Author Archives: Editor

Animal Testing and Human Trials: Alternatives or Complements?

The Animal Justice Project, a British-based animal rights group, is no stranger to misinformation. Previously we have debunked their factual errors regarding malaria studies in Sweden and eye injury studies. There was also the time they produced a press release which suggested 52oC (125oF) was the same as boiling water (which admittedly might be true if you tried to make a cup of tea in the lower stratosphere).

Recently on their website, a blog by Judith Snaith has been put up. The blog is a mash up of animal rights myths and misinformation, but one line was of particular interest.

More than 100,000 humans are killed yearly by prescription drugs that passed animal testing. Animal research is not the final phase, 90 per cent of drugs that pass the animal tests fail in human trials. So if we have to test on humans to be accurate, can we not skip out the middle monkey?

Let’s break this down bit by bit. The figure of 100,000 is an American one (Lazarou et al, 1998) with the figures for the UK approximated at around 10,000 (Pirmohamed et al, 2000) using a similar methodology. We have mentioned the flaws in these figures in our “Animal Rights Pseudoscience” page:

The statistic of 100,000 deaths in a year is taken from a 1998 meta-analysis by Lazarou and colleagues that examined rates of adverse drug reactions (ADRs) observed in 39 studies undertaken between 1966 and 1996 (Lazarou et al, 1998). The methods used in this meta-analysis were subsequently criticised for failing to adequately take into account differences between the 39 studies examined, a failing which may have lead to an over estimation of the number of deaths due to ADRs (Kvasz et al, 2000).

Between 2001 and 2002 Pirmohamed and colleagues analysed admissions to two hospitals in Merseyside, in order to determine if the cause of admission was an adverse drug reaction (Pirmohamed et al, 2000). Their results indicated that ADRs accounted for 6.5% of hospital admissions, and that ADRs may be responsible for up to 10,000 deaths a year in the United Kingdom. The study also found that:

  • 95% of ADRs were predictable from the known pharmacology of the drugs (i.e. from animal testing and human clinical data).

  • A large majority of ADRs were caused by older drugs.

  • About 70% of ADRs were either possibly or definitely avoidable.

So a large amount of these deaths come down to human error as the adverse drug reactions were both predictable and avoidable.

Judith mentions that these 100,000 deaths came from drugs which had passed animal tests. What she chooses not to mention is that these 100,000 deaths came from drugs which had also passed clinical trials in humans. There is no logical reason to put these deaths at the feet of animal tests – particularly as the animal tests do not check for the common causes of drug deaths – accidental overdose, negative drug-drug interactions from secondary medications, incorrectly prescribed medication etc.

Judith then goes on to mention that 90% of drugs that pass animal tests go on to fail in humans:

Animal research is not the final phase, 90 per cent of drugs that pass the animal tests fail in human trials

We’ve definitely seen and debunked this statistic before. The inference is that animal tests are not effective as many drugs fail later on. Prof Lovell-Badge explains some of the many flaws in this argument. Firstly, there is a similarly high failure rate in the human trials:

Consider that of all the drugs which pass Phase 1 clinical trials in humans, 86% will fail in later stage human trials. Yet, we do not hear activists suggesting that humans are an entirely inappropriate model for drug development (though we should note that one human is not a perfect model for another).

Furthermore, this whole argument is premised on a misunderstanding of the different role of animal and human trials:

The role of preclinical animal tests is to check if the drug offers any potential therapeutic value and, importantly, if it is safe enough to move to Phase 1 trials in humans. This does not even mean free of all side effects, but to learn whether a drug can safely be given to humans and at what approximate dosage.

Put another way, every stage of drug testing acts as a safety barrier for dangerous drugs being sold. Pre-clinical in vitro tests, pre-clinical animal tests, Phase I clinical trials, and Phase II-III clinical trials all work successively to remove potentially dangerous compounds from reaching the market. These are not their only functions, animal tests may help assess appropriate therapeutic doses, which can be later refined during clinical trials. These tests (animals and humans) may also help discover potential side effects (this does not mean the drug will be rejected – it depends on the seriousness of the condition it is intended to treat).

Judith Snaith goes on to combine her two assertions to claim that we don’t need to do the animal tests – we can just move straight to humans.

So if we have to test on humans to be accurate, can we not skip out the middle monkey?

This ignores the huge number of dangerous compounds which are removed from the drug development process because they show toxic effects in animals. To skip this step would be to allow these compounds to be trialled in humans. Furthermore, when one safety check doesn’t guarantee safety, that doesn’t mean removing the check makes anyone safer.

Animal testing is not an alternative to human trials, it complements it. Medieval castles had high walls and soldiers in them – both protect the defenceless people in the keep. Sometimes high walls and soldiers were not sufficient, and the castle was sacked, but no one would conclude that high walls were pointless and that everyone would be safer if there were just the soldiers. In reality, doing away with the castle would mean more soldiers would die, just as doing away with animal tests would likely lead to more deaths in Phase I and II clinical trials; the consequence of this would be that fewer people would volunteer for clinical trials (just as fewer soldiers would wish to defend a low-walled castle).

We use a variety of methods in biomedical science – computer simulations, tissue studies, animal models, clinical trials, epidemiology etc. Different methods can teach us different things and the results are often used in combination to build our knowledge and understanding of physiology and disease. The same is true in safety testing – all methods of screening drugs have advantages and drawbacks, but if we use them effectively, in combination, we can see that safe and effective drugs make it to market.

Would the French soldiers have taunted King Arthur if they didn’t have high walls? (Monty Python’s Holy Grail)

Speaking of Research

Animal experiments in Israel rise by 51% in 2016

Israel used 507,018 animals for research and testing on animals in 2016 according to statistics released by The Ministry of Health’s Council for Animal Experimentation. This represents a 51% rise on 2015 – with the increase mainly due to a fourteen-fold increase in the number of cold-blooded mammals used (99% fish).

Testing on Animals in Israel for research in 2016. Click to Enlarge

There were moderate decreases in the number of rabbits, but the huge increase came from cold-blood animals, up from 12,784 in 2015 to 180,253 in 2016. According to the chairman of the National Council for Animal Experimentation, Prof Jacob Gopas, who spoke to Haaretz:

“If it’s possible to use fish, you don’t use mice, for example, and if it’s possible to use mice then you don’t use pigs,” Gopas says. Both the move toward using fish rather than mice in experiments and the efforts being made to raise fish with as few diseases as possible have contributed to the spike in the number of fish being used. Gopas notes that the vast majority of the fish used in research, 154,000 of the 178,000 that were used last year, were returned to their previous habitats.

No cats or dogs have been used in experiments in Israel since 2012. Primate numbers have edged up, increasing from 42 to 46 in 2016, though this is still less than 0.01% of total animal numbers. Primate experiments were under threat in 2014, resulting in seven Nobel Laureates, and seven major universities writing to President Netanyahu urging him not to further restrict animal studies.

Animals used in research in Israel in 2016. Click to Enlarge

Mice are still the most commonly used species in Israel, accounting for 51% of total animal numbers. Fish are the next most common at 35% (36% when other cold-blooded mammals are included). Rats and birds take the next two slots, with 8% and 4% respectively.

Trends in Israeli animal experiments 2004-16. Click to Enlarge.

Historical statistics show that until the spike in 2016, the number of animals has been fairly constant, fluctuating between around 275,000 and 340,000. The slight variations may account for individual projects which used a lot of animals, or from slight changes in science funding over the years. It appears that the sharp rise in 2016 is due to one or more research projects specifically working with fish – that account for most of the 170 thousand rise in animal numbers.

It should also be noted that Israel works hard to rehabilitate animals used in research. According to Israel Hayom,

The council noted that in 2016, its post-testing animal rehabilitation rate for monkeys, carnivores, farm animals and wildlife, excluding rodents and poultry, stood at 88%.

“The rates of animal rehabilitation in Israel are outstanding by any standard. Israel has been a leader in this field for years compared with the data published worldwide,” the council said, adding that it has so far funded nine projects aimed at developing methods that would minimize animal testing by finding alternatives that would not compromise research studies.

More information (in Hewbrew) can be found about the severity of animal experiments in Israel in 2016. The statistics show that 14% of projects were categorised as severe, 31% as moderate, 28% as mild, 18% as below mild, and 9% killed humanely for the purpose of collecting organs (not all countries collect this data). It is likely that projects are estimated at or above the actual severity level, and researchers would be in breach of protocol if they exceed their estimated severity.

Check out all the latest international statistics on our Animal Research Statistics page.

Speaking of Research

monkey animal experiment playing

Monkey on an Israeli primate breeding facility

Sources:

Context matters: How a veterinary image became “cruel animal testing”

Recently, a photo depicting a rabbit with pretty serious hair loss was tweeted by an image sharing Twitter account, and then retweeted over 4,300 times. The photo appears quite shocking, and the post by the Twitter account reflected that.

Uber_Pix has written, in all caps: “NEVER WANTED A PIC TO SPREAD MORE IN MY LIFE”. The image is a screenshot of a post with comments from Tumblr, where the user “the_vegan_mothership” writes:

“This is a bunny at L’oreal lab. L’oreal does a lot of cruel needless animal testing. Please don’t buy products made by L’oreal. The more products they sell, the more animals are tortured.”

Twitter users saw this image and were shocked. Many upset responses resulted:

The problem with the shared image is that the origin is just not true. The image is definitely that of a rabbit suffering from hair loss, but the image comes from a Florida veterinary clinic’s website. The image was posted to the clinic website to illustrate some of the cases they have dealt with in rabbits and other less common mammalian pets that the clinic sees.

Click image to go to page

The rabbit is suffering from an ear mite infection, caused by the parasite Psoroptes cuniculi. The rabbit in the photo actually appears to be on the (long) road to recovery, as the commonly seen thick scales usually present in an infection that has spread this badly have cleared up. When an ear mite infection goes untreated, it can easily spread to the neck, abdomen, and limbs, as seen with this rabbit.

Ear mites in rabbits are commonly treated with a potent but effective drug called Ivermectin, which kills the mites as they take blood meals from the treated host. Ivermectin itself is a fascinating drug, discovered by an international team of scientists, working with isolates from Japanese soil microorganisms. While Ivermectin is a very commonly used antiparasitic medication in veterinary medicine, it is also considered a “wonder drug” in human medicine, improving the lives of millions of people in the developing world who suffer from neglected tropical diseases.

When shocking images such as this one appear, it is very easy to get caught up in the emotion of the moment and want to react and share with your social media circles. However, it is important that we try our best to check sources, look for the origins of a photo, or get a second opinion. This rabbit image has been making its rounds on the internet since 2013, with the claims that the rabbit is a “victim” of animal testing. L’Oreal even responded to the claim, stating that they no longer test their products, or ingredients on animals, and that they do not contract the testing out to other facilities, either. The exception being for parts of the world where such testing is mandated by law (e.g. China). However, they are also actively working with nations where testing is required by law, in order to find suitable alternatives.

Keep in mind as well, what the real purpose is of Twitter accounts such as @Uber_Pix. These image “scrapers” actively take images and videos off of social media, strip the credit from them, and re-upload them in order to gain as much traffic, subscribers, and click-through as possible. Why do they do this? To spam subscribers with ads, to sell stuff. Don’t give them the time of day.

This is not the first time we have seen images repurposed to tell a story fitting the animal rights agenda. In 2014, we noticed a picture of cats tied to boards was being described as animal testing when in fact it was cats being prepared for spay and neuter in order to be adopted out.

This picture was used to misrepresent animal research

In both cases, thousands of internet users have been tricked by someone who is willing to lie to create a false case against animal research. Next time you see an image criticizing “cruel animal testing”, try to find the original image source, and make sure you’ve got the full context of the picture before you click to retweet!

Christine

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.