Statistically speaking, you – yes, you, reading this right now – are probably not some kind of militant vegan. Chances are pretty much equally low, however, that you’re a complete psychopath – which means that you’ll probably get a bit uncomfortable if we inform you of how every year, thousands of mice, rats, cats, dogs, monkeys, and little fluffy bunnies are forced to inhale, ingest, or be otherwise exposed to toxic and painful chemicals in increasing amounts until it eventually kills half of them.
It’s true: it’s called the LD50, or “lethal dose 50”, test, and while it’s fallen out of favor in recent decades, it definitely still happens. The whole point of the experiment is to kill 100 percent of the animals involved: they either die because of the things they’re forced to endure, or else they survive and are killed at the end anyway, so as to be dissected and the extent of the damage they suffered analyzed.
There are, it’s probably safe to say, very few of us who would happily sign up to perform this experiment. And yet, for a long time, it was seen as at worst a necessary evil. Why? Because it does yield information – specifically, information on how much of a substance constitutes a lethal dose. As one 2003 explainer from the University of Bristol summed it up: “This test has many downfalls […] Unfortunately, there is not a more accurate or humane test.”
But that was 20 years ago. Is that claim still true? Is animal testing truly necessary to keep humans safe? Or do we now have better options?
Do we need to test on animals?
Testing a product – whether it be a potentially life-saving drug, a household chemical, or even a cosmetic – on animal subjects before humans is a concept generally accepted as common sense. After all, you may balk at all those dead Neuralink monkeys, but let’s face it: at least they weren’t dead Neuralink usses, right?
“Even though scientists are continually trying to minimize the use of animals and to replace them with non-animal alternatives, animal research remains critical and necessary,” says Harvard Medical School – both “to comply with legal requirements, for ethical and safety reasons, and to address other scientific and practical considerations.”
It’s not just a case of valuing humans more than other species. “Certain experiments are simply impossible in humans,” the article explains. “For example, researchers who study the gut microbiome must often feed different groups of animals strictly controlled diets [and] keep them in an entirely sterile environment free of any germs or engineer them to have guts completely free of any microbes.”
“For some types of research, animals must be engineered to have or lack certain genes,” it points out. “None of this is possible in humans.”
Nevertheless, in a culture that claims to love animals, the idea of intentionally harming these critters is undoubtedly controversial – especially when you read some of the horror stories from days gone by. As a result, researchers are increasingly claiming to follow what’s known as the “3Rs principle”: the replacement, reduction, and refinement of experimentation on animals.
“As yet, there is no complete alternative to biomedical research with animals,” says the Foundation for Biomedical Research. “Since even the most sophisticated technology cannot mimic the complex cellular interactions that occur in a living system, there is still an essential need to develop surgical procedures, drugs, medical devices, and other promising treatments with some animals before there are human trials.”
“However, prospects are favorable for reducing the use of animals in the area of product development and testing,” it adds. “And conceivably, the day may come when animal research is no longer necessary.”
What alternatives are there to animal testing?
So, just how close are we to that future? According to an article published Thursday in Science, the answer is “potentially further than you may think”.
Today’s more humane testing methods can be split into three main categories. There’s “in chemico”, in which experiments are performed on specific pieces removed from cells – things like proteins or DNA; there’s “in vitro”, in which researchers use cells, including artificially grown cultures, outside of the body; and there’s “in silico”, a relatively new term referring to the use of computer or machine learning models.
The upshot? Gone – or at least, going – are the days of dripping harsh chemicals into the eyes of rabbits to test whether you should avoid spraying perfume directly into your face. These days, we have all kinds of futuristic alternatives, from using the membranes within eggs, to artificially grown human corneal cells, to high-tech computer simulations.
“Development of these alternative ocular methods took years of method development and validation,” the authors of the new article write – and now, their “acceptance […] has essentially eliminated the reliance on in vivo eye irritation studies to support new human drug applications for the past several years.”
Known as NAMs – an initialism which stands for variously “New Approach Methodologies”, “Novel Alternative Methods”, “Non-Animal Methods”, or “New Alternative Methods”, depending on who you’re reading – the opportunities aren’t limited to just eye experiments. Other success stories highlighted by the authors include “[an] investigation with simulated gastric fluid, which found that ranitidine, a drug used to reduce stomach acid, did not produce [a] probable human carcinogen”, as well as helping along the approval of remdesivir to treat COVID-19.
“Furthermore, NAMs have proven invaluable in the investigation of drug efficacy,” the article adds, “an example of which includes the use of cell models to express genetic variants of two rare diseases: cystic fibrosis and Fabry disease.”
“In both cases, an in vitro cell-based approach was used to assess the functional and biochemical response of mutated or dysfunctional protein(s) in the presence of drug to make inferences about the potential for response in vivo,” the authors write. “The findings from these data supported expanding the indications for the drugs to mutations not tested clinically.”
The future of NAMs
We’ve certainly come a long way in the past few years – but we still have a way to go before we can even think of phasing animal testing out completely.
Luckily, we’re still making progress. “[The] FDA has qualification programs that provide for alternative methods to be evaluated and qualified within a specific context of use, on the basis of data that justify that use,” the new article notes. “Once qualified, tools are publicly available to be used in relevant product development and evaluation programs for the qualified context of use and can be included in regulatory submissions without the need to reconsider or reconfirm its suitability.”
It’s good news for the more than 50 percent of US adults who oppose animal testing – it’s actually one of the few issues left that is pretty bipartisan, politically speaking. It’s also good news for the few hundred million animals who are currently used, usually fatally, as lab subjects in experiments each year.
That said, animal welfare isn’t the only reason we ought to be looking for alternatives to traditional experimentation. The fact is, as close as we are genetically to our non-human cousins, we are still pretty different in some fundamental ways – which is why, as the National Institute of Environmental Health Sciences (NIEHS) points out, “the relevance to human health is not always certain.”
Take, for example, paracetamol (aka acetaminophen, aka Tylenol). A mild, everyday painkiller in humans, this drug would never have been approved if it had been tested in cats – it’s extremely toxic to them, with as little as a single pill being enough to kill Tiddles. Conversely, we can look at the thalidomide tragedy of the 1960s, in which extensive but ill-informed animal testing led to researchers concluding the drug was safe – only for it to cause severe birth defects in tens of thousands of children across the world.
With that in mind, moving away from animal testing is really a win-win. “Recent advances in alternative methods, such as computational, biochemical, or cell-based model systems that can replicate human biology, have been shown in some cases to perform the same as or even better than standard animal models,” the NIEHS notes.
“[NAMs] can offer a way to improve understanding of the human system and its susceptibility to toxic effects, and to discover effective treatments for human conditions.”
The new article, “Advancing alternative methods to reduce animal testing”, is published in the journal Science.
Source Link: Is Animal Testing Necessary – And Where Are We On Alternatives?