By Jody McCutcheon
Back in the 1970s, a naive and rather irresponsible researcher, Herb Terrace, launched Project Nim, a study on teaching chimps sign language and documented it on film. But what should have been an interesting and heartwarming story of human-ape interaction soon turned into a horror movie: after having raised baby chimp Nim as a little human and taught him how to sign, Terrace passed the communicative primate on to other researchers after he bit one of his trainers on the face. The end result: Nim ended up in the Laboratory for Experimental Medicine and Surgery In Primates (LEMSIP), where he was used to test medicines for humans.
As you can imagine, after having eaten at a dining table with people, played with human children and even being given his own kitten, being subjected to painful medical experiments and living in a cage was nothing short of nightmarish for poor Nim. As one of the LEMSIP researchers himself put it: “There is no way you can carry out research on animals and for it to be humane… Because you’ve already put them in a cage!”
As suggested by the above sentiment—from an unexpected source, no less—animal testing is a contentious issue and has been for decades. Back in 1959, scientists William Russell and Rex Burch first described the basic principles behind the ethics surrounding animal testing, known as the 3 R’s.
- Reduction: the use of methods that provide researchers with comparable amounts of data from fewer animals, or more data from the same number of animals
- Refinement: the use of methods that minimize potential for animal pain, suffering and distress and maximize animal welfare
- Replacement: the use of non-animal subjects wherever possible
But those 3 Rs were – and are – largely ignored, sparking animal activists to call for an outright ban on vivisection (a.k.a. animal testing). Lately, animal activists have been winning battles, with public support for animal rights having risen steadily in the last decade. Consequently, the US National Institute of Health has fully retired its chimp-testing program.
Some governments also support animal rights, to an extent. In 2013, the European Union banned the testing of finished cosmetic products and cosmetic ingredients on animals, as well as the marketing of any such products. The EU hasn’t outright banned animal testing for scientific purposes, but has passed legislation that protects them in such cases, under the auspices of the (generally ignored) 3 R’s.
Earlier this year, US president Barack Obama signed a revised Toxic Substances Control Act with a provision to restrict animal testing in drug experiments. Moreover, a group of regulatory bodies from the US, Canada, Brazil, Japan and the EU, jointly called the International Cooperation on Cosmetics Regulation (ICCR), is working toward the elimination of cosmetic animal testing while offering alternatives (e.g., here and here).
What may surprise you is the fact that neither the U.S. Food and Drug Administration (FDA) nor the U.S. Consumer Product Safety Commission requires that cosmetics or household products be tested on animals at all. So if activists and various governments are on board, and if animal testing isn’t even required half the time, why does it persist? And persist it does: according to a study in the Indian Journal of Pharmacology, a whopping fifty to a hundred million animals are used worldwide in scientific experiments each year.
A main reason is, of course, corporate resistance from Big Pharma, leery as they are of potential lost profits and skeptical shareholders. Another reason is the scientific community’s stubborn conservatism. For decades, researchers have relied on animal testing, so it’s comfortable and easy, as results can be compared to previous tests on animals. In terms of pure paperwork, alternative methods must overcome bureaucratic hurdles before they can be implemented.
Further to this conservatism, some scientists believe the decision to ban all animal testing will interfere with research on HIV, hepatitis and epilepsy. They also insist that certain conditions such as blindness and high blood pressure can’t be studied in non-animal subjects like bacteria and tissue cultures.
They also make the rather spurious claim that animal testing is the best way to bring benefits to animal as well as human health, with the development of vaccines for diseases such as rabies, feline leukemia and heartworm. Overall, the conservative camp will tell you that any alternatives to animal testing are years of research and development away from practical reality. But is this just the rhetoric of the invested?
Consider that while animal testing may be the more comfortable and familiar option, it’s also unreliable and in many cases unnecessary (not to mention cruel). Oh, and keeping caged animals in some semblance of comfort is expensive. They must remain comfortable in captivity, because testing on animals in distress is the kind of shoddy science that can skew results (though it’s hard to imagine how animals such as chimps or dogs kept in small cages over long periods of time can not be in distress – as the LEMSIP researcher remarked, above).
As for reliability, results from animal testing are often inapplicable to humans. Compounds that seem to be safe in animals may be toxic to humans, and vice versa – don’t forget you can actually kill a dog by feeding it chocolate, but we humans love it! The US Food and Drug Administration has said that up to ninety percent of drugs that pass animal testing fail when administered to humans. And by “failing” they mean the drug either doesn’t work or is dangerous. Differences between species, and even between animals of the same species, can produce unreliable results due to variances in absorption, distribution, metabolism and excretion of chemicals. For example, rabbits subjected to the Draize skin test, used in cosmetic testing, often experience skin redness, bleeding, ulcers and even blindness. That’s the price rabbits pay for a mere sixty-percent prediction rate of skin irritation in humans. What’s more, certain alternative skin-test methods are up to eighty-six percent accurate. Drug testing results even vary from person to person, depending on their age, gender and race – but these factors are rarely, if ever, considered when doing drug testing.
How to Stop Animal Testing Now
While the odd case may require animal testing, there can be little doubt that in most cases researchers should be looking to reduce the number of animals used in testing, refine experimental methods to minimize animal pain and suffering or replace animals altogether with alternative testing methods. Several alternatives exist that are potentially far more effective in determining toxicity effects on humans from new drugs or chemicals. Many organizations fund exploration and development of such alternatives, including People for the Ethical Treatment of Animals, the European Centre for the Validation of Alternative Methods and SEURAT-1 (Safety Evaluation Ultimately Replacing Animal Testing), a joint effort between the European Commission and European cosmetics industry.
The most common alternatives include in vitro testing, computer (in silico) modelling, stem cell testing, human volunteer studies and human-patient simulators.
In Vitro Testing
They make babies in test tubes, and they also reproduce other human materials. The hope is to eventually test new substances and procedures on artificially reproduced human cell, organ and tissue cultures, thus ending animal experimentation. Many in vitro methods aren’t yet widely used, and are still being evaluated, but early returns suggest greater accuracy of data than that provided by animal testing. Furthermore, this promising “culture” culture has already inspired progress in treatments of AIDS, cancers, sepsis and kidney disease, and is already regularly used in chemical safety testing, vaccine production and drug development.
One type of in vitro testing ground consists of what is called a three-dimensional “human skin equivalent,” such as EpiDerm and SkinEthic. These anatomy models allow for an assessment of allergic reactions without any harm coming to cute little creatures like guinea pigs and rabbits. In a nod to corporate responsibility, cosmetic company L’Oreal has partnered with SkinEthic to conceive of one particular model called Episkin.
Another example is the organ-on-a-chip program that many labs are exploring, including the Lawrence Livermore National Laboratory in California. These devices mimic human organs such as kidney, lung and heart, on which drugs and chemicals are tested for toxicity, with responses measured via electric signals. Cells can survive and function on chips for several weeks, in some cases, allowing for many different experiments to be done. The lofty, ultimate goal is to replicate an entire human on a chip.
Similar to in vitro methods, the use of human embryonic stem cells on which to trial toxicity and other effects of new drugs may yield quicker and more accurate results than those predicted by animal testing.
Heart, ocular and other human tissues can be replicated from stem cells, which are then exposed to developmental-stage drugs in order to monitor stem cell behavior, with researchers watching for key changes. The theory is that exposure to toxic substances may alter concentrations of the stem cell molecules responsible during normal development for cellular metabolism and differentiation, thus disrupting cell-to-cell interactions and producing a “biological cascade” that may lead to potential developmental disorders. Stem cell testing of this type is a new concept, so more research is needed to determine whether the approach is viable and trustworthy, especially on a system as complex as the human body.
Advanced Computer Modeling
As with in vitro and stem cell models, computer (in silico) models allow for testing of new drugs and treatments. Researchers have developed several sophisticated in silico simulations of human biology—including heart, lung, kidney, skin, musculoskeletal and digestive system—on which they can track progression of developing diseases. Early studies indicate these simulations can reliably predict how trial drugs interact with the body, thus acting as a replacement for animal testing.
Quantitative structure-activity relationship (QSAR) models are specific kinds of in silico methods that produce accurate estimates of a substance’s hazard potential to humans, basing estimates on comparisons to existing substances and our understanding of human biology. Another type is brain-imaging technology, which allows researchers to see inside the brain to study the progression and treatment of brain diseases on volunteer subjects. The results can then be compared to healthy volunteers.
What better way to eliminate animal testing than to instead test drugs on human volunteers? The practice of microdosing consists of giving volunteer subjects a tiny, one-time dose of a drug to assess (via advanced imaging techniques) how the drug behaves in the body. Microdosing helps to screen out compounds that won’t work on humans, obviating the need to test these on animals. Note that while microdosing offers details about pharmacokinetics and pharmacodynamics, it offers no information about toxicity or toxicology.
Another way for human volunteers to help eliminate animal testing is through organ and tissue donations from surgeries and post-mortems. These donations can be used in the same ways as tissues developed in vitro. But since they’re mature tissues (unlike those grown in a lab), they offer a more reliable response to stimuli.
Lifelike human-patient simulators have replaced animal test subjects in ninety-seven percent of US medical schools. These high-tech simulators breathe, bleed, convulse, talk and even die. They mimic illnesses and injuries, providing accurate biological responses in medical interventions and introduction of medications.
For example, the TraumaMan system replicates a breathing, bleeding human torso, with multiple layers of skin and tissue as well as internal organs. It teaches emergency surgical techniques without the need to cut into live dogs, pigs or goats. Generally, human-patient simulators are better teaching aids for physiology and pharmacology students than exercises in which animals are cut up.
From governments, researchers and animal activists alike, much support exists for seeking alternative methods to animal testing. After all, why expose animals to unnecessary suffering? The biggest argument from the anti-alternatives camp is that the human body is too complex for simulations and in vitro models to accurately mimic. The perfect rebuttal for this argument, of course, is: Necessity is the mother of invention! Who knows what is possible until the only choice is to try something else?
Despite common belief, not every significant breakthrough in medical history has required animal testing. While the discovery of insulin therapy is said to have relied on the removal of dogs’ pancreases, the real research legwork had been done earlier in observations of human patients. Or consider that the best location for electrodes to be placed in the brain for the Parkinson’s treatment known as Deep Brain Stimulation was first identified not through research on monkeys, but decades earlier, through brain surgery on Parkinson’s patients.
Common ground exists between animal activists and researchers. To quote from a Huffington Post blog by Alan Kelly, founder and CEO of strategy and simulations firm Playmaker Systems: “No researcher would rather probe than pet an animal. And no activist would rather lose their child to a disease than spare the mice and monkeys that help cure it.” Only the most insensitive (or sadistic) researcher would still be willing to gamble on the cruelty of animals as test subjects. It’s time to go all in on exploring every alternative—in short, to replace, reduce, refine. Heck, maybe it’s good chimps only learned basic sign language. Imagine the terror of the chimp that learned the sign for LEMSIP’s full name.
Main image: Wikicommons