Tag Archives: animal testing

Give lab mice a better life and the science will also get better

The long-term emotional wellbeing of mice can affect their behavior — and that’s important for researchers using them for models.

To say that lab mice are important to science is a hell of an understatement. Mice have been used in biomedical research for centuries. Entire fields of research wouldn’t even exist without animal models. The humble mouse has proven valuable in everything from genetics to psychology.

But, in recent years, researchers have become more and more aware that there is a problem with lab mice; or rather, several. For instance, there’s almost no diversity in lab mice, which means that the vast majority of studies are carried out on male mice. This has cascading effects on multiple levels, and to put it simply, it means that mouse studies might not be all that representative for women.

Here’s another issue that researchers should no longer ignore: mice’s feelings.

Animals experience a broad range of emotions that are crucial for their decisions, behavior, and biology. For the most part, however, science has largely been uninterested in the positive emotions lab mice can exhibit. That’s a problem, a team of British researchers is saying. If we’d focus a bit more on making them happy, we’d be getting better results in lab tests, according to a new study.

“Our results also demonstrate that repeated negative events can have a cumulative effect to reduce resilience in laboratory animals, which has significant implications for animal welfare,” the authors write.

To test how mice react to negative emotions, researchers… well… gave rats negative emotions. They lifted the mice by the tail when it was time to handle them, a process known to annoy and startle mice. This tail-lifted group was compared with another group that was handled via the less stressful “tunnel handling” technique, where mice hang out in a plastic tube instead of being physically grasped.

When it came to positive stimuli (like being given some sugar water), the two groups responded the same. But when it came to negative stimuli, there were big differences between the two groups.

Lead researcher, Dr. Jasmine Clarkson notes:

“Animals have emotions that are affected by what happens to them in their everyday lives. Like us, they can get anxious and depressed, but how does that change their experiences of the good and the bad things in life? We found that anxious and depressed laboratory mice are more disappointed when something bad happens, but their low mood has no effect on how elated they are when something good happens.”

“So if we apply that to the welfare of our lab animals, it means poor welfare still allows animals to appreciate reward but it makes them less resilient and potentially reduces the reliability of biomedical experiments. These are important findings which emphasize the benefits of the highest level of care that we should adhere to.”

For starters, this suggests that the tunnel handling method should be used more widely, ensuring that handling is the least stressful treatment possible.

But more importantly, it suggests that lab animal welfare and good science go hand in hand — and it’s not a trivial matter. Psychology and medicine are plagued by a replication crisis, and it’s plausible that a part of that problem comes from animal model studies. Researchers are struggling to recreate each other’s findings for reasons that are not clear. For instance, if someone carried out a study handling mice directly, and someone else tried to replicate it using a tunnel, they might get different results.

If something as simple as handling can help address this issue, then it’s definitely something worth addressing; and if it makes the lives of lab mice a bit more pleasant, what’s not to like?

The study was published in Proceedings of the Royal Society B.

Lab-grown human skin might finally spell the end for animal testing

L’Oreal’s EpiSkin promises to revolutionize the cosmetic industry and reduce (if not eliminate) the need for animal testing. Image credits: L’Oreal.

Animal testing is an ethical problem which has been going on for decades, with no clear end in sight. We don’t like it, but then again, we like having safe products which we know for sure aren’t going to cause us any harm. We also like new medicine and drugs, which are virtually always tested on animals. Thankfully, technology has advanced so much that we might yet have a solution to this conundrum: developing tissues tissues that mimic the real thing.

The need for a change

According to the USDA, in 2005 about 668,000 animals (57%) were used in animal testing without anything to relieve their pain or distress. Another 425,000 (36%) were used in procedures in which pain or distress was relieved by anesthesia, while 85,000 (7%) were used in studies that would cause pain or distress that would not be relieved. Think this figure is large? It doesn’t even include rats and mice, birds, or invertebrates — of course, mice and rats are the most commonly used creatures, but in the USA, they (along with birds and amphibians) are not defined as animals under animal experiments regulations. Therefore, no one is forced to publish these figures and they are not included in any statistics.

In animal testing, animals are routinely subjected to irritating or painful substances, radiation, and stress. Their are often forced to ingest substances which are harmful or even lethal to them, to gauge the effects. Sometimes, some organs are removed to see how their bodies react in this situation. In modern society, we shield ourselves from knowing just how much suffering even the simplest product can cause — but just because we ignore it doesn’t mean it goes away, and consumers area starting to realize it.

According to a Pew Research poll, almost half of Americans are against using animals for lab testing, while 67% of Americans are “somewhat concerned” or “very concerned” by the use of animals in research. But without any easy alternative in sight, the big industry held on to its inertia, in an attempt to continue “business as usual.”

It seems that animal testing is a big problem, and it’s here to stay. Or is it?

Under my skin

In recent years, researchers have developed so-called ‘organs on a chip‘ — simple devices which mimic the function of human organs. The idea is gaining more and more traction, but there’s always a big leap when it comes to getting a product out of the lab and into the market. Especially when it comes to the beauty industry, a notorious “consumer” of animal testing. This is why it is encouraging to see L’Oreal taking major steps in their EpiSkin project. EpiSkin is an in vitro, reconstructed human skin (just the epidermis) cultured on a collagen matrix at the air-liquid interface. This model exists at different stages of maturity. It already works so good that it’s outperforming animal testing in most scenarios.

“They are a much better simulation of human skin than animals are,” Carol Treasure, whose company XCellR8 test products for various brands, told Wired.

Already, the L’Oreal grows more than 100,000 human skin samples a year. They’re not doing it just out of the kindness of their heart, but they’re also doing it to make a profit — and there’s nothing wrong with that. Having a positive impact in society while also making some money is what modern economy should strive to be.

“EpiSkin models are also available to the global scientific community to support academic and corporate research and development activities across industries,” Charbel Bouez, vice president of advanced research at L’Oréal’s America Zone and president of EpiSkin, told CNBC.

They’re also not the only ones dabbling with this type of project. MatTek, whose product EpiDerm was launched back in 1993, is also taking strides, and they grow about two adult humans worth of skin in petri dishes on a weekly basis. However, their approach is different — they source real human skin cells from surgical waste after cosmetic surgeries and circumcisions, and from tissue banks, to provide real human skin. These two competitors, along with several research labs in the world, are also trying to expand this approach to other organs. If successful, this could not only eliminate the need for animal testing, but it could also make the tests more accurate.

It’s not clear how this field will evolve in the near future, but with the way science and technology are advancing, it seems that we’re on the right track — and it’s about time.

In the meantime, if you want to be sure you’re an ethical consumer, you can also check the label of the products you buy and favor products without animal testing.

$0.25 “mini-brains” could replace animal testing

Scientists have developed devices that move us one step closer towards eliminating the need for animal testing. These working miniature artificial brains would be ideal for testing drugs research, neural tissue transplants, or experiments with stem cells.

Image: Hoffman-Kim lab/Brown University

The results were published in a new paper by researchers from Brown University in the US; these little balls aren’t actually cognitive, but they do produce electrical signals and form their own neural connections (synapses) which is basically what you want for testing. The authors themselves are quite confident in what they’ve accomplished:

“We think of this as a way to have a better in vitro [lab] model that can maybe reduce animal use,” said co-lead author Molly Boutin. “A lot of the work that’s done right now is in two-dimensional culture, but this is an alternative that is much more relevant to the in vivo [living] scenario.”

The “brains” are pretty simply to make – with one small sample of living tissue from a single rodent they can make thousands of them. The way it works is they isolate and concentrate the brain cells they want through centrifuge and then they grow the samples in a in medium in an agarose spherical mold. The resulting molds, about a third of a millimeter in diameter, are not the first (nor are they the most complex) alternative proposed to replace animal testing. The thing is, they’re by far the cheapest and easiest to make. Earlier this year, Harvard also proposed “organs on a chip“, which could, in time, complement other areas of animal testing.

“The materials are easy to get and the mini-brains are simple to make,” said co-lead author Yu-Ting Dingle, who earned her Ph.D. at Brown in May 2015. She compared them to retail 3-D printers which have proliferated in recent years, bringing that once-rare technology to more of a mass market. “We could allow all kinds of labs to do this research.”

So, for all practicalities, this could actually work – especially as with all the equipment being available, the price is only $0.25. Here’s what properties these brains can fill:

  • Diverse cell types: the cultures contain both inhibitory and excitatory neurons, supporting various neural support cells
  • Electrically active: the neurons fire and spike and form synaptic connections, producing complex networks
  • 3-D: this is actually a major advantage. Cells actually connect and communicate within a realistic geometry like a real brain, rather than merely across a flat plane as in a 2-D culture
  • Natural density: The balls have a density of a few hundred thousand cells per cubic millimeter, which is similar to a natural rodent brain
  • Physical structure: The cells in the mini-brain produce their own extracellular matrix, not relying on foreign materials such as scaffolds of collagen, which makes it cheaper
  • Longevity: In testing, cultured tissues live for at least a month.
organ-on-a-chip

Organ on a chip might end animal testing and improve drug research

organ-on-a-chip

Photos: National Center for Advancing Translational Sciences

Here at ZME Science we often report on cutting edge developments and various medical breakthroughs that offer novel treatments and such. Most of these drugs or techniques are first studied on animal models, and while they hold great promise, it’s most often than not that the desired response isn’t replicated in humans. This translates in millions flushed down the drain as scientists have to get back to the drawing board. A team of US researchers is developing a tool that might change all this; they plan on devising a chip that mimics various biological functions in the human body. If it’s found effective, drug companies could forego animal testing, and significantly cut down costs and research time.

A while ago, Andrei wrote a feature explaining why drug research takes so long – 10-15 years and $4 billion spent on average. Even so, 90% of drugs never hit the market.

One 2008 study estimated 115 million animals are used a year for scientific research alone. Moreover, it’s believed  ‘animal models’ are only typically 30% to 60% predictive of human responses to new drugs. That drug that prevents autism might work nicely for rats, but not that much for humans. This is why the US Food and Drug Administration (FDA) and the US military’s research and development wing, DARPA, are funding a project that seeks to develop alternatives to animals in drug testing development.

Namely, the ‘Organs-on-chip’ – a series of interconnected plastic chips, fitted with vessels, flexible membranes and tiny channels that are lineup with human cells. These are thought to mimic human cellular response far more effectively and realistically than petri dish cultures.

“The first program began about five years, ago, with lung-on-a-chip,” says Geraldine Hamilton, a senior staff scientist at Harvard University’s Wyss Institute for Biologically Inspired Engineering, which has led the technology’s development and is launching a new startup company this week to bring it to the commercial market. “We’ve also got the lung, gut, liver and kidney. We’re working on skin. The goal is really to do the whole human body, and then we can fluidically link multiple chips to capture interactions between different organs and eventually recreate a body on a chip.”

The structure can mimic the inhalation of, say, an asthma medication into the lungs and, later, how it’s broken down in the liver. More than 10 different organ-on-a-chip models, including chips that mimic liver, gut, kidney, and bone marrow have been developed thus far.

Is this the end of animal testing?

Let’s not kid ourselves. Even if the organ-on-a-chip proves to be extremely accurate, animal testing won’t end anytime soon. The entire model currently in use that guides drug development would have to change. The FDA, for instance, would have to stop requiring animal test data before a drug enters human trials. This means the alternative technology needs to prove itself that it can provide data at least just as accurate as animal models do. Overall, personally, I have faith this is the best route science needs to take. Years from now, hopefully not that many, animal testing will be seen as obsolete and unnecessarily barbaric.

“This is a big win towards achieving our institute’s mission of transforming medicine and the environment by developing breakthrough technologies and facilitating their translation from the benchtop to the marketplace,” said Wyss Institute Director Donald Ingber, who led the organs-on-chips effort.

source: Harvard