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Research Roundup: Biosensors, breast cancer and the benefits of antiretrovirals

Welcome to this week’s (slightly late!) Research Roundup. These 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.

  • A new experimental technology can monitor and maintain drug levels in body. The device has a biosensor to monitor drug levels in the body; this can relay information every few seconds to a control unit and pump, which releases additional drugs as necessary. Using rabbits, the researchers were able to keep a constant dosage among all animals in their study – despite physiological and metabolic differences between individual animals. Taking it a step further, the research team introduced secondary drugs that, due to acute drug-drug interactions, would disrupt the levels of the initial drug. However they found levels of the initial drug were stabilised by the sensor.  This paper was published in Nature Biomedical Engineering.

Image courtesy of the Soh Lab, Stanford.

  • A gene associated with the growth of cancer cells is also implicated with the growth of stem cells. Previous research by this group has implicated the high-mobility group (HMG) gene in the formation of polyps, abnormal growths projecting from the intestinal lining that can be precursors of cancer, in mice. Examining the intestinal cells of these mice localized the HMG active gene and its protein to stem cells buried within the deep grooves in the intestinal lining. These stem cells carrying the HMG gene multiplied far more rapidly and also increased the number of Paneth cells, a type of niche cell known to support intestinal stem cells. This research provides an exciting avenue for future research into processes that could disrupt cancer growth and prevent tumour progression. This study was published in Nature Communications.

  • Young people who contract HIV in the UK can now expect to live to a near-normal age thanks to anti-retrovirals. A study in the Lancet of almost 90,000 people showed, “Patients who started Anti-Retroviral Therapy (ART) during 2008–10 whose CD4 counts exceeded 350 cells per μL 1 year after ART initiation have estimated life expectancy approaching that of the general population”. This is 10 years longer than those who started ART in 1996. This breakthrough owes much of its success to animal research that eventually lead to such clinical trials in humans. For example, the ability of AZT, an anti-retroviral medicine more commonly known as Retrovir and Retrovis, to act against HIV (without toxic side effects) was discovered in mice and rats.

Czech Republic sees 2% fall in animal research numbers for 2016

The Czech Republic has reported a 2.1% fall in the number of animal research procedures in 2016, with 229,465 procedures on animals. This is down from 234,366 procedures in 2015. The falls were mainly in fish (down 11%) and rats (down 17%), while the biggest rise was in birds (up 17%).

Procedures on animals in the Czech Republic for research and testing in 2016. Click to Enlarge

Fish were the most common animal used (35%), followed by mice (33%), birds (13%) and rats (11%). Collectively these four species accounted for over 92% of animal research in the Czech Republic (in line with other European countries). Dogs, cats and primates together continued to account for less than 0.5% of research procedures (919)

The most common areas of research were “basic research” (35.4%),  “Conservation of the natural environment in the interests of the health or welfare of people or animals” (21.0%) and “Translational and applied research” (11.4%).

The trend in animal experiments in the Czech Republic. Click to Enlarge.

The number of animals used since 2013 has remained quite flat, at around 230,000 procedures, though it is not immediately clear why. The drop since 2012 may be a result of the new reporting criteria brought about by EU Directive 2010/63, which came into force in 2014 (though some countries implemented new counting procedures before then).

Source of Czech Statistics: http://eagri.cz/public/web/file/1497/EPZ16t_resorty.pdf

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

Speaking of Research

How animal enclosures are designed to meet the needs of laboratory animals

Having worked in animal research for over 14 years now I have not only gained a comprehensive knowledge of the requirements for animals used in research but have also seen significant improvements in this field. Currently, I work at King’s College London as a Site Manager where I oversee three animal units.

The role of an animal technologist varies dependent on experience but all are there to provide the best possible life to animals in research. Trainee animal technologists will often perform general husbandry duties such as cleaning cages, feeding, and watering, whereas senior technologists may be involved in colony management, scientific procedures etc.

During my career, and the many tours of research labs I’ve given, one of the common discussion is the type of cages used and how they vary so much between species.

Requirements for housing research animals in the UK are stipulated by Home Office and Animals (Scientific Procedures) Act, 1986 as well as any additional institutional requirements beyond this law. Providing the correct type of environment is essential for species to exhibit their natural behaviour.

Example of UK minimum cage sizing for M. mulatta

Housing requirements vary between species but here are some examples of why cages are designed in such a way:

Primates

Primate caging is typically tall as this enables the animals to feel more secure, as in the wild they would use the trees to climb high and get away from prey. Providing higher cages also allows for a more complex environment. Bars are often horizontal to allow the animal to climb the cage and maximise this as much as possible. Cages are normally made out of steel to ensure the animals are safely contained and also withstand potential damage in what are often a strong and intelligent species.

Cages are often multi-tiered to allow primates better utilisation of cage height and enable primates to get away from each other when necessary.  Environmental enrichment such as mirrors and perches provide further security to primates.

Primates are socially housed in multi-tier caging. The perches allow the primates to watch what is going on around the room.

Rodents

Rodents have much smaller cages which are normally made up of a plastic, such as polysulfone. These plastics can withstand high temperatures during cleaning and have been shown to last a long time. Traditionally, animals were kept in open top caging but in recent years there has been a movement towards individually ventilated cages (IVCs). IVCs provide a more stable environment by having sealed caging and using air handling units for filtration; this has, in turn, provided a better environment for animal welfare and research. Controlling for the environment can both help control experimental variables, and prevent risks to animal health from external pathogens.

While the caging appears to be relatively small for rodents it is designed around the need of the animals. Rodents are often social species and in some cases larger spaces can cause anxiety due predator/prey relationships.

Environmental enrichment is used to encourage natural nesting behaviours which can be seen in the wild. In recent years red boxes have been implemented in some cages, humans can see through these but animals don’t see through this colour in the same way, therefore this allows better monitoring while making animals feel safe and secure.

Individually Ventilated Cages

Rabbits

Rabbits are often housed in floor pens as this provides space to exercise and express their social behaviour. Rabbits which are kept grouped housed tend to show less stereotypic behaviour and greater activity. Previously, rabbits were predominantly housed in single cages which caused more stress to the animals.  Enclosures are normally made up of wood frame with metal bars or completely metal frame with very small holes to prevent animals escaping.

Environmental enrichment such as cardboard boxes, hay/straw and raised areas can also provide more security and natural behaviours therefore reducing any abnormal behaviour which may be seen otherwise.  As albino rabbits are often used in research, boxes also provide a darker place to prevent damage to the retina of the eye.

Final thoughts

As humans we often believe that larger housing is better, just look at people who often want a huge home, but this doesn’t mean that an animal will be comfortable with this. The key is to tailor this to each species/individual’s needs for the highest welfare standards. Animals which naturally live in holes, or nests, often feel comfortable with less space compared with other animals. Other additions to accommodation such as environmental enrichment can enable expression of natural behaviour further and have significantly increased in recent years, no more barren cages!

In my 14+ years working with research animals, I have seen a huge amount of change. Improvements in caging and enrichment benefit not only the animals, but the pursuit of good science as well, and we should welcome it. I am also a strong believer that this has also improved the morale of staff, after all we all want the best for animal welfare which in turn will lead to good science.

Stephen Woodley

Animal Research in South Korea in 2016

In February 2017 the Animal and Plant Quarantine Agency (APQA) of South Korea released its animal research numbers for 2016. We spoke to the Animal Protection & Welfare Division and have been able to get a translated copy of these figures. The tables below were produced by the APQA, and we thank Dr Lee for providing these figures.

In 2016, South Korea used 2,878,907 animals in research, up 14.8% from the previous year.

Animal research in South Korea for 2016 by species

Rodents, fish and birds accounted for over 97% of animals used in research – similar to figures found in Europe. Most of the rise in animal experiments came from an increase in rodents (+19.5%), though numbers for fish (+15.2%) and birds (+60.7%) also contributed. There were falls in several categories, including primate experiments, which fell 18.8%.

Severity of animal experiments in South Korea

South Korea also produced severity statistics, similar to those in Europe. 2.6% of research showed no harm to the animal, 28.4% was mild, 35.5% was moderate and was 33.4% severe.We are unclear if these categorizations are based on pre-experiment licenses (what the researcher believed the severity would be) or post-experiment evaluation (what the researcher saw the severity to be).

Trends in South Korean animal experiments 2008-2016

The number of animals used in research has risen sharply over the last nine years, up 279% over the period, rising at a fairly steady rate of over 250,000 animals per year. To see why, take a look at a graph, produced by Nature, on the growth of R&D in South Korea over the same period.

The huge rise in spending on basic and applied research means that animal experiments were likely to rise (and did) over the same period. In 2013, South Korea had more researchers per thousand people in employment (12.84) than Japan (10.19), the USA  (8.81) or Germany (8.54). Medical and health sciences were the largest discipline (by publications) in South Korea (see Nature article).

If you know of any animal research statistics not on our list, please contact us.

Research Roundup: A new approach to treating Parkinson’s, designer pig organs, the benefits of dragon blood, 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.

  • Scientists may have discovered a new way to treat Parkinson’s disease (PD), a devastating neurological disease that causes tremors, rigid muscles, and changes in speech. In PD, a person’s brain cells (neurons) die causing a reduction in the neurotransmitter, dopamine. Researchers in Sweden were able to reprogram human astrocytes – brain cells that normally support the functions of neurons – to behave more like dopamine producing neurons. They did this by bathing the astrocytes in a petri dish in a number of molecules that affect changes in the cell’s DNA. This proof of concept allowed researchers to take the next step and try this therapy in a mouse model of PD. Injecting the same cocktail of molecules into the brains of PD mice caused the astrocytes to become more like the dopamine producing neurons, and this change lessened the PD symptoms in the mice. Obviously, many more studies are needed before this potential therapy can be tried in human patients with PD, but this is an exciting advancement in our quest to treat this disease. This research was published in Nature Biotechnology.
animal testing, animal research, vivisection, animal experiment

Mice were key to this Parkinson’s breakthrough

  • A new study finds that a reovirus may be implicated in the development of celiac disease. Celiac disease is a serious autoimmune disease where the ingestion of gluten, leads to damage of the small intestine. Gluten is found in many common foods, and is the general name for wheat derived proteins. “It affects 1 in 100 people worldwide, and 2.5 million Americans are undiagnosed and are at risk for long-term health complications”. Mice, were infected orally with two derived forms of a human reovirus, T1L and T3D; both capable of infecting the hosts` intestine but affecting its functioning in different ways. They found that while mice were able to successfully clear the virus from the system; exposure to the virus can disrupt intestinal homeostasis, lead to a loss of oral tolerance to the antigens produced by the body, and promote immunopathology similar to the symptoms of celiac disease. This study will of course need to replicated and further research investigating other reoviruses and the subsequent link to the development of celiac diseases firmly established. This study, using mice, does however, provide hope for the millions of individuals suffering from celiac disease and if a strong link to reoviruses is established; can lead to the development of a vaccination. The research was published in Science.
  • A promising vaccination for Zika virus has been found, reducing the occurrence of congenital abnormalities in mice. Zika virus is an emergent global health threat, that is transmitted by mosquito bites and more recently it has been discovered that it can be passed on via sex with an infected person. The most debilitating effects of the virus are death in the young and elderly are with compromised immune systems and perhaps most strikingly birth defects — in particular, microcephaly; a sign of incomplete brain development. For the first time, these researchers tested a live attenuated version of the Zika virus in mice. In comparison to an inactivated vaccine, live attenuated vaccinations have the advantage of single-dose immunization, rapid and robust immune response, and potentially long-lived protection. They found that this live attenuated vaccination was able to confer sterilizing immunity (complete protection from infection), a robust T-cell immune response, and a promising safety profile; similar to that of other clinically approved vaccinations. This study was published in Nature Medicine.

Illustration of a baby with microcephaly (left) compared to a baby with a typical head size

  • A new study finds that the human body’s peripheral nervous system could be capable of interpreting its environment and modulating pain. The sensation and perception of pain has historically been associated with the brain and the spinal cord (central nervous system(CNS)) and drugs for pain target the CNS. However, these drugs sometimes lead to unintended side effects such as addiction and tolerance. Drugs which target the peripheral system may allows us to avoid these unintended side effects. Using mice, these researchers demonstrated that the peripheral nervous system was able to interpret the type of stimulation it was sensing, although further research is needed to figure out how these sensations are interpreted by the brain. While further replication and validation is needed, this study widens our view of pain, its sensation and potential means of treatment. This study was published in the Journal of Clinical Investigation.

  • Luhan Yang, Chief Scientific Officer at eGenesis, is working to create ‘designer pigs’ which could be used to help alleviate the organ crisis. By inserting up to 12 human genes into pig ova they hope to overcome the rejection problems which currently prevent xenotransplantation from providing viable organs for human use. Yang hopes the use of the gene-editing technique CRISPR will make it possible to create human-animal hybrid organs that can be used to save lives.

  • New study finds that variant of protein in komodo dragon blood (VK25) contains antimicrobials that may one day form the basis of a new antibiotic. Researchers at George Mason University synthesized a new molecule,DRGN-1, based on a peptide found in the blood of the Indonesian lizard. This molecule was shown to promote healing in mice with wounds infected with Pseudomonas aeruginosa and Staphylococcus aureus. This synthetic compound also made these bacteria cell membrane more permeable – making it easier to kill these bacteria. The research was published in Biofilms and Microbiomes

Research Roundup: Fighting antibiotic resistance with maple syrup, epigenetic effects from light and diet, and HPV vaccine success

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 research finds that phenolic extract from maple syrup may boost antibiotic action. Antibiotic resistance is on the rise, with at least 2 million people becoming infected with bacteria that are resistant to antibiotics each year. Producing antibiotics to fight these “superbugs” is proving to be extremely difficult with the first new antibiotic being discovered in thirty years occurring in 2016. Researchers, learning of the anti-cancer properties of maple syrup, decided to investigate its antimicrobial properties. By mixing the syrup’s phenolic compounds — which gives syrup its characteristic golden color with the antibiotics ciprofloxacin and carbenicillin, they found the same antimicrobial effect with less than 90 percent of the antibiotic. They then tested the extract in fruit flies and moth larvae and found a similar effect. Further experiments are now planned in mice and the researchers are hopeful that one day this extract will be turned into a widely available, plant-based medicine.
  • Parental exposure to dim light at night may lead to a decreased immune response in offspring — Researchers at the Ohio State University exposed male and female adult hamsters to either a standard light/dark cycle or one with dim light at night for nine weeks. Offspring with parent(s) that experienced dim light exposure had an impaired immune response and decreased endocrine activity compared to offspring from standard light exposure parents. What is most interesting is that these epigenetic effects were transferred from the sperm and/or egg, and they were independent of light exposure in utero. The study suggests further research into light exposure at night from sources such as tablets, phones, and TVs should be done in humans.
  • A new study using mice finds that paternal diet affects offspring cognitive ability. Increasing evidence suggests that offspring development is not only impacted my maternal factors, such as the mother’s diet, but also by factors that the father has been exposed to. Epigenetic modification of germline cells has been implicated as one major causal pathway for the transmission of such changes to the offspring. In the present study, one group of male mice were fed a diet containing nutrients required for methyl group metabolism — methionine, folic acid, vitamin B12, choline, betaine and zinc, while another group was fed a standard diet of lab chow. After six weeks on the respective diets, the male mice were mated with female mice, and the offspring tested on a series of learning and memory tasks. The offspring of the male mice fed with methyl donors performed less well in all learning and memory tests. Related changes were also observed with poor activity in the hippocampus (associated with learning and memory) and downregulation of a gene associated with neuroplasticity. The study has implications for countries such as the USA, where dietary supplementation is prevalent.
animal testing, animal research, vivisection, animal experiment

Research mouse being held

  • A new function for the cerebellum has been found — the encoding of expectation of reward. The cerebellum accounts for approximately 10% of the brain volume, but contains more than 50% of its neurons. The cerebellum is often thought to function outside the realm of consciousness, being primarily involved in motor function and processing sensory input. The present study used genetically modified mice that expressed a green fluorescent protein (GFP) and photon microscopy. Scientists trained mice to push a lever to obtain a sugared reward. They found that one set of cells in the cerebellum fired when the mice pushed the lever (motor response), another set fired when the mice were waiting for the reward to arrive (cognitive response in regard to expected event) and third group fired when the reward was removed entirely (cognitive response in regard to unexpected event). This study challenges the current way of thinking about the role of the cerebellum and highlights how more research is needed to further understand how structures within the brain function in an interconnected way.
  • Discovery of a gene related to congenital blindness in zebrafish may lead to a cure for similar disease in humans. One type of congenital blindness is termed Leber Congenital Amaurosis (LBA), and leads to deformed or absent rods and cones in the eyes of children — resulting in blindness. While researching blindness in zebrafish, scientist have manipulated genes associated with rods and cones, and discovered a mutant. These genetically mutated zebrafish also have degenerated cones in their eyes, similar to humans with LBA, but the rods are not affected. Future research investigating the molecular and cellular mechanisms of rod and cone development using this new animal model may lead to a possible cure in humans.

  • In the news, we sometimes hear stories about miracle drugs being created to save loved ones from debilitating diseases. Sometimes these drugs work, in part because of some previous validation in pre-clinical work using non-human animals. Other times, they result in devastating effects because they have not gone through appropriate safety trials. It is important that our readers and the public in general understand why clinical safety trials are important and have a proper understanding of the associated risks if they are not conducted.
  • Vrije Universiteit Brussel (VUB) has restarted animal experiments at its lab in Brussels. Work was temporarily suspended late last year after an undercover video was made by the animal rights group GAIA. The institution began both internal and external audits to assess its own processes, and they have taken various measures to further improve animal wellbeing, administration, and infrastructure – with a further €13.8m earmarked for a new animal facility in the future. The decision to restart means that 27 approved projects that were on hold can now begin.
  • The human papillomavirus (HPV) vaccine, provided free to girls in Scotland aged 12-13 years old has resulted in a 90% reduction in levels of the virus. HPV is believed to account for around 90% of cervical cancer cases. The HPV vaccine owes much of its development and subsequent efficacy testing to animal models, including rabbits (Shope papillomavirus), cows (Bovine papillomavirus) and dogs (Canine oral papilloma virus). It is forecast that the HPV vaccine will lead to a 90% drop in cervical cancer cases in Scotland.

Jeremy Bailoo and Justin Varholick

Slovakia releases 2016 animal research data

Slovakia has become the first EU country to report back on the number of animal procedures it conducted in 2016.

There were 12,855 procedures on animals in Slovakia in 2016, a 5% decline from 2015.

Animal research in Slovakia for 2016 by species [Click to Enlarge]

Rodents accounted for over 95% of research procedures in Slovakia. Less usual, was that there were more rats used than mice – though this was not true in 2015. No dogs were used in 2016 (34 procedures in 2015), and the number of procedures on cats fell from 29 to 11. The main changes were a 13% fall in procedures on mice, and a 59% rise in the use of rabbits.

Looking at the severity statistics, we can see 52% were mild or non-recovery, with 46% moderate (up from 27% in 2015) and 1.2% were severe (down from 2.0% in 2015).

Severity of animal experiments in Slovakia

Other facts found in the 2016 statistics:

  • The most common use of research animals was Basic Research (71.3%), followed by Regulatory use and Routine Production (23.4%), Maintenance of breeding colonies (3.1%) and Translational/Applied research (2.2%).
  • Within the basic research, common areas of study were the Nervous system (30%), Reproductive system (16%) and Immune system (14%).
  • 99.67% of the animals used were bred within the EU
  • No animals were re-used.
  • 7% were genetically modified and 93% were not

Source:
Slovakia: EU Statistical Data of all uses of animals, 2015
Slovakia: EU Statistical Data of all uses of animals, 2016

Speaking of Research