the food. We hope that research on this topic continues to both help the aging effects in normal humans and patients with Hutchinson-Gilford progeria syndrome, a rare genetic disorder of accelerated aging. This study was published in the journal Scientific Reports.

  • New study finds that having a stroke may be a risk factor for increased alcohol consumption. It is generally accepted that excessive alcohol consumption is a risk factor for having a stroke. However, it is virtually unknown how having a stroke may later affect the inclination to consume alcohol — a question that these researchers investigated using rats. These Rats were first trained to consume alcohol using an operant self administration procedure. Next, an ischemic stroke was induced in these animals. In these animals they found an increased inclination to consume alcohol compared to prior to stroke induction. These researchers found that inhibition of a dopamine receptor (D1) was sufficient to reduce this alcohol seeking behaviour in animals with a stroke — suggesting that this is an underlying cause of this effect. “As much as possible, we tried to use a model that would replicate the experience of a human patient,” Sohrabji said. “Therefore, we think that these findings, although preliminary, might eventually help people who have experienced any type of brain injury, whether a stroke or an accident that causes traumatic brain injury.” This study was published in the journal Scientific Reports.